bluuebunny/crossref_metadata_2025_split huggingface dataset:
Recent progress in 3D printing degradable polylactic acid‐based bone repair scaffold for the application of cancellous bone defect
Authors: Hu Xulin , Lin Zhidong , He Jian , Zhou Minchang , Yang Shuhao , Wang Yao , Li Kainan 
Published: July 2022

AbstractLarge size bone defects have become a growing clinical challenge. Cancellous bone, which has the highest volume ratio, the fastest replacement rate, and interconnected porous structure, plays a major role in bone repairing. Considering the structure and composition of cancellous bone, building a bionic 3D scaffold via customized‐3D printing technology is the key to solving the problem. As the earliest degradable medical polymer material approved by Food and Drug Administration, polylactic acid has been proved to have excellent biosafety and can be copolymerized or blended with other synthetic polymers, natural polymers, and inorganic materials to improve its performance to better meet clinical applications. A series of biodegradable bone repair scaffolds based on polylactic acid composites and 3D printing technology are developed to achieve large bone defects. Here, we review the composition and structure of cancellous bone, highlighting the relationship to the requirements of bone repair scaffolds. The different types of polylactic‐acid‐based materials applied in 3D printing technology are described, emphasizing the connection between materials, preparation methods, and applications.
Standing on the parent's shoulder or in its shadow? Alliance partner overlap between employee spinouts and their parents
Authors: Gaonkar Shweta , Moeen Mahka 
Published: July 2022

AbstractResearch SummaryEmployee spinouts, defined as startups founded by prior employees of an industry firm, play a critical role in firm creation and knowledge transfer. Their superior performance often arises from resources and knowledge accrued during employment in parent firms. An understudied question is whether prior employment in parent firms affects an employee spinout's alliance formation, given that alliances are critical to startups' survival and commercial success. This article examines when an employee spinout's alliance partners overlap with the parent's partners. Drawing on alliance formation patterns of U.S. medical device spinouts founded between 1990 and 2013, we find that spinouts building on their parents' technologies tend to have a greater partner overlap with their parents, whereas product market overlap leads to fewer overlapping partners.Managerial SummaryA rich context for entrepreneurs to identify new opportunities is through their employment in existing industry firms. When employees leave their job and create a spinout, their employment experience often provides them superior knowledge and expertise. Our study of medical device startups uncovers another distinctive feature of employee spinouts, that is, access to their employer's alliance partners. However, for such opportunities to come to fruition, entrepreneurs need to pay attention to their technical and product market positioning relative to their past employers. When spinouts build on their employer's technologies without challenging them in the product space, they can leverage connections to their employer's partners. This alliance strategy may free spinouts from the alliance formation struggles faced by resource‐deficient startups.
Light‐Harvesting Artificial Cells Containing Cyanobacteria for CO2 Fixation and Further Metabolism Mimicking
Authors: Yang Boyu , Li Shubin , Mu Wei , Wang Zhao , Han Xiaojun 
Published: July 2022

AbstractThe bottom‐up constructed artificial cells help to understand the cell working mechanism and provide the evolution clues for organisms. The energy supply and metabolism mimicry are the key issues in the field of artificial cells. Herein, an artificial cell containing cyanobacteria capable of light harvesting and carbon dioxide fixation is demonstrated to produce glucose molecules by converting light energy into chemical energy. Two downstream “metabolic” pathways starting from glucose molecules are investigated. One involves enzyme cascade reaction to produce H2O2 (assisted by glucose oxidase) first, followed by converting Amplex red to resorufin (assisted by horseradish peroxidase). The other pathway is more biologically relevant. Glucose molecules are dehydrogenated to transfer hydrogens to nicotinamide adenine dinucleotide (NAD+) for the production of nicotinamide adenine dinucleotide hydride (NADH) molecules in the presence of glucose dehydrogenase. Further, NADH molecules are oxidized into NAD+ by pyruvate catalyzed by lactate dehydrogenase, meanwhile, lactate is obtained. Therefore, the cascade cycling of NADH/NAD+ is built. The artificial cells built here pave the way for investigating more complicated energy‐supplied metabolism inside artificial cells.
X‐Ray Photon Correlation Spectroscopy Towards Measuring Nanoparticle Diameters in Biological Environments Allowing for the In Situ Analysis of their Bio‐Nano Interface
Authors: Otto Ferdinand , Sun Xing , Schulz Florian , Sanchez‐Cano Carlos , Feliu Neus , Westermeier Fabian , Parak Wolfgang J. 
Published: July 2022

