bluuebunny/crossref_metadata_2025 huggingface dataset:
Resonant tunneling of electrons in biased symmetric triangular double barrier nanostructure triodes
Authors: Elabsy A M , Attia M T
Published: August 2023

The present work investigates the resonant tunneling of electrons in symmetric triangular double barrier triodes composed of GaAs-Ga1-yAlyAs nanostructures under a step bias voltage. This work employs the complex energy method to compute the resonant tunneling energy and the associated lifetimes. In the mathematical analysis of this work, the matching conditions are taken at specific points on both lateral sides of the triangular barrier. Results showed decreasing the resonant tunneling energies for both the lowest and excited states by applying step bias voltage and disappearing the lowest energy states at a specific applied bias voltage. The resonant tunneling lifetimes of the present structure exhibited nearly constant behavior at constant values of both well half-width and barrier half-thickness although the enhancement of the bias voltage. Moreover, the lifetimes of both the lowest and the first excited states increased nearly non-linearly by increasing the aluminum concentration, with the enhancement of the lowest resonant lifetimes over those values associated with the first excited states. The results showed considerable agreement with the data published in the literature for both magnitude and tendency. The present work highlights the importance of employing the mass-mismatch condition in studying heterostructures. It is found from the present study that resonant tunneling energies and their related lifetimes are more affected by the variations of the aluminum concentration in the barrier region, barrier thickness, and well width, which can be adjusted to improve the performance of the resonant tunneling triangular triodes and other nanostructure devices.
Prospects for measuring the Hubble constant and dark energy using gravitational-wave dark sirens with neutron star tidal deformation
Authors: Jin Shang-Jie , Li Tian-Nuo , Zhang Jing-Fei , Zhang Xin
Published: August 2023

Using the measurements of tidal deformation in the binary neutron star (BNS) coalescences can obtain the information of redshifts of gravitational wave (GW) sources, and thus actually the cosmic expansion history can be investigated using solely such GW dark sirens. To do this, the key is to get a large number of accurate GW data, which can be achieved with the third-generation (3G) GW detectors. Here we wish to offer an answer to the question of whether the Hubble constant and the equation of state (EoS) of dark energy can be precisely measured using solely GW dark sirens. We find that in the era of 3G GW detectors 𝒪(105 – 106) dark siren data (with the NS tidal measurements) could be obtained in three-year observation if the EoS of NS is perfectly known, and thus using only dark sirens can actually achieve the precision cosmology. Based on a network of 3G detectors, we obtain the constraint precisions of 0.15% and 0.95% for the Hubble constant H
0 and the constant EoS of dark energy w, respectively; for a two-parameter EoS parametrization of dark energy, the precision of w
0 is 2.04% and the error of wa
is 0.13. We conclude that 3G GW detectors would lead to breakthroughs in solving the Hubble tension and revealing the nature of dark energy provided that the EoS of NS is perfectly known.
Prospects for annihilating dark matter from M31 and M33 observations with the Cherenkov Telescope Array
Authors: Michailidis Miltiadis , Marafatto Lorenzo , Malyshev Denys , Iocco Fabio , Zaharijas Gabrijela , Sergijenko Olga , Bernardos Maria Isabel , Eckner Christopher , Boyarsky Alexey , Sokolenko Anastasia , Santangelo Andrea
Published: August 2023

M31 and M33 are the closest spiral galaxies and the largest members (together with the Milky Way) of the Local group, which makes them interesting targets for indirect dark matter searches. In this paper we present studies of the expected sensitivity of the Cherenkov Telescope Array (CTA) to an annihilation signal from weakly interacting massive particles from M31 and M33. We show that a 100 h long observation campaign will allow CTA to probe annihilation cross-sections up to 〈συ〉 ≈ 5·10-25 cm3 s-1 for the τ
+
τ
- annihilation channel (for M31, at a DM mass of 0.3 TeV), improving the current limits derived by HAWC by up to an order of magnitude.
We present an estimate of the expected CTA sensitivity, by also taking into account the contributions of the astrophysical background and other possible sources of systematic uncertainty.
We also show that CTA might be able to detect the extended emission from the bulge of M31, detected at lower energies by the Fermi/LAT.
Lyapunov functions for studying global asymptotic stability of two rumor spreading models
Authors: Hoang Manh Tuan
Published: August 2023

In a previous work (2018, Commun. Theor. Phys.
70, 795–802), a new compartment model for the spreading of rumors was introduced and analyzed. However, only the local asymptotic stability of this model was discussed. In the present work, we first provide a rigorous mathematical analysis for the global asymptotic stability (GAS) of the above-mentioned rumor spreading model. By constructing suitable Lyapunov candidate functions, we obtain the GAS of a rumor-free (boundary) equilibrium point and a unique rumor-spreading (positive) equilibrium point. After that, we utilize the approach based on the Lyapunov candidate functions to study the GAS of another rumor spreading model with control strategies, which was proposed in (2022, Physica A
606, 128157). As an important consequence, the GAS of the rumor spreading model with control strategies is determined fully without resorting to technical hypotheses used in the benchmark work. Lastly, the theoretical findings are supported by a set of illustrative numerical examples. The obtained results not only improve the ones constructed in the two above-mentioned benchmark papers but also can be extended to study the global dynamics of other rumor propagation models in the context of both integer-order and fractional-order derivatives.
Energetics of silicon in the bulk and near surfaces of tungsten: a first-principles study
Authors: Yang L. , Wirth B.D.
Published: August 2023

