bluuebunny/crossref_metadata_2025 huggingface dataset:
A Bayesian network model to disentangle the effects of stand and climate factors on tree mortality of Chinese fir plantations
Authors: Jiang Yihang , Wang Zhen , Chen Hanyue , Hu Yuxin , Qu Yancheng , Chhin Sophan , Zhang Jianguo , Zhang Xiongqing
Published: October 2023

Tree mortality is a complex process that not only be affected by the various factors, such as stand and climate factors, but also the various long-term effects of the factors to each other. In this study, based on the long-term spacing trials of Chinese fir in four regions of southern China, a Bayesian network was used to model tree mortality in response to stand and climate factors, as well as comparing this approach with logistic regression and random forest method. The results showed that the Bayesian network method had the highest accuracy in predicting tree mortality. In addition, the Bayesian network approach could find the dependency in the relationship between data and provide a theoretical framework for modeling uncertainty by using probabilistic calculus and underlying graph structure. Sensitivity analysis showed relative diameter was the most important factor, and temperature was the most important climate factor. Furthermore, climate factors not only directly affected tree mortality, but also indirectly affected tree mortality through affecting relative diameter, stand density and Gini coefficient. We also found that stand competition, structural heterogeneity and age affected tree mortality under climate change, and a moderate level of competition condition and stand structure heterogeneity weakened the negative impact of climate factors on tree mortality. Old trees were more sensitive to climate change than young trees, especially under extreme climate conditions. Besides, we found that tree mortality was negatively correlated with moderate annual precipitation, winter mean minimum temperature, and stand structure (Gini), and low age, but positively correlated with low relative diameter, high density and age. The results will provide adaptive options for effective forest management of Chinese fir plantations under the backdrop of global climate change in the future.
Genome-wide association analysis of tan spot disease resistance in durum wheat accessions from Tunisia
Authors: Laribi Marwa , Fredua-Agyeman Rudolph , Ben M’Barek Sarrah , Sansaloni Carolina P. , Dreisigacker Susanne , Gamba Fernanda M. , Abdedayem Wided , Nefzaoui Meriem , Araar Chayma , Hwang Sheau-Fang , Yahyaoui Amor H. , Strelkov Stephen E.
Published: October 2023

Background: Tunisia harbors a rich collection of unexploited durum wheat landraces (Triticum durum ssp. durum) that have been gradually replaced by elite cultivars since the 1970s. These landraces represent an important potential source for broadening the genetic background of elite durum wheat cultivars and for the introgression of novel genes for key traits, including disease resistance, into these cultivars.

Methods: In this study, single nucleotide polymorphism (SNP) markers were used to investigate the genetic diversity and population structure of a core collection of 235 durum wheat accessions consisting mainly of landraces. The high phenotypic and genetic diversity of the fungal pathogen Pyrenophora tritici-repentis (cause of tan spot disease of wheat) in Tunisia allowed the assessment of the accessions for tan spot resistance at the adult plant stage under field conditions over three cropping seasons. A genome-wide association study (GWAS) was performed using a 90k SNP array.

Results: Bayesian population structure analysis with 9191 polymorphic SNP markers classified the accessions into two groups, where groups 1 and 2 included 49.79% and 31.49% of the accessions, respectively, while the remaining 18.72% were admixtures. Principal coordinate analysis, the unweighted pair group method with arithmetic mean and the neighbor-joining method clustered the accessions into three to five groups. Analysis of molecular variance indicated that 76% of the genetic variation was among individuals and 23% was between individuals. Genome-wide association analyses identified 26 SNPs associated with tan spot resistance and explained between 8.1% to 20.2% of the phenotypic variation. The SNPs were located on chromosomes 1B (1 SNP), 2B (4 SNPs), 3A (2 SNPs), 3B (2 SNPs), 4A (2 SNPs), 4B (1 SNP), 5A (2 SNPs), 5B (4 SNPs), 6A (5 SNPs), 6B (2 SNPs), and 7B (1 SNP). Four markers, one on each of chromosomes 1B, and 5A, and two on 5B, coincided with previously reported SNPs for tan spot resistance, while the remaining SNPs were either novel markers or closely related to previously reported SNPs. Eight durum wheat accessions were identified as possible novel sources of tan spot resistance that could be introgressed into elite cultivars.

Conclusion: The results highlighted the significance of chromosomes 2B, 5B, and 6A as genomic regions associated with tan spot resistance.
Identification and validation of a prognostic-related mutant gene DNAH5 for hepatocellular carcinoma
Authors: Song Zebing , Song Xiaodong , Li Hang , Cheng Zongbing , Mo Zengyi , Yang Xuewei
Published: October 2023

Background

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths worldwide and has a poor prognosis. Thus, there is a need for an effective biomarker to improve and predict the prognosis of HCC.

Methods

RNA sequencing data, simple nucleotide variation data, and clinical data of HCC patients from The Cancer Genome Atlas (TCGA) to identify mutant genes, simple nucleotide variation data, and clinical data of HCC patients from the International Cancer Genome Consortium (ICGC) to validate the prognostic value of mutant genes were the data sources of the present study. To identify the overall survival (OS)-related mutant genes, a Kaplan–Meier (KM) analysis was conducted. We carried out univariate Cox and multivariate Cox regression analyses to identify the independent prognostic factors. We also conducted a correlation analysis of immune cells and mutant genes. To explore the molecular mechanisms of mutant genes, we conducted a gene set enrichment analysis (GSEA). A nomogram was constructed to help predict the prognosis of HCC. In addition, we explored the expression profile of mutant genes in HCC based on a TCGA dataset, an ICGC dataset, and our own HCC tissue samples.

