bluuebunny/crossref_metadata_2025 huggingface dataset:
Long-term outcomes and risk factors for recurrence after lung segmentectomy
Authors: Uchida Shinsuke , Hattori Aritoshi , Fukui Mariko , Matsunaga Takeshi , Takamochi Kazuya , Suzuki Kenji
Published: June 2024

OBJECTIVES

The long-term oncological outcomes and risk factors for recurrence after lung segmentectomy are unclear. The aims of this study were to investigate the long-term prognosis and to evaluate risk factors for recurrence after segmentectomy.

METHODS

Between January 2008 and December 2012, a total of 177 patients underwent segmentectomy for clinical stage I non-small cell lung cancer. The median follow-up period was 120.1 months. The overall survival (OS) and recurrence-free survival curves were analysed using the Kaplan–Meier method with a log-rank test. Univariable and multivariable analyses were used to identify significant factors that predicted recurrence.

RESULTS

The study included 177 patients with a median age of 67 years. The median operative time was 155 min. No 30-day deaths were observed. Nine patients (5.1%) had recurrences: loco-regional in 3, distant in 3 and both in 3. The 5-year and 10-year recurrence-free survival rates were 89.7% and 79.8%, and the OS rates were 90.9% and 80.4%, respectively. On multivariable analysis, the risk factor associated with recurrence was a pure solid tumour [hazard ratio, 23.151; 95% confidence interval 2.575–208.178; P = 0.005]. The non-pure solid tumour group had a significantly better probability of survival (5-year OS: 95.4% vs 77.2%; 10-year OS: 86.5% vs 61.8%; P < 0.0001). A total of 113 patients received preoperative positron emission tomography/computed tomography. Patients with a higher maximum standardized uptake value had a significantly higher recurrence rate.

CONCLUSIONS

Segmentectomy for clinical stage I non-small cell lung cancer produced acceptable long-term outcomes. Pure solid radiographic appearance was associated with recurrence and decreased survival.
Rethinking Exclusivity – A Review of Artificial Intelligence & Intellectual Property by Jyh-An Lee, Reto M Hilty and Kung-Chung Liu
Authors: van Dongen Lisa
Published: June 2024

This review evaluates the edited work ‘Artificial Intelligence & Intellectual Property’. The book’s aim and audience are defined and its contents summarized both generally and chapter by chapter. The review also considers how the book has fared with its challenging scope, the difficult subject matter it covers, and the delivery of a coherent story and conclusions. It is concluded in this review that it speaks for the quality of both the cooperation among contributors and the editors’ vision that the book was quite successful on all accounts despite the difficulty of its project. The review highlights a few of the book’s arguments in the patent and copyright context put forth in support of two of the main discernible conclusions, briefly commenting on their persuasiveness, strengths, and limits. Concluding with some general words of reflecting, the book is recommended as an enlightening read.
Association of Antibodies to Helminth Defense Molecule 1 With Inflammation, Organomegaly, and Decreased Nutritional Status in Schistosomiasis Japonica
Authors: Ruiz Amanda E , Pond-Tor Sunthorn , Stuart Ronald , Acosta Luz P , Coutinho Hannah M , Leenstra Tjalling , Fisher Sydney , Fahey Owen , McDonald Emily A , Jiz Mario A , Olveda Remigio M , McGarvey Stephen T , Friedman Jennifer F , Wu Hannah Wei , Kurtis Jonathan D
Published: June 2024

Immunomodulation enhances parasite fitness by reducing inflammation-induced morbidity in the mammalian host, as well as by attenuating parasite-targeting immune responses. Using a whole-proteome differential screening method, we identified Schistosoma japonicum helminth defense molecule 1 (SjHDM-1) as a target of antibodies expressed by S. japonicum–resistant but not S. japonicum–susceptible individuals. In a longitudinal cohort study (n = 644) conducted in a S. japonicum–endemic region of the Philippines, antibody levels to SjHDM-1 did not predict resistance to reinfection but were associated with increased measures of inflammation. Individuals with high levels of anti–SjHDM-1 immunoglobulin G had higher levels of C-reactive protein than those with low anti–SjHDM-1. High anti–SjHDM-1 immunoglobulin G responses were also associated with reduced biomarkers of nutritional status (albumin), as well as decreased anthropometric measures of nutritional status (weight-for-age and height-for-age z scores) and increased measures of hepatomegaly. Our results suggest that anti–SjHDM-1 responses inhibit the immunomodulatory function of SjHDM-1, resulting in increased morbidity rates.
Stability and expression of K-ras mimotopes in freeze-dried recombinant Lactococcus lactis NZ3900-fermented milk powder during storage in vacuum packaging
Authors: How Yu Hsuan , Teo Michelle Yee Mun , In Lionel Lian Aun , Yeo Siok Koon , Bhandari Bhesh , Yusof Yus Aniza , Pui Liew Phing
Published: June 2024

Aims

This study aims to evaluate the storage stability of the freeze-dried recombinant Lactococcus lactis NZ3900-fermented milk powder expressing K-ras (Kristen rat sarcoma viral oncogene homolog) mimotopes targeting colorectal cancer in vacuum packaging.

