bluuebunny/crossref_metadata_2025 huggingface dataset:
Petrogenesis of lunar granulitic breccia meteorites Northwest Africa 15062 and 15063
Authors: Xia Zhipeng , Yang Baochen , Si Bowen , Chen Guozhu , Wang Xi , Chen Hongyi , Zhang Chuantong , Miao Bingkui
Published: November 2024

We present petrology and mineralogy for two lunar granulitic breccia meteorites that were detected in Northwest Africa (NWA), the samples NWA 15062 and NWA 15063. The fragments primarily consist of plagioclase and olivine mineral clasts, with minor amounts of anorthosite clasts and one troctolite clast. The anorthosite clasts are dominated by plagioclase/maskelynite, with minor olivine and pyroxene. A troctolite clast, composed of olivine and maskelynite, occurs in NWA 15063. The olivine clasts display mosaic extinction and usually have a homogeneous Mg‐rich composition. However, all olivine mineral clasts exhibit two distinct ranges of their major element composition (Mg#: 85–88 and 77–78, respectively). Large individual plagioclase clasts show heterogeneous compositions (Ab content: 2.5–4.8) and have different Raman peak positions in different domains. The matrix of the meteorites appears semitransparent and is composed of olivine and pyroxene aggregates associated with maskelynite, constituting a granoblastic texture. Pyroxenes of the matrix are dominantly enstatites, associated with a few augites. Both meteorite samples exhibit shock‐induced melt veins ranging from 50 to 200 μm width. These melt veins traverse the entire samples and contain rare, very fine‐grained (2–3 μm) Mg‐rich olivine clasts (Mg# = 90–93) and mafic silicate glass. Some Cr‐spinel grains exhibit slight compositional zonation, characterized by a magnesium‐rich core (Mg# = 56, Cr# = 23) and Cr‐rich rims (Mg# = 50, Cr# = 28), with decomposition at the edges. The significantly differing Mg# contents of the mafic silicate minerals in the matrix, lithic clasts, and mineral clasts of the two meteorites indicate a diverse origin of the clasts. Based on their petrology, mineral chemistry, and bulk composition, NWA 15062 and NWA 15063 are classified as anorthositic troctolitic granulitic polymict breccia. Textural evidence suggests that the parent rocks of NWA 15062 and NWA 15063 were affected by high pressure of up to 30 GPa during impact‐induced shock metamorphism, causing crystal structure deformation in olivine and the transformation of plagioclase to maskelynite. During cooling from peak temperatures of 1600–1700°C, the coarse‐grained maskelynite mineral clasts were partially devitrified, and the granoblastic texture of the matrix was developed. Mg‐rich anorthosite was formed before this shock event. Cr‐spinel was formed in a troctolitic melt, which was probably differentiated after the crystallization of anorthite and magnesium‐rich olivine. However, the possibility of the formation of the Mg‐rich melt through interaction with the lunar anorthositic crust cannot be ruled out. The meteorite NWA 15062/15063 strongly resembles the textural, chemical, and mineralogical characteristics of the NWA 5744 meteorite group. Therefore, we interpret the two samples as a new member of the NWA 5744 meteorite group.
‘Re‐Wilding’ an Animal Model With Microbiota Shifts Immunity and Stress Gene Expression During Infection
Authors: Will Ian , Stevens Emily J. , Belcher Thomas , King Kayla C.
Published: November 2024

The frequency of emerging disease is growing with ongoing human activity facilitating new host–pathogen interactions. Novel infection outcomes can also be shaped by the host microbiota. Caenorhabditis elegans nematodes experimentally colonised by a wild microbiota community and infected by the widespread animal pathogen, Staphylococcus aureus, have been shown to suffer higher mortality than those infected by the pathogen alone. Understanding the host responses to such microbiota–pathogen ecological interactions is key to pinpointing the mechanism underlying severe infection outcomes. We conducted transcriptomic analyses of C. elegans colonised by its native microbiota, S. aureus and both in combination. Correlations between altered collagen gene expression and heightened mortality in co‐colonised hosts suggest the microbiota modified host resistance to infection. Furthermore, microbiota colonised hosts showed increased expression of immunity genes and variable expression of stress response genes during infection. Changes in host immunity and stress response could encompass both causes and effects of severe infection outcomes. ‘Re‐wilding’ this model nematode host with its native microbiota indicated that typically commensal microbes can mediate molecular changes in the host that are costly when challenged by a novel emerging pathogen.
In vivo detection of spectral reflectance changes associated with regulated heat dissipation mechanisms complements fluorescence quantum efficiency in early stress diagnosis
Authors: Pescador‐Dionisio Sara , Cendrero‐Mateo Maria Pilar , Moncholí‐Estornell Adrián , Robles‐Fort Aida , Arzac Miren I. , Renau‐Morata Begoña , Fernández‐Marín Beatriz , García‐Plazaola José Ignacio , Molina Rosa V. , Rausell Carolina , Moreno José , Nebauer Sergio G. , García‐Robles Inmaculada , Van Wittenberghe Shari
Published: November 2024

Early stress detection of crops requires a thorough understanding of the signals showing the very first symptoms of the alterations in the photosynthetic light reactions. Detection of the activation of the regulated heat dissipation mechanism is crucial to complement passively induced fluorescence to resolve ambuiguities in energy partitioning.

