bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficient PCR‐based gene targeting in isolates of the nonconventional yeast Debaryomyces hansenii
Authors: Alhajouj Sondos , Turkolmez Selva , Abalkhail Tarad , Alwan Zeena Hadi Obaid , James Gilmour Daniel , Mitchell Phil J. , Hettema Ewald H. 
Published: October 2023

AbstractDebaryomyces hansenii is a yeast with considerable biotechnological potential as an osmotolerant, stress‐tolerant oleaginous microbe. However, targeted genome modification tools are limited and require a strain with auxotrophic markers. Gene targeting by homologous recombination has been reported to be inefficient, but here we describe a set of reagents and a method that allows gene targeting at high efficiency in wild‐type isolates. It uses a simple polymerase chain reaction (PCR)‐based amplification that extends a completely heterologous selectable marker with 50 bp flanks identical to the target site in the genome. Transformants integrate the PCR product through homologous recombination at high frequency (>75%). We illustrate the potential of this method by disrupting genes at high efficiency and by expressing a heterologous protein from a safe chromosomal harbour site. These methods should stimulate and facilitate further analysis of D. hansenii strains and open the way to engineer strains for biotechnology.
Spectral Decomposition of Compliance and Stiffness Fourth‐Rank Tensors Suitable for Orthotropic Materials
Authors: Theocaris P. S. , Philippidis T. P. 
Published: October 2023

AbstractThe spectral decomposition of the compliance and stiffness tensors related with tranversely isotropic materials was developed and their characteristic values were calculated by using the components of these fourth‐rank tensors in a Cartesian frame defining the principal material directions. Imposing the eigenvalues of the 6 × 6 matrix associated with the contracted 4th rank symmetric tensor to be strictly positive, as implied by the positive definiteness of the elastic potential, bounds of the values of Poisson 's ratios were established. They were shown to restrain considerably the existing limits of variations of this fundamental property of the orthotropic materials. Energy orthogonal states of stress for the tranversely isotropic material were also established decomposing the elastic potential in distinct parts associated with the deformation eigen‐states of the material symmetry. Thus, the unsolved as yet important problem of extension of separation of the elastic energy to anisotropic materials was achieved by an effective manner which is useful in practical applications.
Scaling up Roundoff Analysis of Functional Data Structure Programs
Authors: Isychev Anastasia , Darulova Eva 
Published: October 2023

AbstractFloating-point arithmetic is counter-intuitive due to inherent rounding errors that potentially occur at every arithmetic operation. A selection of automated tools now exists to ensure correctness of floating-point programs by computing guaranteed bounds on rounding errors at the end of a computation, but these tools effectively consider only straight-line programs over scalar variables. Much of numerical codes, however, use data structures such as lists, arrays or matrices and loops over these. To analyze such programs today, all data structure operations need to be unrolled, manually or by the analyzer, reducing the analysis to straight-line code, ultimately limiting the analyzers’ scalability.We present the first rounding error analysis for numerical programs written over vectors and matrices that leverages the data structure information to speed up the analysis. We facilitate this with our functional domain-specific input language that we design based on a new set of numerical benchmarks that we collect from a variety of domains. Our DSL explicitly carries semantic information that is useful for avoiding duplicate and thus unnecessary analysis steps, as well as enabling abstractions for further speed-ups. Compared to unrolling-based approaches in state-of-the-art tools, our analysis retains adequate accuracy and is able to analyze more benchmarks or is significantly faster, and particularly scales better for larger programs.
High-LET charged particles: radiobiology and application for new approaches in radiotherapy
Authors: Helm Alexander , Fournier Claudia 
Published: October 2023

