bluuebunny/crossref_metadata_2025_split huggingface dataset:
Circular disruption: Digitalisation as a driver of circular economy business models
Authors: Neligan Adriana , Baumgartner Rupert J. , Geissdoerfer Martin , Schöggl Josef‐Peter 
Published: May 2022

AbstractNew circular business models can evolve at all stages of the life cycle of a product. Digitalisation can drive disruptive innovations, new business models and novel ways of collaboration and thus can accelerate the economic transition to more resource‐efficient and circular production systems. Yet, there is little empirical research on the enabling role of digitalisation for a circular economy. To address this gap, this paper investigates the role of digitalisation in facilitating circular business models, based on the empirical analysis of a data set of 599 German manufacturing firms and 296 industrial service providers. While relatively few German firms rely on new business models to foster their resource efficiency strategy, we find this share higher for companies with a strong digital focus in the manufacturing sector. This suggests that digitalisation can indeed be a driving force for the implementation of circular business models.
SPP1 promotes radiation resistance through JAK2/STAT3 pathway in esophageal carcinoma
Authors: Wang Meijie , Sun Xiaozheng , Xin Huixian , Wen Zhihua , Cheng Yufeng 
Published: May 2022

AbstractBackgroundTherapeutic resistance to radiotherapy is one of the major obstacles in clinical practice that significantly affect the therapeutic efficiency and prognosis of human esophageal carcinoma (ESCA). Thus, it is critical to understand the molecular mechanisms of radiation resistance in ESCA. Secreted phosphoprotein 1 (SPP1) plays an essential role in various human cancers, but its role in radiation resistance remains unclear.MethodCell culture and transfection; Cell Counting Kit‐8 (CCK‐8) assays; EdU incorporation assays; Patient sample collection and medical records review; Transwell assays; Colony formation assays; Wound healing assays; Western blot; Immunofluorescence; Immunohistochemistry; Irradiation; Flow cytometry; Animal studies; Human Apoptosis Array Kit; Bioinformatics.ResultIn the current study, we reported the novel phenomenon that radiation‐treated human ESCA cells upregulated SPP1 expression, which in turn contributed to the ESCA resistance to radiotherapy. We also reported the tumor‐promoting effect of SPP1 in ESCA systematically and comprehensively. Furthermore, subsequent studies by knocking down or overexpressing SPP1 in human ESCA cells showed that SPP1 could facilitate the repair of DNA damage and the survival of tumor cells post‐radiation in ESCA, which might contribute to the development of radiation resistance during the radiotherapy process. More detailed investigations on the downstream molecular pathway suggested that radiation could increase the phosphorylation level of JAK2 and STAT3 by increasing SPP1 expression. Further in vivo validation using a mouse ESCA xenograft model showed that SPP1 overexpression significantly increased tumor volume while either SPP1 knockdown or pharmacological inhibition of the JAK2‐STAT3 pathway reduced tumor volume in a synergistic manner with radiotherapy.ConclusionCollectively, these findings suggested that the SPP1/JAK2/STAT3 axis is a critical player in ESCA progression and radiation resistance, which is a potential therapeutic target for combined therapy with the standard radiotherapy regimen to improve curative effect and increase patients' survival with ESCA.
Identifying tumor antigens and immuno‐subtyping in colon adenocarcinoma to facilitate the development of mRNA vaccine
Authors: Tan Huaicheng , Yu Ting , Liu Chunhua , Wang Yang , Jing Fangqi , Ding Zhenyu , Liu Jiyan , Shi Huashan 
Published: May 2022

