bluuebunny/crossref_metadata_2025 huggingface dataset:
Strategic Ontologies: Narrative and Meso-Level Theorizing in International Politics
Authors: Lerner Adam B , O'Loughlin Ben
Published: June 2023

This paper offers a theory of incremental theoretical evolution connecting the practice of international politics with disciplinary IR. It theorizes how international political actors engaged in strategic local decision-making exert productive power over dominant scientific ontologies of the international system. We refer to the narratives emerging from these processes as strategic ontologies, defined as gradual reformulations of the subjects, objects, and relational logics of the international system according to positionally determined priorities. As strategic ontologies gain acceptance, their innovations endure beyond the context of their utterance, leading to meso-level theoretical evolution. We substantiate this account with comparative case studies of contested strategic ontologies that have yet to become dominant in either the international arena or IR theory. Without strategic ontology as an analytical lens, scholarship might miss embryonic theoretical innovations in the process of gaining traction. First, we examine how Israel and West Germany engaged in strategic ontological contestation when negotiating a reparations agreement following the Holocaust. Second, we analyze how states have used vulnerability in climate negotiations in 2020–2021 to recast global policy priorities. Recognition of strategic ontologies across contexts illuminates theoretical innovations in real-time and opens a path for dynamic new bridges between the academy and policymaking.
DEPLOYR: a technical framework for deploying custom real-time machine learning models into the electronic medical record
Authors: Corbin Conor K , Maclay Rob , Acharya Aakash , Mony Sreedevi , Punnathanam Soumya , Thapa Rahul , Kotecha Nikesh , Shah Nigam H , Chen Jonathan H
Published: June 2023

Objective

Heatlhcare institutions are establishing frameworks to govern and promote the implementation of accurate, actionable, and reliable machine learning models that integrate with clinical workflow. Such governance frameworks require an accompanying technical framework to deploy models in a resource efficient, safe and high-quality manner. Here we present DEPLOYR, a technical framework for enabling real-time deployment and monitoring of researcher-created models into a widely used electronic medical record system.

Materials and Methods

We discuss core functionality and design decisions, including mechanisms to trigger inference based on actions within electronic medical record software, modules that collect real-time data to make inferences, mechanisms that close-the-loop by displaying inferences back to end-users within their workflow, monitoring modules that track performance of deployed models over time, silent deployment capabilities, and mechanisms to prospectively evaluate a deployed model’s impact.

Results

We demonstrate the use of DEPLOYR by silently deploying and prospectively evaluating 12 machine learning models trained using electronic medical record data that predict laboratory diagnostic results, triggered by clinician button-clicks in Stanford Health Care’s electronic medical record.

Discussion

Our study highlights the need and feasibility for such silent deployment, because prospectively measured performance varies from retrospective estimates. When possible, we recommend using prospectively estimated performance measures during silent trials to make final go decisions for model deployment.

Conclusion

Machine learning applications in healthcare are extensively researched, but successful translations to the bedside are rare. By describing DEPLOYR, we aim to inform machine learning deployment best practices and help bridge the model implementation gap.
Integrating sperm cell transcriptome and seminal plasma metabolome to analyze the molecular regulatory mechanism of sperm motility in Holstein stud bulls
Authors: Li Wenlong , Mi Siyuan , Zhang Jinning , Liu Xueqin , Chen Siqian , Liu Shuli , Feng Xia , Tang Yongjie , Li Yanhua , Liu Lin , Fang Lingzhao , Zhang Shengli , Yu Ying
Published: June 2023

Considering that artificial insemination is the most widely used assisted reproductive technique in the dairy industry, the semen quality of bulls is very important for selecting excellent stud bulls. Sperm motility is one of the important traits of semen quality, and related genes may be regulated by environmental factors. Seminal plasma can affect sperm cell transcriptome and further affect sperm motility through exosome or other processes. However, the molecular regulation mechanism of bull sperm motility has not been studied by combining the sperm cell transcriptome with seminal plasma metabolome. The number of motile sperm per ejaculate (NMSPE) is an integrated indicator for assessing sperm motility in stud bulls. In the present study, we selected 7 bulls with higher NMSPE (5,698.55 million +/− 945.40 million) as group H and 7 bulls with lower NMSPE (2,279.76 million +/− 1,305.69 million) as group L from 53 Holstein stud bulls. The differentially expressed genes (DEGs) in sperm cells were evaluated between the two groups (H vs. L). We conducted gene co-expression network analysis (WGCNA) on H and L groups of bulls, as well as two monozygotic twin Holstein bulls with different NMSPE values, to screen candidate genes for NMSPE. The regulatory effect of seminal plasma metabolome on the candidate genes of NMSPE was also investigated. A total of 1,099 DEGs were identified in the sperm cells of H and L groups. These DEGs were primarily concentrated in energy metabolism and sperm cell transcription. The significantly enriched Kyoto encyclopedia of genes and genomes (KEGG) pathways of the 57 differential metabolites were the aminoacyl–tRNA biosynthesis pathway and vitamin B6 metabolism pathway. Our study discovered 14 genes as the potential candidate markers for sperm motility, including FBXO39. We observed a broad correlation between transcriptome of sperm cells and seminal plasma metabolome, such as three metabolites, namely, mesaconic acid, 2-coumaric acid, and 4-formylaminoantipyrine, might regulate FBXO39 expression through potential pathways. The genes related to seminal plasma metabolites expressed in sperm cells are not only located near the quantitative trait loci of reproductive traits, but also enriched in the genome-wide association study signal of sire conception rate. Collectively, this study was the first to investigate the interplays among transcriptome of sperm cells and seminal plasma metabolome from Holstein stud bulls with different sperm motility.
Data processing, analysis, and evaluation methods for co-design of coreless filament-wound building systems
Authors: Gil Pérez Marta , Mindermann Pascal , Zechmeister Christoph , Forster David , Guo Yanan , Hügle Sebastian , Kannenberg Fabian , Balangé Laura , Schwieger Volker , Middendorf Peter , Bischoff Manfred , Menges Achim , Gresser Götz T , Knippers Jan
Published: June 2023

