bluuebunny/crossref_metadata_2025 huggingface dataset:
Oral microbiome mediated inflammation, a potential inductor of vascular diseases: a comprehensive review
Authors: Gualtero Diego F. , Lafaurie Gloria Inés , Buitrago Diana Marcela , Castillo Yormaris , Vargas-Sanchez Paula Katherine , Castillo Diana Marcela
Published: August 2023

The dysbiosis of the oral microbiome and vascular translocation of the periodontopathic microorganism to peripheral blood can cause local and systemic extra-oral inflammation. Microorganisms associated with the subgingival biofilm are readily translocated to the peripheral circulation, generating bacteremia and endotoxemia, increasing the inflammation in the vascular endothelium and resulting in endothelial dysfunction. This review aimed to demonstrate how the dysbiosis of the oral microbiome and the translocation of oral pathogen-induced inflammation to peripheral blood may be linked to cardiovascular diseases (CVDs). The dysbiosis of the oral microbiome can regulate blood pressure and activate endothelial dysfunction. Similarly, the passage of periodontal microorganisms into the peripheral circulation and their virulence factors have been associated with a vascular compartment with a great capacity to activate endothelial cells, monocytes, macrophages, and plaquettes and increase interleukin and chemokine secretion, as well as oxidative stress. This inflammatory process is related to atherosclerosis, hypertension, thrombosis, and stroke. Therefore, oral diseases could be involved in CVDs via inflammation. The preclinic and clinical evidence suggests that periodontal disease increases the proinflammatory markers associated with endothelial dysfunction. Likewise, the evidence from clinical studies of periodontal treatment in the long term evidenced the reduction of these markers and improved overall health in patients with CVDs.
Decadal modulation of ENSO and IOD impacts on the Indian Ocean upwelling
Authors: Zhang Xiaolin , Mochizuki Takashi
Published: August 2023

The decadal modulations are observed in impacts of El Niño and Southern Ocean (ENSO) and Indian Ocean Dipole (IOD) on the tropical Indian Ocean upwelling. Here, we explore important contributors to the decadal modulations by combining the observational data since 1958 and statistical model simulations. A Bayesian Dynamic Linear Model (BDLM), which represents the temporal modulations of the IOD and ENSO impacts, reproduces the timeseries of the eastern and western Indian Ocean (EIO and WIO) upwellings more realistically than a conventional Static Linear regression Model does. The time-varying regression coefficients in BDLM indicate that the observed shift of the IOD impact on the EIO upwelling around 1980 is mainly due to the changes of alongshore wind stress forcing and the sensitivity of the upper ocean temperature in the EIO through the surface warming tendency and the enhanced ocean stratification. In contrast, the impacts of ENSO and IOD on the WIO are modulated in relation to the decadal variability of the tropical Pacific Ocean. When the eastern tropical Pacific Ocean is observed warmer on decadal timescales, the accompanying changes of the dominant ENSO flavors contribute to modulating the strengths of the atmospheric convective activity over the Indian-Pacific warm pool and the easterly wind variations in the equatorial Indian Ocean.
Lithosphere density structure of southeastern South America sedimentary basins from the analysis of residual gravity anomalies
Authors: Moura Denise Silva de , Marangoni Yára Regina
Published: August 2023

We conduct a gravity study of the lithosphere beneath three large sedimentary basins in southeastern South America: Paraná, Chaco-Paraná, and Pantanal. We compile a massive gravity database and estimate the free-air and Bouguer gravity anomalies, resulting in a novel complete Bouguer anomaly map for the study area. To discern the influence of crustal loads with known lithologies, including sediments, basalts, and topography variations of the Moho discontinuity, we calculate their gravity effects and subsequently remove them from the complete Bouguer anomaly, leading to the development of our residual Bouguer anomaly map. This map highlights unknown anomalous masses within the lithosphere. To aid in the interpretation of these residual anomalies, we perform a 2D forward modeling. Based on our results, we propose new boundaries for the Paranapanema block and the Luiz Alves craton. Additionally, we propose that the Ponta Grossa swarm dike has a more substantial impact on the crust and lithosphere than previously considered, and delimit the region of influence of this magmatism in the lithosphere. Moreover, tectonic features such as the São Francisco paleocontinent and the Rio de La Plata craton appear to be associated with negative residual Bouguer anomaly regions. Furthermore, we identify and emphasize the significance of the Western Paraná Suture, which acts as a demarcation between the Paraná Basin region and the Pantanal and Chaco-Paraná basins. Remarkably, this suture appears to play a more important role in shaping the density structure of the southwest of South America than the age and tectonic history of the sedimentary basins.
Equitable global health research collaborations with a mind of human dignity
Authors: Achana Felix , Boah Michael , Chirawurah Dennis , Owusu-Marfo Joseph , Ndago Joyce Aputere , Santah Colette , Mohammed Abdul-Raheem , Adokiya Martin Nyaaba
Published: August 2023

This paper explores the importance of equitable global health research collaborations that prioritize human dignity. It addresses the need for Global North partners to increase their efforts in raising awareness among all actors in global health. The aim is to bridge the gap in research collaborations and promote equitable practices that uphold the principles of human dignity and equity. A comprehensive review of existing literature and case studies was conducted to examine current practices and challenges in global health research collaborations. The review focused on the role of Global North partners in promoting equitable collaborations, capacity building efforts, and the impact of colonial legacies on research dynamics. The findings highlight the need for deliberate actions by Global North partners to raise awareness and promote equitable research collaborations. Initiatives such as Principal Investigator positions to partners from low- and middle-income countries (LMICs) during grant applications have been observed. Assigning first/last authorship positions to LMIC members is gaining momentum. However, further efforts are necessary to enhance the inclusivity of global health research collaborations. We emphasize the need for standardized definitions of global health that encompass human dignity and equity. Urgent action is required to ensure that all actors in global health research collaborations embrace human dignity. By deploying new techniques and tools where they are most needed, we can effectively promote equitable research collaborations that contribute to improving the health of individuals worldwide.
Academic identity and “education for sustainable development”: a grounded theory
Authors: Shephard Kerry
Published: August 2023

