bluuebunny/crossref_metadata_2025_split huggingface dataset:
Coordinated metabolic adaptation of Arabidopsis thaliana to high light
Authors: Balcke Gerd Ulrich , Vahabi Khabat , Giese Jonas , Finkemeier Iris , Tissier Alain 
Published: August 2024

SUMMARYIn plants, exposure to high light irradiation induces various stress responses, which entail complex metabolic rearrangements. To explore these dynamics, we conducted time‐course experiments spanning 2 min to 72 h with Arabidopsis thaliana under high and control light. Comparative metabolomics, transcriptomics, redox proteomics, and stable isotope labeling on leaf rosettes identified a series of synchronous and successive responses that provide a deeper insight into well‐orchestrated mechanisms contributing to high‐light acclimation. We observed transient transcriptome downregulation related to light harvesting and electron flow before the profound remodeling of the photosynthetic apparatus. Throughout the entire time course, redox homeostasis is tightly balanced between downregulation of production and enhanced transformation of NADPH accompanied by redistribution of reducing equivalents across several subcellular compartments. In both light conditions, C4 acids such as malate and fumarate are produced via anaplerosis. In carbon units, their accumulation in vacuoles surpasses plastidic levels of starch and intensifies notably under high light. In parallel, citrate synthesis from pyruvate is significantly hindered diurnally. Isotopic labeling in 2‐oxoglutarate and glutamate suggests a moderate de novo synthesis of C5 acids from a vacuolar citrate reservoir during the light phase while they are largely renewed during the night. In the absence of a diurnal clockwise flow through the tricarboxylic acid (TCA) cycle, increased oxidation of photorespiratory glycine takes over as a source of reductants to fuel mitochondrial ATP production. These findings, along with previous research, contribute to a model integrating redox balance and linking increased carbon assimilation and nitrogen metabolism, especially in the context of an incomplete TCA cycle.
Gaelic Games Players’ and Practitioners’ Perceptions of Recovery Strategies
Authors: Daly Lorcan S. , Catháin Ciarán Ó. , Kelly David T. 
Published: August 2024

Purpose: This study both investigated and compared Gaelic games players’ and practitioners’ perceptions of the importance of postexercise recovery strategies. Methods: Gaelic players (n = 1178 [n = 574 female], age 24.6 [6.6] y) and practitioners (n = 148 [n = 29 female], age 35.9 [8.7] y) completed a questionnaire assessing their perceptions of various postexercise recovery strategies (importance ranked out of 5 [1 “not important at all” to 5 “extremely important”]). Players were further categorized by playing standard into developmental (club/collegiate; n = 869) and national (intercounty; n = 309) levels and by sport: Gaelic football (n = 813), camogie/hurling (n = 342), and Gaelic handball (n = 23). Practitioners were categorized as sport coaches (n = 67), strength and conditioning staff (n = 34), nutrition staff (n = 15), and athletic rehabilitation staff (n = 32). Results: Gaelic players prevalently perceived sleep (76.4%), rehydration (72.5%), postexercise meal (48.4%), stretching (47.6%), active cool-down (25.1%), foam rolling (23.1%), and massage by therapist (22.6%) as “extremely important.” Practitioners prevalently perceived sleep (90.1%), rehydration (83.6%), postexercise meal (76.6%), daytime naps (36.2%), stretching (25.4%), discussion with teammates (24.6%), and getting into nature (19.4%) as “extremely important.” Conclusions: While strategies with well-documented efficacy such as sleep, nutrition, and rehydration were rated as most important, a distinct and possibly problematic disconnect exists between the perceived importance of many strategies and their empirically demonstrated effectiveness. For instance, active cool-downs and stretching were perceived as highly important despite prevailing evidence suggesting that their effects are often small in magnitude. Collectively, work promoting optimal recovery practices and aligning player-practitioner perspectives would be beneficial to maximize time and resource allocation and enhance player buy-in.
Dual feedback inhibition of ATP-dependent caffeate activation economizes ATP in caffeate-dependent electron bifurcation
Authors: Xu Fengjun , Thoma Calvin J. , Zhao Weiyang , Zhu Yiwen , Men Yujie , Wackett Lawrence P. 
Published: August 2024

