bluuebunny/crossref_metadata_2025 huggingface dataset:
The Role of Interleukin 10 Genetic Variations in Pulmonary Tuberculosis: Perspectives of Genetics, Pathogenesis and Immunology
Authors: Anggraini Debie
Published: April 2024

Pulmonary tuberculosis remains a significant global public health challenge. In efforts to overcome this disease, a deeper understanding of the role of individual genetics, such as IL-10 genetic variation, in the response to M. tuberculosis infection is critical. Research that has been conducted shows that IL-10, which has an important role in regulating the immune response, can also influence the development of TB. Genetic variations in the IL-10 gene play a role in determining the extent of the immune response to TB infection and an individual's risk of this disease. The interaction between Treg cells, IL-10, and TB is also an important aspect in the pathogenesis and management of TB. Although Treg cells and IL-10 have a role in controlling excessive inflammation, too much of either can dampen the immune response needed to overcome infections. The implication of this research is that the development of more targeted and personalized therapy is an important step in overcoming TB. The use of individual genetic knowledge, such as IL-10 genetic variations, can help design more effective therapies and improve patient prognosis. However, challenges such as drug resistance and the complexity of genetic-immunological interactions remain challenges that need to be overcome in TB management. Overall, this study shows the importance of involving the fields of genetics and immunology in global efforts to address pulmonary tuberculosis. With a deeper understanding of the factors that influence the immune response to TB infection, we can hope to develop more effective strategies in the prevention, diagnosis and treatment of this disease and reduce the burden of TB worldwide.
Evasion of the Immune System by Mycobacterium tuberculosis: A Special Review on Macrophages
Authors: Handayani Kurnia Maidarmi , Iswanti Febriana Catur
Published: April 2024

Mycobacterium tuberculosis, the bacterium that caused tuberculosis, is estimated to affect 10 million people worldwide in 2019. This bacterium is an intracellular pathogen that is spread through the inhalation of bacterial aerosol particles. The innate immune system in the lungs is prepared to phagocytize these bacteria, particularly macrophages, dendritic cells, monocytes, and neutrophils. M. tuberculosis can evade attacks by the host immune system and has developed strategies to infect successfully, especially macrophages. This intracellular bacterium can inhibit phagolysosome fusion, which is associated with lipoarabinomannan (LAM) in the bacterial cell wall. M. tuberculosis also can persist in phagolysosomes by inhibiting acidification and also inhibiting the action of NOX2 from producing ROS. This ability also allows these bacteria to avoid autophagy within macrophages. Knowledge of the power of these bacteria to manipulate and evade the immune system, especially macrophages, is beneficial in developing medicines and vaccines in the future.
Korelasi Kadar Vitamin D Serum dan Derajat Keparahan Psoriasis Vulgaris Berdasarkan Skor PASI dan DLQI
Authors: Pramudita Adelia Wuri , Mulianto Nur M Rachmat , Evanti Annisa Marsha , Widyastuti Zilpa , Asaduddin Aiman Hilmi
Published: April 2024

Latar Belakang: Derajat keparahan psoriasis vulgaris ditentukan berdasarkan skor Psoriasis Area and Severity Index (PASI) dan Dermatology Life Quality Index (DLQI). Perjalanan psoriasis dapat dipengaruhi oleh abnormalitas sistem imun, kerentanan genetik, lingkungan dan gaya hidup. Vitamin D juga diduga berperan pada perjalanan berbagai penyakit autoimun termasuk psoriasis. Tujuan: Untuk mengetahui korelasi antara kadar vitamin D serum dengan derajat keparahan psoriasis vulgaris berdasarkan skor  PASI dan DLQI. Metode: Penelitian ini merupakan penelitian analitik eksperimental terhadap 10 subjek dan dilakukan pengukuran kadar vitamin D serum dengan metode Enzyme Linked Immunosorbent Assay (ELISA). Data klinis dan derajat keparahan psoriasis vulgaris dilakukan dengan skoring PASI dan DLQI. Data dianalisis secara deskriptif dan disajikan dalam tabel distribusi frekuensi. Pengolahan data menggunakan uji statistik Spearman untuk menilai korelasi antara kadar vitamin D serum dengan derajat keparahan psoriasis vulgaris berdasarkan skor PASI dan DLQI. Hasil: Analisis data menunjukkan tidak ada korelasi antara kadar vitamin D serum dengan derajat keparahan psoriasis vulgaris berdasarkan PASI (nilai p=0,751 dan koefisien korelasi r=-0,116) dan berdasarkan skor DLQI (nilai p=0,751 dan koefisien korelasi r=-0,116). Kesimpulan: Kadar vitamin D serum tidak berkorelasi dengan derajat keparahan psoriasis vulgaris.
Osteomielitis Kronis Pada Fraktur Kalkaneus Tertutup: Laporan Kasus
Authors: Mahayana I Dewa Komang Surya , D.Pemayun Cok Khrisna , Soraya Fira
Published: April 2024