Results

We identified and validated a mutant gene, dynein axonemal heavy chain 5 (DNAH5), which was negatively related to the OS of HCC patients. Univariate Cox and multivariate Cox regression analyses revealed that the mutant gene DNAH5 could act as an independent prognostic factor for HCC. Most pathways of the mutant gene DNAH5 were involved in cancer development and progression based on GSEA analysis. The mutant gene DNAH5 was negatively correlated with monocytes, naive CD4 T cells, activated dendritic cells, and activated mast cells. In addition, the mRNA and protein levels of DNAH5 had a significantly higher level of expression in the tissue samples of patients with HCC. A nomogram consisting of the pathological stage, DNAH5, and tumor mutation burden (TMB) performed well.

Conclusion

The mutant gene DNAH5 had a significantly higher level of expression in the tissue samples of patients with HCC, could act as an independent prognostic factor for HCC, and is a potential new immunotherapy target for HCC.
Impact of a booster dose on SARS-CoV2 mRNA vaccine-specific humoral-, B- and T cell immunity in pediatric stem cell transplant recipients
Authors: Thole Linda Marie Laura , Tóth Laura , Proß Vanessa , Siegle Janine , Stahl Carolin , Hermsdorf Georg , Knabe Annette , Winkler Annika , Schrezenmeier Eva , Ludwig Carolin , Eckert Cornelia , Eggert Angelika , Schrezenmeier Hubert , Sattler Arne , Schulte Johannes H. , Kotsch Katja
Published: October 2023

Stem cell transplant recipients (SCTR) are imperiled to increased risks after SARS-CoV2 infection, supporting the need for effective vaccination strategies for this vulnerable group. With respect to pediatric patients, data on immunogenicity of SARS-CoV2 mRNA-based vaccination is limited. We therefore comprehensively examined specific humoral, B- and T cell responses in a cohort of 2-19 year old SCTR after the second and third vaccine dose. Only after booster vaccination, transplant recipients reached similar levels of vaccine-specific IgG, IgA and neutralizing antibodies against omicron variant as age-matched controls. Although frequencies of SARS-CoV2 specific B cells increased after the third dose, they were still fourfold reduced in patients compared to controls. Overall, the majority of individuals enrolled mounted SARS-CoV2 Spike protein-specific CD4+ T helper cell responses with patients showing significantly higher portions than controls after the third dose. With respect to functionality, however, SCTR were characterized by reduced frequencies of specific interferon gamma producing CD4+ T cells, along with an increase in IL-2 producers. In summary, our data identify distinct quantitative and qualitative impairments within the SARS-CoV2 vaccination specific B- and CD4+ T cell compartments. More importantly, humoral analyses highlight the need for a booster vaccination of SCTR particularly for development of neutralizing antibodies.
Development and function of chicken XCR1+ conventional dendritic cells
Authors: Wu Zhiguang , Shih Barbara , Macdonald Joni , Meunier Dominique , Hogan Kris , Chintoan-Uta Cosmin , Gilhooley Hazel , Hu Tuanjun , Beltran Mariana , Henderson Neil C. , Sang Helen M. , Stevens Mark P. , McGrew Michael J. , Balic Adam
Published: October 2023

Conventional dendritic cells (cDCs) are antigen-presenting cells (APCs) that play a central role in linking innate and adaptive immunity. cDCs have been well described in a number of different mammalian species, but remain poorly characterised in the chicken. In this study, we use previously described chicken cDC specific reagents, a novel gene-edited chicken line and single-cell RNA sequencing (scRNAseq) to characterise chicken splenic cDCs. In contrast to mammals, scRNAseq analysis indicates that the chicken spleen contains a single, chemokine receptor XCR1 expressing, cDC subset. By sexual maturity the XCR1+ cDC population is the most abundant mononuclear phagocyte cell subset in the chicken spleen. scRNAseq analysis revealed substantial heterogeneity within the chicken splenic XCR1+ cDC population. Immature MHC class II (MHCII)LOW XCR1+ cDCs expressed a range of viral resistance genes. Maturation to MHCIIHIGH XCR1+ cDCs was associated with reduced expression of anti-viral gene expression and increased expression of genes related to antigen presentation via the MHCII and cross-presentation pathways. To visualise and transiently ablate chicken XCR1+ cDCs in situ, we generated XCR1-iCaspase9-RFP chickens using a CRISPR-Cas9 knockin transgenesis approach to precisely edit the XCR1 locus, replacing the XCR1 coding region with genes for a fluorescent protein (TagRFP), and inducible Caspase 9. After inducible ablation, the chicken spleen is initially repopulated by immature CD1.1+ XCR1+ cDCs. XCR1+ cDCs are abundant in the splenic red pulp, in close association with CD8+ T-cells. Knockout of XCR1 prevented this clustering of cDCs with CD8+ T-cells. Taken together these data indicate a conserved role for chicken and mammalian XCR1+ cDCs in driving CD8+ T-cells responses.
Seafloor Observation Scenario Exploration Tool: enabling representative exploration of the global deep seafloor
Authors: Johannes Kristen N. , Kennedy Brian R. C. , Bell Katherine L. C.
Published: October 2023

