bluuebunny/crossref_metadata_2025 huggingface dataset:
Decolonizing global health curriculum: from fad to foundation
Authors: Kalbarczyk Anna , Perkins Sylvie , Robinson Sabreena N. , Ahmed Mahnoor K.
Published: August 2023

Introduction

Increasing calls have been made to decolonize global health education but there has been a lack of consensus and clarity on how this should be done. We conducted a qualitative study to understand current educational programs and curricula that aim to educate public health and allied health students to increase awareness of how colonialist structures of power influence current global health practice and provide students with tools to decolonize global health. Our goal is to inform related curriculum development and provide recommendations.

Methods

We conducted key-informant interviews with 14 study coordinators and faculty from institutions of higher learning with global health programs who are involved in developing educational approaches. All interviews were audio recorded, transcribed, and analyzed using an ‘up from the data’ approach.

Results

Participants varied in their understanding of decolonizing global health and recognized that there is a lack of guidance in the field; this has an impact on how curriculum is developed and taught. Participants described a range of decolonizing global health educational activities in the classrooms and in applied learning activities. Most programming was situated in Diversity, Equity, and Inclusion Initiatives and participants did not always feel this was the best ‘home’ for such work; to some this reflected a lack of institutional support. Other institutional barriers included lack of protected time for faculty and limited budgets for speaker honoraria, co-creation, and related teaching expenses.

Discussion

Institutes of higher learning can play an important role, either positively or negatively, in decolonizing global health education. At a minimum such institutions should financially support faculty to incorporate decolonizing global health in their pedagogy and strengthen scholarship towards common understandings. More substantive institutional support is needed however to meaningfully transform institutional relationships that actively support equitable partnerships, co-creation, and responsiveness to local community priorities.
Pre-hospital delays among patients with acute coronary syndrome in the Russian Federation: a multicentre prospective observational cohort study (the AMIR Study)
Authors: Bates Katie , Schirmer Henrik , Kontsevaya Anna , Bobrova Natalia , Leon David A. , McKee Martin
Published: August 2023

Objective

This study aimed to describe total pre-hospital delays (symptom onset to admission), patient delays (symptom onset to calling for help), and transport delays (calling for help to admission) experienced by patients with acute coronary syndrome (ACS) in Russia and identify factors associated with longer delays.

Methods

A prospective observational cohort study of ACS patients with myocardial infarction recruited in hospitals providing percutaneous coronary intervention (PCI) and those that do not (non-PCI) in 13 regions and at multiple levels of the health system in Russia. Data were collected on pre-hospital delays between symptom onset and admission to the hospital providing definitive treatment, divided into patient delay (time between symptom onset and calling for help) and transport delay (time between calling for help and admission).

Results

Of 902 patients, 701 (77.7%) had full data on pre-hospital delays. The median total pre-hospital delay in our study was 5.1 h, the median patient delay was 1.5 h, and the median transport delay was 2.1 h. Patient delays did not differ by age and sex, although having an ST-elevation myocardial infarction (STEMI) and certain symptom presentations, including severe pain, reduced delays. Transport delays were markedly reduced in those transported by emergency medical services (EMS) and taken directly to the hospital of definitive treatment (rather than to one closer but unable to offer PCI).

Although transport delays were reduced in those using EMS, just half of the patients using EMS had a transport delay of <2 h (first medical contact to admission). Among all patients taken directly to the hospital by EMS, 70% were STEMI patients. Of these STEMI patients, 78% had a transport delay of 2 h or more. Among these patients, only 16.0% received thrombolysis in the ambulance. As expected, regional differences were apparent with all types of delay, with the greatest variation found in transport delays.

Conclusion

Delays are currently longer than the European Society of Cardiology guidelines for STEMI patients and other severe cases. Reducing patient delays will reduce overall delays. Transport delays are inevitable in many regions of Russia, but better triage of patients, increased use of EMS, and early thrombolysis in EMS, particularly for STEMI patients facing excessive transport delays, will reduce delays and buy time before PCI.
The role of GABAB receptors in the subcortical pathways of the mammalian auditory system
Authors: Tureček Rostislav , Melichar Adolf , Králíková Michaela , Hrušková Bohdana
Published: August 2023

GABAB receptors are G-protein coupled receptors for the inhibitory neurotransmitter GABA. Functional GABAB receptors are formed as heteromers of GABAB1 and GABAB2 subunits, which further associate with various regulatory and signaling proteins to provide receptor complexes with distinct pharmacological and physiological properties. GABAB receptors are widely distributed in nervous tissue, where they are involved in a number of processes and in turn are subject to a number of regulatory mechanisms. In this review, we summarize current knowledge of the cellular distribution and function of the receptors in the inner ear and auditory pathway of the mammalian brainstem and midbrain. The findings suggest that in these regions, GABAB receptors are involved in processes essential for proper auditory function, such as cochlear amplifier modulation, regulation of spontaneous activity, binaural and temporal information processing, and predictive coding. Since impaired GABAergic inhibition has been found to be associated with various forms of hearing loss, GABAB dysfunction could also play a role in some pathologies of the auditory system.
Matrix scaffolds for endometrium-derived organoid models
Authors: De Vriendt Silke , Casares Celia Mesias , Rocha Susana , Vankelecom Hugo
Published: August 2023

