bluuebunny/crossref_metadata_2025_split huggingface dataset:
On the Sensitivity of Coastal Hypoxia to Its External Physical Forcings
Authors: St‐Laurent P. , Friedrichs M. A. M. 
Published: January 2024

AbstractThe development of low‐oxygen zones threatening marine life (hypoxia) occurs annually in multiple coastal regions of the world. The largest estuary of the continental United States, the Chesapeake Bay, typically has ≈10 km3 of water with dioxygen concentrations <3 mg L−1 in July. As numerical methods for refining model resolutions in targeted areas are becoming common, there is interest in assessing the feasibility of simulating coastal hazards such as hypoxia in Earth System Models (ESMs). These coupled models are typically not constrained by observations and thus likely to feature systematic biases in their land, atmosphere, or ocean components. This study relies on four numerical experiments to evaluate the sensitivity of Chesapeake Bay hypoxia to changes or biases in its external physical forcings. Hypoxia exhibits only a minor decrease (−1.6%) after reducing the Bay's terrestrial freshwater discharge by 9.5% (but keeping terrestrial nutrient loadings the same). Changes in freshwater discharges have their largest impact on hypoxia during one extreme event (−37% during 2011 tropical storm Lee). Similarly, changing oceanic conditions on the shelf or their temporal frequency impact hypoxia by only 5%–6%, indicating that the latter is predominantly dictated by local conditions. Although these results are promising from the perspective of ESMs, additional components of ESMs will need to be evaluated before general conclusions can be reached. We notably speculate that the Bay's hypoxia would exhibit higher sensitivity to other forcings not examined here, notably air temperatures and nutrient loadings.
Socio-economic differences in body mass index: the contribution of genetic factors
Authors: Silventoinen Karri , Lahtinen Hannu , Kilpi Fanny , Morris Tim T. , Davey Smith George , Martikainen Pekka 
Published: January 2024

Abstract
Background
Higher mean body mass index (BMI) among lower socioeconomic position (SEP) groups is well established in Western societies, but the influence of genetic factors on these differences is not well characterized.

Methods
We analyzed these associations using Finnish health surveys conducted between 1992 and 2017 (N = 33 523; 53% women) with information on measured weight and height, polygenic risk scores of BMI (PGS-BMI) and linked data from administrative registers to measure educational attainment, occupation-based social class and personal income.

Results
In linear regressions, largest adjusted BMI differences were found between basic and tertiary educated men (1.4 kg/m2, 95% confidence interval [CI] 1.2; 1.6) and women (2.5 kg/m2, 95% CI 2.3; 2.8), and inverse BMI gradients were also found for social class and income. These SEP differences arose partly because mean PGS-BMI was higher and partly because PGS-BMI predicted BMI more strongly in lower SEP groups. The inverse SEP gradients of BMI were steeper in women than in men, but sex differences were not found in the genetic contributions to these differences.

Conclusions
Better understanding of the interplay between genes and environment provides insight into the mechanisms explaining SEP differences in BMI.
Effects of swimming training in hot and cold temperatures combined with cinnamon supplementation on HbA1C levels, TBC1D1, and TBC1D4 in diabetic rats
Authors: Tayebi Seyed Morteza , Nouri Amir Hossein , Tartibian Bakhtyar , Ahmadabadi Somayeh , Basereh Aref , Jamhiri Iman 
Published: January 2024

Abstract
Aims
Diabetes is one of the main causes of mortality in developing countries. Performing physical activity in various ways and different environments using herbal supplements can be used as a non-pharmacological solution to prevent and improve diabetes. Hence, this study aimed to investigate the effects of eight weeks of cold water swimming exercise training combined with cinnamon supplementation on HbA1C (Hemoglobin A1c) levels, TBC1D1 (TBC1 domain family member 1), and TBC1D4 (TBC1 Domain Family Member 4) in diabetic rats.

Materials and methods
Ninety-one rats (n = 78 diabetic, n = 13 healthy) were divided into seven groups (n = 13 per group): (1) healthy control (HC), (2) diabetic control (DC), (3) swimming training in cold water (5 °C) (S5), (4) swimming training in cold water (5 °C) with a cinnamon supplementation (200 mg/kg body weight) (S5+Ci), (5) swimming training in warm water (36-35 °C) (S35), (6) swimming training in warm water (35–36 °C) with a cinnamon supplementation (S35+Ci), and (7) a cinnamon supplementation only (Ci). To evaluate the hypothesis, a one-way ANOVA and Tukey’s post hoc test were used.