AbstractThe mRNA vaccine has provided a promising approach for cancer immunotherapies. However, only a few mRNA vaccines have been developed against colon adenocarcinoma (COAD). Screening potential targets for mRNA vaccines from numerous candidates is a substantial challenge. Considering the tumor heterogeneity, only a subset of patients might respond to vaccinations. This study was conducted to identify potential candidates for mRNA vaccines, and distinguish appropriate subgroups of COAD patients for vaccination. A total of five tumor antigens with prognostic values were identified, including IGF2BP3, DPCR1, HOXD10, TRIM7, and ZIC5. The COAD patients were stratified into five immune subtypes (IS1‐IS5), according to consensus clustering analysis. Higher tumor mutation burden (TMB) was observed in IS1 and IS5 subtypes. The IS1 and IS5 subtypes have shown the baseline of immune‐hot tumor microenvironment, while other subtypes displayed immune desert phenotype. Distinct expressions of immune checkpoints (ICPs)‐related genes and immunogenic cell death (ICD) modulators were observed among five immune subtypes. Finally, the immune landscape was conducted to narrow the immune components for better personalized mRNA‐based vaccination. The IFIT3, PARP9, TAP1, STAT1, and OAS2 were confirmed as hub genes, and COAD patients with higher expressions of these genes might be more appropriate for mRNA vaccination. In conclusion, the IGF2BP3, DPCR1, HOXD10, TRIM7, and ZIC5 were identified as potential candidates for developing mRNA vaccines against COAD, and patients in IS1 and IS5 subtypes might respond better to mRNA vaccination.
Isolation and Structural Characterization of Two Polysaccharides from Dracocephalum moldavica and Their Anti‐Complementary Activity
Authors: Hu Zhengyu , Wang Jiaming , Jin Long , Duan Yuanqi , Zhang Xiaohui , Sun Jinfeng , Zhou Wei , Li Gao 
Published: May 2022

AbstractThe two novel polysaccharides, DMP‐1 and DMP‐2, with molecular weights of 4.1553×105 kDa and 1.9764×105 kDa, respectively, were isolated from Dracocephalum moldavica. The structural characterization indicated that DMP‐1 and DMP‐2 shared a similar backbone consisting of →5)‐Araf‐(1→, Manp‐(1→, Glcp‐(1→, →2)‐Manp‐(1→, →6)‐Glcp‐(1→ and →3,6)‐Galp‐(1→ with a different molar ratios and triple‐helix structures with α‐ and β‐type glycosidic bonds. The anti‐complementary activity evaluation showed that DMP‐1 and DMP‐2 had strong complement inhibition through the classical pathway (CP), alternative pathway (AP) and lectin pathway (LP). Mechanistic studies indicated that DMP‐1 can block the activation cascade of the complement system by targeting C2, C3, C5, C9, Factor B and Factor P, and that DMP‐2 inhibited complement activation by blocking C2, C3, C4, C5, C9 and Factor B.
Real‐world experience with the new Watchman FLX device: Data from two high‐volume Sicilian centers. The FLX‐iEST registry
Authors: Vizzari Giampiero , Grasso Carmelo , Sardone Andrea , Mazzone Paolo , Laterra Giulia , Frazzetto Marco , Sacchetta Giorgio , Micari Antonio , Tamburino Corrado , Contarini Marco 
Published: May 2022

AbstractIntroductionThe Watchman‐FLX left atrial appendage closure (LAAC) device presents innovative features: higher conformability, reduced length, closed distal "flex‐ball" during deployment, and flattened surface. We report our real‐world experience with the Watchman‐FLX device in two centers with consolidated LAAC expertise.MethodsWe enrolled 200 consecutive Watchman‐FLX patients (2019–2021) in a nonrandomized double‐center registry; procedural data and follow‐up for midterm clinical outcomes were collected. A control group of 100 patients treated with first‐generation Watchman (2.5) was included.ResultsAccording to mean CHAD2DS2‐VASc (5 ± 1.40) and HAS‐BLED (3.8 ± 1.01) scores, the population included in this study was at high risk: 29% had a previous stroke and 56.5% a bleeding event. Main LAAC indications were symptomatic hemorrhage (39.5%), need for triple antithrombotic therapy (39%), gastrointestinal bleeding (32%), and oral anticoagulation intolerance (18%). Transesophageal echocardiography guidance was followed in 93% of cases (48% in general anesthesia and 45% under conscious sedation). Repositioning an FLX device was required in 20% of cases and no complication occurred. In 96% of patients, the first selected device was delivered, while in 4% a device size change was required after the first choice (7% with Watchman 2.5). Peridevice leaks (<5 mm) were found postimplant in two cases (1%). Overall, the procedural success rate was 99.5%. One patient's procedure was unsuccessful (0.5%), due to left atrial appendage (LAA) anatomy; differently, the mean failure rate with Watchman 2.5 was 2%. No device embolization was reported. Complications (8.5%) were mainly related to the access site (3%); major bleedings (1%), and in‐hospital death (0.5%) rarely occurred. After a follow‐up of 272 ± 173 days, 2.3% of cases experienced a non‐device‐related stroke and 0.6% fatal bleeding.ConclusionOur registry showed a high procedural success rate of the Watchman‐FLX in a high‐risk population. According to our experience, the main advantages include easy implanting and repositioning, absence of embolization, good LAA sealing, and low rate of complications in the follow‐up period.
Hyaluronic acid augmentation pharyngoplasty complicated by retropharyngeal abscess and grisel syndrome: Case report and literature review
Authors: Alkhaldi Abdullah , Alwadi Fahad , Alenezi Mazyad , Alshammari Jaber 
Published: May 2022