Using leaf spectroscopy, we evaluated the capability of pigment spectral unmixing to calculate the fluorescence quantum efficiency (FQE) and simultaneously retrieve fast absorption changes in a drought and nitrogen deficiency experiment with tomato. In addition, active fluorescence measurements and pigment analyses of xanthophylls, carotenes and chlorophylls were conducted.

We observed notable responses in noninvasive proximal sensing‐retrieved FQE values under stress, but as expected, these alone were not enough to identify the constraints in photosynthetic efficiency. Reflectance‐based detection of the 535‐nm peak absorption change was able to complement FQE and indicate the activation of regulated heat dissipation for both stress treatments under growing light conditions. However, further complexity in the light harvesting energy regulation needs to be accounted for when considering additional light stress.

Our results underscore the potential of complementary in vivo quantitative spectroscopy‐based products in the early and nondestructive stress diagnosis of plants, marking the path for further applications.
Immunomodulatory metabolites in IgE‐mediated food allergy and oral immunotherapy outcomes based on metabolomic profiling
Authors: Virkud Yamini V. , Styles Jennifer N. , Kelly Rachel S. , Patil Sarita U. , Ruiter Bert , Smith Neal P. , Clish Clary , Wheelock Craig E. , Celedón Juan C. , Litonjua Augusto A. , Bunyavanich Supinda , Weiss Scott T. , Baker Erin S. , Lasky‐Su Jessica A. , Shreffler Wayne G.
Published: November 2024

Background

The immunometabolic mechanisms underlying variable responses to oral immunotherapy (OIT) in patients with IgE‐mediated food allergy are unknown.

Objective

To identify novel pathways associated with tolerance in food allergy, we used metabolomic profiling to find pathways important for food allergy in multiethnic cohorts and responses to OIT.

Methods

Untargeted plasma metabolomics data were generated from the VDAART healthy infant cohort (N = 384), a Costa Rican cohort of children with asthma (N = 1040), and a peanut OIT trial (N = 20) evaluating sustained unresponsiveness (SU, protection that lasts after therapy) versus transient desensitization (TD, protection that ends immediately afterward). Generalized linear regression modeling and pathway enrichment analysis identified metabolites associated with food allergy and OIT outcomes.

Results

Compared with unaffected children, those with food allergy were more likely to have metabolomic profiles with altered histidines and increased bile acids. Eicosanoids (e.g., arachidonic acid derivatives) (q = 2.4 × 10−20) and linoleic acid derivatives (q = 3.8 × 10−5) pathways decreased over time on OIT. Comparing SU versus TD revealed differing concentrations of bile acids (q = 4.1 × 10−8), eicosanoids (q = 7.9 × 10−7), and histidine pathways (q = .015). In particular, the bile acid lithocholate (4.97 [1.93, 16.14], p = .0027), the eicosanoid leukotriene B4 (3.21 [1.38, 8.38], p = .01), and the histidine metabolite urocanic acid (22.13 [3.98, 194.67], p = .0015) were higher in SU.

Conclusions

We observed distinct profiles of bile acids, histidines, and eicosanoids that vary among patients with food allergy, over time on OIT and between SU and TD. Participants with SU had higher levels of metabolites such as lithocholate and urocanic acid, which have immunomodulatory roles in key T‐cell subsets, suggesting potential mechanisms of tolerance in immunotherapy.

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Is honesty valued today?: New evidence from Thailand
Authors: Tangtammaruk Peera , Chavanovanich Jennifer , Siwareepan Nattapon , Witvorapong Nopphol
Published: November 2024

Objectives

As a fundamental ethical principle, honesty plays a pivotal role in trust‐building, social cohesion, and effective governance. This study examined how honesty was valued in Thailand, an upper middle‐income Asian economy steeped in Buddhist values. It also explored the relationship between honesty and socioeconomic characteristics.

Methods

Using primary data from 1230 Bangkok residents aged 18–75, collected through stratified multi‐stage sampling, an instrument to measure honesty was developed and validated. Honesty was operationalized with three components: truthfulness, respect for ownership, and accountability. Ordinary Least Squares (OLS)  and Tobit regression analyses were performed.

Results

Honesty was valued highly in Thai society. The average scores for accountability and respect for ownership were notably higher than for truthfulness. Socioeconomic characteristics, including gender, age, birth cohort, place of birth, religiosity, and self‐rated economic status, were statistically associated with overall honesty and influenced the three components of honesty differently. The effects of age and birth cohorts were distinct. Younger birth cohorts were associated with a higher level of honesty. However, within each cohort, honesty increased with age.

Conclusions

This study proposes recommendations aimed at promoting honesty in Thai society and provides ideas for future studies.
INVESTIGATION ON CORROSION AND FLEXURAL BEHAVIOUR OF REINFORCED CONCRETE USING MARINE SAND
Authors: Ganesan Karthikeyan , Kanagarajan Vijai , Joseph Dominic Jerlin Regin
Published: November 2024

