bluuebunny/crossref_metadata_2025 huggingface dataset:
Nickel as a potential disruptor of thyroid function: benchmark modelling of human data
Authors: Maric Djurdjica , Baralic Katarina , Javorac Dragana , Mandic-Rajcevic Stefan , Zarkovic Milos , Antonijevic Biljana , Djukic-Cosic Danijela , Bulat Zorica , Djordjevic Aleksandra Buha
Published: September 2023

Introduction

Nickel (Ni) is one of the well-known toxic metals found in the environment. However, its influence on thyroid function is not explored enough. Hence, the aim of this study was to analyse the potential of Ni to disrupt thyroid function by exploring the relationship between blood Ni concentration and serum hormone levels (TSH, T4, T3, fT4 and fT3), as well as the parameters of thyroid homeostasis (SPINA-GT and SPINA-GD) by using correlation analysis and Benchmark (BMD) concept.

Methods

Ni concentration was measured by ICP-MS method, while CLIA was used for serum hormone determination. SPINA Thyr software was used to calculate SPINA-GT and SPINA-GD parameters. BMD analysis was performed by PROAST software (70.1). The limitations of this study are the small sample size and the uneven distribution of healthy and unhealthy subjects, limited confounding factors, as well as the age of the subjects that could have influenced the obtained results.

Results and discussion

The highest median value for blood Ni concentration was observed for the male population and amounted 8,278 µg/L. Accordingly, the statistically significant correlation was observed only in the male population, for Ni-fT4 and Ni-SPINA-GT pairs. The existence of a dose-response relationship was established between Ni and all the measured parameters of thyroid functions in entire population and in both sexes. However, the narrowest BMD intervals were obtained only in men, for Ni - SPINA-GT pair (1.36-60.9 µg/L) and Ni - fT3 pair (0.397-66.8 µg/L), indicating that even 78.68 and 83.25% of men in our study might be in 10% higher risk of Ni-induced SPINA-GT and fT3 alterations, respectively. Due to the relationship established between Ni and the SPINA-GT parameter, it can be concluded that Ni has an influence on the secretory function of the thyroid gland in men. Although the further research is required, these findings suggest possible role of Ni in thyroid function disturbances.
Statins and risk of type 2 diabetes: mechanism and clinical implications
Authors: Laakso Markku , Fernandes Silva Lilian
Published: September 2023

Statins are widely used to prevent cardiovascular disease events. Cardiovascular diseases and type 2 diabetes are tightly connected since type 2 diabetes is a major risk factor for cardiovascular diseases. Additionally, cardiovascular diseases often precede the development of type 2 diabetes. These two diseases have common genetic and environmental antecedents. Statins are effective in the lowering of cardiovascular disease events. However, they have also important side effects, including an increased risk of type 2 diabetes. The first study reporting an association of statin treatment with the risk of type 2 diabetes was the WOSCOPS trial (West of Scotland Coronary Prevention Study) in 2001. Other primary and secondary cardiovascular disease prevention studies as well as population-based studies have confirmed original findings. The purpose of our review is to examine and summarize the most important findings of these studies as well as to describe the mechanisms how statins increase the risk of type 2 diabetes.
Global incidence and prevalence of differentiated thyroid cancer in childhood: systematic review and meta-analysis
Authors: Moleti Mariacarla , Aversa Tommaso , Crisafulli Salvatore , Trifirò Gianluca , Corica Domenico , Pepe Giorgia , Cannavò Laura , Di Mauro Maria , Paola Giuseppe , Fontana Andrea , Calapai Fabrizio , Cannavò Salvatore , Wasniewska Malgorzata
Published: September 2023

Objective

Differentiated thyroid cancer (DTC) is rare in childhood and adolescence although it represents the most frequent endocrine malignancy in this population. DTC includes both papillary thyroid carcinoma (PTC) and follicular thyroid carcinoma (FTC). Most pediatric DTCs are PTCs, while FTCs are rare. To date, no systematic reviews on the global epidemiology of pediatric and adolescent DTC have been published. This systematic review and meta-analysis aims to estimate the overall incidence and prevalence of DTCs in patients aged 0–19 years.

Methods

The systematic research was conducted from January 2000 to December 2021 through MEDLINE via PubMed, Cochrane Library, and Embase databases. Two separate meta-analyses were performed for PTC and FTC.

Results

After the selection phase, a total of 15 studies (3,332 screened) met the inclusion criteria and are reported in the present systematic review. Five studies were conducted in Europe, five in North America, two in South America, one in Asia, one reported data for 49 countries and territories across the five continents, and one from both the USA and Africa. Most of the studies (n = 14) reported data obtained from national registries, and only one provided information collected from hospital medical records. Beyond the actual trend over time, our study reported a pooled global incidence rate (IR) of PTC and FTC in the pediatric age of 0.46 (95% CI: 0.33–0.59) and 0.07 (95% CI: 0.02–0.12) per 100,000 person-years, respectively. The highest IRs were recorded among Caucasian girls, and the lowest in black or other races/ethnicities.