The uterus-lining endometrium is essential to mammalian reproduction, receiving and accommodating the embryo for proper development. Despite its key role, mechanisms underlying endometrial biology (menstrual cycling, embryo interaction) and disease are not well understood. Its hidden location in the womb, and thereby-associated lack of suitable research models, contribute to this knowledge gap. Recently, 3D organoid models have been developed from both healthy and diseased endometrium. These organoids closely recapitulate the tissue’s epithelium phenotype and (patho)biology, including in vitro reproduction of the menstrual cycle. Typically, organoids are grown in a scaffold made of surrogate tissue extracellular matrix (ECM), with mouse tumor basement membrane extracts being the most commonly used. However, important limitations apply including their lack of standardization and xeno-derivation which strongly hinder clinical translation. Therefore, researchers are actively seeking better alternatives including fully defined matrices for faithful and efficient growth of organoids. Here, we summarize the state-of-the-art regarding matrix scaffolds to grow endometrium-derived organoids as well as more advanced organoid-based 3D models. We discuss remaining shortcomings and challenges to advance endometrial organoids toward defined and standardized tools for applications in basic research and translational/clinical fields.
H syndrome treated with Tocilizumab: two case reports and literature review
Authors: Jacquot Robin , Jouret Maurine , Valentin Mathieu Gerfaud , Richard Maël , Jamilloux Yvan , Rousset Florent , Emile Jean-François , Haroche Julien , Steinmüller Lars , Zekre Franck , Phan Alice , Belot Alexandre , Seve Pascal
Published: August 2023

H syndrome is a rare autosomal recessive genetic disorder characterized by the following clinical features: cutaneous hyperpigmentation, hypertrichosis, hepatosplenomegaly, heart anomalies, hearing loss, hypogonadism, short stature, hallux valgus, hyperglycemia, fixed flexion contractures of the toe joints, and the proximal interphalangeal joints. In rare cases, autoinflammatory and lymphoproliferative manifestations have also been reported. This disorder is due to loss-of-function mutations in SLC29A3 gene, which encode the equilibrative nucleoside transporter ENT3. This deficiency leads to abnormal function and proliferation of histiocytes. H syndrome is part of the R-group of histiocytosis. We report two different cases, one was diagnosed in adulthood and the other in childhood. The first case reported is a 37-year-old woman suffering from H syndrome with an autoinflammatory systemic disease that begins in adulthood (fever and diffuse organ’s infiltration) and with cutaneous, articular, auditory, and endocrinological manifestations since childhood. The second case reported is a 2-year-old girl with autoinflammatory, endocrine, and cutaneous symptoms (fever, lymphadenopathy, organomegaly, growth delay, and cutaneous hyperpigmentation). Homozygous mutations in SLC29A3 confirmed the diagnosis of H syndrome in both cases. Each patient was treated with Tocilizumab with a significant improvement for lymphoproliferative, autoinflammatory, and cutaneous manifestations. Both cases were reported to show the multiple characteristics of this rare syndrome, which can be diagnosed either in childhood or in adulthood. In addition, an overview of the literature suggested Tocilizumab efficiency.
The Janus face of proliferating plasmablasts in dengue and COVID-19 infections
Authors: Nayak Priya , Mukund Kavitha , Subramaniam Shankar
Published: August 2023

Introduction

B cells play an integral role in the immune response to both dengue fever and COVID-19. Prior scRNAseq analyses of peripheral plasmablasts in COVID-19 have revealed a heterogeneous population with distinct cell subsets associated with proliferation; prior studies in patients with dengue fever have likewise shown the presence of proliferative pre-plasmablasts in the circulation. These findings may have implications for disease severity. In this study, we sought to gain a mechanistic understanding of the intracellular processes in naive and memory B cells that are associated with and may lead to an expanded proliferative plasmablast population in the circulation.

Methods

We analyzed age-controlled (pediatric and adult), peripheral blood mononuclear cell scRNAseq datasets from patients infected with either dengue (primary or secondary) or COVID-19 (non-severe or severe) from previously published studies. Our preliminary analysis showed that pediatric patients with dengue and adults with COVID-19 had an expanded proliferative plasmablast (p-PB) population. By contrast, neither the adults with dengue nor the children with COVID-19 in our dataset had p-PBs. We used this distinctive preliminary signature to guide our analyses design and expanded our analyses to naive and memory B cells.

Results

In age/disease conditions with and without p-PBs, we found differences in cell sensing and activation, including via the B cell receptor and downstream signal transduction. Likewise, inflammation was mediated differently: relative to groups without p-PBs, those with p-PBs had increased expression of interferon response and S100 genes (particularly severe COVID-19). Furthermore, several transcription factors at the nexus of activation, inflammation, and cell fate decisions were expressed differently in groups with and without p-PBs.

Discussion

We used dengue and COVID-19 infections in adult and pediatric patients (focusing on naive B, memory B, and plasmablast cells) as a model to better understand the mechanisms that may give rise to p-PB populations in the circulation. Our results indicate that a more pro-inflammatory state in naive and memory B cells correlated with - and could influence the generation of- proliferating plasmablasts. Further exploration of these mechanisms will have implications for immune memory, vaccine development, and post-viral autoimmune syndromes.
Four types of adenine-related RNA modification writers -mediated molecular subtypes contribute to predicting clinical outcomes and treatment options in bladder cancer
Authors: Zhang Yao , Chen Ying , Wen Wen
Published: August 2023

Rationale

RNA modifications, containing m6A, m1A, alternative polyadenylation and adenosine-to-inosine RNA editing, involve in critical cancerous immunity and cancerous processes. However, the functional roles of RNA modification writers in bladder cancer (BLCA) are largely unknown.

