bluuebunny/crossref_metadata_2025 huggingface dataset:
A new radiomics approach combining the tumor and peri-tumor regions to predict lymph node metastasis and prognosis in gastric cancer
Authors: Yang Yutao , Chen Hao , Ji Min , Wu Jianzhang , Chen Xiaoshan , Liu Fenglin , Rao Shengxiang
Published: January 2023

Objective

The development of non-invasive methods for evaluating lymph node metastasis (LNM) preoperatively in gastric cancer (GC) is necessary. In this study, we developed a new radiomics model combining features from the tumor and peri-tumor regions for predicting LNM and prognoses.

Methods

This was a retrospective observational study. In this study, two cohorts of patients with GC treated in Zhongshan Hospital Fudan University (Shanghai, China) were included. In total, 193 patients were assigned to the internal training/validation cohort; another 98 patients were assigned to the independent testing cohort. The radiomics features were extracted from venous phase computerized tomography (CT) images. The radiomics model was constructed and the output was defined as the radiomics score (RS). The performance of the RS and CT-defined N status (ctN) for predicting LNM was compared using the area under the curve (AUC). The 5-year overall survival and progression-free survival were compared between different subgroups using Kaplan–Meier curves.

Results

In both cohorts, the RS was significantly higher in the LNM-positive group than that in the LNM-negative group (all P < 0.001). The radiomics model combining features from the tumor and peri-tumor regions achieved the highest AUC in predicting LNM (AUC, 0.779 and 0.724, respectively), which performed better than the radiomics model based only on the tumor region and ctN (AUC, 0.717, 0.622 and 0.710, 0.603, respectively). The differences in 5-year overall survival and progression-free survival between high-risk and low-risk groups were significant (both P < 0.001).

Conclusions

The radiomics model combining features from the tumor and peri-tumor regions could effectively predict the LNM in GC. Risk stratification based on the RS was capable of distinguishing patients with poor prognoses.
X Chromosome Factor Kdm6a Enhances Cognition Independent of Its Demethylase Function in the Aging XY Male Brain
Authors: Shaw Cayce K , Abdulai-Saiku Samira , Marino Francesca , Wang Dan , Davis Emily J , Panning Barbara , Dubal Dena B
Published: January 2023

Males exhibit shorter life span and more cognitive deficits, in the absence of dementia, in aging human populations. In mammals, the X chromosome is enriched for neural genes and is a major source of biologic sex difference, in part, because males show decreased expression of select X factors (XY). While each sex (XX and XY) harbors one active X due to X chromosome inactivation in females, some genes, such as Kdm6a, transcriptionally escape silencing in females—resulting in lower transcript levels in males. Kdm6a is a known histone demethylase (H3K27me2/3) with multiple functional domains that is linked with synaptic plasticity and cognition. Whether elevating Kdm6a could benefit the aged male brain and whether this requires its demethylase function remains unknown. We used lentiviral-mediated overexpression of the X factor in the hippocampus of aging male mice and tested their cognition and behavior in the Morris water-maze. We found that acutely increasing Kdm6a—in a form without demethylase function—selectively improved learning and memory, in the aging XY brain, without altering total activity or anxiety-like measures. Further understanding the demethylase-independent downstream mechanisms of Kdm6a may lead to novel therapies for treating age-induced cognitive deficits in both sexes.
Slc9a6 mutation causes Purkinje cell loss and ataxia in theshakerrat
Authors: Figueroa Karla P , Anderson Collin J , Paul Sharan , Dansithong Warunee , Gandelman Mandi , Scoles Daniel R , Pulst Stefan M
Published: January 2023

The shaker rat carries a naturally occurring mutation leading to progressive ataxia characterized by Purkinje cell (PC) loss. We previously reported on fine-mapping the shaker locus to the long arm of the rat X chromosome. In this work, we sought to identify the mutated gene underlying the shaker phenotype and confirm its identity by functional complementation. We fine-mapped the candidate region and analyzed cerebellar transcriptomes, identifying a XM_217630.9 (Slc9a6):c.[191_195delinsA] variant in the Slc9a6 gene that segregated with disease. We generated an adeno-associated virus (AAV) targeting Slc9a6 expression to PCs using the mouse L7–6 (L7) promoter. We administered the AAV prior to the onset of PC degeneration through intracerebroventricular injection and found that it reduced the shaker motor, molecular and cellular phenotypes. Therefore, Slc9a6 is mutated in shaker and AAV-based gene therapy may be a viable therapeutic strategy for Christianson syndrome, also caused by Slc9a6 mutation.
The UK Supreme Court’s Miller II: Keeping the Court out of politics’ way?
Authors: Helmich Maurits
Published: January 2023

In recent years, the legitimacy of the United Kingdom’s Supreme Court has come under increasing pressure, with critics accusing the Court of unduly entering the domain of “politics.” Using the September 2019 Miller/Cherry “prorogation” judgment as a case study, this article analyzes the tension underpinning the criticisms. In particular, it makes two theoretical claims. First, three normative worries guide attempts to distance adjudicative judgment from the political sphere. Courts should not disrespect settled law (the “lawmaking worry”), interfere with the autonomy of politics (“the interventionism worry”), or answer political questions (“non-justiciability worry”). Second, though all three worries represent coherent norms in the abstract, in deeply controversial cases like Miller/Cherry, those norms fail to be of independent help. Attempts to distinguish the judicial domain from the domain of politics, the article argues, are themselves rooted in ideologically deeply colored definitions and acts of political stance-taking.
Standing in the shadows of balancing: Proportionality and the necessity test
Authors: da Silva Virgílio Afonso
Published: January 2023

