bluuebunny/crossref_metadata_2025 huggingface dataset:
Demographic differences in willingness to share electronic health records in the All of Us Research Program
Authors: Joseph Christine L M , Tang Amy , Chesla David W , Epstein Mara M , Pawloski Pamala A , Stevens Alan B , Waring Stephen C , Ahmedani Brian K , Johnson Christine C , Peltz-Rauchman Cathryn D
Published: April 2022

Objective

Participant willingness to share electronic health record (EHR) information is central to success of the National Institutes of Health All of Us Research Program (AoURP). We describe the demographic characteristics of participants who decline access to their EHR data.

Materials and Methods

We included participants enrolling in AoURP between June 6, 2017 and December 31, 2019 through the Trans-American Consortium for the Health Care Systems Research Network (TACH). TACH is a consortium of health care systems spanning 6 states, and an AoURP research partner.

Results

We analyzed data for 25 852 participants (89.3% of those enrolled). Mean age = 52.0 years (SD 16.8), with 66.5% White, 18.7% Black/African American, 7.7% Hispanic, 32.5% female, and 76% with >a high school diploma. Overall, 2.3% of participants declined to share access to their EHR data (range across TACH sites = 1.3% to 3.5%). Younger age, female sex, and education >high school were significantly associated with decline to share EHR data, odds ratio (95% confidence interval) = 1.26 (1.19–1.33), 1.74 (1.42–2.14), and 2.44 (1.86–3.21), respectively. Results were similar when several sensitivity analyses were performed.

Discussion

AoURP seeks a dataset reflecting our nation’s diversity in all aspects of participation. Those under-represented in biomedical research may be reluctant to share access to their EHR data.

Conclusion

In our data, race and ethnicity were not independently related to participant decision to decline access to their EHR information. Results suggest that the value of the AoURP dataset is unlikely to be constrained by the size or the racial/ethnic composition of this subgroup.
A research agenda to support the development and implementation of genomics-based clinical informatics tools and resources
Authors: Wiley Ken , Findley Laura , Goldrich Madison , Rakhra-Burris Tejinder K , Stevens Ana , Williams Pamela , Bult Carol J , Chisholm Rex , Deverka Patricia , Ginsburg Geoffrey S , Green Eric D , Jarvik Gail , Mensah George A , Ramos Erin , Relling Mary V , Roden Dan M , Rowley Robb , Alterovitz Gil , Aronson Samuel , Bastarache Lisa , Cimino James J , Crowgey Erin L , Del Fiol Guilherme , Freimuth Robert R , Hoffman Mark A , Jeff Janina , Johnson Kevin , Kawamoto Kensaku , Madhavan Subha , Mendonca Eneida A , Ohno-Machado Lucila , Pratap Siddharth , Taylor Casey Overby , Ritchie Marylyn D , Walton Nephi , Weng Chunhua , Zayas-Cabán Teresa , Manolio Teri A , Williams Marc S
Published: April 2022

Objective

The Genomic Medicine Working Group of the National Advisory Council for Human Genome Research virtually hosted its 13th genomic medicine meeting titled “Developing a Clinical Genomic Informatics Research Agenda”. The meeting’s goal was to articulate a research strategy to develop Genomics-based Clinical Informatics Tools and Resources (GCIT) to improve the detection, treatment, and reporting of genetic disorders in clinical settings.

Materials and Methods

Experts from government agencies, the private sector, and academia in genomic medicine and clinical informatics were invited to address the meeting's goals. Invitees were also asked to complete a survey to assess important considerations needed to develop a genomic-based clinical informatics research strategy.

Results

Outcomes from the meeting included identifying short-term research needs, such as designing and implementing standards-based interfaces between laboratory information systems and electronic health records, as well as long-term projects, such as identifying and addressing barriers related to the establishment and implementation of genomic data exchange systems that, in turn, the research community could help address.

Discussion

Discussions centered on identifying gaps and barriers that impede the use of GCIT in genomic medicine. Emergent themes from the meeting included developing an implementation science framework, defining a value proposition for all stakeholders, fostering engagement with patients and partners to develop applications under patient control, promoting the use of relevant clinical workflows in research, and lowering related barriers to regulatory processes. Another key theme was recognizing pervasive biases in data and information systems, algorithms, access, value, and knowledge repositories and identifying ways to resolve them.
Use of unstructured text in prognostic clinical prediction models: a systematic review
Authors: Seinen Tom M , Fridgeirsson Egill A , Ioannou Solomon , Jeannetot Daniel , John Luis H , Kors Jan A , Markus Aniek F , Pera Victor , Rekkas Alexandros , Williams Ross D , Yang Cynthia , van Mulligen Erik M , Rijnbeek Peter R
Published: April 2022

Objective

This systematic review aims to assess how information from unstructured text is used to develop and validate clinical prognostic prediction models. We summarize the prediction problems and methodological landscape and determine whether using text data in addition to more commonly used structured data improves the prediction performance.

Materials and Methods

We searched Embase, MEDLINE, Web of Science, and Google Scholar to identify studies that developed prognostic prediction models using information extracted from unstructured text in a data-driven manner, published in the period from January 2005 to March 2021. Data items were extracted, analyzed, and a meta-analysis of the model performance was carried out to assess the added value of text to structured-data models.