Methods and results

The freeze-dried L. lactis-fermented milk powder stored in 4-ply retortable polypropylene (RCPP)-polyamide (PA)-aluminium (AL)-polyethylene terephthalate (PET) and aluminium polyethylene (ALPE) was evaluated throughout 49 days of accelerated storage (38°C and 90% relative humidity). The fermented milk powder stored in 4-ply packaging remained above 6 log10 CFU g−1 viability, displayed lower moisture content (6.1%), higher flowability (43° angle of repose), water solubility (62%), and survivability of L. lactis after simulated gastric and intestinal digestion (>82%) than ALPE packaging after 42 days of accelerated storage. K-ras mimotope expression was detected intracellularly and extracellularly in the freeze-dried L. lactis-fermented milk powder upon storage.

Conclusions

This suggests that fermented milk powder is a suitable food carrier for this live oral vaccine.
Towards objective and systematic evaluation of bias in artificial intelligence for medical imaging
Authors: Stanley Emma A M , Souza Raissa , Winder Anthony J , Gulve Vedant , Amador Kimberly , Wilms Matthias , Forkert Nils D
Published: June 2024

Objective

Artificial intelligence (AI) models trained using medical images for clinical tasks often exhibit bias in the form of subgroup performance disparities. However, since not all sources of bias in real-world medical imaging data are easily identifiable, it is challenging to comprehensively assess their impacts. In this article, we introduce an analysis framework for systematically and objectively investigating the impact of biases in medical images on AI models.

Materials and Methods

Our framework utilizes synthetic neuroimages with known disease effects and sources of bias. We evaluated the impact of bias effects and the efficacy of 3 bias mitigation strategies in counterfactual data scenarios on a convolutional neural network (CNN) classifier.

Results

The analysis revealed that training a CNN model on the datasets containing bias effects resulted in expected subgroup performance disparities. Moreover, reweighing was the most successful bias mitigation strategy for this setup. Finally, we demonstrated that explainable AI methods can aid in investigating the manifestation of bias in the model using this framework.

Discussion

The value of this framework is showcased in our findings on the impact of bias scenarios and efficacy of bias mitigation in a deep learning model pipeline. This systematic analysis can be easily expanded to conduct further controlled in silico trials in other investigations of bias in medical imaging AI.

Conclusion

Our novel methodology for objectively studying bias in medical imaging AI can help support the development of clinical decision-support tools that are robust and responsible.
RhoGDI in RBL-2H3 cells acts as a negative regulator of Rho GTPase signaling to inhibit granule exocytosis
Authors: Zhang Eric L , Van Petten Jennifer , Eitzen Gary
Published: June 2024

Mast cells are hematopoietic-derived immune cells that possess numerous cytoplasmic granules containing immune mediators such as cytokines and histamine. Antigen stimulation triggers mast cell granule exocytosis, releasing granule contents in a process known as degranulation. We have shown that Rho GTPase signaling is an essential component of granule exocytosis, however, the proteins that regulate Rho GTPases during this process are not well defined. Here we examined the role of Rho guanine-nucleotide dissociation inhibitors (RhoGDIs) in regulating Rho GTPase signaling using RBL-2H3 cells as a mast cell model. We found that RBL-2H3 cells express two RhoGDI isoforms which are primarily localized to the cytosol. Knockdown of RhoGDI1 and RhoGDI2 greatly reduced the levels of all Rho GTPases tested: RhoA, RhoG, Rac1, Rac2, and Cdc42. The reduction in Rho GTPase levels was accompanied by an increase in their membrane-localized fraction and an elevation in the levels of active Rho GTPases. All RhoGDI knockdown strains had altered resting cell morphology, although each strain was activation competent when stimulated. Live cell imaging revealed that the RhoGDI1/2 double knockdown (DKD) strain maintained its activated state for prolonged periods of time compared to the other strains. Only the RhoGDI1/2 DKD strain showed a significant increase in granule exocytosis. Conversely, RhoGDI overexpression in RBL-2H3 cells did not noticeably affect Rho GTPases or degranulation. Based on these results, RhoGDIs act as negative regulators of Rho GTPases during mast cell degranulation, and inhibit exocytosis by sequestering Rho GTPases in the cytosol.
Solitary behavior at high population density in tuco-tucos (Ctenomys sp.) from Parque Nacional Los Cardones, Argentina
Authors: Lacey Eileen A , Sánchez R Tatiana , Tarquino-Carbonell Andrea P , Ojeda Agustina A , Amaya Juan P
Published: June 2024

Population density is a potentially significant determinant of social organization, with high densities often expected to result in greater spatial and social contact among conspecifics. As part of ongoing efforts to document behavioral diversity among tuco-tucos (Rodentia: Ctenomyidae: Ctenomys), we characterized the social organization of a population in Valle Encantado, Parque Nacional Los Cardones, Salta Province, Argentina. Live-trapping and radiotelemety data revealed that despite one of the highest densities recorded for the genus Ctenomys (~75 adults per ha), members of the study population were solitary, with each adult occupying a distinct burrow system and nest site. Co-occurrence of adults at the same point in space and time was detected only twice (<0.5% of data points, n = 997 telemetry fixes). Spatial overlap between neighboring animals was limited and resulted from occasional incursions by 1 individual into the area occupied by a conspecific, with most (87.5%, n = 8) such events occurring when an adult male entered the area occupied by an adult female. Comparisons with other species of Ctenomys for which telemetry data are available did not suggest a relationship between population density and social organization within this genus. Although a formal taxonomic assessment of the tuco-tucos from Valle Encantado is needed, our findings add to a growing comparative understanding of variation in social organization within Ctenomys.
Organizational Capacity for Sexual Assault Prevention Within a U.S. Army Installation
Authors: Hazlett Abigail D , Benzer Justin K , Montejos Kendra , Pittman Demietrice L , Creech Suzannah K , Claborn Kasey R , Acosta Joie , Chinman Matthew
Published: June 2024

