bluuebunny/crossref_metadata_2025 huggingface dataset:
Shrub expansion in maritime forest responding to sea level rise
Authors: Sward Rheya , Philbrick Abigail , Morreale Jonah , Baird Cora Johnston , Gedan Keryn
Published: May 2023

Expansion of shrubs has been observed in a number of biomes and in response to diverse global change drivers. Noting shrub expansion in coastal forests affected by sea level rise, we began to monitor shrub populations in a transgressing loblolly pine forest in coastal Virginia. Forest study plots spanned a gradient of salinity and progression toward a ghost forest state, from high forest with a relatively closed canopy, to mid and low forest, where there were few remaining live canopy trees. Shrubs of the species Morella cerifera were censused for 3 years from 2019 to 2021. Shrub distributions were compared to distributions of the invasive grass Phragmites australis to test if competition with this invasive species played a role in the observed shrub distribution. Shrubs were most abundant in the mid forest, whereas P. australis was most abundant in the low forest, but we did not detect a negative correlation between changes in occupancy of P. australis and shrubs. Rapid growth of shrubs in the mid and high forest radically changed the forest understory structure during the study period. Basal area of shrubs in the mid and high forest tripled, and shrub occupancy increased from 45 to 66% in the high forest, with high patchiness between plots. A flooding event salinized the site in late 2019, during the study. Following the flood, soil porewater salinities in the low forest remained above levels known to cause mortality in M. cerifera for several months. We postulate that high salinity, rather than competition with P. australis, filters M. cerifera from the low forest, whereas moderate salinity in the mid and high forest favors M. cerifera growth and expansion. The increase in shrubs appears to be a hallmark of salt-affected maritime forest, with the shrub front occurring in advance of other indicators of transgression such as P. australis invasion.
Classification of tree symbiotic fungi based on hyperspectral imagery and hybrid convolutional neural networks
Authors: Liu Zhuo , Al-Sarayreh Mahmoud , Li Yanjie , Yuan Zhilin
Published: May 2023

Hyperspectral imagery and machine learning have proven to be powerful, non-invasive, and chemical-free tools for studying tree symbiotic fungi. However, traditional machine learning requires manual feature extraction (feature engineering) of spectral and spatial features of tree symbiotic fungi. Deep convolutional neural networks (CNNs) can extract self and robust features directly from the raw data. In the current study, a deep CNN architecture is proposed to recognize the isolates of dark septate endophytic (DSE) fungal in hyperspectral images. The performance of different CNN approaches (two-dimensional and three-dimensional CNNs) was compared and evaluated based on two independent datasets collected using visible-near-infrared (VNIR) and short-wave-infrared (SWIR) hyperspectral imaging systems. Moreover, the impact of different spectral pre-processing techniques was investigated. The results show that a hybrid CNN architecture (3D-2D CNN), which combines three and two-dimensional CNNs, achieved the best performance for the classification of fungal isolates on SWIR hyperspectral data compared to the same architecture on VNIR hyperspectral data. The best performance is 100% for precision, recall, and overall accuracy. The results also demonstrate that combining different pre-processing techniques on raw SWIR spectra can significantly improve the performance of the CNN models for fungal classification. The hybrid CNN approach with SWIR hyperspectral data provides an efficient method for classifying fungal isolates, which can contribute to the development of accurate and non-destructive tools for evaluating the occurrence of fungal isolates on trees. Such tools can be beneficial for both sustainable agriculture and preserving fungal diversity.
Case report: further delineation of AEBP1-related Ehlers–Danlos Syndrome (classical-like EDS type 2) in an additional patient and comprehensive clinical and molecular review of the literature
Authors: Yamaguchi Tomomi , Hayashi Shujiro , Nagai So , Uchiyama Akihiko , Motegi Sei-Ichiro , Fujikawa Tomomi , Takiguchi Yuri , Kosho Tomoki
Published: May 2023

The Ehlers–Danlos Syndromes (EDS), a group of hereditary connective tissue disorders, were classified into 13 subtypes in the 2017 International Classification. Recently, a new subtype of EDS called classical-like EDS type 2 (clEDS2), which is caused by biallelic variants in the adipocyte enhancer binding protein 1 (AEBP1) gene, was identified. We describe the 11th patient (9th family) with clEDS2, who was complicated by a critical vascular event (superior mesenteric artery aneurysm and rupture). A next-generation sequencing panel-based analysis revealed compound heterozygous variants in AEBP1: NM_001129.5:c.[2296G>T]; [2383dup], p.[(Glu766*)]; [(Glu795Glyfs*3)]. Light microscopic analyses showed increased interfibrillar spaces in the reticular dermis, a disorganized arrangement of collagen fibers, and decreased collagen content. An electron microscopic analysis showed the presence of collagen fibrils with irregular contours (flower-like appearance) and small collagen fibrils. A biochemical analysis showed reduced secretion of type I and type III procollagen. Clinical and molecular features of the current patient and all previously reported patients were reviewed comprehensively. Manifestations noted in most cases (>80%) included skin features (hyperextensibility, atrophic scars, easy bruising, excessive skin/skin folding, delayed wound healing, translucency, piezogenic papules), skeletal features (generalized joint hypermobility, dislocations/subluxations, pes planus), dental abnormalities, and neuromuscular abnormalities. Critical complications, each occurring in a single case, included superior mesenteric artery multiple aneurysm and rupture, aortic root dilation requiring surgery, and bowel rupture. Most AEBP1 variants were predicted or experimentally confirmed to lead to nonsense-mediated mRNA decay, whereas one variant resulted in a protein that was retained intracellularly and not secreted. Clinical, molecular, pathological, and biochemical features of the current patient, as well as a review of all previously reported patients, suggest the importance of the aortic carboxypeptidase-like protein encoded by AEBP1 in collagen fibrillogenesis.
Evaluation of triple negative breast cancer with heterogeneous immune infiltration
Authors: Quintana Ángela , Arenas Enrique Javier , Bernadó Cristina , Navarro José Fernández , González Jonatan , Esteve-Codina Anna , Moliné Teresa , Marti Merce , Curigliano Giuseppe , Schmid Peter , Peg Vicente , Arribas Joaquín , Cortés Javier
Published: May 2023