Methods

In this study, unsupervised clustering was used to identify novel RNA modification writers -mediated molecular subtypes in BLCA. A corresponding quantitative indicator called WriterScore was developed using univariate Cox and Least absolute shrinkage and selection operator (LASSO) analysis. Then, we systematically analyzed the correlation between RNA modification writer-related clusters (WriterScore) and immunological characteristics, classical molecular subtypes, clinicopathologic features and treatment options in BLCA. Finally, we validated the WriterScore in multiple other external BLCA datasets, clinical sample dataset in Shengjing Hospital and pancancer.

Results

Two RNA modification writer-related clusters and three DEGclusters were obtained. These RNA modification writer-related clusters (WriterScore) were strongly associated with immunological characteristics, classical molecular subtypes, clinicopathologic features of BLCA. Moreover, WriterScore can properly predict the clinical outcomes and immunotherapy of BLCA patients.

Conclusion

Our study systematically investigated the role of RNA modification writers and developed a significant WriterScore to guide several treatment options in BLCA, which might bring some potential benefits for BLCA patients.
Acute murine cytomegalovirus infection boosts cell-type specific response and lipid metabolism changes in the liver of infant mice
Authors: Gao Juanzi , Wang Anmin , Bu Xiangyi , Jia Weidong
Published: August 2023

Introduction

Human cytomegalovirus (HCMV) infection in infants can lead to severe diseases, including neonatal hepatitis. The single-cell dimensional changes in immune cells after the initial CMV infection remain elusive, as do the effects of CMV infection on hepatic lipid metabolism.

Methods

We employed single-cell RNA-sequencing to investigate the changes in liver cell types and immune responses in infant mice following murine CMV (MCMV) infection. Additionally, we examined alterations in protein expression profiles related to lipid metabolism in hepatocytes and the role of the key transcription factor PPAR-γ in hepatocytes during CMV infection.

Results

Our study revealed that MCMV infects most liver cell types in infant mice, leading to an increase in the proportion of proliferating CD8 effector T cells and a subset of Nos2+ monocytes, potentially playing an essential role in early anti-viral responses. Furthermore, MCMV infection resulted in altered protein expression of lipid metabolism in hepatocytes. Knocking down the transcription factor PPAR-γ in hepatocytes effectively inhibited CMV infection.

Discussion

Our findings underscore the immune system's response to early-stage MCMV infection and the subsequent impact on hepatic lipid metabolism in infant mice. This research provides new insights into the mechanisms of CMV infection and could pave the way for novel therapeutic strategies.
Bridging the gaps to overcome major hurdles in the development of next-generation tuberculosis vaccines
Authors: Kim Hongmin , Choi Han-Gyu , Shin Sung Jae
Published: August 2023

Although tuberculosis (TB) remains one of the leading causes of death from an infectious disease worldwide, the development of vaccines more effective than bacille Calmette-Guérin (BCG), the only licensed TB vaccine, has progressed slowly even in the context of the tremendous global impact of TB. Most vaccine candidates have been developed to strongly induce interferon-γ (IFN-γ)-producing T-helper type 1 (Th1) cell responses; however, accumulating evidence has suggested that other immune factors are required for optimal protection against Mycobacterium tuberculosis (Mtb) infection. In this review, we briefly describe the five hurdles that must be overcome to develop more effective TB vaccines, including those with various purposes and tested in recent promising clinical trials. In addition, we discuss the current knowledge gaps between preclinical experiments and clinical studies regarding peripheral versus tissue-specific immune responses, different underlying conditions of individuals, and newly emerging immune correlates of protection. Moreover, we propose how recently discovered TB risk or susceptibility factors can be better utilized as novel biomarkers for the evaluation of vaccine-induced protection to suggest more practical ways to develop advanced TB vaccines. Vaccines are the most effective tools for reducing mortality and morbidity from infectious diseases, and more advanced technologies and a greater understanding of host-pathogen interactions will provide feasibility and rationale for novel vaccine design and development.
Activation and pro-inflammatory cytokine production by unswitched memory B cells during SARS-CoV-2 infection
Authors: Castleman Moriah J. , Santos Adriana Luna , Lesteberg Kelsey E. , Maloney James P. , Janssen William J. , Mould Kara J. , Beckham J. David , Pelanda Roberta , Torres Raul M.
Published: August 2023

Memory B cells are comprised of unswitched (CD27+IgD+) and switched (CD27+IgD-) subsets. The origin and function of unswitched human memory B cells are debated in the literature, whereas switched memory B cells are primed to respond to recurrent infection. Unswitched memory B cells have been described to be reduced in frequency with severe SARS-CoV2 infection and here we characterize their activation status, BCR functionality, and contribution to virally-induced cytokine production. Analyses of whole blood from healthy individuals, people immunized against SARS-CoV2, and those who have had mild and severe SARS-CoV2 infection, confirm a reduction in the frequency of unswitched memory B cells during severe SARS-CoV2 infection and demonstrate this reduction is associated with increased levels of systemic TNFα. We further document how severe viral infection is associated with an increased frequency of ‘IgD+’ only memory B cells that correlate with increased IgG autoantibody levels. Unswitched and switched memory B cells from severe SARS-CoV2 infection displayed evidence of heightened activation with a concomitant reduction in the expression of the inhibitory receptor CD72. Functionally, both populations of memory B cells from severe SARS-COV2 infection harbored a signaling-competent BCR that displayed enhanced BCR signaling activity in the unswitched population. Finally, we demonstrate that B cells from mild SARS-CoV2 infection are poised to secrete pro-inflammatory cytokines IL-6 and TNFα. Importantly, unswitched memory B cells were a major producer of IL-6 and switched memory B cells were a major producer of TNFα in response to viral TLR ligands. Together these data indicate that B cells contribute to the inflammatory milieu during viral infection.
Activation of thousands of genes in the lungs and kidneys by sepsis is countered by the selective nuclear blockade
Authors: Qiao Huan , Zienkiewicz Jozef , Liu Yan , Hawiger Jacek
Published: August 2023