Osteomielitis merupakan inflamasi tulang akut maupun kronis pada pasien dengan fraktur terbuka dan (walaupun jarang) fraktur tertutup. Osteomielitis dapat terjadi pada semua usia dengan angka kejadian lebih tinggi pada anak dan lebih sering terjadi pada laki-laki. Hingga saat ini belum ada angka pasti tentang insidensi osteomielitis di Indonesia. Osteomielitis dapat menyebar secara hematogen dan inokulasi langsung atau penyebaran langsung infeksi ke tulang. Tatalaksana osteomielitis memiliki tantangan tersendiri karena perlu mempertimbangkan patogen penyebab infeksi yang pada beberapa kasus disebabkan oleh patogen yang tidak umum menyebabkan osteomielitis. Penderita diabetes seringkali akan mengalami diabetic foot infection (DFI), terutama pada kadar gula yang tidak terkontrol. Diabetic foot osteomyelitis (DFO) merupakan konsekuensi paling umum penyebaran infeksi jaringan lunak ke tulang pada DFI. Keterlibatan tulang harus dicurigai pada seluruh pasien diabetes dengan ulkus terutama pada ulkus kronik dan rekuren serta temuan klinis yang mendukung adanya infeksi. Kami melaporkan pasien laki-laki dengan riwayat diabetes mellitus berusia 38 tahun dengan osteomielitis kronis yang terjadi pada fraktur tertutup pada tulang calcaneus. Pasien memiliki riwayat trauma. Hasil pemeriksaan kultur dan sensitivitas antiobiotik didapatkan patogen infeksi Acinetobacter baumannii yang sensitif terhadap Amikacin. Debridement, sequestrectomy dan pemberian bone cement serta pemberian antibiotik empirik Amikacin dilakukan pada pasien ini. Hasil evaluasi post pembedahan pasien baik. Penegakkan diagnosis yang cepat dan akurat dengan mempertimbangkan temuan klinis, riwayat penyakit atau komorbid dan temuan laboratoris, serta tatalaksana yang tepat seperti debridement dan intervensi pembedahan dapat memberikan hasil dan prognosis yang baik pada osteomielitis kronis.
Profile And Risk Factors of Stevens Johnson Syndrome–Toxic Epidermal Necrolysis on Adult Patients in Dr. Moewardi General Hospital Surakarta from January 2019 – December 2022
Authors: Putri Osdatilla Esa , Oktavriana Triasari , Octarica Stella Gracia , Anandita Benedikta Lauda , Pradestine Sesia , Oktaviani Trya
Published: April 2024

Background: Steven Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are acute and life-threatening skin diseases, commonly induced by medications. Study on SJS/TEN in Indonesia was still limited, hence knowledge about the profile and risk factors of SJS/TEN patients is still required to provide appropriate management and reduce patient mortality rate. This study aimed to determine the profile and risk factors of adult SJS/TEN patients in the inpatient installation of RSDM Surakarta. Methods: We conducted a cross sectional study using secondary data from medical records of SJS/TEN patients at the inpatient installation of Dr. Moewardi hospital, Surakarta from 2019 – 2022. Correlation tests on characteristics, comorbidity with length of stay (LoS) and discharge status were analyzed. Results: Of the total 147,531 inpatients, 35 (0.02%) of them were diagnosed with SJS/TEN, dominated by females (57.14%) with the mean  of 45.74 years old.  Most subjects were diagnosed with SJS (48.57%), followed by SJS/TEN (40.0%) and TEN (11.43%). The mean LoS was  ± 8 days. Most subjects were discharged alive (85.71%). Paracetamol was the most common causative drug (25.71%), followed by cefadroxil (11.43%). Acute kidney injury (AKI) was the most common comorbidity (14.29%, p = 0.040). Spearman Rank test obtained no correlation between comorbidities and LoS (r = 0.028 ; p = 0.842) as well as discharge status (r = 0.063 ; p = 0.651). Conclusion: SJS/TEN is rare case with high mortality rate. Patients’ comorbidities have a very weak correlation with LoS and discharge status. Initial knowledge of the patient’s profile and risk factors including comorbidity and causative drugs can optimise comprehensive therapy for SJS/TEN patients.
O trânsito das companhias líricas entre as cidades de Desterro e Rio Grande de 1850 a 1880
Authors: Pedrotti Dutra Meneses Marcele , Holler Marcos
Published: April 2024

Os espaços teatrais existentes na segunda metade do século XIX abrigavam espetáculos de companhias líricas que percorriam a costa marítima para apresentar-se em diversas cidades do Brasil, incluindo em sua rota as cidades de Desterro e Rio Grande. Neste texto são abordadas questões com o objetivo de compreender uma parcela dessas rotas desenvolvidas pelas formações musicais. O referencial teórico centra-se sobretudo no processo civilizatório a partir de Norbert Elias (1994, 2001).
RACE, MILIEU, AND MOMENT IN GONE WITH THE WIND BY MARGARET MITCHELL
Authors: Son Wel , Satria Robby
Published: April 2024

Abstract
The purpose of creating this research is to reveal race, milieu, and moment in the novel “Gone with the Wind” written by Margaret Mitchell. In this research, researchers focused on applying historical approach by Hippolyte Adolphe Taine in Guerin et al. (2005) that consists race, milieu and moment to analyze “Gone with the Wind” novel as the data source. Besides applying the theory, descriptive qualitative research by Sugiyono (2012) was also applied by researchers due to the phenomena that were found in written form. To collect the data, researchers applied library research method by George (2008) by following four steps, they are: took “Gone with the Wind” novel as the data source, read the novel carefully, find the race, milieu, and moment, and collect and divide the data found. In analyzing the data, researchers focused on analyzing the extrinsic element explained by Wellek & Warren (1949) by applying race, milieu, and moment theory and presented them descriptively. For the findings, researcher found the race or racial differences on the skin color and their nationality in United States of America on North Georgia, in the Old South region. The milieu was discovered in the character’s occupation where they worked as businessman, plantation owner, breeding farm owner, student, farmer, soldier, maid, horse coachman, doctor, and prostitute. In addition, researchers also found the moment in the incident of Civil War and the slavery.
Keywords: Historical approach, Racial Differences, Slavery.
LEXICAL COHESION ANALYSIS OF DONALD TRUMP’S SCRIPT SPEECH
Authors: Silaen Elperinda , Afriana Afriana
Published: April 2024

