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Direct electron detectors in scanning transmission electron microscopy give unprecedented possibilities for structure analysis at the nanoscale. In electronic and quantum materials, this new capability gives access to, for example, emergent chiral structures and symmetry-breaking distortions that underpin functional properties. Quantifying nanoscale structural features with statistical significance, however, is complicated by the subtleties of dynamic diffraction and coexisting contrast mechanisms, which often results in a low signal-to-noise ratio and the superposition of multiple signals that are challenging to deconvolute. Here we apply scanning electron diffraction to explore local polar distortions in the uniaxial ferroelectric Er(Mn,Ti)O3. Using a custom-designed convolutional autoencoder with bespoke regularization, we demonstrate that subtle variations in the scattering signatures of ferroelectric domains, domain walls, and vortex textures can readily be disentangled with statistical significance and separated from extrinsic contributions due to, e.g., variations in specimen thickness or bending. The work demonstrates a pathway to quantitatively measure symmetry-breaking distortions across large areas, mapping structural changes at interfaces and topological structures with nanoscale spatial resolution.

We report the p+p and p+d differential cross sections measured in the SeaQuest experiment for J/ψ and ψ(2S) production at [Formula presented] beam energy covering the forward x-Feynman (xF) range of 0.5

The Data Acquisition System (DAQ) for the LUX-ZEPLIN (LZ) dark matter detector is described. The signals from 745 PMTs, distributed across three subsystems, are sampled with 100-MHz 32-channel digitizers (DDC-32s). A basic waveform analysis is carried out on the on-board Field Programmable Gate Arrays (FPGAs) to extract information about the observed scintillation and electroluminescence signals. This information is used to determine if the digitized waveforms should be preserved for offline analysis. The system is designed around the Kintex-7 FPGA. In addition to digitizing the PMT signals and providing basic event selection in real time, the flexibility provided by the use of FPGAs allows us to monitor the performance of the detector and the DAQ in parallel to normal data acquisition. The hardware and software/firmware of this FPGA-based Architecture for Data acquisition and Realtime monitoring (FADR) are discussed and performance measurements are described.

Abstract: Antarctic sea ice, a key component in the complex Antarctic climate system, is an important driver and indicator of the global climate. In the relatively short satellite‐observed period from 1979 to 2022 the sea ice extent has continuously increased (contrasting a major decrease in Arctic sea ice) up to a dramatic decrease between 2014 and 2017. Recent years have seen record sea ice lows in February 2022–February 2023. We use a statistical ensemble reconstruction of Antarctic sea ice to put the observed changes into the historical context of the entire 20th century. We propose a seasonal Vector Auto‐Regressive Moving Average (VARMA) model fit in a Bayesian framework using regularized horseshoe priors on the regression coefficients to create a stochastic ensemble reconstruction of monthly Antarctic Sea ice extent from 1900 to 1979. This novel model produces a set of 2,500 plausible sea ice extent reconstructions for the sea ice by sector that incorporate the autocorrelation structure of sea ice over time as well as the dependence of sea ice between the sectors. These fully observed reconstructions exhibit plausible month‐to‐month changes in reconstructed sea ice as well as plausible interactions between the sectors and the total. We reconstruct an overall higher sea ice extent earlier in the 20th century with a relatively sharp decline in the 1970s. These trends agree well with previous reconstructions of Antarctic sea ice based on ice core data, whaling locations, and climatological data, as well as early satellite observations in the reconstruction period.

LUX-ZEPLIN (LZ) is a tonne-scale experiment searching for direct dark matter interactions and other rare events. It is located at the Sanford Underground Research Facility (SURF) in Lead, South Dakota, USA. The core of the LZ detector is a dual-phase xenon time projection chamber (TPC), designed with the primary goal of detecting Weakly Interacting Massive Particles (WIMPs) via their induced low energy nuclear recoils. Surrounding the TPC, two veto detectors immersed in an ultra-pure water tank enable reducing background events to enhance the discovery potential. Intricate calibration systems are purposely designed to precisely understand the responses of these three detector volumes to various types of particle interactions and to demonstrate LZ’s ability to discriminate between signals and backgrounds. In this paper, we present a comprehensive discussion of the key features, requirements, and performance of the LZ calibration systems, which play a crucial role in enabling LZ’s WIMP-search and its broad science program. The thorough description of these calibration systems, with an emphasis on their novel aspects, is valuable for future calibration efforts in direct dark matter and other rare-event search experiments.