Visual observation of the seafloor is invaluable in understanding deep-sea biogeography, uncovering and expanding key global geological, oceanographic, and climate processes. And yet, due to the expense, inefficiency, and inequitable distribution of deep-sea tools, we have barely explored a small, biased fraction of it. Systematic and efficient exploration of the entire deep sea will require a concerted global effort. The current study uses global-coverage geospatial data to develop an interactive online tool for deep seafloor observation planning (i.e., depths below 200 m). The Seafloor Observation Scenario Exploration Tool integrates stakeholder goals and constraints into a dynamic modeling process that combines information about seafloor depth, seafloor geomorphology features, sites of past seafloor observation, Exclusive Economic Zones, and vessel traffic density. With the tool, users can identify maximally suitable areas for seafloor observation, which we envision supporting seafloor expedition planning and marine conservation action.
Dissemination and characteristics of carbapenem-resistant Klebsiella pneumoniae in nine district hospitals in southwestern China
Authors: Wang Yonghong , Ouyang Yan , Xu Xiuyu , Sun Shan , Tian Xiaolang , Liu Hang , Xia Yun
Published: October 2023

Background

Carbapenem-resistant Klebsiella pneumoniae (CRKP) is epidemically transmitted globally, but few studies focused on the prevalence in district-level hospitals. In this study, we investigated CRKP strains collected from nine district hospitals from September 2019 to September 2020, aiming to determine the resistance mechanisms, virulence profiles, and molecular epidemiological characteristics of CRKP in district hospitals in Southwest China.

Methods

A total of 51 CRKP strains were collected from 9 district-level hospitals. Matrix-assisted laser desorption/ionization-time of flight mass spectrometer was used for strain identification review, and the micro-broth dilution method was used for antibiotic sensitivity detection. Molecular epidemiological investigation of strains was performed by multilocus sequence typing (MLST) and pulsed-field gel electrophoresis (PFGE) methods. PCR and efflux pump inhibition tests were used to detect CRKP resistance mechanisms. PCR and serum killing tests were used to detect capsular serotype, virulence-related genes, and virulence validation.

Results

The CRKP strains in district hospitals presented high levels of MIC50 and MIC90 in carbapenem antibiotics especially ertapenem and meropenem. A total of 90.2% (46/51) CRKP strains were detected as carbapenemase producers, and the proportion of strains co-expressing carbapenemases was 11.8% (6/51). All CRKP strains were grouped into eight MLST types, and ST11 was the most prevalent genotype. A total of 11.8% (6/51) CRKP isolates were positive for the string test, and three strains of hypervirulent and carbapenem-resistant K. pneumoniae (HV-CRKP) were positive in serum killing test. The molecular typing of all the CRKP isolates was grouped into 29 different PFGE patterns, and 40 ST11 isolates belonged to 20 different PFGE clusters.

Conclusion

CRKP strains showed high-level antibiotic resistance and virulence phenotype in district hospitals in Southwest China, which suggested that we should immediately pay attention to the rapid dissemination of the CRKP in regional hospitals. Our study will provide new insights into the epidemiology of CRKP in regional hospitals, which will help regional hospitals develop nosocomial infection prevention and control policies tailored to local conditions.
Clinical effect of a modified superficial temporal artery-middle cerebral artery bypass surgery in Moyamoya disease treatment
Authors: Lu Liang , Huang Yimin , Han Yang , Li Yu , Wan Xueyan , Chen Juan , Zhang Xincheng , Shu Kai , Lei Ting , Wang Sheng , Gan Chao , Zhang Huaqiu
Published: October 2023

Background

Cerebral extracranial-intracranial (EC-IC) revascularization technique (superficial temporal artery-middle cerebral artery (STA-MCA) bypass grafting) has become the preferred surgical method for the treatment of Moyamoya disease (MMD). We attempted to completely free the two branches of the superficial temporal artery without disconnection. Extracranial and intracranial blood flow reconstruction were then modified by selectively performing a direct bypass technique on one branch and a patch fusion technique on the other of the STA based on the blood flow and the vascular diameter of the intracranial surface blood vessels.

Methods

A series of modified STA-MCA bypass surgeries performed consecutively between March 2022 and March 2023 were reviewed and compared to conventional combined bypass surgeries performed during the same period. The following information was collected from all enrolled patients: demographic characteristics, clinical symptoms, and preoperative and postoperative imaging, including Suzuki stage and Matsushima grade. The modified Rankin scale (mRS) was used to assess the changes in neurological status before and after surgery.

Results

A total of 41 patients with Moyamoya disease (MMD) who underwent cerebral revascularization were included in this study, of which 30 were conventional revascularization and 11 were modified revascularization. The mean age was 49.91 years, and 18 (43.9%) of the patients were women. The modified group had a lower incidence of cerebral hyperperfusion syndrome (18.2%) than the conventional group (23.3%). After at least 3 months of follow-up, the bypass patency rate remained 100% in the modified group and 93.3% in the conventional group. All patients in the modified group achieved a better Matsushima grade (A + B), with six (54.5%) having an A and five (45.5%) having a B. In contrast, four patients (13.3%) in the conventional group had a Matsushima grade of C. In all, 72.8% of the modified group had postoperative mRS scores of 0 and 1, which was higher than that of the traditional group (63.3%).

