bluuebunny/crossref_metadata_2025 huggingface dataset:
Vanadium‐Doped Ni3S2: Morphological Evolution for Enhanced Industrial‐Scale Water and Urea Electrolysis
Authors: Sharma Pooja J. , Joshi Kinjal K. , Siraj Sohel , Sahatiya Parikshit , Sumesh C. K. , Pataniya Pratik M.
Published: August 2024

The development of an earth abundant, cost‐effective, facile and multifunctional 3D‐porous catalytic network for green hydrogen production is a tremendous challenge. Herein, we report the V‐Ni3S2 self‐supported catalytic network with optimized morphology grown directly on nickel foam (NF) by the one‐step hydrothermal technique for water and urea electrolysis at industrial scale hydrogen generation. The morphology of Ni3S2 was modulated by doping of different concentrations of vanadium from granules to cross‐linked wires to hierarchal nanosheets arrays, which is beneficial in electrochemical charge and mass transport, and generates more exposed active sites. The V‐Ni3S2 catalyst requires the overpotential of 147 mV for hydrogen evolution reaction (HER). The OER and UOR half‐cell reaction on V‐Ni3S2 catalyst requires potential 1.57 V and 1.39 V (vs RHE), respectively to generate current 100 mA/cm2. The water electrolysis cell developed by V‐Ni3S2 as both anode and cathode generates 100 mA/cm2 at cell voltage of 1.88 V in laboratory condition (1 M KOH, 25 °C) and 1.61 V at industrial condition (5 M KOH, 80 °C) and also shows considerable stability for 82 hr at current 300 mA/cm2. The urea electrolysis cell with 1 M KOH and 0.33 M urea generates 100 mA/cm2 at a cell voltage of 1.73 V, which is 150 mV less than that required for water electrolysis and demonstrate stability for 85 hr at a current of 100 mA/cm2. The results provide an innovative plan for the considerate synthesis and design of bifunctional catalysts for energy storage and water splitting.
Complete organelle genomes of the threatened aquatic species Scheuchzeria palustris (Scheuchzeriaceae): Insights into adaptation and phylogenomic placement
Authors: He Xiang‐Yan , Chen Jin‐Ming , Li Zhi‐Zhong
Published: August 2024

Scheuchzeria palustris, the only species in the Scheuchzeriaceae family, plays a crucial role in methane production and transportation, influencing the global carbon cycle and maintaining ecosystem stability. However, it is now threatened by human activities and global warming. In this study, we generated new organelle genomes for S. palustris, with the plastome (pt) measuring 158,573 bp and the mitogenome (mt) measuring 420,724 bp. We predicted 296 RNA editing sites in mt protein‐coding genes (PCGs) and 142 in pt‐PCGs. Notably, abundant RNA editing sites in pt‐PCGs likely originated from horizontal gene transfer between the plastome and mitogenome. Additionally, we identified positive selection signals in four mt‐PCGs (atp4, ccmB, nad3, and sdh4) and one pt‐PCG (rps7), which may contribute to the adaptation of S. palustris to low‐temperature and high‐altitude environments. Furthermore, we identified 35 mitochondrial plastid DNA (MTPT) segments totaling 58,479 bp, attributed to dispersed repeats near most MTPT. Phylogenetic trees reconstructed from mt‐ and pt‐PCGs showed topologies consistent with the APG IV system. However, the conflicting position of S. palustris can be explained by significant differences in the substitution rates of its mt‐ and pt‐PCGs (p < .001). In conclusion, our study provides vital genomic resources to support future conservation efforts and explores the adaptation mechanisms of S. palustris.
Beta‐blocker use and outcomes in patients with heart failure and mildly reduced and preserved ejection fraction
Authors: Matsumoto Shingo , Henderson Alasdair D. , Shen Li , Kondo Toru , Yang Mingming , Campbell Ross T. , Anand Inder S. , de Boer Rudolf A. , Desai Akshay S. , Lam Carolyn S.P. , Maggioni Aldo P. , Martinez Felipe A. , Packer Milton , Redfield Margaret M. , Rouleau Jean L. , Van Veldhuisen Dirk J. , Vaduganathan Muthiah , Zannad Faiez , Zile Michael R. , Jhund Pardeep S. , Solomon Scott D. , McMurray John J.V.
Published: August 2024

Aims

In the absence of randomized trial evidence, we performed a large observational analysis of the association between beta‐blocker (BB) use and clinical outcomes in patients with heart failure (HF) and mildly reduced (HFmrEF) and preserved ejection fraction (HFpEF).

Methods and results

We pooled individual patient data from four large HFmrEF/HFpEF trials (I‐Preserve, TOPCAT, PARAGON‐HF, and DELIVER). The primary outcome was the composite of cardiovascular death or HF hospitalization. Among the 16 951 patients included, the mean left ventricular ejection fraction (LVEF) was 56.8%, and 13 400 (79.1%) had HFpEF (LVEF ≥50%). Overall, 12 812 patients (75.6%) received a BB. The median bisoprolol‐equivalent dose of BB was 5.0 (Q1–Q3: 2.5–5.0) mg with BB continuation rates of 93.1% at 2 years (in survivors). The unadjusted hazard ratio (HR) for the primary outcome did not differ between BB users and non‐users (HR 0.98, 95% confidence interval [CI] 0.91–1.05), but the adjusted HR was lower in BB users than non‐users (0.81, 95% CI 0.74–0.88), and this association was maintained across LVEF (pinteraction = 0.88). In subgroup analyses, the adjusted risk of the primary outcome was similar in BB users and non‐users with or without a history of myocardial infarction, hypertension, or a baseline heart rate <70 bpm. By contrast, a better outcome with BB use was seen in patients with atrial fibrillation compared to those without atrial fibrillation (pintreraction = 0.02).