Siliconization of the tokamak walls is a candidate method to improve plasma confinement in fusion tokamaks containing tungsten plasma facing components (W PFCs). To understand the interactions of silicon (Si) with W, the Si behavior in bulk W, and near three low-index W surfaces ((100), (110) and (111)) has been investigated using first-principles density functional theory. In bulk W, Si interstitial atoms have a low solution ability and high mobility, and Si atoms can be strongly trapped by W vacancies. The interaction between two Si adatoms is responsible for the stability of adatom superstructures on W surfaces, consistent with previous experimental observation (Tsong and Casanova 1981 Phys. Rev. Lett.
47 113). Although the coverage dependence of Si adsorption and diffusion energetics on surfaces is related to surface orientation, the W(110) surface has lower Si adsorption affinity and higher Si diffusivity than either the W(111) or W(100) surfaces. The most stable Si adatom superstructure on W surfaces is: square c(2 × 2) pattern on W(100) covered with 0.5 ML Si; rectangular c(4 × 2) pattern on W(110) with 0.25 ML Si; and rhombus p(1 × 1) pattern on W(111) with 1 ML Si. The coverage dependence of Si mobility on/toward W surfaces is generally related to the stability of the Si superstructures as a function of coverage on each surface. Interestingly, Si adatoms prefer to transport below the surface and into W subsurface by an exchange mechanism with W atoms, indicating the likelihood of epitaxial growth of W silicide layers on W surfaces during the operation of W PFCs.
What factors are associated with public support for climate change adaptation policy in the U.S.?
Authors: Harris Brittany S , Howe Peter D
Published: August 2023

As climate change impacts increase in frequency and magnitude, policies, and actions to promote climate change adaptation are critical to reduce negative consequences to infrastructure and society. Despite the urgency of adaptation, there have been few systematic efforts to understand the dynamics of public support for adaptation efforts at the local level in the U.S., partly because of the context- and location-specific nature of many adaptation actions. In this paper we use novel survey data to identify the role of demographics, extreme weather experience, awareness of climate change adaptation, risk perceptions, and perceived efficacy in predicting general support for local climate adaptation policy. We utilize a large national sample of U.S. adults (N = 37,088) collected over 12 waves between 2019 and 2022. We find that risk perceptions, beliefs about global warming, awareness of climate change adaptation, and perceived efficacy of local governments are key drivers of support for local adaptation policy. We provide policymakers, educators, and communicators with key guidelines for enhancing public support for adaptation policies. These insights are critical to expanding climate adaptation efforts and policy implementation at the local and national levels in the U.S.
Surfactant-free synthesis and magnetic property evaluation of air-stable cobalt oxide nanostructures
Authors: Joshi Naveen , Shivashankar S A , Narayan Roger
Published: August 2023

We report the synthesis of metastable cobalt oxide (CoO) nanostructures via the low-temperature microwave-assisted solvothermal (MAS) process. An alcoholic solution of cobalt (II) acetylacetonate in a sealed vessel was irradiated with microwaves at a temperature <150 °C and a pressure below 100 psi. As-synthesized powder material was characterized in terms of its structure and morphology. X-ray diffractometry (XRD) indicates the formation of well-crystallized CoO nanoparticles without the need for post-synthesis annealing. The mean crystallite size of the nanoparticles was estimated to be 41 nm. The morphology of the as-prepared powder sample was evaluated by field-emission scanning electron microscopy (FESEM), which revealed the formation of densely packed nanospheres of diameter <100 nm. The CoO nanospheres were obtained without the need for any surfactants or capping agents; they were found to be quite resistant to oxidation in ambient air over several months. We attribute the stability of CoO nanospheres to their dense packing, the driving force being the minimization of surface energy and surface area. Fourier-transform infrared (FT-IR) spectroscopy and Raman spectroscopy confirm the formation of phase-pure CoO nanostructures. The deconvolution of the active modes in Raman spectra obtained at room temperature reveals the Oh symmetry in rock-salt CoO produced by the MAS route. We have analyzed its effect on the magnetic characteristics of the CoO nanostructures. Isothermal field-dependent magnetization (MH) and inverse magnetic susceptibility measurements show a phase transition from antiferromagnetic to ferromagnetic interactions in the CoO nanostructures at around 10 K. The results indicate that the phenomenon of magnetic phase transition as a function of temperature is unique to CoO nanoparticles. This finding reveals the magnetic behavior of CoO nanostructures and presents opportunities for its possible application as an anisotropy source for magnetic recording.
Lack of intergenerational reproductive conflict, rather than lack of inclusive fitness benefits, explains absence of post-reproductive lifespan in long-finned pilot whales
Authors: McCormack Jack L , Arbuckle Kevin , Fullard Karen , Amos William , Nichols Hazel J
Published: August 2023

