bluuebunny/crossref_metadata_2025 huggingface dataset:
Co-Expression of TIGIT and Helios Marks Immunosenescent CD8+ T Cells During Aging
Authors: Pieren Daan K. J. , Smits Noortje A. M. , Postel Rimke J. , Kandiah Vinitha , de Wit Jelle , van Beek Josine , van Baarle Debbie , Guichelaar Teun
Published: May 2022

Aging leads to alterations in the immune system that result in ineffective responsiveness against pathogens. Features of this process, collectively known as immunosenescence, accumulate in CD8+ T cells with age and have been ascribed to differentiation of these cells during the course of life. Here we aimed to identify novel markers in CD8+ T cells associated with immunosenescence. Furthermore, we assessed how these markers relate to the aging-related accumulation of highly differentiated CD27-CD28- cells. We found that co-expression of the transcription factor Helios and the aging-related marker TIGIT identifies CD8+ T cells that fail to proliferate and show impaired induction of activation markers CD69 and CD25 in response to stimulation in vitro. Despite this, in blood of older adults we found TIGIT+Helios+ T cells to become highly activated during an influenza-A virus infection, but these higher frequencies of activated TIGIT+Helios+ T cells associate with longer duration of coughing. Moreover, in healthy individuals, we found that TIGIT+Helios+ CD8+ T cells accumulate with age in the highly differentiated CD27-CD28- population. Interestingly, TIGIT+Helios+ CD8+ T cells also accumulate with age among the less differentiated CD27+CD28- T cells before their transit into the highly differentiated CD27-CD28- stage. This finding suggests that T cells with immunosenescent features become prominent at old age also within the earlier differentiation states of these cells. Our findings show that co-expression of TIGIT and Helios refines the definition of immunosenescent CD8+ T cells and challenge the current dogma of late differentiation stage as proxy for T-cell immunosenescence.
Half-Life Extended Nanobody-Based CD38-Specific Bispecific Killercell Engagers Induce Killing of Multiple Myeloma Cells
Authors: Hambach Julia , Fumey William , Stähler Tobias , Gebhardt Anna Josephine , Adam Gerhard , Weisel Katja , Koch-Nolte Friedrich , Bannas Peter
Published: May 2022

CD38 is a target for immunotherapy of multiple myeloma. Llama-derived CD38-specific nanobodies allow easy reformatting into mono-, bi- and multispecific proteins. To evaluate the utility of nanobodies for constructing CD38-specific nanobody-based killer cell engagers (nano-BiKEs), we generated half-life extended nano-BiKEs (HLE-nano-BiKEs) by fusing a CD38-specific nanobody to a CD16-specific nanobody for binding to the Fc-receptor on NK cells and further to an albumin-specific nanobody to extend the half-life in vivo. HLE-nano-BiKEs targeting three different epitopes (E1, E2, E3) of CD38 were expressed in transiently transfected HEK-6E cells. We verified specific and simultaneous binding to CD38 on myeloma cells, CD16 on NK cells, and to albumin. We tested the capacity of these HLE-nano-BiKEs to mediate cytotoxicity against CD38-expressing multiple myeloma cell lines and primary myeloma cells from human bone marrow biopsies in bioluminescence and flowcytometry assays with NK92 cells as effector cells. The results revealed specific time- and dose-dependent cytolysis of CD38+ myeloma cell lines and effective depletion of CD38-expressing multiple myeloma cells from primary human bone marrow samples. Our results demonstrate the efficacy of CD38-specific HLE-nano-BiKEs in vitro and ex vivo, warranting further preclinical evaluation in vivo of their therapeutic potential for the treatment of multiple myeloma.
Molecular Identification of Two DNA Methyltransferase Genes and Their Functional Characterization in the Anti-Bacterial Immunity of Antheraea pernyi
Authors: Kausar Saima , Abbas Muhammad Nadeem , Gul Isma , Liu Ruochen , Li Qianqian , Zhao Erhu , Lv Muhan , Cui Hongjuan
Published: May 2022

Under different physiological conditions, such as microbial infection, epigenetic mechanisms regulate genes at the transcription level in living organisms. DNA methylation is a type of epigenetic mechanism in which DNA methyltransferases modify the expression of target genes. Here, we identified a full-length sequence of DNMT-1 and DNMT-2 from the Chinese oak silkworm, A. pernyi, which was highly similar to the homologous sequences of Bombyx mori. ApDNMT-1 and ApDNMT-2 have unique domain architectures of insect DNMTs, highlighting their conserved functions in A. pernyi. ApDNMT-1 and ApDNMT-2 were found to be widely expressed in various tissues, with the highest levels of expression in hemocytes, the ovary, testis, and fat bodies. To understand the biological role of these genes in microbial resistance, we challenged the fifth instar larvae of A. pernyi by administrating Gram-positive and Gram-negative bacteria and fungi. The results revealed that transcript levels of ApDNMT-1 and ApDNMT-2 were increased compared to the control group. The inhibition of these genes by a DNMTs inhibitor [5-azacytidine (5-AZA)] significantly reduced bacterial replication and larvae mortality. In addition, 5-AZA treatment modified the expression patterns of antimicrobial peptides (AMPs) in the A. pernyi larvae. Our results suggest that ApDNMT-1 and ApDNMT-2 seem to have a crucial role in innate immunity, mediating antimicrobial peptide responses against bacterial infection in A. pernyi.
Targeting Differential Roles of Tumor Necrosis Factor Receptors as a Therapeutic Strategy for Glaucoma
Authors: Lambuk Lidawani , Ahmad Suhana , Sadikan Muhammad Zulfiqah , Nordin Nor Asyikin , Kadir Ramlah , Nasir Nurul Alimah Abdul , Chen Xin , Boer Jennifer , Plebanski Magdalena , Mohamud Rohimah
Published: May 2022