Abstract
This study has target to find lexical cohesion in the text of a speech delivered by a controversial president, Donald Trump. The researcher also reveals several reasons why the writing problem is on lexical cohesion where cohesive devices play an important role in shaping a speech and the use of language that is organized and easily understood by others in delivering a speech will have an impact on communication that goes well, so as to avoid misunderstandings between speakers and listeners. Therefore, the method used in this research is qualitative and this descriptive qualitative research also used observational method and note taking technique. In supporting data collection techniques, researchers use the theory of Creswell (2018) and also support by Merriam &Tisdell (2016) .The next by Litosseliti (2010). The lexical cohesion proposed by Matthienssen & Halliday, (2014) has several types of lexical cohesion consist of repetition, synonymy, antonymy, hyponymy, and meronymy. For the results of data analysis, there are 50 repetitions then 1 hyponymy then 1 meronym, 2 synonyms, and finally 1 antonym.
Keywords: Speech Script, Cohesion, Lexical cohesion, Qualitative
Deciphering the triad of endothelial glycocalyx, von Willebrand Factor, and P-selectin in inflammation-induced coagulation
Authors: Ferreira Guinevere , Taylor Alexandra , Mensah Solomon A.
Published: April 2024

This review examines the endothelial glycocalyx’s role in inflammation and explores its involvement in coagulation. The glycocalyx, composed of proteins and glycosaminoglycans, interacts with von Willebrand Factor and could play a crucial role in anchoring it to the endothelium. In inflammatory conditions, glycocalyx degradation may leave P-selectin as the only attachment point for von Willebrand Factor, potentially leading to uncontrolled release of ultralong von Willebrand Factor in the bulk flow in a shear stress-dependent manner. Identifying specific glycocalyx glycosaminoglycan interactions with von Willebrand Factor and P-selectin can offer insights into unexplored coagulation mechanisms.
SIRT1 exerts protective effects by inhibiting endoplasmic reticulum stress and NF-κB signaling pathways
Authors: Zhao Kaixuan , Zhang Haoyue , Yang Dong
Published: April 2024

Silent information regulator two homolog 1 (SIRT1), an NAD + -dependent histone deacetylase, plays a pivotal regulatory role in a myriad of physiological processes. A growing body of evidence suggests that SIRT1 can exert protective effects in metabolic disorders and neurodegenerative diseases by inhibiting endoplasmic reticulum (ER) stress and the nuclear factor-κB (NF-κB) inflammatory signaling pathway. This review systematically elucidates the molecular mechanisms and biological significance of SIRT1 in regulating ER stress and the NF-κB pathway. On one hand, SIRT1 can deacetylate key molecules in the ER stress pathway, such as glucose-regulated protein 78 (GRP78), X-box binding protein 1 (XBP1), PKR-like ER kinase (PERK), inositol-requiring enzyme 1α (IRE1α), and activating transcription factor 6 (ATF6), thereby alleviating ER stress. On the other hand, SIRT1 can directly or indirectly remove the acetylation modification of the NF-κB p65 subunit, inhibiting its transcriptional activity and thus attenuating inflammatory responses. Through these mechanisms, SIRT1 can ameliorate insulin resistance in metabolic diseases, exert cardioprotective effects in ischemia-reperfusion injury, and reduce neuronal damage in neurodegenerative diseases. However, it is important to note that while these findings are promising, the complex nature of the biological systems involved warrants further investigation to fully unravel the intricacies of SIRT1’s regulatory mechanisms. Nevertheless, understanding the regulatory mechanisms of SIRT1 on ER stress and the NF-κB pathway is of great significance for expanding our knowledge of the pathogenesis of related diseases and exploring new preventive and therapeutic strategies targeting SIRT1.
Establishment of two serological methods for detecting IgG and neutralizing antibodies against Crimean-Congo hemorrhagic fever virus glycoprotein
Authors: Wang Qi , Wang Shen , Shi Zhikang , Li Zhengrong , Zhao Yongkun , Feng Na , Wang Tiecheng , Yan Feihu , Xia Xianzhu
Published: April 2024

Introduction

The Crimean-Congo hemorrhagic fever virus (CCHFV), the most geographically widespread tick-borne virus, is endemic in Africa, Eastern Europe and Asia, with infection resulting in mortality in up to 30% of cases. Currently, there are no approved vaccines or effective therapies available for CCHF. The CCHFV should only be manipulated in the BSL-4 laboratory, which has severely hampered basic seroprevalence studies.

Methods

In the present study, two antibody detection methods in the forms of an enzyme-linked immunosorbent assay (ELISA) and a surrogate virus neutralization test (sPVNT) were developed using a recombinant glycoprotein (rGP) and a vesicular stomatitis virus (VSV)-based virus bearing the CCHFV recombinant glycoprotein (rVSV/CCHFV) in a biosafety level 2 (BSL-2) laboratory, respectively.

Results

The rGP-based ELISA and rVSV/CCHFV-based sVNT were established by using the anti-CCHFV pre-GC mAb 11E7, known as a broadly cross-reactive, potently neutralizing antibody, and their applications as diagnostic antigens were validated for the specific detection of CCHFV IgG and neutralizing antibodies in experimental animals. In two tests, mAb clone 11E7 (diluted at 1:163840 or 512) still displayed positive binding and neutralization, and the presence of antibodies (IgG and neutralizing) against the rGP and rVSV/CCHFV was also determined in the sera from the experimental animals. Both mAb 11E7 and animal sera showed a high reactivity to both antigens, indicating that bacterially expressed rGP and rVSV/CCHFV have good immunoreactivity. Apart from establishing two serological testing methods, their results also demonstrated an imperfect correlation between IgG and neutralizing antibodies.