Conclusion

The improved STA-MCA bypass could provide blood flow to multiple cerebral ischemic areas, reduce excessive blood perfusion, and ensure blood supply to the scalp, with lower complications and better clinical benefits than the traditional combined bypass.
Whole exome sequencing of patients with varicella-zoster virus and herpes simplex virus induced acute retinal necrosis reveals rare disease-associated genetic variants
Authors: Heinz Johanna L. , Swagemakers Sigrid M. A. , von Hofsten Joanna , Helleberg Marie , Thomsen Michelle M. , De Keukeleere Kerstin , de Boer Joke H. , Ilginis Tomas , Verjans Georges M. G. M. , van Hagen Peter M. , van der Spek Peter J. , Mogensen Trine H.
Published: October 2023

Purpose

Herpes simplex virus (HSV) and varicella-zoster virus (VZV) are neurotropic human alphaherpesviruses endemic worldwide. Upon primary infection, both viruses establish lifelong latency in neurons and reactivate intermittently to cause a variety of mild to severe diseases. Acute retinal necrosis (ARN) is a rare, sight-threatening eye disease induced by ocular VZV or HSV infection. The virus and host factors involved in ARN pathogenesis remain incompletely described. We hypothesize an underlying genetic defect in at least part of ARN cases.

Methods

We collected blood from 17 patients with HSV-or VZV-induced ARN, isolated DNA and performed Whole Exome Sequencing by Illumina followed by analysis in Varseq with criteria of CADD score > 15 and frequency in GnomAD < 0.1% combined with biological filters. Gene modifications relative to healthy control genomes were filtered according to high quality and read-depth, low frequency, high deleteriousness predictions and biological relevance.

Results

We identified a total of 50 potentially disease-causing genetic variants, including missense, frameshift and splice site variants and on in-frame deletion in 16 of the 17 patients. The vast majority of these genes are involved in innate immunity, followed by adaptive immunity, autophagy, and apoptosis; in several instances variants within a given gene or pathway was identified in several patients.

Discussion

We propose that the identified variants may contribute to insufficient viral control and increased necrosis ocular disease presentation in the patients and serve as a knowledge base and starting point for the development of improved diagnostic, prophylactic, and therapeutic applications.
Role of sex and sex hormones in PD-L1 expression in NSCLC: clinical and therapeutic implications
Authors: Rodriguez-Lara Vianey , Soca-Chafre Giovanny , Avila-Costa Maria Rosa , Whaley Juan Jose Juarez-Vignon , Rodriguez-Cid Jeronimo Rafael , Ordoñez-Librado José Luis , Rodriguez-Maldonado Emma , Heredia-Jara Nallely A.
Published: October 2023

Currently, immunotherapy based on PD-1/PD-L1 pathway blockade has improved survival of non-small cell lung cancer (NSCLC) patients. However, differential responses have been observed by sex, where men appear to respond better than women. Additionally, adverse effects of immunotherapy are mainly observed in women. Studies in some types of hormone-dependent cancer have revealed a role of sex hormones in anti-tumor response, tumor microenvironment and immune evasion. Estrogens mainly promote immune tolerance regulating T-cell function and modifying tumor microenvironment, while androgens attenuate anti-tumor immune responses. The precise mechanism by which sex and sex hormones may modulate immune response to tumor, modify PD-L1 expression in cancer cells and promote immune escape in NSCLC is still unclear, but current data show how sexual differences affect immune therapy response and prognosis. This review provides update information regarding anti-PD-1/PD-L immunotherapeutic efficacy in NSCLC by sex, analyzing potential roles for sex hormones on PD-L1 expression, and discussing a plausible of sex and sex hormones as predictive response factors to immunotherapy.
Multimodal imaging features of retroperitoneal anastomosing hemangioma: a case report and literature review
Authors: Zhang Liqing , Wu Jian
Published: October 2023

Background

Anastomotic hemangioma is a rare subtype of capillary hemangioma primarily found in the genitourinary tract. We present a case of a patient with an anastomotic hemangioma located in the retroperitoneal space; then, we explore and summarize the imaging features from previously reported cases for accurate diagnosis.

Case presentation

A 57-year-old woman complained of left lower back pain. Contrast-enhanced ultrasound revealed a hypoechoic mass with “slow-in and slow-out” enhancement. Abdominal CT scan displayed a well-defined, round soft tissue mass in the right retroperitoneal region with obvious enhancement. MRI indicated low signal on T1-weighted imaging, high signal on T2-weighted imaging and diffusion-weighted imaging, and progressive enhancement after enhancement. Surgical removal of the tumor was performed. Histopathological examination exhibited a distinct tumor border with interconnected blood vessels and a cavity lined by a single layer of cubic endothelial cells. Immunohistochemistry confirmed the presence of CD31[+] and CD34[+]. The final pathological diagnosis was anastomotic hemangioma. No recurrence was observed during a 40-month follow-up.

