bluuebunny/crossref_metadata_2025 huggingface dataset:
Inhibitory TCR Coreceptor PD-1 Is a Sensitive Indicator of Low-Level Replication of SIV and HIV-1
Authors: Salisch Nadine C. , Kaufmann Daniel E. , Awad Amany S. , Reeves R. Keith , Tighe Daniel P. , Li Yuan , Piatak Michael , Lifson Jeffrey D. , Evans David T. , Pereyra Florencia , Freeman Gordon J. , Johnson R. Paul
Published: December 2009

Ongoing antigenic stimulation appears to be an important prerequisite for the persistent expression of programmed death 1 (PD-1), an inhibitory TCR coreceptor of the CD28 family. Although recent publications have emphasized the utility of PD-1 as a marker for dysfunctional T cells in chronic viral infections, its dependence on antigenic stimulation potentially renders it a sensitive indicator of low-level viral replication. To explore the antigenic threshold for the maintenance of PD-1 expression on virus-specific T cells, we compared PD-1 expression on virus-specific and memory T cell populations in controlled and uncontrolled SIV and HIV-1 infection. In both controlled live attenuated SIV infection in rhesus macaques and HIV-1 infection in elite controllers, elevated levels of PD-1 expression were observed on SIV- and HIV-1–specific CD8+ T cells. However, in contrast to chronic wild-type SIV infection and uncontrolled HIV-1 infection, controlled SIV/HIV-1 infection did not result in increased expression of PD-1 on total memory T cells. PD-1 expression on SIV-specific CD8+ T cells rapidly decreased after the emergence of CTL escape in cognate epitopes, but was maintained in the setting of low or undetectable levels of plasma viremia in live attenuated SIV-infected macaques. After inoculation of naive macaques with a single-cycle SIV, PD-1 expression on SIV-specific CD8+ T cells initially increased, but was rapidly downregulated. These results demonstrate that PD-1 can serve as a sensitive indicator of persistent, low-level virus replication and that generalized PD-1 expression on T lymphocytes is a distinguishing characteristic of uncontrolled lentiviral infections.
Staphylococcal Complement Inhibitor Modulates Phagocyte Responses by Dimerization of Convertases
Authors: Jongerius Ilse , Puister Manon , Wu Jin , Ruyken Maartje , van Strijp Jos A.G. , Rooijakkers Suzan H.M.
Published: December 2009

The human pathogen Staphylococcus aureus produces several complement-evasion molecules that enable the bacterium to withstand the host immune response. The human-specific staphylococcal complement inhibitor (SCIN) blocks the central C3 convertase enzymes that trigger critical complement functions, such as C3b deposition, phagocytosis, and C5a generation. SCIN effectively blocks the conversion of C3 by alternative pathway C3 convertases (C3bBb), but also induces dimerization of these enzymes. In this study, we show that formation of dimeric convertases by SCIN is important for S. aureus immune evasion because it modulates complement recognition by phagocytic receptors. Dimeric, but not monomeric, SCIN convertases showed an impaired binding to complement receptor 1 and the complement receptor of the Ig superfamily. The dimerization site of SCIN is essential for its strong antiphagocytic properties. These studies provide critical insights into the unique immune-evasion strategies used by S. aureus.
Mitochondria Positioning Controls Local Calcium Influx in T Cells
Authors: Schwindling Christian , Quintana Ariel , Krause Elmar , Hoth Markus
Published: December 2009

Formation of an immunological synapse (IS) between APC and T cells activates calcium entry through ORAI channels, which is indispensable for T cell activation. Successful proliferation and maturation of naive T cells is possible only if premature inactivation of ORAI channels is prevented. Although it is undisputed that calcium entry through ORAI channels is required for T cell function, it is not known if calcium influx is uniformly distributed over the plasma membrane or if preferential local calcium entry sites (for instance, at the IS) exist. In this study, we show that mitochondrial positioning determines the magnitude of local calcium entry anywhere in the plasma membrane by reducing local calcium-dependent channel inactivation: if mitochondria are close to any given local calcium entry site, calcium influx is large; if they are not close, calcium influx is small. Following formation of the IS, mitochondria are preferentially translocated to the IS in a calcium influx-dependent manner but independent of the exact calcium influx site. Mitochondrial enrichment at the IS favors local calcium entry at the IS without the necessity to enrich ORAI channels at the IS. We conclude that local calcium entry rather than global calcium entry is the preferential mechanism of calcium entry at stable ISs in Th cells.
Mechanisms for Glycolipid Antigen-Driven Cytokine Polarization by Vα14i NKT Cells
Authors: Sullivan Barbara A. , Nagarajan Niranjana A. , Wingender Gerhard , Wang Jing , Scott Iain , Tsuji Moriya , Franck Richard W. , Porcelli Steven A. , Zajonc Dirk M. , Kronenberg Mitchell
Published: December 2009

Certain glycolipid Ags for Vα14i NKT cells can direct the overall cytokine balance of the immune response. Th2-biasing OCH has a lower TCR avidity than the most potent agonist known, α-galactosylceramide. Although the CD1d-exposed portions of OCH and α-galactosylceramide are identical, structural analysis indicates that there are subtle CD1d conformational differences due to differences in the buried lipid portion of these two Ags, likely accounting for the difference in antigenic potency. Th1-biasing C-glycoside/CD1d has even weaker TCR interactions than OCH/CD1d. Despite this, C-glycoside caused a greater downstream activation of NK cells to produce IFN-γ, accounting for its promotion of Th1 responses. We found that this difference correlated with the finding that C-glycoside/CD1d complexes survive much longer in vivo. Therefore, we suggest that the pharmacokinetic properties of glycolipids are a major determinant of cytokine skewing, suggesting a pathway for designing therapeutic glycolipids for modulating invariant NKT cell responses.
Cutting Edge: Resistance to Bacillus anthracis Infection Mediated by a Lethal Toxin Sensitive Allele of Nalp1b/Nlrp1b
Authors: Terra Jill K. , Cote Christopher K. , France Bryan , Jenkins Amy L. , Bozue Joel A. , Welkos Susan L. , LeVine Steven M. , Bradley Kenneth A.
Published: December 2009