Context: The rice-wheat (RW) system, spanning 13.5 million hectares in South Asia, is crucial for food security and livelihoods. However, intensive conventional tillage-based practices have harmed soil and environmental health, decreased productivity trends and increased greenhouse gas emissions. Objective: This study aims to develop resilient, climate-smart cropping systems within the RW system, focusing on soil and crop productivity, economic viability, and reduced greenhouse gas (GHG) emissions. Methods: Over eight years, the study evaluated diverse parameters compared to farmer practices (FP) in seven scenarios (Sc), including one representing FP (Sc1) and six based on conservation agriculture (CA) principles. The study assessed system crop productivity, economic returns, soil quality (organic carbon; OC, nitrogen; N, phosphorus; P, potassium; K contents, bulk density; BD, soil aggregation, infiltration rates, microbial counts, and earthworm density), and GHG emissions. Results: CA-based scenarios (Sc2 to Sc7) showed improved soil quality, lower bulk density, enhanced soil aggregation, and increased infiltration rates compared to Sc1. In the 0–15 cm layer, surface soil organic carbon (OC) and C stock were 63.7 % and 49.6 % higher, respectively, in CA-based scenarios. Additionally, available N, P and K contents in the surface layer increased by 10.2 %, 28.6 %, and 21.8 % under CA-based scenarios. Adoption of CA in intensified maize-based scenarios (Sc4 and Sc5) led to the increased system and economic yields, higher soil quality index (SQI), reduced GHG emissions and increased C stock compared to Sc1. Implications: The study highlights that Conservation Agriculture (CA) practices and diversified crop rotations can address issues like falling crop productivity, reduced economic returns, soil degradation, and increasing environmental impacts in northwestern India's traditional rice-wheat system. However, widespread adoption requires government policies, including C credit payments and guaranteed markets with supportive pricing.

This White Paper presents an overview of the current status and future perspective of QCD research, based on the community inputs and scientific conclusions from the 2022 Hot and Cold QCD Town Meeting. We present the progress made in the last decade toward a deep understanding of both the fundamental structure of the sub-atomic matter of nucleon and nucleus in cold QCD, and the hot QCD matter in heavy ion collisions. We identify key questions of QCD research and plausible paths to obtaining answers to those questions in the near future, hence defining priorities of our research over the coming decades.

Increasing evidence suggests that urbanization is associated with higher mutation rates, which can affect the health and evolution of organisms that inhabit cities. Elevated pollution levels in urban areas can induce DNA damage, leading to de novo mutations. Studies on mutations induced by urban pollution are most prevalent in humans and microorganisms, whereas studies of non-human eukaryotes are rare, even though increased mutation rates have the potential to affect organisms and their populations in contemporary time. Our Perspective explores how higher mutation rates in urban environments could impact the fitness, ecology and evolution of populations. Most mutations will be neutral or deleterious, and higher mutation rates associated with elevated pollution in urban populations can increase the risk of cancer in humans and potentially other species. We highlight the potential for urban-driven increased deleterious mutational loads in some organisms, which could lead to a decline in population growth of a wide diversity of organisms. Although beneficial mutations are expected to be rare, we argue that higher mutation rates in urban areas could influence adaptive evolution, especially in organisms with short generation times. Finally, we explore avenues for future research to better understand the effects of urban-induced mutations on the fitness, ecology and evolution of city-dwelling organisms.

Searches for dark matter with liquid xenon time projection chamber experiments have traditionally focused on the region of the parameter space that is characteristic of weakly interacting massive particles, ranging from a few GeV/c2 to a few TeV/c2. Models of dark matter with a mass much heavier than this are well motivated by early production mechanisms different from the standard thermal freeze-out, but they have generally been less explored experimentally. In this work, we present a reanalysis of the first science run of the LZ experiment, with an exposure of 0.9 tonne×yr, to search for ultraheavy particle dark matter. The signal topology consists of multiple energy deposits in the active region of the detector forming a straight line, from which the velocity of the incoming particle can be reconstructed on an event-by-event basis. Zero events with this topology were observed after applying the data selection calibrated on a simulated sample of signal-like events. New experimental constraints are derived, which rule out previously unexplored regions of the dark matter parameter space of spin-independent interactions beyond a mass of 1017 GeV/c2.

Following the first science results of the LUX-ZEPLIN (LZ) experiment, a dual-phase xenon time projection chamber operating from the Sanford Underground Research Facility in Lead, South Dakota, USA, we report the initial limits on a model-independent nonrelativistic effective field theory describing the complete set of possible interactions of a weakly interacting massive particle (WIMP) with a nucleon. These results utilize the same 5.5 t fiducial mass and 60 live days of exposure collected for the LZ spin-independent and spin-dependent analyses while extending the upper limit of the energy region of interest by a factor of 7.5 to 270 keV. No significant excess in this high energy region is observed. Using a profile-likelihood ratio analysis, we report 90% confidence level exclusion limits on the coupling of each individual nonrelativistic WIMP-nucleon operator for both elastic and inelastic interactions in the isoscalar and isovector bases.

The electromagnetic form factors of the proton and neutron encode information on the spatial structure of their charge and magnetization distributions. While measurements of the proton are relatively straightforward, the lack of a free neutron target makes measurements of the neutron's electromagnetic structure more challenging and more sensitive to experimental or model-dependent uncertainties. Various experiments have attempted to extract the neutron form factors from scattering from the neutron in deuterium, with different techniques providing different, and sometimes large, systematic uncertainties. We present results from a novel measurement of the neutron magnetic form factor using quasielastic scattering from the mirror nuclei ^{3}H and ^{3}He, where the nuclear effects are larger than for deuterium but expected to largely cancel in the cross-section ratios. We extracted values of the neutron magnetic form factor for low-to-modest momentum transfer, 0.6

We measure triangular flow relative to the reaction plane at 3 GeV center-of-mass energy in Au+Au collisions at the BNL Relativistic Heavy Ion Collider. A significant v3 signal for protons is observed, which increases for higher rapidity, higher transverse momentum, and more peripheral collisions. The triangular flow is essentially rapidity-odd with a slope at midrapidity, dv3/dy|(y=0), opposite in sign compared to the slope for directed flow. No significant v3 signal is observed for charged pions and kaons. Comparisons with models suggest that a mean field potential is required to describe these results, and that the triangular shape of the participant nucleons is the result of stopping and nuclear geometry.

