bluuebunny/crossref_metadata_2025 huggingface dataset:
El cerebro estresado y su implicación en el comportamiento desadaptativo durante la pandemia por COVID-19
Authors: Gordillo León Fernando
Published: April 2023

Los seres humanos se enfrentan a diario a situaciones estresantes ante las que deben responder con eficacia para sobrevivir y adaptarse al entorno. Sin embargo, la elevada intensidad y persistencia del estresor, como sucedió durante la pandemia del COVID-19, podría tener un efecto negativo sobre la neurología, cognición y conducta de las personas. Estructuras como la amígdala y la corteza prefrontal se ven afectadas por el estrés agudo y persistente, siendo la base explicativa de las actitudes y conductas desadaptativas que ocurren en situaciones de emergencia. Procesos como la latencia entre el estrés y la toma de decisiones, la reevaluación cognitiva, y la imitación, todos dependientes de la corteza prefrontal y la amígdala, permiten explicar la rápida difusión de las fake news, el negacionismo, y las compras compulsivas durante la pandemia del COVID-19. A partir del análisis realizado de la información, se pueden establecer unas pautas de abordaje, basadas en los conocimientos neurocognitivos, con las que afrontar situaciones de emergencia: 1) Monitorear el nivel de estrés poblacional; 2) Gestionar la información trasmitida (intensidad/frecuencia); 3) Evitar contradicciones informativas (incertidumbre); 4) Promover modelos de imitación; 5) Establecer sistemas de ayuda a grupos vulnerables; 6) Facilitar el ocio controlado.
Issues in the identification, assessment and treatment of children and adolescents with ADHD
Authors: Francisco Balbuena Rivera
Published: April 2023

Many studies into Attention-Deficit/hyperactivity Disorder (ADHD) have documented that this neurodevelopment disorder may be under-identified. Early diagnosis of children and adolescents with ADHD is important, and consequently school-based interventions represent an essential tool for work in this area. To identify issues in the diagnosis, assessment and treatment of children and adolescents with ADHD, is reviewed here research findings which could lead to significantly better outcomes for children and adolescents with ADHD. Accordingly, we briefly review studies retrieved in a MEDLINE search, using the terms “ADHD”, “identification”, prevalence”, “assessment”, “treatment”, “learning disabilities” and “ADHD” and “comorbidity” combined, as these pinpoint diagnosis, for the years 2009 to 2022. In this respect, the literature reviewed suggests that multiple aspects associated with psychometric features, as well as clinical and/or pharmacological factors should be considered of highly clinical significance in identifying, assessing and treating individuals diagnosed with ADHD. For this reason, it is important to investigate about difficulties immersed in identifying, assessing and treating to children and adolescents with ADHD in different settings.
Application of data-driven surrogate models for active human model response prediction and restraint system optimization
Authors: Hay Julian , Schories Lars , Bayerschen Eric , Wimmer Peter , Zehbe Oliver , Kirschbichler Stefan , Fehr Jörg
Published: April 2023

Surrogate models are a must-have in a scenario-based safety simulation framework to design optimally integrated safety systems for new mobility solutions. The objective of this study is the development of surrogate models for active human model responses under consideration of multiple sampling strategies. A Gaussian process regression is chosen for predicting injury values based on the collision scenario, the occupant's seating position after a pre-crash movement and selected restraint system parameters. The trained models are validated and assessed for each sampling method and the best-performing surrogate model is selected for restraint system parameter optimization.
Onset of pain to surgery time in acute aortic dissections type A: a mandatory factor for evaluating surgical results?
Authors: Kaufeld Tim , Martens Andreas , Beckmann Erik , Rudolph Linda , Krüger Heike , Natanov Ruslan , Arar Morsi , Korte Wilhelm , Schilling Tobias , Haverich Axel , Shrestha Malakh
Published: April 2023

Objective

An acute aortic dissection type A (AADA) is a rare but life-threatening event. The mortality rate ranges between 18% to 28% and mortality is often within the first 24 h and up to 1%–2% per hour. Although the onset of pain to surgery time has not been a relevant factor in terms of research in the field of AADA, we hypothesize that a patient's preoperative conditions depend on the length of this time.

Methods

Between January 2000 and January 2018, 430 patients received surgical treatment for acute aortic dissection DeBakey type I at our tertiary referral hospital. In 11 patients, the exact time point of initial onset of pain was retrospectively not detectable. Accordingly, a total of 419 patients were included in the study. The cohort was categorized into two groups: Group A with an onset of pain to surgery time < 6 h (n = 211) and Group B > 6 h (n = 208), respectively.

Results

Median age was 63.5 years (y) ((IQR: 53.3–71.4 y); (67.5% male)). Preoperative conditions differed significantly between the cohorts. Differences were detected in terms of malperfusion (A: 39.3%; B: 23.6%; P: 0.001), neurological symptoms (A: 24.2%; B: 15.4%; P: 0.024), and the dissection of supra-aortic arteries (A: 25.1%; B: 16.8%; P: 0.037). In particular, cerebral malperfusion (A 15.2%: B: 8.2%; P: 0.026) and limb malperfusion (A: 18%, B: 10.1%; P: 0.020) were significantly increased in Group A. Furthermore, Group A showed a decreased median survival time (A: 1,359.0 d; B: 2,247.5 d; P: 0.001), extended ventilation time (A: 53.0 h; B: 44.0 h; P: 0.249) and higher 30-day mortality rate (A: 25.1%; B: 17.3%; P: 0.051).