ABSTRACT

The acetogen
Acetobacterium woodii
couples caffeate reduction with ferredoxin reduction and NADH oxidation via electron bifurcation, providing additional reduced ferredoxin for energy conservation and cell synthesis. Caffeate is first activated by an acyl-CoA synthetase (CarB), which ligates CoA to caffeate at the expense of ATP. After caffeoyl-CoA is reduced to hydrocaffeoyl-CoA, the CoA moiety in hydrocaffeoyl-CoA could be recycled for caffeoyl-CoA synthesis by an ATP-independent CoA transferase (CarA) to save energy. However, given that CarA and CarB are co-expressed, it was not well understood how ATP could be saved when both two competitive pathways of caffeate activation are present. Here, we reported a dual feedback inhibition of the CarB-mediated caffeate activation by the intermediate hydrocaffeoyl-CoA and the end-product hydrocaffeate. As the product of CarA, hydrocaffeate inhibited CarB-mediated caffeate activation by serving as another substrate of CarB with hydrocaffeoyl-CoA produced. It effectively competed with caffeate even at a concentration much lower than caffeate. Hydrocaffeoyl-CoA formed in this process can also inhibit CarB-mediated caffeate activation. Thus, the dual feedback inhibition of CarB, together with the faster kinetics of CarA, makes the ATP-independent CarA-mediated CoA loop the major route for caffeoyl-CoA synthesis, further saving ATP in the caffeate-dependent electron-bifurcating pathway. A genetic architecture similar to
carABC
has been found in other anaerobic bacteria, suggesting that the feedback inhibition of acyl-CoA ligases could be a widely employed strategy for ATP conservation in those pathways requiring substrate activation by CoA.

IMPORTANCE

This study reports a dual feedback inhibition of caffeoyl-CoA synthetase by two downstream products, hydrocaffeate and hydrocaffeoyl-CoA. It elucidates how such dual feedback inhibition suppresses ATP-dependent caffeoyl-CoA synthesis, hence making the ATP-independent route the main pathway of caffeate activation. This newly discovered mechanism contributes to our current understanding of ATP conservation during the caffeate-dependent electron-bifurcating pathway in the ecologically important acetogen
Acetobacterium woodii
. Bioinformatic mining of microbial genomes revealed contiguous genes homologous to
carABC
within the genomes of other anaerobes from various environments, suggesting this mechanism may be widely used in other CoA-dependent electron-bifurcating pathways.
Tectonic Basis for Oil and Gas Potential in the North Kara Prospective Oil and Gas Region (Western Arctic, Russia)
Authors: Tarasenko A. K. , Alekseeva A. K. , Khohlova Yu. N. , Inshakova N. Yu. 
Published: August 2024

Abstract—
Russia’s Arctic shelf and, in particular, the Kara Sea shelf, is one of the unique regions in the world with enormous hydrocarbon potential; however, due to the harsh climate conditions, it has been studied unevenly. The lack of deep and parametric drilling data in the northern Kara Sea leads to numerous uncertainties in regional geological structure models and, as a consequence, in assessing the resource potential of this Arctic region. A vast number of 2D CDP seismic explorations were carried out in the northern Kara Sea. The results of these studies made it possible to refine the geological structure of the Kara Plate, substantiate the boundaries of the North Kara independent prospective oil and gas region and promising areas within it, and assess hydrocarbon resources.
Pseudomyxoma peritonei peritonitis
Authors: Yannamani Pranathi , Chungu Lillian , Shetty Rajesh , Oyewole Bankole 
Published: August 2024

Pseudomyxoma peritonei (PMP) is a rare neoplastic condition characterised by gelatinous ascites, which generally arise from mucin-producing appendiceal tumours. Presentation is variable but requires prompt recognition to ensure appropriate specialist management due to risk of malignancy.A male in his 40s presented with a 1-day history of sudden onset, non-migratory abdominal pain, worse in the right iliac fossa. He had no significant medical history nor known drug allergies. Examination revealed right iliac fossa peritonism and blood tests revealed raised inflammatory markers. CT scan showed a right-sided abdominal collection. Intraoperatively, a diagnostic laparoscopy was performed, which revealed extensive mucin in the abdominal cavity. This was washed out and a laparoscopic appendectomy was performed; histopathology confirmed PMP from the ruptured appendix.
A framework for identifying opportunities for multisectoral action for drowning prevention in health and sustainable development agendas: a multimethod approach
Authors: Scarr Justin-Paul , Meddings David R , Lukaszyk Caroline , Vincenten Joanne Adrienne , Rahman Aminur , Wills Steve , Jagnoor Jagnoor 
Published: August 2024