The necessity test is one of the steps of the proportionality test. However, in the literature on the subject, written both by supporters as well as by critics of proportionality, the role of the necessity test has been frequently downplayed, sometimes plainly ignored. The spotlight has always been on balancing. This article shows that proportionality is not just about balancing, and that the necessity test has a much more important role to play than has been acknowledged so far. Its strengths are emphasized, especially its connection to politics, knowledge from other areas, time, and technological development. The article argues that shedding the appropriate light on these strengths has important implications for several ongoing debates around the proportionality test.
A critical reflection on the ‘Public Interest Exemption’ in China’s merger control regime
Authors: Ai Huizi , Philipsen Niels J
Published: January 2023

The Anti-Monopoly Law (AML) in China allows the responsible authority for merger control to consider not only the competition interest but also other public interest reasons when it reviews a takeover or merger. Where the responsible authority considers that the benefits of a takeover or merger to the public interest outweigh the harms to competition, it may ‘exempt’ the transaction. This ‘public interest exemption’ has never been formally applied since the introduction of the law in 2008. One explanation for this can be found in the ambiguity of the law: there are no legal provisions that clarify the public interest considerations. A second explanation is that China did not establish a separate review procedure for this public interest exemption. In practice, some approval decisions made by the enforcement authority led to confusion, as it was unclear whether the transactions were ‘exempted’ for public interest reasons or for industrial policies. This article reflects on the role of the public interest exemption in China. By drawing lessons from the past and examining the public interest exemption regime in Germany, it aims to provide suggestions for future reforms, against the background of the promulgation of the Amendment to the AML in 2022.
Optimizing Equity: Working towards Fair Machine Learning Algorithms in Laboratory Medicine
Authors: Azimi Vahid , Zaydman Mark A
Published: January 2023

Background

Methods of machine learning provide opportunities to use real-world data to solve complex problems. Applications of these methods in laboratory medicine promise to increase diagnostic accuracy and streamline laboratory operations leading to improvement in the quality and efficiency of healthcare delivery. However, machine learning models are vulnerable to learning from undesirable patterns in the data that reflect societal biases. As a result, irresponsible application of machine learning may lead to the perpetuation, or even amplification, of existing disparities in healthcare outcomes.

Content

In this work, we review what it means for a model to be unfair, discuss the various ways that machine learning models become unfair, and present engineering principles emerging from the field of algorithmic fairness. These materials are presented with a focus on the development of machine learning models in laboratory medicine.

We hope that this work will serve to increase awareness, and stimulate further discussion, of this important issue among laboratorians as the field moves forward with the incorporation of machine learning models into laboratory practice.
A Statistical Simulation to Evaluate the Robustness of Hb A1c Measurement in the Presence of Quantitative Error
Authors: Lyon Oliver A S , Inman Mark
Published: January 2023

Background

The performance requirements for hemoglobin (Hb) A1c analysis have been questioned as analytic methods have improved. We developed a statistical simulation that relates error to the clinical utility of an oft-used laboratory test, as a means of assessing test performance expectations.

Methods

Finite mixture modeling of the Centers for Disease Control and Prevention—National Health and Nutrition Examination Survey (NHANES) 2017–2020 Hb A1c data in conjunction with Monte Carlo sampling were used to model and simulate a population prior to the introduction of error into the results. The impact of error on clinical utility was assessed by categorizing the results using the American Diabetes Association (ADA) diagnostic criteria and assessing the sensitivity and specificity of Hb A1c under various degrees of error (bias and imprecision).

Results

With the current allowable total error threshold of 6% for Hb A1c measurement, the simulation estimated a worst case between 50% and 60% for both test sensitivity and specificity for the non-diabetic category. Similarly, sensitivity and specificity estimates for the pre-diabetic category were 30% to 40% and 60% to 70%, respectively. Finally, estimates for the diabetic category yielded values of 80% to 90% for sensitivity and >90% for specificity.

Conclusions

Bias and imprecision greatly affect the clinical utility of Hb A1c for all patient groups. The simulated error demonstrated in this modeling impacts 3 critical applications of the Hb A1c in diabetes management: the capacity to reliably screen, diagnostic accuracy, and utility in diabetes monitoring.
Choice Architecture to Assist Clinicians with Appropriate COVID-19 Test Ordering
Authors: Sangal Rohit B , Venkatesh Arjun K , Cahill Justin , Pettker Christian M , Peaper David R
Published: January 2023

Background

Despite improving supplies, SARS-CoV-2 nucleic acid amplification tests remain limited during surges and more so given concerns around COVID-19/influenza co-occurrence. Matching clinical guidelines to available supplies ensures resources remain available to meet clinical needs. We report a change in clinician practice after an electronic health record (EHR) order redesign to impact emergency department (ED) testing patterns.

Methods

We included all ED visits between December 1, 2021 and January 18, 2022 across a hospital system to assess the impact of EHR order changes on provider behavior 3 weeks before and after the change. The EHR order redesign included embedded symptom-based order guidance. Primary outcomes were the proportion of COVID-19 + flu/respiratory syncytial virus (RSV) testing performed on symptomatic, admitted, and discharged patients, and the proportion of COVID-19 + flu testing on symptomatic, discharged patients.