Conclusion

Our data confirm that DTC in the pediatric population is a rare condition. The pooled IRs of the studies included in this meta-analysis are ~0.5 for PTC, which is the most common histological type when both genders and all age groups are considered. The implementation of a prospective international registry on pediatric DTC, as part of the wider European Registries for Rare Endocrine Conditions, has been recently proposed. In addition to providing relevant information on the clinical behavior of this rare disease, standardization of data collection will be pivotal to fill current gaps and allow an accurate estimation of the real incidence and risk factors of DTC.
A systematic literature review on the decarbonisation of the building sector—a case for Nigeria
Authors: Abam Fidelis Ibiang , Nwachukwu Chinedum Oscar , Emodi Nnaemeka Vincent , Okereke Chukwumerije , Diemuodeke Ogheneruona E. , Owolabi Abdulhameed Babatunde , Owebor Kesiena , Suh Dongjun , Huh Jeung-Soo
Published: September 2023

The buildings sector is responsible for over 36% of total global end-use energy utilization and nearly 40% of the total indirect and direct carbon emissions. Low-carbon or zero-energy buildings remain the only option to lessen the sector’s energy consumption and CO2 emissions. The current systematic study examines low-carbon buildings under deep decarbonization scenarios in selected global south regions from 2010 to 2021. The study was channelled by the PRISMA (“Preferred Reporting Items for Systematic reviews and Meta-Analyses”) review process, which identified 29 related articles from Scopus, Web of Science., and Google Scholar databases. The identified critical drivers of emissions were population, gross domestic product, dwelling characteristics, and urbanization. The dwelling characteristics contributed about 12% and 27% to the total CO2 emissions in the selected regions. The population varies between 23% and 27% across the areas. Specific findings were made for inclusion in the Nigeria model while the general results were observed and further studies proposed. Total investment from the private and public sectors was identified as key to achieving the transition process of decarbonization in the building sector.
Stackelberg game-based three-stage optimal pricing and planning strategy for hybrid shared energy storage
Authors: Xu Chenxuan , Zhang Tianhan , Si Linjun , Yang Junjie , Yu Hongfei , Wen Binbin , Chen Gang , Qiu Weiqiang
Published: September 2023

Inspired from sharing economy and advanced energy storage technologies, hybrid shared energy storage (HSES), as an innovative business model, can provide flexible storage leasing services to new energy stations (NESs) and bring additional profits to the energy storage owner. Under this business model, pricing and planning issues are the main focus of the HSES operator to increase revenues but are rarely considered in current studies. Therefore, a Stackelberg game-based three-stage optimal pricing and planning strategy of HSES is formulated for the operator. First, an HSES model considering two leasing options is developed to provide two kinds of short-term use rights of energy storage resources for NESs. Then, the interactions between selfish NESs and the HSES operator are characterized as a Stackelberg game, and a bi-level pricing and planning strategy optimization model is developed to help the HSES operator make optimal decisions. Finally, considering different characteristics in each stage of the Stackelberg game, a three-stage solution method based on the genetic algorithm (GA) and mixed-integer linear programming (MILP) models is proposed to solve the optimization problem. Case studies on six NESs in a certain region are taken to verify the effectiveness of the proposed strategy. Simulation results show that the HSES operator can obtain maximum profit under the proposed pricing and planning strategy. In addition, the proposed HSES leasing model can provide additional benefits to both the operator and NESs.
Comprehensive analysis of ceRNA network composed of circRNA, miRNA, and mRNA in septic acute kidney injury patients based on RNA-seq
Authors: Ma Si-Rong , Ma Qi , Ma Ya-Nan , Zhou Wen-Jie
Published: September 2023

Background: Sepsis is a complex, life-threatening clinical syndrome that can cause other related diseases, such as acute kidney injury (AKI). Circular RNA (circRNA) is a type of non-coding RNA with a diverse range of functions, and it plays essential roles in miRNA sponge. CircRNA plays a huge part in the development of various diseases. CircRNA and the competing endogenous RNA (ceRNA) regulatory network are unknown factors in the onset and progression of septic AKI (SAKI). This study aimed to clarify the complex circRNA-associated regulatory mechanism of circRNAs in SAKI.

Methods: We collected 40 samples of whole blood of adults, including 20 cases of SAKI and 20 cases of healthy controls. Moreover, five cases were each analyzed by RNA sequencing, and we identified differentially expressed circRNA, miRNA, and mRNA (DEcircRNAs, DEmiRNAs, and DEmRNAs, respectively). All samples were from SAKI patients with intraperitoneal infection.

Results: As a result, we screened out 236 DEcircRNAs, 105 DEmiRNAs, and 4065 DEmRNAs. Then, we constructed two co-expression networks based on RNA–RNA interaction, including circRNA–miRNA and miRNA–mRNA co-expression networks. We finally created a circRNA–miRNA–mRNA regulation network by combining the two co-expression networks. Functional and pathway analyses indicated that DEmRNAs in ceRNA were mostly concentrated in T cell activation, neutrophils and their responses, and cytokines. The protein–protein interaction network was established to screen out the key genes participating in the regulatory network of SAKI. The hub genes identified as the top 10 nodes included the following: ZNF727, MDFIC, IFITM2, FOXD4L6, CIITA, KCNE1B, BAGE2, PPIAL4A, USP17L7, and PRSS2.

