bluuebunny/crossref_metadata_2025 huggingface dataset:
Diagnostic performance of adult-based ultrasound risk stratification systems in pediatric thyroid nodules: a systematic review and meta-analysis
Authors: Xing Zhichao , Qiu Yuxuan , Zhu Jingqiang , Su Anping , Wu Wenshuang
Published: May 2023

Purpose

Ultrasound (US) is the first choice in the detection of thyroid nodules in pediatric and adult patients. The purpose of this study was to evaluate the diagnostic performance of adult-based US risk stratification systems (RSSs) when applied to the pediatric population.

Methods

Medline, Embase, and Cochrane Library (CENTRAL) were searched up to 5 March 2023 for studies about the diagnostic performance of adult-based US RSS in pediatric patients. The pooled sensitivity, specificity, positive likelihood ratio (LR), negative LR, and diagnostic odds ratio (DOR) were calculated. The summary receiver operating characteristic (SROC) curves and area under the curve (AUC) were also analyzed.

Results

The sensitivity was highest in American College of Radiology-Thyroid Imaging Reporting and Data System (ACR-TIRADS) category 4–5 and American Thyroid Association RSS high-intermediate risk (ATA), which was 0.84 [0.79, 0.88] and 0.84 [0.75, 0.90], respectively. The specificity was highest in ACR-TIRADS category 5 and Europe-TIRADS (EU-TIRADS) category 5, which was 0.93 [0.83, 0.97] and 0.93 [0.88, 0.98], respectively. The ACR-TIRADS, ATA, and EU-TIRADS showed moderate diagnostic performance in pediatric thyroid nodule patients. For Korea-TIRADS (K-TRADS) category 5, the summary sensitivity and specificity with a 95% CI were 0.64 [0.40, 0.83] and 0.84 [0.38, 0.99], respectively.

Conclusions

In conclusion, the ACR-TIRADS, ATA, and EU-TIRADS have moderate diagnostic performance in pediatric thyroid nodule patients. The diagnostic efficacy of the K-TIRADS was not as high as expected. However, the diagnostic performance of Kwak-TIRADS was uncertain because of the small sample size and small number of studies included. More studies are needed to evaluate these adult-based RSSs in pediatric patients with thyroid nodules. RSSs specific for pediatric thyroid nodules and thyroid malignancies were necessary.
Spatial distribution of non-point source pollution from total nitrogen and total phosphorous in the African city of Mwanza (Tanzania)
Authors: Zong Yunlong , Chen Sophia Shuang , Kattel Giri Raj , Guo Zheng
Published: May 2023

Rapid urbanization has caused widespread environmental pollution in Africa, restricting sustainable development programs. Today, non-point source pollution has become a major threat to many African cities. In this study, we have classified urban land use followed by the identification of urban functional areas based on multi-source data. We have then evaluated non-point source pollution based on nitrogen and phosphorus loads at a spatial scale in Mwanza city (Tanzania). We have estimated the spatial distribution of total nitrogen (TN) and total phosphorus (TP) loads at a scale of 1 square kilometer grid. The results show that ① the built-up area of the city was identified as 28.9 km2, accounting for 6.8% of the total area of the city. The area of informal settlements was 56.9 km2, accounting for 13.4% of the total area of the city. About 90.38% of 2.41×105 kg of the total TN load and 87.23% of 4.00×104 kg of the total TP load in the city were derived from the informal settlements alone in 2020. ② The average load intensities of TN and TP in Mwanza city were 6.90 kg·hm-2·yr-1 and 1.14 kg·hm-2·yr-1, respectively. The average TN and TP intensities in Mwanza city were slightly higher than the average TN and TP load intensities in the Lake Victoria basin. However, given the high population density of the Mwanza city area, the average TN and TP intensities were found to be consistent. ③ The TN and TP pollution loads were relatively concentrated in the inner urban area, including the lower reaches of the Mirongo River basin, the eastern side of the Nyamagana Peninsula, and the lakeside area extending north and south from the peninsula, and gradually decreased toward the city’s outskirts. We propose that the identified riparian areas in our study should be prioritized as potentially key construction zones for pollution treatment plant facilities and urban renewal pilot programs for restraining the widespread informal settlements. This study contributes to the development of an innovative urban non-point source pollution control measure, which may be applicable to low-income countries in Africa and elsewhere.
Long-term impact of manuring on soil organic matter quality indicators under field cropping systems
Authors: Yadav Rajendra Kumar , Purakayastha Tapan Jyoti , Kumar Dhiraj , Jha Prakash Kumar , Mahala Deep Mohan , Yadav Dinesh Kumar , Khan M. A. , Singh Surendra , Singh Shikha , Vara Prasad P. V.
Published: May 2023

Introduction: Soil organic matter (SOM) quality is the major driving force for nutrient cycles impacting the productivity of cropping systems. Identification of sensitive indicators and developing metrics to assess SOM quality is a major challenge under field conditions.

Methods: Data from a continuing long-term experiment since 2005 at Modipuram, India, were analyzed with key objectives to 1) observe the long-term effect of vermicompost/crop residues alone or in conjunction with NPK chemical fertilizers on crop yield and quality of SOM, 2) identify and develop SOM quality indicators (SOMQI) by encompassing sensitive indicators, and 3) predict system productivity by using SOMQI under rice (Oryza sativa L.)–potato (Solanum tuberosum L.)–wheat (Triticum aestivum L.) (RPW) and maize (Zea mays L.)–potato–onion (Allium cepa L.) (MPO) cropping systems. The treatments comprised of 100% NPK fertilizer; 100% N from vermicompost (N-VC); 50% NPK from fertilizer + 50% N from VC; 100% NPK from fertilizer + crop residue (CR); 100% N from VC + CR.