The steady rise of sepsis globally has reached almost 49 million cases in 2017, and 11 million sepsis-related deaths. The genomic response to sepsis comprising multi-system stage of raging microbial inflammation has been reported in the whole blood, while effective treatment is lacking besides anti-microbial therapy and supportive measures. Here we show that, astoundingly, 6,237 significantly expressed genes in sepsis are increased or decreased in the lungs, the site of acute respiratory distress syndrome (ARDS). Moreover, 5,483 significantly expressed genes in sepsis are increased or decreased in the kidneys, the site of acute injury (AKI). This massive genomic response to polymicrobial sepsis is countered by the selective nuclear blockade with the cell-penetrating Nuclear Transport Checkpoint Inhibitor (NTCI). It controlled 3,735 sepsis-induced genes in the lungs and 1,951 sepsis-induced genes in the kidneys. The NTCI also reduced without antimicrobial therapy the bacterial dissemination: 18-fold in the blood, 11-fold in the lungs, and 9-fold in the spleen. This enhancement of bacterial clearance was not significant in the kidneys. Cumulatively, identification of the sepsis-responsive host’s genes and their control by the selective nuclear blockade advances a better understanding of the multi-system mechanism of sepsis. Moreover, it spurs much-needed new diagnostic, therapeutic, and preventive approaches.
Considerations for the clinical development of immuno-oncology agents in cancer
Authors: Pandiella Atanasio , Calvo Emiliano , Moreno Victor , Amir Eitan , Templeton Arnoud , Ocana Alberto
Published: August 2023

Targeting of the immune system has shown to be a successful therapeutic approach in cancer, with the development of check point inhibitors (ICI) or T-cell engagers (TCE). As immuno-oncology agents modulate the immune system to attack cancer cells and do not act directly on oncogenic vulnerabilities, specific characteristics of these compounds should be taken in consideration during clinical development. In this review we will discuss relevant concepts including limitations of preclinical models, special pharmacologic boundaries, clinical development strategies such as the selection of clinical indication, line of treatment and backbone partner, as well as the endpoints and expected magnitude of benefit required at different stages of the drug development. In addition, future directions for early and late trial designs will be reviewed. Examples from approved drugs or those currently in clinical development will be discussed and options to overcome these limitations will be provided.
Lipocalin 2 receptors: facts, fictions, and myths
Authors: Schröder Sarah K. , Gasterich Natalie , Weiskirchen Sabine , Weiskirchen Ralf
Published: August 2023

The human 25-kDa Lipocalin 2 (LCN2) was first identified and purified as a protein that in part is associated with gelatinase from neutrophils. This protein shows a high degree of sequence similarity with the deduced sequences of rat α2-microglobulin-related protein and the mouse protein 24p3. Based on its typical lipocalin fold, which consists of an eight-stranded, anti-parallel, symmetrical β-barrel fold structure it was initially thought that LCN2 is a circulating protein functioning as a transporter of small lipophilic molecules. However, studies in Lcn2 null mice have shown that LCN2 has bacteriostatic properties and plays a key role in innate immunity by sequestering bacterial iron siderophores. Numerous reports have further shown that LCN2 is involved in the control of cell differentiation, energy expenditure, cell death, chemotaxis, cell migration, and many other biological processes. In addition, important roles for LCN2 in health and disease have been identified in Lcn2 null mice and multiple molecular pathways required for regulation of Lcn2 expression have been identified. Nevertheless, although six putative receptors for LCN2 have been proposed, there is a fundamental lack in understanding of how these cell-surface receptors transmit and amplify LCN2 to the cell. In the present review we summarize the current knowledge on LCN2 receptors and discuss inconsistencies, misinterpretations and false assumptions in the understanding of these potential LCN2 receptors.
S1PR-1/5 modulator RP-101074 shows beneficial effects in a model of central nervous system degeneration
Authors: Sindi Mustafa , Hecker Christina , Issberner Andrea , Ruck Tobias , Meuth Sven G. , Albrecht Philipp , Dietrich Michael
Published: August 2023

Introduction

In multiple sclerosis (MS), chronic disability primarily stems from axonal and neuronal degeneration, a condition resistant to conventional immunosuppressive or immunomodulatory treatments. Recent research has indicated that selective sphingosine-1-phosphate receptor S1PR-1 and -5 modulators yield positive effects in progressive MS and mechanistic models of inflammation-driven neurodegeneration and demyelination.

