bluuebunny/crossref_metadata_2025 huggingface dataset:
Exploring shape memory alloys in haptic wearables for visually impaired people
Authors: Ghodrat Sepideh , Sandhir Preeti , Huisman Gijs
Published: May 2023

Wearable haptic assistive devices can provide tactile information to visually impaired people (VIP) to support independent living. However, electromechanical haptic feedback has a number of disadvantages, including hardware being relatively heavy, large, and producing excessive sound. Here, we present a design-driven investigation of the potential of shape memory alloy-based haptic feedback for VIP. We followed an iterative approach, focusing on hands-on material explorations, in which we identified challenges and subsequent solutions that designers of SMA-based wearable haptic assistive devices may be faced with when incorporating SMAs in their designs. We present several prototype iterations and an initial evaluation with VIP to offer insights into the potential of SMA-based wearable haptic devices for VIP.
Heterogeneity extends criticality
Authors: Sánchez-Puig Fernanda , Zapata Octavio , Pineda Omar K. , Iñiguez Gerardo , Gershenson Carlos
Published: May 2023

Criticality has been proposed as a mechanism for the emergence of complexity, life, and computation, as it exhibits a balance between order and chaos. In classic models of complex systems where structure and dynamics are considered homogeneous, criticality is restricted to phase transitions, leading either to robust (ordered) or fragile (chaotic) phases for most of the parameter space. Many real-world complex systems, however, are not homogeneous. Some elements change in time faster than others, with slower elements (usually the most relevant) providing robustness, and faster ones being adaptive. Structural patterns of connectivity are also typically heterogeneous, characterized by few elements with many interactions and most elements with only a few. Here we take a few traditionally homogeneous dynamical models and explore their heterogeneous versions, finding evidence that heterogeneity extends criticality. Thus, parameter fine-tuning is not necessary to reach a phase transition and obtain the benefits of (homogeneous) criticality. Simply adding heterogeneity can extend criticality, making the search/evolution of complex systems faster and more reliable. Our results add theoretical support for the ubiquitous presence of heterogeneity in physical, biological, social, and technological systems, as natural selection can exploit heterogeneity to evolve complexity “for free”. In artificial systems and biological design, heterogeneity may also be used to extend the parameter range that allows for criticality.
The challenges of a randomised placebo-controlled trial of CTO PCI vs. placebo with optimal medical therapy: The ORBITA-CTO pilot study design and protocol
Authors: Khan Sarosh , Fawaz Samer , Simpson Rupert , Robertson Craig , Kelly Paul , Mohdnazri Shah , Tang Kare , Cook Christopher M. , Gallagher Sean , O’Kane Peter , Spratt James , Brilakis Emmanouil S. , Karamasis Grigoris V. , Al-Lamee Rasha , Keeble Thomas R. , Davies John R.
Published: May 2023

Background

Percutaneous coronary intervention (PCI) for coronary chronic total occlusion (CTO) has been performed for the improvement of symptoms and quality of life in patients with stable angina. The ORBITA study demonstrated the role of the placebo effect in contemporary PCI in non-CTO chronic coronary syndromes. However, the benefit of CTO PCI beyond that of a placebo has not been demonstrated.

Aims

The ORBITA-CTO pilot study will be a double-blind, placebo-controlled study of CTO PCI randomising patients who have: (1) been accepted by a CTO operator for PCI; (2) experienced symptoms due to a CTO; (3) evidence of ischaemia; (4) evidence of viability within the CTO territory; and (5) a J-CTO score ≤3.

Methods

Patients will undergo medication optimisation that will ensure they are on at least a minimum amount of anti-anginals and complete questionnaires. Patients will record their symptoms on an app daily throughout the study. Patients will undergo randomisation procedures, including an overnight stay, and be discharged the following day. All anti-anginals will be stopped after randomisation and re-initiated on a patient-led basis during the 6-month follow-up period. At follow-up, patients will undergo repeat questionnaires and unblinding, with a further 2-week unblinded follow-up.

Results

The co-primary outcomes are feasibility (blinding) in this cohort and angina symptom score using an ordinal clinical outcome scale for angina. Secondary outcomes include changes in quality-of-life measures, Seattle Angina Questionnaire (SAQ), peak VO2, and anaerobic threshold on the cardiopulmonary exercise test.

Conclusion

The feasibility of a placebo-controlled CTO PCI study will lead to future studies assessing efficacy. The impact of CTO PCI on angina measured using a novel daily symptom app may provide improved fidelity in assessing symptoms in patients with CTO's.
Secondary school students’ competencies and motivation to engage in mathematical modelling tasks in a virtual learning environment
Authors: Cohen-Nissan Orit , Kohen Zehavit
Published: May 2023

This study explores secondary school students’ competencies and motivation to engage in mathematical modelling (MM) tasks in a Virtual Learning Environment (VLE). The study is based theoretically on the didactical modelling cycle and the sub-competencies required for its application, the situated expectancy-value theory, and the VLEs’ design literature. Participants were 770 ninth graders who took part in a 5-day online summer camp, designed as a VLE, aiming at introducing them to mathematics within the tech industry. Research tools include Padlet MM tasks and observations for assessing students’ MM sub-competencies, as well as a pre-post motivation questionnaire for assessing students’ motivation to engage in MM tasks within the VLE. Observations and motivation questionnaires were also used to identify design features of the VLE that support students’ competencies and motivation. Findings show students’ demonstration of diverse levels of MM sub-competencies in forming a mathematical model, and mainly moderate-high levels in solving mathematical questions within the model and in interpreting the results. Students improved their self-concept of ability and task difficulty expectancies, as well as their attainment and interest values of MM tasks. Finally, the VLE’s structured activities and learning materials, along with instructional support and collaborative learning, supported students’ demonstration of MM sub-competencies and motivation to engage in MM. The study contributes to the literature regarding students’ demonstration of MM sub-competencies and their motivation to engage in MM in a VLE setting.
Expression of placental glycans and its role in regulating peripheral blood NK cells during preeclampsia: a perspective
Authors: Bueno-Sánchez Julio C. , Gómez-Gutiérrez Alejandra M. , Maldonado-Estrada Juan G. , Quintana-Castillo Juan C.
Published: May 2023

