bluuebunny/crossref_metadata_2025 huggingface dataset:
Celebrity Refugees and Foreign Policy: The Politics of Fame in International Protection
Authors: Micinski Nicholas R , Lindey Caroline
Published: September 2022

Celebrity refugees are a foreign policy tool whereby states grant international protection to famous artists, scientists, or politicians in exchange for some sort of strategic value in international relations. Celebrity refugees bring different types of strategic value—intellectual or ideological capital—and serve the role in propaganda to affirm domestic legitimacy, gain strategic advantage, and embarrass enemy regimes. This article develops an analytical framework for understanding why states offer international protection to celebrities. We apply our theory to four historical cases—Enrico Fermi, Robert F. Williams, Maxim Shostakovich, and Julian Assange—to understand the impact of their strategic value for both the host state and celebrity refugees. The utility of celebrity refugees for states is a global strategy that is not constrained to the Cold War period, as one might initially expect. Ultimately, both powerful and smaller states can protect celebrity refugees to bolster their domestic legitimacy, gain scientific or military advantage, and embarrass their rivals.
Piloting a Proficiency Testing Program for Laboratory Sampling of Animal Feed Materials
Authors: Thiex Nancy J , Ramsey Charles A
Published: September 2022

Background

Laboratory sampling is a significant source of error in feed testing. Proficiency testing programs such as the Association of American Feed Control Officials Proficiency Testing Program are an effective means of assessing error in and among analytical methods. However, all proficiency test items are comminuted and blended to control variability among items, effectively minimizing sampling error. Currently there is no mechanism for monitoring sampling error among laboratories.

Objective

The objective of this work was to investigate the feasibility of a proficiency testing program for laboratory sampling methods and provide insight into a program to advance the performance of sampling in laboratories.

Methods

The study involved the fabrication of identical feed test items from feed ingredients and shipping the uncomminuted materials to volunteer laboratories. The volunteer laboratories followed in-house procedures for selecting test portions for routine feed tests. Tests on all the test portions for a single analyte were performed by a single laboratory, so that the variability in test results could be attributed to laboratory sampling processes to select test portions.

Results

The average RSD, %, for Item A and Item B, respectively, were as follows: protein, 5.08 and 5.23; non-protein nitrogen, 8.90 and 16.6; crude fat, 3.45 and 5.67; vitamin A, 33.9 and 26.9; calcium, 21.9 and 23.6; zinc, 17.9 and 27.9; and copper, 17.4 and 27.9.

Conclusion

This study suggests that a proficiency testing program for laboratory sampling is feasible with manual manufacture of the test items, and data can be used to monitor laboratory sampling proficiency and also to compare the performance of different laboratory sampling methods.

Highlights

The data illustrates that each analyte has unique distributional and compositional heterogeneity, thus unique sampling error, even when multiple analytes are determined from a single test portion.
Value choices in European COVID-19 vaccination schedules: how vaccination prioritization differs from other forms of priority setting
Authors: Wiśniowska Karolina , Żuradzki Tomasz , Ciszewski Wojciech
Published: September 2022

With the limited initial availability of COVID-19 vaccines in the first months of 2021, decision-makers had to determine the order in which different groups were prioritized. Our aim was to find out what normative approaches to the allocation of scarce preventive resources were embedded in the national COVID-19 vaccination schedules. We systematically reviewed and compared prioritization regulations in 27 members of the European Union, the United Kingdom, and Israel. We differentiated between two types of priority categories: groups that have increased infection fatality rate (IFR) compared to the average for the general population and groups chosen because their members experience increased risk of being infected (ROI). Our findings show a clear trend: all researched schedules prioritized criteria referring to IFR (being over 65 years old and coexisting health conditions) over the ROI criteria (eg occupation and housing conditions). This is surprising since, in the context of treatment, it is common and justifiable to adopt different allocation principles (eg introducing a saving more life-year approach or prioritizing younger patients). We discuss how utilitarian, prioritarian, and egalitarian principles can be applied to interpret normative differences between the allocation of curative and preventive interventions.
Effect of mood and worker incentives on workplace productivity
Authors: Coviello Decio , Deserranno Erika , Persico Nicola , Sapienza Paola
Published: September 2022

We study the causal effect of mood on the productivity of call-center workers. Mood is measured through an online “mood questionnaire” which the workers are encouraged to fill out daily. We find that better mood actually decreases worker productivity for workers whose compensation is largely fixed. The negative effect of mood is attenuated for workers whose compensation is based on performance (high-powered incentives). This finding holds both at a correlational level and in two IV settings, where mood is instrumented for by weather or, alternatively, by whether the local professional sports team played/won the day before. We rule out a number of threats to the exclusion restrictions, and discuss the mechanisms that could generate our findings (JEL J24, J28, M52, C26).
Abdominal wall intramuscular desmoid fibromatosis: a case report
Authors: Choe Erica , Kata Anna , Mahadevan Lakshmi Shree Kulumani , Bhanot Parag
Published: September 2022

Desmoid tumors are rare benign myofibroblastic neoplasms that do not have metastatic potential. In this study, we report a case of a desmoid tumor in the left rectus abdominis muscle of a female patient. Computed tomography, abdominal ultrasound and magnetic resonance imaging were obtained preoperatively. We performed a complete resection with negative margins. Microscopic evaluation revealed a desmoid tumor. To definitively diagnose abdominal wall masses, imaging modalities must be used in conjunction with clinical history and histologic findings. For these masses, surgical resection is the preferred line of treatment.
Uniform Laws and Projects
Authors: Schwenzer Ingeborg , Muñoz Edgardo
Published: September 2022