Introduction

Preventing military sexual assault (SA) is a DoD priority. Building prevention capacity could strengthen the impact of prevention programs and improve outcomes. Capacity was conceptualized as implementation knowledge and skills using the Getting To Outcomes (GTO) process and organizational-level capacities using the Prevention Evaluation Framework, a framework that applies best practices in prevention and implementation science to prevention at the program and organizational level. The present study assesses implementation knowledge and skills currently possessed by SA prevention personnel in one U.S. Army installation with the goal of identifying preexisting proficiencies and potential gaps. The study uses the Prevention Evaluation Framework organizational-level domains to identify organizational capacities that could be improved.

Materials and Methods

Fifteen SA prevention program personnel were recruited for individual 1-hour interviews from one U.S. Army installation. A semi-structured interview guide was developed by the study team to assess knowledge and skills within the GTO framework. Applied thematic analysis guided data coding and analysis.

Results

Participants reported a range of proficiencies and gaps in capacity for SA prevention. Within the prevention workforce capacity, proficiencies were skill in tailoring training, and an existing train-the-trainer model. Gaps were training to facilitate difficult conversations, and an inability to tailor trainings to audience needs. Two proficiencies related to the comprehensive approach were having a victim advocate present during trainings, and providing training across leadership levels. The final proficiency involved data. Existing data sources were viewed as useful for identifying the nature and extent of local problems. However, participants reported a lack of confidence and skill in selecting appropriate outcome measures and collecting and using primary data. Gaps in leadership capacity were cultural norms, lack of trust, leader investment, logistical difficulty working with leaders, and comfort engaging with leaders. Gaps in collaborative relationships were the lack of informal networking within the SA prevention area to include civilians.

Conclusions

The GTO-specific knowledge and skills of SA prevention personnel at one U.S. Army installation revealed proficiencies and gaps in organizational capacities influencing the prevention mission. Findings indicate that GTO support could be useful for improving the quality of program activities. However, results also indicate that GTO support would be more effective if they were paired with sufficient prevention infrastructure at the organizational level.
Magnetorotational dynamo can generate large-scale vertical magnetic fields in 3D GRMHD simulations of accreting black holes
Authors: Jacquemin-Ide Jonatan , Rincon François , Tchekhovskoy Alexander , Liska Matthew
Published: June 2024

Jetted astrophysical phenomena with black hole engines, including binary mergers, jetted tidal disruption events, and X-ray binaries, require a large-scale vertical magnetic field for efficient jet formation. However, a dynamo mechanism that could generate these crucial large-scale magnetic fields has not been identified and characterized. We have employed three-dimensional global general relativistic magnetohydrodynamical simulations of accretion discs to quantify, for the first time, a dynamo mechanism that generates large-scale magnetic fields. This dynamo mechanism primarily arises from the non-linear evolution of the magnetorotational instability (MRI). In this mechanism, large non-axisymmetric MRI-amplified shearing wave modes, mediated by the axisymmetric azimuthal magnetic field, generate and sustain the large-scale vertical magnetic field through their non-linear interactions. We identify the advection of magnetic loops as a crucial feature, transporting the large-scale vertical magnetic field from the outer regions to the inner regions of the accretion disc. This leads to a larger characteristic size of the, now advected, magnetic field when compared to the local disc height. We characterize the complete dynamo mechanism with two time-scales: one for the local magnetic field generation, $t_{\rm gen}$, and one for the large-scale scale advection, $t_{\rm adv}$. Whereas the dynamo we describe is non-linear, we explore the potential of linear mean field models to replicate its core features. Our findings indicate that traditional $\alpha$-dynamo models, often computed in stratified shearing box simulations, are inadequate and that the effective large-scale dynamics is better described by the shear current effects or stochastic $\alpha$-dynamos.
The AstroSat UV deep field north: direct determination of the UV luminosity function and its evolution from z ~ 0.8–0.4
Authors: Bhattacharya Souradeep , Saha Kanak , Mondal Chayan
Published: June 2024

We characterize the evolution of the rest-frame 1500 Å UV luminosity function (UVLF) from AstroSat/UVIT F154W and N242W imaging in the Great Observatories Origins Survey North (GOODS-N) field. With deep FUV observations, we construct the UVLF for galaxies at z$\lt 0.13$ and subsequently characterize it with a Schechter function fit. The fitted parameters are consistent with previous determinations. With deep NUV observations, we are able to construct the UVLF in seven redshift bins in the range z$\sim$0.4–0.8, with galaxies identified till $\sim$2 mag fainter than previous surveys, owing to the high angular-resolution of UVIT. The fitted Schechter function parameters are obtained for these UVLFs. At z$\sim$0.7–0.8, we also utilize Hubble Space Telescope (HST) F275W observations in the GOODS-N field to construct the UVLF in 2 redshift bins, whose fitted Schechter function parameters are then found to be consistent with that determined from UVIT at z$\sim$0.75. We thus probe the variation of the fitted UVLF parameters over z$\sim$0.8–0.4, a span of $\sim$2.7 Gyr in age. We find that the slope of the Schechter function, $\alpha$, is at its steepest at z$\sim$0.65, implying highest star-formation at this instant with galaxies being relatively more passive before and after this time. We infer that this is a short-lived instance of increased cosmic star-formation in the GOODS-N field even though cosmic star-formation may be winding-down over longer time-span at this redshift range.
Chemical evolution of complex organic molecules in turbulent protoplanetary discs: effect of stochastic ultraviolet irradiation
Authors: Suzuki T , Furuya K , Aikawa Y , Shibata T , Majumdar L
Published: June 2024

