bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cas12a-mediated gene targeting by sequential transformation strategy in Arabidopsis thaliana
Authors: Li Jing , Wei Qi , Cheng Yiqiu , Kong Dali , Kong Zhe , Ke Yongping , Dang Xiaofei , Zhu Jian-Kang , Shimada Hiroaki , Miki Daisuke 
Published: July 2024

AbstractGene targeting (GT) allows precise manipulation of genome sequences, such as knock-ins and sequence substitutions, but GT in seed plants remains a challenging task. Engineered sequence-specific nucleases (SSNs) are known to facilitate GT via homology-directed repair (HDR) in organisms. Here, we demonstrate that Cas12a and a temperature-tolerant Cas12a variant (ttCas12a) can efficiently establish precise and heritable GT at two loci in Arabidopsis thaliana (Arabidopsis) through a sequential transformation strategy. As a result, ttCas12a showed higher GT efficiency than unmodified Cas12a. In addition, the efficiency of transcriptional and translational enhancers for GT via sequential transformation strategy was also investigated. These enhancers and their combinations were expected to show an increase in GT efficiency in the sequential transformation strategy, similar to previous reports of all-in-one strategies, but only a maximum twofold increase was observed. These results indicate that the frequency of double strand breaks (DSBs) at the target site is one of the most important factors determining the efficiency of genetic GT in plants. On the other hand, a higher frequency of DSBs does not always lead to higher efficiency of GT, suggesting that some additional factors are required for GT via HDR. Therefore, the increase in DSB can no longer be expected to improve GT efficiency, and a new strategy needs to be established in the future. This research opens up a wide range of applications for precise and heritable GT technology in plants.
Trace of delirium after robotic lower abdominal tumor resection at different end-tidal carbon dioxide: a RCT trial
Authors: Chen Jingwen , Liang Si , Wei Ming , Ma Yue , Bi Tianpeng , Liu Zheng , Song Yang , Chen Hong , Wang Yu 
Published: July 2024

Abstract
Background
Postoperative delirium (POD) often occurs in oncology patients, further increasing the medical and financial burden. Robotic technology in lower abdominal tumors resection reduces surgical trauma but increases risks such as carbon dioxide (CO2) absorption. This study aimed to investigate the differences in their occurrence of POD at different end-tidal CO2 levels.

Method
This study was approved by the Ethics Committee of Affiliated Hospital of He Bei University (HDFY-LL-2022-169). The study was registered with the Chinese Clinical Trials Registry on URL: http://www.chictr.org.cn, Registry Number: ChiCTR2200056019 (Registry Date: 27/08/2022). In patients scheduled robotic lower abdominal tumor resection from September 1, 2022 to December 31, 2022, a comprehensive delirium assessment was performed three days postoperatively using the CAM scale with clinical review records. Intraoperative administration of different etCO2 was performed depending on the randomized grouping after intubation. Group L received lower level etCO2 management (31-40mmHg), and Group H maintained the higher level(41-50mmHg) during pneumoperitoneum. Data were analyzed using Pearson Chi-Square or Wilcoxon Rank Sum tests and multiple logistic regression. Preoperative mental status score, alcohol impairment score, nicotine dependence score, history of hypertension and diabetes, duration of surgery and worst pain score were included in the regression model along with basic patient information for covariate correction analysis.

Results
Among the 103 enrolled patients, 19 (18.4%) developed postoperative delirium. The incidence of delirium in different etCO2 groups was 21.6% in Group L and 15.4% in Group H, respectively, with no statistical differences. In adjusted multivariate analysis, age and during of surgery were statistically significant predictors of postoperative delirium. The breath-hold test was significantly lower postoperatively, but no statistical differences were found between two groups.

