bluuebunny/crossref_metadata_2025_split huggingface dataset:
The FGF/FGFR system in the microglial neuroinflammation with Borrelia burgdorferi: likely intersectionality with other neurological conditions
Authors: Parthasarathy Geetha , Pattison Melissa B. , Midkiff Cecily C. 
Published: January 2023

Abstract
Background
Lyme neuroborreliosis, caused by the bacterium Borrelia burgdorferi affects both the central and peripheral nervous systems (CNS, PNS). The CNS manifestations, especially at later stages, can mimic/cause many other neurological conditions including psychiatric disorders, dementia, and others, with a likely neuroinflammatory basis. The pathogenic mechanisms associated with Lyme neuroborreliosis, however, are not fully understood.

Methods
In this study, using cultures of primary rhesus microglia, we explored the roles of several fibroblast growth factor receptors (FGFRs) and fibroblast growth factors (FGFs) in neuroinflammation associated with live B. burgdorferi exposure. FGFR specific siRNA and inhibitors, custom antibody arrays, ELISAs, immunofluorescence and microscopy were used to comprehensively analyze the roles of these molecules in microglial neuroinflammation due to B. burgdorferi.

Results
FGFR1-3 expressions were upregulated in microglia in response to B. burgdorferi. Inhibition of FGFR 1, 2 and 3 signaling using siRNA and three different inhibitors showed that FGFR signaling is proinflammatory in response to the Lyme disease bacterium. FGFR1 activation also contributed to non-viable B. burgdorferi mediated neuroinflammation. Analysis of the B. burgdorferi conditioned microglial medium by a custom antibody array showed that several FGFs are induced by the live bacterium including FGF6, FGF10 and FGF12, which in turn induce IL-6 and/or CXCL8, indicating a proinflammatory nature. To our knowledge, this is also the first-ever described role for FGF6 and FGF12 in CNS neuroinflammation. FGF23 upregulation, in addition, was observed in response to the Lyme disease bacterium. B. burgdorferi exposure also downregulated many FGFs including FGF 5, 7, 9, 11, 13, 16, 20 and 21. Some of the upregulated FGFs have been implicated in major depressive disorder (MDD) or dementia development, while the downregulated ones have been demonstrated to have protective roles in epilepsy, Parkinson’s disease, Alzheimer’s disease, spinal cord injury, blood–brain barrier stability, and others.

Conclusions
In this study we show that FGFRs and FGFs are novel inducers of inflammatory mediators in Lyme neuroborreliosis. It is likely that an unresolved, long-term (neuro)-Lyme infection can contribute to the development of other neurologic conditions in susceptible individuals either by augmenting pathogenic FGFs or by suppressing ameliorative FGFs or both.
Development of an assay system for the analysis of host RISC activity in the presence of a potyvirus RNA silencing suppressor, HC-Pro
Authors: Hong Syuan-Fei , Fang Ru-Ying , Wei Wei-Lun , Jirawitchalert Supidcha , Pan Zhao-Jun , Hung Yu-Ling , Pham Thanh Ha , Chiu Yen-Hsin , Shen Tang-Long , Huang Chien-Kang , Lin Shih-Shun 
Published: January 2023

Abstract
Background
To investigate the mechanism of RNA silencing suppression, the genetic transformation of viral suppressors of RNA silencing (VSRs) in Arabidopsis integrates ectopic VSR expression at steady state, which overcomes the VSR variations caused by different virus infections or limitations of host range. Moreover, identifying the insertion of the transgenic VSR gene is necessary to establish a model transgenic plant for the functional study of VSR.

Methods
Developing an endogenous AGO1-based in vitro RNA-inducing silencing complex (RISC) assay prompts further investigation into VSR-mediated suppression. Three P1/HC-Pro plants from turnip mosaic virus (TuMV) (P1/HC-ProTu), zucchini yellow mosaic virus (ZYMV) (P1/HC-ProZy), and tobacco etch virus (TEV) (P1/HC-ProTe) were identified by T-DNA Finder and used as materials for investigations of the RISC cleavage efficiency.