Preeclampsia is a pregnancy-related multisystem disorder characterized by altered trophoblast invasion, oxidative stress, exacerbation of systemic inflammatory response, and endothelial damage. The pathogenesis includes hypertension and mild-to-severe microangiopathy in the kidney, liver, placenta, and brain. The main mechanisms involved in its pathogenesis have been proposed to limit trophoblast invasion and increase the release of extracellular vesicles from the syncytiotrophoblast into the maternal circulation, exacerbating the systemic inflammatory response. The placenta expresses glycans as part of its development and maternal immune tolerance during gestation. The expression profile of glycans at the maternal–fetal interface may play a fundamental role in physiological pregnancy changes and disorders such as preeclampsia. It is unclear whether glycans and their lectin-like receptors are involved in the mechanisms of maternal–fetal recognition by immune cells during pregnancy homeostasis. The expression profile of glycans appears to be altered in hypertensive disorders of pregnancy, which could lead to alterations in the placental microenvironment and vascular endothelium in pregnancy conditions such as preeclampsia. Glycans with immunomodulatory properties at the maternal–fetal interface are altered in early-onset severe preeclampsia, implying that innate immune system components, such as NK cells, exacerbate the systemic inflammatory response observed in preeclampsia. In this article, we discuss the evidence for the role of glycans in gestational physiology and the perspective of glycobiology on the pathophysiology of hypertensive disorders in gestation.
Sex ratio potentially influence the complexity of social calls in Himalayan leaf-nosed bat groups
Authors: Gu Hao , Sun Congnan , Gong Lixin , Zhao Xin , Feng Jiang , Luo Bo , Jiang Tinglei , Liu Ying
Published: May 2023

Animals living in a complex social environment emit diverse acoustic signals and thus serve as excellent subjects for understanding the evolution of acoustic communication. Previous studies have focused on the complexity of social calls in some group-living animals, yet the determinants of vocal complexity at the intraspecific level remain unclear. Here, we aimed to assess the influence of group composition on social call complexity in Himalayan leaf-nosed bats (Hipposideros armiger) in the non-breeding season. The bats divided into three groups with the same number of individuals but with different sex ratio compositions. We monitored social vocalizations for the all-male group, the all-female group, the mixed group, and also quantified vocal complexity for each group based on multiple acoustic metrics, including vocal repertoire, call sequences, the diversity index, and information capacity. The results showed that there were significant differences in the composition of call sequences among the three bat groups. The number of vocalizations was the highest in the mixed group, while the social call complexity was the highest in the all-male group, followed by the all-female group, and was the lowest in the mixed group. The results suggest that sex ratio potentially influence the vocal repertoire in Himalayan leaf-nosed bats. Our findings might provide a cue for vocalization research to investigate sex ratio in social groups as a potential driver for vocal complexity.
Tubeimuside I improves the efficacy of a therapeutic Fusobacterium nucleatum dendritic cell-based vaccine against colorectal cancer
Authors: Tong Yanan , Lu Guoxiu , Wang Zhiguo , Hao Shanhu , Zhang Guoxu , Sun Hongwu
Published: May 2023

Introduction

Fusobacterium nucleatum (F. nucleatum) infection has been confirmed to be associated with the development, chemoresistance, and immune evasion of colorectal cancer (CRC). The complex relationship between the microorganism, host cells, and the immune system throughout all stages of CRC progression, which makes the development of new therapeutic methods difficult.

Methods

We developed a new dendritic cell (DC) vaccine to investigate the antitumor efficacy of CRC immunotherapy strategies. By mediating a specific mode of interaction between the bacteria, tumor, and host, we found a new plant-derived adjuvant, tubeimuside I (TBI), which simultaneously improved the DC vaccine efficacy and inhibited the F. nucleatum infection. Encapsulating TBI in a nanoemulsion greatly improved the drug efficacy and reduced the drug dosage and administration times.

Results

The nanoemulsion encapsulated TBI DC vaccine exhibited an excellent antibacterial and antitumor effect and improved the survival rate of CRC mice by inhibiting tumor development and progression.

Discussion

In this study, we provide a effective strategy for developing a DC-based vaccine against CRC and underlies the importance of further understanding the mechanism of CRC processes caused by F. nucleatum.
Analysis of T-cell alloantigen response via a direct pathway in kidney transplant recipients with donor-specific antibodies
Authors: Iwahara Naoya , Hotta Kiyohiko , Iwami Daiki , Tanabe Tatsu , Tanaka Yuka , Ito Yoichi M. , Otsuka Takuya , Murai Sachiyo , Takada Yusuke , Higuchi Haruka , Sasaki Hajime , Hirose Takayuki , Harada Hiroshi , Shinohara Nobuo
Published: May 2023