Conclusions

Patients with a short onset of pain to surgery time in cases of AADA present themselves not only with more severe preoperative symptoms but are also the more compromised cohort. Despite early presentation and emergency aortic repair, these patients show increased chances of early mortality. The “onset of pain to surgery time” should become a mandatory factor when making comparable surgical evaluations in the field of AADA.
Multimodality imaging methods and systemic biomarkers in classical low-flow low-gradient aortic stenosis: Key findings for risk stratification
Authors: Lopes Maria Antonieta Albanez A. de M. , Campos Carlos M. , Rosa Vitor Emer Egypto , Sampaio Roney O. , Morais Thamara C. , de Brito Júnior Fábio Sândoli , Vieira Marcelo L. C. , Mathias Wilson , Fernandes Joao Ricardo Cordeiro , de Santis Antonio , Santos Luciano de Moura , Rochitte Carlos E. , Capodanno Davide , Tamburino Corrado , Abizaid Alexandre , Tarasoutchi Flavio
Published: April 2023

Objectives

The aim of the present study is to assess multimodality imaging findings according to systemic biomarkers, high-sensitivity troponin I (hsTnI) and B-type natriuretic peptide (BNP) levels, in low-flow, low-gradient aortic stenosis (LFLG-AS).

Background

Elevated levels of BNP and hsTnI have been related with poor prognosis in patients with LFLG-AS.

Methods

Prospective study with LFLG-AS patients that underwent hsTnI, BNP, coronary angiography, cardiac magnetic resonance (CMR) with T1 mapping, echocardiogram and dobutamine stress echocardiogram. Patients were divided into 3 groups according to BNP and hsTnI levels: Group 1 (n = 17) when BNP and hsTnI levels were below median [BNP < 1.98 fold upper reference limit (URL) and hsTnI < 1.8 fold URL]; Group 2 (n = 14) when BNP or hsTnI were higher than median; and Group 3 (n = 18) when both hsTnI and BNP were higher than median.

Results

49 patients included in 3 groups. Clinical characteristics (including risk scores) were similar among groups. Group 3 patients had lower valvuloarterial impedance (P = 0.03) and lower left ventricular ejection fraction (P = 0.02) by echocardiogram. CMR identified a progressive increase of right and left ventricular chamber from Group 1 to Group 3, and worsening of left ventricular ejection fraction (EF) (40 [31–47] vs. 32 [29–41] vs. 26 [19–33]%; p < 0.01) and right ventricular EF (62 [53–69] vs. 51 [35–63] vs. 30 [24–46]%; p < 0.01). Besides, there was a marked increase in myocardial fibrosis assessed by extracellular volume fraction (ECV) (28.4 [24.8–30.7] vs. 28.2 [26.9–34.5] vs. 31.8 [28.9–35.5]%; p = 0.03) and indexed ECV (iECV) (28.7 [21.2–39.1] vs. 28.8 [25.4–39.9] vs. 44.2 [36.4–51.2] ml/m2, respectively; p < 0.01) from Group 1 to Group 3.

Conclusions

Higher levels of BNP and hsTnI in LFLG-AS patients are associated with worse multi-modality evidence of cardiac remodeling and fibrosis.
Hazard-based risk grouping effectively stratifying breast cancer patients in post-irradiation long-term heart diseases: a population-based cohort study
Authors: Lee Moon-Sing , Tsai Wei-Ta , Yang Hsuan-Ju , Hung Shih-Kai , Chiou Wen-Yen , Liu Dai-Wei , Chen Liang-Cheng , Chew Chia-Hui , Yu Ben-Hui , Hsu Feng-Chun , Wu Tung-Hsin , Lin Hon-Yi
Published: April 2023

Background

Even though advanced radiotherapy techniques provide a better protective effect on surrounding normal tissues, the late sequelae from radiation exposure to the heart are still considerable in breast cancer patients. The present population-based study explored the role of cox-regression-based hazard risk grouping and intended to stratify patients with post-irradiation long-term heart diseases.

Materials and methods

The present study investigated the Taiwan National Health Insurance (TNHI) database. From 2000 to 2017, we identified 158,798 breast cancer patients. Using a propensity score match of 1:1, we included 21,123 patients in each left and right breast irradiation cohort. Heart diseases, including heart failure (HF), ischemic heart disease (IHD), and other heart diseases (OHD), and anticancer agents, including epirubicin, doxorubicin, and trastuzumab, were included for analysis.

Results

Patients received left breast irradiation demonstrated increased risks on IHD (aHR, 1.16; 95% CI, 1.06–1.26; p < 0.01) and OHD (aHR, 1.08; 95% CI, 1.01–1.15; p < 0.05), but not HF (aHR, 1.11; 95% CI, 0.96–1.28; p = 0.14), when compared with patients received right breast irradiation. In patients who received left breast irradiation dose of >6,040 cGy, subsequent epirubicin might have a trend to increase the risk of heart failure (aHR, 1.53; 95% CI, 0.98–2.39; p = 0.058), while doxorubicin (aHR, 0.59; 95% CI, 0.26–1.32; p = 0.19) and trastuzumab (aHR, 0.93; 95% CI, 0.33–2.62; p = 0.89) did not. Older age was the highest independent risk factor for post-irradiation long-term heart diseases.