Life-history theory suggests that individuals should reproduce until death, yet females of a small number of mammals live for a significant period after ceasing reproduction, a phenomenon known as post-reproductive lifespan. It is thought that the evolution of this trait is facilitated by increasing local relatedness throughout a female’s lifetime. This allows older females to gain inclusive fitness through helping their offspring (known as a mother effect) and/or grandoffspring (known as a grandmother effect), rather than gaining direct fitness through reproducing. However, older females may only benefit from stopping reproducing when their direct offspring compete with those of their daughters. Here, we investigate whether a lack of post-reproductive lifespan in long-finned pilot whales (Globicephala melas) results from minimal benefits incurred from the presence of older females, or from a lack of costs resulting from mother–daughter co-reproduction. Using microsatellite data, we conducted parentage analysis on individuals from 25 pods and find that younger females were more likely to have offspring if their mother was present in their pod, indicating that mothers may assist inexperienced daughters to reproduce. However, we found no evidence of reproductive conflict between co-reproducing mothers and daughters, indicating that females may be able to reproduce into old age while simultaneously aiding their daughters in reproduction. This highlights the importance of reproductive conflict in the evolution of a post-reproductive lifespan and demonstrates that mother and grandmother effects alone do not result in the evolution of a post-reproductive lifespan.
DCAlign v1.0: aligning biological sequences using co-evolution models and informed priors
Authors: Muntoni Anna Paola , Pagnani Andrea
Published: August 2023

DCAlign is a new alignment method able to cope with the conservation and the co-evolution signals that characterize the columns of multiple sequence alignments of homologous sequences. However, the pre-processing steps required to align a candidate sequence are computationally demanding. We show in v1.0 how to dramatically reduce the overall computing time by including an empirical prior over an informative set of variables mirroring the presence of insertions and deletions.

Availability and implementation

DCAlign v1.0 is implemented in Julia and it is fully available at https://github.com/infernet-h2020/DCAlign.
Complications after open and laparoscopic right-sided colectomy with central lymphadenectomy for colon cancer: randomized controlled trial
Authors: Lygre Kristin B , Eide Geir E , Forsmo Havard M , Dicko Aly , Storli Kristian E , Pfeffer Frank
Published: August 2023

Background

A central lymphadenectomy in right-sided colon cancer involves dissection along the superior mesenteric axis, but the extent is debated due to a lack of consensus and the fear of major complications. This randomized controlled trial compared the rate of postoperative morbidity in patients undergoing laparoscopic versus open right-sided colectomy with central lymphadenectomy.

Methods

This open, prospective, randomized controlled trial compared patients operated on with open and laparoscopic right-sided colectomy (cStages I–III) with a central lymphadenectomy at two Norwegian institutions between October 2016 and December 2021. Dissections were conducted along the superior mesenteric vein in the laparoscopic group, and along the left anterior border of the superior mesenteric artery in the open group, both according to complete mesocolic excision principles. Surgery was standardized and performed by three experienced surgeons for each study group. The primary outcome of interest was to measure postoperative 30-day complications (Clavien–Dindo ≥ grade II).

Results

Of 273 eligible patients, 135 were randomized and 128 analysed (63 operated on with open and 65 using laparoscopic procedures). Postoperative complications occurred in 42.8 per cent of the patients treated with open and 38.4 per cent of the patients treated using laparoscopic surgery, P = 0.372. The incidence of Clavien–Dindo grade IIIb complications was 7.9 per cent in the open versus 4.6 per cent in the laparoscopic group, P = 0.341. There were no grade IV or V complications, and no re-operations due to anastomotic leakages. There was no significant difference in the mean(s.e.m.) number of removed lymph nodes (open versus laparoscopic respectively: 31.9(1.8) versus 29.3(1.3); P = 0.235).

Conclusion

There was no significant difference in complications between the two groups. Standardized oncologic right-sided colectomy with central lymphadenectomy along the mesenterial root was performed safely, both open and laparoscopic, with incidence of major complications ranging between 4.6 and 7.9 per cent and no re-operations for anastomotic leakage. Radicality in terms of lymphadenectomy was comparable between the two groups.

Registration number: NCT03776591 (http://www.clinicaltrials.gov).
Antibiotics on Demand: Advances in Asynchronous Telemedicine Call for Increased Antibiotic Surveillance
Authors: O’Toole Rebecca , Martinez Kathryn A , Rothberg Michael B , Diiorio Gillian , Stenehjem Edward A , Ward Kristina E , LaPlante Kerry L
Published: August 2023

The rapid growth of telehealth services has brought about direct-to-consumer telemedicine platforms, enabling patients to request antibiotics online without a virtual or face-to-face consultation. While telemedicine aims to enhance accessibility, this trend raises significant concerns regarding appropriate antimicrobial use and patient safety. In this viewpoint, we share our first-hand experience with 2 direct-to-consumer platforms, where we intentionally sought inappropriate antibiotic prescriptions for nonspecific symptoms strongly indicative of a viral upper respiratory infection. Despite the lack of clear necessity, requested antibiotic prescriptions were readily transmitted to our local pharmacy following a simple monetary transaction. The effortless acquisition of patient-selected antibiotics online, devoid of personal interactions or consultations, underscores the urgent imperative for intensified antimicrobial stewardship initiatives led by state and national public health organizations in telehealth settings. By augmenting oversight and regulation, we can ensure the responsible and judicious use of antibiotics, safeguard patient well-being, and preserve the efficacy of these vital medications.
Extracorporeal Membrane Oxygenation–Dependent Fulminant Melioidosis From Caspase 4 Mutation Reversed by Interferon Gamma Therapy
Authors: Amali Aseervatham Anusha , Ravikumar Sharada , Chew Wei Leong , Tan Zhaohong , Sam Qi Hui , Chen Kaiwen W , Boucher Dave , MacLaren Graeme , Chai Louis Yi Ann
Published: August 2023