Results: Results showed that continuous application of 100% N-VC and 100% N-VC+CR for eight years considerably increased the soil’s particulate organic matter carbon (POM-C), light fraction organic matter carbon (LFOM-C), and nitrogen (LFOM-N), dissolved organic carbon (DOC) and nitrogen (DON), as well as the available N (AN), available P (AP) and available S (AS) over control. Principal component analysis (PCA) identified AN, POM-C, LFOM-C: N, and DON in RPW and AN, POM-C, microbial biomass carbon (MBC), and LFOM-C: N in MPO cropping system as sensitive SOM quality indicators for the development of SOMQI. Under the MPO cropping system, results were more pronounced with 100% N-VC and 50% NPK+50% N-VC at 0–15 cm soil depth. Furthermore, at 15–30 cm depth, the effect was more prominent in 100% NPK + CR over other treatments.

Discussion: Overall MPO cropping system exhibited better SOMQI than the RPW system. Rice, wheat, and maize yields increased significantly under different fertilizer treatments with organic or inorganic amendments. Substitution of fertilizer N with organic sources showed comparable yields obtained under 100% NPK treatment. Partial substitution of chemical fertilizers either by VC and/or CR enhanced the SOM quality and productivity under both cropping systems. The use of PCA-based SOMQI can be helpful in assessing SOM quality and predicting the productivity of cropping systems.
Environmental protection tax law and total factor productivity of listed firms: promotion or inhibition?
Authors: Yang Shuwang , Wang Chao , Lyu Kangni , Li Jiapeng
Published: May 2023

The trade-off between environment and economy has been one of the hot topics discussed in academia, but there are many disputes among them. Based on the micro data of Chinese listed companies from 2016 to 2020, this paper uses the shock of the Environmental Protection Tax Law (EPTL) in 2018 as a quasi-natural experiment. Our Differences-in-Differences (DID) method is used to study the impact of the environmental governance pressure caused by the EPTL on firms’ total factor productivity (TFP). The conclusions suggest that: 1) The EPTL has significantly improved heavily polluting enterprises’ TFP, and this finding remains stable after a range of robustness checks. 2) The subgroup analysis shows that. The smaller the size of the administrative expenses paid by the enterprises, the larger the effect of the EPTL on firms’ TFP; the positive effect of the EPTL on the TFP of heavily polluting enterprises is not pronounced in the sample of small-scale enterprises; when the degree of financial slack is small, the effect of the EPTL on firms’ TFP is greater; the effect of the EPTL is greater when the enterprises are located in provincial capital and municipalities. 3) Meanwhile, we also find that promoting firm value and stimulating green innovation may be the potential mechanisms of the EPTL affecting firms’ TFP. This paper provides experience summary for the firms’ high-quality development under the background of government environmental governance.
Long-term functional recovery and associated microbial community structure after sediment drying and bedform migration
Authors: Oprei Anna , Schreckinger José , Kholiavko Tatiana , Frossard Aline , Mutz Michael , Risse-Buhl Ute
Published: May 2023

Climate change and erosion from agricultural areas cause increased drying periods and bedform migration of riverbeds, respectively, worldwide. Both sediment drying and bedform migration can independently stress the microbial community residing in the riverbed. Here, we investigated the microbial response after exposure to these stressors with a focus on long-term recovery. We conducted an in situ experiment to investigate the long-term (8 months) functional and structural recovery of benthic microbial communities from either sediment drying (episodic severe stressor) or bedform migration (frequent moderate stressor). Stressed sediment associated communities were rewetted (dried sediments) and immobilized (migrated sediments) and exposed in the River Spree (north-eastern Germany) to initiate the recovery process. We then evaluated the microbial function (community respiration, net community production and extracellular enzymatic activities) as well as the bacterial, fungal and diatom community structure (16S rRNA gene and ITS region metabarcoding, and microscopic diatom morphotype classification). We observed different recovery times for community respiration (less than 7 days) and gross primary production (more than 5 months), implying a shift toward net heterotrophy in the first few months after stress exposure. Similarly, we observed a strong autotrophic community response (particularly associated with the diatoms Navicula and Fragilaria), especially in migrated sediments. The bacterial and fungal community response to sediment drying was stronger than to bedform migration (particularly associated with the bacterium Flavobacterium and the fungi Alternaria sp. and Aureobasidium pullulans). Our results show that sediment drying and bedform migration had a significant impact on the microbial community function and structure, which persisted for several months after the stress. Due to the surprising long period of recovery, successive stress events combined with seasonal effects will likely hamper the ongoing recovery process with severe alterations to the microbial function and structure. These findings extend the concept of ecosystem resilience and stability on the dimensions of timescale and seasonal environmental variations. Legacy effects are expected to play a key role when facing future stress.
Soft tissue preservation in the Triassic pachypleurosaur Keichousaurus hui: evidence for digestive tract anatomy, diet, and feeding behavior
Authors: Li Ji , Lehrmann Daniel J. , Luo Yong-ming , Adams Thomas L. , Yu Mei-yi , Liao Jun-ling , Qin Yan-jiao , Li Yu-lan , Wang Yue
Published: May 2023