This chapter focuses on uniform laws and projects. English law was the common language of international trade for a long time. Legal development led to the creation of international instruments establishing the framework for international trade. The three international instruments are international conventions, uniform projects, and sets of rules on uniform trade practice. Additionally, the instruments address aspects of sales transactions beyond the relationship of buyer and seller in the fields of transportation and payment. The limitation of international sales law was covered at the 1974 United Nations Convention. The chapter also mentions how all uniform projects contain rules on the most important issues of validity.
General Remarks on the Ambit of Sales Law
Authors: Schwenzer Ingeborg , Muñoz Edgardo
Published: September 2022

This chapter discusses the ambit of sales law. It clarifies how sales law is expected to protect different interests between the merchants and consumers. Many civil law jurisdictions operate on the dual system which meant there are numerous laws layers to apply to a sales transaction. One of the examples is commercial codes which impose a duty to give notice of any defects if both seller and buyer are merchants. A sales contract is subject to the rules of respective commercial codes determines by the parties involved. The chapter also tackles the matter of modern consumer protection laws.
General Remarks on Contract Formation
Authors: Schwenzer Ingeborg , Muñoz Edgardo
Published: September 2022

This chapter cites the causes and considerations in the process of contract formation. Traditionally, sales law is treated as a specialized subset of contract law. The elements of cause and consideration originated from the French legal tradition. All legal systems employing the concept of cause have traditionally distinguished the classes of cause: Impulsive cause, efficient cause, and final cause. On the other hand, consideration can be described as something of value exchanged for the promise of another. The doctrine of consideration, moreover, is one of the classic differences between common law and civil law.
Offer and Acceptance
Authors: Schwenzer Ingeborg , Muñoz Edgardo
Published: September 2022

This chapter looks into offer and acceptance. Almost all legal systems act on the assumption that a contract is based on offer and acceptance. The essentialia negotii in a sales contract should be principally understood as the goods, their quantity, and the price. Additionally, an offer of a contract should be created with legally enforceable obligations. Acceptance is effectuated by express declaration, thus silence or inactivity are invalid responses. The chapter also includes the significance of a letter of intent or memorandum of understanding in modern trade. It mentions the possible issues with language during international business transactions.
Illegality and Immorality
Authors: Schwenzer Ingeborg , Muñoz Edgardo
Published: September 2022

This chapter focuses on illegality and immorality. Every legal system claims the right to void a contract if it is legally or morally offensive while it principally protects societal and political interests. In terms of the sale of goods, civil law and religious legal systems tend to expressly deal with immorality, whereas common law systems remain vague over it. The chapter clarifies that illegal transactions are often treated differently from immoral transactions, but legislation can often blur the line. However, not every instance of illegality or immorality will render a contract incapable of performance. Many civil law systems can give restitution where a contract is found to be invalid.
Industrial and Intellectual Property Rights
Authors: Schwenzer Ingeborg , Muñoz Edgardo
Published: September 2022

This chapter focuses on industrial and intellectual property rights. Intellectual property rights do not affect the principal legal position of the buyer, as a title can be acquired without any problems, and the goods in principle can be resold and the title retransferred to other parties. Industrial and intellectual property rights can impact the seller-buyer relationship, however, it has not sparked a wave of legal reform. The chapter also tackles the issue of non-conformity and CISG in terms of industrial and intellectual property rights. Moreover, the awareness of the buyer of the intellectual or industrial property right excludes the seller from liability.
Specific Performance
Authors: Schwenzer Ingeborg , Muñoz Edgardo
Published: September 2022

This chapter tackles specific performances. Legal systems disagree as to whether the default system should envisage an obligee’s claim for specific performance at all. The chapter notes how interests are considered before granting specific performance. It also includes how specific performances are often referred to as either right or remedy. Civil law legal systems are favorable due to their claims for specific performance. The chapter then explains the special rules that enable the obligee to effect specific performance outside genuine enforcement proceedings. It mentions the possibility of substitute performance at the obligor’s expense.
Price Reduction
Authors: Schwenzer Ingeborg , Muñoz Edgardo
Published: September 2022

This chapter covers price reduction. It notes how price reduction is primarily known as a remedy in civil law countries. Price reduction is also regarded as partial avoidance of the contract. In history, most legal systems explicitly conduct price reduction for the non-conformity of the goods and performance. However, a special problem arises where the seller’s liability is based upon the goods being subject to a third party’s intellectual property right. The chapter also discusses the calculation of price reduction. The consequence of price reduction is largely similar to the consequence of avoidance.
Concurrent Remedies
Authors: Schwenzer Ingeborg , Muñoz Edgardo
Published: September 2022

