bluuebunny/crossref_metadata_2025_split huggingface dataset:
The impact of bisphenol A on the placenta
Authors: Adu-Gyamfi Enoch Appiah , Rosenfeld Cheryl S , Tuteja Geetu 
Published: January 2022

Abstract
Bisphenol A (BPA), an endocrine-disrupting chemical, is used to produce a wide variety of plastic and common house-hold items. Therefore, there is potential continual exposure to this compound. BPA exposure has been linked to certain placenta-associated obstetric complications such as preeclampsia, fetal growth restriction, miscarriage, and preterm birth. However, how BPA exposure results in these disorders remains uncertain. Hence, we have herein summarized the reported impacts of BPA on the morphology and metabolic state of the placenta and have proposed mechanisms by which BPA affects placentation, potentially leading to obstetric complications. Current findings suggest that BPA induces pathological changes in the placenta and disrupts its metabolic activities. Based on exposure concentrations, BPA can elicit apoptotic or anti-apoptotic signals in the trophoblasts, and can exaggerate trophoblast fusion while inhibiting trophoblast migration and invasion to affect pregnancy. Accordingly, the usage of BPA products by pregnant women should be minimized and less harmful alternative chemicals should be explored and employed where possible.
Association between ultrasonography foetal anomalies and autism spectrum disorder
Authors: Regev Ohad , Hadar Amnon , Meiri Gal , Flusser Hagit , Michaelovski Analya , Dinstein Ilan , Hershkovitz Reli , Menashe Idan 
Published: January 2022

Abstract
Multiple pieces of evidence support the prenatal predisposition of autism spectrum disorder (ASD). Nevertheless, robust data about abnormalities in foetuses later developing into children diagnosed with ASD are lacking. Prenatal ultrasound is an excellent tool to study abnormal foetal development as it is frequently used to monitor foetal growth and identify foetal anomalies throughout pregnancy.
We conducted a retrospective case-sibling-control study of children diagnosed with ASD (cases); their own typically developing, closest-in-age siblings (TDS); and typically developing children from the general population (TDP), matched by year of birth, sex and ethnicity to investigate the association between ultrasonography foetal anomalies and ASD. The case group was drawn from all children diagnosed with ASD enrolled at the National Autism Research Center of Israel. Foetal ultrasound data from the foetal anatomy survey were obtained from prenatal ultrasound clinics of Clalit Health Services in southern Israel.
The study comprised 659 children: 229 ASD, 201 TDS and 229 TDP. Ultrasonography foetal anomalies were found in 29.3% of ASD cases versus only 15.9% and 9.6% in the TDS and TDP groups [adjusted odds ratio (aOR) = 2.23, 95% confidence interval (CI) = 1.32–3.78, and aOR = 3.50, 95%CI = 2.07–5.91, respectively]. Multiple co-occurring ultrasonography foetal anomalies were significantly more prevalent among ASD cases. Ultrasonography foetal anomalies in the urinary system, heart, and head and brain were the most significantly associated with ASD diagnosis (aORUrinary = 2.08, 95%CI = 0.96–4.50 and aORUrinary = 2.90, 95%CI = 1.41–5.95; aORHeart = 3.72, 95%CI = 1.50–9.24 and aORHeart = 8.67, 95%CI = 2.62–28.63; and aORHead&Brain = 1.96, 95%CI = 0.72–5.30 and aORHead&Brain = 4.67, 95%CI = 1.34–16.24; versus TDS and TDP, respectively). ASD females had significantly more ultrasonography foetal anomalies than ASD males (43.1% versus 25.3%, P = 0.013) and a higher prevalence of multiple co-occurring ultrasonography foetal anomalies (15.7% versus 4.5%, P = 0.011). No sex differences were seen among TDS and TDP controls. ASD foetuses were characterized by a narrower head and a relatively wider ocular-distance versus TDP foetuses (ORBPD = 0.81, 95%CI = 0.70–0.94, and aOROcular distance = 1.29, 95%CI = 1.06–1.57). Ultrasonography foetal anomalies were associated with more severe ASD symptoms.
Our findings shed important light on the multiorgan foetal anomalies associated with ASD.
CMTM6: increased circulating level and up-regulated expression in labial salivary glands in patients with primary Sjogren’s syndrome
Authors: Qian Sirui , Xu Jingyi , Zhao Shan , Yang Pingting , Yang Chunshu 
Published: January 2022