Traditionally, the construction industry relies on both manufactured sand (known as MF-Sand) and river sand as primary constituents for fine aggregates. However, in response to the dwindling supply of river sand, the contemporary preference is firmly in favor of MF-Sand. This research focuses the utilization of meticulously cleaned marine sand (referred to as MR-Sand) as a superior substitute for MF-Sand, aiming to curtail the reliance on and depletion of river sand, a finite natural resource. The objective of this research is to examine the mechanical property of flexural performance of Reinforced Cement Concrete (RCC) Beam and durability study of concrete using corrosion test in which washed MR - Sand as a fine aggregate in partial replacement of MF-Sand from 20% to 60%. The physical and chemical characteristics of treated and untreated marine sand are compared with a view to better comprehending the features of MR and MF-Sand. Experimental research works have been carried out to look into the corrosion test and flexural strength in order to better understanding the strength and durability attributes of concrete. The values for flexural strength, ultimate load, load-deflection, load-strain, and crack pattern have been compared for the RCC beam specimens MF100, MR20, MR40 and MR60. The findings indicate that 60% of MR-Sand possesses the desired properties of strength and durability of concrete. Additionally, Finite Element Analysis is carried out using the ABAQUS software to further validate the experimental findings of load-deflection, load carrying capacity, crack pattern and flexural strength.
WASTE EGGSHELL AND SAWDUST AS REINFORCEMENTS FOR SUSTAINABLE POLYESTER COMPOSITES: MECHANICAL CHARACTERIZATION AND ENVIRONMENTAL DURABILITY ASSESSMENT
Authors: Khalid Hamdan Zahra , Farhan Ogaili Ahmed Ali , Abdulwahid Jebur Nazik , Abbas Abdulla Fadhel , S. Al-Ameen Ehsan , Warid Meteab Zainab
Published: November 2024

This research endeavor undertakes an experimental investigation into the bending and tensile properties of polyester composites reinforced with waste eggshell powder and sawdust particles at 35 wt.%. Valorizing these waste materials as reinforcements contributes to sustainable practices, waste minimization, and environmental pollution mitigation. Composite samples were fabricated using hand lay-up and compression molding techniques. The effects of environmental exposure to water, acidic, and basic media immersion on the mechanical performance were evaluated to assess durability. Experimental characterization through tensile and three-point bending tests determined mechanical properties, stress-strain behavior, and failure mechanisms. Additionally, finite element analysis (FEA) simulations complemented the experiments by providing insights into stress distributions, deformations, and potential failure initiation sites within the composites under flexural loading. The computational models accurately captured the reinforcing effects of the waste materials and the degradation induced by environmental exposure, validating the experimental trends. Incorporating waste natural fibers significantly enhanced polyester's bending strength by 140% (sawdust) and 75% (eggshell), and tensile strength by 13% (sawdust) and 10% (eggshell). However, environmental exposure degraded properties to varying extents, with water immersion reducing tensile strength by 63% (sawdust) and 3% (eggshell), and flexural strength by 63% (sawdust) and 3% (eggshell). The acidic medium caused 58% (sawdust) and 23% (eggshell) reductions in tensile strength, and similar flexural strength degradations. Strikingly, the basic medium decreased eggshell composite tensile strength by 170% and flexural strength by 6%, while sawdust composite strengths declined by 44%.
MICROWAVE REFLECTOMETRY CIRCUITS INTEGRATION WITH COAXIAL PROBE FOR INITIAL BREAST TUMOR DETECTION
Authors: You Kok Yeow , Al-Areqi Nadera Najib , Lim Wei Jer , Lee Kim Yee , Cheng Ee Meng , Khe Cheng Seong
Published: November 2024

A six-port reflectometry (SPR) system was developed to predict the dielectric properties of both tumor and normal breast tissue, intended for medical diagnostic applications. Ensuring precise measurements, the SPR underwent calibration using a well-established four-step procedure, which will be briefly outlined. Afterward, the investigated coaxial probe was connected to the SPR through the calibrated measurement port. Subsequently, the exposed end of the probe aperture was immersed into synthetic samples representing both healthy and cancerous breast tissue to assess the dielectric constant, εrʹ and loss factor, εrʺ across frequencies ranging from 1.5 GHz to 3.3 GHz. The dielectric constant, εrʹ and loss factor, εrʺ were derived from the measured reflection coefficient using a closed-form equation associated with the coaxial probe. An examination was undertaken to compare the performance of a commercially available vector network analyzer (VNA) outfitted with a Keysight 85070E dielectric probe against an SPR-probe system. The comparison was based on analyzing the reflection coefficient magnitude, phase shift, dielectric constant, and loss factor of synthetic breast tissue samples. The study revealed maximum absolute errors of 0.01, 1.07°, 1.12, and 0.75 for the measured reflection coefficient magnitude, phase shift, dielectric constant, and loss factor, respectively. The calibrated reflection coefficient and predicted relative permittivity, εr can be effectively utilized to distinguish between normal (εrʹ < 50) and tumor (εrʹ > 50) breast tissue.
Intracellular ATP concentration is a key regulator of bacterial cell fate
Authors: Li Bo , Chen Xiao , Yang Jin-Yu , Gao Song , Bai Fan
Published: November 2024

ATP, most widely known as the primary energy source for numerous cellular processes, also exhibits the characteristics of a biological hydrotrope. The viable but nonculturable (VBNC) and persister states are two prevalent dormant phenotypes employed by bacteria to survive challenging environments, both of which are associated with low metabolic activity. Here, we investigate the intracellular ATP concentration of individual VBNC and persister cells using a sensitive ATP biosensor QUEEN-7μ and reveal that both types of cells possess a lower intracellular ATP concentration than culturable and sensitive cells, although there is a certain overlap in the intracellular ATP concentrations between antibiotic-sensitive cells and persisters. Moreover, we successfully separated VBNC cells from culturable cells using fluorescence-activated cell sorting based on the intracellular ATP concentration threshold of 12.5 µM. Using an enriched VBNC cell population, we confirm that the precipitation of proteins involved in key biological processes promotes VBNC cell formation. Notably, using green light-illuminated proteorhodopsin (PR), we demonstrate that VBNC cells can be effectively resuscitated by elevating their intracellular ATP concentration. These findings highlight the crucial role of intracellular ATP concentration in the regulation of bacterial cell fate and provide new insights into the formation of VBNC and persister cells.

