bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development of a counterselectable system for rapid and efficient CRISPR-based genome engineering in Zymomonas mobilis
Authors: Zheng Yanli , Fu Hongmei , Chen Jue , Li Jie , Bian Yuejie , Hu Ping , Lei Lei , Liu Yihan , Yang Jiangke , Peng Wenfang 
Published: October 2023

Abstract
Background
Zymomonas mobilis is an important industrial bacterium ideal for biorefinery and synthetic biology studies. High-throughput CRISPR-based genome editing technologies have been developed to enable targeted engineering of genes and hence metabolic pathways in the model ZM4 strain, expediting the exploitation of this biofuel-producing strain as a cell factory for sustainable chemicals, proteins and biofuels production. As these technologies mainly take plasmid-based strategies, their applications would be impeded due to the fact that curing of the extremely stable plasmids is laborious and inefficient. Whilst counterselection markers have been proven to be efficient for plasmid curing, hitherto only very few counterselection markers have been available for Z. mobilis.

Results
We constructed a conditional lethal mutant of the pheS gene of Z. mobilis ZM4, clmPheS, containing T263A and A318G substitutions and coding for a mutated alpha-subunit of phenylalanyl-tRNA synthetase to allow for the incorporation of a toxic analog of phenylalanine, p-chloro-phenylalanine (4-CP), into proteins, and hence leading to inhibition of cell growth. We demonstrated that expression of clmPheS driven by a strong Pgap promoter from a plasmid could render the Z. mobilis ZM4 cells sufficient sensitivity to 4-CP. The clmPheS-expressing cells were assayed to be extremely sensitive to 0.2 mM 4-CP. Subsequently, the clmPheS-assisted counterselection endowed fast curing of genome engineering plasmids immediately after obtaining the desired mutants, shortening the time of every two rounds of multiplex chromosome editing by at least 9 days, and enabled the development of a strategy for scarless modification of the native Z. mobilis ZM4 plasmids.

Conclusions
This study developed a strategy, coupling an endogenous CRISPR-based genome editing toolkit with a counterselection marker created here, for rapid and efficient multi-round multiplex editing of the chromosome, as well as scarless modification of the native plasmids, providing an improved genome engineering toolkit for Z. mobilis and an important reference to develope similar genetic manipulation systems in other non-model organisms.
Urinary biomarkers for hepatocellular carcinoma: current knowledge for clinicians
Authors: Deng Kaige , Xing Jiali , Xu Gang , Jin Bao , Wan Xueshuai , Zheng Yongchang , Du Shunda , Sang Xinting 
Published: October 2023

AbstractHepatocellular carcinoma (HCC) is the most predominant primary liver cancer, causing many illnesses and deaths worldwide. The insidious clinical presentation, difficulty in early diagnosis, and the highly malignant nature make the prognosis of HCC extremely poor. The complex and heterogeneous pathogenesis of HCC poses significant challenges to developing therapies. Urine-based biomarkers for HCC, including diagnostic, prognostic, and monitoring markers, may be valuable supplements to current tools such as serum α-fetoprotein (AFP) and seem promising for progress in precision medicine. Herein, we reviewed the major urinary biomarkers for HCC and assessed their potential for clinical application. Molecular types, testing platforms, and methods for building multimolecule models in the included studies have shown great diversity, thus providing abundant novel tools for future clinical transformation and applications.
Flexible multilevel nonvolatile biocompatible memristor with high durability
Authors: Chen Xiaoping , Zhao Xu , Huang Xiaozhong , Tang Xiu-Zhi , Sun Ziqi , Ni Da-Long , Hu Hailong , Yue Jianling 
Published: October 2023