Glaucoma is an irreversible sight-threatening disorder primarily due to elevated intraocular pressure (IOP), leading to retinal ganglion cell (RGC) death by apoptosis with subsequent loss of optic nerve fibers. A considerable amount of empirical evidence has shown the significant association between tumor necrosis factor cytokine (TNF; TNFα) and glaucoma; however, the exact role of TNF in glaucoma progression remains unclear. Total inhibition of TNF against its receptors can cause side effects, although this is not the case when using selective inhibitors. In addition, TNF exerts its antithetic roles via stimulation of two receptors, TNF receptor I (TNFR1) and TNF receptor II (TNFR2). The pro-inflammatory responses and proapoptotic signaling pathways predominantly mediated through TNFR1, while neuroprotective and anti-apoptotic signals induced by TNFR2. In this review, we attempt to discuss the involvement of TNF receptors (TNFRs) and their signaling pathway in ocular tissues with focus on RGC and glial cells in glaucoma. This review also outlines the potential application TNFRs agonist and/or antagonists as neuroprotective strategy from a therapeutic standpoint. Taken together, a better understanding of the function of TNFRs may lead to the development of a treatment for glaucoma.
Switch Tandem Repeats Influence the Choice of the Alternative End-Joining Pathway in Immunoglobulin Class Switch Recombination
Authors: Oudinet Chloé , Zhang Xuefei , Puget Nadine , Kyritsis Nia , Leduc Claire , Braikia Fatima-Zohra , Dauba Audrey , Alt Frederick W. , Khamlichi Ahmed Amine
Published: May 2022

Immunoglobulin class switch recombination (CSR) plays an important role in humoral imm\une responses by changing the effector functions of antibodies. CSR occurs between highly repetitive switch (S) sequences located upstream of immunoglobulin constant gene exons. Switch sequences differ in size, the nature of their repeats, and the density of the motifs targeted by the activation-induced cytidine deaminase (AID), the enzyme that initiates CSR. CSR involves double-strand breaks (DSBs) at the universal Sµ donor region and one of the acceptor S regions. The DSBs ends are fused by the classical non-homologous end-joining (C-NHEJ) and the alternative-NHEJ (A-NHEJ) pathways. Of the two pathways, the A-NHEJ displays a bias towards longer junctional micro-homologies (MHs). The Sµ region displays features that distinguish it from other S regions, but the molecular basis of Sµ specificity is ill-understood. We used a mouse line in which the downstream Sγ3 region was put under the control of the Eµ enhancer, which regulates Sµ, and analyzed its recombination activity by CSR-HTGTS. Here, we show that provision of Eµ enhancer to Sγ3 is sufficient to confer the recombinational features of Sµ to Sγ3, including efficient AID recruitment, enhanced internal deletions and robust donor function in CSR. Moreover, junctions involving Sγ3 display a bias for longer MH irrespective of sequence homology with switch acceptor sites. The data suggest that the propensity for increased MH usage is an intrinsic property of Sγ3 sequence, and that the tandem repeats of the donor site influence the choice of the A-NHEJ.
Prospects on Repurposing a Live Attenuated Vaccine for the Control of Unrelated Infections
Authors: Seo Sang-Uk , Seong Baik-Lin
Published: May 2022

Live vaccines use attenuated microbes to acquire immunity against pathogens in a safe way. As live attenuated vaccines (LAVs) still maintain infectivity, the vaccination stimulates diverse immune responses by mimicking natural infection. Induction of pathogen-specific antibodies or cell-mediated cytotoxicity provides means of specific protection, but LAV can also elicit unintended off-target effects, termed non-specific effects. Such mechanisms as short-lived genetic interference and non-specific innate immune response or long-lasting trained immunity and heterologous immunity allow LAVs to develop resistance to subsequent microbial infections. Based on their safety and potential for interference, LAVs may be considered as an alternative for immediate mitigation and control of unexpected pandemic outbreaks before pathogen-specific therapeutic and prophylactic measures are deployed.
Advances in Nanotechnology-Based Immunotherapy for Glioblastoma
Authors: Tang Lin , Zhang Ming , Liu Chaoyong
Published: May 2022

Glioblastoma (GBM) is the most aggressive type of brain tumor. Despite the multimodal therapies, the effectiveness of traditional treatments is not much satisfying. In recent years, immunotherapy has become the focus of tumor treatment. Unlike traditional treatments that directly target tumor cells, immunotherapy uses the body’s immune system to kill tumors. However, due to the severe immunosuppressive microenvironment of GBM, it generally has a poor response to immunotherapy. In addition, the existence of the blood-brain barrier (BBB) also compromises the immunotherapeutic efficacy. Therefore, effective immunotherapy of GBM requires the therapeutic agents to not only efficiently cross the BBB but also relieve the strong immunosuppression of the tumor microenvironment of GBM. In this review, we will first introduce the CNS immune system, immunosuppressive mechanism of GBM, and current GBM immunotherapy strategies. Then, we will discuss the development of nanomaterials for GBM immunotherapy based on different strategies, roughly divided into four parts: immune checkpoint therapy, targeting tumor-associated immune cells, activating immune cells through immunogenic cell death, and combination therapy, to provide new insights for future GBM immunotherapy.
Computational Discovery of Cancer Immunotherapy Targets by Intercellular CRISPR Screens
Authors: Yim Soorin , Hwang Woochang , Han Namshik , Lee Doheon
Published: May 2022