Results

We identified 126 studies that described 145 clinical prediction problems. Combining text and structured data improved model performance, compared with using only text or only structured data. In these studies, a wide variety of dense and sparse numeric text representations were combined with both deep learning and more traditional machine learning methods. External validation, public availability, and attention for the explainability of the developed models were limited.

Conclusion

The use of unstructured text in the development of prognostic prediction models has been found beneficial in addition to structured data in most studies. The text data are source of valuable information for prediction model development and should not be neglected. We suggest a future focus on explainability and external validation of the developed models, promoting robust and trustworthy prediction models in clinical practice.
Identification of functional single nucleotide polymorphisms in the porcine SLC6A4 gene associated with aggressive behavior in weaned pigs after mixing
Authors: Guo Yanli , Zhao Jing , Xu Qinglei , Gao Siyuan , Liu Mingzheng , Zhang Chunlei , Schinckel Allan P , Zhou Bo
Published: April 2022

Variation in genes of the serotonergic system influences aggressive behavior by affecting serotonin levels in the central and cortical nervous system. SLC6A4 (serotonin transporter) is a master regulator of 5-HT signaling and involved in the regulation of aggressive behavior in humans and rodents. To identify potential functional single nucleotide polymorphisms (SNPs) for the porcine SLC6A4 gene associated with aggressive behavior, a total of 500 pigs (268 barrows and 232 gilts) were selected and mixed in 51 pens. Their behavior was recorded and observed for 72 h after mixing. Based on a composite aggressive score (CAS), the most aggressive and the least aggressive pigs within each pen were selected separately (a total of 204 pigs). Ear tissue was sampled to extract genomic DNA. Eight SNPs in the 5ʹ-flanking region, coding region, and 3ʹ-untranslated region (3ʹ-UTR) of SLC6A4 were genotyped, of which 6 SNPs had significant differences (P < 0.05) in allele frequency between the most aggressive and least aggressive pigs. Luciferase activity was greater in plasmids of genotype GG than plasmids of genotype CC of rs345058216 (P < 0.01). Computational analysis nominated MAZ as putative transcription factor (TF) with higher probability to bind the SLC6A4 promoter at the SNP (rs345058216) site. Also, we demonstrated that MAZ overexpression modulates SLC6A4 promoter activity in allele-specific manner with an in vitro assay. In addition, we demonstrated that SLC6A4 was a direct target of miR-671-5p. The dual luciferase reporter gene assay and cell transfection were performed to examine the role of miR-671-5p in regulating SLC6A4 expression. The luciferase assays revealed that the SNP rs332335871 affects regulation of miR-671-5p in SLC6A4 expression. After overexpression of miR-671-5p in porcine primary neural cells, the SLC6A4 mRNA levels can be significantly reduced. In conclusion, we here found that miR-671-5p and MAZ mediated porcine SLC6A4 expression level, which provides the possible molecular mechanism of aggressive behavior.
ASAS-NANP Symposium: Mathematical Modeling in Animal Nutrition: Limitations and potential next steps for modeling and modelers in the animal sciences
Authors: Jacobs Marc , Remus Aline , Gaillard Charlotte , Menendez Hector M , Tedeschi Luis O , Neethirajan Suresh , Ellis Jennifer L
Published: April 2022

The field of animal science, and especially animal nutrition, relies heavily on modeling to accomplish its day-to-day objectives. New data streams (“big data”) and the exponential increase in computing power have allowed the appearance of “new” modeling methodologies, under the umbrella of artificial intelligence (AI). However, many of these modeling methodologies have been around for decades. According to Gartner, technological innovation follows five distinct phases: technology trigger, peak of inflated expectations, trough of disillusionment, slope of enlightenment, and plateau of productivity. The appearance of AI certainly elicited much hype within agriculture leading to overpromised plug-and-play solutions in a field heavily dependent on custom solutions. The threat of failure can become real when advertising a disruptive innovation as sustainable. This does not mean that we need to abandon AI models. What is most necessary is to demystify the field and place a lesser emphasis on the technology and more on business application. As AI becomes increasingly more powerful and applications start to diverge, new research fields are introduced, and opportunities arise to combine “old” and “new” modeling technologies into hybrids. However, sustainable application is still many years away, and companies and universities alike do well to remain at the forefront. This requires investment in hardware, software, and analytical talent. It also requires a strong connection to the outside world to test, that which does, and does not work in practice and a close view of when the field of agriculture is ready to take its next big steps. Other research fields, such as engineering and automotive, have shown that the application power of AI can be far reaching but only if a realistic view of models as whole is maintained. In this review, we share our view on the current and future limitations of modeling and potential next steps for modelers in the animal sciences. First, we discuss the inherent dependencies and limitations of modeling as a human process. Then, we highlight how models, fueled by AI, can play an enhanced sustainable role in the animal sciences ecosystem. Lastly, we provide recommendations for future animal scientists on how to support themselves, the farmers, and their field, considering the opportunities and challenges the technological innovation brings.
Mineral-salt supplementation to ameliorate larkspur poisoning in cattle
Authors: Stonecipher Clinton A , Green Ben T , Welch Kevin D , Gardner Dale R , Fritz Scott A , Cook Daniel , Pfister James A
Published: April 2022