Abstract
Chemokine-like factor (CKLF)-like MARVEL transmembrane domain containing family member 6 (CMTM6), which is a key regulator of programmed death-1 (PD-1)/programmed death ligand-1 (PD-L1) signaling in patients with primary Sjögren’s syndrome (pSS). In this study, we analyzed the serum levels of CMTM6, PD-1, and PD-L1 in 50 patients with pSS, 42 patients with non-pSS (simply dry mouth and/or eyes symptoms) and 50 healthy controls (HC). The expression of CMTM6, PD-1, and PD-L1 in labial glands of the same 50 pSS patients and 42 non-pSS patients were assessed by immunohistochemistry (IHC). The clinical significance of CMTM6, PD-1, and PD-L1 were analyzed. We found that levels of CMTM6, PD-L1 as well as PD-1 in sera were all increased significantly in patients with pSS compared with non-pSS controls and HC. Serum CMTM6 level showed significantly correlation with PD-L1, PD-1, as well as clinical laboratory indicators and disease activity of pSS patients. CMTM6, PD-1, and PD-L1 expression in labial glands was also higher significantly in pSS patients than non-pSS controls. pSS patients with higher CM grade or ESSDAI score have higher CMTM6, PD-L1, and PD-1 expression in labial glands. These results suggest that CMTM6 may affect peripheral tolerance and lymphocytes activation by PD-1/PD-L1 pathway in sera and target tissue in pSS.
Evaluation of a fit-for-purpose assay to monitor antigen-specific functional CD4+ T-cell subpopulations in rheumatoid arthritis using flow cytometry–based peptide-MHC class-II tetramer staining
Authors: Patel Swati , Ramnoruth Nishta , Wehr Pascale , Rossjohn Jamie , Reid Hugh H , Campbell Kim , Nel Hendrik J , Thomas Ranjeny 
Published: January 2022

Abstract
Antigen-specific T cells can serve as a response biomarker in non-clinical or clinical immunotherapy studies in autoimmune disease. There are protocols with optimized multimer staining methods to detect peptide (p)MHCII+ CD4+ T cells, and some qualified and validated protocols for pMHCI+ CD8+ T cells. However, no protocol is fully or partially qualified to enumerate and characterize antigen-specific pMHCII+ CD4+ T cells from patient samples. Implementing such an assay requires a desired level of specificity and precision, in terms of assay repeatability and reproducibility. In transgenic type II collagen (CII)-immunized HLA-DR1/DR4 humanized mouse models of collagen-induced arthritis (CIA), CII259-273-specific T cells dominantly expand. Therefore antigen-specific T cells recognizing this epitope presented by rheumatoid arthritis (RA)-associated risk HLA-DR allomorphs are of interest to understand disease progression and responses to immunotherapy in RA patients. Using HLA-DRB1∗04:01 or ∗01:01-collagen type II (CII)259–273 tetramers, we evaluated parameters influencing precision and reproducibility of an optimized flow cytometry–based method for antigen-specific CD4+ T cells and eight specific subpopulations with and without tetramer positivity. We evaluated specificity, precision, and reproducibility for research environments and non-regulated laboratories. The assay has excellent overall precision with %CV&lt;25% for intra-assay repeatability, inter-analyst precision, and inter-assay reproducibility. The precision of the assay correlated negatively with the cell viability after thawing, indicating that post-thaw viability is a critical parameter for reproducibility. This assay is suitable for longitudinal analysis of treatment response and disease activity outcome in RA patients, and adaptable for translational or immunotherapy clinical trial settings.
miR-155-overexpressing monocytes resemble HLAhighISG15+ synovial tissue macrophages from patients with rheumatoid arthritis and induce polyfunctional CD4+ T-cell activation
Authors: Olsson Anton M , Povoleri Giovanni A M , Somma Domenico , Ridley Michael L , Rizou Tatiana , Lalnunhlimi Sylvine , Macdonald Lucy , Rajasekhar Megha , Martinez-Nunez Rocio T , Kurowska-Stolarska Mariola , Taams Leonie S 
Published: January 2022

