bluuebunny/crossref_metadata_2025 huggingface dataset:
Validación de un cuestionario para evaluar el nivel de conocimiento de traumatismos dentoalveolares en niños
Authors: Mercado-Hermoza Adriana Elizabeth , Gonzales-Mendoza Julio César , Díaz-Suyo Antonio , Viviano Llave Carlos
Published: October 2022

El traumatismo dentoalveolar es una de las injurias más prevalentes tratadas por el odontólogo y de mayor incidencia en la población infantil; no todos los profesionales se han actualizado en los últimos protocolos para su manejo. Objetivo: El propósito del estudio fue validar un cuestionario para medir el nivel de conocimiento de traumatismos dentoalveolares en niños en base a los protocolos actualizados. Material y métodos: Se realizó una investigación de tipo observacional, descriptivo, transversal y prospectivo mediante la validación de un instrumento compuesto por 21 preguntas de opción múltiple. Se sometió el instrumento a juicio de expertos, evaluación de confiabilidad y reproducibilidad aplicándola a una muestra de 150 participantes (50 estudiantes de pregrado de Estomatología, 50 odontólogos generales y 50 especialistas en odontopediatría). Resultados: El cuestionario alcanzó una alta validez de contenido al obtener un puntaje de 0.98. El análisis KR20 evidenció una confiabilidad alta de 0.64 y el coeficiente de Pearson una reproducibilidad muy alta de 0.87. Conclusión: El presente instrumento es válido, confiable y reproducible para ser ejecutado en futuras investigaciones con las recomendaciones sugeridas en la investigación.
Consideraciones en el manejo dental de un paciente con hiperinsulinismo congénito. Reporte de un caso
Authors: Butrón-Téllez Girón Claudia , Hernández-Pérez Daniela , Pierdant-Pérez Mauricio
Published: October 2022

Introducción: El Hiperinsulismo Congénito se caracteriza por una desregulación de la secreción de insulina, que causa hipoglucemia grave en los recién nacidos, lactantes y niños. El exceso de estrés y ansiedad que se produce en la consulta dental puede inducir a la excesiva producción del cortisol aumentando la glucosa sanguínea con mayor producción de insulina compensatoria la cual nos puede llevar a una hipoglucemia durante el tratamiento, asimismo, el uso de algunos medicamentos y el consumo alto de hidratos de carbono de estos pacientes para mantener niveles adecuados de glucosa, pueden causar alteraciones en la cavidad bucal. Presentación del caso: Se presenta el caso de paciente masculino de 5 años 4 meses de edad con historial médico de hiperinsulinismo congénito. Durante la anamnesis, los padres mencionan que el niño realiza de 5 a 6 comidas al día y alto consumo de hidratos de carbono entre estas, para mantener los niveles de glucemia en sangre. A la inspección de su cavidad oral del niño, presentó lesiones cariosas en varios órganos dentarios requiriendo distintos tratamientos. Durante la atención dental se utilizó la técnica de manejo de conducta decir-mostrar-hacer para evitar desarrollar ansiedad y estrés en el niño. Conclusión: Debido a las múltiples comidas y alto consumo de carbohidratos, es necesario un régimen estricto en relación a higiene bucal y medidas preventivas, así como visitas periódicas al odontólogo, además, es importante realizar un buen manejo de conducta evitando la ansiedad y el estrés durante el tratamiento para prevenir una crisis hipoglucémica.
Small widths wall-attached Coandă jets for flow control
Authors: El Mokkadem Oussama , Chen Xintong , Phan Charlene , Delva Jérôme , Joseph Pierric , Dazin Antoine , Romanò Francesco
Published: October 2022

The flow dynamics of small widths wall-attached jets generated by a Coand\v{a} effect nozzle is investigated by URANS simulations. The data are validated by comparison to hot-wire velocity measurements performed on the same flow configurations. The jets exhibit a complex topology strongly influenced not only by the spanwise vorticity (as usually observed in wall jets) but also by a vorticity component normal to the wall and induced by the shear layer developing on the jet sides. This results in an original U-shaped jet whose characteristics are studied in detail for three different mass flow rates. The robustness of the flow topology on a larger range of injected mass flow rates is finally presented.
Closed-loop control of continuous piperacillin delivery: An in silico study
Authors: Herrero Pau , Wilson Richard C. , Armiger Ryan , Roberts Jason A. , Holmes Alison , Georgiou Pantelis , Rawson Timothy M.
Published: October 2022

Background and objective: Sub-therapeutic dosing of piperacillin-tazobactam in critically-ill patients is associated with poor clinical outcomes and may promote the emergence of drug-resistant infections. In this paper, an in silico investigation of whether closed-loop control can improve pharmacokinetic-pharmacodynamic (PK-PD) target attainment is described.

Method: An in silico platform was developed using PK data from 20 critically-ill patients receiving piperacillin-tazobactam where serum and tissue interstitial fluid (ISF) PK were defined. Intra-day variability on renal clearance, ISF sensor error, and infusion constraints were taken into account. Proportional-integral-derivative (PID) control was selected for drug delivery modulation. Dose adjustment was made based on ISF sensor data with a 30-min sampling period, targeting a serum piperacillin concentration between 32 and 64 mg/L. A single tuning parameter set was employed across the virtual population. The PID controller was compared to standard therapy, including bolus and continuous infusion of piperacillin-tazobactam.