Results
Our results indicated that the P1/HC-ProTu plant has slightly lower RISC activity than P1/HC-ProZy plants. In addition, the phenomena are consistent with those observed in TuMV-infected Arabidopsis plants, which implies that HC-ProTu could directly interfere with RISC activity.

Conclusions
In this study, we demonstrated the application of various plant materials in an in vitro RISC assay of VSR-mediated RNA silencing suppression.
Achieving long-term goals through early personalized management of schizophrenia: expert opinion on the role of a new fast-onset long-acting injectable antipsychotic
Authors: Vita Antonio , Fagiolini Andrea , Maina Giuseppe , Mencacci Claudio , Spina Edoardo , Galderisi Silvana 
Published: January 2023

AbstractDefinition of an appropriate and personalized treatment plan focused on long-term outcomes is crucial in the management of schizophrenia. Following review of the literature, a panel of six leading psychiatrists discussed the importance of clear and shared long-term goals when initiating antipsychotic treatment in light of their clinical experience. The importance of establishing shared and progressive treatment objectives was stressed, which should be tailored based on the patient’s characteristics, goals, and preferences. Consensus emerged on the key role that therapeutic alliance and patient empowerment play throughout the course of treatment. Reduction in symptoms in the acute phase along with good efficacy and tolerability in the maintenance phase emerged as essential features of a therapy that can favor achievement of long-term outcomes. Long-acting injectable (LAI) antipsychotics enhance adherence to treatment compared to oral formulations and have been shown to be effective in the maintenance phase. Currently available LAIs are characterized by a delayed onset of action and require a loading dose or oral supplementation to achieve therapeutic concentrations. Risperidone ISM® is a novel LAI antipsychotic with fast and sustained release of antipsychotic, reaching therapeutic plasma levels within a few hours after administration without oral supplementation or loading doses. Risperidone ISM® has been shown to rapidly control symptoms in patients with an acute exacerbation of schizophrenia and to be effective and well tolerated as maintenance treatment irrespective of the severity of initial symptoms. It thus represents a valuable and novel therapeutic option in management of schizophrenia.
Circular RNA hsa_circ_0075323 promotes glioblastoma cells proliferation and invasion via regulation of autophagy
Authors: Zhang Wenrui , Shi Zhonggang , Chen Shouren , Shen Shaoshan , Tu Songjie , Yang Jian , Qiu Yongming , Lin Yingying , Dai Xuejun 
Published: January 2023

Abstract
Background
Protein p62 (sequestosome 1) encoded by gene SQSTM1 plays a vital role in mediating protectively selective autophagy in tumor cells under stressed conditions. CircSQSTM1 (hsa_circ_0075323) is a circular transcript generated from gene SQSTM1 (chr5:179260586–179260782) by back-splicing. However, the potential role of hsa_hsa_circ_0075323 in glioblastoma (GBM) remains unclear. Here, we aimed to explore the biological function of hsa_circ_0075323 in GBM and its relationship with autophagy regulation.

Results
Hsa_circ_0075323 is highly expressed in GBM cells and mainly locates in the cytoplasm. Inhibition of hsa_circ_0075323 in U87-MG and T98G cells attenuated proliferation and invasion ability significantly, while upregulation of has_ circ_0075323 enhanced proliferation and migration of U251-MG and A172 cells. Mechanistically, depletion of hsa_circ_0075323 in GBM cells resulted in impaired autophagy, as indicated by increased expression of p62 and decreased expression of LC3B.

Conclusions
Hsa_circ_0075323 regulates p62-mediated autophagy pathway to promote GBM progression and may serve as a prognostic biomarker potentially.
Clinical outcomes of a novel porcine small intestinal submucosa patch for full-thickness hand skin defects: a retrospective investigation
Authors: Zang Chengwu , Xian Hang , Zhang Hang , Che Min , Chen Yongxiang , Zhang Fanliang , Cong Rui 
Published: January 2023

Abstract
Objective
To investigate the clinical outcomes of a novel soft tissue repair patch (porcine small intestinal submucosa patch, SIS patch) in the treatment of full-thickness hand skin defects.