Conclusion
With robotic assistant, the incidence of postoperative delirium in patients undergoing lower abdominal tumor resection was not modified by different end-tidal carbon dioxide management, however, age and duration of surgery were positively associated risk factors.
Dapagliflozin, inflammation and left ventricular remodelling in patients with type 2 diabetes and left ventricular hypertrophy
Authors: Dihoum Adel , Brown Alexander JM , McCrimmon Rory J , Lang Chim C , Mordi Ify R 
Published: July 2024

Abstract
Background and Aims
Sodium-glucose co-transporter 2 (SGLT2) inhibitors have beneficial effects in heart failure (HF), including reverse remodelling, but the mechanisms by which these benefits are conferred are unclear. Inflammation is implicated in the pathophysiology of heart failure (HF) and there are some pre-clinical data suggesting that SGLT2 inhibitors may reduce inflammation. There is however a lack of clinical data. The aim of our study was to investigate whether improvements in cardiac remodelling caused by dapagliflozin in individuals with type 2 diabetes (T2D) and left ventricular hypertrophy (LVH) were associated with its effects on inflammation.

Methods
We measured C-reactive protein (CRP), tumor necrosis factor alpha (TNF-α), interleukin-1β (IL-1β), interleukin 6 (IL-6), and interleukin 10 (IL-10) and neutrophil-to-lymphocyte ratio (NLR) in plasma samples of 60 patients with T2D and left ventricular hypertrophy (LVH) but without symptomatic HF from the DAPA-LVH trial in which participants were randomised dapagliflozin 10 mg daily or placebo for 12 months and underwent cardiac magnetic resonance imaging (CMR) at baseline and end of treatment. The primary analysis was to investigate the effect of dapagliflozin on inflammation and to assess the relationships between changes in inflammatory markers and LV mass and global longitudinal strain (GLS) and whether the effect of dapagliflozin on LV mass and GLS was modulated by baseline levels of inflammation.

Results
Following 12 months of treatment dapagliflozin significantly reduced CRP compared to placebo (mean difference of -1.96; 95% CI -3.68 to -0.24, p = 0.026). There were no significant statistical changes in other inflammatory markers. There were modest correlations between improvements in GLS and reduced inflammation (NLR (r = 0.311), IL-1β (r = 0.246), TNF-α (r = 0.230)) at 12 months.

Conclusions
Dapagliflozin caused a significant reduction in CRP compared to placebo. There were correlations between reductions in inflammatory markers including IL-1β and improvements in global longitudinal strain (but not reduced LV mass). Reductions in systemic inflammation might play a contributory role in the cardiovascular benefits of dapagliflozin.

Trial registration
Clinicaltrials.gov NCT02956811 (06/11/2016).
Assessing seropositivity of MMR antibodies in individuals aged 2–22: evaluating routine vaccination effectiveness after the 2003 mass campaign-a study from Iran’s National Measles Laboratory
Authors: Ghafoori Fateme , Mokhtari-Azad Talat , Foroushani Abbas Rahimi , Farahmand Mohammad , shadab Azade , Salimi Vahid 
Published: July 2024

Abstract
Background and purpose
The seroprevalence of antibodies against measles, mumps, and rubella (MMR) was evaluated 17 years following a mass vaccination campaign in individuals aged 2 to 22 years who had received routine immunization but were not eligible for an extended immunization program.

Methods
Samples were acquired from Iran’s National Measles Laboratory (NML), with individuals showing positive IgM results excluded. Out of the samples collected in 2020, a random selection of 290 serum samples was chosen, representing individuals between the ages of 2 and 22 years from diverse regions in the country. These samples were subjected to analysis using an enzyme-linked immunosorbent assay (ELISA) to quantify specific IgG antibodies against MMR.

Results
The seroprevalence rates of antibodies for measles, mumps, and rubella were determined to be 76.2%, 89.3%, and 76.9%, respectively. Younger age groups exhibited higher seropositivity rates for measles and mumps, whereas the 7- to 11-year-old group demonstrated the highest seropositivity rate for rubella. A reduction in antibody status was observed from younger to older age groups, particularly those aged 17–22.