Conclusion

Retroperitoneal anastomotic hemangioma is a rare and benign neoplasm that may be misdiagnosed as ectopic pheochromocytoma or angiosarcoma. This case report presents and analyzes the imaging characteristics of a series of retroperitoneal anastomotic hemangiomas, which can be valuable for future diagnoses and help prevent unnecessary surgeries.
Plasma EBV DNA as a prognostic factor in EBV associated gastric cancer: a multicenter, prospective study (EBV PRESAGE study)
Authors: Alberti Andrea , Stocker Gertraud , Lordick Florian , Hacker Ulrich T. , Kobitzsch Benjamin , Haffner Ivonne , Baiocchi Gian Luca , Zamparini Manuel , Tiberio Guido A. M. , Baronchelli Carla , Caruso Arnaldo , Bossi Paolo , Berruti Alfredo
Published: October 2023

Purpose

The Cancer Genome Atlas Research Network identified Epstein-Barr-Virus (EBV)-positive gastric cancer as a distinct molecular subtype. The prevalence is 8-9% and the histological examination shows pronounced lymphocytic infiltration, elevated levels of IFN-γ and consequently overexpression of PD-L1. The role of plasma EBV DNA load as a prognostic factor in patients with this cancer subtype is still to be defined.

Methods and analysis

The present multicenter prospective observational study “EBV PRESAGE”, involving German and Italian cancer centers, aims to evaluate the prognostic role of plasma EBV DNA in EBV-related gastric cancer (GC). The objective is to study the association between plasma EBV DNA load at different consecutive time points and the patient’s prognosis. Every patient with a new diagnosis of gastric cancer (including gastroesophageal junction adenocarcinoma) will be screened for Epstein-Barr encoded small Region (EBER) on tissue biopsies using in situ hybridization (ISH). If EBER ISH is positive, blood analysis for plasma EBV DNA will be conducted. The plasma EBV quantitative analysis will be centralized, and extraction, detection, and quantification of EBV DNA in plasma samples will be performed using real-time PCR.

Discussion

We hypothesized that plasma EBV DNA represents a non-invasive tool for monitoring EBV-related GC and might be valuable as a prognostic marker.
Retrospective study of efficacy and adverse events of immune checkpoint inhibitors in 22 xeroderma pigmentosum patients with metastatic or unresectable cancers
Authors: Fernandez Elvelyn R. , Tamura Deborah , Khan Sikandar G. , Momen Sophie , Fassihi Hiva , Sarkany Robert , DiGiovanna John J. , Kraemer Kenneth H.
Published: October 2023

Background

Xeroderma pigmentosum (XP), a rare disease with defects in DNA repair genes, has >1,000-fold increased risk of ultraviolet-induced skin cancers. Immune checkpoint inhibitors (ICIs) are used for treating cancers with large numbers of mutations but may also promote adverse events (AEs). Deficient DNA repair in XP patients may lead to increased numbers of mutations, leading to enhanced efficacy of cancer response or, alternatively, to increased AE in response to ICI. We sought to compare the efficacy and AE of ICI in XP patients with metastatic or unresectable cancers to that of ICI-treated patients in the general population.

Methods

In this retrospective study, we reviewed medical records of XP patients treated in the United States and in London (UK). We also reviewed published reports of ICI-treated XP patients and patients in the general population.

Results

Metastatic or unresectable cancers in all 22 (100%) XP patients showed regression or remission in response to ICI. The types and frequencies of AE in XP patients were similar to those reported among ICI-treated patients in the general population. However, two XP patients had concurrent additional cancers that did not respond to ICI, two XP patients had cancer recurrence or progression after initial response, and eight XP patients developed new skin cancers during or after ICI treatment.

Conclusion

In this retrospective study with small sample size, XP patients demonstrated positive responses to ICI and the treatment was well tolerated but some patients developed new skin cancers while being treated. ICIs can be considered in treating metastatic or unresectable cancers in XP patients.
Similar adverse outcome rates with high or low oxygen saturation targets in an area with low background mortality
Authors: Willgerodt Nina , Bührer Christoph , Rossi Rainer , Kühn Thomas , Rüdiger Mario , Avenarius Stefan , Böttger Ralf , Olbertz Dirk M. , Proquitte Hans , Bittrich Hans-Jörg , Haase Roland , Fröhlich Matthias , Höhne Sybille , Thome Ulrich H.
Published: October 2023

Background

Randomized controlled trials have indicated reduced mortality rates in very preterm infants assigned to high compared to low oxygen saturation (SpO2) target levels, accompanied by higher rates of retinopathy of prematurity and bronchopulmonary dysplasia. However, the benefit-to-harm ratio may depend on the local background mortality risk. We therefore aimed to quantify the risk–benefit ratios of different SpO2 target ranges in 10 tertiary newborn intensive care units (NICUs) in East Germany.

Methods

In a retrospective multicenter study, 1,399 infants born between 2008 and 2012 at a gestational age between 24 0/7 and 27 6/7 weeks and with a birthweight below 1,250 g were grouped according to the hospital's target SpO2 range [high oxygen saturation group (HOSG) above 90%], low oxygen saturation group (LOSG) below 90%] and the compliance of units with their target SpO2 range. The association between neonatal morbidities, neurodevelopmental outcomes, selected treatment strategies, and target SpO2 ranges was calculated using chi-squared and Mann Whitney U tests.

Results

Nine of the ten participating NICUs met their SpO2 target ranges. Five units were considered as HOSG, and five units were considered as LOSG. Necrotizing enterocolitis and intraventricular hemorrhage grade ≥ 2 occurred significantly more frequently in the HOSG than in the LOSG (8.4% vs. 5.1%, p = 0.02; and 26.6% vs. 17.7%, p < 0.001). No significant differences in the mortality rate and the rate of retinopathy of prematurity were found.