Keichousaurus huiis the most abundant and representative species in the Xingyi biota in South China.K. huihas been studied in many aspects, including its functional morphology, osteology, ontogeny, allometric growth, sexual dimorphism, and reproduction. Previous studies have assumed thatKeichousaurus’ anteriorly curved teeth were used to impale prey and to tear and swallow either the whole or partially fragmented prey. Prey items have been assumed to be small fish or soft-bodied invertebrates, such as squid and shrimp, that were also present in the Xingyi biota. However, there has been no direct evidence for the anatomy of the digestive tract or the diet of theKeichousaurus. There are few reports of the soft tissue preservation ofK. hui. In this study, we present relatively complete preservation of the digestive tract with food remains in several well-preserved specimens ofK. hui. By comparing with modern reptiles, we reconstructed the internal distribution and organ composition of the digestive tract ofK. hui.Through the analysis of the alimentary canal remnants by microscope and X-ray computed microtomography, we infer thatK. huiwas a frequently piscivorous species that usually swallowed its prey whole.
Leaf litter decomposition rates: influence of successional age, topography and microenvironment on six dominant tree species in a tropical dry forest
Authors: Morffi-Mestre Hernán , Ángeles-Pérez Gregorio , Powers Jennifer S. , Andrade José Luis , Feldman Richard Evan , May-Pat Filogonio , Chi-May Francisco , Dupuy-Rada Juan Manuel
Published: May 2023

Litter decomposition is a central process in forest ecosystems because of its role in carbon and nutrient cycling and maintaining soil fertility. Decomposition is affected by plant traits, soil and microenvironmental conditions, topography, and vegetation structure, which varies with successional age. However, it is unclear how all these factors affect leaf decomposition of dominant tree species in tropical dry forests (TDFs). The objective of this study was to compare the decomposition rates of six dominant tree species: three legumes (Caesalpinia gaumeri,Lysiloma latisiliquum,Piscidia piscipula) and three non-legumes (Bursera simaruba,Gymnopodium floribundum,Neomillspaughia emarginata) in five successional age categories (8–10, 15–22, 23–30, 65–84, > 85 years-old) and two topographic conditions (flat and sloping sites) in a TDF, and to analyze the association with leaf traits (toughness, N, C and total phenols content) soil properties (bulk density, organic carbon, pH, clay), microenvironmental (litter and soil moisture, leaf area index), and vegetation variables (basal area, aboveground biomass, tree diameter, tree height). Litterbags were placed in 30–400 m2circular plots distributed in forests of the Yucatan, Mexico, and collected on six occasions spread over 230 days (540 samples per species).L. latisiliquumandC. gaumerihad the highest decomposition rates (as well as leaf nitrogen concentration and the lowest leaf toughness). Conversely,G. floribundumhad the lowest decay rate. Decomposition rate reached high values at intermediate successional ages, suggesting that soil fertility recovers rapidly after disturbance, although onlyL. latisiliquumshowed significant differences among stand age categories. Decomposition rate was consistently higher at flat sites than on slopes but the difference was significant only forL. latisiliquum. The soil, vegetation structure and microenvironmental variables that contributed most to explaining variation in decay rates varied among species. Decomposition tended to increase with soil moisture and clay content, and to decrease with soil organic carbon and pH suggesting susceptibility to climate change and soil erosion, particularly in sloping areas. Our results highlight the importance of analyzing species-specific responses, especially for dominant species, which likely contribute most to leaf litter decomposition, and to consider key ecological factors that influence this key process.
Ethical and legal challenges in nanomedical innovations: a scoping review
Authors: Wasti Sophia , Lee Il Ho , Kim Sumin , Lee Jae-Hyun , Kim Hannah
Published: May 2023

Background:Rapid advancements in research and development related to nanomedical technology raise various ethical and legal challenges in areas relevant to disease detection, diagnosis, and treatment. This study aims to outline the existing literature, covering issues associated with emerging nanomedicine and related clinical research, and identify implications for the responsible advancement and integration of nanomedicine and nanomedical technology throughout medical networks in the future.

Methods:A scoping review, designed to cover scientific, ethical, and legal literature associated with nanomedical technology, was conducted, generating and analyzing 27 peer-reviewed articles published between 2007–2020.

Results:Results indicate that articles referencing ethical and legal issues related to nanomedical technology were concerned with six key areas: 1) harm exposure and potential risks to health, 2) consent to nano-research, 3) privacy, 4) access to nanomedical technology and potential nanomedical therapies, 5) classification of nanomedical products in relation to the research and development of nanomedical technology, and 6) the precautionary principle as it relates to the research and development of nanomedical technology.

Conclusion:This review of the literature suggests that few practical solutions are comprehensive enough to allay the ethical and legal concerns surrounding research and development in fields related to nanomedical technology, especially as it continues to evolve and contribute to future innovations in medicine. It is also clearly apparent that a more coordinated approach is required to ensure global standards of practice governing the study and development of nanomedical technology, especially as discussions surrounding the regulation of nanomedical research throughout the literature are mainly confined to systems of governance in the United States.
Investigating the effects of long-term Aroclor 1260 exposure on fatty liver disease in a diet-induced obesity mouse model
Authors: Head Kimberly Z. , Bolatimi Oluwanifemi E. , Gripshover Tyler C. , Tan Min , Li Yan , Audam Timothy N. , Jones Steven P. , Klinge Carolyn M. , Cave Matthew C. , Wahlang Banrida
Published: May 2023

Introduction

Polychlorinated biphenyls (PCBs) are persistent environmental toxicants that have been implicated in numerous health disorders including liver diseases such as non-alcoholic fatty liver disease (NAFLD). Toxicant-associated NAFLD, also known as toxicant-associated fatty liver disease (TAFLD), consists of a spectrum of disorders ranging from steatosis and steatohepatitis to fibrosis and hepatocellular carcinoma. Previously, our group demonstrated that 12-week exposure to the PCB mixture, Aroclor 1260, exacerbated steatohepatitis in high-fat diet (HFD)-fed mice; however, the longer-term effects of PCBs on TAFLD remain to be elucidated. This study aims to examine the longer-term effects of Aroclor 1260 (>30 weeks) in a diet-induced obesity model to better understand how duration of exposure can impact TAFLD.