Methods

In this study, the S1PR-1/-5 modulator RP-101074 was evaluated as a surrogate for ozanimod in the non-inflammatory, primary degenerative animal model of light-induced photoreceptor loss (LI-PRL) in CX3CR1-GFP mice to assess potential neuroprotective effects, independent of its immunomodulatory mechanism of action.

Results

Prophylactic administration of RP-101074 demonstrated protective effects in the preclinical, non-inflammatory LI-PRL animal model, following a bell-shaped dose-response curve. RP-101074 treatment also revealed activity-modulating effects on myeloid cells, specifically, CX3CR1+ cells, significantly reducing the marked infiltration occurring one week post-irradiation. Treatment with RP-101074 produced beneficial outcomes on both retinal layer thickness and visual function as evidenced by optical coherence tomography (OCT) and optomotor response (OMR) measurements, respectively. Additionally, the myelination status and the quantity of neural stem cells in the optic nerve suggest that RP-101074 may play a role in the activation and/or recruitment of neural stem cells and oligodendrocyte progenitor cells, respectively.

Conclusion/Discussion

The data from our study suggest that RP-101074 may have a broader role in MS treatment beyond immunomodulation, potentially offering a novel approach to mitigate neurodegeneration, a core contributor to chronic disability in MS.
450 million years in the making: mapping the evolutionary foundations of germinal centers
Authors: Matz Hanover , Dooley Helen
Published: August 2023

Germinal centers (GCs) are distinct microanatomical structures that form in the secondary lymphoid organs of endothermic vertebrates (i.e., mammals and some birds). Within GCs, B cells undergo a Darwinian selection process to identify clones which can respond to pathogen insult as well as affinity mature the B cell repertoire. The GC response ultimately generates memory B cells and bone marrow plasma cells which facilitate humoral immunological memory, the basis for successful vaccination programs. GCs have not been observed in the secondary lymphoid organs of ectothermic jawed vertebrates (i.e., fishes, reptiles, and amphibians). However, abundant research over the past decades has indicated these organisms can produce antigen specific B cell responses and some degree of affinity maturation. This review examines data demonstrating that the fundamentals of B cell selection may be more conserved across vertebrate phylogeny than previously anticipated. Further, research in both conventional mammalian model systems and comparative models raises the question of what evolutionary benefit GCs provide endotherms if they are seemingly unnecessary for generating the basic functional components of jawed vertebrate humoral adaptive immune responses.
Association between sexual function in women and sleep quality
Authors: Martínez Vázquez Sergio , Hernández Martínez Antonio , Peinado Molina Rocío Adriana , Martínez Galiano Juan Miguel
Published: August 2023

Objective

To determine the relationship between sexual dysfunction and sleep disorders.

Methods

Observational study was conducted in 2021 and 2022 including 975 Spanish women over 18 years of age. The Women’s Sexual Function Questionnaire (FSM-12) was used as a source of information, and the Pittsburgh Sleep Quality Index (PSQI) was used to assess sleep quality. A bivariate and multivariate analysis was performed using binary logistic regression, adjusting for confounding variables. Crude (OR) and adjusted (aOR) odds ratios were estimated with their respective 95% confidence intervals (CI).

Results

Around 29.2% (285) of the women presented some type of sexual dysfunction, and 73.4% (716) showed sleep disturbance with scores ≥5 on the PSQI scale. The mean score on the PSQI was 8.23 points (SD = 3.93). All the dimensions of the sexual function scale were statistically related to sleep disturbance (p  ≤ 0.05), except for sexual activity and the reasons for sexual activity not having penetration. In the multivariable analysis, women with sexual dysfunction presented an aOR of sleep disturbance of 1.88 (95% CI: 1.29–2.76) compared to women without dysfunction.

Conclusion

Global sexual dysfunction and almost all the dimensions that make up sexual function are related to changes in sleep quality.
High myopia control is comparable between multifocal rigid gas-permeable lenses and spectacles
Authors: Yu Li-hua , Zhuo Ran , Song Guan-xing , Lin Meng , Jin Wan-qing
Published: August 2023

Purpose

Ocular pathology may be reduced by slowing myopia progression. The purpose of this study was to evaluate the potential of a novel custom-designed rigid gas permeable (RGP) contact lens to control high myopia by comparing the efficacy of multifocal RGP lenses and single-vision spectacles for high myopia control.

Methods

The medical records of children fitted with spectacles or multifocal rigid gas-permeable lenses between January 2018 and May 2020 were retrospectively reviewed. Children (5–17 years) with non-cycloplegic spherical equivalent refraction of ≤ −6.00 D or spherical equivalent refraction > − 6.00 D with baseline axial length ≥ 26.5 mm, and astigmatism of ≥ −2.00 D were included. Axial length and refraction were measured at baseline, before fitting the participants with multifocal rigid gas-permeable lenses or spectacles, and at 1- and 2-year follow-up visits. Changes in axial length were compared between the groups.

Results

Among the 77 children with 1-year follow-up data, the mean axial elongation was 0.20 ± 0.17 mm and 0.21 ± 0.14 mm in the multifocal rigid gas-permeable and control groups, respectively, without significant differences between groups (F = 0.004, p = 0.835). Among the 41 patients who completed 2 years of follow-up, the mean axial elongation values in the multifocal rigid gas-permeable and control groups were 0.21 ± 0.15 mm and 0.24 ± 0.13 mm, respectively, at the 1-year follow-up, and 0.37 ± 0.27 mm and 0.43 ± 0.23 mm, respectively, at the 2-year follow-up, without significant between-group differences at either time point (p = 0.224).