Results
Findings showed that the TBC1D1 and TBC1D4 levels in the DC and S35 groups were higher than in the HC group (p < 0.001). Also, swimming training in cold water (5 °C) with cinnamon supplementation (S5+Ci) decreased the level of TBC1D1, TBC1D4, HbA1c, and glucose compared to other groups (p < 0.05).

Conclusions
The study revealed that the combination of swimming training in cold water and cinnamon consumption led to a significant reduction in TBC1D1, TBC1D4, and HbA1c. Therefore, this non-traditional exercise approach coupled with cinnamon supplementation can be considered an effective method for improving insulin sensitivity, fasting blood glucose, and HbA1c levels and is proposed as an optimal method to improve glucose indices.
A therapeutic antibody targeting annexin-A1 inhibits cancer cell growth in vitro and in vivo
Authors: Al-Ali Hussein N. , Crichton Scott J. , Fabian Charlene , Pepper Chris , Butcher David R. , Dempsey Fiona C. , Parris Christopher N. 
Published: January 2024

AbstractIn this study we conducted the first investigation to assess the efficacy of a novel therapeutic antibody developed to target annexin-A1 (ANXA1). ANXA1 is an immunomodulatory protein which has been shown to be overexpressed in, and promote the development and progression of, several cancer types. In particular, high ANXA1 expression levels correlate with poorer overall survival in pancreatic and triple-negative breast cancers, two cancers with considerable unmet clinical need. MDX-124 is a humanised IgG1 monoclonal antibody which specifically binds to ANXA1 disrupting its interaction with formyl peptide receptors 1 and 2 (FPR1/2). Here we show that MDX-124 significantly reduced proliferation (p < 0.013) in a dose-dependent manner across a panel of human cancer cell lines expressing ANXA1. The anti-proliferative effect of MDX-124 is instigated by arresting cell cycle progression with cancer cells accumulating in the G1 phase of the cell cycle. Furthermore, MDX-124 significantly inhibited tumour growth in both the 4T1-luc triple-negative breast and Pan02 pancreatic cancer syngeneic mouse models (p < 0.0001). These findings suggest ANXA1-targeted therapy is a viable and innovative approach to treat tumours which overexpress ANXA1.
Intratumoural microbiota: a new frontier in cancer development and therapy
Authors: Cao Yaqi , Xia Hui , Tan Xueyun , Shi Chunwei , Ma Yanling , Meng Daquan , Zhou Mengmeng , Lv Zhilei , Wang Sufei , Jin Yang 
Published: January 2024

AbstractHuman microorganisms, including bacteria, fungi, and viruses, play key roles in several physiological and pathological processes. Some studies discovered that tumour tissues once considered sterile actually host a variety of microorganisms, which have been confirmed to be closely related to oncogenesis. The concept of intratumoural microbiota was subsequently proposed. Microbiota could colonise tumour tissues through mucosal destruction, adjacent tissue migration, and hematogenic invasion and affect the biological behaviour of tumours as an important part of the tumour microenvironment. Mechanistic studies have demonstrated that intratumoural microbiota potentially promote the initiation and progression of tumours by inducing genomic instability and mutations, affecting epigenetic modifications, promoting inflammation response, avoiding immune destruction, regulating metabolism, and activating invasion and metastasis. Since more comprehensive and profound insights about intratumoral microbiota are continuously emerging, new methods for the early diagnosis and prognostic assessment of cancer patients have been under examination. In addition, interventions based on intratumoural microbiota show great potential to open a new chapter in antitumour therapy, especially immunotherapy, although there are some inevitable challenges. Here, we aim to provide an extensive review of the concept, development history, potential sources, heterogeneity, and carcinogenic mechanisms of intratumoural microorganisms, explore the potential role of microorganisms in tumour prognosis, and discuss current antitumour treatment regimens that target intratumoural microorganisms and the research prospects and limitations in this field.
Phase 1 study of high-dose DFMO, celecoxib, cyclophosphamide and topotecan for patients with relapsed neuroblastoma: a New Approaches to Neuroblastoma Therapy trial
Authors: Hogarty Michael D. , Ziegler David S. , Franson Andrea , Chi Yueh-Yun , Tsao-Wei Denice , Liu Kangning , Vemu Rohan , Gerner Eugene W. , Bruckheimer Elizabeth , Shamirian Anasheh , Hasenauer Beth , Balis Frank M. , Groshen Susan , Norris Murray D. , Haber Michelle , Park Julie R. , Matthay Katherine K. , Marachelian Araz 
Published: January 2024

Abstract
Background
MYC genes regulate ornithine decarboxylase (Odc) to increase intratumoral polyamines. We conducted a Phase I trial [NCT02030964] to determine the maximum tolerated dose (MTD) of DFMO, an Odc inhibitor, with celecoxib, cyclophosphamide and topotecan.