Results: Despite significant inter-subject and simulated intra-day PK variability and sensor error, PID demonstrated a significant improvement in target attainment compared to traditional bolus and continuous infusion approaches.

Conclusion: A PID controller driven by ISF drug concentration measurements has the potential to precisely deliver piperacillin-tazobactam in critically-ill patients undergoing treatment for sepsis.
Engineering of Escherichia coli for D-allose fermentative synthesis from D-glucose through izumoring cascade epimerization
Authors: Zheng Ling-Jie , Guo Qiang , Zhang Ya-Xing , Liu Chen-Yang , Fan Li-Hai , Zheng Hui-Dong
Published: October 2022

D-Allose is a potential alternative to sucrose in the food industries and a useful additive for the healthcare products in the future. At present, the methods for large-scale production of D-allose are still under investigation, most of which are based on in vitro enzyme-catalyzed Izumoring epimerization. In contrast, fermentative synthesis of D-allose has never been reported, probably due to the absence of available natural microorganisms. In this work, we co-expressed D-galactose: H+ symporter (GalP), D-glucose isomerase (DGI), D-allulose 3-epimerase (DAE), and ribose-5-phosphate isomerase (RPI) in Escherichia coli, thereby constructing an in vivo Izumoring pathway for yielding D-allose from D-glucose. The carbon fluxes and carbon catabolite repression (CCR) were rationally regulated by knockout of FruA, PtsG, Glk, Mak, PfkA, and PfkB involved in the pathways capable of phosphorylating D-fructose, D-glucose, and fructose-6-phosphate. Moreover, the native D-allose transporter was damaged by inactivation of AlsB, thus driving the reversible Izumoring reactions towards the target product. Fermentation was performed in the M9 medium supplemented with glycerol as a carbon source and D-glucose as a substrate. The results show that the engineered E. coli cell factory was able to produce approximately 127.35 mg/L of D-allose after 84 h. Our achievements in the fermentative production of D-allose in this work may further promote the green manufacturing of rare sugars.
Optimization of the driver’s seat belt and injury biomechanical analysis in real-world minivan small offset impact accident scenarios
Authors: Yang Xiuju , Shi Jingjing , Fu Qianying , Pu Shanshan , Lian Chunxiao , Li Kui , Yin Zhiyong , Liu Shengxiong , Wang Guixue
Published: October 2022

To minimize injuries and protect the safety of the driver in minivan small offset collisions, an optimized pre-tensioned force-limiting seat belt was proposed herein. An accident with detailed information, such as medical reports, vehicle inspection reports, and accident scene photographs, was reconstructed using HyperMesh software. The effectiveness of both the accident model and the pre-tensioned force-limiting seat belt was evaluated. To obtain the optimal seat belt parameters for driver protection, first, force-limiting A, pre-tensioned force B, and pre-tensioned time C factors were selected in designing an orthogonal test with different factor levels. The influence laws of each factor on the injury biomechanical characteristics of the driver were analyzed via the direct analysis method. Moreover, each kind of critical injury value of the human body was synthesized, and the radial basis function surrogate model was constructed. The three seat belt parameters were optimized using the NSGA-II multi-objective genetic algorithm. The results showed that the optimal balance variable parameter of the seat belt was 4751.618 N–2451.839 N–17.554 ms (A–B–C). Finally, the optimal scheme was verified in a system simulating a minivan small offset collision. The results showed that after optimization, the skull von Mises stress was reduced by 36.9%, and the stress of the cervical vertebra cortical bone and cancellous bone decreased by 29.1% and 30.8%, respectively. In addition, the strains of the ribs and lungs decreased by 31.2% and 30.7%, respectively.
Benefits of SGLT2 inhibitors in arrhythmias
Authors: Gao Jinghan , Xue Genlong , Zhan Ge , Wang Xinying , Li Jiatian , Yang Xiaolei , Xia Yunlong
Published: October 2022

Some studies have shown that sodium-glucose cotransporter (SGLT) 2 inhibitors can definitively attenuate the occurrence of cardiovascular diseases such as heart failure (HF), dilated cardiomyopathy (DCM), and myocardial infarction. With the development of research, SGLT2 inhibitors can also reduce the risk of arrhythmias. So in this review, how SGLT2 inhibitors play a role in reducing the risk of arrhythmia from the perspective of electrical remodeling and structural remodeling are explored and then the possible mechanisms are discussed. Specifically, we focus on the role of SGLT2 inhibitors in Na+ and Ca2 + homeostasis and the transients of Na+ and Ca2 +, which could affect electrical remodeling and then lead to arrythmia. We also discuss the protective role of SGLT2 inhibitors in structural remodeling from the perspective of fibrosis, inflammation, oxidative stress, and apoptosis. Ultimately, it is clear that SGLT2 inhibitors have significant benefits on cardiovascular diseases such as HF, myocardial hypertrophy and myocardial infarction. It can be expected that SGLT2 inhibitors can reduce the risk of arrhythmia.
RETRACTED: A modified approach to professional learning communities in mathematics: Fostering teacher reflection around formative assessments of students’ thinking
Authors: Needs Makayla , Bahr Damon L. , McMillan Brandon G. , Nixon Ryan S. , Braden Quinn H. , Royster Rachel
Published: October 2022