The linear design workflow for structural systems, involving a multitude of iterative loops and specialists, obstructs disruptive innovations. During design iterations, vast amounts of data in different reference systems, origins, and significance are generated. This data is often not directly comparable or is not collected at all, which implies a great unused potential for advancements in the process. In this paper, a novel workflow to process and analyse the data sets in a unified reference frame is proposed. From this, differently sophisticated iteration loops can be derived. The developed methods are presented within a case study using coreless filament winding as an exemplary fabrication process within an architectural context. This additive manufacturing process, using fiber-reinforced plastics, exhibits great potential for efficient structures when its intrinsic parameter variations can be minimized. The presented method aims to make data sets comparable by identifying the steps each data set needs to undergo (acquisition, pre-processing, mapping, post-processing, analysis, and evaluation). These processes are imperative to provide the means to find domain interrelations, which in the future can provide quantitative results that will help to inform the design process, making it more reliable, and allowing for the reduction of safety factors. The results of the case study demonstrate the data set processes, proving the necessity of these methods for the comprehensive inter-domain data comparison.
Dynamic phosphorylation of CENP-N by CDK1 guides accurate chromosome segregation in mitosis
Authors: Liu Ran , Dou Zhen , Tian Tian , Gao Xinjiao , Chen Lili , Yuan Xiao , Wang Chunyue , Hao Jiahe , Gui Ping , Mullen McKay , Aikhionbare Felix , Niu Liwen , Bi Guoqiang , Zou Peng , Zhang Xuan , Fu Chuanhai , Yao Xuebiao , Zang Jianye , Liu Xing
Published: June 2023

In mitosis, accurate chromosome segregation depends on the kinetochore, a supermolecular machinery that couples dynamic spindle microtubules to centromeric chromatin. However, the structure–activity relationship of the constitutive centromere-associated network (CCAN) during mitosis remains uncharacterized. Building on our recent cryo-electron microscopic analyses of human CCAN structure, we investigated how dynamic phosphorylation of human CENP-N regulates accurate chromosome segregation. Our mass spectrometric analyses revealed mitotic phosphorylation of CENP-N by CDK1, which modulates the CENP-L–CENP-N interaction for accurate chromosome segregation and CCAN organization. Perturbation of CENP-N phosphorylation is shown to prevent proper chromosome alignment and activate the spindle assembly checkpoint. These analyses provide mechanistic insight into a previously undefined link between the centromere–kinetochore network and accurate chromosome segregation.
From Refugees to Citizens? How Refugee Youth in the Dadaab Camps of Kenya Use Education to Challenge Their Status as Non-Citizens
Authors: Aden Hassan , Edle Abdirahman , Horst Cindy
Published: June 2023

The Dadaab camps of Kenya have ‘warehoused’ refugees from Somalia and elsewhere since 1991, providing their inhabitants with little hope to (re)gain the legal rights, participation, and membership that citizenship provides. Refugee youth in Dadaab hope that education can enable their access to citizenship rights—in particular, physical mobility and the right to work. Drawing on ethnographic research, semi-structured interviews, and life history interviews conducted in Dadaab and Mogadishu, this article discusses how refugee youth from Dadaab attempt to challenge their status as non-citizens through secondary education. Our study underscores that achieving citizenship rights, as well as civic participation and belonging, are key aspirations for these young people independent of whether they remain in Dadaab or (re)turn to Mogadishu. Yet, their ideas about what these key aspects of citizenship are and how to achieve them shift with their geographical location and in the presence or absence of citizenship rights.
Two-stage estimation and bias-corrected empirical likelihood in a partially linear single-index varying-coefficient model
Authors: Xue Liugen
Published: June 2023

The estimation and empirical likelihood (EL) of the parameters of interest in a partially linear single-index varying-coefficient model are studied. A two-stage method is presented to estimate the regression parameters and the coefficient functions. The asymptotic distributions of the proposed estimators are obtained. Meanwhile, a bias-corrected EL ratio for the regression parameters is proposed. It is shown that the ratio is asymptotically standard chi-squared. The result can be directly used to construct the EL confidence regions of the regression parameters. Simulation studies are carried out to evaluate the finite sample behaviour of the proposed method. An application example of a real data set is given.
Bayesian estimation of real-time epidemic growth rates using Gaussian processes: local dynamics of SARS-CoV-2 in England
Authors: Guzmán-Rincón Laura M , Hill Edward M , Dyson Louise , Tildesley Michael J , Keeling Matt J
Published: June 2023