Results

A total of 52 215 ED visits were included. For symptomatic, discharged patients, COVID-19 + flu/RSV testing decreased from 11.4 to 5.8 tests per 100 symptomatic visits, and the rate of COVID-19 + flu testing increased from 7.4 to 19.1 before and after the intervention, respectively. The rate of COVID-19 + flu/RSV testing increased from 5.7 to 13.1 tests per 100 symptomatic visits for symptomatic patients admitted to the hospital. All changes were significant (P < 0.0001).

Conclusions

A simple EHR order redesign was associated with increased adherence to institutional guidelines for SARS-CoV-2 and influenza testing amidst supply chain limitations necessitating optimal allocation of scarce testing resources. With continually shifting resource availability, clinician education is not sufficient. Rather, system-based interventions embedded within exiting workflows can better align resources and serve testing needs of the community.
Data-Driven Anomaly Detection in Laboratory Medicine: Past, Present, and Future
Authors: Spies Nicholas C , Farnsworth Christopher W , Jackups Ronald
Published: January 2023

Background

Anomaly detection is an integral component of operating a clinical laboratory. It covers both the recognition of laboratory errors and the rapid reporting of clinically impactful results. Procedures for identifying laboratory errors and highlighting critical results can be improved by applying modern data-driven approaches.

Content

This review will prepare the reader to appraise anomaly detection literature, identify common sources of anomalous results in the clinical laboratory, and offer potential solutions for common shortcomings in current laboratory practices.

Laboratories should implement data-driven approaches to detect technical anomalies and keep them from entering the medical record, while also using the full array of clinical metadata available in the laboratory information system for context-dependent, patient-centered result interpretations.
Monitoring Insect Resistance to Bt Maize in the European Union: Update, Challenges, and Future Prospects
Authors: García Matías , García-Benítez Carlos , Ortego Félix , Farinós Gema P
Published: January 2023

Transgenic maize producing the Cry1Ab toxin of Bacillus thuringiensis (Bt maize) was approved for cultivation in the European Union (EU) in 1998 to control the corn borers Sesamia nonagrioides (Lefèbvre) and Ostrinia nubilalis (Hübner). In the EU since then, Cry1Ab is the only Bt toxin produced by Bt maize and Spain is the only country where Bt maize has been planted every year. In 2021, about 100,000 hectares of Bt maize producing Cry1Ab were cultivated in the EU, with Spain accounting for 96% and Portugal 4% of this area. In both countries, Bt maize represented less than 25% of all maize planted in 2021, with a maximum regional adoption of 64% Bt maize in northeastern Spain. Insect resistance management based on the high-dose/refuge strategy has been implemented in the EU since 1998. This has been accompanied by monitoring to enable early detection of resistance. The monitoring data from laboratory bioassays show no decrease in susceptibility to Cry1Ab had occurred in either pest as of 2021. Also, control failures have not been reported, confirming that Bt maize producing Cry1Ab remains effective against both pests. Conditions in the EU preventing approval of new genetically modified crops, including maize producing two or more Bt toxins targeting corn borers, may limit the future effectiveness of resistance management strategies.
A Modified F2 Screen for Estimating Cry1Ac and Cry2Ab Resistance Allele Frequencies in Helicoverpa zea (Lepidoptera: Noctuidae)
Authors: Santiago-González José C , Kerns David L , Head Graham P , Yang Fei
Published: January 2023

Evaluating the frequency of resistance alleles is important for resistance management and sustainable use of transgenic crops that produce insecticidal proteins from Bacillus thuringiensis. Helicoverpa zea (Boddie) (Lepidoptera: Noctuidae) is a major crop pest in the United States that has evolved practical resistance to the crystalline (Cry) proteins in Bt corn and cotton. The standard F2 screen for estimating resistance allele frequency does not work well for H. zea because successful single-pair matings are rare. In this study, we developed and implemented a modified F2 screen for H. zea that generates F1 progeny by crossing three laboratory susceptible female moths with one feral male moth instead of single-pair crosses. During 2019–2020, we used this modified method to establish 192 F2 families from 623 matings between susceptible females and feral males from Arkansas, Louisiana, Mississippi, and Tennessee. From each F2 family, we screened 128 neonates against discriminating concentrations of Cry1Ac and Cry2Ab in diet overlay bioassays. Based on these discriminating concentration bioassays, families were considered positive for resistance if at least five larvae survived to second instar, including at least one to third instar. The percentage of positive families was 92.7% for Cry1Ac and 38.5% for Cry2Ab, which yields an estimated resistance allele frequency (with 95% confidence interval) of 0.722 (0.688–0.764) for Cry1Ac and 0.217 (0.179–0.261) for Cry2Ab. The modified F2 screen developed and implemented here may be useful for future resistance monitoring studies of H. zea and other pests.
Population Genomics of Nonrecessive Resistance to Bt Toxin Cry1Ac in Helicoverpa armigera From Northern China
Authors: Guan Fang , Dai Xiaoguang , Yang Yihua , Tabashnik Bruce E , Wu Yidong
Published: January 2023