A team of three third grade teachers utilized a modified approach to Professional Learning Communities (PLCs) based on principles and procedures that characterize Lesson Study to collaborate about their mathematics instruction. They gathered to design mathematical tasks and anticipate the thinking those tasks might elicit. Subsequent to facilitating lessons based on those tasks, they gathered again to compare the thinking they observed to the thinking they anticipated they would see, and then designed additional tasks informed by their observations. This paper reports on an investigation conducted by one of the teachers who assumed the role of a native, participant researcher as she qualitatively studied the nature of the teachers’ reflections as they collaborated on five occasions. The six domains of Mathematical Knowledge for Teaching (MKT) were used as a conceptual framework for analysis, particularly in looking for connections the teachers were making between or among MKT domains. Our analysis revealed that the teachers learned to consistently engage in very complex thinking that involved interconnected webs representing multiple MKT domains. Furthermore, evidence suggests that the construction of these webs influenced changes in teacher perspectives on the nature of mathematics teaching and learning and produced an increased interest and ability in “making serious use of student thinking,” (p. 11). Such an approach to conducting PLCs appears to possess some potential as a grass roots means of promoting mathematics education reform.
Exploring the driving forces of CO2 emission changes in Chinese cities: A production-theoretical decomposition analysis
Authors: Cao Ruili , Zhao Zhibo
Published: October 2022

Analyzing the forces driving CO2 emissions in cities could provide valuable information for carbon reduction policies in China. This study uses an improved production-theoretical decomposition analysis to evaluate the CO2 emissions of 282 cities in China during 2003–2017. The empirical results show that the scale, energy intensity, and desirable output productivity effects contributed to about 15.03%, 3.64%, and 2.3% growths in CO2 emissions on average, respectively, while the potential CO2 emission and undesirable output productivity effects were responsible for 5.81% and 5.72% reductions in CO2 emissions. By classifying the sample cities and analyzing them further, it was found that the potential CO2 emission effect has a stronger inhibitory impact in resource-based cities. However, the promoting effects of the scale effect is more obvious in non-resource-based cities. From a spatial distribution perspective, the potential CO2 emission effect has a more obvious inhibitory role, and the energy intensity effect is a strong measure for controlling the growth of CO2 emissions in the eastern region. However, the contribution of the scale effect to CO2 emissions is more pronounced in the western region. In addition, we found that the desirable output productivity effects had a suppressive effect in the eastern region and facilitating effects in the central and western regions. The undesirable output productivity effect had a suppressive effect on the growth of CO2 emissions in all three regions, but the suppressive effects were more pronounced in the eastern region.
Does environmental regulation affect global value chain position in service sectors? Evidence from 41 major economies
Authors: Liu Huiqun , Chen Lixin , Shan Yibing
Published: October 2022

The increasing international division of production and stringent environmental policies coexist, which lets people focus more on the research on the relationship between environmental regulation and the global value chain (GVC). Based on the characteristics of service sectors, this study proposes hypotheses of how environmental regulation affects GVC position in service sectors and empirically investigates it by using panel data of the GVC position index in service sectors and the environmental performance index (EPI) from selected 41 major economies during 2006–2014. Our empirical study found the following: first, environmental regulation has significantly promoted the increase of GVC position in service sectors, which obviously can verify the validity of the Porter hypothesis. Second, environmental health has a greater effect on GVC position in service sectors than on ecosystem vitality. Third, the influence of environmental regulation on GVC position in service sectors is heterogeneous under different quantiles. The higher per capita income, the more stringent their environmental regulation and the stronger their impact on GVC position in service sectors. In general, this study will contribute to a better understanding of the relationship between environmental regulation and GVC.
Agricultural practices of the Qin people from the Warring States period to the Qin Dynasty: A case from the Matengkong site in Guanzhong Basin, China
Authors: Tang Liya , Zhou Hui , Wang Zhiyou , Zhu Jing , Liu Jiaqi , Gao Ziheng , Zhao Zhijun
Published: October 2022

In archeological studies, the Qin people have often been a subject of research. The areas of investigation about the Qin include their origin, structure of tombs, funeral rites and interment processes, and cities and settlements. Although there are some studies on the Qin people’s diet which were conducted through isotope analyses, research on the agricultural system of the Qin people is still limited, especially during the period from the Qin people’s settlement in the Guanzhong Basin to the First Emperor bringing the seven states under his dominion. In the backdrop of the Warring States Period, it is necessary to investigate the nature of the Qin people’s agricultural economy and how it impacted their social progress. This study evaluates the Qin people’s agricultural practices based on flotation results from the Matengkong site, located southeast of the Guanzhong Basin in Shaanxi province. The results showed that the inhabitants practiced multi-cropping, and the crop assemblage comprised five categories, including dominant foxtail millet (Setaria italica) and wheat (Triticum aestivum), important broomcorn millet (Panicum miliaceum), less important soybean (Glycine max) and adzuki bean (Vigna angularis), less utilized barley (Hordeum vulgare), and cannabis (Cannabis sativa), and rice (Oryza sativa) of the lowest utilization. Wheat planting played a consistent and important role in agricultural production, and it appears to have had a high yield as same as foxtail millet. However, it appears to have contributed a small part of dietary intake. Rice does not appear to have been an important part of the Qin people’s subsistence at the site and there is no supporting evidence that rice was grown at Matengkong. Rather, it is possible that rice might have been imported from Chu, a neighboring state to the south of Qin, through the ancient mountain passage. Adzuki bean, as a kind of crop resource, was widely used during the Zhou Dynasty. Moreover, Chenopodium sp. and Vitex negundo appear to have been intentionally used because of the high density in each single sample, but they might be multifunctional in nature.
Peripheral blood markers predict immunotherapeutic efficacy in patients with advanced non-small cell lung cancer: A multicenter study
Authors: Liu Shuai , Zhao Liuyuan , Zhou Guohua
Published: October 2022

