bluuebunny/crossref_metadata_2025 huggingface dataset:
Spatial profiling of the placental chorioamniotic membranes reveals upregulation of immune checkpoint proteins during Group B Streptococcus infection in a nonhuman primate model
Authors: Manuel Gygeria , Coleman Michelle , Orvis Austyn S. , Munson Jeff , Li Amanda , Kapur Raj P. , Li Miranda , Li Edmunda , Armistead Blair , Rajagopal Lakshmi , Adams Waldorf Kristina M.
Published: January 2024

Background

Preterm birth is a leading cause of neonatal mortality, which is often complicated by intrauterine infection and inflammation. We have established a nonhuman primate model of Group B Streptococcus (GBS, Streptococcus agalactiae) infection-associated preterm birth. Immune checkpoints are modulators of the immune response by activating or suppressing leukocyte function and are understudied in preterm birth. The objective of this study was to spatially profile changes in immune protein expression at the maternal-fetal interface during a GBS infection with a focus on immune checkpoints.

Methods

Twelve nonhuman primates (pigtail macaques, Macaca nemestrina) received a choriodecidual inoculation of either: 1) 1-5 X 108 colony forming units (CFU) of hyperhemolytic/hypervirulent GBS (GBSΔcovR, N=4); 2) an isogenic/nonpigmented strain (GBS ΔcovRΔcylE, N=4); or, 3) saline (N=4). A Cesarean section was performed at preterm labor or 3 days after GBS infection or 7 days after saline inoculation. Nanostring GeoMx® Digital Spatial Profiling technology was used to segment protein expression within the amnion, chorion, and maternal decidua at the inoculation site using an immuno-oncology panel targeting 56 immunoproteins enriched in stimulatory and inhibitory immune checkpoint proteins or their protein ligands. Statistical analysis included R studio, Kruskal-Wallis, Pearson and Spearman tests.

Results

Both inhibitory and stimulatory immune checkpoint proteins were significantly upregulated within the chorioamniotic membranes and decidua (VISTA, LAG3, PD-1, CD40, GITR), as well as their ligands (PD-L1, PD-L2, CD40L; all p<0.05). Immunostaining for VISTA revealed positive (VISTA+) cells, predominantly in the chorion and decidua. There were strong correlations between VISTA and amniotic fluid concentrations of IL-1β, IL-6, IL-8, and TNF-α (all p<0.05), as well as maternal placental histopathology scores (p<0.05).

Conclusion

Differential regulation of multiple immune checkpoint proteins in the decidua at the site of a GBS infection indicates a major perturbation in immunologic homeostasis that could benefit the host by restricting immune-driven pathologies or the pathogen by limiting immune surveillance. Protein expression of VISTA, an inhibitory immune checkpoint, was upregulated in the chorion and decidua after GBS infection. Investigating the impact of innate immune cell expression of inhibitory immune checkpoints may reveal new insights into placental host-pathogen interactions at the maternal-fetal interface.
Regulatory role of Mss11 in Candida glabrata virulence: adhesion and biofilm formation
Authors: Wang Lu-Ling , Huang Si-Jia , Zhao Jun-Tao , Liu Jin-Yan , Xiang Ming-Jie
Published: January 2024

Introduction

Candida glabrata has emerged as a fungal pathogen with high infection and mortality rates, and its primary virulence factors are related to adhesion and biofilm formation. These virulence factors in C.glabrata are primarily mediated by epithelial adhesins (Epas), most of which are encoded in subtelomeric regions and regulated by subtelomeric silencing mechanisms. The transcription factor Mss11, known for its regulatory role in adhesion, biofilm formation, and filamentous growth in Saccharomyces cerevisiae and Candida albicans, has also been implicated in the expression of EPA6, suggesting its potential influence on C.glabrata virulence. The present study aims to determine the regulatory role of Mss11 in the virulence of C. glabrata.

Methods

In this work, a Δmss11 null mutant and its complemented strain were constructed from a C.glabrata standard strain. The impact of the transcription factor Mss11 on the virulence of C.glabrata was investigated through a series of phenotypic experiments, including the microbial adhesion to hydrocarbons (MATH) test, adherence assay, biofilm assay, scanning electron microscopy and Galleria mellonella virulence assay. Furthermore, transcriptome sequencing, quantitative reverse transcription polymerase chain reaction (RT-qPCR), and chromatin immunoprecipitation sequencing (ChIP-seq) were employed to investigate the molecular mechanisms behind the regulation of Mss11.

Results

In C.glabrata, the loss of MSS11 led to a significant reduction in several virulence factors including cell surface hydrophobicity, epithelial cell adhesion, and biofilm formation. These observations were consistent with the decreased virulence of the Δmss11 mutant observed in the Galleria mellonella infection model. Further exploration demonstrated that Mss11 modulates C. glabrata virulence by regulating EPA1 and EPA6 expression. It binds to the upstream regions of EPA1 and EPA6, as well as the promoter regions of the subtelomeric silencing-related genes SIR4, RIF1, and RAP1, indicating the dual regulatory role of Mss11.