Quantitative assessments of the recent state of an epidemic and short-term projections for the near future are key public-health tools that have substantial policy impacts, helping to determine if existing control measures are sufficient or need to be strengthened. Key to these quantitative assessments is the ability to rapidly and robustly measure the speed with which an epidemic is growing or decaying. Frequently, epidemiological trends are addressed in terms of the (time-varying) reproductive number R. Here, we take a more parsimonious approach and calculate the exponential growth rate, r, using a Bayesian hierarchical model to fit a Gaussian process to the epidemiological data. We show how the method can be employed when only case data from positive tests are available, and the improvement gained by including the total number of tests as a measure of the heterogeneous testing effort. Although the methods are generic, we apply them to SARS-CoV-2 cases and testing in England, making use of the available high-resolution spatio-temporal data to determine long-term patterns of national growth, highlight regional growth, and spatial heterogeneity.
Survey Consent to Administrative Data Linkage: Five Experiments on Wording and Format
Authors: Jäckle Annette , Burton Jonathan , Couper Mick P , Crossley Thomas F , Walzenbach Sandra
Published: June 2023

To maximize the value of the data while minimizing respondent burden, survey data are increasingly linked to administrative records. Record linkage often requires the informed consent of survey respondents and failure to obtain consent reduces sample size and may lead to selection bias. Relatively little is known about how best to word and format consent requests in surveys. We conducted a series of experiments in a probability household panel and an online access panel to understand how various features of the design of the consent request can affect informed consent. We experimentally varied: (i) the readability of the consent request, (ii) placement of the consent request in the survey, (iii) consent as default versus the standard opt-in consent question, (iv) offering additional information, and (v) a priming treatment focusing on trust in the data holder. For each experiment, we examine the effects of the treatments on consent rates, objective understanding of the consent request (measured with knowledge test questions), subjective understanding (how well the respondent felt they understood the request), confidence in their decision, response times, and whether they read any of the additional information materials. We find that the default wording and offering additional information do not increase consent rates. Improving the readability of the consent question increases objective understanding but does not increase the consent rate. However, asking for consent early in the survey and priming respondents to consider their trust in the administrative data holder both increase consent rates without negatively affecting understanding of the request.
What If God is a ‘Pagan Amalgam’: Marilynne Robinson and Historical Bible Scholarship
Authors: Douglas Christopher
Published: June 2023

Marilynne Robinson is one of the most influential Christian writers and public intellectuals alive today, and her views on a range of topics should be taken seriously. In her 2015 essay entitled ‘Memory’, she argues that the ‘liberal side’ of American Christianity has retreated from scriptural theology under pressure from academic biblical criticism. Her dismissal of Hebrew Bible scholarship is centred on two primary and interrelated ideas. First is the idea that Israelite religion was embedded in a broader context of Ancient Near East (ANE) religious cultures, such that biblical stories and characters sometimes borrow from other ancient sources. Second is the problem that the scholarly understanding of ancient Israelite polytheism threatens to make God into a ‘pagan amalgam’. The interrelated problem, that is, is the uniqueness and transcendence of the Hebrew Bible, and the God who is its main character. In this article, I review the scholarship on ancient Israelite religion and Robinson’s complaints about it. I argue that Robinson treats the critical scholarship only at a distance, allusively, (mis)representing it and sometimes (mis)understanding it in superficial ways, but that her theological anxiety is warranted.
Lasiurus villosissimus(Chiroptera: Vespertilionidae)
Authors: Díaz M Mónica , Núñez-Rodríguez Álvaro , Allendes Juan Luis , Barquez Rubén M , Rodríguez-San Pedro Annia
Published: June 2023

The South American hoary bat, Lasiurus villosissimus (É. Geoffroy Saint-Hilaire, 1806), is a vespertilionid bat, endemic to South America and occurring in all countries except Guyana, French Guiana, and Suriname. It is one of the four species included in the subgenus Aeorestes. Lasiurus villosissimus is distinguishable from all other species of the genus by its larger size and coloration (except Lasiurus cinereus, but it only occurs in Mexico, Central America, and the Hawaiian Islands). Pelage is dark brownish and grayish mixed with yellow, tinged with white, producing a frosty or hoary appearance which is always evident. It is an insectivorous species that inhabits a great variety of habitats.
P53-negative status and gross total resection as predictive factors for autologous tumor vaccine treatment in newly diagnosed glioblastoma patients
Authors: Yamada Erika , Ishikawa Eiichi , Miyazaki Tsubasa , Miki Shunichiro , Sugii Narushi , Kohzuki Hidehiro , Tsurubuchi Takao , Sakamoto Noriaki , Watanabe Shinya , Matsuda Masahide
Published: June 2023

Background

Among primary brain tumors, glioblastoma (GBM) is the most common and aggressive in adults, with limited treatment options. Our previous study showed that autologous formalin-fixed tumor vaccine (AFTV) contributed to prognostic improvements in newly diagnosed GBM patients. However, some patients died early despite the treatment. The discovery of predictive factors in the treatment was warranted for efficient patient recruitment and studies to overcome resistance mechanisms. Identifying prognostic factors will establish AFTV guidelines for patients who may respond to the therapy.

