bluuebunny/crossref_metadata_2025_split huggingface dataset:
NOD2 in monocytes negatively regulates macrophage development through TNFalpha
Authors: Chauvin Camille , Alvarez-Simon Daniel , Radulovic Katarina , Boulard Olivier , Laine William , Delacre Myriam , Waldschmitt Nadine , Segura Elodie , Kluza Jérome , Chamaillard Mathias , Poulin Lionel F. 
Published: June 2023

ObjectiveIt is believed that intestinal recruitment of monocytes from Crohn’s Disease (CD) patients who carry NOD2 risk alleles may repeatedly give rise to recruitment of pathogenic macrophages. We investigated an alternative possibility that NOD2 may rather inhibit their differentiation from intravasating monocytes.DesignThe monocyte fate decision was examined by using germ-free mice, mixed bone marrow chimeras and a culture system yielding macrophages and monocyte-derived dendritic cells (mo-DCs).ResultsWe observed a decrease in the frequency of mo-DCs in the colon of Nod2-deficient mice, despite a similar abundance of monocytes. This decrease was independent of the changes in the gut microbiota and dysbiosis caused by Nod2 deficiency. Similarly, the pool of mo-DCs was poorly reconstituted in a Nod2-deficient mixed bone marrow (BM) chimera. The use of pharmacological inhibitors revealed that activation of NOD2 during monocyte-derived cell development, dominantly inhibits mTOR-mediated macrophage differentiation in a TNFα-dependent manner. These observations were supported by the identification of a TNFα-dependent response to muramyl dipeptide (MDP) that is specifically lost when CD14-expressing blood cells bear a frameshift mutation in NOD2.ConclusionNOD2 negatively regulates a macrophage developmental program through a feed-forward loop that could be exploited for overcoming resistance to anti-TNF therapy in CD.
Self-assembled ferritin nanoparticles displaying PcrV and OprI as an adjuvant-free Pseudomonas aeruginosa vaccine
Authors: Li Yuhang , Pu Ruixue , Zhang Yi , Zhang Yiwen , Wei Yujie , Zeng Sheng , Gao Chen , Wang Ying , Yin Daijiajia , Zhang Yueyue , Wan Jiqing , Zou Quanming , Gu Jiang 
Published: June 2023

IntroductionSerious infections of Pseudomonas aeruginosa (PA) in hospitals and the emergence and increase of multidrug resistance have raised an urgent need for effective vaccines. However, no vaccine has been approved to date. One possible reason for this is the limited immune response due to the lack of an efficient delivery system. Self-assembled ferritin nanoparticles are good carriers of heterogeneous antigens, which enhance the activation of immunological responses.MethodsIn this study, two well-studied antigen candidates, PcrV and OprI, were selected and connected to the ferritin nanoparticle by the Spytag/SpyCatcher system to generate the nanovaccine rePO-FN.ResultsCompared to recombinant PcrV-OprI formulated with aluminum adjuvants, intramuscular immunization with adjuvant-free rePO-FN induced quick and efficient immunity and conferred protection against PA pneumonia in mice. In addition, intranasal immunization with adjuvant-free rePO-FN enhanced protective mucosal immunity. Moreover, rePO-FN exhibited good biocompatibility and safety.DiscussionOur results suggest that rePO-FN is a promising vaccine candidate, as well as, provide additional evidence for the success of ferritin-based nanovaccines.
The role of interleukin-18 and interleukin-18 binding protein in K/BxN serum transfer-induced arthritis
Authors: Fauteux-Daniel Sebastien , Merlo Pich Laura M. , Girard-Guyonvarc’h Charlotte , Caruso Assunta , Rodriguez Emiliana , Gabay Cem 
Published: June 2023