We investigate the chemical evolution of complex organic molecules (COMs) in turbulent discs using gas-ice chemical reaction network simulations. We trace trajectories of dust particles considering advection, turbulent diffusion, gas drag, and vertical settling, for 10$^6$ yr in a protoplanetary disc. Then, we solve a gas-ice chemical reaction network along the trajectories and obtain the temporal evolution of molecular abundances. We find that the COM abundances in particles can differ by more than two orders of magnitude even when the ultraviolet (UV) fluence (i.e. the time integral of UV flux) received by the particles are similar, suggesting that not only the UV fluence but also the time variation of the UV flux does matter for the evolution of COMs in discs. The impact of UV fluence on molecular abundances differs between oxygen-bearing and nitrogen-bearing COMs. While higher UV fluence results in oxygen being locked into CO$_2$, leading to reduced abundances of oxygen-bearing COMs such as CH$_3$OCH$_3$, mild UV exposure can promote their formation by supplying the precursor radicals. On the other hand, nitrogen is not locked up into specific molecules, allowing the formation of nitrogen-bearing COMs, particularly CH$_3$NH$_2$, even for the particle that receives the higher UV fluence. We also find that the final COM abundances are mostly determined by the inherited abundances from the protostellar core when the UV fluence received by dust particles is less than a critical value, while they are set by both the inherited abundances and the chemistry inside the disc at higher UV fluence.
Diagnostics of 3D explosion asymmetries of stripped-envelope supernovae by nebular line profiles
Authors: van Baal Bart F A , Jerkstrand Anders , Wongwathanarat Annop , Janka Hans-Thomas
Published: June 2024

Understanding the explosion mechanism and hydrodynamic evolution of core-collapse supernovae (SNe) is a long-standing quest in astronomy. The asymmetries caused by the explosion are encoded into the line profiles which appear in the nebular phase of the SN evolution – with particularly clean imprints in He star explosions. Here, we carry out nine different supernova simulations of He-core progenitors, exploding them in 3D with parametrically varied neutrino luminosities using the prometheus-hotb code, hydrodynamically evolving the models to the homologous phase. We then compute nebular phase spectra with the 3D Non-Local Thermodynamic Equilibrium spectral synthesis code extrass (EXplosive TRAnsient Spectral Simulator). We study how line widths and shifts depend on progenitor mass, explosion energy, and viewing angle. We compare the predicted line profile properties against a large set of Type Ib observations, and discuss the degree to which current neutrino-driven explosions can match observationally inferred asymmetries. With self-consistent 3D modelling – circumventing the difficulties of representing $^{56}$Ni mixing and clumping accurately in 1D models – we find that neither low-mass He cores exploding with high energies nor high-mass cores exploding with low energies contribute to the Type Ib SN population. Models which have line profile widths in agreement with this population give sufficiently large centroid shifts for calcium emission lines. Calcium is more strongly affected by explosion asymmetries connected to the neutron star kicks than oxygen and magnesium. Lastly, we turn to the near-infrared spectra from our models to investigate the potential of using this regime to look for the presence of He in the nebular phase.
The variable stars in the field of the bulge cluster NGC 6558
Authors: Ferro A Arellano , Guillen L J Zerpa , Yepez M A , Fierro I H Bustos , Prudil Z , Parra C E Pérez
Published: June 2024

We made a survey of the variable stars in a 13.2 × 13.2 arcmin$^{2}$ centred on the field of the Galactic bulge cluster NGC 6558. A total of 78 variables were found in the field of the cluster. Many of these variables are included in the catalogue of variable stars in Galactic globular clusters (Clement et al. 2001), OGLE or Gaia DR3 data releases. A membership analysis based on the proper motions of Gaia DR3 revealed that many of these variables do not belong to the cluster. We employed the data from the aforementioned surveys and our own data in the VI photometric system to estimate the periods, which along with the light-curves morphology and position in a deferentially dereddened colour–magnitude diagram (CMD), help classifying the variable types. Two new member variables were found; an eclipsing binary (V18) and a semiregular SR/L (V19). In the end, we conclude that only nine variables are likely cluster members. Member variables were used to discuss the mean metallicity and distance of the parental cluster and find the average values.
TMPyP binding evokes a complex, tunable nanomechanical response in DNA
Authors: Kretzer Balázs , Herényi Levente , Csík Gabriella , Supala Eszter , Orosz Ádám , Tordai Hedvig , Kiss Bálint , Kellermayer Miklós
Published: June 2024