Larkspurs (Delphinium spp.) are native forbs that are poisonous to cattle and cost livestock producers millions of dollars in losses each year. Macro and micro minerals are required for normal functioning of essentially all metabolic processes in ruminants. The role that mineral status may play in larkspur poisoning in cattle is not clear. In this study, we seek to determine the effects a mineral-salt supplement, commonly used by cattle producers, to potentially reduce cattle losses to larkspur. The ability of mineral-salt supplementation to alter susceptibility to larkspur toxicosis was evaluated in a pen study. Animals supplemented with mineral-salt were found to be less susceptible to larkspur poisoning than the non-supplemented animals. A separate group of animals were then grazed on larkspur infested rangelands. One group was supplemented with a mineral-salt mix and the other group did not receive any mineral-salt. Supplementing cattle with the mineral-salt mix did not alter larkspur consumption (P > 0.05). However, overall larkspur consumption was low and averaged 3 ± 1.0% and 2 ± 1.1% for cattle supplemented with mineral and non-supplemented, respectively. Serum was collected from animals once a week during the grazing study. Average and maximum serum concentrations of toxic larkspur alkaloids were numerically higher in mineral-salt supplemented cattle compared with the non-supplemented animals. Results from the pen study suggest that a good mineral supplementation program will provide a protective effect for animals grazing in larkspur-infested ranges. The mineral-salt supplemented steers, in the grazing study, were not observed to consume less larkspur than the non-supplemented animals; however, the mineral-salt supplemented animals had higher concentrations of larkspur alkaloids in their serum indicating they may be able to tolerate higher larkspur consumption. The data also indicate that mineral-salt supplementation must be continuous throughout the time the animals are grazing these rangelands as the positive effects can be lost within 30 d post supplementation.
Effects of salinity on the absorption and elimination of residues of the fungicide ridomil in Procambarus clarkii (Girard, 1852) (Decapoda: Astacidea: Cambaridae)
Authors: Li Jiehang , Zheng Ruizhou , Hu Kun
Published: April 2022

We explored the pharmacokinetics of the antimicrobial agent ridomil in the crayfish Procambarus clarkii (Girard, 1852) under different salinity conditions. The concentration of ridomil in hemolymph, liver, and muscle of individuals soaked in ridomil in fresh water and brackish water with a salinity of 3‰ was determined by high-performance liquid chromatography. Hemolymph was in line with the first-order absorption, two-compartment open model, and the liver and muscles were in line with the first-order absorption, one-compartment open model. The maximum concentration(Cmax) in the hemolymph in fresh and brackish-water groups were 296 mg l–1 and 452 mg l–1, respectively. The maximum time (Tmax) of hemolymph in the fresh and brackish-water groups were 8h and 24h, respectively. The Cmax in liver and muscle in the freshwater group were 4,125 mg l–1 and 2,702 mg l–1, respectively, and 2,362 mg l–1 and 2,274 mg l–1, respectively, in the brackish-water group. The Tmax of liver and muscle in the freshwater group were 0.25 h and 18 h, respectively, 36 h and 24 h, respectively, in the brackish-water group. Results indicate that the concentration of ridomil in the hemolymph was lower in the freshwater group than that in the brackish-water group, but the concentration in liver and muscle tissues in the freshwater group was higher than that in the brackish-water group. Salinity can therefore affect the drug absorption rate of ridomil in the hemolymph of Procambarus clarkii.
Seismic analysis and optimization of concrete bridge under the moving train utilizing numerical methods and adaptive improved harmony search algorithm
Authors: Kalashemi Sajad Haghdadi , Bidgoli Mahmood Rabani , Mazaheri Hamid
Published: April 2022

In this paper, the simultaneous actions of moving force and seismic load on the dynamic displacement and optimization of the concrete bridge are studied. The sinusoidal shear deformation beam theory is employed for the modelling of the concrete bridge mathematically. The structural damping of the concrete bridge is assumed by the Kelvin–Voigt theory. Utilizing the method of energy and Hamilton’s law, the equations of motion are obtained. Three mixed numerical methods, including the integral quadrature, harmonic differential quadrature method, and Newmark technique, are presented for the numerical outcomes of the differential equations. Utilizing adaptive improved harmony search, improved harmony search, harmony search, and global harmony search algorithms, the optimization process of the concrete bridge is examined. The mentioned algorithm is improved adaptively by utilizing dynamic deflection. The harmony memory is corrected at first and second adjustments, respectively, based on emotional bandwidth and step size randomly. The optimum conditions of the concrete bridge are evaluated with various harmony existing search methods. The role of multiple parameters, including the velocity and acceleration of moving load, length and thickness of bridge, boundary conditions, and the amplitude of carrying load, in the dynamic displacement of the bridge is studied. The numerical results indicate that with increasing the velocity and acceleration of the moving train, the dynamic displacement of the concrete bridge increases. In addition, with increasing the length of the bridge, the time of maximum deflection (i.e. when the train is in the middle of the bridge) is increased. It is concluded for the concrete bridge under the seismic load that the optimum values of the bridge’s length and thickness are decreased (about 24%) and increased (about 21%), respectively. The optimum values of amplitude, velocity, and acceleration of moving train are decreased, respectively, about 34%, 33%, and 29% in the case of the concrete bridge under the earthquake load. In addition, the optimum length of the concrete bridge is decreased significantly, with increasing the moving load amplitude, velocity, and acceleration.
Repatriating Foreign Terrorist Fighters and Their Family Members: What International Law Requires, and What National Courts Will Do
Authors: McKeever David
Published: April 2022

