bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical adoption patterns of 0.35 Tesla MR-guided radiation therapy in Europe and Asia
Authors: Slotman Berend J. , Clark Mary Ann , Özyar Enis , Kim Myungsoo , Itami Jun , Tallet Agnès , Debus Jürgen , Pfeffer Raphael , Gentile PierCarlo , Hama Yukihiro , Andratschke Nicolaus , Riou Olivier , Camilleri Philip , Belka Claus , Quivrin Magali , Kim BoKyong , Pedersen Anders , van Overeem Felter Mette , Kim Young Il , Kim Jin Ho , Fuss Martin , Valentini Vincenzo 
Published: August 2022

Abstract
Background
Magnetic resonance-guided radiotherapy (MRgRT) utilization is rapidly expanding, driven by advanced capabilities including better soft tissue imaging, continuous intrafraction target visualization, automatic triggered beam delivery, and the availability of on-table adaptive replanning. Our objective was to describe patterns of 0.35 Tesla (T)-MRgRT utilization in Europe and Asia among early adopters of this novel technology.

Methods
Anonymized administrative data from all 0.35T-MRgRT treatment systems in Europe and Asia were extracted for patients who completed treatment from 2015 to 2020. Detailed treatment information was analyzed for all MR-linear accelerators (linac) and -cobalt systems.

Results
From 2015 through the end of 2020, there were 5796 completed treatment courses delivered in 46,389 individual fractions. 23.5% of fractions were adapted. Ultra-hypofractionated (UHfx) dose schedules (1–5 fractions) were delivered for 63.5% of courses, with 57.8% of UHfx fractions adapted on-table. The most commonly treated tumor types were prostate (23.5%), liver (14.5%), lung (12.3%), pancreas (11.2%), and breast (8.0%), with increasing compound annual growth rates (CAGRs) in numbers of courses from 2015 through 2020 (pancreas: 157.1%; prostate: 120.9%; lung: 136.0%; liver: 134.2%).

Conclusions
This is the first comprehensive study reporting patterns of utilization among early adopters of a 0.35T-MRgRT system in Europe and Asia. Intrafraction MR image-guidance, advanced motion management, and increasing adoption of on-table adaptive RT have accelerated a transition to UHfx regimens. MRgRT has been predominantly used to treat tumors in the upper abdomen, pelvis and lungs, and increasingly with adaptive replanning, which is a radical departure from legacy radiotherapy practices.
Sutureless aortic valve replacement in pure aortic regurgitation: expanding the indications
Authors: Zubarevich Alina , Rad Arian Arjomandi , Amanov Lukman , Szczechowicz Marcin , Osswald Anja , Torabi Saeed , Schmack Bastian , Ruhparwar Arjang , Weymann Alexander 
Published: August 2022

Abstract
Background
In the era of transcatheter methods, patients presenting with a pure aortic regurgitation (AR) are not considered eligible for transcatheter treatment and therefore require another less invasive surgical option. We sought to review our experience with sutureless aortic valve replacement (SU-AVR) in patients presenting with symptomatic pure AR, which until now is a contraindication for implementation of sutureless valve prostheses in Europe.

Methods
Between April 2018 and June 2021, 80 consecutive patients underwent a SU-AVR for various indications at our institution. We analyzed the outcomes and postoperative complications of 12 patients presenting with a pure severe AR undergoing SU-AVR using Perceval (Corcym).

Results
The mean age of the patients was 67 ± 9.1 years old. All patients presented with symptomatic pure AR. Patients presented with multiple comorbidities as reflected by the mean EuroSCORE-II of 3.6 ± 2.6%. Six patients (50%) underwent a concomitant CABG procedure. The mean operating- and cross clamp time was 127.25 ± 45.9 and 40.33 ± 17.3 min respectively. All isolated SU-AVR were performed via J-sternotomy or right anterolateral thoracotomy. There were no cases of device dislocation. No patients presented with a paravalvular leakage. We observed excellent mean postoperative pressure gradient at follow-up 5.7 ± 1.5 mmHg.