AbstractThe number of patients treated with charged-particle radiotherapy as well as the number of treatment centers is increasing worldwide, particularly regarding protons. However, high-linear energy transfer (LET) particles, mainly carbon ions, are of special interest for application in radiotherapy, as their special physical features result in high precision and hence lower toxicity, and at the same time in increased efficiency in cell inactivation in the target region, i.e., the tumor. The radiobiology of high-LET particles differs with respect to DNA damage repair, cytogenetic damage, and cell death type, and their increased LET can tackle cells’ resistance to hypoxia. Recent developments and perspectives, e.g., the return of high-LET particle therapy to the US with a center planned at Mayo clinics, the application of carbon ion radiotherapy using cost-reducing cyclotrons and the application of helium is foreseen to increase the interest in this type of radiotherapy. However, further preclinical research is needed to better understand the differential radiobiological mechanisms as opposed to photon radiotherapy, which will help to guide future clinical studies for optimal exploitation of high-LET particle therapy, in particular related to new concepts and innovative approaches. Herein, we summarize the basics and recent progress in high-LET particle radiobiology with a focus on carbon ions and discuss the implications of current knowledge for charged-particle radiotherapy. We emphasize the potential of high-LET particles with respect to immunogenicity and especially their combination with immunotherapy.
Female sex is a risk factor for painful diabetic peripheral neuropathy: the EURODIAB prospective diabetes complications study
Authors: Elliott Jackie , Sloan Gordon , Stevens Lynda , Selvarajah Dinesh , Cruccu Giorgio , Gandhi Rajiv A. , Kempler Peter , Fuller John H. , Chaturvedi Nishi , Tesfaye Solomon ,   for the EURODIAB Prospective Complications Study Group
Published: October 2023

Abstract
Aims/hypothesis
While the risk factors for diabetic peripheral neuropathy (DPN) are now well recognised, the risk factors for painful DPN remain unknown. We performed analysis of the EURODIAB Prospective Complications Study data to elucidate the incidence and risk factors of painful DPN.

Methods
The EURODIAB Prospective Complications Study recruited 3250 participants with type 1 diabetes who were followed up for 7.3±0.6 (mean ± SD) years. To evaluate DPN, a standardised protocol was used, including clinical assessment, quantitative sensory testing and autonomic function tests. Painful DPN (defined as painful neuropathic symptoms in the legs in participants with confirmed DPN) was assessed at baseline and follow-up.

Results
At baseline, 234 (25.2%) out of 927 participants with DPN had painful DPN. At follow-up, incident DPN developed in 276 (23.5%) of 1172 participants. Of these, 41 (14.9%) had incident painful DPN. Most of the participants who developed incident painful DPN were female (73% vs 48% painless DPN p=0.003) and this remained significant after adjustment for duration of diabetes and HbA1c (OR 2.69 [95% CI 1.41, 6.23], p=0.004). The proportion of participants with macro- or microalbuminuria was lower in those with painful DPN compared with painless DPN (15% vs 34%, p=0.02), and this association remained after adjusting for HbA1c, diabetes duration and sex (p=0.03).

Conclusions/interpretation
In this first prospective study to investigate the risk factors for painful DPN, we definitively demonstrate that female sex is a risk factor for painful DPN. Additionally, there is less evidence of diabetic nephropathy in incident painful, compared with painless, DPN. Thus, painful DPN is not driven by cardiometabolic factors traditionally associated with microvascular disease. Sex differences may therefore play an important role in the pathophysiology of neuropathic pain in diabetes. Future studies need to look at psychosocial, genetic and other factors in the development of painful DPN.

Graphical Abstract
Combined in vivo metabolic effects of quetiapine and methadone in brain and blood of rats
Authors: Heisel Laura Smedegaard , Andersen Freja Drost , Joca Sâmia , Sørensen Lambert Kristiansen , Simonsen Ulf , Hasselstrøm Jørgen Bo , Andersen Charlotte Uggerhøj , Nielsen Kirstine Lykke 
Published: October 2023

AbstractChanges in pharmacokinetics and endogenous metabolites may underlie additive biological effects of concomitant use of antipsychotics and opioids. In this study, we employed untargeted metabolomics analysis and targeted analysis to examine the changes in drug metabolites and endogenous metabolites in the prefrontal cortex (PFC), midbrain, and blood of rats following acute co-administration of quetiapine and methadone. Rats were divided into four groups and received cumulative increasing doses of quetiapine (QTP), methadone (MTD), quetiapine + methadone (QTP + MTD), or vehicle (control). All samples were analyzed using liquid chromatography-mass spectrometry (LC–MS). Our findings revealed increased levels of the quetiapine metabolites: Norquetiapine, O-dealkylquetiapine, 7-hydroxyquetiapine, and quetiapine sulfoxide, in the blood and brain when methadone was present. Our study also demonstrated a decrease in methadone and its metabolite 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP) in the rat brain when quetiapine was present. Despite these findings, there were only small differences in the levels of 225–296 measured endogenous metabolites due to co-administration compared to single administrations. For example, N-methylglutamic acid, glutaric acid, p-hydroxyphenyllactic acid, and corticosterone levels were significantly decreased in the brain of rats treated with both compounds. Accumulation of serotonin in the midbrain was additionally observed in the MTD group, but not in the QTP + MTD group. In conclusion, this study in rats suggests a few but important additive metabolic effects when quetiapine and methadone are co-administered.
Feasibility of GPT-3 and GPT-4 for in-Depth Patient Education Prior to Interventional Radiological Procedures: A Comparative Analysis
Authors: Scheschenja Michael , Viniol Simon , Bastian Moritz B. , Wessendorf Joel , König Alexander M. , Mahnken Andreas H. 
Published: October 2023