IMPORTANCE

The viable but nonculturable (VBNC) and persister states are two dormant phenotypes employed by bacteria to counter stressful conditions and play a crucial role in chronic and recurrent bacterial infections. However, the lack of precise detection methods poses significant threats to public health. Our study reveals lower intracellular ATP concentrations in these states and establishes an ATP threshold for distinguishing VBNC from culturable cells. Remarkably, we revive VBNC cells by elevating their intracellular ATP levels. This echoes recent eukaryotic studies where modulating metabolism impacts outcomes like osteoarthritis treatment and lifespan extension in
Caenorhabditis elegans
. Our findings underscore the crucial role of intracellular ATP levels in governing bacterial fate, emphasizing ATP manipulation as a potential strategy to steer bacterial behavior.
Dimming the corona: studying SARS-coronavirus-2 at reduced biocontainment level using replicons and virus-like particles
Authors: Neilsen Grace , Mathew Asha Maria , Castro Jose M. , McFadden William M. , Wen Xin , Ong Yee T. , Tedbury Philip R. , Lan Shuiyun , Sarafianos Stefan G.
Published: November 2024

The coronavirus-induced disease 19 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infections, has had a devastating impact on millions of lives globally, with severe mortality rates and catastrophic social implications. Developing tools for effective vaccine strategies and platforms is essential for controlling and preventing the recurrence of such pandemics. Moreover, molecular virology tools that facilitate the study of viral pathogens, impact of viral mutations, and interactions with various host proteins are essential. Viral replicon- and virus-like particle (VLP)-based systems are excellent examples of such tools. This review outlines the importance, advantages, and disadvantages of both the replicon- and VLP-based systems that have been developed for SARS-CoV-2 and have helped the scientific community in dimming the intensity of the COVID-19 pandemic.
Genomic surveillance of SARS-CoV-2 in Nepal
Authors: Khadka Binod , Napit Rajindra , Mihindukulasuriya Kathie A. , Shrestha Smita , Rauniyar Ramanuj , Tuladhar Eans T. , Droit Lindsay , Paredes Anne M. , Jha Runa , Raut Roji , Jha Bimalesh K. , Handley Scott A. , Elong-Ngono Annie , Shresta Sujan , Wang David , Manandhar Krishna D.
Published: November 2024

During the COVID-19 pandemic, Nepal, like other countries, faced emerging SARS-CoV-2 variants. To evaluate the circulating variants, 278 samples collected between September 2021 and March 2022 were sequenced in the country. From these, 229 high-quality genomes were obtained (82.97% Omicron and 17.03% Delta) highlighting the genomic diversity of SARS-CoV-2 in Nepal.
MecA in
Streptococcus mutans
is a multi-functional protein
Authors: Ellepola Kassapa , Shields Robert C. , Kajfasz Jessica K. , Zhang Hua , Lemos Jose A. , Wu Hui , Wen Zezhang T.
Published: November 2024

Our recent studies have shown that deficiency of MecA in
Streptococcus mutans
significantly affects cell division, growth, and biofilm formation. In this study, an
in vitro
mixed-species model, proteomics, and affinity pull-down assays were used to further characterize the MecA-mediated regulation in
S. mutans
. The results showed that compared with the wild type, UA159, the
mecA
mutant significantly reduced its production of glucans and weakened its ability to facilitate mixed-species biofilm formation. Relative to the wild type, the
mecA
mutant also displayed unique characteristics, including colony morphology, growth rate, and biofilm formation that did not fully resemble any of the
clpP, clpX, clpE, clpCE,
and
clpC
individual or combinational mutants. Deletion of
mecA
was shown to result in alteration of >337 proteins, including down expression of GtfBC&D and adhesin P1. More than 277 proteins were differentially expressed in response to
clpP
deletion, including increased expression of GtfB. By cross-referencing the two proteomes, a distinctive set of proteins was found to be altered in the
mecA
mutant, indicating a ClpP-independent role of MecA in the regulation of
S. mutans
. When analyzed using affinity pull-down, ClpC, ClpX, ClpE, and CcpA were among the members identified in the MecA-associated complex. Further analysis using a bacterial two-hybrid system confirmed CcpA, ClpX, and ClpE as members of the MecA interactome. These results further suggest that MecA in
S. mutans
is more than an adapter of the Clp-proteolytic machinery, although the mechanism that underlies the Clp-independent regulation and its impact on
S. mutans
pathophysiology await further investigation.