Introduction

Tumor infiltrating lymphocytes (TILs) are known to be a prognostic and predictive biomarker in breast cancer, particularly in triple negative breast cancer (TNBC) patients. International guidelines have been proposed to evaluate them in the clinical setting as a continuous variable, without a clear defined cut-off. However, there are scenarios where the immune infiltration is heterogeneous that some areas of the patient’s tumour have high numbers of TILs while other areas completely lack them. This spontaneous presentation of a heterogeneous immune infiltration could be a great opportunity to study why some tumours present TILs at diagnosis but others do not, while eliminating inter patient’s differences.

Methods

In this study, we have identified five TNBC patients that showed great TIL heterogeneity, with areas of low (≤5%) and high (≥50%) numbers of TILs in their surgical specimens. To evaluate immune infiltration heterogeneity, we performed and analyzed bulk RNA-sequencing in three independent triplicates from the high and low TIL areas of each patient.

Results

Gene expression was homogeneous within the triplicates in each area but was remarkable different between TILs regions. These differences were not only due to the presence of TILs as there were other non-inflammatory genes and pathways differentially expressed between the two areas.

Discussion

This highlights the importance of intratumour heterogeneity driving the immune infiltration, and not patient’s characteristics like the HLA phenotype, germline DNA or immune repertoire.
Cell-penetrating TLR inhibitor peptide alleviates ulcerative colitis by the functional modulation of macrophages
Authors: Thapa Bikash , Pak Seongwon , Chung Dohyeon , Shin Hye Kyoung , Lee Seong Ho , Lee Keunwook
Published: May 2023

Toll-like receptors (TLRs) have a crucial role not only in triggering innate responses against microbes but in orchestrating an appropriate adaptive immunity. However, deregulated activation of TLR signaling leads to chronic inflammatory conditions such as inflammatory bowel disease (IBD). In this study, we evaluated the immunomodulatory potential of a TLR inhibitor in the form of a cell-penetrating peptide using an ulcerative colitis animal model. A peptide derived from the TIR domain of the TLR adaptor molecule TIRAP that was conjugated with a cell-penetrating sequence (cpTLR-i) suppressed the induction of pro-inflammatory cytokines such as TNF-α and IL-1β in macrophages. In DSS-induced colitis mice, cpTLR-i treatment ameliorated colitis symptoms, colonic tissue damage, and mucosal inflammation. Intriguingly, cpTLR-i attenuated the induction of TNF-α-expressing proinflammatory macrophages while promoting that of regulatory macrophages expressing arginase-1 and reduced type 17 helper T cell (Th17) responses in the inflamed colonic lamina propria. An in vitro study validated that cpTLR-i enhanced the differentiation of monocyte-driven macrophages into mature macrophages with a regulatory phenotype in a microbial TLR ligand-independent manner. Furthermore, the cocultivation of CD4 T cells with macrophages revealed that cpTLR-i suppressed the activation of Th17 cells through the functional modulation of macrophages. Taken together, our data show the immunomodulatory potential of the TLR inhibitor peptide and suggest cpTLR-i as a novel therapeutic candidate for the treatment of IBD.
The shed P2X7 receptor is an index of adverse clinical outcome in COVID-19 patients
Authors: Vultaggio-Poma Valentina , Sanz Juana Maria , Amico Andrea , Violi Alessandra , Ghisellini Sara , Pizzicotti Stefano , Passaro Angelina , Papi Alberto , Libanore Marco , Di Virgilio Francesco , Giuliani Anna Lisa
Published: May 2023

Introduction

The pathophysiology of the Corona Virus Disease 2019 (COVID-19) is incompletely known. A robust inflammatory response caused by viral replication is a main cause of the acute lung and multiorgan injury observed in critical patients. Inflammasomes are likely players in COVID-19 pathogenesis. The P2X7 receptor (P2X7R), a plasma membrane ATP-gated ion channel, is a main activator of the NLRP3 inflammasome, of the ensuing release of inflammatory cytokines and of cell death by pyroptosis. The P2X7R has been implicated in COVID-19-dependent hyperinflammation and in the associated multiorgan damage. Shed P2X7R (sP2X7R) and shed NLRP3 (sNLRP3) have been detected in plasma and other body fluids, especially during infection and inflammation.