TMPyP is a porphyrin capable of DNA binding and used in photodynamic therapy and G-quadruplex stabilization. Despite its broad applications, TMPyP’s effect on DNA nanomechanics is unknown. Here we investigated, by manipulating λ-phage DNA with optical tweezers combined with microfluidics in equilibrium and perturbation kinetic experiments, how TMPyP influences DNA nanomechanics across wide ranges of TMPyP concentration (5–5120 nM), mechanical force (0–100 pN), NaCl concentration (0.01–1 M) and pulling rate (0.2–20 μm/s). Complex responses were recorded, for the analysis of which we introduced a simple mathematical model. TMPyP binding, which is a highly dynamic process, leads to dsDNA lengthening and softening. dsDNA stability increased at low (<10 nM) TMPyP concentrations, then decreased progressively upon increasing TMPyP concentration. Overstretch cooperativity decreased, due most likely to mechanical roadblocks of ssDNA-bound TMPyP. TMPyP binding increased ssDNA’s contour length. The addition of NaCl at high (1 M) concentration competed with the TMPyP-evoked nanomechanical changes. Because the largest amplitude of the changes is induced by the pharmacologically relevant TMPyP concentration range, this porphyrin derivative may be used to tune DNA’s structure and properties, hence control the wide array of biomolecular DNA-dependent processes including replication, transcription, condensation and repair.
A RAD18–UBC13–PALB2–RNF168 axis mediates replication fork recovery in BRCA1-deficient cancer cells
Authors: Cybulla Emily , Wallace Sierra , Meroni Alice , Jackson Jessica , Agashe Sumedha , Tennakoon Mithila , Limbu Mangsi , Quinet Annabel , Lomonosova Elena , Noia Hollie , Tirman Stephanie , Wood Matthew , Lemacon Delphine , Fuh Katherine , Zou Lee , Vindigni Alessandro
Published: June 2024

BRCA1/2 proteins function in genome stability by promoting repair of double-stranded DNA breaks through homologous recombination and by protecting stalled replication forks from nucleolytic degradation. In BRCA1/2-deficient cancer cells, extensively degraded replication forks can be rescued through distinct fork recovery mechanisms that also promote cell survival. Here, we identified a novel pathway mediated by the E3 ubiquitin ligase RAD18, the E2-conjugating enzyme UBC13, the recombination factor PALB2, the E3 ubiquitin ligase RNF168 and PCNA ubiquitination that promotes fork recovery in BRCA1- but not BRCA2-deficient cells. We show that this pathway does not promote fork recovery by preventing replication fork reversal and degradation in BRCA1-deficient cells. We propose a mechanism whereby the RAD18–UBC13–PALB2–RNF168 axis facilitates resumption of DNA synthesis by promoting re-annealing of the complementary single-stranded template strands of the extensively degraded forks, thereby allowing re-establishment of a functional replication fork. We also provide preliminary evidence for the potential clinical relevance of this novel fork recovery pathway in BRCA1-mutated cancers, as RAD18 is over-expressed in BRCA1-deficient cancers, and RAD18 loss compromises cell viability in BRCA1-deficient cancer cells.
Acute kidney injury in acute heart failure–when to worry and when not to worry?
Authors: Banerjee Debasish , Ali Mahrukh Ayesha , Wang Angela Yee-Moon , Jha Vivekanand
Published: June 2024

Acute kidney injury is common in patients with acute decompensated heart failure. It is more common in patients with acute heart failure who suffer from chronic kidney disease. Worsening renal function is often defined as a rise in serum creatinine of more than 0.3 mg/dL (26.5 µmol/L) which, by definition, is acute kidney injury (AKI) stage 1. Perhaps the term AKI is more appropriate than worsening renal function as it is used universally by nephrologists, internists and other medical practitioners. In health, the heart and the kidney support each other to maintain the body's homeostasis. In disease, the heart and the kidney can adversely affect each other's function, causing further clinical deterioration. In patients presenting with acute heart failure and fluid overload, therapy with diuretics for decongestion often causes a rise in serum creatinine and AKI. However, in the longer term the decongestion improves survival and prevents hospital admissions despite rising serum creatinine and AKI. It is important to realize that renal venous congestion due to increased right-sided heart pressures in acute heart failure is a major cause of kidney dysfunction and hence decongestion therapy improves kidney function in the longer term. This review provides a perspective on the acceptable AKI with decongestion therapy, which is associated with improved survival, as opposed to AKI due to tubular injury related to sepsis or nephrotoxic drugs, which is associated with poor survival.
Detecting biomarkers by dynamic nuclear polarization enhanced magnetic resonance
Authors: Chen Shizhen , Zhang Lei , Li Sha , Yuan Yaping , Jiang Bin , Jiang Zhongxing , Zhang Xu , Zhou Xin , Liu Maili
Published: June 2024