Abstract
Purpose
This study explores the utility of the large language models, GPT-3 and GPT-4, for in-depth patient education prior to interventional radiology procedures. Further, differences in answer accuracy between the models were assessed.

Materials and methods
A total of 133 questions related to three specific interventional radiology procedures (Port implantation, PTA and TACE) covering general information as well as preparation details, risks and complications and post procedural aftercare were compiled. Responses of GPT-3 and GPT-4 were assessed for their accuracy by two board-certified radiologists using a 5-point Likert scale. The performance difference between GPT-3 and GPT-4 was analyzed.

Results
Both GPT-3 and GPT-4 responded with (5) “completely correct” (4) “very good” answers for the majority of questions ((5) 30.8% + (4) 48.1% for GPT-3 and (5) 35.3% + (4) 47.4% for GPT-4). GPT-3 and GPT-4 provided (3) “acceptable” responses 15.8% and 15.0% of the time, respectively. GPT-3 provided (2) “mostly incorrect” responses in 5.3% of instances, while GPT-4 had a lower rate of such occurrences, at just 2.3%. No response was identified as potentially harmful. GPT-4 was found to give significantly more accurate responses than GPT-3 (p = 0.043).

Conclusion
GPT-3 and GPT-4 emerge as relatively safe and accurate tools for patient education in interventional radiology. GPT-4 showed a slightly better performance. The feasibility and accuracy of these models suggest their promising role in revolutionizing patient care. Still, users need to be aware of possible limitations.

Graphical Abstract
Prognostic MRI features to predict postresection survivals for very early to intermediate stage hepatocellular carcinoma
Authors: Jiang Hanyu , Qin Yun , Wei Hong , Zheng Tianying , Yang Ting , Wu Yuanan , Ding Chengyu , Chernyak Victoria , Ronot Maxime , Fowler Kathryn J. , Chen Weixia , Bashir Mustafa R. , Song Bin 
Published: October 2023

Abstract
Objectives
Contrast-enhanced MRI can provide individualized prognostic information for hepatocellular carcinoma (HCC). We aimed to investigate the value of MRI features to predict early (≤ 2 years)/late (> 2 years) recurrence-free survival (E-RFS and L-RFS, respectively) and overall survival (OS).

Materials and methods
Consecutive adult patients at a tertiary academic center who received curative-intent liver resection for very early to intermediate stage HCC and underwent preoperative contrast-enhanced MRI were retrospectively enrolled from March 2011 to April 2021. Three masked radiologists independently assessed 54 MRI features. Uni- and multivariable Cox regression analyses were conducted to investigate the associations of imaging features with E-RFS, L-RFS, and OS.

Results
This study included 600 patients (median age, 53 years; 526 men). During a median follow-up of 55.3 months, 51% of patients experienced recurrence (early recurrence: 66%; late recurrence: 34%), and 17% died. Tumor size, multiple tumors, rim arterial phase hyperenhancement, iron sparing in solid mass, tumor growth pattern, and gastroesophageal varices were associated with E-RFS and OS (largest p = .02). Nonperipheral washout (p = .006), markedly low apparent diffusion coefficient value (p = .02), intratumoral arteries (p = .01), and width of the main portal vein (p = .03) were associated with E-RFS but not with L-RFS or OS, while the VICT2 trait was specifically associated with OS (p = .02). Multiple tumors (p = .048) and radiologically-evident cirrhosis (p < .001) were the only predictors for L-RFS.