The research described in this article set out to explore the nature of higher education institutions’ commitment to teaching for social, environmental and economic justice in the context of the SDGs and to develop a theory of this phenomenon to support further research. The research used grounded theory methodology and took place over a two-month period in 2023. Cases were collected in four universities in New Zealand, India and Sweden and included interviews with individuals, participation in group activities including a higher education policy meeting, seminars and workshops, unplanned informal conversations, institutional policy documents and media analyses in the public domain. Cases were converted to concepts using a constant comparative approach and selective coding reduced 46 concepts to three broad and overlapping interpretations of the data collected, focusing on academic identity, the affective (values-based) character of learning for social, environmental and economic justice, and the imagined, or judged, rather than measured, portrayal of the outcomes or consequences of the efforts of this cultural group in teaching contexts. The grounded theory that derives from these three broad interpretations suggests that reluctance to measure, monitor, assess, evaluate, or research some teaching outcomes is inherent to academic identity as a form of identity protection, and that this protection is essential to preserve the established and preferred identity of academics.
Effects of clearcutting on species composition and community renewal of Rhododendron shrubs in northwest Guizhou Province, China
Authors: Zhang Yaoyao , Zhao Xuechun , Wang Lingjun , Wang Zhaoyi , Shuai Honggang , Wang Yuefeng , Jin Baocheng , Chen Chao
Published: August 2023

Tree base sprouting is the main reproduction and expansion mode of Rhododendron plants. By leveraging the plot survey method, the species composition, community renewal, and species diversity in three Rhododendron shrub communities in control, and before and after clearcutting (CK, D3yr, and D6yr, respectively) were studied. Moreover, the dissimilarity of Rhododendron communities in CK, D3yr and D6yr were analyzed. The results showed that there were 26 plant species belonging to 14 families and 22 genera, in 3 communities in total, with 19 species of shrub plants and 7 species of herbaceous plants. The number of species increased from 13 in CK to 23 in D3yr and then decreased to 20 in D6yr. The height and coverage of D3yr and D6yr reached 39.3% and 58.9% of that of CK, respectively. The relative height of CK, D3yr, and D6yr was 43.79%, 65.4%, and 58.54%, respectively. The coverage of D3yr and D6yr reached 60.8% and 114.70% of that of CK, respectively. The relative coverage of CK, D3yr, and D6yr was 19.05%, 83.24%, and 77.32%, respectively. The important value of Rhododendron plants in the communities increased from 0.42 in CK to 0.74 in D3yr, and then decreased to 0.67 in D6yr. The α diversity in the shrub layer of D3yr and D6yr were generally lower than those of CK except Pielou evenness index. The β diversity indicates that the similarity between CK and D3yr was lower, that between CK and D6yr was moderate, and that between D3yr and D6yr was higher. The sprouting height and coverage of Rhododendron plants was significantly correlated with age and sprouting time. The sprouting ability of Rhododendron plants increased first and then decreased with age, while the sprouting ability of Rhododendron plants with age of 10–12 years was the strongest. Clearcutting measures can improve the dominance of Rhododendron plants in the communities, promote the sprouting and renewal of Rhododendron population, and accelerate the succession rate of communities.
Energy efficiency optimization and carbon emission reduction targets of resource-based cities based on BiLSTM-CNN-GAN model
Authors: Wan Qunyan , Liu Jing
Published: August 2023

Introduction

Energy consumption and carbon emissions are major global concerns, and cities are responsible for a significant portion of these emissions. To address this problem, deep learning techniques have been applied to predict trends and influencing factors of urban energy consumption and carbon emissions, and to help formulate optimization programs and policies.

Methods

In this paper, we propose a method based on the BiLSTM-CNN-GAN model to predict urban energy consumption and carbon emissions in resource-based cities. The BiLSTMCNN-GAN model is a combination of three deep learning techniques: Bidirectional Long Short-Term Memory (BiLSTM), Convolutional Neural Networks (CNN), and Generative Adversarial Networks (GAN). The BiLSTM component is used to process historical data and extract time series information, while the CNN component removes spatial features and local structural information in urban energy consumption and carbon emissions data. The GAN component generates simulated data of urban energy consumption and carbon emissions and optimizes the generator and discriminator models to improve the quality of generation and the accuracy of discrimination.

Results and discussion

The proposed method can more accurately predict future energy consumption and carbon emission trends of resource-based cities and help formulate optimization plans and policies. By addressing the problem of urban energy efficiency and carbon emission reduction, proposed method contributes to sustainable urban development and environmental protection.
Variable clinical expression of a Belgian TGFB3 founder variant suggests the presence of a genetic modifier
Authors: Perik Melanie H. A. M. , Govaerts Emmanuela , Laga Steven , Goovaerts Inge , Saenen Johan , Van Craenenbroeck Emeline , Meester Josephina A. N. , Luyckx Ilse , Rodrigus Inez , Verstraeten Aline , Van Laer Lut , Loeys Bart L.
Published: August 2023

Background:TGFB3 variants cause Loeys–Dietz syndrome type 5, a syndromic form of thoracic aortic aneurysm and dissection. The exact disease phenotype is hard to delineate because of few identified cases and highly variable clinical representation.