This chapter explicated concurrent remedies. It compares the remedies for breach against remedies for mistakes, misinterpretation, and tort remedies. A breach of contract could extend beyond its set of rules and into other provisions of applicable sales law. The consequences of concurrent remedies have caused significant debate in both doctrine, civil law jurisdictions, and court practice at the domestic level. The argument is relatively harmless as most remedies come from the same legal system. However, the same could not be said for the international level if a set of rules does not cover all issues or applicable domestic law will be enforced.
A regulatory network comprising let-7 miRNA and SMUG1 is associated with good prognosis in ER+ breast tumours
Authors: Lirussi Lisa , Ayyildiz Dilara , Liu Yan , Montaldo Nicola P , Carracedo Sergio , Aure Miriam R , Jobert Laure , Tekpli Xavier , Touma Joel , Sauer Torill , Dalla Emiliano , Kristensen Vessela N , Geisler Jürgen , Piazza Silvano , Tell Gianluca , Nilsen Hilde
Published: September 2022

Single-strand selective uracil–DNA glycosylase 1 (SMUG1) initiates base excision repair (BER) of uracil and oxidized pyrimidines. SMUG1 status has been associated with cancer risk and therapeutic response in breast carcinomas and other cancer types. However, SMUG1 is a multifunctional protein involved, not only, in BER but also in RNA quality control, and its function in cancer cells is unclear. Here we identify several novel SMUG1 interaction partners that functions in many biological processes relevant for cancer development and treatment response. Based on this, we hypothesized that the dominating function of SMUG1 in cancer might be ascribed to functions other than BER. We define a bad prognosis signature for SMUG1 by mapping out the SMUG1 interaction network and found that high expression of genes in the bad prognosis network correlated with lower survival probability in ER+ breast cancer. Interestingly, we identified hsa-let-7b-5p microRNA as an upstream regulator of the SMUG1 interactome. Expression of SMUG1 and hsa-let-7b-5p were negatively correlated in breast cancer and we found an inhibitory auto-regulatory loop between SMUG1 and hsa-let-7b-5p in the MCF7 breast cancer cells. We conclude that SMUG1 functions in a gene regulatory network that influence the survival and treatment response in several cancers.
Hydrazone chemistry-mediated CRISPR/Cas12a system for bacterial analysis
Authors: Sheng Anzhi , Yang Jingyi , Tang Longfei , Niu Lili , Cheng Liangfen , Zeng Yujing , Chen Xu , Zhang Juan , Li Genxi
Published: September 2022

In this study, a hydrazone chemistry-mediated clustered regularly interspaced palindromic repeats (CRISPR)/CRISPR-associated protein 12a (Cas12a) system has been proposed for the fist time and constructed. In our system, hydrazone chemistry is designed and employed to accelerate the formation of a whole activation strand by taking advantage of the proximity effect induced by complementary base pairing, thus activating the CRISPR/Cas12a system quickly and efficiently. Moreover, the introduction of hydrazone chemistry can improve the specificity of the CRISPR/Cas12a system, allowing it to effectively distinguish single-base mismatches. The established system has been further applied to analyze Pseudomonas aeruginosa by specific recognition of the probe strand with a characteristic fragment in 16S rDNA to release the hydrazine group-modified activation strand. The method shows a wide linear range from 3.8 × 102 colony-forming units (CFU)/ml to 3.8 × 106 CFU/ml, with the lowest detection limit of 24 CFU/ml. Therefore, the introduction of hydrazone chemistry may also broaden the application of the CRISPR/Cas12a system.
The yeast 2-micron plasmid Rep2 protein has Rep1-independent partitioning function
Authors: Mereshchuk Anastasiia , Johnstone Peter S , Chew Joyce S K , Dobson Melanie J
Published: September 2022

Equal partitioning of the multi-copy 2-micron plasmid of the budding yeast Saccharomyces cerevisiae requires association of the plasmid Rep1 and Rep2 proteins with the plasmid STB partitioning locus. Determining how the Rep proteins contribute has been complicated by interactions between the components. Here, each Rep protein was expressed fused to the DNA-binding domain of the bacterial repressor protein LexA in yeast harboring a replication-competent plasmid that had LexA-binding sites but lacked STB. Plasmid transmission to daughter cells was increased only by Rep2 fusion expression. Neither Rep1 nor a functional RSC2 complex (a chromatin remodeler required for 2-micron plasmid partitioning) were needed for the improvement. Deletion analysis showed the carboxy-terminal 65 residues of Rep2 were required and sufficient for this Rep1-independent inheritance. Mutation of a conserved basic motif in this domain impaired Rep1-independent and Rep protein/STB-dependent plasmid partitioning. Our findings suggest Rep2, which requires Rep1 and the RSC2 complex for functional association with STB, directly participates in 2-micron plasmid partitioning by linking the plasmid to a host component that is efficiently partitioned during cell division. Further investigation is needed to reveal the host factor targeted by Rep2 that contributes to the survival of these plasmids in their budding yeast hosts.
Human NOP2/NSUN1 regulates ribosome biogenesis through non-catalytic complex formation with box C/D snoRNPs
Authors: Liao Han , Gaur Anushri , McConie Hunter , Shekar Amirtha , Wang Karen , Chang Jeffrey T , Breton Ghislain , Denicourt Catherine
Published: September 2022

