bluuebunny/crossref_metadata_2025_split huggingface dataset:
A clinical, radiological and isokinetic evaluation in patients with recurrent patellar dislocation undergoing MPFL reconstruction according to Avikainen: a prospective study evaluating early degenerative changes after a minimum 10-year follow-up period
Authors: Małecki Krzysztof , Niedzielski Kryspin , Korczyc-Stępnicka Agnieszka , Stelmach Wojciech , Beczkowski Jacek , Fabiś Jarosław , Fabiś-Strobin Anna 
Published: February 2023

Abstract
Background
The aim of the study was to conduct a comprehensive functional and radiological follow-up assessment in patients at least 10 years after adductor magnus MPFL reconstruction, and to assess the presence of early degenerative changes.

Methods
The mean age at the time of surgery was 16 years (range: 8 to 18 years, SD 2.5). The follow-up examination was performed at least 10 years following adductor magnus MPFL reconstruction (mean 11 years). Twenty-one patients (26 operated knees) attended the follow-up. The mean age at follow-up was 25.1 years (range 20–29 years).

Results
The significant improvement observed at 3 years, indicated by the Kujala and Lysholm scores, was maintained after 10 years of follow-up (p < 0.001). A single recurrence of dislocation was noted in three patients. A significant improvement in radiological parameters was noted. No significant difference in the incidence of chondromalacia, of any degree, was observed compared to controls.
Significantly higher quadriceps peak torque was noted for both angular velocities (60 and 180°/sec) compared to the preoperative readings (p < 0.001). Knee flexors were found to be significantly stronger at both 60 and 180°/sec at 10 years follow-up examination (p = 0.008 and p < 0.001 respectively).

Conclusion
The use of MPFL reconstruction according to Avikainen yields improvements in clinical and radiological results which are maintained throughout the observation period. No significantly greater articular cartilage degeneration was noted in patients after surgical treatment for recurrent patellar dislocation compared to healthy peers.

Trial registration
Registered on Clinical Trails.gov with ID: PMMHRI-BCO.67/2021-A.
Plantamajoside alleviates hypoxia-reoxygenation injury through integrin-linked kinase/c-Src/Akt and the mitochondrial apoptosis signaling pathways in H9c2 myocardial cells
Authors: Du Yuying , Li Jia , Cai Chao , Gong Fanying , Zhou Guoliang , Liu Fang , Wu Qiang , Liu Fuming 
Published: February 2023

AbstractMyocardial ischemia–reperfusion injury(MIRI) is one of the common complications after myocardial infarction surgery, Oxidative stress is among the main mechanisms of myocardial ischemia–reperfusion injury. Plantamajoside (PMS), the main effective ingredient in the genus Plantain, has been reported to possess an antioxidation, anti-inflammatory and anti-apoptosis role. However, whether PMS can attenuate myocardial ischemia–reperfusion injury is not yet known. Herein, we explored the effects of PMS on hypoxia-reoxygenation (H/R) injury in H9c2 cardiomyocytes and the underling molecular mechanisms of the treatment. Network pharmacological analysis screened the top 31 key genes in the treatment of MIRI disease treated with PMS, and the result of molecular docking further illustrated the roles that the PMS play in the treatment of MIRI through its interference with integrin-linked kinase (ILK) target protein. PMS was not cytotoxic in the concentration range of 5–40 μM and increased cell survival after H/R injury in a concentration-dependent manner without affecting proliferation or growth. PMS significantly reduced the levels of lactate dehydrogenase, malonic dialdehyde, reactive oxygen species and cell apoptosis, and increased soperoxide dismutase activity compared with those of the H/R injury group. PMS promoted the protein and mRNA expression of ILK and Bcl-2, the protein expression of p-Akt, and reduced the protein and mRNA expression of Bax, Caspase-3, and Cytochrome c, the protein expression of p–c-Src. PMS has protective effects against H/R injury in H9c2 cells, and its protective mechanism may be related to reactive oxygen species clearance, activation of the ILK/c-Src/Akt pathway and inhibition of the mitochondrial apoptosis.
Mining of EHR for interface terminology concepts for annotating EHRs of COVID patients
Authors: Keloth Vipina K. , Zhou Shuxin , Lindemann Luke , Zheng Ling , Elhanan Gai , Einstein Andrew J. , Geller James , Perl Yehoshua 
Published: February 2023