Pathogenesis of Bacillus anthracis is associated with the production of lethal toxin (LT), which activates the murine Nalp1b/Nlrp1b inflammasome and induces caspase-1–dependent pyroptotic death in macrophages and dendritic cells. In this study, we investigated the effect of allelic variation of Nlrp1b on the outcome of LT challenge and infection by B. anthracis spores. Nlrp1b allelic variation did not alter the kinetics or pathology of end-stage disease induced by purified LT, suggesting that, in contrast to previous reports, macrophage lysis does not contribute directly to LT-mediated pathology. However, animals expressing a LT-sensitive allele of Nlrp1b showed an early inflammatory response to LT and increased resistance to infection by B. anthracis. Data presented here support a model whereby LT-mediated activation of Nlrp1b and subsequent lysis of macrophages is not a mechanism used by B. anthracis to promote virulence, but rather a protective host-mediated innate immune response.
Robust, Vaccine-Induced CD8+ T Lymphocyte Response against an Out-of-Frame Epitope
Authors: Maness Nicholas J. , Wilson Nancy A. , Reed Jason S. , Piaskowski Shari M. , Sacha Jonah B. , Walsh Andrew D. , Thoryk Elizabeth , Heidecker Gwendolyn J. , Citron Michael P. , Liang Xiaoping , Bett Andrew J. , Casimiro Danilo R. , Watkins David I.
Published: December 2009

Rational vaccines designed to engender T cell responses require intimate knowledge of how epitopes are generated and presented. Recently, we vaccinated 8 Mamu-A*02+ rhesus macaques with every SIV protein except Envelope (Env). Surprisingly, one of the strongest T cell responses engendered was against the Env protein, the Mamu-A*02–restricted epitope, Env788–795RY8. In this paper, we show that translation from an alternate reading frame of both the Rev-encoding DNA plasmid and the rAd5 vector engendered Env788–795RY8-specific CD8+ T cells of greater magnitude than “normal” SIV infection. Our data demonstrate both that the pathway from vaccination to immune response is not well understood and that products of alternate reading frames may be rich and untapped sources of T cell epitopes.
Cutting Edge: The Th1 Response Inhibits the Generation of Peripheral Regulatory T Cells
Authors: Caretto David , Katzman Shoshana D. , Villarino Alejandro V. , Gallo Eugenio , Abbas Abul K.
Published: December 2009

The possibility that effector T cells can be converted into forkhead box P3+ regulatory T cells (Tregs) has potential therapeutic implications. To analyze the relationship between Th1 effectors and Tregs, we have used a model of systemic autoimmunity in which both effector and Tregs arise from a single population specific for a transgene-encoded systemic protein. In vitro, the presence of IFN-γ inhibits Treg generation during activation. Using IFN-γ reporter mice, we demonstrate that IFN-γ–producing cells tend not to develop into Tregs, and Th1 priming of T cells prior to cell transfer limits the number of forkhead box P3+ T cells generated in vivo. Moreover, transfer of IFN-γ−/− or STAT1−/− T cells resulted in an increase in the number of Tregs. These data support a role for Th1 effector molecules and transcription factors in the control of peripheral Treg generation and demonstrates the limited plasticity of Th1 populations.
The Impact of Rapid Climate Change on Prehistoric Societies during the Holocene in the Eastern Mediterranean
Authors: Weninger Bernhard , Clare Lee , Rohling Eelco , Bar-Yosef Ofer , Böhner Utz , Budja Mihael , Bundschuh Manfred , Feurdean Angelica , Gebe Hans Georg , Jöris Olaf , Linstädter Jörg , Mayewski Paul , Mühlenbruch Tobias , Reingruber Agathe , Rollefson Gary , Schyle Daniel , Thissen Laurens , Todorova Henrieta , Zielhofer Christoph
Published: December 2009

In this paper we explore the impact of Rapid Climate Change (RCC) on prehistoric communities in the Eastern Mediterranean during the Early and Middle Holocene. Our focus is on the social implications of the four major climate cold anomalies that have recently been identified as key time-windows for global RCC (Mayewski et al. 2004). These cooling anomalies are well-dated, with Greenland ice-core resolution, due to synchronicity between warm/cold foraminifera ratios in Mediterranean core LC21 as a proxy for surface water temperature, and Greenland GISP2 non sea-salt (nss) [K+] ions as a proxy for the intensification of the Siberian High and for polar air outbreaks in the northeast Mediterranean (Rohling et al. 2002). Building on these synchronisms, the GISP2 agemodel supplies the following precise time-intervals for archaeological RCC research: (i) 8.6–8.0 ka, (ii) 6.0–5.2 ka, (iii) 4.2–4.0 ka and (iv) 3.1–2.9 ka calBP. For each of these RCC time intervals, based on detailed 14C-based chronological studies, we investigate contemporaneous cultural developments. From our studies it follows that RCC-related climatic deterioration is a major factor underlying social change, although always at work within a wide spectrum of social, cultural, economic and religious factors.
Trends in Travel Time to Obtain Surgical Care for Rural Patients
Authors: Mullens Cody Lendon , Collins Reagan A. , Kunnath Nicholas , Probst Janice C. , Ibrahim Andrew M.
Published: February 2025

This study investigates changes in travel time for rural and nonrural US patients undergoing surgical care from 2010 to 2020.
Patient Enrollment for Cardiovascular Clinical Trials in the United States
Authors: Khan Muhammad Shahzeb , Jamil Adeena , Shakoor Muteia , Greene Stephen J. , Fonarow Gregg C. , Bhatt Deepak L. , DiMaio J. Michael , Mack Michael J. , Butler Javed
Published: February 2025

This cross-sectional study evaluates enrollment trends in recent cardiovascular clinical trials.
Immune Checkpoint Inhibitors in Field Cancerization and Keratinocyte Cancer Prevention
Authors: Cox Charlotte , Brown Susan , Walpole Euan , Roy Edwige , Dousset Lea , Ladwa Rahul , Khosrotehrani Kiarash
Published: February 2025

Importance

Therapies for individual keratinocyte carcinomas (KCs) do not prevent the onset of new KCs in a field of sun damage, and therefore the KC burden remains unchanged.