Conclusion: To our knowledge, this research is the first study to describe changes in the expression profiles of circRNAs, miRNAs, and mRNAs in patients with SAKI. These findings provide a new treatment target for SAKI treatment and novel ideas for its pathogenesis.
Integrated omics and machine learning-assisted profiling of cysteine-rich-receptor-like kinases from three peanut spp. revealed their role in multiple stresses
Authors: Fatima Kinza , Sadaqat Muhammad , Azeem Farrukh , Rao Muhammad Junaid , Albekairi Norah A. , Alshammari Abdulrahman , Tahir ul Qamar Muhammad
Published: September 2023

Arachis hypogaea (peanut) is a leading oil and protein-providing crop with a major food source in many countries. It is mostly grown in tropical regions and is largely affected by abiotic and biotic stresses. Cysteine-rich receptor-like kinases (CRKs) is a family of transmembrane proteins that play important roles in regulating stress-signaling and defense mechanisms, enabling plants to tolerate stress conditions. However, almost no information is available regarding this gene family in Arachis hypogaea and its progenitors. This study conducts a pangenome-wide investigation of A. hypogaea and its two progenitors, A. duranensis and A. ipaensis CRK genes (AhCRKs, AdCRKs, and AiCRKs). The gene structure, conserved motif patterns, phylogenetic history, chromosomal distribution, and duplication were studied in detail, showing the intraspecies structural conservation and evolutionary patterns. Promoter cis-elements, protein–protein interactions, GO enrichment, and miRNA targets were also predicted, showing their potential functional conservation. Their expression in salt and drought stresses was also comprehensively studied. The CRKs identified were divided into three groups, phylogenetically. The expansion of this gene family in peanuts was caused by both types of duplication: tandem and segmental. Furthermore, positive as well as negative selection pressure directed the duplication process. The peanut CRK genes were also enriched in hormones, light, development, and stress-related elements. MicroRNA (miRNA) also targeted the AhCRK genes, which suggests the regulatory association of miRNAs in the expression of these genes. Transcriptome datasets showed that AhCRKs have varying expression levels under different abiotic stress conditions. Furthermore, the multi-stress responsiveness of the AhCRK genes was evaluated using a machine learning-based method, Random Forest (RF) classifier. The 3D structures of AhCRKs were also predicted. Our study can be utilized in developing a detailed understanding of the stress regulatory mechanisms of the CRK gene family in peanuts and its further studies to improve the genetic makeup of peanuts to thrive better under stress conditions.
Synergistic regulation of Notch signaling by different O-glycans promotes hematopoiesis
Authors: Tanwar Ankit , Stanley Pamela
Published: September 2023

Glycosylation of Notch receptors by O-fucose glycans regulates Notch ligand binding and Notch signaling during hematopoiesis. However, roles in hematopoiesis for other O-glycans that modify Notch receptors have not been determined. Here we show that the EGF domain specific GlcNAc transferase EOGT is required in mice for the optimal production of lymphoid and myeloid cells. The phenotype of Eogt null mice was largely cell-autonomous, and Notch target gene expression was reduced in T cell progenitors. Moreover, EOGT supported residual Notch signaling following conditional deletion of Pofut1 in hematopoietic stem cells (HSC). Eogt : Pofut1 double mutant HSC had more severe defects in bone marrow and in T and B cell development in thymus and spleen, compared to deletion of Pofut1 alone. The combined results show that EOGT and O-GlcNAc glycans are required for optimal hematopoiesis and T and B cell development, and that they act synergistically with POFUT1 and O-fucose glycans to promote Notch signaling in lymphoid and myeloid differentiation.
Comprehensive immunophenotyping of solid tumor-infiltrating immune cells reveals the expression characteristics of LAG-3 and its ligands
Authors: Garman Bradley , Jiang Can , Daouti Sherif , Kumar Sanah , Mehta Priyanka , Jacques Miye K. , Menard Laurence , Manjarrez-Orduno Nataly , Dolfi Sonia , Mukherjee Piali , Rai Sharmila Chamling , Lako Ana , Koenitzer Jennifer D. , David Justin M.
Published: September 2023

Background

Immune cell expression profiling from patient samples is critical for the successful development of immuno-oncology agents and is useful to understand mechanism-of-action, to identify exploratory biomarkers predictive of response, and to guide treatment selection and combination therapy strategies. LAG-3 is an inhibitory immune checkpoint that can suppress antitumor T-cell responses and targeting LAG-3, in combination with PD-1, is a rational approach to enhance antitumor immunity that has recently demonstrated clinical success. Here, we sought to identify human immune cell subsets that express LAG-3 and its ligands, to characterize the marker expression profile of these subsets, and to investigate the potential relationship between LAG-3 expressing subsets and clinical outcomes to immuno-oncology therapies.

Methods

Comprehensive high-parameter immunophenotyping was performed using mass and flow cytometry of tumor-infiltrating lymphocytes (TILs) and peripheral blood mononuclear cells (PBMCs) from two independent cohorts of samples from patients with various solid tumor types. Profiling of circulating immune cells by single cell RNA-seq was conducted on samples from a clinical trial cohort of melanoma patients treated with immunotherapy.

Results

LAG-3 was most highly expressed by subsets of tumor-infiltrating CD8 T central memory (TCM) and effector memory (TEM) cells and was frequently co-expressed with PD-1. We determined that these PD-1+ LAG-3+ CD8 memory T cells exhibited a unique marker profile, with greater expression of activation (CD69, HLA-DR), inhibitory (TIM-3, TIGIT, CTLA-4) and stimulatory (4-1BB, ICOS) markers compared to cells that expressed only PD-1 or LAG-3, or that were negative for both checkpoints. In contrast to tumors, LAG-3 expression was more limited in circulating immune cells from healthy donors and solid tumor patients. Additionally, we found abundant expression of the LAG-3 ligands MHC-II and galectin-3 in diverse immune cell types, whereas FGL1 and LSECtin were minimally expressed by immune cells in the tumor microenvironment (TME). Lastly, we found an inverse relationship between baseline and on-treatment levels of circulating LAG3 transcript-expressing CD8 memory T cells and response to combination PD-1 and CTLA-4 blockade in a clinical trial cohort of melanoma patients profiled by scRNAseq.