We describe bedside-to-bench immunological and genetic elucidation of defective pyroptosis attributable to novel caspase 4 defect mediating pathogen-triggered inflammatory programmed cell death, in the setting of severe pneumonia and abscess-forming melioidosis in an overtly healthy host failing to clear Burkholderia pseudomallei infection, and how targeted adjunctive biological therapy led to a successful outcome.
Clinical Outcomes and Management of NAAT-Positive/Toxin-Negative Clostridioides difficile Infection: A Systematic Review and Meta-Analysis
Authors: Prosty Connor , Hanula Ryan , Katergi Khaled , Longtin Yves , McDonald Emily G , Lee Todd C
Published: August 2023

Background

Standalone nucleic acid amplification tests (NAATs) are frequently used to diagnose Clostridioides difficile infections (CDI), although they may be unable to distinguish colonization from disease. A 2-stage algorithm pairing NAATs with toxin immunoassays (Toxin) may improve specificity. We evaluated clinical outcomes of patients who were NAAT+/Toxin+ versus NAAT+/Toxin− and treated versus untreated NAAT+/Toxin− cases through systematic review and meta-analysis.

Methods

We searched EMBASE and MEDLINE from inception to April 1, 2023 for articles comparing CDI outcomes among symptomatic patients tested by NAAT and Toxin tests. The risk differences (RD) of all-cause mortality and CDI recurrence were computed by random effects meta-analysis between patients who were NAAT+/Toxin+ and NAAT+/Toxin−, as well as between patients who were NAAT+/Toxin− and treated or untreated.

Results

Twenty-six observational studies comprising 12 737 patients were included. The 30-day all-cause mortality was not significantly different between those who were NAAT+/Toxin+ (8.4%) and NAAT+/Toxin− (6.7%) (RD = 0.41%, 95% confidence interval [CI] = −.67, 1.49). Recurrence at 60 days was significantly higher among patients who were NAAT+/Toxin+ (19.8%) versus NAAT+/Toxin− (11.0%) (RD = 7.65%, 95% CI = 4.60, 10.71). Among treated compared to untreated NAAT+/Toxin- cases, the all-cause 30-day mortalities were 5.0% and 12.7%, respectively (RD = −7.45%, 95% CI = −12.29, −2.60), but 60-day recurrence was not significantly different (11.6% vs 7.0%, respectively; RD = 5.25%, 95% CI −1.71, 12.22).

Conclusions

Treatment of patients who were NAAT+/Toxin− was associated with reduced all-cause mortality but not recurrence. Although subject to the inherent limitations of observational studies, these results suggest that some patients who are NAAT+/Toxin− may benefit from treatment.
A Hybrid Solution For The Cold Start Problem In Recommendation
Authors: Jafri Syed Irteza Hussain , Ghazali Rozaida , Javid Irfan , Mazwin Mohmad Hassim Yana , Hayat Khan Mubashir
Published: August 2023

Recommender systems are becoming more and more significant in today’s digital world and in the modern economy. They make a substantial contribution to company operations by offering tailored advice and decreasing overwhelm. Collaborative filtering, being popular in the domain of recommendation, is used to offer recommendations to attract the target audience based on the feedback of people with comparable interests. This method has some limitations, such as a cold-start issue, which makes the system less effective in anticipating unknown objects. We provide a hybrid deep-learning-based strategy centered on a method to enrich user and item profiles to address the cold-start issue in the recommendation process using a collaborative filtering approach. We employ pretrained deep learning models to produce rich user and item feature vectors that aid in the creation of useful suggestions and handling of user and item cold-start issues. The creation of more precise and tailored similarity matrices is made possible by adding metadata to the extracted features of the user and item. The results of the experiment demonstrate that in terms of precision and rate coverage, the proposed method performs better than the baseline techniques.
Provider–patient experiences and HIV care utilization among people living with HIV who inject drugs in St. Petersburg, Russia
Authors: Raj Anita , Gnatienko Natalia , Cheng Debbie M , Blokhina Elena , Dey Arnab K , Wagman Jennifer A , Toussova Olga , Truong Ve , Rateau Lindsey , Lunze Karsten , Krupitsky Evgeny , Samet Jeffrey H
Published: August 2023