5-Methylcytosine (m5C) is a base modification broadly found on various RNAs in the human transcriptome. In eukaryotes, m5C is catalyzed by enzymes of the NSUN family composed of seven human members (NSUN1-7). NOP2/NSUN1 has been primarily characterized in budding yeast as an essential ribosome biogenesis factor required for the deposition of m5C on the 25S ribosomal RNA (rRNA). Although human NOP2/NSUN1 has been known to be an oncogene overexpressed in several types of cancer, its functions and substrates remain poorly characterized. Here, we used a miCLIP-seq approach to identify human NOP2/NSUN1 RNA substrates. Our analysis revealed that NOP2/NSUN1 catalyzes the deposition of m5C at position 4447 on the 28S rRNA. We also find that NOP2/NSUN1 binds to the 5′ETS region of the pre-rRNA transcript and regulates pre-rRNA processing through non-catalytic complex formation with box C/D snoRNAs. We provide evidence that NOP2/NSUN1 facilitates the recruitment of U3 and U8 snoRNAs to pre-90S ribosomal particles and their stable assembly into snoRNP complexes. Remarkably, expression of both WT and catalytically inactive NOP2/NSUN1 in knockdown background rescues the rRNA processing defects and the stable assembly of box C/D snoRNP complexes, suggesting that NOP2/NSUN1-mediated deposition of m5C on rRNA is not required for ribosome synthesis.
Composition and Petrology of a Mush-Bearing Magma Reservoir beneath Tenerife
Authors: Horn Emma L , Taylor Rex N , Gernon Thomas M , Stock Michael J , Farley E M Ruth
Published: September 2022

Deciphering the dynamics of sub-volcanic magmatic processes requires a detailed understanding of the compositional and textural relationships between melt and crystals. To examine these relationships, we investigated material from one of the largest caldera-forming explosive eruptions on the ocean island of Tenerife, the 312-ka Fasnia event. This eruption ejected juvenile pyroclasts of melt-bearing, partially crystalline cumulate nodules alongside phonolitic pumice and accidental lithic clasts. Nodules contain an average of 26% melt that is preserved as vesiculated and microcrystalline basanite in segregations, pathways and interstitial domains. Both the microcrystalline groundmass and crystal framework are generally unaltered as this crystal ‘mush’ remained supra-solidus until the eruption. We find no surficial or intrinsic evidence that the nodules were transported from their reservoir in a ‘carrier’ magma, and it is most likely that the mush was in situ when it was explosively fragmented and ejected during eruption. As such, the nodules preserve a record of the proportions and relationships between the crystal framework and pre-eruptive melt in an active magma mush reservoir, importantly, capturing a snapshot of the sub-volcanic system at a single point in time. We have analysed >100 of the mush nodules from the massive lithic breccia facies within the Fasnia Member of the Diego Hernández Formation. These cumulates span a diverse range of alkaline plutonic lithologies, from wehrlite and pyroxenite, through hornblende gabbros, to monzodiorite and syenite. Their textures record a range of crystallization environments, including both crystal- and melt-rich groundmass domains, and invasion of near-solidus domains by ascending reactive melts. In addition, the cumulus phases record complex interactions between felsic and mafic magmas throughout their development, providing evidence for mush remobilization and disequilibrium. Relative homogeneity of melt compositions through the mafic and felsic lithologies testifies to melt mobility through the cumulates. Nevertheless, all melts are of different basanite-intermediate composition to the juvenile phonolitic pumice ejected during the same eruption. This observation implies that the mafic–felsic cumulate mush and the phonolite did not experience significant two-way mixing and existed as separate crustal reservoirs. However, the Fasnia eruption simultaneously fragmented and removed material from both reservoirs, implying the mafic system was subjacent to the felsic, but they did not form a contiguous body.
Search for axion-like particles with electron and positron beams at the KEK linac
Authors: Ishikawa Akimasa , Sakaki Yasuhito , Takubo Yosuke
Published: September 2022

We perform a feasibility study of a fixed-target experiment to search for axion-like particles (ALPs) coupling to photons, utilizing electron and positron beams available at the KEK linac. The sensitivity to ALPs is evaluated for two shielding setups in conjunction with other beam dump experiments, fixed-target experiments, and e+e− collider experiments. This study shows that the two setups explore the region that cannot be searched by other proposed experiments. In particular, these are sensitive to regions with shorter lifetimes that have not been explored by previous beam dump experiments.
Tannic acid-loaded hydrogel coating endues polypropylene mesh with hemostatic and anti-inflammatory capacity for facilitating pelvic floor repair
Authors: Wu Chenghao , Zhou Zixuan , You Xi , Guo Yi , Chen Ping , Li Huaifang , Tong Xiaowen
Published: September 2022

The application of polypropylene mesh (PPM) in pelvic organ prolapse (POP) treatment was severely limited by the complications associated with PPM, such as mesh exposure, chronic inflammatory reactions and postoperative hematoma. This study applied a method of fabricating a hydrogel-mesh complex (PPM + TA@GelMA) to cross-link tannic acid (TA) directly with Methacrylate Gelatin (GelMA) hydrogel and thus to form a coating for PPM. This one-step coating modification improved the hydrophilicity and cyto-compatibility of PPM. The hemostatic effect of PPM+TA@GelMA was confirmed through tail amputation test. Through the defect tissue repair experiments in vivo, it was proved that PPM+TA@GelMA had effects of anti-inflammation and promoting tissue repair and regulated the M2 subtype macrophages polarization for tissue repair. The TA-loaded hydrogel coating endued PPM with multiple functions. It is believed that the novel hydrogel-mesh complex and its fabrication method will have great significance in basic research and clinical application.
SPREAD 4: online visualisation of pathogen phylogeographic reconstructions
Authors: Nahata Kanika D , Bielejec Filip , Monetta Juan , Dellicour Simon , Rambaut Andrew , Suchard Marc A , Baele Guy , Lemey Philippe
Published: September 2022