Conclusion

Generally, systemic anticancer agents are safe in conjunction with radiotherapy for managing post-operative breast cancer patients. Hazard-based risk grouping may help stratify breast cancer patients associated with post-irradiation long-term heart diseases. Notably, radiotherapy should be performed cautiously for elderly left breast cancer patients who received epirubicin. Limited irradiation dose to the heart should be critically considered. Regular monitoring of potential signs of heart failure may be conducted.
Learning processes, memory development, and knowledge sharing via mobile applications using MOOCs
Authors: Al-Said Khaleel , Berestova Anna , Shterts Olga
Published: April 2023

This paper aims to analyse the impact of MOOC-based mobile applications on the learning process, memory development, knowledge sharing, and student motivation to study. The study analyzes the existing electronic educational resources of universities. The study design includes two types of surveys (before and after MOOC-based training). The sample population included 662 students of 1–4 courses. A survey conducted before the training showed that 54% of respondents rated their technical competence level as average, 43% rated it as high, and 3% rated it as low. About 83% of respondents noted that mobile applications and online educational courses have affected their academic performance in learning, memory development, and learning ability. The post-training survey results indicated an improvement in the group performance of students who learned with mobile applications on MOOC platforms. The practical significance of the research is determined by the possibility of using the program based on MOOC mobile applications at different faculties of the university. The paper also supplements existing studies with new data on the impact of learning using MOOCs mobile applications on the educational process.
Sharpening the mesowear tool: geometric morphometric analysis of cusp shape and diet in ruminants
Authors: Mihlbachler Matthew C. , Barrón-Ortiz Christina I. , Rankin Brian D. , Theodor Jessica M.
Published: April 2023

Mesowear is a dietary proxy that relates attritive wear and abrasive wear to the shape of worn tooth cusps of ungulates. Traditional mesowear methods categorize cusps according to relief and sharpness. A geometric morphometric approach has the potential to measure shape with higher precision and to discover unrecognized aspects of cusp shape, possibly improving the efficacy of mesowear. We quantified mesowear in extant Ruminantia, using a 2-D semilandmark outline technique on upper second molar metacones generated from photographs. Among the 91 species sampled, 65 were preassigned to dietary categories, browser, grazer, mixed feeder, and frugivore based on substantiated documentation of diet in the wildlife literature. Metacone cusp shape and metacone mesowear score were found to be independent of size. Principal component and discriminant function analyses of Procrustes transformed semilandmark coordinates revealed two diet-related components of cusp shape. The primary component is related to the traditional mesowear variables of cusp height and side steepness. The secondary shape component reveals variation in the mesiodistal symmetry of the metacone and may relate to a proal vector during the power stroke phase or the relative orientation of the cusps with respect to the chewing stroke vector. Discriminant function analysis of semilandmark data accurately classified the diets of species more frequently (67.2%) than the traditional mesowear method (56.1%). The semilandmark data successfully recognized the diets of grazing and browsing species with correct classification rates ranging from 69% to 95%. The diets of frugivorous and mixed feeding species were less frequently correctly recognized (33%–53%). Mixed feeding diets may be more difficult to recognize due to more heterogeneous diets when compared to browsers and grazers. Frugivores are more difficult to recognize because their rounded cusp apices resemble those of mixed feeders and grazers. We conclude that quantitative shape analysis improves the potential of mesowear. When used as a dietary proxy, we anticipate that mesowear analysis will correctly categorize the diets of most species. When misclassifications are made, they may most often be misclassifications of generalist mixed feeders and frugivores as either browsers or grazers.
Vertical heterogeneity of hydrocarbon-degrading bacteria in a core sediment sample from the Central Indian Ridge
Authors: Hao Tong , Cui Zhisong , Luan Xiao , Zhou Guangzhu , Li Yingchao , Liu Jinyan , Chen Junhui , Wang Zongling
Published: April 2023

Hydrocarbons are ubiquitous in marine environments and might fuel hydrocarbon-metabolizing microbes in the ocean. Numerous studies have documented microbial hydrocarbon degradation in water columns and deep-sea surface sediment. However, the degradation potential and biogeochemical cycling of hydrocarbons in subsurface sediments remain largely unknown. In this study, we used two different hydrocarbons, n-hexadecane (HEX) and methylcyclohexane (MCH), to investigate the distribution and diversity of hydrocarbon-consuming bacteria in a core sediment sample from the Central Indian Ridge (CIR), which is adjacent to mid-ridge hydrothermal vents in the Indian Ocean. We observed different vertical profiles of HEX- and MCH-degrading bacteria in the core sediments. Specifically, HEX-degrading bacteria were universally distributed, while MCH-degrading bacteria were found only in the intermediate layers of the core sediments. Changing factors including dissolved oxygen might affect the natural distribution of different hydrocarbon consumers. We found that a novel species of the genus C1-B045 might play a pivotal role in metabolizing MCH in the CIR deep biosphere. Through amino acid identity comparison with published sequences, we determined that C1-B045 harbors two novel classes of cyclohexanone monooxygenases involved in MCH metabolism. This study sheds light on the structure and function of hydrocarbon-consuming microbes in deep biospheres.
NaCl-induced hot corrosion behaviors of NiSiAlY coatings
Authors: Yu Miao , Zhou Dapeng , Zhu Bing , Cui Tiancheng , Lu Yang , Wang Yongxin
Published: April 2023

In the marine environments, NiCrAlY coatings with high content of Cr would suffer much severer corrosion due to the effect of NaCl. Thus, NiSiAlY coatings with different Si content were proposed and deposited on Ni-based superalloys by multi-arc ion plating. The as-deposited coating was mainly composed of γ’-Ni3Al phase with a small amount of β-NiAl phase. NaCl-induced hot corrosion tests were performed on the coatings at 500°C, 600°C, and 700°C, respectively. Compared with Ni-based alloy substrates, the NiSiAlY coatings exhibited a good corrosion resistance to NaCl at elevated temperatures. However, with an excessive amount of Si, the NiSiAlY coating showed a degradation in the hot corrosion resistance. In this work, the corrosion mechanisms of the tested coatings were discussed. Moreover, the role of Si was also investigated.
Case report: Successful experience using continuous infusion of meropenem in a geriatric patient with hip fracture complicated by sepsis
Authors: Kadralinova Assiya , Bekniyazova Assema Zh. , Konkayeva Maiya E. , Yeltayeva Aigerim A. , Konkayev Aidos K.
Published: April 2023