Donor-specific antibodies (DSAs) are the main cause of graft loss over time. The direct pathway of alloantigen recognition is important in the pathogenesis of acute rejection. Recent studies have suggested that the direct pathway also contributes to the pathogenesis of chronic injury. Nevertheless, there are no reports on T-cell alloantigen response via the direct pathway in kidney recipients with DSAs. We analyzed the T-cell alloantigen response via the direct pathway in kidney recipients with DSAs (DSA+) or without DSAs (DSA−). A mixed lymphocyte reaction assay was implemented to assess the direct pathway response. DSA+ patients showed significantly higher CD8+ and CD4+ T cell responses to donor cells than DSA− patients. Furthermore, proliferating CD4+ T cells showed a marked increase in Th1 and Th17 responses in DSA+ patients than in DSA− patients. In a comparison between anti-donor and third-party responses, the anti-donor CD8+ and CD4+ T cell response was significantly lower than the anti-third-party response. In contrast, the donor-specific hyporesponsiveness was absent in DSA+ patients. Our study demonstrated that DSA+ recipients have a greater potential for developing immune responses against the donor tissues via the direct alloantigen recognition pathway. These data contribute to an understanding of DSAs pathogenicity during kidney transplantation.
Expression of Cartilage Oligomeric Matrix Protein in colorectal cancer is an adverse prognostic factor and correlates negatively with infiltrating immune cells and PD-L1 expression
Authors: Blom Anna M. , Gialeli Chrysostomi , Hagerling Catharina , Berntsson Jonna , Jirström Karin , Papadakos Konstantinos S.
Published: May 2023

Introduction

Cartilage Oligomeric Matrix Protein (COMP) is an oncogenic protein that has been associated with a decrease in infiltrating T-cells in periampullary adenocarcinoma. This study aimed to investigate whether this is also the case for colorectal cancer (CRC) and to evaluate the relationship between COMP expression and clinopathological features.

Methods

Immunohistochemistry was used to determine the expression levels of COMP in tumor cells and stroma in primary tumors from a cohort of 537 CRC patients. The expression of immune cell markers, including CD3+, CD8+, FoxP3+, CD68+, CD56+, CD163+, and PD-L1, was evaluated previously. Tumor fibrosis was assessed by Sirius Red staining and evaluation of collagen fiber organization.

Results

COMP expression correlated positively with TNM-stage and grade of differentiation. Patients with CRC expressing high levels of COMP had significantly shorter OS than those with low COMP expression (p<0.0001), and fewer infiltrating T-cells were detected in tumors with high COMP expression. Additionally, a negative correlation was identified between the expression of COMP and PD-L1 on both tumor cells and immune cells. Cox regression analysis showed that tumors expressing high levels of COMP had significantly shorter OS, independent of all evaluated immune cell markers. Tumor fibrosis was correlated with high expression of COMP in the stroma (p<0.0001), and tumors with high levels of COMP expression and denser fibrosis displayed more sparse immune cell infiltration.

Discussion

The results suggest that COMP expression in CRC may exert an immune regulatory effect by increasing dense fibrosis and decreasing immune cell infiltration. These findings support the notion that COMP is an important factor in the development and progression of CRC.
The adaptor protein TRAF3 is an immune checkpoint that inhibits myeloid-derived suppressor cell expansion
Authors: Zhu Sining , Lalani Almin I. , Jin Juan , Sant’Angelo Derek , Covey Lori R. , Liu Kebin , Young Howard A. , Ostrand-Rosenberg Suzanne , Xie Ping
Published: May 2023

Myeloid-derived suppressor cells (MDSCs) are aberrantly expanded in cancer patients and under other pathological conditions. These cells orchestrate the immunosuppressive and inflammatory network to facilitate cancer metastasis and mediate patient resistance to therapies, and thus are recognized as a prime therapeutic target of human cancers. Here we report the identification of the adaptor protein TRAF3 as a novel immune checkpoint that critically restrains MDSC expansion. We found that myeloid cell-specific Traf3-deficient (M-Traf3-/-) mice exhibited MDSC hyperexpansion during chronic inflammation. Interestingly, MDSC hyperexpansion in M-Traf3-/- mice led to accelerated growth and metastasis of transplanted tumors associated with an altered phenotype of T cells and NK cells. Using mixed bone marrow chimeras, we demonstrated that TRAF3 inhibited MDSC expansion via both cell-intrinsic and cell-extrinsic mechanisms. Furthermore, we elucidated a GM-CSF-STAT3-TRAF3-PTP1B signaling axis in MDSCs and a novel TLR4-TRAF3-CCL22-CCR4-G-CSF axis acting in inflammatory macrophages and monocytes that coordinately control MDSC expansion during chronic inflammation. Taken together, our findings provide novel insights into the complex regulatory mechanisms of MDSC expansion and open up unique perspectives for the design of new therapeutic strategies that aim to target MDSCs in cancer patients.
Elevated MPP6 expression correlates with an unfavorable prognosis, angiogenesis and immune evasion in hepatocellular carcinoma
Authors: Cheng Qianqian , Wang Wei , Liu Jing , Lv Zhenyu , Ji Wenbin , Yu Jinhui , Zhang Wenting , Yang Yan
Published: May 2023

Background

Membrane palmitoylated proteins (MPPs) are engaged in various biological processes, such as cell adhesion and cell polarity. Dysregulated MPP members have different effects on hepatocellular carcinoma (HCC) development. However, the role of MPP6 in HCC has been unknown.

Method

HCC transcriptome and clinical data from different public databases were downloaded and analyzed, and the results were further validated by qRT−PCR, Western blotting and immunohistochemistry (IHC) using HCC cell lines and tissues. The association between MPP6 and prognosis, potential pathogenic mechanisms, angiogenesis, immune evasion, tumor mutation burden (TMB) and treatment response in HCC patients was analyzed by bioinformatics and IHC staining.