Conclusion

In our patient population, a lower SpO2 target range was not associated with increased safety risks in extremely preterm infants. We cannot be sure that our outcome differences are associated with differences in oxygen saturations due to the retrospective study design and the differences in site practices.
Apelin receptor inhibition in ischemia-reperfused mouse hearts protected by endogenous n-3 polyunsaturated fatty acids
Authors: Zheng Shuang , Tan Weijiang , Li Xiang , Wang Lijing , Zhu Caiyi , Pyle W. Glen , Chen Jianxin , Wu Jian , Ren Xuecong , Chen Honghua , Zou Yunzeng , Backx Peter H. , Yang Feng Hua
Published: October 2023

Background: While the protective effects of n-3 polyunsaturated fatty acids (PUFAs) on cardiac ischemia-reperfusion (IR) injury have been previously reported, limited data are available regarding how these fatty acids affect membrane receptors and their downstream signaling following IR injury. We aimed to identify potential receptors activated by n-3 PUFAs in IR hearts to understand the regulatory mechanisms of these receptors.

Methods: We used fat-1 mice, which naturally have elevated levels of n-3 PUFAs, and C57BL/6J mice as a control group to create a myocardial IR injury model through Langendorff perfusion. We assessed the impact of endogenous n-3 PUFAs on left ventricular function, myocardial infarct size, myocardial apoptosis, and ATP production. RNA sequencing (RNA-seq) and bioinformatics analysis were conducted to identify molecular targets affected by n-3 PUFAs. Based on these analyses we then treated IR hearts of WT and fat-1 mice with an antagonist (ML221) or an agonist (apelin-13) for the predicted receptor to assess cardiac contractile function and intracellular signaling pathways. An in vitro hypoxia-reoxygenation (HR) model was also used to confirm the effects of n-3 PUFAs on the examined intracellular signaling pathways.

Results: Endogenous n-3 PUFAs protected cardiac structure and function in post-IR hearts, and modulated phosphorylation patterns in the PI3K-AKT-mTOR signaling pathways. RNA-seq analysis revealed that n-3 PUFAs affected multiple biological processes as well as levels of the apelin receptor (APLNR). Consistent with a role for the PLNNR, ML221 synchronized the activation of the PI3K-AKT-mTOR signaling axis, suppressed the expression of PKCδ and phosphorylated p38α, upregulated PKCε expression, upregulated or restored the phosphorylation of myofilaments, and prevented myocardial injury and contractile dysfunction in WT IR hearts. By contrast, apelin-13 disrupted the PI3K-AKT-mTOR signaling axis in post-IR fat-1 hearts. The phosphorylation signaling targeted by APLNR inhibition in post-IR fat-1 hearts was also observed after treating HR cells with eicosatetraenoic acid (EPA).

Conclusion: Endogenous n-3 PUFAs protect against post-IR injury and preserve cardiac contractile function possibly through APLNR inhibition. This inhibition synchronizes the PI3K-AKT-mTOR axis, suppresses detrimental phosphorylation signaling, and restores or increases myofilament phosphorylation in post-IR hearts. The beneficial effects observed in fat-1 transgenic mouse hearts can be attributed, at least in part, to elevated EPA levels. This study is the first to demonstrate that n-3 PUFAs protect hearts against IR injury through APLNR inhibition.
Effectiveness of dapagliflozin as an insulin adjunct in type 1 diabetes: a semi-mechanistic exposure-response model
Authors: Sokolov Victor , Yakovleva Tatiana , Penland Robert C. , Boulton David W. , Tang Weifeng
Published: October 2023

Introduction: Dapagliflozin-induced improvement of glycemic control in patients with inadequately controlled type 1 diabetes (T1D) is complicated by the delicate balance between blood glucose and exogenous insulin. In this work, we developed a semi-mechanistic population exposure-response model using pooled patient-level data to characterize the joint effect of dapagliflozin and insulin on average daily glucose concentrations and glycated hemoglobin (HbA1c) levels in patients with T1D.

Methods: A non-linear mixed-effects model was developed in Monolix (Lixoft, France) and R software (R Project, www.r-project.org) using pooled patient-level data from phase 2 and phase 3 trials (NCT01498185, NCT02460978, NCT02268214).

Results: Because of the apparent lack of association between bolus insulin dose and glucose concentrations measured by continuous glucose monitoring the model was able to capture the quantitative link between basal, but not bolus, insulin dose and plasma glucose. Even so, this association remained flat, with a 50% decrease in the basal insulin dose from pretreatment level, resulting in ∼5% increase in glucose exposure. Therefore, dapagliflozin efficacy was not significantly affected by the insulin dose adjustment, with 24-week HbA1c reduction on 10-mg dapagliflozin treatment changing from −0.5 [95% CI: −0.55, −0.45] to −0.42 [95%CI: −0.48, −0.36] after adjustment. At the same time, the analysis revealed ∼2-fold steeper slope of glucose-HbA1c relationship in dapagliflozin-treated patients vs. control group, suggesting the presence of additional dapagliflozin treatment–related benefits, not explained by the dapagliflozin-mediated ∼4% increase in plasma hemoglobin levels. Finally, the efficacy of 5 and 10-mg doses, represented by the mean HbA1c reduction at week 24 of dapagliflozin treatment, was shown to be notably greater than the 1- and 2.5-mg doses.

