bluuebunny/crossref_metadata_2025_split huggingface dataset:
Independent flavonoid and anthocyanin biosynthesis in the flesh of a red-fleshed table grape revealed by metabolome and transcriptome co-analysis
Authors: Lu Renxiang , Song Miaoyu , Wang Zhe , Zhai Yanlei , Hu Chaoyang , Perl Avihai , Ma Huiqin 
Published: July 2023

Abstract
Background
Red flesh is a desired fruit trait, but the regulation of red flesh formation in grape is not well understood. ‘Mio Red’ is a seedless table grape variety with light-red flesh and blue-purple skin. The skin color develops at veraison whereas the flesh color develops at a later stage of berry development. The flesh and skin flavonoid metabolomes and transcriptomes were analyzed.

Results
A total of 161 flavonoids were identified, including 16 anthocyanins. A total of 66 flavonoids were found at significantly different levels in the flesh and skin (fold change ≥ 2 or ≤ 0.5, variable importance in projection (VIP) ≥ 1). The main anthocyanins in the flesh were pelargonidin and peonidin, and in the skin were peonidin, delphinidin, and petunidin. Transcriptome comparison revealed 57 differentially expressed structural genes of the flavonoid-metabolism pathway (log2fold change ≥ 1, FDR < 0.05, FPKM ≥ 1). Two differentially expressed anthocyanin synthase (ANS) genes were annotated, ANS2 (Vitvi02g00435) with high expression in flesh and ANS1 (Vitvi11g00565) in skin, respectively. One dihydro flavonol 4-reductase (DFR, Vitvi18g00988) gene was differentially expressed although high in both skin and flesh. Screened and correlation analysis of 12 ERF, 9 MYB and 3 bHLH genes. The Y1H and dual luciferase assays showed that MYBA1 highly activates the ANS2 promoter in flesh and that ERFCBF6 was an inhibitory, EFR23 and bHLH93 may activate the DFR gene. These genes may be involved in the regulation of berry flesh color.

Conclusions
Our study revealed that anthocyanin biosynthesis in grape flesh is independent of that in the skin. Differentially expressed ANS, MYB and ERF transcription factors provide new clues for the future breeding of table grapes that will provide the health benefits as red wine.
Development and assessment of the performance of a shared ventilatory system that uses clinically available components to individualize tidal volumes
Authors: Hannon David M. , Jones Tim , Conolly Jack , Judge Conor , Iqbal Talha , Shahzad Atif , Madden Michael , Kirrane Frank , Conneely Peter , Harte Brian H. , O’Halloran Martin , Laffey John G. 
Published: July 2023

Abstract
Objectives
To develop and assess a system for shared ventilation using clinically available components to individualize tidal volumes.

Design
Evaluation and in vitro validation study

Setting
Ventilator shortage during the SARS-CoV-2 pandemic.

Participants
The team consisted of physicians, bioengineers, computer programmers, and medical technology professionals.

Methods
Using clinically available components, a system of ventilation consisting of two ventilatory limbs was assembled and connected to a ventilator. Monitors for each limb were developed using open-source software. Firstly, the effect of altering ventilator settings on tidal volumes delivered to each limb was determined. Secondly, the impact of altering the compliance and resistance of one limb on the tidal volumes delivered to both limbs was analysed. Experiments were repeated three times to determine system variability.

Results
The system permitted accurate and reproducible titration of tidal volumes to each limb over a range of ventilator settings and simulated lung conditions. Alteration of ventilator inspiratory pressures, of respiratory rates, and I:E ratio resulted in very similar tidal volumes delivered to each limb. Alteration of compliance and resistance in one limb resulted in reproducible alterations in tidal volume to that test lung, with little change to tidal volumes in the other lung. All tidal volumes delivered were reproducible.

Conclusions
We demonstrate the reliability of a shared ventilation system assembled using commonly available clinical components that allows titration of individual tidal volumes. This system may be useful as a strategy of last resort for Covid-19, or other mass casualty situations, where the need for ventilators exceeds supply.
Association of cardiovascular health at old age with all-cause mortality: a prospective cohort study in China
Authors: Chen Shimin , Li Haowei , Wang Shengshu , Yang Shanshan , Liu Shaohua , Song Yang , Li Xuehang , Li Rongrong , Wang Jianhua , Liu Miao , He Yao 
Published: July 2023

Abstract
Background
Cardiovascular disease has become the leading cause of death worldwide, but there is a lack of data on whether cardiovascular health (CVH) is associated with elderly mortality in China. We investigated the relationship between the ideal CVH score of Chinese elderly and the all-cause mortality.