Conclusions
Our experience with SU-AVR shows the feasibility of sutureless technologies in the aortic valve surgery due to pure AR. Besides the great technical success and excellent hemodynamics, SU-AVR in severe AR offers a great opportunity of reducing the invasivity of the surgical procedure and potentially reducing hospital cost without compromising the postoperative outcomes and in-hospital length of stay.
Fisetin induces DNA double-strand break and interferes with the repair of radiation-induced damage to radiosensitize triple negative breast cancer cells
Authors: Khozooei Shayan , Lettau Konstanze , Barletta Francesca , Jost Tina , Rebholz Simone , Veerappan Soundaram , Franz-Wachtel Mirita , Macek Boris , Iliakis George , Distel Luitpold V. , Zips Daniel , Toulany Mahmoud 
Published: August 2022

Abstract
Background
Triple-negative breast cancer (TNBC) is associated with aggressiveness and a poor prognosis. Besides surgery, radiotherapy serves as the major treatment modality for TNBC. However, response to radiotherapy is limited in many patients, most likely because of DNA damage response (DDR) signaling mediated radioresistance. Y-box binding protein-1 (YB-1) is a multifunctional protein that regulates the cancer hallmarks among them resisting to radiotherapy-induced cell death. Fisetin, is a plant flavonol of the flavonoid family of plant polyphenols that has anticancer properties, partially through inhibition of p90 ribosomal S6 kinase (RSK)-mediated YB-1 phosphorylation. The combination of fisetin with radiotherapy has not yet been investigated.

Methods
Activation status of the RSK signaling pathway in total cell lysate and in the subcellular fractions was analyzed by Western blotting. Standard clonogenic assay was applied to test post-irradiation cell survival. γH2AX foci assay and 3 color fluorescence in situ hybridization analyses were performed to study frequency of double-strand breaks (DSB) and chromosomal aberrations, respectively. The underlying repair pathways targeted by fisetin were studied in cells expressing genomically integrated reporter constructs for the DSB repair pathways via quantifying the expression of green fluorescence protein by flow cytometry. Flow cytometric quantification of sub-G1 cells and the protein expression of LC3-II were employed to measure apoptosis and autophagy, respectively. Kinase array and phosphoproteomics were performed to study the effect of fisetin on DDR response signaling.

Results
We showed that the effect of fisetin on YB-1 phosphorylation in TNBC cells is comparable to the effect of the RSK pharmacological inhibitors. Similar to ionizing radiation (IR), fisetin induces DSB. Additionally, fisetin impairs repair of IR-induced DSB through suppressing the classical non-homologous end-joining and homologous recombination repair pathways, leading to chromosomal aberration as tested by metaphase analysis. Effect of fisetin on DSB repair was partially dependent on YB-1 expression. Phosphoproteomic analysis revealed that fisetin inhibits DDR signaling, which leads to radiosensitization in TNBC cells, as shown in combination with single dose or fractionated doses irradiation.

Conclusion
Fisetin acts as a DSB-inducing agent and simultaneously inhibits repair of IR-induced DSB. Thus, fisetin may serve as an effective therapeutic strategy to improve TNBC radiotherapy outcome.
The efficacy and safety of angiogenesis inhibitors for recurrent ovarian cancer: a meta‑analysis
Authors: Zhang Chunmei , Zhao Wancheng 
Published: August 2022

Abstract
Objective
To investigate the efficacy and safety of angiogenesis inhibitors in the treatment of recurrent ovarian cancer (OC).

Methods
Electronic databases including PubMed, Web of Science, and the Cochrane Library were searched to find eligible studies until August 10, 2021. The data on overall survival (OS), progression-free survival (PFS), and objective response rate (ORR) were pooled. Furthermore, grade ≥ 3 adverse events (AEs) were investigated.

Results
A total of 13 studies with 3953 patients were included. Compared with control group, angiogenesis inhibitors resulted in significant improvement in PFS (hazard ratio (HR) = 0.61, 95%CI, 0.54–0.69), OS (HR = 0.88, 95%CI, 0.81–0.95), and ORR (odds ratio (OR) = 2.15, 95% CI, 1.74–2.65). However, angiogenesis inhibitors were associated with a higher risk of grade ≥ 3 AEs (relative risk (RR), 1.20, 95% CI, 1.04–1.38).

Conclusion
Angiogenesis inhibitors can improve ORR, PFS, and OS in patients with recurrent OC, but they can increase the incidence of AEs ≥ 3.
Human dyskerin binds to cytoplasmic H/ACA-box-containing transcripts affecting nuclear hormone receptor dependence
Authors: Zacchini Federico , Venturi Giulia , De Sanctis Veronica , Bertorelli Roberto , Ceccarelli Claudio , Santini Donatella , Taffurelli Mario , Penzo Marianna , Treré Davide , Inga Alberto , Dassi Erik , Montanaro Lorenzo 
Published: August 2022

Abstract
Background
Dyskerin is a nuclear protein involved in H/ACA box snoRNA-guided uridine modification of RNA. In humans, its defective function is associated with cancer development and induces specific post-transcriptional alterations of gene expression. In this study, we seek to unbiasedly identify mRNAs regulated by dyskerin in human breast cancer-derived cells.