Abstract
MicroRNAs (miRs) are known to regulate pro-inflammatory effector functions of myeloid cells, and miR dysregulation is implicated in rheumatoid arthritis (RA), a condition characterized by inflammation and destruction of the joints. We showed previously that miR-155 is increased in myeloid cells in RA and induces pro-inflammatory activation of monocytes and macrophages; however, its role at the interface between innate and adaptive immunity was not defined. Here, RNA-sequencing revealed that overexpression of miR-155 in healthy donor monocytes conferred a specific gene profile which bears similarities to that of RA synovial fluid-derived CD14+ cells and HLAhighISG15+ synovial tissue macrophages, both of which are characterized by antigen-presenting pathways. In line with this, monocytes in which miR-155 was overexpressed, displayed increased expression of HLA-DR and both co-stimulatory and co-inhibitory molecules, and induced activation of polyfunctional T cells. Together, these data underpin the notion that miR-155-driven myeloid cell activation in the synovium contributes not only to inflammation but may also influence the adaptive immune response.
SARS-CoV-2 vaccine responses following CD20-depletion treatment in patients with haematological and rheumatological disease: a West Midlands Research Consortium study
Authors: Shields Adrian M , Venkatachalam Srinivasan , Shafeek Salim , Paneesha Shankara , Ford Mark , Sheeran Tom , Kelly Melanie , Qureshi Iman , Salhan Beena , Karim Farheen , De Silva Neelakshi , Stones Jacqueline , Lee Sophie , Khawaja Jahanzeb , Kaudlay Praveen Kumar , Whitmill Richard , Kakepoto Ghulam Nabi , Parry Helen M , Moss Paul , Faustini Sian E , Richter Alex G , Drayson Mark T , Basu Supratik 
Published: January 2022

Abstract
B-cell-depleting agents are among the most commonly used drugs to treat haemato-oncological and autoimmune diseases. They rapidly induce a state of peripheral B-cell aplasia with the potential to interfere with nascent vaccine responses, particularly to novel antigens. We have examined the relationship between B-cell reconstitution and SARS-CoV-2 vaccine responses in two cohorts of patients previously exposed to B-cell-depleting agents: a cohort of patients treated for haematological B-cell malignancy and another treated for rheumatological disease. B-cell depletion severely impairs vaccine responsiveness in the first 6 months after administration: SARS-CoV-2 antibody seroprevalence was 42.2% and 33.3% in the haemato-oncological patients and rheumatology patients, respectively and 22.7% in patients vaccinated while actively receiving anti-lymphoma chemotherapy. After the first 6 months, vaccine responsiveness significantly improved during early B-cell reconstitution; however, the kinetics of reconstitution was significantly faster in haemato-oncology patients. The AstraZeneca ChAdOx1 nCoV-19 vaccine and the Pfizer BioNTech 162b vaccine induced equivalent vaccine responses; however, shorter intervals between vaccine doses (&lt;1 m) improved the magnitude of the antibody response in haeamto-oncology patients. In a subgroup of haemato-oncology patients, with historic exposure to B-cell-depleting agents (&gt;36 m previously), vaccine non-responsiveness was independent of peripheral B-cell reconstitution. The findings have important implications for primary vaccination and booster vaccination strategies in individuals clinically vulnerable to SARS-CoV-2.
The autoimmune encephalitis-related cytokine TSLP in the brain primes neuroinflammation by activating the JAK2-NLRP3 axis
Authors: Yu Xueyuan , Lv Jiajia , Wu Jun , Chen Yong , Chen Fei , Wang Li 
Published: January 2022

SummaryNLRP3 inflammasome hyperactivation contributes to neuroinflammation in autoimmune disorders, but the underlying regulatory mechanism remains to be elucidated. We demonstrate that compared with wild-type (WT) mice, mice lacking thymic stromal lymphopoietin (TSLP) receptor (TSLPR) (Tslpr−/− mice) exhibit a significantly decreased experimental autoimmune encephalomyelitis (EAE) score, reduced CD4+ T cell infiltration, and restored myelin basic protein (MBP) expression in the brain after EAE induction by myelin oligodendrocyte glycoprotein35–55 (MOG35–55). TSLPR signals through Janus kinase (JAK)2, but not JAK1 or JAK3, to induce NLRP3 expression, and Tslpr−/− mice with EAE show decreased JAK2 phosphorylation and NLRP3 expression in the brain. JAK2 inhibition by ruxolitinib mimicked loss of TSLPR function in vivo and further decreased TSLP expression in the EAE mouse brain. The NLRP3 inhibitor MCC950 decreased CD4+ T cell infiltration, restored MBP expression, and decreased IL-1β and TSLP levels, verifying the pro-inflammatory role of NLRP3. In vitro experiments using BV-2 murine microglia revealed that TSLP directly induced NLRP3 expression, phosphorylation of JAK2 but not JAK1orJAK3, and IL-1β release, which were markedly inhibited by ruxolitinib. Furthermore, EAE induction led to an increase in the Th17 cell number, a decrease in the regulatory T (Treg) cell number in the blood, and an increase in the expression of the cytokine IL-17A in the WT mouse brain, which was drastically reversed in Tslpr−/− mice. In addition, ruxolitinib suppressed the increase in IL-17A expression in the EAE mouse brain. These findings identify TSLP as a prospective target for treating JAK2-NLRP3 axis-associated autoimmune inflammatory disorders.
Immunological findings in patients with migraine and other primary headaches: a narrative review
Authors: Biscetti Leonardo , De Vanna Gioacchino , Cresta Elena , Bellotti Alessia , Corbelli Ilenia , Letizia Cupini Maria , Calabresi Paolo , Sarchielli Paola 
Published: January 2022