Conclusions

In this observational analysis of non‐randomized BB treatment, there was no suggestion that BB use was associated with worse HF outcomes in HFmrEF/HFpEF, even after extensive adjustment for other prognostic variables.
Shelf‐life extension of fresh mushrooms: From conventional practices to novel technologies—A comprehensive review
Authors: Sharma Vaibhav , Singh Poornima , Singh Anurag
Published: August 2024

Mushroom is an edible fungus grown worldwide because of its nutritional and commercial value. The demand for mushrooms is rising annually because of increased awareness of the dietary benefits of mushrooms. Mushrooms are a perishable commodity as they respire continuously after harvesting. Adequate packaging or processing is required to increase mushrooms' shelf life. The quality of mushrooms continues to decline after harvesting, including browning, moisture loss, texture changes, increased bacteria, and loss of flavor and nutrients. Postharvest preservation methods, including physical, chemical, and thermal treatments, are necessary to preserve postharvest quality and increase the shelf life of mushrooms. The postharvest technology of mushrooms must be improved to fulfill the increasing demand for mushrooms. There are many conventional techniques to protect the quality and increase the shelf life of mushrooms. Conventional procedures frequently result in considerable nutritional, texture, and flavor losses and shorter shelf lives. In contrast, modern technologies preserve mushrooms with increased nutritional retention, improved texture and flavor profiles, and longer shelf life. This review covers not only the conventional technologies like drying and cooling but also elaborates on the shelf‐life extension of mushrooms through novel technologies like pulse electric field, pulsed light, electrolyzed water, etc.
Loss of prohibitin 2 in Schwann cells dysregulates key transcription factors controlling developmental myelination
Authors: Wilson Emma R. , Nunes Gustavo Della‐Flora , Shen Shichen , Moore Seth , Gawron Joseph , Maxwell Jessica , Syed Umair , Hurley Edward , Lanka Meghana , Qu Jun , Désaubry Laurent , Wrabetz Lawrence , Poitelon Yannick , Feltri M. Laura
Published: August 2024

Schwann cells are critical for the proper development and function of the peripheral nervous system (PNS), where they form a collaborative relationship with axons. Past studies highlighted that a pair of proteins called the prohibitins play major roles in Schwann cell biology. Prohibitins are ubiquitously expressed and versatile proteins. We have previously shown that while prohibitins play a crucial role in Schwann cell mitochondria for long‐term myelin maintenance and axon health, they may also be present at the Schwann cell‐axon interface during development. Here, we expand on this, showing that drug‐mediated modulation of prohibitins in vitro disrupts myelination and confirming that Schwann cell‐specific ablation of prohibitin 2 (Phb2) in vivo results in severe defects in radial sorting and myelination. We show in vivo that Phb2‐null Schwann cells cannot effectively proliferate and the transcription factors EGR2 (KROX20), POU3F1 (OCT6), and POU3F2 (BRN2), necessary for proper Schwann cell maturation, are dysregulated. Schwann cell‐specific deletion of Jun, a transcription factor associated with negative regulation of myelination, confers partial rescue of the developmental defect seen in mice lacking Schwann cell Phb2. Finally, we identify a pool of candidate PHB2 interactors that change their interaction with PHB2 depending on neuronal signals, and thus are potential mediators of PHB2‐associated developmental defects. This work develops our understanding of Schwann cell biology, revealing that Phb2 may modulate the timely expression of transcription factors necessary for proper PNS development, and proposing candidates that may play a role in PHB2‐mediated integration of axon signals in the Schwann cell.
Association between immune checkpoint inhibitor and cytomegalovirus infection: A pharmacovigilance study based on the adverse event reporting system
Authors: Okada Naoto , Yanagi Tomoyuki , Sasaki Takaaki , Tamura Miho , Ozaki Masakazu , Saisyo Atsuyuki , Kitahara Takashi
Published: August 2024