The evolution of ISIL and the foreign terrorist fighter phenomenon has raised many legal and practical challenges. Some of the most pressing and debated relate to the thousands of men, women and children, previously affiliated (to varying degrees) to ISIL and now held in camps in northern Syria. The call for repatriation of these persons has met mixed responses. Much of the debate has focused on policy considerations rather than examining, in depth, what international law prescribes here: that is, to what extent does international law oblige the States of origin to repatriate their nationals? This article will answer this question, looking at relevant rules of human rights law (including the emerging ‘functional approach’ to extra-territorial jurisdiction) as well as international humanitarian law. It will also examine an important principle of domestic law which is likely to play a major role in how these issues are adjudicated: namely, judicial deference to the executive in matters of foreign policy. The article argues that the international legal rules invoked in favour of an obligation to repatriate are far less prescriptive than generally asserted, while the principle of judicial deference to the executive in matters of foreign policy—particularly in cases involving national security considerations—means that national courts are likely to give States yet further latitude in this regard. For both legal and practical reasons, actions aimed at convincing national courts that a State is obliged to repatriate its nationals will not suffice to resolve these complex challenges.
A Case Study on Tropical Bed Bug,Cimex hemipterus(Hemiptera: Cimicidae) Infestation and Management in Dormitories
Authors: Kong Delong , Han Dongliang , Zhai Ruyue , Wang Changlu , Zhang Jingsheng , Xia Yanwei , Nian Xiaoge , Liu Chaofeng , He Yurong , Wang Desen
Published: April 2022

Numerous bed bug research papers have been published in the past 20 yr as a result of bed bug (Cimex spp.) (Hemiptera: Cimicidae) resurgence in the world. Yet, few of them focused on the management of the tropical bed bug, C. hemipterus (F.). Here, we describe a case of tropical bed bug infestation in two dormitory buildings and effectiveness of a tropical bed bug treatment program. The study site consisted of 125 dormitories in two buildings. An initial building-wide monitoring with ClimbUp interceptors revealed 25 infestations. The spatial distribution of bed bug infested rooms showed a significant aggregated distribution pattern with same infestation status for neighboring units sharing walls. All infested rooms were monitored every 2 wk and treated using a combination of steam and diatomaceous earth (DE) dust application if bed bugs were still found. For the 25 initially identified infested rooms, after 14 wk treatment, 44% of them no longer had bed bugs, and the mean number of bed bugs captured per room decreased by 94.1%. A combination of steam and DE dust treatment is an effective strategy for suppressing tropical bed bug infestations in dormitory environment.
Efficacy of Various Low Temperature and Exposure Time Combinations for Thaumatotibia leucotreta (Meyrick) (Lepidoptera: Tortricidae) Larvae
Authors: Moore Sean D , Peyper Mellissa , Kirkman Wayne , Marsberg Tamryn , Albertyn Sonnica , Stephen Peter R , Thackeray Sean R , Grout Tim G , Sharp Gary , Sutton Guy , Hattingh Vaughan
Published: April 2022

A systems approach was developed as an alternative to a standalone quarantine disinfestation treatment for Thaumatotibia leucotreta in citrus fruit exported from South Africa. The systems approach consists of three measures: pre and postharvest controls and measurements, postpacking inspection, and postharvest exposure to low temperatures. Different cold treatment conditions with a range of efficacy levels can be used for this last measure. A series of trials reported here evaluated the efficacy of seven temperatures ranging from 0 to 5°C for durations from 14 d to 26 d. Mortality of the most cold-tolerant larval stages of T. leucotreta was determined. Temperatures of 0, 1, 2, and 3°C for 16, 19, 20, and 24 d respectively, induced 100% mortality of the tested populations. Probit 9 level treatment efficacy was achieved at 0 and 1°C for 16 and 19 d respectively. Mortalities higher than 90% were obtained with temperatures of 4, 4.5, and 5°C, after exposure for the longer durations. We demonstrated a significant difference in cold-induced insecticidal efficacy between 1, 2, 3, and 4°C. There was no significant difference in insecticidal efficacy between 4 and 4.5°C, but both of these temperatures were more efficacious than 5°C. The results of this study are valuable to support the use of cold treatment conditions with lower risk of fruit chilling injury in an effective systems approach, where the cold treatment efficacy can be augmented with other components of the systems approach.
What does the state do in China’s state-led infrastructure financialisation?
Authors: Liu Imogen T , Dixon Adam D
Published: April 2022

China’s state-led financialisation of infrastructure is an alternative narrative to prevailing accounts of neoliberal financialisation in the advanced capitalist core, where the expansion of private market-based finance-led growth is theorised to transform traditional forms of public infrastructure development and production-based growth. Drawing on the case of Chinese state capital investment in Europe, we demonstrate empirically how the imperative to financialise infrastructure development is emergent from and contingent upon a productivist mode of capitalist development. We articulate two key transformations in which Chinese state capital is being used to leverage financial best practice and its network properties in service of the real economy.
Regulation of Cyber Risk in the Banking System: A Canadian Case Study
Authors: Peihani Maziar
Published: April 2022