AbstractCurrent protein or glucose based biomemristors have low resistance-switching performance and require complex structural designs, significantly hindering the development of implantable memristor devices. It is imperative to discover novel candidate materials for biomemristor with high durability and excellent biosafety for implantable health monitoring. Herein, we initially demonstrate the resistance switching characteristics of a nonvolatile memristor in a configuration of Pt/AlOOH/ITO consisting of biocompatible AlOOH nanosheets sandwiched between a Indium Tin Oxides (ITO) electrode and a platinum (Pt) counter-electrode. The hydrothermally synthesized AlOOH nanosheets have excellent biocompatibility as confirmed through the Cell Counting Kit-8 (CCK-8) tests. Four discrete resistance levels are achieved in this assembled device in responsible to different compliance currents (ICC) for the set process, where the emerging multilevel states show high durability over 103 cycles, outperforming the protein-based biomemristors under similar conditions. The excellent performance of the Pt/AlOOH/ITO memristor is attributed to the significant role of hydrogen proton with pipe effect, as confirmed by both experimental results and density functional theory (DFT) analyses. The present results indicate the nonvolatile memristors with great potential as the next generation implantable multilevel resistive memories for long-term human health monitoring.
Graphical Abstract
Low expression of PINK1 and PARK2 predicts poor prognosis in patients with esophageal squamous cell carcinoma
Authors: Lu Xiangyun , Yao Yongkun , Ma Yandi , Zhang Xudong , Peng Hao , Pei Yuhui , Lu Yulin , Wang Lianghai 
Published: October 2023

Abstract
Background
The Parkinson’s disease (PD) gene family expression is strongly linked to tumor development and progression; PINK1 and PARK2 are essential members of the PD gene family. However, the relationship between PINK1 and PARK2 and esophageal squamous cell carcinoma (ESCC) remains unknown. This research aims to clarify the prognostic value of PINK1 and PARK2 in ESCC.

Methods
PINK1 and PARK2 protein levels in 232 ESCC specimens, and 125 matched adjacent normal tissues were detected by immunohistochemistry. The relationship between PINK1 and PARK2 protein expression and clinicopathological features were analyzed. Kaplan–Meier survival analysis was performed to estimate the prognostic value of the PINK1 and PARK2 proteins in patients. Cox univariate and multivariate analyses were used to assess the risk factors affecting the OS for patients with ESCC.

Results
PINK1 and PARK2 had low expression in ESCC. Patients with low PINK1 had worse differentiation and advanced T and TNM stages. Lower PARK2 expression was linked to lymph node metastases and an advanced TNM stage. Furthermore, reduced PINK1 and PARK2 levels were associated with a poor prognosis for ESCC. Cox univariate and multivariate analyses revealed that PINK1, PARK2, and tumor size were closely associated with the prognosis of patients with ESCC, and PARK2 was an independent risk factor for patients with ESCC. Finally, the PINK1 and PARK2 proteins were closely related and shared the same signal pathway.

Conclusions
PINK1 and PARK2 could work as tumor suppressors in ESCC and are likely to become new treatment targets for ESCC.
Behaviour change techniques used in lifestyle interventions that aim to reduce cancer-related fatigue in cancer survivors: a systematic review
Authors: de Vries-ten Have Judith , Winkels Renate M. , Kampman Ellen , Winkens Laura H.H. 
Published: October 2023

Abstract
Background
Lifestyle interventions that target dietary and/or physical activity behaviours may impact cancer-related fatigue in cancer survivors. Changing lifestyle may be especially difficult for cancer survivors suffering from cancer-related fatigue. To increase effectiveness of lifestyle interventions, behaviour change techniques (BCTs) can be applied. The aim of this review is to systematically describe which BCTs are applied in lifestyle interventions targeting cancer-related fatigue among cancer survivors who finished primary treatment.

Methods
PubMed, Scopus, PsycINFO, Cochrane Library and Web of Science were searched to identify randomised controlled trials (RCTs) of dietary and/or physical activity interventions targeting cancer-related fatigue in cancer survivors. The BCT taxonomy was used to code the BCTs that were applied in those interventions. BCTs that were reported in at least 25% of effective interventions were indicated as ‘promising BCT’, but only retained this classification when these BCTs were present in less than 25% of ineffective interventions.

Results
Twenty-nine RCTs were identified, of which 17 were effective in reducing cancer-related fatigue. The most frequently applied BCTs were Goal setting (behaviour), Instruction on how to perform the behaviour, Demonstration of the behaviour, Behavioural practice/rehearsal, and Credible Source. The BCT ‘Generalisation of the target behaviour’ was identified as promising. These results should be interpreted with caution as only three studies screened their participants on level of cancer-related fatigue and most studies focused only on physical activity. Furthermore, many studies did not include a measure for actual behaviour change and had no follow-up period after the intervention ended.