Discussion

Within this limited number of samples, the rGP and rVSV/CCHFV could be safe and convenient tools with significant potential for research on specific antibodies and serological samples.
Incomplete Plasmodium falciparum growth inhibition following piperaquine treatment translates into increased parasite viability in the in vitro parasite reduction ratio assay
Authors: Walz Annabelle , Sax Sibylle , Scheurer Christian , Tamasi Balint , Mäser Pascal , Wittlin Sergio
Published: April 2024

Antimalarial resistance to the first-line partner drug piperaquine (PPQ) threatens the effectiveness of artemisinin-based combination therapy. In vitro piperaquine resistance is characterized by incomplete growth inhibition, i.e. increased parasite growth at higher drug concentrations. However, the 50% inhibitory concentrations (IC50) remain relatively stable across parasite lines. Measuring parasite viability of a drug-resistant Cambodian Plasmodium falciparum isolate in a parasite reduction ratio (PRR) assay helped to better understand the resistance phenotype towards PPQ. In this parasite isolate, incomplete growth inhibition translated to only a 2.5-fold increase in IC50 but a dramatic decrease of parasite killing in the PRR assay. Hence, this pilot study reveals the potential of in vitro parasite viability assays as an important, additional tool when it comes to guiding decision-making in preclinical drug development and post approval. To the best of our knowledge, this is the first time that a compound was tested against a drug-resistant parasite in the in vitro PRR assay.
Automatic assessment of atherosclerotic plaque features by intracoronary imaging: a scoping review
Authors: Biccirè Flavio Giuseppe , Mannhart Dominik , Kakizaki Ryota , Windecker Stephan , Räber Lorenz , Siontis George C. M.
Published: April 2024

Background

The diagnostic performance and clinical validity of automatic intracoronary imaging (ICI) tools for atherosclerotic plaque assessment have not been systematically investigated so far.

Methods

We performed a scoping review including studies on automatic tools for automatic plaque components assessment by means of optical coherence tomography (OCT) or intravascular imaging (IVUS). We summarized study characteristics and reported the specifics and diagnostic performance of developed tools.

Results

Overall, 42 OCT and 26 IVUS studies fulfilling the eligibility criteria were found, with the majority published in the last 5 years (86% of the OCT and 73% of the IVUS studies). A convolutional neural network deep-learning method was applied in 71% of OCT- and 34% of IVUS-studies. Calcium was the most frequent plaque feature analyzed (26/42 of OCT and 12/26 of IVUS studies), and both modalities showed high discriminatory performance in testing sets [range of area under the curve (AUC): 0.91–0.99 for OCT and 0.89–0.98 for IVUS]. Lipid component was investigated only in OCT studies (n = 26, AUC: 0.82–0.86). Fibrous cap thickness or thin-cap fibroatheroma were mainly investigated in OCT studies (n = 8, AUC: 0.82–0.94). Plaque burden was mainly assessed in IVUS studies (n = 15, testing set AUC reported in one study: 0.70).

Conclusion

A limited number of automatic machine learning-derived tools for ICI analysis is currently available. The majority have been developed for calcium detection for either OCT or IVUS images. The reporting of the development and validation process of automated intracoronary imaging analyses is heterogeneous and lacks critical information.

Systematic Review Registration

Open Science Framework (OSF), https://osf.io/nps2b/.
A path model analysis of preform students’ factors and comprehension strategies on cognitive learning outcomes associated with text comprehension
Authors: Hunsu Nathaniel J. , Adesope Olusola Olalekan , Yli-Piipari Sami R.
Published: April 2024

Introduction

The ability to understand text is influenced by various factors, including the learner’s cognitive abilities and previous experiences. This study examined the correlation between two pre-existing learner characteristics, three comprehension strategies used while reading, and two cognitive outcomes related to text comprehension.

Methods

The study involved 109 undergraduate Biology students, who were instructed to perform think-aloud exercises while reading biology texts and complete post-reading tests. The participants typed out their thoughts about the text when prompted. Their verbal protocols were coded and analyzed.

Results

Statistically significant correlations were only observed between prior knowledge, presage skill, recall, and comprehension. The direct relationships between prior knowledge and cognitive strategies were not significant, and the relationship between participants’ presage skills and the comprehension strategies they employed while reading was not significant.

Discussion

The study revealed that prior knowledge had a more significant impact on cognitive learning outcomes than the students’ prior cognitive skills and the comprehension strategies they employed while reading. Additionally, the participant’s performance on the learning outcomes was influenced by at least one of the comprehension strategies and their prior knowledge.
The model for predicting the central lymph node metastasis in cN0 papillary thyroid microcarcinoma with Hashimoto’s thyroiditis
Authors: Lin Yuyang , Cui Na , Li Fei , Wang Yixuan , Wang Bei
Published: April 2024

Background

The relationship between Hashimoto’s thyroiditis (HT) and papillary thyroid microcarcinoma (PTMC) is controversial. These include central lymph node metastasis (CLNM), which affects the prognosis of PTMC patients. This study aimed to establish a predictive model combining ultrasonography and clinicopathological features to accurately evaluate latent CLNM in PTMC patients with HT at the clinical lymph node-negative (cN0) stage.

Methods

In this study, 1102 PTMC patients who received thyroidectomy and central cervical lymph node dissection (CLND) from the First Affiliated Hospital of Shandong First Medical University from January 2021 to December 2022 and the 960th Hospital of PLA from January 2021 to December 2022 were jointly collected. The clinical differences between PTMCs with HT and those without HT were compared. A total of 373 PTMCs with HT in cN0 were randomly divided into a training cohort and a validation cohort. By analyzing and screening the risk factors of CLNM, a nomogram model was established and verified. The predictive performance was measured by the receiver operating characteristic (ROC) curve, calibration curve, and clinical decision curve analysis (DCA).