Transgenic crops that produce insecticidal proteins from Bacillus thuringiensis (Bt) have provided control of some key pests since 1996. However, the evolution of resistance by pests reduces the benefits of Bt crops. Resistance to Bt crops that is not recessively inherited is especially challenging to manage. Here we analyzed nonrecessive resistance to Bt toxin Cry1Ac in eight field populations of Helicoverpa armigera sampled in 2018 from northern China, where this global pest has been exposed to Cry1Ac in Bt cotton since 1997. Bioassays revealed 7.5% of field-derived larvae were resistant to Cry1Ac of which 87% had at least one allele conferring nonrecessive resistance. To analyze this nonrecessive resistance, we developed and applied a variant of a genomic mapping approach called quantitative trait locus (QTL)-seq. This analysis identified a region on chromosome 10 associated with nonrecessive resistance to Cry1Ac in all 21 backcross families derived from field-collected moths. Individual sequencing revealed that all 21 field-collected resistant grandparents of the backcross families had a previously identified dominant point mutation in the tetraspanin gene HaTSPAN1 that occurs in the region of chromosome 10 identified by QTL-seq. QTL-seq also revealed a region on chromosome 26 associated with nonrecessive resistance in at most 14% of the backcross families. Overall, the results imply the point mutation in HaTSPAN1 is the primary genetic basis of nonrecessive resistance to Cry1Ac in field populations of H. armigera from northern China. Moreover, because nonrecessive resistance is predominant, tracking the frequency of this point mutation could facilitate resistance monitoring in the region.
History of Medicine in the Clerkships: A Novel Model for Integrating Medicine and History
Authors: Barr Justin , Ingold Rachel , Baker Jeffrey P
Published: January 2023

The history of medicine has only unevenly been integrated into medical education. Previous attempts to incorporate the subject have focused either on the first year, with its already over-subscribed curriculum, or the fourth year in the form of electives that reach a small minority of students. Duke University provides an alternative model for other universities to consider. At our institution we have overcome many of the curricular limitations by including history during the mandatory third year clerkships. Reaching 100% of the medical school class, these sessions align with clinical disciplines, providing students a longitudinal perspective on what they are seeing and doing on the hospital wards. They are taught in conjunction with a medical history librarian and rely heavily on the utilization and interpretation of physical artifacts and archival manuscripts. The surgery, obstetrics/gynecology, and pediatrics rotations now feature successful and popular history of medicine sessions. Describing our lesson plans and featuring a list of both physical and online resources, we provide a model others can implement to increase the use, the framing, and the accessibility of history in their medical schools.
Evaluating Note Frequency and Velocity During Improvised Active Music Therapy in Clients With Parkinson’s Disease
Authors: Kogutek Demian , Ready Emily , Holmes Jeffrey D , Grahn Jessica A
Published: January 2023

The purpose of this article was to report on the findings of the note frequency and velocity measures during Improvised Active Music Therapy (IAMT) sessions with individuals with Parkinson’s disease (PD). In this single-subject multiple baseline design across subjects, the article reports the note frequency (note count) and velocity of movement (mean note velocity) played by three right-handed participants while playing uninterrupted improvised music on a simplified electronic drum-set. During baseline, the music therapist played rhythmic accompaniment on guitar using a low–moderate density of syncopation. During treatment, the Music Therapist introduced rhythms with a moderate–high density of syncopation. The music content of the sessions was transformed into digital music using a musical instrument digital interface. Results of this study indicated that all participants exhibited an increase in note count during baseline until reaching a plateau at treatment condition and were found to be significantly positively correlated with the Music Therapist’s note count. All participants played more notes with upper extremity (UE) across conditions than with lower extremity. All participants also scored similar total mean velocity across conditions. Two participants demonstrated higher mean note velocity with UE than right foot, whereas the other participant did not demonstrate this difference. Two participants also exhibited greater mean note velocity variability with left foot within and across conditions. More research is required to identify commonalities in note count and mean note velocity measures in individuals with PD during IAMT sessions.
Success or Self-Sufficiency? The Role of Race in Refugees’ Long-Term Economic Outcomes
Authors: Tesfai Rebbeca
Published: January 2023

The United States has always prided itself as providing safe haven to those who are persecuted. Yet, the United States did not develop policy for admitting and resettling refugees until 1980. Unlike Asians and Europeans, African refugees in the 1980s were chosen primarily based on skill, but no research thus far examines whether this strategy led to greater long-term economic success for African refugees. This article examines racial differences in refugees’ likelihood of living in poverty, receiving welfare income, engaging in full-time employment and wages between 1990 and 2019. I find that refugees show improvement in all four outcomes. African refugees, however, earn less than nearly all other groups in all time periods suggesting blocked mobility, particularly among men. Analyses focus on the 1982–1987 entry cohort of refugees who had access to more assistance than future cohorts. Consequently, these findings likely show the best-case scenario for refugees’ long-term economic outcomes.
En-bloc resection including SMV and duodenum in patient of locally advanced colon cancer
Authors: Han Jeong Hee , Lee Byoung Chul , Noh Byeong Gwan , Park Jae Kyun , Choi Jung Bum , Park Young Mok , Jung Hyuk Jae , Jo Hong Jae
Published: January 2023

Tumor could directly invade or is adherent to other organs, but superior mesentery vein (SMV) and duodenum invasion are very rare. A 62-year-old woman was diagnosed with abdominal pain for several months. Multiple erythematous brownish skin patches and palpable mass were found at epigastric area. Computed tomography imaging showed focal wall thickening at the transverse colon that invaded to the rectus muscle and anterior abdominal wall. On exploration, we identified tumor invaded or was adherent to the duodenum and superior mesenteric vein and performed en-bloc resection. After surgery, the patient received chemotherapy and was followed up without any recurrence for 16 months. Adhesion and invasion of tumor to surrounding organs can be unexpectedly found during surgery. In our case, we found duodenum and SMV invasion and achieved R0 resection by SMV and duodenum resection, which could improve the patient’s prognosis.
Port site intramuscular abscess from retained gallstone post laparoscopic cholecystectomy – an unusual complication
Authors: Syed Faisal , Quah Gaik Si , Di Re Angelina
Published: January 2023