Methodology: We provide the results of a haplotype analysis and a medical record review of clinical features of 27 individuals from 5 different families, originating from the Campine region in Flanders, carrying the NM_003239.5(TGFB3):c.787G>C p.(Asp263His) likely pathogenic variant, dbSNP:rs796051886, ClinVar:203492. The Asp263 residue is essential for integrin binding to the Arg-Gly-Asp (RGD) motif of the TGFβ3-cytokine.

Results: The haplotype analysis revealed a shared haplotype of minimum 1.92 Mb and maximum 4.14 Mb, suggesting a common founder originating >400 years ago. Variable clinical features included connective tissue manifestations, non-aneurysmal cardiovascular problems such as hypertrophic cardiomyopathy, bicuspid aortic valve, mitral valve disease, and septal defects. Remarkably, only in 4 out of the 27 variant-harboring individuals, significant aortic involvement was observed. In one family, a 31-year-old male presented with type A dissection. In another family, the male proband (65 years) underwent a Bentall procedure because of bicuspid aortic valve insufficiency combined with sinus of Valsalva of 50 mm, while an 80-year-old male relative had an aortic diameter of 43 mm. In a third family, the father of the proband (75 years) presented with ascending aortic aneurysm (44 mm).

Conclusion: The low penetrance (15%) of aortic aneurysm/dissection suggests that haploinsufficiency alone by the TGFB3 variant may not result in aneurysm development but that additional factors are required to provoke the aneurysm phenotype.
Combined germline and tumor mutation signature testing identifies new families with NTHL1 tumor syndrome
Authors: Pinto Carla , Guerra Joana , Pinheiro Manuela , Escudeiro Carla , Santos Catarina , Pinto Pedro , Porto Miguel , Bartosch Carla , Silva João , Peixoto Ana , Teixeira Manuel R.
Published: August 2023

NTHL1 tumor syndrome is an autosomal recessive rare disease caused by biallelic inactivating variants in the NTHL1 gene and which presents a broad tumor spectrum. To contribute to the characterization of the phenotype of this syndrome, we studied 467 index patients by KASP assay or next-generation sequencing, including 228 patients with colorectal polyposis and 239 patients with familial/personal history of multiple tumors (excluding multiple breast/ovarian/polyposis). Three NTHL1 tumor syndrome families were identified in the group of patients with polyposis and none in patients with familial/personal history of multiple tumors. Altogether, we identified nine affected patients with polyposis (two of them diagnosed after initiating colorectal cancer surveillance) with biallelic pathogenic or likely pathogenic NTHL1 variants, as well as two index patients with one pathogenic or likely pathogenic NTHL1 variant in concomitance with a missense variant of uncertain significance. Here we identified a novel inframe deletion classified as likely pathogenic using the ACMG criteria, supported also by tumor mutational signature analysis. Our findings indicate that the NTHL1 tumor syndrome is a multi-tumor syndrome strongly associated with polyposis and not with multiple tumors without polyposis.
Positive effects of dietary Clostridium butyricum supplementation on growth performance, antioxidant capacity, immunity and viability against hypoxic stress in largemouth bass
Authors: Li Peijia , Chen Xiaoying , Hou Dongqiang , Chen Bing , Peng Kai , Huang Wen , Cao Junming , Zhao Hongxia
Published: August 2023

The effects of dietary supplementation of Clostridium butyricum (CB) on growth performance, serum biochemistry, antioxidant activity, mRNA levels of immune-related genes and resistance to hypoxia stress were studied in largemouth bass. Feed with CB0 (control, 0 CFU/kg), CB1 (4.3×108 CFU/kg), CB2 (7.5×108 CFU/kg), CB3 (1.5×109 CFU/kg) and CB4 (3.2×109 CFU/kg) CB for 56 days, and then a 3 h hypoxic stress experiment was performed. The results showed that dietary CB significantly increased the WGR (weight gain rate), SGR (specific growth rate), PDR (protein deposition rate) and ISI (Intestosomatic index) of largemouth bass (P<0.05). Hepatic GH (growth hormone)/IGF-1 (insulin-like growth factor-1) gene expression was significantly upregulated in the CB3 and CB4 groups compared with the CB0 group (P<0.05), while the FC (feed conversion) was significantly decreased (P<0.05). Serum TP (total protein) and GLU (glucose) levels were significantly higher in the CB4 group than in the CB0 group (P<0.05), while the contents of serum AST (aspartate transaminase), ALT (alanine transaminase), AKP (alkline phosphatase) and UN (urea nitrogen) in CB4 were significantly lower than those in CB0 (P<0.05). T-AOC (total antioxidant capacity), SOD (superoxide dismutase), CAT (catalase), POD (peroxidase) and GSH-Px (glutathione peroxidase) activities were significantly higher in CB3 and CB4 groups than in CB0 group (P<0. 05). The liver MDA (malondialdehyde) content of CB1, CB2, CB3 and CB4 groups was significantly higher than that of CB0 group (P<0. 05). The relative expressions of IL-1β (interleukin 1β), TNF-α (tumor necrosis factor α) and TLR22 (toll-like receptor-22) genes in CB2, CB3 and CB4 groups were significantly lower than those in CB0 group (P<0.05). The relative expression of IL-8 (malondialdehyde) and MyD88 (Myeloid differentiation factor 88) genes in the CB4 group was significantly lower than that in the CB0 group (P<0.05). The liver LZM (lysozyme) content of CB2, CB3 and CB4 groups was significantly higher than that of CB0 group (P<0. 05). The relative expression of IL-10 (interleukin 10) and TGF-β (transforming growth factor β) genes in the CB4 group was significantly higher than that in the CB0 group (P<0.05). Under hypoxic stress for 3 h, the CMR of CB0 group was significantly higher than that of CB1, CB2, CB3 and CB4 groups (P<0.05). Dietary CB can improve the growth performance and resistance to hypoxic stress of largemouth bass by regulating the expression of GH/IGF-1 gene and inflammatory factors and inhibiting TLR22/MyD88 signaling pathway.
Urine L-selectin reflects clinical and histological renal disease activity and treatment response in lupus nephritis across multi-ethnicity
Authors: Shen Yiwei , Vanarsa Kamala , Yin Zhihua , Zhang Ting , Castillo Jessica , Dai Min , Zou Linghua , Qin Ling , Wang Jieying , Guo Qiang , Saxena Ramesh , Petri Michelle , Shen Nan , Ye Zhizhong , Mohan Chandra , Ding Huihua
Published: August 2023