Abstract
Background
Two years into the COVID-19 pandemic and with more than five million deaths worldwide, the healthcare establishment continues to struggle with every new wave of the pandemic resulting from a new coronavirus variant. Research has demonstrated that there are variations in the symptoms, and even in the order of symptom presentations, in COVID-19 patients infected by different SARS-CoV-2 variants (e.g., Alpha and Omicron). Textual data in the form of admission notes and physician notes in the Electronic Health Records (EHRs) is rich in information regarding the symptoms and their orders of presentation. Unstructured EHR data is often underutilized in research due to the lack of annotations that enable automatic extraction of useful information from the available extensive volumes of textual data.

Methods
We present the design of a COVID Interface Terminology (CIT), not just a generic COVID-19 terminology, but one serving a specific purpose of enabling automatic annotation of EHRs of COVID-19 patients. CIT was constructed by integrating existing COVID-related ontologies and mining additional fine granularity concepts from clinical notes. The iterative mining approach utilized the techniques of 'anchoring' and 'concatenation' to identify potential fine granularity concepts to be added to the CIT. We also tested the generalizability of our approach on a hold-out dataset and compared the annotation coverage to the coverage obtained for the dataset used to build the CIT.

Results
Our experiments demonstrate that this approach results in higher annotation coverage compared to existing ontologies such as SNOMED CT and Coronavirus Infectious Disease Ontology (CIDO). The final version of CIT achieved about 20% more coverage than SNOMED CT and 50% more coverage than CIDO. In the future, the concepts mined and added into CIT could be used as training data for machine learning models for mining even more concepts into CIT and further increasing the annotation coverage.

Conclusion
In this paper, we demonstrated the construction of a COVID interface terminology that can be utilized for automatically annotating EHRs of COVID-19 patients. The techniques presented can identify frequently documented fine granularity concepts that are missing in other ontologies thereby increasing the annotation coverage.
Patients’ and healthcare professionals’ perceived facilitators and barriers for shared decision-making for frail and elderly patients in perioperative care: a scoping review
Authors: Vogel Amyn , Guinemer Camille , Fürstenau Daniel 
Published: February 2023

AbstractBackgroundShared decision-making (SDM) in perioperative care, is an organizational approach to instituting sharing of information and decision-making around surgery. It aims at enabling patient autonomy and patient-centered care. Frail and elderly patients suffering from multiple health conditions and increased surgical vulnerability might particularly benefit from SDM. However, little is known about the facilitators and barriers to implementing SDM in perioperative care for the specific needs of frail and elderly patients.Our objective is twofold: First, we aim at collecting, analyzing, categorizing, and communicating facilitators and barriers. Second, we aim at collecting and mapping conceptual approaches and methods employed in determining and analyzing these facilitators and barriers.MethodsThe search strategy focused on peer-reviewed studies. We employed a taxonomy which is based on the SPIDER framework and added the items general article information, stakeholder, barriers/facilitators, category, subcategory, and setting/contextual information. This taxonomy is based on preceding reviews. The scoping review is reported under the Preferred Reporting Items for Systematic Reviews and Meta-analyses extension for Scoping Reviews. Based on the databases MEDLINE, Embase, CINAHL, and Web of Science, we screened 984 articles, identified, and reviewed 13 original studies.ResultsWithin this review, two primary facilitators concerning patients’ willingness to participate in SDM emerged: Patients want to be informed on their medical condition and procedures. Patients prefer sharing decisions with healthcare professionals, compared to decision-making solely by patients or decision-making solely by healthcare professionals. Communication issues and asymmetric power relationships between patients and clinical healthcare professionals are barriers to SDM. Regarding the methodological approaches, the evaluation of the conceptual approaches demonstrates that the selected articles lack employing a distinct theoretical framework. Second, the selected studies mainly used surveys and interviews, observational studies, like ethnographic or video-based studies are absent.ConclusionDiverging findings perceived by patients or clinical healthcare professionals were identified. These imply that SDM research related to elderly and frail patients should become more encompassing by employing research that incorporates theory-based qualitative analysis, and observational studies of SDM consultations for understanding practices by patients and clinical healthcare professionals. Observational studies are particularly relevant as these were not conducted.Trial registrationhttps://osf.io/8fjnb/
Rare mutation-dominant compound EGFR-positive NSCLC is associated with enriched kinase domain-resided variants of uncertain significance and poor clinical outcomes
Authors: Zhao Weixin , Song Ailing , Xu Yang , Wu Qian , Liu Cuicui , Yin Jiani C. , Ou Qiuxiang , Wu Xue , Shao Yang , Zhao Xinmin 
Published: February 2023