This study aims to investigate the prognostic impact of peripheral blood markers in patients with advanced non-small cell lung cancer (NSCLC) undergoing immunotherapy. In the current multicenter study, 157 advanced NSCLC cases treated by immunotherapy at three institutions were included. Biochemical parameters in baseline peripheral blood were collected. The associations between biochemical parameters and prognosis were investigated by the Kaplan–Meier survival analyses and Cox regression, and the predictive performances of biomarkers were evaluated via receiver operating characteristic analysis. The neutrophil-to-lymphocyte ratio (NLR) (progression-free survival [PFS]: hazard ratio [HR], 1.766; 95% confidence interval [CI], 1.311–2.380; p < 0.001; overall survival [OS]: HR, 1.283; 95% CI, 1.120–1.469; p < 0.001) and red blood cell distribution width (RDW) (PFS: HR, 1.052; 95% CI, 1.005–1.102; p = 0.031; OS: HR, 1.044; 95% CI, 1.001–1.091; p = 0.042) were revealed as independent predictors for both PFS and OS. In addition, NLR ≥3.79 (1-year PFS, 24.2% [95% CI, 15.2%–38.4%] versus 27.3% [95% CI, 18.2%–41.1%], p = 0.041; 1-year OS, 44.2% [95% CI, 32.5%–60.1%] versus 71.8% [95% CI, 60.6%–85.2%], p < 0.001) or RDW ≥44.8 g/L (1-year PFS, 19.2% [95% CI, 11.4%–32.3%] versus 31.7% [95% CI, 21.9%–46.0%], p = 0.049; 1-year OS, 54.0% [95% CI, 42.7%–68.3%] versus 63.1% [95% CI, 50.6%–78.6%], p = 0.014) was significantly correlated to poorer PFS and OS than NLR < 3.79 or RDW <44.8 g/L. Moreover, NLR and RDW achieved areas under the curve with 0.651 (95% CI, 0.559–0.743) and 0.626 (95% CI, 0.520–0.732) for predicting PFS, and 0.660 (95% CI, 0.567–0.754) and 0.645 (95% CI, 0.552–0.739), for OS. Therefore, PLR and RDW could help predict the immunotherapeutic efficacy of advanced NSCLC.
Candidate genes and sequence variants for susceptibility to mycobacterial infection identified by whole-exome sequencing
Authors: Varzari Alexander , Deyneko Igor V. , Bruun Gitte Hoffmann , Dembic Maja , Hofmann Winfried , Cebotari Victor M. , Ginda Sergei S. , Andresen Brage S. , Illig Thomas
Published: October 2022

Inborn errors of immunity are known to influence susceptibility to mycobacterial infections. The aim of this study was to characterize the genetic profile of nine patients with mycobacterial infections (eight with BCGitis and one with disseminated tuberculosis) from the Republic of Moldova using whole-exome sequencing. In total, 12 variants in eight genes known to be associated with Mendelian Susceptibility to Mycobacterial Disease (MSMD) were detected in six out of nine patients examined. In particular, a novel splice site mutation c.373–2A>C in STAT1 gene was found and functionally confirmed in a patient with disseminated tuberculosis. Trio analysis was possible for seven out of nine patients, and resulted in 23 candidate variants in 15 novel genes. Four of these genes - GBP2, HEATR3, PPP1R9B and KDM6A were further prioritized, considering their elevated expression in immune-related tissues. Compound heterozygosity was found in GBP2 in a single patient, comprising a maternally inherited missense variant c.412G>A/p.(Ala138Thr) predicted to be deleterious and a paternally inherited intronic mutation c.1149+14T>C. Functional studies demonstrated that the intronic mutation affects splicing and the level of transcript. Finally, we analyzed pathogenicity of variant combinations in gene pairs and identified five patients with putative oligogenic inheritance. In summary, our study expands the spectrum of genetic variation contributing to susceptibility to mycobacterial infections in children and provides insight into the complex/oligogenic disease-causing mode.
Sex difference in the expression of PD-1 of non-small cell lung cancer
Authors: Gu Yong , Tang Ying Y. , Wan Jian X. , Zou Jian Y. , Lu Chuan G. , Zhu Hao S. , Sheng Si Y. , Wang Yan F. , Liu Hai Ch. , Yang Jia , Hong Hai
Published: October 2022

Evidence increasingly indicated that lung cancer incidence in female individuals continue to rise, and women have a higher risk to develop adenocarcinoma than men. Male and female individuals differ in their innate and adaptive immune responses, and there are sex differences in response to the PD-1/PD-L1-dependent blocking immunotherapy. Whether the differential expression of PD-1 between genders affect the response to blocking treatment is currently unknown. In this study, we examined sex differences in serum sPD-1, mPD-1 expression on T cells, and sex hormone levels in non-small cell lung cancer (NSCLC) patients. Our results revealed a higher level of sPD-1 and expression of PD-1 on CD4+T cell in female patients than in male patients; we identified that serum sPD-1 level and the expression of mPD-1 on T cells were significantly reduced in NSCLC; we also found that serum testosterone level increased in female patients compared with control subjects and that increased testosterone downregulated the expression of mPD-1 on T cell. These findings provide a better understanding of the differences in PD-1 expression between genders in NSCLC patients and the effect of sex hormones on PD-1 expression and supply evidence for early lung cancer diagnosis and responsiveness to immune checkpoint inhibitors.
Advancing immune checkpoint blockade in colorectal cancer therapy with nanotechnology
Authors: Liu Zefan , Xiang Yucheng , Zheng Yaxian , Kang Xin
Published: October 2022