Phylogeographic analyses aim to extract information about pathogen spread from genomic data, and visualising spatio-temporal reconstructions is a key aspect of this process. Here we present SPREAD 4, a feature-rich web-based application that visualises estimates of pathogen dispersal resulting from Bayesian phylogeographic inference using BEAST on a geographic map, offering zoom-and-filter functionality and smooth animation over time. SPREAD 4 takes as input phylogenies with both discrete and continuous location annotation and offers customised visualisation as well as generation of publication-ready figures. SPREAD 4 now features account-based storage and easy sharing of visualisations by means of unique web addresses. SPREAD 4 is intuitive to use and is available online at https://spreadviz.org, with an accompanying web page containing answers to frequently asked questions at https://beast.community/spread4.
General Anesthesia Versus Nongeneral Anesthesia for Patients With Acute Posterior Circulation Stroke Undergoing Endovascular Therapy: A Systematic Review and Meta-analysis
Authors: Wang Xinyan , Wu Youxuan , Liang Fa , Jian Minyu , Yu Yun , Wang Yunzhen , Han Ruquan
Published: September 2022

There is continued controversy regarding the optimal anesthetic technique for endovascular therapy in patients with acute posterior circulation ischemic stroke. To compare the clinical outcomes general anesthesia (GA) and non-GA, we performed a systematic review and meta-analysis of randomized controlled trials and observational studies focused on the anesthetic management for endovascular therapy in patients with acute posterior circulation stroke, without language restriction. In addition, we compared clinical outcomes among the studies with different non-GA types (conscious sedation or local anesthesia). Outcome variables were functional independence, excellent outcomes, favorable outcomes, mortality, successful recanalization, hemodynamic instability, intracerebral hemorrhage, and respiratory or vascular complications. Eight studies including 1777 patients were identified. Although GA was associated with a lower odds of functional independence at 90 days (odds ratio [OR]: 0.55; 95% confidence interval [CI] 0.38 to 0.81; P=0.009), substantial heterogeneity was noted (I
2=65%). Subgroup analysis showed that GA was associated with higher odds of mortality than conscious sedation (OR: 1.83; 95% CI, 1.30 to 2.57; I
2=0%), but there was no difference between GA and local anesthesia (I
2=0%). Interestingly, subgroup analysis did not identify a relationship between functional independence and GA compared with local anesthesia (OR: 0.90; 95% CI, 0.64 to 1.25; P=0.919; I
2=0%). This meta-analysis demonstrates that GA is associated with worse outcomes in patients with acute posterior circulation stroke undergoing endovascular therapy based on current studies.
A Comparison of 2 Abbreviated Methods for Assessing Adolescent Bone Age: The Shorthand Bone Age Method and the SickKids/Columbia Method
Authors: Bixby Elise C. , Skaggs Kira , Berube Emma , Howard Andrew W. , Wong Tony T. , Redler Lauren H. , Popkin Charles A.
Published: September 2022

Background:

Radiographic assessment of bone age is critically important to decision-making on the type and timing of operative interventions in pediatric orthopaedics. The current widely accepted method for determining bone age is time and resource-intensive. This study sought to assess the reliability and accuracy of 2 abbreviated methods, the Shorthand Bone Age (SBA) and the SickKids/Columbia (SKC) methods, to the widely accepted Greulich and Pyle (GP) method.

Methods:

Standard posteroanterior radiographs of the left hand of 125 adolescent males and 125 adolescent females were compiled, with bone ages determined by the GP method ranging from 9 to 16 years for males and 8 to 14 years for females. Blinded to the chronologic age and GP bone age of each child, the bone age for each radiograph was determined using the SBA and SKC methods by an orthopaedic surgery resident, 2 pediatric orthopaedic surgeons, and a musculoskeletal radiologist. Measurements were then repeated 2 weeks later after rerandomization of the radiographs. Intrarater and interrater reliability for the 2 abbreviated methods as well as the agreement between all 3 methods were calculated using weighted κ values. Mean absolute differences between methods were also calculated.

Results:

Both bone age methods demonstrated substantial to almost perfect intrarater reliability, with a weighted κ ranging from 0.79 to 0.93 for the SBA method and from 0.82 to 0.96 for the SKC method. Interrater reliability was moderate to substantial (weighted κ: 0.55 to 0.84) for the SBA method and substantial to almost perfect (weighted κ: 0.67 to 0.92) for the SKC method. Agreement between the 3 methods was substantial for all raters and all comparisons. The mean absolute difference, been GP-derived and SBA-derived bone age, was 7.6±7.8 months, as compared with 8.8±7.4 months between GP-derived and SKC-derived bone ages.

Conclusions:

The SBA and SKC methods have comparable reliability, and both correlate well to the widely accepted GP methods and to each other. However, they have relatively large absolute differences when compared with the GP method. These methods offer simple, efficient, and affordable estimates for bone age determination, but at best provide an estimate to be used in the appropriate setting.

