bluuebunny/crossref_metadata_2025_split huggingface dataset:
Survey of Information Encoding Techniques for DNA
Authors: Heinis Thomas , Sokolovskii Roman , Alnasir Jamie J. 
Published: October 2023

The yearly global production of data is growing exponentially, outpacing the capacity of existing storage media, such as tape and disk, and surpassing our ability to store it. DNA storage—the representation of arbitrary information as sequences of nucleotides—offers a promising storage medium. DNA is nature’s information-storage molecule of choice and has a number of key properties: It is extremely dense, offering the theoretical possibility of storing 455 EB/g; it is durable, with a half-life of approximately 520 years that can be increased to thousands of years when DNA is chilled and stored dry; and it is amenable to automated synthesis and sequencing. Furthermore, biochemical processes that act on DNA potentially enable highly parallel data manipulation.
While biological information is encoded in DNA via a specific mapping from triplet sequences of nucleotides to amino acids, DNA storage is not limited to a single encoding scheme, and there are many possible ways to map data to chemical sequences of nucleotides for synthesis, storage, retrieval, and data manipulation. However, there are several biological, error-tolerance, and information-retrieval considerations that an encoding scheme needs to address to be viable.
This comprehensive review focuses on comparing existing work done in encoding arbitrary data within DNA in terms of their encoding schemes, methods to address biological constraints, and measures to provide error correction. We compare encoding approaches on the overall information density and coverage they achieve, as well as the data-retrieval method they use (i.e., sequential or random access). We also discuss the background and evolution of the encoding schemes.
NKG2A Is a Therapeutic Vulnerability in Immunotherapy Resistant MHC-I Heterogeneous Triple-Negative Breast Cancer
Authors: Taylor Brandie C. , Sun Xiaopeng , Gonzalez-Ericsson Paula I. , Sanchez Violeta , Sanders Melinda E. , Wescott Elizabeth C. , Opalenik Susan R. , Hanna Ann , Chou Shu-Ting , Van Kaer Luc , Gomez Henry , Isaacs Claudine , Ballinger Tarah J. , Santa-Maria Cesar A. , Shah Payal D. , Dees Elizabeth C. , Lehmann Brian D. , Abramson Vandana G. , Pietenpol Jennifer A. , Balko Justin M. 
Published: October 2023

Abstract

Despite the success of immune checkpoint inhibition (ICI) in treating cancer, patients with triple-negative breast cancer (TNBC) often develop resistance to therapy, and the underlying mechanisms are unclear. MHC-I expression is essential for antigen presentation and T-cell–directed immunotherapy responses. This study demonstrates that TNBC patients display intratumor heterogeneity in regional MHC-I expression. In murine models, loss of MHC-I negates antitumor immunity and ICI response, whereas intratumor MHC-I heterogeneity leads to increased infiltration of natural killer (NK) cells in an IFNγ-dependent manner. Using spatial technologies, MHC-I heterogeneity is associated with clinical resistance to anti-programmed death (PD) L1 therapy and increased NK:T-cell ratios in human breast tumors. MHC-I heterogeneous tumors require NKG2A to suppress NK-cell function. Combining anti-NKG2A and anti–PD-L1 therapies restores complete response in heterogeneous MHC-I murine models, dependent on the presence of activated, tumor-infiltrating NK and CD8+ T cells. These results suggest that similar strategies may enhance patient benefit in clinical trials.

Significance:
Clinical resistance to immunotherapy is common in breast cancer, and many patients will likely require combination therapy to maximize immunotherapeutic benefit. This study demonstrates that heterogeneous MHC-I expression drives resistance to anti–PD-L1 therapy and exposes NKG2A on NK cells as a target to overcome resistance.
This article is featured in Selected Articles from This Issue, p. 201
Mitochondria Dictate Function and Fate of HSCs and T Cells
Authors: Xu Yingxi , Chiang Yi-Hsuan , Ho Ping-Chih , Vannini Nicola 
Published: October 2023

