bluuebunny/crossref_metadata_2025_split huggingface dataset:
Risk factors and a nomogram model for postoperative delirium in elderly gastric cancer patients after laparoscopic gastrectomy
Authors: Chen Jie , Ji Xiaoli , Xing Hailin 
Published: September 2022

Abstract
Background
To evaluate the risk factors of postoperative delirium (POD) in elderly gastric cancer (GC) patients after laparoscopic gastrectomy and construct a predictive model.

Methods
Elderly GC patients undergoing laparoscopic gastrectomy were enrolled and grouped based on the status of POD development within postoperative 7 days. Independent risk factors were selected out by univariate and multivariate logistic regression analyses and then enrolled in the nomogram prediction model.

Results
A total of 270 elderly GC patients were enrolled, and POD occurred in 74 (27.4%) patients within postoperative 7 days. The results of multivariate regression analysis indicated that age (OR: 3.30, 95% CI: 1.41–6.85, P < 0.001), sleeping pills (OR: 1.87, 95% CI: 1.12–3.09, P = 0.012), duration of ICU stay (OR: 1.55, 95% CI: 1.02–2.37, P = 0.029), albumin/fibrinogen ratio (AFR) (OR: 1.74, 95% CI: 1.03–2.76, P = 0.019), and neutrophils/lymphocytes ratio (NLR) (OR: 2.12, 95% CI: 1.11–4.01, P = 0.016) were five independent risk factors for POD in elderly GC patients. The AUC of the constructed nomogram model based on these five factors was 0.807.

Conclusions
This study highlighted that age, AFR, NLR, sleeping pills taking, and duration of ICU stay were independent risk factors for POD, and the nomogram model based on these factors could effectively predict POD in elderly GC patients.
Assessing the causal association between human blood metabolites and the risk of epilepsy
Authors: Cai Jiahao , Li Xiaoyu , Wu Shangbin , Tian Yang , Zhang Yani , Wei Zixin , Jin Zixiang , Li Xiaojing , Chen Xiong , Chen Wen-Xiong 
Published: September 2022

Abstract
Background
Metabolic disturbance has been reported in patients with epilepsy. Still, the evidence about the causal role of metabolites in facilitating or preventing epilepsy is lacking. Systematically investigating the causality between blood metabolites and epilepsy would help provide novel targets for epilepsy screening and prevention.

Methods
We conducted two-sample Mendelian randomization (MR) analysis. Data for 486 human blood metabolites came from a genome-wide association study (GWAS) comprising 7824 participants. GWAS data for epilepsy were obtained from the International League Against Epilepsy (ILAE) consortium for primary analysis and the FinnGen consortium for replication and meta-analysis. Sensitivity analyses were conducted to evaluate heterogeneity and pleiotropy.

Results
482 out of 486 metabolites were included for MR analysis following rigorous genetic variants selection. After IVW and sensitivity analysis filtration, six metabolites with causal effects on epilepsy were identified from the ILAE consortium. Only four metabolites remained significant associations with epilepsy when combined with the FinnGen consortium [uridine: odds ratio (OR) = 2.34, 95% confidence interval (CI) = 1.48–3.71, P = 0.0003; 2-hydroxystearate: OR = 1.61, 95% CI = 1.19–2.18, P = 0.002; decanoylcarnitine: OR = 0.82, 95% CI = 0.72–0.94, P = 0.004; myo-inositol: OR = 0.77, 95% CI = 0.62–0.96, P = 0.02].

Conclusion
The evidence that the four metabolites mentioned above are associated with epilepsy in a causal way provides a novel insight into the underlying mechanisms of epilepsy by integrating genomics with metabolism, and has an implication for epilepsy screening and prevention.
A genetic map of the chromatin regulators to drug response in cancer cells
Authors: Chen Bo , Li Pengfei , Liu Mingyue , Liu Kaidong , Zou Min , Geng Yiding , Zhuang Shuping , Xu Huanhuan , Wang Linzhu , Chen Tingting , Li Yawei , Zhao Zhangxiang , Qi Lishuang , Gu Yunyan 
Published: September 2022

Abstract
Background
Diverse drug vulnerabilities owing to the Chromatin regulators (CRs) genetic interaction across various cancers, but the identification of CRs genetic interaction remains challenging.

Methods
In order to provide a global view of the CRs genetic interaction in cancer cells, we developed a method to identify potential drug response-related CRs genetic interactions for specific cancer types by integrating the screen of CRISPR-Cas9 and pharmacogenomic response datasets.