Conclusion

Mss11 plays a crucial role in C. glabrata adhesion and biofilm formation, and thus has a broad influence on virulence. This regulation is achieved by regulating the expression of EPA1 and EPA6 through both promoter-specific regulation and subtelomeric silencing.
How well can we predict climate migration? A review of forecasting models
Authors: Schewel Kerilyn , Dickerson Sarah , Madson B. , Nagle Alverio Gabriela
Published: January 2024

Climate change will have significant impacts on all aspects of human society, including population movements. In some cases, populations will be displaced by natural disasters and sudden-onset climate events, such as tropical storms. In other cases, climate change will gradually influence the economic, social, and political realities of a place, which will in turn influence how and where people migrate. Planning for the wide spectrum of future climate-related mobility is a key challenge facing development planners and policy makers. This article reviews the state of climate-related migration forecasting models, based on an analysis of thirty recent models. We present the key characteristics, strengths, and weaknesses of different modeling approaches, including gravity, radiation, agent-based, systems dynamics and statistical extrapolation models, and consider five illustrative models in depth. We show why, at this stage of development, forecasting models are not yet able to provide reliable numerical estimates of future climate-related migration. Rather, models are best used as tools to consider a range of possible futures, to explore systems dynamics, to test theories or potential policy effects. We consider the policy and research implications of our findings, including the need for improved migration data collection, enhanced interdisciplinary collaboration, and scenarios-based planning.
Contemporary review on pediatric hypertrophic cardiomyopathy: insights into detection and management
Authors: Shafqat Areez , Shaik Abdullah , Koritala Snygdha , Mushtaq Ali , Sabbah Belal Nedal , Nahid Elshaer Ahmed , Baqal Omar
Published: January 2024

Hypertrophic cardiomyopathy is the most common genetic cardiac disorder and is defined by the presence of left ventricular (LV) hypertrophy in the absence of a condition capable of producing such a magnitude of hypertrophy. Over the past decade, guidelines on the screening, diagnostic, and management protocols of pediatric primary (i.e., sarcomeric) HCM have undergone significant revisions. Important revisions include changes to the appropriate screening age, the role of cardiac MRI (CMR) in HCM diagnosis, and the introduction of individualized pediatric SCD risk assessment models like HCM Risk-kids and PRIMaCY. This review explores open uncertainties in pediatric HCM that merit further attention, such as the divergent American and European recommendations on CMR use in HCM screening and diagnosis, the need for incorporating key genetic and imaging parameters into HCM-Risk Kids and PRIMaCY, the best method of quantifying myocardial fibrosis and its prognostic utility in SCD prediction for pediatric HCM, devising appropriate genotype- and phenotype-based exercise recommendations, and use of heart failure medications that can reverse cardiac remodeling in pediatric HCM.
Investigating shared decision-making during the use of a digital health tool for physical activity planning in cardiac rehabilitation
Authors: Wurhofer Daniela , Neunteufel Julia , Strumegger Eva-Maria , Höppchen Isabel , Mayr Barbara , Egger Andreas , Sareban Mahdi , Reich Bernhard , Neudorfer Michael , Niebauer Josef , Smeddinck Jan David , Kulnik Stefan Tino
Published: January 2024

Background

Shared decision making (SDM) between healthcare professionals and persons with CVD can have a positive impact on motivation, adherence, or sustainability regarding long-term goals and integration of cardiovascular disease (CVD) rehabilitation in the everyday lives of persons with CVD. SDM can foster the transition between regular heart-healthy activity at rehabilitation facilities and more independent activity at home, but it is often challenging to implement SDM given limited time and resources, e.g., in the daily practice of rehabilitation. Digital tools can help but must be appropriately tailored for situated use and user needs.

Objective

We aimed to (1) describe in how far SDM is manifested in the situated context when using a digital tool developed by our group, and, based on that, (2) reflect on how digital health tools can be designed to facilitate and improve the SDM process.

Methods

In the context of a field study, we investigated how SDM is already naturally applied and manifested when using a digital tool for joint physical activity planning in cardiac rehabilitation in clinical practice. In a two-week qualitative study, we collected data on expectations, experiences and interactions during the use of a digital health tool by seven persons with CVD and five healthcare professionals. Data was collected by means of observations, interviews, questionnaires and a self-reported diary, and analysed with a particular focus on episodes related to SDM.

Results

We found that SDM was manifested in the situated context to limited extent. For example, we identified high improvement potential for more structured goal-setting and more explicit consideration of preferences and routines. Based on mapping our findings to temporal phases where SDM can be adopted, we highlight implications for design to further support SDM in clinical practice. We consider this as “SDM supportive design in digital health apps,” suggesting for example step-by-step guidance to be used during the actual consultation.

Conclusion

This study contributes to further understanding and integration of SDM in digital health tools with a focus on rehabilitation, to empower and support both persons with CVD and healthcare professionals.
Exploring internet inclusivity and effectiveness of e-learning initiatives during the pandemic – a comparative analysis
Authors: Ehsan Muhammad Mubashir , Zaidan Esmat
Published: January 2024