Immune checkpoint blockade (ICB) has gained unparalleled success in the treatment of colorectal cancer (CRC). However, undesired side effects, unsatisfactory response rates, tumor metastasis, and drug resistance still hinder the further application of ICB therapy against CRC. Advancing ICB with nanotechnology can be game-changing. With the development of immuno-oncology and nanomaterials, various nanoplatforms have been fabricated to enhance the efficacy of ICB in CRC treatment. Herein, this review systematically summarizes these recent nano-strategies according to their mechanisms. Despite their diverse and complex designs, these nanoplatforms have four main mechanisms in enhancing ICB: 1) targeting immune checkpoint inhibitors (ICIs) to tumor foci, 2) increasing tumor immunogenicity, 3) remodeling tumor microenvironment, and 4) pre-sensitizing immune systems. Importantly, advantages of nanotechnology in CRC, such as innovating the mode-of-actions of ICB, modulating intestinal microbiome, and integrating the whole process of antigen presentation, are highlighted in this review. In general, this review describes the latest applications of nanotechnology for CRC immunotherapy, and may shed light on the future design of ICB platforms.
Precise strategies for selecting probiotic bacteria in treatment of intestinal bacterial dysfunctional diseases
Authors: Yang Jiajun , Qin Shunyi , Zhang Hao
Published: October 2022

Abundant microbiota resides in the organs of the body, which utilize the nutrition and form a reciprocal relationship with the host. The composition of these microbiota changes under different pathological conditions, particularly in response to stress and digestive diseases, making the microbial composition and health of the hosts body interdependent. Probiotics are living microorganisms that have demonstrated beneficial effects on physical health and as such are used as supplements to ameliorate symptoms of various digestive diseases by optimizing microbial composition of the gut and restore digestive balance. However, the supplementary effect does not achieve the expected result. Therefore, a targeted screening strategy on probiotic bacteria is crucial, owing to the presence of several bacterial strains. Core bacteria work effectively in maintaining microbiological homeostasis and stabilization in the gastrointestinal tract. Some of the core bacteria can be inherited and acquired from maternal pregnancy and delivery; others can be acquired from contact with the mother, feces, and the environment. Knowing the genera and functions of the core bacteria could be vital in the isolation and selection of probiotic bacteria for supplementation. In addition, other supporting strains of probiotic bacteria are also needed. A comprehensive strategy for mining both core and supporting bacteria before its clinical use is needed. Using metagenomics or other methods of estimation to discern the typically differentiated strains of bacteria is another important strategy to treat dysbiosis. Hence, these two factors are significant to carry out targeted isolation and selection of the functional strains to compose the resulting probiotic preparation for application in both research and clinical use. In conclusion, precise probiotic supplementation, by screening abundant strains of bacteria and isolating specific probiotic strains, could rapidly establish the core microbiota needed to confer resilience, particularly in bacterial dysfunctional diseases. This approach can help identify distinct bacteria which can be used to improve supplementation therapies.
Aging envisage imbalance of the periodontium: A keystone in oral disease and systemic health
Authors: Villalobos Verónica , Garrido Mauricio , Reyes Antonia , Fernández Christian , Diaz Catalina , Torres Vicente A. , González Pablo A. , Cáceres Mónica
Published: October 2022

Aging is a gradual and progressive deterioration of integrity across multiple organ systems that negatively affects gingival wound healing. The cellular responses associated with wound healing, such as collagen synthesis, cell migration, proliferation, and collagen contraction, have been shown to be lower in gingival fibroblasts (the most abundant cells from the connective gingival tissue) in aged donors than young donors. Cellular senescence is one of the hallmarks of aging, which is characterized by the acquisition of a senescence-associated secretory phenotype that is characterized by the release of pro-inflammatory cytokines, chemokines, growth factors, and proteases which have been implicated in the recruitment of immune cells such as neutrophils, T cells and monocytes. Moreover, during aging, macrophages show altered acquisition of functional phenotypes in response to the tissue microenvironment. Thus, inflammatory and resolution macrophage-mediated processes are impaired, impacting the progression of periodontal disease. Interestingly, salivary antimicrobial peptides, such as histatins, which are involved in various functions, such as antifungal, bactericidal, enamel-protecting, angiogenesis, and re-epithelization, have been shown to fluctuate with aging. Several studies have associated the presence of Porphyromonas gingivalis, a key pathogen related to periodontitis and apical periodontitis, with the progression of Alzheimer’s disease, as well as gut, esophageal, and gastric cancers. Moreover, herpes simplex virus types 1 and 2 have been associated with the severity of periodontal disease, cardiovascular complications, and nervous system-related pathologies. This review encompasses the effects of aging on periodontal tissues, how P. gingivalis and HSV infections could favor periodontitis and their relationship with other pathologies.
Human placental hematopoietic stem cell-derived natural killer cells (CYNK) recognize and eliminate influenza A virus-infected cells
Authors: Gunasekaran Manojkumar , Difiglia Andrea , Fitzgerald John , Hariri Robert , van der Touw William , Mahlakõiv Tanel
Published: October 2022