Methods

Blood samples from 96 patients with confirmed SARS-CoV-2 infection with various degrees of disease severity were tested at the time of diagnosis at hospital admission. Standard haematological parameters and IL-6, IL-10, IL-1β, sP2X7R and sNLRP3 levels were measured, compared to reference values, statistically validated, and correlated to clinical outcome.

Results

Most COVID-19 patients included in this study had lymphopenia, eosinopenia, neutrophilia, increased inflammatory and coagulation indexes, and augmented sNLRP3, IL-6 and IL-10 levels. Blood concentration of sP2X7R was also increased, and significantly positively correlated with lymphopenia, procalcitonin (PCT), IL-10, and alanine transaminase (ALT). Patients with increased sP2X7R levels at diagnosis also showed fever and respiratory symptoms, were more often transferred to Pneumology division, required mechanical ventilation, and had a higher likelihood to die during hospitalization.

Conclusion

Blood sP2X7R was elevated in the early phases of COVID-19 and predicted an adverse clinical outcome. It is suggested that sP2X7R might be a useful marker of disease progression.
Evidence for broad cross-reactivity of the SARS-CoV-2 NSP12-directed CD4+ T-cell response with pre-primed responses directed against common cold coronaviruses
Authors: Westphal Tim , Mader Maria , Karsten Hendrik , Cords Leon , Knapp Maximilian , Schulte Sophia , Hermanussen Lennart , Peine Sven , Ditt Vanessa , Grifoni Alba , Addo Marylyn Martina , Huber Samuel , Sette Alessandro , Lütgehetmann Marc , Pischke Sven , Kwok William W. , Sidney John , Schulze zur Wiesch Julian
Published: May 2023

Introduction

The nonstructural protein 12 (NSP12) of the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) has a high sequence identity with common cold coronaviruses (CCC).

Methods

Here, we comprehensively assessed the breadth and specificity of the NSP12-specific T-cell response after in vitro T-cell expansion with 185 overlapping 15-mer peptides covering the entire SARS-CoV-2 NSP12 at single-peptide resolution in a cohort of 27 coronavirus disease 2019 (COVID-19) patients. Samples of nine uninfected seronegative individuals, as well as five pre-pandemic controls, were also examined to assess potential cross-reactivity with CCCs.

Results

Surprisingly, there was a comparable breadth of individual NSP12 peptide-specific CD4+ T-cell responses between COVID-19 patients (mean: 12.82 responses; range: 0–25) and seronegative controls including pre-pandemic samples (mean: 12.71 responses; range: 0–21). However, the NSP12-specific T-cell responses detected in acute COVID-19 patients were on average of a higher magnitude. The most frequently detected CD4+ T-cell peptide specificities in COVID-19 patients were aa236–250 (37%) and aa246–260 (44%), whereas the peptide specificities aa686–700 (50%) and aa741–755 (36%), were the most frequently detected in seronegative controls. In CCC-specific peptide-expanded T-cell cultures of seronegative individuals, the corresponding SARS-CoV-2 NSP12 peptide specificities also elicited responses in vitro. However, the NSP12 peptide-specific CD4+ T-cell response repertoire only partially overlapped in patients analyzed longitudinally before and after a SARS-CoV-2 infection.

Discussion

The results of the current study indicate the presence of pre-primed, cross-reactive CCC-specific T-cell responses targeting conserved regions of SARS-CoV-2, but they also underline the complexity of the analysis and the limited understanding of the role of the SARS-CoV-2 specific T-cell response and cross-reactivity with the CCCs.
Natural products in attenuating renal inflammation via inhibiting the NLRP3 inflammasome in diabetic kidney disease
Authors: Wang Yan , Sui Zhun , Wang Mi , Liu Peng
Published: May 2023

Diabetic kidney disease (DKD) is a prevalent and severe complications of diabetes and serves as the primary cause of end-stage kidney disease (ESKD) globally. Increasing evidence indicates that renal inflammation is critical in the pathogenesis of DKD. The nucleotide - binding oligomerization domain (NOD) - like receptor family pyrin domain containing 3 (NLRP3) inflammasome is the most extensively researched inflammasome complex and is considered a crucial regulator in the pathogenesis of DKD. The activation of NLRP3 inflammasome is regulated by various signaling pathways, including NF- κB, thioredoxin—interacting protein (TXNIP), and non-coding RNAs (ncRNA), among others. Natural products are chemicals extracted from living organisms in nature, and they typically possess pharmacological and biological activities. They are invaluable sources for drug design and development. Research has demonstrated that many natural products can alleviate DKD by targeting the NLRP3 inflammasome. In this review, we highlight the role of the NLRP3 inflammasome in DKD, and the pathways by which natural products fight against DKD via inhibiting the NLRP3 inflammasome activation, so as to provide novel insights for the treatment of DKD.
Daily temporal homeostasis in the coral Acropora digitifera
Authors: Rosenberg Yaeli , Doniger Tirza , Lampert Sarit , Sinniger Frederic , Harii Saki , Levy Oren
Published: May 2023