A wooden house frame consists of many different lumber pieces, but because of the regularity of these building blocks, the structure can be designed using straightforward geometrical principles. The design of multicomponent protein assemblies, in comparison, has been much more complex, largely owing to the irregular shapes of protein structures1. Here we describe extendable linear, curved and angled protein building blocks, as well as inter-block interactions, that conform to specified geometric standards; assemblies designed using these blocks inherit their extendability and regular interaction surfaces, enabling them to be expanded or contracted by varying the number of modules, and reinforced with secondary struts. Using X-ray crystallography and electron microscopy, we validate nanomaterial designs ranging from simple polygonal and circular oligomers that can be concentrically nested, up to large polyhedral nanocages and unbounded straight 'train track' assemblies with reconfigurable sizes and geometries that can be readily blueprinted. Because of the complexity of protein structures and sequence-structure relationships, it has not previously been possible to build up large protein assemblies by deliberate placement of protein backbones onto a blank three-dimensional canvas; the simplicity and geometric regularity of our design platform now enables construction of protein nanomaterials according to 'back of an envelope' architectural blueprints.

The Alaskan Layered Pollution And Chemical Analysis (ALPACA) field experiment was a collaborative study designed to improve understanding of pollution sources and chemical processes during winter (cold climate and low-photochemical activity), to investigate indoor pollution, and to study dispersion of pollution as affected by frequent temperature inversions. A number of the research goals were motivated by questions raised by residents of Fairbanks, Alaska, where the study was held. This paper describes the measurement strategies and the conditions encountered during the January and February 2022 field experiment, and reports early examples of how the measurements addressed research goals, particularly those of interest to the residents. Outdoor air measurements showed high concentrations of particulate matter and pollutant gases including volatile organic carbon species. During pollution events, low winds and extremely stable atmospheric conditions trapped pollution below 73 m, an extremely shallow vertical scale. Tethered-balloon-based measurements intercepted plumes aloft, which were associated with power plant point sources through transport modeling. Because cold climate residents spend much of their time indoors, the study included an indoor air quality component, where measurements were made inside and outside a house to study infiltration and indoor sources. In the absence of indoor activities such as cooking and/or heating with a pellet stove, indoor particulate matter concentrations were lower than outdoors; however, cooking and pellet stove burns often caused higher indoor particulate matter concentrations than outdoors. The mass-normalized particulate matter oxidative potential, a health-relevant property measured here by the reactivity with dithiothreiol, of indoor particles varied by source, with cooking particles having less oxidative potential per mass than pellet stove particles.

By directly altering microscopic interactions, pressure provides a powerful tuning knob for the exploration of condensed phases and geophysical phenomena1. The megabar regime represents an interesting frontier, in which recent discoveries include high-temperature superconductors, as well as structural and valence phase transitions2-6. However, at such high pressures, many conventional measurement techniques fail. Here we demonstrate the ability to perform local magnetometry inside a diamond anvil cell with sub-micron spatial resolution at megabar pressures. Our approach uses a shallow layer of nitrogen-vacancy colour centres implanted directly within the anvil7-9; crucially, we choose a crystal cut compatible with the intrinsic symmetries of the nitrogen-vacancy centre to enable functionality at megabar pressures. We apply our technique to characterize a recently discovered hydride superconductor, CeH9 (ref. 10). By performing simultaneous magnetometry and electrical transport measurements, we observe the dual signatures of superconductivity: diamagnetism characteristic of the Meissner effect and a sharp drop of the resistance to near zero. By locally mapping both the diamagnetic response and flux trapping, we directly image the geometry of superconducting regions, showing marked inhomogeneities at the micron scale. Our work brings quantum sensing to the megabar frontier and enables the closed-loop optimization of superhydride materials synthesis.

Selvi Apriliana Putri,1 Rani Maharani,1 Iman Permana Maksum,1 Teruna J Siahaan2 1Department of Chemistry, Faculty of Mathematics and Natural Sciences, Padjadjaran University, Bandung, 40173, Indonesia; 2Department of Pharmaceutical Chemistry, School of Pharmacy, The University of Kansas, Lawrence, KS, 66047, USACorrespondence: Iman Permana Maksum, Department of Chemistry, Faculty of Mathematics and Natural Sciences, Padjadjaran University, Bandung, 40173, Indonesia, Email iman.permana@unpad.ac.idAbstract: Melanogenesis is a biochemical process that regulates skin pigmentation, which is crucial role in protecting against ultraviolet radiation. It is also associated with hyperpigmentation conditions such as melasma and age spots, which negatively impact aesthetics and self-confidence. Tyrosinase (TYR), a key enzyme in the melanogenesis pathway, catalyzes the biosynthesis of melanin in the skin. Inhibition of tyrosinase particularly by blocking its active site and preventing the binding of natural substrates such as tyrosine, can reduce melanin production, making it a promising therapeutic target for treating hyperpigmentation. Peptides have emerged as promising therapeutics to regulate melanogenesis by minimizing the side effects associated with conventional skin whitening therapeutics. This review is designed to offer a comprehensive analysis of current strategies in peptide design aimed at optimizing anti-melanogenic activity, by focusing on the role of molecular weight, polarity, and cyclization strategies in enhancing peptide efficacy and stability. It was found that optimal peptide size was within the range of 400– 600 Da. The balance between hydrophilic and hydrophobic properties in peptides is crucial for effective TYR inhibition, as higher hydrophilicity enhances affinity for the TYR active site and stronger catalytic inhibition, while hydrophobicity can contribute through alternative mechanisms. Cyclization of peptides enhances their structural stability, serum resistance, and binding affinity while reducing toxicity. This process increases resistance to enzymatic degradation and improves target specificity by limiting conformational flexibility. Additionally, the rigidity and internal hydrogen bonding of cyclic peptides can aid in membrane permeability, making them more effective for therapeutic use. Peptide optimizations through size modification, polarity change, and cyclization strategies have been shown to be promising as reliable and safe agents for melanin inhibition. Future studies exploring specific amino acid in peptide chains are required to improve efficacy and potential clinical applications of these anti-melanogenic peptides as a hyperpigmentation treatment. Keywords: anti-hyperpigmentation, anti-melanogenesis, amino acid, tyrosinase, TYR