BackgroundInterleukin-18 is a proinflammatory cytokine, the activity of which is regulated by its natural inhibitor, IL-18 binding protein (IL-18BP). Elevated circulating levels of IL-18 have been observed in patients with systemic juvenile idiopathic arthritis (sJIA) and adult-onset Still’s disease (AOSD), two conditions associated with dysregulated innate immune responses. This study examines the expression and function of IL-18 and IL-18BP in K/BxN serum transfer arthritis (STA), a model that is uniquely dependent on innate immune responses.MethodsNaïve and serum transfer-induced arthritis (STA) wild-type (WT) mice were used to examine the articular levels of IL-18 and IL-18BP mRNA by RT-qPCR. The cellular sources of IL-18BP in the joints were determined by using Il18bp-tdTomato reporter knock-in mice. The incidence and severity of arthritis, including mRNA levels of different cytokines, were compared in IL-18BP or IL-18 knock-out (KO) mice and their WT littermates.ResultsIL-18 and IL-18BP mRNA levels were significantly increased in arthritic as compared to normal joints. Synovial neutrophils, macrophages, and endothelial cells represented the cellular sources of IL-18BP in arthritic joints, whereas IL-18BP production was limited to endothelial cells in non-inflamed joints. The incidence and severity of arthritis were similar in IL-18BP KO and IL-18 KO compared to their WT littermates. Transcript levels of different inflammatory cytokines were not different in the two KO mouse lines compared to WT mice.ConclusionAlthough IL-18 and IL-18BP levels were increased in arthritic joints, our results show that the IL-18/IL-18BP balance is not involved in the regulation of STA.
Prediction of medication-related osteonecrosis of the jaws using machine learning methods from estrogen receptor 1 polymorphisms and clinical information
Authors: Choi Seo-Yong , Kim Jin-Woo , Oh Sang-Hyeon , Cheon Seunghyun , Yee Jeong , Kim Sun-Jong , Gwak Hye Sun , Chung Jee-Eun 
Published: June 2023

ObjectiveThe purpose of this study was to evaluate the effect of estrogen receptor 1 (ESR1) polymorphisms on the development of medication-related osteonecrosis of the jaws (MRONJ) in women with osteoporosis.MethodsA total of 125 patients taking bisphosphonates was evaluated the relationship between MRONJ occurrence and single nucleotide polymorphisms (SNPs) of ESR1. Clinical information was collected, including current age, treatment duration, and comorbidity. Univariate and Multivariable regression analyzes were performed to evaluate the independent predictive factors for MRONJ occurrence. Predictive models were constructed using machine learning methods such as Lasso regression, Random forest (RF), and Support vector machine (SVM). The area under the receiver-operating curve (AUROC) was used to evaluate the performance of a binary classifier.ResultTwo SNPs of ESR1 (rs4870056 and rs78177662) were significantly associated with MRONJ development. Patients with variant allele (A) of rs4870056 showed 2.45 times (95% CI, 1.03–5.87) the odds of MRONJ occurrence compared to those with wild-type homozygote (GG) after adjusting covariates. Additionally, carriers with variant allele (T) of rs78177662 had higher odds than those with wild-type homozygote (CC) (adjusted odds ratio (aOR), 2.64, 95% CI, 1.00–6.94). Among demographic variables, age ≥ 72 years (aOR, 3.98, 95% CI, 1.60–9.87) and bisphosphonate exposure ≥48 months (aOR, 3.16, 95% CI, 1.26–7.93) were also significant risk factors for MRONJ occurrence. AUROC values of machine learning methods ranged between 0.756–0.806 in the study.ConclusionOur study showed that the MRONJ occurrence was associated with ESR1 polymorphisms in osteoporotic women.
Cardiovascular events in delayed presentation of HIV: the prospective PISCIS cohort study
Authors: Martín-Iguacel Raquel , Vazquez-Friol Mari Carmen , Burgos Joaquin , Bruguera Andreu , Reyes-Urueña Juliana , Moreno-Fornés Sergio , Aceitón Jordi , Díaz Yesika , Domingo Pere , Saumoy Maria , Knobel Hernando , Dalmau David , Borjabad Beatriz , Johansen Isik Somuncu , Miro Jose M. , Casabona Jordi , Llibre Josep M. 
Published: June 2023