The paper presents a cross-country analysis of 25 low and lower-middle-income countries to investigate the impact of COVID-19 on educational policymaking. The study utilises variables from the Internet Inclusive Index and the Digital Skills Gap Index to explore the relationship between internet access and digital skills gaps in these countries. A descriptive and correlation analysis is conducted to understand trends and associations between the variables from data for the selected countries. The analysis shows a positive correlation between internet domains and digital skills gap scores. The paper also presents insights from low and middle-income countries to understand the challenges and responses to e-learning policy during the Pandemic. The evidence from the analysis suggests that countries with higher scores on internet domains pre-pandemic were in a better position to absorb the external shocks caused by the Pandemic. The paper’s findings highlight the importance of addressing the digital divide and promoting internet inclusivity in these countries to improve their ability to adapt to external shocks and ensure continuity of learning during crises such as the COVID-19 Pandemic.
Predicting the survival probability of functional neuroendocrine tumors treated with peptide receptor radionuclide therapy: Serbian experience
Authors: Vukomanovic Vladimir , Nedic Katarina Vuleta , Radojevic Marija Zivkovic , Dagovic Aleksandar , Milosavljevic Neda , Markovic Marina , Ignjatovic Vladimir , Simic Vukomanovic Ivana , Djukic Svetlana , Sreckovic Marijana , Backovic Milena , Vuleta Marko , Djukic Aleksandar , Vukicevic Verica , Ignjatovic Vesna
Published: January 2024

Introduction

Peptide receptor radionuclide therapy (PRRT) is a treatment option for well-differentiated, somatostatin receptor positive, unresectable or/and metastatic neuroendocrine tumors (NETs). Although high disease control rates seen with PRRT a significant number NET patients have a short progression-free interval, and currently, there is a deficiency of effective biomarkers to pre-identify these patients. This study is aimed at determining the prognostic significance of biomarkers on survival of patients with NETs in initial PRRT treatment.

Methodology

We retrospectively analyzed 51 patients with NETs treated with PRRT at the Department for nuclear medicine, University Clinical Center Kragujevac, Serbia, with a five-year follow-up. Eligible patients with confirmed inoperable NETs, were retrospectively evaluated hematological, blood-based inflammatory markers, biochemical markers and clinical characteristics on disease progression. In accordance with the progression og the disease, the patients were divided into two groups: progression group (n=18) and a non-progression group (n=33). Clinical data were compared between the two groups.

Results

A total of 51 patients (Md=60, age 25-75 years) were treated with PRRT, of whom 29 (56.86%) demonstrated stable disease, 4 (7.84%) demonstrated a partial response, and 14 (27.46%) demonstrated progressive disease and death was recorded in 4 (7.84%) patients. The mean PFS was a 36.22 months (95% CI 30.14-42.29) and the mean OS was 44.68 months (95% CI 37.40-51.97). Univariate logistic regression analysis displayed that age (p<0.05), functional tumors (p<0.05), absolute neutrophil count (p<0.05), neutrophil-lymphocyte ratio-NLR (p<0.05), C-reactive protein-CRP (p<0.05), CRP/Albumin (p<0.05), alanine aminotransferase-ALT (p<0.05), were risk factors for disease progression. Multivariate logistic regression analysis exhibited that functional tumors (p<0.001), age (p<0.05), CRP (p<0.05), and ALT (p<0.05), were independent risk factors for the disease progression in patients with NETs. Tumor functionality was the most powerful prognostic factor. The median PFS (11.86 ± 1.41 vs. 43.38 ± 3.16 months; p=0.001) and OS (21.81 ± 2.70 vs 53.86 ± 3.70, p=0.001) were significantly shorter in patients with functional than non-functional NETs respectively.

Conclusion

The study’s results suggest that tumor functionality, and certain biomarkers may serve as prognostic survival indicators for patients with NETs undergoing PRRT. The findings can potentially help to identify patients who are at higher risk of disease progression and tailor treatment strategies accordingly.
Association between neutrophil-to-lymphocyte ratio and diabetic kidney disease in type 2 diabetes mellitus patients: a cross-sectional study
Authors: Li Xiaowan , Wang Lanyu , Liu Min , Zhou Hongyi , Xu Hongyang
Published: January 2024

Aims

This investigation examined the possibility of a relationship between neutrophil-to-lymphocyte ratio (NLR) and diabetic kidney disease (DKD) in type 2 diabetes mellitus (T2DM) patients.

Methods

Adults with T2DM who were included in the National Health and Nutrition Examination Survey (NHANES) between 1999 and 2020 were the subjects of the current cross-sectional investigation. Low estimated glomerular filtration rate (eGFR) (< 60 mL/min/1.73 m2) or albuminuria (urinary albumin-to-creatinine ratio (ACR) ≥ 30 mg/g) in T2DM patients were the diagnostic criteria for DKD. Weighted multivariable logistic regression models and generalized additive models were used to investigate the independent relationships between NLR levels with DKD, albuminuria, and low-eGFR. Additionally, we examined the relationships between DKD, albuminuria, and low-eGFR with other inflammatory markers, such as the aggregate index of systemic inflammation (AISI), systemic immune-inflammation index (SII), system inflammation response index (SIRI), and platelet-to-lymphocyte ratio (PLR) and monocyte-to-lymphocyte ratio (MLR). Their diagnostic capabilities were evaluated and contrasted using receiver operating characteristic (ROC) curves.

Results

44.65% of the 7,153 participants who were recruited for this study were males. DKD, albuminuria, and low-eGFR were prevalent in 31.76%, 23.08%, and 14.55% of cases, respectively. Positive correlations were seen between the NLR with the prevalences of DKD, albuminuria, and low-eGFR. Subgroup analysis and interaction tests revealed that the associations of NLR with DKD, albuminuria, and low-eGFR were not significantly different across populations. In addition, MLR, SII and SIRI showed positive associations with the prevalence of DKD. ROC analysis discovered that when compared to other inflammatory markers (MLR, PLR, SII, SIRI, and AISI), NLR may demonstrate more discriminatory power and accuracy in assessing the risk of DKD, albuminuria, and low-eGFR.