Hyperpolarization stands out as a technique capable of significantly enhancing the sensitivity of nuclear magnetic resonance (NMR) and magnetic resonance imaging (MRI). Dynamic nuclear polarization (DNP), among various hyperpolarization methods, has gained prominence for its efficacy in real-time monitoring of metabolism and physiology. By administering a hyperpolarized substrate through dissolution DNP (dDNP), the biodistribution and metabolic changes of the DNP agent can be visualized spatiotemporally. This approach proves to be a distinctive and invaluable tool for non-invasively studying cellular metabolism in vivo, particularly in animal models. Biomarkers play a pivotal role in influencing the growth and metastasis of tumor cells by closely interacting with them, and accordingly detecting pathological alterations of these biomarkers is crucial for disease diagnosis and therapy. In recent years, a range of hyperpolarized DNP molecular bioresponsive agents utilizing various nuclei, such as 13C, 15N, 31P, 89Y, etc., have been developed. In this context, we explore how these magnetic resonance signals of nuclear spins enhanced by DNP respond to biomarkers, including pH, metal ions, enzymes, or redox processes. This review aims to offer insights into the design principles of responsive DNP agents, target selection, and the mechanisms of action for imaging. Such discussions aim to propel the future development and application of DNP-based biomedical imaging agents.
CELLULOSE SYNTHASE-LIKE C proteins modulate cell wall establishment during ethylene-mediated root growth inhibition in rice
Authors: Zhou Yang , Gao Yi-Hong , Zhang Bao-Cai , Yang Han-Lei , Tian Yan-Bao , Huang Yi-Hua , Yin Cui-Cui , Tao Jian-Jun , Wei Wei , Zhang Wan-Ke , Chen Shou-Yi , Zhou Yi-Hua , Zhang Jin-Song
Published: June 2024

The cell wall shapes plant cell morphogenesis and affects the plasticity of organ growth. However, the way in which cell wall establishment is regulated by ethylene remains largely elusive. Here, by analyzing cell wall patterns, cell wall composition and gene expression in rice (Oryza sativa, L.) roots, we found that ethylene induces cell wall thickening and the expression of cell wall synthesis-related genes, including CELLULOSE SYNTHASE-LIKE C1, 2, 7, 9, 10 (OsCSLC1, 2, 7, 9, 10) and CELLULOSE SYNTHASE A3, 4, 7, 9 (OsCESA3, 4, 7, 9). Overexpression and mutant analyses revealed that OsCSLC2 and its homologs function in ethylene-mediated induction of xyloglucan biosynthesis mainly in the cell wall of root epidermal cells. Moreover, OsCESA-catalyzed cellulose deposition in the cell wall was enhanced by ethylene. OsCSLC-mediated xyloglucan biosynthesis likely plays an important role in restricting cell wall extension and cell elongation during the ethylene response in rice roots. Genetically, OsCSLC2 acts downstream of ETHYLENE-INSENSITIVE3-LIKE1 (OsEIL1)-mediated ethylene signaling, and OsCSLC1, 2, 7, 9 are directly activated by OsEIL1. Furthermore, the auxin signaling pathway is synergistically involved in these regulatory processes. These findings link plant hormone signaling with cell wall establishment, broadening our understanding of root growth plasticity in rice and other crops.
Lateral atlanto-axial joint access using the C2 pedicle
Authors: Zarembinski Christopher , Wright Robert
Published: June 2024

Background

Neck pain and headaches can arise from the lateral atlanto-axial (LAA) joint. This pain can be diagnosed with intra-articular injections of local anesthetic. A widely used technique for access to the lateral atlanto-axial joint uses a posterior approach, but this approach can be hazardous because of the proximity of the vertebral artery, the dural sac, and the C2 spinal nerve and dorsal root ganglion.

Objective

The objective was to describe and test a new technique for accessing the LAA joint that avoids structures that lie behind the joint.

Interventions

The new technique was described and tested for tolerance in 10 patients with unilateral suboccipital pain and tenderness over the LAA joint, along with evidence of LAA joint arthropathy on SPECT CT. The technique requires inserting a needle along a trajectory tangential to the dorsal surface of the C2 lamina. It involves obtaining a declined view of the C2 lamina and C2 pedicle.

Conclusions

In all cases, the C2 pedicle was easily identified and allowed the needle to pass asymptomatically underneath the neurovascular structures behind the joint. The tactile response of the lamina of C2 provided important feedback regarding needle depth caudal to the LAA joint.
Numeric social-media posts engage people with climate science
Authors: Peters Ellen , Markowitz David M , Nadratowski Ariel , Shoots-Reinhard Brittany
Published: June 2024

Innumeracy (lack of math skills) among nonscientists often leads climate scientists and others to avoid communicating numbers due to concerns that the public will not understand them and may disengage. However, people often report preferring to receive numbers; providing them also can improve decisions. Here, we demonstrated that the presence vs. absence of at least one Arabic integer in climate-related social-media posts increased sharing up to 31.7% but, counter to hypothesis, decreased liking of messages 5.2% in two preregistered observational studies (climate scientists on Twitter, N  > 8 million Tweets; climate subreddit, N  > 17,000 posts and comments). We speculated that the decreased liking was due, not to reduced engagement, but to more negative feelings towards climate-related content described with numeric precision. A preregistered within-participant experiment (N = 212) then varied whether climate consequences were described using Arabic integers (e.g. “90%”) or another format (e.g. verbal terms, “almost all”). The presence of Arabic integers about consequences led to more sharing, wanting to find out more, and greater trust and perceptions of an expert messenger; perceived trust and expertise appeared to mediate effects on sharing and wanting to find out more. Arabic integers about consequences again led to more negative feelings about the Tweets as if numbers clarified the dismaying magnitude of climate threats. Our results indicate that harnessing the power of numbers could increase public trust and concern regarding this defining issue of our time. Communicators, however, should also consider counteracting associated negative feelings—that could halt action—by providing feasible solutions to increase people's self-efficacy.
Evaluating antiretroviral therapy–induced insulin resistance syndrome using the homeostasis model assessment method: an important global clarion call for concern among people living with HIV-disease
Authors: Fasipe Olumuyiwa John , Ayoade Olufisayo Gabriel , Enikuomehin Adenike Christiana , Falade Catherine Olufunke
Published: June 2024

Background

Antiretroviral treatment advances have been accompanied by a new spectrum of adverse drug reactions that affect metabolism and body composition.