Cancer immunotherapy targets the interplay between immune and cancer cells. In particular, interactions between cytotoxic T lymphocytes (CTLs) and cancer cells, such as PD-1 (PDCD1) binding PD-L1 (CD274), are crucial for cancer cell clearance. However, immune checkpoint inhibitors targeting these interactions are effective only in a subset of patients, requiring the identification of novel immunotherapy targets. Genome-wide clustered regularly interspaced short palindromic repeats (CRISPR) screening in either cancer or immune cells has been employed to discover regulators of immune cell function. However, CRISPR screens in a single cell type complicate the identification of essential intercellular interactions. Further, pooled screening is associated with high noise levels. Herein, we propose intercellular CRISPR screens, a computational approach for the analysis of genome-wide CRISPR screens in every interacting cell type for the discovery of intercellular interactions as immunotherapeutic targets. We used two publicly available genome-wide CRISPR screening datasets obtained while triple-negative breast cancer (TNBC) cells and CTLs were interacting. We analyzed 4825 interactions between 1391 ligands and receptors on TNBC cells and CTLs to evaluate their effects on CTL function. Intercellular CRISPR screens discovered targets of approved drugs, a few of which were not identifiable in single datasets. To evaluate the method’s performance, we used data for cytokines and costimulatory molecules as they constitute the majority of immunotherapeutic targets. Combining both CRISPR datasets improved the recall of discovering these genes relative to using single CRISPR datasets over two-fold. Our results indicate that intercellular CRISPR screens can suggest novel immunotherapy targets that are not obtained through individual CRISPR screens. The pipeline can be extended to other cancer and immune cell types to discover important intercellular interactions as potential immunotherapeutic targets.
Dissecting Tissue Compartment-Specific Protein Signatures in Primary and Metastatic Oropharyngeal Squamous Cell Carcinomas
Authors: Sadeghirad Habib , Monkman James , Mehdi Ahmed M. , Ladwa Rahul , O’Byrne Ken , Hughes Brett G. M. , Kulasinghe Arutha
Published: May 2022

Head and neck squamous cell carcinoma (HNSCC) often presents with locoregional or distant disease, despite multimodal therapeutic approaches, which include surgical resection, chemoradiotherapy, and more recently, immunotherapy for metastatic or recurrent HNSCC. Therapies often target the primary and nodal regional HNSCC sites, and their efficacy at controlling occult distant sites remains poor. While our understanding of the tumor microenvironment conducive to effective therapies is increasing, the biology underpinning locoregional sites remains unclear. Here, we applied targeted spatial proteomic approaches to primary and lymph node metastasis from an oropharyngeal SCC (OPSCC) cohort to understand the expression of proteins within tumors, and stromal compartments of the respective sites in samples of both matched and unmatched patients. In unmatched analyses of n = 43 primary and 11 nodal metastases, our data indicated that tumor cells in nodal metastases had higher levels of Ki-67, PARP, BAD, and cleaved caspase 9, suggesting a role for increased proliferation, DNA repair, and apoptosis within these metastatic cells. Conversely, in matched analyses (n = 7), pro-apoptotic markers BIM and BAD were enriched in the stroma of primary tumors. Univariate, overall survival (OS) analysis indicated CD25 in tumor regions of primary tumors to be associated with reduced survival (HR = 3.3, p = 0.003), while progesterone receptor (PR) was associated with an improved OS (HR = 0.33, p = 0.015). This study highlights the utility of spatial proteomics for delineating the tumor and stromal compartment composition, and utility toward understanding these properties in locoregional metastasis. These findings indicate unique biological properties of lymph node metastases that may elucidate further understanding of distant metastatic in OPSCC.
Variability in Foraging Range and Direction Among Colonies in a Widespread Seabird, the Magellanic Penguin
Authors: Rebstock Ginger A. , García Borboroglu Pablo , Boersma P. Dee
Published: May 2022

Most seabirds forage far from land, making them hard to observe when foraging. Satellite tracking of seabirds shows where they come into conflict with human uses of the ocean, and whether they use protected areas. Because tracking data are expensive, data from one colony and/or year are sometimes used to design marine protection for a species across its range. Two assumptions commonly made are that foraging distance increases with colony size and individuals are uniformly distributed around colonies. We tested these assumptions using Magellanic penguinsSpheniscus magellanicusas an example. We used a large tracking dataset of 338 penguins foraging for chicks at 10 colonies in Argentina from 1996 to 2019. Foraging distance increased with population size among colonies, but predicted distances would not cover foraging areas for all colonies. There was no relationship between population size and foraging distance within colony among years for colonies with ten and 23 years of data. Penguins were not uniformly distributed around colonies. Penguins used ~24% (12-40%) of the ocean available within the colony’s maximum foraging distance. We also show that overlap between penguin foraging areas and marine protected areas (MPA) and hydrocarbon concessions varied among colonies partly because of variation in how far offshore penguins forage. Overlap with MPAs was low (0% – 20%) for seven of the ten colonies and high (23% – 100%) for the other three. Overlap with a large area permitted for hydrocarbon exploration (seismic surveys) was relatively high (23% – 81%) for seven colonies where penguins forage offshore. Data from one colony are unlikely to indicate the most effective marine spatial planning for all colonies. Our data show that to be effective, marine planning should consider the temporal and spatial dynamics of ocean conditions and the response of marine wildlife to these changes. Climate variability is predicted to increase, making knowledge of foraging-location variation among colonies and years critical to conservation planning.
Sustainable Alkali-Activated Slag Binders Based on Alternative Activators Sourced From Mineral Wool and Glass Waste
Authors: Pavlin Majda , König Katja , König Jakob , Javornik Uroš , Ducman Vilma
Published: May 2022