Conclusion
Twelve visually-assessed MRI features predicted postoperative E-RFS (≤ 2 years), L-RFS (> 2 years), and OS for very early to intermediate-stage HCCs.

Clinical relevance statement
The prognostic MRI features may help inform personalized surgical planning, neoadjuvant/adjuvant therapies, and postoperative surveillance, thus may be included in future prognostic models.

Key Points
• Tumor size, multiple tumors, rim arterial phase hyperenhancement, iron sparing, tumor growth pattern, and gastroesophageal varices predicted both recurrence-free survival within 2 years and overall survival.
• Nonperipheral washout, markedly low apparent diffusion coefficient value, intratumoral arteries, and width of the main portal vein specifically predicted recurrence-free survival within 2 years, while the VICT2 trait specifically predicted overall survival.
• Multiple tumors and radiologically-evident cirrhosis were the only predictors for recurrence-free survival beyond 2 years.

Graphical Abstract
Efficacy and influencing factors of cervical perivascular sympathectomy in children with cerebral palsy
Authors: Wu Junjie , Yan Baofeng , Mutalifu Nurehemaiti , Guan Qi , Bai Chao , Li Jianglong , Luan Xinping 
Published: October 2023

Abstract
Background
There is a lack of research to determine the efficacy of cervical perivascular sympathectomy (CPVS) in children with cerebral palsy (CP).

Objective
This study aimed to evaluate the efficacy of CPVS in children with CP and analyze the associated influential factors.

Methods
Using the method of retrospective cohort studies, children who underwent CPVS were included in the CPVS group, whereas those who underwent selective posterior rhizotomy (SPR) were included in the SPR group. The Communication Function Classification System (CFCS) and Teacher Drooling Scale (TDS) were used to evaluate the communication function and salivation in the two groups before and 12 months after surgery and compare the surgical efficiency between the two groups, and the factors affecting the efficacy were screened by binary logistic regression.

Results
The study included 406 patients, 202 in the CPVS group and 204 in the SPR group. No significant differences were observed in the baseline characteristics (p > 0.05). The surgical efficacy of the CPVS group (47.01%) was significantly higher than that in the SPR group (9.81%) (χ2 = 71.08, p < 0.001). Binary logic regression analysis showed that preterm birth and Gross Motor Function Classification System (GMFCS) grade were influencing factors of surgical efficacy. Eighteen patients developed postoperative complications.

Conclusion
CPVS is a safe and effective surgery for cerebral palsy. Preterm birth and GMFCS grade are independent factors affecting the efficacy of surgery.
TSH receptor autoantibody levels post-total thyroidectomy in Graves’ ophthalmopathy: a meta-analysis
Authors: Anees Arsalan , Ayeni Femi E. , Eslick Guy D. , Edirimanne Senarath 
Published: October 2023

Abstract
Background
TSH receptor autoantibodies (TRAbs) are pathognomonic for Graves’ disease and are thought to also underly the pathogenesis of Graves’ ophthalmopathy (GO). A decline in TRAb levels has been documented post-total thyroidectomy (TTx) in GO, however with conflicting correlations with disease outcomes. The aim of the study was to compare the effectiveness of TTx to other treatment modalities of Graves’ disease and examine whether the lowering of TRAbs is associated with GO improvements.

Method
We searched electronic databases including Medline, Embase, Scopus, and Web of Science until 31 September 2022 using a broad range of keywords. Patients with GO undergoing TTx with measurements of both TRAbs and progression of the disease using a validated GO scoring system were included. Fourteen studies encompassing data from 1047 patients with GO met our eligibility criteria. The PRISMA guidelines were followed, and five studies had comparable data that were suitable for a meta-analysis.

Results
The Cochrane Risk of Bias tool for RCTs showed low risk of bias across most domains. The pooled odds ratio showed that more patients significantly had normalized TRAb levels post-TTx as compared to other interventions (OR: 1.36, 95% CI: 1.02–1.81, p = 0.035). But, there was no significant difference in GO improvement post-TTx as compared with other intervention groups.