Methods

Data from 58 patients with newly diagnosed GBM, including 29 who received standard therapy plus AFTV (AFTV group) and 29 who received standard treatment (control group) were analyzed. Several data including patient age, sex, the extent of removal, and various cell immunohistochemistry (IHC) parameters were also included in the analysis.

Results

Both univariate and multivariate analyses revealed that gross total resection (GTR) and negative p53 were associated with a better prognosis only in the AFTV group. In the IHC parameters, CD8 staining status was also one of the predictive factors in the univariate analysis. For blood cell-related data, lymphocyte counts of 1100 or more and monocyte counts of 280 or more before chemo-radiotherapy were significant factors for good prognosis in the univariate analysis.

Conclusions

A p53-negative status in IHC and GTR were the predictive factors for AFTV treatment in newly diagnosed GBM patients. Microenvironment-targeted treatment and pretreatment blood cell status may be key factors to enhance therapy effects.
N4-acetylation of cytidine in mRNA plays essential roles in plants
Authors: Wang Wenlei , Liu Huijie , Wang Feifei , Liu Xiaoye , Sun Yu , Zhao Jie , Zhu Changhua , Gan Lijun , Yu Jinping , Witte Claus-Peter , Chen Mingjia
Published: June 2023

The biological function of RNA can be modulated by base modifications. Here, we unveiled the occurrence of N4-acetylation of cytidine in plant RNA, including mRNA, by employing LC-MS/MS and acRIP-seq. We identified 325 acetylated transcripts from the leaves of 4-week-old Arabidopsis (Arabidopsis thaliana) plants and determined that 2 partially redundant N-ACETYLTRANSFERASEs FOR CYTIDINE IN RNA (ACYR1 and ACYR2), which are homologous to mammalian NAT10, are required for acetylating RNA in vivo. A double-null mutant was embryo lethal, while eliminating 3 of the 4 ACYR alleles led to defects in leaf development. These phenotypes could be traced back to the reduced acetylation and concomitant destabilization of the transcript of TOUGH, which is required for miRNA processing. These findings indicate that N4-acetylation of cytidine is a modulator of RNA function with a critical role in plant development and likely many other processes.
A Lipopolysaccharide O-Antigen Synthesis Gene in Mesorhizobium huakuii Plays Differentiated Roles in Root Nodule Symbiotic Compatibility with Astragalus sinicus
Authors: Tang Zhide , Cai Shuyun , Liu Yuan , Li Dongzhi , Xie Fuli , Lin Hui , Chen Dasong , Li Youguo
Published: June 2023

Lipopolysaccharide (LPS) is a ubiquitous microbial-associated molecular pattern. Plants can sense the three components of LPS, including core polysaccharide, lipid A, and O-antigen. LPS biosynthesis is an essential factor for the successful establishment of symbiosis in the rhizobium–legume plant system. The MCHK_1752 gene ( Mesorhizobium huakuii 7653R gene) encodes O-antigen polymerase and affects the synthesis of O-antigen. Here, we investigated the symbiotic phenotypes of six Astragalus sinicus accessions inoculated with the MCHK_1752 deletion mutant strain. The results revealed that the MCHK_1752 deletion mutant strain had a suppressing effect on the symbiotic nitrogen fixation of two A. sinicus accessions, a promoting effect in three A. sinicus accessions, and no significant effect in one A. sinicus accessions. In addition, the effect of MCHK_1752 on the phenotype was confirmed by its complementary strains and LPS exogenous application. Deletion of MCHK_1752 showed no effect on the growth of a strain, but affected biofilm formation and led to higher susceptibility to stress in a strain. At the early symbiotic stage, Xinzi formed more infection threads and nodule primordia than Shengzhong under inoculation with the mutant, which might be an important reason for the final symbiotic phenotype. A comparison of early transcriptome data between Xinzi and Shengzhong also confirmed the phenotype at the early symbiotic stage. Our results suggest that O-antigen synthesis genes influence symbiotic compatibility during symbiotic nitrogen fixation.

[Formula: see text] Copyright © 2023 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
Leaf Endophyte Community Composition and Network Structures Differ Between Tolerant and Susceptible English Boxwood
Authors: Kong Ping , Li Xiaoping , Sharifi Melissa , Bordas Adria , Hong Chuanxue
Published: June 2023

Differential tolerance of English boxwood to boxwood blight has been linked to the ratio of culturable bacterial and fungal dominance in the leaf tissue of representative samples. To further understand how the whole endophyte communities may involve the tolerance of large samples, we extracted DNA from healthy leaf tissue of previously identified 28 tolerant (T), 41 moderately tolerant (M), and 21 susceptible (S) English boxwood plants, then sequenced associated bacterial and fungal amplicons using the Nanopore MinION platform. The endophyte community did not differ in diversity among the T, M, and S plants but differed in the abundance of bacteria and fungi, particularly between T and S samples. The bacterial genera Brevundimonas and Ammonifex had higher relative abundance in the T and M communities than in the S community, in which the fungal genera Botrytis and Thermothelomyces and family Chaetomiaceae were more dominant. The same results were obtained when mother and daughter samples in the T community were compared with controls in the S community, suggesting bacteria as a work force in the T community. Cooccurrence network analyses revealed that the T network had more fungal hubs but was less complex, with more positive connections than the S network, suggesting that the T community was supported by a healthier network. The resistance of English boxwood to blight is likely attributed to bacteria dominance and a synergic community network. This study is foundational to constructing synthetic communities and using whole communities of tolerant plants through vegetative propagation for microbe-modulated immunity.
Genome Sequence Resource of Cladosporium velox Strain C4 Causing Cotton Boll Disease in Xinjiang, China
Authors: Li Jingwen , Zhang Dandan , Du Yejuan , Song Jian , Li Ran , Dai Xiaofeng , Chen Jieyin , Li Guoying , Liu Zheng
Published: June 2023