Results
Totally, 625 drug response-related CRs synthetic lethality (CSL) interactions and 288 CRs synthetic viability (CSV) interactions were detected. Systematically network analysis presented CRs genetic interactions have biological function relationship. Furthermore, we validated CRs genetic interactions induce multiple omics deregulation in The Cancer Genome Atlas. We revealed the colon adenocarcinoma patients (COAD) with mutations of a CRs set (EP300, MSH6, NSD2 and TRRAP) mediate a better survival with low expression of MAP2 and could benefit from taxnes. While the COAD patients carrying at least one of the CSV interactions in Vorinostat CSV module confer a poor prognosis and may be resistant to Vorinostat treatment.

Conclusions
The CRs genetic interaction map provides a rich resource to investigate cancer-associated CRs genetic interaction and proposes a powerful strategy of biomarker discovery to guide the rational use of agents in cancer therapy.
Determinants of mother to child HIV transmission (HIV MTCT); a case control study in governmental health centers of East Gojjam Zone, Northwest Ethiopia, 2019
Authors: Tariku Mengistie Kassahun 
Published: September 2022

Abstract
Background
Mother to child human immune virus (HIV) transmission is the passage of HIV from mother to her child during pregnancy, labor, delivery or breast-feeding. The objective of this study was to identify determinants of mother to child HIV transmission among HIV exposed infants who were born from HIV positive mothers at Governmental health centers of East Gojjam Zone, Northwestern Ethiopia, 2019.

Methods
A case–control study was conducted on 210(42 cases and 168 controls) from April 1 to 30/ 2019. All cases were included in the study. Controls were selected by simple random sampling. Secondary data were extracted by using checklists from the document of 8 health centers ART register book, antenatal care (ANC) follow up register book, PMTCT service registration log book charts and infant dried blood sample (DBS) tally sheets. After Bivariable logistic regression analysis, all variables with p-value $$\le$$
≤
0.25 were entered into multivariable logistic regression and p value < 0.05 considered as significantly associated with the outcome variable.

Results
HIV exposed infants who were being rural dweller versus (vs) those infants who were being urban dweller [adjusted odds ratio (AOR) = 3.73; 95% CI; 1.27–10.69], have no history of antenatal care follow up of HIV exposed infants’ HIV positive mothers versus (vs) those mothers who have been having history of ANC follow up [ AOR = 5.0;95%CI; 2.02–12.16] and initial CD4 count of HIV infants’ mothers $$\le 350$$

≤
350

vs those mothers whose CD4 > 350 [AOR = 2.7;95%CI;1.35–5.52] were significantly associated with HIV infection.

Conclusion
Mother to child HIV transmission was significantly associated with history of ANC follow up of exposed infants’ mothers and initial CD4 counts of mothers. Strong effort should be made to further increase the ANC service utilization of HIV positive pregnant women.
Cardiovascular disease, self-care and emotional regulation processes in adult patients: balancing unmet needs and quality of life
Authors: Cilli Eleonora , Ranieri Jessica , Guerra Federica , Ferri Claudio , Di Giacomo Dina 
Published: September 2022

Abstract
Background
Cardiovascular disease is a chronic non-communicable illness that causes more than half of all deaths across Europe. Unhealthy lifestyle, inadequate adherence to medical prescriptions, themselves associated with psycho-emotional disorders are considered risk factors for reduced quality of life as well physical condition.

Objective
Aim of our study was to understand predictive factors for disease management by evaluating psychological aspects, self-care processes and emotional regilati0on in CVD outpatients.

Methods
An observational study was conducted. Sixty-one patients, age 18–75 years (M 56.4 ± sd 12.0), diagnosed with CVD participated in the study. The psychological battery was administered during clinical follow-up oriented to detect emotional and psychological dimensions as well adaptive behavioral and quality of life by standardized questionnaire/scales.

Results
Finding showed that emotional dysregulation might influence QoL, particularly significant effect of awareness (β= 0.022; SE = 1.826; p < 0.002), goals (β = - 0.54; SE = 1.48; p < 0.001) and clarity (β = - 0.211; SE = 2.087; p < 0.003). The results also suggest that the mediated effect accounted for awareness index was 18.7% (R2 = 0.187) of the variance; goals index 62.8% (R2 = 0.628) of the variance and, then significant mediated effect of clarity was 58.8% (R2 = 0.588) of the variance. This evidence suggests that the relationship between triggers and QoL is mediated by emotional dysregulation indexes.