Methods
Patients 2–30 years of age with relapsed/refractory high-risk neuroblastoma received oral DFMO at doses up to 9000 mg/m2/day, with celecoxib (500 mg/m2 daily), cyclophosphamide (250 mg/m2/day) and topotecan (0.75 mg/m2/day) IV for 5 days, for up to one year with G-CSF support.

Results
Twenty-four patients (median age, 6.8 years) received 136 courses. Slow platelet recovery with 21-day courses (dose-levels 1 and 2) led to subsequent dose-levels using 28-day courses (dose-levels 2a-4a). There were three course-1 dose-limiting toxicities (DLTs; hematologic; anorexia; transaminases), and 23 serious adverse events (78% fever-related). Five patients (21%) completed 1-year of therapy. Nine stopped for PD, 2 for DLT, 8 by choice. Best overall response included two PR and four MR. Median time-to-progression was 19.8 months, and 3 patients remained progression-free at >4 years without receiving additional therapy. The MTD of DFMO with this regimen was 6750 mg/m2/day.

Conclusion
High-dose DFMO is tolerable when added to chemotherapy in heavily pre-treated patients. A randomized Phase 2 trial of DFMO added to chemoimmunotherapy is ongoing [NCT03794349].
Neutrophil extracellular traps and neutrophilic dermatosis: an update review
Authors: Li Sheng , Ying Shuni , Wang Yuqian , Lv Yelu , Qiao Jianjun , Fang Hong 
Published: January 2024

AbstractNeutrophils have both antimicrobial ability and pathogenic effect in the immune system, neutrophil extracellular traps (NETs) formation is one of the representative behaviors of their dual role. NETs formation was triggered by pathogen-related components and pathogen non-related proteins as cytokines to exert its effector functions. Recent studies indicate that the pathogenicity of NETs contributed to several skin diseases such as psoriasis, Stevens-Johnson syndrome, toxic epidermal necrolysis, and neutrophilic dermatosis. Especially in neutrophilic dermatosis, a heterogeneous group of inflammatory skin disorders characterized with sterile neutrophilic infiltrate on dermis, NETs formation was reported as the way of participation of neutrophils in the pathogenesis of these diseases. In this review, we describe the different processes of NETs formation, then summarized the most recent updates about the pathogenesis of neutrophilic dermatosis and the participation of NETs, including pyoderma gangrenosum and PAPA syndrome, Behçet syndrome, hidradenitis suppurativa, Sweet Syndrome, pustular dermatosis and other neutrophilic dermatosis. Furthermore, we discuss the link between NETs formation and the development of neutrophilic dermatosis.
Accelerated prime-and-trap vaccine regimen in mice using repRNA-based CSP malaria vaccine
Authors: MacMillen Zachary , Hatzakis Kiara , Simpson Adrian , Shears Melanie J. , Watson Felicia , Erasmus Jesse H. , Khandhar Amit P. , Wilder Brandon , Murphy Sean C. , Reed Steven G. , Davie James W. , Avril Marion 
Published: January 2024