Abstract
Hematopoietic stem cells (HSC) and T cells are intimately related, lineage-dependent cell populations that are extensively used as therapeutic products for the treatment of hematologic malignancies and certain types of solid tumors. These cellular therapies can be life-saving treatments; however, their efficacies are often limited by factors influencing their activity and cellular properties. Among these factors is mitochondrial metabolism, which influences the function and fate commitment of both HSCs and T cells. Mitochondria, besides being the “cellular powerhouse,” provide metabolic intermediates that are used as substrates for epigenetic modifications and chromatin remodeling, thus, driving cell fate decisions during differentiation. Moreover, mitochondrial fitness and mitochondrial quality control mechanisms are closely related to cellular function, and impairment of these mitochondrial properties associates with cellular dysfunction due to factors such as T-cell exhaustion and aging. Here, we give an overview of the role of mitochondria in shaping the behavior of these lineage-related cell populations. Moreover, we discuss the potential of novel mitochondria-targeting strategies for enhancing HSC- and T cell–based cancer immunotherapies and highlight how design and application of such approaches requires consideration of the metabolic similarities and differences between HSCs and T cells.
See related article on p. 1302.
Blood Pressure and Oxygen Targets on Kidney Injury After Cardiac Arrest
Authors: Rasmussen Sebastian Buhl , Jeppesen Karoline Korsholm , Kjaergaard Jesper , Hassager Christian , Schmidt Henrik , Mølstrøm Simon , Beske Rasmus Paulin , Grand Johannes , Ravn Hanne Berg , Winther-Jensen Matilde , Meyer Martin Abild Stengaard , Møller Jacob Eifer 
Published: October 2023

BACKGROUND:
Acute kidney injury (AKI) represents a common and serious complication to out-of-hospital cardiac arrest. The importance of post-resuscitation care targets for blood pressure and oxygenation for the development of AKI is unknown.

METHODS:

This is a substudy of a randomized 2-by-2 factorial trial, in which 789 comatose adult patients who had out-of-hospital cardiac arrest with presumed cardiac cause and sustained return of spontaneous circulation were randomly assigned to a target mean arterial blood pressure of either 63 or 77 mm Hg. Patients were simultaneously randomly assigned to either a restrictive oxygen target of a partial pressure of arterial oxygen (Pa
o
2
) of 9 to 10 kPa or a liberal oxygenation target of a Pa
o
2
of 13 to 14 kPa. The primary outcome for this study was AKI according to KDIGO (Kidney Disease: Improving Global Outcomes) classification in patients surviving at least 48 hours (N=759). Adjusted logistic regression was performed for patients allocated to high blood pressure and liberal oxygen target as reference.

RESULTS:
The main population characteristics at admission were: age, 64 (54–73) years; 80% male; 90% shockable rhythm; and time to return of spontaneous circulation, 18 (12–26) minutes. Patients allocated to a low blood pressure and liberal oxygen target had an increased risk of developing AKI compared with patients with high blood pressure and liberal oxygen target (84/193 [44%] versus 56/187 [30%]; adjusted odds ratio, 1.87 [95% CI, 1.21–2.89]). Multinomial logistic regression revealed that the increased risk of AKI was only related to mild-stage AKI (KDIGO stage 1). There was no difference in risk of AKI in the other groups. Plasma creatinine remained high during hospitalization in the low blood pressure and liberal oxygen target group but did not differ between groups at 6- and 12-month follow-up.

CONCLUSIONS:
In comatose patients who had been resuscitated after out-of-hospital cardiac arrest, patients allocated to a combination of a low mean arterial blood pressure and a liberal oxygen target had a significantly increased risk of mild-stage AKI. No difference was found in terms of more severe AKI stages or other kidney-related adverse outcomes, and creatinine had normalized at 1 year after discharge.

REGISTRATION:

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT03141099.
Effects of Wind Stress Uncertainty on Short-Term Prediction of the Kuroshio Extension State Transition Process
Authors: Zhang Hui , Wang Qiang , Mu Mu , Zhang Kun , Geng Yu 
Published: October 2023