Objective

To investigate the association of immune checkpoint inhibitors (ICIs) with changes in field cancerization evaluated by the number of actinic keratoses (AKs) and KCs at baseline compared with 12 months after starting ICI therapy.

Design, Setting, and Participants

This prospective cohort study was performed at the outpatient oncology clinic of a single tertiary public hospital in Brisbane, Australia, from April 1, 2022, to November 30, 2023. Consecutive immunocompetent adults starting therapy with an inhibitor for programmed cell death 1 (PD-1) or programmed cell death ligand 1 (PDL-1) for any active cancer, with a planned treatment duration of at least 6 months, and who exhibited clinical AKs on their forearms were eligible. Those with immunosuppression, concurrent chemotherapy or radiotherapy, or recent topical fluorouracil use were excluded.

Exposures

Intravenous ICI therapy, either PD-1 or PDL-1 inhibitors with or without a cytotoxic T-lymphocyte–associated protein 4 inhibitor, with therapy duration determined by the treating oncologist.

Main Outcomes and Measures

Clinical AKs were counted and photographed before and 3, 6, and 12 months after starting ICI therapy. KC numbers were evaluated based on histopathology reports of all skin lesions excised 12 months before and after starting ICI therapy. Participants’ medical history, primary cancer tumor response using Response Evaluation Criteria in Solid Tumors, and adverse events were recorded.

Results

A total of 23 participants were recruited, of whom 17 (73.9%) were male, with a mean (SD) age of 69.7 (9.6) years. No participants withdrew; however, 4 died during the study due to disease progression. The mean (SD) AK number significantly decreased from 47.2 (33.8) at baseline to 14.3 (12.0) at 12 months (P < .001). Younger patients (8 of 12 [66.7%] vs 4 of 12 [33.3%]; P = .007) and those with a history of blistering sunburn (12 of 12 [100%] vs 0; P = .005) were more likely to reduce their AK numbers by 65% or greater. KC total numbers decreased from 42 in the 12 months before starting ICI therapy to 17 in the 12 months after. The number of cutaneous squamous cell carcinomas decreased from 16 to 5 in the same period.

Conclusions and Relevance

This pilot cohort study found that ICIs used for any cancer were associated with a significant reduction of AKs, suggesting potential as an immunopreventive strategy for high-risk individuals. Given the known effects of other chemopreventive agents on KCs, further investigation into ICIs managing field cancerization is required, especially considering toxicity and cost.
The Role of Formulation in Benzene Formation in Benzoyl Peroxide Products
Authors: Barbieri John S. , Rubin Courtney B. , Pham James P. , Wong Michelle
Published: February 2025

This quality improvement study examines the effects of formulation on benzene levels detected in over-the-counter benzoyl peroxide products.
Long-Term Survival by Number of Immune Checkpoint Inhibitors in PD-L1–Negative Metastatic NSCLC
Authors: Ponvilawan Ben , Bansal Dhruv , Abdel Karim Nagla , Ramakrishnan Rahul , Subramanian Janakiraman
Published: February 2025

This systematic review and meta-analysis evaluates long-term survival outcomes by number of immune checkpoint inhibitors among patients with programmed death-ligand 1 (PD-L1)–negative non–small cell lung cancer (NSCLC).
Stress About Eviction or Loss of Housing and Child Mental Health
Authors: Hanson Jamie L.
Published: February 2025

Importance

Eviction and housing loss are pressing public health concerns. Understanding how caregivers’ stress about eviction or loss of housing is associated with specific childhood psychiatric issues across development is important.

Objective

To examine associations between stress about eviction or loss of housing and caregiver-reported child depression, anxiety, attention-deficit/hyperactivity disorder (ADHD), and behavioral problems, while adjusting for sociodemographic factors.

Design, Setting, and Participants

This cross-sectional study analyzed data from the 2022 National Survey of Children's Health, a nationally representative survey of caregivers and children in the US. Data were collected between July 2022 and January 2023.

Exposure

Eviction or loss of housing.

Main Outcomes and Measures

Caregiver-reported child depression, anxiety, ADHD, and behavioral problems. Generalized linear mixed models were used to test associations with stress about eviction or loss of housing.

Results

From a sample of 54 103 families, 36 638 were included in the analytic sample (analytic sample mean [SD] age: 9.91 [4.62] years; sex assigned at birth, 18 901 male [52%]). In this study, stress about eviction or loss of housing was associated with depression in children (adjusted odds ratio [aOR], 1.10; 95% CI, 1.02-1.18). Stress about eviction or loss of housing was significantly associated with higher odds of reported anxiety in the base model (aOR, 1.26 (95% CI, 1.22-1.31) but not in the stringently adjusted model (aOR, 1.04; 95% CI, 1.00-1.08]). Associations were sometimes moderated by age, with stronger associations for younger children. Stress about eviction or loss of housing was not associated with ADHD or behavioral problems after adjustment.

