bluuebunny/crossref_metadata_2025 huggingface dataset:
Positive correlation between lipid accumulation product index and arterial stiffness in Chinese patients with type 2 diabetes
Authors: Mao Jing , Gan Shenglian , Zhou Quan , Yu Fang , Zhou Haifeng , Lu Huilin , Jin Jing , Liu Qin , Deng Zhiming
Published: November 2023

Background

Many studies have confirmed that lipid accumulation products (LAP) predict arterial stiffness (AS) in hypertensive patients. But there is little research on the use of LAP in identifying early atherosclerosis in patients with type 2 diabetes mellitus (T2DM). The aim of this study was to determine the relationship between the LAP index and brachial-ankle pulse wave velocity (baPWV) in Chinese patients with T2DM.

Methods

A total of 1471 Chinese participants with T2DM, ranging in age from 18 to 80, were included in this cross-sectional study. BaPWV measurements were used to calculate the AS. A baPWV greater than the 75th percentile (1700 cm/s) was defined as indicating increased AS. The LAP index was calculated from the combination of waist circumference (WC) and triglycerides (TG).

Results

According to the quartiles of the LAP index, baPWV tended to increase after adjusting for sex and age. Multiple linear regression analysis showed that the beta coefficient (β) of baPWV increased by 31.0 cm/s for each unit of lnLAP that was increased, and the 95% confidence interval (CI) was (6.5, 55.5) cm/s. In multivariate logistic regression analyses, after fully adjusting for confounders, the risk of elevated baPWV increased with each unit increase in lnLAP, with an odds ratio (OR) of 1.3 (95% CI: 1.0, 1.8). According to the generalized additive model (GAM), we found that lnLAP was positively correlated with baPWV and baPWV elevation. The results were the same for males and females. Subgroup analyses showed that the positive correlation between lnLAP and elevated baPWV did not interact across all subgroups.

Conclusions

In Chinese patients with T2DM, LAP was strongly and positively correlated with baPWV and elevated baPWV.
Optimal scheduling of pumped storage hydropower plants with multi-type of units in day-ahead electricity market considering water head effects
Authors: Cao Minjian , Hu Zechun , Cai Jilin
Published: November 2023

Pumped-storage hydropower plant (PSHP) is a type of valuable energy storage system and a flexible resource to the modern power system with increasing renewable energy integration. As independent market participants, a PSHP can participate in both the energy market and frequency regulation market to maximize its revenue and contribution to the secure and economic operation of the power system. In some PSHPs, both fixed-speed and variable-speed units are installed to improve the flexibility, especially when operating in the pumping mode. However, it’s difficult to deal with the nonlinear relationships among power, flow, and water head in pumping and generating modes. This paper proposes iterative solution methods for scheduling the PSHP by considering the relationship between power and flow at different water heads for different types of units. The scheduling problem is established as a scenario-based optimization formulation by considering PSHP’s participation in both the energy market and frequency regulation market. In each iteration, the optimal dispatch model is formulated as a Mixed Integer Linear Programming (MILP) problem. Case studies are performed and simulation results validate the effectiveness of the model and the iterative solution methods.
Putative roles of terpenoids in primitive membranes
Authors: King Joshua P. , Wang Anna
Published: November 2023

For the continuation and evolution of life, primitive membranes formed from prebiotically available components must have fulfilled certain essential requirements. Candidate amphiphiles, such as straight-chain fatty acids, that can self-assemble into cell-like structures have been shown to be capable of performing many life-like functions. However, obstacles that preclude a cohesive description of the evolution of modern-day cells from the origins of primitive membranes remain. Terpenoids are uniquely placed in terms of their derivation and chemical motifs to play an important role in primitive membranes, as they do in extant cells. Here, we discuss the principles behind primitive membrane formation and offer a biophysics perspective regarding the potential role of terpenoids in membrane function. By doing so, we identify opportunities in the realm of protocell research.
De novo assembly and comparative analysis of the mitochondrial genome of Reynoutria japonica
Authors: Chen Jianhui , Ma Hongping , Fan Haili , Lin Fan , Chai Tuanyao , Wang Hong
Published: November 2023

Reynoutria japonica Houtt. is an important medical plant with a long history of thousands of years in China, however, its mitochondrial genome (mitogenome) has not been reported yet. In this work, we reported and analyzed the R. japonica mitogenome. The main results include: The R. japonica mitogenome was 302,229 bp in length and encoded 48 genes, including 27 protein-coding genes (PCGs), 3 rRNA genes, and 18 tRNA genes. Repeat sequence analysis revealed that there were 54 repeat sequences ranging from 193 bp to 1,983 bp in the R. japonica mitogenome. Relative synonymous codon usage (RSCU) analysis showed that leucine (900, 11.01%) and serine (732, 8.96%) were the two most abundant amino acids, and the codons with RSCU values showed the preference of A or T ending when greater than 1. The RNA editing sites of PCGs in the R. japonica mitogenome were characterized, and 299 RNA editing sites were found. Extensive sequences transfer between mitochondrion and chloroplast were found in R. japonica, where 11 complete plastid-derived tRNA genes stayed intact in the R. japonica mitogenome. Three genes (ccmFC, cox1, and nad1) were seen to play essential roles in the evolution through selection pressure analysis. The phylogenetic analysis showed that Fallopia multiflora was the closest species with R. japonica, in consistency with the results of chloroplast genome. Overall, the current work presents the first mitogenome of R. japonica and could contribute to the phylogenetic analysis of the family Polygonaceae.
Second harmonic generation imaging of head and neck squamous cell carcinoma
Authors: Stocker Magdalena , Baumeister Philipp , Canis Martin , Vogel Martin , Gires Olivier
Published: November 2023