Results

MPP6 was significantly overexpressed in HCC, and its expression was related to T stage, pathologic stage, histologic grade and adverse prognosis in HCC patients. Gene set enrichment analysis revealed that differentially expressed genes were mainly enriched in the synthesis of genetic materials and the WNT signaling pathway. GEPIA database analysis and IHC staining suggested that MPP6 expression had a positive correlation with angiogenesis. Single-cell dataset analysis indicated that MPP6 was associated with features of the tumor microenvironment. Additional analyses discovered that MPP6 expression was inversely related to immune cell infiltration and was involved in tumor immune evasion. MPP6 expression was positively associated with TMB, and patients with high TMB had an adverse prognosis. Immunotherapy was more effective in HCC patients with low MPP6 expression, whereas those with high MPP6 expression responded better to sorafenib, gemcitabine, 5-FU, and doxorubicin.

Conclusions

Elevated MPP6 expression is associated with an unfavorable prognosis, angiogenesis and immune evasion in HCC. Moreover, MPP6 has the potential to be used to assess TMB and treatment response. Therefore, MPP6 might serve as a novel prognostic biomarker and therapeutic target for HCC.
HBSP improves kidney ischemia-reperfusion injury and promotes repair in properdin deficient mice via enhancing phagocytosis of tubular epithelial cells
Authors: Wu Yuanyuan , Huang Lili , Sai Wenli , Chen Fei , Liu Yu , Han Cheng , Barker Joanna M. , Zwaini Zinah D. , Lowe Mark P. , Brunskill Nigel J. , Yang Bin
Published: May 2023

Phagocytosis plays vital roles in injury and repair, while its regulation by properdin and innate repair receptor, a heterodimer receptor of erythropoietin receptor (EPOR)/β common receptor (βcR), in renal ischaemia-reperfusion (IR) remains unclear. Properdin, a pattern recognition molecule, facilitates phagocytosis by opsonizing damaged cells. Our previous study showed that the phagocytic function of tubular epithelial cells isolated from properdin knockout (PKO) mouse kidneys was compromised, with upregulated EPOR in IR kidneys that was further raised by PKO at repair phase. Here, helix B surface peptide (HBSP), derived from EPO only recognizing EPOR/βcR, ameliorated IR-induced functional and structural damage in both PKO and wild-type (WT) mice. In particular, HBSP treatment led to less cell apoptosis and F4/80+ macrophage infiltration in the interstitium of PKO IR kidneys compared to the WT control. In addition, the expression of EPOR/βcR was increased by IR in WT kidneys, and furthered increased in IR PKO kidneys, but greatly reduced by HBSP in the IR kidneys of PKO mice. HBSP also increased PCNA expression in IR kidneys of both genotypes. Moreover, iridium-labelled HBSP (HBSP-Ir) was localized mainly in the tubular epithelia after 17-h renal IR in WT mice. HBSP-Ir also anchored to mouse kidney epithelial (TCMK-1) cells treated by H2O2. Both EPOR and EPOR/βcR were significantly increased by H2O2 treatment, while further increased EPOR was showed in cells transfected with small interfering RNA (siRNA) targeting properdin, but a lower level of EPOR was seen in EPOR siRNA and HBSP-treated cells. The number of early apoptotic cells was increased by EPOR siRNA in H2O2-treated TCMK-1, but markedly reversed by HBSP. The phagocytic function of TCMK-1 cells assessed by uptake fluorescence-labelled E.coli was enhanced by HBSP dose-dependently. Our data demonstrate for the first time that HBSP improves the phagocytic function of tubular epithelial cells and kidney repair post IR injury, via upregulated EPOR/βcR triggered by both IR and properdin deficiency.
Pathogen recognition by sensory neurons: hypotheses on the specificity of sensory neuron signaling
Authors: Millet Antoine , Jendzjowsky Nicholas
Published: May 2023

Sensory neurons cooperate with barrier tissues and resident immune cells to form a significant aspect of defensive strategies in concert with the immune system. This assembly of neuroimmune cellular units is exemplified across evolution from early metazoans to mammalian life. As such, sensory neurons possess the capability to detect pathogenic infiltrates at barrier surfaces. This capacity relies on mechanisms that unleash specific cell signaling, trafficking and defensive reflexes. These pathways exploit mechanisms to amplify and enhance the alerting response should pathogenic infiltration seep into other tissue compartments and/or systemic circulation. Here we explore two hypotheses: 1) that sensory neurons’ potential cellular signaling pathways require the interaction of pathogen recognition receptors and ion channels specific to sensory neurons and; 2) mechanisms which amplify these sensing pathways require activation of multiple sensory neuron sites. Where possible, we provide references to other apt reviews which provide the reader more detail on specific aspects of the perspectives provided here.
UK long-term monitoring dataset: assessing factors affecting biomarkers commonly used in environmental programmes
Authors: Dalessandri Shannon , Franco Aldina M. A. , Assunção Marta G. L.
Published: May 2023

