bluuebunny/crossref_metadata_2025 huggingface dataset:
Concomitant Discontinuation of Cardiovascular Therapy and Adjuvant Hormone Therapy Among Patients With Breast Cancer
Authors: He Wei , Zeng Erwei , Sjölander Arvid , Hübbert Laila , Hedayati Elham , Czene Kamila
Published: July 2023

Importance

A large proportion of patients with breast cancer concomitantly use adjuvant hormone therapy and cardiovascular therapy.

Objective

To examine the relative risk of discontinuing cardiovascular therapy during the periods before and after discontinuation of adjuvant hormone therapy.

Design, Setting, and Participants

This population-based cohort study included all women aged 40 to 74 years in Stockholm, Sweden, who were diagnosed with breast cancer and concomitantly using adjuvant hormone therapy and cardiovascular therapy. Patients were enrolled from July 1, 2005, to August 31, 2020, with a median follow-up of 7.2 years. Data were analyzed from November 3, 2021, to May 12, 2022.

Exposure

Discontinuation of adjuvant hormone therapy.

Main Outcomes and Measures

The main outcome was discontinuation of cardiovascular therapy (cardiovascular drugs, statins, or aspirin) within 1 year before and after discontinuation of adjuvant hormone therapy. Incidence rate ratios with 95% CIs were estimated using Poisson regression. Furthermore, hazard ratios (HRs) with 95% CIs for cause-specific mortality were estimated using Cox proportional hazards regression models, comparing those who discontinued and continued adjuvant hormone therapy.

Results

A total of 5493 patients with breast cancer who concomitantly used cardiovascular therapy were identified; 1811 who discontinued adjuvant hormone therapy were individually matched to 1 patient each who continued therapy by year of breast cancer diagnosis, age at diagnosis, and use of the same cardiovascular therapy. Most patients (4070 [74.1%]) were aged 60 years or older at diagnosis. At the time when patients discontinued adjuvant hormone therapy, 248 (12.2%) concomitantly discontinued their cardiovascular therapy. During follow-up, a higher discontinuation rate of cardiovascular therapy was also observed among those who discontinued adjuvant hormone therapy. Consistently, adjuvant hormone therapy discontinuation was associated with an increased risk of death not only due to breast cancer (HR, 1.43; 95 CI%, 1.01-2.01) but also cardiovascular disease (HR, 1.79; 95 CI%, 1.15-2.81). Stratifying the analyses on baseline type of adjuvant hormone therapy yielded consistent results.

Conclusions and Relevance

In this cohort study of data from population-based registers in Sweden, patients who discontinued adjuvant hormone therapy were also more likely to discontinue cardiovascular therapy, especially at the time when they discontinued adjuvant hormone therapy. These findings suggest that clinicians should shift from single- to multiple-disease focus to prevent discontinuation of therapies for other diseases among patients with breast cancer.
Presence and Quantity of Botanical Ingredients With Purported Performance-Enhancing Properties in Sports Supplements
Authors: Cohen Pieter A. , Avula Bharathi , Katragunta Kumar , Travis John C. , Khan Ikhlas
Published: July 2023

This case series study examines the accuracy of labels of dietary sports supplements containing botanical ingredients.
Effect of a Gun Safety Video on Children’s Behavior Around Real Guns
Authors: Kjærvik Sophie L. , Bushman Brad J.
Published: July 2023

Importance

Firearms are the leading cause of death for children in the US. It is therefore crucial to identify effective ways to reduce firearm injuries among children.

Objective

To test the effectiveness of a gun safety video vs a car safety video on decreasing unsafe behaviors around real guns after exposure to a violent movie with vs without guns.

Design, Setting, and Participants

Of 245 participants aged 8 to 12 years, 226 were tested (13 did not complete the laboratory portion, 4 had technical problems, and 2 did not respond to follow-up inquiries). Data were collected from February 2 to October 16, 2022. Participants were recruited via Facebook ads, ResearchMatch, and parent or guardian referrals. The study was conducted in 2 parts. Children watched a safety video at home 1 week before coming to the laboratory at The Ohio State University.

Interventions

Pairs of children were randomly assigned to watch a 1-minute gun or car safety video at home. In the laboratory, they were randomly assigned to watch a 20-minute clip from a violent PG-rated movie with or without guns. Next, they played with games and toys for 20 minutes in another room that contained 2 disabled 9-mm handguns hidden in a file cabinet drawer. Sessions were videotaped via a hidden camera.

Main Outcomes and Measures

Outcomes were whether children told an adult, touched a handgun, handled it, or pulled the trigger. Control variables were age, gender, race and ethnicity, trait aggressiveness, age-inappropriate media exposure, firearm attitude and interest, presence of firearms at home, and whether children had taken a firearm safety course.

Results

Of 226 children (mean [SD] age, 9.99 [1.38] years; 113 [52.3%] male), 216 (95.6%) found a gun and were included in analyses. Those who saw the gun (vs car) safety video were more likely to tell an adult about the gun they found (38 of 112 [33.9%] vs 11 of 104 [10.6%]), were less likely to touch the gun (44 of 112 [39.3%] vs 70 of 104 [67.3%]), held the gun fewer seconds if they did touch it (mean [SD], 42.04 [121.46] vs 98.96 [195.10]), were less likely to pull the trigger at all (10 of 112 [8.9%] vs 31 of 104 [29.8%]), and pulled the trigger fewer times (mean [SD], 4.20 [20.17] vs 7.23 [15.75]). Being male, exposure to age-inappropriate movies, and gun interest were related to unsafe behavior. Prior completion of a firearm safety course, having guns at home, and negative gun attitudes were related to safe behavior.