Abstract
Background
Compound epidermal growth factor receptor (EGFR) mutations are less responsive to tyrosine kinase inhibitors (TKIs) than single EGFR mutations in non-small cell lung cancer (NSCLC). However, the detailed clinical characteristics and prognosis of various compound EGFR mutations remain to be elucidated.

Methods
We retrospectively studied the next-generation sequencing (NGS) data of treatment-naïve tumors from 1025 NSCLC patients with compound EGFR mutations, which were sub-categorized into different combinations of common mutations (19-Del and EGFR exon 21 p.L858R), rare mutations, and variants of uncertain significance (VUSs). Prognosis and drug resistance to first-line TKIs were analyzed in 174 and 95 patients, respectively.

Results
Compound EGFR mutations were enriched with EGFR exon 21 p.L858R and rare mutations, but not 19-Del (P < 0.001). The common + rare and rare + rare subtypes had fewer concurrent mutations in the PI3K pathway (P = 0.032), while the rare + rare and common + VUSs subtypes showed increased association with smoking- and temozolomide-related mutational signatures, respectively (P < 0.001). The rare mutation-dominant subtypes (rare + VUSs and rare + rare) had the worst clinical outcomes to first-line TKIs (P < 0.001), which was further confirmed using an external cohort (P = 0.0066). VUSs in the rare + VUSs subtype selectively reside in the EGFR kinase domain (P < 0.001), implying these tumors might select additional mutations to disrupt the regulation/function of the kinase domain.

Conclusions
Different subtypes of compound EGFR mutations displayed distinct clinical features and genetic architectures, and rare mutation-dominant compound EGFR mutations were associated with enriched kinase domain-resided VUSs and poor clinical outcomes. Our findings help better understand the oncogenesis of compound EGFR mutations and forecast prognostic outcomes of personalized treatments.
Targeted plasma proteomics reveals signatures discriminating COVID-19 from sepsis with pneumonia
Authors: Palma Medina Laura M. , Babačić Haris , Dzidic Majda , Parke Åsa , Garcia Marina , Maleki Kimia T. , Unge Christian , Lourda Magda , Kvedaraite Egle , Chen Puran , Muvva Jagadeeswara Rao , Cornillet Martin , Emgård Johanna , Moll Kirsten ,   Karolinska K. I./K. COVID-19 Study Group, Michaëlsson Jakob , Flodström-Tullberg Malin , Brighenti Susanna , Buggert Marcus , Mjösberg Jenny , Malmberg Karl-Johan , Sandberg Johan K. , Gredmark-Russ Sara , Rooyackers Olav , Svensson Mattias , Chambers Benedict J. , Eriksson Lars I. , Pernemalm Maria , Björkström Niklas K. , Aleman Soo , Ljunggren Hans-Gustaf , Klingström Jonas , Strålin Kristoffer , Norrby-Teglund Anna 
Published: February 2023