Cladosporium spp., as one of the largest and most heterogeneous genera of hyphomycetes, are widely distributed worldwide. This genus is usually adaptable to a wide variety of extreme environments. However, only 11 genomes of Cladosporium genus have been publicly released. From 2017, we found for the first time that Cladosporium velox could cause cotton boll disease and lead to stiffness and cracking boll in Xinjiang, China. Herein, we provide a high-quality reference genome for the C. velox strain C4 isolated from cotton boll in Xinjiang, China. The genome size and encoding gene number of the C. velox strain C4 and C. cucumerinum strain CCNX2, which was recently released and caused the cucumber scab, showed minor differences. This resource will contribute to future research that aims to elucidate the genetic basis of C. velox pathogenicity and could expand our knowledge of Cladosporium spp. genomic characteristics that will be valuable for the development of Cladosporium disease control measures.
A Breakthrough in Kitavirids: Genetic Variability, Reverse Genetics, Koch's Postulates, and Transmission of Hibiscus Green Spot Virus 2
Authors: Olmedo-Velarde Alejandro , Larrea-Sarmiento Adriana , Wang Xupeng , Hu John , Melzer Michael
Published: June 2023

Hibiscus green spot virus 2 (HGSV-2), a member of the genus Higrevirus (family Kitaviridae), is a positive-stranded RNA virus associated with leprosis-like symptoms in citrus and green spots on leaves in hibiscus. HGSV-2 has only been reported in Hawaii, and while it is speculated that mites in the genus Brevipalpus might be responsible for its transmission, proper transmission assays have yet to be conducted. This study characterizes additional citrus and hibiscus isolates of HGSV-2 collected from two Hawaiian Islands. We constructed an infectious cDNA clone from a hibiscus isolate of HGSV-2 collected on Oahu and demonstrated its ability to infect several experimental hosts, including Phaseolus vulgaris, Nicotiana tabacum, and N. benthamiana, as well as natural hosts, Citrus reticulata and Hibiscus arnottianus. Bacilliform virions with varied sizes of 33 to 120 nm (length) and 14 to 70 nm (diameter) were observed in partially purified preparations obtained from agroinoculated leaves. Virus progeny from the infectious cDNA clone was found to be infectious after mechanical transmission to N. benthamiana and to cause local lesions. Finally, an isoline colony of the mite Brevipalpus azores had vector competence to transmit a citrus isolate of HGSV-2 collected from Maui to citrus and hibiscus plants, demonstrating the mite-borne nature of HGSV-2. The infectious cDNA clone developed in this study is the first reverse-genetics system for a kitavirid and will be fundamental to better characterize basic biology of HGSV-2 and its interactions with host plants and mite vectors.
Seasonal Dynamics of Various Scab-Causing Streptomyces Genotypes Among Potato Fields on Prince Edward Island
Authors: Hudec Cindy , Biessy Adrien , Léger Geneviève , Albert Daphné , Novinscak Amy , Filion Martin
Published: June 2023

Potato common scab is an important bacterial plant disease caused by numerous Streptomyces species and strains. A better understanding of the genetic diversity and population dynamics of these microorganisms in the field is crucial to develop effective control methods. Our research group previously studied the genetic diversity of scab-causing Streptomyces spp. in Prince Edward Island, one of Canada's most important potato-growing provinces. Fourteen distinct Streptomyces genotypes were identified and displayed contrasting aggressiveness toward potato tubers. To better understand the distribution and occurrence of these genotypes over time under field conditions, the population dynamics were studied in nine commercial potato fields throughout a growing season. A comparative genomic-driven approach was used to design genotype-specific primers and probes, allowing us to quantify, using quantitative polymerase chain reaction, the abundance of each of the 14 genotypes in field soil. Thirteen of the previously identified genotypes were detected in at least one soil sample, with various frequencies and population sizes across the different fields under study. Interestingly, weakly virulent genotypes dominated, independent of time or location. Among them, three genotypes accounted for more than 80% of the genotypes’ combined population. Although the highly virulent genotypes were detected in lower relative abundance than the weakly virulent ones, an increase in the highly virulent genotypes’ population size was observed over the growing season in most fields. The results will ultimately be useful for the development of targeted common scab control strategies.
The effects of intermittent fasting and a low-carbohydrate diet on type 2 diabetes
Authors: Pelc Miri Ann
Published: June 2023