This article highlights a clinical case of successful treatment of a 79-year-old multimorbid patient with a hip fracture resulting from a household injury. On the first day, the patient’s injury was complicated by infection and pneumonia. As a result, arterial hypotension, tachysystole, and respiratory failure progressed. With manifestations of sepsis, the patient was transferred to the intensive care unit. Surgical treatment in such a situation was contraindicated due to the high operational and anesthesiological risks, the unstable severe condition of the patient, as well as the presence of concomitant pathology in the form of coronary heart disease, obesity, and schizophrenia. According to the new sepsis management guideline, it was decided to use a continuous 24-h infusion of meropenem in addition to the complex treatment of sepsis. The use of continuous infusion of meropenem in this clinical situation may have caused the patient’s clinical improvement, which increased her quality of life and decreased the length of ICU stay and total hospital stay, despite an unfavorable cumulative prognosis and a high risk of in-hospital mortality.
Identification of subphenotypes in critically ill thrombocytopenic patients with different responses to therapeutic interventions: a retrospective study
Authors: Jiang Xuandong , Zhang Weimin , Pan Yuting , Cheng Xuping
Published: April 2023

Introduction

The causes of thrombocytopenia (TP) in critically ill patients are numerous and heterogeneous. Currently, subphenotype identification is a popular approach to address this problem. Therefore, this study aimed to identify subphenotypes that respond differently to therapeutic interventions in patients with TP using routine clinical data and to improve individualized management of TP.

Methods

This retrospective study included patients with TP admitted to the intensive care unit (ICU) of Dongyang People’s Hospital during 2010–2020. Subphenotypes were identified using latent profile analysis of 15 clinical variables. The Kaplan–Meier method was used to assess the risk of 30-day mortality for different subphenotypes. Multifactorial Cox regression analysis was used to analyze the relationship between therapeutic interventions and in-hospital mortality for different subphenotypes.

Results

This study included a total of 1,666 participants. Four subphenotypes were identified by latent profile analysis, with subphenotype 1 being the most abundant and having a low mortality rate. Subphenotype 2 was characterized by respiratory dysfunction, subphenotype 3 by renal insufficiency, and subphenotype 4 by shock-like features. Kaplan–Meier analysis revealed that the four subphenotypes had different in-30-day mortality rates. The multivariate Cox regression analysis indicated a significant interaction between platelet transfusion and subphenotype, with more platelet transfusion associated with a decreased risk of in-hospital mortality in subphenotype 3 [hazard ratio (HR): 0.66, 95% confidence interval (CI): 0.46–0.94]. In addition, there was a significant interaction between fluid intake and subphenotype, with a higher fluid intake being associated with a decreased risk of in-hospital mortality for subphenotype 3 (HR: 0.94, 95% CI: 0.89–0.99 per 1 l increase in fluid intake) and an increased risk of in-hospital mortality for high fluid intake in subphenotypes 1 (HR: 1.10, 95% CI: 1.03–1.18 per 1 l increase in fluid intake) and 2 (HR: 1.19, 95% CI: 1.08–1.32 per 1 l increase in fluid intake).

Conclusion

Four subphenotypes of TP in critically ill patients with different clinical characteristics and outcomes and differential responses to therapeutic interventions were identified using routine clinical data. These findings can help improve the identification of different subphenotypes in patients with TP for better individualized treatment of patients in the ICU.
Comparison of freeze-thaw and sonication cycle-based methods for extracting AMR-associated metabolites from Staphylococcus aureus
Authors: Singh Rita , Thakur Lovnish , Kumar Ashok , Singh Sevaram , Kumar Shailesh , Kumar Manoj , Kumar Yashwant , Kumar Niraj
Published: April 2023

Emerging antimicrobial resistance (AMR) among Gram-positive pathogens, specifically in Staphylococcus aureus (S. aureus), is becoming a leading public health concern demanding effective therapeutics. Metabolite modulation can improve the efficacy of existing antibiotics and facilitate the development of effective therapeutics. However, it remained unexplored for drug-resistant S. aureus (gentamicin and methicillin-resistant), primarily due to the dearth of optimal metabolite extraction protocols including a protocol for AMR-associated metabolites. Therefore, in this investigation, we have compared the performance of the two most widely used methods, i.e., freeze-thaw cycle (FTC) and sonication cycle (SC), alone and in combination (FTC + SC), and identified the optimal method for this purpose. A total of 116, 119, and 99 metabolites were identified using the FTC, SC, and FTC + SC methods, respectively, leading to the identification of 163 metabolites cumulatively. Out of 163, 69 metabolites were found to be associated with AMR in published literature consisting of the highest number of metabolites identified by FTC (57) followed by SC (54) and FTC + SC (40). Thus, the performances of FTC and SC methods were comparable with no additional benefits of combining both. Moreover, each method showed biasness toward specific metabolite(s) or class of metabolites, suggesting that the choice of metabolite extraction method shall be decided based on the metabolites of interest in the investigation.
The molybdate-binding protein ModA is required for Proteus mirabilis-induced UTI
Authors: Huang Yi , Chen Jinbin , Jiang Qiao , Huang Nan , Ding Xin , Peng Liang , Deng Xiaoyan
Published: April 2023

Background

Proteus mirabilis is one of the pathogens commonly causing urinary tract infections (UTIs). The molybdate-binding protein ModA encoded by modA binds molybdate with high affinity and transports it. Increasing evidence shows that ModA promotes the survival of bacteria in anaerobic environments and participates in bacterial virulence by obtaining molybdenum. However, the role of ModA in the pathogenesis of P. mirabilis remains unknown.