AbstractAugmentation pharyngoplasty, in which tissue filler or grafts are used to augment the posterior nasopharynx, is an accepted option to treat velopharyngeal insufficiency. It is generally well tolerated and safe with limited side effects. In this study, we describe a case of a retropharyngeal abscess and Grisel syndrome following hyaluronic acid augmentation pharyngoplasty. Grisel syndrome is a serious condition that requires early diagnosis and prompt intervention to prevent further complications.
Enriching Cations Using Electric Field Gradients Generated by Bipolar Electrodes in the Absence of Buffer
Authors: Thompson Jonathan R. , Crooks Richard M. 
Published: May 2022

AbstractWe report that ionic current gradients and corresponding electric field gradients formed at bipolar electrodes are useful for enriching cations up to ∼350‐fold at specific locations in microfluidic devices. The enrichment mechanism is determined by collecting current data, measuring solution conductivity, and by performing pH indicator experiments. These data reveal the dynamic nature of the enrichment mechanism. Specifically, they show the complex relationship between the ionic current gradients formed at the bipolar electrode and the extent of cation enrichment. Finally, we demonstrate cation enrichment is possible in buffer‐free solutions containing up to 50.0 mM KCl. This finding is significant because it broadens the range of solutions in which membrane‐free, electrochemical separations using bipolar electrodes can be performed.
Single‐Molecule Sensing of Acidic Catecholamine Metabolites Using a Programmable Nanopore
Authors: Hu Chengzhen , Jia Wendong , Liu Yao , Wang Yuqin , Zhang Panke , Chen Hong‐Yuan , Huang Shuo 
Published: May 2022

AbstractAcidic catecholamine metabolites, which could serve as diagnostic markers for many diseases, demonstrate an importance of accurate sensing. However, they share a highly similar chemical structure, which is a challenge in the design of sensing strategies. A nanopore may be engineered to sense these metabolites in a single molecule manner. To achieve this, a recently developed programmable nano‐reactor for stochastic sensing (PNRSS) technique adapted with a phenylboronic acid (PBA) adaptor was applied. Three acidic catecholamine metabolites, including 3,4‐dihydroxyphenylacetic acid (DOPAC), 3,4‐dihydroxymandelic acid (DHMA) and 3‐methoxy‐4‐hydroxymandetic acid (VMA) were investigated by PNRSS. Specifically, DHMA, which contains an α‐hydroxycarboxylate moiety and an adjacent cis‐hydroxyl groups on its benzene ring, reports two binding modes simultaneously resolvable by PNRSS. Assisted with the high resolution of PNRSS, direct regulation of these two binding modes by pH can also be observed. A custom machine learning algorithm was also developed to achieve automatic event classification.
First phase 1 clinical study of olaparib in pediatric patients with refractory solid tumors
Authors: Takagi Masatoshi , Ogawa Chitose , Iehara Tomoko , Aoki‐Nogami Yuki , Ishibashi Eri , Imai Minoru , Kimura Toshimi , Nagata Masashi , Yasuhara Masato , Masutani Mitsuko , Yoshimura Kenichi , Tomizawa Daisuke , Ogawa Atsushi , Yonemori Kan , Morishita Aoi , Miyamoto Satoshi , Takita Junko , Kihara Tetsuro , Nobori Kiyoshi , Hasebe Kazuhisa , Miya Fuyuki , Ikeda Sadakatsu , Shioda Yoko , Matsumoto Kimikazu , Fujimura Junya , Mizutani Shuki , Morio Tomohiro , Hosoi Hajime , Koike Ryuji 
Published: May 2022