Conclusions

In this trial of children assigned to watch a gun or car safety video, watching a gun safety video reduced children’s unsafe behavior around real guns. Children who had previously taken a gun safety course, had guns in the home, and had negative attitudes toward guns were less likely to engage in unsafe behavior around real guns. To encourage safe firearm behavior, children should be educated about gun safety and should not watch age-inappropriate media.

Trial Registration

ClinicalTrials.gov Identifier: NCT05257837
Tricuspid Annular Plane Systolic Excursion/Systolic Pulmonary Artery Pressure Ratio and Cardiorenal Syndrome Type 2 in the Systemic Sclerosis EUSTAR Cohort
Authors: Colalillo Amalia , Pellicano Chiara , Ananyeva Lidia P. , Hachulla Eric , Cuomo Giovanna , Györfi Andrea‐Hermina , Czirják László , de Vries‐Bouwstra Jeska , Mouthon Luc , Poormoghim Hadi , Del Galdo Francesco , Hunzelmann Nicolas , Spierings Julia , Kuwana Masataka , Rosato Edoardo ,   and the EUSTAR Collaborators
Published: July 2023

Objective

The aim of the study was to evaluate the association between the tricuspid annular plane systolic excursion (TAPSE)/systolic pulmonary artery pressure (sPAP) ratio and estimated glomerular filtration rate (eGFR) and their association with mortality in the European Scleroderma Trials and Research (EUSTAR) cohort.

Methods

Patients with systemic sclerosis (SSc) from the EUSTAR database with TAPSE, sPAP, and parameters required to calculate eGFR were included. Logistic regression and Cox regression analysis were performed to evaluate TAPSE/sPAP as a risk factor for chronic kidney disease (CKD) and overall survival.

Results

A total of 2,370 patients with SSc were included; 284 (12%) patients had CKD stage 3a–5. TAPSE/sPAP (odds ratio [OR] 0.479; 95% CI 0.310–0.743; P < 0.001), arterial hypertension (OR 3.118; 95% CI 2.173–4.475; P < 0.001), diastolic dysfunction (OR 1.670; 95% CI 1.148–2.428; P < 0.01), and N‐terminal pro‐B‐type natriuretic peptide (OR 1.165; 95% CI 1.041–1.304; P < 0.01) were associated with CKD stage 3a–5. TAPSE/sPAP ≤0.32 mm/mm Hg (hazard ratio [HR] 3.589; 95% CI 2.236–5.761; P < 0.001), eGFR <60 mL/min per 1.73 m2 (HR 2.818; 95% CI 1.777–4.468; P < 0.001), and age (HR 1.782; 95% CI 1.348–2.356; P < 0.001) were the most significant predictive factors for all‐cause mortality. A total of 276 patients with SSc had pulmonary hypertension (PH) confirmed by right‐sided heart catheterization, with 69 (25%) having CKD stage 3a–5. No difference was found in eGFR between patients with PH with reduced or normal cardiac index.

Conclusion

Reduced TAPSE/sPAP ratio is independently associated with CKD. TAPSE/sPAP ratio ≤0.32 mm/mm Hg and eGFR <60 mL/min per 1.73 m2 are prognostic factors for all‐cause mortality. In patients with SSc with PH, eGFR is independent by reduced cardiac output.
Prevalence of Alzheimer's disease dementia in the 50 US states and 3142 counties: A population estimate using the 2020 bridged‐race postcensal from the National Center for Health Statistics
Authors: Dhana Klodian , Beck Todd , Desai Pankaja , Wilson Robert S. , Evans Denis A. , Rajan Kumar B.
Published: July 2023

INTRODUCTION

This study estimates the prevalence and number of people living with Alzheimer's disease (AD) dementia in 50 US states and 3142 counties.

METHODS

We used cognitive data from the Chicago Health and Aging Project, a population‐based study, and combined it with the National Center for Health Statistics 2020 bridged‐race population estimates to determine the prevalence of AD in adults ≥65 years.

RESULTS

A higher prevalence of AD was estimated in the east and southeastern regions of the United States, with the highest in Maryland (12.9%), New York (12.7%), and Mississippi (12.5%). US states with the highest number of people with AD were California, Florida, and Texas. Among larger counties, those with the highest prevalence of AD were Miami‐Dade County in Florida, Baltimore city in Maryland, and Bronx County in New York.

DISCUSSION

The state‐ and county‐specific estimates could help public health officials develop region‐specific strategies for caring for people with AD.
Phase Separation of DNA‐Encoded Artificial Cells Boosts Signal Amplification for Biosensing
Authors: Li Juncai , Yang Cai , Zhang Lizhuan , Li Chunying , Xie Sitao , Fu Ting , Zhang Ziwen , Li Longjie , Qi Lubin , Lyu Yifan , Chen Fengming , He Lei , Tan Weihong
Published: July 2023

Life‐like hierarchical architecture shows great potential for advancing intelligent biosensing, but modular expansion of its sensitivity and functionality remains a challenge. Drawing inspiration from intracellular liquid‐liquid phase separation, we discovered that a DNA‐encoded artificial cell with a liquid core (LAC) can enhance peroxidase‐like activity of Hemin and its DNA G‐quadruplex aptamer complex (DGAH) without substrate‐selectivity, unlike its gelled core (GAC) counterpart. The LAC is easily engineered as an ultrasensitive biosensing system, benefiting from DNA′s high programmability and unique signal amplification capability mediated by liquid‐liquid phase separation. As proof of concept, its versatility was successfully demonstrated by coupling with two molecular recognition elements to monitor tumor‐related microRNA and profile cancer cell phenotypes. This scalable design philosophy offers new insights into the design of next generation of artificial cells‐based biosensors.
Unlocking Reversible Silicon Redox for High‐Performing Chlorine Batteries
Authors: Yuan Bin , Wu Liang , Geng Shitao , Xu Qiuchen , Zhao Xiaoju , Wang Yan , Liao Meng , Ye Lei , Qu Zongtao , Zhang Xiao , Wang Shuo , Ouyang Zhaofeng , Tang Shanshan , Peng Huisheng , Sun Hao
Published: July 2023