Conclusion

Axial length increased at a similar rate in both the control (spectacles) and multifocal rigid gas-permeable lens groups, suggesting that multifocal rigid gas-permeable lenses have no significant impact on controlling high myopia progression compared with spectacles.
Interaction analysis of tobacco leaf microbial community structure and volatiles flavor compounds during cigar stacking fermentation
Authors: Wu Qiaoyin , Peng Zheng , Pan Yong , Liu Liping , Li Linlin , Zhang Juan , Wang Jian
Published: August 2023

Introduction

Cigar stacking fermentation is a key step in tobacco aroma enhancement and miscellaneous gas reduction, which both have a great influence on increasing cigar flavor and improving industrial availability.

Methods

To analyze the effect of cigar tobacco leaf (CTLs) microbial community on volatiles flavor compounds (VFCs), this study used multi-omics technology to reveal the changes in microbial community structure and VFCs of different cigar varieties during stacking fermentation, in addition to exploring the interaction mechanism of microbiome and VFCs.

Results

The results showed that the dominant microbial compositions of different CTL varieties during stacking fermentation were similar, which included Staphylococcus, Corynebacterium 1, Aerococcus, and Aspergillus. These dominant microbes mainly affected the microbial community structure and characteristic microorganisms of CTLs through microbial interactions, thereby influencing the transformation of VFCs. Characteristic microorganisms of different CTLs varieties such as Trichothecium, Trichosporon, Thioalkalicoccus and Jeotgalicoccus, were found to positively correlate with characteristic VFCs like megastigmatrienone 4, pyrazine, tetramethyl-, geranyl acetone, and 2-undecanone, 6,10-dimethyl-, respectively. This in turn affected the aroma and sensory quality of the CTLs.

Discussion

This study provides theoretical support for the analysis of the mechanism of microorganisms on VFCs and aroma, and development of microbial agents during cigar stacking fermentation.
HTLV-1 p12 modulates the levels of prion protein (PrPC) in CD4+ T cells
Authors: Silva De Castro Isabela , Granato Alessandra , Mariante Rafael Meyer , Lima Marco Antonio , Leite Ana Claudia Celestino , Espindola Otávio de Melo , Pise-Masison Cynthia A. , Franchini Genoveffa , Linden Rafael , Echevarria-Lima Juliana
Published: August 2023

Introduction

Infection with human T cell lymphotropic virus type 1 (HTLV-1) is endemic in Brazil and is linked with pro-inflammatory conditions including HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), a chronic neuroinflammatory incapacitating disease that culminates in loss of motor functions. The mechanisms underlying the onset and progression of HAM/TSP are incompletely understood. Previous studies have demonstrated that inflammation and infectious agents can affect the expression of cellular prion protein (PrPC) in immune cells.

Methods

Here, we investigated whether HTLV-1 infection affected PrPC content in cell lines and primary CD4+cells in vitro using flow cytometry and western blot assays.

Results

We found that HTLV-1 infection decreased the expression levels of PrPC and HTLV-1 Orf I encoded p12, an endoplasmic reticulum resident protein also known to affect post-transcriptionally cellular proteins such as MHC-class I and the IL-2 receptor. In addition, we observed a reduced percentage of CD4+ T cells from infected individuals expressing PrPC, which was reflected by IFN type II but not IL-17 expression.

Discussion

These results suggested that PrPC downregulation, linked to both HTLV-1 p12 and IFN-γ expression in CD4+ cells, may play a role in the neuropathogenesis of HTLV-1 infection.
Characterization, complete genome sequencing, and CRISPR/Cas9 system-based decontamination of a novel Escherichia coli phage TR1 from fermentation substrates
Authors: Dong Yuqi , Huang Yunfei , Fan Huahao , Song Lihua , An Xiaoping , Xu Shan , Li Mengzhe , Tong Yigang
Published: August 2023

Phage contamination has become a major concern for industrial bacteria, such as Escherichia coli BL21(DE3), used in fermentation processes. Herein, we report a CRISPR/Cas9 defense system-based strategy to precisely prey and degrade phage DNA to decontaminate target phages. First, we isolated a novel phage from fermentation substrates with BL21(DE3) as the host, named TR1. It showed a typical podovirus morphology with a head diameter of 51.46 ± 2.04 nm and a tail length of 9.31 ± 2.77 nm. The burst size of phage TR1 was 151 PFU/cell, suggesting its strong fecundity in the fermentation system. Additionally, whole-genome sequencing revealed that phage TR1 has a DNA genome of 44,099 bp in length with a 43.8% GC content, encoding a total of 68 open reading frames. Comparative genomics and phylogenetic analysis designated this phage to be a new species of the genus Christensenvirus. To counteract phage TR1, we employed the CRISPR/Cas9 system-based strategy and constructed two phage-resistant E. coli strains, BL21-C and BL21-T, based on conserved genes. Both EOP assays and growth curves indicated strong phage resistance of the recombinant strains, without affecting cell growth. Therefore, this study aimed to provide a resilient strategy to respond to ever-changing phages and ongoing phage–host arm race in industrial fermentation environments by the personalized design of spacers in the recombinant CRISPR/Cas system-containing plasmid. More importantly, our research sparks the use of phage defense mechanism to prevent phage contamination in extensive biotechnological applications.
Human-to-swine introductions and onward transmission of 2009 H1N1 pandemic influenza viruses in Brazil
Authors: Junqueira Dennis Maletich , Tochetto Caroline , Anderson Tavis K. , Gava Danielle , Haach Vanessa , Cantão Maurício E. , Baker Amy L. Vincent , Schaefer Rejane
Published: August 2023

Introduction

Once established in the human population, the 2009 H1N1 pandemic virus (H1N1pdm09) was repeatedly introduced into swine populations globally with subsequent onward transmission among pigs.