Purpose

This review was principally designed to focus on how to comprehensively evaluate for the occurrence of antiretroviral therapy-induced insulin resistance syndrome with associated impaired glucose metabolism disorder(s) among people living with HIV disease.

Data sources and materials

During the course of this present study, original peer-reviewed articles reported in English language that investigated antiretroviral therapy-induced insulin resistance were identified by exploring the Medline-Entrez-PubMed search, Web of Science database, Google Scholar search, and Science Direct database online facilities. Also, information was sourced from printed textbooks and the reports documented by some recognized medically inclined and health professional bodies. These published materials containing documented reports relating to the subject matter of focus in this review were accessed and adequately referenced. This study spanned for 12-month duration from March 2023 to February 2024.

Study selection and manuscript preparation with limitations

A total number of 92 published articles were reviewed, out of which 55 referenced articles were found to contain information pertinent to this present study; while those parts of the referenced articles inapt to this study were neglected. Antiretroviral therapy-induced insulin resistance syndrome can be broadly classified into mild, moderate, and severe categories; based on the severity grading reviews of homeostasis model assessment-insulin resistance index values.

Conclusion

The clinical assessment of antiretroviral therapy-induced insulin resistance syndrome should be given utmost importance in HIV-disease individuals with considerably high-risk factor(s) for its occurrence.
Corticostriatal ensemble dynamics across heroin self-administration to reinstatement
Authors: Clarke Rachel E. , Grant Roger I. , Woods Shannon N. , Pagoota Bayleigh E. , Buchmaier Sophie , Bordieanu Bogdan , Tsyrulnikov Anna , Westphal Annaka M. , Paniccia Jacqueline E , Doncheck Elizabeth M , Carroll-Deaton Jayda , Vollmer Kelsey M , Ward Amy L. , Winston Kion T. , King Danielle I. , Baek Jade , Martino Mike R. , Green Lisa M. , McGinty Jacqueline F. , Scofield Michael D. , Otis James M.
Published: June 2024

Corticostriatal projection neurons from prelimbic medial prefrontal cortex to the nucleus accumbens core critically regulate drug-seeking behaviors, yet the underlying encoding dynamics whereby these neurons contribute to drug seeking remain elusive. Here we use two-photon calcium imaging to visualize the activity of corticostriatal neurons in mice from the onset of heroin use to relapse. We find that the activity of these neurons is highly heterogeneous during heroin self-administration and seeking, with at least 8 distinct neuronal ensembles that display both excitatory and inhibitory encoding dynamics. These neuronal ensembles are particularly apparent during relapse, where excitatory responses are amplified compared to heroin self-administration. Moreover, we find that optogenetic inhibition of corticostriatal projection neurons attenuates heroin seeking regardless of the relapse trigger. Our results reveal the precise corticostriatal activity dynamics underlying drug-seeking behaviors and support a key role for this circuit in mediating relapse to drug seeking.
Enhancing PDAC Therapy: Decitabine-Olaparib Synergy Targets KRAS-Dependent Tumors
Authors: Anastasio Giorgia , Felaco Michela , Lamolinara Alessia , del Pizzo Francesco , Cacciagrano Elisa , Mottini Carla , Mutarelli Margherita , Di Modugno Francesca , Iezzi Manuela , Cardone Luca
Published: June 2024

Current chemotherapies provide limited clinical benefits to patients with pancreatic ductal adenocarcinoma (PDAC), partly due to the lack of effective biomarkers for personalized therapy. KRAS activating mutations occur in almost 90% of PDAC cases, leading to a subset of tumorsdependent onKRASfor survival (dKRAS). Assessing dKRAS in PDAC can be achieved using gene expression signature scores, independent of specific KRAS mutations, allowing for personalized therapies. Previous studies have shown that dKRAS-PDAC cells are more sensitive to the FDA-approved drug decitabine (DEC), although the mechanism remains unclear. While DEC is approved for hematological tumors, its repurposing in solid tumors poses challenges due to high-dose hematological side effects. Identifying optimal pharmacological approaches and response biomarkers is crucial for the successful clinical implementation of DEC in PDAC and other solid tumors. Our investigation revealed that low-dose DEC combined with the PARP inhibitor olaparib (OLA) enhances antitumor activity in dKRAS-PDAC. Mechanistically, DEC induces DNA damage and activates an ATR/ATM-mediated DNA damage response (DDR), with PARP1-mediated DNA repair playing a crucial role. Inhibiting PARP activity with OLA enhances antitumor activity, even inBRCA1/2wild-typeand homologous recombination (HR)-proficient tumors, but it is ineffective in KRAS-independent tumors. Thus, transcriptomic-based KRAS dependency scores effectively predict the efficacy of combined therapy. Additionally, in dKRAS-PDAC tumors carrying aBRCA2mutation, low-dose DEC enhances OLA’s antitumor activity, completely inhibiting metastasis growth compared to single-drug treatments. Our findings support further clinical evaluation of DEC+OLA combination therapy in PDAC, particularly in dKRAS-positive tumors, irrespective of BRCA1/2 status. This approach extends the clinical benefit of OLA beyond BRCA status, addressing a limitation in targeted PARP inhibitor therapies. Furthermore, we highlight DDR as a key mechanism of action for DEC, beyond its role in gene expression regulation, underscoring the mode of action of this widely used anticancer drug.
Early Cretaceous Origin and Evolutionary History of Palms (Arecaceae) inferred from 1,033 Nuclear Genes and a New Synthesis of Fossil Evidence
Authors: Bellot Sidonie , Condamine Fabien L , Matsunaga Kelly KS , Morley Robert J , Cano Ángela , Couvreur Thomas LP , Cowan Robyn , Eiserhardt Wolf L , Kuhnhäuser Benedikt G , Maurin Olivier , Siros Michelle , Forest Félix , Leitch Ilia J , Baker William John
Published: June 2024