Providers’ disrespect and abuse of patients is a recognized but understudied issue affecting quality of care and likely affecting healthcare utilization. Little research has examined this issue among people living with HIV (PWH) who inject drugs, despite high stigmatization of this population. No research has examined this issue in the context of Russia. This study assesses patients’ reports of disrespect and abuse from providers as a barrier to healthcare and examines the association between these reports and HIV care outcomes.We conducted a cross-sectional analysis of the associations between disrespect/abuse from health providers as a barrier to care and the following HIV care outcomes: (i) anti-retroviral treatment (ART) uptake ever, (ii) past 6-month visit to HIV provider, and (iii) CD4 count. Participants (N = 221) were people living with HIV who injected drugs and were not on ART at enrollment.Two in five participants (42%) reported a history disrespect/abuse from a healthcare provider that they cited as a barrier to care. Those reporting this concern had lower odds of ever use of ART (adjusted odds ratio 0.46 [95% CI 0.22, 0.95]); we found no significant associations for the other HIV outcomes. We additionally found higher representation of women among those reporting prevalence of disrespect/abuse from provider as a barrier to care compared to those not reporting this barrier (58.1% versus 27.3%).Almost half of this sample of PWH who inject drugs report disrespect/abuse from a provider as a barrier to healthcare, and this is associated with lower odds of receipt of ART but not with other HIV outcomes studied. There is need for improved focus on quality of respectful and dignified care from providers for PWH who inject drugs, and such focus may improve ART uptake in Russia.
Contact semilattices
Authors: Lipparini Paolo
Published: August 2023

We devise exact conditions under which a join semilattice with a weak contact relation can be semilattice embedded into a Boolean algebra with an overlap contact relation, equivalently, into a distributive lattice with additive contact relation. A similar characterization is proved with respect to Boolean algebras and distributive lattices with weak contact, not necessarily additive, nor overlap.
Optimizing the strain engineering process for industrial-scale production of bio-based molecules
Authors: Abbate Eric , Andrion Jennifer , Apel Amanda , Biggs Matthew , Chaves Julie , Cheung Kristi , Ciesla Anthony , Clark-ElSayed Alia , Clay Michael , Contridas Riarose , Fox Richard , Hein Glenn , Held Dan , Horwitz Andrew , Jenkins Stefan , Kalbarczyk Karolina , Krishnamurthy Nandini , Mirsiaghi Mona , Noon Katherine , Rowe Mike , Shepherd Tyson , Tarasava Katia , Tarasow Theodore M , Thacker Drew , Villa Gladys , Yerramsetty Krishna
Published: August 2023

Biomanufacturing could contribute as much as ${\$}$30 trillion to the global economy by 2030. However, the success of the growing bioeconomy depends on our ability to manufacture high-performing strains in a time- and cost-effective manner. The Design–Build–Test–Learn (DBTL) framework has proven to be an effective strain engineering approach. Significant improvements have been made in genome engineering, genotyping, and phenotyping throughput over the last couple of decades that have greatly accelerated the DBTL cycles. However, to achieve a radical reduction in strain development time and cost, we need to look at the strain engineering process through a lens of optimizing the whole cycle, as opposed to simply increasing throughput at each stage. We propose an approach that integrates all 4 stages of the DBTL cycle and takes advantage of the advances in computational design, high-throughput genome engineering, and phenotyping methods, as well as machine learning tools for making predictions about strain scale-up performance. In this perspective, we discuss the challenges of industrial strain engineering, outline the best approaches to overcoming these challenges, and showcase examples of successful strain engineering projects for production of heterologous proteins, amino acids, and small molecules, as well as improving tolerance, fitness, and de-risking the scale-up of industrial strains.
Production of S-methyl-methionine using engineered Saccharomyces cerevisiae sake K6
Authors: Lee Jun-Min , Park Min-Ho , Park Bu-Soo , Oh Min-Kyu
Published: August 2023

S-methyl-methionine (SMM), also known as vitamin U, is an important food supplement produced by various plants. In this study, we attempted to produce it in an engineered microorganism, Saccharomyces cerevisiae, by introducing an MMT gene encoding a methionine S-methyltransferase from Arabidopsis thaliana. The S. cerevisiae sake K6 strain, which is a Generally Recognized as Safe (GRAS) strain, was chosen as the host because it produces a significant amount of S-adenosylmethionine (SAM), a precursor of SMM. To increase SMM production in the host, MHT1 and SAM4 genes encoding homocysteine S-methyltransferase were knocked out to prevent SMM degradation. Additionally, MMP1, which encodes S-methyl-methionine permease, was deleted to prevent SMM from being imported into the cell. Finally, ACS2 gene encoding acetyl-CoA synthase was overexpressed, and MLS1 gene encoding malate synthase was deleted to increase SAM availability. Using the engineered strain, 1.92 g/L of SMM was produced by fed-batch fermentation.

One-Sentence Summary

Introducing a plant-derived MMT gene encoding methionine S-methyltransferase into engineered Saccharomyces cerevisiae sake K6 allowed microbial production of S-methyl-methionine (SMM).
In-office dispensing of oral targeted agents by urology practices in men with advanced prostate cancer
Authors: Hill Dawson , Kaufman Samuel R , Oerline Mary K , Faraj Kassem , Caram Megan E V , Shahinian Vahakn B , Hollenbeck Brent K , Maganty Avinash
Published: August 2023

Background

Management of men with advanced prostate cancer has evolved to include urologists, made possible by oral targeted agents (eg, abiraterone or enzalutamide) that can be dispensed directly to patients in the office. We sought to investigate whether this increasingly common model improves access to these agents, especially for Black men who are historically undertreated.