Chern-Horng Lee,1 Yu-Han Huang,2 Tzu-Ju Hsu,3 Tzung-Hai Yen,4 Sen-Yung Hsieh5,6 1Department of Geriatric Medicine and General Internal Medicine, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan, 333, Taiwan; 2Department of Management Office for Health Data, China Medical University Hospital, Taichung, Taiwan, College of Medicine, China Medical University, Taichung, Taiwan; 3Management Office for Health Data (DryLab), Clinical Trial Research Center (CTC), China Medical University Hospital, Taichung, Taiwan; 4Department of Nephrology, Chang Gung Memorial Hospital, Linkou Branch, Taoyuanm, 333, Taiwan; 5Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan, 333, Taiwan; 6College of Medicine, Chang Gung University, Taoyuan, 333, TaiwanCorrespondence: Sen-Yung Hsieh, Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou, Taoyuan, 333, Taiwan, Tel +886-975368031, Fax +886-33272324, Email siming@cgmh.org.tw; siming.shia@msa.hinet.netPurpose: Metabolic dysfunction-associated fatty liver disease (MAFLD) and metabolic dysfunction-associated steatohepatitis (MASH) pose significant risks for liver cirrhosis and hepatocellular carcinoma (HCC). Daily aspirin and statins could reduce HCC in patients with MAFLD/MASH. We aimed to clarify whether combined aspirin and statins exert a synergistic effect on prevention of cirrhosis and HCC in patients with MAFLD/MASH.Patients and Methods: Patients and their clinical data were collected from the National Health Insurance Research Database (NHIRD), encompassing about 20 million population. A total of 735,574 MAFLD/MASH patients between January 1, 2009, and December 31, 2020 were identified. After applying exclusion criteria, 662,004 cases were enrolled, with a follow-up period of 3 years. Propensity score matching was employed for comparative analysis.Results: Our findings indicate that combined statin and aspirin use significantly reduced the incidence of liver cirrhosis (p < 0.001) compared to statin or aspirin alone, or non-use of both drugs. However, the combined therapy did not confer additional benefits in reducing mortality rates and HCC. Furthermore, statin monotherapy exhibited a more pronounced effect in reducing mortality and HCC compared to aspirin alone or combined therapy.Conclusion: Our study underscores that statin monotherapy was not inferior to aspirin or aspirin-statin combined therapies in terms of chemoprevention of cirrhosis, HCC, and overall mortality in MAFLD/MASH patients.Keywords: MAFLD, MASH, statin, aspirin, cirrhosis, hepatocellular carcinoma

Zheng-lun Lin,1– 3,&ast; Li Liu,4,&ast; Kai Shi,1– 3 Tian-jie Chen,1– 3 Lin-ming Chen,1– 3 Hong-da Cai1– 3 1Department of Anesthesiology, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, 350212, People’s Republic of China; 2Department of Anesthesiology, the First Affiliated Hospital, Fujian Medical University, Fuzhou, 350005, People’s Republic of China; 3Institute of Anesthesiology, Fujian Medical University, Fuzhou, 350005, People’s Republic of China; 4Department of Anesthesiology, Fuzhou Traditional Chinese Medicine Hospital, Fujian University of Traditional Chinese Medicine, Fuzhou, 350001, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hong-da Cai, Email caihd2000@163.comObjective: To evaluate the effect of intravenous lidocaine injection on the half-maximum effective concentration (EC50) of remifentanil in preventing cough due to tracheal extubation in female patients undergoing thyroid surgery by Dixon’s sequential method.Methods: A total of 50 female patients underwent elective thyroidectomy were randomly divided into two groups of a 1:1 ratio. Group L (lidocaine group) was given intravenous lidocaine (1.5 mg/kg) and then continuous infusion (2 mg/kg/h) until the end of surgery. Group C (control group) received 0.9% sodium chloride solution infusion in the same way. The primary outcome was effective concentration EC50 of remifentanil in preventing cough due to tracheal extubation in female patients undergoing thyroid surgery. The secondary outcomes were as follows: mean arterial pressure (MAP), oxygen saturation (SpO2), heart rate (HR), PetCO2 and respiratory rate at the time of tracheal extubation. The incidence of postoperative nausea and vomiting, and symptoms associated with lidocaine toxicity.Results: Finally, 44 subjects completed the study. The EC50 values of remifentanil calculated using probit regression were 1.40 ng/mL (95% CI, 1.15– 1.65 ng/mL) in Group C and 0.83 ng/mL (95% CI, 0.58– 1.08 ng/mL) in Group L. A lower concentration of remifentanil can inhibit the cough reaction during intravenous lidocaine infusion. PetCO2 in the lidocaine group was lower than that in the control group (Z=− 2.162, P < 0.05). The respiratory rate of the lidocaine group after extubation was higher than that of the control group (Z=− 3.287, P < 0.05).Conclusion: Intravenous injection of lidocaine can reduce the effective concentration EC50 of remifentanil in preventing tracheal extubation cough in female patients undergoing thyroid surgery.Keywords: lidocaine, thyroid surgery, remifentanil, extubation cough