BackgroundThe survival of patients with high‐risk, refractory, relapsed, or metastatic solid tumors remains dismal. A poly(ADP‐ribose) polymerase (PARP) inhibitor could be effective for the treatment of pediatric solid tumors with defective homologous recombination.MethodsThis open‐label, multicenter phase 1 clinical trial evaluated the safety, tolerability, and efficacy of olaparib, a PARP inhibitor, in pediatric patients with refractory solid tumors to recommend a dose for Phase 2 trials. Olaparib (62.5, 125, and 187.5 mg/m2 twice daily) was administered orally every day (1 cycle = 28 days) using a standard 3 + 3 dose‐escalation design. Patients aged 3–18 years with recurrent pediatric solid tumors were eligible. Pharmacokinetic and pharmacodynamic analyses were performed.ResultsFifteen patients were enrolled and received olaparib monotherapy, which was well tolerated. The recommended phase 2 dose for daily administration was 187.5 mg/m2 twice daily. Pharmacokinetics were dose proportional. The area under the concentration‐time curve from 0 to 12 h and the peak plasma concentration for 187.5 mg/m2 twice daily in children were comparable to previous data obtained in a 200‐mg, twice‐daily cohort and lower than those in the 300‐mg twice‐daily cohort in adults. Pharmacodynamic studies demonstrated substantial inhibition of PARP activity. Two partial responses were observed in patients with Wilms tumor and neuroblastoma.ConclusionsThis report is the first clinical trial to describe the use of a PARP inhibitor as monotherapy in children. Olaparib was well tolerated, with preliminary antitumor responses observed in DNA damage response‐defective pediatric tumors.Lay summary

This Phase 1 trial evaluated the efficacy and safety of olaparib in patients with refractory childhood solid tumors.

Olaparib was well tolerated, achieving objective response in 2/15 patients.

The DNA damage response was attenuated in nearly one‐half of advanced neuroblastoma patients, demonstrating the utility of the PARP inhibitor.

The results support further investigation of olaparib as a new treatment for DNA damage‐response or repair‐defective pediatric cancers.
PD‐L1 in oral squamous cell carcinoma: A key biomarker from the laboratory to the bedside
Authors: Nocini Riccardo , Vianini Matteo , Girolami Ilaria , Calabrese Luca , Scarpa Aldo , Martini Maurizio , Morbini Patrizia , Marletta Stefano , Brunelli Matteo , Molteni Gabriele , Parwani Anil , Pantanowitz Liron , Eccher Albino 
Published: May 2022

AbstractObjectives and background: Oral squamous cell carcinoma (OSCC) is a highly malignant disease with an increasing incidence. The need to improve therapeutic strategies for patients affected by OSCC is an urgent challenge. Currently, the advent of immunotherapy represents an important step toward this aim. Programmed cell death‐ligand 1 (PD‐L1), a membrane protein that can be expressed on tumor and inflammatory cells is a key biomarker whose expression is determined by means of immunohistochemistry and is necessary for selecting patients for immunotherapy. Methods: In this study, we review the methods of PD‐L1 assessment and outcomes achieved with immunotherapy in the treatment of OSCC patients. Results: Based on a meta‐analysis we demonstrate a lack of prognostic significance of PD‐L1 in OSCC. Conclusions: We also highlight unresolved issues including difficulties in standardizing PD‐L1 evaluation and discuss future opportunities such as leveraging digital pathology.
Genotypic and environmental effects on the compounds associated with garlic flavor, health‐enhancing properties, and postharvest conservation
Authors: Barboza Karina , Salinas María Cecilia , Pérez María Belén , Dhall Rajinder Kumar , Cavagnaro Pablo Federico 
Published: May 2022