Immune checkpoint inhibitor (ICI)‐induced adverse events due to excessive immune stimulation are problematic in immunotherapy. The activation of viral infection triggered by ICI‐induced dysregulated immunity has been proposed; however, this association remains inconsistent. This study investigated the association between ICI administration and cytomegalovirus (CMV) infections, a pathogen linked to immune abnormalities and reactivation, using the Food and Drug Administration Adverse Event Reporting System. We used the crude data set and immunocompromise‐free data set from the fourth quarter of 2012 to 2023. The disproportionality between CMV infection and ICI was analyzed using reporting odds ratio (ROR) and information component (IC) methodologies. Disproportionality between ipilimumab and nivolumab combination case and CMV infection was observed in the crude (ROR: 2.83, 95% confidence interval [CI]: 2.32–3.47; IC: 1.48, 95% CI: 1.14–1.73) and immunocompromise‐free data set (ROR: 1.76, 95% CI: 1.33–2.33; IC: 0.80, 95% CI: 0.33–1.14), whereas disproportionality between other ICI and CMV infection was not observed in the immunocompromise‐free data set. Multiple sensitivity analyses and time‐scan analysis also revealed the consistent disproportionality between ipilimumab and nivolumab combination cases and CMV infection, regardless of the host's immune status. While further research is warranted to validate our findings, these results highlight new insights into ICI‐induced viral infections and suggest the importance of considering the possibility of CMV infections during ipilimumab and nivolumab combination therapy, regardless of the host's immune status.
CircETV6 acts as an oncogenic driver in hepatocellular carcinoma progression
Authors: Li Xiaoqin , Jiang Xuemei , Lu Jing , Jiang Lan , Li Yan , Lin Yuting , Wan Feng , Wang Changmin
Published: August 2024

Circular RNA (circRNA) plays important role in hepatocellular carcinoma (HCC) progression. However, the role and mechanism of circETV6 in HCC progression remain unclear. The levels of circETV6, ETV6, miR‐383‐5p, and PTPRE were tested by quantitative reverse‐transcription polymerase chain reaction. Cell functions were assessed using the 3‐(4,5‐dimethyl‐2‐thiazolyl)‐2,5‐diphenyl‐2H‐tetrazolium bromide assay, 5‐ethynyl‐2′‐deoxyuridine assay, colony formation assay, wound healing assay, transwell assay, and flow cytometry. The protein levels of poptosis‐related markers and PTPRE were determined by western blot analysis. RNA interaction was analyzed by dual‐luciferase reporter assay and RNA pull‐down assay. A xenograft model was established to assess circETV6 roles in vivo. CircETV6 was highly expressed in HCC tissues and cells. CircETV6 knockdown repressed HCC cell proliferation, migration, invasion, and cell cycle, while accelerated apoptosis. CircETV6 targeted miR‐383‐5p, and miR‐383‐5p inhibition reversed the regulation of circETV6 knockdown on HCC cell progression. CircETV6 promoted PTPRE level via targeting miR‐383‐5p. Overexpressed PTPRE abolished the inhibition effect of miR‐383‐5p on HCC cell progression. In addition, circETV6 knockdown slowed HCC tumor growth in vivo. CircETV6 might facilitate HCC progression via the miR‐383‐5p/PTPRE axis, providing a novel target for HCC treatment.
Incidence, description, and timing of serious and opportunistic infections in patients with hairy cell leukemia
Authors: Kapoor Nilesh , Zhao Qiuhong , Stiff Andrew , Bhat Seema A. , Anghelina Mirela I. , Andritsos Leslie A. , Blachly James S. , Epperla Narendranath , Boghdadly Zeinab El , Grever Michael R. , Rogers Kerry A.
Published: August 2024

Hairy cell leukemia is an uncommon B‐cell malignancy with excellent response to purine analogs and to targeted therapies such as ibrutinib and vemurafenib. However, purine analogs are known to be highly immunosuppressive and the infection burden in this patient population with current therapies is unknown. We therefore conducted a retrospective cohort study following 149 patients. Median follow‐up time was 6.9 years. Thirty‐six percent developed an opportunistic or serious infection requiring hospitalization. Most cases were bacterial and most coincided with neutropenia and/or CD4 T‐lymphopenia. No single treatment agent was significantly associated with increased or decreased incidence of infection. Reassuringly, the cumulative incidence of infections plateaued 2 months after initial treatment suggesting clinically significant immune recovery. Only one patient in our cohort passed away due to infection. Estimated 10‐year overall survival was 99% suggesting that infections may not cause as much mortality as was seen prior to current therapies.
Collaborative dynamics in open source software development: Unveiling the influence of team interaction and the role of project manager
Authors: Pal Sukrit , Nair Anand , Zuo Zhiya
Published: August 2024

As the world becomes increasingly reliant on open‐source software (OSS) development platforms, collaborative communication networks are becoming more complex, resulting in non‐trivial effects on project performance. This study examines the impact of communication network characteristics on project performance, measured in terms of the number of issues closed within OSS projects. Additionally, this research examines how this project outcome is affected by project managers' active participation in these communication networks. Using a panel dataset of 1599 projects spanning 104 weeks, with a total of 120,243 observations, we find that the density of communication network has an inverted U‐shaped relationship with project performance, that is, as the density of the communication network formed by team member interactions increases, project performance initially increases but then starts to decrease. Meanwhile, a project manager's participation in the communication network has no direct positive impact on project performance, but it flattens the inverted U‐shaped relationship, that is, it reduces the rate of decrease in project performance after the density of the communication network formed by project team members crosses the inflection point. These results provide valuable insights into the dynamics of communication networks in OSS projects and can help develop strategies for improving project performance.
Development of analytical method for determination of 1,3‐dimethylamylamine in sports nutrition and bodybuilding supplements using pH‐switchable deep eutectic solvents followed by high‐performance liquid chromatography‐diode array detector
Authors: Shen Dijun , Zhang Jie , Zhang Ying , Du Xiru
Published: August 2024