Xin Xue,1 Zhe Zhao,2 Li-Bo Zhao,2 Ying-Hui Gao,3 Wei-Hao Xu,4 Wei-Meng Cai,5 Shao-Hua Chen,5 Tian-Jiao Li,6 Ting-Yu Nie,6 Dong Rui,5 Yao Ma,5 Xiao-Shun Qian,1 Jun-Ling Lin,7 Lin Liu1 1Department of Pulmonary and Critical Care Medicine of the Second Medical Center, Chinese PLA General Hospital, Beijing, People’s Republic of China; 2Department of Vasculocardiology, Second Medical Center of Chinese PLA General Hospital, Beijing, People’s Republic of China; 3PKU-Upenn Sleep Center, Peking University International Hospital, Beijing, People’s Republic of China; 4Department of Geriatrics, Guangdong Provincial Geriatrics Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, Guangzhou, People’s Republic of China; 5Department of Pulmonary and Critical Care Medicine, Second Medical Center of Chinese PLA General Hospital, Beijing, People’s Republic of China; 6Medical College, Yan’ an University, Yan’ an, People’s Republic of China; 7Department of Respiratory and Critical Care Medicine, Beijing Chaoyang Hospital Affiliated to Capital Medical University, Beijing, People’s Republic of ChinaCorrespondence: Lin Liu, Department of Pulmonary and Critical Care Medicine of the Second Medical Center, Chinese PLA General Hospital, Beijing, People’s Republic of China, Email liulin715@qq.com Jun-Ling Lin, Department of Respiratory and Critical Care Medicine, Beijing Chaoyang Hospital Affiliated to Capital Medical University, Beijing, 100020, People’s Republic of China, Email 18611521849@163.comBackground: Previous studies have demonstrated a significant correlation between obstructive sleep apnea (OSA) and frailty. However, the association of mean pulse oxygen saturation (MSpO2) with frailty among OSA patients remains unconfirmed. This study aimed to explore this potential association using data from a multicenter, prospective cohort.Methods: A total of 1006 elderly patients diagnosed with OSA through polysomnography (PSG) from January 2015 to October 2017 were enrolled. Patients were stratified into four groups according to their MSpO2 levels to assess differences in frailty onset. Multivariate Cox regression analysis, Kaplan-Meier curves, restricted cubic splines, and subgroup analyses were employed to evaluate variations in frailty onset across different MSpO2 levels.Results: Over a median follow-up period of 52 months, 275 patients developed frailty. Analysis using restricted cubic splines revealed a U-shaped trend between MSpO2 and frailty risk (non-linear p-value = 0.028). Patients in the lowest quartile (MSpO2