Methods

We used 20% national Medicare data to perform a retrospective cohort study of men with advanced prostate cancer from 2011 through 2019, managed by urology practices with and without in-office dispensing. Using a difference-in-difference framework, generalized estimating equations were used to measure the effect of in-office dispensing on prescriptions for abiraterone and/or enzalutamide, adjusting for differences between patients, including race.

Results

New prescription fills for oral targeted agents increased after the adoption of in-office dispensing (+4.4%, 95% confidence interval [CI] = 3.4% to 5.4%) relative to that for men managed by practices without dispensing (+2.4%, 95% CI = 1.4% to 3.4%). The increase in the postintervention period (difference-in-difference estimate) was 2% higher (95% CI = 0.6% to 3.4%) for men managed by practices adopting dispensing relative to men managed by practices without dispensing. The effect was strongest for practices adopting dispensing in 2015 (difference-in-difference estimate: +4.2%, 95% CI = 2.3% to 6.2%). The effect of dispensing adoption did not differ by race.

Conclusion

Adoption of in-office dispensing by urology practices increased prescription fills for oral targeted agents in men with advanced prostate cancer. This model of delivery may improve access to this important class of medications.
Flexible marked spatio-temporal point processes with applications to event sequences from association football
Authors: Narayanan Santhosh , Kosmidis Ioannis , Dellaportas Petros
Published: August 2023

We develop a new family of marked point processes by focusing the characteristic properties of marked Hawkes processes exclusively on the space of marks, allowing a separate model specification for the occurrence times. We develop a Bayesian framework for their inference and prediction that can naturally accommodate covariate information to drive cross-excitations, offering broad flexibility for real-world applications. The framework is applied to in-game event sequences from association football, resulting in inferences about previously unquantified characteristics of game dynamics, extraction of event-specific team abilities and predictions for event occurrences, such as goals or fouls in a specified interval of time.
Physical properties of methanol (CH3OH) ice as a function of temperature: density, infrared band strengths, and crystallization
Authors: Carrascosa H , Satorre M Á , Escribano B , Martín-Doménech R , Muñoz Caro G M
Published: August 2023

The presence of methanol among the common ice components in interstellar clouds and protostellar envelopes has been confirmed by the James Webb Space Telescope (McClure et al. 2023). Methanol is often detected in the gas phase towards lines of sight shielded from UV radiation. We measured the volumetric density of methanol ice grown under simulated interstellar conditions and the infrared spectroscopy at different deposition temperatures and during the warm-up. The IR band strengths are provided, and the experimental spectra are compared to those computed with a model. The transition from amorphous to crystalline methanol ice was also explored. Finally, we propose new observations of methanol ice at high resolution to probe the methanol ice structure.
Steady states of the Parker instability
Authors: Tharakkal Devika , Shukurov Anvar , Gent Frederick A , Sarson Graeme R , Snodin Andrew P , Rodrigues Luiz Felippe S
Published: August 2023

We study the linear properties, non-linear saturation, and a steady, strongly non-linear state of the Parker instability in galaxies. We consider magnetic buoyancy and its consequences with and without cosmic rays. Cosmic rays are described using the fluid approximation with anisotropic, non-Fickian diffusion. To avoid unphysical constraints on the instability (such as boundary conditions often used to specify an unstable background state), non-ideal magnetohydrodynamic equations are solved for deviations from a background state representing an unstable magnetohydrostatic equilibrium. We consider isothermal gas and neglect rotation. The linear evolution of the instability is in broad agreement with earlier analytical and numerical models; but we show that most of the simplifying assumptions of the earlier work do not hold, such that they provide only a qualitative rather than quantitative picture. In its non-linear stage the instability has significantly altered the background state from its initial state. Vertical distributions of both magnetic field and cosmic rays are much wider, the gas layer is thinner, and the energy densities of both magnetic field and cosmic rays are much reduced. The spatial structure of the non-linear state differs from that of any linear modes. A transient gas outflow is driven by the weakly non-linear instability as it approaches saturation.
Work Hours Volatility and Child Poverty: The Potential Mitigating Role of Safety Net Programs
Authors: Cai Julie
Published: August 2023

Despite established links among persistent unemployment, low wages, and children’s economic well-being, social scientists have yet to document how variability in work hours is linked to child poverty. Our knowledge of the safety net’s heterogeneous responses to work-hour instability is also limited. This is of critical importance for scholars and policymakers. Using nationally representative data collected every 4 months, this paper examines how intra-year work-hour volatility is related to child poverty, measured through both the official poverty measure (OPM) and the supplemental poverty measure (SPM). It further assesses varying degrees of buffering effects of cash, in-kind benefits, and tax transfers on income in the context of work-hour volatility. Results indicate that more than one in four households (26%) facing the greatest volatility lived under the poverty line. Black and Hispanic children, as well as those living with unpartnered single mothers, faced substantially higher variability in household market hours worked. Hispanic children experienced not only greater volatility in their caregivers’ work hours but also higher poverty level, even after taking government programs into account. In-kind benefits are more effective in buffering household income declines resulting from unstable work hours, followed by tax transfers and cash benefits. The effectiveness of near-cash benefits is particularly salient among Black children and children of single mothers. These results provide new evidence to inform policy discussions surrounding the best ways to help socioeconomically disadvantaged families to retain benefits and smooth their income in the face of frequent variation in work hours and, thus, earnings.
Endometriosis in the era of precision medicine and impact on sexual and reproductive health across the lifespan and in diverse populations
Authors: Giudice Linda C. , Oskotsky Tomiko T. , Falako Simileoluwa , Opoku‐Anane Jessica , Sirota Marina
Published: August 2023