Tropical rainforests are home to almost half of all known plant diversity, yet a shortfall in tropical plant phylogenetic hypotheses is hindering our understanding of how rainforests have formed and adapted to past global changes. Phylogenetic and historical biogeographic evidence from key rainforest lineages, including palms (Arecaceae), are required to illuminate the history of these ecosystems. However, our current understanding of the palm tree of life is based on uneven sampling of data from the plastid and nuclear genome, and numerous palm genera and palm fossils have been described or revised over the past decade, casting doubt on many palm relationships, ages and ancestral ranges inferred in previous studies. Here, we infer the phylogenetic relationships of all palm genera based on data from 1,033 nuclear genes generated using target sequence capture. Our palm tree of life is highly resolved and supported. Remaining areas of ambiguity reflect the complex dynamics of palm evolution, including many rapid diversification events in subfamily Arecoideae and putative cases of ancient reticulation throughout the family. We review the phylogenetic placement and age of hundreds of palm fossils and use a vetted selection to estimate divergence times and ancestral ranges for all palm genera. We show that the family is older than previously thought, likely first diversifying in the Early Cretaceous in Laurasia, and that three quarters of the genera had originated by the Oligocene. The early spread of palms across the world involved at least 40 long-distance dispersals across oceanic gaps. Dispersals away from northern latitudes vastly outnumber dispersals into these latitudes, consistent with the ancient affinity of palms for megathermal climates, and suggesting that global cooling during the Oligocene was a major constraint on early palm distribution. Our dated phylogenomic tree and curated fossil dataset provide a new foundation for evolutionary studies on palms, opening the door to deeper research on the rainforest biome in which they thrive.
Mapping the impact of age and APOE risk factors for late onset Alzheimer’s disease on long range brain connections through multiscale bundle analysis
Authors: Stout Jacques , Anderson Robert J , Mahzarnia Ali , Han Zay , Beck Kate , Browndyke Jeffrey , Johnson Kim , O’Brien Richard J , Badea Alexandra
Published: June 2024

Alzheimer’s disease currently has no cure and is usually detected too late for interventions to be effective. In this study we have focused on cognitively normal subjects to study the impact of risk factors on their long-range brain connections. To detect vulnerable connections, we devised a multiscale, hierarchical method for spatial clustering of the whole brain tractogram and examined the impact of age and APOE allelic variation on cognitive abilities and bundle properties including texture e.g., mean fractional anisotropy, variability, and geometric properties including streamline length, volume, and shape, as well as asymmetry. We found that the third level subdivision in the bundle hierarchy provided the most sensitive ability to detect age and genotype differences associated with risk factors. Our results indicate that frontal bundles were a major age predictor, while the occipital cortex and cerebellar connections were important risk predictors that were heavily genotype dependent, and showed accelerated decline in fractional anisotropy, shape similarity, and increased asymmetry. Cognitive metrics related to olfactory memory were mapped to bundles, providing possible early markers of neurodegeneration. In addition, physiological metrics such as diastolic blood pressure were associated with changes in white matter tracts. Our novel method for a data driven analysis of sensitive changes in tractography may differentiate populations at risk for AD and isolate specific vulnerable networks.
Reduction in olfactory ability in agingMitfmutant mice without neurodegeneration
Authors: Mechmet Fatich , Steingrímsson Eiríkur , Henry Petersen Pétur
Published: June 2024

Age-related decline occurs in most brain structures and sensory systems. An illustrative case is olfaction, where the olfactory bulb (OB) undergoes deterioration with age, resulting in reduced olfactory ability. Decline in olfaction is also associated with early symptoms of neurodegenerative diseases including Alzheimer’s disease (AD) and Parkinson’s disease (PD). However, the underlying reasons are unclear. The microphthalmia-associated transcription factor (MITF) is expressed in the projection neurons (PNs) of the OB – the mitral and tufted (M/T) cells. Primary M/T cells fromMitfmutant mice show hyperactivity, potentially attributed to reduced expression of a key potassium channel subunit,Kcnd3/Kv4.3. This influences intrinsic plasticity, an essential mechanism involving the non-synaptic regulation of neuronal activity. As neuronal hyperactivity often precedes neurodegenerative conditions, the current study aimed to determine whether the absence ofMitfhas degenerative effects during aging. AgedMitfmutant mice showed reduced olfactory ability without inflammation. However, an increase in the expression of potassium channel subunit genes in the OB suggests that during aging compensatory mechanisms lead to stabilization.

Significance statement

This study highlights the age-related decline in olfaction and elucidates compensatory mechanisms mediated by potassium channels. These findings improve our comprehension of the processes underlying age-related changes in olfaction.