Long-term programmes like the UK Clean Seas Environmental Monitoring Programme (CSEMP) rely on biological effects techniques, including biomarkers, to assess if chemical pollutants are affecting sentinel species in the aquatic environment. In this study, we have applied mixed and fixed effect linear models to the long-term CSEMP dataset (2005-2018) to evaluate if factors such as region (location), sex, age, gonadosomatic index (GSI) and condition factor (CF), contribute to the variability observed in the levels of 3 well established biomarkers (inhibition of acetylcholinesterase in muscle-AChE, induction of hepatic 7-ethoxyresorufin-O-deethylase-EROD and presence of biliary 1-hydroxypyrene-1-OH pyrene) used to monitor biological effects of contaminants in dab (Limanda limanda) around UK waters. Regional differences (location) were a significant explanatory variable for the 3 biomarkers. Substantial differences were found in regional average muscle AChE activity, overall indicating the East Coast regions as likely more impacted by acetylcholinesterase inhibitors (e.g. organophosphates and carbamates). We report for the first time that, while accounting for region, sex and gonadosomatic index are significant predictors of muscle acetylcholinesterase isoform in dab (R2 = 0.13-0.15), and therefore advise the future analysis of this marker should be done by sex when reporting for marine environmental purposes. Dab condition factor is also a significant predictor for both enzymatic markers (AChE and EROD) but not for 1-OH pyrene. Sex and age, and their interaction, were the strongest variables (R2 = 0.46) influencing hepatic EROD, showing that although overall females had higher hepatic EROD, male dab hepatic EROD increased with age. Correlations between the three biomarkers might assist in discerning types of prevalent regional contamination over the studied period. Our results highlight the factors to account for when assessing if environmental contamination is contributing to the responses of these 3 biomarkers in dab, and other flatfish species, used in marine environmental monitoring programmes.
Cyclic threshold shear strain for pore water pressure generation and stiffness degradation in marine clays at Yangtze estuary
Authors: Xiao Xing , Ji Dong-Wei , Hang Tian-Zhu , Cai Zi-Yang , Zhang Lei , Wu Qi , Chen Guo-Xing
Published: May 2023

Cyclic threshold shear strain is a fundamental property of saturated soils under cyclic loading. To investigate the cyclic threshold shear strain for pore water pressure generation (γtp) and stiffness degradation (γtd), a series of strain-controlled multistage undrained cyclic triaxial tests were carried out on in-situ saturated marine clay in the Yangtze estuary with different plasticity index Ip. The test results show that both γtp and γtd increase with increasing Ip, and γtp is larger than γtd for the same marine clay tested under the same conditions, with γtp = 0.017 ~ 0.019%, γtd = 0.008 ~ 0.012% for Ip of 17, γtp = 0.033 ~ 0.039%, γtd = 0.020 ~ 0.025% for Ip of 32, and γtp = 0.040 ~ 0.048%, γtd = 0.031 ~ 0.036% for Ip of 40. Moreover, the development of stiffness degradation may not necessarily require the generation of pore water pressure but can be aggravated by it. Furthermore, the γtp and γtd of marine clay are compared with terrestrial soils and marine clays cited from the published literature, the results indicate that the special marine sedimentary environment and the combined action of flow and tidal wave system cause the γtp and γtd of marine clay in the Yangtze estuary to be smaller than that of the terrestrial clays and marine clays in other sea areas.
Abiotrophia defectiva causing infective endocarditis with brain infarction and subarachnoid hemorrhage: a case report
Authors: Yang Miaojuan , Lin Yanxia , Peng Xin , Wu Jingsong , Hu Bo , He Yitao , Lu Jian
Published: May 2023

Introduction

A rare pathogen of Infective Endocarditis (IE), the Abiotrophia defectiva, has been known to trigger life-threatening complications. The case discussed here is of a teenager with brain infarction and subarachnoid hemorrhage caused by IE due to A. defectiva.

Case report

A 15-year-old girl with movement disorders involving the left limbs and intermittent fevers was admitted to the hospital. A head CT scan revealed cerebral infarction in the right basal ganglia and subarachnoid hemorrhage. Moreover, vegetation on the mitral valve were confirmed by echocardiography. The blood cultures were found to be positive for Gram-positive streptococcus and identified by Vitek mass spectrometry as A. defectiva. She was prescribed vancomycin antibacterial therapy and underwent a surgical mitral valve replacement.

Conclusion

This case is suggestive of the fact that A. defectiva is a rare but crucial pathogen of IE-associated stroke. Obtaining early blood cultures and using microbial mass spectrometry could help achieve an accurate diagnosis. Moreover, reasonable anti-infective medications and surgical interventions need to be combined to avoid and/or manage severe complications.
Incidence of lymphomas in inflammatory bowel disease: report of an emblematic case, systematic review, and meta-analysis
Authors: Russo Maria Francesca , Diddoro Annalisa , Iodice Alessandra , Severi Carola , Castagneto-Gissey Lidia , Casella Giovanni
Published: May 2023

Introduction

Over the past 20 years, the increasing use of combined therapy with immunosuppressants and biologic agents has markedly reduced the use of steroids in the management of inflammatory bowel diseases (IBD). However, medical therapy seems to promote, in the long run, carcinogenesis resulting in an increased risk of developing different types of malignancies, including lymphomas. The aim of this study was to systematically review the current incidence and prognosis of lymphoid neoplasms occurring in patients with IBD.

Methods

Studies analyzing the incidence of lymphomas in subjects of age >18 years affected by IBD were included in this systematic review and meta-analysis. Studies focusing on pediatric populations, not reporting person-years of follow-up, or with a duration < 1 year were excluded. PubMed, Embase, Web of Science Core Collection, and Cochrane Central Register were searched from inception through January 2022. Publication bias within studies was assessed using Begg's and Egger's tests and random effects model. Quantitative results were synthesized using relative-risk meta-analysis. PRISMA guidelines were used to carry out this systematic review (PROSPERO Registration Number: CRD42023398348).

Results

A total of 345 studies published between 1985 and 2022, with a total of 6,17,386 patients were included in the meta-analysis. Substantial heterogeneity between studies prevented the pooling of estimates (I2 = 97.19%). Evidence of publication bias was overall low (p = 0.1941). Patients affected by Crohn's disease (CD) were 1,86,074 (30.13%), while 2,78,876 (46.17%) were diagnosed with UC. The remaining 23.7% of cases were diagnosed with indeterminate colitis. Immunomodulators and biologic therapy were used in 24,520 (5.27%), and 17,972 (3.86%) patients, respectively. Reported incidence rates for lymphoma in IBD ranged from 0.0/100,000 person/years (py) (95% CI 0.0–3.7/100,000) to 89/100,000 py (95% CI 36–160/100,000). Reported incidence rates of lymphoma in CD ranged from 0.0/100,000 py (95% CI 0.0–3.7/100,000) to 91/100,000 py (95% CI 18–164/100,000). For UC, the incidence rate ranged from 0.0/100,000 py (95% CI 0.0–3.7/100,000) to 95/100,000 py (95% CI 0–226/100,000). Male-to-female ratio was ~4:1. Therapy with immunomodulators was directly associated with an increased incidence of lymphoma (p < 0.0001). Evidence of publication bias was overall low (p = 0 .1941).

