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BackgroundCOVID-19 is associated with acute risk of major adverse cardiac events (MACE), including myocardial infarction, stroke, and mortality (all-cause). However, the duration and underlying determinants of heightened risk of cardiovascular disease and MACE post-COVID-19 are not known.MethodsData from the UK Biobank was used to identify COVID-19 cases (n=10 005) who were positive for polymerase chain reaction (PCR+)-based tests for SARS-CoV-2 infection (n=8062) or received hospital-based International Classification of Diseases version-10 (ICD-10) codes for COVID-19 (n=1943) between February 1, 2020 and December 31, 2020. Population controls (n=217 730) and propensity score-matched controls (n=38 860) were also drawn from the UK Biobank during the same period. Proportional hazard models were used to evaluate COVID-19 for association with long-term (>1000 days) risk of MACE and as a coronary artery disease risk equivalent. Additional analyses examined whether COVID-19 interacted with genetic determinants to affect the risk of MACE and its components.ResultsThe risk of MACE was elevated in COVID-19 cases at all levels of severity (HR, 2.09 [95% CI, 1.94-2.25]; P

Terrestrial production and export of dissolved organic and inorganic carbon (DOC and DIC) to streams depends on water flow and biogeochemical processes in and beneath soils. Yet, understanding of these processes in a rapidly changing climate is limited. Using the watershed-scale reactive-transport model BioRT-HBV and stream data from a snow-dominated catchment in the Rockies, we show deeper groundwater flow averaged about 20% of annual discharge, rising to ∼35% in drier years. DOC and DIC production and export peaked during snowmelt and wet years, driven more by hydrology than temperature. DOC was primarily produced in shallow soils (1.94 ± 1.45 gC/m2/year), stored via sorption, and flushed out during snowmelt. Some DOC was recharged to and further consumed in the deeper subsurface via respiration (−0.27 ± 0.02 gC/m2/year), therefore reducing concentrations in deeper groundwater and stream DOC concentrations at low discharge. Consequently, DOC was primarily exported from the shallow zone (1.62 ± 0.96 gC/m2/year, compared to 0.12 ± 0.02 gC/m2/year from the deeper zone). DIC was produced in both zones but at higher rates in shallow soils (1.34 ± 1.00 gC/m2/year) than in the deep subsurface (0.36 ± 0.02 gC/m2/year). Deep respiration elevated DIC concentrations in the deep zone and stream DIC concentrations at low discharge. In other words, deep respiration is responsible for the commonly-observed increasing DOC concentrations (flushing) and decreasing DIC concentrations (dilution) with increasing discharge. DIC export from the shallow zone was ~66% of annual export but can drop to ∼53% in drier years. Numerical experiments suggest lower carbon production and export in a warmer, drier future, and a higher proportion from deeper flow and respiration processes. These results underscore the often-overlooked but growing importance of deeper processes in a warming climate.

Climate change-induced shifts in snow storage and snowmelt patterns pose risks for adverse impacts to people, the environment, and irrigated agriculture. Existing research primarily focuses on evaluating these risks to irrigated agriculture at large scales, overlooking the role of local context in shaping risk dynamics. Consequently, many “at-risk” areas lack insight into how adaptation strategies for managing risk through water supply augmentation or water conservation vary across contexts and over time. To address this gap, we develop a comprehensive index for evaluating irrigated agriculture's risk and adaptation potential to changes in snow at local scales and apply it throughout the western US. Results confirm trends toward escalating risk for changes in snow storage and snowmelt patterns over the century. However, substantial heterogeneity in the extent and drivers of risk exists due to variability in localized interactions between declines in water supply (approximately −9% ± 13% by 2100) and increased agricultural demand (approximately 7% ± 5% by 2100). Despite an existing focus on supply augmentation as a critical adaptation strategy to reduce risk, we show its effectiveness diminishes for many areas over time, declining to an average of −54% of historical augmentation potential by 2100. Conserving water through historical changes in crop acreage and type emerges as a more stable adaptation measure, reducing demand by 7%–8% regardless of time. While particularly relevant for higher elevation, less intensive agricultural settings in snowmelt-dependent regions, findings underscore the need for strategies that support local-scale, context-appropriate adaptation to effectively manage escalating risk as snow changes.

Geologic features (e.g., fractures and alluvial fans) can play an important role in the locations and volumes of groundwater discharge and degree of groundwater-surface water (GW-SW) interactions. However, the role of these features in controlling GW-SW dynamics and streamflow generation processes are not well constrained. GW-SW interactions and streamflow generation processes are further complicated by variability in precipitation inputs from summer and fall monsoon rains, as well as declines in snowpack and changing melt dynamics driven by warming temperatures. Using high spatial and temporal resolution radon and water stable isotope sampling and a 1D groundwater flux model, we evaluated how groundwater contributions and GW-SW interactions varied along a stream reach impacted by fractures (fractured-zone) and downstream of the fractured hillslope (non-fractured zone) in Coal Creek, a Colorado River headwater stream affected by summer monsoons. During early summer, groundwater contributions from the fractured zone were high, but declined throughout the summer. Groundwater contributions from the non-fractured zone were constant throughout the summer and became proportionally more important later in the summer. We hypothesize that groundwater in the non-fractured zone is dominantly sourced from a high-storage alluvial fan at the base of a tributary that is connected to Coal Creek throughout the summer and provides consistent groundwater influx. Water isotope data revealed that Coal Creek responds quickly to incoming precipitation early in the summer, and summer precipitation becomes more important for streamflow generation later in the summer. We quantified the change in catchment dynamic storage and found it negatively related to stream water isotope values, and positively related to modeled groundwater discharge and the ratio of fractured zone to non-fractured zone groundwater. We interpret these relationships as declining hydrologic connectivity throughout the summer leading to late summer streamflow supported predominantly by shallow flow paths, with variable response to drying from geologic features based on their storage. As groundwater becomes more important for sustaining summer flows, quantifying local geologic controls on groundwater inputs and their response to variable moisture conditions may become critical for accurate predictions of streamflow.

Understanding connectivity between the soil and deeper bedrock groundwater is needed to accurately predict a watershed's response to perturbation, such as drought. Yet, the bedrock groundwater dynamics in mountainous environments are typically under-constrained and excluded from watershed hydrologic models. Here, we investigate the role of groundwater characterized with decadal and longer water ages on the hydrologic and mass-transport processes within a steep snow-dominated mountain hillslope in the Central Rocky Mountains (USA). We quantify subsurface and surface water mass-balance, groundwater flowpaths, and age distributions using the ParFlow-CLM integrated hydrologic and EcoSLIM particle tracking models, which are compared to hydrometric and environmental tracer observations. An ensemble of models with varied soil and hydrogeologic parameters reproduces observed groundwater levels and century-scale mean ages inferred from environmental tracers. The numerical models suggest soil water near the toe of the hillslope contains considerable (>60 % of the mass-flux) contributions from bedrock flowpaths characterized with water ages >10 years. Flowpath connectivity between the deeper bedrock and soil systems is present throughout the year, highlighting the potentially critical role of groundwater with old ages on processes such as evapotranspiration and streamflow generation. The coupled numerical model and groundwater age observations show the bedrock groundwater system influences the hillslope hydrodynamics and should be considered in mountain watershed conceptual and numerical models.

We report the first measurement of discrimination between low-energy helium recoils and electron recoils in liquid xenon. This result is relevant to proposed low-mass dark matter searches which seek to dissolve light target nuclei in the active volume of liquid-xenon time projection chambers. Low-energy helium recoils were produced by degrading α particles from ^{210}Po with a gold foil situated on the cathode of a liquid xenon time-projection chamber. The resulting population of helium recoil events is well separated from electron recoils and is also offset from the expected position of xenon nuclear recoil events.

The ability to discern the content of the view through a window is referred to as view clarity. It is often overlooked in the design process, and the methods of shading daylight can affect window views. We conducted a narrative review of building standards and the scientific literature to better understand how shades can be designed so as to retain the window view. View clarity was characterised by three main dimensions: (1) the shading solution, (2) the view content and (3) the observer. Each dimension and the interactions between them influence view clarity. These interactions make it difficult to predict view clarity for all the situations that can occur in buildings. Nonetheless, we highlighted the effects of different shades on the view clarity. Our insights can help designers consider these impacts within the context of overall window design.

The path of tokamak fusion and International thermonuclear experimental reactor (ITER) is maintaining high-performance plasma to produce sufficient fusion power. This effort is hindered by the transient energy burst arising from the instabilities at the boundary of plasmas. Conventional 3D magnetic perturbations used to suppress these instabilities often degrade fusion performance and increase the risk of other instabilities. This study presents an innovative 3D field optimization approach that leverages machine learning and real-time adaptability to overcome these challenges. Implemented in the DIII-D and KSTAR tokamaks, this method has consistently achieved reactor-relevant core confinement and the highest fusion performance without triggering damaging bursts. This is enabled by advances in the physics understanding of self-organized transport in the plasma edge and machine learning techniques to optimize the 3D field spectrum. The success of automated, real-time adaptive control of such complex systems paves the way for maximizing fusion efficiency in ITER and beyond while minimizing damage to device components.