AbstractX‐ray photon correlation spectroscopy (XPCS), a synchrotron source‐based technique to measure sample dynamics, is used to determine hydrodynamic diameters of gold nanoparticles (Au NPs) of different sizes in biological environments. In situ determined hydrodynamic diameters are benchmarked with values obtained by dynamic light scattering. The technique is then applied to analyze the behavior of the Au NPs in a biological environment. First, a concentration‐dependent agglomeration in the presence of NaCl is determined. Second, concentration‐dependent increase in hydrodynamic diameter of the Au NPs upon the presence of proteins is determined. As X‐rays in the used energy range are barely scattered by biological matter, dynamics of the Au NPs can be also detected in situ in complex biological environments, such as blood. These measurements demonstrate the possibility of XPCS for in situ analytics of nanoparticles (NPs) in biological environments where similar detection techniques based on visible light would severely suffer from scattering, absorption, and reflection effects.
Statistical Methods for the Quantitative Genetic Analysis of High-Throughput Phenotyping Data
Authors: Morota Gota , Jarquin Diego , Campbell Malachy T. , Iwata Hiroyoshi 
Published: July 2022

AbstractThe advent of plant phenomics, coupled with the wealth of genotypic data generated by next-generation sequencing technologies, provides exciting new resources for investigations into and improvement of complex traits. However, these new technologies also bring new challenges in quantitative genetics, namely, a need for the development of robust frameworks that can accommodate these high-dimensional data. In this chapter, we describe methods for the statistical analysis of high-throughput phenotyping (HTP) data with the goal of enhancing the prediction accuracy of genomic selection (GS). Following the Introduction in Sec. 1, Sec. 2 discusses field-based HTP, including the use of unoccupied aerial vehicles and light detection and ranging, as well as how we can achieve increased genetic gain by utilizing image data derived from HTP. Section 3 considers extending commonly used GS models to integrate HTP data as covariates associated with the principal trait response, such as yield. Particular focus is placed on single-trait, multi-trait, and genotype by environment interaction models. One unique aspect of HTP data is that phenomics platforms often produce large-scale data with high spatial and temporal resolution for capturing dynamic growth, development, and stress responses. Section 4 discusses the utility of a random regression model for performing longitudinal modeling. The chapter concludes with a discussion of some standing issues.
The Dyadic Representation Theorem Using Smooth Wavelets with Compact Support
Authors: Hytönen Tuomas , Lappas Stefanos 
Published: July 2022

AbstractThe representation of a general Calderón–Zygmund operator in terms of dyadic Haar shift operators first appeared as a tool to prove the $$A_2$$

A
2

theorem, and it has found a number of other applications. In this paper we prove a new dyadic representation theorem by using smooth compactly supported wavelets in place of Haar functions. A key advantage of this is that we achieve a faster decay of the expansion when the kernel of the general Calderón–Zygmund operator has additional smoothness.
Evaluating the efficacy and mechanism of metformin targets on reducing Alzheimer’s disease risk in the general population: a Mendelian randomisation study
Authors: Zheng Jie , Xu Min , Walker Venexia , Yuan Jinqiu , Korologou-Linden Roxanna , Robinson Jamie , Huang Peiyuan , Burgess Stephen , Au Yeung Shiu Lun , Luo Shan , Holmes Michael V. , Davey Smith George , Ning Guang , Wang Weiqing , Gaunt Tom R. , Bi Yufang 
Published: July 2022

Abstract
Aims/hypothesis
Metformin use has been associated with reduced incidence of dementia in diabetic individuals in observational studies. However, the causality between the two in the general population is unclear. This study uses Mendelian randomisation (MR) to investigate the causal effect of metformin targets on Alzheimer’s disease and potential causal mechanisms in the brain linking the two.