Cyber risk is one of the greatest threats facing any modern financial system; a result of increasing dependence on technology and the appeal of troves of personal data to well-equipped hackers. This article examines the governance of cyber risk in the Canadian banking system in the context of the Covid-19 crisis, which has led to a surge in cyber-attacks. It argues that the existing Canadian regime, which draws heavily on the Basel operational risk framework, is unfit to handle the unique challenges posed by cyber risk. Cyber incidents are unlike traditional operational disruptions in both their dynamism and impact, and are not adequately captured by backward-looking proxies, such as historical losses. There is also a mismatch between the traditional risk-based supervision, which relies on annual risk rating of banks, and the quickly changing cyber profile of regulated entities. Furthermore, the bilateral and institution-specific nature of such supervision leaves out the crucial systemic perspective on cyber risk. This article calls for the current quantitative paradigm, which underlies capital adequacy regulation, to be complemented with a resilience-centric approach aimed at better accommodating and learning from unpredictable cyber incidents. This shift requires revisiting traditional supervisory practices, such as extensive reliance on centralized decision-making and planning—which may prove ineffective in the face of a firm-wide cyber incident—and a dynamic approach that keeps regulation in line with emergent knowledge. The article outlines a number of strategies which can help banks and regulators navigate and adapt to the ever-changing cyber landscape.
Prince Albert’s donations to the library of the South Kensington Museum
Authors: Willis Frances
Published: April 2022

Prince Albert’s drive to encourage the United Kingdom to forge ahead in the applied arts and industry has been well documented. The masterminding of the Great Exhibition of the Works of Industry of all Nations of 1851, and its legacy in the form of the South Kensington quarter, are testament to his endeavours. Albert’s imprint left behind through his interaction with libraries, and the reasoning behind his choice of manuscript and printed book donations to these institutions are areas that provide a subtler avenue of exploration. Taking as a case-study the donations he made to the South Kensington Museum library, now in the National Art Library at the Victoria and Albert Museum, while also looking further afield, I explore here Albert’s contribution of texts made available for researchers. The donations demonstrate, particularly, his promotion of the capacity for progress through research in science and the arts, and the potential for these fields to be connected and utilized through industry.
In Conversation: Fighters for Peace
Authors: Saab Ziad , Foerch Christina , Moffett Luke
Published: April 2022

This dialogue piece is an interview conducted with Fighters for Peace on reparations and non-state armed groups.
The European Court of Human Rights—Can there be too much Success?
Authors: Lemmens Paul
Published: April 2022

During its more than 60 years of operation, the European Court of Human Rights has proven to be a real beacon for many individuals. Through its case law, it has contributed to the development of human rights law as well as to the development of the principles of the rule of law and of democracy in Europe. However, the Court faces two central problems: the caseload it has to deal with and challenges to its authority and legitimacy. The present contribution will study the history and the achievements of the Court, and address the challenges and the Court’s response to them. The latter has particularly included measures aimed at making its working methods more effective and attempts to increase awareness of its subsidiary role within the Convention protection system, especially regarding its approach to the review of decisions of national authorities. In this context, the development of the principle of process-based review in the Court’s jurisprudence is examined. What will characterize the Convention system in the future is closer cooperation between the Court and national courts. Whether this will effectively lead to an increased protection of human rights on the ground remains to be seen. It is not only for the Court to earn such confidence through its work, but also for others to maintain a climate in which that confidence can continue to be enjoyed.
The Committee on Economic, Social and Cultural Rights—The Power of Subjective Rights: Comment with Special Focus on the Case Law of the Inter-American and the European Courts of Human Rights
Authors: Binder Christina
Published: April 2022

This comment approaches the subjectivity and justiciability of economic and social rights by analysing the recent jurisprudence of the Inter-American Court of Human Rights and the European Court of Human Rights. In line with Dzidek Kędzia’s contribution ‘The Committee on Economic, Social and Cultural Rights—The Power of Subjective Rights’ in this special issue, it argues that the development towards the recognition of economic and social rights as subjective rights is ongoing. The comment finds that notwithstanding certain constraints, both courts increasingly recognize economic and social rights in their jurisprudence. In doing so, they employ similar concepts and argumentative techniques as the Committee on ESCR, partly with explicit reference to the findings of the Committee, and also refer to each other. This process of mutual cross-referencing is understood to be the form of judicial dialogue that strengthens and reinforces the justiciability of economic and social rights. It is key to move one step further in the process towards the full recognition of economic and social rights as subjective and enforceable rights.
Identification of distinct genomic features reveals frequent somatic AHNAK and PTEN mutations predominantly in primary malignant melanoma presenting in the ureter
Authors: Huang Yan , Wei Lai , Huang Yuanbin , Wen Shuang , Liu Tianqing , Duan Xu , Wang Yutong , Zhang Hongshuo , Fan Bo , Hu Bin
Published: April 2022

Background

Primary malignant melanoma of the ureter is extremely rare. Genetic variants to the increased risk of developing the disease have not yet been investigated.