In this study, we develop a machine-learning (ML)-enabled strategy for selecting hillslope-scale ecohydrological monitoring sites within snow-dominated mountainous watersheds, with a particular focus on snow-soil–plant interactions. Data layers rely on spatial data layers from both remote sensing and hydrological model simulations. Specifically, a Landsat-based foresummer drought sensitivity index is used to define the dependency of the annual peak plant productivity on the Palmer drought severity index in the early growing season. Hydrological simulations provide the spatiotemporal dynamics of near-surface soil moisture and snow depth. In this framework, a regression analysis identifies the key hydrological variables relevant to the spatial heterogeneity of drought sensitivity. We then apply unsupervised clustering to these key variables, using the Gaussian mixture model, to group hillslopes into several zones that have divergent relationships regarding soil moisture, snow dynamics, and drought sensitivity. Using the datasets collected in the East River Watershed (Crested Butte, Colorado, United States), results show that drought sensitivity is significantly correlated with model-derived soil moisture and snow-free timing over space and time. The relationship is, however, non-linear, such that the correlation decreases above a threshold elevation and in a heavy snow year due to large snowpacks, lateral flow, and soil storage limitations. Clustering is then able to define the zones that have high or low sensitivity to drought, as well as the mid-elevation regions where sensitivity is associated with the topographic aspect and net potential radiation. In addition, the algorithm identifies the most representative hillslopes with road/trail access within each zone for installing monitoring sites. Our method also aims to significantly increase the use of ML and model-simulation results to guide critical zone and watershed monitoring activities.

About 80 % of the precipitation at the Colorado River s headwaters is snow, and the resulting snowmeltdriven hydrograph is a crucial water source for about 40 million people. Snowmelt from alpine and subalpine snowpack contributes substantially to groundwater recharge and river flow. However, the dynamics of snowmelt progression are not well understood because observations of the highelevation snowpack are difficult due to challenging access in complex mountainous terrain as well as the cost and labor intensity of currently available methods. We present a novel approach to infer the processes and dynamics of highelevation snowmelt contributions predicated upon stable hydrogen and oxygen isotope ratios observed in streamflow. We show that deuterium-excess (d-excess) values of stream water could serve as a comparatively cost-effective proxy for a catchment-integrated signal of high-elevation snowmelt contributions to catchment runoff. We sampled stable hydrogen and oxygen isotope ratios of the precipitation, snowpack, and stream water in the East River, a headwater catchment of the Colorado River, and the stream water of larger catchments at sites on the Gunnison River and Colorado River. The d-excess of snowpack increased with elevation; the upper subalpine and alpine snowpack (> 3200 m) had substantially higher d-excess compared to lower elevations (< 3200 m) in the study area. The d-excess values of stream water reflected this because d-excess values increased as the higher-elevation snowpack contributed more to stream water generation later in the snowmelt/runoff season. End-member mixing analyses based on the d-excess data showed that the share of high-elevation snowmelt contributions within the snowmelt hydrograph was on average 44 % and generally increased during melt period progression, up to 70 %. The observed pattern was consistent during 6 years for the East River, and a similar relation was found for the larger catchments on the Gunnison and Colorado rivers. High-elevation snowpack contributions were found to be higher for years with lower snowpack and warmer spring temperatures. Thus, we conclude that the d-excess of stream water is a viable proxy to observe changes in high-elevation snowmelt contributions in catchments at various scales. Inter-catchment comparisons and temporal trends of the d-excess of stream water could therefore serve as a catchment-integrated measure to monitor if mountain systems rely on high-elevation water inputs more during snow drought compared to years of average snowpack depths.

Whereas traditional histology and light microscopy require multiple steps of formalin fixation, paraffin embedding, and sectioning to generate images for pathologic diagnosis, Microscopy using Ultraviolet Surface Excitation (MUSE) operates through UV excitation on the cut surface of tissue, generating images of high resolution without the need to fix or section tissue and allowing for potential use for downstream molecular tests. Here, we present the first study of the use and suitability of MUSE microscopy for neuropathological samples. MUSE images were generated from surgical biopsy samples of primary and metastatic brain tumor biopsy samples (n = 27), and blinded assessments of diagnoses, tumor grades, and cellular features were compared to corresponding hematoxylin and eosin (H&E) images. A set of MUSE-treated samples subsequently underwent exome and targeted sequencing, and quality metrics were compared to those from fresh frozen specimens. Diagnostic accuracy was relatively high, and DNA and RNA integrity appeared to be preserved for this cohort. This suggests that MUSE may be a reliable method of generating high-quality diagnostic-grade histologic images for neuropathology on a rapid and sample-sparing basis and for subsequent molecular analysis of DNA and RNA.

Objective: A national survey was conducted to determine the extent of use of compounded hormone therapy(C-HT) and to characterize the differences between C-HT users and users of hormone therapy approved by the USFood and Drug Administration (FDA-HT users).Methods: This Internet survey enrolled 3,725 women aged 40 to 84 years who were postmenopausal orexperiencing the menopause transition. The sample was weighted slightly by age, region, education, and race toreflect population attributes based on US Census data.Results: Overall, 9% of women were current users of HT, and 28% of all respondents were ever-users of HT.C-HT users represented 31% of ever-users of HT, 35% of current users of HT, and 41% of ever-users aged 40 to 49years. Approximately 13% of ever-users indicated current or past use of testosterone. The most cited reason forusing HT was vasomotor symptoms ( 70%). Nonapproved indications for using HT were selected more often byC-HT users. There were four reports of endometrial cancer among the 326 C-HT users compared with none reportedamong the 738 FDA-HT users. Significance was not determined because of small numbers.Conclusions: This survey indicates substantial use of C-HT across the country and the possibility of higher ratesof endometrial side effects with such products. There is a need for standardized data collection on the extent of use ofcompounded hormones and their potential risks.

Lai-Xi Zhao,1,&ast; Qiong Sun,2,&ast; Chong Wang,3,&ast; Jia-Jia Liu,1 Xiao-Rong Yan,1 Meng-Ci Shao,1 Li Yu,3 Wen-Hua Xu,1 Rui Xu1 1College & Hospital of Stomatology, Anhui Medical University, Key Laboratory of Oral Diseases Research of Anhui Province, Hefei, 230032, People’s Republic of China; 2Department of Stomatology, Anhui Province Direct Subordinate Hospital, Hefei, 230601, People’s Republic of China; 3Department of Microbiology and Parasitology, School of Basic Medical Sciences, Anhui Medical University, Anhui Province Key Laboratory of Zoonoses, The Provincial Key Laboratory of Zoonoses of High Institutions in Anhui, Hefei, Anhui Province, 230032, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wen-Hua Xu; Rui Xu, Email xuwenhua@ahmu.edu.cn; dentistxr@126.comAbstract: Immunotherapies such as immune checkpoint blockade (ICB) therapy and chimeric antigen receptor T-cell (CAR-T) therapy have ushered in a new era of tumor treatment. However, most patients do not benefit from immunotherapy due to limitations such as narrow indications, low response rates, and high rates of adverse effects. Toxoplasma gondii (T. gondii), a specialized intracellular protozoan, can modulate host immune responses by inhibiting or stimulating cytokines. The ability of T. gondii to enhance an organism’s immune response was found to have a direct anti-tumor effect and enhance the sensitivity of patients with tumors to ICB therapy. However, the application of T. gondii for tumor therapy faces several challenges, such as biosafety concerns. Exosomes, a subtype of extracellular vesicle that contains active components such as proteins, nucleic acids, and lipids, have become effective therapeutic tools for various diseases, including tumors. Parasites, such as T. gondii, mediate the communication of pathogens with immune cells and modulate host cellular immune responses through exosomes. Growing evidence indicates that T. gondii-derived exosomes mediate communication between pathogens and immune cells, modulate host immune responses, and have great potential as new tools for tumor therapy. In this review, we highlight recent advances in isolation and identification techniques, profiling analysis, host immunomodulatory mechanisms, and the role of T. gondii-derived exosomes in tumor immunotherapy. Additionally, we emphasize the potential of T. gondii-derived exosomes as delivery platform to enhance anti-tumor efficacy in combination with other therapies. This review proposes that T. gondii-derived exosomes may serve as a novel tool for tumor immunotherapy owing to their ability to activate host immune function and properties such as high modifiability, stability, and low toxicity. This work will assist in promoting the application of parasite exosomes in tumor therapy. Keywords: Toxoplasma gondii, exosomes, tumor, immune regulation, immunotherapy