Conclusions and Relevance

This study found that stress about eviction or loss of housing was associated with increased odds of internalizing issues, such as depression and anxiety, among children. Prospective longitudinal research is still needed to fully understand these complex associations over time. These findings underscore the importance of policies and interventions to address housing instability and its mental health consequences for children.
Electronic Nicotine Delivery System Advertisement Trends After US Federal Policy Changes
Authors: Shi Rui , Khayat Amal , Lee Juhan , Garrison Kathleen A. , Jebai Rime , Wackowski Olivia A. , Ozga Jenny E. , Stanton Cassandra A.
Published: February 2025

Importance

The US has implemented several regulatory measures to govern the sale and marketing of electronic nicotine delivery systems (ENDS). A nicotine warning statement requirement became effective in September 2018, the minimum legal age for tobacco and nicotine sales was raised to 21 years (Tobacco to 21 Act [T21]) in December 2019, and a January 2020 enforcement policy limited the sale of cartridge-based ENDS to only tobacco and menthol flavors.

Objective

To track the presence of the nicotine warning statement, youth appeals, and flavor cues in the advertisements of 3 ENDS brands with marketing authorization during the implementation of the US federal tobacco policies.

Design, Setting, and Participants

In this qualitative study, a content analysis was conducted on ENDS advertisements in the market from November 18, 2015, to June 26, 2022. All mobile, online display, outdoor, and print advertisements from the 3 US ENDS brands with marketing granted orders as of June 2022 were collected through Vivvix, a commercial advertisement intelligence company. Advertisements were excluded if they targeted businesses rather than consumers, contained display errors that were unretrievable, or were duplicates. Data analysis was completed in March 2024.

Exposure

The nicotine warning statement requirement, T21, and the flavor enforcement policy.

Main Outcomes and Measures

Nicotine warning statement compliance and presence of youth-appealing features (eg, young models, sports, and sex appeal) and nonmenthol, nontobacco flavor cues (eg, images of food, characterizing words like sweet or fruity) in ENDS advertisements before and after policy implementation.

Results

Of the 614 advertisements analyzed, the proportion containing the nicotine warning statement increased from 18 of 83 (21.7%) in the year preceding policy implementation to 147 of 152 (96.7%) in the subsequent year (χ21 = 144.5; P < .001). The proportion of advertisements containing any youth-appealing features increased from 35 of 171 (20.5%) in the year before T21 to 64 of 143 (44.8%) in the year after T21 (χ21 = 21.28; P < .001). There was no significant difference in flavor cues in the advertisements in the year before the flavor enforcement policy (30 of 161 [18.6%]) and those in the following year (38 of 149 [25.5%]) (χ21 = 2.13; P = .14).

Conclusions and Relevance

This qualitative study found immediate compliance with nicotine warning statements but no significant reduction in use of flavor cues and an increase in youth-appealing features in the first year after regulatory measures. The findings suggest a need for continued close monitoring of youth appeals in ENDS advertisements on all platforms to inform potential policies and interventions that can be used to counter the reach, appeal, and impact of these advertisements.
Disparities in Substance Use Disorder Telehealth Services
Authors: Walker Lauryn Saxe , Cui Manying , Cantor Jonathan , Craff Melody , Damberg Cheryl L. , Mafi John N. , Kahn Katherine L.
Published: February 2025

This cross-sectional study evaluates whether telehealth utilization is associated with changes in payer-based and rural-urban disparities in substance use disorder treatment.
Strengthening Safeguards for Psychiatric Uses of Ketamine
Authors: Barnett Brian S. , Weiss Roger D. , Sanacora Gerard
Published: February 2025

This Viewpoint discusses challenges related to ketamine use within psychiatry and offers recommendations for optimizing patient safety.
Once-Weekly Semaglutide in Adults With Alcohol Use Disorder
Authors: Hendershot Christian S. , Bremmer Michael P. , Paladino Michael B. , Kostantinis Georgios , Gilmore Thomas A. , Sullivan Neil R. , Tow Amanda C. , Dermody Sarah S. , Prince Mark A. , Jordan Robyn , McKee Sherry A. , Fletcher Paul J. , Claus Eric D. , Klein Klara R.
Published: February 2025

Importance

Preclinical, observational, and pharmacoepidemiology evidence indicates that glucagon-like peptide 1 receptor agonists (GLP-1RAs) may reduce alcohol intake. Randomized trials are needed to determine the clinical significance of these findings.

Objective

To evaluate the effects of once-weekly subcutaneous semaglutide on alcohol consumption and craving in adults with alcohol use disorder (AUD).

Design, Setting, and Participants

This was a phase 2, double-blind, randomized, parallel-arm trial involving 9 weeks of outpatient treatment. Enrollment occurred at an academic medical center in the US from September 2022 to February 2024. Of 504 potential participants assessed, 48 non–treatment-seeking participants with AUD were randomized.

Intervention

Participants received semaglutide (0.25 mg/week for 4 weeks, 0.5 mg/week for 4 weeks, and 1.0 mg for 1 week) or placebo at weekly clinic visits.

Main Outcomes and Measures

The primary outcome was laboratory alcohol self-administration, measured at pretreatment and posttreatment (0.5 mg/week). Secondary and exploratory outcomes, including prospective changes in alcohol consumption and craving, were assessed at outpatient visits.

Results

Forty-eight participants (34 [71%] female; mean [SD] age, 39.9 [10.6] years) were randomized. Low-dose semaglutide reduced the amount of alcohol consumed during a posttreatment laboratory self-administration task, with evidence of medium to large effect sizes for grams of alcohol consumed (β, −0.48; 95% CI, −0.85 to −0.11; P = .01) and peak breath alcohol concentration (β, −0.46; 95% CI, −0.87 to −0.06; P = .03). Semaglutide treatment did not affect average drinks per calendar day or number of drinking days, but significantly reduced drinks per drinking day (β, −0.41; 95% CI, −0.73 to −0.09; P = .04) and weekly alcohol craving (β, −0.39; 95% CI, −0.73 to −0.06; P = .01), also predicting greater reductions in heavy drinking over time relative to placebo (β, 0.84; 95% CI, 0.71 to 0.99; P = .04). A significant treatment-by-time interaction indicated that semaglutide treatment predicted greater relative reductions in cigarettes per day in a subsample of individuals with current cigarette use (β, −0.10; 95% CI, −0.16 to −0.03; P = .005).