Conclusions

The evidence arising from this study highlights a correlation between the use of immunomodulators and subsequent lymphoma development. Combined multidisciplinary approach and long-term follow-up are warranted in order to decrease mortality deriving from the coexistence of both conditions.

Systematic review registration

Identifier: CRD42023398348.
Birt-Hogg-Dubé syndrome with c.1579_1580insA variant in a Chinese family: a case report
Authors: Tang Shijie , Wei Chuanqi , Wang Xiaoyu , Xiao Min , Luo Fengming , Chen Lei
Published: May 2023

Birt-Hogg-Dubé (BHD) syndrome, is a rare genetic disease with heterogeneous manifestations in different populations. In this study, we reported a Chinese female BHD case and her family members with c.1579_1580insA variant in FLCN gene, who were characterized by diffused pulmonary cysts/bulla, and reviewed another five familial BHD cases in China. Based on these cases, recurrent spontaneous pneumothorax is likely to be the first symptom for BHD in Chinese patients, with particularly but not limited to c.1579_1580insA variant. Therefore, attention to the early diagnosis of BHD in China should focus on pulmonary signs, but skin or kidney lesions still can not be neglected.
Biocontrol and plant growth promoting traits of two avocado rhizobacteria are orchestrated by the emission of diffusible and volatile compounds
Authors: Cortazar-Murillo Elvis M. , Méndez-Bravo Alfonso , Monribot-Villanueva Juan L. , Garay-Serrano Edith , Kiel-Martínez Ana L. , Ramírez-Vázquez Mónica , Guevara-Avendaño Edgar , Méndez-Bravo Alejandro , Guerrero-Analco José A. , Reverchon Frédérique
Published: May 2023

Avocado (Persea americana Mill.) is a tree crop of great social and economic importance. However, the crop productivity is hindered by fast-spreading diseases, which calls for the search of new biocontrol alternatives to mitigate the impact of avocado phytopathogens. Our objectives were to evaluate the antimicrobial activity of diffusible and volatile organic compounds (VOCs) produced by two avocado rhizobacteria (Bacillus A8a and HA) against phytopathogens Fusarium solani, Fusarium kuroshium, and Phytophthora cinnamomi, and assess their plant growth promoting effect in Arabidopsis thaliana. We found that, in vitro, VOCs emitted by both bacterial strains inhibited mycelial growth of the tested pathogens by at least 20%. Identification of bacterial VOCs by gas chromatography coupled to mass spectrometry (GC–MS) showed a predominance of ketones, alcohols and nitrogenous compounds, previously reported for their antimicrobial activity. Bacterial organic extracts obtained with ethyl acetate significantly reduced mycelial growth of F. solani, F. kuroshium, and P. cinnamomi, the highest inhibition being displayed by those from strain A8a (32, 77, and 100% inhibition, respectively). Tentative identifications carried out by liquid chromatography coupled to accurate mass spectrometry of diffusible metabolites in the bacterial extracts, evidenced the presence of some polyketides such as macrolactins and difficidin, hybrid peptides including bacillaene, and non-ribosomal peptides such as bacilysin, which have also been described in Bacillus spp. for antimicrobial activities. The plant growth regulator indole-3-acetic acid was also identified in the bacterial extracts. In vitro assays showed that VOCs from strain HA and diffusible compounds from strain A8a modified root development and increased fresh weight of A. thaliana. These compounds differentially activated several hormonal signaling pathways involved in development and defense responses in A. thaliana, such as auxin, jasmonic acid (JA) and salicylic acid (SA); genetic analyses suggested that developmental stimulation of the root system architecture by strain A8a was mediated by the auxin signaling pathway. Furthermore, both strains were able to enhance plant growth and decreased the symptoms of Fusarium wilt in A. thaliana when soil-inoculated. Collectively, our results evidence the potential of these two rhizobacterial strains and their metabolites as biocontrol agents of avocado pathogens and as biofertilizers.
Characterization of two novel HIV-1 second-generation recombinants (CRF01_AE/CRF07_BC) identified in Hebei Province, China
Authors: Yang Xuegang , Zhao Na , Su Miaomiao , Meng Juan , Du Jian , An Weina , Shi Haoxi , Fan Weiguang
Published: May 2023

Introduction

The unique recombinant forms (URFs) of HIV-1 consist of a mixture of subtypes, and each URF has a unique breakpoint. In this study, we identified the near fulllength genome (NFLG) sequences of two novel HIV-1 URFs (Sample ID: BDD034A and BDL060) isolated during HIV-1 molecular surveillance in 2022 in Baoding city, Hebei Province, China.

Methods

The two sequences were aligned with subtype reference sequences and CRFs from China using MAFFT v7.0, and the alignments were adjusted manually using BioEdit (v7.2.5.0). Phylogenetic and subregion trees were constructed using MEGA11 with the neighbor-joining (N-J) method. Recombination breakpoints were identified by SimPlot (v3.5.1) based on Bootscan analyses.