Conclusion

Compared to other inflammatory markers (MLR, PLR, SII, SIRI, and AISI), NLR may serve as the more effective potential inflammatory marker for identifying the risk of DKD, albuminuria, and low-eGFR in US T2DM patients. T2DM patients with elevated levels of NLR, MLR, SII, and SIRI should be closely monitored for their potential risk to renal function.
Process systems engineering perspectives on eco-efficient downstream processing of volatile biochemicals from fermentation
Authors: Janković Tamara , Straathof Adrie J. J. , Kiss Anton A.
Published: January 2024

Increasing concerns over environmental pollution, climate change and energy security are driving a necessary transition from fossil carbon sources to more sustainable alternatives. Due to lower environmental impact, biochemicals are rapidly gaining significance as a potential renewable solution, particularly of interest in Europe. In this context, process systems engineering (PSE) helps with the decision-making at multiple scales and levels, aiming for optimum use of (renewable) resources. Fermentation using waste biomass or industrial off-gases is a promising way for the production of these products. However, due to the inhibitory effects or low substrate concentrations, relatively low product concentrations can be obtained. Consequently, significant improvements in downstream processing are needed to increase the competitiveness of the overall bioprocesses. This paper supports sustainable development by providing new PSE perspectives on the purification of volatile bioproducts from dilute fermentation broths. Since purification significantly contributes to the total cost of biochemical production processes (20%–40% of the total cost), enhancing this part may substantially improve the competitiveness of the overall bioprocesses. The highly advanced downstream process offers the possibility of recovering high-purity products while enhancing the fermentation step by continuously removing inhibitory products, and recycling microorganisms with most of the present water. Besides higher productivity, the upstream process can be greatly improved by avoiding loss of biomass, enabling closed-loop operation and decreasing the need for fresh water. Applying heat pumping, heat integration and other methods of process intensification (PI) can drastically reduce energy requirements and CO2 emissions. Additionally, the opportunity to use renewable electricity instead of conventional fossil energy presents a significant step toward (green) electrification and decarbonization of the chemical industry.
Carbon emission scenario prediction for highway construction projects
Authors: Wu Qixian , Chen Yun , Li Congying , Shi Xiaoya
Published: January 2024

In order to carry out the research on the measurement and prediction of carbon emissions from highway projects, the prediction index system is constructed by selecting seven influencing factors, namely, urbanization rate, industrial structure, energy intensity, energy structure, key low-carbon technologies, highway construction planning, and green financial support. The carbon emission coefficient method is used to measure the carbon emissions of highway projects from the perspective of energy consumption, and finally, a carbon emission scenario prediction model based on the scenario analysis method and the LSTM algorithm of the recurrent neural network is constructed to put forward a new way of predicting the carbon emissions of highway projects. Taking Hunan province as a case study object, the carbon emission trends in the next 15 years are predicted under three scenarios: low carbon, baseline, and high carbon. The results show that the highway project in Hunan province is expected to peak in 2031 under the low-carbon scenario, in 2037 under the baseline scenario, and around 2044 under the high-carbon scenario. It is also found that energy saving and emission reduction measures have a certain lag in the emission reduction effect of highway projects. Finally, based on this, suggestions and countermeasures for carbon emission reduction of highway development in Hunan province are proposed.
Identification of key areas for ecological restoration of territorial space based on ecological security pattern: a case study of Kangbao County
Authors: Jiao Xinying , Tian Zhipeng , Yang Huicai , Shang Guofei , Ma Jingtao
Published: January 2024

Accurate identification of key areas for ecological restoration is an important foundation for orderly promotion of ecological restoration of territorial space. This study identified the key areas for ecological restoration in Kangbao County according to the research paradigm of “source identification – resistance surface construction – corridor extraction”. First, ecological source sites were identified and screened based on habitat quality modeling, morphological spatial pattern analysis and landscape connectivity analysis. Then, the base resistance surface was constructed using ArcGIS software and nighttime light data. Thereafter, ecological corridors were extracted and ecological pinch points and ecological barrier points identified with the Linkage Mapper plug-in. Forty ecological source sites with a total area of 68.06 km2 were identified in Kangbao County. These sites were dominated by woodland and grassland, and the integrity of these ecological source sites still needed to be improved. The 96 ecological corridors (total length of 743.81 km) were identified, which were densely distributed in the south and east parts of the study area, and there is still much room for improvement of the habitat connectivity. Additionally, 75 ecological pinch points (total area of 31.72 km2) and 69 ecological obstacles (total area of 16.42 km2) were identified. The key areas to be restored were mainly distributed in Yan Yufang, Har Chimega, Tuchengzi, Zhangji, and Danchenghe Townships. This study can lay a firm foundation for the ecological restoration in Kangbao County.
“A very big challenge”: a qualitative study to explore the early barriers and enablers to implementing a national genomic medicine service in England
Authors: Friedrich Bettina , Vindrola-Padros Cecilia , Lucassen Anneke M. , Patch Chris , Clarke Angus , Lakhanpaul Monica , Lewis Celine
Published: January 2024

Background: The Genomic Medicine Service (GMS) was launched in 2018 in England to create a step-change in the use of genomics in the NHS, including offering whole genome sequencing (WGS) as part of routine care. In this qualitative study on pediatric rare disease diagnosis, we used an implementation science framework to identify enablers and barriers which have influenced rollout.