Conclusions and Relevance

These findings provide initial prospective evidence that low-dose semaglutide can reduce craving and some drinking outcomes, justifying larger clinical trials to evaluate GLP-1RAs for alcohol use disorder.

Trial Registration

ClinicalTrials.gov Identifier: NCT05520775
Management of Perforated Peptic Ulcer
Authors: Arshad Seyed A. , Murphy Patrick , Gould Jon C.
Published: February 2025

Importance

Perforated peptic ulcer disease (PUD) affects 4 million people annually worldwide, with a lifetime prevalence of 5% to 10%. Of those affected, 5% will progress to the point of perforation. Despite advances in the understanding and treatment, perforated PUD continues to have a high rate of morbidity (50%) and mortality (30%). This review summarizes the current evidence on management of perforated PUD, including management of failed repairs.

Observations

Approaches for repair include primary closure and omental patch closure. Omental patch may be most useful in large perforations with friable tissue. Minimally invasive surgery is the preferred approach in perforated PUD, with improved outcomes compared with open techniques. Leak from the ulcer after repair is seen in approximately 12% to 17% of cases. Approaches to releak include expectant management, radiologic and/or endoscopic intervention, and repeat surgery. Morbidity and mortality after releak are especially high, and complete healing of the leak may take time.

Conclusions and Relevance

Despite advances in medical management and surgical techniques, perforated PUD continues to have a relatively high rate of morbidity and mortality. Minimally invasive surgery is the current preferred treatment approach.
Temporal Trends and Demographic Insights into Mortality from Systemic Lupus Erythematosus, 1999‐2020
Authors: Daoud Ansaam , Dweik Loai , Pamuk Omer
Published: February 2025

Objective

Previous studies showed a decline in Systemic Lupus Erythematosus (SLE) mortality rates from 1968 to 2013, yet mortality rates remained high relative to non‐SLE mortality, with notable disparities. We aimed to delineate demographic characteristics associated with SLE mortality and map out the national and geographic trends of the last two decades.

Methods

We analyzed SLE mortality data from 1999 to 2020 using the Centers for Disease Control and Prevention's Wide‐Ranging Online Data for Epidemiologic Research Multiple Cause of Death database. Age‐adjusted mortality rates (AAMRs) were computed based on sex, race and ethnicity, and state. Trends over the study period were evaluated using a simple linear regression model.

Results

From 1999 to 2020, we identified 27,213 deaths with SLE as the underlying cause in the United States. Females experienced higher AAMR (6.21/per million, 95%CI: 6.13‐6.29) than males (1.20/per million, 95%CI: 1.16‐1.24). African Americans (AA) had the highest AAMR (10.7/per million, 95% CI: 10.48‐10.92), particularly among females (17.68/per million, 95%CI: 17.29‐18.06). Linear regression analysis found a significant decline in the SLE AAMR from 1999 to 2020 (R2=0.902), with decreases noticed across all demographic groups. The SLE AAMR to the non‐SLE AAMR ratio showed a sustained decline from 2005 to 2020 (R2 =0.8552). Analysis of the geographic distribution of SLE AAMR in the US reveals a pronounced concentration in Southern states.

Conclusions

Since 1999, SLE‐related mortality rates have consistently declined across various demographic groups, though rates remain disproportionately high in AAs, particularly among AA females and in Southern states.
Long Cycle Stability of All‐Solid‐State Lithium‐Sulfur Batteries at Low Pressure and Ambient Temperature: Addressing Contact and Diffusion Kinetics
Authors: Chen Peng , Qu Huainan , Zheng Dong , Zhang Xiaoxiao , Qu Deyang
Published: February 2025

The commercialization of all‐solid‐state lithium‐sulfur batteries (ASSLSBs) depends on maintaining high performance under low stack pressure. However, conventional ASSLSBs experience significant performance degradation under low pressure due to contact losses and diffusion kinetics challenges at solid‐solid triphase interfaces. This study decouples electrochemical contact area (ECA) losses from diffusion kinetics losses for the first time through a series of pressure‐dependent electrochemical tests. Additionally, the cathode volume changes are investigated using an isolated real‐time displacement test. Findings reveal that contact losses primarily occur during charging, while diffusion kinetics are more sensitive to reduced stack pressure during discharging. To mitigate this issue, metallic indium (In) is incorporated into cathode composites to enhance the triphase interfaces. During cycling, In spheres transform in situ into In2S3/InS, significantly reducing volume fluctuations and improving ECA retention and diffusion kinetics under various pressures (0.5–7 MPa). As a result, ASSLSBs with In additive demonstrate markedly enhanced electrochemical performance under low stack pressure at room temperature, achieving 810 mAh g−1 at 1 MPa and 1198 mAh g−1 at 7 MPa, (0.1C, 28 °C). The work provides revolutionary insights for the development of high‐energy ASSLSBs and other systems suffering large volume changes.
Aerosol Jet Printing of Superhydrophobic Surfaces
Authors: Zhong Ke , Rozsa Jace , Patel Dinesh K. , Yao Lining , Fedder Gary K. , Islam Mohammad F.
Published: February 2025