Influenza A virus (IAV) infections are a significant recurrent threat to public health and a significant burden on global economy, highlighting the need for developing more effective therapies. Natural killer (NK) cells play a pivotal role in the control of pulmonary IAV infection, however, little is known about the therapeutic potential of adoptively transferred NK cells for viral infections. Here, we investigated the antiviral activity of CYNK, human placental hematopoietic stem cell-derived NK cells, against IAV infectionin vitro. Virus infection induced the expression of NK cell activating ligands on respiratory epithelial cells, resulting in enhanced recognition by CYNK cells. Upon co-culture with IAV-infected epithelial cells, CYNK exhibited elevated degranulation and increased production of IFN-γ, TNF-α and GM-CSF in a virus dose-dependent manner. Furthermore, CYNK showed virus dose-dependent cytotoxicity against IAV-infected cells. The antiviral activity of CYNK was mediated by NKp46 and NKG2D. Together, these data demonstrate that CYNK possesses potent antiviral function against IAV and warrant clinical investigations for adoptive NK cell therapies against viral infections.
Strongyloidiasis stercoralis coinfection is associated with altered iron status biomarkers in tuberculous lymphadenitis
Authors: Kathamuthu Gokul Raj , Rajamanickam Anuradha , Sridhar Rathinam , Baskaran Dhanaraj , Babu Subash
Published: October 2022

Soil-transmitted helminth [mainly Strongyloidiasis stercoralis (Ss)] and tuberculous lymphadenitis (TBL) coinfection in humans is a significant public health problem. We have previously shown that TBL+Ss+ coinfection significantly alters diverse cytokine, matrix metalloproteinase, and tissue inhibitors of metalloproteinase profiles. However, no data is available to understand the influence of Ss coinfection in TBL disease with respect to iron status biomarkers. Hence, we have studied the effect of Ss coinfection on the circulating levels of iron status (ferritin, transferrin [TF], apotransferrin [ApoT], hepcidin, hemopexin) biomarkers in TBL disease. Our results show that TBL+Ss+ and/or TBL+Ss- individuals are associated with significantly altered biochemical and hematological (red blood cell (RBC) counts, hemoglobin (Hb), hematocrit (HCT), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH) were decreased, and platelets were increased) parameters compared to TBL-Ss+ individuals. Our results also show that TBL+Ss+ coinfection is associated with diminished circulating levels of ferritin, ApoT, hepcidin, and hemopexin compared to TBL+Ss- individuals. TBL+Ss+ and TBL+Ss- groups are associated with altered iron status biomarkers (decreased ferritin [TBL+Ss+ alone] and increased TF, ApoT, hepcidin and hemopexin [TBL+Ss- alone]) compared to TBL-Ss+ group. The heat map expression profile and principal component analysis (PCA) analysis of iron status biomarkers were significantly altered in TBL+Ss+ compared to TBL+Ss- and/or TBL-Ss+ individuals. A significant correlation (positive/negative) was obtained among the biochemical and hematological parameters (white blood cells (WBC)/ferritin, TF, and hepcidin, mean corpuscular hemoglobin concentration (MCHC)/ferritin and hemopexin) with iron status biomarkers. Finally, receiver operating characteristic (ROC) analysis revealed that hemopexin was significantly associated with greater specificity and sensitivity in discriminating TBL+Ss+ and TBL+Ss- coinfected individuals. Thus, our data conclude that Ss coinfection is associated with altered iron status biomarkers indicating that coinfection might alter the host-Mtb interface and could influence the disease pathogenesis.
Renal X-inactivation in female individuals with X-linked Alport syndrome primarily determined by age
Authors: Günthner Roman , Knipping Lea , Jeruschke Stefanie , Satanoskij Robin , Lorenz-Depiereux Bettina , Hemmer Clara , Braunisch Matthias C. , Riedhammer Korbinian M. , Ćomić Jasmina , Tönshoff Burkhard , Tasic Velibor , Abazi-Emini Nora , Nushi-Stavileci Valbona , Buiting Karin , Gjorgjievski Nikola , Momirovska Ana , Patzer Ludwig , Kirschstein Martin , Gross Oliver , Lungu Adrian , Weber Stefanie , Renders Lutz , Heemann Uwe , Meitinger Thomas , Büscher Anja K. , Hoefele Julia
Published: October 2022

X-linked Alport syndrome (AS) caused by hemizygous disease-causing variants in COL4A5 primarily affects males. Females with a heterozygous state show a diverse phenotypic spectrum ranging from microscopic hematuria to end-stage kidney disease (ESKD) and extrarenal manifestations. In other X-linked diseases, skewed X-inactivation leads to preferential silencing of one X-chromosome and thus can determine the phenotype in females. We aimed to show a correlation between X-inactivation in blood and urine-derived renal cells and clinical phenotype of females with a heterozygous disease-causing variant in COL4A5 compared to healthy controls. A total of 56 females with a heterozygous disease-causing COL4A5 variant and a mean age of 31.6 ± 18.3 SD years were included in this study. A total of 94% had hematuria, 62% proteinuria >200 mg/day, yet only 7% had decreased eGFR. Using human androgen receptor assay X-inactivation was examined in blood cells of all 56 individuals, in urine-derived cells of 27 of these individuals and in all healthy controls. X-inactivation did not correlate with age of first manifestation, proteinuria or eGFR neither in blood, nor in urine. The degree of X-inactivation showed a moderate association with age, especially in urine-derived cells of the patient cohort (rho = 0.403, p = 0.037). Determination of X-inactivation allelity revealed a shift of X-inactivation toward the COL4A5 variant bearing allele. This is the first study examining X-inactivation of urine-derived cells from female individuals with AS. A correlation between phenotype and X-inactivation could not be observed suspecting other genetic modifiers shaping the phenotype in female individuals with AS. The association of X-inactivation with age in urine-derived cells suggests an escape-mechanism inactivating the COL4A5 variant carrying allele in female individuals with AS.
Machine learning models for predicting in-hospital mortality in patient with sepsis: Analysis of vital sign dynamics
Authors: Cheng Chi-Yung , Kung Chia-Te , Chen Fu-Cheng , Chiu I-Min , Lin Chun-Hung Richard , Chu Chun-Chieh , Kung Chien Feng , Su Chih-Min
Published: October 2022