Type 2 diabetes is a known complication of obesity and a financial burden on the US healthcare system. The 2022 American Diabetes Association (ADA) guidelines support reducing overall carbohydrate intake for patients with type 2 diabetes to improve hyperglycemia. The ADA has no recommendations about intermittent fasting for patients with type 2 diabetes. This article describes a patient who successfully and safely used a low-carbohydrate diet and intermittent fasting and was able to discontinue medications for type 2 diabetes.
Integrated care and the behavioral health primary care provider
Authors: Nelson Christopher
Published: June 2023

Primary care remains the main setting for delivery of psychiatric care. An integrated approach improves the ability of primary care providers (PCPs) to care for complex patients with behavioral health needs. This article describes integrated care and how physician associates/assistants can gain additional training to become behavioral health specialists.
Systemic lupus erythematosus
Authors: El Hussein Mohamed Toufic , Wong Cayla
Published: June 2023

Drug therapy for patients with systemic lupus erythematosus (SLE) aims to decrease symptom severity. Pharmacologic interventions are divided into four categories: antimalarials, glucocorticoids (GCs), immunosuppressants (ISs), and biological agents. Hydroxychloroquine, the most commonly used antimalarial treatment for this disease, is a mainstay in treating all patients with SLE. The multitude of adverse reactions of GCs has led clinicians to minimize their dosages or discontinue them whenever possible. To speed up the discontinuation or minimization of GCs, ISs are used for their steroid-sparing properties. Furthermore, certain ISs such as cyclophosphamide are recommended as maintenance agents to prevent flares and reduce the reoccurrence and severity of the disease state. Biological agents are recommended when other treatment options have failed due to intolerance or inefficacy. This article presents pharmacologic approaches for managing SLE in patients based on clinical practice guidelines and data from randomized controlled trials.
The Use of Artificial Intelligence Tools to Prepare Medical School Applications
Authors: Hashimoto Daniel A. , Johnson Kevin B.
Published: June 2023

Advances in artificial intelligence (AI) have been changing the landscape in daily life and the practice of medicine. As these tools have evolved to become consumer-friendly, AI has become more accessible to many individuals, including applicants to medical school. With the rise of AI models capable of generating complex passages of text, questions have arisen regarding the appropriateness of using such tools to assist in the preparation of medical school applications.

In this commentary, the authors offer a brief history of AI tools in medicine and describe large language models, a form of AI capable of generating natural language text passages. They question whether AI assistance should be considered inappropriate in preparing applications and compare it with the assistance some applicants receive from family, physician friends, or consultants. They call for clearer guidelines on what forms of assistance—human and technological—are permitted in the preparation of medical school applications. They recommend that medical schools steer away from blanket bans on AI tools in medical education and instead consider mechanisms for knowledge sharing about AI between students and faculty members, incorporation of AI tools into assignments, and the development of curricula to teach the use of AI tools as a competency.
Easing the Entry of Qualified International Medical Graduates to U.S. Medical Practice
Authors: Andrews John S. , Ryan Amber L. , Elliott Victoria Stagg , Brotherton Sarah E.
Published: June 2023

Almost one quarter of physicians and physicians-in-training in the United States are international medical graduates (IMGs), meaning they have graduated from a medical school not accredited in the United States. Some IMGs are U.S. citizens and others are foreign nationals. IMGs, many of whom have years of training and experience gained in their countries of origin, have long contributed to the U.S. health care system, especially by providing care to populations that have been historically underserved. Additionally, many IMGs contribute to the diversity of the health care workforce, which can enhance the health of the population. The diversity of the United States is increasing, and racial and ethnic concordance between a physician and a patient has been linked to improved health outcomes.

IMGs must meet national- and state-level licensing and credentialing standards like any other U.S. physician. This assures the ongoing quality of the care provided by the medical workforce and protects the public. However, at the state level, variation in standards and standards that may be more challenging to meet than those for U.S. medical school graduates may hamper IMGs’ contributions. IMGs who are not U.S. citizens also face visa and immigration barriers.

In this article, the authors present insights gleaned from Minnesota’s model IMG integration program as well as changes made in 2 states in response to the COVID-19 pandemic. Improving and streamlining processes for IMGs to be licensed and credentialed as well as the policies governing visas and immigration, where appropriate, can ensure that IMGs will be willing and able to continue to practice when and where they are needed. This, in turn, could increase the contribution of IMGs to addressing health care inequities, improving health care access through service in federally designated Health Professional Shortage Areas, and reducing the impact of potential physician shortages.
Role of External Fixator Assistance in Tibial Rotation Osteotomy—Technique and Results
Authors: Bor Noam , Dujovny Eytan , Rozen Nimrod , Rubin Guy
Published: June 2023

Background:

Idiopathic torsional deformities in children tend to resolve without intervention; however, pathologic torsion, which is primarily associated with neuromuscular diseases, requires surgical correction. We present a technique to assess the magnitude of tibial rotational osteotomy intraoperatively based on clinically simulating the degree of correction.

Methods:

A surgical technique is described, and a review of 8 rotational deformities of the tibia in 7 patients is presented. The data being collected included age, sex, date of surgery, diagnosis, and the magnitude of rotational deformity preoperatively and postoperatively.

Results:

There were 7 patients, of which 3 were females. The mean age was 10.5 years (5.5–18 y). The mean preoperative medial tibial rotation deformity in 7 segments was 20° (10–30°), and a lateral rotation of 40° was present in another segment. All deformities except one were corrected to an average of 10° external rotation.