Results

The ratio of central lymph node metastasis (CLNMR) in PTMCs with HT was 0.0% (0.0%, 15.0%) and 7.7% (0.0%, 40.0%) in the non-HT group (P<0.001). Multivariate logistic regression analysis showed that age, gender, calcification, adjacent to trachea or capsule, and TPOAB were predictors of CLNM in PTMCs with HT. The areas under the curve (AUC) of the prediction models in the training cohort and the validation cohort were 0.835 and 0.825, respectively, which showed good differentiation ability. DCA indicates that the prediction model also has high net benefit and clinical practical value.

Conclusion

This study found that CLN involvement was significantly reduced in PTMC patients with HT, suggesting that different methods should be used to predict CLNM in PTMC patients with HT and without HT, to more accurately assist preoperative clinical evaluation. The actual CLNM situation of PTMCs with HT in cN0 can be accurately predicted by the combination of ultrasonography and clinicopathological features.
Physical performance strongly predicts all-cause mortality risk in a real-world population of older diabetic patients: machine learning approach for mortality risk stratification
Authors: Montesanto Alberto , Lagani Vincenzo , Spazzafumo Liana , Tortato Elena , Rosati Sonia , Corsonello Andrea , Soraci Luca , Sabbatinelli Jacopo , Cherubini Antonio , Conte Maria , Capri Miriam , Capalbo Maria , Lattanzio Fabrizia , Olivieri Fabiola , Bonfigli Anna Rita
Published: April 2024

Background

Prognostic risk stratification in older adults with type 2 diabetes (T2D) is important for guiding decisions concerning advance care planning.

Materials and methods

A retrospective longitudinal study was conducted in a real-world sample of older diabetic patients afferent to the outpatient facilities of the Diabetology Unit of the IRCCS INRCA Hospital of Ancona (Italy). A total of 1,001 T2D patients aged more than 70 years were consecutively evaluated by a multidimensional geriatric assessment, including physical performance evaluated using the Short Physical Performance Battery (SPPB). The mortality was assessed during a 5-year follow-up. We used the automatic machine-learning (AutoML) JADBio platform to identify parsimonious mathematical models for risk stratification.

Results

Of 977 subjects included in the T2D cohort, the mean age was 76.5 (SD: 4.5) years and 454 (46.5%) were men. The mean follow-up time was 53.3 (SD:15.8) months, and 209 (21.4%) patients died by the end of the follow-up. The JADBio AutoML final model included age, sex, SPPB, chronic kidney disease, myocardial ischemia, peripheral artery disease, neuropathy, and myocardial infarction. The bootstrap-corrected concordance index (c-index) for the final model was 0.726 (95% CI: 0.687–0.763) with SPPB ranked as the most important predictor. Based on the penalized Cox regression model, the risk of death per unit of time for a subject with an SPPB score lower than five points was 3.35 times that for a subject with a score higher than eight points (P-value <0.001).

Conclusion

Assessment of physical performance needs to be implemented in clinical practice for risk stratification of T2D older patients.
Specific biomarkers and neurons distribution of different brain regions in largemouth bass (Micropterus salmoides)
Authors: Li Meijia , Yang Leshan , Zhang Lei , Zhang Qian , Liu Ying
Published: April 2024

The brain regulates multiple physiological processes in fish. Despite this, knowledge about the basic structure and function of distinct brain regions in non-model fish species remains limited due to their diversity and the scarcity of common biomarkers. In the present study, four major brain parts, the telencephalon, diencephalon, mesencephalon and rhombencephalon, were isolated in largemouth bass, Micropterus salmoides. Within these parts, nine brain regions and 74 nuclei were further identified through morphological and cytoarchitectonic analysis. Transcriptome analysis revealed a total of 7153 region-highly expressed genes and 176 region-specifically expressed genes. Genes related to growth, reproduction, emotion, learning, and memory were significantly overexpressed in the olfactory bulb and telencephalon (OBT). Feeding and stress-related genes were in the hypothalamus (Hy). Visual system-related genes were predominantly enriched in the optic tectum (OT), while vision and hearing-related genes were widely expressed in the cerebellum (Ce) region. Sensory input and motor output-related genes were in the medulla oblongata (Mo). Osmoregulation, stress response, sleep/wake cycles, and reproduction-related genes were highly expressed in the remaining brain (RB). Three candidate marker genes were further identified for each brain regions, such as neuropeptide FF (npff) for OBT, pro-melanin-concentrating hormone (pmch) for Hy, vesicular inhibitory amino acid transporter (viaat) for OT, excitatory amino acid transporter 1 (eaat1) for Ce, peripherin (prph) for Mo, and isotocin neurophysin (itnp) for RB. Additionally, the distribution of seven neurotransmitter-type neurons and five types of non-neuronal cells across different brain regions were analyzed by examining the expression of their marker genes. Notably, marker genes for glutamatergic and GABAergic neurons showed the highest expression levels across all brain regions. Similarly, the marker gene for radial astrocytes exhibited high expression compared to other markers, while those for microglia were the least expressed. Overall, our results provide a comprehensive overview of the structural and functional characteristics of distinct brain regions in the largemouth bass, which offers a valuable resource for understanding the role of central nervous system in regulating physiological processes in teleost.
Analysis of immunogenetics interlaboratory comparisons’ success rates. External quality assurance system of the Spanish Society for Immunology GECLID-SEI
Authors: Martín M. Carmen
Published: April 2024

Background:

For many years, transplantation outcomes were uncertain and not hopeful, until histocompatibility testing spread. Common criteria for histocompatibility assays and communications’ improvement allowed an efficient organ sharing system. The possibility of organ exchanges is closely linked to the importance of interlaboratory comparisons for histocompatibility and immunogenetics methods. The external proficiency testing (EPT) systems are the most powerful quality assurance tools. They help achieve harmonization of analyses, set a standard of performance, and a common interpretation.