Purpose

To build machine learning models for predicting the risk of in-hospital death in patients with sepsis within 48 h, using only dynamic changes in the patient's vital signs.

Methods

This retrospective observational cohort study enrolled septic patients from five emergency departments (ED) in Taiwan. We adopted seven variables, i.e., age, sex, systolic blood pressure, diastolic blood pressure, heart rate, respiratory rate, and body temperature.

Results

Among all 353,253 visits, after excluding 159,607 visits (45%), the study group consisted of 193,646 ED visits. With a leading time of 6 h, the convolutional neural networks (CNNs), long short-term memory (LSTM), and random forest (RF) had accuracy rates of 0.905, 0.817, and 0.835, respectively, and the area under the receiver operating characteristic curve (AUC) was 0.840, 0.761, and 0.770, respectively. With a leading time of 48 h, the CNN, LSTM, and RF achieved accuracy rates of 0.828, 0759, and 0.805, respectively, and an AUC of 0.811, 0.734, and 0.776, respectively.

Conclusion

By analyzing dynamic vital sign data, machine learning models can predict mortality in septic patients within 6 to 48 h of admission. The performance of the testing models is more accurate if the lead time is closer to the event.
Optical coherence tomography evaluation of choroidal structure changes in diabetic retinopathy patients: A systematic review and meta-analysis
Authors: Jiang Jikuan , Liu Jingyuan , Yang Jia , Jiang Bing
Published: October 2022

Introduction

Diabetic retinopathy (DR) is one of the major causes of blindness among working-aged adults worldwide. This study aimed to evaluate the differences in the subfoveal choroidal thickness (SFCT) and choroidal vascularity index (CVI) using optical coherence tomography (OCT) of patients with diabetic eyes with no retinopathy (NDR) and with diabetic retinopathy (DR).

Methods

We performed a comprehensive literature search of the PubMed, Embase, and Cochrane Library databases up to October 2021. The weighted mean difference (WMD) with the 95% confidence interval (CI) was pooled for continuous outcomes.

Results

Twenty-three cross-sectional studies comprising 2,534 eyes including 1,070 NDR eyes, 1,464 DR eyes were included in the systematic review and meta-analysis. The pooled results showed SFCT was significantly thicker in DR than in NDR patients after adjusting for axial length (WMD = 27.90 μm; 95% CI: 11.51 to 44.28; P = 0.001), and the CVI was significantly lower in DR patients (WMD = −1.59; 95% CI: −2.67 to −0.52; P = 0.004).

Conclusion

We described changes in the SFCT and CVI in DR. Resultantly, the CVI and SFCT may be valuable parameters for monitoring the onset of DR and helpful for a better understanding of the role of the choroid in the pathological process of DR.

Systematic review registration

https://www.crd.york.ac.uk/prospero/#myprospero, CRD42021228738.
Topical application of the plant extract SDTL-E in ovariectomized rats: A potential new approach for treating osteoporosis
Authors: Shih Hui-Yuan , Lu Jun-Hua , Xiong Ai-Hua , Tse Juliana Man-Wai , Wong Ben Siu-Tak
Published: October 2022

Current osteoporosis medications have drawbacks of causing side effects and having slow onset, therefore developing osteoporosis drugs with faster onset and less side effects is essential. This study investigated the effects of the natural plant extract, SDTL-E, in ovariectomized (OVX)-induced osteoporosis rats. Rats were randomly assigned to sham operation control group (Control Group); OVX rat model group (Model Group) or OVX rat SDTL-E treatment group (SDTL-E Group). All groups underwent ovariectomy, but the Control Group did not have the ovaries removed. SDTL-E Group was treated with SDTL-E, Model and Control Groups were treated with vegetable oil, treatments were topically applied twice daily for 20 days. Results showed when compared with Model Group, SDTL-E Group significantly restored serum estradiol back to near Control Group level, serum ALP activity, serum and urinary calcium were significantly decreased, bone mechanics indicators increased and trabecular bone numbers slightly increased. These results demonstrated 20 days of SDTL-E topical treatment improved bone strength and trabecular bone structure in OVX-induced osteoporosis rats. The underlying mechanisms include restoring estradiol level, reducing bone turnover, net bone resorption, bone calcium loss, and calcium excretion through kidney. These findings suggest topical application of plant extract is a potential new approach with quick efficacy for treating osteoporosis.
Systematic review and meta-analysis of oral squamous cell carcinoma associated oral microbiome
Authors: Peter Tabitha K. , Withanage Miyuraj H. H. , Comnick Carissa L. , Pendleton Chandler , Dabdoub Shareef , Ganesan Sukirth , Drake David , Banas Jeffrey , Xie Xian Jin , Zeng Erliang
Published: October 2022