Endometriosis is a common estrogen‐dependent disorder wherein uterine lining tissue (endometrium) is found mainly in the pelvis where it causes inflammation, chronic pelvic pain, pain with intercourse and menses, and infertility. Recent evidence also supports a systemic inflammatory component that underlies associated co‐morbidities, e.g., migraines and cardiovascular and autoimmune diseases. Genetics and environment contribute significantly to disease risk, and with the explosion of omics technologies, underlying mechanisms of symptoms are increasingly being elucidated, although novel and effective therapeutics for pain and infertility have lagged behind these advances. Moreover, there are stark disparities in diagnosis, access to care, and treatment among persons of color and transgender/nonbinary identity, socioeconomically disadvantaged populations, and adolescents, and a disturbing low awareness among health care providers, policymakers, and the lay public about endometriosis, which, if left undiagnosed and under‐treated can lead to significant fibrosis, infertility, depression, and markedly diminished quality of life. This review summarizes endometriosis epidemiology, compelling evidence for its pathogenesis, mechanisms underlying its pathophysiology in the age of precision medicine, recent biomarker discovery, novel therapeutic approaches, and issues around reproductive justice for marginalized populations with this disorder spanning the past 100 years. As we enter the next revolution in health care and biomedical research, with rich molecular and clinical datasets, single‐cell omics, and population‐level data, endometriosis is well positioned to benefit from data‐driven research leveraging computational and artificial intelligence approaches integrating data and predicting disease risk, diagnosis, response to medical and surgical therapies, and prognosis for recurrence.
The pathogenetic role of Th17 immune response in atopic dermatitis
Authors: David Eden , Czarnowicki Tali
Published: August 2023

Purpose of review

As we continue to unravel the pathophysiology and immune mechanisms underlying atopic dermatitis (AD), the emergence of targeted treatments has provided new options for management. Although there are available therapies targeting various immune pathways in AD, the precise pathogenic role of interleukin (IL)-17 in AD pathogenesis remains unclear. The objective of this review is to examine the existing data pertaining to the role of IL-17 in AD and shed light on the potential of targeting this pathway as a therapeutic approach in AD treatment.

Recent findings

IL-17 has a dual role of pro-inflammatory and immune protective function, making it an important player in several autoimmune and inflammatory conditions. The extent of IL-17 axis involvement in AD pathogenesis is still debatable. Emerging data show that Th17-related cytokines/chemokines are elevated in skin and sera samples of AD patients, with some articles reporting correlations with disease severity. Particularly increased Th17 signature in specific AD patient subsets, such as Asian-origin or pediatric patients, suggests that certain patients’ disease presentations are more predominantly influenced by Th17, and, thus, they may benefit more from Th17 therapeutic targeting approaches. Lack of clinical efficacy with anti-Th17 biologics in AD patients, underscores the need to better elucidate the role of Th17 in AD pathogenesis, along with its utility in therapy.

The well established role of IL-17 in autoimmune disorders hints for its possible participation in AD disease pathogenesis. Subsequent investigations are needed to assess whether the targeting of specific IL-17 isoforms, homodimers, or heterodimers in specific subpopulations of AD can modify treatment outcomes.
Association of Discontinuing Preinjury Beta-Adrenergic Blockade Medications With Mortality in Severe Blunt Traumatic Brian Injury
Authors: Tignanelli Christopher J. , Arbabi Saman , Iskander Gaby , Kralovich Kurt , Scott John , Sangji Naveen F. , Hemmila Mark R.
Published: August 2023

Background:

Beta-adrenergic receptor blocker (BB) administration has been shown to improve survival after traumatic brain injury (TBI). However, studies to date that observe a benefit did not distinguish between continuation of preinjury BB versus de novo initiation of BB.

Objectives:

To determine the effect of continuation of preinjury BB and de novo initiation of BB on risk-adjusted mortality and complications for patients with TBI.

Methods:

Trauma quality collaborative data (2016–2021) were analyzed. Patients were excluded with hospitalization <48 hours, direct admission, or penetrating injury. Severe TBI was identified as a head abbreviated injury scale (AIS) value of 3 to 5. Patients were placed into 4 groups based on the preinjury BB use and administration of BB during hospitalization. Propensity score matching was used to create 1:1 matched cohorts of patients for comparisons. Odd ratios of mortality accounting for hospital clustering were calculated. A sensitivity analysis was performed excluding patients with AIS >2 injuries in all other body regions to create a cohort of isolated TBI patients.