In this work, an easy, safe, simple, and efficient pH‐switchable deep eutectic solvents (DESs)‐based liquid phase microextraction followed by high‐performance liquid chromatography‐diode array detector analysis was developed for the determination of 1,3‐dimethylamylamine (DMAA). The switchability of the obtained DESs was investigated by changing the pH. Then the best‐selected DES was characterized and the application of the selected DES in the extraction of DMAA from sports nutrition and bodybuilding supplements was investigated. The DES synthesized from l‐menthol: oleic acid in a molar ratio of 1:2 had the highest efficiency in the extraction of the target compound. Under the optimum conditions, (50 µL of DES, 100 µL of 4 mol/L KOH, 100 µL of 4 mol/L HCl, extraction time of 40 s and without salt addition) the calibration graph was linear in the range of 0.05–100 µg/kg and limit of detection was 0.02 µg/kg. The relative standard deviations including intra‐day and inter‐day for 10.0 µg/kg of DMAA in real samples were 2.7% (n = 7) and 5.3% (n = 7), respectively. The enrichment factor and percentage extraction recovery of the method were 283 and 85%, respectively. The relative recoveries for DMAA in different samples were in the range of 90%–109%.
Socioeconomic Disparities and Other Factors Affecting Time to Dispensing of Pediatric Hearing Aids
Authors: Coleman Kayla C. , Behzadpour Hengameh K. , Ambrose Tracey , Sideris Irene , Buxton Claire , Preciado Juan A. , Reilly Brian K. , Preciado Diego A. , Robinson Tommie L.
Published: August 2024

Introduction

Pediatric hearing loss can significantly impact speech, language, social, and educational development. Providing access to speech and environmental sounds using amplification devices, such as hearing aids, can help improve developmental outcomes. However, timely rehabilitation and intervention may be delayed due to limited access to resources, further prolonging the adverse effects of childhood hearing loss. The aim of this study was to investigate socioeconomic barriers in time to dispensing hearing aids in a diverse pediatric patient population.

Methods

Data from an existing internal database from a tertiary pediatric hospital were analyzed from January 2020 through August 2022 for barriers associated with hearing aid (HA) dispensing delays. Demographic and clinical characteristics were obtained. Multivariate regression and survival analysis statistics were used to identify factors associated with delayed time to dispensing hearing aids.

Results

Of the 121 patients who had been appropriately diagnosed and fit, 108 (89.3%) had received hearings aids and 13 (10.7%) had not at the time of the study. Of those who had received HA, time to dispensing was not significantly impacted by sex, race, ethnicity, language, or income level. Insurance was found to be an influencing factor in time to receiving the HA.

Conclusion

Factors such as insurance and hearing loss laterality contribute to delays in receiving hearing aids. Identifying these specific barriers and disparities in hearing rehabilitation services will prove vital in facilitating an expedited and equitable pathway to receiving hearing aids.

Level of Evidence

3 Laryngoscope, 135:923–928, 2025
How to Make Semi‐Polar InGaN Light Emitting Diodes with High Internal Quantum Efficiency: The Importance of the Internal Field
Authors: Pristovsek Markus , Hu Nan
Published: August 2024

The theoretical expectation of semi‐polar light emitting diodes (LEDs) is reviewed and compared it to the experimental data. The reported peak internal quantum efficiency (IQE) of non‐polar, and semi‐polar InGaN LEDs are always much lower than the standard polar (0001) oriented LEDs. Calculating the band structure and states including the n‐ and p‐doped layer of LEDs in many orientations, It is found that the inverted polarization‐induced fields for most common semi‐polar orientations like (112) or (201) causes the hole ground state to leak out of the quantum well (QW) into the p‐doped GaN above and by this a low wavefunction overlap and a strongly increased probability for non‐radiative recombination with point defect outside the QW. Based on the calculations, (111), (102), or (103) are predicted as best candidates for LEDs with higher IQE at higher current densities than (0001). LEDs in the uncommon semi‐polar (103) orientation on sapphire have been realized. The (103) LEDs showed the same IQE as (0001) LEDs but at a much higher current density due to the higher overlap of electron and hole wave functions, which is especially useful for micro‐LEDs.
Near‐Infrared Mechanoluminescence of Gd3Ga5O12: Cr3+, La3+ for Biological Stress Imaging
Authors: Bu Weifang , Wang Ting , Wang Yuan , Huang Wenlong , Guo Longchao , Yue Yang , Zhu Xuanyu , Xiao Jianqiang , Yu Xue
Published: August 2024