AbstractMalaria, caused by Plasmodium parasites, remains one of the most devastating infectious diseases worldwide, despite control efforts to lower morbidity and mortality. Both advanced candidate vaccines, RTS,S and R21, are subunit (SU) vaccines that target a single Plasmodium falciparum (Pf) pre-erythrocytic (PE) sporozoite (spz) surface protein known as circumsporozoite (CS). These vaccines induce humoral immunity but fail to elicit CD8 + T-cell responses sufficient for long-term protection. In contrast, whole-organism (WO) vaccines, such as Radiation Attenuated Sporozoites (RAS), achieved sterile protection but require a series of intravenous doses administered in multiple clinic visits. Moreover, these WO vaccines must be produced in mosquitos, a burdensome process that severely limits their availability. To reduce reliance on WO while maintaining protection via both antibodies and Trm responses, we have developed an accelerated vaccination regimen that combines two distinct agents in a prime-and-trap strategy. The priming dose is a single dose of self-replicating RNA encoding the full-length P. yoelii CS protein, delivered via an advanced cationic nanocarrier (LIONTM). The trapping dose consists of one dose of WO RAS. Our vaccine induces a strong immune response when administered in an accelerated regimen, i.e., either 5-day or same-day immunization. Additionally, mice after same-day immunization showed a 2-day delay of blood patency with 90% sterile protection against a 3-week spz challenge. The same-day regimen also induced durable 70% sterile protection against a 2-month spz challenge. Our approach presents a clear path to late-stage preclinical and clinical testing of dose-sparing, same-day regimens that can confer sterilizing protection against malaria.
Encoding a magic state with beyond break-even fidelity
Authors: Gupta Riddhi S. , Sundaresan Neereja , Alexander Thomas , Wood Christopher J. , Merkel Seth T. , Healy Michael B. , Hillenbrand Marius , Jochym-O’Connor Tomas , Wootton James R. , Yoder Theodore J. , Cross Andrew W. , Takita Maika , Brown Benjamin J. 
Published: January 2024

AbstractTo run large-scale algorithms on a quantum computer, error-correcting codes must be able to perform a fundamental set of operations, called logic gates, while isolating the encoded information from noise1–8. We can complete a universal set of logic gates by producing special resources called magic states9–11. It is therefore important to produce high-fidelity magic states to conduct algorithms while introducing a minimal amount of noise to the computation. Here we propose and implement a scheme to prepare a magic state on a superconducting qubit array using error correction. We find that our scheme produces better magic states than those that can be prepared using the individual qubits of the device. This demonstrates a fundamental principle of fault-tolerant quantum computing12, namely, that we can use error correction to improve the quality of logic gates with noisy qubits. Moreover, we show that the yield of magic states can be increased using adaptive circuits, in which the circuit elements are changed depending on the outcome of mid-circuit measurements. This demonstrates an essential capability needed for many error-correction subroutines. We believe that our prototype will be invaluable in the future as it can reduce the number of physical qubits needed to produce high-fidelity magic states in large-scale quantum-computing architectures.
A lethal mitonuclear incompatibility in complex I of natural hybrids
Authors: Moran Benjamin M. , Payne Cheyenne Y. , Powell Daniel L. , Iverson Erik N. K. , Donny Alexandra E. , Banerjee Shreya M. , Langdon Quinn K. , Gunn Theresa R. , Rodriguez-Soto Rebecca A. , Madero Angel , Baczenas John J. , Kleczko Korbin M. , Liu Fang , Matney Rowan , Singhal Kratika , Leib Ryan D. , Hernandez-Perez Osvaldo , Corbett-Detig Russell , Frydman Judith , Gifford Casey , Schartl Manfred , Havird Justin C. , Schumer Molly 
Published: January 2024

AbstractThe evolution of reproductive barriers is the first step in the formation of new species and can help us understand the diversification of life on Earth. These reproductive barriers often take the form of hybrid incompatibilities, in which alleles derived from two different species no longer interact properly in hybrids1–3. Theory predicts that hybrid incompatibilities may be more likely to arise at rapidly evolving genes4–6 and that incompatibilities involving multiple genes should be common7,8, but there has been sparse empirical data to evaluate these predictions. Here we describe a mitonuclear incompatibility involving three genes whose protein products are in physical contact within respiratory complex I of naturally hybridizing swordtail fish species. Individuals homozygous for mismatched protein combinations do not complete embryonic development or die as juveniles, whereas those heterozygous for the incompatibility have reduced complex I function and unbalanced representation of parental alleles in the mitochondrial proteome. We find that the effects of different genetic interactions on survival are non-additive, highlighting subtle complexity in the genetic architecture of hybrid incompatibilities. Finally, we document the evolutionary history of the genes involved, showing signals of accelerated evolution and evidence that an incompatibility has been transferred between species via hybridization.
Nasopharyngeal lymphatic plexus is a hub for cerebrospinal fluid drainage
Authors: Yoon Jin-Hui , Jin Hokyung , Kim Hae Jin , Hong Seon Pyo , Yang Myung Jin , Ahn Ji Hoon , Kim Young-Chan , Seo Jincheol , Lee Yongjeon , McDonald Donald M. , Davis Michael J. , Koh Gou Young 
Published: January 2024