Methods

Male C57BL/6 mice were exposed to Aroclor 1260 (20 mg/kg) or vehicle control by oral gavage at the beginning of the study period and fed either a low-fat diet (LFD) or HFD throughout the study period.

Results

Aroclor 1260 exposure (>30 weeks) led to steatohepatitis only in LFD-fed mice. Several Aroclor 1260 exposed LFD-fed mice also developed hepatocellular carcinoma (25%), which was absent in HFD-fed mice. The LFD+Aroclor1260 group also exhibited decreased hepatic Cyp7a1 expression and increased pro-fibrotic Acta2 expression. In contrast, longer term Aroclor 1260 exposure in conjunction with HFD did not exacerbate steatosis or inflammatory responses beyond those observed with HFD alone. Further, hepatic xenobiotic receptor activation by Aroclor 1260 was absent at 31 weeks post exposure, suggesting PCB redistribution to the adipose and other extra-hepatic tissues with time.

Discussion

Overall, the results demonstrated that longer-term PCB exposure worsened TAFLD outcomes independent of HFD feeding and suggests altered energy metabolism as a potential mechanism fueling PCB mediated toxicity without dietary insult. Additional research exploring mechanisms for these longer-term PCB mediated toxicity in TAFLD is warranted.
Activated tissue resident memory T-cells (CD8+CD103+CD39+) uniquely predict survival in left sided “immune-hot” colorectal cancers
Authors: Talhouni Shahd , Fadhil Wakkas , Mongan Nigel P. , Field Lara , Hunter Kelly , Makhsous Sogand , Maciel-Guerra Alexandre , Kaur Nayandeep , Nestarenkaite Ausrine , Laurinavicius Arvydas , Willcox Benjamin E. , Dottorini Tania , Spendlove Ian , Jackson Andrew M. , Ilyas Mohammad , Ramage Judith M.
Published: May 2023

Introduction

Characterization of the tumour immune infiltrate (notably CD8+ T-cells) has strong predictive survival value for cancer patients. Quantification of CD8 T-cells alone cannot determine antigenic experience, as not all infiltrating T-cells recognize tumour antigens. Activated tumour-specific tissue resident memory CD8 T-cells (TRM) can be defined by the co-express of CD103, CD39 and CD8. We investigated the hypothesis that the abundance and localization of TRM provides a higher-resolution route to patient stratification.

Methods

A comprehensive series of 1000 colorectal cancer (CRC) were arrayed on a tissue microarray, with representative cores from three tumour locations and the adjacent normal mucosa. Using multiplex immunohistochemistry we quantified and determined the localization of TRM.

Results

Across all patients, activated TRM were an independent predictor of survival, and superior to CD8 alone. Patients with the best survival had immune-hot tumours heavily infiltrated throughout with activated TRM. Interestingly, differences between right- and left-sided tumours were apparent. In left-sided CRC, only the presence of activated TRM (and not CD8 alone) was prognostically significant. Patients with low numbers of activated TRM cells had a poor prognosis even with high CD8 T-cell infiltration. In contrast, in right-sided CRC, high CD8 T-cell infiltration with low numbers of activated TRM was a good prognosis.

Conclusion

The presence of high intra-tumoural CD8 T-cells alone is not a predictor of survival in left-sided CRC and potentially risks under treatment of patients. Measuring both high tumour-associated TRM and total CD8 T-cells in left-sided disease has the potential to minimize current under-treatment of patients. The challenge will be to design immunotherapies, for left-sided CRC patients with high CD8 T-cells and low activate TRM,that result in effective immune responses and thereby improve patient survival.
Potential angiogenic, immunomodulatory, and antifibrotic effects of mesenchymal stem cell-derived extracellular vesicles in systemic sclerosis
Authors: Zhao Kelin , Kong Chenfei , Shi Naixu , Jiang Jinlan , Li Ping
Published: May 2023

Systemic sclerosis (SSc) is an intricate systemic autoimmune disease with pathological features such as vascular injury, immune dysregulation, and extensive fibrosis of the skin and multiple organs. Treatment options are limited; however, recently, mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) have been acknowledged in preclinical and clinical trials as being useful in treating autoimmune diseases and are likely superior to MSCs alone. Recent research has also shown that MSC-EVs can ameliorate SSc and the pathological changes in vasculopathy, immune dysfunction, and fibrosis. This review summarizes the therapeutic effects of MSC-EVs on SSc and the mechanisms that have been discovered to provide a theoretical basis for future studies on the role of MSC-EVs in treating SSc.
Peripheral nerve repair is associated with augmented cross-tissue inflammation following vascularized composite allotransplantation
Authors: Shah Ashti M. , Aral Ali Mubin , Zamora Ruben , Gharpure Nitin , El-Dehaibi Fayten , Zor Fatih , Kulahci Yalcin , Karagoz Huseyin , Barclay Derek A. , Yin Jinling , Breidenbach Warren , Tuder Dmitry , Gorantla Vijay S. , Vodovotz Yoram
Published: May 2023