IntroductionThe 2023 World Health Assembly resolution 76.18 committed the World Health Organization to the coordination of drowning prevention efforts, including those of United Nations (UN) agencies. Here, we aim to map drowning prevention linkages across UN Agency agendas, make recommendations to guide global strategies and inform the development of the Global Alliance and a Global Strategy for drowning prevention.MethodsWe applied a qualitative multimethod approach, including document review, key informant interviews, an interagency workshop and international conference panel discussion, to refine data and create our recommendations. We developed a framework to identify intersections between health and sustainable development agendas and applied it to map intersections and opportunities for the integration of drowning prevention across relevant UN Agency agendas.ResultsOur framework categorised intersections for drowning prevention in UN Agendas according to potential for (a) shared understandings of problems and solutions, (b) shared capacities, guidelines and resources and (c) shared governance and strategic pathways, noting that some factors overlap. We present our Position, Add, Reach and Reframe approach to outlining opportunities for the integration of drowning prevention in health and sustainable development agendas. Our results emphasise the importance of establishing approaches to the Global Alliance and Global Strategy that ensure high-level political advocacy is converted into solutions for affected communities. We recommend using research to inform effective action, building capacity and best practices, and promoting evaluation frameworks to incentivise and verify progress.ConclusionOur study identifies opportunities to expand drowning prevention efforts and to build Member State capacity to reduce drowning risk through evidence-informed measures that address vulnerabilities, exposures, hazards and build population-level resilience to drowning. Our framework for identifying opportunities for integration of drowning prevention across a multisectoral set of agendas offers a research and policy toolkit that may prove useful for other policy areas.
Correlation between choroidal parameters and primary angle-closure suspect in different age groups
Authors: Li Mengyang , Li Zhi , Xiang Fei , Li Caixia , Zhang Ye , Li Shuning 
Published: August 2024

ObjectiveTo investigate the correlations between choroidal parameters and primary angle-closure suspect (PACS) in different age subgroups.Methods and analysisParticipants aged 50 years or older in a rural area of Daxing District, Beijing, were recruited. Swept-source optical coherence tomography was used to measure the choroidal parameters. Demographic, ocular biometry parameters and choroidal parameters were compared between the PACS and non-PACS (NPACS) eyes. Logistic analysis was performed to explore the association between the choroidal parameters and PACS.Results192 (26.89%) subjects with PACS and 509 (71.29%) with PACS were analysed. Subjects were divided into two groups: group 1 (50–60 years, n=286) and group 2 (>60 years, n=415). In group 1, the mean subfoveal choroidal thickness of PACS eyes was 341.82±88.23 µm and thicker than NPACS eyes (315.07±83.53 µm, p=0.035). The choroidal volume was greater in PACS eyes (10.61±2.78 mm3) compared with NPACS eyes (9.66±2.49 mm3, p=0.013). In group 2, no significant difference in any choroidal parameters between PACS and NPACS was found. Multivariate regression demonstrated that increased choroidal volume was associated with PACS (OR 1.298, 95% CI 1.117 to 1.510, p<0.001) in group 1.ConclusionsIn the age group of 50–60 years, PACS eyes had greater choroidal thickness and volume than NPACS eyes, and the increased total choroidal volume was a predisposing factor for PACS.Trial registration numberChiCTR2000037944.
Patient safety and the COVID-19 pandemic: a qualitative study of perspectives of front-line clinicians
Authors: Schulson Lucy , Bandini Julia , Bialas Armenda , Huilgol Shreya , Timmins George , Ahluwalia Sangeeta , Gidengil Courtney 
Published: August 2024

IntroductionStudies on the impacts of COVID-19 on patient safety are emerging. However, few studies have elicited the perspectives of front-line clinicians.MethodsWe interviewed clinicians from 16 US hospitals who worked in the emergency department, intensive care unit or inpatient unit during the COVID-19 pandemic. We asked about their experiences with both clinician well-being and patient care throughout the pandemic. We used a rigorous thematic analysis to code the interview transcripts. This study was part of a larger randomised control trial of an intervention to improve healthcare worker well-being during the COVID-19 pandemic; the findings described here draw from clinicians who spontaneously raised issues related to patient safety.Results11 physicians and 16 nurses in our sample raised issues related to patient safety. We identified two primary themes: (1) compromised access to healthcare and (2) impaired care delivery. First, clinicians discussed how changes in access to healthcare early in the pandemic–including a shift to telehealth and deferred care–led to delays in accurate diagnosis and patients presenting later in their disease course. Second, clinicians discussed the effects of COVID-19 on care delivery related to staffing, equipment shortages and space constraints and how they deviated from the standard of care to manage these constraints. Clinicians noted how these issues led to patient safety events such as central line infections, patient falls and serious medication administration errors.ConclusionsSeveral well-intentioned interventions implemented in the early weeks of the pandemic created a unique context that affected patient safety throughout the pandemic. Future pandemic preparedness should consider planning that incorporates a patient safety lens to mitigate further harm from occurring during a public health crisis.
ON THE SOLUTION UNIQUENESS IN PORTFOLIO OPTIMIZATION AND RISK ANALYSIS
Authors: GRECHUK BOGDAN , PALCZEWSKI ANDRZEJ , PALCZEWSKI JAN 
Published: August 2024