Head and neck squamous cell carcinomas (HNSCC) are a heterogenous group of tumors with a poor prognosis and treatments impairing the patients' quality of life. We assessed post-surgical human head and neck squamous cell carcinomas (HNSCC) and healthy tissue (n = 10 each) via HHG (higher harmonic generation) imaging to differentiate healthy from tumor tissue. Qualitative imaging analysis compared collagen fibrils detected via immunohistology and SHG (second harmonic generation). Quantitative analysis measured the forward to backward intensity ratio (fSHG/bSHG) of SHG images. Assessments of the tissue samples demonstrated a structural difference of collagen matrix organization from healthy to malignant tissue. Healthy tissue was characterized by a high f/b ratio, describing highly organized tissue, whereas a low f/b ratio was observed in malignant tissue, indicative of reduced organization. Properly distinguishing tumor from healthy tissue is crucial to a successful treatment and best possible outcome for the individual patient. SHG provides broad possibilities to analyze extracellular changes in diseased tissue, such as solid tumors and to distinguish tumor from healthy tissue.
In vitro analysis of anti-HPA-1a dependent platelet phagocytosis and its inhibition using a new whole blood phagocytosis assay (WHOPPA)
Authors: Ames Paula , Baal Nelli , Speckmann Martin , Michel Gabriela , Ratke Judith , Klesser Christina , Cooper Nina , Takahashi Daisuke , Bayat Behnaz , Bein Gregor , Santoso Sentot
Published: November 2023

Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is a serious bleeding condition mostly caused by the reaction between maternal anti-HPA-1a antibodies and fetal platelets. This reaction leads to Fc-dependent platelet phagocytosis. Although several serological methods have been developed to identify maternal antibodies, a reliable laboratory parameter as a prognostic tool for FNAIT severity is still lacking. In this study, we developed whole blood platelet phagocytosis assay (WHOPPA), a flow cytometry-based phagocytosis assay that uses a pH-sensitive fluorescent dye (pHrodo-SE) to analyze anti-HPA-1a-dependent platelet phagocytosis in whole blood. WHOPPA revealed a high phagocytosis rate for the anti-HPA-1a opsonized platelets by monocytes but not by neutrophils. Analysis of different monocyte populations showed that all monocyte subsets, including classical (CD14++CD16−), intermediate (CD14++CD16+), and nonclassical (CD14+CD16++) monocytes, were able to engulf opsonized platelets. A unique monocyte subset, termed shifted monocytes (CD14+CD16−), showed the highest phagocytosis rate and was detected after platelet engulfment. FcγR inhibition tests revealed that except for FcγRIIa, FcγRI and FcγRIII on monocytes were responsible for the phagocytosis of anti-HPA-1a opsonized platelets. Analysis of anti-HPA-1a antibodies from FNAIT cases (n = 7) showed the phagocytosis of HPA-1aa but not of HPA-1bb platelets by monocytes. The phagocytosis rate was highly correlated with bound antibodies measured by flow cytometry (p < 0001; r = 0.9214) and MAIPA assay (p < 0.001; r = 0.7692). The phagocytosis rates were equal for type I and II anti-HPA-1a antibodies recognizing the plexin–semaphoring–integrin (PSI) domain and PSI/epidermal growth factor 1 domain of β3 integrin, respectively. By contrast, type III anti-HPA-1a antibodies reacting with αvβ3 integrin did not induce platelet phagocytosis. Furthermore, effector-silenced mAbs against HPA-1a inhibited the phagocytosis of anti-HPA-1a opsonized platelets. In conclusion, WHOPPA is a reliable in vitro platelet phagocytosis assay that mimics the phagocytosis of anti-HPA-1a opsonized platelets in whole blood. This assay allows to prove platelet phagocytosis ex vivo and evaluate the inhibitory capacity of different inhibitors as therapeutically strategies for the prevention of fetal thrombocytopenia in FNAIT in the future.
Intragraft regulatory T cells in the modern era: what can high-dimensional methods tell us about pathways to allograft acceptance?
Authors: Bei Ke Fan , Moshkelgosha Sajad , Liu Bo Jie , Juvet Stephen
Published: November 2023

Replacement of diseased organs with transplanted healthy donor ones remains the best and often only treatment option for end-stage organ disease. Immunosuppressants have decreased the incidence of acute rejection, but long-term survival remains limited. The broad action of current immunosuppressive drugs results in global immune impairment, increasing the risk of cancer and infections. Hence, achievement of allograft tolerance, in which graft function is maintained in the absence of global immunosuppression, has long been the aim of transplant clinicians and scientists. Regulatory T cells (Treg) are a specialized subset of immune cells that control a diverse array of immune responses, can prevent allograft rejection in animals, and have recently been explored in early phase clinical trials as an adoptive cellular therapy in transplant recipients. It has been established that allograft residency by Tregs can promote graft acceptance, but whether intragraft Treg functional diversification and spatial organization contribute to this process is largely unknown. In this review, we will explore what is known regarding the properties of intragraft Tregs during allograft acceptance and rejection. We will summarize recent advances in understanding Treg tissue residency through spatial, transcriptomic and high-dimensional cytometric methods in both animal and human studies. Our discussion will explore properties of intragraft Tregs in mediating operational tolerance to commonly transplanted solid organs. Finally, given recent developments in Treg cellular therapy, we will review emerging knowledge of whether and how these adoptively transferred cells enter allografts in humans. An understanding of the properties of intragraft Tregs will help lay the foundation for future therapies that will promote immune tolerance.
T cells specific to multiple Bet v 1 peptides are highly cross-reactive toward the corresponding peptides from the homologous group of tree pollens
Authors: Lund Gitte , Christensen Lars Harder , Ihlemann Jacob , Andersen Peter Sejer , Wambre Erik , Würtzen Peter Adler , Gupta Shashank
Published: November 2023