Abstract
Experimental findings suggest an involvement of neuroinflammatory mechanisms in the pathophysiology of migraine. Specifically, preclinical models of migraine have emphasized the role of neuroinflammation following the activation of the trigeminal pathway at several peripheral and central sites including dural vessels, the trigeminal ganglion, and the trigeminal nucleus caudalis. The evidence of an induction of inflammatory events in migraine pathophysiological mechanisms has prompted researchers to investigate the human leukocyte antigen (HLA) phenotypes as well as cytokine genetic polymorphisms in order to verify their potential relationship with migraine risk and severity. Furthermore, the role of neuroinflammation in migraine seems to be supported by evidence of an increase in pro-inflammatory cytokines, both ictally and interictally, together with the prevalence of Th1 lymphocytes and a reduction in regulatory lymphocyte subsets in peripheral blood of migraineurs. Cytokine profiles of cluster headache (CH) patients and those of tension-type headache patients further suggest an immunological dysregulation in the pathophysiology of these primary headaches, although evidence is weaker than for migraine. The present review summarizes available findings to date from genetic and biomarker studies that have explored the role of inflammation in primary headaches.
The effect of short-chain fatty acids on M2 macrophages polarizationin vitroandin vivo
Authors: Huang Chunrong , Du Wei , Ni Yingmeng , Lan Gelei , Shi Guochao 
Published: January 2022

AbstractAlternatively activated macrophages (M2 polarization) play an important role in asthma. Short-chain fatty acids (SCFAs) possessed immune-regulatory functions, but their effects on M2 polarization of alveolar macrophages and its underlying mechanisms are still unclear. In our study, murine alveolar macrophage MH-S cell line and human monocyte-derived macrophages were used to polarize to M2 subset with interleukin-4 (IL-4) treatment. The underlying mechanisms involved were investigated using molecule inhibitors/agonists. In vivo, female C57BL/6 mice were divided into five groups: CON group, ovalbumin (OVA) asthma group, OVA+Acetate group, OVA+Butyrate group, and OVA+Propionate group. Mice were fed with or without SCFAs (Acetate, Butyrate, Propionate) in drinking water for 20 days before developing OVA-induced asthma model. In MH-S, SCFAs inhibited IL-4-incuced protein or mRNA expressions of M2-associated genes in a dose-dependent manner. G-protein-coupled receptor 43 (GPR43) agonist 4-CMTB and histone deacetylase (HDAC) inhibitor (trichostatin A, TSA), but not GPR41 agonist AR420626 could inhibit the protein or mRNA expressions M2-associated genes. 4-CMTB, but not TSA, had no synergistic role in the inhibitory effect of SCFAs on M2 polarization. In vivo study indicated Butyrate and Propionate, but not Acetate, attenuated OVA-induced M2 polarization in the lung and airway inflammation. We also found the inhibitory effect of SCFAs on M2 polarization in human-derived macrophages. Therefore, SCFAs inhibited M2 polarization in MH-S likely through GPR43 activation and/or HDAC inhibition. Butyrate and Propionate but not Acetate could inhibit M2 polarization and airway inflammation in asthma model. SCFAs also abrogated M2 polarization in human-derived macrophages.
Kidney infiltrating NK cells and NK-like T-cells in lupus nephritis: presence, localization, and the effect of immunosuppressive treatment
Authors: Scheffschick Andrea , Fuchs Sina , Malmström Vivianne , Gunnarsson Iva , Brauner Hanna 
Published: January 2022