Methods
The Beijing Elderly Comprehensive Health Cohort Study included a total of 4,499 participants aged 60 years and above. The CVH metric was calculated at baseline and had a score ranging from 0 to 12. The relationship of CVH metrics with all-cause mortality was investigated using Cox proportional hazard regression analysis. The robustness of results was tested using subgroup and sensitivity analysis.

Results
The median CVH score among participants was 8.00 (2.00), with only 8.0% scoring 11–12 points. 667 deaths were observed during an average follow-up time of 8.2 years. Participants with a CVH score of 11–12 had a decreased risk of all-cause mortality when compared to those with a CVH score of 0–4(HR = 0.584, 95% CI: 0.373–0.913). Participants had a 7.5% lower risk of all-cause death with each unit higher CVH score (HR = 0.925, 95%CI: 0.885–0.967) with a linearly decreasing trend (P nonlinear = 0.575). The relationships were greater in younger elderly people and stroke patients (P interaction = 0.011 and 0.037. respectively). The consistency of significant trends in sensitivity analysis shows the robustness of association (P trend < 0.001).

Conclusions
Among the Chinese elderly, there was a linear relationship between improving CVH scores and a lower risk of all-cause mortality. Because of the enormous benefits brought by one point, strategies are essential for improving cardiovascular health attainment.

Trial registration
This study was registered at China Clinical Trial Registration Center (ChiCTR2100049866).
Association of gut microbiome with risk of intracranial aneurysm: a mendelian randomization study
Authors: Ma Chencheng , Zhang Weiwei , Mao Lei , Zhang Guangjian , Shen Yuqi , Chang Hanxiao , Xu Xiupeng , Jin Huiru , Li Zheng , Lu Hua 
Published: July 2023

Abstract
Objective
To investigate the potential causal link between genetic variants associated with gut microbiome and risk of intracranial aneurysm (IA) using two-sample mendelian randomization (MR).

Methods
We performed two sets of MR analyses. At first, we selected the genome-wide statistical significant(P < 5 × 10–8) single nucleotide polymorphisms (SNPs) as instrumental variables (IVs). Then, we selected the locus-wide significant (P < 1 × 10–5) SNPs as IVs for the other set of analyses to obtain more comprehensive conclusions. Gut microbiome genetic association estimates were derived from a genome-wide association study (GWAS) of 18,473 individuals. Summary-level statistics for IA were obtained from 79,429 individuals, which included 7,495 cases and 71,934 controls.

Results
On the basis of locus-wide significance level, inverse variance weighted(IVW) showed that Clostridia [(odds ratio (OR): 2.60; 95% confidence interval (CI): 1.00—6.72, P = 0.049)], Adlercreutzia (OR: 1.81; 95% CI: 1.10—2.99, P = 0.021) and Victivallis (OR: 1.38; 95% CI: 1.01—1.88, P = 0.044) were positively related with the risk of unruptured intracranial aneurysm(UIA); Weighted median results of MR showed Oscillospira (OR: 0.37; 95% CI: 0.17—0.84, P = 0.018) was negatively with the risk of UIA and Sutterella (OR: 1.84; 95% CI: 1.04—3.23, P = 0.035) was positively related with the risk of UIA; MR-Egger method analysis indicated that Paraprevotella (OR: 0.32; 95% CI: 0.13—0.80, P = 0.035) was negatively with the risk of UIA and Rhodospirillaceae (OR: 13.39; 95% CI: 1.44—124.47, P = 0.048) was positively related with the risk of UIA. The results suggest that Streptococcus (OR: 5.19; 95% CI: 1.25—21.56; P = 0.024) and Peptostreptococcaceae (OR: 4.92; 95% CI: 1.32—18.32; P = 0.018) may increase the risk of UIA according to genome-wide statistical significance thresholds.

Conclusion
This MR analysis indicates that there exists a beneficial or detrimental causal effect of gut microbiota composition on IAs.
Anisocoria without extraocular muscle impairment due to moderate traumatic brain injury with midbrain contusion: a case report
Authors: Ota Koshi , Kobata Hitoshi , Hamada Yoshisuke , Mizutani Saki , Okuyama Terunari , Ota Kanna , Takeda Yuriko , Takasu Akira 
Published: July 2023

Abstract
Background
New-onset anisocoria is an important clinical clue to life-threatening intracranial injury. Anisocoria alone without impairment of extraocular muscles is a rare presentation of moderate traumatic brain injury (TBI).