Introduction

Vascularized composite allotransplantation (VCA), with nerve repair/coaptation (NR) and tacrolimus (TAC) immunosuppressive therapy, is used to repair devastating traumatic injuries but is often complicated by inflammation spanning multiple tissues. We identified the parallel upregulation of transcriptional pathways involving chemokine signaling, T-cell receptor signaling, Th17, Th1, and Th2 pathways in skin and nerve tissue in complete VCA rejection compared to baseline in 7 human hand transplants and defined increasing complexity of protein-level dynamic networks involving chemokine, Th1, and Th17 pathways as a function of rejection severity in 5 of these patients. We next hypothesized that neural mechanisms may regulate the complex spatiotemporal evolution of rejection-associated inflammation post-VCA.

Methods

For mechanistic and ethical reasons, protein-level inflammatory mediators in tissues from Lewis rats (8 per group) receiving either syngeneic (Lewis) or allogeneic (Brown-Norway) orthotopic hind limb transplants in combination with TAC, with and without sciatic NR, were compared to human hand transplant samples using computational methods.

Results

In cross-correlation analyses of these mediators, VCA tissues from human hand transplants (which included NR) were most similar to those from rats undergoing VCA + NR. Based on dynamic hypergraph analyses, NR following either syngeneic or allogeneic transplantation in rats was associated with greater trans-compartmental localization of early inflammatory mediators vs. no-NR, and impaired downregulation of mediators including IL-17A at later times.

Discussion

Thus, NR, while considered necessary for restoring graft function, may also result in dysregulated and mis-compartmentalized inflammation post-VCA and therefore necessitate mitigation strategies. Our novel computational pipeline may also yield translational, spatiotemporal insights in other contexts.
Origin, phenotype and autoimmune potential of T cells in human immune system mice receiving neonatal human thymus tissue
Authors: Talaie Tara , Wang Hui , Kuo Wan-I , Danzl Nichole , Gulsen Mert R. , Wolabaugh Amber N. , Ding Xiaolan , Sykes Megan , Li Hao Wei
Published: May 2023

Robust human immune system (HIS) mice are created using human fetal thymus tissue and hematopoietic stem cells (HSCs). A HIS mouse model using neonatal human thymus tissue and umbilical cord blood (CB) HSCs (NeoHu) was recently described. We improved the model by removing the native murine thymus, which can also generate human T cells, and demonstrated definitively the capacity of human T cells to develop in a grafted neonatal human thymus. Human T cells derived from the neonatal thymus tissue appeared in peripheral blood early post-transplantation and CB-derived T cells appeared later. Naïve T cells were demonstrated in peripheral blood but effector memory and T peripheral helper phenotypes predominated later, in association with development of autoimmunity in some animals. Treatment of thymus grafts with 2-deoxyglucose (2-DG) increased the proportion of stem cells derived from injected HSCs, delayed onset of autoimmune disease, reduced early T cell reconstitution, and reduced effector/memory T cell conversion. Younger neonatal human thymus tissue was associated with improved T cell reconstitution. While the NeoHu model bypasses the need for fetal tissue, it has yet to demonstrate equivalent reconstitution to fetal tissue, though 2-DG can improve results by removing native thymocytes prior to transplantation.
Perspective: Daniela Novick, cytokines and their receptors
Authors: Ghezzi Pietro , Fantuzzi Giamila , Dinarello Charles A.
Published: May 2023

This Perspective highlights the work of Dr. Daniela Novick in the field of cytokine biology. Using affinity chromatography to characterize cytokine-binding proteins, she identified soluble forms of the receptors as well as binding proteins for several cytokines, including tumor necrosis factor, interleukin (IL) 6, IL-18 and IL-32. Importantly, her work has been key in the development of monoclonal antibodies against interferons and cytokines. This Perspective discusses her contribution to the field and highlights her recent review on this topic.
The role of dendritic cells and their immunometabolism in rheumatoid arthritis
Authors: Suwa Yuichi , Nagafuchi Yasuo , Yamada Saeko , Fujio Keishi
Published: May 2023

Dendritic cells (DCs) play crucial roles in the pathogenesis of rheumatoid arthritis (RA), a prototypic autoimmune disease characterized by chronic synovitis and joint destruction. Conventional dendritic cells (cDCs) with professional antigen-presenting functions are enriched in the RA synovium. In the synovium, the cDCs are activated and show both enhanced migratory capacities and T cell activation in comparison with peripheral blood cDCs. Plasmacytoid dendritic cells, another subtype of DCs capable of type I interferon production, are likely to be tolerogenic in RA. Monocyte-derived dendritic cells (moDCs), once called “inflammatory DCs”, are localized in the RA synovium, and they induce T-helper 17 cell expansion and enhanced proinflammatory cytokine production. Recent studies revealed that synovial proinflammatory hypoxic environments are linked to metabolic reprogramming. Activation of cDCs in the RA synovium is accompanied by enhanced glycolysis and anabolism. In sharp contrast, promoting catabolism can induce tolerogenic DCs from monocytes. Herein, we review recent studies that address the roles of DCs and their immunometabolic features in RA. Immunometabolism of DCs could be a potential therapeutic target in RA.
Molecular treatment trajectories within psoriatic T lymphocytes: a mini review
Authors: Kuczyńska Martyna , Gabig-Cimińska Magdalena , Moskot Marta
Published: May 2023