The study aimed to gain a deeper understanding of the daily fluctuations in gene expression at a transcript level in the coral Acropora digitifera and create a comprehensive map of the biological processes that occur under natural environmental conditions. The coral is a key organism in marine ecosystems, and understanding its physiology and the adaptation mechanisms it uses to cope with daily environmental changes is vital for its survival and the preservation of coral reefs. The study’s results showed that certain genes in the coral exhibit specific patterns of expression at different times of the day. These genes play critical roles in regulating a wide range of physiological and behavioral processes, such as metabolism, development, and DNA damage repair. During the day, the coral expends energy on growth and development, and these genes are actively involved in these processes. On the other hand, at night, the coral’s focus shifts toward repair and recovery. The genes that are active during this period are involved in processes like DNA repair, hypoxia response, and transcription. This is a crucial time for the coral, as it’s exposed to a range of environmental stressors that can damage its DNA and impact its overall health. In conclusion, this study provides valuable insights into the cyclic regulatory processes that help the coral adapt to daily external variations and sustain its physiology. It highlights the importance of understanding the daily rhythms of gene expression in marine organisms and the role they play in maintaining the health of coral reefs. This research can be used to develop strategies to preserve coral reefs and mitigate the effects of environmental changes on coral physiology.
Rapid physiological colouration change is a challenge - but not a hindrance - to successful photo identification of giant sunfish (Mola alexandrini, Molidae)
Authors: Nyegaard Marianne , Karmy Jennifer , McBride Lauren , Thys Tierney M. , Welly Marthen , Djohani Rili
Published: May 2023

Photo ID is a common tool in ecology, but has not previously been attempted for the ocean sunfishes (Mola spp., Molidae; ‘molids’). The technique, based on body patterns, could potentially be informative for studying the seasonal occurrence of giant sunfish (Mola alexandrini) on the Bali reefs (Indonesia), where this species is an important drawcard for the local SCUBA diving tourism. However, molids are capable of rapid physiological colouration change, which may complicate the application of the method. Our study aimed to determine if photo ID is nevertheless achievable and informative. To test this, we created the citizen-science platform ‘Match My Mola’ for crowd-sourcing imagery (photos and video) of M. alexandrini in Bali, and undertook trial matching (n=1,098 submissions). The submitted imagery revealed a wide range of pattern clarity, from fish with no pattern to bold displays. Video confirmed physiological colouration change can occur in seconds in this species from low to high contrast, and cause individuals to look very different between moments. However, individual patterns appear to be stable although at least some parts can become inconspicuous during low contrast displays. Despite of this, photo ID is possible, including in some instances, where only partial patterns are visible on one image compared with another. However, true negatives (confirming two fish are not the same) can be challenging. Most identified matches were of fish photographed by different divers on the same day. Only a small number (n=9) were found with resighting durations ≥1 day (1 – 2,652 days). These matches demonstrate that at least some individuals return to the same reefs both within and between seasons, with the resighting duration of 7.2 years constituting the longest known example of molid site fidelity. Comparing body morphology between resightings of > 1 year (n=6) revealed limited indications of growth, contradicting the current understanding of rapid growth in captive molids (Mola mola), and highlighting the knowledge gap regarding growth in the wild. Continued photo ID in the Bali area could provide valuable complementary information to future growth studies using other methods as well as provide further insights into molid site fidelity.
The subjective perception of the happiness of older adult residents in Colombia
Authors: Segura Alejandra , Cardona Doris , Segura Angela , Robledo Carlos Arturo , Muñoz Diana Isabel
Published: May 2023

Introduction

Happiness is understood as the perception of subjective well-being, it can be a quality, a result, or a state characterized by well-being or satisfaction that every person wants to achieve. In older adults, this satisfaction is a sum of lifelong achievements and triumphs; However, some factors influence this ideal.

Objective

Analyze demographic, family, social, personal, and health factors associated with the subjective perception of happiness in older adults, using data from a study conducted in five cities in Colombia, in order to make a theoretical contribution in the search for improvement of their physical, mental and social health.

Materials and methods

A quantitative, cross-sectional, analytical study was carried out, using primary source information, obtained with 2,506 surveys from voluntary participants aged 60 and over, who had no cognitive impairment, and who reside in urban areas but not in long-term centers. The variable happiness (classified as high or moderate/low) was used for: (1) A univariate explorative characterization of older adult, (2) a bivariate estimation of the relationships with the factors studied, and (3) a multivariate construction of profiles through multiple correspondences.

Results

67.2% reported high happiness levels, with differences by city: Bucaramanga (81.6%), Pereira (74.7%), Santa Marta (67.4), Medellín (64%), and Pereira (48.7%). Happiness was explained by the absence of risk of depression and little hopelessness, strengthened psychological well-being, a perception of high quality of life, and living in a functional family.

Conclusion

This study provided an overview of possible factors that can be enhanced and strengthened with public policies (structural determinant), community empowerment, family strengthening (intermediate determinant), and educational programs (proximal determinant). These aspects are included in the essential functions of public health, in favor of mental and social health in older adults.
Appearance-related concerns in individuals with pathological skin picking—a comparison with individuals with dermatological conditions and skin-healthy controls
Authors: Schmidt Jennifer , Gallinat Christina , Martin Alexandra
Published: May 2023

Introduction

Pathological skin picking (PSP) is an excessive behavior which characterizes Skin Picking Disorder. Individuals repeatedly pick their skin and cause skin lesions, but are unable to control the behavior, which can cause severe distress. Visible self-inflicted skin lesions can additionally affect individuals with PSP due to emerging appearance-related concerns. However, these concerns and their role in PSP have hardly been studied, especially not in comparison with individuals with dermatological conditions and skin-healthy controls.