Objective

There is an urgent need for novel biomarkers in lupus nephritis (LN). We report a non-invasive urinary biomarker, L-selectin, in two independent multi-ethnic cohorts.

Methods

uL-selectin was tested cross-sectionally in a Chinese cohort (n=255) and a US cohort (n=219) of SLE patients and controls using ELISA. A longitudinal cohort includes 20 active Chinese LN patients.

Results

uL-selectin was significantly increased in active LN patients compared to active non-renal SLE, inactive LN, inactive non-renal SLE, chronic kidney disease patients, and healthy controls. uL-selectin positively correlated with global and renal disease activities and was significantly associated with histological activity index and chronicity index (CI). Low uL-selectin was an independent predictor for high CI. During follow-up, uL-selectin levels decreased significantly in the complete renal remission group.

Conclusion

uL-selectin is a novel biomarker of disease activity and renal histopathology in LN across multiple ethnicities. It also reflects treatment response in LN patients during follow up.
The impact of EMA recommendations on the real-life use of Janus kinases inhibitors for rheumatoid arthritis: the Expanded Risk Score in RA as a tool to quantify the risk of cardiovascular events
Authors: Favalli Ennio Giulio , Cincinelli Gilberto , Germinario Sabino , Di Taranto Raffaele , Orsini Francesco , Maioli Gabriella , Biggioggero Martina , Ferrito Matteo , Caporali Roberto
Published: August 2023

Objective

To evaluate in patients with rheumatoid arthritis (RA) the impact of EMA recommendations on the real-life prescription of JAK inhibitors (JAKis) and the use of the Expanded Risk Score in RA (ERS-RA) to quantify the risk of major adverse cardiac events (MACE).

Methods

We conducted a retrospective analysis of real-life RA patients treated with JAKis. Patients were classified as ineligible for JAKis if they fulfilled EMA criteria (>65 years-old, history of malignancy, or increased risk of venous thromboembolic events [VTE] or MACE including smoking). Risk of MACE was defined according to ORAL Surveillance trial inclusion criteria (ORALSURV) or by using the ERS-RA.

Results

Of 194 patients enrolled, 57.9% were classified as ineligible according to EMA definition (ORALSURV criteria). The most frequent reason for ineligibility was increased MACE risk (70.2%), followed by age>65 (34.2%), smoking (30.7%), and increased risk of VTE (20.2%) or malignancy (7%). The use of the ERS-RA reduced the rate of patients carrying an increased CV risk to 18.6% (p<0.001 versus ORALSURV), leading to 46.4% overall ineligible patients. Over a drug-exposure of 337 patient/years, we observed 2 VTE, one MACE (non-fatal stroke), and one solid malignancy (all in the group of patients classified as ineligible according to both the definitions).

Conclusions

Rigorous application of EMA indications in clinical practice could result in the exclusion of a large proportion of RA patients from treatment with JAKis. A proper quantification of the risk for MACE by dedicated tools as ERS-RA is advocated to better tailor the management of RA.
Factor VIII antibody immune complexes modulate the humoral response to factor VIII in an epitope-dependent manner
Authors: Batsuli Glaivy , Ito Jasmine , York Elizabeth S. , Cox Courtney , Baldwin Wallace , Gill Surinder , Lollar Pete , Meeks Shannon L.
Published: August 2023

Introduction

Soluble antigens complexed with immunoglobulin G (IgG) antibodies can induce robust adaptive immune responses in vitro and in animal models of disease. Factor VIII immune complexes (FVIII-ICs) have been detected in individuals with hemophilia A and severe von Willebrand disease following FVIII infusions. Yet, it is unclear if and how FVIII-ICs affect antibody development over time.

Methods

In this study, we analyzed internalization of FVIII complexed with epitope-mapped FVIII-specific IgG monoclonal antibodies (MAbs) by murine bone marrow-derived dendritic cells (BMDCs) in vitro and antibody development in hemophilia A (FVIII-/-) mice injected with FVIII-IC over time.

Results

FVIII complexed with 2-116 (A1 domain MAb), 2-113 (A3 domain MAb), and I55 (C2 domain MAb) significantly increased FVIII uptake by BMDC but only FVIII/2-116 enhanced antibody titers in FVIII-/- mice compared to FVIII alone. FVIII/4A4 (A2 domain MAb) showed similar FVIII uptake by BMDC to that of isolated FVIII yet significantly increased antibody titers when injected in FVIII-/- mice. Enhanced antibody responses observed with FVIII/2-116 and FVIII/4A4 complexes in vivo were abrogated in the absence of the FVIII carrier protein von Willebrand factor.