Near‐infrared (NIR) mechanoluminescence (ML), capable of visualizing internal biological stress, is crucial for advancing in vivo bioimaging applications. Nonetheless, the scope of its applications is significantly constrained by the scarcity of available ML materials as well as unsatisfied ML efficiency. In this work, a NIR‐ML phosphor of Gd3Ga5O12: Cr3+ (GGO: Cr3+) is synthesized, which is characterized by a peak at 725 nm and a full width at half maximum (FWHM) of 100 nm. The NIR‐ML phenomenon of GGO: Cr3+ is demonstrated to stem from contact electrification generated by the interaction between the corresponding oxide powder and the employed elastomer. Accordingly, the NIR‐ML intensity is manipulated to be increased by 340%, attributed to the enhanced surface potential of GGO: Cr3+ for the incorporation of La3+ ions. Furthermore, the NIR‐ML of GGO: Cr3+/polydimethylsiloxane (PDMS) film performs excellent tissue penetration, which indicates its promising potential for in situ monitoring of biological stress. Hence, it paves the way for novel bioimaging within living organisms.
Nonlinear dynamics in a fear‐driven predator–prey system: Bistability, bifurcations, hydra effect, and optimal harvesting
Authors: Umrao Anuj Kumar , Lamba Sonu , Srivastava Prashant K.
Published: August 2024

The impact of predator‐driven fear on ecosystems is significant and can encompass both trophic (direct) and nontrophic (indirect) effects. Previous studies have shown that nontrophic fear effects have an important role in predator–prey dynamics. This study investigates the nontrophic fear effect on prey caused by generalist predators and explores optimal harvesting. We assume that the reproduction rate of prey is reduced due to the fear effect, and generalist predator follows Holling type II foraging strategy for predation. Additionally, we assume that predators are commercially valuable and harvested proportionately to their density. We demonstrate the existence of equilibrium points, their local and global stability, and bifurcation analysis. We observe that the model system undergoes a sequence of codimension one and codimension two bifurcations. Our results show that in the absence of predator harvesting, increasing levels of fear destabilize the predator–prey system, and controlled harvesting is beneficial for the coexistence of both populations. Also, the harvesting of predators may produce hydra and multiple hydra effects. We identify different types of bistability phenomena, which emphasize the importance of initial population size. Further, an optimal harvesting policy is also explored by formulating an optimal control problem (OCP). The harvesting cost‐functional is designed by incorporating the bionomic equilibrium state. We use Pontryagin's maximum principle and solve the OCP numerically. It is observed that implementing optimal harvesting not only contributes to the ecological benefits by maintaining a sustainable balance of predator–prey evolution but also plays a significant role in maximizing the economic benefits.
Global solution of spherically symmetric compressible Navier–Stokes equations with bounded density and density‐dependent viscosity
Authors: Zhang Xueyao
Published: August 2024

We consider the compressible Navier–Stokes equations with viscosities
in bounded domains when the initial data are spherically symmetric, which covers the Saint‐Venant model for the motion of shallow water. First, based on the exploitation of the one‐dimensional feature of symmetric solutions, we prove the global existence of weak solutions with initial vacuum, where the upper bound of the density is obtained. Then, with more conditions imposed on the nonvacuum initial data, we obtain the global weak solution which is a strong one away from the symmetry center. The analysis allows for the possibility that a vacuum state emerges at the symmetry center; in particular, we give the uniform bound of the radius of the vacuum domain.
A family of quadrature formulas with their error bounds for convex functions and applications
Authors: Toseef Muhammad , Mateen Abdul , Aamir Ali Muhammad , Zhang Zhiyue
Published: August 2024

In numerical analysis, the quadrature formulas serve as a pivotal tool for approximating definite integrals. In this paper, we introduce a family of quadrature formulas and analyze their associated error bounds for convex functions. The main advantage of these new error bounds is that from these error bounds, we can find the error bounds of different quadrature formulas. This work extends the traditional quadrature formulas such as the midpoint formula, trapezoidal formula, Simpson's formula, and Boole's formula. We also use the power mean and Hölder's integral inequalities to find more general and sharp bounds. Furthermore, we give numerical example and applications to quadrature formulas of the newly established inequalities.
T‐Duality of a Bosonic String in a Weakly Curved Space‐Time
Authors: Dedić Sonja , Obrić Danijel
Published: August 2024

In this article, the T‐dualization of a 3D closed bosonic string, that is propagating in space‐time metric with an infinitesimal linear dependence on the coordinates xμ, is considered. Other fields, Kalb‐Ramond and dilaton fields are set to zero. Action with this configuration of fields is not invariant to translations. In order to find the T‐dual theory, a generalization of the Buscher procedure is employed, that can be applied to cases with coordinate dependent fields that do not possess translational isometry. Finally, by using transformation laws that connect coordinates of starting and T‐dual theories, authors will be able to examine the geometric structure of T‐dual theory.
Modulating the macroscopic anisotropy of liquid crystalline polymers by polarized light
Authors: Xu Yiyi , Jin Mengshi , Wang Jinyu , Huang Shuai , Li Quan
Published: August 2024

Photoalignment technology is serving as an emerging technology for programming liquid crystalline polymer (LCP) materials due to its advantages including noncontact, high resolution, spatial control, programmability, and high efficiency. In this review, we report the research progress in implementing polarized light to design the anisotropy of LCPs, which is categorized based on the photoalignment mechanisms. The alignment approaches and the different stimulus‐responsive behaviors of the materials after photoalignment are discussed. Additionally, we have summarized the applications of photoaligned LCPs such as liquid crystal displays, optical components, intelligent soft actuators, and beyond. Finally, the challenges and future directions of the technology are outlined.
Impact of Chemical Composition Changes during Ultrasound Atomization and Laser Powder Bed Fusion of Low Alloy Steel
Authors: Ledwig Piotr , Pasiowiec Hubert , Truczka Bartłomiej , Falkus Jan
Published: August 2024