Methods

The present cross-sectional study (n = 453, 83.9% female, 15.9% male, 0.2% diverse) aimed at analyzing appearance-related concerns and mental health outcomes between four groups: Individuals with PSP and dermatological conditions (SP/DC; n = 83), PSP without dermatological conditions (SP; n = 56), dermatological conditions without PSP (DC; n = 176) and skin-healthy controls (SH, n = 138). We compared questionnaire data on dysmorphic concerns, appearance-based rejection sensitivity, and body dysmorphic symptoms, as well as PSP-symptoms and mental health outcomes (depression, anxiety, and self-esteem) between groups.

Results

The analyses showed a significant multivariate group effect in the appearance-related variables, F(6, 896) = 19.92, Wilks’ Λ = 0.78, p < 0.001, and mental health outcomes, F(6, 896) = 16.24, Wilks’ Λ = 0.81, p < 0.001. The SP/DC group had the strongest appearance-related concerns and mental health impairments, followed by the SP group, the DC group and the SH group. The SP/DC group and SP group only differed significantly with regard to dysmorphic concerns, but not in other variables. The DC group was less affected but still showed higher dysmorphic concerns and mental health impairments than skin-healthy controls. In contrast to the PSP groups, the other two groups did not exceed clinically relevant cut-off scores.

Discussion

The present study shows that individuals with PSP exhibit strong appearance-related concerns, regardless of the presence or absence of underlying or comorbid dermatological conditions. These findings shed new light on the importance of appearance-related concerns in Skin Picking Disorder and the role of PSP as a potentially overlooked risk factor in dermatological patients. Therefore, appearance-related concerns should be explicitly addressed in dermatological and psychotherapeutic settings. Future studies should also include longitudinal and experimental analyses to more clearly classify the role of appearance-related concerns in the etiology of PSP and Skin Picking Disorder.
Vibrio cholerae, classification, pathogenesis, immune response, and trends in vaccine development
Authors: Montero David A. , Vidal Roberto M. , Velasco Juliana , George Sergio , Lucero Yalda , Gómez Leonardo A. , Carreño Leandro J. , García-Betancourt Richard , O’Ryan Miguel
Published: May 2023

Vibrio cholerae is the causative agent of cholera, a highly contagious diarrheal disease affecting millions worldwide each year. Cholera is a major public health problem, primarily in countries with poor sanitary conditions and regions affected by natural disasters, where access to safe drinking water is limited. In this narrative review, we aim to summarize the current understanding of the evolution of virulence and pathogenesis of V. cholerae as well as provide an overview of the immune response against this pathogen. We highlight that V. cholerae has a remarkable ability to adapt and evolve, which is a global concern because it increases the risk of cholera outbreaks and the spread of the disease to new regions, making its control even more challenging. Furthermore, we show that this pathogen expresses several virulence factors enabling it to efficiently colonize the human intestine and cause cholera. A cumulative body of work also shows that V. cholerae infection triggers an inflammatory response that influences the development of immune memory against cholera. Lastly, we reviewed the status of licensed cholera vaccines, those undergoing clinical evaluation, and recent progress in developing next-generation vaccines. This review offers a comprehensive view of V. cholerae and identifies knowledge gaps that must be addressed to develop more effective cholera vaccines.
The critical role of pancreatic stone protein/regenerating protein in sepsis-related multiorgan failure
Authors: Hu Ping , Lu Yuan hua , Deng Wei , Li Qi , Zhao Ning , Shao Qiang , Wu Ling , Wang Xu zhen , Qian Ke jian , Liu Fen
Published: May 2023

Introduction

Multiple organ dysfunction syndrome (MODS) is common in patients with sepsistic admitted to an intensive care unit (ICU) and greatly increases mortality. Pancreatic stone protein/regenerating protein (PSP/Reg) is a type of C-type lectin protein that is overexpressed during sepsis. This study aimed to evaluate the potential involvement of PSP/Reg in MODS development in patients with sepsis.

Materials and methods

The relationship between circulating PSP/Reg levels, patient prognosis, and progression to MODS was analyzed in patients with sepsis admitted to the ICU of a general tertiary hospital. Furthermore, to examine the potential involvement of PSP/Reg in sepsis-induced MODS, a septic mouse model was established per the cecal ligation and puncture procedure, randomized into three groups, and subjected to a caudal vein injection of recombinant PSP/Reg at two different doses and phosphate-buffered saline. Survival analyses and disease severity scoring were performed to evaluate the survival status of the mice; enzyme-linked immunosorbent assays were performed to detect the levels of inflammatory factors and organ-damage markers in murine peripheral blood; terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining was performed to measure apoptosis levels in lung, heart, liver, and kidney tissue sections and to visualize the degree of organ damage in the mouse model; myeloperoxidase activity assay, immunofluorescence staining, and flow cytometry were performed to detect neutrophil infiltration levels in vital murine organs and the activation indexes of neutrophils.

Results and discussion

Our findings indicated that Circulating PSP/Reg levels were correlated with patient prognosis and sequential organ failure assessment scores. Furthermore, PSP/Reg administration increased disease severity scores, shortened survival time, increased the TUNEL-positive staining rate, and increased the levels of inflammatory factors, organ-damage markers, and neutrophil infiltration in the organs. Neutrophils can be activated by PSP/Reg to an inflammatory state, both in vivo and in vitro, which is characterized by the increased levels of intercellular adhesion molecule 1 and CD29.