Conclusion

These findings suggest that a subset of FVIII-IC modulates the humoral response to FVIII in an epitope-dependent manner, which may provide insight into the antibody response observed in some patients with hemophilia A.
TCM “medicine and food homology” in the management of post-COVID disorders
Authors: Ng Chester Yan Jie , Bun Hung Hung , Zhao Yan , Zhong Linda L. D.
Published: August 2023

Background

The World Health Organization declared that COVID-19 is no longer a public health emergency of global concern on May 5, 2023. Post-COVID disorders are, however, becoming more common. Hence, there lies a growing need to develop safe and effective treatment measures to manage post-COVID disorders. Investigating the use of TCM medicinal foods in the long-term therapy of post-COVID illnesses may be beneficial given contemporary research’s emphasis on the development of medicinal foods.

Scope and approach

The use of medicinal foods for the long-term treatment of post-COVID disorders is highlighted in this review. Following a discussion of the history of the TCM “Medicine and Food Homology” theory, the pathophysiological effects of post-COVID disorders will be briefly reviewed. An analysis of TCM medicinal foods and their functions in treating post-COVID disorders will then be provided before offering some insight into potential directions for future research and application.

Key findings and discussion

TCM medicinal foods can manage different aspects of post-COVID disorders. The use of medicinal foods in the long-term management of post-COVID illnesses may be a safe and efficient therapy choice because they are typically milder in nature than chronic drug use. These findings may also be applied in the long-term post-disease treatment of similar respiratory disorders.
The bladder cancer immune micro-environment in the context of response to immune checkpoint inhibition
Authors: van Dorp Jeroen , van der Heijden Michiel S.
Published: August 2023

Treatment with neoadjuvant cisplatin-based chemotherapy followed by radical cystectomy is the default treatment for muscle-invasive bladder cancer (BC). However, with the encouraging results of immune checkpoint inhibitiors (ICI) directed against PD-1/PD-L1 and CTLA-4 in recent years, the treatment landscape of BC is rapidly changing. In addition, it is becoming clear that the effect of ICI is highly dependent on the interaction between tumor cells and the tumor immune micro-environment (TIME). Different immune cells are involved in an anti-tumor response in BC. Cytotoxic CD8+ T-cells are the main effector cells, aided by other immune cells including other T-cells, B-cells and pro-inflammatory macrophages. As part of the ongoing anti-tumor immune response, lymphocytes aggregate in clusters called tertiary lymphoid structures (TLS). Tumor mutational burden (TMB) and infiltration of immune cells into the tumor are both important factors for establishing an anti-tumor immune response. In contrast, transforming growth factor beta (TGF-β) signaling in cancer-associated fibroblasts (CAFs) prevents infiltration of lymphocytes and potentially has an immunosuppressive effect. In conclusion, the effect of ICI seems to be reliant on a combination of tumor-intrinsic and TIME-related parameters. More research is needed to fully understand the underlying biological mechanisms to further improve patient care.
Therapeutic strategies targeting folate receptor α for ovarian cancer
Authors: Mai Jia , Wu Limei , Yang Ling , Sun Ting , Liu Xiaojuan , Yin Rutie , Jiang Yongmei , Li Jinke , Li Qintong
Published: August 2023

Epithelial ovarian cancer (EOC) is the deadliest gynecological cancer, and presents a major clinical challenge due to limited treatment options. Folate receptor alpha (FRα), encoded by the FOLR1 gene, is an attractive therapeutically target due to its prevalent and high expression in EOC cells. Recent basic and translational studies have explored several modalities, such as antibody-drug conjugate (ADC), monoclonal antibodies, small molecules, and folate-drug conjugate, to exploit FRα for EOC treatment. In this review, we summarize the function of FRα, and clinical efficacies of various FRα-based therapeutics. We highlight mirvetuximab soravtansine (MIRV), or Elahere (ImmunoGen), the first FRα-targeting ADC approved by the FDA to treat platinum-resistant ovarian cancer. We discuss potential mechanisms and management of ocular adverse events associated with MIRV administration.
Effect of external physical vibration lithecbole in obese patients with lower pole stones <15 mm after ESWL: a single-centre, randomized, open label clinical trial
Authors: Li Yunpeng , Lv Jianlin
Published: August 2023

Objective

To investigate the efficacy and safety of external physical vibration lithecbole (EPVL) in obese patients with <15 mm lower pole stones following extracorporeal shock wave lithotripsy (ESWL).

Methods

Two hundred and ninety-nine obese patients with BMI greater than 30 kg/m2 and lower pole stones smaller than 15 mm were prospectively randomized into two groups. While ESWL was the only option in the control group, patients in the treatment group accepted EPVL after receiving ESWL. Imaging tests were used to compare the stone expulsion status on day 1 and the stone-free rates (SFR) on the first, second, and fourth weekends.

Results

All 299 obese patients were randomly divided into two groups, with 152 patients assigned to the treatment group and 147 assigned to the control group. EPVL was effective in facilitating the expulsion of stone fragments. The treatment group’s stone expulsion rate on the first day following EPVL was significantly greater than the control group’s (66.4% vs. 51.7%, p = 0.009). Stone clearance rates in the treatment and control groups were 63.2 and 55.1% at 1 week (p = 0.041), 84.9 and 70.7% at 2 weeks (p = 0.011), and 90.8 and 79.6% at 4 weeks (p = 0.017), respectively. The complications (hematuria, lumbago, and fever) between the groups did not show any significance (p > 0.05). Patients in the treatment group received an average of 5.2 sessions.