Perforation of the gallbladder and the spillage of gallstones can be a cause of ongoing morbidity and mortality in patients post cholecystectomy. We report on an unusual case of a 58-year-old male who developed a right upper quadrant lump 8 years after laparoscopic cholecystectomy which was eventually determined to be an abscess from a retained gallstone that had become embedded in the musculature of his abdominal wall. We have also discussed some of the considerations taken in the surgical management of this case.
Extracellular RNA: mechanisms of secretion and potential functions
Authors: Borniego M Lucía , Innes Roger W
Published: January 2023

Extracellular RNA (exRNA) has long been considered as cellular waste that plants can degrade and utilize to recycle nutrients. However, recent findings highlight the need to reconsider the biological significance of RNAs found outside of plant cells. A handful of studies suggest that the exRNA repertoire, which turns out to be an extremely heterogenous group of non-coding RNAs, comprises species as small as a dozen nucleotides to hundreds of nucleotides long. They are found mostly in free form or associated with RNA-binding proteins, while very few are found inside extracellular vesicles (EVs). Despite their low abundance, small RNAs associated with EVs have been a focus of exRNA research due to their putative role in mediating trans-kingdom RNAi. Therefore, non-vesicular exRNAs have remained completely under the radar until very recently. Here we summarize our current knowledge of the RNA species that constitute the extracellular RNAome and discuss mechanisms that could explain the diversity of exRNAs, focusing not only on the potential mechanisms involved in RNA secretion but also on post-release processing of exRNAs. We will also share our thoughts on the putative roles of vesicular and extravesicular exRNAs in plant–pathogen interactions, intercellular communication, and other physiological processes in plants.
Plasmopara viticolaRxLR effector PvAvh77 triggers cell death and governs immunity responses in grapevine
Authors: Fu Qingqing , Wang Yunlei , Yang Jing , Jiao Yu , Li Wenjuan , Yang Fan , Yin Xiao , Shang Boxing , Liu Ruiqi , Zhang Yiyuan , Saileke Ayisuwake , Liu Guotian , van Nocker Steven , Hu Huiling , Xu Yan
Published: January 2023

Grapevine downy mildew, caused by the oomycete Plasmopara viticola, is one of the most significant production challenges for the grape and wine industry. P. viticola injects a plethora of effectors into its host cells to disrupt immune processes, but the mechanisms by which these effectors act at the molecular level have not been well characterized. Herein, we show that a candidate P. viticola avirulence homolog (Avh) RxLR effector gene, designated PvAvh77, was strongly up-regulated during the initial stages of P. viticola infection in Vitis vinifera. Further experiments demonstrated that PvAvh77 could trigger non-specific cell death when expressed in the wild grapevine Vitis riparia and in tobacco (Nicotiana benthamiana and Nicotiana tabacum). In addition, a truncated form of PvAvh77, designated PvAvh77-M2, was more active in inducing cell death in N. benthamiana and V. riparia than full-length PvAvh77. Ectopic expression of PvAvh77 in V. vinifera ‘Thompson Seedless’ leaves neutralized host immunity and enhanced colonization by P. viticola, and the immune-inhibiting activity of PvAvh77 on susceptible Eurasian grapevine depended on its nuclear localization. Using a yeast signal sequence trap approach, we showed that the signal peptide of PvAvh77 is functional in yeast. Moreover, PvAvh77 with a signal peptide stimulated plant immune responses in the apoplast. Notably, application of exogenous purified PvAvh77-M2 effectively initiated defence responses in grapevine extracellularly, as evidenced by increased accumulation of salicylic acid and H2O2, and reduced infection of inoculated P. viticola. In summary, we identified a novel effector, PvAvh77, from P. viticola, which has the potential to serve as an inducer of plant immunity.
Building linked lexicography applications with LexO-server
Authors: Bellandi Andrea
Published: January 2023

The adoption of Semantic Web technologies in the lexicographic field, has been driven by the need to ensure the construction of lexical resources that are interoperable and can be shared and reused by the scientific communities. In this context, the OntoLex W3C working group proposed the OntoLex-Lemon model aimed at providing rich linguistic grounding for ontologies. It includes the representation of morphological and syntactic properties of lexical entries as well as their meaning with respect to an ontology or vocabulary. This article aims at presenting LexO-server, a set of REST services for the management of OntoLex-Lemon modeled lexical resources. LexO-server comes as a software backend providing data access and manipulation to frontend developers. The set of services are general enough to make possible the construction of applications oriented at different tasks, such as editing, linking, dictionary making, linguistic annotation, or NLP ones. As a demonstration of the versatility and the potential of LexO-server, we will present three web applications that rely on it.
Large-Scale Chromosomal Changes Lead to Genome-Level Expression Alterations, Environmental Adaptation, and Speciation in the Gayal (Bos frontalis)
Authors: Li Yan , Wang Sheng , Zhang Zhe , Luo Jing , Lin Guo Liang , Deng Wei-Dong , Guo Zhifan , Han Feng Ming , Wang Li-Li , Li Jie , Wu Shi-Fang , Liu He-Qun , He Sheng , Murphy Robert W , Zhang Zi-Jie , Cooper David N , Wu Dong-Dong , Zhang Ya-Ping
Published: January 2023