Chlorine (Cl)‐based batteries such as Li/Cl2 batteries are recognized as promising candidates for energy storage with low cost and high performance. However, the current use of Li metal anodes in Cl‐based batteries has raised serious concerns regarding safety, cost, and production complexity. More importantly, the well‐documented parasitic reactions between Li metal and Cl‐based electrolytes require a large excess of Li metal, which inevitably sacrifices the electrochemical performance of the full cell. Therefore, it is crucial but challenging to establish new anode chemistry, particularly with electrochemical reversibility, for Cl‐based batteries. Here we show, for the first time, reversible Si redox in Cl‐based batteries through efficient electrolyte dilution and anode/electrolyte interface passivation using 1,2‐dichloroethane and cyclized polyacrylonitrile as key mediators. Our Si anode chemistry enables significantly increased cycling stability and shelf lives compared with conventional Li metal anodes. It also avoids the use of a large excess of anode materials, thus enabling the first rechargeable Cl2 full battery with remarkable energy and power densities of 809 Wh kg−1 and 4,277 W kg−1, respectively. The Si anode chemistry affords fast kinetics with remarkable rate capability and low‐temperature electrochemical performance, indicating its great potential in practical applications.
Zeitaufgelöste Mn2+−NO‐ und NO−NO‐Abstandsmessungen zeigen regulierende Funktion der katalytischen Asymmetrie auf den alternierenden Zugang in einem ABC‐Transporter**
Authors: Rudolph Michael , Tampé Robert , Joseph Benesh
Published: July 2023

ATP‐binding cassette Transporter (ABC‐Transporter) transportieren unterschiedlichste Substrate über biologische Membranen. Der Transport erfolgt durch den Übergang zwischen einer nach innen gerichteten (IF) und einer nach außen gerichteten (OF) Konformation der Transmembrandomänen (TMD). Katalytisch asymmetrische Nukleotidbindestellen (NBS) sind in fast allen ABC‐Proteinunterfamilien vorhanden, ihre funktionelle Rolle ist jedoch noch nicht geklärt. Wir haben diese Frage mit Hilfe von gleichzeitigen NO−NO, Mn2+−NO und Mn2+−Mn2+ Abstandsmessungen mittels gepulster Doppel‐Elektron‐Elektron‐Resonanzspektroskopie von TmrAB zeitaufgelöst untersucht. Dieser Typ IV ABC‐Transporter durchläuft in Gegenwart von ATP einen reversiblen Übergang mit einem deutlich schnelleren Vorwärtsübergang (IF‐nach‐OF). Die katalytisch beeinträchtigte, degenerierte NBS bindet Mn2+−ATP stabil, während Mn2+ bevorzugt an der aktiven konsensus NBS freigesetzt wird. Die ATP‐Hydrolyse an der konsensus NBS beschleunigt den Rückwärtsübergang erheblich. Beide NBSs öffnen sich während jedes Konformationszyklus vollständig, und die degenerierte NBS könnte die Kinetik dieses Prozesses regulieren.
Carbon Electrode Materials for Advanced Potassium‐Ion Storage
Authors: Zhang Wenchao , Huang Rui , Yan Xu , Tian Chen , Xiao Ying , Lin Zhang , Dai Liming , Guo Zaiping , Chai Liyuan
Published: July 2023

Tremendous progress has been made in the field of electrochemical energy storage devices that rely on potassium‐ions as charge carriers due to their abundant resources and excellent ion transport properties. Nevertheless, future practical developments not only count on advanced electrode materials with superior electrochemical performance, but also on competitive costs of electrodes for scalable production. In the past few decades, advanced carbon materials have attracted great interest due to their low cost, high selectivity, and structural suitability and have been widely investigated as functional materials for potassium‐ion storage. This article provides an up‐to‐date overview of this rapidly developing field, focusing on recent advanced and mechanistic understanding of carbon‐based electrode materials for potassium‐ion batteries. In addition, we also discuss recent achievements of dual‐ion batteries and conversion‐type K−X (X=O2, CO2, S, Se, I2) batteries towards potential practical applications as high‐voltage and high‐power devices, and summarize carbon‐based materials as the host for K‐metal protection and possible directions for the development of potassium energy‐related devices as well. Based on this, we bridge the gaps between various carbon‐based functional materials structure and the related potassium‐ion storage performance, especially provide guidance on carbon material design principles for next‐generation potassium‐ion storage devices.
Topological Design of Unprecedented Metal‐Organic Frameworks Featuring Multiple Anion Functionalities and Hierarchical Porosity for Benchmark Acetylene Separation
Authors: Zhang Yuanbin , Sun Wanqi , Luan Binquan , Li Jiahao , Luo Dong , Jiang Yunjia , Wang Lingyao , Chen Banglin
Published: July 2023