Results

Recombinant breakpoint analysis revealed that the NFLGs of BDD034A and BDL060 were composed of CRF01_AE and CRF07_BC, containing seven segments, respectively. For BDD034A, three CRF01_AE fragments were inserted into the CRF07_BC main framework, whereas for BDL060, three CRF07_BC fragments were inserted into the CRF01_AE main framework.

Discussion

The emergence of the CRF01_AE/CRF07_BC recombinant strains indicates that HIV-1 co-infection is common. The increasing genetic complexity of the HIV-1 epidemic in China warrants continued investigation.
Lipidomics analysis facilitate insight into the molecular mechanisms of urate nephropathy in a gout model induced by combination of MSU crystals injection and high-fat diet feeding
Authors: Hao Guifeng , Xu Xiaofen , Song Jingyi , Zhang Jida , Xu Kejun
Published: May 2023

Renal injury is one of the most common clinical manifestations of patients with hyperuricaemia/gout. The precise pathophysiological mechanism(s) for the renal injury is still unknown. Furthermore, it is also unclear whether the clinical therapies (e.g., colchicine and febuxostat) could prevent its progression or not. Lipids are involved in almost all of important biological processes and play critical roles in maintaining the renal functions. Herein, shotgun lipidomics was performed for class-targeted lipid analysis of cellular lipidomes in renal tissue of a gouty model induced by combination of monosodium urate crystals injection and high-fat diet feeding with/without treatment with either colchicine or febuxostat. Serum uric acid (UA), proinflammatory cytokines (i.e., TNF-α and IL-6), xanthine oxidase activity, footpad swelling, and pain threshold were determined to evaluate the gouty severity. Renal histopathological changes, blood urea nitrogen, creatinine, and kidney index were used to reflect renal injury. Lipidomics analysis revealed that altered triacylglycerol (TAG) profile, impaired mitochondrial function resulted by decreased tetra 18:2 cardiolipin, reduced 4-hydroxyalkenal (HNE) species, and elevated lysophospholipids were already present in the kidneys at early stage of renal injury, probably contributing to its occurrence and development. In addition to significantly reduce the UA level and relief the gouty severity, treatment with either colchicine or febuxostat could restore HNE bioavailability, thereby delaying the progression of renal injury. However, both of them could not recover the altered TAG profile and the impaired mitochondrial function, indicating that treatment with either of them could not completely prevent the development of renal injury in the gouty model.
Binocular video head impulse test: Normative data study
Authors: Striteska Maja , Chovanec Martin , Steinmetzer Tobias , Chrobok Viktor , Profant Oliver , Schneider Erich , Kremlacek Jan , Valis Martin
Published: May 2023

Introduction

The video head impulse test (vHIT) evaluates the vestibulo-ocular reflex (VOR). It’s usually recorded from only one eye. Newer vHIT devices allow a binocular quantification of the VOR.

Purpose (Aim)

To investigate the advantages of simultaneously recorded binocular vHIT (bvHIT) to detect the differences between the VOR gains of the adducting and the abducting eye, to define the most precise VOR measure, and to assess gaze dys/conjugacy. We aimed to establish normative values for bvHIT adducting/abducting eye VOR gains and to introduce the VOR dysconjugacy ratio (vorDR) between adducting and abducting eyes for bvHIT.

Methods

We enrolled 44 healthy adult participants in a cross-sectional, prospective study using a repeated-measures design to assess test–retest reliability. A binocular EyeSeeCam Sci 2 device was used to simultaneously record bvHIT from both eyes during impulsive head stimulation in the horizontal plane.

Results

Pooled bvHIT retest gains of the adducting eye significantly exceeded those of the abducting eye (mean (SD): 1.08 (SD = 0.06), 0.95 (SD = 0.06), respectively). Both adduction and abduction gains showed similar variability, suggesting comparable precision and therefore equal suitability for VOR asymmetry assessment. The pooled vorDR here introduced to bvHIT was 1.13 (SD = 0.05). The test–retest repeatability coefficient was 0.06.

Conclusion

Our study provides normative values reflecting the conjugacy of eye movement responses to horizontal bvHIT in healthy participants. The results were similar to a previous study using the gold-standard scleral search coil, which also reported greater VOR gains in the adducting than in the abducting eye. In analogy to the analysis of saccade conjugacy, we propose the use of a novel bvHIT dysconjugacy ratio to assess dys/conjugacy of VOR-induced eye movements. In addition, to accurately assess VOR asymmetry, and to avoid directional gain preponderance between adduction and abduction VOR-induced eye movements leading to monocular vHIT bias, we recommend using a binocular ductional VOR asymmetry index that compares the VOR gains of only the abduction or only the adduction movements of both eyes.
Migraine triggers in Asian countries: a narrative review
Authors: Iba Chisato , Ohtani Seiya , Lee Mi Ji , Huh Sunjun , Watanabe Narumi , Nakahara Jin , Peng Kuan-Po , Takizawa Tsubasa
Published: May 2023

Background

Migraine is one of the most common neurological disorders worldwide. Clinical characteristics of migraine may be somewhat different across ethnic groups. Although factors such as stress, lack of sleep, and fasting are known as migraine triggers, the discussion about geographical differences of migraine triggers in Asia is lacking.

Methods

In this study, we performed a narrative review on migraine triggers in Asia. We searched PubMed for relevant papers published between January 2000 and February 2022.

Results

Forty-two papers from 13 Asian countries were included. Stress and sleep are the most frequently reported migraine triggers in Asia. There were some differences in migraine triggers in Asian countries: fatigue and weather common in Eastern Asia and fasting common in Western Asia.