Tai-Jan Liu,1,2 Heng-Chih Pan,3– 6 Chin-Chan Lee,3,4,6 Chun-Yu Chen,3,4,6 I-Wen Wu,3,7,8 Chiao-Yin Sun,3,4 Kuo-Su Chen,3,4 Heng-Jung Hsu,3,4,6 Yih-Ting Chen,3,4 Cheng-Kai Hsu,3,4 Yuan-Chieh Yeh1,9 1Department of Traditional Chinese Medicine, Keelung Chang Gung Memorial Hospital, Keelung, Taiwan; 2Department of Traditional Chinese Medicine, New Taipei Municipal Tucheng Hospital, New Taipei City, Taiwan; 3Division of Nephrology, Department of Internal Medicine, Keelung Chang Gung Memorial Hospital, Keelung, Taiwan; 4Chang Gung University College of Medicine, Taoyuan, Taiwan; 5Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan; 6Community Medicine Research Center, Keelung Chang Gung Memorial Hospital, Keelung, Taiwan; 7Division of Nephrology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; 8Division of Nephrology, Department of Internal Medicine, Taipei Medical University Hospital, Taipei, Taiwan; 9Program in Molecular Medicine, College of Life Sciences, National Yang Ming Chiao Tung University, Taipei, TaiwanCorrespondence: Yuan-Chieh Yeh, Department of Traditional Chinese Medicine, Keelung Chang Gung Memorial Hospital, No. 222, Maijin Road, Anle Dist, Keelung, Taipei, Taiwan, Tel +886975362713, Fax +886224313161, Email b9005030@gmail.comObjective: Intradialytic hypotension (IDH), a common complication of hemodialysis (HD), is associated with increased cardiovascular risk, morbidity, and mortality. Fatigue is one of the most frequent symptoms of IDH, and deteriorates the quality of life of patients. This study aimed to evaluate the efficacy and safety of electronic moxibustion for improving IDH and its associated symptoms.Methods: We prospectively recruited 32 end-stage renal disease patients with IDH who underwent regular HD at our hospital’s dialysis center between April 2019 and April 2020. A randomized, controlled, two-arm crossover trial was performed to evaluate the efficacy of adding one-hour electronic moxibustion during HD. The outcome measurements included patients’ subjective assessment of the degree of fatigue, recovery time of fatigue from HD, cold intolerance before and after each intervention, frequency of IDH episodes and nursing interventions needed during HD, and blood pressure changes during HD.Results: Thirty (94%) patients completed the study. Intervention with electronic moxibustion improved the degree of fatigue (95% CI, − 2.95 to − 0.18, p = 0.027), specifically in patients prescribed with midodrine (95% CI, − 4.20 to − 0.53, p = 0.013). The short-term use of electronic moxibustion during HD did not significantly alter the frequency of IDH or reduce the degree of decrease in blood pressure. Serious adverse effects were not observed. One patient complained of heat, whereas two patients had local transient erythema and pruritus.Conclusion: Electronic moxibustion appears to be safe and efficacious for improving IDH-related fatigue, thus acting as an adjuvant therapy in HD units to enhance patient comfort and treatment adherence. Further studies with larger sample sizes are required to confirm the benefits of this novel technique.Plain Language Summary: Intradialytic hypotension (IDH) during hemodialysis is linked to increased mortality, often results in fatigue, and reduces the patients’ quality of life. This study assessed the effectiveness of electronic moxibustion, an infrared device that mimics traditional moxibustion, in alleviating fatigue in IDH patients. In a 4-week randomized controlled crossover trial, patients underwent 12 sessions of electronic moxibustion at acupoint CV4 during hemodialysis. While the treatment notably improved fatigue, especially in patients on regular midodrine, it did not significantly affect IDH frequency or blood pressure drop. No major adverse events were reported. This pioneering study evaluated this device for IDH-related fatigue and offered insights for future research on its potential to stabilize blood pressure.Keywords: cross-over studies, moxibustion, fatigue, renal dialysis

Weakly interacting massive particles (WIMPs) may interact with a virtual pion that is exchanged between nucleons. This interaction channel is important to consider in models where the spin-independent isoscalar channel is suppressed. Using data from the first science run of the LUX-ZEPLIN dark matter experiment, containing 60 live days of data in a 5.5 tonne fiducial mass of liquid xenon, we report the results on a search for WIMP-pion interactions. We observe no significant excess and set an upper limit of 1.5 × 10−46 cm2 at a 90% confidence level for a WIMP mass of 33 GeV/c2 for this interaction.

Building fair, equitable, and beneficial partnerships between institutions collaborating in research in low- and middle-income countries (LMIC) and high-income countries (HIC) has become an integral part of research capacity building in global health in recent years. In this paper, we offer an example of an academic collaboration between the University of California Los Angeles, Center for Health Policy and Research (UCLA CHPR) and the University of Philippines, Manila, College of Public Health (UPM CPH) that sought to build an equitable partnership between research institutions. The partnership was built on a project to build capacity for research and produce data for policy action for the prevention and care of non-communicable diseases (NCDs) through primary healthcare in the Philippines. The specific objectives of the project were to: (1) locally adapt the Primary Care Assessment Tool for the Philippines and use the adapted tool to measure facility-level primary care delivery, (2) conduct focus group discussions (FGDs) to gather qualitative observations regarding primary care readiness and capacity, and (3) conduct a comprehensive population-based health survey among adults on NCDs and prior healthcare experience. We describe here the progression of the partnership between these institutions to carry out the project and the elements that helped build a stronger connection between the institutions, such as mutual goal setting, cultural bridging, collaborative teams, and capacity building. This example, which can be used as a model depicting new directionality and opportunities for LMIC-HIC academic partnerships, was written based on the review of shared project documents, including study protocols, and written and oral communications with the project team members, including the primary investigators. The innovation of this partnership includes: LMIC-initiated project need identification, LMIC-based funding allocation, a capacity-building role of the HIC institution, and the expansion of scope through jointly offered courses on global health.

We examine the effect of increased book-tax conformity on corporate capital structure. Prior studies document a decrease in the informativeness of accounting earnings for equity markets resulting from higher book-tax conformity. We argue that the decrease in earnings informativeness impacts equity holders more than debt holders because of the differences in payoff structures between debt and equity investments such that increases in book-tax conformity lead to increases in firms’ reliance on debt capital. We exploit a natural experiment in the U.S. and find that firms facing an increase in required book-tax conformity increase leverage relative to other firms. We also provide evidence of an increase in the cost of equity (but not of debt) capital for firms facing an increase in required book-tax conformity relative to control firms and that these increases in cost of equity capital are positively associated with an increase in leverage. Our findings are consistent with firms substituting away from equity and towards more debt in the presence of higher book-tax conformity.