Methods
Genetic proxies for the effects of metformin drug targets were identified as variants in the gene for the corresponding target that associated with HbA1c level (N=344,182) and expression level of the corresponding gene (N≤31,684). The cognitive outcomes were derived from genome-wide association studies comprising 527,138 middle-aged Europeans, including 71,880 with Alzheimer’s disease or Alzheimer’s disease-by-proxy. MR estimates representing lifelong metformin use on Alzheimer’s disease and cognitive function in the general population were generated. Effect of expression level of 22 metformin-related genes in brain cortex (N=6601 donors) on Alzheimer’s disease was further estimated.

Results
Genetically proxied metformin use, equivalent to a 6.75 mmol/mol (1.09%) reduction on HbA1c, was associated with 4% lower odds of Alzheimer’s disease (OR 0.96 [95% CI 0.95, 0.98], p=1.06×10−4) in non-diabetic individuals. One metformin target, mitochondrial complex 1 (MCI), showed a robust effect on Alzheimer’s disease (OR 0.88, p=4.73×10−4) that was independent of AMP-activated protein kinase. MR of expression in brain cortex tissue showed that decreased MCI-related gene (NDUFA2) expression was associated with lower Alzheimer’s disease risk (OR 0.95, p=4.64×10−4) and favourable cognitive function.

Conclusions/interpretation
Metformin use may cause reduced Alzheimer’s disease risk in the general population. Mitochondrial function and the NDUFA2 gene are plausible mechanisms of action in dementia protection.

Graphical abstract
Sirolimus-Coated Balloon Angioplasty of Infra-popliteal Lesions for the Treatment of Chronic Limb-Threatening Ischemia: Study Protocol for the Randomized Controlled LIMES Study
Authors: Teichgräber Ulf , Platzer Stephanie , Lehmann Thomas , Ingwersen Maja , Aschenbach René , Beschorner Ulrich , Scheinert Dierk , Zeller Thomas 
Published: July 2022

Abstract
Purpose
Evidence on efficacy and long-term safety of paclitaxel-coated devices is still conflicting. Therefore, this study aims to assess whether sirolimus-coated balloon angioplasty is safe and effective for the treatment of infra-popliteal occlusions in patients with chronic limb-threatening ischemia (CLTI).

Study design
The randomized controlled, single-blinded, multicentre, investigator-initiated study aims to enrol 230 participants with CLTI and infra-popliteal occlusions at up to 25 centres. Patients will be randomized in a 1:1 ratio to either sirolimus-coated balloon angioplasty or to plain old balloon angioplasty (POBA). Bailout stenting in case of flow-limiting dissection or ≥ 50% residual diameter stenosis is permitted.

Outcome measures
Primary outcome is the Kaplan–Meier estimate of primary patency at 6 months, defined as the absence of target lesion occlusion with restoration of in-line flow to the ankle. Key secondary outcome is non-inferiority in the proportionate occurrence of major adverse limb events and perioperative all-cause death at 30 days. Overall, participants will be followed for 36 months to assess further secondary efficacy and safety outcomes.

Assumed gain of knowledge
If sirolimus-coated balloon angioplasty turns out to be superior to uncoated-balloon angioplasty regarding patency of infra-popliteal lesions without safety signals, it could become a welcome treatment option for patients with CLTI.
Trial Registration ClinicalTrial.gov Identifier: NCT04772300, German Clinical Trials Register: DRKS00024629.
Level of Evidence Level 2a, randomized controlled trial.
HLA-G as a prognostic marker in stage II/III colorectal cancer: not quite there yet
Authors: Gambella Alessandro , Scabini Stefano , Zoppoli Gabriele , De Silvestri Annalisa , Pigozzi Simona , Paudice Michele , Campora Michela , Fiocca Roberto , Grillo Federica , Mastracci Luca 
Published: July 2022