IMPORTANCE

MecA is known as an adaptor protein that works in concerto with ATPase ClpC and protease ClpP in the regulated proteolysis machinery. The results presented here provide further evidence that MecA in
S. mutans
, a keystone cariogenic bacterium, plays a significant role in its ability to facilitate mixed-species biofilm formation, a trait critical to its cariogenicity. Proteomics analysis, along with affinity pull-down and bacterial two-hybrid system, further confirm that MecA can also regulate
S. mutans
physiology and biofilm formation through pathways independent of the Clp proteolytic machinery, although how it functions independently of Clp awaits further investigation.
Dynamic LIA advances hastened the demise of small valley glaciers in central Svalbard
Authors: Mannerfelt Erik S. , Hodson Andrew J. , Håkansson Lena , Lovell Harold
Published: November 2024

Most small land-terminating glaciers in Svalbard have experienced large recession since the Little Ice Age (LIA) and today are thin, cold, and largely inactive. This likely contrasts to their LIA conditions, but the observational record from that time is sparse. We investigate the evolution of five small glaciers in central Nordenskiöld Land, Svalbard, from the LIA to 2019. Photogrammetric reconstructions and ground penetrating radar are used to reconstruct their geometric changes since 1936, and historical observation, photographs, and geomorphological mapping extend this history to before the 1900s. Our results show that from 1936 to 2019, the study glaciers on average lost 49.6% of their area and 77.4% ± 7.7% of their volume, with the greatest volume loss at Scott Turnerbreen of 91% ± 5%. Four out of these five glaciers strongly indicate a history of surge-like advances near the end of the LIA within one or two decades, and the rate of subsequent mass loss seems connected to their previous dynamics. This apparent switch to high activity during a period of rapid climatic change, could have implications for our understanding of past and future glacier evolution; climate change and highly dynamic glacier responses may be more connected than previously thought.
Remission Possible: New Era of SLE Treatment with Biologics Involvement
Authors: Aringer Martin
Published: November 2024

Treat-to-target (T2T) is a therapeutic approach used in several rheumatologic disorders such as rheumatoid arthritis, gout, axial spondylarthritis, and other inflammatory diseases such as inflammatory bowel disease. Developing a T2T strategy for systemic lupus erythematosus (SLE) has been difficult due to the complexity of the disease. The 2019 EULAR recommendations for the management of SLE, reestablished in the 2023 EULAR guideline, specified that the primary treatment goal should be remission or the lowest possible disease activity. In SLE, remission is associated with reduced organ damage, fewer flares, reduced hospitalisation, reduced mortality, and improved health-related quality of life. Previously remission in SLE was seen as an unattainable goal; however, the treatment landscape for SLE has evolved, and recent advancements, particularly the use of biologics, have emerged as promising therapeutic options to improve patient outcomes.

A new post-hoc analysis of the TULIP Phase III programme provides evidence across four years that remission is an achievable goal with anifrolumab, a type I interferon (IFN) receptor antagonist for adult patients with moderate to severe (SLE) who are receiving standard therapy. At Week 208, 30.3% (n=58/194) of patients treated with anifrolumab were in remission compared with 18.3% (n=12/65) of those in the standard therapy alone group. This was an increase from 19.7% (n=49/251) of patients treated with anifrolumab who achieved remission at the first LTE visit (Week 64) compared with 9.9% (n=10/104) of those in the standard therapy alone group. Treatment with anifrolumab was also associated with more frequent, prolonged, and sustained DORIS remission attainment compared with placebo during the 4-year TULIP+LTE period. Real-world case studies have also illustrated the effectiveness of biologics in controlling disease activity, enhancing quality of life, and establishing long-term safety profiles.

In conclusion, biologic therapies have emerged as a valuable treatment option for achieving remission or lupus low disease activity state. Biologics has opened a new era revolutionizing the management of SLE, offering renewed hope for patients living with this challenging autoimmune disease.
How Do We Identify and Manage Progressive CTD-ILD?-Update in Treatment and Guideline
Authors: Distler Oliver , Maher Toby
Published: November 2024

The lung is a frequent target of autoimmune-mediated injury in patients with rheumatic diseases. Not infrequently, respiratory involvement may be the presenting manifestation of connective tissue diseases (CTDs). The prevalence of interstitial lung disease (ILD) in rheumatoid arthritis is about 20 to 30% of patients, while ILD may occur in 20 to 50% of patients with idiopathic inflammatory myositis, 40-50% or more of patients with systemic sclerosis, 2 to 5% of patients with systemic lupus erythematosus, 20 to 60% of patients with mixed connective tissue disease, and up to 25% of patients with Sjögren’s syndrome.

Rheumatic disease-associated lung involvement is a major cause of morbidity and mortality in these patients. It shows a considerable heterogeneity in incidence and prevalence, clinical course, and the involved lung structure depending on the underlying rheumatic disease. Each rheumatic disease is associated with a characteristic pattern of their lung disease.

The standard therapy has traditionally been immunosuppressant. With the evolvement of treatment, anti-fibrotic is now indicated for chronic fibrosing ILDs with a progressive phenotype, including autoimmune disease-associated ILD. By targeting the underlying mechanism of pulmonary fibrosis, it is shown that the annual rate of FVC decline can be reduced by more than 50%.

In this lecture, Prof. Oliver Distler and Prof. Toby Maher will review the importance of timely treatment, the management practices and treatment guidelines for CTD-ILD.
Screening for PAH - How to Reduce Delay in CTD-PAH Diagnosis
Authors: Lee Yeon-Ah
Published: November 2024

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with a diverse clinical presentation, including pulmonary involvement. While pulmonary complications are common in SLE, a subset of patients develop pulmonary arterial hypertension (PAH), a life-threatening condition characterized by elevated pulmonary vascular resistance and right ventricular dysfunction. Early detection and timely management are crucial for improving outcomes in this vulnerable patient population. This lecture will focus on the importance of PAH screening in SLE, highlighting the clinical insights and management strategies for this challenging condition.

The lecture will begin by reviewing the epidemiology and pathophysiology of PAH in SLE, emphasizing the role of autoimmunity, inflammation, and microvascular dysfunction. The clinical manifestations of PAH in SLE, including dyspnea, fatigue, chest pain, and syncope will be discussed. These symptoms may be subtle and often overlap with other SLE manifestations, making early recognition challenging.