Conclusion
The study unveiled suboptimal antibody levels for measles and rubella, highlighting the necessity for further investigation and potential adjustments to future vaccination strategies. Moreover, the decline in antibody status post-vaccination can accumulate in seronegative individuals over time, elevating the risk of outbreaks.
Bow hunter’s syndrome due to an anomalous right vertebral artery origin and contralateral absence: a case report and literature review
Authors: Zhang Li , Gao Yu , Yu Xiao , Guo Ying , Piao Zhe , Nan Guangxian 
Published: July 2024

Abstract
Background
Bow Hunter’s syndrome (BHS), also known as rotational vertebral artery occlusion (RVAO), is a rare condition characterized by dynamic vertebrobasilar insufficiency due to position-dependent occlusion of the vertebral artery (VA). In the existing literature, most cases of BHS are attributed to osteophytic compression originating from the occipital condyle or within the transverse foramen, often accompanied by anatomical abnormalities of the VA. However, cases presenting solely with VA anomalies in the absence of any cervical vertebral structural abnormality are rare. This case report presents a unique instance of BHS in a 56-year-old male, attributed to the anomalous origin of the right VA and the absence of the left VA, without cervical structural abnormalities.

Case presentation
The patient exhibited symptoms like episodic dizziness and vertigo, which were exacerbated by rightward head rotation and alleviated upon returning to a neutral position. Diagnostic evaluation, including digital subtraction angiography, revealed that the right VA originated from the right common carotid artery and compression-induced stenosis of the right VA during head rotation. Conservative management, including avoidance of certain head movements and anti-arteriosclerosis medication, led to symptom resolution over a two-year follow-up period.

Conclusions
This report contributes to the understanding of BHS by highlighting a rare vascular anomaly presentation and incorporates a review of 14 similar case reports in the literature describing that an anatomical abnormality of the VA is mainly responsible for the pathology of BHS in the absence of cervical vertebral anomalies, thus emphasizing the need for careful diagnostic and management strategies.
Promoting men-inclusive maternity services: exploring the expectations, experiences and needs of men as fathers
Authors: Harrison Gai , Fitzgerald Kristy , O’Leary Patrick , Kothari Alka , Callaway Leonie 
Published: July 2024

Abstract
Aim
This study aimed to explore the ‘real time’ expectations, experiences and needs of men who attend maternity services to inform the development of strategies to enhance men’s inclusion.

Methods
A qualitative descriptive design was adopted for the study. Semi-structured face-to-face or telephone interviews were conducted with 48 men attending the Royal Brisbane and Women’s Hospital before and after their partner gave birth. Data were coded and analysed thematically.

Results
Most respondents identified their role as a support person rather than a direct beneficiary of maternity services. They expressed the view that if their partner and baby’s needs were met, their needs were met. Factors that contributed to a positive experience included the responsiveness of staff and meeting information needs. Factors promoting feelings of inclusion were being directly addressed by staff, having the opportunity to ask questions, and performing practical tasks associated with the birth.

Conclusion
Adopting an inclusive communication style promotes men’s feelings of inclusion in maternity services. However, the participants’ tendency to conflate their needs with those of their partner suggests the ongoing salience of traditional gender role beliefs, which view childbirth primarily as the domain of women.
eHSP90α in front-line therapy in EGFR exon 19 deletion and 21 Leu858Arg mutations in advanced lung adenocarcinoma
Authors: Bian Yingzhen , Liu Haizhou , Huang Jinglei , Feng Zhaorong , Lin Yanyan , Li Jilin , Zhang Litu 
Published: July 2024

Abstract
Purpose
Extracellular heat shock protein 90 AA1(eHSP90α) is intricately linked to tumor progression and prognosis. This study aimed to investigate the difference in the value of eHSP90α in post-treatment response assessment and prognosis prediction between exon 19 deletion(19DEL) and exon 21 Leu858Arg(L858R) mutation types in lung adenocarcinoma(LUAD).

Methods
We analyzed the relationship between the expression of eHSP90α and clinicopathological features in 89 patients with L858R mutation and 196 patients with 19DEL mutation in LUAD. The Kaplan-Meier survival curve was used to determine their respective cut-off values and analyze the relationship between eHSP90α expression and the survival time of the two mutation types. The area under the curve (AUC) was used to evaluate the diagnostic performance of biomarkers. Then, the prognostic model was developed using the univariate-Cox multivariate-Cox and LASSO-multivariate logistic methods.