Multiple biological processes in mammalian cells are implicated in psoriasis (Ps) development and progression, as well as in the pathogenic mechanisms associated with this chronic immune-mediated inflammatory disease (IMID). These refer to molecular cascades contributing to the pathological topical and systemic reactions in Ps, where local skin-resident cells derived from peripheral blood and skin-infiltrating cells originating from the circulatory system, in particular T lymphocytes (T cells), are key actors. The interplay between molecular components of T cell signalling transduction and their involvement in cellular cascades (i.e. throughout Ca2+/CaN/NFAT, MAPK/JNK, PI3K/Akt/mTOR, JAK/STAT pathways) has been of concern in the last few years; this is still less characterised than expected, even though some evidence has accumulated to date identifying them as potential objects in the management of Ps. Innovative therapeutic strategies for the use of compounds such as synthetic Small Molecule Drugs (SMDs) and their various combinations proved to be promising tools for the treatment of Ps via incomplete blocking, also known as modulation of disease-associated molecular tracks. Despite recent drug development having mainly centred on biological therapies for Ps, yet displaying serious limitations, SMDs acting on specific pathway factor isoforms or single effectors within T cell, could represent a valid innovation in real-world treatment patterns in patients with Ps. Of note, due to the intricate crosstalk between intracellular pathways, the use of selective agents targeting proper tracks is, in our opinion, a challenge for modern science regarding the prevention of disease at its onset and also in the prediction of patient response to Ps treatment.
Induction of Siglec-FhiCD101hi eosinophils in the lungs following murine hookworm Nippostrongylus brasiliensis infection
Authors: Chetty Alisha , Darby Matthew G. , Pillaye Jamie , Taliep A'ishah , Cunningham Adam F. , O’Shea Matthew K. , Katawa Gnatoulma , Layland Laura E. , Ritter Manuel , Horsnell William G. C.
Published: May 2023

Helminth-induced eosinophils accumulate around the parasite at the site of infection, or in parasite-damaged tissues well after the helminth has left the site. The role of helminth-elicited eosinophils in mediating parasite control is complex. While they may contribute to direct parasite-killing and tissue repair, their involvement in long-term immunopathogenesis is a concern. In allergic Siglec-FhiCD101hi, eosinophils are associated with pathology. Research has not shown if equivalent subpopulations of eosinophils are a feature of helminth infection. In this study, we demonstrate that lung migration of rodent hookworm Nippostrongylus brasiliensis (Nb) results in a long-term expansion of distinct Siglec-FhiCD101hi eosinophil subpopulations. Nb-elevated eosinophil populations in the bone marrow and circulation did not present this phenotype. Siglec-FhiCD101hi lung eosinophils exhibited an activated morphology including nuclei hyper-segmentation and cytoplasm degranulation. Recruitment of ST2+ ILC2s and not CD4+ T cells to the lungs was associated with the expansion of Siglec-FhiCD101hi eosinophils. This data identifies a morphologically distinct and persistent subset of Siglec-FhiCD101hi lung eosinophils induced following Nb infection. These eosinophils may contribute to long-term pathology following helminth infection.
Adaptive immunology of Cryptococcus neoformans infections—an update
Authors: Chen Junsong , Shao Jiasheng , Dai Min , Fang Wei , Yang Ya-li
Published: May 2023

The fungal genus Cryptococcus comprises a group of pathogens with considerable phenotypic and genotypic diversity that can lead to cryptococcosis in both healthy and immunocompromised individuals. With the emergence of the HIV pandemic, cryptococcosis, mainly meningoencephalitis, afflicts HIV-infected patients with severe dysfunction of T cells. It has also been reported in recipients of solid organ transplantation and in patients with autoimmune diseases who take immunosuppressive agents long-term, as well as in those with unidentified immunodeficiency. The clinical outcome of the disease is primarily determined by the immune response resulting from the interplay between the host immune system and the pathogen. Most human infections are caused by Cryptococcus neoformans, and nearly all immunological studies have focused on C. neoformans. This review provides an updated understanding of the role of adaptive immunity during infection with C. neoformans in human and animal models over the past half-decade.
Combined analysis of single-cell and bulk RNA sequencing reveals the expression patterns of circadian rhythm disruption in the immune microenvironment of Alzheimer’s disease
Authors: He Huiling , Yang Yingxia , Wang Lingxing , Guo Zeming , Ye Lichao , Ou-Yang Wanjiong , Yang Meili
Published: May 2023

Background

Circadian rhythm disruption (CRD) represents a critical contributor to the pathogenesis of Alzheimer’s disease (AD). Nonetheless, how CRD functions within the AD immune microenvironment remains to be illustrated.

Methods

Circadian rhythm score (CRscore) was utilized to quantify the microenvironment status of circadian disruption in a single-cell RNA sequencing dataset derived from AD. Bulk transcriptome datasets from public repository were employed to validate the effectiveness and robustness of CRscore. A machine learning-based integrative model was applied for constructing a characteristic CRD signature, and RT-PCR analysis was employed to validate their expression levels.

Results

We depicted the heterogeneity in B cells, CD4+ T cells, and CD8+ T cells based on the CRscore. Furthermore, we discovered that CRD might be strongly linked to the immunological and biological features of AD, as well as the pseudotime trajectories of major immune cell subtypes. Additionally, cell–cell interactions revealed that CRD was critical in the alternation of ligand-receptor pairs. Bulk sequencing analysis indicated that the CRscore was found to be a reliable predictive biomarker in AD patients. The characteristic CRD signature, which included 9 circadian‐related genes (CRGs), was an independent risk factor that accurately predicted the onset of AD. Meanwhile, abnormal expression of several characteristic CRGs, including GLRX, MEF2C, PSMA5, NR4A1, SEC61G, RGS1, and CEBPB, was detected in neurons treated with Aβ1-42 oligomer.