Abstract
Based on the conditional nonlinear optimal perturbation for boundary condition method and Regional Ocean Modeling System (ROMS), this study investigates the influence of wind stress uncertainty on predicting the short-term state transitions of the Kuroshio Extension (KE). The optimal time-dependent wind stress errors that lead to maximum prediction errors are obtained for two KE stable-to-unstable and two reverse transitions, which exhibit local multieddies structures with decreasing magnitude as the end time of prediction approaches. The optimal boundary errors initially induce small oceanic errors through Ekman pumping. Subsequently, these errors grow in magnitude as oceanic internal processes take effect, which exerts significant influences on the short-term prediction of the KE state transition process. Specifically, during stable-to-unstable (unstable-to-stable) transitions, the growing error induces an overestimation (underestimation) of the meridional sea surface height gradient across the KE axis, leading to the predicted KE state being more (less) stable. Furthermore, the dynamics mechanism analysis indicates that barotropic instability is crucial for the error growth in the prediction of both the stable-to-unstable and the reverse transition processes due to the horizontal shear of flow field. But work generated by wind stress error plays a more important role in the prediction of the unstable-to-stable transitions because of the synergistic effect of strong wind stress error and strong oceanic error. Eventually, the sensitive areas have been identified based on the optimal boundary errors. Reducing wind stress errors in sensitive areas can significantly improve prediction skills, offering theoretical guidance for devising observational strategies.
Eddy Acceleration and Decay Driven by Internal Tides
Authors: Shakespeare Callum J. 
Published: October 2023

Abstract
Recent observations and numerical simulations have demonstrated the potential for significant interactions between mesoscale eddies and smaller-scale tidally generated internal waves—also known as internal tides. Here, we develop a simple theoretical model that predicts the one-way upscale transfer of energy from internal tides to mesoscale eddies through a critical level mechanism. We find that—in the presence of a critical level—the internal tide energy flux into an eddy is partitioned according to the wave frequency Ω and local inertial frequency f: a fraction of 1 − f/Ω is transferred to the eddy kinetic energy, while the remainder is viscously dissipated or supports mixing. These predictions are validated by comparison with a suite of numerical simulations. The simulations further show that the wave-driven energization of the eddies also accelerates the onset of hydrodynamical instabilities and the breakdown of the eddies, thereby increasing eddy kinetic energy, but reducing eddy lifetimes. Our estimates suggest that in regions of the ocean with both significant eddy fields and internal tides—such as parts of the Gulf Stream and Antarctic Circumpolar Current—the critical level effect could drive a ∼10% month−1 increase in the kinetic energy of a typical eddy. Our results provide a basis for parameterizing internal tide–eddy interactions in global ocean models where they are currently unrepresented.
How is Flash Drought Understood?—Experts’ Definitions and Decision-Makers’ Perceptions
Authors: Schwartz Caily , Haigh Tonya , Svoboda Mark , Goebel Madeline 
Published: October 2023

Abstract
Because flash drought is a relatively new phenomenon in drought research, defining the concept is critical for scientists and decision-makers. Having detrimental impacts on many sectors, it is important to have a consistent definition and understanding of flash drought, between experts and stakeholders, to provide early warning to the community. This study focuses on onset and progression of conditions and demonstrates the difference in flash drought identification for 15 events across six quantitative definitions of flash drought that use the U.S. Drought Monitor (USDM). Five flash drought events have been studied in the literature while 10 additional events have been perceived as flash drought by stakeholders. The results show that two of six definitions consistently capture the earliest onset of flash drought and include a large percent area in the identification. A qualitative analysis of management challenges and needs determined by stakeholders was completed using survey data. The results found that managing impacts and better communication and education were the top challenges and more data and enhanced and efficient communication as the top needs to better monitor, manage, and respond to flash droughts. The results demonstrate the need for assessing the characteristics of the definitions to enhance communication and monitoring strategies for large and small-scale flash droughts.

Significance Statement
The purpose of this study is to better understand how different numerical flash drought definitions characterize multiple flash drought events and how these definitions are useful in addressing the needs and challenges of stakeholders. This is important because definitions may capture different areas in flash droughts, which can impact how end users identify a flash drought. Further, this study uses events identified by the literature and by people familiar with drought monitoring. From these findings, definitions that capture flash drought earliest would help address the challenge of rapid onset and the need of quicker data. Further, definitions by sector would be beneficial to address the scale of impacts. This study identifies the importance of definitions for early warning systems.
Validation of the Randox colorimetric assays for serum copper and zinc
Authors: Handley Simon A , Wanandy Troy , Prentice Louise 
Published: October 2023