Results

In this study, a series of phenotypic assays and transcriptomic analyses were used to study the role of ModA in the UTIs induced by P. mirabilis. Our data showed that ModA absorbed molybdate with high affinity and incorporated it into molybdopterin, thus affecting the anaerobic growth of P. mirabilis. Loss of ModA enhanced bacterial swarming and swimming and up-regulated the expression of multiple genes in flagellar assembly pathway. The loss of ModA also resulted in decreased biofilm formation under anaerobic growth conditions. The modA mutant significantly inhibited bacterial adhesion and invasion to urinary tract epithelial cells and down-regulated the expression of multiple genes associated with pilus assembly. Those alterations were not due to anaerobic growth defects. In addition, the decreased bacteria in the bladder tissue, the weakened inflammatory damage, the low level of IL-6, and minor weight change was observed in the UTI mouse model infected with modA mutant.

Conclusion

Here, we reported that in P. mirabilis, ModA mediated the transport of molybdate, thereby affecting the activity of nitrate reductase and thus affecting the growth of bacteria under anaerobic conditions. Overall, this study clarified the indirect role of ModA in the anaerobic growth, motility, biofilm formation, and pathogenicity of P. mirabilis and its possible pathway, and emphasized the importance of the molybdate-binding protein ModA to P. mirabilis in mediating molybdate uptake, allowing the bacterium to adapt to complex environmental conditions and cause UTIs. Our results provided valuable information on the pathogenesis of ModA-induced P. mirabilis UTIs and may facilitate the development of new treatment strategies.
A polyphasic taxonomy analysis reveals the presence of an ecotype of Rahnella contaminans associated with the gut of Dendroctonus-bark beetles
Authors: Rivera-Orduña Flor N. , Pineda-Mendoza Rosa María , Vega-Correa Brenda , López María Fernanda , Cano-Ramírez Claudia , Zhang Xiao Xia , Chen Wen Feng , Zúñiga Gerardo
Published: April 2023

Species belonging to the genus Rahnella are dominant members of the core gut bacteriome of Dendroctonus-bark beetles, a group of insects that includes the most destructive agents of pine forest in North and Central America, and Eurasia. From 300 isolates recovered from the gut of these beetles, 10 were selected to describe an ecotype of Rahnella contaminans. The polyphasic approach conducted with these isolates included phenotypic characteristics, fatty acid analysis, 16S rRNA gene, multilocus sequence analyses (gyrB, rpoB, infB, and atpD genes), and complete genome sequencing of two isolates, ChDrAdgB13 and JaDmexAd06, representative of the studied set. Phenotypic characterization, chemotaxonomic analysis, phylogenetic analyses of the 16S rRNA gene, and multilocus sequence analysis showed that these isolates belonged to Rahnella contaminans. The G + C content of the genome of ChDrAdgB13 (52.8%) and JaDmexAd06 (52.9%) was similar to those from other Rahnella species. The ANI between ChdrAdgB13 and JaDmexAd06 and Rahnella species including R. contaminans, varied from 84.02 to 99.18%. The phylogenomic analysis showed that both strains integrated a consistent and well-defined cluster, together with R. contaminans. A noteworthy observation is the presence of peritrichous flagella and fimbriae in the strains ChDrAdgB13 and JaDmexAd06. The in silico analysis of genes encoding the flagellar system of these strains and Rahnella species showed the presence of flag-1 primary system encoding peritrichous flagella, as well as fimbriae genes from the families type 1, α, β and σ mainly encoding chaperone/usher fimbriae and other uncharacterized families. All this evidence indicates that isolates from the gut of Dendroctonus-bark beetles are an ecotype of R. contaminans, which is dominant and persistent in all developmental stages of these bark beetles and one of the main members of their core gut bacteriome.
Integrated metabolite profiling and transcriptome analysis unraveling mechanism of RC catabolism in Paenarthrobacter ilicis CR5301
Authors: Li Hongfei , Sun Daqing , Cao Longkui , Wang Baohui
Published: April 2023

Steviol glycosides are ideal sweeteners that are widely used in food, medicine, and cosmetics. Rebaudioside C (RC) is considered to be the third most abundant steviol glycoside, which has a bitter aftertaste that limits its application. Hydrolysis of RC to generate other bioactive steviol glycosides is an effective way to promote its additional utilization. In our previous study, a bacterium Paenarthrobacter ilicis CR5301 was isolated and identified for hydrolyzing RC with high efficiency. Herein, the expression profiles of P. ilicis CR5301 in the deletion and presence of RC were investigated by RNA-seq. The RC metabolites were identified by high-performance liquid chromatography and ultra-performance liquid chromatography-triple-time of flight mass spectrometry. Novel results were discovered in four aspects of research. First, the identification of metabolites revealed that four metabolites, namely, dulcoside A, dulcoside B, dulcoside A1, and steviol, were produced during RC metabolism. Second, RNA-seq analyses unraveled that 105 genes of P. ilicis CR5301 were significantly differentially expressed, and 7 pathways were significantly enriched. Third, independent RT-qPCR verified the accuracy and reliability of the RNA-seq results. Finally, a complete catabolic model of RC in P. ilicis CR5301 was proposed, and key genes were indicated in the RC catabolic metabolism by combining them with literature and sequence alignments. This study comprehensively unraveled the genes and pathways of RC catabolism in P. ilicis CR5301 at the transcriptional and metabolic levels. It provided new insights and evidence for understanding the mechanism of RC catabolism in bacteria. Key candidate genes may potentially contribute to the RC hydrolysis and preparation of other functional steviol glycosides in the future.
Constructing a prognostic risk model for Alzheimer’s disease based on ferroptosis
Authors: Wang Xiao-Li , Zhai Rui-Qing , Li Zhi-Ming , Li Hong-Qiu , Lei Ya-Ting , Zhao Fang-Fang , Hao Xiao-Xiao , Wang Sheng-Yuan , Wu Yong-Hui
Published: April 2023

Introduction

The aim of this study is to establish a prognostic risk model based on ferroptosis to prognosticate the severity of Alzheimer’s disease (AD) through gene expression changes.