Methods

Tumour mutation profiling for primary malignant melanoma of the ureter was performed by whole-exome sequencing. Immunohistochemistry was performed to verify histopathological features and the variants of predisposing genes and driver mutation genes. Furthermore, we conducted a literature review and Surveillance, Epidemiology and End Result-based study by searching public databases.

Results

We identified 38 somatic single nucleotide variants and 9 somatic insertions and deletions (INDELs) in tumour specimens. After filtering with the Cancer Gene Census database, seven predisposing genes and two driver mutation genes were identified. Moreover, the immunohistochemical profile showed that tumour cells were positive for Melan-A, melanoma gp100 human melanoma black 45 (HMB45), S100 beta and P53. The expression levels of two driver mutation genes (phosphatase and tensin homolog (PTEN) and desmoyokin (AHNAK) and five predisposing genes (AT-rich interaction domain 1B (ARID1B), catalase, eukaryotic translation initiation factor 4 gamma 3 (EIF4G3), ANK3 and collagen type I) were significantly downregulated in tumour tissues compared to paracancerous tissues. In the literature review and Surveillance, Epidemiology and End Results-based study, patients with primary malignant melanoma of the urinary tract had worse clinical outcomes than patients with primary urothelial carcinoma after 1:2 propensity score matching (P = 0.010). Additionally, Cox multivariate analysis for patients with primary malignant melanoma of the urinary tract indicated that distant metastasis (hazard ratio = 1.185; P = 0.044) was an independent predictor for overall survival, and tumour focality (hazard ratio = 0.602; P = 0.017) and non-surgery (hazard ratio = 0.434; P = 0.003) were independent factors for tumour progression.

Conclusions

Our study is the first to provide evidence that the distinct phenotypes of primary malignant melanoma of the ureter may be due to different genetic variations. The prognosis of primary malignant melanoma of the urinary tract was poorer than that of primary urothelial carcinoma of the urinary tract.
Tumor mutational burden measurement using comprehensive genomic profiling assay
Authors: Kage Hidenori , Kohsaka Shinji , Tatsuno Kenji , Ueno Toshihide , Ikegami Masachika , Zokumasu Koichi , Shinozaki-Ushiku Aya , Nagai Sumimasa , Aburatani Hiroyuki , Mano Hiroyuki , Oda Katsutoshi
Published: April 2022

Background

Tumors with a high number of mutations in the genome, or tumor mutational burden, are presumed to be more likely to respond to immune checkpoint inhibitors. However, the optimal method to calculate tumor mutational burden using comprehensive genomic profiling assays is unknown.

Methods

Todai OncoPanel is a dual panel of a deoxyribonucleic acid panel and a ribonucleic acid panel. Todai OncoPanel deoxyribonucleic acid panel version 6 is an improvement over version 3 with increased number of targeted genes and limited targeting of intronic regions. We calculated tumor mutational burden measured by Todai OncoPanel deoxyribonucleic acid panel versions 3 and 6 using three different calculation methods: all mutations within the targeted region (target tumor mutational burden), all mutations within the coding region (all coding tumor mutational burden) and non-synonymous mutations (non-synonymous coding tumor mutational burden). We then compared them with whole exosome sequencing tumor mutational burden. In addition, 16 lung cancer patients whose samples were analyzed using Todai OncoPanel deoxyribonucleic acid version 3 were treated with anti-PD-1 or PD-L1 antibody monotherapy.

Results

When compared with whole exosome sequencing tumor mutational burden as the standard, tumor mutational burden measured by Todai OncoPanel deoxyribonucleic acid version 3 resulted in accuracy of 71% for all three calculation methods. In version 6, accuracy was 96% for target tumor mutational burden and all coding tumor mutational burden and 91% for non-synonymous coding tumor mutational burden. Patients with either partial response or stable disease had higher non-synonymous coding tumor mutational burden (6.7/Mb vs. 1.6/Mb, P = 0.02) and higher PD-L1 expression (40% vs. 3%, P = 0.01) and a trend toward higher target tumor mutational burden (9.2/Mb vs. 2.4/Mb, P = 0.09) compared with patients with progressive disease.

Conclusions

Increase in targeted gene number and limiting intronic regions improved tumor mutational burden measurement by Todai OncoPanel when compared with whole exosome sequencing tumor mutational burden. Target tumor mutational burden may be the method of choice to measure tumor mutational burden.
External validation of the Candiolo nomogram for high-risk prostate cancer patients treated with carbon ion radiotherapy plus androgen deprivation therapy: a retrospective cohort study
Authors: Utsumi Takanobu , Suzuki Hiroyoshi , Ishikawa Hitoshi , Hiroshima Yuichi , Wakatsuki Masaru , Harada Masaoki , Ichikawa Tomohiko , Akakura Koichiro , Tsuji Hiroshi
Published: April 2022