Determining the functional consequences of karyotypic changes is invariably challenging because evolution tends to obscure many of its own footprints, such as accumulated mutations, recombination events, and demographic perturbations. Here, we describe the assembly of a chromosome-level reference genome of the gayal (Bos frontalis) thereby revealing the structure, at base-pair-level resolution, of a telo/acrocentric-to-telo/acrocentric Robertsonian translocation (2;28) (T/A-to-T/A rob[2;28]). The absence of any reduction in the recombination rate or genetic introgression within the fusion region of gayal served to challenge the long-standing view of a role for fusion-induced meiotic dysfunction in speciation. The disproportionate increase noted in the distant interactions across pro-chr2 and pro-chr28, and the change in open-chromatin accessibility following rob(2;28), may, however, have led to the various gene expression irregularities observed in the gayal. Indeed, we found that many muscle-related genes, located synthetically on pro-chr2 and pro-chr28, exhibited significant changes in expression. This, combined with genome-scale structural variants and expression alterations in genes involved in myofibril composition, may have driven the rapid sarcomere adaptation of gayal to its rugged mountain habitat. Our findings not only suggest that large-scale chromosomal changes can lead to alterations in genome-level expression, thereby promoting both adaptation and speciation, but also illuminate novel avenues for studying the relationship between karyotype evolution and speciation.
Single-molecule Sequencing of an Animal Mitochondrial Genome Reveals Chloroplast-like Architecture and Repeat-mediated Recombination
Authors: Sharbrough Joel , Bankers Laura , Cook Emily , Fields Peter D , Jalinsky Joseph , McElroy Kyle E , Neiman Maurine , Logsdon John M , Boore Jeffrey L
Published: January 2023

Recent advances in long-read sequencing technology have allowed for single-molecule sequencing of entire mitochondrial genomes, opening the door for direct investigation of the mitochondrial genome architecture and recombination. We used PacBio sequencing to reassemble mitochondrial genomes from two species of New Zealand freshwater snails, Potamopyrgus antipodarum and Potamopyrgus estuarinus. These assemblies revealed a ∼1.7 kb structure within the mitochondrial genomes of both species that was previously undetected by an assembly of short reads and likely corresponding to a large noncoding region commonly present in the mitochondrial genomes. The overall architecture of these Potamopyrgus mitochondrial genomes is reminiscent of the chloroplast genomes of land plants, harboring a large single-copy (LSC) region and a small single-copy (SSC) region separated by a pair of inverted repeats (IRa and IRb). Individual sequencing reads that spanned across the Potamopyrgus IRa-SSC-IRb structure revealed the occurrence of a “flip-flop” recombination. We also detected evidence for two distinct IR haplotypes and recombination between them in wild-caught P. estuarinus, as well as extensive intermolecular recombination between single-nucleotide polymorphisms in the LSC region. The chloroplast-like architecture and repeat-mediated mitochondrial recombination we describe here raise fundamental questions regarding the origins and commonness of inverted repeats in cytoplasmic genomes and their role in mitochondrial genome evolution.
Antibodies to varicella-zoster virus and three other herpesviruses and survival in adults with glioma
Authors: Guerra Geno , McCoy Lucie , Hansen Helen M , Rice Terri , Molinaro Annette M , Wiemels Joseph L , Wiencke John K , Wrensch Margaret , Francis Stephen S
Published: January 2023

Background

Lifetime exposure to the varicella-zoster virus (VZV) has been consistently inversely associated with glioma risk, however, the relationship of VZV with survival in adults with glioma has not been investigated. In this study, we analyzed the survival of adults with glioma in relation to their antibody measurements to 4 common herpes viral infections, including VZV, measured post-diagnosis.

Methods

We analyzed IgG antibody measurements to VZV, cytomegalovirus (CMV), herpes simplex virus 1/2 (HSV), and Epstein-Barr virus (EBV) collected from 1378 adults with glioma diagnosed between 1991 and 2010. Blood was obtained a median of 3 months after surgery. Associations of patient IgG levels with overall survival were estimated using Cox models adjusted for age, sex, self-reported race, surgery type, dexamethasone usage at blood draw, and tumor grade. Models were stratified by recruitment series and meta-analyzed to account for time-dependent treatment effects.

Results

VZV antibody seropositivity was associated with improved survival outcomes in adults with glioma (Hazard ratio, HR = 0.70, 95% Confidence Interval 0.54–0.90, P = .006). Amongst cases who were seropositive for VZV antibodies, survival was significantly improved for those above the 25th percentile of continuous reactivity measurements versus those below (HR = 0.76, 0.66–0.88, P = .0003). Antibody seropositivity to EBV was separately associated with improved survival (HR = 0.71, 0.53–0.96, P = .028). Antibody positivity to 2 other common viruses (CMV, HSV) was not associated with altered survival.

Conclusions

Low levels of VZV or EBV antibodies are associated with poorer survival outcomes for adults with glioma. Differential immune response rather than viral exposure may explain these findings.
Temporal trends in the incidence of malignant and nonmalignant primary brain and central nervous system tumors by the method of diagnosis in England, 1993–2017
Authors: Ali Usama M , Withrow Diana R , Judge Andrew D , Plaha Puneet , Darby Sarah C
Published: January 2023

Background

Several studies report increases in the incidences of primary central nervous system (CNS) tumors. The reasons for this are unclear.