Conclusion
In clinical practice psychological screening can be an effective tool for detecting predictive factors in the management of the CVD patient's health and adherence to medical treatment: the screening of predictive psychological factors for allowing a good clinical condition management and a self-care empowerment aimed at increasing psychological well-being and the Quality of Life by planning adequate integrated and multidisciplinary support.
SOULMATE: the Swedish study of liver transplantation for isolated colorectal cancer liver metastases not suitable for operation or ablation, compared to best established treatment—a randomized controlled multicenter trial
Authors: Reivell Veronica , Hagman Helga , Haux Johan , Jorns Carl , Lindnér Per , Taflin Helena 
Published: September 2022

Abstract
Background
Around one fourth of patients with colorectal cancer present themselves with distant metastases at the time of diagnosis, and one additional one fifth of the patients will develop distant metastases during the disease, most commonly in the liver.
Surgical treatment such as liver resection or ablation, often combined with chemotherapy and targeted therapy, is the only treatment option with curative potential, but only about 20% of the patients with liver metastases are candidates for surgical intervention. Standard treatment for unresectable patients is palliative oncological therapy; however, less than 10% of these patients will achieve a 5-year survival.
Non-randomized studies indicate that liver transplantation could be an option for selected patients with colorectal liver metastases (CRLM), which are not suitable for operation or ablation due to surgical technical reasons such as massive tumor burden and small future liver remnant, or oncological reasons, for example, early relapse after liver surgery. Since there is a shortage of donated liver grafts, it is important to select the patient group that benefit most from the treatment. Although some studies present positive results from liver transplantation of CRLM, the results must be validated in a randomized controlled trial before this new indication for liver transplantation can be introduced as a clinical routine.

Methods
The SOULMATE study is a randomized study evaluating if liver transplantation with liver grafts, primarily from extended criteria donors, increases overall survival in patients with CRLM, not suitable for resection or ablation, in comparison with best established treatment.
Patients will be randomized to liver transplantation (LT)+ best established treatment (BET) or to best established treatment only.
In the SOULMATE trial, we will evaluate the use of livers from extended criteria donors to decrease the risk of prolonging waiting time for patients on the waiting list for LT.

Discussion
The SOULMATE study has the possibility to confirm the positive results of previous studies in a randomized setting. The use of extended criteria donors will make the results transferable globally, as most countries are struggling with organ shortage.

Trial registration
Clinical Trial number: NCT04161092 registered 13 November 2019.
Construction and yield optimization of a cinnamylamine biosynthesis route in Escherichia coli
Authors: Wang Qi , Ma Linlin , Wang Zhiguo , Chen Quan , Wang Qian , Qi Qingsheng 
Published: September 2022

Abstract
Background
With the development of metabolic engineering and synthetic biology, the biosynthesis of aromatic compounds has attracted much attention. Cinnamylamine is an aromatic compound derived from l-phenylalanine, which is used in the synthesis of biologically active molecules, including drugs, and energetic materials. Cinnamylamine has been mainly synthesized by chemical methods to date, and few reports have focused on the biosynthesis of cinnamylamine. Therefore, it is desirable to establish an efficient biosynthesis method for cinnamylamine.

Results
The ω-aminotransferase Cv-ωTA from Chromobacterium violaceum has been demonstrated to have high enzyme activity in the conversion of cinnamaldehyde to cinnamylamine. To prevent the preferable conversion of cinnamaldehyde to cinnamyl alcohol in wild-type Escherichia coli, the E. coli MG1655 strain with reduced aromatic aldehyde reduction (RARE) in which six aldehyde ketone reductase and alcohol dehydrogenase genes have been knocked out was employed. Then, the carboxylic acid reductase from Neurospora crassa (NcCAR) and phosphopantetheinyl transferase (PPTase) from E. coli were screened for a high conversion rate of cinnamic acid to cinnamaldehyde. To shift the equilibrium of the reaction toward cinnamylamine, saturation mutagenesis of Cv-ωTA at key amino acid residues was performed, and Cv-ωTA Y168G had the highest conversion rate with 88.56 mg/L cinnamylamine obtained after 4 h of fermentation. Finally, by optimizing the substrates and the supply of the cofactors, PLP and NADPH, in the fermentation, the yield of cinnamylamine in engineered E. coli reached 523.15 mg/L.

Conclusion
We achieved the first biosynthesis of cinnamylamine using cinnamic acid as the precursor in E. coli using a combinatorial metabolic engineering strategy. This study provides a reference for the biosynthesis of other amine compounds and lays a foundation for the de novo synthesis of cinnamylamine.
Medullary sponge kidney: unusual finding in kidney transplant recipient
Authors: Righini M. , Felicani C. , Lopez A. , Mazzotta E. , De Molo C. , Mancini E. , Capelli I. , Serra C. , La Manna G. 
Published: September 2022

Abstract
Background
Medullary sponge kidney is generally considered a benign condition, gold standard for the diagnosis is urography but it has almost been replaced by UroCT that did not present the same sensibility. Although it is really rare, our sonography’s findings were consistent with medullary sponge kidney in the transplanted kidneys.