Conclusions

These results provide insights into the nature of LAG-3- and ligand-expressing immune cells within the TME, and suggest a biological basis for informing mechanistic hypotheses, treatment selection strategies, and combination immunotherapy approaches to support continued development of dual PD-1 and LAG-3 blockade.
Expanded Hemodialysis ameliorates uremia-induced impairment of vasculoprotective KLF2 and concomitant proinflammatory priming of endothelial cells through an ERK/AP1/cFOS-dependent mechanism
Authors: Zhao Hongfan , Wu Dashan , Gyamfi Michael Adu , Wang Pinchao , Luecht Christian , Pfefferkorn Anna Maria , Ashraf Muhammad Imtiaz , Kamhieh-Milz Julian , Witowski Janusz , Dragun Duska , Budde Klemens , Schindler Ralf , Zickler Daniel , Moll Guido , Catar Rusan
Published: September 2023

Aims

Expanded hemodialysis (HDx) therapy with improved molecular cut-off dialyzers exerts beneficial effects on lowering uremia-associated chronic systemic microinflammation, a driver of endothelial dysfunction and cardiovascular disease (CVD) in hemodialysis (HD) patients with end-stage renal disease (ESRD). However, studies on the underlying molecular mechanisms are still at an early stage. Here, we identify the (endothelial) transcription factor Krüppel-like factor 2 (KLF2) and its associated molecular signalling pathways as key targets and regulators of uremia-induced endothelial micro-inflammation in the HD/ESRD setting, which is crucial for vascular homeostasis and controlling detrimental vascular inflammation.

Methods and results

First, we found that human microvascular endothelial cells (HMECs) and other typical endothelial and kidney model cell lines (e.g. HUVECs, HREC, and HEK) exposed to uremic serum from patients treated with two different hemodialysis regimens in the Permeability Enhancement to Reduce Chronic Inflammation II (PERCI-II) crossover clinical trial - comparing High-Flux (HF) and Medium Cut-Off (MCO) membranes - exhibited strongly reduced expression of vasculoprotective KLF2 with HF dialyzers, while dialysis with MCO dialyzers led to the maintenance and restoration of physiological KLF2 levels in HMECs. Mechanistic follow-up revealed that the strong downmodulation of KLF2 in HMECs exposed to uremic serum was mediated by a dominant engagement of detrimental ERK instead of beneficial AKT signalling, with subsequent AP1-/c-FOS binding in the KLF2 promoter region, followed by the detrimental triggering of pleiotropic inflammatory mediators, while the introduction of a KLF2 overexpression plasmid could restore physiological KLF2 levels and downmodulate the detrimental vascular inflammation in a mechanistic rescue approach.

Conclusion

Uremia downmodulates vasculoprotective KLF2 in endothelium, leading to detrimental vascular inflammation, while MCO dialysis with the novel improved HDx therapy approach can maintain physiological levels of vasculoprotective KLF2.
SARS-CoV-2 spike antigen-specific B cell and antibody responses in pre-vaccination period COVID-19 convalescent males and females with or without post-covid condition
Authors: Limoges Marc-André , Quenum Akouavi Julite Irmine , Chowdhury Mohammad Mobarak Hussain , Rexhepi Fjolla , Namvarpour Mozhdeh , Akbari Sara Ali , Rioux-Perreault Christine , Nandi Madhuparna , Lucier Jean-François , Lemaire-Paquette Samuel , Premkumar Lakshmanane , Durocher Yves , Cantin André , Lévesque Simon , Dionne Isabelle J. , Menendez Alfredo , Ilangumaran Subburaj , Allard-Chamard Hugues , Piché Alain , Ramanathan Sheela
Published: September 2023

Background

Following SARS-CoV-2 infection a significant proportion of convalescent individuals develop the post-COVID condition (PCC) that is characterized by wide spectrum of symptoms encompassing various organs. Even though the underlying pathophysiology of PCC is not known, detection of viral transcripts and antigens in tissues other than lungs raise the possibility that PCC may be a consequence of aberrant immune response to the viral antigens. To test this hypothesis, we evaluated B cell and antibody responses to the SARS-CoV-2 antigens in PCC patients who experienced mild COVID-19 disease during the pre-vaccination period of COVID-19 pandemic.

Methods

The study subjects included unvaccinated male and female subjects who developed PCC or not (No-PCC) after clearing RT-PCR confirmed mild COVID-19 infection. SARS-CoV-2 D614G and omicron RBD specific B cell subsets in peripheral circulation were assessed by flow cytometry. IgG, IgG3 and IgA antibody titers toward RBD, spike and nucleocapsid antigens in the plasma were evaluated by ELISA.

Results

The frequency of the B cells specific to D614G-RBD were comparable in convalescent groups with and without PCC in both males and females. Notably, in females with PCC, the anti-D614G RBD specific double negative (IgD-CD27-) B cells showed significant correlation with the number of symptoms at acute of infection. Anti-spike antibody responses were also higher at 3 months post-infection in females who developed PCC, but not in the male PCC group. On the other hand, the male PCC group also showed consistently high anti-RBD IgG responses compared to all other groups.