Conclusions:

Our method differs from that of the common method used by most surgeons, in which pins are inserted before the tibial osteotomy at a predetermined angle, which represents the amount of desired final correction. We believe that the technique we present is easier on the surgeon, and the clinical results meet the planned presurgical expectations.
Health Professionals can Sustain Proficiency in Motivational Interviewing With a Moderate Amount of Training: An Intervention Fidelity Study
Authors: Rimayanti Made Utari , Taylor Nicholas F. , Shields Nora , Prendergast Luke A. , O'Halloran Paul D.
Published: June 2023

Introduction:

Motivational interviewing (MI) proficiency may erode quickly, limiting its effectiveness. We examined whether health professionals completing a 2-day workshop, with 3 to 5 hours of personalized coaching, and twice-yearly group reflections sustained proficiency for the duration of a hip fracture rehabilitation trial and whether intervention was implemented as intended.

Methods:

A fidelity study was completed as part of a process evaluation of the trial that tested whether physical activity increased among hip fracture patients randomly allocated to receive MI (experimental) compared with dietary advice (control) over ten 30-minute sessions. Twelve health professionals (none were proficient in MI before trial commencement) delivered the intervention for up to 952 days. Two hundred experimental sessions (24% of all sessions, 83 patients) were randomly selected to evaluate proficiency using the MI Treatment Integrity scale; along with 20 control sessions delivered by four dietitians. Linear mixed-effects regression analyses determined whether proficiency was sustained over time. Dose was assessed from all experimental sessions (n = 840, 98 patients).

Results:

Intervention was implemented as intended; 82% of patients received at least eight 30-minute sessions. All motivational interviewers were proficient, whereas dietitians did not inadvertently deliver MI. Time had no effect on MI proficiency (est < 0.001/d, P = .913, 95% CI, −0.001 to 0.001).

Discussion:

MI proficiency was sustained in a large trial over 2.6 years by completing a 2-day workshop, 3 to 5 hours of personalized coaching, and twice-yearly group reflections, even for those without previous experience; further research needs to establish the maximum duration of training effectiveness.
Using Balancing Weights to Target the Treatment Effect on the Treated when Overlap is Poor
Authors: Ben-Michael Eli , Keele Luke
Published: June 2023

Inverse probability weights are commonly used in epidemiology to estimate causal effects in observational studies. Researchers often focus on either the average treatment effect or the average treatment effect on the treated with inverse probability weighting estimators. However, poor overlap in the baseline covariates between the treated and control groups can produce extreme weights that can result in biased treatment effect estimates. One alternative to inverse probability weights are overlap weights, which target the population with the most overlap on observed covariates. Although estimates based on overlap weights produce less bias in such contexts, the causal estimand can be difficult to interpret. An alternative to model-based inverse probability weights are balancing weights, which directly target imbalances during the estimation process, rather than model fit. Here, we explore whether balancing weights allow analysts to target the average treatment effect on the treated in cases where inverse probability weights lead to biased estimates due to poor overlap. We conduct three simulation studies and an empirical application. We find that balancing weights often allow the analyst to still target the average treatment effect on the treated even when overlap is poor. We show that although overlap weights remain a key tool, more familiar estimands can sometimes be targeted by using balancing weights.
Neuropilin-1 is essential for vascular endothelial growth factor A–mediated increase of sensory neuron activity and development of pain-like behaviors
Authors: Gomez Kimberly , Duran Paz , Tonello Raquel , Allen Heather N. , Boinon Lisa , Calderon-Rivera Aida , Loya-López Santiago , Nelson Tyler S. , Ran Dongzhi , Moutal Aubin , Bunnett Nigel W. , Khanna Rajesh
Published: June 2023

Neuropilin-1 (NRP-1) is a transmembrane glycoprotein that binds numerous ligands including vascular endothelial growth factor A (VEGFA). Binding of this ligand to NRP-1 and the co-receptor, the tyrosine kinase receptor VEGFR2, elicits nociceptor sensitization resulting in pain through the enhancement of the activity of voltage-gated sodium and calcium channels. We previously reported that blocking the interaction between VEGFA and NRP-1 with the Spike protein of SARS-CoV-2 attenuates VEGFA-induced dorsal root ganglion (DRG) neuronal excitability and alleviates neuropathic pain, pointing to the VEGFA/NRP-1 signaling as a novel therapeutic target of pain. Here, we investigated whether peripheral sensory neurons and spinal cord hyperexcitability and pain behaviors were affected by the loss of NRP-1. Nrp-1 is expressed in both peptidergic and nonpeptidergic sensory neurons. A CRIPSR/Cas9 strategy targeting the second exon of nrp-1 gene was used to knockdown NRP-1. Neuropilin-1 editing in DRG neurons reduced VEGFA-mediated increases in CaV2.2 currents and sodium currents through NaV1.7. Neuropilin-1 editing had no impact on voltage-gated potassium channels. Following in vivo editing of NRP-1, lumbar dorsal horn slices showed a decrease in the frequency of VEGFA-mediated increases in spontaneous excitatory postsynaptic currents. Finally, intrathecal injection of a lentivirus packaged with an NRP-1 guide RNA and Cas9 enzyme prevented spinal nerve injury–induced mechanical allodynia and thermal hyperalgesia in both male and female rats. Collectively, our findings highlight a key role of NRP-1 in modulating pain pathways in the sensory nervous system.
GluCl.CreON enables selective inhibition of molecularly defined pain circuits
Authors: Middleton Steven J. , Hu Huimin , Perez-Sanchez Jimena , Zuberi Sana , McGrath Williams Joseph , Weir Greg A. , Bennett David L.
Published: June 2023