Results
We find that dyskerin depletion affects the expression and the association with polysomes of selected mRNA isoforms characterized by the retention of H/ACA box snoRNA-containing introns. These snoRNA retaining transcripts (snoRTs) are bound by dyskerin in the cytoplasm in the form of shorter 3′ snoRT fragments. We then characterize the whole cytoplasmic dyskerin RNA interactome and find both H/ACA box snoRTs and protein-coding transcripts which may be targeted by the snoRTs’ guide properties. Since a fraction of these protein-coding transcripts is involved in the nuclear hormone receptor binding, we test to see if this specific activity is affected by dyskerin. Obtained results indicate that dyskerin dysregulation may alter the dependence on nuclear hormone receptor ligands in breast cancer cells. These results are paralleled by consistent observations on the outcome of primary breast cancer patients stratified according to their tumor hormonal status. Accordingly, experiments in nude mice show that the reduction of dyskerin levels in estrogen-dependent cells favors xenograft development in the absence of estrogen supplementation.

Conclusions
Our work suggests a cytoplasmic function for dyskerin which could affect mRNA post-transcriptional networks relevant for nuclear hormone receptor functions.
Sorbicillinoids hyperproduction without affecting the cellulosic enzyme production in Trichoderma reesei JNTR5
Authors: Li Chengcheng , Gu Ruihan , Lin Fengming , Xiao Huining 
Published: August 2022

Abstract
Background
Microbial production of bioactive secondary metabolites is challenging as most of the encoding genes are silent; and even if they are activated, the biosynthetic pathways are usually complex. Sorbicillinoids with multifunctional bioactivities are examples of these problems, which if solved can result in a more sustainable, simple supply of these important compounds to the pharmaceutical industry. As an excellent producer of cellulosic enzymes, Trichoderma reesei can secrete various sorbicillinoids.

Results
Here, we obtained a T. reesei mutant strain JNTR5 from the random mutation during overexpression of gene Tr69957 in T. reesei RUT-C30. JNTR5 exhibited a significant constitutive increase in sorbicillinoids production without affecting the cellulosic enzyme production. Confocal laser scanning microscope (CLSM) results indicated that sorbicillinoids were distributed in both mycelium and spores of JNTR5 with blue and green fluorescence. Compared with RUT-C30, JNTR5 displayed different cell morphology, reduced growth rate, and increased sporulation, but a similar biomass accumulation. Furthermore, transcriptome analysis revealed that all genes belonging to the sorbicillinoid gene cluster were upregulated, while most cellulase-encoding genes were downregulated. The cell wall integrity of JNTR5 was damaged, which might benefit the cellulase secretion and contribute to the almost unchanged cellulase and hemicellulase activity given that the damaged cell wall can enhance the secretion of the enzymes.

Conclusions
For the first time, we constructed a sorbicillinoids hyperproduction T. reesei platform with comparable cellulosic enzymes production. This outperformance of JNTR5, which is strain-specific, is proposed to be attributed to the overexpression of gene Tr69957, causing the chromosome remodeling and subsequently changing the cell morphology, structure, and the global gene expression as shown by phenotype and the transcriptome analysis of JNTR5. Overall, JNTR5 shows great potential for industrial microbial production of sorbicillinoids from cellulose and serves as an excellent model for investigating the distribution and secretion of yellow pigments in T. reesei.
Instruments to assess the role of the clinical pharmacist: a systematic review
Authors: Chagas Marina Oliveira , de Mendonça Lima Tácio , Rebustini Flávio , Noll Matias , de Carvalho Queiroz Débora Penélope , Hernandes Janete Capel , Chaveiro Neuma , Barbosa Maria Alves , Porto Celmo Celeno 
Published: August 2022

Abstract
Background
The clinical pharmacist is an essential member of the healthcare team and plays an important role in health care in the primary care and the hospital setting. Knowledge regarding the instruments that evaluate the different activities of the clinical pharmacist, as well as the evaluation of the psychometric properties of these instruments, is necessary.