Methods: Semi-structured interviews were conducted with seven participants tasked with designing the GMS and 14 tasked with leading the implementation across the seven Genomic Medicine Service Alliances (GMSAs) and/or Genomic Laboratory Hubs (GLHs) between October 2021 and February 2022.

Results: Overall, those involved in delivering the service strongly support its aims and ambitions. Challenges include: 1) concerns around the lack of trained and available workforce (clinicians and scientists) to seek consent from patients, interpret findings and communicate results; 2) the lack of a digital, coordinated infrastructure in place to support and standardize delivery with knock-on effects including onerous administrative aspects required to consent patients and order WGS tests; 3) that the “mainstreaming agenda”, whilst considered important, encountered reluctance to become engaged from those who did not see it as a priority or viewed it as being politically rather than clinically driven; 4) the timelines and targets set for the GMS were perceived by some as too ambitious. Interviewees discussed local adaptations and strategies employed to address the various challenges they had encountered, including 1) capacity-building, 2) employing genomic associates and other support staff to support the consent and test ordering process, 3) having “genomic champions” embedded in mainstream services to impart knowledge and best practice, 4) enhancing collaboration between genetic and mainstream specialties, 5) building evaluation into the service and 6) co-creating services with patients and the public.

Conclusion: Our findings highlight the challenges of implementing system-wide change within a complex healthcare system. Local as well as national solutions can undoubtedly address many of these barriers over time.
Integration of multi-omics technologies for molecular diagnosis in ataxia patients
Authors: Audet Sebastien , Triassi Valerie , Gelinas Myriam , Legault-Cadieux Nab , Ferraro Vincent , Duquette Antoine , Tetreault Martine
Published: January 2024

Background: Episodic ataxias are rare neurological disorders characterized by recurring episodes of imbalance and coordination difficulties. Obtaining definitive molecular diagnoses poses challenges, as clinical presentation is highly heterogeneous, and literature on the underlying genetics is limited. While the advent of high-throughput sequencing technologies has significantly contributed to Mendelian disorders genetics, interpretation of variants of uncertain significance and other limitations inherent to individual methods still leaves many patients undiagnosed. This study aimed to investigate the utility of multi-omics for the identification and validation of molecular candidates in a cohort of complex cases of ataxia with episodic presentation.

Methods: Eight patients lacking molecular diagnosis despite extensive clinical examination were recruited following standard genetic testing. Whole genome and RNA sequencing were performed on samples isolated from peripheral blood mononuclear cells. Integration of expression and splicing data facilitated genomic variants prioritization. Subsequently, long-read sequencing played a crucial role in the validation of those candidate variants.

Results: Whole genome sequencing uncovered pathogenic variants in four genes (SPG7, ATXN2, ELOVL4, PMPCB). A missense and a nonsense variant, both previously reported as likely pathogenic, configured in trans in individual #1 (SPG7: c.2228T>C/p.I743T, c.1861C>T/p.Q621*). An ATXN2 microsatellite expansion (CAG32) in another late-onset case. In two separate individuals, intronic variants near splice sites (ELOVL4: c.541 + 5G>A; PMPCB: c.1154 + 5G>C) were predicted to induce loss-of-function splicing, but had never been reported as disease-causing. Long-read sequencing confirmed the compound heterozygous variants configuration, repeat expansion length, as well as splicing landscape for those pathogenic variants. A potential genetic modifier of the ATXN2 expansion was discovered in ZFYVE26 (c.3022C>T/p.R1008*).

Conclusion: Despite failure to identify pathogenic variants through clinical genetic testing, the multi-omics approach enabled the molecular diagnosis in 50% of patients, also giving valuable insights for variant prioritization in remaining cases. The findings demonstrate the value of long-read sequencing for the validation of candidate variants in various scenarios. Our study demonstrates the effectiveness of leveraging complementary omics technologies to unravel the underlying genetics in patients with unresolved rare diseases such as ataxia. Molecular diagnoses not only hold significant promise in improving patient care management, but also alleviates the burden of diagnostic odysseys, more broadly enhancing quality of life.
Reduced monocyte proportions and responsiveness in convalescent COVID-19 patients
Authors: Ravkov Eugene V. , Williams Elizabeth S. C. P. , Elgort Marc , Barker Adam P. , Planelles Vicente , Spivak Adam M. , Delgado Julio C. , Lin Leo , Hanley Timothy M.
Published: January 2024

Introduction

The clinical manifestations of acute severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection and coronavirus disease 2019 (COVID-19) suggest a dysregulation of the host immune response that leads to inflammation, thrombosis, and organ dysfunction. It is less clear whether these dysregulated processes persist during the convalescent phase of disease or during long COVID. We sought to examine the effects of SARS-CoV-2 infection on the proportions of classical, intermediate, and nonclassical monocytes, their activation status, and their functional properties in convalescent COVID-19 patients.