The aim of this study was to reclassify high-risk prostate cancer patients treated with carbon-ion radiotherapy and androgen deprivation therapy using the Candiolo nomogram and evaluate usefulness to predict the following 10-year biochemical recurrence. Six hundred seventy-two high-risk prostate cancer patients were reclassified according to the Candiolo nomogram. The cumulative incidence curves for biochemical recurrence were compared by Gray’s test. Furthermore, five predictors of the Candiolo nomogram in our patients were evaluated by Fine and Gray regression hazards model. The higher the Candiolo risk, the worse the biochemical recurrence, especially in high- and very high-risk patients. Out of five predictors, age ≥70 years, cT3 stage, biopsy Gleason score ≥9 or the percentage of positive biopsy cores ≥50% had significant impacts on 10-year biochemical recurrence in our patients. The Candiolo nomogram can reclassify our high-risk prostate cancer patients treated with carbon-ion radiotherapy and androgen deprivation therapy and evaluate the biochemical recurrence preciously.
Management of elderly patients with esophageal squamous cell cancer
Authors: Hamamoto Yasuo , Murakami Kentaro , Kato Ken , Kitagawa Yuko
Published: April 2022

This review focuses on the treatment about elderly esophageal cancer to clarify the current situation regarding our clinical question. Although there are several reviews about elderly esophageal cancer treatment, there are fundamental differences between Japan and the rest of the world. Two main differences are raised: histological differences and treatment strategies for resectable patients. We overview each status according to following clinical questions. First, there are no established evaluation criteria for frail. Second, selection criteria for surgery or non-surgery are not established. Third, few specific treatments for elderly patients (EPs) are investigated. In conclusion, there are many reports about treatment of esophageal squamous cell carcinoma for EPs, although treatment strategy is still controversial. We have to consider well-designed prospective trial to confirm specific treatment strategy according to each stage.
Risk of radiculopathy caused by second course of spine stereotactic body radiotherapy
Authors: Ito Kei , Nakajima Yujiro , Ogawa Hiroaki , Taguchi Kentaro , Sugita Shurei
Published: April 2022

Objective

Stereotactic body radiotherapy is used to treat spinal metastases; however, 10% of patients experience local failure. We aimed to clarify the outcomes of the second course of stereotactic body radiotherapy for spinal metastases with a uniform fractionation schedule at our institution.

Methods

Data of patients treated with a second salvage stereotactic body radiotherapy course at the same spinal level or adjacent level from July 2018 to December 2020 were retrospectively reviewed. The initial prescribed dose was 24 Gy in two fractions, and the second dose 30 or 35 Gy in five fractions. The spinal cord dose constraint at the second course was 15.5 Gy at the maximum point dose. The endpoints were local failure and adverse effects. Local failure was defined as tumor progression using imaging.

Results

We assessed 19 lesions in 17 patients, with radioresistant lesions in 14 (74%) cases, the second stereotactic body radiotherapy to the same/adjacent spinal level in 13/6 cases, the median interval between stereotactic body radiotherapy of 23 (range, 6–52) months, and lesions compressing the cord in 5 (26%) cases. The median follow-up period was 19 months. The 12- and 18-month local failure rates were 0% and 8%, respectively. Radiation-induced myelopathy, radiculopathy and vertebral compression fractures were observed in 0 (0%), 4 (21%) and 2 (11%) lesions, respectively. Three patients with radiculopathy experienced almost complete upper or lower limb paralysis.

Conclusions

The second course of salvage stereotactic body radiotherapy for spinal metastases achieved good local control with a reduced risk of myelopathy. However, a high occurrence rate of radiation-induced radiculopathy has been confirmed.
Co-Skewness across Return Horizons
Authors: Jin Chenglu , Conlon Thomas , Cotter John
Published: April 2022

In this article, the impact of investment horizon on asset co-skewness is examined both empirically and theoretically. We first detail a strong horizon-based estimation bias for co-skewness. An asset that has positive co-skewness at one horizon may have negative co-skewness for others. This phenomenon is particularly evident for small-capitalization stocks. We then propose a theoretical model to estimate long-horizon co-skewness using data observed at the shortest horizon, which emphasizes the role of adjustment delays in the pricing of market-wide information among securities. Co-skewness is only found to be priced in the cross-section of stock returns for a small range of short horizons, calling into question the universal validity of the three-moment model.
Demography of botfly (Cuterebra fontinella) parasitism in white-footed mice (Peromyscus leucopus) in Kansas
Authors: Timm Robert M , Ruedebusch Cory R
Published: April 2022

Botflies (Diptera: Cuterebra sp.) are widely distributed and seasonally abundant parasites of small mammals in North America. To assess their effect on rodent survival, we studied the demography of botfly parasitism on small mammals in northeastern Kansas during 1995–1999. Additional comparisons on botflies parasitizing small mammals were made to a nearby old-field grid where mark–recapture studies continued from 1975 to 2003. White-footed mice, Peromyscus leucopus, were infected by botfly larvae (Cuterebra fontinella) each year during our study. The period of infection for P. leucopus was June–December, with the highest proportion of mice infected in July and August. A smaller, second peak of infection in October and November indicated that C. fontinella reproduced bimodally at this latitude with distinct summer and autumn population peaks. During the botfly seasons of the 5 years, 140 (23.3%) of 602 P. leucopus captured were infected. The percentages of individuals infected during 1995, 1996, 1997, and 1999 were not significantly different (22.4%, 17.3%, 17.1%, and 22.7%, respectively). However, in 1998, 32.4% individuals were infected with a higher incidence of multiple infections and a greater number of botfly larvae per host. Nearly half (47%) of the infected individuals caught in 1998 had infections in both summer and autumn, compared with 25% during the 1995–1997 seasons. In 1999, 63% of infected mice had at least a 2nd infection during the autumn. For all 5 years, 82%, 14%, and 4% of the infected mice had one, two, or three botflies, respectively. In 1998, 24% of the infected mice carried two or more botflies at one time, compared to 14% from 1995–1997 and 11% in 1999. Overall 94% of the infected mice were adults, with no differences between sexes. The variation seen in the prevalence of botfly parasitism of white-footed mice correlates to yearly weather fluctuations. Other demographic aspects of the infected mice, such as sex ratio, age, and longevity of those infected, did not change year to year. Our data suggest that infection with Cuterebra has little negative or positive impact upon populations of white-footed mice.
Boom and bust cycles of black-tailed prairie dog populations in the Thunder Basin grassland ecosystem
Authors: Davidson Ana D , Augustine David J , Jacobsen Hannah , Pellatz Dave , Porensky Lauren M , McKee Gwyn , Duchardt Courtney
Published: April 2022