In this paper, we consider the issue of solution uniqueness of the mean-deviation portfolio optimization problem and its inverse for asset returns distributed over a finite number of scenarios. Due to the asymmetry of returns, the risk is assessed by a general deviation measure introduced by Rockafellar et al. [(2006b) Optimality conditions in portfolio analysis with general deviation measures, Mathematical Programming 108, 515–540] instead of the standard deviation as in the classical Markowitz optimization problem. We demonstrate that, in general, one cannot expect the uniqueness of Pareto-optimal profit sharing in cooperative investment and the uniqueness of solutions in the mean-deviation Black–Litterman asset allocation model. For a large class of deviation measures, we provide a resolution of the above nonuniqueness issues based on the principle of law-invariance. We provide several examples illustrating the nonuniqueness and the law-invariant solution.
ORIC-101, a Glucocorticoid Receptor Antagonist, in Combination with Nab-Paclitaxel in Patients with Advanced Solid Tumors
Authors: Chen Christopher T. , Khanna Vishesh , Kummar Shivaani , Abdul-Karim Raghad M. , Sommerhalder David , Tolcher Anthony W. , Ueno Naoto T. , Davis Sarah Lindsey , Orr Douglas W. , Hamilton Erika , Patel Manish R. , Spira Alexander I. , Jauhari Shekeab , Florou Vaia , Duff Maureen , Xu Rongda , Wang Jian , Barkund Shravani R. , Zhou Haiying , Pankov Aleksandr , Kong Wayne , Jahchan Nadine S. , Jackson Erica L. , Sun Jessica D. , Junttila Melissa R. , Multani Pratik S. , Daemen Anneleen , Chow Maneval Edna , Munster Pamela N. 
Published: August 2024

Abstract
Purpose: In preclinical models, glucocorticoid receptor (GR) signaling drives resistance to taxane chemotherapy in multiple solid tumors via upregulation of antiapoptotic pathways. ORIC-101 is a potent and selective GR antagonist that was investigated in combination with taxane chemotherapy as an anticancer regimen preclinically and in a phase 1 clinical trial.
Patients and Methods: The ability of ORIC-101 to reverse taxane resistance was assessed in cell lines and xenograft models, and a phase 1 study (NCT03928314) was conducted in patients with advanced solid tumors to determine the dose, safety, and antitumor activity of ORIC-101 with nab-paclitaxel.
Results: ORIC-101 reversed chemoprotection induced by glucocorticoids in vitro and achieved tumor regressions when combined with paclitaxel in both taxane-naïve and -resistant xenograft models. In the phase 1 study, 21 patients were treated in dose escalation and 62 patients were treated in dose expansion. All patients in dose expansion had previously progressed on a taxane-based regimen. In dose escalation, five objective responses were observed. A preplanned futility analysis in dose expansion showed a 3.2% (95% confidence interval, 0.4–11.2) objective response rate with a median progression-free survival of 2 months (95% confidence interval, 1.8–2.8) across all four cohorts, leading to study termination. Pharmacodynamic analysis of tissue and plasma showed GR pathway downregulation in most patients in cycle 1.
Conclusions: ORIC-101 with nab-paclitaxel showed limited clinical activity in taxane-resistant solid tumors. Despite clear inhibition of GR pathway signaling, the insufficient clinical signal underscores the challenges of targeting a single resistance pathway when multiple mechanisms of resistance may be in play.
Significance: Glucocorticoid receptor (GR) upregulation is a mechanism of resistance to taxane chemotherapy in preclinical cancer models. ORIC-101 is a small molecule GR inhibitor. In this phase 1 study, ORIC-101 plus nab-paclitaxel did not show meaningful clinical benefit in patients who previously progressed on taxanes despite successful GR pathway downregulation.
Long-Lasting Response to Lorlatinib in Patients with ALK-Driven Relapsed or Refractory Neuroblastoma Monitored with Circulating Tumor DNA Analysis
Authors: Ek Torben , Ibrahim Raghda R. , Vogt Hartmut , Georgantzi Kleopatra , Träger Catarina , Gaarder Jennie , Djos Anna , Rahmqvist Ida , Mellström Elisabeth , Pujol-Calderón Fani , Vannas Christoffer , Hansson Lina , Fagman Henrik , Treis Diana , Fransson Susanne , Österlund Tobias , Chuang Tzu-Po , Verhoeven Bronte Manouk , Ståhlberg Anders , Palmer Ruth H. , Hallberg Bengt , Martinsson Tommy , Kogner Per , Dalin Martin 
Published: August 2024