A method for creating superhydrophobic surfaces is presented by aerosolizing polymer solutions into micrometer‐sized droplets and converting them into microgel particles during spatially controlled deposition using an aerosol jet printer. The polymer solutions are composed of marginally hydrophobic disulfide‐polydimethylsiloxane (DS‐PDMS) in three solvents with varying vapor pressures. The experiments, combined with an analytical model, demonstrate that solvents with high vapor pressures evaporate from the droplets during flight from the printer nozzle to the substrate. This evaporation increases the DS‐PDMS volume fraction in the droplets above the polymer gelation threshold. As a result, the droplets transform into microgel particles. This transformation leads to the formation of rough, superhydrophobic surfaces. Conversely, solvents with lower vapor pressures do not evaporate sufficiently, preventing DS‐PDMS volume fraction from reaching the gelation threshold. These droplets coalesce upon deposition, producing smooth surfaces with hydrophobicity similar to intrinsic DS‐PDMS. Heating the surfaces to 90 °C or above eliminates superhydrophobicity by de‐gelling the DS‐PDMS, allowing droplet coalescence. Potential applications of this method include droplet manipulation, microreactors for reactant mixing, water‐oil separation, and retardation of droplet evaporation.
Laser In Situ Synthesis of Wide Bandgap Tunable Perovskite and Its Application in Micro‐LEDs
Authors: Xu Rongrong , Yin Qianxi , You Junyi , Wang Xiaoting , Li Mulin , Huang Xianliang , Chen Jun , Zeng Haibo
Published: February 2025

Laser patterning of perovskite is a novel technology with the advantages of high speed, programmability, and maskless, which is ideal for fabricating micro light‐emitting diodes (micro‐LED) color conversion layers (CCL). This work reports a method for laser in situ synthesis of wide bandgap tunable perovskite with an emission spectrum from 475 to 667 nm. Based on the photonic effect of continuous wave (CW) laser and the thermal quenching phenomenon of perovskite, ultra‐high precision patterning with a minimum linewidth of 750 nm and a maximum dot‐pixel per inch (PPI) of 5684 is achieved. More importantly, significant improvements in perovskite stability and integration of red‐green dual‐color dot arrays are achieved through in‐depth studies of polymer matrices and precursor solvents. The red‐green dual‐color integrated dot arrays using blue micro‐LED chips, which is a great impetus to the research of micro‐LED full‐color displays, are also successfully excited.
Cobalt/Salox‐Catalyzed Stereoselective C−H Functionalization: Enantioselective Construction of Axially Chiral Cyclic Phosphinamides with P‐Stereogenic Center
Authors: Jiang Bo , Wang Hui , Sun Xiaobin , Qiao Yiyang , Xu Xiufang , Miao Zhiwei
Published: February 2025

We describe a novel cobalt/salicyloxazoline (Salox) catalytic system for enantioselective C−H functionalization, enabling the synthesis of P‐stereogenic and axially chiral cyclic phosphinic amides. Chiral Salox ligands, conveniently prepared in a single step from salicylonitriles and chiral amino alcohols, facilitated this transformation with excellent enantioselectivities (92‐99% ee) and moderate to good yields (31 examples, 45–89%). Mechanistic studies implicate a cobalt (III/IV/II) catalytic cycle in the C−H annulation process, providing valuable insights into the stereoselective reaction pathway.
Synthesis of Nitrogen‐Doped Platinum–Neodymium Nanoalloy Catalyst by Liquid‐Phase Reduction for Oxygen Reduction Reaction
Authors: Jiang Hang , Liu Qianwen , Song Wei , Gong Pei , Yu Zhihong , Liang Zhicheng
Published: February 2025

Proton exchange membrane fuel cells (PEMFCs) have attracted significant research interest due to their ability to generate only water and energy. PEMFCs operate based on the principle of redox reactions, which require a catalyst for the individual half‐reactions. However, the commonly used platinum (Pt)‐based catalysts are expensive, and their performance needs enhancement. In this study, an effective strategy is presented for preparing Pt–rare earth nanoalloy catalysts, achieving improvements in catalytic performance while reducing costs. Additionally, through urea modification, a novel carbon carrier (XC‐72) is successfully developed, which is widely utilized as a catalyst support in fuel cells. The Pt–Nd@HCN‐400 catalyst is synthesized by combining the newly developed carrier with the Pt–Nd alloy. Under standard fuel cell operating conditions, this catalyst exhibited a 5% increase in durability compared to its unmodified counterpart. This study offers a promising approach for enhancing the durability of PEMFC catalysts.
Anti‐Inflammatory Macrophage‐Derived Exosomes Modified With Self‐Antigen Peptides for Treatment of Experimental Autoimmune Encephalomyelitis
Authors: Li Qiaoyun , Park Jinwon , Kim Jung Suk , Le Quoc‐Viet , Lee Jaiwoo , Oh Yu‐Kyoung
Published: February 2025

Current treatments for autoimmune diseases often involve broad‐acting immunosuppressants, which carry risks such as infections and malignancies. This study investigates whether exosomes derived from anti‐inflammatory macrophages (AE) and decorated with myelin oligodendrocyte glycoprotein (MOG) peptide (AE/M) can induce immune tolerance in autoimmune diseases. Experimental autoimmune encephalomyelitis (EAE), a mouse model for multiple sclerosis, serves as the autoimmune disease model. Exosomes derived from myoblasts or fibroblasts are also modified with MOG peptides for comparison. Unlike their myoblast or fibroblast counterparts, exosomes from anti‐inflammatory macrophages demonstrate a targeted capacity toward antigen‐presenting cells. Moreover, AE/M uniquely promotes the differentiation of dendritic cells (DC) into a tolerogenic phenotype. When splenocytes are treated with AE/M, an increased population of tolerogenic DC (tolDC) is observed, even under proinflammatory stimuli. Subcutaneous administration of AE/M in the EAE mouse model results in MOG peptide‐specific immune tolerance and preserves motor coordination. In contrast to treatments with fibroblast‐ or myoblast‐derived exosomes modified with MOG peptides, AE/M treatment provides complete protection from EAE in mice. These findings highlight the potential of self‐antigen modified AE as a versatile and adaptable nanoplatform for the treatment of various autoimmune diseases.
A Smart Visualized Phototherapy Switch: From NIR‐I Imaging‐Guided Photodynamic Therapy to NIR‐II‐Guided Photothermal Therapy for Enhanced Cascade Tumor Photoablation
Authors: Sun Lixin , Wu Hongyu , Zhang Ziwen , Wu Kehuan , Sun Jie , Dong Xuemei , Dong Chengjun , Zhao Chunchang , Gu Xianfeng , Qu Da‐Hui
Published: February 2025