Case presentation
A 45-year-old woman with a long history of double-kidney transplantation complained of frequent urinary tract infections, a history of vague loin pain and came to our attention for sonography follow-up. Her kidney function was normal, we did not find signs of infections in the transplanted kidneys and urinary findings were normal. Curiously, the transplanted kidneys came from a newborn and the patient received a double-kidney transplantation in order to guarantee a satisfactory renal function.

Conclusions
Despite a long history of kidney transplantation, genetic disease should not be forgotten when symptoms and images recall to specific inherited alterations. Sonography has to be considered in diagnostic path of kidney cystic disease.
A blood DNA methylation biomarker for predicting short-term risk of cardiovascular events
Authors: Cappozzo Andrea , McCrory Cathal , Robinson Oliver , Freni Sterrantino Anna , Sacerdote Carlotta , Krogh Vittorio , Panico Salvatore , Tumino Rosario , Iacoviello Licia , Ricceri Fulvio , Sieri Sabina , Chiodini Paolo , McKay Gareth J. , McKnight Amy Jayne , Kee Frank , Young Ian S. , McGuinness Bernadette , Crimmins Eileen M. , Arpawong Thalida Em , Kenny Rose Anne , O’Halloran Aisling , Polidoro Silvia , Solinas Giuliana , Vineis Paolo , Ieva Francesca , Fiorito Giovanni 
Published: September 2022

AbstractBackgroundRecent evidence highlights the epidemiological value of blood DNA methylation (DNAm) as surrogate biomarker for exposure to risk factors for non-communicable diseases (NCD). DNAm surrogate of exposures predicts diseases and longevity better than self-reported or measured exposures in many cases. Consequently, disease prediction models based on blood DNAm surrogates may outperform current state-of-the-art prediction models. This study aims to develop novel DNAm surrogates for cardiovascular diseases (CVD) risk factors and develop a composite biomarker predictive of CVD risk. We compared the prediction performance of our newly developed risk score with the state-of-the-art DNAm risk scores for cardiovascular diseases, the ‘next-generation’ epigenetic clock DNAmGrimAge, and the prediction model based on traditional risk factors SCORE2.ResultsUsing data from the EPIC Italy cohort, we derived novel DNAm surrogates for BMI, blood pressure, fasting glucose and insulin, cholesterol, triglycerides, and coagulation biomarkers. We validated them in four independent data sets from Europe and the USA. Further, we derived aDNAmCVDscorepredictive of the time-to-CVD event as a combination of several DNAm surrogates. ROC curve analyses show thatDNAmCVDscoreoutperforms previously developed DNAm scores for CVD risk and SCORE2 for short-term CVD risk. Interestingly, the performance of DNAmGrimAge andDNAmCVDscorewas comparable (slightly lower for DNAmGrimAge, although the differences were not statistically significant).ConclusionsWe described novel DNAm surrogates for CVD risk factors useful for future molecular epidemiology research, and we described a blood DNAm-based composite biomarker,DNAmCVDscore, predictive of short-term cardiovascular events. Our results highlight the usefulness of DNAm surrogate biomarkers of risk factors in epigenetic epidemiology to identify high-risk populations. In addition, we provide further evidence on the effectiveness of prediction models based on DNAm surrogates and discuss methodological aspects for further improvements. Finally, our results encourage testing this approach for other NCD diseases by training and developing DNAm surrogates for disease-specific risk factors and exposures.
miR-146a-5p-modified hUCMSC-derived exosomes facilitate spinal cord function recovery by targeting neurotoxic astrocytes
Authors: Lai Xunwei , Wang Yang , wang Xiaokang , Liu Bin , Rong Limin 
Published: September 2022

Abstract
Background
Acute spinal cord injury (SCI) is a devastating result of neurological trauma with subsequent microenvironment dyshomeostasis that induces neurotoxic phenotype acquisition by astrocytes, exacerbating neurological function impairment. Exosomes derived from human umbilical cord mesenchymal stem cells (hUCMSCs) have demonstrated essential therapeutic effects after central nervous system trauma. However, whether hUCMSC-derived exosomes exert therapeutic effects on neurotoxic astrocytes to facilitate SCI function recovery remains unclear. Additionally, the limited efficiency of single exosomes may restrict the optimization of exosomal biological functions.