Background Serum copper and zinc are measured to assess deficiency and toxicity. Atomic absorption spectrophotometry and mass spectrometry methods are expensive and require highly trained staff. Colorimetric assays are available from Randox which are inexpensive and can be automated. We validated serum copper and zinc colorimetric assays on the Binding Site Optilite analyser including comparison with flame atomic absorption spectrophotometry (FAAS) and inductively coupled plasma-mass spectrometry (ICP-MS). Methods Accuracy, imprecision, lower limit of quantitation, and linearity were ascertained. The impact of triglycerides, bilirubin, nickel, and iron on assay performance was also investigated. Comparison of results from colorimetric analysis of patient and external quality assurance samples with those obtained by FAAS and ICP-MS was undertaken. Results Intra-, and inter-assay imprecision was <9%. Serum copper and zinc assays were linear between 1.8–35.6 and 2.3–45.7 µmol/L, respectively. Agreement was good between colorimetry and FAAS (intercept = -0.7, slope = 1.04) and ICP-MS (intercept = 0.6, slope = 0.99) for serum copper in patients’ samples. For serum zinc, agreement was poor between colorimetry and FAAS (intercept = 2.2, slope = 0.87) and ICP-MS (intercept = 1.9, slope = 0.98) in patients’ samples. There was a poor concordance in assessment of hypozincaemia between colorimetry and FAAS/ICP-MS. Conclusion The Randox colorimetric assay for serum copper on the Optilite is simple to perform, has a short analysis time, and measured concentrations compare well with FAAS and ICP-MS. Due to poor agreement with FAAS and ICP-MS, colorimetry is not suitable for the measurement of serum zinc.
Modulation of Nrf2/HO1 Pathway by Thymoquinone to Exert Protection Against Diazinon-induced Myocardial Infarction in Rats
Authors: Wang Gang 
Published: October 2023

Background Modern strategies to alleviate the harmful effects of organophosphate pesticide diazinon (DN) abnormalities were focused mainly on using natural compounds or their derivatives. DN is an organophosphate compound that causes many health abnormalities in humans due to its usage as an insecticide in agriculture. TQ is one of the beneficiary active principles derived from plant sources that has pharmacological benefits. Aim This research reveals the therapeutic potential of thymoquinone (TQ) on DN-induced myocardial infarction (MI) in rats. Materials and Methods Male Sprague–Dawley rats were procured, acclimatized, and divided into four groups of six animals each with feed and water ad libitum. MI was induced in rats with a dose of 25 mg/kg DN by oral gavage and TQ in a dose of 20 mg/kg p.o. for the treatment. After animal sacrifice at the end of the experimental period, serum and heart tissue samples were collected and processed appropriately for various analyses such as changes in the body weight, heart weight, marker enzymes, oxidative markers, non-enzymatic and enzymatic antioxidants, inflammatory cytokines, histopathological studies, and cardiac-specific markers. Results DN-induced toxicity depicted decreased body weight (167.83 ± 4.62), heart weight (0.9 ± 0.06), and heart-to-body weight ratio (0.54 ± 0.03). Also, elevated marker enzymes (147.33 ± 20.85, 407.5 ± 31.3, and 110.67 ± 9.65 for CK-MB, AST, and ALT, respectively), elevated oxidative markers (12.87 ± 1.34, 125.17 ± 9.95, and 80.17 ± 5.78 for serum MDA, heart MDA, and heart GSSG, respectively), decreased enzymatic- and non-enzymatic antioxidants (3.15 ± 0.42, 12.23 ± 1.02, 5.75 ± 0.46, 2.02 ± 0.26, 0.72 ± 0.07, 18.05 ± 1.04, 8.62 ± 0.65, and 45.8 ± 2.43 for SOD, CAT, GST, GPx, heart GSH, serum GSH, vit.E, and vit.C, respectively), damaged cellular architecture, elevated inflammatory cytokines, and cardiac-specific markers were noticed. Discussion TQ significantly reduced the toxicities produced by DN in almost all the above parameters. The beneficial effect of DN could be attributed to the influential effect of DN on cardiac-specific Nrf2/HO1-related pathways. Conclusion These results suggest that TQ exerts protection against MI and could serve as a promising candidate for drug development.
Relatives’ Experiences of Being Involved in Assisted Dying: A Qualitative Study
Authors: Boven Charlotte , Dillen Let , Dierickx Sigrid , Van den Block Lieve , Piers Ruth , Van Den Noortgate Nele , Van Humbeeck Liesbeth 
Published: October 2023