Xiao Wang,1,&ast; Ying Cao,2,&ast; Jing Hu,3 Lian-Cheng Jia,4 Bo Li,3 Baoli Liu,5 Wei-Hai Yao,2 Xiao-Lu Pei,6 Wei Peng,2 Shuang Wang,2 Cun-Zhi Liu,1,7 Jian-Feng Tu,1,7 Zhi-Cheng Qu2 1School of Acupuncture-Moxibustion and Tuina, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 2Emergency Department, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, People’s Republic of China; 3Evidence Based Medicine Center, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, People’s Republic of China; 4Urinary Surgery, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, People’s Republic of China; 5Nephrology Department, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, People’s Republic of China; 6Nursing Department, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, People’s Republic of China; 7International Acupuncture and Moxibustion Innovation Institute, Beijing University of Chinese Medicine, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhi-Cheng Qu, Emergency Department, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, 23 Meishuguanhou Street, Dongcheng District, Beijing, 100010, People’s Republic of China, Email qzhch0824@163.com Jian-Feng Tu, School of Acupuncture-Moxibustion and Tuina, Beijing University of Chinese Medicine, No. 11, Bei San Huan Dong Lu, Chaoyang District, Beijing, 100029, People’s Republic of China, Email tujianfeng1@126.comIntroduction: Analgesia is often delayed for suspected acute renal colic due to urinary calculi (ARCUC) even in emergency department. Acupuncture has a rapid onset and is effective for analgesia, however, evidence about early-acupuncture for suspected ARCUC is limited. This trial aims to evaluate the efficacy of early-intervention acupuncture compared with sham acupuncture on pain relief among emergency department suspected ARCUC patients.Methods and Analysis: A total of 84 eligible patients who are suspected diagnosed with ARCUC will be randomly allocated to the acupuncture group or the sham acupuncture group. Each patient will receive 1 session of acupuncture or sham acupuncture before diagnostic imaging. The primary outcome will be the response rate at 10 min after needle manipulation, defined as the proportion of patients whose Numeric Rating Scale (NRS) score decrease by at least 50% from baseline. Secondary outcomes will include pain intensity assessed by NRS, further analgesia requirement, revisit rate, surgical intervention rate, satisfaction evaluation, and adverse events. The final diagnosis rate determined by radiography will be recorded and reported. All patients who receive randomization will be included in the intention-to-treat analysis.Conclusion: This study’s findings are anticipated to evaluate the analgesic effect of early-intervention acupuncture for acute renal colic in emergency department, which could be useful for moving the timing of analgesia forward and aligning pain management for acute renal colic more with the guidelines.Trial Registration Number: ChiCTR2100049069 (https://www.chictr.org.cn/showproj.html?proj=125338).Keywords: acupuncture, complementary medicine, pain management, emergency medicine, renal colic

Wafaa H Hussein,1 Hala Ramadan,2 Safa Labib,2 Gehan A Hegazy,3,4 Olfat G Shaker,5 Sherif M Yusuf,6 Mohammed A Hassanien,7 Maysa M Haroon1 1Rheumatology Department, Faculty of Medicine, Cairo University, Cairo, Egypt; 2Internal Medicine Department, Faculty of Medicine, Cairo University, Cairo, Egypt; 3Clinical Biochemistry Department, Faculty of Medicine, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia; 4Medical Division Department, National Research Centre, Giza, Egypt; 5Medical Biochemistry and Molecular Biology Department, Faculty of Medicine, Cairo University, Cairo, Egypt; 6Internal Medicine Department, Medical Research Institute, Alexandria University, Alexandria, Egypt; 7Pharmacy Practice Department, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Kingdom of Saudi ArabiaCorrespondence: Maysa M Haroon, Rheumatology Department, Faculty of Medicine, Cairo University, 71 El Kasr El Aini Street, P.O. Box 11562, Cairo, Egypt, Tel +201025868370, Email maysaharoon@yahoo.comBackground: Long noncoding ribonucleic acids (lncRNAs), small noncoding RNAs known as microRNAs (miRNAs) as well as some cytokines are recently thought to have a role in many inflammatory and autoimmune disorders including Behçet’s disease (BD). This chronic multisystem disease lacks the particular histological or laboratory findings that might aid in its diagnosis. Therefore, any association with such molecules may have an impact on understanding the disease pathogenesis and/or management. The current study compared the levels of NEAT1, miR-21 and IL17 levels in sera of Egyptian BD patients and healthy individuals. The expression levels of these molecules were further investigated for their association with BD manifestations and activity aiming to explore their potential application in disease management.Results: NEAT1 & miR-21 showed down-regulation while IL-17 showed up-regulation among BD patients as compared to controls. IL-17 had significant correlation with major vessels involvement and cyclophosphamide intake. NEAT1 showed a significant negative correlation with colchicine intake. Disease activity did not correlate significantly with any of NEAT1, miR-21 or IL-17.Conclusion: NEAT1, miR-21 and IL17 might have a role in Behçet’s disease pathogenesis, so more research is needed to unveil that role and their potential usage as biomarkers for the diagnosis or therapeutic targets.Keywords: long noncoding ribonucleic acids, microRNAs, NEAT1, miR-21, IL-17, Behçet’s disease

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

Menyfah Q Alanazi,1– 3,&ast; Eyad K Alkhadhairi,3 Waleed H Alrumi,4 Sami A Alajlan3,&ast; 1Drug Policy and Economics Center, King Abdulaziz Medical City, Ministry of National Guard-Health Affairs, Riyadh, Saudi Arabia; 2King Abdullah International Medical Research Center, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia; 3Logistics and Contracts Management, King Abdulaziz Medical City, Ministry of National Guard - Health Affairs, Riyadh, Saudi Arabia; 4Expenditure Efficiency and Projects Authority, Riyadh, Saudi Arabia&ast;These authors contributed equally to this workCorrespondence: Menyfah Q Alanazi, Drug Policy and Economics Center, King Abdulaziz Medical City, Ministry of National Guard-Health Affairs, Riyadh, 11426, Saudi Arabia, Tel +966118011111, Email menefah@gmail.comAim: To evaluate the prevalence and trend of inventory waste in a tertiary hospital over the last 7 years. This included the type and average monetary value (MV) of inventory waste, as well as the outcome of using the Always-Better-Control (ABC)-Vital-Essential-Non-essential (VEN) matrix as part of a Zero-Waste Strategy.Methods: This was a retrospective observational study conducted at King Abdulaziz Medical City (KAMC) over 7 years.Results: The prevalence of waste was 0.21%, which equates to (SAR) 15 million out of SAR 7 billion. The pharmaceutical inventory had significantly higher waste in terms of MV and the number of items (89.8%, and 80.3%, respectively) (P< 0.001). The expired pharmaceutical inventory had a significantly higher waste of MV than non-moving and obsolete inventory (79.8%, 14.3%, and 5.9%, respectively) (P< 0.001). The ABC-VEN matrix categorized the inventory into Category I, which has the highest MV waste at 82.3%, followed by Category II with 16.8%, and then Category III with 0.9%. However, category II had a significantly higher number of wasted items at (58.2%), followed by Category I (24%) and Category III (17.8%) (P< 0.01). The majority of MV waste consisted of a small number of pharmaceutical items that had a high clinical impact, representing 66% and 18%, respectively. After implementing a zero-waste strategy for landfills using the ABC-VEN matrix, the prevalence of waste declined from 0.9% to 0.21%. The waste sent to the landfill was zero from 2018 through 2020, saving 73.64% of the total money.Conclusion: The use of the ABC-VEN matrix positively impacted the reduction of MV waste. The prevalence and trend rate of inventory waste were lower than the benchmarks of global companies, saving more than two-thirds of the inventory value that would have been wasted. The majority of the wasted MV consisted of a small number of pharmaceutical items that had a significant clinical impact.Keywords: expired pharmaceutical inventory, non-moving inventory, obsolete inventory, Saudi Arabia, prevalance of inventory waste, employee engagement, rate of inventory waste

Li-Yu Chen,1 Chen-Yu Wang,1,2 Chi-Ying Lin,3 Ming-Jui Tsai,3 Wei-Hsun Shen,1 Pei-Jhih Li,1 Lin-Chu Liao,1 Chih-Fen Huang,4,5 Chien-Chih Wu4 1Department of Pharmacy, National Taiwan University Hospital Yunlin Branch, Yunlin, Taiwan; 2National Center for Geriatrics and Welfare Research, National Health Research Institutes, Yunlin, Taiwan; 3Department of Internal Medicine, National Taiwan University Hospital Yunlin Branch, Yunlin, Taiwan; 4Department of Pharmacy, National Taiwan University Hospital, Taipei, Taiwan; 5School of Pharmacy, College of Medicine, National Taiwan University, Taipei, TaiwanCorrespondence: Chien-Chih Wu, Department of Pharmacy, National Taiwan University Hospital, 7 Chung Shan S. Road, Taipei, Taiwan, Email 101440@ntuh.gov.tw; r93451011@gmail.comBackground: In the field of postoperative care, infections caused by Gram-positive bacteria pose a major clinical challenge. Vancomycin is a key therapeutic agent whose efficacy is greatly influenced by renal function, particularly by augmented renal clearance (ARC). The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) estimated glomerular filtration rate (eGFR) is an easy and commonly used method to predict ARC; however, it is not well studied to determine vancomycin dose. In this study, we examined the effectiveness of the CKD-EPI equation in determining ARC and optimizing the dose of vancomycin for surgical ward patients.Methodology: A retrospective observational study was conducted to examine 158 surgical ward patients receiving vancomycin. Data on demographics, medical history, and vancomycin dosing were collected. Renal function was evaluated using the CKD-EPI equation, with ARC defined as eGFR ≥ 96.5 mL/min/1.73 m2. Vancomycin pharmacokinetics were calculated using the ClinCalc tool.Results: ARC was in 54% of the patients. Compared with patients without ARC, those with ARC were younger and had lower serum creatinine levels. They also required higher vancomycin doses but had lower trough concentrations and 24-hour area-under-the-curve values. A significant correlation was observed between eGFR and vancomycin clearance, with eGFR > 96.5 mL/min/1.73 m2 necessitating higher vancomycin doses (> 45 mg/kg/day) to achieve the desired area under the curve to minimum inhibitory concentration ratio.Conclusion: For surgical ward patients with CKD-EPI eGFR ≥ 96.5 mL/min/1.73 m2, a vancomycin dosage of > 45 mg/kg/day may be recommended to reach effective therapeutic levels. Overall, this study emphasizes the importance of tailoring vancomycin therapy depending on renal function to ensure efficacy and mitigate the risk of antimicrobial resistance in surgical ward patients.Keywords: augmented renal clearance, vancomycin, surgery