Conclusions
This meta-analysis shows that TRAb levels may decline largely post-TTx, but may not predict added improvements to the progression of GO. Thus, future studies with uniform designs are required to assess the minimal significant GO improvements.
Home initiation of apomorphine infusion: lessons from the COVID-19 pandemic and implications for current clinical practice
Authors: Kobylecki Christopher , Partington-Smith Lucy 
Published: October 2023

AbstractStarting Parkinson’s disease (PD) patients on subcutaneous apomorphine (APO) infusion is generally undertaken on a hospital day-case basis. During the COVID-19 pandemic, day-case facilities were unavailable. To avoid delays in treatment, a new procedure was developed for initiation of APO therapy in the patient’s home. A home initiation protocol was developed and followed for each patient in this analysis. The hospital team worked in collaboration with APO nurses provided by the manufacturer of APO therapies to implement initiation and undertake follow-up. In this analysis, 27 PD patients were initiated onto APO infusion and 21 (77.8%) achieved a therapeutic response. Home initiation of APO infusion can be undertaken successfully and has benefits for both patients and healthcare teams. This protocol will now continue as a standard of care at our centre.
Retrospective clinical study on the performance and aesthetic outcome of pressed lithium disilicate restorations in posterior teeth up to 8.3 years
Authors: Lindner Stefanie , Frasheri Iris , Hickel Reinhard , Crispin Alexander , Kessler Andreas 
Published: October 2023

Abstract
Objectives
Evaluation of cumulative survival and complication rate of monolithic lithium disilicate inlays and partial crowns performed by supervised undergraduate students up to 8.3 years of clinical service.

Materials and methods
In this retrospective clinical study 143 lithium disilicate posterior restorations (IPS e.max Press) were examined according to the FDI criteria. A standardised questionnaire was used to determine patient satisfaction. The aesthetic outcome was evaluated by dentists and dental technicians using intraoral photographs. Data were descriptively analysed. Cumulative survival and success rates were calculated using Kaplan–Meier estimation.

Results
The cumulative survival rate of lithium disilicate restorations was 97.5% after a mean service time of 5.9 years and 95.0% after 8.3 years. The cumulative success rate decreased from 94.4% after 5.9 years to 30.7% after 8.3 years. Repairs were required for 7 restorations (4.9%), and 5 (3.5%) were classified as failures. The results of the questionnaire indicate a high level of patient satisfaction. The subjective aesthetics were assessed more critically by dental technicians compared to dentists.

Conclusion
Lithium disilicate posterior restorations survived successfully up to 8.3 years when carried out by undergraduate students.

Clinical relevance
Pressed lithium disilicate glass ceramic inlays and partial crowns are reliable treatment options in posterior teeth.
Core genome multilocus sequence typing of Clostridioides difficile to investigate transmission in the hospital setting
Authors: Filippidis Paraskevas , Senn Laurence , Poncet Fabrice , Grandbastien Bruno , Prod’hom Guy , Greub Gilbert , Guery Benoit , Blanc Dominique S. 
Published: October 2023

Abstract
Purpose
Traditional epidemiological investigations of healthcare-associated Clostridioides difficile infection (HA-CDI) are often insufficient. This study aimed to evaluate a procedure that includes secondary isolation and genomic typing of single toxigenic colonies using core genome multilocus sequence typing (cgMLST) for the investigation of C. difficile transmission.

Methods
We analyzed retrospectively all toxigenic C. difficile-positive stool samples stored at the Lausanne University Hospital over 6 consecutive months. All isolates were initially typed and classified using a modified double-locus sequence typing (DLST) method. Genome comparison of isolates with the same DLST and clustering were subsequently performed using cgMLST. The electronic administrative records of patients with CDI were investigated for spatiotemporal epidemiological links supporting hospital transmission. A comparative descriptive analysis between genomic and epidemiological data was then performed.

Results
From January to June 2021, 86 C. difficile isolates were recovered from thawed samples of 71 patients. Thirteen different DLST types were shared by > 1 patient, and 13 were observed in single patients. A genomic cluster was defined as a set of isolates from different patients with ≤ 3 locus differences, determined by cgMLST. Seven genomic clusters were identified, among which plausible epidemiological links were identified in only 4/7 clusters.

Conclusion
Among clusters determined by cgMLST analysis, roughly 40% included unexplained HA-CDI acquisitions, which may be explained by unidentified epidemiological links, asymptomatic colonization, and/or shared common community reservoirs. The use of DLST, followed by whole genome sequencing analysis, is a promising and cost-effective stepwise approach for the investigation of CDI transmission in the hospital setting.