ObjectivesPeople with HIV (PWH) have a higher cardiovascular risk than the general population. It remains unclear, however, whether the risk of cardiovascular disease (CVD) is higher in late HIV presenters (LP; CD4 ≤ 350 cells/μL at HIV diagnosis) compared to PWH diagnosed early. We aimed to assess the rates of incident cardiovascular events (CVEs) following ART initiation among LP compared to non-LP.MethodsFrom the prospective, multicentre PISCIS cohort, we included all adult people with HIV (PWH) initiating antiretroviral therapy (ART) between 2005 and 2019 without prior CVE. Additional data were extracted from public health registries. The primary outcome was the incidence of first CVE (ischemic heart disease, congestive heart failure, cerebrovascular, or peripheral vascular disease). The secondary outcome was all-cause mortality after the first CVE. We used Poisson regression.ResultsWe included 3,317 PWH [26 589.1 person/years (PY)]: 1761 LP and 1556 non-LP. Overall, 163 (4.9%) experienced a CVE [IR 6.1/1000PY (95%CI: 5.3–7.1)]: 105 (6.0%) LP vs. 58 (3.7%) non-LP. No differences were observed in the multivariate analysis adjusting for age, transmission mode, comorbidities, and calendar time, regardless of CD4 at ART initiation [aIRR 0.92 (0.62–1.36) and 0.84 (0.56–1.26) in LP with CD4 count &lt;200 and 200– ≤ 350 cells/μL, respectively, compared to non-LP]. Overall mortality was 8.5% in LP versus 2.3% in non-LP (p &lt; 0.001). Mortality after the CVE was 31/163 (19.0%), with no differences between groups [aMRR 1.24 (0.45–3.44)]. Women vs. MSM and individuals with chronic lung and liver disease experienced particularly high mortality after the CVE [aMRR 5.89 (1.35–25.60), 5.06 (1.61–15.91), and 3.49 (1.08–11.26), respectively]. Sensitivity analyses including only PWH surviving the first 2 years yielded similar results.ConclusionCVD remains a common cause of morbidity and mortality among PWH. LP without prior CVD did not exhibit an increased long-term risk of CVE compared with non-LP. Identifying traditional cardiovascular risk factors is essential for CVD risk reduction in this population.
Changes in musculoskeletal disease activity and patient-reported outcomes in patients with psoriatic arthritis treated with ixekizumab: results from a real-world US cohort
Authors: Tillett William , Birt Julie , Cavanaugh Cristi , Jung Yoojin , Vadhariya Aisha , Ross Sarah , Paulus Jessica , Lubrano Ennio 
Published: June 2023

IntroductionIxekizumab has demonstrated efficacy in pivotal trials in patients with psoriatic arthritis (PsA), both those naïve to prior biologic therapy and those with prior inadequate response or intolerance to biologics; however, minimal information is currently available on the effectiveness of ixekizumab in routine clinical practice. The objective of this study was to investigate the clinical effectiveness of ixekizumab for the treatment of PsA over 6- and 12-month follow-up periods in a real-world setting.MethodsThis retrospective cohort study included patients who initiated treatment with ixekizumab from the OM1 PremiOMTM PsA dataset, a dataset of over 50,000 patients with claims and electronic medical record (EMR) data. Changes in musculoskeletal outcomes, such as tender and swollen joint count and patient-reported pain, as well as physician and patient global assessment, as measured using the Clinical Disease Activity Index (CDAI), and Routine Assessment of Patient Index Data 3 (RAPID3) were summarized at 6 and 12 months. The RAPID3, CDAI score, and their individual components were assessed in multivariable regressions adjusting for age, sex, and baseline value. The results were stratified by biologic disease-modifying antirheumatic drug (bDMARD) status (naïve vs. experienced) and monotherapy status (monotherapy vs. combination therapy with conventional synthetic DMARDs). Changes in a 3-item composite score derived from a physician global assessment, patient global assessment, and patient-reported pain score were summarized.ResultsAmong the 1,812 patients identified receiving ixekizumab, 84% had prior bDMARD treatment and 82% were monotherapy users. All outcomes improved at 6 and 12 months. For RAPID3, the mean (SD) change at 6 and 12 months was −1.2 (5.5) and −1.2 (5.9), respectively. Patients overall, bDMARD experienced, and monotherapy patients achieved statistically significant mean change in CDAI and all components from baseline to 6 and 12 months in adjusted analyses. Patients experienced an improvement in the 3-item composite score at both time points.ConclusionTreatment with ixekizumab was associated with improvements in musculoskeletal disease activity and PROs as assessed by several outcome measures. Future research should assess ixekizumab's clinical effectiveness in the real world across all PsA domains using PsA-specific endpoints.
Species-level microbiota of ticks and fleas from Marmota himalayana in the Qinghai-Tibet Plateau
Authors: Dong Lingzhi , Li Yaben , Yang Caixin , Gong Jian , Zhu Wentao , Huang Yuyuan , Kong Mimi , Zhao Lijun , Wang Feifei , Lu Shan , Pu Ji , Yang Jing 
Published: June 2023