Background

Allergens from Fagales trees frequently cause spring allergy in Europe, North America, and some parts of Asia. The definition of the birch homologous group, which includes birch (Bet v), oak (Que a), alder (Aln g), hazel (Cor a), hornbeam (Car b), beech (Fag s), and chestnut (Cas s), is based on high allergen sequence identity and extensive IgE cross-reactivity. Clinical effect was seen during the alder/hazel, birch, and oak pollen seasons after treatment with tree SLIT-tablets containing only birch allergen extract. Here, we characterize T-cell reactivity with respect to epitope specificities and cross-reactivity toward various Bet v 1 family members, (PR-10/group 1 major allergens). This cross-reactivity may be part of the immunological basis of clinical effect or cross-protection when exposed to birch homologous tree species.

Method

T-cell lines were generated from 29 birch-allergic individuals through stimulation of peripheral blood mononuclear cells (PBMCs) with birch/Bet v or oak/Que a allergen extracts. T-cell responses to allergen extracts, purified group 1 allergens, and overlapping 20-mer peptides (Bet v 1, Aln g 1, Cor a 1, and Que a 1) were investigated by T-cell proliferation and cytokine production. Cross-reactivity was evaluated based on Pearson’s correlations of response strength and further investigated by flow cytometry using tetramer staining for homologous peptide pairs.

Results

T-cell reactivity toward extracts and group 1 allergens from across the birch homologous group was observed for birch/Bet v as well as oak/Que a T-cell lines. T-cell lines responded to multiple Bet v 1 homologous peptides from Aln g 1 and Cor a 1 and a subset of Que a 1 peptides. Significant Pearson’s correlations between frequently recognized peptides derived from Bet v 1 and the corresponding peptides derived from alder, hazel, and oak strongly supported the T-cell cross-reactivity toward these allergens. Cross-reactivity between birch and birch homologous peptides was confirmed by pMHCII tetramer staining.

Conclusion

T cells from birch tree pollen allergic individuals respond to multiple trees within the birch homologous group in accordance with the level of sequence homology between Bet v 1 family members, (PR-10 allergens) from these allergen sources, confirming the basis for clinical cross-protection.
Neutrophil extracellular traps in upper respiratory tract secretions: insights into infectious and allergic rhinitis
Authors: Zawrotniak Marcin , Juszczak Magdalena , Mosio-Wójcik Justyna , Rapala-Kozik Maria
Published: November 2023

Introduction

Neutrophil extracellular traps (NETs) are structures released by neutrophils in response to various infections. NETs have a biocidal role and have been demonstrated to be effective against bacteria, fungi, viruses, and parasites. Depending on the situation, NETs can protect the host from pathogen invasion or contribute to the development of autoimmune diseases such as cystic fibrosis and rheumatoid arthritis. In this study, we aimed to investigate the occurrence of NET as one of the components in upper respiratory tract secretions in infectious and allergic diseases.

Methods

Nasal mucus was collected from donors diagnosed with infectious rhinitis or allergic rhinitis. The extracellular DNA content was determined using SytoxGreen staining, and the total protein pool was determined using the microBCA method. Micrococcal nuclease was used to digest the samples and ELISA was employed to identify the NET proteins. The enzymatic activity of elastase was determined.

Results

Our findings showed that nasal mucus collected from patients with infectious rhinosinusitis contained extracellular DNA that could come from a variety of sources, responsible for increasing the density and viscosity of secretions, as well as NETs proteins. The identified enzymatic activity of NET elastase indicates the possible irritation of nasal tissues. However, the DNA content was not identified in the samples from allergic patients. In addition, we have shown in preliminary studies that therapy using N-acetylcysteine can liquefy nasal secretions.

Discussion

The study suggests that the composition of nasal mucus varies according to the cause of mucosal irritation. The presence of DNA and NET proteins can have severe consequences for the therapeutic process prolonging treatment. The low viscosity of nasal mucus in allergic patients facilitates mucosal flushing and the removal of allergens. Understanding the occurrence and role of NETs in various respiratory diseases is critical for developing effective treatment strategies that consider the complex interaction between the immune system and pathogens. The results of this study suggest that NETs may be present in upper respiratory tract secretions with an infectious background, supporting basic defense mechanisms using eosinophils and EETs. Further research is needed to explore the potential of NETs as a therapeutic target in respiratory diseases.
Has the shortage of fludarabine altered the current paradigm of lymphodepletion in favor of bendamustine?
Authors: Filioglou Dimitrios , Husnain Muhammad , Khurana Sharad , Simpson Richard J. , Katsanis Emmanuel
Published: November 2023