The intersection between the human oral microbiome and oral health is an emerging area of study which has gained momentum over the last decade. This momentum has motivated a search for associations between the oral microbiome and oral cancer, in hopes of identifying possible biomarkers that facilitate earlier diagnosis and improved prognosis for patients with that disease. The present study examined the relationship between the microbiome in the human oral cavity and oral squamous cell carcinoma (OSCC). We searched the literature for case-control studies which focused on the relationship between the human oral microbiome and OSCC. We aggregated three types of data from these studies: bacteriome data at the genus level, predicted functional pathway data, and gene abundance data. From these data, we noted several microbial genera which may be associated with oral cancer status, including Fusobacterium. We also identified functional pathways which merit further investigation, including RNA degradation (ko03018) and primary immunodeficiency (ko05340). In addition, our analysis of gene abundance data identified the gene K06147 (ATP-binding cassette, subfamily B, bacterial) as being over abundant in OSCC samples. Our results are generalizations which identified some currents that we believe could guide further research. Our work faced several limitations related to the heterogeneity of the available data. Wide variation in methods for sample collection, methods for controlling for known behavioral risk factors, computing platform choice, and methods for case-control design all posed confounding factors in this work. We examined the current methods of data collection, data processing, and data reporting in order to offer suggestions toward the establishment of best practices within this field. We propose that these limitations should be addressed through the implementation of standardized data analytic practices that will conform to the rigor and reproducibility standards required of publicly funded research.
Application of a maximal-clique based community detection algorithm to gut microbiome data reveals driver microbes during influenza A virus infection
Authors: Bhar Anirban , Gierse Laurin Christopher , Meene Alexander , Wang Haitao , Karte Claudia , Schwaiger Theresa , Schröder Charlotte , Mettenleiter Thomas C. , Urich Tim , Riedel Katharina , Kaderali Lars
Published: October 2022

Influenza A Virus (IAV) infection followed by bacterial pneumonia often leads to hospitalization and death in individuals from high risk groups. Following infection, IAV triggers the process of viral RNA replication which in turn disrupts healthy gut microbial community, while the gut microbiota plays an instrumental role in protecting the host by evolving colonization resistance. Although the underlying mechanisms of IAV infection have been unraveled, the underlying complex mechanisms evolved by gut microbiota in order to induce host immune response following IAV infection remain evasive. In this work, we developed a novel Maximal-Clique based Community Detection algorithm for Weighted undirected Networks (MCCD-WN) and compared its performance with other existing algorithms using three sets of benchmark networks. Moreover, we applied our algorithm to gut microbiome data derived from fecal samples of both healthy and IAV-infected pigs over a sequence of time-points. The results we obtained from the real-life IAV dataset unveil the role of the microbial familiesRuminococcaceae, Lachnospiraceae, SpirochaetaceaeandPrevotellaceaein the gut microbiome of the IAV-infected cohort. Furthermore, the additional integration of metaproteomic data enabled not only the identification of microbial biomarkers, but also the elucidation of their functional roles in protecting the host following IAV infection. Our network analysis reveals a fast recovery of the infected cohort after the second IAV infection and provides insights into crucial roles ofDesulfovibrionaceaeandLactobacillaceaefamilies in combating Influenza A Virus infection. Source code of the community detection algorithm can be downloaded fromhttps://github.com/AniBhar84/MCCD-WN.
Sodium butyrate mediates histone crotonylation and alleviated neonatal rats hypoxic–ischemic brain injury through gut–brain axis
Authors: He Xuejia , Zhang Ting , Zeng Yubing , Pei Pei , Liu Yulan , Jia Wenbin , Zhao Hongyang , Bi Meirong , Wang Shan
Published: October 2022

Neonatal hypoxic–ischemic encephalopathy (HIE) refers to nervous system damage caused by perinatal hypoxia, which is the major cause of long-term neuro-developmental disorders in surviving infants. However, the mechanisms still require further investigation. In this study, we found that the butanoate metabolism pathway exhibited significantly decreased and short chain fatty acid (SCFAs)-producing bacteria, especially butyrate-producing bacteria, were significantly decreased in fecal of neonatal hypoxic–ischemic brain damage (HIBD) rats. Surprisingly, Sodium butyrate (SB) treatment could ameliorate pathological damage both in the cerebral cortex and hippocampus and facilitate recovery of SCFAs-producing bacteria related to metabolic pathways in neonatal HIBD rats. Moreover, we found that in samples from SB treatment neonatal HIBD rats cortex with high levels of butyrate acid along with aberrant key crotonyl-CoA-producing enzymes ACADS levels were observed compared HIBD rats. We also demonstrated that a decrease in histone 3-lysine 9-crotonylation (H3K9cr) downregulated expression of the HIE-related neurotrophic genes Bdnf, Gdnf, Cdnf, and Manf in HIBD rats. Furthermore, SB restored H3K9cr binding to HIE-related neurotrophic genes. Collectively, our results indicate that SB contributes to ameliorate pathology of HIBD by altering gut microbiota and brain SCFAs levels subsequently affecting histone crotonylation-mediated neurotrophic-related genes expression. This may be a novel microbiological approach for preventing and treating HIE.