Abdulmajeed Saeed Alshahrani,1 Ahmed Ali Alelyani,1 Sadun Mohammad Al Ageel Albeaji,2 Dalia AlHarith,3 Ahmed Abdullah A Al Malwi,4 Abdulrahman Abdullah Aldhbaan,5 Khaled Saleh J Alshehri,6 Alwaleed Essam Bakri,7 Abdullah Ahmed Ali Sahli,8 Wafa Hassan Alaajam,9,10 Mohammed M Al Moaleem11 1Department of Restorative Dentistry, Division of Endodontics, College of Dentistry, Najran University, Najran, Saudi Arabia; 2Consultant Endodontics, Dental Center, Hafar al Batin, Ministry of Health, Hafar al Batin, Saudi Arabia; 3Department of Restorative Dentistry, Riyadh Elm University, Riyadh, Saudi Arabia; 4Department of Restorative Dentistry, Division of Endodontics, College of Dentistry, King Khalid University, Abha, Saudi Arabia; 5Consultant of Endodontic, Endodontic Department, Aseer Specialized Dental Center, Ministry of Health, Abha, Saudi Arabia; 6Consultant of Endodontic, Endodontic Department, Khamis Mushait Dental Center, Ministry of Health, Aseer, Saudi Arabia; 7General Practitioner, Specialized Dental Center, Ministry of Health, Jazan, Saudi Arabia; 8General Practitioner, Al-Kharish Primary Health Care Center, Ministry of Health, Jazan, Saudi Arabia; 9Department of Restorative Dental Science, Division of Endodontics, College of Dentistry, King Khalid University, Abha, Saudi Arabia; 10Department of Conservative Dentistry, Faculty of Dentistry, Sana’a University, Sana’a, Yemen; 11Department of Prosthetic Dental Science, College of Dentistry, Jazan University, Jazan, 45142, Saudi ArabiaCorrespondence: Ahmed Ali Alelyani, Department of Restorative Dentistry, Division of Endodontics, College of Dentistry, Najran University, Najran, Saudi Arabia, Email aaalelyani1@gmail.com Mohammed M Al Moaleem, Department of Prosthetic Dental Science, College of Dentistry, Jazan University, Jazan, 45142, Saudi Arabia, Email malmoaleem@jazanu.edu.saAim: Root canal treatment (RCT) is a common procedure practiced daily by dentists worldwide. The current systematic review aimed to evaluate and compare clinical studies on the quality of root canal fillings (RCFs) carried out by dentists with different levels of experience conducted worldwide with those conducted specifically in Saudi Arabia (SA).Materials and Methods: A full literature search was conducted in Clarivate Analytics’ Web of Science, Elsevier’s Scopus, Embase, CINHAL, and PubMed, without a restriction to studies published before January 2015. Also, a manual search was carried out by checking papers that may have been missed during the electronic search. The following keywords were used: [(quality of root canal filling(s)) OR (quality of root canal obturation)) and dental practitioners as (general dental practitioners; final year students; endodontist; specialist) AND (root canal obturation) OR (endodontic treatment)]. Parameters of the quality of RCFs, such as length, density, and taper, were assessed and counted.Results: A total of 13 worldwide and nine SA studies were included in this review, published between 2015 and 2023. Molars were the most treated teeth, at 42.3% and 40.2% for the worldwide and SA studies, respectively. Cases treated by final year students had the highest percentage, at 60.0% for both study groups. The percentages of acceptable quality, with regard to the length, density, and taper of RCFs, were 70.9%, 77.6%, and 84.3%, and 73.2%, 64.6%, and 67.8% for the worldwide and SA studies, respectively.Conclusion: The overall acceptable quality of RCFs was marginally higher in worldwide studies than in SA studies. Both prevalences can be considered as good, which indicates that the quality of RCFs is moving in the right direction.Keywords: root canal filling, quality, obturation, Saudi Arabia, clinical studies, procedural errors

Maturation schedules shape the age structure of a population and influence productivity and exposure to fishing. Fish cultivated and raised in artificial environments such as hatcheries may mature at different ages compared to their natural-origin counterparts. We evaluated whether endangered Sacramento River winter-run Chinook salmon Oncorhynchus tshawytscha produced in a conservation hatchery had different maturation schedules compared to naturalorigin fish, and how any differences affected their exposure to, and impact from, the ocean salmon fishery. Using coded-wire tags collected from hatchery fish in the ocean and in-river fisheries and on the spawning grounds, and scales collected from natural-origin spawner carcasses, we reconstructed the life history of hatchery and natural-origin cohorts from 2002-2015 brood years. Hatchery fish had similar age-2 maturation rates but higher age-3 maturation rates compared to natural-origin fish, resulting in fewer age-4 individuals and an overall more truncated age structure. Because natural-origin winter-run Chinook salmon were more likely to remain at sea until age 4, they were exposed to fishing for an additional year and experienced greater reduction in escapement. Compared to natural-origin males, hatchery-origin males were much less likely to return at an older age, possibly because sexual selection that is occurring on the spawning grounds is not occurring to the same extent in the hatchery. Identifying how reproductive maturation differs across sources, sex, and life histories is critical to understanding how fisheries can disproportionately impact subsets of a population and affect its long-term population dynamics and sustainability.

The LUX-ZEPLIN (LZ) experiment is a dark matter detector centered on a dual-phase xenon time projection chamber. We report searches for new physics appearing through few-keV-scale electron recoils, using the experiment's first exposure of 60 live days and a fiducial mass of 5.5 t. The data are found to be consistent with a background-only hypothesis, and limits are set on models for new physics including solar axion electron coupling, solar neutrino magnetic moment and millicharge, and electron couplings to galactic axionlike particles and hidden photons. Similar limits are set on weakly interacting massive particle (WIMP) dark matter producing signals through ionized atomic states from the Migdal effect.

Sami Abdulsalam Ali Hasan,1 Ibrahim Zaid Al-Shami,1 Mohsen Ali Al-Hamzi,1 Ghadeer Saleh Alwadai,2 Nada Ahmad Alamoudi,2 Saleh Ali Alqahtani,2 Arwa Daghrery,3 Wafa H Alaajam,4,5 Mansoor Shariff,6 Hussain Mohammed Kinani,7 Mohammed M Al Moaleem8 1Department of Conservative Dentistry, Faculty of Dentistry, Sana’a University, Sanaa, Yemen; 2Department: Restorative Dental Science, College of Dentistry, King Khalid University, Abha, Saudi Arabia; 3Department of Restorative Dental Sciences, College of Dentistry, Jazan University, Jazan, 45142, Saudi Arabia; 4Department of Restorative Dental Science, College of Dentistry, King Khalid University, Abha, Saudi Arabia; 5Department of Restorative Dentistry, Faculty of Dentistry, Sana’a University, Sana’a, Yemen; 6Prosthetic Department, College of Dentistry, King Khalid University, Abha, 62529, Saudi Arabia; 7Ministry of Health, Sabya General Hospital, Department of Dentistry, Jazan, Saudi Arabia; 8Department of Prosthetic Dental Science, College of Dentistry, Jazan University, Jazan, 45142, Saudi ArabiaCorrespondence: Mohammed M Al Moaleem, Department of Prosthetic Dental Science, College of Dentistry, Jazan University, Jazan, 45142, Saudi Arabia, Email malmoaleem@jazanu.edu.saBackground: To evaluate the radiant power of the light cure units (LCUs) in relation to their type, radiant exitance, number of years in clinical use, and condition of LCUs tips in governmental and public clinics in Dental Faculties in Sana’a City.Materials and Methods: LCUs were collected from different colleges at Sanaa City, Yemen, then LCU data as type, clinical age (< 1 year, between 1– 5 and ˃ 5-years), tip condition was visually inspected for damage and adhering debris, and the radiant exitance values of the tested LCUs. Radiant exitance values were subcategorized into three groups: < 400, 400– 850, and > 850 mW/cm², labeled as inadequate, marginal, and adequate radiant exitances, respectively. A Woodpecker radiometer was used with a mode lasting of 20 seconds was used with each LCU. Descriptive statistics of the different parameters were evaluated with SPSS version 25. One-way ANOVA and Mann–Whitney tests were performed to determine the mean difference between the groups with a significance value of ˂ 0.05 was considered.Results: Two hundred twenty-three LCUs were surveyed, and the majority were Light–emitting diode (LED). Forty-nine (21.9%), 117 (52.4%), 57 (25.6%) recorded lesser than, 400– 850, and more than 850 mW/cm², respectively. Radiant exitances of < year-old units were found to be higher than those of units used for ˃ 5 years with significant differences (p=0.001). The ANOVA test showed significant differences between the radiant exitance with clinical age and LCU tip conditions and a strong correlation p ˃ 0.050.Conclusion: LED curing lights were the most used in the tested Dental Faculties. More than half of the used LCU offered sufficient radiant exitance. Clinical age, the presence or absence of composite buildups, and damage to curing tips showed significantly affect radiant exitance values.Keywords: dental light cure, radiant exitance, contaminated tip, radiometer