This study investigates the effect of changing the chemical composition during ultrasonic atomization (UA) and laser powder bed fusion (LPBF) of low‐alloy steel. UA is used to produce a spherical powder with d50 equal to 49 μm. During UA, the chemical composition of the material changes, which is associated with selective evaporation of Mn from 1.42% to 0.35% and B from 0.0012% to <0.0001%. Thermodynamic calculations confirm that during atomization, mostly Mn and Fe evaporate. To achieve a high density of 3D printed parts, in situ remelting in LPBF is applied. A microstructure consisting of fine grains of tempered martensite and bainite in crystallized meltpools is observed. The selected high‐quality LPBF samples are austenitized in the temperature range of 900–1200 °C for 20 min and quenched in oil. The samples are characterized by light and scanning electron microscopy, as well as Vickers hardness. Changes in chemical composition result in a decrease in the hardenability of the material, and quenching only at 1200 °C produces a martensitic microstructure. LPBF samples show a hardness higher than that of the postheat‐treated sample, but still significantly lower than that of the as‐delivery condition, which is related to the change in chemical composition.
9 Laboratory Needs for Research Response
Authors: Hensley Lisa E. , Klena John D. , DeBoer Jason T. , Montgomery Joel M. , Mbala Placide , Moses Melissa E. , Knapek Katie J. , Olinger Gene G.
Published: August 2024

Public health emergencies are complex and dynamic situations. Outbreaks vary in size and geographical location, and the populations affected may not be limited to humans. Over the last decade, there has been a growing recognition of the need to respond aggressively and comprehensively as early as possible to minimize the potential public health and economic impacts. At the most basic level, laboratory testing identifies infected individuals, animals, and/or contaminated environmental inputs. Laboratories provide data to inform control measures, guide clinical care, and enable response research. For clinical studies, the laboratory may generate data that determine participant eligibility, assist with monitoring participant safety and well-being, or address primary and secondary endpoints. The laboratory’s capacity may limit the study enrollment rate and the completion of essential analyses. Laboratories must be able to deploy rapidly, adapt to changing needs, and generate the highest quality data to protect public health and response efforts. Reliable clinical laboratory data are essential in the determination of candidate therapeutic and vaccine safety and efficacy. In this chapter, we discuss the factors that should be considered for planning and establishing laboratory capabilities, the roles of the laboratory in conducting emergency response research, unique challenges of low-resource environments, potential challenges in establishing and maintaining high-quality laboratory support, as well as recent advances in response-based laboratory science.
10 Understanding How and Where Pathogens Emerge: Preparedness and Response for Zoonotic Diseases
Authors: Clements Andrew , Mendenhall Ian , Schar Daniel
Published: August 2024

This chapter covers emerging zoonotic diseases, with a focus on the current understanding of how and where zoonotic pathogens circulate, their pathways to emergence, potential for sustained human-to-human transmission, and gaps in our knowledge. The first cluster of infections among people may be recognized well after a zoonotic pathogen has spilled over from its primary animal host to other intermediate hosts or directly to people. The collection and use of “pre-outbreak” information improve global health security through better preparedness for infectious disease threats, particularly when up-to-date information is promptly shared by an interlinked, global early surveillance and warning system that can provide timely signals for response to zoonotic threats at the earliest stage of emergence. The chapter also discusses actions to bolster preparedness and response to emerging and re-emerging infectious diseases (EID), which can aid policymakers, scientists, health systems, businesses, and communities to reduce the frequency and impact of zoonotic pathogen spillover (spillover is defined as the transmission of a microbe from one species to another and includes animal-to-animal, animal-to human, and human-to-animal transmission). Recommendations on how countries and the international community can improve prevention, detection, and response to future epidemic and pandemic threats are included.
12.1 In Focus: Novel Manufacturing Platforms for Pandemic Preparedness and Emergency Response
Authors: Bok Karin
Published: August 2024

This feature focuses on several relatively novel (mRNA, DNA, and vector-based) manufacturing platforms for vaccine design that can facilitate rapid response to infectious disease emergencies caused by emerging and re-emerging pathogens, such as Ebola virus and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Both gene- and vector-based platforms can deliver well-designed vaccine antigens inducing humoral and cellular immunity while avoiding most vaccine-associated safety concerns and limitations (integration into the host cell genome or anti-vector immunity). The manufacture of vector-based vaccines can be easily standardized and scaled up and is suitable for single-dose vaccine regimens. However, the mRNA platform has clear advantages over DNA and vector-based platforms. Establishing global mRNA supply chain, manufacturing, and fill/finish capacities is essential for promptly controlling emerging epidemics and pandemics. Aggressive “100 Day Mission” preparedness plans to improve on the lessons learned from the COVID-19 pandemic and further accelerate global access to lifesaving vaccines will depend on progress in this field.
13 Accelerating Vaccine Development: The 100 Days Mission
Authors: Aatresh Aishani , Lurie Nicole , Hatchett Richard
Published: August 2024