The most common lymphodepletion regimen used prior to infusion of chimeric antigen receptor-T cells (CAR-T) is cyclophosphamide (CY) in combination with fludarabine (Flu) (CY-FLU). While cyclophosphamide (CY) possesses lymphotoxic effects, it concurrently preserves regulatory T cell activity, potentially affecting the efficacy of CAR-T cells. Moreover, the use of fludarabine (FLU) has been linked to neurotoxicity, which could complicate the early detection of immune effector cell-associated neurotoxicity syndrome (ICANS) observed in CAR-T cell therapy. Given the ongoing shortage of FLU, alternative lymphodepleting agents have become necessary. To date, only a limited number of studies have directly compared different lymphodepleting regimens, and most of these comparisons have been retrospective in nature. Herein, we review the current literature on lymphodepletion preceding CAR-T cell therapies for lymphoid hematologic malignancies, with a specific focus on the use of bendamustine (BEN). Recent evidence suggests that administering BEN before CAR-T cell infusion yields comparable efficacy, possibly with a more favorable toxicity profile when compared to CY-FLU. This warrants further investigation through randomized prospective studies.
Comparison of case and control groups in terms of postoperative complications, outcomes, and survival in total hip arthroplasty patients with and without COVID-19
Authors: Cinar Fadime , Bulbuloglu Semra
Published: November 2023

Introduction

Total hip aarthroplasty (THA) is not performed worldwide as an emergency surgical procedure and has often been postponed during the COVID-19 pandemic. The hypothesis of this study was that COVID-19 caused the extra burden and mortality of THA patients. This study aimed to investigate the problems caused by comorbid COVID-19 in addition to the current clinical status in patients who had undergone THA.

Materials and methods

A case–control group study was conducted with the participation of patients with COVID-19 and without COVID-19 who had undergone THA and were hospitalized in an orthopedic clinic and intensive care unit at a research and training hospital. IBM Statistical Package for Social Sciences 25.0 was used for data analysis.

Results

A total of 291 patients who had undergone THA were included in the study: 161 patients with COVID-19 constituted the control group and 130 patients without COVID-19 constituted the case group. In this study, the authors found that THA patients with COVID-19 had higher rates of nausea, vomiting, diarrhea, musculo-articular pain, and headache compared to those without COVID-19, and the difference was statistically significant (p < 0.01); 17.7% of the patients with COVID-19 died, and delirium developed in 35.4%. The difference between the case and the control groups was statistically significant in terms of delirium and death (p < 0.01).

Discussion

COVID-19 increases the risk of delirium and death in THA patients, as well as extending the hospital stay. The fact that the pandemic is not over yet and that despite vaccination, COVID-19 continues to have its devastating effects experienced, especially by individuals in their advanced age.
Clinical and laboratory characteristics of children with sickle cell disease on hydroxyurea treated with artemether-lumefantrine for acute uncomplicated malaria
Authors: Segbefia Catherine , Amponsah Seth Kwabena , Afrane Adwoa K. A. , Nyarko Mame Yaa , Brew Yvonne , Salifu Nihad , Ahorhorlu Samuel Yao , Sulley Abdul Malik , Hviid Lars , Ofori Michael Fokuo , Adjei George Obeng
Published: November 2023

Introduction

Limited information exists on any interactions between hydroxyurea (HU) and antimalarials in sickle cell disease (SCD). We evaluated changes in clinical and laboratory parameters among children with SCD on HU therapy treated with artemether-lumefantrine (AL) for acute uncomplicated malaria (UM).

Methods

A prospective, non-randomized, pilot study of 127 children with SCD (23, UM; 104, steady state) were recruited from three hospitals in Accra. UM participants were treated with standard doses of AL and followed up, on days 1, 2, 3, 7, 14, and 28. Venous blood was collected at baseline and follow-up days in participants with UM for determination of malaria parasitaemia, full blood count, reticulocytes, and clinical chemistry. Further, Plasmodium falciparum identification of rapid diagnostic test (RDT) positive samples was done using nested polymerase chain reaction (PCR).

Results

Among SCD participants with UM, admission temperature, neutrophils, alanine-aminotransferase, gamma-glutamyl-transferase, and haemoglobin significantly differed between HU recipients (HU+) and steady state, while white blood cell, neutrophils, reticulocytes, bilirubin, urea, and temperature differed significantly between non-HU recipients (no-HU), and steady state. Mean parasitaemia (HU+, 2930.3 vs. no-HU, 1,060, p = 0.74) and adverse events (HU+, 13.9% vs. no-HU, 14.3%), were comparable (p = 0.94). Day 28 reticulocyte count was higher in the HU+ (0.24) (0.17 to 0.37) vs. no-HU, [0.15 (0.09 to 0.27), p = 0.022]. Significant differences in lymphocyte [HU+ 2.74 95% CI (−5.38 to 58.57) vs. no-HU −0.34 (−3.19 to 4.44), p = 0.024]; bilirubin [HU+, −4.44 (−16.36 to 20.74) vs. no-HU −18.37 (−108.79 to −7.16)]; and alanine aminotransferase, [HU+, −4.00 (−48.55 to 6.00) vs. no-HU, 7.00 (−22.00 to 22.00)] were observed during follow up.

Conclusion

Parasite clearance and adverse event occurrence were comparable between SCD children treated with AL irrespective of HU status. However, distinct patterns of changes in laboratory indices suggest the need for larger, more focused studies.
Comparative analysis of simulated in-situ colonization and degradation by Lentinula edodes on oak wafer and corn stalk
Authors: Mou Chunye , Gong Yuhua , Chen Lianfu , Martin Francis , Kang Heng , Bian Yinbing
Published: November 2023

Introduction

The depolymerization of lignocellulose biomass by white-rot fungi has been an important research topic. However, few simulated in-situ analyses have been conducted to uncover the decay.

Methods

In this study, the white-rot Lentinula edodes was used to colonize the wood and non-wood substrates, and then hyphal transcriptional response and substrate degradation were analyzed during the spatial-temporal colonization on different type substrates to better understand the depolymerization of lignocellulose.