The lecture will then delve into the importance of PAH screening in SLE. We will discuss the current recommendations for screening, including the use of blood markers to evaluate the PAH risk factors, echocardiography to assess right ventricular function and pulmonary artery pressure. We will also explore the role of other diagnostic tools, such as NT-proBNP test, pulmonary function tests and right heart catheterization, in confirming the diagnosis of PAH.

The management strategies for PAH in SLE will then be focused, emphasizing the importance of multidisciplinary care involving rheumatologists, pulmonologists, cardiologists, and other specialists. We will explore the current evidence-based guidelines for pharmacotherapy, including the role of vasodilators, endothelin receptor antagonists, and phosphodiesterase type 5 inhibitors.

Finally, the lecture will end with real-world cases, highlighting the heterogeneity of the disease, the need of identifying the disease early, and the need for personalized medicine approaches to improve outcomes for this vulnerable patient population.

This lecture aims to equip clinicians with the knowledge and tools to effectively identify PAH in SLE, facilitating early diagnosis and timely initiation of appropriate management strategies, ultimately improving patient outcomes.
Difficult to Treat (D2T) RA: What is the Missing Link?
Authors: Watanabe Ryu
Published: November 2024

Over the past several decades, the treatment of rheumatoid arthritis (RA) has advanced significantly, and clinical, structural, and functional remission are achievable therapeutic goals. However, a substantial number of patients show resistance to multiple drugs. In particular, patients whose disease activity cannot be controlled despite the use of two or more biological disease-modifying antirheumatic drugs (DMARDs) or targeted synthetic DMARDs with different mechanisms of action have recently been referred to as having difficult-to-treat RA (D2T RA). D2T RA is a heterogeneous and multifactorial disease state, and the major problems are uncontrolled disease activity and decreased quality of life, as well as the economic burden. Since the concept of D2T RA is relatively new and publication regarding D2T RA is limited, the mechanism underlying DMARD inefficacy and which factors form a “difficult-to-treat” state are not yet fully understood. It is also possible that factors contributing to D2T RA may differ by patient, sex, country, and race. The present seminar introduces the current concept and unsolved problems of D2T RA, including the definition, prevalence, and factors contributing to D2T RA. Then, the management and therapeutic strategies for D2T RA are discussed including our multicentre ANSWER cohort experience. Finally, a clinical approach to prevent patients from developing D2T RA is explored.
Axial Spondyloarthritis Unresponsive to Secukinumab, an IL-17A Inhibitor Therapy, a Case Report
Authors: Danasasmita Gantira , Ariane Anna , Hidayat Rudy
Published: November 2024

Introduction

Axial spondyloarthritis (axSpA) is a group of autoinflammatory disease that hypothetically caused by tumor necrosis factor (TNF) axis and interleukin (IL)-23/IL-17 axis. Based on algorithm of treatment from ASAS/EULAR 2022, biologic agent is indicated if patient did not response to NSAIDs, the first line treatment. TNF inhibitor and IL-17 inhibitor are two biologic agent that has been approved and gave significant result in improving disease activity.

Case Description

A 47 years old woman who has been diagnosed with axSpA since 2022. At first she was given medication with NSAIDs. She has also been given conventional DMARD, sulfasalazine an methotrexate, until maximum dose but still no response in controlling the disease activity.

After about one year of treatment, she finally tried using the biologic agent, Secukinumab. She was given 150 milligram weekly initial dose for a month, followed by monthly administration. After administering the eight dose, she achieved inactive disease activity. However, after the fourteenth dose, symptoms began to reappear and disease activity became very high like the first time of diagnosis.

Discussion

IL-17A inhibitor (IL-17Ai) has been widely used for treating axSpA since ASAS20/40 and partial response at 16 week was reached 61,36 and 14%. IL-17Ai seem more effective in ameliorating entheseal inflammation and new bone formation, in accordance with role of IL-23/IL-17 axis in stimulating osteoclast.

ASAS/EULAR recommend patients who fail therapy with one biological agent in 12 weeks to switch to another type of biological agent. However there’s still no publication data for efficacy to give TNF inhibitor after IL-17Ai or JAK inhibitor failure.

Conclusion

The effectiveness of biological agents in axSpA is quite similar. In cases where therapy fails, it is still an open question whether the optimal therapy choice is to change the type of drug or a combination of two types of biological agents.
Unveiling Predictive Parameters for Rheumatoid Arthritis Development in Arthralgia Patients: Insights from a Prospective Longitudinal Study
Authors: Tam Cheuk Yin , Cheng Tsz Ho , Tam Lai Shan , So Ho
Published: November 2024

Background:

Early diagnosis of rheumatoid arthritis (RA) is crucial for timely intervention and improved outcomes. Although research on the preclinical phase of RA is a prominent topic, there remains an unmet need to effectively stratify patients at risk of developing RA based on basic clinical assessment and laboratory investigations. This prospective longitudinal study aimed to identify risk factors for RA development in individuals experiencing arthralgia.

Method:

Two hundred consecutive adults with arthralgia were enrolled from new referrals to our rheumatology clinic. Patients with synovitis or a known arthritis diagnosis were excluded. Follow-up assessments were conducted every 6 months, or sooner if symptoms worsened, for a maximum of 2 years. The study endpoint was the development of RA, according to the 2010 ACR/EULAR classification criteria. Baseline demographic characteristics, clinical parameters, serology, and acute phase reactant levels were compared between patients who developed RA and those who did not. In addition, the classification score based on the 2010 ACR/EULAR classification criteria was utilised as a composite weighted score summarising the clinical presentation in the cohort, although the patients were deemed not fulfilling the mandatory criteria of having synovitis at baseline.