IntroductionTicks and fleas, as blood-sucking arthropods, carry and transmit various zoonotic diseases. In the natural plague foci of China, monitoring of Yersinia pestis has been continuously conducted in Marmota himalayana and other host animals, whereas other pathogens carried by vectors are rarely concerned in the Qinghai-Tibet Plateau.MethodsIn this study, we investigated the microbiota of ticks and fleas sampling from M. himalayana in the Qinghai-Tibet Plateau, China by metataxonomics combined with metagenomic methods.ResultsBy metataxonomic approach based on full-length 16S rDNA amplicon sequencing and operational phylogenetic unit (OPU) analyses, we described the microbiota community of ticks and fleas at the species level, annotated 1,250 OPUs in ticks, including 556 known species and 492 potentially new species, accounting for 48.50% and 41.71% of the total reads in ticks, respectively. A total of 689 OPUs were detected in fleas, consisting of 277 known species (40.62% of the total reads in fleas) and 294 potentially new species (56.88%). At the dominant species categories, we detected the Anaplasma phagocytophilum (OPU 421) and potentially pathogenic new species of Wolbachia, Ehrlichia, Rickettsia, and Bartonella. Using shotgun sequencing, we obtained 10 metagenomic assembled genomes (MAGs) from vector samples, including a known species (Providencia heimbachae DFT2), and six new species affliated to four known genera, i.e., Wolbachia, Mumia, Bartonella, and Anaplasma. By the phylogenetic analyses based on full-length 16S rRNA genes and core genes, we identified that ticks harbored pathogenic A. phagocytophilum. Moreover, these potentially pathogenic novel species were more closely related to Ehrlichia muris, Ehrlichia muris subsp. eauclairensis, Bartonella rochalimae, and Rickettsia limoniae, respectively. The OPU 422 Ehrlichia sp1 was most related to Ehrlichia muris and Ehrlichia muris subsp. eauclairensis. The OPU 230 Bartonella sp1 and Bartonella spp. (DTF8 and DTF9) was clustered with Bartonella rochalimae. The OPU 427 Rickettsia sp1 was clustered with Rickettsia limoniae.DiscussionThe findings of the study have advanced our understanding of the potential pathogen groups of vectors in marmot (Marmota himalayana) in the Qinghai-Tibet Plateau.
Dysregulated NAD(H) homeostasis associated with ciprofloxacin tolerance in Escherichia coli investigated on a single-cell level with the Peredox [NADH:NAD+] biosensor
Authors: Urbaniec Joanna , Sanderson-Smith Martina , McFadden Johnjoe , Hai Faisal I. , Hingley-Wilson Suzanne M. 
Published: June 2023

IntroductionAntibiotic persistence (subpopulation tolerance) occurs when a subpopulation of antibiotic sensitive cells survives prolonged exposure to a bactericidal concentration of an antibiotic, and is capable of regrowth once the antibiotic is removed. This phenomenon has been shown to contribute to prolonged treatment duration, infection recurrence, and accelerated development of genetic resistance. Currently, there are no biomarkers which would allow for segregation of these antibiotic-tolerant cells from the bulk population prior to antibiotic exposure, limiting research on this phenomenon to retrograde analyses. However, it has been previously shown that persisters often have a dysregulated intracellular redox homeostasis, warranting its investigation as a potential marker for antibiotic tolerance. Furthermore, it is currently unknown whether another antibiotic tolerant subpopulation - viable but non-culturable cells (VBNCs), are simply persisters with extreme lag phase, or are formed through separate pathways. VBNCs similarly to persisters remain viable following antibiotic exposure, however, are not capable of regrowth in standard conditions.MethodsIn this article we employed an NADH:NAD+ biosensor (Peredox) to investigate NADH homeostasis of ciprofloxacin-tolerant E. coli cells on a single-cell level. [NADH:NAD+] was used as a proxy for measuring intracellular redox homeostasis and respiration rate.Results and DiscussionFirst, we demonstrated that ciprofloxacin exposure results in a high number of VBNCs, several orders of magnitude higher than persisters. However, we found no correlation in the frequencies of persister and VBNC subpopulations. Ciprofloxacin-tolerant cells (persisters &amp; VBNCs) were actively undergoing respiration, although at a significantly lower rate on average when compared to the bulk population. We also noted significant heterogeneity on a single-cell level within the subpopulations, however were unable to segregate persisters from VBNCs based on these observations alone. Finally, we showed that in the highly-persistent strain of E. coli, E. coli HipQ, ciprofloxacin-tolerant cells have a significantly lower [NADH:NAD+] ratio than tolerant cells of its parental strain, providing further link between disturbed NADH homeostasis and antibiotic tolerance.
Sex differences in acute telestroke care: more to the story
Authors: Sevilis Theresa , Avila Amanda , McDonald Mark , Fowler Mariecken , Chalfin Renata , Amir Murtaza , Heath Gregory , Zaman Mohammed , Avino Lorianne , Boyd Caitlyn , Gao Lan , Devlin Thomas 
Published: June 2023