Separation of acetylene (C2H2) from carbon dioxide (CO2) or ethylene (C2H4) is industrially important but still challenging so far. Herein, we developed two novel robust metal organic frameworks AlFSIX‐Cu‐TPBDA (ZNU‐8) with znv topology and SIFSIX‐Cu‐TPBDA (ZNU‐9) with wly topology for efficient capture of C2H2 from CO2 and C2H4. Both ZNU‐8 and ZNU‐9 feature multiple anion functionalities and hierarchical porosity. Notably, ZNU‐9 with more anionic binding sites and three distinct cages displays both an extremely large C2H2 capacity (7.94 mmol/g) and a high C2H2/CO2 (10.3) or C2H2/C2H4 (11.6) selectivity. The calculated capacity of C2H2 per anion (4.94 mol/mol at 1 bar) is the highest among all the anion pillared metal organic frameworks. Theoretical calculation indicated that the strong cooperative hydrogen bonds exist between acetylene and the pillared SiF62− anions in the confined cavity, which is further confirmed by in situ IR spectra. The practical separation performance was explicitly demonstrated by dynamic breakthrough experiments with equimolar C2H2/CO2 mixtures and 1/99 C2H2/C2H4 mixtures under various conditions with excellent recyclability and benchmark productivity of pure C2H2 (5.13 mmol/g) or C2H4 (48.57 mmol/g).
Time‐Resolved Mn2+−NO and NO−NO Distance Measurements Reveal That Catalytic Asymmetry Regulates Alternating Access in an ABC Transporter**
Authors: Rudolph Michael , Tampé Robert , Joseph Benesh
Published: July 2023

ATP‐binding cassette (ABC) transporters shuttle diverse substrates across biological membranes. Transport is often achieved through a transition between an inward‐facing (IF) and an outward‐facing (OF) conformation of the transmembrane domains (TMDs). Asymmetric nucleotide‐binding sites (NBSs) are present among several ABC subfamilies and their functional role remains elusive. Here we addressed this question using concomitant NO−NO, Mn2+−NO, and Mn2+−Mn2+ pulsed electron–electron double‐resonance spectroscopy of TmrAB in a time‐resolved manner. This type‐IV ABC transporter undergoes a reversible transition in the presence of ATP with a significantly faster forward transition. The impaired degenerate NBS stably binds Mn2+−ATP, and Mn2+ is preferentially released at the active consensus NBS. ATP hydrolysis at the consensus NBS considerably accelerates the reverse transition. Both NBSs fully open during each conformational cycle and the degenerate NBS may regulate the kinetics of this process.
Efficient C(sp3)−H Carbonylation of Light and Heavy Hydrocarbons with Carbon Monoxide via Hydrogen Atom Transfer Photocatalysis in Flow**
Authors: Raymenants Fabian , Masson Tom M. , Sanjosé‐Orduna Jesús , Noël Timothy
Published: July 2023

Despite their abundance in organic molecules, considerable limitations still exist in synthetic methods that target the direct C−H functionalization at sp3‐hybridized carbon atoms. This is even more the case for light alkanes, which bear some of the strongest C−H bonds known in Nature, requiring extreme activation conditions that are not tolerant to most organic molecules. To bypass these issues, synthetic chemists rely on prefunctionalized alkyl halides or organometallic coupling partners. However, new synthetic methods that target regioselectively C−H bonds in a variety of different organic scaffolds would be of great added value, not only for the late‐stage functionalization of biologically active molecules but also for the catalytic upgrading of cheap and abundant hydrocarbon feedstocks. Here, we describe a general, mild and scalable protocol which enables the direct C(sp3)−H carbonylation of saturated hydrocarbons, including natural products and light alkanes, using photocatalytic hydrogen atom transfer (HAT) and gaseous carbon monoxide (CO). Flow technology was deemed crucial to enable high gas‐liquid mass transfer rates and fast reaction kinetics, needed to outpace deleterious reaction pathways, but also to leverage a scalable and safe process.
Numerical modeling of novel cage‐like cross‐linked membranes for enhanced proton conductivity in a high temperature‐polymer electrolyte membrane fuel cell
Authors: Kashi Prahlad Venkatesh Babu , Varghese Geethu , Joseph Thadathil Varghese , Chippar Purushothama
Published: July 2023

Phosphoric acid (PA)‐doped polybenzimidazole (PBI) membranes have encountered several problems associated with high cost, chemical instability, poor solubility in organic solvents, and higher doping level which results in poor mechanical properties and faster degradation of the membrane. Alternative membranes with high proton conductivity and mechanical strength for high‐temperature applications are of great interest, one such membrane being cPBI‐IL X. The cage‐like cross‐linked structure of these membranes shows a dual proton transport path due to which proton conductivity is elevated. The ionic liquid content of these membranes improves the PA absorbing capability and shortens the proton transfer path. These membranes exhibit the highest proton conductivity of 13.3 S/m and better durability compared to existing PBI Membranes. A mathematical model is developed and validated versus published experimental results to account for the proton conductivity of these membranes. The developed model is further investigated for a detailed understanding of polarization phenomena and species distribution.
Miscibility and phase behavior of reactively compatibilized poly(lactic acid)/poly(butylene succinate) bio‐blends using various rheological analyses
Authors: Saeed Ullah Muhammad , Yildirim Rumeysa , Caraseva Lulia , Zuza Ester , Ozkoc Guralp , Kodal Mehmet
Published: July 2023