Results:

By May 2024, 104 patients had been followed up for at least one year, with a median duration of 78 weeks (IQR: 58-97). The baseline symptom duration was 51 weeks (IQR: 29 – 97). Among these patients, 23 (22.1%) developed RA after a median follow-up duration of 41 weeks (IQR: 25 – 52). Patients who developed RA had a significantly higher proportion of joint symptoms <1 year, difficulty making a fist, positive rheumatoid factor (RF), anti-CCP antibodies, and elevated ESR and CRP levels at baseline. Multivariate logistic regression identified difficulty making a fist (OR: 4.87, 95% CI: 1.40 – 17.04, p = 0.013) and positive anti-CCP antibodies (OR: 13.04, 95% CI: 3.74 – 45.44, p < 0.001) as independent predictors for RA development. Meanwhile, patients who developed RA had significantly higher baseline scores extrapolating from the 2010 ACR/EULAR classification criteria compared to the non-RA group.

Conclusion:

Difficulty making a fist and positive anti-CCP antibodies are independent predictors of RA development. Additionally, patients who developed RA exhibited significantly higher baseline scores on the 2010 ACR/EULAR classification criteria. Early recognition of these variables and taking reference from the score of classification criteria may aid in RA risk stratification. Further research is needed to validate these findings and explore additional predictive markers.
The Neutrophil-to-C3 Ratio: Unveiling Diagnostic Efficacy for Lupus Nephritis and Association with Reduced Retinal Vascular Density in Systemic Lupus Erythematosus
Authors: Maitiyaer Maierhaba , Li Peiyi , Li Huangdong , Jiang Dingwen , Zhang Jingyu , Yang Chuwei , Yang Xiaobin , Chen Chengmei , Huang Wenhui , Liu Zhiping , Yu Shuilian
Published: November 2024

Background:

Lupus nephritis (LN) frequently manifests as a significant complication in systemic lupus erythematosus (SLE) patients, with emerging research indicating a plausible correlation between subclinical retinal involvement and renal manifestations. This study aims to investigate the relationship between the neutrophil-to-C3 ratio (NC3R) and both LN as well as retinal microvasculature damage among SLE patients.

Methods:

In this cross-sectional study, a cohort of 220 participants was recruited, consisting of 78 LN patients and 142 patients without LN.

We assessed clinical indicators and organ involvement and conducted correlation analyses between NC3R and markers of lupus activity. Additionally, we analyzed the diagnostic performance of NC3R in diagnosing LN and constructing ROC curves. Logistic regression analysis was performed to investigate the impact of NC3R on LN. We further examined the influence of NC3R on retinal vasculature density based on its cutoff value and conducted correlation analyses accordingly.

Results:

The LN group exhibited a significant increase in NC3R compared to the group without LN (5.9 vs 4.5, P=0.007). NC3R demonstrated positive correlations with 24-hour proteinuria (R=0.329, P<0.001) and systemic lupus erythematosus disease activity index (SLEDAI) score (R=0.268, P<0.001). Multiple regression analysis revealed NC3R as an independent risk factor for LN (OR: 2.01, P=0.035). NC3R was proven valuable in distinguishing LN patients (AUC: 0.613), with an optimal cutoff value of 6.40 (sensitivity: 48.1%, specificity: 72%). Our results indicated that the lower NC3R group (NC3R<6.40) exhibited reduced vascular density, particularly within the macular region. Furthermore, we observed a positive correlation between NC3R levels and vascular density.

Conclusions:

NC3R demonstrated promising potential as a reliable indicator for predicting both LN and retinal microvasculature involvement. Consequently, the pre-treatment evaluation of NC3R had the potential to assist clinicians in identifying potential organ involvement among SLE patients.
Performance of the ASAS-proposed Cut-offs for Positive MRI Typical of Axial Spondyloarthritis for Discriminating Axial Involvement in Patients with Psoriatic Arthritis
Authors: Yan Xianfeng , Cheng Isaac T , So Jacqueline , So Ho , Lee Ryan Ka Lok , Griffith James Francis , Tam Lai-Shan
Published: November 2024

Background:

Unlike axial spondyloarthritis (axSpA), no classification criteria are currently available for axial psoriatic arthritis (axPsA). This study aimed to evaluate the performance of the proposed cut-offs from the Assessment of Spondyloarthritis International Society (ASAS) data-driven definitions for active and structural magnetic resonance imaging (MRI) lesions typical of axSpA in distinguishing axial involvement in patients with psoriatic arthritis (PsA).

Methods:

Seventy-two consecutive PsA patients (67% male, aged 45± 14 years) meeting the CASPAR classification criteria, regardless of the presence of back pain, were included. All patients underwent radiography of the pelvis and spine, as well as sacroiliac joint (SIJ) MRI, while 52 (72%) of 72 patients also underwent whole-spine MRI. The final diagnosis of axPsA was ascertained by two experienced rheumatologists. One rheumatologist with expertise in imaging and one trained reader evaluated the radiography and MRI images.