Insight into nociceptive circuits will ultimately build our understanding of pain processing and aid the development of analgesic strategies. Neural circuit analysis has been advanced greatly by the development of optogenetic and chemogenetic tools, which have allowed function to be ascribed to discrete neuronal populations. Neurons of the dorsal root ganglion, which include nociceptors, have proved challenging targets for chemogenetic manipulation given specific confounds with commonly used DREADD technology. We have developed a cre/lox dependant version of the engineered glutamate-gated chloride channel (GluCl) to restrict and direct its expression to molecularly defined neuronal populations. We have generated GluCl.CreON that selectively renders neurons expressing cre-recombinase susceptible to agonist-induced silencing. We have functionally validated our tool in multiple systems in vitro, and subsequently generated viral vectors and tested its applicability in vivo. Using Nav1.8Cre mice to restrict AAV-GluCl.CreON to nociceptors, we demonstrate effective silencing of electrical activity in vivo and concomitant hyposensitivity to noxious thermal and noxious mechanical pain, whereas light touch and motor function remained intact. We also demonstrated that our strategy can effectively silence inflammatory-like pain in a chemical pain model. Collectively, we have generated a novel tool that can be used to selectively silence defined neuronal circuits in vitro and in vivo. We believe that this addition to the chemogenetic tool box will facilitate further understanding of pain circuits and guide future therapeutic development.
The Efficacy and Feasibility of a High Intensity Interval Training Program to Improve Cardiorespiratory Fitness in Truck Drivers
Authors: Gilson Nicholas D. , Mielke Gregore I. , Coombes Jeff S. , Duncan Mitch J. , Brown Wendy J.
Published: June 2023

Objective

This cluster-controlled pilot study assessed the efficacy and feasibility of “Fit2Drive,” a depot-delivered, high-intensity interval training (HIIT) program to improve the cardiorespiratory fitness (CRF) of truck drivers.

Methods

Companies of local delivery drivers (44 men; mean [SD] age = 50.5 [9.8] years; Brisbane, Australia) were assigned to “Fit2Drive” (4 clusters; 27 drivers; 1 × 4 minutes supervised to self-managed HIIT, 3 times a week, 12 weeks) or a control (5 clusters; 17 drivers). Analyses assessed between group changes in CRF (VO2peak), HIIT session attendance, and delivery costs.

Results

Driver clusters allocated to “Fit2Drive” significantly improved CRF compared to a control (mean difference of 3.6 mL·kg-1·min-1; P < 0.019; 95% confidence interval = 0.7–6.5 mL·kg-1·min-1). Drivers who completed the program attended 70% of sessions (25/36) with delivery costs averaging $710 AUD per driver.

Conclusions

The findings support the efficacy and feasibility of Fit2Drive but also highlight challenges for in-person delivery at scale.
Tympanoplasty Healing Outcomes With Use of Postoperative Otic Quinolones
Authors: Kolb Casey L. , Dirain Carolyn O. , Antonelli Patrick J.
Published: June 2023

Objective

Tympanoplasty usually results in tympanic membrane perforation (TMP) closure, but healing may be suboptimal (e.g., excess scarring). Factors that have been linked to impaired TM healing have become widely adopted (especially, postoperative use of quinolone ear drops). The aim of this study is to assess the frequency of suboptimal tympanoplasty healing with the use of otic quinolones postoperatively.

Study Design

Retrospective chart review.

Setting

Tertiary care facility.

Patients

One hundred patients undergoing tympanoplasty for TMP.

Intervention(s)

Tympanoplasty +/− canalplasty.

Main Outcome Measure(s)

Healing complications (e.g., granulation tissue, TMP, myringitis, bone exposure, lateralization, anterior blunting, medial canal fibrosis, and canal stenosis) and hearing loss.

Methods

Charts were reviewed for postoperative healing issues and hearing outcomes at 1 to 2 years postoperatively.

Results

TMP closure was found in 93.2%, but 34.2% had healing issues at 1 to 2 years postoperatively, with 20.6% having adverse healing outcomes (perforation (6.9%), granulation tissue (6.9%), medial fibrosis (4.1%), and myringitis, bone exposure, and webbing (all 1.4%). Another 13.7% had notable postoperative issues, such as protracted otorrhea (11.0%), otitis externa (9.6%), otitis media (1.4%), and atelectasis (2.7%). No medical, surgical, or patient factors impacted outcomes. Average air–bone gap at 1 to 2 years did not differ between patients with and without healing issues and patients with other postoperative issues (p = 0.5).

Conclusions

Suboptimal healing is common after tympanoplasty. There may be significant opportunity to improve post-tympanoplasty healing beyond improving the TMP closure rate.