Case presentation
A 79-year-old woman was transported to hospital soon after falling off a bicycle. Glasgow Coma Scale score on arrival was 11 (E3V3M5). On examination at admission, she was found to be drowsy. Bruising was seen around the right eye and pupil diameters differed (right, 4.5 mm; left, 3.0 mm; both reactive to light). Computed tomography of the head revealed hemorrhagic contusion in the left temporal lobe and left pretectal area of the midbrain, right clavicular fracture, and pulmonary contusion with fractures of the 3rd and 4th ribs. Magnetic resonance imaging confirmed hemorrhagic contusion of the midbrain. The patient achieved full recovery of motor and mental functions with conservative treatment and was discharged on hospital day 17.

Conclusion
We encountered a case of anisocoria without major extraocular muscle impairment due to moderate TBI with midbrain contusion.
The relationship of maternal hepatitis B e antigen and response to vaccination of infants born to women with chronic infection
Authors: Jiang Hongxiu , Chen Chao , Yuan Deping , Ye Xiajun , Chen Yan , Han Guorong , Zhou Guanlun , Ju Yuhao , Cao Minkai 
Published: July 2023

Abstract
Background
The relationship of maternal HBeAg and infants’ response to hepatitis B vaccine remains controversial. This study aims to observe the dynamic changes in infant birth HBV markers and study the time-varying effects of maternal HBeAg on vaccination response of infants born to women with chronic HBV infection.

Methods
3163 infants born to HBsAg positive mothers including 1737 with maternal HBeAg positive in group A and 1426 negative in group B were enrolled eventually. Demographic information and laboratory tests were collected at birth, 7-12th and 24th month. The dynamic changes of infant HBV markers and HBsAb titers at different time points were compared between the two groups.

Results
The infant HBV markers at birth displayed different modes. During the follow-up, we observed a significant downward trend in the positive rates of HBsAg, HBeAg, HBeAb and HBcAb. The HBsAg of two groups switched to negative at 7–12 months and HBeAg in Group A became negative at 24 months. The HBsAb titers of the infants in the two groups were 576.91(192.8–1000.0) vs 719.67(208.1–1000.0) at 7–12 months (Z = -3.049, P = 0.002) and 783.5(227.8–1000.0) vs 891.4(234.0–1000.0) at 24 months (Z = -0.853, P = 0.394). High HBV DNA viral load (OR 1.260, 95% CI 1.139–1.395, P < 0.001) and maternal HBeAg level (OR 1.003, 95% CI 1.002–1.003, P < 0.001) were associated with the higher HBeAg positive rate of infants.

Conclusions
Maternal HBeAg did affect the infants’ immune response to vaccination and reduce the anti-response at 7-12th month temporarily, but these influences were negligible by 24th months after birth, which proved that the maternal HBeAg would not induce immune tolerance of infants from a long-term perspective.
Helicobacter bizzozeronii infection in a girl with severe gastric disorders in México: case report
Authors: Montijo-Barrios Ericka , Celestino-Pérez Omaha Y. , Morelia-Mandujano Luis , Rojas-Maruri Cesar Mauricio , Smet Annemieke , Haesebrouck Freddy , De Witte Chloë , Romo-González Carolina 
Published: July 2023

Abstract
Background
Gastric non-Helicobacter pylori helicobacters (NHPH) naturally colonize the stomach of animals. In humans, infection with these bacteria is associated with chronic active gastritis, peptic ulceration and MALT-lymphoma. H. bizzozeronii belongs to these NHPH and its prevalence in children is unknown.

Case presentation
This case report describes for the first time a NHPH infection in a 20-month-old girl with severe gastric disorders in Mexico. The patient suffered from melena, epigastric pain, and bloating. Gastroscopy showed presence of a Hiatus Hill grade I, a hemorrhagic gastropathy in the fundus and gastric body, and a Forrest class III ulcer in the fundus. Histopathologic examination revealed a chronic active gastritis with presence of long, spiral-shaped bacilli in the glandular lumen. Biopsies from antrum, body and incisure were negative for presence of H. pylori by culture and PCR, while all biopsies were positive for presence of H. bizzozeronii by PCR. Most likely, infection occurred through intense contact with the family dog. The patient received a triple therapy consisting of a proton pump inhibitor, clarithromycin, and amoxicillin for 14 days, completed with sucralfate for 6 weeks, resulting in the disappearance of her complaints.