This chapter explores the role of the Coalition for Epidemic Preparedness Innovations (CEPI) in global health preparedness and response. It specifically focuses on emergency research response and the 100 Days Mission—the goal of having vaccines ready for use with initial emergency authorization within 100 days from the identification of a novel pathogen with pandemic potential. If this can be accomplished, the world will have a better chance of containing or controlling future infectious disease outbreaks and averting global pandemics or at least minimizing their consequences. Meeting this timeline would require advances in scientific research, production technology, clinical trial readiness, governance and coordination, financing, and the policy ecosystems within which such preparedness and response efforts take place. A “second 100 days” must follow, with the goal of scaling up global vaccine production and delivering vaccines equitably to the world’s population and preventing excess morbidity and mortality as broadly as possible. Multiple countries have followed CEPI’s lead in developing plans consistent with the 100 Days Mission to accelerate vaccine development and delivery. The key to achieving such a goal is a rapid, coordinated research response to smaller outbreaks and epidemics. Smaller responses build the infrastructure and provide practice for testing products quickly in a new crisis, while revealing gaps and generating relevant data to strengthen a bidirectional relationship between preparedness and response.
14.1 In Practice: RECOVERY Trial
Authors: Horby Peter , Peto Leon , Landray Martin
Published: August 2024

The Randomised Evaluation of coronavirus disease 2019 (COVID-19) Therapy Trial (RECOVERY) has been the largest COVID-19 treatment study conducted. It provided compelling evidence on the safety and efficacy, or lack thereof, of a multitude of therapies postulated to be of benefit to COVID-19 patients. This chapter describes the background and environment that led to the protocol design, the key characteristics of the protocol, the operational elements facilitating speedy execution of the study, and the impact and subsequent international expansion of the study.
15 ACTIV: A U.S. Public-Private Partnership Responds to COVID-19
Authors: Wholley David , Collins Francis S. , Stoffels Paul
Published: August 2024

In March 2020, as the threat of the oncoming coronavirus disease 2019 (COVID-19) pandemic became clearer, officials of the U.S. National Institutes of Health (NIH) and the Foundation for NIH (FNIH) rushed to put together a government-industry-academia coalition to promote and coordinate research to counter the virus. The resulting structure—called ACTIV (Accelerating COVID-19 Therapeutic Interventions and Vaccines) soon included eight U.S. government agencies, 20 biopharmaceutical companies and several nonprofit organizations. Early on, ACTIV leaders organized their mission into four working groups of selected scientists: a Preclinical Working Group to evaluate the status of ongoing preclinical research, such as animal studies; a Clinical Therapeutics Working Group to screen potential drug candidates, prioritize them for further study, and then coordinate clinical trials for safety and efficacy; a Clinical Trial Capacity Working Group, to identify and qualify potential clinical trial sites; and a Vaccines Working Group, to harmonize ongoing vaccine trials and ensure robust determination of safety and efficacy. ACTIV replaced a plethora of small individual trials—many too small or insufficiently well designed to produce meaningful results—with a national research agenda for developing therapeutic countermeasures to a rapidly emerging infectious disease. ACTIV provides a model for how medical research can be effectively coordinated in a country without a centralized health system.
16.1 In Practice: Responding to an Infectious Disease Outbreak amid a Humanitarian Emergency
Authors: Ross Elizabeth , Rasinski Emily , Han Carol , Paganini Francesco
Published: August 2024

This chapter highlights the work and leadership of the United States Agency for International Development (USAID) Bureau for Humanitarian Assistance (BHA) and its humanitarian partners to respond to humanitarian needs that arise from international health emergencies. To accomplish these tasks, aid workers strive to learn from the challenges and successes of the immediate past: the 2010 cholera outbreak that ravaged Haitian communities reeling from a catastrophic earthquake; the 2014 West Africa Ebola epidemic that required a multisectoral, multinational global response in three countries; the 2018 Ebola “Outbreak 10” in the Democratic Republic of the Congo (DRC) during an ongoing, multifaceted humanitarian crisis; and the 2020 coronavirus disease 2019 (COVID-19) pandemic that further complicated the DRC Ebola outbreak response (aside from its historic global effects). While learning from these humanitarian crises, response workers actively plan for an uncertain future in which populations everywhere—most acutely in disaster-prone countries with the fewest resources—face climate change and environmental degradation pressures likely to make infectious disease outbreaks more frequent globally in decades to come.
17.1 In Practice: Integration of Clinical Research and Patient Care in the DRC PALM Ebola Therapeutics Trial
Authors: Kojan Richard
Published: August 2024

Clinical research can be integrated with emergency medical treatment even amid civil conflict in a low-resource setting. With researchers and response personnel working together, research and treatment can be not merely compatible but synergistic. The Pamoja Tulinde Maisha (PALM) trial, which showed two of the four treatment candidates used in a multi-arm trial to be safe and efficacious, took place during the 2018–2020 Ebola outbreak in the northeastern Democratic Republic of the Congo (DRC). It would not have been possible without the full cooperation of medical response organizations providing care for Ebola patients in the region; it improved rather than interfering with the quality of care; and it led to the licensing of two new treatments for Ebola virus disease (EVD).
20 Turning Research Results into Clinical Practice Guidelines in Public Health Emergencies
Authors: Jacobsen Donna M. , Masur Henry , Saag Michael S. , Volberding Paul A.
Published: August 2024

Clinical practice guidelines (CPGs) assist clinicians with medical decision making for diagnosis, prevention, and management of medical conditions. Traditional CPGs for established diseases generally follow a lengthy process during which robust, peer-reviewed published data are used to formulate recommendations in a CPG panel. In public health challenges such as HIV and hepatitis C, a different paradigm is necessary. HIV and hepatitis C are areas in which changing data emerged rapidly, and as such CPGs needed to be done carefully but quickly.