Conclusion

Patient prognosis and progression to MODS can be visualized by monitoring PSP/Reg levels upon ICU admission. Additionally, PSP/Reg administration in animal models exacerbates the inflammatory response and severity of multiorgan damage, which may be accomplished by promoting the inflammatory state of neutrophils.
Chemical synthesis and mechanism of a natural product from endolichenic fungus with a broad-spectrum anti microorganism activity
Authors: Zhou Xuan , Wang Ming-Yi , Cao Qian-Ping , Yang Ze , Meng Qing-Feng , Fu Shao-Bin
Published: May 2023

Background

The antibiotic resistance in various bacteria is consistently increasing and is posing a serious threat to human health, prompting the need for the discovery of novel structurally featured natural products with promising biological activities in drug research and development. Endolichenic microbes have been proven to be a fertile source to produce various chemical components, and therefore these microbes have been on a prime focus for exploring natural products. In this study, to explore potential biological resources and antibacterial natural products, the secondary metabolites of an endolichenic fungus have been investigated.

Methods

The antimicrobial products were isolated from the endolichenic fungus using various chromatographic methods, and the antibacterial and antifungal activities of the compounds were evaluated by the broth microdilution method under in vitro conditions. The antimicrobial mechanism has been discussed with measuring the dissolution of nucleic acid and protein, as well as the activity of alkaline phosphatase (AKP) in preliminary manner. Chemical synthesis of the active product compound 5 was also performed, starting from commercially available 2,6-dihydroxybenzaldehyde through a sequence of transformations that included methylation, the addition of propylmagnesium bromide on formyl group, the oxidation of secondary alcohol, and the deprotection of methyl ether motif.

Results

Among the 19 secondary metabolites of the endolichenic fungus, Daldinia childiae (compound 5) showed attractive antimicrobial activities on 10 of the 15 tested pathogenic strains, including Gram-positive bacteria, Gram-negative bacteria, and fungus. The Minimum Inhibitory Concentration (MIC) of compound 5 for Candida albicans 10213, Micrococcus luteus 261, Proteus vulgaris Z12, Shigella sonnet, and Staphylococcus aureus 6538 was identified as 16 μg/ml, whereas the Minimum Bactericidal Concentration (MBC) of other strains was identified as 64 μg/ml. Compound 5 could dramatically inhibit the growth of S. aureus 6538, P. vulgaris Z12, and C. albicans 10213 at the MBC, likely affecting the permeability of the cell wall and cell membrane. These results enriched the library of active strains and metabolites resources of endolichenic microorganisms. The chemical synthesis of the active compound was also performed in four steps, providing an alternative pathway to explore antimicrobial agents.
Validation of the European Cross-Cultural Neuropsychological Test Battery (CNTB) for the assessment of mild cognitive impairment due to Alzheimer's disease and Parkinson's disease
Authors: Delgado-Álvarez Alfonso , Nielsen Thomas Rune , Delgado-Alonso Cristina , Valles-Salgado María , López-Carbonero Juan I. , García-Ramos Rocío , Gil-Moreno María José , Díez-Cirarda María , Matías-Guiu Jorge , Matias-Guiu Jordi A.
Published: May 2023

Background

The Cross-Cultural Neuropsychological Test Battery (CNTB) is a novel test battery specifically designed to reduce the impact of multiculturality in cognitive assessment.

Objective

We aimed to validate the CNTB in Spaniards in patients with Alzheimer's disease (AD), including patients at mild cognitive impairment (MCI) and mild dementia stages, and Parkinson's disease with MCI (PD-MCI).

Methods

Thirty patients with AD-MCI, 30 with AD-dementia (AD-D), and 30 with PD-MCI were recruited. Each clinical group was compared against a healthy control group (HC) with no differences in sex, age, or years of education. Intergroup comparisons, ROC analysis, and cut-off scores were calculated.

Results

AD-MCI scored lower than HC in those subtests associated with episodic memory and verbal fluency. AD-D also showed lower scores in executive functions and visuospatial tests. Effect sizes for all the subtests were large. PD-MCI showed lower performance than HC in memory and executive functions, particularly on error scores, with large effect sizes. Comparing AD-MCI and PD-MCI, AD-MCI had lower memory scores, while PD-MCI showed the worst performance in executive functions. CNTB showed appropriate convergent validity with standardized neuropsychological tests measuring the same cognitive domains. We obtained similar cut-off scores to previous studies performed in other populations.

Conclusions

The CNTB showed appropriate diagnostic properties in AD and PD, including those stages with mild cognitive impairment. This supports the utility of the CNTB for the early detection of cognitive impairment in AD and PD.
Binaural acoustic stimulation in patients with Parkinson’s disease
Authors: Calvano Alexander , Timmermann Lars , Loehrer Philipp Alexander , Oehrn Carina Renate , Weber Immo
Published: May 2023