Black-tailed prairie dogs (Cynomys ludovicianus) exhibit boom and bust cycles in landscapes where they are affected by outbreaks of plague caused by the introduced bacterium Yersinia pestis. We examined spatiotemporal dynamics of black-tailed prairie dog colonies in the Thunder Basin National Grassland, Wyoming over a period of 21 years. The colony complex experienced three plague epizootics during that time, and consequently three boom and bust cycles. The entire prairie dog colony complex collapsed over a 1-year period during the first and third epizootics, and over a 3-year period during the second epizootic. The boom and bust cycles were characterized by relatively rapid contractions in total area occupied by prairie dogs during a plague outbreak (e.g., >99% decline from 10,604 ha to 47 ha over 1 year [2017–2018]) followed by much slower recovery times (e.g., an increase from 410 ha to 10,604 ha over 11 years [2006–2017]). Prairie dogs occupied a total of 10,604 ha during at least one survey within the study period, but much of the area was not continuously occupied over time. We found that each of the three plague outbreaks occurred in years with highly connected prairie dog colonies and slightly above-average temperatures and summer precipitation, which were preceded by a dry year. Although plague outbreaks were associated with climatic conditions, we were unable to detect a role of climate in driving colony expansion. Our results illustrate the cyclic and extreme nature of fluctuations in black-tailed prairie dog colony size and distribution in a landscape where plague occurs and illuminate some of the drivers of these cycles. Further, our work shows how introduced diseases can dramatically influence populations of a keystone species, with important consequences for the broader ecological system.
Shape variability in the periotics of odontocetes (Cetacea) distributed along the Pacific coast of northern Mexico
Authors: Esteves-Ponte María Alejandra Rosa , González-Barba Gerardo , García-Rodríguez Francisco Javier
Published: April 2022

Twenty-three species and four subspecies of odontocete belonging to five families (Delphinidae, Physeteridae, Kogiidae, Phocoenidae, and Ziphiidae) are distributed along the Pacific coast of northern Mexico. The morphological variability of these species has been studied extensively and a number of taxonomic studies have focused on cranial characteristics. The goal of this study was to describe the periotics of the odontocetes of the Pacific coast of northern Mexico and develop a taxonomic tool using descriptions of each species. We used a geometric morphometric analysis of 186 periotics housed in local and national osteological collections. Our results show the taxonomic value of periotics and a significant phylogenetic signal associated with this structure. Based on these results we present a descriptive catalog that can be used for identification purposes.
Body Size at Different Ages and Risk of 6 Cancers: A Mendelian Randomization and Prospective Cohort Study
Authors: Mariosa Daniela , Smith-Byrne Karl , Richardson Tom G , Ferrari Pietro , Gunter Marc J , Papadimitriou Nikos , Murphy Neil , Christakoudi Sofia , Tsilidis Konstantinos K , Riboli Elio , Muller David , Purdue Mark P , Chanock Stephen J , Hung Rayjean J , Amos Christopher I , O’Mara Tracy A , Amiano Pilar , Pasanisi Fabrizio , Rodriguez-Barranco Miguel , Krogh Vittorio , Tjønneland Anne , Halkjær Jytte , Perez-Cornago Aurora , Chirlaque María-Dolores , Skeie Guri , Rylander Charlotta , Borch Kristin Benjaminsen , Aune Dagfinn , Heath Alicia K , Ward Heather A , Schulze Matthias , Bonet Catalina , Weiderpass Elisabete , Davey Smith George , Brennan Paul , Johansson Mattias
Published: April 2022

It is unclear if body weight in early life affects cancer risk independently of adult body weight. To investigate this question for 6 obesity-related cancers, we performed univariable and multivariable analyses using 1) Mendelian randomization (MR) analysis and 2) longitudinal analyses in prospective cohorts. Both the MR and longitudinal analyses indicated that larger early life body size was associated with higher risk of endometrial (odds ratioMR = 1.61, 95% confidence interval = 1.23 to 2.11) and kidney (odds ratioMR = 1.40, 95% confidence interval = 1.09 to 1.80) cancer. These associations were attenuated after accounting for adult body size in both the MR and cohort analyses. Early life body mass index (BMI) was not consistently associated with the other investigated cancers. The lack of clear independent risk associations suggests that early life BMI influences endometrial and kidney cancer risk mainly through pathways that are common with adult BMI.