Conclusions
There is a need for studies that screen their participants on level of cancer-related fatigue and a need for studies that focus more on dietary behaviours as a possible intervention to reduce fatigue. Also, studies should include follow-up timepoints after the interventions ends to examine long-term behaviour change. Future lifestyle interventions should describe interventions in detail to allow for easier coding of BCTs, and report on actual behaviour change following the intervention. Interventions may apply the BCT ‘Generalisation of the target behaviour’ to incorporate lifestyle behaviours in daily life. This may increase the chance that interventions will effectively reduce cancer-related fatigue.
Association between HMGCR, CRP, and CETP gene polymorphisms and metabolic/inflammatory serum profile in healthy adolescents
Authors: Perrone Benedetta , Ruffo Paola , Augimeri Giuseppina , Sisci Diego , Sinicropi Maria Stefania , Tripepi Giovanni , Mammì Corrado , Bonofiglio Daniela , Conforti Francesca Luisa 
Published: October 2023

Abstract
Background
The complex interplay between health, lifestyle and genetics represents a critical area of research for understanding and promoting human well-being. Importantly, genetics plays a key role in determining individual susceptibility to disease and response to lifestyle. The aim of the present study was to identify genetic factors related to the metabolic/inflammatory profile of adolescents providing new insights into the individual predisposition to the different effects of the substances from the environment.

Methods
Association analysis of genetic variants and biochemical parameters was performed in a total of 77 healthy adolescents recruited in the context of the DIMENU study.

Results
Polymorphisms of 3-hydroxy-3-methylglutaril coenzyme A reductase (HMGCR; rs142563098), C-reactive protein gene (CRP; rs1417938, rs1130864), cholesteryl ester transfer protein (CETP; rs5030708), interleukin (IL)—10 (IL-10; rs3024509) genes were significantly associated (p < 0.05) with various serum metabolic parameters. Of particular interest were also the correlations between the HMGCRpolymorphism (rs3846663) and tumor necrosis factor (TNF)-α levels, as well Fatty-acid desaturase (FADS) polymorphism (rs7481842) and IL-10 level opening a new link between lipidic metabolism genes and inflammation.

Conclusion
In this study, we highlighted associations between single nucleotide polymorphisms (SNPs) and serum levels of metabolic and inflammatory parameters in healthy young individuals, suggesting the importance of genetic profiling in the prevention and management of chronic disease.
Chronic neuroinflammation during aging leads to cholinergic neurodegeneration in the mouse medial septum
Authors: Gamage Rashmi , Rossetti Ilaria , Niedermayer Garry , Münch Gerald , Buskila Yossi , Gyengesi Erika 
Published: October 2023

Abstract
Background
Low-grade, chronic inflammation in the central nervous system characterized by glial reactivity is one of the major hallmarks for aging-related neurodegenerative diseases like Alzheimer’s disease (AD). The basal forebrain cholinergic neurons (BFCN) provide the primary source of cholinergic innervation of the human cerebral cortex and may be differentially vulnerable in various neurodegenerative diseases. However, the impact of chronic neuroinflammation on the cholinergic function is still unclear.

Methods
To gain further insight into age-related cholinergic decline, we investigated the cumulative effects of aging and chronic neuroinflammation on the structure and function of the septal cholinergic neurons in transgenic mice expressing interleukin-6 under the GFAP promoter (GFAP-IL6), which maintains a constant level of gliosis. Immunohistochemistry combined with unbiased stereology, single cell 3D morphology analysis and in vitro whole cell patch-clamp measurements were used to validate the structural and functional changes of BFCN and their microglial environment in the medial septum.

Results
Stereological estimation of MS microglia number displayed significant increase across all three age groups, while a significant decrease in cholinergic cell number in the adult and aged groups in GFAP-IL6 mice compared to control. Moreover, we observed age-dependent alterations in the electrophysiological properties of cholinergic neurons and an increased excitability profile in the adult GFAP-IL6 group due to chronic neuroinflammation. These results complimented the significant decrease in hippocampal pyramidal spine density seen with aging and neuroinflammation.