Results and discussion

Faster growth and thicker mat of hyphae on corn stalk were observed in comparison to oak wafer. Coincide with the higher levels of gene transcripts related to protein synthesis on corn stalk. The higher lignin oxidase activity of hyphae was detected on oak wafer, and the higher cellulase activity was observed on corn stalk containing a much higher content of soluble sugars. A large number of carbohydrate-binding module (CBM1 and CBM20)-containing enzyme genes, including lytic polysaccharide monooxygenase (AA9), cellobiohydrolase (GH6 and GH7), glucanase (GH5), xylanase (GH10 and GH11), glucoamylase (GH15), and alpha-amylase (GH13), were significantly upregulated in the back-distal hyphae colonized on corn stalk. The hyphae tended to colonize and degrade the secondary cell wall, and the deposited oxalate crystal suggested that oxalate may play an important role during lignocellulose degradation. In addition, lignin was degraded in priority in oak wafer. Of note, three lignin monomers were degraded simultaneously in oak wafer but sequentially in corn stalk. This growth Our results indicated that the white-rot degradation pattern of lignocellulose is determined by the chemical composition and structure of the colonized biomass.
Superior efficacy of combination antibiotic therapy versus monotherapy in a mouse model of Lyme disease
Authors: Alruwaili Yasir , Jacobs Mary B. , Hasenkampf Nicole R. , Tardo Amanda C. , McDaniel Celine E. , Embers Monica E.
Published: November 2023

Lyme disease (LD) results from the most prevalent tick-borne infection in North America, with over 476,000 estimated cases annually. The disease is caused by Borrelia burgdorferi (Bb) sensu lato which transmits through the bite of Ixodid ticks. Most cases treated soon after infection are resolved by a short course of oral antibiotics. However, 10–20% of patients experience chronic symptoms because of delayed or incomplete treatment, a condition called Post-Treatment Lyme Disease (PTLD). Some Bb persists in PTLD patients after the initial course of antibiotics and an effective treatment to eradicate the persistent Bb is needed. Other organisms that cause persistent infections, such as M. tuberculosis, are cleared using a combination of therapies rather than monotherapy. A group of Food and Drug Administration (FDA)-approved drugs previously shown to be efficacious against Bb in vitro were used in monotherapy or in combination in mice infected with Bb. Different methods of detection were used to assess the efficacy of the treatments in the infected mice including culture, xenodiagnosis, and molecular techniques. None of the monotherapies eradicated persistent Bb. However, 4 dual combinations (doxycycline + ceftriaxone, dapsone + rifampicin, dapsone + clofazimine, doxycycline + cefotaxime) and 3 triple combinations (doxycycline + ceftriaxone+ carbomycin, doxycycline + cefotaxime+ loratadine, dapsone+ rifampicin+ clofazimine) eradicated persistent Bb infections. These results suggest that combination therapy should be investigated in preclinical studies for treating human Lyme disease.
Molecular detection reveals diverse tick-borne bacterial and protozoan pathogens in two tick species from Yingshan County of Hubei Province, China in 2021–2022
Authors: Zhao Na , Pan Kai , Teng Zhongqiu , Wang Hongliang , Zhang Xue , Ren Hongyu , Yi Lei , He Jia , Cai Kun , Qin Tian
Published: November 2023

In this study, a total of 179 ticks infesting ruminant livestock, including 166 Haemaphysalis longicornis ticks and 13 Rhipicephalus microplus ticks were collected from Yingshan county of Hubei province, China in 2021–2022. PCR testing and sequence analysis revealed that the ticks infected with various species of pathogens including Rickettsia (R. japonica), Anaplasma (A. bovis, A. ovis, A. platys, and Ca. A. boleense), Ehrlichia (E. minasensis and Ehrlichia sp.), Theileria (T. orientalis and T. luwenshuni), and Babesia (B. bigemina). The infection rates of these pathogens were 0.56, 16.76, 7.26, 2.79 and 0.56%. respectively, while only 3 of 13 R. microplus ticks were detected to be infected wth Ehrlichia sp., A. bove., or T. luwenshuni. Our results revealed that a variety of tick-borne pathogens highly carried by these ticks, specially Ha. longicornis. Therefore, it is necessary to make effective control of the ticks and the tick-borne diseases in the County.
Biochemical and genetic studies define the functions of methylthiotransferases in methanogenic and methanotrophic archaea
Authors: Boswinkle Kaleb , Dinh Thuc-Anh , Allen Kylie D.
Published: November 2023

Methylthiotransferases (MTTases) are radical S-adenosylmethionine (SAM) enzymes that catalyze the addition of a methylthio (-SCH3) group to an unreactive carbon center. These enzymes are responsible for the production of 2-methylthioadenosine (ms2A) derivatives found at position A37 of select tRNAs in all domains of life. Additionally, some bacteria contain the RimO MTTase that catalyzes the methylthiolation of the S12 ribosomal protein. Although the functions of MTTases in bacteria and eukaryotes have been established via detailed genetic and biochemical studies, MTTases from the archaeal domain of life are understudied and the substrate specificity determinants of MTTases remain unclear. Here, we report the in vitro enzymatic activities of an MTTase (C4B56_06395) from a thermophilic Ca. Methanophagales anaerobic methanotroph (ANME) as well as the MTTase from a hyperthermophilic methanogen – MJ0867 from Methanocaldococcus jannaschii. Both enzymes catalyze the methylthiolation of N6-threonylcarbamoyladenosine (t6A) and N6-hydroxynorvalylcarbamoyladenosine (hn6A) residues to produce 2-methylthio-N6-threonylcarbamoyladenosine (ms2t6A) and 2-methylthio-N6-hydroxynorvalylcarbamoyladenosine (ms2hn6A), respectively. To further assess the function of archaeal MTTases, we analyzed select tRNA modifications in a model methanogen – Methanosarcina acetivorans – and generated a deletion of the MTTase-encoding gene (MA1153). We found that M. acetivorans produces ms2hn6A in exponential phase of growth, but does not produce ms2t6A in detectable amounts. Upon deletion of MA1153, the ms2A modification was absent, thus confirming the function of MtaB-family MTTases in generating ms2hn6A modified nucleosides in select tRNAs.
Immunoinformatics and reverse vaccinology approach in designing a novel highly immunogenic multivalent peptide-based vaccine against the human monkeypox virus
Authors: Choudhury Abhigyan , Chandra Anshuman , Dawoud Turki M. , Nafidi Hiba-Allah , Singh Nagendra , Bourhia Mohammed
Published: November 2023