Methods
A literature search was performed in the PubMed and Scopus electronic databases without time and language restrictions. For the search strategy, the “pharmaceutical services,” “validity studies,” and “professional performance” domains were used. To assess the quality of the instruments, the five sources of validity evidence of contemporary psychometry were used, and the Joanna Briggs Institute’s standardized instrument was used to assess the methodological quality of the studies. After screening 4096 articles, 32 studies were selected.

Results
A total of 32 studies were included, and 32 instruments were identified to be used by pharmacists acting in various pharmaceutical practice scenarios. It was found that the available instruments were developed or adapted from others, with variation in the methods, constructs, dimensions, and domains, as well as the psychometric properties. Most of the instruments addressed community pharmacies, and evidence of content validity and internal structure was found most frequently. A standardized and validated instrument that comprehensively assessed the performance of the clinical pharmacist, addressing clinical activities, was not identified for all practice environments.

Conclusions
Without standardized and validated instruments specifics to assess the performance of the clinical pharmacist, it is hard to establish the main clinical activities performed by pharmacists in their pharmaceutical practice environments and to propose training actions to improve professional practice. Despite the large number of instruments available and considered validated by the authors, it is questioned to what extent the validity indicators presented in the different studies really show the validation status.

Systematic review registration
PROSPERO CRD 42018099912.
SCP2 variant is associated with alterations in lipid metabolism, brainstem neurodegeneration, and testicular defects
Authors: Galano Melanie , Ezzat Shereen , Papadopoulos Vassilios 
Published: August 2022

Abstract
Background
The detoxification of very long-chain and branched-chain fatty acids and the metabolism of cholesterol to form bile acids occur largely through a process called peroxisomal β-oxidation. Mutations in several peroxisomal proteins involved in β-oxidation have been reported, resulting in diseases characterized by neurological defects. The final step of the peroxisomal β-oxidation pathway is catalyzed by sterol carrier protein-x (SCPx), which is encoded by the SCP2 gene. Previously, there have been two reports of SCPx deficiency, which resulted from a homozygous or compound heterozygous SCP2 mutation. We report herein the first patient with a heterozygous SCP2 mutation leading to SCPx deficiency.

Results
Clinical presentations of the patient included progressive brainstem neurodegeneration, cardiac dysrhythmia, muscle wasting, and azoospermia. Plasma fatty acid analysis revealed abnormal values of medium-, long-, and very long-chain fatty acids. Protein expression of SCPx and other enzymes involved in β-oxidation were altered between patient and normal fibroblasts. RNA sequencing and lipidomic analyses identified metabolic pathways that were altered between patient and normal fibroblasts including PPAR signaling, serotonergic signaling, steroid biosynthesis, and fatty acid degradation. Treatment with fenofibrate or 4-hydroxytamoxifen increased SCPx levels, and certain fatty acid levels in patient fibroblasts.

Conclusions
These findings suggest that the patient’s SCP2 mutation resulted in decreased protein levels of SCPx, which may be associated with many metabolic pathways. Increasing SCPx levels through pharmacological interventions may reverse some effects of SCPx deficiency. Collectively, this work provides insight into many of the clinical consequences of SCPx deficiency and provides evidence for potential treatment strategies.
BDNF-dependent modulation of axonal transport is selectively impaired in ALS
Authors: Tosolini Andrew P. , Sleigh James N. , Surana Sunaina , Rhymes Elena R. , Cahalan Stephen D. , Schiavo Giampietro 
Published: August 2022

AbstractAxonal transport ensures long-range delivery of essential cargoes between proximal and distal compartments, and is needed for neuronal development, function, and survival. Deficits in axonal transport have been detected at pre-symptomatic stages in the SOD1G93A and TDP-43M337V mouse models of amyotrophic lateral sclerosis (ALS), suggesting that impairments in this critical process are fundamental for disease pathogenesis. Strikingly, in ALS, fast motor neurons (FMNs) degenerate first whereas slow motor neurons (SMNs) are more resistant, and this is a currently unexplained phenomenon. The main aim of this investigation was to determine the effects of brain-derived neurotrophic factor (BDNF) on in vivo axonal transport in different α-motor neuron (MN) subtypes in wild-type (WT) and SOD1G93A mice. We report that despite displaying similar basal transport speeds, stimulation of wild-type MNs with BDNF enhances in vivo trafficking of signalling endosomes specifically in FMNs. This BDNF-mediated enhancement of transport was also observed in primary ventral horn neuronal cultures. However, FMNs display selective impairment of axonal transport in vivo in symptomatic SOD1G93A mice, and are refractory to BDNF stimulation, a phenotype that was also observed in primary embryonic SOD1G93A neurons. Furthermore, symptomatic SOD1G93A mice display upregulation of the classical non-pro-survival truncated TrkB and p75NTR receptors in muscles, sciatic nerves, and Schwann cells. Altogether, these data indicate that cell- and non-cell autonomous BDNF signalling is impaired in SOD1G93A MNs, thus identifying a new key deficit in ALS.
The Qianlong Emperor's order: scientific analysis helps find French painted enamel among Palace Museum collections
Authors: Liu Hanwen , Wang He , Duan Peiquan , Gao Han , Zhang Rong , Qu Liang 
Published: August 2022