Molecular systems with coincident cyclic and superhelical symmetry axes have considerable advantages for materials design as they can be readily lengthened or shortened by changing the length of the constituent monomers. Among proteins, alpha-helical coiled coils have such symmetric, extendable architectures, but are limited by the relatively fixed geometry and flexibility of the helical protomers. Here we describe a systematic approach to generating modular and rigid repeat protein oligomers with coincident C2 to C8 and superhelical symmetry axes that can be readily extended by repeat propagation. From these building blocks, we demonstrate that a wide range of unbounded fibres can be systematically designed by introducing hydrophilic surface patches that force staggering of the monomers; the geometry of such fibres can be precisely tuned by varying the number of repeat units in the monomer and the placement of the hydrophilic patches.

Alex S Huang,1 Anthony P Mai,2 Jeffrey L Goldberg,3 Thomas W Samuelson,4 William H Morgan,5 Leon Herndon,6 Tanner J Ferguson,2 Robert N Weinreb7 1Doheny Eye Institute, Department of Ophthalmology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA; 2Vance Thompson Vision, Sioux Falls, SD, USA; 3Byers Eye Institute, Department of Ophthalmology, Stanford University School of Medicine, Palo Alto, CA, USA; 4Minnesota Eye Consultants, University of Minnesota, Minneapolis, MN, USA; 5Lions Eye Institute, Centre for Ophthalmology and Visual Science, University of Western Australia, Perth, Western Australia, Australia; 6Department of Ophthalmology, Duke Eye Center, Duke University, Durham, NC, USA; 7Hamilton Glaucoma Center, Viterbi Family Department of Ophthalmology and Shiley Eye Institute, University of California San Diego, La Jolla, CA, USACorrespondence: Anthony P Mai, Email anthonymai.md@gmail.comAbstract: Nocturnal intraocular pressure (IOP) profiling has shown that the peak IOP usually occurs at night, particularly in patients with glaucoma. Multiple studies have demonstrated that these nocturnal IOP elevations drive glaucomatous progression, often despite stable daytime IOP. Existing vascular dysregulation and decreased nighttime blood pressure compound the damage via low ocular perfusion pressure while elevated nocturnal IOP disrupts axonal transport. These findings are consistent with studies that indicate lowering nocturnal IOP is important for slowing glaucoma progression. Many of the current treatment options lower nighttime IOP significantly less than daytime IOP. Non-invasive IOP-lowering treatments that effectively lower nocturnal IOP remain an unmet need in the treatment of glaucoma.Keywords: glaucoma, nocturnal intraocular pressure, translaminar pressure differential

Yue-Chen Zhao,1,2 Xin Li,3 Chao-Qun Wang,4 Yan Jiao,5 Yan-Nan Shen,2 Tie-Jun Wang,1,2,&ast; Chao-He Zhang6,&ast; 1Department of Radiation Oncology, The Second Hospital of Jilin University, Changchun, Jilin, People’s Republic of China; 2NHC Key Laboratory of Radiobiology, School of Public Health, Jilin University, Changchun, Jilin, People’s Republic of China; 3Department of Radiology, The Second Hospital of Jilin University, Changchun, Jilin, People’s Republic of China; 4Department of Gynaecology, Aviation General Hospital, Beijing, People’s Republic of China; 5Department of Hepatobiliary and Pancreatic Surgery, General Surgery Center, First Hospital of Jilin University, Changchun, People’s Republic of China; 6Department of Hematology and Oncology, The Second Hospital of Jilin University, Changchun, Jilin, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Tie-Jun Wang, Department of Radiation Oncology, The Second Hospital of Jilin University, NO. 218 Ziqiang Street, Changchun, 130041, People’s Republic of China, Email tjwang@jlu.edu.cn Chao-He Zhang, Department of Hematology and Oncology, The Second Hospital of Jilin University, NO. 218 Ziqiang Street, Changchun, 130041, People’s Republic of China, Email zhangchaohe@jlu.edu.cnPurpose: Abraxane (nanoparticle albumin-bound paclitaxel) is a chemotherapeutic employed commonly for the management of various cancers including breast cancer, non-small cell lung cancer, and pancreatic adenocarcinoma. Although it has clinically beneficial properties, Abraxane is accompanied by multiple adverse events (AEs) that require close observation. This study aims to evaluate the AE profile of Abraxane using recently available data from January 2004 through December 2023 in the FDA Adverse Event Reporting System (FAERS).Patients and Methods: The data for Abraxane-related AEs were obtained from the FAERS database. The dataset consisted of patient demographic characteristics as well as information on the types and outcomes of AEs reported. Reporting odds ratios (ROR) as well as proportional reporting ratio (PRR), considering the used definition of anti-cancer agent and AEs, were calculated to investigate any association with Abraxane.Results: A total of 10,310 reports associated with Abraxane AEs were identified. Blood and lymphatic system disorders were the most frequent (ROR 6.44), followed by hepatobiliary (ROR 3.16), infections (ROR 1.45), and gastrointestinal disorders (ROR 1.42). Serious outcomes included hospitalization in 36.35% and death in 29.76% of cases. The top adverse reactions matched known profiles, including peripheral sensory neuropathy (ROR: 49.48). The analysis also found new adverse reactions, such as scleroderma-like reactions (ROR: 95.4) and vascular pseudoaneurysm ruptures (ROR: 87.71).Conclusion: Our results re-emphasize the importance of a robust Post Marketing Surveillance system and suggest this FAERS database based analysis provides an updated, independent information on Abraxane related AEs to enrich its safety profile. A process of continuous vigilance and additional investigations on specific areas that may have some undesired events are imperative to increase our knowledge on how Abraxane should be handled in terms of its safety.Keywords: Abraxane, FAERS database, adverse events, signal detection, pharmacovigilance