Background: Monkeypox is a highly infectious zoonotic disease, often resulting in complications ranging from respiratory illnesses to vision loss. The escalating global incidence of its cases demands prompt attention, as the absence of a proven post-exposure treatment underscores the criticality of developing an effective vaccine.

Methods: Interactions of the viral proteins with TLR2 and TLR4 were investigated to assess their immunogenic potentials. Highly immunogenic proteins were selected and subjected to epitope mapping for identifying B-cell and MHC class I and II epitopes. Epitopes with high antigenicity were chosen, considering global population coverage. A multi-target, multi-epitope vaccine peptide was designed, incorporating a beta-defensin 2 adjuvant, B-cell epitopes, and MHC class I and II epitopes.

Results: The coordinate structure of the engineered vaccine was modeled and validated. In addition, its physicochemical properties, antigenicity, allergenicity, and virulence traits were evaluated. Molecular docking studies indicated strong interactions between the vaccine peptide and the TLR2 receptor. Furthermore, molecular dynamics simulations and immune simulation studies reflected its potent cytosolic stability and robust immune response dynamics induced by the vaccine.

Conclusion: This study explored an innovative structure-guided approach in the use of immunoinformatics and reverse vaccinology in pursuit of a novel multi-epitope vaccine against the highly immunogenic monkeypox viral proteins. The simulation studies indicated the engineered vaccine candidate to be promising in providing prophylaxis to the monkeypox virus; nevertheless, further in vitro and in vivo investigations are required to prove its efficacy.
Hemoglobin to red cell distribution width ratio as a prognostic marker for ischemic stroke after mechanical thrombectomy
Authors: Feng Xianrong , Zhang Yaodan , Li Qizheng , Wang Baojia , Shen Jie
Published: November 2023

Background

The hemoglobin to red cell distribution width ratio (HRR) has been experimentally associated with the prognosis of acute ischemic stroke (AIS). However, its relationship with mechanical thrombectomy (MT) for AIS remains unclear. Therefore, this study aimed to investigate the relationship between HRR at admission, follow-up HRR, and clinical outcomes in patients undergoing MT.

Methods

Acute ischemic stroke patients undergoing MT were consecutively enrolled from January 2017 to December 2022. Demographic, clinical, and laboratory information were collected. HRR was measured by dividing hemoglobin (Hb) by red cell distribution width (RDW) at admission and after 24 h of MT. Clinical outcomes after 3 months were evaluated using the modified Rankin Scale (mRS). The primary outcome was poor prognosis (mRS > 2) at 3 months, while the secondary outcome was death within 3 months.

Results

A total of 310 patients were analyzed, of whom 216 patients (69.7%) had poor prognosis, and 92 patients (29.6%) died. Patients with a poor prognosis and death had significantly lower HRR levels at admission and after 24 h. HRR at admission was not associated with clinical outcomes according to multivariable logistic regression analysis. However, HRR after 24 h was significantly associated with poor prognosis (adjusted odds ratio [OR]: 0.646, 95% confidence interval [CI]: 0.520–0.803, p < 0.001) and death (adjusted OR: 0.615, 95% CI: 0.508–0.744, p < 0.001). Receiver-operating characteristic curve analysis demonstrated the predictive ability of HRR after 24 h, with areas under the curves of 0.790 for poor prognosis and 0.771 for death.

Conclusion

Rapidly measurable HRR levels are an independent marker of outcome after MT in AIS patients. This may provide a reliable auxiliary outcome measure for clinical routine and interventional therapy.
Larger deep white matter hyperintensity volume correlates with more severe social behavioral changes in patients with subacute ischemic stroke
Authors: Qu Jian-Feng , Hu Hui-Hong , Liu Jian-Fei , Zhou Yue-Qiong , Cheng Wei-Yang , Shi Lin , Luo Yi-Shan , Zhao Lei , Chen Yang-Kun
Published: November 2023

Background

Changes in social behavior can occur after ischemic stroke. We aimed to investigate the potential correlations between neuroimaging variables and changes in social behavior in patients who experienced subacute ischemic stroke.

Methods

We prospectively screened patients with first-ever ischemic stroke. Three months after the index stroke, changes in patients’ social behavior were investigated by the Frontal Behavioral Inventory (FBI), which consists of both deficit and positive groups of behaviors. The protocol of brain magnetic resonance imaging (MRI) including the baseline MRI at the acute stage and additional MRI with three-dimensional T1-weighted imaging on follow-up. Using these MRI scans, we assessed the acute infarction and the volumes of various brain structures by an automatic volumetry tool.