Methods

Peripheral blood mononuclear cells (PBMCs) from convalescent COVID-19 patients and uninfected controls were analyzed by multiparameter flow cytometry to determine relative percentages of total monocytes and monocyte subsets. The expression of activation markers and proinflammatory cytokines in response to LPS treatment were measured by flow cytometry and ELISA, respectively.

Results

We found that the percentage of total monocytes was decreased in convalescent COVID-19 patients compared to uninfected controls. This was due to decreased intermediate and non-classical monocytes. Classical monocytes from convalescent COVID-19 patients demonstrated a decrease in activation markers, such as CD56, in response to stimulation with bacterial lipopolysaccharide (LPS). In addition, classical monocytes from convalescent COVID-19 patients showed decreased expression of CD142 (tissue factor), which can initiate the extrinsic coagulation cascade, in response to LPS stimulation. Finally, we found that monocytes from convalescent COVID-19 patients produced less TNF-α and IL-6 in response to LPS stimulation, than those from uninfected controls.

Conclusion

SARS-CoV-2 infection exhibits a clear effect on the relative proportions of monocyte subsets, the activation status of classical monocytes, and proinflammatory cytokine production that persists during the convalescent phase of disease.
Phytoplankton physiology and functional traits under artificial upwelling with varying Si:N
Authors: Ortiz Joaquin , Arístegui Javier , Goldenberg Silvan Urs , Fernández-Méndez Mar , Taucher Jan , Archer Stephen D. , Baumann Moritz , Riebesell Ulf
Published: January 2024

Introduction

Artificial upwelling has been discussed as a nature-based solution to fertilize currently unproductive areas of the ocean to enhance food web productivity and atmospheric CO2 sequestration. The efficacy of this approach may be closely tied to the nutrient stoichiometry of the upwelled water, as Si-rich upwelling should benefit the growth of diatoms, who are key players for primary production, carbon export and food web efficiency.

Methods

With a mesocosm experiment in subtropical waters, we assessed the physiological and functional responses of an oligotrophic phytoplankton community to artificial upwelling under varying Si:N ratios (0.07-1.33).

Results

Deep water fertilization led to strongly enhanced primary productivity rates and net autotrophy across Si scenarios. At the community level, Si-rich upwelling50 temporarily increased primary production and consistently enhanced diatom growth, producing up to 10-fold higher abundances compared to Si-deficient upwelling. At the organism level, contrasting effects were observed. On the one hand, silicification and size of diatom cells remained unaffected by Si:N, which is surprising given the direct dependency of these traits on Si. On the other hand, diatom Chlorophyll a density and carbon density were strongly reduced and particulate matter C:N was elevated under Si-rich upwelling.

Discussion

This suggests a reduced nutritional value for higher trophic levels under high Si:N ratios. Despite these strong qualitative changes under high Si, diatom cells appeared healthy and showed high photosynthetic efficiency. Our findings reveal great physiological plasticity and adaptability in phytoplankton under artificial upwelling, with Si-dependent trade-offs between primary producer quantity and quality.
Optimization of virtual design and machining time of the mold master ceramic jewelry products with Indonesian batik motifs
Authors: Bawono B. , Yuniarto T. , Sanusi C. E. P. , Felasari S. , Widyanarka O. K. W. , Anggoro P. W.
Published: January 2024

Batik has been the cultural heritage of the Indonesian nation since the 17th century. On 2 October 2009, the United Nations Educational, Scientific, and Cultural Organization (UNESCO) designated Batik as part of Indonesia’s traditional clothing as Indonesia’s cultural heritage. This research proves that Batik is an attractive and artistic ornament of ceramic jewelry products. This ornament can increase the selling value and storytelling of the product. Naruna is a local handmade porcelain ceramic factory in Indonesia with excellence in unique colored tableware and consistently trying to develop new designs in ceramic jewelry. Modern technology in computer-based virtual design and machining on dining plate tableware with the Batik Kawung motif is also applied in this paper to obtain a master design for ceramic jewelry prints. The design stage begins with selecting ornament patterns with creative methods to form a 3D CAD model of ceramic jewelry using artistic Art CAM. The optimization of computer-aided manufacturing-based to obtain machining strategy using the software. The software is Autodesk Power Mill, whose NC Code can be directly manufactured on a CNC router machine. This combination can speed up the production process time to meet the production capacity at Naruna and get detailed, accurate, precise, and consistent textures and ornaments, thereby meeting NCS consumer demand for ceramic jewelry products. The simulation results of the two master print patterns are 141 h, 56 min, and 46 s; the machining time is estimated at 153 h. This research saves about 11 h of time processing. The resulting NC Code can be appropriately processed on a CNC router machine with a Mach 3 post-processor.
The clinical course of hospitalized COVID-19 patients and aggravation risk prediction models: a retrospective, multi-center Korean cohort study
Authors: Moon Min Kyong , Ham Hyeonjung , Song Soo Min , Lee Chanhee , Goo Taewan , Oh Bumjo , Lee Seungyeoun , Kim Shin-Woo , Park Taesung
Published: January 2024

Background

Understanding the clinical course and pivotal time points of COVID-19 aggravation is critical for enhancing patient monitoring. This retrospective, multi-center cohort study aims to identify these significant time points and associate them with potential risk factors, leveraging data from a sizable cohort with mild-to-moderate symptoms upon admission.