Methods

Data on all 188 340 individuals diagnosed with a primary CNS tumor in England (1993–2017) were obtained from the National Cancer Registration and Analysis Service. Data on all computerized tomography (CT) head and magnetic resonance imaging (MRI) brain scans in England (2013–2017) were obtained from the National Health Service Digital. Age-sex-standardized annual incidence rates per 100 000 population (ASR) were calculated by calendar year, tumor behavior, tumor location, and method of diagnosis. Temporal trends were quantified using average annual percent change (AAPC).

Results

The ASR for all CNS tumors increased from 13.0 in 1993 to 18.6 in 2017 (AAPC: +1.5%, 95% CI: 1.3, 1.7). The ASR for malignant tumors (52% overall) remained stable (AAPC: +0.5%, 95% CI: −0.2, 1.3), while benign tumors (37% overall) increased (AAPC: +2.6%, 95% CI: 1.2, 4.0). Among the 66% of benign tumors that were microscopically confirmed, the ASR increased modestly (AAPC: +1.3%, 95% CI: 0.5, 2.1). However, among the 25% of benign tumors that were radiographically confirmed, the ASR increased substantially (AAPC: 10.2%, 95% CI: 7.9, 12.5), principally driven by large increases in those who are aged 65+ years. The rate of CT head scans in Accident & Emergency (A&E) increased during 2013–2017, with especially large increases in 65–84 and 85+-year-olds (AAPCs: +18.4% and +22.5%).

Conclusions

Increases in CNS tumor incidence in England are largely attributable to the greater detection of benign tumors. This could be the result of the increasing use of neuroimaging, particularly CT head scans in A&E in people who are aged 65+ years.
Cell Cycle Dynamics during Stomatal Development: Window of MUTE Action and Ramification of Its Loss-of-Function on an Uncommitted Precursor
Authors: Zuch Daniel T , Herrmann Arvid , Kim Eun-Deok , Torii Keiko U
Published: January 2023

Plants develop in the absence of cell migration. As such, cell division and differentiation need to be coordinated for functional tissue formation. Cellular valves on the plant epidermis, stomata, are generated through a stereotypical sequence of cell division and differentiation events. In Arabidopsis, three master regulatory transcription factors, SPEECHLESS (SPCH), MUTE and FAMA, sequentially drive initiation, proliferation and differentiation of stomata. Among them, MUTE switches the cell cycle mode from proliferative asymmetric division to terminal symmetric division and orchestrates the execution of the single symmetric division event. However, it remains unclear to what extent MUTE regulates the expression of cell cycle genes through the symmetric division and whether MUTE accumulation itself is gated by the cell cycle. Here, we show that MUTE directly upregulates the expression of cell cycle components throughout the terminal cell cycle phases of a stomatal precursor, not only core cell cycle engines but also check-point regulators. Time-lapse live imaging using the multicolor Plant Cell Cycle Indicator revealed that MUTE accumulates up to the early G2 phase, whereas its successor and direct target, FAMA, accumulate at late G2 through terminal mitosis. In the absence of MUTE, meristemoids fail to differentiate and their G1 phase elongates as they reiterate asymmetric divisions. Together, our work provides the framework of cell cycle and master regulatory transcription factors to coordinate a single symmetric cell division and suggests a mechanism for the eventual cell cycle arrest of an uncommitted stem-cell-like precursor at the G1 phase.
Building an Academic Transgender Medicine Center of Excellence: The 5-Year Johns Hopkins Experience
Authors: Marano Andrew A. , Noyes Melissa , Eisenbeis Lauren , Hedian Helene F. , Segna Kara , Neira Paula M. , Thomas Kate , Lee W.P. Andrew , Redett Richard J. , Coon Devin
Published: January 2023

Gender-affirming care for transgender and gender diverse (TGD) individuals is a multidisciplinary endeavor that requires organized efforts of many specialized practitioners. TGD individuals experience many health care barriers, including the scarcity of multidisciplinary teams formed to coordinate and deliver complex care in an efficient and affirming way. The Johns Hopkins Center for Transgender Health was founded in 2017 with the mission of decreasing health disparities and improving the health of the TGD community. The authors present their experience building the center around a service line model in which patients have 1 point of contact, they are tracked throughout the care process, and the multidepartmental practitioners involved in their care are aligned. This model allowed for a patient-centered experience in which all involved disciplines were seamlessly integrated and the patient could navigate easily among them. With the structure and mission in place, the next challenge was to develop an infrastructure for culturally competent care. Through competency training and adjustment of systems-based logistics, measures were put in place to prevent traumatic experiences, such as misgendering, use of culturally inappropriate vocabulary, and use of incorrect names. Partnerships among colleagues in the fields of plastic surgery, urology, gynecology, otolaryngology, anesthesia, psychiatry/mental health, internal medicine, endocrinology, fertility, nursing, social work, speech therapy, and pediatrics/adolescent care were necessary to provide the appropriate breadth of services to care for TGD patients. Since its inception, the center has seen steady and continual growth, with more than 2,800 patients in its first 5 years. By sharing their experience in creating and developing a center of excellence, the authors hope to provide a blueprint for others to expand health care quality and access for TGD individuals.
ALKBH5 ALLEVIATES HYPOXIA POSTCONDITIONING INJURY IN d-GALACTOSE–INDUCED SENESCENT CARDIOMYOCYTES BY REGULATING STAT3
Authors: Zhang Xuan , Li Feixiang , Ma Ji , Zhang Xiaobei , Yin Yiqing
Published: January 2023