Methods:

The external quality assurance program for diagnostic immunology laboratories (Garantía Externa de Calidad para Laboratorios de Inmunología Diagnóstica, GECLID) program nowadays runs 13 external quality assurance (EQA) histocompatibility and immunogenetics schemes, with the first of them from 2011 to date: serological and molecular: low- and high-resolution human leukocyte antigen (HLA), human platelet antigen (HPA), and killer inhibitory receptor (KIR) typing(HLA-B*27, HLA-B*57:01, and coeliac disease-related HLA), cell-dependent cytotoxicity (CDC) and flow cytometry (FC) crossmatches, anti-HLA and anti-HPA antibodies, and chimerism.

Results:

A total of 85 laboratories participated in this subprogram in the last 12 years reporting over 1.69 M results: 1.46 M for anti-HLA and anti-HPA antibodies, 203.810 molecular typing data (HLA, HPA, and KIR genes), 2.372 for chimerism analyses, and 39.352 for crossmatches. Based on the European Federation for Immunogenetics (EFI) standards for EPT providers, the mean success rates ranged from 99.2% for molecular typing schemes and antibodies and 94.8% for chimerism, was 96.7% regarding crossmatches, and was 98.9% in serological typing. In 2022, 61.3% of the participating laboratories successfully passed every HLA EQA scheme, although 87.9% annual reports were satisfactory. Most penalties were due to nomenclature errors or misreporting of the risk associated to HLA and disease.

Conclusion:

This EQA confirms the reliability of HLA and immunogenetics assays in routine care. There is little heterogeneity of results of different assays used by participating laboratories, even when in-house assays are used. Reliability of test results is reasonably granted.
H-intensity scale score to estimate CSF GluN1 antibody titers with one-time immunostaining using a commercial assay
Authors: Iizuka Masaki , Nagata Naomi , Kanazawa Naomi , Iwami Tomomi , Nagashima Makoto , Nakamura Masaaki , Kaneko Juntaro , Kitamura Eiji , Nishiyama Kazutoshi , Mamorita Noritaka , Iizuka Takahiro
Published: April 2024

Introduction

Anti-NMDA receptor encephalitis is an autoimmune disorder caused by autoantibodies (abs) against the conformational epitope on GluN1 subunits. GluN1-abs have been determined with cell-based assay (CBA) co-expressing GluN1/GluN2 subunits. However, commercial fixed CBA expressing only GluN1 subunit has increasingly been used in clinical practice. The ab titers can be determined with serial dilutions, but its clinical significance remains unclear. We aimed to develop an H-intensity scale (HIS) score to estimate GluN1-ab titers in cerebrospinal fluid (CSF) with one-time immunostaining using both commercial CBA and immunohistochemistry and report its usefulness. “H” is the initial of a patient with high CSF GluN1-ab titers (1:2,048).

Methods

We first determined the reliability of CBA in 370 patients with suspected autoimmune encephalitis by comparing the results between commercial CBA and established assay in Dalmau’s Lab. Then, we made positive control panels using the patient H’s CSF diluted in a fourfold serial dilution method (1:2, 1:8, 1:32, 1:128, 1:512, and 1:2,048). Based on the panels, we scored the intensity of ab reactivity of 79 GluN1-ab-positive patients’ CSF (diluted at 1:2) on a scale from 0 to 6 (with ≥1 considered positive). To assess inter-assay reliability, we performed immunostaining twice in 21 patients’ CSF. We investigated an association between the score of CSF obtained at diagnosis and the clinical/paraclinical features.

Results

The sensitivity and specificity of CBA were 93.7% (95% CI: 86.0–97.3) and 98.6% (95% CI: 96.5–99.5), respectively. Linear regression analysis showed a good agreement between the scores of the first and second assays. Patients with a typical spectrum, need for mechanical ventilation support, autonomic symptoms/central hypoventilation, dyskinesias, speech dysfunction, decreased level of consciousness, preceding headache, ovarian teratoma, and CSF leukocyte count >20 cells/µL had a higher median HIS score than those without, but HIS score was not associated with sex, age at onset, or seizure. HIS score at diagnosis had a significant effect on 1-year functional status.

Discussion

The severity of disease and four of the six core symptoms were associated with higher GluN1-ab titers in CSF at diagnosis, which may play a role in poor 1-year functional status. An incomplete phenotype can be attributed to low CSF GluN1-ab titers.
PD-L1 targeted peptide demonstrates potent antitumor and immunomodulatory activity in cancer immunotherapy
Authors: Liang Yulai , Luo Huazao , Li Xue , Liu Shuang , Habib Arslan , Liu Baoxiu , Huang Jiansheng , Wang Jingbo , Yi Han , Hu Bo , Zheng Liuhai , Xie Jun , Zhu Naishuo
Published: April 2024

Background

In recent years, immunotherapy has been emerging as a promising alternative therapeutic method for cancer patients, offering potential benefits. The expression of PD-L1 by tumors can inhibit the T-cell response to the tumor and allow the tumor to evade immune surveillance. To address this issue, cancer immunotherapy has shown promise in disrupting the interaction between PD-L1 and its ligand PD-1.

Methods

We used mirror-image phage display technology in our experiment to screen and determine PD-L1 specific affinity peptides (PPL-C). Using CT26 cells, we established a transplanted mouse tumor model to evaluate the inhibitory effects of PPL-C on tumor growth in vivo. We also demonstrated that PPL-C inhibited the differentiation of T regulatory cells (Tregs) and regulated the production of cytokines.

Results

In vitro, PPL-C has a strong affinity for PD-L1, with a binding rate of 0.75 μM. An activation assay using T cells and mixed lymphocytes demonstrated that PPL-C inhibits the interaction between PD-1 and PD-L1. PPL-C or an anti-PD-L1 antibody significantly reduced the rate of tumor mass development in mice compared to those given a control peptide (78% versus 77%, respectively). The results of this study demonstrate that PPL-C prevents or retards tumor growth. Further, immunotherapy with PPL-C enhances lymphocyte cytotoxicity and promotes proliferation in CT26-bearing mice.