Yu-Kai Li,1,&ast; Song Wu,2,&ast; Yu-Shan Wu,3,&ast; Wei-Hu Zhang,4,&ast; Yan Wang,5,&ast; Yue-Hua Li,1,&ast; Qiang Kang,1,&ast; Song-Quan Huang,1,&ast; Kai Zheng,1 Gai-Ming Jiang,1 Qing-Bo Wang,1 Yu-Bo Liang,1 Jin Li,1 Yawhan Lakang,1 Chen Yang,1 Jing Li,1 Jia-Ping Wang,4 Xiang Kui,5 Yang Ke1,6,7 1Department of Hepato-Biliary-Pancreatic, the Second Affiliated Hospital, Kunming Medical University, Kunming, YN, 650101, People’s Republic of China; 2Preventive Medicine Division, School of Life Science, Anhui University of Chinese Medicine, Hefei, AH, 230012, People’s Republic of China; 3The Second Clinical Medical College, Kunming Medical University, Kunming, YN, 650101, People’s Republic of China; 4Department of Radiology, the Second Affiliated Hospital, Kunming Medical University, Kunming, YN, 650101, People’s Republic of China; 5Department of Pathology, the Second Affiliated Hospital, Kunming Medical University, Kunming, YN, 650101, People’s Republic of China; 6Department of Surgical Education and Research, the Second Affiliated Hospital, Kunming Medical University, Kunming, YN, 650101, People’s Republic of China; 7Yunnan Yunke Bio-Technology Institution, Kunming, YN, 650201, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiang Kui, Department of Pathology, the Second Affiliated Hospital, Kunming Medical University, No. 374 Kunrui Road, Wuhua District, Kunming, YN, 650101, People’s Republic of China, Tel +8613708729335, Email kuixiang@foxmail.com Yang Ke, Department of Hepato-Biliary-Pancreatic, the Second Affiliated Hospital, Kunming Medical University, No. 374 Kunrui Road, Wuhua District, Kunming, YN, 650101, People’s Republic of China, Tel +8615808875159, Email keyang1218@126.comBackground: The dominant artery blood supply is a characteristic of hepatocellular carcinoma (HCC). However, it is not known whether the blood supply can predict the post-hepatectomy prognosis of patients with HCC. This retrospective study investigated the prognostic value of the portal venous and arterial blood supply estimated on triphasic liver CT (as a portal venous coefficient, PVC, and hepatic arterial coefficient, HAC, respectively) in patients with HCC following hepatectomy.Methods: HCC patients who were tested by triphasic liver CT 2 weeks before hepatectomy and received R0 hepatectomy at the Second Affiliated Hospital, Kunming Medical University between January 1, 2016 and December 31, 2020, were retrospectively screened. Their PVC and HAC, and other variables were analyzed for the prediction of overall survival (OS) and recurrence-free survival (RFS) using the least absolute shrinkage and selection operator and Cox proportional hazard regression models.Results: Four hundred and nineteen patients (53.2 ± 10.6 years of age and 370 men) were evaluated. A shorter OS was independently associated with higher blood albumin and total bilirubin grade [hazard ratio (HR) 2.020, 95% confidence interval (CI) 1.534– 2.660], higher Barcelona Clinic Liver Cancer (BCLC) stage (HR 1.514, 95% CI 1.290– 1.777), PVC ≤ 0.386 (HR 1.628, 95% CI 1.149– 2.305), and HAC > 0.029 (HR 1.969, 95% CI 1.380– 2.809). A shorter RFS was independently associated with male (HR 1.652, 95% CI 1.005– 2.716), higher serum α-fetoprotein ≥ 400 ng/mL (HR 1.672, 95% CI 1.236– 2.263), higher BCLC stage (HR 1.516, 95% CI 1.300– 1.768), tumor PVC ≤ 0.386 (HR 1.641, 95% CI 1.198– 2.249), and tumor HAC > 0.029 (HR 1.455, 95% CI 1.060– 1.997).Conclusion: Tumor PVC or HAC before hepatectomy is valuable for independently predicting postoperative survival of HCC patients. Keywords: blood supply, computed tomography, hepatectomy, hepatocellular carcinoma, recurrence, survival

Vital pulp therapy (VPT) has been one of the standard treatments for immature teeth and young permanent teeth affected by caries or trauma, aiming to preserve the apical tissue's growth potential and ensure the teeth's long-term retention and functionality. Nowadays, its application in mature teeth has garnered attention from professionals due to promising outcomes in numerous cases. Biomaterials play a crucial role in VPT success, as they facilitate an optimal environment for stem cell growth and promote the formation of thicker dentinal walls. Despite significant advancements in biomaterials, such as the introduction of calcium silicate-based cements (CSCs) in recent decades, knowledge regarding the immunological reactions these materials provoke, both locally and systemically, remains limited, calling for more research. This review intends to provide a summary of biomaterials currently used in VPT, focusing on the immune responses they trigger. This retrospective and informative examination aims to deepen the understanding of the interactions between these materials and the organism, offering insights that could redefine VPT's clinical application scope in the future. It may also aid in developing potential diagnostic biomarkers for assessing pulp vitality and guide the ongoing development of new VPT materials.

Summer streamflow predictions are critical for managing water resources; however, warming-induced shifts from snow to rain regimes impact low-flow predictive models. Additionally, reductions in snowpack drive earlier peak flows and lower summer flows across the western United States increasing reliance on groundwater for maintaining summer streamflow. However, it remains poorly understood how groundwater contributions vary interannually. We quantify recession limb groundwater (RLGW), defined as the proportional groundwater contribution to the stream during the period between peak stream flow and low flow, to predict summer low flows across three diverse western US watersheds. We ask (a) how do snow and rain dynamics influence interannual variations of RLGW contributions and summer low flows?; (b) which watershed attributes impact the effectiveness of RLGW as a predictor of summer low flows? Linear models reveal that RLGW is a strong predictor of low flows across all sites and drastically improves low-flow prediction compared to snow metrics at a rain-dominated site. Results suggest that strength of RLGW control on summer low flows may be mediated by subsurface storage. Subsurface storage can be divided into dynamic (i.e., variability saturated) and deep (i.e., permanently saturated) components, and we hypothesize that interannual variability in dynamic storage contribution to streamflow drives RLGW variability. In systems with a higher proportion of dynamic storage, RLGW is a better predictor of summer low flow because the stream is more responsive to dynamic storage contributions compared to deep-storage-dominated systems. Overall, including RLGW improved low-flow prediction across diverse watersheds.

The LUX-ZEPLIN experiment recently reported limits on WIMP-nucleus interactions from its initial science run, down to 9.2×10-48 cm2 for the spin-independent interaction of a 36 GeV/c2 WIMP at 90% confidence level. In this paper, we present a comprehensive analysis of the backgrounds important for this result and for other upcoming physics analyses, including neutrinoless double-beta decay searches and effective field theory interpretations of LUX-ZEPLIN data. We confirm that the in-situ determinations of bulk and fixed radioactive backgrounds are consistent with expectations from the ex-situ assays. The observed background rate after WIMP search criteria were applied was (6.3±0.5)×10-5 events/keVee/kg/day in the low-energy region, approximately 60 times lower than the equivalent rate reported by the LUX experiment.

Eos is a technology demonstrator, designed to explore the capabilities of hybrid event detection technology, leveraging both Cherenkov and scintillation light simultaneously. With a fiducial mass of four tons, Eos is designed to operate in a high-precision regime, with sufficient size to utilize time-of-flight information for full event reconstruction, flexibility to demonstrate a range of cutting edge technologies, and simplicity of design to facilitate potential future deployment at alternative sites. Results from Eos can inform the design of future neutrino detectors for both fundamental physics and nonproliferation applications. This paper describes the conceptual design and potential applications of the Eos detector.