Conclusion
The eradication could not be confirmed, although it was suggested by clear improvement of symptoms. This case report further emphasizes the zoonotic importance of NHPH. It can be advised to routinely check for presence of both H. pylori and NHPH in human patients with gastric complains.
An explorative study on proteomic analyses related to inflammation and pain in children with juvenile idiopathic arthritis
Authors: Elfving Andreas , Harila-Saari Arja , Nilsson Ludwig , Berntson Lillemor 
Published: July 2023

AbstractBackgroundOur aim was attempting to find proteins involved in the pain process and correlating with pain but not degree of inflammation in children with juvenile idiopathic arthritis (JIA), using a proteomics panel.MethodsA total of 87 plasma samples were collected from 51 children with JIA (51 at diagnosis in a higher disease activity state, 18 at follow-up in a lower disease activity state) and 18 healthy controls. Relative levels of 92 proteins related to a wide range of biological processes in inflammation were obtained using a proximity extension assay panel. Comparisons between children with and without JIA, in different disease categories, by juvenile disease activity score (JADAS27) and degree of pain on a visual analogue scale (VAS), were performed using parametric and non-parametric statistical methods.ResultsNineteen proteins involved in arthritic inflammation, such as interleukin 6 (IL-6) and S100 protein A12, were higher in patients with JIA than controls, seven decreased significantly during treatment, and 18 correlated significantly with JADAS27. Three proteins correlated with pain VAS scores in unadjusted analyses: the glial cell line-derived neurotrophic factor (GDNF), transforming growth factor beta, and IL-18R1. Levels of GDNF correlated significantly with pain VAS scores but not with JADAS27.ConclusionsPlasma levels of 18 of 92 tested proteins correlated with degree of disease activity. Levels of three proteins correlated with pain, and levels of one, GDNF, originating from neural cells, correlated with pain without correlating with inflammatory degree, suggesting that it may play a role in pain in JIA. Further studies in larger cohorts are warranted.
Global, regional, and national time trends in cancer mortality attributable to high fasting plasma glucose: an age-period cohort analysis
Authors: Xie Jing , Liu Zeye , Ren Liqun , He Liyun , Lu Shan , Meng Xiangzhi , Zhang Xin , Su Zhanhao , Jing Shenqi , Shan Tao , Wang Junjie , Xia Ruibing , Feng Wei , Li Yakun , Liu Naifeng , Liu Yun 
Published: July 2023

Abstract
Background
High fasting plasma glucose (HFPG) is the fastest-growing risk factor for cancer deaths worldwide. We reported the cancer mortality attributable to HFPG at global, regional, and national levels over the past three decades and associations with age, period, and birth cohort.

Methods
Data for this study were retrieved from the Global Burden of Disease Study 2019, and we used age-period-cohort modelling to estimate age, cohort and period effects, as well as net drift (overall annual percentage change) and local drift (annual percentage change in each age group).

Results
Over the past 30 years, the global age-standardized mortality rate (ASMR) attributable to HFPG has increased by 27.8%. The ASMR in 2019 was highest in the male population in high sociodemographic index (SDI) areas (8.70; 95% CI, 2.23–18.04). The net drift for mortality was highest in the female population in low SDI areas (2.33; 95% CI, 2.12–2.55). Unfavourable period and cohort effects were found across all SDI quintiles. Cancer subtypes such as "trachea, bronchus, and lung cancers", "colon and rectal cancers", "breast cancer" and "pancreatic cancer" exhibited similar trends.

Conclusions
The cancer mortality attributable to HFPG has surged during the past three decades. Unfavourable age-period-cohort effects on mortality were observed across all SDI quintiles, and the cancer mortality attributable to HFPG is expected to continue to increase rapidly in the future, particularly in lower SDI locations. This is a grim global public health issue that requires immediate attention.
Socioeconomic position, perceived weight, lifestyle risk, and multimorbidity in young adults aged 18 to 35 years: a Multi-country Study
Authors: Craig Ashleigh , Mtintsilana Asanda , Mapanga Witness , Dlamini Siphiwe N. , Norris Shane A. 
Published: July 2023

Abstract
Background
Multimorbidity-risk is established early in life, therefore reducing modifiable risk factors such as overweight or obesity may, in part, tackle the burden of multimorbidity in later life.