BackgroundPrevious studies have shown sex differences in stroke care. Female patients have both lower thrombolytic treatment rates with OR reported as low as 0.57 and worse outcomes. With updated standards of care and improved access to care through telestroke, there is potential to reduce or alleviate these disparities.MethodsAcute stroke consultations seen by TeleSpecialists, LLC physicians in the emergency department in 203 facilities (23 states) from January 1, 2021 to April 30, 2021 were extracted from the Telecare by TeleSpecialists™ database. The encounters were reviewed for demographics, stroke time metrics, thrombolytics candidate, premorbid modified Rankin Score, NIHSS score, stroke risk factors, antithrombotic use, admitting diagnosis of suspected stroke, and reason not treated with thrombolytic. The treatment rates, door to needle (DTN) times, stroke metric times, and variables of treatment were compared for females and males.ResultsThere were 18,783 (10,073 female and 8,710 male) total patients included. Of the total, 6.9% of females received thrombolytics compared to 7.9% of males (OR 0.86, 95% CI 0.75–0.97, p = 0.006). Median DTN times were shorter for males than females (38 vs. 41 min, p &lt; 0.001). Male patients were more likely to have an admitting diagnosis of suspected stroke, p &lt; 0.001. Analysis by age showed the only decade with significant difference in thrombolytics treatment rate was 50–59 with increased treatment of males, p = 0.047. When multivariant logistic regression analysis was performed with stroke risk factors, NIHSS score, age, and admitting diagnosis of suspected stroke, the adjusted odds ratio for females was 0.9 (95% CI 0.8, 1.01), p = 0.064.ConclusionWhile treatment differences between sexes existed in the data and were apparent in univariate analysis, no significant difference was seen in multivariate analysis once stroke risk factors, age, NIHSS score and admitting diagnosis were taken into consideration in the telestroke setting. Differences in rates of thrombolysis between sexes may therefore be reflective of differences in risk factors and symptomatology rather than a healthcare disparity.
The accuracy of ultrasound-guided fine-needle aspiration and core needle biopsy in diagnosing axillary lymph nodes in women with breast cancer: a systematic review and meta-analysis
Authors: Zheng Haining , Zhao Rui , Wang Wei , Liu Xiaona , Wang Xiaoqing , Wen Chaoyang , Ren Yubo 
Published: June 2023

BackgroundThis study evaluates the diagnostic accuracy of ultrasound-guided fine needle aspiration (US-FNA) and core needle biopsy (US-CNB) for detecting axillary lymph nodes in women with breast cancer.MethodsEligible studies and pertinent literature resources were identified in Cochrane, PubMed, Embase, CNKI, VIP, and Wanfang databases using subject-specific keywords. Study outcomes were tested for heterogeneity, and meta-analyses were performed to estimate sensitivity, specificity, and diagnostic odds ratios (DORs). The summary receiver operating characteristic (SROC) curve analysis was also performed.ResultsA total of 22 studies involving 3,548 patients were included to evaluate the diagnostic accuracy of US-FNA and 11 studies involving 758 patients were included to evaluate the diagnostic accuracy of US-CNB in identifying axillary lymph nodes in women with breast cancer. The accuracy of US-FNA in identifying suspicious axillary lymph nodes was as follows: overall sensitivity, 79% (95% CI: 73%–84%); global specificity, 96% (95% CI: 92%–98%); overall positive likelihood ratio, 18.55 (95% CI: 10.53–32.69); overall negative likelihood ratio, 0.22 (95% CI: 0.17–0.28); DOR, 71.68 (95% CI: 37.19–138.12); and the area under the SROC curve, 0.94 (95% CI: 0.92–0.96). The accuracy of US-CNB in identifying suspicious axillary lymph nodes was as follows: overall sensitivity, 85% (95% CI: 81%–89%); global specificity, 93% (95% CI: 87%–96%); overall positive likelihood ratio, 11.88 (95% CI: 6.56–21.50); overall negative likelihood ratio, 0.16 (95% CI: 0.12–0.21); overall DOR, 66.83 (95% CI: 33.28–134.21), and the area under SROC curve 0.96 (95% CI: 0.94–0.97).ConclusionsThe results indicate that both US-FNA and US-CNB have high accuracy for suspicious axillary lymph nodes.