Acoustic stimulation can improve motor symptoms in Parkinson’s disease (PD) and might therefore represent a potential non-invasive treatment option. Scalp electroencephalography studies in healthy subjects indicate that specifically binaural beat stimulation (BBS) in the gamma frequency range is associated with synchronized cortical oscillations at 40 Hertz (Hz). Several studies suggest that oscillations in the gamma-frequency range (>30 Hz) serve a prokinetic function in PD. In this double-blind, randomized study, 25 PD patients were recruited. The study was conducted with (ON) and without dopaminergic medication (OFF). Each drug condition consisted of two phases (no stimulation and acoustic stimulation). The acoustic stimulation phase was divided into two blocks including BBS and conventional acoustic stimulation (CAS) as a control condition. For BBS, a modulated frequency of 35 Hz was used (left: 320 Hz; right: 355 Hz) and for CAS 340 Hz on both sides. We assessed effects on motor performance using Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) and two validated commercially available portable devices (Kinesia ONE™ and Kinesia 360™) measuring motor symptoms such as dyskinesia, bradykinesia, and tremor. Repeated measures ANOVA revealed that BBS improved resting tremor on the side of the more affected limb in the OFF condition, as measured by wearables (F(2,48) = 3.61, p = 0.035). However, BBS did not exert a general positive effect on motor symptoms as assessed via MDS-UPDRS (F(2,48) = 1.00, p = 0.327). For CAS, we did not observe an improvement in specific symptoms but rather an overall beneficial effect on motor performance (MDS-UPDRS total score OFF medication: F(2,48) = 4.17, p = 0.021; wearable scores: F(2,48) = 2.46, p = 0.097). In this study, we found an improvement of resting tremor when applying BBS in the gamma frequency band OFF medication. Moreover, the positive effects of CAS underline the general positive potential for improvement of motor function by acoustically supported therapeutic approaches. However, more studies are needed to fully characterize the clinical relevance of BBS and to further optimize its ameliorating effects.
Motor imagery electroencephalogram classification algorithm based on joint features in the spatial and frequency domains and instance transfer
Authors: Wang Ximiao , Dai Xisheng , Liu Yu , Chen Xiangmeng , Hu Qinghui , Hu Rongliang , Li Mingxin
Published: May 2023

Introduction

Motor imagery electroencephalography (MI-EEG) has significant application value in the field of rehabilitation, and is a research hotspot in the brain-computer interface (BCI) field. Due to the small training sample size of MI-EEG of a single subject and the large individual differences among different subjects, existing classification models have low accuracy and poor generalization ability in MI classification tasks.

Methods

To solve this problem, this paper proposes a electroencephalography (EEG) joint feature classification algorithm based on instance transfer and ensemble learning. Firstly, the source domain and target domain data are preprocessed, and then common space mode (CSP) and power spectral density (PSD) are used to extract spatial and frequency domain features respectively, which are combined into EEG joint features. Finally, an ensemble learning algorithm based on kernel mean matching (KMM) and transfer learning adaptive boosting (TrAdaBoost) is used to classify MI-EEG.

Results

To validate the effectiveness of the algorithm, this paper compared and analyzed different algorithms on the BCI Competition IV Dataset 2a, and further verified the stability and effectiveness of the algorithm on the BCI Competition IV Dataset 2b. The experimental results show that the algorithm has an average accuracy of 91.5% and 83.7% on Dataset 2a and Dataset 2b, respectively, which is significantly better than other algorithms.

Discussion

The statement explains that the algorithm fully exploits EEG signals and enriches EEG features, improves the recognition of the MI signals, and provides a new approach to solving the above problem.
Increased serum fibroblast growth factor 21 levels are associated with adverse clinical outcomes after intracerebral hemorrhage
Authors: Chen Keyang , Huang Wenting , Wang Jing , Xu Huiqin , Ruan Lixin , Li Yongang , Wang Zhen , Wang Xue , Lin Li , Li Xiaokun
Published: May 2023

Introduction

Intracerebral hemorrhage (ICH) is the most prevalent cause of death. We sought to explore whether serum Fibroblast growth factor 21 (FGF21) is of substantial benefit in predicting poor prognosis in ICH patient.

Methods

A prospective, multicenter cohort analysis of serum FGF21 levels in 418 ICH patients was carried out. At three months following ICH start, the primary endpoint was death or major disability, whereas the secondary endpoint was death. We investigated the association between serum FGF21 and clinical outcomes. We added FGF21 to the existing rating scale to assess whether it enhanced the prediction ability of the original model. Effectiveness was determined by calculating the C-statistic, net reclassification index (NRI), absolute integrated discrimination improvement (IDI) index.

Results

Among 418 enrolled patients, 217 (51.9%) of the all subjects had death or significant disability. Compared with patients in the lowest quartile group, those in the first quartile group had higher risk of the primary outcome (Odds ratio, 2.73 [95%CI,1.42–5.26, p < 0.05]) and second outcome (Hazard ratio, 4.28 [95%CI,1.61–11.42, p < 0.001]). The integration of FGF21 into many current ICH scales improved the discrimination and calibration quality for the integrated discrimination index’s prediction of main and secondary findings (all p < 0.05).