Discussion: This research is an attempt to deconvolute and reconstruct dapagliflozin-HbA1c dose-response relationship in T1D by accounting for the drug’s action on both daily insulin dose and plasma glucose on a subject-level. While the model is able to adequately capture the observed data, it also revealed that the variability in CGM is poorly approximated by the variability in insulin dose alone. Furthermore, the slope of CGM/HbA1c relationship may differ depending on the population and treatment scenarios. As such, a deeper dive into the physiological mechanisms is required to better quantify the intricate network of glycemic response under dapagliflozin treatment.
Mitochondrial dysfunction as a possible trigger of neuroinflammation at post-traumatic stress disorder (PTSD)
Authors: Dmytriv Tetiana R. , Tsiumpala Sviatoslav A. , Semchyshyn Halyna M. , Storey Kenneth B. , Lushchak Volodymyr I.
Published: October 2023

Post-traumatic stress disorder (PTSD) is a neuropsychiatric disorder that occurs in approximately 15% of people as a result of some traumatic events. The main symptoms are re-experiencing and avoidance of everything related to this event and hyperarousal. The main component of the pathophysiology of PTSD is an imbalance in the functioning of the hypothalamic-pituitary-adrenal axis (HPA) and development of neuroinflammation. In parallel with this, mitochondrial dysfunction is observed, as in many other diseases. In this review, we focus on the question how mitochondria may be involved in the development of neuroinflammation and its maintaining at PTSD. First, we describe the differences in the operation of the neuro-endocrine system during stress versus PTSD. We then show changes in the activity/expression of mitochondrial proteins in PTSD and how they can affect the levels of hormones involved in PTSD development, as well as how mitochondrial damage/pathogen-associated molecule patterns (DAMPs/PAMPs) trigger development of inflammation. In addition, we examine the possibility of treating PTSD-related inflammation using mitochondria as a target.
Exploring the interplay between metabolic power and equivalent distance in training games and official matches in soccer: a machine learning approach
Authors: Manzi Vincenzo , Savoia Cristian , Padua Elvira , Edriss Saeid , Iellamo Ferdinando , Caminiti Giuseppe , Annino Giuseppe
Published: October 2023

Introduction: This study aimed to explore the interplay between metabolic power (MP) and equivalent distance (ED) and their respective roles in training games (TGs) and official soccer matches. Furthermore, the secondary objective was to investigate the connection between external training load (ETL), determined by the interplay of metabolic power and equivalent distance, and internal training load (ITL) assessed through HR-based methods, serving as a measure of criterion validity.

Methods: Twenty-one elite professional male soccer players participated in the study. Players were monitored during 11 months of full training and overall official matches. The study used a dataset of 4269 training games and 380 official matches split into training and test sets. In terms of machine learning methods, the study applied several techniques, including K-Nearest Neighbors, Decision Tree, Random Forest, and Support-Vector Machine classifiers. The dataset was divided into two subsets: a training set used for model training and a test set used for evaluation.

Results: Based on metabolic power and equivalent distance, the study successfully employed four machine learning methods to accurately distinguish between the two types of soccer activities: TGs and official matches. The area under the curve (AUC) values ranged from 0.90 to 0.96, demonstrating high discriminatory power, with accuracy levels ranging from 0.89 to 0.98. Furthermore, the significant correlations observed between Edwards’ training load (TL) and TL calculated from metabolic power metrics confirm the validity of these variables in assessing external training load in soccer. The correlation coefficients (r values) ranged from 0.59 to 0.87, all reaching statistical significance at p < 0.001.

Discussion: These results underscore the critical importance of investigating the interaction between metabolic power and equivalent distance in soccer. While the overall intensity may appear similar between TGs and official matches, it is evident that underlying factors contributing to this intensity differ significantly. This highlights the necessity for more comprehensive analyses of the specific elements influencing physical effort during these activities. By addressing this fundamental aspect, this study contributes valuable insights to the field of sports science, aiding in the development of tailored training programs and strategies that can optimize player performance and reduce the risk of injuries in elite soccer.
Development of a novel Guinea Pig model producing transgenerational endothelial transcriptional changes driven by maternal food restriction and a second metabolic insult of high fat diet
Authors: Le Hillary H. , Hagen Matthew W. , Louey Samantha , Tavori Hagai , Thornburg Kent L. , Giraud George D. , Hinds Monica T. , Barnes Anthony P.
Published: October 2023

Developmental programming of chronic adverse cardiovascular health outcomes has been studied both using numerous human populations and an array of animal models. However, the mechanisms that produce transgenerational effects have been difficult to study due to a lack of developmentally relevant models. As such, how increased disease risk is carried to the second generation has been poorly studied. We hypothesized that the endothelium which mediates many acute and chronic vascular inflammatory responses is a key player in these effects, and epidemiological studies implicate transgenerational nutritional effects on endothelial health. To study the mutigenerational effects of maternal undernutrition on offspring endothelial health, we developed a model of transgenerational nutritional stress in guinea pigs, a translationally relevant precocial species with a relatively short lifespan. First- and second-generation offspring were subjected to a high fat diet in adolescence to exacerbate negative cardiovascular health. To assess transcriptional changes, we performed bulk RNA-sequencing in carotid artery endothelial cells, with groups stratified as prenatal control or food restricted, and postnatal control or high fat diet. We detected statistically significant gene alterations for each dietary permutation, some of which were unique to treatments and other transcriptional signatures shared by multiple or all conditions. These findings highlight a core group of genes altered by high fat diet that is shared by all cohorts and a divergence of transgenerational effects between the prenatal ad libitum and dietary restriction groups. This study establishes the groundwork for this model to be used to better understand the interplay of prenatal stress and genetic reprogramming.
Comparative analysis of chloroplast genome and new insights into phylogenetic relationships of Ajuga and common adulterants
Authors: Shang Mingyue , Wang Jiale , Dai Guona , Zheng Jiamei , Liao Binbin , Wang Jing , Duan Baozhong
Published: October 2023