In the present study, four different locally available waste glass materials (bottle glass-BG, glass wool-GW, stone wool-SW and cathode-ray tube glass-CRTG) were treated with hot concentrated potassium hydroxide (KOH) in order to obtain alternative alkali activators (AAAs). We evaluated the suitability of the solutions obtained for use as AAAs in the production of AAMs. AAMs were prepared using electric arc furnace slag and selected AAAs with a higher content of dissolved Si. We evaluated the performance of the AAMs in comparison to that of slags activated with KOH or potassium-silicate (K-silicate). The compressive strength of the AAMs prepared with KOH-based AAAs were high when Si and Al were simultaneously abundant in the AAA (9.47 MPa when using the activator sourced from the CRTG), and low with the addition of KOH alone (1.97 MPa). The AAM produced using commercial K-silicate yielded the highest compressive strength (27.7 MPa). The porosity of the KOH-based AAM was lowest when an alternative BG-based activator was used (24.1%), when it was similar to that of the AAM prepared with a K-silicate. The BG-based activator had the highest silicon content (33.1 g/L), and NMR revealed that Si was present in the form of Q0, Q1 and Q2. The concentrations of toxic trace elements in the AAAs used for alkali activation of the slag were also determined, and leaching experiments were performed on the AAMs to evaluate the immobilisation potential of alkali-activated slag. In the SW AAAs the results show acceptable concentrations of trace and minor elements with respect to the regulations on waste disposal sites, while in the activators prepared from BG, CRTG and GW some elements exceeded the allowable limits (Pb, Ba, Sb, and As).
Medical Humanities Education and Its Influence on Students' Outcomes in Taiwan: A Systematic Review
Authors: Hoang Bao Lan , Monrouxe Lynn Valerie , Chen Kuo-Su , Chang Shu-Ching , Chiavaroli Neville , Mauludina Yosika Septi , Huang Chien-Da
Published: May 2022

Background

Medical education has emphasized the importance of integrating medical humanities training into the curriculum to benefit medical and nursing students' future practice, featuring in the list of national funding priorities for healthcare education research in Taiwan for many years. However, the extent to which this drive has resulted in medical humanities training, what rationales underpin its inclusion, and its efficacy is largely unknown. This study aims to address these issues across medical humanities programs within the Taiwanese context.

Methods

We conducted a systematic review. Inclusion criteria included studies in English or Mandarin reporting outcomes of medical humanities courses in healthcare education settings in Taiwan between 2000 and 2019. We searched across five electronic databases (PubMed, Embase, ERIC, PsycInfo, Web of Science), following PRISMA guidelines. The Best Evidence Medical Education (BEME) Global Scale and Kirkpatrick Levels are used for identifying the strength of evidence.

Results

17 articles were extracted from the 134 identified. Intrinsic and instrumental rationales for the inclusion of medical humanities education were common, compared with epistemological-based and critical-based approaches. Several positive impacts were identified in relation to participation including modification of attitudes, knowledge, and skills. However, the highest level (i.e., unequivocal) of evidence characterized by effects on students' behaviors or ongoing interaction with colleagues and patients is lacking.

Conclusion

Findings suggest that although medical humanities education is widely implemented in Taiwan, no clear consensus has been reached regarding the rationale for inclusion or how it is localized from Western to Asian contexts. Future research still needs to explore the long-term impact of medical humanities education for medical and nursing students and its impact on patient care.

Systematic Review Registration

https://www.crd.york.ac.uk/PROSPERO, identifier: CRD42019123967.
The Therapeutic Potential of Anticoagulation in Organ Fibrosis
Authors: Oh Hanna , Park Hye Eun , Song Min Su , Kim HaYoung , Baek Jea-Hyun
Published: May 2022

Fibrosis, also known as organ scarring, describes a pathological stiffening of organs or tissues caused by increased synthesis of extracellular matrix (ECM) components. In the past decades, mounting evidence has accumulated showing that the coagulation cascade is directly associated with fibrotic development. Recent findings suggest that, under inflammatory conditions, various cell types (e.g., immune cells) participate in the coagulation process causing pathological outcomes, including fibrosis. These findings highlighted the potential of anticoagulation therapy as a strategy in organ fibrosis. Indeed, preclinical and clinical studies demonstrated that the inhibition of blood coagulation is a potential intervention for the treatment of fibrosis across all major organs (e.g., lung, liver, heart, and kidney). In this review, we aim to summarize our current knowledge on the impact of components of coagulation cascade on fibrosis of various organs and provide an update on the current development of anticoagulation therapy for fibrosis.
Biomechanical Considerations of Patching Material for Posterior Scleral Reinforcement Surgery
Authors: Ma Jinlei , Wu Fangyuan , Liu Zhiyong , Fang Yijiong , Chu Xu , Zheng Linyan , Xue Anquan , Nan Kaihui , Qu Jia , Cheng Lingyun
Published: May 2022

Purpose

To characterize biomechanical properties of genipin-crosslinked human dura mater as reinforcing material for posterior scleral reinforcement (PSR) and to compare it with crosslinked human sclera.