Methods

The GSE138260 dataset was initially downloaded from the Gene expression Omnibus database. The ssGSEA algorithm was used to evaluate the immune infiltration of 28 kinds of immune cells in 36 samples. The up-regulated immune cells were divided into Cluster 1 group and Cluster 2 group, and the differences were analyzed. The LASSO regression analysis was used to establish the optimal scoring model. Cell Counting Kit-8 and Real Time Quantitative PCR were used to verify the effect of different concentrations of Aβ1–42 on the expression profile of representative genes in vitro.

Results

Based on the differential expression analysis, there were 14 up-regulated genes and 18 down-regulated genes between the control group and Cluster 1 group. Cluster 1 and Cluster 2 groups were differentially analyzed, and 50 up-regulated genes and 101 down-regulated genes were obtained. Finally, nine common differential genes were selected to establish the optimal scoring model. In vitro, CCK-8 experiments showed that the survival rate of cells decreased significantly with the increase of Aβ1–42 concentration compared with the control group. Moreover, RT-qPCR showed that with the increase of Aβ1–42 concentration, the expression of POR decreased first and then increased; RUFY3 was firstly increased and then decreased.

Discussion

The establishment of this research model can help clinicians make decisions on the severity of AD, thus providing better guidance for the clinical treatment of Alzheimer’s disease.
Nimodipine augments cerebrovascular reactivity in aging but runs the risk of local perfusion reduction in acute cerebral ischemia
Authors: Kecskés Szilvia , Menyhárt Ákos , Bari Ferenc , Farkas Eszter
Published: April 2023

Introduction

The efficacy of cerebrovascular reactivity (CVR) is taken as an indicator of cerebrovascular health.

Methods and Results

We found that CVR tested with the inhalation of 10 % CO2 declined in the parietal cortex of 18-20-month-old rats. The CVR deficit in old rats was coincident with cerebrovascular smooth muscle cell and astrocyte senescence, revealed by the immuno-labeling of the cellular senescence marker p16 in these cells. In a next series of experiments, CVR was severely impaired in the acute phase of incomplete global forebrain ischemia produced by the bilateral occlusion of the common carotid arteries in young adult rats. In acute ischemia, CVR impairment often manifested as a perfusion drop rather than blood flow elevation in response to hypercapnia. Next, nimodipine, an L-type voltage-gated calcium channel antagonist was administered topically to rescue CVR in both aging, and cerebra ischemia. Nimodipine augmented CVR in the aged brain, but worsened CVR impairment in acute cerebral ischemia.

Discussion

A careful evaluation of benefits and side effects of nimodipine is recommended, especially in acute ischemic stroke.
The interplay of intracellular calcium and zinc ions in response to electric field stimulation in primary rat cortical neurons in vitro
Authors: Alshawaf Abdullah J. , Alnassar Sarah A. , Al-Mohanna Futwan A.
Published: April 2023

Recent pharmacological studies demonstrate a role for zinc (Zn2+) in shaping intracellular calcium (Ca2+) dynamics and vice versa in excitable cells including neurons and cardiomyocytes. Herein, we sought to examine the dynamic of intracellular release of Ca2+ and Zn2+ upon modifying excitability of primary rat cortical neurons using electric field stimulation (EFS) in vitro. We show that exposure to EFS with an intensity of 7.69 V/cm induces transient membrane hyperpolarization together with transient elevations in the cytosolic levels of Ca2+ and Zn2+ ions. The EFS-induced hyperpolarization was inhibited by prior treatment of cells with the K+ channel opener diazoxide. Chemical hyperpolarization had no apparent effect on either Ca2+ or Zn2+. The source of EFS-induced rise in Ca2+ and Zn2+ seemed to be intracellular, and that the dynamic inferred of an interplay between Ca2+ and Zn2+ ions, whereby the removal of extracellular Ca2+ augmented the release of intracellular Ca2+ and Zn2+ and caused a stronger and more sustained hyperpolarization. We demonstrate that Zn2+ is released from intracellular vesicles located in the soma, with major co-localizations in the lysosomes and endoplasmic reticulum. These studies further support the use of EFS as a tool to interrogate the kinetics of intracellular ions in response to changing membrane potential in vitro.
Novel patients with NHLRC2 variants expand the phenotypic spectrum of FINCA disease
Authors: Tallgren Antti , Kager Leo , O’Grady Gina , Tuominen Hannu , Körkkö Jarmo , Kuismin Outi , Feucht Martha , Wilson Callum , Behunova Jana , England Eleina , Kurki Mitja I. , Palotie Aarno , Hallman Mikko , Kaarteenaho Riitta , Laccone Franco , Boztug Kaan , Hinttala Reetta , Uusimaa Johanna
Published: April 2023

Purpose

FINCA disease (Fibrosis, Neurodegeneration and Cerebral Angiomatosis, OMIM 618278) is an infantile-onset neurodevelopmental and multiorgan disease. Since our initial report in 2018, additional patients have been described. FINCA is the first human disease caused by recessive variants in the highly conserved NHLRC2 gene. Our previous studies have shown that Nhlrc2-null mouse embryos die during gastrulation, indicating the essential role of the protein in embryonic development. Defect in NHLRC2 leads to cerebral neurodegeneration and severe pulmonary, hepatic and cardiac fibrosis. Despite having a structure suggestive of an enzymatic role and the clinical importance of NHLRC2 in multiple organs, the specific physiological role of the protein is unknown.