Level of Evidence:

Diagnostic study—level III.
Project MED (Medicine, Exposure, and Development): Promoting Access to Healthcare Education for Historically Underrepresented Groups Through Community Engagement, Sustainability, and Technology
Authors: Quan Irene L. , Sriram Nikhil , Lam Emily , Jain Rishi , Boadi Nathalie , Singh Aru , Velasco Valentina , O’Brian Catherine A. , Post Sharon L. , Simon Melissa A.
Published: September 2022

In the U.S., disparities in the healthcare workforce have led to inadequate health outcomes in communities of historically underserved groups. To address the lack of resources and opportunities in health career education for historically underserved group students, Project MED was established. The mission is to expose high school students to the breadth of opportunities in the healthcare field and to prepare students for successful careers in healthcare. Through 3 main pillars—Learn, Lead, and Launch—Project MED has developed a robust repository of 20 workshops, recruited and trained eight mentors, and curated a database of ≥100 opportunities for over 50 students.
Extracellular Vesicle-based Drug Delivery System Boosts Phytochemicals’ Therapeutic Effect for Neurodegenerative Diseases
Authors: Zhu Zhenzhu , Liao Liuyue , Qiao Hongzhi
Published: September 2022

Neurodegenerative diseases (NDs) are a major threat to the elderly, and efficient therapy is rarely available. A group of phytochemicals has been shown to ameliorate NDs; however, poor stability, low bioavailability, and reduced drug accumulation in brain tissue limit their application in NDs. Therefore, a targeted drug delivery system is a feasible treatment strategy for NDs. Extracellular vesicles (EVs) possess many favorable bioactivities and are excellent carriers for targeting brain tissue. This review summarizes EVs as novel phytochemical carriers in ND therapy. First, we discuss the current challenges of ND therapy and the therapeutic effects of phytochemicals for NDs. Second, we highlight the ability of EVs to cross the blood-brain barrier and act as drug carriers to enhance the therapeutic efficacy of drugs for NDs. Finally, encapsulation strategies for phytochemicals in EVs are particularly reviewed, as they are critical for obtaining high loading efficacy and stable drug delivery systems. This review provides new insights into EV-based drug delivery systems for improving the therapeutic effect of phytochemicals for ND treatment. Therefore, the release rate and pharmacokinetics of phytochemicals should be well controlled to ensure the therapeutic efficacy of phytochemical-loaded EVs in the brain.
Endoscopic Repair of Round Window Cochleocele
Authors: James Adrian L. , Papsin Blake C.
Published: September 2022

Objective

To describe the novel presentation, implications, and endoscopic management of a congenital round window cochleocele.

Patient

A 16-month old girl with profound hearing loss from bilateral incomplete partition type 1 (IP1) anomaly of the cochlea plus left-sided cochlear nerve aplasia and cochleocele.

Intervention

Anomalies were identified with computed tomographic scanning and magnetic resonance imaging during cochlear implant candidacy assessment. While under general anesthesia for right-sided cochlear implantation, the cochleocele was removed and packed with temporalis fascia using transcanal endoscopic ear surgery. The endoscope was held by an assistant while the surgeon packed the round window using a two-handed technique to counter the gush of cerebrospinal fluid.

Results

The child made an uneventful recovery with no cerebrospinal fluid leak or meningitis.

Conclusions

Cochleocele can protrude through the round window of a cochlea with incomplete partition type 1 anomaly. An increased risk of meningitis secondary to acute otitis media is expected given the known risk from cochleocele arising through a stapes footplate fistula. Care should be taken to check for the presence of a cochleocele in hearing loss from congenital malformations involving the basal turn of the cochlea on imaging and also at the time of cochlear implant surgery. Repair should be considered at the first opportunity to prevent meningitis. If early cochlear implant surgery is not feasible or appropriate (as, for example, with cochlear nerve aplasia), transcanal endoscopic ear surgery provides good access for a low-morbidity approach.
Ophthalmologic Manifestations of Neuroblastoma: A Systemic Review
Authors: Kuchalska Katarzyna , Derwich Katarzyna , Gotz-Więckowska Anna
Published: September 2022

Neuroblastoma (NBL) is the most common extracranial solid tumor found in pediatric patients. It develops from the sympathetic tract tissue. Although the symptoms are associated with tumor localization, sometimes NBL is manifested as ophthalmologic disorders. In this paper, we describe their incidence and the correlation with the prognosis. We searched 2 databases (PubMed and Web of Science) for papers published before April 2022, and concerned pediatric patients with NBL, which caused ophthalmologic changes. We collected 7 papers assessing the occurrence of ophthalmologic findings in the NBL patients, as well as 68 case reports presenting children with orbital changes and NBL, or with other tumors stemming from the sympathetic ganglia. The statistical analysis was performed to synthetize the data. The ophthalmologic signs occurred in 17.89% of the NBL cases; however, they were observed on presentation in 10.68%. The isolated ocular presentation was found in 2.56% of patients, whereas Horner syndrome was most frequent. The ophthalmologic symptoms correlated with patients’ age, primary tumor site, and survival rate. NBL may be challenging to diagnose in cases with isolated ophthalmologic manifestations. Numerous possible ocular signs can be observed, which emphasize the need for multidisciplinary care with regard to the NBL patients.
PI3K Inhibition for Squamous Cell Head and Neck Carcinoma
Authors: Desilets Antoine , Soulières Denis
Published: September 2022