Conclusion

PPL-C exhibited antitumor and immunoregulatory properties in the colon cancer. Therefore, PPL-C peptides of low molecular weight could serve as effective cancer immunotherapy.
The gut lactic acid bacteria metabolite, 10-oxo-cis-6,trans-11-octadecadienoic acid, suppresses inflammatory bowel disease in mice by modulating the NRF2 pathway and GPCR-signaling
Authors: Ando Miki , Nagata Kazuki , Takeshita Ryuki , Ito Naoto , Noguchi Sakura , Minamikawa Natsuki , Kodama Naoki , Yamamoto Asuka , Yashiro Takuya , Hachisu Masakazu , Ichihara Gaku , Kishino Shigenobu , Yamamoto Masayuki , Ogawa Jun , Nishiyama Chiharu
Published: April 2024

Various gut bacteria, including Lactobacillus plantarum, possess several enzymes that produce hydroxy fatty acids (FAs), oxo FAs, conjugated FAs, and partially saturated FAs from polyunsaturated FAs as secondary metabolites. Among these derivatives, we identified 10-oxo-cis-6,trans-11-octadecadienoic acid (γKetoC), a γ-linolenic acid (GLA)-derived enon FA, as the most effective immunomodulator, which inhibited the antigen-induced immunoactivation and LPS-induced production of inflammatory cytokines. The treatment with γKetoC significantly suppressed proliferation of CD4+ T cells, LPS-induced activation of bone marrow-derived dendritic cells (BMDCs), and LPS-induced IL-6 release from peritoneal cells, splenocytes, and CD11c+ cells isolated from the spleen. γKetoC also inhibited the release of inflammatory cytokines from BMDCs stimulated with poly-I:C, R-848, or CpG. Further in vitro experiments using an agonist of GPR40/120 suggested the involvement of these GPCRs in the effects of γKetoC on DCs. We also found that γKetoC stimulated the NRF2 pathway in DCs, and the suppressive effects of γKetoC and agonist of GPR40/120 on the release of IL-6 and IL-12 were reduced in Nrf2-/- BMDCs. We evaluated the role of NRF2 in the anti-inflammatory effects of γKetoC in a dextran sodium sulfate-induced colitis model. The oral administration of γKetoC significantly reduced body weight loss, improved stool scores, and attenuated atrophy of the colon, in wild-type C57BL/6 and Nrf2+/- mice with colitis. In contrast, the pathology of colitis was deteriorated in Nrf2-/- mice even with the administration of γKetoC. Collectively, the present results demonstrated the involvement of the NRF2 pathway and GPCRs in γKetoC-mediated anti-inflammatory responses.
A universal recombinant adenovirus type 5 vector-based COVID-19 vaccine
Authors: Li Xingxing , Peng Qinhua , Liu Xinyu , Xu Hongshan , Liu Jingjing , Wu Xiaohong , Ye Qiang , Li Min , Li Yuhua
Published: April 2024

A universal recombinant adenovirus type-5 (Ad5) vaccine against COVID19 (Ad-US) was constructed, and immunogenicity and broad-spectrum of Ad5-US were evaluated with both intranasal and intramuscular immunization routes. The humoral immune response of Ad5-US in serum and bronchoalveolar lavage fluid were evaluated by the enzyme-linked immunosorbent assay (ELISA), recombinant vesicular stomatitis virus based pseudovirus neutralization assay, and angiotensin-converting enzyme-2 (ACE2) -binding inhibition assay. The cellular immune response and Th1/Th2 biased immune response of Ad5-US were evaluated by the IFN-γ ELISpot assay, intracellular cytokine staining, and Meso Scale Discovery (MSD) profiling of Th1/Th2 cytokines. Intramuscular priming followed by an intranasal booster with Ad5-US elicited the broad-spectrum and high levels of IgG, IgA, pseudovirus neutralizing antibody (PNAb), and Th1-skewing of the T-cell response. Overall, the adenovirus type-5 vectored universal SARS-CoV-2 vaccine Ad5-US was successfully constructed, and Ad5-US was highly immunogenic and broad spectrum. Intramuscular priming followed by an intranasal booster with Ad5-US induced the high and broad spectrum systemic immune responses and local mucosal immune responses.
A case report of IgG4-related hepatic inflammatory pseudotumor in a 3-year old boy
Authors: Wan Qian , Xu Zhongjin , Liu Xiaohui , Wu Zhuqiang , Zhong Qingmei , Wu Chongjun
Published: April 2024

Background

Hepatic Inflammatory Pseudotumor (IPT) is an infrequent condition often masquerading as a malignant tumor, resulting in misdiagnosis and unnecessary surgical resection. The emerging concept of IgG4-related diseases (IgG4-RD) has gained widespread recognition, encompassing entities like IgG4-related hepatic IPT. Clinically and radiologically, corticosteroids and immunosuppressive therapies have proven effective in managing this condition.

Case Presentation

A 3-year-old Chinese boy presented to the clinic with an 11-month history of anemia, fever of unknown origin, and a tender hepatic mass. Blood examinations revealed chronic anemia (Hb: 6.4 g/L, MCV: 68.6 fl, MCH: 19.5 pg, reticulocytes: 1.7%) accompanied by an inflammatory reaction and an elevated serum IgG4 level (1542.2 mg/L). Abdominal contrast-enhanced computed tomography unveiled a 7.6 cm low-density mass in the right lateral lobe, while magnetic resonance imaging demonstrated slight hypointensity on T1-weighted images and slight hyperintensity on T2-weighted images, prompting suspicion of hepatic malignancy. A subsequent liver biopsy revealed a mass characterized by fibrous stroma and dense lymphoplasmacytic infiltration. Immunohistochemical analysis confirmed the presence of IgG4-positive plasma cells, leading to the diagnosis of IgG4-related hepatic IPT. Swift resolution occurred upon initiation of corticosteroid and mycophenolate mofetil therapies.