Conclusion

Majority of the common triggers reported by patients with migraine in Asia were stress and sleep, similar to those reported globally, thus showing they are universally important. Some triggers linked to internal homeostasis are influenced by culture (e.g., alcohol, food/eating habit), and triggers related to environmental homeostasis, such as weather, are highly heterogenous between regions.
Liquid biopsy can cure early colorectal cancer recurrence – Case Report
Authors: Baraniskin Alexander , Baba Hideo A. , Theegarten Dirk , Mika Thomas , Schroers Roland , Klein-Scory Susanne
Published: May 2023

In the context of colorectal cancer (CRC), circulating tumor DNA (ctDNA) is frequently used to monitor the minimal residual disease (MRD). ctDNA has become an excellent biomarker to predict which patients with CRC are likely to relapse due to the persistence of micrometastases. MRD diagnosis via analysis of ctDNA may allow much earlier detection of relapse compared with conventional diagnosis during follow-up. It should lead to an increased rate of curative-intended complete resection of an asymptomatic relapse. Besides, ctDNA can provide crucial information on whether and how intensively adjuvant or additive therapy should be administered. In the present case, analysis of ctDNA gave us a crucial hint to the use of more intensive diagnostics (MRI and Positron emission tomography–computed tomography PET-CT) which led to earlier detection of CRC relapse. Metastasis detected early are more likely to be completely resectable with curative intent.
Preoperative diagnosis of solitary pulmonary nodules with a novel hematological index model based on circulating tumor cells
Authors: Zhou Qiuxi , He Qiao , Peng Ling , Huang Yecai , Li Kexun , Liu Kun , Li Da , Zhao Jing , Sun Kairong , Li Aoshuang , He Wenwu
Published: May 2023

Objective

Preoperative noninvasive diagnosis of the benign or malignant solitary pulmonary nodule (SPN) is still important and difficult for clinical decisions and treatment. This study aimed to assist in the preoperative diagnosis of benign or malignant SPN using blood biomarkers.

Methods

A total of 286 patients were recruited for this study. The serum FR+CTC, TK1, TP, TPS, ALB, Pre-ALB, ProGRP, CYFRA21-1, NSE, CA50, CA199, and CA242 were detected and analyzed.

Results

In the univariate analysis, age, FR+CTC, TK1, CA50, CA19.9, CA242, ProGRP, NSE, CYFRA21-1, and TPS showed the statistical significance of a correlation with malignant SPNs (P <0.05). The highest performing biomarker is FR+CTC (odd ratio [OR], 4.47; 95% CI: 2.57–7.89; P <0.001). The multivariate analysis identified that age (OR, 2.69; 95% CI: 1.34–5.59, P = 0.006), FR+CTC (OR, 6.26; 95% CI: 3.09–13.37, P <0.001), TK1 (OR, 4.82; 95% CI: 2.4–10.27, P <0.001), and NSE (OR, 2.06; 95% CI: 1.07–4.06, P = 0.033) are independent predictors. A prediction model based on age, FR+CTC, TK1, CA50, CA242, ProGRP, NSE, and TPS was developed and presented as a nomogram, with a sensitivity of 71.1% and a specificity of 81.3%, and the AUC was 0.826 (95% CI: 0.768–0.884).

Conclusions

The novel prediction model based on FR+CTC showed much stronger performance than any single biomarker, and it can assist in predicting benign or malignant SPNs.
Predictive potential of angiopoietin-2 in a mCRC subpopulation treated with vanucizumab in the McCAVE trial
Authors: Ferreira Cláudia S. , Babitzki Galina , Klaman Irina , Krieter Oliver , Lechner Katharina , Bendell Johanna , Vega Harring Suzana , Heil Florian
Published: May 2023

Introduction

Angiopoetin-2 (Ang-2) is a key mediator of tumour angiogenesis. When upregulated it is associated with tumour progression and poor prognosis. Anti-vascular endothelial growth factor (VEGF) therapy has been widely used in the treatment of metastatic colorectal cancer (mCRC). The potential benefit of combined inhibition of Ang-2 and VEGF-A in previously untreated patients with mCRC was evaluated in the phase II McCAVE study (NCT02141295), assessing vanucizumab versus bevacizumab (VEGF-A inhibitor), both in combination with mFOLFOX-6 (modified folinic acid [leucovorin], fluorouracil and oxaliplatin) chemotherapy. To date, there are no known predictors of outcome of anti-angiogenic treatment in patients with mCRC. In this exploratory analysis, we investigate potential predictive biomarkers in baseline samples from McCAVE participants.

Methods

Tumour tissue samples underwent immunohistochemistry staining for different biomarkers, including Ang-2. Biomarker densities were scored on the tissue images using dedicated machine learning algorithms. Ang-2 levels were additionally assessed in plasma. Patients were stratified by KRAS mutation status determined using next generation sequencing. Median progression-free survival (PFS) for each treatment group by biomarker and KRAS mutation was estimated using Kaplan–Meier plots. PFS hazard ratios (and 95% confidence intervals) were compared using Cox regression.

Results

Overall low tissue baseline levels of Ang-2 were associated with longer PFS, especially in patients with wild-type KRAS status. In addition, our analysis identified a new subgroup of patients with KRAS wild-type mCRC and high levels of Ang-2 in whom vanucizumab/mFOLFOX-6 prolonged PFS significantly (log-rank p=0.01) by ~5.5 months versus bevacizumab/mFOLFOX-6. Similar findings were seen in plasma samples.

Discussion

This analysis demonstrates that additional Ang-2 inhibition provided by vanucizumab shows a greater effect than single VEGF-A inhibition in this subpopulation. These data suggest that Ang-2 may be both a prognostic biomarker in mCRC and a predictive biomarker for vanucizumab in KRAS wild-type mCRC. Thus, this evidence can potentially support the establishment of more tailored treatment approaches for patients with mCRC.