This study focuses on the compatibilization of PLA/poly(butylene succinate) (PBS) blends using mono‐ and multi‐epoxide POSS (MoEpPOSS and MuEpPOSS) nanoparticles, from a rheological point of view for the first time in the literature. The addition of PBS to PLA decreased the complex viscosity, storage modulus, and loss modulus, indicating weak interactions between polymers. However, the incorporation of MoEpPOSS and MuEpPOSS increased the complex viscosity and storage modulus due to the formation of long polymeric chains or complex polymeric structures through interactions between the epoxide groups of POSS and the end groups of the polymers. The effect was more significant with MuEpPOSS because MuEpPOSS has multiple epoxide groups in its cage structure, leading to stronger interactions with the polymers. POSS incorporation resulted in semicircular and arc‐shaped curves in the Cole‐Cole plots, indicating better dispersion, phase homogeneity, and compatibility. The introduction of POSS also influenced the dynamic loss tangent (tan δ) versus frequency (ω) plot. When POSS was introduced, the tan δ peak decreased and shifted to a higher frequency, indicating improved compatibility, and enhanced interfacial adhesion. These findings indicated that the addition of epoxy‐POSS nanoparticles can effectively compatibilize PLA/PBS blends and enhance their rheological properties, potentially improving their overall performance for various applications.
Immune responses of the Asian onion moth, Acrolepiopsis sapporensis, and their genetic factors from RNA‐Seq analysis
Authors: Hrithik Md Tafim Hossain , Kim Yonggyun
Published: July 2023

A nonmodel insect, Acrolepiopsis sapporensis, has been analyzed in immune responses. The total hemocytes in the fifth instar larvae were 2.33 × 106 cells/mL. These hemocytes comprised at least five different types and different relative ratios: 47% granulocytes, 26% plasmatocytes, 11% oenocytoid, 8% prohemocytes, and 5% spherulocytes. Upon bacterial challenge, some of the hemocytes exhibited typical hemocyte‐spreading behaviors, such as focal adhesion, and filopodial and lamellipodial cytoplasmic extensions. The hemocyte behaviors induced cellular immune responses demonstrated by nodule formation. In addition, the plasma collected from the immune‐challenged larvae exhibited humoral immune responses by bacterial growth inhibition along with enhanced phenoloxidase enzyme activity. These cellular and humoral immune responses were further analyzed by determining the immune‐associated genes from a transcriptome generated by RNA‐Seq. A total of about 12 Gb sequences led to about 218,116 contigs, which were predicted to encode about 46,808 genes. Comparative expression analysis showed 8392 uniquely expressed genes in the immune‐challenged larvae. Differentially expressed gene (DEG) analysis among the commonly expressed genes indicated that 782 genes were upregulated and 548 genes were downregulated in the expressions after bacterial challenge. These immune‐associated genes included pattern recognition receptors, immune mediation/signaling genes, and various immune effectors. Specifically, the genetic components of the Toll, IMD, and JAK/STAT immune signaling pathways were included in the DEG database. These results demonstrate the immune responses of A. sapporensis larvae and suggest the genes associated with the immune responses in this nonmodel insect.
Association Between Severe Nonadherence to Hydroxychloroquine and Systemic Lupus Erythematosus Flares, Damage, and Mortality in 660 Patients From the SLICC Inception Cohort
Authors: Nguyen Yann , Blanchet Benoît , Urowitz Murray B. , Hanly John G. , Gordon Caroline , Bae Sang‐Cheol , Romero‐Diaz Juanita , Sanchez‐Guerrero Jorge , Clarke Ann E. , Bernatsky Sasha , Wallace Daniel J. , Isenberg David A. , Rahman Anisur , Merrill Joan T. , Fortin Paul R. , Gladman Dafna D. , Bruce Ian N. , Petri Michelle , Ginzler Ellen M. , Dooley Mary Anne , Ramsey‐Goldman Rosalind , Manzi Susan , Jönsen Andreas , Alarcón Graciela S. , Van Vollenhoven Ronald F. , Aranow Cynthia , Le Guern Véronique , Mackay Meggan , Ruiz‐Irastorza Guillermo , Lim S. Sam , Inanc Murat , Kalunian Kenneth C. , Jacobsen Søren , Peschken Christine A. , Kamen Diane L. , Askanase Anca , Buyon Jill , Costedoat‐Chalumeau Nathalie
Published: July 2023

Objective

The goals of this study were to assess the associations of severe nonadherence to hydroxychloroquine (HCQ), objectively assessed by HCQ serum levels, and risks of systemic lupus erythematosus (SLE) flares, damage, and mortality rates over five years of follow‐up.

Methods

The Systemic Lupus International Collaborating Clinics (SLICC) Inception Cohort is an international multicenter initiative (33 centers throughout 11 countries). The serum of patients prescribed HCQ for at least three months at enrollment were analyzed. Severe nonadherence was defined by a serum HCQ level <106 ng/mL or <53 ng/mL for HCQ doses of 400 or 200 mg/day, respectively. Associations with the risk of a flare (defined as a Systemic Lupus Erythematosus Disease Activity Index 2000 increase ≥4 points, initiation of prednisone or immunosuppressive drugs, or new renal involvement) were studied with logistic regression, and associations with damage (first SLICC/American College of Rheumatology Damage Index [SDI] increase ≥1 point) and mortality with separate Cox proportional hazard models.

Results

Of the 1,849 cohort participants, 660 patients (88% women) were included. Median (interquartile range) serum HCQ was 388 ng/mL (244–566); 48 patients (7.3%) had severe HCQ nonadherence. No covariates were clearly associated with severe nonadherence, which was, however, independently associated with both flare (odds ratio 3.38; 95% confidence interval [CI] 1.80–6.42) and an increase in the SDI within each of the first three years (hazard ratio [HR] 1.92 at three years; 95% CI 1.05–3.50). Eleven patients died within five years, including 3 with severe nonadherence (crude HR 5.41; 95% CI 1.43–20.39).

Conclusion

Severe nonadherence was independently associated with the risks of an SLE flare in the following year, early damage, and five‐year mortality.