Abstract
Painted enamel holds special significance in the study of the history of Chinese ceramic and glass. Painted enamel also represents interesting evidence of cultural communication between China and European countries. In the past, studies on painted enamel have mainly focused on archival research. Although modern scientific techniques have complemented research on enameled artifacts, the quality of the samples has usually been inferior. This study combines scientific analysis and archival work to explore four similar pots from the Palace Museum collection, along with the specific documentation information attached to them. Raman spectra, XRF and CT scanning were applied to compare the four pots. Results show that one of the pots is made of gold and use cassiterite and Naples yellow as opacifier and pigments, this pot bears the hidden hallmarks of a Parisian goldsmith, providing direct evidence that the pot was made in France in 1783. The other pots are proven to have been made in China, which are made of copper gilded with gold and use lead arsenate and lead tin yellow as opacifier and pigments. This work reveals a previously unnoticed route by which enamel artifacts reached the Chinese court.
FTIR study on the phase transition of experimental and archaeological burnt ivory
Authors: Wang Kai , He Yuhang , Shao Ruiqi , Zhao Hao , Ran Honglin , Lei Yu , Zhou Yihang 
Published: August 2022

Abstract
Recent excavation of the elephant ivories at the Sanxingdui site of the Shang Dynasty in Sichuan, China brings attention to the burnt features of the ivories. However, burnt ivories cannot be assessed by the same criteria established for burnt bones because of the differences in the ways that the two materials respond to heat. This study examines differences in the phase transition characteristics of ivory and bone, and confirms that the threshold temperature of the alteration in ivories is lower than that in bones. In our analysis, elephant ivories and bovine bones burnt at the temperatures between 200 and 1000 °C in oxidizing or reducing atmosphere are prepared and comparatively investigated by attenuated total reflection Fourier transform infrared spectroscopy. The results show that the transformation from magnesium-substituted hydroxyapatite (Mg-HAp) to magnesium-substituted β-tricalcium phosphate in ivory dentin takes place at the temperature as low as 800 °C, while β-tricalcium phosphate is not observed in bovine bones burnt at 1000 °C or below mainly because of the different magnesium contents. Due to the destruction of Mg-HAp at 800 °C in ivories, cyanamidapatite that could form in bones burnt under reducing atmosphere is absent in burnt ivories. With reference to the experimental burnt ivories, archaeological burnt ivories from the Sanxingdui site can now be clearly determined to be burnt unevenly at temperatures up to around 800 °C. This study may provide further information for archaeological research on ivories from the Sanxingdui site and identification of burnt bioapatite materials in other archaeological findings.
'What do doctors think they need to know about nutrition?’—a qualitative study of doctors with formal nutrition training
Authors: Caldow G , Palermo C , Wilson AN 
Published: August 2022

Abstract
Background
Doctors are on the frontline of patient care and in an ideal position to provide nutritional advice, yet can feel ill-equipped to do so. The aim of this study was to explore the nutrition knowledge, skills and practice required for nutrition-competent medical graduates, and their role in providing nutrition advice and care, from the perspective of doctors with formal nutrition training.

Methodology
We conducted an exploratory qualitative research study. A purposive sample of 12 medical doctors and students with formal nutrition training across Australia participated in in-depth semi structured interviews. Data were analysed thematically.

Results
There were four main themes identified: 1. Identifying the role of doctors in nutrition care; 2. Understanding the interrelatedness of the social determinants of health and nutrition status is key; 3. Optimising nutrition care through multidisciplinary collaboration; and 4. Providing evidence-based nutrition care.

Conclusion
This exploratory study suggests that doctors consider that nutrition competent medical graduates require skills in referring to dietitians, an understanding and application of the social determinants of health, and practise applying multidisciplinary and evidence-based nutrition care.