Methods

To identify and characterize human-to-swine H1N1pdm09 introductions in Brazil, we conducted a large-scale phylogenetic analysis of 4,141 H1pdm09 hemagglutinin (HA) and 3,227 N1pdm09 neuraminidase (NA) gene sequences isolated globally from humans and swine between 2009 and 2022.

Results

Phylodynamic analysis revealed that during the period between 2009 and 2011, there was a rapid transmission of the H1N1pdm09 virus from humans to swine in Brazil. Multiple introductions of the virus were observed, but most of them resulted in self-limited infections in swine, with limited onward transmission. Only a few sustained transmission clusters were identified during this period. After 2012, there was a reduction in the number of human-to-swine H1N1pdm09 transmissions in Brazil.

Discussion

The virus underwent continuous antigenic drift, and a balance was established between swine-to-swine transmission and extinction, with minimal sustained onward transmission from humans to swine. These results emphasize the dynamic interplay between human-to-swine transmission, antigenic drift, and the establishment of swine-to-swine transmission in shaping the evolution and persistence of H1N1pdm09 in swine populations.
Cellular heterogeneity and plasticity during NAFLD progression
Authors: Park Hyun-Ju , Choi Juyong , Kim Hyunmi , Yang Da-Yeon , An Tae Hyeon , Lee Eun-Woo , Han Baek-Soo , Lee Sang Chul , Kim Won Kon , Bae Kwang-Hee , Oh Kyoung-Jin
Published: August 2023

Nonalcoholic fatty liver disease (NAFLD) is a progressive liver disease that can progress to nonalcoholic steatohepatitis (NASH), NASH-related cirrhosis, and hepatocellular carcinoma (HCC). NAFLD ranges from simple steatosis (or nonalcoholic fatty liver [NAFL]) to NASH as a progressive form of NAFL, which is characterized by steatosis, lobular inflammation, and hepatocellular ballooning with or without fibrosis. Because of the complex pathophysiological mechanism and the heterogeneity of NAFLD, including its wide spectrum of clinical and histological characteristics, no specific therapeutic drugs have been approved for NAFLD. The heterogeneity of NAFLD is closely associated with cellular plasticity, which describes the ability of cells to acquire new identities or change their phenotypes in response to environmental stimuli. The liver consists of parenchymal cells including hepatocytes and cholangiocytes and nonparenchymal cells including Kupffer cells, hepatic stellate cells, and endothelial cells, all of which have specialized functions. This heterogeneous cell population has cellular plasticity to adapt to environmental changes. During NAFLD progression, these cells can exert diverse and complex responses at multiple levels following exposure to a variety of stimuli, including fatty acids, inflammation, and oxidative stress. Therefore, this review provides insights into NAFLD heterogeneity by addressing the cellular plasticity and metabolic adaptation of hepatocytes, cholangiocytes, hepatic stellate cells, and Kupffer cells during NAFLD progression.
Factors associated with changes in psychological resilience of older adults with mild cognitive impairment during the COVID-19 pandemic
Authors: Matsumoto Nanae , Kuroda Yujiro , Sugimoto Taiki , Fujita Kosuke , Uchida Kazuaki , Kishino Yoshinobu , Arai Hidenori , Sakurai Takashi
Published: August 2023

Introduction

Psychological resilience is an indicator of mental health, but there has been no research to date on changes in psychological resilience among older adults with mild cognitive impairment (MCI) during the stress of the coronavirus disease 2019 (COVID-19) pandemic including factors related to those changes. To fill the gap, this study examined the factors and the changes in psychological resilience of older adults with MCI during the COVID-19 pandemic.

Methods

One hundred thirty participants completed the 10-item version of the Connor-Davidson Resilience Scale (CD-RISC-10) between December 2020 and June 2021 as a baseline assessment and between December 2021 and February 2022 as a follow-up. Participants also answered questions on sleep quality, depression symptoms, activities in daily living (ADL), instrumental ADL and social participation to explore factors associated with changes.

Results

In this cohort, the mean CD-RISC-10 scores were significantly higher than the baseline at follow-up (p < 0.05), indicating the improvement of psychological resilience. In multiple regression analyses, sleep quality was significantly correlated with change in CD-RISC-10 score (coefficient = 3.94, 95% confidence interval = 1.11 to 6.78).

Discussion

Psychological resilience could improve even during the stress of the COVID-19 pandemic in older adults with MCI who were at risk of developing dementia. The factor associated with improved psychological resilience was good sleep quality.
Reduced neurite density index in the prefrontal cortex of adults with autism assessed using neurite orientation dispersion and density imaging
Authors: Arai Takashi , Kamagata Koji , Uchida Wataru , Andica Christina , Takabayashi Kaito , Saito Yuya , Tuerxun Rukeye , Mahemuti Zaimire , Morita Yuichi , Irie Ryusuke , Kirino Eiji , Aoki Shigeki
Published: August 2023

Background

Core symptoms of autism-spectrum disorder (ASD) have been associated with prefrontal cortex abnormalities. However, the mechanisms behind the observation remain incomplete, partially due to the challenges of modeling complex gray matter (GM) structures. This study aimed to identify GM microstructural alterations in adults with ASD using neurite orientation dispersion and density imaging (NODDI) and voxel-wise GM-based spatial statistics (GBSS) to reduce the partial volume effects from the white matter and cerebrospinal fluid.