Methods

The clinical histories of five novel FINCA patients diagnosed with whole exome sequencing were reviewed. Segregation analysis of the biallelic, potentially pathogenic NHLRC2 variants was performed using Sanger sequencing. Studies on neuropathology and NHLRC2 expression in different brain regions were performed on autopsy samples of three previously described deceased FINCA patients.

Results

One patient was homozygous for the pathogenic variant c.442G > T, while the other four were compound heterozygous for this variant and two other pathogenic NHLRC2 gene variants. All five patients presented with multiorgan dysfunction with neurodevelopmental delay, recurrent infections and macrocytic anemia as key features. Interstitial lung disease was pronounced in infancy but often stabilized. Autopsy samples revealed widespread, albeit at a lower intensity than the control, NHLRC2 expression in the brain.

Conclusion

This report expands on the characteristic clinical features of FINCA disease. Presentation is typically in infancy, and although patients can live to late adulthood, the key clinical and histopathological features are fibrosis, infection susceptibility/immunodeficiency/intellectual disability, neurodevelopmental disorder/neurodegeneration and chronic anemia/cerebral angiomatosis (hence the acronym FINCA) that enable an early diagnosis confirmed by genetic investigations.
A comprehensive diagnostic scheme of morphological combined molecular methylation under bronchoscopy
Authors: Zhang Jinze , Huang Haoran , Yu Fan , Bian Yuanyuan , Wang Rui , Liu Hui , Kang Saisai , She Bin , Shi Zhihua
Published: April 2023

Methylated SHOX2 and RASSF1A genes are potential biomarkers for lung cancer diagnosis. Therefore, we explored the role of methylation detection combined with morphological bronchoscopic evaluation for lung cancer diagnosis. Bronchoscopy, methylation outcome, and pathological data were collected from 585 patients with lung cancer and 101 controls. The methylation status of the SHOX2 and RASSF1A genes were detected using real-time polymerase chain reaction quantification. Further, the sensitivity and area under the receiver operating characteristic curve of the three methods were analyzed. Among 686 patients, 57.1% had new lesions detected through bronchoscopy and 93.1% of these patients were diagnosed with malignant tumors. Besides, 42.9% of patients had no visible changes under bronchoscopy but there were still 74.8% of them diagnosed with malignant tumors. Bronchoscopy revealed that lung adenocarcinoma, lung squamous cell carcinoma, and small cell lung cancer mainly occurred in the upper and middle lobes. The sensitivity and specificity of methylation detection were 72.8% and 87.1% (vs. cytology 10.4% & 100%), respectively. Therefore, methylated SHOX2 and RASSF1A genes may be promising tumor markers in lung cancer diagnosis. Methylation detection can be an excellent supplementary tool for cytological diagnosis and, combined with bronchoscopy, could form a more effective diagnostic process.
Case Report: A novel heterozygous nonsense mutation in KRIT1 cause hereditary cerebral cavernous malformation
Authors: Liu Zhenxing , Guo Kaikai , Hu Xuebin , Zhang Xianqin
Published: April 2023

Cerebral cavernous malformation (CCM) is a vascular malformation of the central nervous system and mainly characterized by enlarged capillary cavities without intervening brain parenchyma. Genetic studies have identified three disease-causing genes (CCM1/KRIT1, CCM2/MGC4607 and CCM3/PDCD10) responsible for CCM. Here, we characterized a four-generation family diagnosed with CCM and identified a novel heterozygous mutation c.1159C>T, p.Q387X in KRIT1 gene by whole exome sequencing and Sanger sequencing. The Q387X mutation resulted in premature termination of KRIT1 protein, which was predicted to be deleterious by the ACMG/AMP 2015 guideline. Our results provide novel genetic evidence support that KRIT1 mutations cause CCM, and are helpful to the treatment and genetic diagnosis of CCM.
Pathogenic variant profile in DNA damage response genes correlates with metastatic breast cancer progression-free survival in a Mexican-mestizo population
Authors: Vázquez-Romo Rafael , Millan-Catalan Oliver , Ruíz-García Erika , Martínez-Gutiérrez Antonio D. , Alvarado-Miranda Alberto , Campos-Parra Alma D. , López-Camarillo César , Jacobo-Herrera Nadia , López-Urrutia Eduardo , Guardado-Estrada Mariano , Cantú de León David , Pérez-Plasencia Carlos
Published: April 2023

Introduction

Metastatic breast cancer causes the most breast cancer-related deaths around the world, especially in countries where breast cancer is detected late into its development. Genetic testing for cancer susceptibility started with the BRCA 1 and 2 genes. Still, recent research has shown that variations in other members of the DNA damage response (DDR) are also associated with elevated cancer risk, opening new opportunities for enhanced genetic testing strategies.

Methods

We sequenced BRCA1/2 and twelve other DDR genes from a Mexican-mestizo population of 40 metastatic breast cancer patients through semiconductor sequencing.

Results

Overall, we found 22 variants –9 of them reported for the first time– and a strikingly high proportion of variations in ARID1A. The presence of at least one variant in the ARID1A, BRCA1, BRCA2, or FANCA genes was associated with worse progression-free survival and overall survival in our patient cohort.