Results

Eighty patients were enrolled. In univariate analyses, patients with deficit behavioral changes had more left cortical infarction (r = 0.271, p = 0.015), Cholinergic Pathways Hyperintensities Scale scores (r = 0.227, p = 0.042), DWMH volumes (r = 0.349, p = 0.001), and modified Rankin Scale (mRS) scores (r = 0.392, p < 0.001). Patients with positive behavioral changes had more frequency of men (r = 0.229, p = 0.041) and a history of hypertension (r = 0.245, p = 0.028). In multiple stepwise linear regression models, after adjusting for age, deep WMH volumes (β = 0.849, 95% confidence interval = 0.352–1.346, p = 0.001) and mRS scores on follow-up (β = 1.821, 95% confidence interval = 0.881–2.76, p < 0.001) were significantly correlated with deficit behavioral changes (R2 = 0.245).

Conclusion

Larger deep WMH volumes and poorer mRS scores on follow-up were significantly correlated with deficit behavioral changes in patients with subacute ischemic stroke.
Automated pipeline for nerve fiber selection and g-ratio calculation in optical microscopy: exploring staining protocol variations
Authors: Thomson Bart R. , Martin Louise Françoise , Schmidle Paul L. , Schlierbach Hannah , Schänzer Anne , Richter Henning
Published: November 2023

G-ratio is crucial for understanding the nervous system’s health and function as it measures the relative myelin thickness around an axon. However, manual measurement is biased and variable, emphasizing the need for an automated and standardized technique. Although deep learning holds promise, current implementations lack clinical relevance and generalizability. This study aimed to develop an automated pipeline for selecting nerve fibers and calculating relevant g-ratio using quality parameters in optical microscopy. Histological sections from the sciatic nerves of 16 female mice were prepared and stained with either p-phenylenediamine (PPD) or toluidine blue (TB). A custom UNet model was trained on a mix of both types of staining to segment the sections based on 7,694 manually delineated nerve fibers. Post-processing excluded non-relevant nerves. Axon diameter, myelin thickness, and g-ratio were computed from the segmentation results and its reliability was assessed using the intraclass correlation coefficient (ICC). Validation was performed on adjacent cuts of the same nerve. Then, morphometrical analyses of both staining techniques were performed. High agreement with the ground truth was shown by the model, with dice scores of 0.86 (axon) and 0.80 (myelin) and pixel-wise accuracy of 0.98 (axon) and 0.94 (myelin). Good inter-device reliability was observed with ICC at 0.87 (g-ratio) and 0.83 (myelin thickness), and an excellent ICC of 0.99 for axon diameter. Although axon diameter significantly differed from the ground truth (p = 0.006), g-ratio (p = 0.098) and myelin thickness (p = 0.877) showed no significant differences. No statistical differences in morphological parameters (g-ratio, myelin thickness, and axon diameter) were found in adjacent cuts of the same nerve (ANOVA p-values: 0.34, 0.34, and 0.39, respectively). Comparing all animals, staining techniques yielded significant differences in mean g-ratio (PPD: 0.48 ± 0.04, TB: 0.50 ± 0.04), myelin thickness (PPD: 0.83 ± 0.28 μm, TB: 0.60 ± 0.20 μm), and axon diameter (PPD: 1.80 ± 0.63 μm, TB: 1.78 ± 0.63 μm). The proposed pipeline automatically selects relevant nerve fibers for g-ratio calculation in optical microscopy. This provides a reliable measurement method and serves as a potential pre-selection approach for large datasets in the context of healthy tissue. It remains to be demonstrated whether this method is applicable to measure g-ratio related with neurological disorders by comparing healthy and pathological tissue. Additionally, our findings emphasize the need for careful interpretation of inter-staining morphological parameters.
Correlation between temporal muscle thickness and grip strength in hemiplegic patients with acute stroke
Authors: Park Jisoo , Park Jihye , Kim Soye , Kim Dong Chan
Published: November 2023

Recently, temporal muscle thickness (TMT) has been investigated as a novel surrogate marker for muscle mass and function in neurologic patients. This study aimed to assess the correlation of TMT with grip strength to establish a new parameter for predicting pre-stroke sarcopenia. A total of 358 patients who were newly diagnosed with acute ischemic stroke at our institution between November 2021 and August 2022 were enrolled. Eighty-four patients met the eligibility criteria. The mean TMT was measured within initial brain MRI using previously described methods. Pearson's correlation analyses assessed the relationship between grip strength and TMT. Multiple logistic regression analyses were performed to identify associations between TMT and other associated factors including grip strength, sarcopenia risk, body mass index, age, Charlson Comorbidity Index and Geriatric nutrition risk index. Mean TMT values indicated a strong correlation with the grip strength of the non-hemiplegic hand in both male and female patients. Multiple logistic regression analyses showed that TMT was associated with grip strength and sarcopenia risk in hemiplegic patients. Measuring TMT using cranial MR images during the initial stages of stroke could help predict a patient's pre-stroke muscle strength status. Further studies are required to apply TMT in pre-stroke sarcopenia diagnosis.
Multi-classifier fusion based on belief-value for the diagnosis of autism spectrum disorder
Authors: Zhao Feng , Ye Shixin , Zhang Mingli , Lv Ke , Qiao Xiaoyan , Li Yuan , Mao Ning , Ren Yande , Zhang Meiying
Published: November 2023

Introduction

Autism Spectrum Disorder (ASD) has a significant impact on the health of patients, and early diagnosis and treatment are essential to improve their quality of life. Machine learning methods, including multi-classifier fusion, have been widely used for disease diagnosis and prediction with remarkable results. However, current multi-classifier fusion methods lack the ability to measure the belief level of different samples and effectively fuse them jointly.