Abstract
Systemic lupus erythematosus (SLE) is a multi-organ inflammatory disease with kidney inflammation, lupus nephritis (LN), being one of the most severe manifestations. Immune complex deposits, particularly in glomeruli, and T cells, B cells, and myeloid cells, mainly with extraglomerular localization, contribute to the inflammatory process. Natural killer (NK) cells have been suggested to play a role in autoimmune diseases, but have not been investigated in detail in renal lupus before. In this exploratory study, we performed the first characterization of NK cell number and distribution in LN kidney biopsies. Twelve SLE patients were analyzed in the active phase of disease and five patients following immunosuppressive therapy. CD56+ cells, corresponding to NK cells or NK-like T-cells, were identified in all patients; however, with reduced numbers in four out of five patients at follow-up. Furthermore, cells were present in the kidney interstitium and peri-glomerular areas, but only rarely in glomeruli. Fluorescent co-staining of CD56 or NKp46 and CD3 revealed the presence of both CD56+/NKp46+CD3-NK cells and CD56+/NKp46+CD3+NK-like T-cells. Compared to healthy kidney sections, one out of four LN patients showed increased numbers of NK cells. A correlation between CD56+ and NK cells with clinical parameters could not be observed, perhaps due to the small patient cohort. In conclusion, we have identified NK cells and NK-like T-cells in the LN kidney and performed the first detailed analysis of their localization during active and inactive diseases. Their role in LN pathogenesis is, however, unclear and deserves further studies.
Does CCL19 act as a double-edged sword in cancer development?
Authors: Gowhari Shabgah Arezoo , Al-Obaidi Zaid Mahdi Jaber , Sulaiman Rahman Heshu , Kamal Abdelbasset Walid , Suksatan Wanich , Bokov Dmitry O , Thangavelu Lakshmi , Turki Jalil Abduladheem , Jadidi-Niaragh Farhad , Mohammadi Hamed , Mashayekhi Kazem , Gholizadeh Navashenaq Jamshid 
Published: January 2022

AbstractCancer is considered a life-threatening disease, and several factors are involved in its development. Chemokines are small proteins that physiologically exert pivotal roles in lymphoid and non-lymphoid tissues. The imbalance or dysregulation of chemokines has contributed to the development of several diseases, especially cancer. CCL19 is one of the homeostatic chemokines that is abundantly expressed in the thymus and lymph nodes. This chemokine, which primarily regulates immune cell trafficking, is involved in cancer development. Through the induction of anti-tumor immune responses and inhibition of angiogenesis, CCL19 exerts tumor-suppressive functions. In contrast, CCL19 also acts as a tumor-supportive factor by inducing inflammation, cell growth, and metastasis. Moreover, CCL19 dysregulation in several cancers, including colorectal, breast, pancreatic, and lung cancers, has been considered a tumor biomarker for diagnosis and prognosis. Using CCL19-based therapeutic approaches has also been proposed to overcome cancer development. This review will shed more light on the multifarious function of CCL19 in cancer and elucidate its application in diagnosis, prognosis, and even therapy. It is expected that the study of CCL19 in cancer might be promising to broaden our knowledge of cancer development and might introduce novel approaches in cancer management.
T-cell responses to SARS-CoV-2 in healthy controls and primary immunodeficiency patients
Authors: Awuah Arnold , Zamani Ava , Tahami Fariba , Davis Mark , Grandjean Louis , Buckland Matthew , Gilmour Kimberly 
Published: January 2022

AbstractUnderstanding the T-cell response to SARS-CoV-2 is key in patients who lack antibody production. We demonstrate the applicability of a functional assay to measure the T-cell response in a cohort of patients with immunodeficiency.
Theta:gamma phase coupling and evoked gamma activity reflect the fidelity of mental templates during memory matching in visual perception
Authors: Peylo Charline , Friedrich Elisabeth V C , Minarik Tamas , Biel Anna Lena , Sauseng Paul 
Published: January 2022

Abstract
Top-down predictions of future events shaped by prior experience are an important control mechanism to allocate limited attentional resources more efficiently and are thought to be implemented as mental templates stored in memory. Increased evoked gamma activity and theta:gamma phase-phase coupling over parieto-occipital areas have previously been observed when mental templates meet matching visual stimuli. Here, we investigated how these signatures evolve during the formation of new mental templates and how they relate to the fidelity of such. Based on single-trial feedback, participants learned to classify target shapes as matching or mismatching with preceding cue sequences. In the end of the experiment, they were asked to freely reproduce targets as means of template fidelity. We observed fidelity-dependent increments of matching-related gamma phase locking and theta:gamma phase coupling in early visual areas around 100–200-ms poststimulus over time. Theta:gamma phase synchronization and evoked gamma activity might serve as complementary signatures of memory matching in visual perception; theta:gamma phase synchronization seemingly most important in early phases of learning and evoked gamma activity being essential for transition of mental templates into long-term memory.