AbstractIdentifying innovative molecules involved in the tumor immune escape process could help refine the survival stratification of colorectal cancer (CRC) patients. HLA-G, a non-classical HLA molecule, physiologically involved in tolerogenic mechanisms, has recently emerged as a relevant prognostic marker in other tumor types, but ambiguous data are reported in the CRC setting. This study aims to evaluate the HLA-G expression and prognostic potential in a series of stage II/III CRCs. HLA-G expression was evaluated in 100 pT3 CRC cases by means of immunohistochemistry using the 4H84 and MEM-G/2 monoclonal antibodies. We observed heterogeneous expression of HLA-G showing different ranges: 4H84 expression ranged from > 1 to 40%—median 7%; MEM-G/2 expression ranged from 20 to 90%—median 50%. HLA-G positivity (any intensity > 1%) varied according to the antibody employed, identifying: 8 4H84 positive, 34 MEM-G/2 positive, 6 double-positive and 52 negative cases. Correlation with clinico-pathologic data showed a significant association with a poor tumor differentiation in stage III right-sided CRC subgroup (p = 0.043), while no other pathologic variable was significantly associated. Survival analysis revealed a reduced disease-free survival rate (HR 4.304613; p = 0.031) in the subgroup of CRC-related death cases, while no correlations were observed considering the whole series and the overall survival. In conclusion, HLA-G is a promising CRC prognostic marker however much work is still required regarding technical aspects and evaluation of expression.
Perioperative functional imaging after extracranial carotid endarterectomy for the detection of cerebral hyperperfusion syndrome
Authors: Hoffmann-Wieker Carola Marie , Ronellenfitsch U. , Rengier F. , Otani K. , Stepina E. , Böckler D. 
Published: July 2022

Abstract

Introduction
SyngoDynaPBVNeuro® is a tool to perform cerebral blood volume (CBV) measurements intraoperatively by functional imaging producing CT-like images. Aim of this prospective study was to analyze the clinical relevance and benefit of CBV measurement with regard to neurological complications like cerebral hyperfusion syndrome (CHS).

Methods
Forty-five patients undergoing endarterectomy (CEA) of the internal carotid artery were included; functional imaging with CBV measurement was performed before and after CEA. To evaluate and analyze CBV, six regions of interest (ROI) were identified for all patients with an additional ROI in patients with symptomatic ICA stenosis and previous stroke. The primary endpoint of the study was a perioperative change in CBV measurements. Secondary outcomes were incidence of stroke, TIA, CHS, and perioperative morbidity and mortality.

Results
Thirty-day stroke incidence and thirty-day mortality were 0%. Thirty-day morbidity was 6.7%. Two patients from the asymptomatic group suffered from transient neurological symptoms without signs of intracerebral infarction in CT or MR scan, meeting diagnostic criteria for CHS. In 83.3% of ROIs in these patients, an increase of blood volume was detected. Overall, 26.7% patients suffered from unilateral headache as expression of potential CHS. A total of 69.4% of ROIs in patients with postoperative unilateral headache showed an increase when comparing pre- and postoperative CBV measurements.

Conclusion
The results show that increased CBV measured by functional imaging is a possible surrogate marker of neurological complications like CHS after CEA. By using intraoperative CBV measurement, the risk of CHS can be estimated early and appropriate therapeutic measures can be applied.
Risk of all-cause mortality according to the European Society of Cardiology risk categories in individuals with type 2 diabetes: the Renal Insufficiency And Cardiovascular Events (RIACE) Italian Multicenter Study
Authors: Orsi Emanuela , Solini Anna , Bonora Enzo , Vitale Martina , Garofolo Monia , Fondelli Cecilia , Trevisan Roberto , Vedovato Monica , Cavalot Franco , Laviola Luigi , Morano Susanna , Pugliese Giuseppe ,   for the Renal Insufficiency And Cardiovascular Events (RIACE) Study Group
Published: July 2022

Abstract
Aims
The 2019 and 2021 European Society of Cardiology (ESC) classifications stratified patients with type 2 diabetes into three categories according to the 10-year risk of death from atherosclerotic cardiovascular disease (ASCVD). The very high-risk category included individuals with established ASCVD, target organ damage (TOD), and/or, in the 2019 classification only, ≥ 3 additional ASCVD risk factors. We assessed risk of all-cause mortality according to the two ESC classifications in the Renal Insufficiency And Cardiovascular Events cohort.

Methods
Participants (n = 15,773) were stratified based on the presence of ASCVD, TOD, and ASCVD risk factors at baseline (2006–2008). Vital status was retrieved in 2015.

Results
Less than 1% of participants fell in the moderate-risk category. According to the 2019 classification, ~ 1/3 fell in the high-risk and ~ 2/3 in the very high-risk category, whereas the opposite occurred with the 2021 classification. Mortality risk increased across categories according to both classifications. Among very high-risk patients, mortality was much lower in those with ≥ 3 additional ASCVD risk factors and almost equal in those with TOD and ASCVD ± TOD, using the 2019 classification, whereas it was much higher in those with ASCVD + TOD and, to a lesser extent, TOD only than in those with ASCVD only, using the 2021 classification.