Conclusion

EPVL is an efficient and secure procedure that facilitates lower pole stone discharge in obese patients following ESWL treatment. To support the aforementioned conclusions, additional large-scale multi-center prospective studies are required.
Incidence of wound dehiscence after keratoplasty: a meta-analysis of observational studies
Authors: Zheng Na , He Wenjing , Zhu Siquan
Published: August 2023

Background

The comprehensive investigation of the association between keratoplasty and wound dehiscence remains limited, despite corneal disease being a leading cause of visual impairment.

Methods

A meticulous search strategy was executed across prominent databases such as Web of Science, PubMed, Cochrane Library, and Embase. Data relevant to our research objective were extracted from eligible studies. The methodological quality of each study was assessed using the ROBINS-I tool, while statistical analysis was conducted utilizing STATA 17.0. To evaluate potential publication bias, the Funnel plot and Egger’s test were employed.

Results

A total of 11 articles were deemed suitable for inclusion in our analysis. Our findings indicate that the overall incidence of wound dehiscence following keratoplasty was estimated to be 1.9% (95% CI: 0.013, 0.026), although substantial heterogeneity was observed (I2 = 72.798%). Notably, developed countries exhibited a higher incidence of wound dehiscence compared to their developing counterparts. Furthermore, the occurrence of wound dehiscence was found to be lower in deep anterior lamellar keratoplasty (DALK) procedures when compared to penetrating keratoplasty (PK). Analysis utilizing Egger’s linear regression method yielded no evidence of publication bias (p = 0.91). Moreover, within the first year post-keratoplasty, approximately 31.4% of patients experienced wound dehiscence (95% CI: 0.149, 0.503), and 43.1% exhibited a decline in best-corrected visual acuity (BCVA) (95% CI, 0.341, 0.522).

Conclusion

The results of our study unveiled the occurrence rate of wound dehiscence following keratoplasty, exhibiting variations based on economic level and the specific surgical procedure employed. Furthermore, onset time of wound dehiscence and visual acuity warrant consideration.
An exploratory study of unexplained concentration of 18F-PSMA-1007 in the bladder for prostate cancer PET/CT imaging
Authors: Dang Jun , Yao Yutang , Li Yingchun , Tan Xiaofei , Ye Zhenyan , Zhao Yi , Qing Shiwei , Kou Ying , Jiang Xiao , Lu Hao , Chen Shirong , Zhao Meng , Cheng Zhuzhong
Published: August 2023

18F-PSMA-1007 PET/CT imaging is increasingly used for the diagnosis, staging, and efficacy assessment of patients with prostate cancer. Compared with other PSMA tracers, 18F-PSMA-1007 is mainly cleared by the liver and bile and has lower urinary clearance, thus allowing a better assessment of the lesions around the bladder. However, there were some patients who showed an obvious concentration of the 18F-PSMA-1007 in the bladder, which may affect the observation of peripheral lesions, but the mechanism of this change is unknown. The aim of this study was to explore the cause of bladder 18F-PSMA-1007 concentration by assessing the clinical and imaging characteristics of 18F-PSMA-1007 PET/CT scans. A total of 284 patients were included in this retrospective study, and their clinical characteristics such as age, height, weight, Gleason score, metastases, different treatment methods, the level of liver and kidney function, PSA level, and imaging characteristics such as 18F-PSMA-1007 injected activity, the interval between injection to scan, physiological distribution (parotid gland, kidney, liver, spleen, intestine, obturator internus), pathological distribution (prostate lesions, metastases) were collected, and were compared after subgrouping using bladder urine SUVmax. This study showed that the distribution of bladder 18F-PSMA-1007 was not correlated with the above clinical and imaging characteristics, so further studies are needed to find the explanations, and thus to improve the disease assessment of this type of prostate cancer patients.
Differential modulation of IL-4, IL-10, IL-17, and IFN-γ production mediated by IgG from Human T-lymphotropic virus-1 (HTLV-1) infected patients on healthy peripheral T (CD4+, CD8+, and γδ) and B cells
Authors: Machado Nicolle Rakanidis , Fagundes Beatriz Oliveira , Fernandes Lorena Abreu , Oliveira Augusto César Penalva de , Nukui Youko , Casseb Jorge , Cunha Fernando Roberto Machado , Nali Luiz Henrique da Silva , Sanabani Sabri Saeed , Victor Jefferson Russo
Published: August 2023

Human T-lymphotropic virus 1 (HTLV-1) infected individuals remain as asymptomatic carriers (ACs) or can develop the chronic neurological disorder HTLV-1-associated myelopathy/Tropical Spastic Paraparesis (HAM/TSP) or the adult T-cell leukemia/lymphoma (ATLL), and the immunological mechanisms involved in this pathologies need to be elucidated. Recently, it has been demonstrated that induced or naturally developed IgG repertoires obtained from different groups of donors, grouped by immune status, can modulate human T and B cell functions. Here we aimed to evaluate if the IgG obtained from HTLV-1-infected ACs, HAM/TSP, and ATLL patients can differentially modulate the production of cytokines by human T and B cells. With this purpose, we cultured PBMCs with IgG purified from ACs, HAM/TSP, or ATLL donors and evaluated the frequency and intracellular cytokine production by flow cytometry. Our results indicate that IgG from HAM/TSP patients could induce an augment of IL-17-producing CD4+ T cells, reduce the frequency of IL-4-producing CD4+ T cells, increase IFN-γ-producing CD8+ T cells, and reduce IL-4-producing CD8+ T cells. IgG from ATLL could reduce the frequency of IL-4-producing CD4+ T cells, similarly to IgG from HAM/TSP /TSP, and could reduce the frequency of IFN-γ-producing γδT cells without influence on IL-17- and IL4-producing γδT and could reduce the frequency of IL-10- producing B cells. Finally, IgG from both HAM/TSP and ATLL patients could reduce the frequency of IFN-γ producing B cells. In conclusion, these results suggest that these preparations are active, partly overlapping in their effects, and able to elicit distinct effects on target populations.
Spatiotemporal diversity and community structure of cyanobacteria and associated bacteria in the large shallow subtropical Lake Okeechobee (Florida, United States)
Authors: Lefler Forrest W. , Barbosa Maximiliano , Zimba Paul V. , Smyth Ashley R. , Berthold David E. , Laughinghouse H. Dail
Published: August 2023