Methods

Donor dura mater and sclera were crosslinked in the same optimized genipin solution. Resistance to enzyme degradation for both materials were investigated by exposing the materials to accelerated enzyme degrading. Elastic modulus and tensile strength were measured by biomechanics testing equipment. Crosslinked human dura mater was used as reinforcing patch in PSR on 57 adult pathologic myopic eyes. The patients were followed up for an average 3 years. The main outcome was eye globe axial length change and safety profile of the reinforcing material.

Results

Crosslinked dura mater demonstrated similar percentage weight loss to crosslinked sclera when exposed to enzymatic solution. Dura mater has higher density than sclera. The retaining elastic modulus after enzyme exposure was 72.02 MPa for crosslinked dura mater while 53.88 MPa for crosslinked sclera, 34% greater for crosslinked dura mater, P = 0.0186). At the end of 3 years follow-up, the mean globe axis of the surgery eyes was reduced by 1.29 mm (from 30.81 to 29.51 mm, P < 0.0001, paired t-test). Visual acuity (BCVA logMar) improved by 0.10 logMar unit which is an improvement of five letters (P = 0.0184, paired t-test). No material specific complication was noted.

Conclusion

Crosslinked human dura mater may be superior to crosslinked human sclera as reinforcing material for PSR to manage progression of high myopia. This material was well tolerated on human eye.
Clinical Outcomes and Microbiological Characteristics of Sequence Type 11 Klebsiella pneumoniae Infection
Authors: Yang Ping , Wu Zhenchao , Liu Chao , Zheng Jiajia , Wu Nan , Wu Zhangli , Yi Juan , Lu Ming , Shen Ning
Published: May 2022

Background

Sequence type 11 (ST11) Klebsiella pneumoniae (Kp) is highly prevalent in China and is a typical sequence type among KPC-producing isolates. This study aimed to evaluate the clinical outcomes and microbiological features of ST11 Kp infections.

Methods

A retrospective cohort study was conducted at Peking University Third Hospital from January 2017 to March 2021. Clinical data were collected from medical records. Antimicrobial susceptibility testing and string tests were performed. Whole-genome sequencing was used to analyze the capsular serotypes, detect virulence-associated genes, and perform multilocus sequence typing. The risk of all-cause mortality in ST11 Kp-infected patients was compared to that in non-ST11 Kp-infected patients.

Results

From 139 patients infected with Kp, 49 ST11 Kp (35.3%) strains were isolated. The Charlson comorbidity index in the ST11 group was higher than that in the non-ST11 group (3.94 ± 1.59 vs. 2.41 ± 1.54, P = 0.001). A greater number of ST11 Kp-infected patients required ICU admission (46.9 vs. 16.7%, P < 0.001) and mechanical ventilation (28.6 vs. 10.0%, P = 0.005). All ST11 isolates presented a multidrug-resistant (MDR) phenotype, and twenty-nine (59.2%) hypervirulent Kp (hvKp) were identified. Twenty-four ST11 strains presented with hypermucoviscosity. The presence of capsular types K47 and K64 was frequent in the ST11 Kp strains (P < 0.001). The key virulence-associated genes rmpA, rmpA2, iucA, iroB, and peg344 were present in 26.5, 42.9, 59.2, 0, and 26.5% of the isolates, respectively, in the ST11 group. Twenty-one ST11 isolates harbored the combination of iucA+rmpA2. The 30-day mortality rate and sequential organ failure assessment (SOFA) score were significantly higher in ST11 Kp-infected patients than in non-ST11 Kp-infected patients (P < 0.01). ST11 Kp infection appeared to be an independent risk factor for mortality in ST11 Kp-infected patients.

Conclusions

A high prevalence of the ST11 clone was found in the hospital, which accounted for elevated antimicrobial resistance and exhibited great molecularly inferred virulence. Patients with ST11 Kp infection had a tendency toward increased 30-day mortality and SOFA scores. ST11 Kp infection was an independent risk factor for mortality, suggesting that enhanced surveillance and management are essential.
B-Cell Lymphoma Producing IgM Anti-B Antibody: A Case Report
Authors: Jiang Feiyu , Song Tiejun , Wang Yingjian , Liu Zhiwei
Published: May 2022

ABO blood group system is the most important blood group system in transfusion and transplantation medicine. Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphomas (NHLs) worldwide. There have been some studies that lymphoma could affect ABO blood group system and thus affect blood transfusion strategy. However, the mechanisms lymphoma affecting ABO blood group system have not been fully elucidated so far. Here, we report a case of a patient who was a 72-year-old Chinese man came to our hospital for medical advice because of cervical lymphadenophathy. The patient was subsequently diagnosed with diffuse large B-cell lymphoma by lymph-node biopsy. His ABO blood group was initially typed as B on November 7, 2020. He was transfusing B type leukocyte poor RBCs (LPR) before we found the patient’s ABO blood group discrepancy on December 2, 2020 by forward and reverse typing methods, which the discrepancy was verified by genotyping. The patient began to transfuse O type washed RBCs (WRBC) since then. Compared to transfuse B type leukocyte poor RBCs (LPR), the efficiency of transfusing O type washed RBCs (WRBC) was better. Although hemoglobin level did not greatly improve, indirect bilirubin level evidently decreased. Furthermore, we found B-cell lymphoma affected blood transfusion strategy by producing IgM anti-B antibody in this case. Clinicians should need to be aware of the effect of B-cell lymphoma on blood transfusion strategy.
Seasonality of Glacial Snow and Ice Microbial Communities
Authors: Winkel Matthias , Trivedi Christopher B. , Mourot Rey , Bradley James A. , Vieth-Hillebrand Andrea , Benning Liane G.
Published: May 2022