Methods
From January 2017 to July 2019, 80 patients with hand soft tissue defects, who met the inclusion criteria, were retrospectively reviewed and divided into two groups. After debridement, patients in group A were treated with the novel SIS patch to cover the wound, and patients in group B were treated with autologous skin graft. The dimensions of skin defect area and healing outcome were evaluated and recorded. Scar assessment was carried out using Scar Cosmesis Assessment and Rating Scale (SCAR scale) at the last follow-up postoperation, and the recovery of wound sensation was assessed at the same time using British Medical Research Council (BMRC) grading of sensorimotor recovery. All the data were collected and statistically analyzed.

Results
A total of 80 patients were enrolled in the study with 40 patients in each group. Four patients in group A and 5 patients in group B were excluded due to wound infection and lost to follow-up. There were 36 patients in group A and 35 patients in group B finally got follow-up postoperation with mean interval of 12.75 ± 5.61 months in group A and 14.11 ± 5.42 months in group B. The dimensions of skin defect area in group A ranged from 7.5 to 87.5 cm2 (mean 25.97 ± 18.66 cm2) and in group B ranged from 7.5 to 86.25 cm2 (mean 33.61 ± 19.27 cm2) which have no significant difference (P > 0.05). SCAR scale results of group A and group B were 10.98 ± 0.33 and 9.49 ± 0.35, respectively, and the difference was statistically significant (P < 0.05). BMRC grading results showed 6 cases of S4, 11 cases of S3+, 5 cases of S3, 6 cases of S2, 6 cases of S1 and 2 cases of S0 in group A, and 8 cases of S4, 10 cases of S3+, 7 cases of S3, 4 cases of S2, 5 cases of S1, and 1 case of S0 in group B, which had no significant difference between them (P > 0.05).

Conclusions
The novel SIS patch is an applicable biological material in the treatment of hand skin defect, which could achieve a better cosmetic appearance of the newborn skin tissue.
Study of the accuracy of a radial arterial pressure waveform cardiac output measurement device after cardiac surgery
Authors: Ordoñez-Rufat Pilar , Mancho-Fora Nuria , Tebe-Cordomi Cristian , Polit-Martinez Victoria , Abellan-Lencina Ricardo , Fernandez-Alvarez Joaquin , Lopez-Delgado Juan Carlos 
Published: January 2023

Abstract
Background
Less invasive monitoring, such as radial arterial pulse contour analysis (ProAQT® sensor), represents an alternative when hemodynamic monitoring is necessary to guide postoperative management and invasive monitoring is not technically feasible. The aim of the study is to evaluate the accuracy of the ProAQT® sensor cardiac output measurements in comparison with Pulmonary Artery Catheter (PAC) during the postoperative course of patients who underwent cardiac surgery with cardiopulmonary bypass.

Case presentation
Prospective observational study in a Surgical Intensive Care Unit of a tertiary university hospital. Ten patients with a mean age of 73.5 years were included. The main comorbidities were hypertension, diabetes, dyslipidemia and the preoperative left ejection fraction was 43.8 ± 14.5%. Regarding the type of surgery, six patients underwent valve surgery, two underwent coronary artery bypass grafting and two underwent aortic surgery. The cardiac index measured simultaneously by the ProAQT® sensor was compared with the PAC. The parameters were evaluated at predefined time points during the early postoperative courses (6 h, 12 h, 24 h, 48 h and 72 h). The degree of agreement with the cardiac index between the PAC and the ProAQT® sensor along the time points was measured using the concordance correlation coefficient, Bland–Altman analysis, and four-quadrant plot. Sixty-three pairs of measurements were analyzed. We showed that measurements of cardiac index were slightly higher with PAC (β ̂ = − 0.146, p-value = 0.094). The concordance correlation coefficient for the additive model of cardiac index was 0.64 (95% Confidence Interval: 0.36, 0.82), indicating a high concordance between both sensors. Bland-Altmann analysis showed a mean bias of 0.45 L·min−1·m−2, limits of agreement from − 1.65 to 2.3 L·min−1·m−2, and percentage of error was 82.5%. Four-quadrant plot of changes in cardiac index showed a good concordance rate (75%), which increases after applying the exclusion zone (87%).