Conclusion

This study underscores the diagnostic approach to hepatic IPT, utilizing histopathology, immunostaining, imaging, serology, organ involvement, and therapeutic response. Early histological examination plays a pivotal role in clinical guidance, averting misdiagnosis as a liver tumor and unnecessary surgical interventions.
Exacerbated lung inflammation in offspring with high maternal antibody levels following secondary RSV exposure
Authors: Ma Jinhua , Gong Ting , Luo Tingting , Li Shuanglian , Zhong Li , Zhao Xin , Mei Chenghao , Bu Huaqin , Jia Zhenxing , Kuang Xiaohu , Wang Xiaoli , Fu Zhou , Tian Daiyin
Published: April 2024

Respiratory syncytial virus (RSV) is the primary cause of bronchiolitis-related hospitalizations among children under 5 years of age, with reinfection being common throughout life. Maternal vaccination has emerged as a promising strategy, delivering elevated antibody levels to newborns for immediate protection. However, limited research has explored the protective efficacy of maternal antibodies (matAbs) against secondary RSV infections in offspring. To address this gap, we employed a mouse model of maternal RSV vaccination and secondary infection of offspring to evaluate lung pathology following RSV reinfection in mice with varying levels of maternal antibody (matAb). Additionally, we aimed to investigate the potential causes of exacerbated lung inflammation in offspring with high matAb levels following secondary RSV exposure. Our findings revealed that offspring with elevated levels of maternal pre-F antibody demonstrated effective protection against lung pathology following the initial RSV infection. However, this protection was compromised upon reinfection, manifesting as heightened weight loss, exacerbated lung pathology, increased expression of RSV-A N genes, eosinophilia, enhanced IL-5, IL-13, MUC5AC, and eosinophils Major Basic Protein (MBP) production in lung tissue compared to offspring lacking matAbs. Importantly, these unexpected outcomes were not attributed to antibody-dependent enhancement (ADE) resulting from declining matAb levels over time. Notably, our findings showed a decline in secretory IgA (sIgA), mucosal IgA, and mucosal IgG levels in offspring with high matAb levels post-primary RSV challenge. We propose that this decline may be a critical factor contributing to the ineffective protection observed during secondary RSV exposure. Overall, these findings offer valuable insights into maternal vaccination against RSV, contributing to a comprehensive understanding and mitigation of potential risks associated with maternal RSV vaccination.
Case report: Preventive infusion of donor-derived CD7 chimeric antigen receptor T cells after allogeneic hematopoietic stem cell transplantation
Authors: Jiang Ying , Feng Dan , Zhu Jun , Wei Daolin , Zhao Chuxian , Liu Huixia , Shao Shan , Wang Chun
Published: April 2024

Chimeric antigen receptor T cells (CAR T) targeting CD7 for T-cell acute lymphoblastic leukemia/lymphoma (T-ALL/LBL) showed promising efficacy and safety in some clinical trials. However, most of them were bridged with allogeneic hematopoietic stem cell transplantation (allo-HSCT). We described successful treatment with preventive donor-derived anti-CD7 CAR-T therapy in a case of refractory T lymphoblastic lymphoma following allo-HSCT, who could not receive autologous anti-CD7 CAR-T products due to the low-quality of T lymphocytes. To date, the patient’s complete remission has persisted for 20 months after HSCT.
Single-cell transcriptome reveals highly complement activated microglia cells in association with pediatric tuberculous meningitis
Authors: Mo Siwei , Shi Chenyan , Cai Yi , Xu Maozhu , Xu Hongmei , Xu Yuzhong , Zhang Kehong , Zhang Yue , Liu Jiao , Che Siyi , Liu Xiangyu , Xing Chaonan , Long Xiaoru , Chen Xinchun , Liu Enmei
Published: April 2024

Background

Tuberculous meningitis (TBM) is a devastating form of tuberculosis (TB) causing high mortality and disability. TBM arises due to immune dysregulation, but the underlying immune mechanisms are unclear.

Methods

We performed single-cell RNA sequencing on peripheral blood mononuclear cells (PBMCs) and cerebrospinal fluid (CSF) cells isolated from children (n=6) with TBM using 10 xGenomics platform. We used unsupervised clustering of cells and cluster visualization based on the gene expression profiles, and validated the protein and cytokines by ELISA analysis.

Results

We revealed for the first time 33 monocyte populations across the CSF cells and PBMCs of children with TBM. Within these populations, we saw that CD4_C04 cells with Th17 and Th1 phenotypes and Macro_C01 cells with a microglia phenotype, were enriched in the CSF. Lineage tracking analysis of monocyte populations revealed myeloid cell populations, as well as subsets of CD4 and CD8 T-cell populations with distinct effector functions. Importantly, we discovered that complement-activated microglial Macro_C01 cells are associated with a neuroinflammatory response that leads to persistent meningitis. Consistently, we saw an increase in complement protein (C1Q), inflammatory markers (CRP) and inflammatory factor (TNF-α and IL-6) in CSF cells but not blood. Finally, we inferred that Macro_C01 cells recruit CD4_C04 cells through CXCL16/CXCR6.

Discussion

We proposed that the microglial Macro_C01 subset activates complement and interacts with the CD4_C04 cell subset to amplify inflammatory signals, which could potentially contribute to augment inflammatory signals, resulting in hyperinflammation and an immune response elicited by Mtb-infected tissues.