Conclusion

Our study revealed CRD-based cell subtypes in the AD microenvironment at single-cell level and proposed a robust and promising CRD signature for AD diagnosis. A deeper knowledge of these mechanisms may provide novel possibilities for incorporating “circadian rhythm-based anti-dementia therapies” into the treatment protocols of individualized medicine.
Delayed diagnosis of pneumonia in the emergency department: factors associated and prognosis
Authors: Bouam Maria , Binquet Christine , Moretto Florian , Sixt Thibault , Vourc’h Michèle , Piroth Lionel , Ray Patrick , Blot Mathieu
Published: May 2023

Introduction

Whether a delayed diagnosis of community-acquired pneumonia (CAP) in the emergency department (ED) is associated with worse outcome is uncertain. We sought factors associated with a delayed diagnosis of CAP in the ED and those associated with in-hospital mortality.

Methods

Retrospective study including all inpatients admitted to an ED (Dijon University Hospital, France) from 1 January to 31 December 2019, and hospitalized with a diagnosis of CAP. Patients diagnosed with CAP in the ED (n = 361, early diagnosis) were compared with those diagnosed later, in the hospital ward, after the ED visit (n = 74, delayed diagnosis). Demographic, clinical, biological and radiological data were collected upon admission to the ED, as well as administered therapies and outcomes including in-hospital mortality.

Results

435 inpatients were included: 361 (83%) with an early and 74 (17%) with a delayed diagnosis. The latter less frequently required oxygen (54 vs. 77%; p < 0.001) and were less likely to have a quick-SOFA score ≥ 2 (20 vs. 32%; p = 0.056). Absence of chronic neurocognitive disorders, of dyspnea, and of radiological signs of pneumonia were independently associated with a delayed diagnosis. Patients with a delayed diagnosis less frequently received antibiotics in the ED (34 vs. 75%; p < 0.001). However, a delayed diagnosis was not associated with in-hospital mortality after adjusting on initial severity.

Conclusion

Delayed diagnosis of pneumonia was associated with a less severe clinical presentation, lack of obvious signs of pneumonia on chest X-ray, and delayed antibiotics initiation, but was not associated with worse outcome.
Multimorbidity and adverse longitudinal outcomes among patients attending chronic outpatient medical care in Bahir Dar, Northwest Ethiopia
Authors: Eyowas Fantu Abebe , Schneider Marguerite , Alemu Shitaye , Getahun Fentie Ambaw
Published: May 2023

Background

Multimorbidity is becoming more prevalent in low-and middle-income countries (LMICs). However, the evidence base on the burden and its longitudinal outcomes are limited. This study aimed to determine the longitudinal outcomes of patients with multimorbidity among a sample of individuals attending chronic outpatient non communicable diseases (NCDs) care in Bahir Dar, northwest Ethiopia.

Methods

A facility-based longitudinal study was conducted among 1,123 participants aged 40+ attending care for single NCD (n = 491) or multimorbidity (n = 633). Data were collected both at baseline and after 1 year through standardized interviews and record reviews. Data were analyzed using Stata V.16. Descriptive statistics and longitudinal panel data analyzes were run to describe independent variables and identify factors predicting outcomes. Statistical significance was considered at p-value <0.05.

Results

The magnitude of multimorbidity has increased from 54.8% at baseline to 56.8% at 1 year. Four percent (n = 44) of patients were diagnosed with one or more NCDs and those having multimorbidity at baseline were more likely than those without multimorbidity to develop new NCDs. In addition, 106 (9.4%) and 22 (2%) individuals, respectively were hospitalized and died during the follow up period. In this study, about one-third of the participants had higher quality of life (QoL), and those having higher high activation status were more likely to be in the higher versus the combined moderate and lower QoL [AOR1 = 2.35, 95%CI: (1.93, 2.87)] and in the combined higher and moderate versus lower level of QoL [AOR2 = 1.53, 95%CI: (1.25, 1.88)].

Conclusion

Developing new NCDs is a frequent occurrence and the prevalence of multimorbidity is high. Living with multimorbidity was associated with poor progress, hospitalization and mortality. Patients having a higher activation level were more likely than those with low activation to have better QoL. If health systems are to meet the needs of the people with chronic conditions and multimorbidity, it is essential to understand diseases trajectories and of impact of multimorbidity on QoL, and determinants and individual capacities, and to increase their activation levels for better health improve outcomes through education and activation.
Case report: Tissue positivity for SARS-CoV-2 in a preterm born infant death of thrombosis: possible intrauterine transmission
Authors: Greco Salvatore , Sanz Juana Maria , Bortolotti Daria , Semprini Chiara Marina , Braga Carlotta , Gafà Roberta , Santi Erica , Maestri Iva , Rizzo Roberta , Greco Pantaleo , Passaro Angelina
Published: May 2023