Conclusions
The negligible number of moderate-risk patients suggests that these classifications might overestimate risk of ASCVD death. Downgrading patients with ≥ 3 additional ASCVD risk factors to the high-risk category is consistent with mortality data. Risk of death is very high in the presence of TOD irrespective of established ASCVD.
Trial registration: ClinicalTrials.gov, NCT00715481.
Heart rate thresholds for cardiovascular risk and sympathetic activation in the metabolic syndrome
Authors: Seravalle Gino , Vanoli Jennifer , Molisano Concetta , Merati Valeria , Grassi Guido 
Published: July 2022

Abstract
Aims
We examined whether to what extent resting heart rate (HR) values are capable to reflect in the metabolic syndrome (MS) a different degree of sympathetic activation. We also thought to determine at which HR cutoff values the sympathetic nervous system becomes more activated in the MS.

Methods
In 70 MS patients aged 55.5 ± 1.8 (mean ± SEM) years we evaluated muscle sympathetic nerve traffic (MSNA, microneurography) and venous plasma norepinephrine (NE, HPLC assay), subdividing the study population in three different subgroups according to resting clinic and 24-h HR values (< 70, 70–79 and ≥ 80 beats/min).

Results
MS patients with clinic HR values ≥ 80 beats/min displayed MSNA and NE values significantly increased when compared to those found in MS with HR between 70 and 79 beats/min or below 70 beats/min (MSNA: 55.2 ± 0.9 vs 44.6 ± 0.6 and 39.2 ± 0.6 bursts/min, P < 0.01, NE: 403.9 ± 6.9 vs 330.1 ± 4.3 and 258.3 ± 6.8 pg/ml, respectively, P < 0.01). A similar behavior was observed for 24-h HR. In the group as a whole both MSNA and plasma NE showed highly significant direct relationships with clinic HR, the correlation being similar for MSNA and NE (r = 0.89 and r = 0.91, P < 0.01 for both) Similar significant relationships were also found between 24-h HR values and MSNA or NE.

Conclusions
In the MS HR values ≥ 80 beats/min are associated with an increased sympathetic activation, both when assessed by direct recording of MSNA and when evaluated as plasma NE. The sympathetic overdrive parallels for magnitude the HR elevations, this being the case for both clinic and 24-h HR.
Prognostic value of lymph node involvement in oral squamous cell carcinoma
Authors: Voss Jan Oliver , Freund Lea , Neumann Felix , Mrosk Friedrich , Rubarth Kerstin , Kreutzer Kilian , Doll Christian , Heiland Max , Koerdt Steffen 
Published: July 2022

Abstract
Objectives
Different parameters have been identified in patients with oral squamous cell carcinomas (OSCC) that have a serious impact on survival, including residual tumour and extracapsular spread. Moreover, other factors, including the lymph node ratio (LNR) and lymph node yield (LNY), have been suggested as prognostic markers.

Material and methods
This retrospective study included patients diagnosed with OSCC and cervical lymph node metastases during the years 2010–2020. Patients’ records were evaluated regarding lymph node status, final therapy regime, tumour recurrence, time to death, tumour association with death, disease-free survival (DSF), and overall survival (OS).

Results
In 242 patients with a mean age of 63.57 ± 11.24 years, treated either by selective neck dissection (SND; n = 70) or by modified radical neck dissection (MRND; n = 172), 5772 lymph nodes were detected. The LNR and LNY were identified as independent risk factors in OS and DFS. The optimal cut-off point for the LNY was ≥ 17 lymph nodes in the SND and ≥ 27 lymph nodes in the MRND group.
The metastatic lymph node clearance (MLNC) was established as a score to relate the LNR and LNY to the extent of lymph node removal. Survival analysis showed statistically significant differences among score levels.

Conclusions
As information about the extent of nodal dissection is excluded from LNR and LNY, we propose the use of a new scoring system comprising individual cut-off values for LNY and LNR with regard to the extent of neck dissection.

Clinical Relevance
MLNC might help to identify high-risk OSCC patients with metastatic lymph nodes.