The magnitude of the coronavirus disease 2019 (COVID-19) public health emergency, the rapid emergence of important new epidemiologic and clinical data, the availability of an immense amount of information from non-peer-reviewed sources such as the Internet, social media platforms, and pre-prints, along with public expectations for current and objective advice regarding prevention and treatment of COVID-19, warranted the creation of an emergency CPG panel that was quite different from any previous CPG, including those for HIV and hepatitis C.

For healthcare practitioners, public health officials, and other stakeholders, there are many lessons to be learned here about the creation of CPGs that can rapidly provide much-needed guidance in a credible, current, understandable format, which can have a major impact on healthcare, patient outcomes, and the trajectory of an epidemic or pandemic.
3 Guiding Principles for Emergency Research Response
Authors: Higgs Elizabeth S.
Published: August 2024

Accelerated clinical research in response to infectious disease health emergencies is a critical element of advancing health security and future freedom from infectious disease threats. An effective research response requires preparedness to ensure an expeditious assessment of candidate medical countermeasures (MCMs) for safety and efficacy through rigorous clinical trials. Ideally, a research response is simply a pivot from ongoing conduct of rigorous clinical trials within a continuously operating global clinical trials network based on national clinical research infrastructure. This chapter identifies and explains six principles that apply throughout an accelerated emergency research response:

Research should be an integral part of preparedness and emergency response.

Response research must align with the three primary goals of an emergency response to: (a) save lives, (b) accelerate the end of the outbreak, and (c) develop measures to prevent and mitigate future outbreaks.

Response research should be implemented quickly and efficiently based on preparedness plans.

Scientific and ethical standards for human subject research do not change during a health emergency.

Research response should be led by the government of the country experiencing the health emergency.

Good participatory practice (GPP) applies to research in health emergencies.

The first three of these apply specifically to public health emergencies, while the last three are in effect reminders that the fundamental principles of clinical research still hold in an emergency situation, even though the temptation to cut corners may don the cloak of compassion for suffering humanity. These six principles involve both moral and practical considerations for emergency response research to develop and reliably assess MCMs in a public health emergency.
23.1 In Practice: Monitoring the PALM Ebola Therapeutics Study in the Democratic Republic of the Congo
Authors: Proschan Michael A. , DeMets David L.
Published: August 2024

This chapter outlines the demanding, complex task of monitoring an expedited clinical trial in a resource-limited, insecure setting. The PALM Ebola therapeutics trial was implemented in the Democratic Republic of the Congo (DRC) despite minimal basic infrastructure, widespread suspicion and hostility among the population, and outbreaks of violence in the region. In order to keep participant enrollment numbers manageable, the PALM trial was designed to detect a large treatment effect, and its primary endpoint was mortality within 28 days after randomization. The course of an Ebola epidemic can wax and wane unpredictably, causing fluctuations in enrollment and a lag in information presented to the data and safety monitoring board (DSMB). The DSMB had to meet frequently, usually virtually, to monitor the four treatments being investigated and detect safety and efficacy signals. Since both resources and medical personnel were at their limits, collecting and verifying all data was difficult. Therefore, streamlining data collection and focusing on the most critical outcomes for safety and efficacy monitoring were paramount. Results indicated that two of the four agents under study, MAb114 and REGN-EB3, were clearly superior to the ZMapp control arm, so much so that the trial was stopped early.
25.1 Case Study: Modeling Fractional-Dose Emergency Vaccination Campaigns for Yellow Fever
Authors: Wu Joseph T. , Peak Corey M.
Published: August 2024

Yellow fever (YF) is a mosquito-borne disease with no specific treatment. The burden of YF was much reduced around the world in the 1950s, but many mosquito control programs were allowed to lapse thereafter, and the World Health Organization (WHO) has been warning for decades that explosive outbreaks of urban YF were likely. YF resurged and spread widely in urban Angola in late 2015, then to Kenya, China, and the Democratic Republic of the Congo (DRC). The existing WHO YF vaccine stockpile was insufficient, and WHO proposed using a fractional dose (one-fifth of that previously used) against the spreading epidemic. We used mathematical modeling to assess the impact of potentially reduced vaccine efficacy with fractional dosing on the infection attack rate. Our rapid risk assessment model showed that the proposed WHO dose-sparing strategy for the YF vaccination campaign in Kinshasa would be robust and effective and would prevent many more infections than using the available vaccine at standard dosage, even with a large margin for error in case fivefold fractional-dose vaccine efficacy turned out to be lower than expected. WHO implemented the strategy in August 2016, and subsequent studies found it to be a viable control strategy, with possible implications for other situations of vaccine shortage.