Intrauterine transmission of SARS-CoV-2 (Severe Acute Respiratory Syndrome Corona Virus 2) is still matter of debate among scientists and there is limited information concerning this aspect of research. This could lead to severe complications of the growing fetus and, theoretically, of the newborn as well. We report the case of a male infant of 1,100 grams, born at 27th week of gestation to a SARS-CoV-2 mother, tested negative for viral detection at delivery. He was immediately admitted to neonatal Intensive Care Unit (ICU) for severe complications, where he died after 37 days by pulmonary embolism and thrombosis of the superior vena cava. After autopsy, SARS-CoV-2 N-protein and Spike RBD were detected in several tissues, particularly in the esophagus, stomach, spleen, and heart, with a significantly higher H-Score than the placenta. In conclusion, immunohistochemical analysis demonstrated SARS-CoV-2 NP and Spike RBD positivity in different tissues suggesting a possible intrauterine transmission. Newborn thrombo-embolism could be a complication of SARS-CoV-2 infection as observed in adult patients.
Differential diagnosis of pulmonary sarcoidosis: a review
Authors: Valeyre Dominique , Brauner Michel , Bernaudin Jean-François , Carbonnelle Etienne , Duchemann Boris , Rotenberg Cécile , Berger Ingrid , Martin Antoine , Nunes Hilario , Naccache Jean-Marc , Jeny Florence
Published: May 2023

Diagnosing pulmonary sarcoidosis raises challenges due to both the absence of a specific diagnostic criterion and the varied presentations capable of mimicking many other conditions. The aim of this review is to help non-sarcoidosis experts establish optimal differential-diagnosis strategies tailored to each situation. Alternative granulomatous diseases that must be ruled out include infections (notably tuberculosis, nontuberculous mycobacterial infections, and histoplasmosis), chronic beryllium disease, hypersensitivity pneumonitis, granulomatous talcosis, drug-induced granulomatosis (notably due to TNF-a antagonists, immune checkpoint inhibitors, targeted therapies, and interferons), immune deficiencies, genetic disorders (Blau syndrome), Crohn’s disease, granulomatosis with polyangiitis, eosinophilic granulomatosis with polyangiitis, and malignancy-associated granulomatosis. Ruling out lymphoproliferative disorders may also be very challenging before obtaining typical biopsy specimen. The first step is an assessment of epidemiological factors, notably the incidence of sarcoidosis and of alternative diagnoses; exposure to risk factors (e.g., infectious, occupational, and environmental agents); and exposure to drugs taken for therapeutic or recreational purposes. The clinical history, physical examination and, above all, chest computed tomography indicate which differential diagnoses are most likely, thereby guiding the choice of subsequent investigations (e.g., microbiological investigations, lymphocyte proliferation tests with metals, autoantibody assays, and genetic tests). The goal is to rule out all diagnoses other than sarcoidosis that are consistent with the clinical situation. Chest computed tomography findings, from common to rare and from typical to atypical, are described for sarcoidosis and the alternatives. The pathology of granulomas and associated lesions is discussed and diagnostically helpful stains specified. In some patients, the definite diagnosis may require the continuous gathering of information during follow-up. Diseases that often closely mimic sarcoidosis include chronic beryllium disease and drug-induced granulomatosis. Tuberculosis rarely resembles sarcoidosis but is a leading differential diagnosis in regions of high tuberculosis endemicity.
Case report: A case of incontinentia pigmenti
Authors: Xie Lingfeng , Zhu Yong , He Liya , Yu Bing , Wang Jiajue , Fan Ruiqiang , Mo Xiumei , Zhang Yu , Xie Ting
Published: May 2023

Incontinentia pigmenti (IP) is a rare neuroectodermal dysplasia caused by mutations in the IKBKG gene. We present a case of a 4-month-old female infant with erythematous vesicular skin lesions on the trunk and extremities. Histopathologic examination of the blisters revealed an eosinophilic infiltrate. Further investigation revealed that her mother had three unexplained miscarriages and two normal uncomplicated pregnancies, resulting in the birth of two male infants. We performed a comprehensive genetic evaluation to rule out the interference of pseudogene IKBKGP, and the infant was finally diagnosed with IP. During the subsequent 2-year follow-up, we observed a significant improvement in her dermatologic symptoms, with no evidence of recurrence, and there were no other associated symptoms in the hair, nails, oral mucosa, eyes, or central nervous system.
Case report: Acne vulgaris treatment with 5-Aminolaevulinic acid photodynamic therapy and adalimumab: a novel approach
Authors: Ping Yang , Jian Bo Zhong , Xing Yun Zhao , Ali Kamran , Jun Chen , Xu Lou Inmaculada , Wu Li Ming
Published: May 2023

Acne vulgaris is a common skin condition that affects a large proportion of teenagers and young adults. Despite the availability of various treatment options, many patients experience inadequate relief or intolerable side effects. Photodynamic therapy (PDT) is a growing interest in the treatment of acne vulgaris, with 5-Aminolaevulinic acid (ALA) being one of the most commonly used photosensitizers. Adalimumab is a biologic medication used to treat inflammatory skin conditions such as Psoriasis and Hidradenitis suppurativa (HS), which targets TNF-α. Combining different therapies, such as ALA-PDT and adalimumab, can often provide more effective and longer-lasting results. This report presents the case of a patient with severe and refractory acne vulgaris who was treated with a combination of ALA-PDT and adalimumab, resulting in significant improvement in the condition. The literature review highlights the significant comorbidity associated with acne, emphasizing the need for potential of TNF-α inhibitors for its effective treatments that address physical symptoms and ALA-PDT is known to treat scar hyperplasia, and to prevent or minimize the formation of post-acne hypertrophic scars. The combination of TNF inhibitors and ALA-PDT or adalimumab has shown promising results in treating inflammatory skin conditions, including severe and refractory acne vulgaris, as per recent studies.