Introdução: Neoplasias mieloproliferativas BCR::ABL1 negativas são doenças clonais das células-tronco hematopoiéticas, caracterizadas por panmielose, com maturação eficaz. Trombocitemia essencial (TE) e policitemia vera (PV) são as mais frequentes, diferenciadas por parâmetros laboratoriais, clínicos e achados genéticos. JAK2V617F é responsável por 95% dos casos de PV e de 50-60% de TE, ao passo que variantes genéticas em MPL e CARL são encontradas em 3% e 30% dos casos de TE, respectivamente. A predisposição hereditária para neoplasias mieloproliferativas é rara e caracteriza-se por baixa penetrância, a presença de variantes genéticas somáticas e um risco aumentado de progressão para leucemia mieloide aguda. A condição pode ocorrer em dois ou mais membros da mesma família, tornando os casos familiares particularmente notáveis. Este estudo descreve um caso raro de neoplasias mieloproliferativas familiares identificadas entre pacientes atendidos na Fundação Hospitalar de Hematologia e Hemoterapia do Amazonas. Métodos: Análise dos prontuários médicos de pacientes que consentiram em participar da pesquisa entre 2021 e 2022. Foram avaliados dados clínicos, laboratoriais, eventos hemorrágicos e trombóticos. Análise molecular foi realizada para identificação de JAK2V617F, haplótipo 46/1 (rs10974944 C>G), MPL (éxon 10) e CALR (éxon 9). Resultados: foram identificados casos de neoplasia mieloproliferativa em dois membros do mesmo grupo familiar: NMP102, mulher, 86 anos diagnosticada com trombocitemia essencial, sem histórico de esplenomegalia ou eventos trombóticos, mas teve eventos hemorrágicos e história de tratamento com hidroxiureia. Exames citogenéticos revelaram uma deleção 3q; foi identificada uma variante tipo 2 no gene CALR (rs765476509 - c.1154_1155insTTGTC; p.K385fs*47). Seu filho, NMP35, de 60 anos, apresenta diagnostico para policitemia vera, histórico de esplenomegalia, sem eventos trombóticos ou hemorrágicos relatados, tratado com hidroxiuréia e ácido acetilsalicílico. Foi identificada a variante JAK2V617F em homozigose (T/T). Ambos apresentaram o haplótipo 46/1 (C/G e G/G, respectivamente). Discussão: O presente estudo relata pela primeira vez um caso de diferentes tipos de neoplasias mieloproliferativas em um único grupamento familiar no Amazonas. A identificação de diferentes tipos de variantes drivers dos casos está de acordo com os achados genéticos drivers envolvidos na etiopatogênese das doenças, assim como o haplótipo 46/1 é enriquecido em casos familiares, elevando o risco de 5 a 7 vezes de desenvolvimento dessas doenças em parentes de primeiro grau. Variantes somáticas (como JAK2V617F e c.1154_1155insTTGTC) contribuem para a vantagem proliferativa e a subsequente clonalidade celular, enquanto o componente hereditário (haplótipo 46/1 - rs10974944 C>G), predispõe à aquisição dessas alterações somáticas, estabelecendo o distúrbio mieloproliferativo clonal. Conclusão: É relevante analisar as variantes associadas ao haplótipo germinativo 46/1 em contextos familiares para entender seu papel na hereditariedade e sua possível conexão com a neoplasia mieloproliferativa familiar.

Renal cell carcinoma (RCC) is the most common solid tumour of the kidney and accounts for 3% of all cancers. While immune checkpoint inhibitor (ICI)-based combination therapies have emerged as the first-line treatment for metastatic renal cell carcinoma (mRCC), the role of surgery has become more controversial. This review summarizes the evidence, current role and future directions for surgery in mRCC management. The survival benefits of cytoreductive nephrectomy (CN) shown in the interferon era have encountered increasing disputes in the tyrosine-kinase inhibitor (TKI) and ICI eras. Undoubtedly, several systematic reviews based on retrospective data have supported the survival benefits of CN. Nevertheless, 2 prospective trials, CARMENA and SURTIME, proved that sunitinib as the upfront therapy resulted in noninferior survival outcomes compared with immediate CN. The safety of CN does have solid ground in the current literature. Several studies suggested that preoperative systemic therapy did not seem to aggravate perioperative complications or mortality rates, in experienced centres. Meticulous patient selection is the rule of thumb in the modern management of mRCC patients. The limitations of the existing prognostication models, however, must be acknowledged. Clinicians should adopt a multidisciplinary and holistic approach and contemplate all patient, disease, surgeon and socio-economical factors, before deciding who should go for surgery. The advent of metastasis-directed therapy (MDT) and survival benefits of adjuvant pembrolizumab shown in the oligometastatic subgroup, where complete metastasectomy could be achieved (M1 NED), calls for more comparative studies against upfront ICI combinations. In summary, CN brings survival benefits to well-selected good-to-intermediate-risk mRCC patients. Individualized and multidisciplinary care is pivotal.

Shi-hao Zhao,1 Wen-hui Wang,1 Yu-cong Liang,1 Kai-xin Zhang,1 Kuan Chen,1 Hong-ling Wang,2 Xiang-qi Wang2 1Acupuncture and Moxibustion Massage College, Henan University of Traditional Chinese Medicine, Zhengzhou, Henan, 450046, People’s Republic of China; 2Department of Oncology, Third Affiliated Hospital of Henan University of Traditional Chinese Medicine, Zhengzhou, Henan, 450008, People’s Republic of ChinaCorrespondence: Xiang-qi Wang, Email wangxiangqi777@163.comAbstract: Baihe Gujin decoction is one of the most commonly used decoction in traditional Chinese medicine for the treatment of lung cancer. It can nourish yin and moisten the lung as well as prevent phlegm from forming and stop coughing. On the one hand, Baihe Gujin decoction is characterized with extensive application, proven efficacy, a long history, and high safety. On the other hand, Baihe Gujin decoction can induce apoptosis of tumor cells, improve immune function and inhibit inflammation. The main anti-tumor components of this include kaempferol, quercetin, isorhamnetin, glycyrrhizin and β-sitosterol. Clinically, Baihe Gujin decoction can improve the adverse reactions caused by radiotherapy, chemotherapy and immunotherapy for lung cancer, enhance the quality of life of patients, and prolong their survival time. At present, there are a large number of clinical and basic researches on the treatment of lung cancer with Baihe Gujin decoction. In this paper, we mainly discussed the treatment of lung cancer with Baihe Gujin decoction through analyzing basic and clinical researches at home and abroad in the past 20 years. Through the discussion, we aimed to probe deeper into Baihe Gujin decoction for the treatment of lung cancer, thereby providing a broader idea for clinical diagnosis and treatment of lung cancer.Keywords: Baihe Gujin decoction, lung cancer, traditional Chinese medicine, basic research, clinical study

Chun-Yu Zhao,1 Wan-Hong Shi,2 Zheng-Qi Wen,3 Yong-Mei Jin,4 Yun-Bo Shang,5 Lei Zheng,3 Juan Li,2 Xin-Min Chen2 1School of Nursing, Dali University, Dali, 671000, People’s Republic of China; 2Department of General Surgery, Third People’s Hospital of Yunnan Province, Kun Ming, 650000, People’s Republic of China; 3Department of Surgical Oncology, the First Affiliated Hospital of Kunming Medical University, Kun Ming, 650000, People’s Republic of China; 4Department of Nursing, Shanghai Seventh People’s Hospital, Shanghai, 200137, People’s Republic of China; 5Department of Emergency, Third People’s Hospital of Yunnan Province, Kun Ming, 650000, People’s Republic of ChinaCorrespondence: Yun-Bo Shang, Department of Emergency, Third People’s Hospital of Yunnan Province, No. 292 of Beijing Road, Guandu District, Kun Ming, 650000, People’s Republic of China, Tel +86-13708876606, Fax +8663196549, Email shangyunbo9@sina.com Zheng-Qi Wen, Department of Surgical oncology, The First Affiliated Hospital of Kunming Medical University, Kun Ming, 650000, People’s Republic of China, Tel +86-13888079932, Email 1292333927@qq.comObjective: The objective of this study was to search for, evaluate, and summarize data related to a faster postoperative recovery in patients with colorectal cancer (CRC) based on literature from China as well as internationally. This will serve as an evidence-based foundation for the clinical implementation of enhanced postoperative recovery of gastrointestinal function in patients with CRC.Methods: Based on the hierarchical “ 6S” evidence model, we conducted a systematic search of computerized decision-support systems, guideline websites, as well as domestic and international databases for evidence, guidelines, expert consensus statements, clinical decision-making, best practices, evidence summaries, and systematic reviews of interventions focusing on accelerating gastrointestinal function rehabilitation after CRC surgery. The time limit for the search was from the date of creation of the database to January 2023. Two researchers evaluated the quality of the literature that was included, and we extracted data and summarized the evidence from those publications that fulfilled the quality criteria.Results: The review included a total of 21 publications, comprising 6 guidelines, 6 systematic reviews, 3 expert consensus statements, 4 randomized controlled trials, and 2 evidence summaries. We summarized 51 best evidence findings across five areas: organizational management, preoperative risk assessment, education, intraoperative monitoring, and postoperative management.Conclusion: There is a wide variety and wealth of information available on interventions to promote enhanced postoperative recovery of gastrointestinal function in patients with CRC. The use of evidence is discussed, keeping in mind the practical situation in China.Keywords: colorectal cancer, evidence-based nursing, evidence summary, gastrointestinal function recovery, postoperative

Megasynthase enzymes such as type I modular polyketide synthases (PKSs) and nonribosomal peptide synthetases (NRPSs) play a central role in microbial chemical warfare because they can evolve rapidly by shuffling parts (catalytic domains) to produce novel chemicals. If we can understand the design rules to reshuffle these parts, PKSs and NRPSs will provide a systematic and modular way to synthesize millions of molecules including pharmaceuticals, biomaterials, and biofuels. However, PKS and NRPS engineering remains difficult due to a limited understanding of the determinants of PKS and NRPS fold and function. We developed ClusterCAD to streamline and simplify the process of designing and testing engineered PKS variants. Here, we present the highly improved ClusterCAD 2.0 release, available at https://clustercad.jbei.org. ClusterCAD 2.0 boasts support for PKS-NRPS hybrid and NRPS clusters in addition to PKS clusters; a vastly enlarged database of curated PKS, PKS-NRPS hybrid, and NRPS clusters; a diverse set of chemical 'starters' and loading modules; the new Domain Architecture Cluster Search Tool; and an offline Jupyter Notebook workspace, among other improvements. Together these features massively expand the chemical space that can be accessed by enzymes engineered with ClusterCAD.