Conclusions

The antibody responses to the spike protein, but not the anti-RBD B cell responses diverge between convalescent males and females who develop PCC. Our findings also suggest that sex-related factors may also be involved in the development of PCC via modulating antibody responses to the SARS-CoV-2 antigens.
Identification of SKOR2 IgG as a novel biomarker of paraneoplastic neurologic syndrome
Authors: Rezk Mohamed , Pittock Sean J. , Kapadia Ronak K. , Knight Andrew M. , Guo Yong , Gupta Pranjal , LaFrance-Corey Reghann G. , Zekeridou Anastasia , McKeon Andrew , Dasari Surendra , Mills John R. , Dubey Divyanshu
Published: September 2023

Introduction

The development of new autoantigen discovery techniques, like programmable phage immunoprecipitation sequencing (PhIP-Seq), has accelerated the discovery of neural-specific autoantibodies. Herein, we report the identification of a novel biomarker for paraneoplastic neurologic syndrome (PNS), Sloan-Kettering-Virus-Family-Transcriptional-Corepressor-2 (SKOR2)-IgG, utilizing PhIP-Seq. We have also performed a thorough clinical validation using normal, healthy, and disease/cancer control samples.

Methods

Stored samples with unclassified staining at the junction of the Purkinje cell and the granule cell layers were analyzed by PhIP-Seq for putative autoantigen identification. The autoantigen was confirmed by recombinant antigen-expressing cell-based assay (CBA), Western blotting, and tissue immunofluorescence assay colocalization.

Results

PhIP-Seq data revealed SKOR2 as the candidate autoantigen. The target antigen was confirmed by a recombinant SKOR-2-expressing, and cell lysate Western blot. Furthermore, IgG from both patient samples colocalized with a commercial SKOR2–specific IgG on cryosections of the mouse brain. Both SKOR2 IgG-positive patients had central nervous system involvement, one presenting with encephalitis and seizures (Patient 1) and the other with cognitive dysfunction, spastic ataxia, dysarthria, dysphagia, and pseudobulbar affect (Patient 2). They had a refractory progressive course and were diagnosed with adenocarcinoma (Patient 1: lung, Patient 2: gallbladder). Sera from adenocarcinoma patients without PNS (n=30) tested for SKOR2-IgG were negative.

Discussion

SKOR2 IgG represents a novel biomarker for PNS associated with adenocarcinoma. Identification of additional SKOR2 IgG-positive cases will help categorize the associated neurological phenotype and the risk of underlying malignancy.
Marine litter-fauna interactions: a standardised reporting framework and critical review of the current state of research with a focus on submarine canyons
Authors: Bruemmer Alice Lauren , Dissanayake Awantha , Davies Jaime Selina
Published: September 2023

Litter is ubiquitous in the ocean, interacting with fauna and causing impacts that are unquantified at present. Mainly sourced from land, marine litter is very persistent, and undergoes slow degradation upon settling on the ocean floor. Submarine canyons contain more litter than other oceanographic features due to hydrological processes, but study of litter in canyons is made difficult by logistical requirements. Monitoring and quantification of marine litter often do not consider interactions between fauna and litter, meaning impacts are largely unconsidered and unknown. Among publications that have reported litter-fauna (L-F) interactions in canyons, the large majority occur in the Mediterranean Sea, and the most reported interaction is of corals entangled in fishing gear. When it occurs, the reporting of L-F interactions is unstandardised, resulting in a lack of global comparison and trend analysis. A standardised, comprehensive framework for the reporting of L-F interactions has been created and includes 6 major categories: entanglement, ingestion, smothering, habitat provision, adaptive behaviour, and encountering (entanglement and smothering occur on abiotic features as well). Use of the framework will aid in research collaboration and creation of a global dataset of L-F interactions. Impacts resulting from interactions are plentiful, most coming from entanglement and smothering.
Monsoon-driven seasonal hypoxia along the northern coast of Oman
Authors: DiMarco Steven F. , Wang Zhankun , Chapman Piers , al-Kharusi Lubna , Belabbassi Leila , al-Shaqsi Hilal , Stoessel Marion , Ingle Stephanie , Jochens Ann E. , Howard Matthew K.
Published: September 2023

Dissolved oxygen and current observations from a cabled ocean observatory in the Sea of Oman show that the annual recurrence of coastal hypoxia, defined as dissolved oxygen concentrations ≤63 μM, is associated with the seasonal cycle of local monsoon winds. The observations represent the first long-term (5+ years) continuous moored observations off the northern Omani coast. During the summer/fall southwest (SW) monsoon season (Jun-Nov), winds in the Sea of Oman generate ocean currents that result in coastal upwelling of subsurface waters with low dissolved oxygen concentrations. The source of the poorly oxygenated water is the oxygen minimum zone (OMZ) in the Arabian Sea, a layer approximately 1000-m thick within the 100 to 1200 m depth range, where dissolved oxygen values approach anoxia. During the winter monsoon season (Dec-Feb), the Sea of Oman winds are from the northwest, forcing strong and persistent southeast currents. These winds generate oceanic downwelling conditions along the coastal ocean that ventilate waters at depth. Possible impacts of the monsoon-driven seasonal hypoxia on local fisheries and implications due to climate change are also discussed in this study.
Challenges of refractive cataract surgery in the era of myopia epidemic: a mini-review
Authors: Du Yu , Meng Jiaqi , He Wenwen , Lu Yi , Zhu Xiangjia
Published: September 2023