Conclusions
We provide evidence of the significant impact of both aging and chronic glial activation on the cholinergic and microglial numbers and morphology in the MS, and alterations in the passive and active electrophysiological membrane properties of septal cholinergic neurons, resulting in cholinergic dysfunction, as seen in AD. Our results indicate that aging combined with gliosis is sufficient to cause cholinergic disruptions in the brain, as seen in dementias.
Cordycepin from Cordyceps militaris ameliorates diabetic nephropathy via the miR-193b-5p/MCL-1 axis
Authors: Zheng Rong , Zhang Weijie , Song Jufang , Zhong Yifei , Zhu Rong 
Published: October 2023

Abstract
Background
Diabetic nephropathy (DN) is a chronic kidney disease that develops in patients with diabetes mellitus. Cordycepin (CRD), a secondary metabolite produced by Cordyceps militaris, has a variety of bioactive properties. In this study, DN mice and high glucose (HG)-treated HK-2 were used to evaluate the diagnostic value of CRD.

Methods
Quantitative real-time PCR (qRT-PCR), western blotting, immunofluorescence analysis, and immunohistochemical staining were used to assess changes in mRNA and protein expression. Oxidative stress was evaluated by detecting the production of reactive oxygen species (ROS) and the activity of antioxidant enzymes. Cell apoptosis was detected by the TUNEL and flow cytometric methods. The interaction of miR-193b-5p and myeloid leukemia 1 (MCL-1) was examined by bioinformatics analysis and luciferase reporter assay. The protective effects of CRD on DN mice were evaluated by examining DN related biochemical indicators and renal histopathology.

Results
In response to HG, the level of miR-193b-5p was elevated, whilst the level of MCL-1 was downregulated, and CRD therapy reversed this behavior. MCL-1 was further identified to be miR-193b-5p target. CRD attenuated HG-induced cell damage, inflammation and abnormal energy metabolism. Mechanistic investigations on in vitro models confirmed that protective effect of CRD against HG challenge to HK-2 cells is mediated through the regulation of expression of miR-193b-5p/MCL-1 axis. By examining DN related biochemical markers and renal histopathology, the protective effects of CRD on DN mice was assessed.

Conclusions
In summary, CRD decreased oxidative stress and inflammation by increasing miR-193b-5p and inactivating downstream MCL-1 in DN, hinting the pivotal values of CRD and miR-193b-5p in the management of DN.
The Tuscany Regional Network for rare diseases: from European Reference Networks’ experience to registry based organisation and management model for rare diseases
Authors: Pieroni Federica , Marrucci Sonia , Di Pietro Linda , Berni Cecilia , Scaletti Cristina 
Published: October 2023

Abstract
Background
In the European Union, a disease is defined as rare when it affects fewer than 1 in 2000 people. Currently, there are up to 8000 described rare diseases (RDs), collectively affecting 30 million people in the European Union. In 2004 Tuscany region (Italy) established a Regional Network of hospital units to ensure highly specialised medical care in the field of RDs. Shortly after the Rare Diseases Registry of Tuscany (Registro Toscano Malattie Rare—RTMR) was implemented. Here we describe the analysis performed on RTMR data which has recently allowed to remap the Network based on European Reference Networks’ model.

Results
Data analysis was performed on 60,367 cases registered in RTMR, regarding 628 RDs. Two-hundred and fifteen active presidia have been evaluated. The assignment of each RD to the suitable European Reference Network has been made considering not only the number of registered cases, certifications and treatment plans for each Regional Presidium but also the competence in multidisciplinary management of the patient, from diagnosis to treatment. This evaluation has led to the establishment of twenty-one Regional Coordination Centres. They aggregate and coordinate Hospital Units which diagnose and treat one or a group of related RDs. In case of wide groups of RDs, Clinical Subnets are instituted. Updated statistics regarding RDs in Tuscany, list of RDs and Coordination Centres, as well as information about single Presidia are published and freely available on a designated webpage. Regional Decrees are regularly updated according to the network evolution.