Ischemic postconditioning (I/Post) reduces I/R injury by activating endogenous cardioprotection mechanisms, such as the JAK/signal transducer and activator of transcription 3 (STAT3) and PI3K/Akt pathways, which offer a traditional approach to myocardial protection. According to a previous study, cardioprotection by I/Post may be lost in aged mice, and in our previous research, hypoxic postconditioning (H/Post) lacked a protective effect in senescent cardiomyocytes, which was associated with low expression of long noncoding RNA H19. The N6-methyladenosine (m6A) modification is a dynamic and reversible process that has been confirmed to play a role in cardiovascular diseases. However, the mechanisms of m6A modification in myocardial I/Post remain to be explored. Neonatal cardiomyocytes were isolated from 2-day-old Sprague-Dawley rats, and senescence was induced by d-galactose, followed by stimulation of hypoxia-reoxygenation and H/Post. Hypoxic injury was evaluated by cell viability and the Bcl-2/Bax protein ratio. Total m6A levels were measured using a colorimetric m6A RNA Methylation Quantification Kit, and the m6A modified and differentially expressed mRNA was determined by MeRIP (methylated RNA immunoprecipitation). We found that H/Post increased m6A methylation and decreased RNA mA demethylase alkB homolog 5 (ALKBH5) expression in aged cardiomyocytes. Furthermore, ALKBH5 knockdown exacerbated injury following H/Post in senescent cardiomyocytes. In addition, ALKBH5 regulated STAT3 expression by mediating its m6A modification and long noncoding RNA H19/miR-124-3p. ALKBH5 also alleviated the H/Post injury induced by the low expression of STAT3 in senescent cardiomyocytes.
CircNRIP1 KNOCKDOWN ALLEVIATES LIPOPOLYSACCHARIDE-INDUCED HUMAN KIDNEY 2 CELL APOPTOSIS AND INFLAMMATION THROUGH miR-339-5p/OXSR1 PATHWAY
Authors: Li Pei , Liu Yu , You Ting
Published: January 2023

Background: CircRNA regulates sepsis-induced acute kidney injury (AKI). CircNRIP1 is overexpressed in the blood of AKI patients, but its role in septic AKI occurrence remains unknown. Methods: Human kidney 2 (HK2) cells were stimulated using lipopolysaccharide (LPS) to generate a septic AKI cell model. The expression levels of circNRIP1, miR-339-5p, oxidative stress-responsive kinase 1 (OXSR1), B-cell lymphoma-2 (Bcl2), BCL2-associated x protein (Bax), and cleaved-caspase 3 were detected by quantitative real-time polymerase chain reaction or Western blotting analysis. Cell viability and apoptosis were investigated by cell counting kit-8 and flow cytometry analysis. The release of proinflammatory cytokines was monitored using commercial kits. The associations among circNRIP1, miR-339-5p, and OXSR1 were identified by mechanism assays. Results: CircNRIP1 was dramatically upregulated in the blood of septic AKI patients and LPS-induced HK2 cells. CircNRIP1 depletion protected HK2 cells from LPS-induced apoptosis and inflammation. MiR-339-5p expression was downregulated in the blood of septic AKI patients, and miR-339-5p combined with circNRIP1. Moreover, circNRIP1 knockdown-induced effects involved the upregulation of miR-339-5p in LPS-treated HK2 cells. Comparatively, OXSR1 expression was increased in the blood of septic AKI patients. MiR-339-5p bound to OXSR1, and circNRIP1 modulated OXSR1 expression by interacting with miR-339-5p. Further, ectopic expression of OXSR1 relieved circNRIP1 knockdown-mediated effects in LPS-induced HK2 cells. Conclusion: CircNRIP1 depletion ameliorated LPS-induced HK2 cell damage by regulating the miR-339-5p/OXSR1 pathway.
Linear contraction of stress fibers generates cell body rotation
Authors: Okimura Chika , Akiyama Syu , Nishigami Yukinori , Zaitsu Ryota , Sakurai Tatsunari , Iwadate Yoshiaki
Published: January 2023

Wounds are healed by crawling migration of the epidermal cells around the injured area. Fish epidermal keratocytes that rapidly repair wounds comprise a frontal crescent-shaped lamellipodium and a rear rugby ball-shaped cell body. The cell body rotates like a wheel during migration. Stress fibers, which are bundles of contractile actomyosin filaments, are arranged along the seams of the rugby ball. Here we show the linear contraction of stress fibers to be the driving force for rotation. We constructed a mechanical model of the cell body that consisted of a soft cylinder with a contractile coil. From the motion of the model, it was predicted that contraction of the stress fibers would deform the soft cell body, as a result of which the deformed cell body would push against the substrate to generate torque. This prediction was confirmed by the observation of stress fiber dynamics in migrating cells. Linear-to-rotation conversion in migrating keratocytes is realized by simple soft-body mechanics. Conversion from linear motion to rotation is widely used in machines with moving parts, but requires somewhat complicated mechanics. An understanding of linear-to-rotation conversion in keratocytes has potential for use in the design of biomimetic soft robots.