AbstractCerebrospinal fluid (CSF) in the subarachnoid space around the brain has long been known to drain through the lymphatics to cervical lymph nodes1–17, but the connections and regulation have been challenging to identify. Here, using fluorescent CSF tracers in Prox1-GFP lymphatic reporter mice18, we found that the nasopharyngeal lymphatic plexus is a major hub for CSF outflow to deep cervical lymph nodes. This plexus had unusual valves and short lymphangions but no smooth-muscle coverage, whereas downstream deep cervical lymphatics had typical semilunar valves, long lymphangions and smooth muscle coverage that transported CSF to the deep cervical lymph nodes. α-Adrenergic and nitric oxide signalling in the smooth muscle cells regulated CSF drainage through the transport properties of deep cervical lymphatics. During ageing, the nasopharyngeal lymphatic plexus atrophied, but deep cervical lymphatics were not similarly altered, and CSF outflow could still be increased by adrenergic or nitric oxide signalling. Single-cell analysis of gene expression in lymphatic endothelial cells of the nasopharyngeal plexus of aged mice revealed increased type I interferon signalling and other inflammatory cytokines. The importance of evidence for the nasopharyngeal lymphatic plexus functioning as a CSF outflow hub is highlighted by its regression during ageing. Yet, the ageing-resistant pharmacological activation of deep cervical lymphatic transport towards lymph nodes can still increase CSF outflow, offering an approach for augmenting CSF clearance in age-related neurological conditions in which greater efflux would be beneficial.
Capturing the generation and structural transformations of molecular ions
Authors: Heo Jun , Kim Doyeong , Segalina Alekos , Ki Hosung , Ahn Doo-Sik , Lee Seonggon , Kim Jungmin , Cha Yongjun , Lee Kyung Won , Yang Jie , Nunes J. Pedro F. , Wang Xijie , Ihee Hyotcherl 
Published: January 2024

AbstractMolecular ions are ubiquitous and play pivotal roles1–3 in many reactions, particularly in the context of atmospheric and interstellar chemistry4–6. However, their structures and conformational transitions7,8, particularly in the gas phase, are less explored than those of neutral molecules owing to experimental difficulties. A case in point is the halonium ions9–11, whose highly reactive nature and ring strain make them short-lived intermediates that are readily attacked even by weak nucleophiles and thus challenging to isolate or capture before they undergo further reaction. Here we show that mega-electronvolt ultrafast electron diffraction (MeV-UED)12–14, used in conjunction with resonance-enhanced multiphoton ionization, can monitor the formation of 1,3-dibromopropane (DBP) cations and their subsequent structural dynamics forming a halonium ion. We find that the DBP+ cation remains for a substantial duration of 3.6 ps in aptly named ‘dark states’ that are structurally indistinguishable from the DBP electronic ground state. The structural data, supported by surface-hopping simulations15 and ab initio calculations16, reveal that the cation subsequently decays to iso-DBP+, an unusual intermediate with a four-membered ring containing a loosely bound17,18 bromine atom, and eventually loses the bromine atom and forms a bromonium ion with a three-membered-ring structure19. We anticipate that the approach used here can also be applied to examine the structural dynamics of other molecular ions and thereby deepen our understanding of ion chemistry.
Public platform with 39,472 exome control samples enables association studies without genotype sharing
Authors: Artomov Mykyta , Loboda Alexander A. , Artyomov Maxim N. , Daly Mark J. 
Published: January 2024

AbstractAcquiring a sufficiently powered cohort of control samples matched to a case sample can be time-consuming or, in some cases, impossible. Accordingly, an ability to leverage genetic data from control samples that were already collected elsewhere could dramatically improve power in genetic association studies. Sharing of control samples can pose significant challenges, since most human genetic data are subject to strict sharing regulations. Here, using the properties of singular value decomposition and subsampling algorithm, we developed a method allowing selection of the best-matching controls in an external pool of samples compliant with personal data protection and eliminating the need for genotype sharing. We provide access to a library of 39,472 exome sequencing controls at http://dnascore.net enabling association studies for case cohorts lacking control subjects. Using this approach, control sets can be selected from this online library with a prespecified matching accuracy, ensuring well-calibrated association analysis for both rare and common variants.