Conclusion

Elevated serum FGF21 is associated with increased risks of adverse clinical outcomes at 3 months in ICH patients, suggesting FGF21 may be a valuable prognostic factor.
Retinal alpha-synuclein accumulation correlates with retinal dysfunction and structural thinning in the A53T mouse model of Parkinson’s disease
Authors: Tran Katie K. N. , Wong Vickie H. Y. , Hoang Anh , Finkelstein David I. , Bui Bang V. , Nguyen Christine T. O.
Published: May 2023

Abnormal alpha-synuclein (α-SYN) protein deposition has long been recognized as one of the pathological hallmarks of Parkinson’s disease’s (PD). This study considers the potential utility of PD retinal biomarkers by investigating retinal changes in a well characterized PD model of α-SYN overexpression and how these correspond to the presence of retinal α-SYN. Transgenic A53T homozygous (HOM) mice overexpressing human α-SYN and wildtype (WT) control littermates were assessed at 4, 6, and 14  months of age (male and female, n = 15–29 per group). In vivo retinal function (electroretinography, ERG) and structure (optical coherence tomography, OCT) were recorded, and retinal immunohistochemistry and western blot assays were performed to examine retinal α-SYN and tyrosine hydroxylase. Compared to WT controls, A53T mice exhibited reduced light-adapted (cone photoreceptor and bipolar cell amplitude, p < 0.0001) ERG responses and outer retinal thinning (outer plexiform layer, outer nuclear layer, p < 0.0001) which correlated with elevated levels of α-SYN. These retinal signatures provide a high throughput means to study α-SYN induced neurodegeneration and may be useful in vivo endpoints for PD drug discovery.
Transcriptomic analysis of Chinese yam (Dioscorea polystachya Turcz.) variants indicates brassinosteroid involvement in tuber development
Authors: Riekötter Jenny , Oklestkova Jana , Muth Jost , Twyman Richard M. , Epping Janina
Published: May 2023

Dioscoreais an important but underutilized genus of flowering plants that grows predominantly in tropical and subtropical regions. Several species, known as yam, develop large underground tubers and aerial bulbils that are used as food. The Chinese yam (D. polystachyaTurcz.) is one of the fewDioscoreaspecies that grows well in temperate regions and has been proposed as a climate-resilient crop to enhance food security in Europe. However, the fragile, club-like tubers are unsuitable for mechanical harvesting, which is facilitated by shorter and thicker storage organs. Brassinosteroids (BRs) play a key role in plant cell division, cell elongation and proliferation, as well as in the gravitropic response. We collected RNA-Seq data from the head, middle and tip of two tuber shape variants: F60 (long, thin) and F2000 (short, thick). Comparative transcriptome analysis of F60 vs. F2000 revealed 30,229 differentially expressed genes (DEGs), 1,393 of which were differentially expressed in the growing tip. Several DEGs are involved in steroid/BR biosynthesis or signaling, or may be regulated by BRs. The quantification of endogenous BRs revealed higher levels of castasterone (CS), 28-norCS, 28-homoCS and brassinolide in F2000 compared to F60 tubers. The highest BR levels were detected in the growing tip, and CS was the most abundant (439.6 ± 196.41 pmol/g in F2000 and 365.6 ± 112.78 pmol/g in F60). Exogenous 24-epi-brassinolide (epi-BL) treatment (20 nM) in an aeroponic system significantly increased the width-to-length ratio (0.045 ± 0.002) compared to the mock-treated plants (0.03 ± 0.002) after 7 weeks, indicating that exogenous epi-BL produces shorter and thicker tubers. In this study we demonstrate the role of BRs inD. polystachyatuber shape, providing insight into the role of plant hormones in yam storage organ development. We found that BRs can influence tuber shape in Chinese yam by regulating the expression of genes involved cell expansion. Our data can help to improve the efficiency of Chinese yam cultivation, which could provide an alternative food source and thus contribute to future food security in Europe.
Outcome of immune checkpoint inhibitors in patients with extensive-stage small-cell lung cancer and brain metastases
Authors: Wang Chunyu , Mu Shuai , Yang Xuhui , Li Lingling , Tao Haitao , Zhang Fan , Li Ruixin , Hu Yi , Wang Lijie
Published: May 2023

Objectives

Brain metastases (BMs) are common in extensive-stage small-cell lung cancer (SCLC) and are underrepresented in pivotal clinical trials that demonstrate the efficacy of immune checkpoint inhibitors (ICIs). We conducted a retrospective analysis to assess the role of ICIs in BM lesions in less selected patients.

Materials and methods

Patients with histologically confirmed extensive-stage SCLC who were treated with ICIs were included in this study. Objective response rates (ORRs) were compared between the with-BM and without-BM groups. Kaplan−Meier analysis and the log-rank test were used to evaluate and compare progression-free survival (PFS). The intracranial progression rate was estimated using the Fine-Gray competing risks model.

Results

A total of 133 patients were included, 45 of whom started ICI treatment with BMs. In the whole cohort, the overall ORR was not significantly different for patients with and without BMs (p = 0.856). The median progression-free survival for patients with and without BMs was 6.43 months (95% CI: 4.70-8.17) and 4.37 months (95% CI: 3.71-5.04), respectively (p =0.054). In multivariate analysis, BM status was not associated with poorer PFS (p = 0.101). Our data showed that different failure patterns occurred between groups, with 7 patients (8.0%) without BM and 7 patients (15.6%) with BM having intracranial-only failure as the first site progression. The cumulative incidences of brain metastases at 6 and 12 months were 15.0% and 32.9% in the without-BM group and 46.2% and 59.0% in the BM group, respectively (Gray’s p<0.0001).

Conclusions

Although patients with BMs had a higher intracranial progression rate than patients without BMs, the presence of BMs was not significantly associated with a poorer ORR and PFS with ICI treatment in multivariate analysis.