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Uninterrupted real‐time cerebral stress level monitoring using wearable biosensors: A review
Authors: Mishra Anuja , Agrawal Mukti , Ali Aaliya , Garg Prakrati
Published: July 2023

Stress is the major unseen bug for the health of humans with the increasing workaholic era. Long periods of avoidance are the main precursor for chronic disorders that are quite tough to treat. As precaution is better than cure, stress detection and monitoring are vital. Although there are ways to measure stress clinically, there is still a constant need and demand for methods that measure stress personally and in an ex vitro manner for the convenience of the user. The concept of continuous stress monitoring has been introduced to tackle the issue of unseen stress accumulating in the body simultaneously with being user‐friendly and reliable. Stress biosensors nowadays provide real‐time, noninvasive, and continuous monitoring of stress. These biosensors are innovative anthropogenic creations that are a combination of biomarkers and indicators like heart rate variation, electrodermal activity, skin temperature, galvanic skin response, and electroencephalograph of stress in the body along with machine learning algorithms and techniques. The collaboration of biological markers, artificial intelligence techniques, and data science tools makes stress biosensors a hot topic for research. These attributes have made continuous stress detection a possibility with ease. The advancement in stress biosensing technologies has made a great impact on the lives of human beings so far. This article focuses on the comprehensive study of stress‐indicating biomarkers and the techniques along with principles of the biosensors used for continuous stress detection. The precise overview of wearable stress monitoring systems is also sectioned to pave a pathway for possible future research studies.
Methodology for fast development of digital solutions in integrated continuous downstream processing
Authors: Andersson Niklas , Fons Joaquín Gomis , Isaksson Madelène , Tallvod Simon , Espinoza Daniel , Sjökvist Linnea , Andersson Gusten Zandler , Nilsson Bernt
Published: July 2023

The methodology for production of biologics is going through a paradigm shift from batch‐wise operation to continuous production. Lot of efforts are focused on integration, intensification, and continuous operation for decreased foot‐print, material, equipment, and increased productivity and product quality. These integrated continuous processes with on‐line analytics become complex processes, which requires automation, monitoring, and control of the operation, even unmanned or remote, which means bioprocesses with high level of automation or even autonomous capabilities. The development of these digital solutions becomes an important part of the process development and needs to be assessed early in the development chain. This work discusses a platform that allows fast development, advanced studies, and validation of digital solutions for integrated continuous downstream processes. It uses an open, flexible, and extendable real‐time supervisory controller, called Orbit, developed in Python. Orbit makes it possible to communicate with a set of different physical setups and on the same time perform real‐time execution. Integrated continuous processing often implies parallel operation of several setups and network of Orbit controllers makes it possible to synchronize complex process system. Data handling, storage, and analysis are important properties for handling heterogeneous and asynchronous data generated in complex downstream systems. Digital twin applications, such as advanced model‐based and plant‐wide monitoring and control, are exemplified using computational extensions in Orbit, exploiting data and models. Examples of novel digital solutions in integrated downstream processes are automatic operation parameter optimization, Kalman filter monitoring, and model‐based batch‐to‐batch control.
Injection of a PMMA‐doped MSC spheroid gel for the treatment of painful osteoporotic vertebral compression fractures
Authors: Ko Wan‐Kyu , Lee Daye , Kim Seong Jun , Han Gong Ho , Lee Donghyun , Sheen Seung Hun , Sohn Seil
Published: July 2023

We aimed to develop a biocompatible treatment to overcome the limitations of polymethyl methacrylate (PMMA) vertebroplasty for osteoporotic compression fracture patients. We synthesized an injectable hydrogel containing PMMA. Mesenchymal stem cell (MSC) spheroids were included in the injectable PMMA‐doped gel (= PMMA‐doped spheroid gel). In vitro, the osteogenic/anti‐inflammatory effects of the embedded spheroids were investigated by the quantitative real‐time polymerase chain reaction method. In vivo, we used ovariectomy (OVX)‐induced osteoporotic rats with injured femurs to investigate the pain‐relief effects. The OVX rats were divided into four groups according to the materials injected (non, PMMA, PMMA gel, and PMMA‐spheroid gel) into the lesion. The immunofluorescence (IF) intensity levels of painful markers in dorsal root ganglia (DRG) were measured. In vitro, a volumetric ratio of the gel of 8 (gel):2 (PMMA) was non‐cytotoxic for MSCs and promoted the expression of osteogenic/anti‐inflammatory markers. In vivo, the values of several bone parameters in the PMMA‐doped spheroid gel group showed remarkable increases compared to those in the PMMA group. In addition, the IF intensity levels of the painful markers were noticeably decreased in the PMMA‐spheroid gel group. We, therefore, suggest that this treatment can be useful for osteoporotic vertebral compression fracture patients.
The contribution of prognostic factors to socio‐demographic inequalities in breast cancer survival in Victoria, Australia
Authors: Stuart Geoffrey W. , Chamberlain James A. , te Marvelde Luc
Published: July 2023

Background

Breast cancer survival in Australia varies according to socio‐economic status (SES) and between rural and urban places of residence. Part of this disparity may be due to differences in prognostic factors at the time of diagnosis.

Methods

Women with invasive breast cancer diagnosed from 2008 until 2012 (n = 14,165) were identified from the Victorian Cancer Registry and followed up for 5 years, with death from breast cancer or other causes recorded. A prognostic score, based on stage at diagnosis, cancer grade, whether the cancer was detected via screening, reported comorbidities and age at diagnosis, was constructed for use in a mediation analysis.

Results

Five‐year breast cancer mortality for women with breast cancer who were in the lowest quintile of SES (10.3%) was almost double that of those in the highest quintile (5.7%). There was a small survival advantage (1.7% on average, within each socio‐economic quintile) of living in inner‐regional areas compared with major cities. About half of the socio‐economic disparity was mediated by prognostic factors, particularly stage at diagnosis and the presence of comorbidities. The inner‐regional survival advantage was not due to differences in prognostic factors.