Introduction

The potential contamination of herbal medicinal products poses a significant concern for consumer health. Given the limited availability of genetic information concerning Ajuga species, it becomes imperative to incorporate supplementary molecular markers to enhance and ensure accurate species identification.

Methods

In this study, the chloroplast (cp) genomes of seven species of the genus Ajuag were sequenced, de novo assembled and characterized.

Results

exhibiting lengths ranging from 150,342 bp to 150,472 bp, encompassing 86 - 88 protein-coding genes (PCGs), 35 - 37 transfer RNA, and eight ribosomal RNA. The repetitive sequences, codon uses, and cp genomes of seven species were highly conserved, and PCGs were the reliable molecular markers for investigating the phylogenetic relationship within the Ajuga genus. Moreover, four mutation hotspot regions (accD-psaI, atpH-atpI, ndhC-trnV(UAC), and ndhF-rpl23) were identified within cp genomes of Ajuga, which could help distinguish A. bracteosa and its contaminants. Based on cp genomes and PCGs, the phylogenetic tree preliminary confirmed the position of Ajuga within the Lamiaceae family. It strongly supported a sister relationship between Subsect. Genevense and Subsect. Biflorae, suggesting the merger of Subsect. Biflorae and Subsect. Genevenses into one group rather than maintaining separate categorizations. Additionally, molecular clock analysis estimated the divergence time of Ajuga to be around 7.78 million years ago.

Discussion

The species authentication, phylogeny, and evolution analyses of the Ajuga species may benefit from the above findings.
Eyes-state-dependent alterations of magnetoencephalographic connectivity associated with delayed recall in Alzheimer’s disease via graph theory approach
Authors: Yuasa Keigo , Hirosawa Tetsu , Soma Daiki , Furutani Naoki , Kameya Masafumi , Sano Masuhiko , Kitamura Koji , Ueda Minehisa , Kikuchi Mitsuru
Published: October 2023

Introduction

Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by memory impairment and cognitive decline. Electroencephalography (EEG) and magnetoencephalography (MEG) studies using graph theory show altered “Small-Worldness (SW)” properties in AD. This study aimed to investigate whether eye-state-dependent alterations in SW differ between patients with AD and healthy controls, considering the symptoms of AD.

Methods

Nineteen patients with AD and 24 healthy controls underwent MEG under different conditions (eyes-open [EO] and eyes-closed [EC]) and the Wechsler Memory Scale-Revised (WMS-R) with delayed recall. After the signal sources were mapped onto the Desikan–Killiany brain atlas, the statistical connectivity of five frequency bands (delta, theta, alpha, beta, and gamma) was calculated using the phase lag index (PLI), and binary graphs for each frequency band were constructed based on the PLI. Next, we measured SW as a graph metric and evaluated three points: the impact of AD and experimental conditions on SW, the association between SW and delayed recall, and changes in SW across experimental conditions correlated with delayed recall.

Results

SW in the gamma band was significantly lower in patients with AD (z = −2.16, p = 0.031), but the experimental conditions did not exhibit a significant effect in any frequency band. Next, in the AD group, higher scores on delayed recall correlated with diminished SW across delta, alpha, and beta bands in the EO condition. Finally, delayed recall scores significantly predicted relative differences in the SW group in the alpha band (t = −2.98, p = 0.009).

Discussion

Given that network studies could corroborate the results of previous power spectrum studies, our findings contribute to a multifaceted understanding of functional brain networks in AD, emphasizing that the SW properties of these networks change according to disease status, cognitive function, and experimental conditions.
Variations in cognition by human capital characteristics: a cross-sectional analysis of Brazilian older adults
Authors: Vicerra Paolo Miguel Manalang
Published: October 2023

Introduction

The productivity of individuals is assumed to decline upon reaching old age when cognitive ability is considered. This assumption is false, especially if the human development characteristics of people are analyzed, which highlights the need to recognize the heterogeneity among subpopulations.

Methods

Using Wave two of the Brazilian Longitudinal Study on Aging, conducted from 2019 to 2021, this study explored the onset and speed of cognitive aging among older individuals aged at least 60 in Brazil, with reference to their education and income levels.

Results

It was observed that although higher human capital characteristics yielded results toward later cognitive decline, women benefited more from having higher educational attainment levels. Such a pattern was similar among men and increased income levels. Disparities in cognitive performance, whether from education or income, were greatest at age 60, and this advantage diminished as age progressed.

Conclusion

Viewing the older population as homogeneous in terms of health function is restrictive. It should be recognized that variations in social status affect individuals’ health status into old age and therefore their respective potential for productivity should be maximized.