Tanner J Ferguson,1 Kristen Walton,2 John G Goertz,2 Brandon J Baartman2 1Vance Thompson Vision, Sioux Falls, SD, USA; 2Vance Thompson Vision, Omaha, NE, USACorrespondence: Tanner J Ferguson, Vance Thompson Vision, 3101 W. 57 th Street, Sioux Falls, SD, 57108, USA, Email tannerferg@gmail.comPurpose: To evaluate the use of varenicline solution nasal spray 0.03 mg (VNS) as a treatment option for the signs and symptoms of dry eye disease following photorefractive keratectomy (PRK).Patients and methods: Subjects electing to undergo PRK were randomized to VNS (study group) or vehicle (control group) twice daily and started treatment with VNS 28 days prior to surgery with continued use of the treatment for 84 days after PRK. After starting treatment, subjects were seen on the day of the procedure and postoperatively at days 2, 3, 4, 7, 28 and 84. The primary outcome measure was the mean change in NEI-VFQ-25, a dry eye item questionnaire, from baseline to day 84. The second primary outcome measure was the rate of corneal epithelial healing following PRK. Secondary outcome measures included eye dryness score (EDS), tear break up time and visual outcomes. The use of rescue therapy was also evaluated.Results: Twenty-one subjects were enrolled in the study group, and twenty subjects were enrolled in the control group. Results from the NEI-VFQ-25 questionnaire revealed positive results in both groups and the between-group difference was not statistically significant (P > 0.05). There was a trend towards faster re-epithelialization in patients treated with VNS vs placebo, where 100% epithelial closure was observed by Day 3 in the VNS group versus Day 4 in the control group; however, the between-group difference was not statistically significant (P > 0.05). Three subjects had rescue therapy in the control group while a single subject was rescued in the study group. A higher rate of eyes achieved vision of 20/16 or better in the study group (82.5%) versus the control group (72.5%) at 3 months.Conclusion: VNS is a favorable dry eye treatment option for patients following PRK, particularly in patients hoping to avoid additional topical medications or punctal occlusion. The higher percentage of eyes with UCDVA of 20/16 or better in the treatment group may suggest optimization of epithelial recovery after PRK.Keywords: dry eye disease, dry eye syndrome, varenicline, neurostimulation, ocular inflammation, ocular pain

Hui-Hui Yang,1,&ast; Jie Dou,1,&ast; Ruo-Ling Guo,1 Jie Gao,1 Hui-Zhe Li,2 Kun Wang,2 Tian-Hua Hou,2 Tie-Jun Wei,2 Jing-Tao Guo,2 Jian-Wei Liu,3 Dong-Lei Luo2 1Chengde Medical University, Chengde, People’s Republic of China; 2Department of Cardiology, Chengde Central Hospital/Second Clinical College of Chengde Medical University, Chengde, People’s Republic of China; 3Department of Cardiothoracic Interventional Vascular Surgery, Chengde Central Hospital/Second Clinical College of Chengde Medical University, Chengde, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Dong-Lei Luo, Department of Cardiology, Chengde Central Hospital/Second Clinical College of Chengde Medical, Chengde, People’s Republic of China, Email dongleiluocn@aliyun.com Jian-Wei Liu, Department of Cardiothoracic Interventional Vascular Surgery, Chengde Central Hospital/Second Clinical College of Chengde Medical University, Chengde, People’s Republic of China, Email Ljw2112@126.comObjective: The study aimed to explore the clinical diagnostic significance of lipoprotein(a) [Lp(a)] and neck circumference (NC) in patients with coronary heart disease (CHD).Methods: This cross-sectional study was conducted at Chengde Central Hospital from September 2021 to June 2023, enrolling 791 patients with suspected CHD who underwent selective coronary angiography (CAG). Patients were categorized into CHD and non-CHD groups based on the severity of arterial narrowing. Subsequently, the diagnostic value of Lp(a) combined with NC in patients with CHD was assessed using receiver operating characteristic (ROC) curves. Based on the results of multivariate logistic regression, a nomogram was constructed, and its clinical applicability was validated using decision curve analysis (DCA) and clinical impact curve (CIC).Results: Multivariate logistic regression proved that high Lp(a) and high NC are risk factors for CHD, with OR of 1.836 (95% CI: 1.282– 2.630) and 1.383 (1.0.978– 1.955), respectively. Patients in the high NC or Lp(a) group exhibited a higher prevalence of multi-vessel disease. The area under the ROC curve (AUC) of the predictive model combining high Lp(a) and high NC was 0.710 (95% CI: 0.670– 0.751) and also demonstrated good calibration (Hosmer-Lemeshow goodness-of-fit test P value=0.494). The DCA and CIC confirmed the clinical utility of the nomogram developed to predict CHD based on the combination of high Lp(a) and high NC.Conclusion: The levels of Lp(a) and NC exhibit a significant correlation with the presence of CHD, and their combined assessment holds specific clinical value in the diagnosis of CHD.Keywords: coronary heart disease, lipoprotein(a), neck circumference, sensitivity, specificity