The phosphoinositide 3-kinase (PI3K) pathway is aberrantly activated in most head and neck squamous cell carcinomas, making it a prized target for targeted therapy development. Multiple PI3K inhibitors have been studied in early phase trials, with unfavorable risk-benefit ratios in molecularly unselected patient populations. Buparlisib, a potent pan–class I PI3K inhibitor, shows promising efficacy in combination with paclitaxel for advanced head and neck squamous cell carcinoma. Results of the phase III BURAN trial are awaited.
Absorbable Suture Anchor Technique
Authors: Li Hanbo , Zhao Yanyong
Published: September 2022

Postblepharoplasty ectropion is a very complex problem to deal with because its relevance is far to be only a functional complaint. Therefore, the best surgical approach requires both aesthetic and functional consideration. Here, we introduce the absorbable suture anchor technique, which can meet both needs, and its surgical procedure is simple and effective and has excellent stability for long-term results. This series included only ectropion patients caused by lower eyelid blepharoplasty, with or without receiving revision surgery. Forty-seven cases (64 eyes) were treated by a single surgeon through this method. Forty-six patients (97.9%) displayed adequate correction of the eyelid ectropion and a marked degree of improvement both in aesthetic terms and with regard to the functional disorders reported. One patient (2.1%) presented complications but brought under control after drainage and dressing change. His previous symptoms were also largely relieved. Absorbable suture anchor technique is an effective, minimally invasive, and safe method to correct postblepharoplasty ectropion.

Objective

In this study, we describe an absorbable suture anchor technique and its outcomes in the repair of ectropion caused by lower eyelid blepharoplasty.

Methods

From December 2017 to January 2021, 47 patients (64 eyes) with lower eyelid ectropion were treated with this technique (mean age, 43 years; age range, 27–61 years). This series included only patients with ectropion caused by lower eyelid blepharoplasty, with or without revision surgery. Patients were assessed with the Ectropion Grading Scale and distraction test preoperatively. All patients first underwent the release of middle lamellar adhesions and scar tissue, and then, the absorbable suture anchor technique was used to suspend the lower eyelid; 9 patients also underwent eyelid wedge excision because of severe lower eyelid laxity.

Results

The success rate was 100% for grade I–III and V ectropion and 95% for grade IV. The overall success rate was 98%. In terms of correction iterations, the success rate 100% for patients undergoing their first reconstructive surgery and 90% for patients who had 1 or more reconstructive surgeries. Surgical success was defined in terms of the Ectropion Grading Scale and clinical examination. One patient (1 eye) developed a lower eyelid tissue infection that was controlled with drainage and dressing changes; his previous symptoms were largely relieved.

Conclusions

The absorbable suture anchor technique is an effective, minimally invasive, and safe method for correcting postblepharoplasty lower eyelid ectropion.
INCIDENCE, RISK FACTORS, AND OUTCOME OF SUSPECTED CENTRAL VENOUS CATHETER-RELATED INFECTIONS IN CRITICALLY ILL COVID-19 PATIENTS: A MULTICENTER RETROSPECTIVE COHORT STUDY
Authors: Smit Jasper M. , Exterkate Lotte , van Tienhoven Arne J. , Haaksma Mark E. , Heldeweg Micah L.A. , Fleuren Lucas , Thoral Patrick , Dam Tariq A. , Heunks Leo M.A. , Gommers Diederik , Cremer Olaf L. , Bosman Rob J. , Rigter Sander , Wils Evert-Jan , Frenzel Tim , Vlaar Alexander P. , Dongelmans Dave A. , de Jong Remko , Peters Marco , Kamps Marlijn J.A , Ramnarain Dharmanand , Nowitzky Ralph , Nooteboom Fleur G.C.A. , de Ruijter Wouter , Urlings-Strop Louise C. , Smit Ellen G.M. , Mehagnoul-Schipper D. Jannet , Dormans Tom , de Jager Cornelis P.C. , Hendriks Stefaan H.A. , Achterberg Sefanja , Oostdijk Evelien , Reidinga Auke C. , Festen-Spanjer Barbara , Brunnekreef Gert B. , Cornet Alexander D. , van den Tempel Walter , Boelens Age D. , Koetsier Peter , Lens Judith , Faber Harald J. , Karakus A. , Entjes Robert , de Jong Paul , Rettig Thijs C.D. , Arbous Sesmu , Vonk Bas , Machado Tomas , Girbes Armand R.J. , Sieswerda Elske , Elbers Paul W.G. , Tuinman Pieter R.
Published: September 2022

Background: Aims of this study were to investigate the prevalence and incidence of catheter-related infection, identify risk factors, and determine the relation of catheter-related infection with mortality in critically ill COVID-19 patients. Methods: This was a retrospective cohort study of central venous catheters (CVCs) in critically ill COVID-19 patients. Eligible CVC insertions required an indwelling time of at least 48 hours and were identified using a full-admission electronic health record database. Risk factors were identified using logistic regression. Differences in survival rates at day 28 of follow-up were assessed using a log-rank test and proportional hazard model. Results: In 538 patients, a total of 914 CVCs were included. Prevalence and incidence of suspected catheter-related infection were 7.9% and 9.4 infections per 1,000 catheter indwelling days, respectively. Prone ventilation for more than 5 days was associated with increased risk of suspected catheter-related infection; odds ratio, 5.05 (95% confidence interval 2.12–11.0). Risk of death was significantly higher in patients with suspected catheter-related infection (hazard ratio, 1.78; 95% confidence interval, 1.25–2.53). Conclusions: This study shows that in critically ill patients with COVID-19, prevalence and incidence of suspected catheter-related infection are high, prone ventilation is a risk factor, and mortality is higher in case of catheter-related infection.
Microglia are involved in regulating histamine dependent and non-dependent itch transmissions with distinguished signal pathways
Authors: Yang Yuxiu , Mou Bin , Zhang Qi-Ruo , Zhao Hong-Xue , Zhang Jian-Yun , Yun Xiao , Xiong Ming-Tao , Liu Ying , Liu Yong U. , Pan Haili , Ma Chao-Lin , Li Bao-Ming , Peng Jiyun
Published: September 2022