Myopia is the leading cause of visual impairment in the world. With ever-increasing prevalence in these years, it creates an alarming global epidemic. In addition to the difficulty in seeing distant objects, myopia also increases the risk of cataract and advances its onset, greatly affecting the productivity of myopes of working age. Cataract management in myopic eyes, especially highly myopic eyes is originally more complicated than that in normal eyes, whereas the growing population of cataract with myopia, increasing popularity of corneal and lens based refractive surgery, and rising demand for spectacle independence after cataract surgery all further pose unprecedented challenges to ophthalmologists. Previous history of corneal refractive surgery and existence of implantable collamer lens will both affect the accuracy of biometry including measurement of corneal curvature and axial length before cataract surgery, which may result in larger intraocular lens (IOL) power prediction errors and a compromise in the surgical outcome especially in a refractive cataract surgery. A prudent choice of formula for cataract patients with different characteristics is essential in improving this condition. Besides, the characteristics of myopic eyes might affect the long-term stability of IOL, which is important for the maintenance of visual outcomes especially after the implantation of premium IOLs, thus a proper selection of IOL accordingly is crucial. In this mini-review, we provide an overview of the impact of myopia epidemic on treatment for cataract and to discuss new challenges that surgeons may encounter in the foreseeable future when planning refractive cataract surgery for myopic patients.
Microbial community diversity and potential functionality in response to dam construction along the Three Gorge Reservoir, China
Authors: Wang Huan , Yan Bin , Wu Yan , Yin Maoyun , Wang Maoqing , Fu Chuan
Published: September 2023

River and reservoir bacterial communities are the most basic part of river biomes and ecosystem structure, and play an important role in river biological processes. Yet, it remains unclear how highly regulated dam reservoirs affect both soil and sediment bacterial communities. A temporal distribution pattern of bacterial communities was investigated using Illumina MiSeq sequencing in a transition section of the Three Gorges Reservoir (TGR). In total, 106,682 features belong to the bacteria kingdom, encompassing 95 phyla, 228 classes, 514 orders, 871 families, 1959 genera, and 3,053 species. With water level regulation, Shannon diversity index, and observed species differed significantly, with no significant difference in Simpson evenness. Both in the high water level period (October) and the low water level period (June), Proteobacteria, Acidobacteri, and Chloroflexi were the most abundant phyla. Whereas, based on PCA plots and Circos plot, the microbial community structure has changed significantly. LEfSe method was used to identify the classified bacterial taxa with significant abundance differences between the low water level and high water level periods. KOs (KEGG Orthology) pathway enrichment analysis were conducted to investigate functional and related metabolic pathways in groups. To some extent, it can be inferred that water level regulation affects community growth by affecting the metabolism of the microbial community.
Native circulating Brucella melitensis lineages causing a brucellosis epidemic in Qinghai, China
Authors: Xue Hongmei , Zhao Zhijun , Wang Jianling , Ma Li , Li Jiquan , Yang Xuxin , Ren Lingling , Xu Liqing , Liu Zhiguo , Li Zhenjun
Published: September 2023

Since 2010, the cases and incidences of human brucellosis have been increasing annually in Qinghai (QH) Province. Molecular epidemiology and phylogenetic analyses of strains from this region are crucial to better understand the transmission of the disease and the evolutionary patterns ofBrucellastrains. In this study, classical bio-typing assay, multilocus variable-number tandem repeat analysis, and the whole-genome sequencing–single-nucleotide polymorphism approach were used to illustrate the epidemiological and evolutionary patterns ofBrucella melitensis. A total of 54B. melitensisbv. 3 strains were isolated and molecularly characterized, with all strains belonging to the East Mediterranean lineages. Cross-regional transmission events (i.e., between counties) were caused by common sources of infection, suggesting that predominant circulating genotypes are endemic in different regions. Strengthening surveillance in animal brucellosis and controlling infected animals’ cross-border movement are necessary. Two strains isolated from humans and marmots were clustered in the same sub-clade, implying the possible existence of direct and/or indirect contact between sheep (and goats) and wildlife (marmots), but this needs to be verified by further investigations. The global-scale phylogenetic analysis indicated that 54 strains sorted into six subclades, four of which formed independent lineages, suggesting that the increase in the incidence rate of human brucellosis may be caused by local circulating lineages. Further strengthening the serology and pathogen surveillance of animals (wildlife) and humans will contribute to an in-depth understanding of the transmission chain of human brucellosis in this region.
Evaluation of whole and core genome multilocus sequence typing allele schemes for Salmonella enterica outbreak detection in a national surveillance network, PulseNet USA
Authors: Leeper Molly M. , Tolar Beth M. , Griswold Taylor , Vidyaprakash Eshaw , Hise Kelley B. , Williams Grant M. , Im Sung B. , Chen Jessica C. , Pouseele Hannes , Carleton Heather A.
Published: September 2023