Blooms of microalgae on glaciers and ice sheets are amplifying surface ice melting rates, which are already affected by climate change. Most studies on glacial microorganisms (including snow and glacier ice algae) have so far focused on the spring and summer melt season, leading to a temporal bias, and a knowledge gap in our understanding of the variations in microbial diversity, productivity, and physiology on glacier surfaces year-round. Here, we investigated the microbial communities from Icelandic glacier surface snow and bare ice habitats, with sampling spanning two consecutive years and carried out in both winter and two summer seasons. We evaluated the seasonal differences in microbial community composition using Illumina sequencing of the 16S rRNA, 18S rRNA, and ITS marker genes and correlating them with geochemical signals in the snow and ice. During summer, Chloromonas, Chlainomonas, Raphidonema, and Hydrurus dominated surface snow algal communities, while Ancylonema and Mesotaenium dominated the surface bare ice habitats. In winter, algae could not be detected, and the community composition was dominated by bacteria and fungi. The dominant bacterial taxa found in both winter and summer samples were Bacteriodetes, Actinobacteria, Alphaproteobacteria, and Gammaproteobacteria. The winter bacterial communities showed high similarities to airborne and fresh snow bacteria reported in other studies. This points toward the importance of dry and wet deposition as a wintertime source of microorganisms to the glacier surface. Winter samples were also richer in nutrients than summer samples, except for dissolved organic carbon—which was highest in summer snow and ice samples with blooming microalgae, suggesting that nutrients are accumulated during winter but primarily used by the microbial communities in the summer. Overall, our study shows that glacial snow and ice microbial communities are highly variable on a seasonal basis.
Comparative Analysis of the Microbial Community Structures Between Healthy and Anthracnose-Infected Strawberry Rhizosphere Soils Using Illumina Sequencing Technology in Yunnan Province, Southwest of China
Authors: Su Daifa , Chen Shanyan , Zhou Wenxing , Yang Junyu , Luo Zhiwei , Zhang Zhenrong , Tian Yunxia , Dong Qionge , Shen Xuemei , Wei Shijie , Tong Jiangyun , Cui Xiaolong
Published: May 2022

Anthracnose caused by Colletotrichum spp. was widespread in recent years and resulted in great damage to strawberry production. Soil microbial communities were key contributors to host nutrition, development, and immunity; however, the difference between the microbial communities of healthy and anthracnose-infected strawberry rhizosphere soils remains unclear. In this study, the Illumina sequencing technique was used to comparatively study the prokaryotic and fungal community compositions and structures between healthy and anthracnose-infected strawberry rhizosphere soils in Yuxi, Yunnan Province. Both microbial community diversities and richness of anthracnose-infected strawberry rhizosphere soils were higher than those of healthy strawberry rhizosphere soils. A total of 2,518 prokaryotic and 556 fungal operational taxonomic units (OTUs) were obtained at the 97% similarity threshold. Proteobacteria, Thaumarchaeota, and Acidobacteria were the dominant prokaryotic phyla; Ascomycota, unclassified_k__Fungi, and Mortierellomycota were the dominant fungal phyla. The relative abundances of beneficial bacterial phyla Actinobacteria and Firmicutes, genera Streptomyces, Azospirillum, and Bacillus were significantly reduced in anthracnose-infected strawberry rhizosphere soils; the relative abundance of beneficial fungal species Trichoderma asperellum shows a similar tendency with bacterial abundance. Besides Colletotrichum, 15 other potential fungal pathogen genera and seven fungal pathogen species were identified; among the potential pathogen genera and species, eight pathogen genera and Fusarium oxysporum showed significant differences between healthy and anthracnose-infected strawberry rhizosphere soils. The results suggested that strawberry planted in this area may be infected by other fungal pathogens except for Colletotrichum spp. Our present research will provide theoretical basis and data reference for the isolation and identification of strawberry pathogens and potential probiotics in future works.
Mechanistic Analysis of the VirA Sensor Kinase in Agrobacterium tumefaciens Using Structural Models
Authors: Swackhammer Addison , Provencher Edward A. P. , Donkor Akua K. , Garofalo Jessica , Dowling Sinead , Garchitorena Kathleen , Phyo Ahkar , Ramírez Veliz Nicky , Karen Matthew , Kwon Annie , Diep Rich , Norris Michael , Safo Martin K. , Pierce B. Daniel
Published: May 2022

Agrobacterium tumefaciens pathogenesis of plants is initiated with signal reception and culminates with transforming the genomic DNA of its host. The histidine sensor kinase VirA receives and reacts to discrete signaling molecules for the full induction of the genes necessary for this process. Though many of the components of this process have been identified, the precise mechanism of how VirA coordinates the response to host signals, namely phenols and sugars, is unknown. Recent advances of molecular modeling have allowed us to test structure/function predictions and contextualize previous experiments with VirA. In particular, the deep mind software AlphaFold has generated a structural model for the entire protein, allowing us to construct a model that addresses the mechanism of VirA signal reception. Here, we deepen our analysis of the region of VirA that is critical for phenol reception, model and probe potential phenol-binding sites of VirA, and refine its mechanism to strengthen our understanding of A. tumefaciens signal perception.
Implication of miR-122, miR-483, and miR-335 Expression Levels as Potential Signatures in HCV-Related Hepatocellular Carcinoma (HCC) in Egyptian Patients
Authors: Elfert Ashraf Y. , Salem Amel , Abdelhamid Amr M. , Salama Ahmad , Sourour Doaa A. , Shaker Olfat , Keshk Mofida
Published: May 2022