AbstractTo estimate genetic and environmental effects on traits associated with garlic (Allium sativum L.) functional value and postharvest quality, the content of total organosulfur compounds, phenolics, and solids were determined in selected garlic cultivars grown at four locations in Mendoza, Argentina. An initial experiment considered five cultivars grown in two locations and 2 yr, and a second experiment evaluated 12 cultivars across four locations. Among all the cultivars and locations, pyruvate levels, an estimator of total organosulfur content, varied more than fourfold (with a range of 24.7–111.1 μmol/g fresh weight), phenolics varied ∼fivefold (132.1–703.1 mg gallic acid equivalents/kg fresh weight), and solids varied within a range of 28.4 to 41.2%. Strong environmental influence and genotype × environment interactions were found for all traits, together accounting for 54.8 to 63.2% of the variation found for pyruvate, 63.3 to 81% for phenolics, and 35.1 to 50.8% for solids. The impact of genotype was higher for solids (31.9–50.9% of total variation) than for pyruvate (33.6–40.4%) and phenolics (16.1–34.1%). Despite the substantial environmental influence and genotype × environment interaction found, individual garlic cultivars with consistently high levels for all of these compounds were identified. We conclude that garlic pyruvate, phenolic, and solids levels are genetically and environmentally conditioned. The identified genotypes with consistently high phytochemicals content are valuable to breeders aiming at increasing garlic flavor, functional value, and postharvest quality, whereas locations yielding contrastingly high or low pyruvate levels are of interest for producing pungent and mild garlics, respectively.
Full spectrum flow cytometry and mass cytometry: A 32‐marker panel comparison
Authors: Jaimes Maria C. , Leipold Michael , Kraker Geoffrey , Amir El‐ad , Maecker Holden , Lannigan Joanne 
Published: May 2022

AbstractHigh‐dimensional single‐cell data has become an important tool in unraveling the complexity of the immune system and its involvement in homeostasis and a large array of pathologies. As technological tools are developed, researchers are adopting them to answer increasingly complex biological questions. Up until recently, mass cytometry (MC) has been the main technology employed in cytometric assays requiring more than 29 markers. Recently, however, with the introduction of full spectrum flow cytometry (FSFC), it has become possible to break the fluorescence barrier and go beyond 29 fluorescent parameters. In this study, in collaboration with the Stanford Human Immune Monitoring Center (HIMC), we compared five patient samples using an established immune panel developed by the HIMC using their MC platform. Using split samples and the same antibody panel, we were able to demonstrate highly comparable results between the two technologies using multiple data analysis approaches. We report here a direct comparison of two technology platforms (MC and FSFC) using a 32‐marker flow cytometric immune monitoring panel that can identify all the previously described and anticipated immune subpopulations defined by this panel.
Restoration and fuel hazard reduction result in equivalent reductions in crown fire behavior in dry conifer forests
Authors: Ritter Scott M. , Hoffman Chad M. , Battaglia Mike A. , Jain Theresa B. 
Published: May 2022

AbstractOver the past several decades, the management of historically frequent‐fire forests in the western United States has received significant attention due to the linked ecological and social risks posed by the increased occurrence of large, contiguous patches of high‐severity fire. As a result, efforts are underway to simultaneously reduce potential fire and fuel hazards and restore characteristics indicative of historical forest structures and ecological processes that enhance the diversity and quality of wildlife habitat across landscapes. Despite widespread agreement on the need for action, there is a perceived tension among scientists concerning silvicultural treatments that modify stands to optimally reduce potential fire behavior (fuel hazard reduction) versus those that aim to emulate historical forest structures and create structurally complex stands (restoration). In this work, we evaluated thinning treatments in the Black Hills National Forest that exemplify the extremes of a treatment continuum that ranges from fuel hazard reduction to restoration. The goal of this work was to understand how the differing three‐dimensional stand structures created by these treatment approaches altered potential fire behavior. Our results indicate that restoration treatments created higher levels of vertical and horizontal structural complexity than the fuel hazard reduction treatments but resulted in similar reductions to potential crown fire behavior. There were some trade‐offs identified as the restoration treatments created larger openings, which generated faster mean rates of fire spread; however, these increased spread rates did not translate to higher levels of canopy consumption. Overall, our results suggest that treatments can create vertical and horizontal complexity desired for restoration and wildlife habitat management while reducing fire hazard and that they can be used in concert with traditional fuel hazard reduction treatments to reduce landscape scale fire risk. We also provide some suggestions to land managers seeking to design and implement prescriptions that emulate historical structures and enhance forest complexity.