Results
In LUAD patients, eHSP90α was positively correlated with carcinoembryonic antigen(CEA), carbohydrate antigen 125(CA125), and carbohydrate antigen 153(CA153). The truncated values of eHSP90α in L858R and 19DEL patients were 44.5 ng/mL and 40.8 ng/mL, respectively. Among L858R patients, eHSP90α had the best diagnostic performance (AUC = 0.765), and higher eHSP90α and T helper cells(Th cells) expression were significantly related to shorter overall survival(OS) and worse treatment response. Also, high eHSP90a expression and short progression-free survival(PFS) were significantly correlated. Among 19DEL patients, CEA had the best diagnostic efficacy (AUC = 0.734), and CEA and Th cells were independent prognostic factors that predicted shorter OS. Furthermore, high CA125 was significantly associated with short PFS and poor curative effect.

Conclusions
eHSP90α has a better prognostic value in LUAD L858R patients than 19DEL, which provides a new idea for clinical diagnosis and treatment.
Association between neural prosody discrimination and language abilities in toddlers: a functional near-infrared spectroscopy study
Authors: Guo YanRu , Li YanWei , Liu FuLin , Lin HuanXi , Sun YuYing , Zhang JiaLin , Hong Qin , Yao MengMeng , Chi Xia 
Published: July 2024

Abstract
Background
Language delay affects near- and long-term social communication and learning in toddlers, and, an increasing number of experts pay attention to it. The development of prosody discrimination is one of the earliest stages of language development in which key skills for later stages are mastered. Therefore, analyzing the relationship between brain discrimination of speech prosody and language abilities may provide an objective basis for the diagnosis and intervention of language delay.

Methods
In this study, all cases(n = 241) were enrolled from a tertiary women’s hospital, from 2021 to 2022. We used functional near-infrared spectroscopy (fNIRS) to assess children’s neural prosody discrimination abilities, and a Chinese communicative development inventory (CCDI) were used to evaluate their language abilities.

Results
Ninety-eight full-term and 108 preterm toddlers were included in the final analysis in phase I and II studies, respectively. The total CCDI screening abnormality rate was 9.2% for full-term and 34.3% for preterm toddlers. Full-term toddlers showed prosody discrimination ability in all channels except channel 5, while preterm toddlers showed prosody discrimination ability in channel 6 only. Multifactorial logistic regression analyses showed that prosody discrimination of the right angular gyrus (channel 3) had a statistically significant effect on language delay (odd ratio = 0.301, P < 0.05) in full-term toddlers. Random forest (RF) regression model presented that prosody discrimination reflected by channels and brain regions based on fNIRS data was an important parameter for predicting language delay in preterm toddlers, among which the prosody discrimination reflected by the right angular gyrus (channel 4) was the most important parameter. The area under the model Receiver operating characteristic (ROC) curve was 0.687.

Conclusions
Neural prosody discrimination ability is positively associated with language development, assessment of brain prosody discrimination abilities through fNIRS could be used as an objective indicator for early identification of children with language delay in the future clinical application.
Etiology-specific incidence and mortality of diarrheal diseases in the African region: a systematic review and meta-analysis
Authors: Thystrup Cecilie , Majowicz Shannon E. , Kitila Dinaol B. , Desta Binyam N. , Fayemi Olanrewaju E. , Ayolabi Christianah I. , Hugho Ephrasia , Buys Elna M. , Akanni Gabriel B. , Machava Norgia E. , Monjane Celso , Hald Tine , Pires Sara M. 
Published: July 2024

Abstract
Background
Diarrheal diseases substantially affect public health impact in low- and middle-income countries (LMIC), particularly in Africa, where previous studies have indicated a lack of comprehensive data. With a growing number of primary studies on enteric infections in Africa, this study aimed to estimate the incidence and mortality of diarrheal pathogens across all ages in Africa in the year 2020. We also explored different methodological assumptions to allow comparison with other approaches.

Methods
Through a systematic review and meta-analysis of data from African LMICs, we estimated the etiology proportions for diarrheal diseases and deaths. We combined the etiology proportions with incidence data collected from a population survey in Africa from 2020 and mortality data from the Global Health Observatory of WHO.