Conclusions

Part of the socio‐economic disparity in breast cancer survival could be addressed by earlier detection in, and improved general health for, more disadvantaged women. Further research is required to identify additional causes of socio‐economic disparities as well as the observed inner‐regional survival advantage.
Advances in the use of ECMO in oncology patient
Authors: Teng Xiangnan , Wu Jiali , Liao Jing , Xu Shanling
Published: July 2023

Background

Over the past decade, ECMO has provided temporary cardiopulmonary support to an increasing number of patients, but the use of extracorporeal membrane oxygenation (ECMO) to provide temporary respiratory and circulatory support to adult patients with malignancy remains controversial.

Objectives

This paper reviews the specific use of extracorporeal membrane oxygenation (ECMO) in oncology patients.

Methods

We searched PubMed, CINAHL, Cochrane Library, and Embase databases for studies on the use of ECMO in cancer patients between 1998 and 2022. Twenty‐four retrospective, prospective, and case reports were included. The primary outcome was survival during extracorporeal membrane oxygenation.

Results

Most studies suggest that ECMO can be used in oncology patients requiring life support during surgery, solid tumor patients with respiratory failure, and hematological tumor patients requiring ECOM as a supportive means of chemotherapy; however, in patients with hematologic oncology undergoing hematopoietic stem cell transplantation, there was no clear benefit after the use of ECMO.

Conclusion

Current research suggests that ECMO may be considered as a salvage support in specific cancer patients. Future studies should include larger sample sizes than those already conducted, including studies on efficacy, adverse events, and health.
The effects of coagulation factors and their inhibitors on proliferation and migration in colorectal cancer
Authors: Rees Peter Adam , Castle John , Clouston Hamish William , Lamb Rebecca , Singh Urvashi , Duff Sarah Elizabeth , Kirwan Cliona Clare
Published: July 2023

Background/Aim

Clotting factors promote cancer development. We investigated if coagulation proteins promote proliferation and migration in colorectal cancer (CRC) cell lines and whether their direct inhibitors can attenuate these effects.

Materials and Methods

DLD‐1 and SW620 cells were treated with tissue factor (0, 50, 100 and 500 pg/mL ± 10 μg/mL 10H10 [anti‐tissue factor antibody]), thrombin (0.0, 0.1, 1.0 and 10.0 U/mL ± 0.5 μM dabigatran [thrombin inhibitor]) and Factor Xa, FXa (0.0, 0.1, 1.0 and 10.0 U/mL ± 100 ng/mL rivaroxaban [FXa inhibitor]) and their effects on proliferation and migration were quantified using the PrestoBlue® and transwell migration assays, respectively.

Results

Thrombin increased proliferation from 48 h treatment compared to its control (48 h 6.57 ± 1.36 u vs. 2.42 ± 0.13 u, p = 0.001, 72 h 9.50 ± 1.54 u vs. 4.50 ± 0.47 u, p = 0.004 and 96 h 10.77 ± 1.72 u vs. 5.57 ± 0.25 u, p = 0.008). This increase in proliferation was attenuated by dabigatran at 72 h (2.23 ± 0.16 u vs. 3.26 ± 0.43 u, p = 0.04).

Tissue factor (0 pg/mL 20.7 ± 1.6 cells/view vs. 50 pg/mL 32.4 ± 1.9 cells/view, p = 0.0002), FXa (0.0 U/mL 8.9 ± 1.1 cells/view vs. 10.0 U/mL 17.7 ± 1.7 cells/view, p < 0.0001) and thrombin (0.0 U/mL 8.9 ± 1.3 cells/view vs. 10.0 U/mL 20.2 ± 2.0 cells/view, p < 0.0001) all increased migration compared to their controls. However, their direct inhibitors did not attenuate these increases.

Conclusion

Thrombin, FXa and TF all increase migration in CRC in vitro. Thrombin induced increase in proliferation is abrogated by dabigatran. Dabigatran may have potential as an anti‐cancer therapy in CRC.
Nanotechnology Formulations Designed with Herbal Extracts and Their Therapeutic Applications – A Review
Authors: Oliveira da Silva Lucas , Assunção Ferreira Magda Rhayanny , Lira Soares Luiz Alberto
Published: July 2023

Because of the increasing demand for natural products, the development of nanoformulations containing natural active ingredients requires in‐depth knowledge of the substances used, methods of obtaining, and stability profiles to ensure product quality, efficacy, and safety. Considering this, the bibliography of the last five years presented in databases (PubMed and Science Direct) was discussed in this work, discussing the study with medicinal plants to obtain active metabolites with therapeutic properties, as well as the different nano‐systems responsible for carrying these molecules. Due to the wealth of biodiversity found in the world, many species are submitted to the extraction process for several purposes. However, identifying, classifying, and quantifying the constituents of herbal matrices are crucial steps to verify their therapeutic potential. In addition, knowing the techniques of production and elaboration of nanotechnology products allows the optimization of the incorporation of herbal extracts as an innovation target. For studies to be successful, it is necessary to exhaust experimental results that guarantee the efficacy, safety, and quality of natural nanosystems, with the objective of obtaining reliable answers in nanotechnology therapy.
Design of Cationic Lipids with Acetal Linkers: Conformational Preferences, Hydrolytic Stability, and High Drug‐Loading Abilities
Authors: Kumar Awasthi Anand , Bhagat Somnath D. , Banerjee Aditi , Srivastava Aasheesh
Published: July 2023