Salmonella enterica is a leading cause of bacterial foodborne and zoonotic illnesses in the United States. For this study, we applied four different whole genome sequencing (WGS)-based subtyping methods: high quality single-nucleotide polymorphism (hqSNP) analysis, whole genome multilocus sequence typing using either all loci [wgMLST (all loci)] and only chromosome-associated loci [wgMLST (chrom)], and core genome multilocus sequence typing (cgMLST) to a dataset of isolate sequences from 9 well-characterized Salmonella outbreaks. For each outbreak, we evaluated the genomic and epidemiologic concordance between hqSNP and allele-based methods. We first compared pairwise genomic differences using all four methods. We observed discrepancies in allele difference ranges when using wgMLST (all loci), likely caused by inflated genetic variation due to loci found on plasmids and/or other mobile genetic elements in the accessory genome. Therefore, we excluded wgMLST (all loci) results from any further comparisons in the study. Then, we created linear regression models and phylogenetic tanglegrams using the remaining three methods. K-means analysis using the silhouette method was applied to compare the ability of the three methods to partition outbreak and sporadic isolate sequences. Our results showed that pairwise hqSNP differences had high concordance with cgMLST and wgMLST (chrom) allele differences. The slopes of the regressions for hqSNP vs. allele pairwise differences were 0.58 (cgMLST) and 0.74 [wgMLST (chrom)], and the slope of the regression was 0.77 for cgMLST vs. wgMLST (chrom) pairwise differences. Tanglegrams showed high clustering concordance between methods using two statistical measures, the Baker’s gamma index (BGI) and cophenetic correlation coefficient (CCC), where 9/9 (100%) of outbreaks yielded BGI values ≥ 0.60 and CCCs were ≥ 0.97 across all nine outbreaks and all three methods. K-means analysis showed separation of outbreak and sporadic isolate groups with average silhouette widths ≥ 0.87 for outbreak groups and ≥ 0.16 for sporadic groups. This study demonstrates that Salmonella isolates clustered in concordance with epidemiologic data using three WGS-based subtyping methods and supports using cgMLST as the primary method for national surveillance of Salmonella outbreak clusters.
Bioinformatic and functional characterization of cyclic-di-GMP metabolic proteins in Vibrio alginolyticus unveils key diguanylate cyclases controlling multiple biofilm-associated phenotypes
Authors: Gong Xiao-Xiao , Zeng Yan-Hua , Chen Hai-Min , Zhang Na , Han Yue , Long Hao , Xie Zhen-Yu
Published: September 2023

The biofilm lifestyle is critical for bacterial survival and proliferation in the fluctuating marine environment. Cyclic diguanylate (c-di-GMP) is a key second messenger during bacterial adaptation to various environmental signals, which has been identified as a master regulator of biofilm formation. However, little is known about whether and how c-di-GMP signaling regulates biofilm formation in Vibrio alginolyticus, a globally dominant marine pathogen. Here, a large set of 63 proteins were predicted to participate in c-di-GMP metabolism (biosynthesis or degradation) in a pathogenic V. alginolyticus strain HN08155. Guided by protein homology, conserved domains and gene context information, a representative subset of 22 c-di-GMP metabolic proteins were selected to determine which ones affect biofilm-associated phenotypes. By comparing phenotypic differences between the wild-type and mutants or overexpression strains, we found that 22 c-di-GMP metabolic proteins can separately regulate different phenotypic outputs in V. alginolyticus. The results indicated that overexpression of four c-di-GMP metabolic proteins, including VA0356, VA1591 (CdgM), VA4033 (DgcB) and VA0088, strongly enhanced rugose colony morphotypes and strengthened Congo Red (CR) binding capacity, both of which are indicators of biofilm matrix overproduction. Furthermore, rugose enhanced colonies were accompanied by increased transcript levels of extracellular polysaccharide (EPS) biosynthesis genes and decreased expression of flagellar synthesis genes compared to smooth colonies (WTpBAD control), as demonstrated by overexpression strains WTp4033 and ∆VA4033p4033. Overall, the high abundance of c-di-GMP metabolic proteins in V. alginolyticus suggests that c-di-GMP signaling and regulatory system could play a key role in its response and adaptation to the ever-changing marine environment. This work provides a robust foundation for the study of the molecular mechanisms of c-di-GMP in the biofilm formation of V. alginolyticus.
Exploration of probiotic attributes in lactic acid bacteria isolated from fermented Theobroma cacao L. fruit using in vitro techniques
Authors: Nandha Mausamy C. , Shukla Rachana M.
Published: September 2023

Probiotics are known for their health-promoting properties and are recognized as beneficial microorganisms. The current investigation delves into the isolation and comprehensive in vitro characterization of lactic acid bacteria (LAB) obtained from the Indian-origin Theobroma cacao L. Forastero variety to assess their potential as probiotic candidates. Eleven LAB isolates were obtained, and among them, five exhibited classical LAB traits. These five isolates underwent rigorous in vitro characterization to evaluate their suitability as probiotics. The assessments included resilience against acid and bile salts, which are crucial for probiotic viability. Additionally, the isolates were subjected to simulated gastric and pancreatic fluids and lysozyme exposure to assess their survival rates. Auto- aggregation, co-aggregation, hydrophobicity, and exopolysaccharide production were also examined. The inhibitory potential of α-glucosidase, an enzyme related to glucose metabolism, was measured, and antioxidant activity was evaluated using DPPH and ABTS assays. A safety assessment was conducted to confirm the non-pathogenic nature of the isolates. Among the five isolates, CR2 emerged as a standout candidate with maximal bile salt hydrolase activity, phenol resistance, and lysozyme resistance. CR2 and CYF3 exhibited notable survival rates under simulated conditions. The isolates displayed variable degrees of auto-aggregation, co-aggregation, and hydrophobicity. CR2 exhibited the highest exopolysaccharide production (0.66 mg/mL), suggesting diverse applications in the food industry. CR2 also demonstrated the highest inhibition rate against α-glucosidase (56.55%) and substantial antioxidant activity (79.62% DPPH, 83.45% ABTS). Safety assessment confirmed the non- pathogenic nature of the isolates. Molecular characterization identified CR2 as Lactococcus lactis subsp. lactis and CYF3 as Limnosilactobacillus fermentum. Both strains exhibited commendable probiotic and technological attributes, positioning them as promising candidates for functional foods and beyond. This study provides valuable insights into the in vitro characterization of LAB isolated from Indian Theobroma cacao L., highlighting their potential as probiotic candidates with advantageous traits, including survival in hostile conditions, beneficial enzymatic activities, bioactivity, and other essential attributes.
Blood pressure trajectory of inpatient stroke rehabilitation patients from the Determining Optimal Post-Stroke Exercise (DOSE) trial over the first 12 months post-stroke
Authors: Hung Stanley H. , Tierney Christopher , Klassen Tara D. , Schneeberg Amy , Bayley Mark T. , Dukelow Sean P. , Hill Michael D. , Krassioukov Andrei , Pooyania Sepideh , Poulin Marc J. , Yao Jennifer , Eng Janice J.
Published: September 2023