Conclusions
In patients undergoing cardiac surgery, the ProAQT® sensor may be useful to monitor cardiac index during the postoperative period, especially when more invasive monitoring is not possible.
Allelic prevalence and geographic distribution of cerebrotendinous xanthomatosis
Authors: Pramparo Tiziano , Steiner Robert D. , Rodems Steve , Jenkinson Celia 
Published: January 2023

Abstract
Background
Cerebrotendinous xanthomatosis (CTX) is a rare recessive genetic disease characterized by disruption of bile acid synthesis due to inactivation of the CYP27A1 gene. Treatment is available in the form of bile acid replacement. CTX is likely underdiagnosed, and prevalence estimates based on case diagnosis are probably inaccurate. Large population-based genomic databases are a valuable resource to estimate prevalence of rare recessive diseases as an orthogonal unbiased approach building upon traditional epidemiological studies.

Methods
We leveraged the Hardy–Weinberg principle and allele frequencies from gnomAD to calculate CTX prevalence. ClinVar and HGMD were used to identify high-confidence pathogenic missense variants and to calculate a disease-specific cutoff. Variant pathogenicity was also assessed by the VarSome implementation of the ACMG/AMP algorithm and the REVEL in silico predictor.

Results
CTX prevalence estimates were highest in Asians (1:44,407–93,084) and lowest in the Finnish population (1:3,388,767). Intermediate estimates were found in Europeans, Americans, and Africans/African Americans (1:70,795–233,597). The REVEL-predicted pathogenic variants accounted for a greater increase in prevalence estimates for Europeans, Americans, and Africans/African Americans compared with Asians. We identified the most frequent alleles designated pathogenic in ClinVar (p.Gly472Ala, p.Arg395Cys), labeled pathogenic based on sequence consequence (p.Met1?), and predicted to be pathogenic by REVEL (p.Met383Lys, p.Arg448His) across populations. Also, we provide a prospective geographic map of estimated disease distribution based on CYP27A1 variation queries performed by healthcare providers from selected specialties.

Conclusions
Prevalence estimates calculated herein support and expand upon existing evidence indicating underdiagnosis of CTX, suggesting that improved detection strategies are needed. Increased awareness of CTX is important for early diagnosis, which is essential for patients as early treatment significantly slows or prevents disease progression.
Tenofovir versus entecavir on decreasing risk of HBV-related hepatocellular carcinoma recurrence after liver transplantation
Authors: Yang Jianming , Chen Yewu , Sun Haobin , Zhang Xijian , Wang Jianfeng , Liang Zhixing , Fu Binsheng , Zhang Tong , Yi Shuhong , Deng Yinan , Yang Yang 
Published: January 2023

Abstract
Background
Recent studies have proved that tenofovir disoproxil fumarate (TDF) is associated with a lower risk of hepatocellular carcinoma (HCC) occurrence in chronic hepatitis B (CHB) patients and HCC recurrence in patients who underwent hepatectomy when compared to ETV. However, it is unclear whether TDF and ETV treatment, which are both recommended as first-line antiviral agents to prevent the hepatitis B (HBV) recurrence after liver transplantation (LT), are associated with equivalent prognosis. We aim to compare risk of HCC recurrence and survival of patients recieving TDF or ETV after LT for HBV-related HCC.

Method
We performed a retrospective study including 316 patients who received treatment with ETV or TDF after LT for HBV-related HCC from 2015 January to 2021 Augest. The Recurrence-free survival (RFS) and overall survival (OS) of TDF and ETV groups were analyzed and compared by propensity score-matched (PSM), multivariable Cox regression analysis, competing risk analysis, sensitivity analyses and subgroup analyses.

Result
Compared with ETV, TDF therapy was associated with significantly higher RFS rates in the entire cohort (P < 0.01), PSM cohort (P < 0.01) and beyond-Milan cohort (P < 0.01). By multivariable analysis, TDF group was associated with significantly lower rates of HCC recurrence (HR, 0.33; 95%CI, 0.14–0.75; P < 0.01). In subgroup analyses, the similar results were observed in patients with following tumor characteristics: Maximum diameter plus number of viable tumor ≥ 5, with MIV or MAT, AFP at LT ≥ 20 ng/ml, and well or moderate tumor grade.