Hepatocellular carcinoma (HCC) is the second most common cause of cancer-related deaths worldwide with chronic hepatitis C virus (HCV) infection as a major risk factor of HCC. Circulating microRNAs are deregulated in HCC and are candidate biomarkers. The aim of this study was to explore the expression profile of miRNA-122, miR-483, and miR-335 in the serum of HCV-related hepatocellular carcinoma (HCC). 90 HCV-related hepatocellular carcinoma (HCC) patients, 90 non-malignant HCV patients, and 60 healthy controls were included. Serum microRNAs were measured by a qRT-PCR custom array. The expression levels of miR-122 and miR-483 were upregulated in HCC patients, while the miR-335 expression level was downregulated versus controls and HCV groups. Receiver-operating characteristic (ROC) curve analysis was created to examine miRNAs. miR-483 presented the best diagnostic potential because it showed the highest diagnostic accuracy for distinguishing HCV-related HCC patients from controls (AUC = 0.98) with 100% sensitivity. Moreover, there was obvious prognostic power in distinguishing HCV from HCC (AUC = 0.95) with 88% sensitivity. In conclusion, studied microRNAs (miR-122, miR-483, and miR-335) could serve as potential non-invasive early diagnostic biomarkers for HCC, and we identified a panel of three serum microRNAs with high accuracy in HCC diagnosis. Additional studies are required to confirm this panel and test its prognostic significance.
A Prospective Study on the Relationship Between Driving and Non-occupational Computer Use With Risk of Dementia
Authors: Takeuchi Hikaru , Kawashima Ryuta
Published: May 2022

Sedentary behaviors have been associated with the risk of dementia in older adults. Whether driving and computer use are associated with the risk of dementia in older adults is an important research question. The participants of a longitudinal cohort study that included European middle- and old-aged adults at the baseline (2006–2010) who had not been diagnosed with dementia before 5 years after the baseline and had not died within 5 years after the baseline were followed up (until 2018) and analyzed. The associations between driving and non-occupational computer use time measured by the questionnaire at the baseline and incident dementia 5 years after the baseline were analyzed after correcting for confounding variables. Each analysis included approximately 370,000 participants and 1,000 cases. According to Cox proportional hazard models that divide subjects into four groups of habit duration levels [(a) 0 h; (b) less than 1 h, 1 h; (c), 2 h, 3 h; (d) 4 h or more, per/day)], the group with 0 h < driving time ≤1 h at the baseline exhibited a significantly lower risk of incident dementia than the other groups. In addition, in the analysis of non-occupational computer use duration, the 0 h group exhibited a significantly higher risk than the other groups. Our results indicate that different sedentary behaviors have different associations with dementia risk over time and have no simple dose–response relationship with dementia risk. The sedentary behavior risk assessments must consider these factors.
Characterization of Mild and Moderate Dysarthria in Parkinson’s Disease: Behavioral Measures and Neural Correlates
Authors: Steurer Hanna , Schalling Ellika , Franzén Erika , Albrecht Franziska
Published: May 2022

Purpose

Alterations in speech and voice are among the most common symptoms in Parkinson’s disease (PD), often resulting in motor speech disorders such as hypokinetic dysarthria. We investigated dysarthria, verbal fluency, executive functions, and global cognitive function in relation to structural and resting-state brain changes in people with PD.

Methods

Participants with mild-moderate PD (n = 83) were recruited within a randomized controlled trial and divided into groups with varying degrees of dysarthria: no dysarthria (noDPD), mild dysarthria (mildDPD), moderate dysarthria (modDPD), and also combined mildDPD and modDPD into one group (totDPD). Voice sound level and dysphonia, verbal fluency, motor symptoms, executive functions, disease severity, global cognition, and neuroimaging were compared between groups. Gray matter volume and intensity of spontaneous brain activity were analyzed. Additionally, regressions between behavioral and neuroimaging data were performed.

Results

The groups differed significantly in mean voice sound level, dysphonia, and motor symptom severity. Comparing different severity levels of dysarthria to noDPD, groups differed focally in resting-state activity, but not in brain structure. In totDPD, lower scores on semantic verbal fluency, a composite score of executive functions, and global cognition correlated with lower superior temporal gyrus volume.

Conclusion

This study shows that severity of dysarthria may be related to underlying structural and resting-state brain alterations in PD as well as behavioral changes. Further, the superior temporal gyrus may play an important role in executive functions, language, and global cognition in people with PD and dysarthria.
Sentence Comprehension in Primary Progressive Aphasia: A Study of the Application of the Brazilian Version of the Test for the Reception of Grammar (TROG2-Br)
Authors: Carthery-Goulart Maria Teresa , de Oliveira Rosimeire , de Almeida Isabel Junqueira , Campanha Aline , da Silva Souza Dayse , Zana Yossi , Caramelli Paulo , Machado Thais Helena
Published: May 2022

Sentence-comprehension deficits have been described in patients with primary progressive aphasia (PPA). However, most instruments to address this domain in more detail and in a clinical context have not been adapted and translated into several languages, posing limitations to clinical practice and cross-language research.

Objectives

The study aimed to (1) test the applicability of the Brazilian version of the Test for Reception of Grammar (TROG2-Br) to detect morphosyntactic deficits in patients with PPA; (2) investigate the association between performance in the test and sociodemographic and clinical variables (age, years of formal education, and disease duration); (3) characterize the performance of individuals presenting with the three more common variants of PPA (non-fluent, semantic, and logopenic) and mixed PPA (PPA-Mx) and analyze whether TROG-2 may assist in the distinction of these clinical profiles.