Background

High blood pressure (BP) is the primary risk factor for recurrent strokes. Despite established clinical guidelines, some stroke survivors exhibit uncontrolled BP over the first 12 months post-stroke. Furthermore, research on BP trajectories in stroke survivors admitted to inpatient rehabilitation hospitals is limited. Exercise is recommended to reduce BP after stroke. However, the effect of high repetition gait training at aerobic intensities (>40% heart rate reserve; HRR) during inpatient rehabilitation on BP is unclear. We aimed to determine the effect of an aerobic gait training intervention on BP trajectory over the first 12 months post-stroke.

Methods

This is a secondary analysis of the Determining Optimal Post-Stroke Exercise (DOSE) trial. Participants with stroke admitted to inpatient rehabilitation hospitals were recruited and randomized to usual care (n = 24), DOSE1 (n = 25; >2,000 steps, 40–60% HRR for >30 min/session, 20 sessions over 4 weeks), or DOSE2 (n = 25; additional DOSE1 session/day) groups. Resting BP [systolic (SBP) and diastolic (DBP)] was measured at baseline (inpatient rehabilitation admission), post-intervention (near inpatient discharge), 6- and 12-month post-stroke. Linear mixed-effects models were used to examine the effects of group and time (weeks post-stroke) on SBP, DBP and hypertension (≥140/90 mmHg; ≥130/80 mmHg, if diabetic), controlling for age, stroke type, and baseline history of hypertension.

Results

No effect of intervention group on SBP, DBP, or hypertension was observed. BP increased from baseline to 12-month post-stroke for SBP (from [mean ± standard deviation] 121.8 ± 15.0 to 131.8 ± 17.8 mmHg) and for DBP (74.4 ± 9.8 to 78.5 ± 10.1 mmHg). The proportion of hypertensive participants increased from 20.8% (n = 15/72) to 32.8% (n = 19/58). These increases in BP were statistically significant: an effect [estimation (95%CI), value of p] of time was observed on SBP [0.19 (0.12–0.26) mmHg/week, p < 0.001], DBP [0.09 (0.05–0.14) mmHg/week, p < 0.001], and hypertension [OR (95%CI): 1.03 (1.01–1.05), p = 0.010]. A baseline history of hypertension was associated with higher SBP by 13.45 (8.73–18.17) mmHg, higher DBP by 5.57 (2.02–9.12) mmHg, and 42.22 (6.60–270.08) times the odds of being hypertensive at each timepoint, compared to those without.

Conclusion

Blood pressure increased after inpatient rehabilitation over the first 12 months post-stroke, especially among those with a history of hypertension. The 4-week aerobic gait training intervention did not influence this trajectory.
Arterial spin labeling image findings in the acute phase in paediatric patients with acute encephalopathy with biphasic seizures and late reduced diffusion
Authors: Kawano Go , Tokutomi Kentaro , Kikuchi Yoshitomo , Sakata Kensuke , Sakaguchi Hirotaka , Yokochi Takaoki , Akita Yukihiro , Matsuishi Toyojiro
Published: September 2023

Introduction

Diagnosing acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) after the first seizure (early seizure/seizures, ES/ESs) is challenging because a reduced apparent diffusion coefficient (ADC) in the cortical or subcortical white matter, often described as having a “bright-tree appearance (BTA),” is usually not observed until secondary seizures (late seizures, LSs) occur. Previous studies have reported hypoperfusion on arterial spin labeling (ASL) within 24 h after ES/ESs in patients with AESD and hyperperfusion within 24 h after LS onset. This study aimed to investigate cerebral blood flow in the hyperacute phase (between ES/ESs and LSs) using ASL in patients with AESD.

Methods

Eight ASL images were acquired in six patients with AESD admitted to our hospital from October 2021 to October 2022. ASL findings in the hyperacute phase were investigated and video-electroencephalogram findings obtained around ASL image acquisition in the hyperacute phase were evaluated.

Results

Four ASL images were obtained for three patients before LS onset, with three images showing hyperperfusion areas and one image showing hypoperfusion areas. These hyperperfuion regions coincided with BTA on subsequent images of these patients.

In one patient, the first ASL image was obtained in the late hyperacute phase and revealed hyperperfusion areas with a slightly abnormal change on diffusion-weighted image (DWI), which were not accompanied by ADC abnormalities. The second ASL image obtained 51 h after the first ASL, and before LS onset revealed more prominent hyperperfusion areas than the first ASL image, which were accompanied by BTA. In another patient, the ASL image obtained 82 h after ES revealed hyperperfusion areas without abnormal change on DWI or ADC.

Conclusion

This study revealed that two patients exhibited hyperperfusion regions and another patient exhibited hypoperfusion regions among three patients who underwent ASL imaging during the period from 24 h after ES/ESs to LSs in patients with LSs or cooling initiation in patients without LSs due to early anaesthesia induction (late hyperacute phase). Further prospective studies on cerebral blood flow are required to explore the relationship among the timing of image acquisition, the presence of electrographic seizures, and ASL findings in patients with AESD.