Methods

To address these issues, a multi-classifier fusion classification framework based on belief-value for ASD diagnosis is proposed in this paper. The belief-value measures the belief level of different samples based on distance information (the output distance of the classifier) and local density information (the weight of the nearest neighbor samples on the test samples), which is more representative than using a single type of information. Then, the complementary relationships between belief-values are captured via a multilayer perceptron (MLP) network for effective fusion of belief-values.

Results

The experimental results demonstrate that the proposed classification framework achieves better performance than a single classifier and confirm that the fusion method used can effectively fuse complementary relationships to achieve accurate diagnosis.

Discussion

Furthermore, the effectiveness of our method has only been validated in the diagnosis of ASD. For future work, we plan to extend this method to the diagnosis of other neuropsychiatric disorders.
A mini-review of the evidence for cerebrovascular changes following gender-affirming hormone replacement therapy and a call for increased focus on cerebrovascular transgender health
Authors: Wright Melissa Emily , Murphy Kevin
Published: November 2023

Gender-affirming hormone replacement therapy (gaHRT) is an important step for many in the gender diverse community, associated with increased quality-of-life and lower self-reported scores of depression and anxiety. However, considering the interactions that the involved sex hormones have on vasculature (with oestrogen and testosterone demonstrating vasodilatory and vasoconstricting properties, respectively), it is important for transgender healthcare research to examine how the manipulation of these hormones interact with cerebrovascular structure and functioning. There is a stark lack of research in this area. This mini-review outlines the research suggesting a vascular impact of these sex hormones using evidence from a range of cohorts (e.g., menopause, polycystic ovary syndrome) and discusses the work that has been done into cerebrovascular changes following gaHRT. Finally, recommendations for future research into cerebrovascular health in transgender cohorts following gaHRT are outlined.
Activation of the spinal and brainstem locomotor networks during free treadmill stepping in rats lacking dopamine transporter
Authors: Veshchitskii Aleksandr , Shkorbatova Polina , Mikhalkin Aleksandr , Fesenko Zoja , Efimova Evgeniya V. , Gainetdinov Raul R. , Merkulyeva Natalia
Published: November 2023

Dopamine is extremely important for the multiple functions of the brain and spinal cord including locomotor behavior. Extracellular dopamine levels are controlled by the membrane dopamine transporter (DAT), and animals lacking DAT (DAT-KO) are characterized by hyperdopaminergia and several alterations of locomotion including hyperactivity. Neuronal mechanisms of such altered locomotor behavior are still not fully understood. We believe that in hyperdopaminergic animals both the spinal and brain neuronal networks involved in locomotion are modified. Using the c-fos technique, we studied activated neuronal networks of the spinal cord and two brainstem structures related to locomotor control and being under the strong dopaminergic influence, the cuneiform nucleus (CnF) and ventrolateral periaqueductal gray (VLPAG), in wild-type (DAT-WT) and DAT-KO rats. In the spinal cord, most c-fos-positive cells were located in the dorsal laminae II-IV and in the central gray matter (laminae V-VI). No differences were revealed for the central areas. As for the dorsal areas, in the DAT-WT group, labeled cells mostly occupied the lateral region, whereas, in the DAT-KO group, c-fos-positive cells were observed in both medial and lateral regions in some animals or in the medial regions in some animals. In the brainstem of the DAT-WT group, approximately the same number of labeled cells were found in the CnF and VLPAG, but in the DAT-KO group, the VLPAG contained a significantly smaller number of c-fos-positive cells compared to the CnF. Thereby, our work indicates an imbalance in the sensorimotor networks located within the dorsal horns of the spinal cord as well as a disbalance in the activity of brainstem networks in the DAT-deficient animals.
Milk fat globule membrane promotes brain development in piglets by enhancing the connection of white matter fiber trace
Authors: Zhang Yingqian , Zhao Bangcheng , Man-Yau Szeto Ignatius , Pan Zhixiang , Gao Lijuan , Li Qinxi , Tang Cheng , Wang Yu , Tang Xun , Zhao Zifu , Hao Jingyu , Duan Sufang , Yan Yalu , Li Ting , Zhong Zhihui
Published: November 2023

Introduction

Brain development during infancy is crucial for later health and development. Although Milk Fat Globule Membrane (MFGM) has been demonstrated to enhance brain development, further investigation is needed to determine the optimal dose.

Methods

In this study, 80 piglets aged 2 days were randomly assigned to four groups: Control group, MFGM-L (1.74 g MFGM per 100 g diet), MFGM-M (4.64 g MFGM per 100 g diet), and MFGM-H (6.09 g MFGM per 100 g diet). Daily body weight and milk intake of the piglets were recorded until 31 days postnatal. Learning and memory abilities were evaluated using the spatial T-maze test on day 15. MRI analysis was conducted to assess functional and structural changes in brain tissues. Additionally, mRNA and protein expression of brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NTF-3) in the hippocampus and prefrontal cortex were evaluated.

Results

The results indicated that the MFGM supplemented diet significantly improved the accuracy of the piglets in the T-maze test, with the MFGM-L group exhibiting the best performance. MRI showed no volumetric differences in the gray and white matter between the groups. However, the fractional anisotropy in the left and right hippocampus of piglets in the MFGM-L group was significantly higher than in the other three groups. Furthermore, there was a strong correlation between the accuracy of the T-maze test and hippocampal fractional anisotropy.

Discussion

The MFGM supplemented diet also increased the expression of BDNF in the cerebral cortex. However, the changes in BDNF were not consistent with the results of the T-maze test. In conclusion, adding 1.74 g MFGM per 100 g diet can significantly improve neonatal piglets’ learning and memory abilities, potentially by enhancing the connection of white matter fiber bundles in the brain.