Metabolic fluxes, the number of metabolites traversing each biochemical reaction in a cell per unit time, are crucial for assessing and understanding cell function. 13C Metabolic Flux Analysis (13C MFA) is considered to be the gold standard for measuring metabolic fluxes. 13C MFA typically works by leveraging extracellular exchange fluxes as well as data from 13C labeling experiments to calculate the flux profile which best fit the data for a small, central carbon, metabolic model. However, the nonlinear nature of the 13C MFA fitting procedure means that several flux profiles fit the experimental data within the experimental error, and traditional optimization methods offer only a partial or skewed picture, especially in "non-gaussian" situations where multiple very distinct flux regions fit the data equally well. Here, we present a method for flux space sampling through Bayesian inference (BayFlux), that identifies the full distribution of fluxes compatible with experimental data for a comprehensive genome-scale model. This Bayesian approach allows us to accurately quantify uncertainty in calculated fluxes. We also find that, surprisingly, the genome-scale model of metabolism produces narrower flux distributions (reduced uncertainty) than the small core metabolic models traditionally used in 13C MFA. The different results for some reactions when using genome-scale models vs core metabolic models advise caution in assuming strong inferences from 13C MFA since the results may depend significantly on the completeness of the model used. Based on BayFlux, we developed and evaluated novel methods (P-13C MOMA and P-13C ROOM) to predict the biological results of a gene knockout, that improve on the traditional MOMA and ROOM methods by quantifying prediction uncertainty.

A coupled hydrologic and snowpack stable water isotope model assesses controls on isotopic inputs across a mountainous basin. Annually, the most depleted isotope conditions occur in the upper subalpine where snow accumulation is high, and rainfall is low. Snowmelt isotopic evolution over time indicates fractionation processes account for

Dual-phase xenon time projection chamber (TPC) detectors have demonstratedsuperior search sensitivities to dark matter over a wide range of particlemasses. To extend their sensitivity to include low-mass dark matterinteractions, it is critical to characterize both the light and chargeresponses of liquid xenon to sub-keV nuclear recoils. In this work, we report anew nuclear recoil calibration in the LUX detector $\textit{in situ}$ usingneutron events from a pulsed Adelphi Deuterium-Deuterium neutron generator. Wedemonstrate direct measurements of light and charge yields down to 0.45 keV(1.4 scintillation photons) and 0.27 keV (1.3 ionization electrons),respectively, approaching the physical limit of liquid xenon detectors. Wediscuss the implication of these new measurements on the physics reach ofdual-phase xenon TPCs for nuclear-recoil-based low-mass dark matter detection.

We present the results from combining machine learning with the profile likelihood fit procedure, using data from the Large Underground Xenon (LUX) dark matter experiment. This approach demonstrates reduction in computation time by a factor of 30 when compared with the previous approach, without loss of performance on real data. We establish its flexibility to capture nonlinear correlations between variables (such as smearing in light and charge signals due to position variation) by achieving equal performance using pulse areas with and without position-corrections applied. Its efficiency and scalability furthermore enables searching for dark matter using additional variables without significant computational burden. We demonstrate this by including a light signal pulse shape variable alongside more traditional inputs, such as light and charge signal strengths. This technique can be exploited by future dark matter experiments to make use of additional information, reduce computational resources needed for signal searches and simulations, and make inclusion of physical nuisance parameters in fits tractable.

Xin Xue,1,2 Li-Bo Zhao,3 Zhe Zhao,3 Wei-Hao Xu,4 Wei-Meng Cai,1 Shao-Hua Chen,1 Tian-Jiao Li,5 Ting-Yu Nie,5 Dong Rui,1 Xiao-Shun Qian,1 Lin Liu1 1Department of Pulmonary and Critical Care Medicine, Second Medical Center of Chinese PLA General Hospital, Beijing, People’s Republic of China; 2National Clinical Research Center for Geriatric Diseases, Chinese PLA General Hospital, Beijing, People’s Republic of China; 3Department of Vasculocardiology, Second Medical Center of Chinese PLA General 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; 5Medical College, Yan’ an University, Yan’ an, People’s Republic of ChinaCorrespondence: Lin Liu; Xiao-Shun Qian, Department of Pulmonary and Critical Care Medicine, Second Medical Center of Chinese PLA General Hospital, Beijing, People’s Republic of China, Tel +86 132 6318 9578 ; +86 135 2127 9287, Email liulin715@qq.com; 13521279287@163.comBackground: The concomitant rise in the prevalence of obstructive sleep apnea (OSA) and frailty among the elderly population has been linked to an increase in mortality rates. Despite continuous positive airway pressure (CPAP) being the gold standard treatment for OSA, its impact on incident frailty remains inadequately explored.Methods: In this cohort study, we analyzed data from 1290 patients diagnosed with OSA, aged 60 years and older. A subset of 71 patients who demonstrated high adherence to CPAP therapy were categorized as the CPAP group. Propensity score matching (PSM) was employed at a 1:4 ratio, matching for variables such as age, gender, body mass index (BMI), and sleep apnea-hypopnea index (AHI), to establish a non-CPAP group for comparison. The FRAIL scale was utilized to evaluate the frailty status of participants. Logistic regression analysis examined the relationship between CPAP therapy and incident frailty, as well as its individual components, in elderly patients with OSA.Results: During a median follow-up period of 52 months, incident frailty was observed in 70 patients (19.7%). Patients with OSA receiving CPAP therapy exhibited a lower incidence of frailty compared to those not receiving CPAP (11.26% vs 21.83%, P=0.045). In the multivariate model, CPAP therapy was significantly correlated with a reduced risk of incident frailty (OR = 0.36, 95% CI, 0.15– 0.88; P = 0.025). Subcomponent analyses revealed that CPAP was associated with a lower risk of fatigue (OR=0.35, 95% CI, 0.19– 0.63; P < 0.001), resistance (OR = 0.32, 95% CI, 0.14– 0.74; P=0.008), and weight loss (OR = 0.38, 95% CI, 0.19– 0.75; P = 0.007).Conclusion: CPAP therapy was associated with a reduced risk of incident frailty among elderly patients with OSA.Keywords: obstructive sleep apnea, frailty, continuous positive airway pressure, elderly

Juyoung Khwarg,1 Soyoung Lee,1,2 In-Jin Jang,1 Won-Ho Kang,3 Hye Jung Lee,4 Kyu Yeon Kim,4 Ki-Sun Jeong,4 Chongho Won,4 Youn Woong Choi,5 Dae Chul Ha,5 RaeHoon Jung,5 Min-Gu Han,5 Won Tae Jung,6 Kyu-Yeol Nam,6 YeSeul Kim,6 Kyung-Sang Yu,1 Jaeseong Oh1,7 1Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, Republic of Korea; 2Integrated Major in Innovative Medical Science, Seoul National University Graduate School, Seoul, Republic of Korea; 3R&D Center, Korea United Pharm. Inc., Seoul, Republic of Korea; 4Caleb Multilab, Inc., Seoul, Republic of Korea; 5R&D Center, Korea United Pharm.Inc., Sejong, Republic of Korea; 6Global R&D, Korea United Pharm. Inc., Seoul, Republic of Korea; 7Department of Pharmacology, Jeju National University College of Medicine, Jeju, Republic of KoreaCorrespondence: Jaeseong Oh, Department of Pharmacology, Jeju National University College of Medicine, 15, Aran 13-gil, Jeju-si, Jeju-do, 63241, Republic of Korea, Email jaeseong5@jejunu.ac.krPurpose: Statins are widely used in combination with omega-3 fatty acids for the treatment of patients with dyslipidemia. The aim of this study was to compare the pharmacokinetic (PK) profiles of atorvastatin and omega-3-acid ethyl esters between fixed-dose combination (FDC) and loose combination in healthy subjects.Methods: A randomized, open-label, single-dose, 2-sequence, 2-treatment, 4-period replicated crossover study was performed. Subjects were randomly assigned to one of the 2 sequences and alternately received four FDC soft capsules of atorvastatin/omega-3-acid ethyl esters (10/1000 mg) or a loose combination of atorvastatin tablets (10 mg × 4) and omega-3-acid ethyl ester soft capsules (1000 mg× 4) for four periods, each period accompanied by a high-fat meal. Serial blood samples were collected for PK analysis of atorvastatin, eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA). PK parameters were calculated by a non-compartmental analysis. The geometric mean ratio (GMR) and its 90% confidence interval (CI) of the FDC to the loose combination were calculated to compare PK parameters.Results: A total of 43 subjects completed the study as planned. The GMR (90% CI) of FDC to loose combination for maximum concentration (Cmax) and area under the time-concentration curve from zero to the last measurable point (AUClast) were 1.0931 (1.0054– 1.1883) and 0.9885 (0.9588– 1.0192) for atorvastatin, 0.9607 (0.9068– 1.0178) and 0.9770 (0.9239– 1.0331) for EPA, and 0.9961 (0.9127– 1.0871) and 0.9634 (0.8830– 1.0512) for DHA, respectively. The intra-subject variability for Cmax and AUClast of DHA was 30.8% and 37.5%, respectively, showing high variability. Both the FDC and the loose combination were safe and well tolerated.Conclusion: The FDC of atorvastatin and omega-3-acid ethyl esters showed comparable PK characteristics to the corresponding loose combination, offering a convenient therapeutic option for the treatment of dyslipidemia. Keywords: pharmacokinetics, cardiovascular disease