Lipids are key constituents of numerous biomedical drug delivery technologies. Here, we present the design, synthesis and biophysical characterizations of a library of cationic lipids containing an acetal residue in their linker region. These cationic acetal lipids (CALs) were conveniently prepared through a trans‐acetalization protocol from commercially available precursors. NMR studies highlighted the conformational rigidity at the acetal residue and the high hydrolytic stability of these CALs. Fluorescence anisotropy studies revealed that the CAL with a pyridinium headgroup (CAL1) formed highly cohesive vesicular aggregates in water. These structural and self‐assembly features of the CAL1 allowed up to 196 % w/w loading of curcumin (Cur) as a representative hydrophobic drug. A reconstitutable formulation of Cur was obtained as a result, which could deliver the drug inside mammalian cells with very high efficiency. The hemocompatibility and cytocompatibility of CAL1 was significantly enhanced by creating a coating of polydopamine (PDA) onto its vesicular assemblies to produce hybrid lipid‐polymer nanocapsules. This work demonstrates rapid access to the useful synthetic lipid formulations with high potential in drug and gene delivery applications.
Robotic modified Strong procedure for superior mesenteric artery syndrome
Authors: Wasef Kareem , Hudnall Aaron , Schmidt Carl R. , Marsh J. Wallis , Boone Brian A.
Published: July 2023

Key Clinical Message

The robotic modified Strong procedure is a safe and effective approach for surgical management of superior mesenteric artery syndrome in properly selected patients.

Superior mesenteric artery syndrome is a rare syndrome of small bowel obstruction resulting from vascular compression of the duodenum. Here we present our modification of a robotic Strong procedure for the surgical management of SMA syndrome. This procedure is a safe and effective approach for management in properly selected patients.
Surgical resection of a large invasive mucinous adenocarcinoma: A case report
Authors: Yoshino Ryusei , Yoshida Nana , Ito Akane , Ujiie Nanami , Nakatsubo Masaki , Kitada Masahiro
Published: July 2023

Key Clinical Message

Invasive mucinous adenocarcinoma often presents with pneumonia‐like findings on imaging, which complicates its diagnosis. This case demonstrates that aggressive bronchoscopy is useful for examining infiltrating shadows in the lung field and large tumors occupying the entire lung lobe should be treated cautiously when lung parenchyma develops.
Sustainably Scaled Electrochemical Synthesis of 3‐Propyladipic Acid in Line with Fluctuating Grid Supply
Authors: Bednarz Roland J.‐R. , Jiménez‐Meneses Pilar , Gold Annika S. , Monllor‐Satoca Damián , Stenglein Andreas , Gómez Roberto , Waldvogel Siegfried R.
Published: July 2023

Chemical production is a significant contributor to global climate change, which expedites the growing demand for transitioning to more sustainable and climate‐friendly methodologies. Ideally this should include high compatibility with the fluctuating electricity supply which results from renewable energy sources in the electrical grid. Here we show an electrochemical path for the 3‐propyladipic acid synthesis from 4‐propylcyclohexanol implementing a semi‐technical electrochemical continuously stirred tank reactor. Following a Design of Experiments approach, we found a strong influence of the biphasic electrolyte mixing and the continuous feeding in of the substrate. By switching to an electrolyte recirculation mode and efficient mixing, the isolated product yield could be increased up to 31 % for a 10 L total reaction volume, indicating the potential for further scale‐up into the technical range. This reaction proceeds while forming several by‐products, which have not been fully described yet. A proposal for the formation mechanism is included.
FCCat 3 in Ronce‐les‐Bains: First Post‐COVID Catalytic Gathering for the French Catalytic Community
Authors: Boualleg Malika , Laurenti Dorothée , Tanchoux Nathalie
Published: July 2023

We report here on the organization and proceedings of FCCat 3, the 3rd French Conference on Catalysis, and the first in person since GECat 2019 (the annual conference of the French catalysis community) and the COVID pandemic, which took place in Ronce‐les‐Bains from 31 May to 3 June 2022. This international conference is held every 3 years since its first edition in 2016 and aims to bring together all catalysis communities, geographically or thematically.
Ammonia Synthesis by Mechanochemistry
Authors: Cuccu Federico , Browne Duncan L. , Porcheddu Andrea
Published: July 2023

The design and use of organic, inorganic, and metal‐based catalysts is critical to academic and industrial laboratories all around the world. In this framework, ammonia production embodies the most iconic use of catalysis. This review aims to describe the most recent and exciting developments in the mechanocatalytic preparation of ammonia.
“The Gourmet Murderer” – a mobile escape room on food chemistry
Authors: Schmidt Johann , Korte Tatjana , Amel Henning , Beeken Marco
Published: July 2023

„Eingesperrt in einem Restaurant, welches Schauplatz eines Mordes geworden ist, umgeben von hinterlassenen Spuren und unzähligen Verdächtigen, muss der Mörder überführt werden.“ In diesem linearen Escape Room müssen Jugendliche in möglichst kurzer Zeit über verschiedene Experimente der Lebensmittelchemie (u. a. Biuret‐ und Fehlingprobe, Ethanolnachweis) den Täter anhand seiner Ernährungsgewohnheiten enttarnen. Die Konzeption des Gourmet Mörders verfolgt das Ziel der intrinsisch motivierten Beschäftigung mit naturwissenschaftlichen Themen in einem jugendfreizeitlichen Kontext. Der mobile Escape Room wurde angesichts des motivierenden Potentials des Jugendfreizeitbereichs für die Arbeit im außerschulischen und außerunterrichtlichen Kontext konzipiert und erprobt. Ein erstes Feedback zum Escape Room Format mit 145 Teilnehmenden legt nahe, dass es geeignet ist, um in einem außerschulischen und außerunterrichtlichen Rahmen Begeisterung für das Praktizieren von Naturwissenschaften zu wecken.