AbstractBackgroundCOVID-19 remains a major public health challenge, requiring the development of tools to improve diagnosis and inform therapeutic decisions. As dysregulated inflammation and coagulation responses have been implicated in the pathophysiology of COVID-19 and sepsis, we studied their plasma proteome profiles to delineate similarities from specific features.MethodsWe measured 276 plasma proteins involved in Inflammation, organ damage, immune response and coagulation in healthy controls, COVID-19 patients during acute and convalescence phase, and sepsis patients; the latter included (i) community-acquired pneumonia (CAP) caused by Influenza, (ii) bacterial CAP, (iii) non-pneumonia sepsis, and (iv) septic shock patients.ResultsWe identified a core response to infection consisting of 42 proteins altered in both COVID-19 and sepsis, although higher levels of cytokine storm-associated proteins were evident in sepsis. Furthermore, microbiologic etiology and clinical endotypes were linked to unique signatures. Finally, through machine learning, we identified biomarkers, such as TRIM21, PTN and CASP8, that accurately differentiated COVID-19 from CAP-sepsis with higher accuracy than standard clinical markers.ConclusionsThis study extends the understanding of host responses underlying sepsis and COVID-19, indicating varying disease mechanisms with unique signatures. These diagnostic and severity signatures are candidates for the development of personalized management of COVID-19 and sepsis.
Risks of stroke, its subtypes and atrial fibrillation associated with glucagon-like peptide 1 receptor agonists versus sodium-glucose cotransporter 2 inhibitors: a real-world population-based cohort study in Hong Kong
Authors: Lui David Tak Wai , Tang Eric Ho Man , Wu Tingting , Au Ivan Chi Ho , Lee Chi Ho , Woo Yu Cho , Tan Kathryn Choon Beng , Wong Carlos King Ho 
Published: February 2023

Abstract
Background
There are limited data on head-to-head comparative risk of stroke between sodium-glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA). We compared risk of stroke with its subtypes and incident atrial fibrillation (AF) between them.

Methods
A population-based, retrospective cohort of patients with type 2 diabetes between 2008 and 2020 were identified from the electronic health records of Hong Kong Hospital Authority. Patients who received SGLT2i or GLP-1RA were matched pairwise by propensity score. Risks of stroke and AF were evaluated by hazard ratios (HRs) from the Cox proportional hazard regression models.

Results
A total of 5840 patients (2920 SGLT2i users; 2920 GLP-1RA users) were included (mean age 55.5 years, 56.1% men, mean HbA1c 8.9% and duration of diabetes 13.7 years). Upon median follow-up of 17 months, there were 111 (1.9%) events of stroke (SGLT2i: 62, 2.1%; GLP-1RA: 49 1.7%). SGLT2i users had comparable risk of all stroke as GLP-1RA users (HR 1.46, 95% CI 0.99–2.17, p = 0.058). SGLT2i users had higher risk of ischemic stroke (HR 1.53, 95% CI 1.01–2.33, p = 0.044) but similar risk of hemorrhagic stroke compared to GLP-1RA users. Although SGLT2i was associated with lower risk of incident AF (HR 0.43, 95% CI 0.23–0.79, p = 0.006), risk of cardioembolic stroke was similar.

Conclusions
Our real-world study demonstrated that GLP-1RA use was associated with lower risk of ischemic stroke, despite the association between SGLT2i use and lower risk of incident AF. There was no significant difference in hemorrhagic stroke risk. GLP-1RA may be the preferred agent for patients with type 2 diabetes at risk of ischemic stroke.
Effects of Fe2+ addition to sugarcane molasses on poly-γ-glutamic acid production in Bacillus licheniformis CGMCC NO. 23967
Authors: Guo Lifei , Lu Liang , Wang Huichao , Zhang Xiaoxing , Wang Genan , Zhao Tingbin , Zheng Guobao , Qiao Changsheng 
Published: February 2023

Abstract
Background
Poly-γ-glutamic acid (γ-PGA) is biodegradable, water-soluble, environment-friendly, and edible. Consequently, it has a variety of industrial applications. It is crucial to control production cost and increase output for industrial production γ-PGA.