Materials and methods

A total of 48 right-handed participants were included, of which 22 had ASD (17 men; mean age, 34.42 ± 8.27 years) and 26 were typically developing (TD) individuals (14 men; mean age, 32.57 ± 9.62 years). The metrics of NODDI (neurite density index [NDI], orientation dispersion index [ODI], and isotropic volume fraction [ISOVF]) were compared between groups using GBSS. Diffusion tensor imaging (DTI) metrics and surface-based cortical thickness were also compared. The associations between magnetic resonance imaging-based measures and ASD-related scores, including ASD-spectrum quotient, empathizing quotient, and systemizing quotient were also assessed in the region of interest (ROI) analysis.

Results

After controlling for age, sex, and intracranial volume, GBSS demonstrated significantly lower NDI in the ASD group than in the TD group in the left prefrontal cortex (caudal middle frontal, lateral orbitofrontal, pars orbitalis, pars triangularis, rostral middle frontal, and superior frontal region). In the ROI analysis of individuals with ASD, a significantly positive correlation was observed between the NDI in the left rostral middle frontal, superior frontal, and left frontal pole and empathizing quotient score. No significant between-group differences were observed in all DTI metrics, other NODDI (i.e., ODI and ISOVF) metrics, and cortical thickness.

Conclusion

GBSS analysis was used to demonstrate the ability of NODDI metrics to detect GM microstructural alterations in adults with ASD, while no changes were detected using DTI and cortical thickness evaluation. Specifically, we observed a reduced neurite density index in the left prefrontal cortices associated with reduced empathic abilities.
Treatment effects of low-frequency repetitive transcranial magnetic stimulation combined with motor relearning procedure on spasticity and limb motor function in stroke patients
Authors: Chen Ruijun , Zhang Yu , Wang Xiaocheng , Zhao Yunfei , Fan Shasha , Xue Yanping , Zhao Jing , Liu Yinlian , Wang Pingzhi
Published: August 2023

Objective

Limb paralysis, which is a sequela of stroke, limits patients' activities of daily living and lowers their quality of life. The purpose of this study was to investigate the effects of repetitive transcranial magnetic stimulation (rTMS) combined with a motor relearning procedure (MRP) on motor function and limb spasticity in stroke patients.

Methods

Stroke patients were randomly divided into a combined treatment group (rTMS + MRP) and a control group (MRP) (n = 30 per group). The control group was given MRP in addition to conventional rehabilitation, and the combined treatment group was given 1 Hz rTMS combined with MRP. The treatment efficacy was assessed by the modified Ashworth scale (MAS), Fugl-Meyer motor function scale, and motor evoked potential (MEP) testing.

Results

After 4 weeks of treatment, the Brunnstrom score, Fugl-Meyer lower extremity motor function, and Fugl-Meyer balance function were significantly higher in the combination treatment group compared to the control group, while the MAS score was lower in the combination treatment group compared to the control group. The MEP extraction rate was higher in the combined treatment group compared to the control group, while the threshold and central motor conduction time (CMCT) were lower in the combined treatment group compared to the control group.

Conclusion

Low-frequency rTMS combined with MRP had better efficacy on spasticity and motor function in stroke patients with hemiparesis than MRP alone.
Real-world efficacy and tolerability of fremanezumab in adults with chronic migraine: a 3-month, single-center, prospective, observational study
Authors: Cullum Christopher Kjaer , Chaudhry Basit Ali , Do Thien Phu , Amin Faisal Mohammad
Published: August 2023

Background

Following the promising pre-marketing placebo-controlled randomized clinical trials of fremanezumab, post-marketing studies are necessary to verify efficacy and tolerability in various real-world settings. The present study assessed real-world efficacy and safety of fremanezumab.

Methods

A 3-month, single-center, prospective, observation study of adults with chronic migraine who were treated with monthly subcutaneous injections of 225 mg fremanezumab in Denmark. The primary outcome was defined as proportion of patients who achieved ≥30% reduction in monthly migraine days (MMDs) from baseline to weeks 9–12. Among secondary outcomes were ≥50 and ≥75% responder rates and the proportion of patients reporting adverse events.

Results

A total of 91 patients with chronic migraine were enrolled and received at least one dose of fremanezumab of whom 89 patients (98%) completed the 3-months treatment period. At baseline, the mean (SD) number of monthly headache days was 24.3 ± 5.8 and mean number of MMDs was 18.5 ± 7.4. The number of patients who achieved ≥30% reduction in MMDs from baseline to weeks 9–12 was 58 (65%), while 45 (51%) and 21 (24%) had ≥50 and 75% reduction in MMD, respectively. Twenty-one patients (23%) reported adverse event, in which the most common were constipation (4.4%), fatigue (4.4%) and dizziness (3.3%). No serious adverse events were reported.

Conclusion

In adult chronic migraine patients with previous failure of conventional oral migraine preventives, fremanezumab was found to be effective and well-tolerated.