Methods
We made use of a cross-sectional online survey that included young adults (18-35yrs old) from three countries – Kenya, South Africa, and the United Kingdom (n = 3000). Information pertaining to socio-demographic, health, lifestyle, and perceived weight was collected. Additionally, the sum of affirmed morbidities was used to determine a morbidity score. Likewise, a lifestyle risk score was calculated based on information obtained from questions surrounding four unhealthy lifestyle behaviours, namely current smoking, alcohol consumption, physical inactivity, and overweight/obese weight status as a confirmed clinic condition. We further explored differences in socioeconomic position, and the prevalence of perceived weight, multimorbidity, and lifestyle risk factors between the three countries. We also determined the odds ratio of multimorbidity with perceived weight as a main predictor variable. We furthermore performed a generalised structural equation model to determine whether the association between socioeconomic position and multimorbidity was mediated via perceived weight and/or lifestyle risk.

Results
Socioeconomic position, weight perceptions, lifestyle risk, and multimorbidity varied significantly across the different economic countries. Higher morbidity (by > 11.9%) and lifestyle risk (by > 20.7%) scores were observed in those who reported an overweight weight perception when compared to those with an underweight or normal weight perception. In pooled analyses, the odds ratio in developing 2 or more morbidities increased multiple times in those who perceived themselves as overweight (all models: OR ≥ 2.241 [95% CI ≥ 1.693; ≥ 2.966] p < 0.001), showing a larger odds ratio with high significance in those who reported 3 or more morbidities (all models: OR ≥ 3.656 [95% CI ≥ 2.528; ≥ 5.286] p < 0.001). Furthermore, this study showed that an overweight weight perception partially mediated (p ≤ 0.001) the association between socioeconomic position and multimorbidity.

Conclusions
This study confirmed poorer health outcomes in those who perceived themselves as overweight. The findings from this study further emphasise the importance of targeted intervention strategies directed at raising weight-related awareness and potentiating risk factors, specifically in those who reside in lower economic developed countries.
Chemotherapy for advanced pulmonary sarcomatoid carcinoma: a population-based propensity score matching study
Authors: Wang Feng , Yu Xiangyang , Han Yi , Gong Changfan , Yan Dongjie , Yang Lei , Li Jie , Liu Shuku 
Published: July 2023

Abstract
Objectives
Pulmonary sarcomatoid carcinoma (PSC) is a rare histological type of non-small cell lung cancer (NSCLC). There are no specific treatment guidelines for PSC. For advanced PSC (stage II-IV), the role of chemotherapy is still controversial. The purpose of this study was to investigate the effect of chemotherapy on the prognosis of advanced PSC.

Methods
A total of 960 patients with advanced PSC from the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2019 were enrolled in this study. To investigate the prognostic factors, the Cox proportional hazard regression model was conducted. A total of 642 cases were obtained after propensity score matching (PSM). The Kaplan‒Meier method was applied to compare overall survival (OS) and cancer-specific survival (CSS).

Results
For all 960 cases included in this study, the Cox proportional hazard model was applied for prognostic analysis. Univariate and multivariate analyses showed that stage, T stage, N stage, M stage, surgery, and chemotherapy were prognostic factors for OS and CSS (P < 0.05). A total of 642 cases were obtained after PSM, with no significant difference between the two groups for all variables. Kaplan‒Meier curves indicated that for OS and CSS, the prognosis was significantly better in the chemotherapy group than in the no-chemotherapy group.

Conclusions
For advanced PSC, chemotherapy can significantly improve the OS and CSS of patients. Chemotherapy should be an important part of PSC treatment.
Alectinib-induced rash unresponsive to desensitization: a case report and literature review
Authors: Rodriguez Robin Raquel , Dindak Jessie , Kline Janet , Raj Moses S. 
Published: July 2023

Abstract
Background
Since the inception of targeted therapies in treating lung cancer, providers have had to be aware of a new host of side effects when selecting management options for patients. Although targeted therapies are creating increased hope for patients with non-small cell lung cancers (NSCLC), understanding their side effects presents a challenge for providers. Alectinib, a second-generation tyrosine kinase inhibitor, is a targeted therapy used in patients with non-small cell lung cancer found to have anaplastic lymphoma kinase (ALK) mutations. Alectinib is the focus of this case report and literature review as we seek to understand side effects providers may encounter when prescribing these therapies.

Case presentation
We begin our report with the case of a 63-year-old Hispanic female with stage IIIA non-small cell lung cancer found to have the ALK genomic alteration. She was started on Alectinib, and on Day 11, she developed a severe maculopapular rash requiring hospitalization. After complete resolution, desensitization with Alectinib was attempted but unsuccessful.

Conclusions
Despite the unsuccessful desensitization of this patient, it is important to report this rare side effect in order to better understand how providers can pursue management. Case reports such as this can aid providers in potentially preventing, treating, and rechallenging patients on targeted therapies in the future.