Results
Here γ-PGA production from sugarcane molasses by Bacillus licheniformis CGMCC NO. 23967 was studied in shake-flasks and bioreactors, the results indicate that the yield of γ-PGA could reach 40.668 g/L in a 5L stirred tank fermenter. Further study found that γ-PGA production reached 70.436 g/L, γ-PGA production and cell growth increased by 73.20% and 55.44%, respectively, after FeSO4·7H2O was added. Therefore, we investigated the metabolomic and transcriptomic changes following FeSO4·7H2O addition. This addition resulted in increased abundance of intracellular metabolites, including amino acids, organic acids, and key TCA cycle intermediates, as well as upregulation of the glycolysis pathway and TCA cycle.

Conclusions
These results compare favorably with those obtained from glucose and other forms of biomass feedstock, confirming that sugarcane molasses can be used as an economical substrate without any pretreatment. The addition of FeSO4·7H2O to sugarcane molasses may increase the efficiency of γ-PGA production in intracellular.
A versatile multimodal chromatography strategy to rapidly purify protein nanostructures assembled in cell lysates
Authors: Winter Daniel L. , Lebhar Hélène , McCluskey Joshua B. , Glover Dominic J. 
Published: February 2023

AbstractBackgroundProtein nanostructures produced through the self-assembly of individual subunits are attractive scaffolds to attach and position functional molecules for applications in biomaterials, metabolic engineering, tissue engineering, and a plethora of nanomaterials. However, the assembly of multicomponent protein nanomaterials is generally a laborious process that requires each protein component to be separately expressed and purified prior to assembly. Moreover, excess components not incorporated into the final assembly must be removed from the solution and thereby necessitate additional processing steps.ResultsWe developed an efficient approach to purify functionalized protein nanostructures directly from bacterial lysates through a type of multimodal chromatography (MMC) that combines size-exclusion, hydrophilic interaction, and ion exchange to separate recombinant protein assemblies from excess free subunits and bacterial proteins. We employed the ultrastable filamentous protein gamma-prefoldin as a material scaffold that can be functionalized with a variety of protein domains through SpyTag/SpyCatcher conjugation chemistry. The purification of recombinant gamma-prefoldin filaments from bacterial lysates using MMC was tested across a wide range of salt concentrations and pH, demonstrating that the MMC resin is robust, however the optimal choice of salt species, salt concentration, and pH is likely dependent on the protein nanostructure to be purified. In addition, we show that pre-processing of the samples with tangential flow filtration to remove nucleotides and metabolites improves resin capacity, and that post-processing with Triton X-114 phase partitioning is useful to remove lipids and any remaining lipid-associated protein. Subsequently, functionalized protein filaments were purified from bacterial lysates using MMC and shown to be free of unincorporated subunits. The assembly and purification of protein filaments with varying amounts of functionalization was confirmed using polyacrylamide gel electrophoresis, Förster resonance energy transfer, and transmission electron microscopy. Finally, we compared our MMC workflow to anion exchange chromatography with the purification of encapsulin nanocompartments containing a fluorescent protein as a cargo, demonstrating the versatility of the protocol and that the purity of the assembly is comparable to more traditional procedures.ConclusionsWe envision that the use of MMC will increase the throughput of protein nanostructure prototyping as well as enable the upscaling of the bioproduction of protein nanodevices.Graphic Abstract
When AHR signaling pathways meet viral infections
Authors: Hu Jieke , Ding Yuan , Liu Wen , Liu Shuzhen 
Published: February 2023

AbstractAryl hydrocarbon receptor (AHR) is a ligand-dependent transcriptional factor widely expressed among immune, epithelial, endothelial and stromal cells in barrier tissues. It can be activated by small molecules provided by pollutants, microorganisms, food, and metabolism. It has been demonstrated that AHR plays an important role in modulating the response to many microbial pathogens, and the abnormal expression of AHR signaling pathways may disrupt endocrine, cause immunotoxicity, and even lead to the occurrence of cancer. Most humans are infected with at least one known human cancer virus. While the initial infection with these viruses does not cause major disease, the metabolic activity of infected cells changes, thus affecting the activation of oncogenic signaling pathways. In the past few years, lots of studies have shown that viral infections can affect disease progression by regulating the transmission of multiple signaling pathways. This review aims to discuss the potential effects of virus infections on AHR signaling pathways so that we may find a new strategy to minimize the adverse effects of the AHR pathway on diseases.