Conclusions
The Rare Diseases Regional Network in Tuscany, based on the ERN model, has played a pivotal role in enhancing RD management and research. The remapping has led to a dynamic system, following not only scientific research but also the development of Presidia’s expertise. By pooling resources and expertise, the network has improved the availability and accessibility of specialized care for patients with RDs. Collaborative efforts, data sharing, and standardized registries are crucial for advancing RD research, improving diagnosis and treatment, and ultimately enhancing the quality of life for individuals living with RDs.
Assessing the quality of the care offer for people with personality disorders in Italy: the QUADIM project. A multicentre research based on the database of use of Mental Health services
Authors: Sanza Michele , Monzio Compagnoni Matteo , Caggiu Giulia , Allevi Liliana , Barbato Angelo , Campa Jeannette , Carle Flavia , D’avanzo Barbara , Di Fiandra Teresa , Ferrara Lucia , Gaddini Andrea , Saponaro Alessio , Scondotto Salvatore , Tozzi Valeria D , Lorusso Stefano , Giordani Cristina , Corrao Giovanni , Lora Antonio 
Published: October 2023

Abstract
Background
Italy can be viewed as a laboratory to assess the quality of mental healthcare delivered in a community-oriented system, especially for severe mental disorders, such as personality disorders. Although initiatives based on clinical indicators for assessing the quality of mental healthcare have been developed by transnational-organisations, there is still no widespread practice of measuring the quality of care pathways delivered to patients with severe mental disorders in a community-oriented system, especially using administrative healthcare databases. The aim of the study is to evaluate the quality of care delivered to patients with personality disorders taken-in-care by mental health services of four Italian regions (Lombardy, Emilia-Romagna, Lazio, Sicily).

Methods
A set of thirty-three clinical indicators, concerning accessibility, appropriateness, continuity, and safety of care, was implemented using regional healthcare utilization databases, containing data on mental health treatments and diagnosis, hospital admissions, outpatient interventions and exams and drug prescriptions.

RESULTS
31,688 prevalent patients with personality disorders treated in 2015 were identified, of whom 2,331 newly taken-in-care. One-in-10 patients received a standardized assessment, the treatment discontinuity affected half of the cases. 12.7% of prevalent patients received at least one hospitalization, 10.6% in the newly taken-in-care cohort. 6-out-of-10 patients had contact with community-services within 14 days from hospital discharge. Access to psychotherapy and psychoeducational treatments was low and delivered with a low intensity. The median of psychosocial interventions per person-year was 19.1 and 9.4, respectively, in prevalent and newly taken-in-care cases. Nearly 50% of patients received pharmacological treatments.

Conclusions
Healthcare utilization databases were used to systematically evaluate and assess service delivery across regional mental health systems; suggesting that in Italy the public mental health services provide to individuals with personality disorders suboptimal treatment paths.
Factors affecting cumulative live birth rate after the 1st oocyte retrieved in polycystic ovary syndrome patients in women during IVF/ICSI-ET
Authors: Li You , Xia Leizhen , Li Zengming , Zhang Ziyu , Jiang Ru 
Published: October 2023

Abstract
Background
The factors affecting the cumulative live birth rate (CLBR) of PCOS (Polycystic ovary syndrom) patients who received in vitro fertilization/intracytoplasmic sperm injection-embryo transfer (IVF/ICSI-ET) needs more research for a better outcome.

Methods
Here we carried out a retrospective analysis of 1380 PCOS patients who received IVF/ICSI-ET for the first time from January 2014 to December 2016. We divided them into cumulative live birth group (group A) and non-cumulative live birth group (group B) according to whether there were live births.

Results
The conservative cumulative live birth rate was 63.48%. There were 876 cumulative live births (group A) and 504 non-cumulative live births (group B) according to whether the patients had live births or not. Competition analysis showed that duration of infertility, primary/secondary type of infertility, stimulation protocols, starting dose of gonadotrophins and oocyte retrieved numbers were significantly correlated with CLBR. The Cox proportional risk regression model of PCOS patients showed that stimulation protocols had a significant impact on CLBR. Patients in the GnRH (Gonadotropin-releasing hormone)-antagonist protocol group and the mild stimulation protocol had lower CLBR than those in the prolonged GnRH-agonist protocol, which was statistically significant. PCOS patients with the starting dose of gonadotrophins greater than 112.5u had lower CLBR than those with less than 100u, which was statistically significant. Women with 11–15 oocytes and 16–20 oocytes had higher CLBR than women with 1–9 oocytes, which was statistically significant.

Conclusions
When we used Prolonged GnRH-agonist protocol, or the first starting dose of gonadotrophins was 100u-112.5u, or the number of oocytes obtained was 11–15 and 16–20, the CLBR of PCOS patients increased significantly after the 1st oocyte collection.