Methods
We first determined that exosomes reduce the deleterious effects of neurotoxic astrocytes in vitro and in vivo. Then, we identified critical functional microRNAs (miRNAs). miR-146a-5p was overexpressed in exosomes, and then, miR-146a-5p-modified exosomes were used to investigate the ability of exosomes to reduce neurotoxic astrocyte effects, preserve neurons and promote neurological function recovery in rats with SCI.

Results
Cell counting kit-8 and neurite length analyses revealed that exosomes partially reduced the negative effects of neurotoxic astrocytes on PC12 cell viability and neurites in vitro. The exosomes also attenuated inflammatory responses, reduced the number of neurotoxic astrocytes and preserved neural tissue in rats with SCI. Immunofluorescence assays suggested that the number of neurotoxic astrocytes was rapidly increased by injury, reaching a peak 5 days post-injury (dpi) and returning to the normal level 14dpi. Exosomal miR-146a-5p was identified as the critical functional miRNA. Overexpression of miR-146a-5p in exosomes strengthened the biological function of the exosomes. Therefore, the modified exosomes exerted more powerful therapeutic effects than the unmodified exosomes, reducing the deleterious effects of neurotoxic astrocytes both in vitro and in vivo and promoting locomotor function of the hindlimbs in the rats with SCI. Through a series of gain- and loss-of-function experiments, Traf6 and Irak1 were identified as targets of exosomal miR-146a-5p. Ultimately, we found that miR-146a-5p-modified exosomes exerted their function by targeting Traf6/Irak1/NFκB pathway in neurotoxic astrocytes.

Conclusions
In summary, miR-146a-5p-modified exosomes exerted a more powerful effect than unmodified exosomes to promote neurological function recovery in rats with SCI by targeting neurotoxic astrocytes. Therefore, miR-146a-5p-modified exosomes are promising therapeutics for SCI.
Gestational hypoxia in late pregnancy differentially programs subcortical brain maturation in male and female rat offspring
Authors: Wilson E. Nicole , Mabry Steve , Bradshaw Jessica L. , Gardner Jennifer J. , Rybalchenko Nataliya , Engelland Rachel , Fadeyibi Oluwadarasimi , Osikoya Oluwatobiloba , Cushen Spencer C. , Goulopoulou Styliani , Cunningham Rebecca L. 
Published: September 2022

Abstract
Background
Hypoxia is associated with pregnancy complications, such as preeclampsia, placental abruption, and gestational sleep apnea. Hypoxic insults during gestation can impact the brain maturation of cortical and subcortical pathways, such as the nigrostriatal pathway. However, the long-term effects of in utero hypoxic stress exposure on brain maturation in offspring are unclear, especially exposure during late gestation. The purpose of this study was to determine the impact of gestational hypoxia in late pregnancy on developmental programming of subcortical brain maturation by focusing on the nigrostriatal pathway.

Methods
Timed pregnant Long–Evans rats were exposed to chronic intermittent hypoxia or room air normoxia from gestational day (GD) 15–19 (term 22–23 days). Male and female offspring were assessed during two critical periods: puberty from postnatal day (PND) 40–45 or young adulthood (PND 60–65). Brain maturation was quantified by examining (1) the structural development of the nigrostriatal pathway via analysis of locomotor behaviors and the substantia nigra dopaminergic neuronal cell bodies and (2) the refinement of the nigrostriatal pathway by quantifying ultrasonic vocalizations (USVs).

Results
The major findings of this study are gestational hypoxia has age- and sex-dependent effects on subcortical brain maturation in offspring by adversely impacting the refinement of the nigrostriatal pathway in the absence of any effects on the structural development of the pathway. During puberty, female offspring were impacted more than male offspring, as evidenced by decreased USV call frequency, chirp USV call duration, and simple call frequency. In contrast, male offspring were impacted more than female offspring during young adulthood, as evidenced by increased latency to first USV, decreased simple USV call intensity, and increased harmonic USV call bandwidth. No effects of gestational hypoxia on the structural development of the nigrostriatal pathway were observed.

Conclusions
These novel findings demonstrate hypoxic insults during pregnancy mediate developmental programming of the cortical and subcortical pathways, in which male offspring exhibit long-term adverse effects compared to female offspring. Impairment of cortical and subcortical pathways maturation, such as the nigrostriatal pathway, may increase risk for neuropsychiatric disorders (e.g., mood disorders, cognitive dysfunction, brain connectivity dysfunction).