Methods

This study included data from 1,696 COVID-19 patients with mild-to-moderate clinical severity upon admission across multiple hospitals in Daegu-Kyungpook Province (Daegu dataset) between February 18 and early March 2020 and 321 COVID-19 patients at Seoul Boramae Hospital (Boramae dataset) collected from February to July 2020. The approach involved: (1) identifying the optimal time point for aggravation using survival analyses with maximally selected rank statistics; (2) investigating the relationship between comorbidities and time to aggravation; and (3) developing prediction models through machine learning techniques. The models were validated internally among patients from the Daegu dataset and externally among patients from the Boramae dataset.

Results

The Daegu dataset showed a mean age of 51.0 ± 19.6 years, with 8 days for aggravation and day 5 being identified as the pivotal point for survival. Contrary to previous findings, specific comorbidities had no notable impact on aggravation patterns. Prediction models utilizing factors including age and chest X-ray infiltration demonstrated promising performance, with the top model achieving an AUC of 0.827 in external validation for 5 days aggravation prediction.

Conclusion

Our study highlights the crucial significance of the initial 5 days period post-admission in managing COVID-19 patients. The identification of this pivotal time frame, combined with our robust predictive models, provides valuable insights for early intervention strategies. This research underscores the potential of proactive monitoring and timely interventions in enhancing patient outcomes, particularly for those at risk of rapid aggravation. Our findings offer a meaningful contribution to understanding the COVID-19 clinical course and supporting healthcare providers in optimizing patient care and resource allocation.
Long axial field of view PET/CT in critically ill patients: lessons from a case report
Authors: van Snick J. H. , van Leer B. , Nijsten M. W. N. , Pillay J. , Slart R. H. J. A. , Glaudemans A. W. J. M. , van Rijsewijk N. D.
Published: January 2024

The introduction of new long axial field of view (LAFOV) scanners is a major milestone in positron emission tomography/computed tomography (PET/CT) imaging. With these new systems a revolutionary reduction in scan time can be achieved, concurrently lowering tracer dose. Therefore, PET/CT has come within reach for groups of patients in whom PET/CT previously was undesirable. In this case report we discuss the procedure of a continuous bed motion (CBM) total-body [18F]FDG PET/CT scan in an intensive care patient. We emphasize the clinical and technical possibilities with this new camera system, a matched clinical protocol, and the added value of a dedicated team.
Identification and characterization of a novel Cytorhabdovirus associated with goji berry (Lycium barbarum L.) crinkle disease
Authors: Wang Rong , Liu Sai , Xu Changqing , Yu Jing , Wei Jianhe , Ding Wanlong , Li Yong
Published: January 2024

Goji berry (Lycium barbarum L.) is a traditional Chinese herbal medicinal plant that is extensively cultivated in the arid and semiarid regions of northwest China. In this study, a novel cytorhabdovirus, tentatively named “goji cytorhabdovirus A (GCVA),” was identified from the goji berry plant exhibiting leaf crinkle symptoms through high-throughput sequencing (HTS). GCVA contains a linear, negative sense single-stranded RNA genome of 14,812 nucleotides and encodes six open reading frames in the order of 3′ leader-N-P-P4-M-G-L-5′ trailer. The genome of GCVA shares the highest nucleotide (nt) identity of 65.80% (16% query coverage) with yerba mate virus A (YmVA) (NC_076472). The N and L proteins also share low amino acid (aa) identities (<35.42 and < 41.23%, respectively) with known cytorhabdoviruses. Typical features of the viruses in the genus Cytorhabdovirus include a highly conserved consensus sequence in the intergenic regions and extensive complementation of the 5′ non-coding trailer and the 3′ leader. These features were also found in GCVA. These data in combination with a phylogenetic analysis that was based on the aa sequences of the N and L proteins support the proposal that GCVA is a new species in the genus Cytorhabdovirus.
Inactivation of lmo0946 (sif) induces the SOS response and MGEs mobilization and silences the general stress response and virulence program in Listeria monocytogenes
Authors: Ładziak Magdalena , Prochwicz Emilia , Gut Karina , Gomza Patrycja , Jaworska Karolina , Ścibek Katarzyna , Młyńska-Witek Marta , Kadej-Zajączkowska Katarzyna , Lillebaek Eva M. S. , Kallipolitis Birgitte H. , Krawczyk-Balska Agata
Published: January 2024

Bacteria have evolved numerous regulatory pathways to survive in changing environments. The SOS response is an inducible DNA damage repair system that plays an indispensable role in bacterial adaptation and pathogenesis. Here we report a discovery of the previously uncharacterized protein Lmo0946 as an SOS response interfering factor (Sif) in the human pathogen Listeria monocytogenes. Functional genetic studies demonstrated that sif is indispensable for normal growth of L. monocytogenes in stress-free as well as multi-stress conditions, and sif contributes to susceptibility to β-lactam antibiotics, biofilm formation and virulence. Absence of Sif promoted the SOS response and elevated expression of mobilome genes accompanied by mobilization of the A118 prophage and ICELm-1 mobile genetic elements (MGEs). These changes were found to be associated with decreased expression of general stress response genes from the σB regulon as well as virulence genes, including the PrfA regulon. Together, this study uncovers an unexpected role of a previously uncharacterized factor, Sif, as an inhibitor of the SOS response in L. monocytogenes.
Programmed cell death and Salmonella pathogenesis: an interactive overview
Authors: Zhang Yu , Xu Maodou , Guo Yujiao , Chen Li , Vongsangnak Wanwipa , Xu Qi , Lu Lizhi
Published: January 2024