Methods

A total of 74 cognitively healthy participants and 34 individuals diagnosed with PPA were assessed with TROG2-Br. Overall scores (correct items, passed blocks), types, and categories of errors were analyzed.

Results

In controls, block scores were significantly correlated with years of formal education (Spearman'sr= 0.33,p= 004) but not with age. In PPA, age, education, and disease duration were not significantly associated with performance in the test. Controls presented a significantly higher performance on TROG2-Br compared to PPA individuals and their errors pattern pointed to mild general cognitive processing difficulties (attention, working memory). PPA error types pointed to processing and morphosyntactic deficits in nonfluent or agrammatic PPA, (PPA-NF/A), logopenic PPA (PPA-L), and PPA-Mx. The semantic PPA (PPA-S) subgroup was qualitatively more similar to controls (processing difficulties and lower percentage of morphosyntactic errors). TROG2-Br presented good internal consistency and concurrent validity.

Discussion

Our results corroborate findings with TROG-2 in other populations. The performance of typical older adults with heterogeneous levels of education is discussed along with recommendations for clinical use of the test and future directions of research.
Comparison of the Results of a Parkinson's Holter Monitor With Patient Diaries, in Real Conditions of Use: A Sub-analysis of the MoMoPa-EC Clinical Trial
Authors: Pérez-López Carlos , Hernández-Vara Jorge , Caballol Nuria , Bayes Àngels , Buongiorno Mariateresa , Lopez-Ariztegui Núria , Gironell Alexandre , López-Sánchez José , Martínez-Castrillo Juan Carlos , Sauco M Alvarez , López-Manzanares Lydia , Escalante-Arroyo Sonia , Pérez-Martínez David A. , Rodríguez-Molinero Alejandro ,   The MoMoPa-EC Research Group
Published: May 2022

Background

For specialists in charge of Parkinson's disease (PD), one of the most time-consuming tasks of the consultations is the assessment of symptoms and motor fluctuations. This task is complex and is usually based on the information provided by the patients themselves, which in most cases is complex and biased. In recent times, different tools have appeared on the market that allow automatic ambulatory monitoring. The MoMoPa-EC clinical trial (NCT04176302) investigates the effect of one of these tools—Sense4Care's STAT-ON—can have on routine clinical practice. In this sub-analysis the agreement between the Hauser diaries and the STAT-ON sensor is analyzed.

Methods

Eighty four patients from MoMoPa-EC cohort were included in this sub-analysis. The intraclass correlation coefficient was calculated between the patient diary entries and the sensor data.

Results

The intraclass correlation coefficient of both methods was 0.57 (95% CI: 0.3–0.73) for the OFF time (%), 0.48 (95% CI: 0.17–0.68) for the time in ON (%), and 0.65 (95% CI%: 0.44–0.78) for the time with dyskinesias (%). Furthermore, the Spearman correlations with the UPDRS scale have been analyzed for different parameters of the two methods. The maximum correlation found was −0.63 (p< 0.001) between Mean Fluidity (one of the variables offered by the STAT-dON) and factor 1 of the UPDRS.

Conclusion

This sub-analysis shows a moderate concordance between the two tools, it is clearly appreciated that the correlation between the different UPDRS indices is better with the STAT-ON than with the Hauser diary.

Trial Registration

https://clinicaltrials.gov/show/NCT04176302(NCT04176302).
Temporal Patterning of Neurofilament Light as a Blood-Based Biomarker for Stroke: A Systematic Review and Meta-Analysis
Authors: Sanchez Jasmin D. , Martirosian Richard A. , Mun Katherine T. , Chong Davis S. , Llorente Irene Lorenzo , Uphaus Timo , Gröschel Klaus , Wölfer Teresa A. , Tiedt Steffen , Hinman Jason D. ,   the DEMDAS Study Group
Published: May 2022

Damage to axons is a core feature of ischemic stroke and cerebrovascular disease. The burden of axonal injury is correlated with the acute clinical deficits, the underlying burden of ischemic brain injury, the prognosis of recovery, and may be a meaningful therapeutic target for brain repair. Neurofilament light chain (NfL) has been identified as a blood-based biomarker that reflects neuroaxonal damage resulting from stroke. However, the utility of NfL as a blood-based biomarker in stroke is confounded by studies examining different temporal windows and patient populations. We conducted a systematic review and meta-analysis to verify the utility of blood NfL as a diagnostic, prognostic, and monitoring stroke biomarker. Nineteen studies reporting serum/plasma NfL values for a total of 4,237 distinct patients with stroke were identified. Using available summary data from the 10 studies that employed a common immunoassay platform, we utilized random effects linear mixed modeling and weighted averages to create a phasic model of serum/plasma NfL values in distinct time periods of acute stroke. Weighted averages show that blood NfL levels vary significantly across three distinct temporal epochs of acute (0–7 days), subacute (9–90 days), and chronic (>90 days) stroke with a steep peak in the early subacute period between 14 and 21 days after stroke. Blood NfL values can function as a diagnostic biomarker in distinguishing acute ischemic stroke from transient ischemic attack as well as amongst other cerebrovascular subtypes. Release of NfL into the bloodstream after stroke follows a distinct temporal dynamic that lags several weeks behind stroke onset and reliably associates with a stroke diagnosis despite some variability based on stroke subtype and severity. Identification of these temporal dynamics and the contribution of co- existent cerebrovascular disease states can improve the value of NfL as a stroke biomarker.