Lake Okeechobee is a large eutrophic, shallow, subtropical lake in south Florida, United States. Due to decades of nutrient loading and phosphorus rich sediments, the lake is eutrophic and frequently experiences cyanobacterial harmful algal blooms (cyanoHABs). In the past, surveys of the phytoplankton community structure in the lake have been conducted by morphological studies, whereas molecular based studies have been seldom employed. With increased frequency of cyanoHABs in Lake Okeechobee (e.g., 2016 and 2018 Microcystis-dominated blooms), it is imperative to determine the diversity of cyanobacterial taxa that exist within the lake and the limnological parameters that drive bloom-forming genera. A spatiotemporal study of the lake was conducted over the course of 1 year to characterize the (cyano)bacterial community structure, using 16S rRNA metabarcoding, with coincident collection of limnological parameters (e.g., nutrients, water temperature, major ions), and cyanotoxins. The objectives of this study were to elucidate spatiotemporal trends of community structure, identify drivers of community structure, and examine cyanobacteria-bacterial relationships within the lake. Results indicated that cyanobacterial communities within the lake were significantly different between the wet and dry season, but not between periods of nitrogen limitation and co-nutrient limitation. Throughout the year, the lake was primarily dominated by the picocyanobacterium Cyanobium. The bloom-forming genera Cuspidothrix, Dolichospermum, Microcystis, and Raphidiopsis were highly abundant throughout the lake and had disparate nutrient requirements and niches within the lake. Anatoxin-a, microcystins, and nodularins were detected throughout the lake across both seasons. There were no correlated (cyano)bacteria shared between the common bloom-forming cyanobacteria Dolichospermum, Microcystis, and Raphidiopsis. This study is the first of its kind to use molecular based methods to assess the cyanobacterial community structure within the lake. These data greatly improve our understanding of the cyanobacterial community structure within the lake and the physiochemical parameters which may drive the bloom-forming taxa within Lake Okeechobee.
Association of low HDL-c levels with severe symptoms and poor clinical prognosis in patients with severe fever and thrombocytopenia syndrome
Authors: Huang Taihong , Fan Yinyin , Xia Yanyan , Xu Xuejing , Chen Xinyue , Ye Hongling , Chen Yuxin , Wang Sen
Published: August 2023

Background

Severe fever with thrombocytopenia syndrome (SFTS) is an acute infectious disease caused by a novel bunyavirus, characterized by high fever, thrombocytopenia, and multiple organ damage. Disturbances in lipid metabolism often occur during viral infections, but the changes and clinical significance of lipid profiles in SFTS patients remain unclear. This study aimed to investigate the alterations in lipid profiles and their clinical significance in SFTS patients.

Methods

A total of 157 SFTS patients and 157 healthy controls were enrolled in this study. Serum lipid levels were collected and analyzed among different groups and prognosis categories. Receiver operating characteristic (ROC) curve analysis was performed to assess the ability of lipid levels in distinguishing between severe and mild cases, as well as surviving and non-surviving patients. Pearson correlation analysis was used to examine the associations between lipid levels and clinical laboratory parameters.

Results

SFTS patients exhibited significantly lower levels of HDL-c, LDL-c, cholesterol, APoAI, and ApoB compared to healthy controls, while triglyceride levels were significantly higher. Serum HDL-c and ApoAI demonstrated good performance as indicators for distinguishing between survivors and non-survivors (AUC of 0.87 and 0.85, respectively). Multivariate regression analysis indicated that HDL-c independently acts as a protective factor in patients with SFTS. HDL-c levels showed decline in non-survivors but recovered in survivors. Moreover, HDL-c exhibited significant correlations with various clinical laboratory parameters (IL-6, CRP, AST, TT, APTT, PLT, ALB, and CD4).

Conclusion

This study identified abnormalities in serum lipid metabolism among SFTS patients. HDL-c and ApoAI levels hold potential as biomarkers for distinguishing survivors from non-survivors. Additionally, HDL-c and ApoAI may serve as therapeutic targets for the management of SFTS patients.
The roles of GpsB and DivIVA in Staphylococcus aureus growth and division
Authors: Sutton Joshua A. F. , Cooke Mark , Tinajero-Trejo Mariana , Wacnik Katarzyna , Salamaga Bartłomiej , Portman-Ross Callum , Lund Victoria A. , Hobbs Jamie K. , Foster Simon J.
Published: August 2023