Programmed cell death (PCD) is the collective term for the intrinsically regulated death of cells. Various types of cell death are triggered by their own programmed regulation during the growth and development of organisms, as well as in response to environmental and disease stresses. PCD encompasses apoptosis, pyroptosis, necroptosis, autophagy, and other forms. PCD plays a crucial role not only in the growth and development of organisms but also in serving as a component of the host innate immune defense and as a bacterial virulence strategy employed by pathogens during invasion. The zoonotic pathogen Salmonella has the ability to modulate multiple forms of PCD, including apoptosis, pyroptosis, necroptosis, and autophagy, within the host organism. This modulation subsequently impacts the bacterial infection process. This review aims to consolidate recent findings regarding the mechanisms by which Salmonella initiates and controls cell death signaling, the ways in which various forms of cell death can impede or restrict bacterial proliferation, and the interplay between cell death and innate immune pathways that can counteract Salmonella-induced suppression of host cell death. Ultimately, these insights may contribute novel perspectives for the diagnosis and treatment of clinical Salmonella-related diseases.
Plasma metabolites distinguish dementia with Lewy bodies from Alzheimer’s disease: a cross-sectional metabolomic analysis
Authors: Pan Xiaobei , Donaghy Paul C. , Roberts Gemma , Chouliaras Leonidas , O’Brien John T. , Thomas Alan J. , Heslegrave Amanda J. , Zetterberg Henrik , McGuinness Bernadette , Passmore Anthony P. , Green Brian D. , Kane Joseph P. M.
Published: January 2024

Background

In multifactorial diseases, alterations in the concentration of metabolites can identify novel pathological mechanisms at the intersection between genetic and environmental influences. This study aimed to profile the plasma metabolome of patients with dementia with Lewy bodies (DLB) and Alzheimer’s disease (AD), two neurodegenerative disorders for which our understanding of the pathophysiology is incomplete. In the clinical setting, DLB is often mistaken for AD, highlighting a need for accurate diagnostic biomarkers. We therefore also aimed to determine the overlapping and differentiating metabolite patterns associated with each and establish whether identification of these patterns could be leveraged as biomarkers to support clinical diagnosis.

Methods

A panel of 630 metabolites (Biocrates MxP Quant 500) and a further 232 metabolism indicators (biologically informative sums and ratios calculated from measured metabolites, each indicative for a specific pathway or synthesis; MetaboINDICATOR) were analyzed in plasma from patients with probable DLB (n = 15; age 77.6 ± 8.2 years), probable AD (n = 15; 76.1 ± 6.4 years), and age-matched cognitively healthy controls (HC; n = 15; 75.2 ± 6.9 years). Metabolites were quantified using a reversed-phase ultra-performance liquid chromatography column and triple-quadrupole mass spectrometer in multiple reaction monitoring (MRM) mode, or by using flow injection analysis in MRM mode. Data underwent multivariate (PCA analysis), univariate and receiving operator characteristic (ROC) analysis. Metabolite data were also correlated (Spearman r) with the collected clinical neuroimaging and protein biomarker data.

Results

The PCA plot separated DLB, AD and HC groups (R2 = 0.518, Q2 = 0.348). Significant alterations in 17 detected metabolite parameters were identified (q ≤ 0.05), including neurotransmitters, amino acids and glycerophospholipids. Glutamine (Glu; q = 0.045) concentrations and indicators of sphingomyelin hydroxylation (q = 0.039) distinguished AD and DLB, and these significantly correlated with semi-quantitative measurement of cardiac sympathetic denervation. The most promising biomarker differentiating AD from DLB was Glu:lysophosphatidylcholine (lysoPC a 24:0) ratio (AUC = 0.92; 95%CI 0.809–0.996; sensitivity = 0.90; specificity = 0.90).

Discussion

Several plasma metabolomic aberrations are shared by both DLB and AD, but a rise in plasma glutamine was specific to DLB. When measured against plasma lysoPC a C24:0, glutamine could differentiate DLB from AD, and the reproducibility of this biomarker should be investigated in larger cohorts.
A review of rigid point cloud registration based on deep learning
Authors: Chen Lei , Feng Changzhou , Ma Yunpeng , Zhao Yikai , Wang Chaorong
Published: January 2024

With the development of 3D scanning devices, point cloud registration is gradually being applied in various fields. Traditional point cloud registration methods face challenges in noise, low overlap, uneven density, and large data scale, which limits the further application of point cloud registration in actual scenes. With the above deficiency, point cloud registration methods based on deep learning technology gradually emerged. This review summarizes the point cloud registration technology based on deep learning. Firstly, point cloud registration based on deep learning can be categorized into two types: complete overlap point cloud registration and partially overlapping point cloud registration. And the characteristics of the two kinds of methods are classified and summarized in detail. The characteristics of the partially overlapping point cloud registration method are introduced and compared with the completely overlapping method to provide further research insight. Secondly, the review delves into network performance improvement summarizes how to accelerate the point cloud registration method of deep learning from the hardware and software. Then, this review discusses point cloud registration applications in various domains. Finally, this review summarizes and outlooks the current challenges and future research directions of deep learning-based point cloud registration.