Abstract

Patients with anaplastic lymphoma kinase (ALK)–driven neuroblastoma may respond to tyrosine kinase inhibitors, but resistance to treatment occurs and methods currently used for detection of residual disease have limited sensitivity. Here, we present a national unselected cohort of five patients with relapsed or refractory ALK-driven neuroblastoma treated with lorlatinib as monotherapy and test the potential of targeted circulating tumor DNA (ctDNA) analysis as a guide for treatment decisions in these patients. We developed a sequencing panel for ultrasensitive detection of ALK mutations associated with neuroblastoma or resistance to tyrosine kinase inhibitors and used it for ctDNA analysis in 83 plasma samples collected longitudinally from the four patients who harbored somatic ALK mutations. All four patients with ALK p.R1275Q experienced major responses and were alive 35 to 61 months after starting lorlatinib. A fifth patient with ALK p.F1174L initially had a partial response but relapsed after 10 months of treatment. In all cases, ctDNA was detected at the start of lorlatinib single-agent treatment and declined gradually, correlating with clinical responses. In the two patients exhibiting relapse, ctDNA increased 9 and 3 months, respectively, before clinical detection of disease progression. In one patient harboring HRAS p.Q61L in the relapsed tumor, retrospective ctDNA analysis showed that the mutation appeared de novo after 8 months of lorlatinib treatment. We conclude that some patients with relapsed or refractory high-risk neuroblastoma show durable responses to lorlatinib as monotherapy, and targeted ctDNA analysis is effective for evaluation of treatment and early detection of relapse in ALK-driven neuroblastoma.

Significance:
We present five patients with ALK-driven relapsed or refractory neuroblastoma treated with lorlatinib as monotherapy. All patients responded to treatment, and four of them were alive after 3 to 5 years of follow-up. We performed longitudinal ctDNA analysis with ultra-deep sequencing of the ALK tyrosine kinase domain. We conclude that ctDNA analysis may guide treatment decisions in ALK-driven neuroblastoma, also when the disease is undetectable using standard clinical methods.
Targeting TREX1 Induces Innate Immune Response in Drug-Resistant Small-Cell Lung Cancer
Authors: Murayama Takahiko , Mahadevan Navin R. , Meador Catherine B. , Ivanova Elena V. , Pan Yuqiao , Knelson Erik H. , Tani Tetsuo , Nakayama Jun , Ma Xueying , Thai Tran C. , Hung Yin P. , Kim William , Watanabe Hideo , Cai Kathy Q. , Hata Aaron N. , Paweletz Cloud P. , Barbie David A. , Cañadas Israel 
Published: August 2024

Abstract
Small-cell lung cancer (SCLC) is the most lethal type of lung cancer. Paradoxically, this tumor displays an initial exquisite response to chemotherapy; however, at relapse, the tumor is highly resistant to subsequent available therapies. Here, we report that the expression of three prime repair exonuclease 1 (TREX1) is strongly induced in chemoresistant SCLCs. Assay for transposase-accessible chromatin using sequencing and chromatin immunoprecipitation sequencing revealed a significant increase in chromatin accessibility and transcriptional activity of TREX1 gene locus in chemoresistant SCLCs. Analyses of human SCLC tumors and patient-derived xenografts (PDX) also showed an increase in TREX1 expression in postchemotherapy samples. TREX1 depletion caused the activation of cyclic GMP-AMP synthase stimulator of interferon gene pathway due to cytoplasmic accumulation of damage-associated double-stranded DNA, inducing immunogenicity and enhancing the sensitivity of drug-resistant cells to chemotherapy. These findings suggest TREX1 upregulation may partially contribute to the survival of resistant cells, and its inhibition may represent a promising therapeutic strategy to enhance antitumor immunity and potentiate the efficacy of chemotherapy and/or immunotherapy in chemoresistant SCLCs.
Significance: In this study, we show that targeting TREX1 induces an innate immune response and resensitizes SCLC cells to chemotherapy, representing a promising novel target for “immunologically” cold tumors, such as SCLC.