Imaging‐guided phototherapy holds promise for precision cancer treatment. However, most photosensitizers have only a singular modality of photodynamic therapy (PDT) or photothermal therapy (PTT), which make their therapeutic efficacy severely limited by the hypoxic and complex tumor microenvironment (TME). In this article, we provide a smart platform design (BOD‐D) based on a visualized light‐triggered phototherapeutic switch for transforming cancer therapy from near‐infrared (NIR)‐I imaging‐guided PDT to activatable NIR‐II‐guided PTT while releasing nitric oxide (NO) for gas therapy (GT). BOD‐D releases native NIR one‐region fluorescence signals in tumors, which is used to direct robust PDT for tumor killing. As PDT is administered, the decreasing oxygen content in TME becomes progressively insufficient to maintain its excellent cell‐killing effect. Subsequently, light triggers the dissociation of NO in BOD‐D, activating a photothermal agent BOD‐T that emits NIR‐II fluorescence, for subsequent PTT. Notably, not only the light‐mediated therapeutic mechanism can be switched from NIR‐I‐guided PDT to NIR‐II‐guided PTT, but also the NO released during this process will be used for GT to sensitize the above PDT and PTT. Our study contributes to the design of intelligent photosensitizers for cascade tumor photoablation.
A brain DNA co‐methylation network analysis of psychosis in Alzheimer's disease
Authors: Kouhsar Morteza , Weymouth Luke , Smith Adam R. , Imm Jennifer , Bredemeyer Claudia , Wedatilake Yehani , Torkamani Ali , Bergh Sverre , Selbæk Geir , Mill Jonathan , Ballard Clive , Sweet Robert A. , Kofler Julia , Creese Byron , Pishva Ehsan , Lunnon Katie
Published: February 2025

INTRODUCTION

The presence of psychosis in Alzheimer's disease (AD) is suggested to be associated with distinct molecular and neuropathological profiles in the brain.

METHODS

We assessed brain DNA methylation in AD donors with psychosis (AD+P) and without psychosis (AD−P) using the EPIC array. Weighted gene correlation network analysis identified modules of co‐methylated genes in a discovery cohort (PITT‐ADRC: N = 113 AD+P, N = 40 AD−P), with validation in an independent cohort (BDR: N = 79 AD+P, N = 117 AD−P), with Gene Ontology and cell‐type enrichment analysis. Genetic data were integrated to identify methylation quantitative trait loci (mQTLs), which were co‐localized with GWAS for related traits.

RESULTS

We replicated one AD+P associated module, which was enriched for synaptic pathways and in excitatory and inhibitory neurons. mQTLs in this module co‐localized with variants associated with schizophrenia and educational attainment.

DISCUSSION

This represents the largest epigenetic study of AD+P to date, identifying pleiotropic relationships between AD+P and related traits.

Highlights

DNA methylation was assessed in the prefrontal cortex in subjects with AD+P and AD−P.

WGCNA identified six modules of co‐methylated loci associated with AD+P in a discovery cohort.

One of the modules was replicated in an independent cohort.

This module was enriched for synaptic genes and in excitatory and inhibitory neurons.

mQTLs mapping to genes in the module co‐localized with GWAS loci for schizophrenia and educational attainment.
Transcriptome analysis of early‐ and late‐onset Alzheimer's disease in Korean cohorts
Authors: Han Sang‐Won , Hwang Jiyun , Park Tamina , Pyun Jung‐Min , Lee Joo‐Yeon , Park Jeong Su , Bice Paula J. , Liu Shiwei , Yun Sunmin , Jeong Jibin , Risacher Shannon L. , Saykin Andrew J. , Byun Min Soo , Yi Dahyun , Sung Joohon , Lee Dong Young , Kim SangYun , Nho Kwangsik , Park Young Ho
Published: February 2025

INTRODUCTION

The molecular mechanisms underlying early‐onset Alzheimer's disease (EOAD) and late‐onset Alzheimer's disease (LOAD) remain incompletely understood, particularly in Asian populations.

METHODS

RNA‐sequencing was carried out on blood samples from 248 participants in the Seoul National University Bundang Hospital cohort to perform differential gene expression (DGE) and weighted gene co‐expression network analysis. Findings were replicated in an independent Korean cohort (N = 275).

RESULTS

DGE analysis identified 18 and 88 dysregulated genes in EOAD and LOAD, respectively. Network analysis identified a LOAD‐associated module showing a significant enrichment in pathways related to mitophagy, 5′ adenosine monophosphate‐activated protein kinase signaling, and ubiquitin‐mediated proteolysis. In the replication cohort, downregulation of SMOX and PLVAP in LOAD was replicated, and the LOAD‐associated module was highly preserved. In addition, SMOX and PLVAP were associated with brain amyloid beta deposition.

DISCUSSION

Our findings suggest distinct molecular signatures for EOAD and LOAD in a Korean population, providing deeper understanding of their diagnostic potential and molecular mechanisms.

Highlights

Analysis identified 18 and 88 dysregulated genes in early‐onset Alzheimer's disease (EOAD) and late‐onset Alzheimer's disease (LOAD), respectively.

Expression levels of SMOX and PLVAP were downregulated in LOAD.

Expression levels of SMOX and PLVAP were associated with brain amyloid beta deposition.

Pathways including mitophagy and 5′ adenosine monophosphate‐activated protein kinase signaling were enriched in a LOAD module.