Discussion

Our results reflected the unique characteristics of the Mexican-mestizo population as the proportion of variants we found differed from that of other global populations. Based on these findings, we suggest routine screening for variants in ARID1A along with BRCA1/2 in breast cancer patients from the Mexican-mestizo population.
Aspirin use and bleeding events during thrombocytopenia after autologous stem-cell transplantation for multiple myeloma
Authors: Neuendorff Nina Rosa , Boshikova Boryana , Frankenstein Lutz , Kirchner Marietta , Rohde Christian , Goldschmidt Hartmut , Frey Norbert , Müller-Tidow Carsten , Jordan Karin , Sauer Sandra , Janssen Maike
Published: April 2023

Background

In patients with cardiovascular (CV) comorbidities that necessitate antiplatelet therapy (APT), its optimal management during chemotherapy-induced thrombocytopenia remains elusive, as the risk of bleeding has to be balanced against the risk of CV events. The purpose of this study was to assess the risk for bleeding with APT during thrombocytopenia in patients with multiple myeloma undergoing high-dose chemotherapy and subsequent autologous stem-cell transplantation (ASCT) with and without acetylsalicylic acid (ASA) as comedication.

Methods

We assessed patients who underwent ASCT at the Heidelberg University Hospital between 2011 and 2020 for bleeding events, management strategies for ASA intake during thrombocytopenia, transfusion requirements, and the occurrence of CV events.

Results

There were 57/1,113 patients who continued ASA until at least 1 day after ASCT; thus, a continuous platelet inhibition during thrombocytopenia was assumed. Most of the patients (41/57) continued ASA until they had a platelet count of 20–50/nl. This range reflects the kinetics of thrombocytopenia and nondaily measurements of platelets during ASCT. A tendency toward a higher risk for bleeding events in the ASA group was demonstrated (1.9% (control group) vs. 5.3% (ASA), p = 0.082). The risk factors for bleeding in multivariate analysis were the duration of thrombocytopenia < 50/nl, a history of gastrointestinal bleeding, and diarrhea. The factors predicting the duration of thrombocytopenia were age >60 years, a hematopoietic stem-cell transplantation comorbidity index ≥3, and an impaired bone marrow reserve at admission. CV events occurred in three patients; none of them took ASA or had an indication for APT.

Conclusions

The intake of ASA until thrombocytopenia with a platelet count of 20–50/nl appears safe, although an elevated risk cannot be excluded. If ASA is indicated for the secondary prevention of CV events, the evaluation of risk factors for bleeding and a prolonged time of thrombocytopenia before conditioning is crucial to adapt the strategy for ASA intake during thrombocytopenia.
Construction and validation of a risk prediction model for aromatase inhibitor-associated bone loss
Authors: Chu Meiling , Zhou Yue , Yin Yulian , Jin Lan , Chen Hongfeng , Meng Tian , He Binjun , Wu Jingjing , Ye Meina
Published: April 2023

Purpose

To establish a high-risk prediction model for aromatase inhibitor-associated bone loss (AIBL) in patients with hormone receptor-positive breast cancer.

Methods

The study included breast cancer patients who received aromatase inhibitor (AI) treatment. Univariate analysis was performed to identify risk factors associated with AIBL. The dataset was randomly divided into a training set (70%) and a test set (30%). The identified risk factors were used to construct a prediction model using the eXtreme gradient boosting (XGBoost) machine learning method. Logistic regression and least absolute shrinkage and selection operator (LASSO) regression methods were used for comparison. The area under the receiver operating characteristic curve (AUC) was used to evaluate the performance of the model in the test dataset.

Results

A total of 113 subjects were included in the study. Duration of breast cancer, duration of aromatase inhibitor therapy, hip fracture index, major osteoporotic fracture index, prolactin (PRL), and osteocalcin (OC) were found to be independent risk factors for AIBL (p < 0.05). The XGBoost model had a higher AUC compared to the logistic model and LASSO model (0.761 vs. 0.716, 0.691).

Conclusion

The XGBoost model outperformed the logistic and LASSO models in predicting the occurrence of AIBL in patients with hormone receptor-positive breast cancer receiving aromatase inhibitors.
Missed opportunities for immunization among children 0 to 11 months of age that were attended to at debre tabor comprehensive specialized hospital, south gondar zone, Ethiopia
Authors: Kassa Bekalu Getnet , Lul Nhial Char
Published: April 2023

Background

The World Health Organization's Expanded Immunization Program was established in 1974 and aimed to provide vaccines to children all over the world. Since the inception of this program, numerous initiatives and campaigns have been launched, and millions of children around the world have been saved from death. Many vaccine-preventable diseases, however, remain prevalent in developing countries. This is because most of those countries have low immunization coverage for an unknown number of reasons. As a result, the goal of this study was to examine missed opportunities for immunization among children aged 0 to 11 months.

Methods

A cross-sectional survey was carried out from May to August 2022. A structured questionnaire was used to collect data, and the sample was chosen using a simple random sampling technique. Before being entered into the Epidata and exported to the Statistical Package for Social Science for analysis, the data were checked for consistency and completeness. The statistical significance was determined using binary and multiple logistic regression analyses. The statistical level of significance was established at p ≤ 0.05.

Result

In this study, 49.1% of immunization opportunities were missed. Education status [AOR = 2.45, 95% CI = 2.14, 4.22], rural residence [AOR = 4.32, 95% CI = 3.11, 6.38], and perception of caretakers [AOR = 2.13, 95% CI = 1.89, 4.07] were associated with the missed opportunity of immunization.

Conclusion

When compared to previous studies, the proportion of missed immunization opportunities was high in this study. The healthcare staff should be applying the multi-dose vial policy, which is recommended by the World Health Organization to increase the services. The doses for BCG and measles should be minimized to lower doses per vial in order to conduct immunization without having to wait for enough children and without worrying about vaccine waste. All infants who visit the hospital should be linked to immunization services.