Recent literature demonstrates an interdependence between relatives and healthcare providers throughout euthanasia processes. Yet, current guidelines and literature scarcely specify the interactions between healthcare providers and bereaved relatives. The aim of this work consisted of providing an insight into bereaved relatives’ experiences (1) of being involved in euthanasia processes and (2) of their interactions with healthcare providers before, during, and after the euthanasia. The research process was guided by the principles of constructivist grounded theory. Nineteen Dutch-speaking bereaved relatives of oncological patients, who received euthanasia at home or in a hospital less than 24 months ago, participated via semi-structured interviews. These interviews were conducted between May 2021 and June 2022. Due to the intensity of euthanasia processes, relatives wanted to be involved as early as possible, in order to receive time, space, and access to professionals’ support whilst preparing themselves for the upcoming loss of a family member with cancer. Being at peace with the euthanasia request facilitated taking a supportive attitude, subsequently aiding in achieving a serene atmosphere. A serene atmosphere facilitated relatives’ grief process because it helped them in creating and preserving good memories. Relatives appreciated support from healthcare providers, as long as overinvolvement on their part was not occurring. This study advocates for a relational approach in the context of euthanasia and provides useful complements to the existing euthanasia guidelines.
Linked color imaging versus white light imaging in the diagnosis of colorectal lesions: a meta-analysis of randomized controlled trials
Authors: Sun Yining , Lv Xiu-He , Zhang Xian , Wang Jin , Wang Huimin , Yang Jin-Lin 
Published: October 2023

Background: Miss rate of colorectal neoplasia is associated with lesion histology, size, morphology, or location. Objectives: We aim to compare the efficacy of Linked color imaging (LCI) versus white light imaging (WLI) for adenoma detection rate (ADR), the detection of sessile serrated lesions (SSLs), serrated lesions (SLs), advanced adenomas (AAs), diminutive lesions (DLs), and flat lesions (FLs) by using per-patient and per-lesion analysis based on randomized controlled trials (RCTs). Design: Systematic review and meta-analysis. Data sources and methods: PubMed, Embase, and Cochrane databases were searched through May 1st, 2023. We calculated risk ratio for dichotomous outcomes and mean difference for continuous outcomes, and performed sensitivity analyses and subgroup analyses. Results: Overall, 17 RCTs (10,624 patients) were included. In per-patient analysis, ADR was higher in the LCI group versus the WLI group ( p < 0.00001). This effect was consistent for SSL ( p = 0.005), SLs ( p = 0.01), AAs ( p = 0.04), DLs ( p < 0.00001), and FLs ( p < 0.0001). In per-lesion analysis, LCI showed a significant superiority over WLI with regard to the mean number of adenomas per patient ( p < 0.00001). This effect was in accordance with mean SSL ( p = 0.001), mean SLs ( p < 0.00001), and mean DLs ( p < 0.0001) per patient. A subgroup analysis showed that the beneficial effect of the LCI group on the detection of AAs, SSL, and FLs was maintained only for studies when experts and trainees were included but not for experts only. Conclusions: Meta-analyses of RCTs data support the use of LCI in clinical practice, especially for trainees.
Adverse childhood experiences in early life increase the odds of depression among adults with multiple sclerosis
Authors: Guerrero Karla S , Horton Mary K , Choudhary Vidhu , Bellesis Kalliope H , Dorin Pete , Mei Jin , Chinn Terrence , Meyers Travis J , Schaefer Catherine A , Barcellos Lisa F 
Published: October 2023

Background Adverse childhood experiences are demonstrated risk factors for depression, a common co-morbidity of multiple sclerosis, but are understudied among people with multiple sclerosis. Objective Estimate the association between adverse childhood experiences and depression among 1,990 adults with multiple sclerosis. Methods Participants were members of Kaiser Permanente Northern California from two studies between 2006 and 2021 and were diagnosed with multiple sclerosis by a neurologist. Adverse childhood experiences were assessed using two instruments, including the Behavioral Risk Factor Surveillance System. Participants self-reported ever experiencing a major depressive episode. Meta-analysis random effects models and logistic regression were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) to assess the relationship between adverse childhood experiences and a history of depression across study samples. Adverse childhood experiences were expressed as any/none, individual events, and counts. Models adjusted for sex, birth year, race, and ethnicity. Results Exposure to any adverse childhood experiences increased the odds of depression in people with multiple sclerosis (OR: 1.71, 95% CI: 1.21–2.42). Several individual adverse childhood experiences were also strongly associated with depression, including “significant abuse or neglect” (OR: 2.79, 95% CI: 2.11–3.68). Conclusion Findings suggest that adverse childhood experiences are associated with depression among people with multiple sclerosis. Screening for depression should be done regularly, especially among people with multiple sclerosis with a history of adverse childhood experiences.