Results:

A total of 15,153 patients treated at 35 trauma centers were available for analysis. Patients were divided into 4 cohort groupings related to preinjury BB use and postinjury receipt of BB. The odds of mortality was significantly reduced for patients with a TBI on a preinjury BB who had the medication continued in the acute setting (as compared with patients on preinjury BB who did not) (odds ratio [OR], 0.73; 95% confidence interval [CI], 0.54–0.98; P = 0.04). Patients with a TBI who were not on preinjury BB did not benefit from de novo initiation of BB with regard to mortality (OR, 0.83; 95% CI, 0.64–1.08; P = 0.2). In the sensitivity analysis, excluding polytrauma patients, patients on preinjury BB who had BB continued had a reduction in mortality when compared with patients in which BB was stopped following a TBI (OR, 0.65; 95% CI, 0.47–0.91; P = 0.01).

Conclusions:

Continuing BB is associated with reduced odds of mortality in patients with a TBI on preinjury BB. We were unable to demonstrate benefit from instituting beta blockade in patients who are not on a BB preinjury.
The Role of Systemic Steroids in Sciatica Due to Herniated Lumbar Disc
Authors: Vale João , Rocha Eduardo , Lemos Carolina , Valente Cristina , Andrade Renato , Espregueira-Mendes João , Rodrigues-Pinto Ricardo
Published: August 2023

Study Design.

Systematic review and meta-analysis.

Objective.

Evaluate the role of systemic steroids in treating patients with sciatica due to lumbar disk herniation (LDH).

Summary of Background Data.

The association between LDH and sciatica has been well described. The use of steroids seems logical in this context; however, their efficacy is not well described, and their use remains controversial.

Methods.

A comprehensive search on PubMed, EMBASE, and Scopus databases (up to February 15, 2022) was performed to identify randomized clinical trials that included patients with symptoms of sciatica due to LDH that were treated with systemic steroids. The risk of bias was judged using the Cochrane risk-of-Bias2 tool. Meta-analysis was conducted using a random-effects model to estimate the between-group effect size for pain and functional outcomes. The risk of developing adverse events (AE) was computed using relative risks. All pooled results are reported with their 95% confidence interval (CI) and certainty of evidence analyzed using the Grading of Recommendations Assessment, Development, and Evaluation framework.

Results.

Ten studies met inclusion criteria, comprising a total of 1017 participants: 540 in the treatment group and 477 in the control group. Steroid treatment was associated with a significant superior reduction of pain (SMD = −0.42, 95% CI −0.76 to −0.08, weak effect, very-low certainty) and reduction in disability (SMD = −0.30, 95% CI −0.51 to −0.10, weak effect, very-low certainty). Corticosteroid administration was associated with a significant increased risk of developing an AE (relative risks = 2.00, 95% CI 1.40 to 2.85, low certainty).

Conclusion.

The use of systemic steroids in the treatment of sciatica due to LDH seems reasonable despite a 2-fold higher risk of developing mild AEs. However, the effect size is small for reducing pain in the short term and improving functional outcomes at long-term follow-up.
A Novel Technique for Lateral Ankle Ligament Reconstruction in a Total Ankle Total Talus Replacement Case
Authors: Lukosius Eric , Anastasio Albert T. , Schweitzer Karl M.
Published: August 2023

In recent years, the tibial component and polyethylene bearing of a total ankle replacement have been used in conjunction with a custom total talus replacement in cases of severe talar loss with concomitant tibiotalar arthritis, referred to as total ankle total talus replacement. Multiple reports have linked ligamentous instability with poor outcomes after total ankle replacement. In the current study, we describe a surgical technique for lateral ankle ligament reconstruction in a total ankle total talus replacement case through the use of 3-dimensionally printed tunnels.

Level of Evidence: Diagnostic Level V—expert opinion. See Instructions for Authors for a complete description of levels of evidence.
Chimeric antigen receptor-immune cells against solid tumors: Structures, mechanisms, recent advances, and future developments
Authors: Li Xudong , Li Wei , Xu Linping , Song Yongping
Published: August 2023

The advent of chimeric antigen receptor (CAR)-T cell immunotherapies has led to breakthroughs in the treatment of hematological malignancies. However, their success in treating solid tumors has been limited. CAR-natural killer (NK) cells have several advantages over CAR-T cells because NK cells can be made from pre-existing cell lines or allogeneic NK cells with a mismatched major histocompatibility complex (MHC), which means they are more likely to become an "off-the-shelf" product. Moreover, they can kill cancer cells via CAR-dependent/independent pathways and have limited toxicity. Macrophages are the most malleable immune cells in the body. These cells can efficiently infiltrate into tumors and are present in large numbers in tumor microenvironments (TMEs). Importantly, CAR-macrophages (CAR-Ms) have recently yielded exciting preclinical results in several solid tumors. Nevertheless, CAR-T, CAR-NK, and CAR-M all have their own advantages and limitations. In this review, we systematically discuss the current status, progress, and the major hurdles of CAR-T cells, CAR-NK cells, and CAR-M as they relate to five aspects: CAR structure, therapeutic mechanisms, the latest research progress, current challenges and solutions, and comparison according to the existing research in order to provide a reasonable option for treating solid tumors in the future.