Wei-Rui Huang,1,&ast; Quan-Hui Fang,1,&ast; Xiang-Bin Yu,1 Wei-Hong Ge,2,3 Yue Yu1 1School of Pharmacy & Fujian Center for New Drug Safety Evaluation, Fujian Medical University, Fuzhou, 350122, People’s Republic of China; 2Department of Pharmacy, Nanjing Drum Tower Hospital, Nanjing, 210008, People’s Republic of China; 3School of Pharmacy, Macau University of Science and Technology, Macau SAR, 999078, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yue Yu, School of Pharmacy & Fujian Center for New Drug Safety Evaluation, Fujian Medical University, Fuzhou, 350122, People’s Republic of China, Email yyu@fjmu.edu.cn Wei-Hong Ge, Department of Pharmacy, Nanjing Drum Tower Hospital, Nanjing, 210008, People’s Republic of China, Email 413811252@163.comAbstract: Aloe barbadensis Mill. has a long history of medicinal use in the annals of traditional Chinese medicine, wherein it has garnered considerable renown. Its multifaceted therapeutic properties, characterized by its anti-inflammatory and antibacterial attributes, alongside its established efficacy as a laxative agent, have been extensively documented. This review commences with an exploration of the nomenclature, fundamental characteristics, and principal constituents of Aloe barbadensis Mill. responsible for its laxative effects. Subsequently, we delve into an extensive examination of the molecular mechanisms underlying Aloe barbadensis Mill.’s laxative properties, types of constipation treatments, commercially available preparations, considerations pertaining to toxicity, and its clinical applications. This review aims to serve as a comprehensive reference point for healthcare professionals and researchers, fostering an enhanced understanding of the optimal utilization of Aloe barbadensis Mill. in the treatment of constipation. Keywords: Aloe barbadensis Mill, constipation, laxative

Hua Bai, Wen-Hui Wang, Fan-Fan Zhou, Dan Yang, Rui-Jun Li Department of Oncology, People’s Hospital of Zhengzhou, Zhengzhou, People’s Republic of ChinaCorrespondence: Rui-Jun Li, Department of Oncology, People’s Hospital of Zhengzhou, No. 33, Huanghe Road, Jin-Shui District, Zhengzhou, 450053, People’s Republic of China, Tel +86 13838508075, Email liruijunzy@163.comObjective: Therapeutic regimens are relatively scarce among patients with treatment-refractory metastatic colorectal cancer (CRC). This study aimed to determine the feasibility and tolerability of anlotinib plus PD-1 blockades in patients with treatment-refractory metastatic CRC retrospectively.Methods: A total of 68 patients with previously treated metastatic CRC who received anlotinib plus PD-1 blockades in clinical practice were included in this study retrospectively. Demographic and clinical characteristics of the patients, therapeutic outcomes and safety profile during administration were collected and briefly analyzed. All subjects were followed up regularly. Therapeutic outcomes, including drug response and prognosis, were presented, and a safety profile was depicted to illustrate the adverse reactions.Results: A total of 68 patients with treatment-refractory metastatic CRC who received anlotinib plus PD-1 blockades in clinical practice were included in the final analysis. Best therapeutic response during treatment indicated that partial response was observed in 11 patients, stable disease was noted in 41 patients, and progressive disease was found in 16 patients, producing an objective response rate of 16.2% (95% CI: 8.4%– 27.1%) and a disease control rate of 76.5% (95% CI: 64.6%– 85.9%). Prognostic analysis suggested that the median progression-free survival (PFS) of the 68 patients was 5.3 months (95% CI: 3.01– 7.59), and the median overall survival (OS) was 12.5 months (95% CI: 9.40– 15.60). Of the 11 patients who responded, the median duration of response was 6.7 months (95% CI: 2.89– 10.53). Safety profile during treatment showed that patients experienced adverse reactions regardless of grade, and grade ≥ 3 adverse reactions were found in 61 patients (89.7%) and 41 patients (60.3%), respectively. Common adverse reactions were hypertension, myelosuppression (including leukopenia, neutropenia, thrombocytopenia, and anemia), fatigue, and hand-foot syndrome.Conclusion: Anlotinib plus PD-1 blockades demonstrated encouraging efficacy and acceptable safety profile in patients with treatment-refractory metastatic CRC preliminarily in clinical practice. This conclusion should be confirmed in prospective clinical trials.Keywords: colorectal cancer, anlotinib, PD-1 blockades, efficacy, safety

Rationale: Adrenal histoplasmosis can present as bilateral adrenal enlargement with constitutional symptoms and/or adrenal insufficiency. Often these patients are initially investigated as secondary adrenal metastases before eventually their diagnosis established by histopathological examination of the adrenal tissues. Patients concerns: We report 4 cases of patients aged 55-78 who presented with hypocortisolism and bilateral adrenal masses. Diagnoses: Bilateral adrenal histoplasmosis. Interventions: Three patients received antifungal treatment for at least one year while 1 patient passed away before the initiation of antifungal treatment. Outcomes: Two patients’ adrenal function recovered not requiring any steroid replacement, while 1 patient still requires long-term steroid replacement. Lessons: Adrenal histoplasmosis should be excluded in patients from endemic areas presenting with bilateral adrenal masses and adrenal insufficiency. Usually patients have an exposure to bird droppings, bat guano or soil contaminated with histoplasmosis fungi. Histopathological examination of biopsied adrenal tissues is still the gold standard investigation as serology and molecular diagnostic methods are still not widely available in most centers in Malaysia.

Chia‐Chi Chen,1– 4 Wei-Hua Tang,5,6 Cheng-Ching Wu,2,7,8 Thung-Lip Lee,7,9 I-Ting Tsai,2,10 Chin-Feng Hsuan,2,7,11 Chao-Ping Wang,7,9 Fu-Mei Chung,7 Yau-Jiunn Lee,12 Teng-Hung Yu,2,7,&ast; Ching-Ting Wei4,13,&ast; 1Department of Pathology, E-Da Hospital, I-Shou University, Kaohsiung, 82445, Taiwan; 2School of Medicine, College of Medicine, I-Shou University, Kaohsiung, 82445, Taiwan; 3Department of Physical Therapy, I-Shou University, Kaohsiung, 82445, Taiwan; 4The School of Chinese Medicine for Post Baccalaureate, College of Medicine, I-Shou University, Kaohsiung, 82445, Taiwan; 5Division of Cardiology, Department of Internal Medicine, Taipei Veterans General Hospital, Yuli Branch, Hualien, 98142, Taiwan; 6Faculty of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, 112304, Taiwan; 7Division of Cardiology, Department of Internal Medicine, E-Da Hospital, I-Shou University, Kaohsiung, 82445, Taiwan; 8Division of Cardiology, Department of Internal Medicine, E-Da Cancer Hospital, I-Shou, University, Kaohsiung, 82445, Taiwan; 9School of Medicine for International Students, College of Medicine, I-Shou University, Kaohsiung, 82445, Taiwan; 10Department of Emergency, E-Da Hospital, I-Shou University, Kaohsiung, 82445, Taiwan; 11Division of Cardiology, Department of Internal Medicine, E-Da Dachang Hospital, I-Shou University, Kaohsiung, Taiwan; 12Lee’s Endocrinologic Clinic, Pingtung, 90000, Taiwan; 13Division of General Surgery, Department of Surgery, E-Da Hospital, I-Shou University, Kaohsiung, 82445, Taiwan&ast;These authors contributed equally to this workCorrespondence: Teng-Hung Yu; Ching-Ting Wei, E-Da Hospital, I-Shou University, No. 1, Yi-Da Road, Jiau-Shu Village, Yan-Chao District, Kaohsiung, 82445, Taiwan, Tel +886-7-615-1100 ext. 5914 or 5018, Email tenghungy@gmail.com; triplet0826@gmail.comObjective: Breast cancer is the second most common malignancy globally and a leading cause of cancer death in women. Analysis of factors related to disease-free survival (DFS) has improved understanding of the disease and characteristics related to recurrence. The aim of this study was to investigate the predictors of DFS in patients with breast cancer to enable the identification of patients at high risk who may benefit from prevention interventions.Methods: We retrospectively analyzed 559 women with breast cancer who underwent treatment between 2004 and 2022. The study endpoint was DFS. Recurrence was defined as local recurrence, regional recurrence, distant metastases, contralateral breast cancer, other second primary cancer, and death. Baseline tumor-related characteristics, treatment-related characteristics, sociodemographic and biochemical data were analyzed using Cox proportional hazards analysis.Results: The median DFS was 45 months (range, 2 to 225 months). Breast cancer recurred in 86 patients (15.4%), of whom 10 had local recurrence, 10 had regional recurrence, 17 had contralateral breast cancer, 29 had distant metastases, 10 had second primary cancer, and 10 patients died. Multivariate forward stepwise Cox regression analysis showed that AJCC stage III, Ki67 ≥ 14%, albumin, platelet, and red cell distribution width-standard deviation (RDW-SD) were predictors of worse DFS. In addition, the effects of albumin, platelet, and RDW-SD on disease recurrence were confirmed by structural equation model (SEM) analysis.Conclusion: In addition to the traditional predictors of worse DFS such as AJCC stage III and Ki67 ≥ 14%, lower pretreatment circulating albumin, higher pretreatment circulating platelet count and RDW-SD could significantly predict worse DFS in this study, and SEM delineated possible causal pathways and inter-relationships of albumin, platelet, and RDW-SD contributing to the disease recurrence among Chinese women with breast cancer.Keywords: breast cancer, albumin, platelet, RDW-SD, disease-free survival