Conclusion
Tenofovir decrease risk of HBV-Related Hepatocellular Carcinoma recurrence after liver transplantation compared to Entecavir.
Payload diversification: a key step in the development of antibody–drug conjugates
Authors: Conilh Louise , Sadilkova Lenka , Viricel Warren , Dumontet Charles 
Published: January 2023

AbstractAntibody–drug conjugates (ADCs) is a fast moving class of targeted biotherapeutics that currently combines the selectivity of monoclonal antibodies with the potency of a payload consisting of cytotoxic agents. For many years microtubule targeting and DNA-intercalating agents were at the forefront of ADC development. The recent approval and clinical success of trastuzumab deruxtecan (Enhertu®) and sacituzumab govitecan (Trodelvy®), two topoisomerase 1 inhibitor-based ADCs, has shown the potential of conjugating unconventional payloads with differentiated mechanisms of action. Among future developments in the ADC field, payload diversification is expected to play a key role as illustrated by a growing number of preclinical and clinical stage unconventional payload-conjugated ADCs. This review presents a comprehensive overview of validated, forgotten and newly developed payloads with different mechanisms of action.
Present and future of telemedicine for pediatric care: an Italian regional experience
Authors: Zuccotti Gianvincenzo , Calcaterra Valeria , Foppiani Andrea 
Published: January 2023

AbstractTelemedicine has been recognized as an integral part of the National Health Service in Italy. Telemedicine can be adopted in the diagnostic therapeutic assistance pathway and in individual assistance plans. In the region of Lombardy, home care models from the perspective of the project of a public virtual hospital have been introduced. A regional operational center was proposed to ensure continuing care utilising organizational and technological solutions to deliver healthcare services remotely, with high quality standards, a positive economic impact and user friendly services for both the user and the professional. In the field of pediatrics telemedicine was also introduced at the Vittore Buzzi Children’ Hospital, in Milan, the capital of the region of Lombardy. These included routine pediatric hospital activities and innovative programs, such as early discharge, telecardiology, online supervised exercise training and preventive healthcare. Telehealth represents the evolution of health care delivery systems to adapt to new technology and the needs of the pediatric population, offering a strategic system to invest in children’s health.
Differential paired stage-specific expression of Babesia bovis cysteine-rich GCC2/GCC3 domain family proteins (BboGDP) during development within Rhipicephalus microplus
Authors: Hussein Hala E. , Johnson Wendell C. , Ueti Massaro W. 
Published: January 2023

Abstract
Background
Babesia bovis, an intra-erythrocytic apicomplexan parasite, is one of the causative agents of bovine babesiosis, the most important tick-borne disease of cattle in tropical and subtropical regions. Babesia bovis has a complex life-cycle that includes sexual development within the tick vector. The development of a transmission blocking vaccine to control bovine babesiosis requires the identification of antigens displayed on the surface of the parasite during its development within tick vectors. Four B. bovis cysteine-rich GCC2/GCC3 domain protein (BboGDP) family members were previously identified and are differentially expressed as discrete pairs by either blood stages or kinetes. In this study we focused on two family members, BboGDP1 and -3, that are expressed by Babesia parasites during tick infection.

Methods and results
Transcription analysis using quantitative PCR demonstrated that BboGDP1 and -3 were upregulated in in vitro-induced sexual stage parasites and during parasite development in the tick midgut. Moreover, protein expression analysis of BboGDP1 and -3 during the development of sexual stages in in vitro culture was consistent with their transcription profile. Live immunofluorescence analysis using polyclonal antibodies confirmed surface expression of BboGDP1 and -3 on in vitro-induced sexual stage parasites. In addition, fixed immunofluorescence analysis showed reactivity of anti-BboGDP1 and -3 polyclonal antibodies to kinetes.

Conclusions
The collective data indicate that BboGDP1 and -3 are expressed by kinetes and on the surface of sexual stages of the parasites. The identified parasite surface membrane proteins BboGDP1 and -3 are potential candidates for the development of a B. bovis transmission blocking vaccine.

Graphical Abstract