Results:

AxPsA was diagnosed in 27/72 (38%) patients. The proposed cut-offs for active sacroiliitis demonstrated high specificity (95.6%) but relatively low sensitivity (51.9%) in distinguishing patients with and without axPsA. When structural lesions of the SIJ were included in addition to active lesions, the sensitivity significantly improved (96.3% vs. 51.9%) with a modest decrease in specificity (86.7% vs. 95.6%). Incorporating MRI spine lesions (using the proposed cut-offs for positive spine MRI from the SPACE cohort) alongside SIJ lesions did not further change sensitivity or specificity compared with assessing SIJ alone.

Conclusion: The ASAS-proposed cut-offs for identifying active and structural lesions of SIJ demonstrated satisfactory performance in discriminating axial involvement in PsA patients.
How Early Should We Use b/tsDMARDs in Active PsA? - Data from a 1-year Prospective Cohort in Hong Kong
Authors: Shek Wai Kit , Cheng Tsz Ho , So Ho , Tam Lai Shan
Published: November 2024

Background

Despite the wide availability of biologic/targeted synthetic disease-modifying anti-rheumatic drugs (b/tsDMARDs) for treating psoriatic arthritis (PsA), there remain controversies regarding the positioning of b/tsDMARDs in the management algorithm for patients with active peripheral disease. While the European League Against Rheumatism (EULAR) recommends conventional synthetic DMARDs (csDMARDs) as the first-line treatment (1), the American College of Rheumatology (ACR) guideline takes a more aggressive approach, and suggests upfront use of b/tsDMARDs (2). The study aimed to evaluate whether earlier use of b/tsDMARDs might increase the likelihood of achieving minimal disease activity (MDA) in patients with PsA under the treat-to-target framework.

Method

Consecutive patients with PsA who fulfilled the CASPSA criteria with active peripheral disease were recruited in this prospective cohort study. The analysis included patients who were (1) given b/tsDMARDs during the study period and (2) completed 1-year follow-up. A standardized treat-to-target strategy was adopted. Patients were categorized into csDMARDs-naïve group, single-csDMARD-inadequate response (IR) group and multiple-csDMARDs-IR group. The rate of achieving MDA at the end of one year was compared.

Result

A total of 100 PsA patients were recruited and 27 patients (mean age: 51± 13, 15 [68%] male, disease duration: 5.6± 6.9 years) were included in the analysis. At baseline, all patients exhibited moderate to high disease activity. Prior to initiating b/tsDMARDs, 4 patients were csDMARDs-naïve, 10 patients had failed 1 csDMARD and 13 patients had failed 2 or more csDMARDs. There was no significant difference between clinical features and disease activity among the 3 groups at baseline (Table 1). Within the study period, 3 (11%) and 24 (89%) patients were given anti-TNF and anti-IL-17 agents respectively. After 1-year, there was substantial improvement in disease activity in the whole cohort (Disease Activity in Psoriatic Arthritis [DAPSA]: 22.7 at baseline vs 9.0 at 1-year, p=0.039), and 17(63%) patients achieved MDA. A differential MDA achievement rate was observed across different groups. All csDMARDs-naïve patients achieved MDA, compared to 70% in the single-csDMARD-IR and 46.2% in the multiple-csDMARDs-IR groups (p=0.046) (Figure 1). There was also a trend of better DAPSA response at one-year in the csDMARDs-naïve group (4.9± 1.6 vs 10.2± 11.8 [single-csDMARD-IR] and 9.4± 8.1 [multiple-csDMARDs-IR]).

Conclusion

A lower MDA achievement rate was observed in b/tsDMARDs users with prior csDMARD exposure. Earlier initiation of b/tsDMARDs might improve treatment outcome in PsA.
Establishment of Prediction Model for Psoriatic Arthritis Based on Logistic Regression
Authors: GUO Qing , Luan Hong , Zhao Xi , Min Xue , Zhen Ying Zhang
Published: November 2024

Background:

Psoriatic arthritis (PsA) is an inflammatory musculoskeletal disease associated with psoriasis (PsO) that appears approximately 7-8 years after psoriasis and remains undiagnosed in most of patients, which is disabled and difficult to treat. So early risk assessment is particularly important. However, at present, the risk assessment of the status quo is not optimistic. The aim of this study was to establish and validate a prediction model for assessing the risk of PsA in psoriasis patients.

Methods:

Ambispective cohort study was conducted. Demographic and clinical records were collected and followed up and blindly reviewed. Single and multiple factors analysis were used to analyze the factors influencing PsA, and Logistic regression equation models were developed to verify their predictive value.

Results:

Among 1141 Pso patients, 221 patients had PsA. Logistic regression equation model showed that Arthralgia (OR= 438.079; 95% CI: 175.154-1095.682), nail dystrophy (OR= 7.453; 95% CI: 4.116-13.498), scalp lesions (OR= 3.047; 95% CI: 1.297-7.159), Inverse (intertriginous) lesions (OR= 2.45; 95% CI: 1.382-4.342) and BMI (OR= 0.909; 95% CI: 0.846-0.977) were identified as potential predictors affecting the risk of transition from PsO to PsA. And the receiver operating characteristic (ROC) curve of PsA was drawn, the area under the curve (AUC) was 0.974 (95% CI 0.963 - 0.985), the prediction sensitivity was 96.40%, the specificity was 92.10%, the calibration curve showed that the predicted results was in good agreement with the observed results.

Conclusion:

The independent predictors of PsA involve Arthralgia, nail dystrophy, scalp lesions, Inverse (intertriginous) lesions, BMI. The Logistic prediction model based on these predictors has reliable predictive value and can help early clinical assessment and treatment.