Although itch and pain have many similarities, they are completely different in perceptual experience and behavioral response. In recent years, we have a deep understanding of the neural pathways of itch sensation transmission. However, there are few reports on the role of non-neuronal cells in itch. Microglia are known to play a key role in chronic neuropathic pain and acute inflammatory pain. It is still unknown whether microglia are also involved in regulating the transmission of itch sensation. In the present study, we used several kinds of transgenic mice to specifically deplete CX3CR1+ central microglia and peripheral macrophages together (whole depletion), or selectively deplete central microglia alone (central depletion). We observed that the acute itch responses to histamine, compound 48/80 and chloroquine were all significantly reduced in mice with either whole or central depletion. Spinal c-fos mRNA assay and further studies revealed that histamine and compound 48/80, but not chloroquine elicited primary itch signal transmission from DRG to spinal Npr1- and somatostatin-positive neurons relied on microglial CX3CL1-CX3CR1 pathway. Our results suggested that central microglia were involved in multiple types of acute chemical itch transmission, while the underlying mechanisms for histamine dependent and non-dependent itch transmission were different that the former required the CX3CL1-CX3CR1 signal pathway.
PKB/AKT attenuates Lewy Body-like pathology in primary neurons via Cathepsins B and D
Authors: Konovalova Julia , Er Safak , Barut Justyna , Rafa-Zabłocka Katarzyna , Luk Kelvin C. , Figiel Małgorzata , Airavaara Mikko , Domanskyi Andrii , Chmielarz Piotr
Published: September 2022

Motor symptoms of Parkinson’s disease (PD) are caused by the loss of dopamine neurons in the substantia nigra pars compacta. Current PD therapies offer only symptomatic relief, and the research on novel ways to stop or slow down the degeneration of dopamine neurons in PD attracts considerable efforts.

A characteristic feature of PD is the abnormal accumulation and spread of misfolded α-synuclein (α-syn) protein leading to the formation of Lewy neurites and bodies in different neuronal populations, including dopamine neurons. The process of Lewy body formation compromises neuronal functions and contributes to the progression of the disease and neurodegeneration in PD patients. Treatments preventing α-syn misfolding, aggregation and/or spread may therefore provide much-needed disease-modifying therapies for PD. We and others have demonstrated that α-syn aggregation and Lewy body formation can be modelled in primary neuronal cultures treated with α-syn pre-formed fibrils (PFFs). Using this approach, we have identified several factors preventing the accumulation of phosphorylated α-syn in dopamine neurons in vitro and in vivo. In particular, we and others have demonstrated a prominent role of PKB/AKT pathway activation in promoting the survival of dopamine neurons.

Here, we utilize lentiviral vectors (LVs) to express constitutively active myristoylated serine-threonine protein kinase AKT1 (mAKT1) in primary dopamine neurons. We show that lentivirally-delivered mAKT1 promoted survival of dopamine neurons after thapsigargin-induced endoplasmic reticulum (ER) stress and prevented fibril-induced accumulation of phosphorylated α-syn. Furthermore, using pharmacological tools, we demonstrate that this activity of mAKT1 is dependent on the functional Cathepsins B and D. These proof-of-principle results demonstrate the critical importance of lysosomal enzymes for processing misfolded α-syn and establish a basis for the use of LVs to develop neuroprotective gene therapy strategies for dopamine neurons in PD.
Predicting treatment outcome using kinome activity profiling in HER2+ breast cancer biopsies
Authors: Debets Donna O. , de Graaf Erik L. , Liefaard Marte C. , Sonke Gabe S. , Lips Esther H. , Ressa Anna , Altelaar Maarten
Published: September 2022

In this study, we measured the kinase activity profiles of 32 pre-treatment tumour biopsies of HER2-positive breast cancer patients. The aim of this study was to assess the prognostic potential of kinase activity levels to identify potential mechanisms of resistance and to predict treatment success of HER2-targeted therapy combined with chemotherapy. Indeed, our system-wide kinase activity analysis, based on targeted mass spectrometry measurement of kinase activation loops, allowed us to link kinase activity to treatment response. Overall, high kinase activity in the HER2-pathway was associated with good treatment outcome. Furthermore, we found eleven kinases differentially regulated between treatment outcome groups. Amongst those, well-known players in therapy resistance were found, such as p38a, ERK and FAK, as well as a potential new player in drug resistance, namely MARK. Lastly, we defined an optimal signature of four kinases in a multiple logistic regression diagnostic test for prediction of treatment outcome (AUC=0.926). This kinase signature showed high sensitivity and specificity, indicating its potential as predictive biomarker for treatment success of HER2-targeted therapy.