The spheroid bacterium Staphylococcus aureus is often used as a model of morphogenesis due to its apparently simple cell cycle. S. aureus has many cell division proteins that are conserved across bacteria alluding to common functions. However, despite intensive study, we still do not know the roles of many of these components. Here, we have examined the functions of the paralogues DivIVA and GpsB in the S. aureus cell cycle. Cells lacking gpsB display a more spherical phenotype than the wild-type cells, which is associated with a decrease in peripheral cell wall peptidoglycan synthesis. This correlates with increased localization of penicillin-binding proteins at the developing septum, notably PBPs 2 and 3. Our results highlight the role of GpsB as an apparent regulator of cell morphogenesis in S. aureus.
Suppression of hnRNP A1 binding to HK1 RNA leads to glycolytic dysfunction in Alzheimer’s disease models
Authors: Ji Xin-Hao , Liu Ting-Ting , Wei Ai-Hong , Lei Hui-Ping , Chen Yue , Wu Ling-Nan , Liu Ju , Zhang Ying , Yan Fei , Chen Mei-Xiang , Jin Hai , Shi Jing-Shan , Zhou Shao-Yu , Jin Feng
Published: August 2023

Objective

To investigate the mechanism of RNA-binding protein hnRNP A1 in mouse hippocampal neurons (HT22) on glycolysis.

Methods

RIP and CLIP-qPCR were performed by HT22 in vitro to observe the mechanism of hnRNP A1 regulating the expression of key proteins in glycolysis. The RNA binding domain of hnRNP A1 protein in HT22 was inhibited by VPC-80051, and the effect of hnRNP A1 on glycolysis of HT22 was observed. Lentivirus overexpression of hnRNP A1 was used to observe the effect of overexpression of hnRNP A1 on glycolysis of Aβ25–35-injured HT22. The expression of hnRNP A1 in brain tissues of wild-type mice and triple-transgenic (APP/PS1/Tau) AD mice at different ages was studied by Western blot assay.

Results

The results of RIP experiment showed that hnRNP A1 and HK1 mRNA were significantly bound. The results of CLIP-qPCR showed that hnRNP A1 directly bound to the 2605-2821 region of HK1 mRNA. hnRNP A1 inhibitor can down-regulate the expression of HK1 mRNA and HK1 protein in HT22 cells. Overexpression of hnRNP A1 can significantly reduce the toxic effect of Aβ25–35 on neurons via the hnRNP A1/HK1/ pyruvate pathway. In addition, inhibition of hnRNP A1 binding to amyloid precursor protein (APP) RNA was found to increase Aβ expression, while Aβ25–35 also down-regulated hnRNP A1 expression by enhancing phosphorylation of p38 MAPK in HT22. They interact to form bidirectional regulation, further down-regulating the expression of hnRNP A1, and ultimately aggravating glycolytic dysfunction. Protein immunoblotting showed that hnRNP A1 decreased with age in mouse brain tissue, and the decrease was greater in AD mice, suggesting that the decrease of hnRNP A1 may be a predisposed factor in the pathogenesis of AD.
A short appraisal of nanodiamonds in drug delivery and targeting: recent advancements
Authors: Singh Dilpreet , Ray Supriya
Published: August 2023

Nanodiamonds have emerged as a powerful tool in the field of drug delivery, offering exciting recent advancements and promising future prospects. Recent research has focused on enhancing drug loading efficiency, targeted delivery, and precision medicine using nanodiamonds. Strategies such as surface functionalization, polymer coatings, and encapsulation techniques have been optimized to improve drug loading, stability, and controlled release. Nanodiamonds have shown potential in targeted drug delivery through the incorporation of targeting ligands, enabling site-specific drug delivery and improved therapeutic outcomes. Additionally, nanodiamonds allow for combination therapy by carrying multiple drugs simultaneously, opening avenues for synergistic treatments. Stimuli-responsive nanodiamonds have been developed for precise and controlled drug release. Overcoming biological barriers, such as the blood-brain barrier, has been investigated by modifying nanodiamonds’ surfaces. Recent studies have highlighted innovative strategies for loading a variety of therapeutic cargoes onto nanodiamond platforms, including small molecules, proteins, nucleic acids, and even gene-editing tools. Future prospects include the integration of nanodiamonds with emerging technologies and addressing biocompatibility and safety concerns. Despite the need for further research and clinical studies, the recent advancements and future prospects of nanodiamonds in drug delivery suggest their potential to revolutionize the field and enhance patient care.
Lamin B1 as a key modulator of the developing and aging brain
Authors: Koufi Foteini-Dionysia , Neri Irene , Ramazzotti Giulia , Rusciano Isabella , Mongiorgi Sara , Marvi Maria Vittoria , Fazio Antonietta , Shin Minkyung , Kosodo Yoichi , Cani Ilaria , Giorgio Elisa , Cortelli Pietro , Manzoli Lucia , Ratti Stefano
Published: August 2023

Lamin B1 is an essential protein of the nuclear lamina that plays a crucial role in nuclear function and organization. It has been demonstrated that lamin B1 is essential for organogenesis and particularly brain development. The important role of lamin B1 in physiological brain development and aging has only recently been at the epicenter of attention and is yet to be fully elucidated. Regarding the development of brain, glial cells that have long been considered as supporting cells to neurons have overturned this representation and current findings have displayed their active roles in neurogenesis and cerebral development. Although lamin B1 has increased levels during the differentiation of the brain cells, during aging these levels drop leading to senescent phenotypes and inciting neurodegenerative disorders such as Alzheimer’s and Parkinson’s disease. On the other hand, overexpression of lamin B1 leads to the adult-onset neurodegenerative disease known as Autosomal Dominant Leukodystrophy. This review aims at highlighting the importance of balancing lamin B1 levels in glial cells and neurons from brain development to aging.