Results
We estimated 1,008 billion diarrhea cases (95% UI 447 million-1,4 billion) and 515,031 diarrhea deaths (95% UI 248,983-1,007,641) in the African region in 2020. In children under five, enteroaggregative E. coli (EAEC) (44,073 cases per 100,000 people, 95% UI 18,818 − 60,922) and G. lamblia (36,116 cases per 100,000 people, 95% UI 15,245 − 49,961) were the leading causes of illness. Enteroinvasive E. coli (EIEC) (155 deaths per 100,000 people, 95% UI 106.5-252.9) and rotavirus (61.5 deaths per 100,000 people, 95% UI 42.3-100.3) were the primary causes of deaths. For children over five and adults, Salmonella spp. caused the largest number of diarrheal cases in the population of children ≥ 5 and adults (122,090 cases per 100,000 people, 95% UI 51,833 − 168,822), while rotavirus (16.4 deaths per 100,000 people, 95% UI 4.2–36.7) and enteroaggregative E. coli (EAEC) (14.6 deaths per 100,000 people, 95% UI 3.9–32.9) causing the most deaths. Geographically, the highest incidence of diarrhea was in Eastern Africa for children under five (114,389 cases per 100,000 people, 95% UI 34,771 − 172,884) and Central Africa for children over five and adults (117,820 cases per 100,000 people, 95% UI 75,111–157,584). Diarrheal mortality was highest in Western Africa for both children below five and above (children < 5: 194.5 deaths per 100,000 people, 95% UI 120-325.4; children ≥ 5 and above: 33.5 deaths per 100,000 people, 95% UI 12.9–75.1).

Conclusion
These findings provide new information on the incidence and mortality of sixteen pathogens and highlight the need for surveillance and control of diarrheal infectious diseases in Africa. The cause-specific estimates are crucial for prioritizing diarrheal disease prevention in the region.
Longitudinal lung function trajectories in response to azithromycin therapy for chronic lung disease in children with HIV infection: a secondary analysis of the BREATHE trial
Authors: Madanhire Tafadzwa , McHugh Grace , Simms Victoria , Ngwira Lucky , Gonzalez-Martinez Carmen , Semphere Robina , Moyo Brewster , Calderwood Claire , Nicol Mark , Bandason Tsitsi , Odland Jon O. , Rehman Andrea M. , Ferrand Rashida A. 
Published: July 2024

Abstract
Background
Chronic lung disease (CLD) is common among children with HIV (CWH) including in those taking antiretroviral therapy (ART). Azithromycin has both antimicrobial and anti-inflammatory effects and has been effective in improving lung function in a variety of lung diseases. We investigated lung function trajectories among CWH with CLD on ART enrolled in a randomized controlled trial of adjuvant azithromycin. We also investigated factors that modified the effect of azithromycin on lung function.

Methods
The study used data from a double-blinded placebo-controlled trial conducted in Malawi and Zimbabwe of 48 weeks on azithromycin (BREATHE: ClinicalTrials.gov NCT02426112) among CWH aged 6 to 19 years taking ART for at least six months who had a forced expiratory volume in one second (FEV1) z-score <-1.0. Participants had a further follow-up period of 24 weeks after intervention cessation. FEV1, forced vital capacity (FVC) and FEV1/FVC were measured at baseline, 24, 48 and 72-weeks and z-scores values calculated. Generalized estimating equations (GEE) models were used to determine the mean effect of azithromycin on lung-function z-scores at each follow-up time point.

Results
Overall, 347 adolescents (51% male, median age 15 years) were randomized to azithromycin or placebo. The median duration on ART was 6.2 (interquartile range: 3.8–8.6) years and 56.2% had an HIV viral load < 1000copies/ml at baseline. At baseline, the mean FEV1 z-score was − 2.0 (0.7) with 44.7% (n = 155) having an FEV1 z-score <-2, and 10.1% had microbiological evidence of azithromycin resistance. In both trial arms, FEV1 and FVC z-scores improved by 24 weeks but appeared to decline thereafter. The adjusted overall mean difference in FEV1 z-score between the azithromycin and placebo arms was 0.004 [-0.08, 0.09] suggesting no azithromycin effect and this was similar for other lung function parameters. There was no evidence of interaction between azithromycin effect and baseline age, lung function, azithromycin resistance or HIV viral load.

Conclusion
There was no observed azithromycin effect on lung function z-scores at any time point suggesting no therapeutic effect on lung function.

Trial registration
ClinicalTrials.gov NCT02426112. First registered on 24/04/2015.