A LOAD module was highly preserved across two independent cohorts.
Engineering Two‐Dimensional Nanomaterials for Photothermal Therapy
Authors: Zhang Haoyuan , Yang Min , Wu Qingyuan , Xue Jiajia , Liu Huiyu
Published: February 2025

Two‐dimensional (2D) nanomaterials offer a transformative platform for photothermal therapy (PTT) due to their unique physicochemical properties and exceptional photothermal conversion efficiencies. This Minireview summarizes the photothermal mechanisms of common 2D nanomaterials and details their synthesis, surface modification, and optimization strategies. Recent advances leveraging 2D nanomaterials for enhanced PTT are highlighted, with particular emphasis on synergistic therapeutic modalities. Despite the significant potential of 2D nanomaterials in PTT, challenges persist, including scalable and reproducible manufacturing, precise targeted delivery, understanding of the underlying biological interactions, and comprehensive assessment of long‐term biocompatibility and toxicity. Looking forward, emerging technologies such as machine learning are expected to play a crucial role in accelerating the design and optimization of 2D nanomaterials for PTT, enabling the prediction of optimal structures, properties, and therapeutic efficacy, and ultimately paving the way for personalized nanomedicine.
Highly Entangled Hydrogels by Photoiniferter‐Mediated Polymerization
Authors: Irvine Gavin , Myronidis Konstantinos , Pinto Fulvio , Kopeć Maciej
Published: February 2025

We report the synthesis of ultra‐high molecular weight (UHMW) poly(N,N‐dimethylacrylamide) (PDMAm) hydrogels with extremely low crosslinking densities by trithiocarbonate photoiniferter‐mediated reversible deactivation radical polymerization (RDRP). Fixing the photoiniferter to crosslinker ratio and gradually increasing the targeted degree of polymerization (DPtarget) allowed for simultaneous control over the crosslinking density and the average molecular weight (Mn) of the primary chains, both below and above the critical molecular weight of entanglement (Mc). Interestingly, a plateau in storage moduli (G’) was observed for UHMW PDMAm hydrogels with a sufficiently high DPtarget (>5,000), indicating a transition to the entanglement‐dominated regime, with no contribution from crosslinks to the overall modulus, thus indicating the formation of highly entangled hydrogels. These hydrogels exhibit enhanced properties such as high toughness and resistance to swelling despite their vanishingly small crosslinking densities. Furthermore, even when equipped with cleavable crosslinkers, the UHMW PDMAm hydrogels resist degradation due to dense entanglements which act as transient crosslinks preventing the gels from swelling, while sparse covalent crosslinks help to maintain their structural integrity and avoid chain disentanglement. This approach allows simple synthesis of elastic and tough hydrogels with a well‐defined structure and tuneable contributions from both crosslinks and entanglements.
Design, Preparation, Physicochemical Characterization, and DFT Calculations of Some Novel Complexes Based on Bi‐Dentate Imine Ligand: Biomedical Applications and Molecular Docking Approach
Authors: Abdel‐Rahman Laila H. , Al‐Farhan Badriah Saad , Nafady Ayman , Omar Inam , Aljohani Faizah S. , Shehata Mohamed R. , Kassem Ahmed M. , Abu‐Dief Ahmed M.
Published: February 2025

The complexes of Pd (II), VO (II), Cu (II), and Ni (II) with Schiff base (ABDS) derived from 2‐aminobenzothiazole with 4‐(diethylamino)salicylaldehyde have been prepared. Various spectroscopic methodologies for analysis, which might include 1H, 13C NMR, infrared spectra (IR), ultraviolet–visible (UV–vis), and magnetic values, have been applied to elucidate the construction of these chemicals. For each complex, the most suitable form has been proposed as a result. The chemical compound behaves as a bi‐dentate via NO donors into the material ions within octahedral shape about Cu2+, octahedral geometry for Ni2+, square pyramidal for VO (II), and square planner form around the Pd2+ ion. The substances were tested against different bacterial and fungal strains. They demonstrated effective inhibition against the harmful bacteria under study and cytotoxic activity (IC50) against (HCT‐116 cell line), (HepG‐2), and (MCF‐7). The metal chelates were shown to possess more antimicrobial activity than the free Schiff base chelate. The ABDS ligand had only moderate antioxidant activity, but the combined forms of V (IV), Ni (II), Cu (II), and Pd (II) exhibit more antioxidant activity than the ligand. These findings also corroborated the hypothesis that the combinations produced have antioxidant effects against DPPH free radicals comparable with those of regular vitamin C.
Bridging the Gap: Eco‐Friendly HPLC Analysis of Metformin and Lobeglitazone Sulfate Despite Polarity and Dosage Differences
Authors: Kevat Honey , Prajapati Ayushi , Parmar Kiran , Maheriya Bhumika , Joshi Hardi , Vadalia Jigna , Thummar Kashyap
Published: February 2025

A precise and stability‐indicating high‐performance liquid chromatographic (HPLC) method was developed and validated for the simultaneous estimation of lobeglitazone sulfate (0.5 mg) and metformin hydrochloride (500 mg) in pharmaceutical formulations. This method effectively addresses the analytical challenge posed by the significantly different dosage strengths and contrasting polarities of lobeglitazone (water insoluble) and metformin (water soluble). Utilizing a Phenomenex Strong Cation Exchange (250 mm × 4.6 mm, 10 μm) column, the method employed a mobile phase of ammonium dihydrogen phosphate (pH 3.0) and a premix of methanol and acetonitrile (80:20), delivered at a flow rate of 1.0 mL/min. The PDA detector was set at 251 nm to monitor eluents, and the column temperature was maintained at 30°C for optimal separation. The method was validated as per ICH guidelines, covering specificity, linearity, accuracy, precision, LOD, LOQ, solution stability, and robustness. Forced degradation studies under various stress conditions (acidic, basic, oxidative, photolytic, and thermal) revealed no significant degradation products. The method was also assessed for greenness using a AGREE tool, achieving a score of 0.68, demonstrating its eco‐friendly nature. Overall, this method is suitable for the routine analysis of these drugs in pharmaceutical formulations.