bluuebunny/crossref_metadata_2025 huggingface dataset:
Mantis Shrimp Locomotion: Coordination and Variation of Hybrid Metachronal Swimming
Authors: Hanson S E , Ray W J , Santhanakrishnan A , Patek S N
Published: May 2023

Synopsis

Across countless marine invertebrates, coordination of closely spaced swimming appendages is key to producing diverse locomotory behaviors. Using a widespread mechanism termed hybrid metachronal propulsion, mantis shrimp swim by moving five paddle-like pleopods along their abdomen in a posterior to anterior sequence during the power stroke and a near-synchronous motion during the recovery stroke. Despite the ubiquity of this mechanism, it is not clear how hybrid metachronal swimmers coordinate and modify individual appendage movements to achieve a range of swimming capabilities. Using high-speed imaging, we measured pleopod kinematics of mantis shrimp (Neogonodactylus bredini), while they performed two swimming behaviors: burst swimming and taking off from the substrate. By tracking each of the five pleopods, we tested how stroke kinematics vary across swimming speeds and the two swimming behaviors. We found that mantis shrimp achieve faster swimming speeds through a combination of higher beat frequencies, smaller stroke durations, and partially via larger stroke angles. The five pleopods exhibit non-uniform kinematics that contribute to the coordination and forward propulsion of the whole system. Micro-hook structures (retinacula) connect each of the five pleopod pairs and differ in their attachment across pleopods—possibly contributing to passive kinematic control. We compare our findings in N. bredini to previous studies to identify commonalities across hybrid metachronal swimmers at high Reynolds numbers and centimeter scales. Through our large experimental dataset and by tracking each pleopod's movements, our study reveals key parameters by which mantis shrimp adjust and control their swimming, yielding diverse locomotor abilities.
Validation of the Thermo Scientific™ SureTect™ Vibrio cholerae, Vibrio parahaemolyticus, and Vibrio vulnificus PCR Assay for the Detection of Vibrio cholerae, Vibrio parahaemolyticus, and Vibrio vulnificus in Seafood Matrixes: AOAC Performance Tested MethodsSM 022301
Authors: Faulds Nikki , Williams Jessica , Evans Katharine , Hughes Annette , Leak Dean , Crabtree David , Prentice Nicole , Sohier Daniele , Heikkinen Pauliina , Hurskainen Emmi , Mcmahon Wendy , Cuthbert Nicole , Matthews Bailey , Ruben Lydia , Sturghill Luvie , Godawski Frank
Published: May 2023

Background

The Thermo Scientific™ SureTect™ Vibrio cholerae, Vibrio parahaemolyticus, and Vibrio vulnificus PCR Assay method is a real-time PCR method for the multiplex detection of Vibrio cholerae, Vibrio parahaemolyticus, and Vibrio vulnificus in seafood.

Objective

The Thermo Scientific SureTect Vibrio cholerae, Vibrio parahaemolyticus, and Vibrio vulnificus Assay was evaluated for AOAC Performance Tested MethodsSM certification.

Method

Inclusivity/exclusivity, matrix, product consistency/stability, and robustness studies were conducted to assess the method’s performance. For the matrix study, the method was validated using the Applied Biosystems™ QuantStudio™ 5 Real-Time PCR Food Safety Instrument and the Applied Biosystems™ 7500 Fast Real-Time PCR Food Safety Instrument against the U.S. Food and Drug Administration Bacteriological Analytical Manual, Chapter 9 (2004), Vibrio and ISO 21872–1:2017 Microbiology of the food chain—Horizontal method for the determination of Vibrio spp.—Part 1: Detection of potentially enteropathogenic Vibrio parahaemolyticus, Vibrio cholerae, and Vibrio vulnificus reference methods.

Results

Matrix studies showed equivalent or superior performance of the candidate method compared to the reference method and, overall, no difference between presumptive and confirmed results, except for one matrix due to high background flora. The inclusivity/exclusivity study correctly identified/excluded all strains analyzed. Robustness testing showed no statistically significant differences in assay performance under varied test conditions. Product consistency and stability studies demonstrated no statistically significant differences between assay lots with different expiration dates.

Conclusions

The data presented show that the assay constitutes a rapid and reliable workflow for the detection of V. cholerae, V. parahaemolyticus, and V. vulnificus in seafood matrixes.

Highlights

The SureTect PCR Assay method allows for fast, reliable detection of stipulated strains in seafood matrixes with results obtained in as little as 80 min post-enrichment.
Authentication of Platycladus Orientalis Leaves and Its Five Adulterants by Combination of Morphology and Microscopic Characteristics, TLC, and HPLC Analysis
Authors: Hao Jin-Hua , Xiao Ping-Ting , Duan Peng-Bo , Miao Dan-Yang , Jiang Xiao-Yu , Kuang Yu-Jia , Liu E -Hu
Published: May 2023

Background

Platycladus orientalis leaves (POL), as the source of the traditional Chinese medicine (TCM) Platycladi Cacumen, has frequently been found to be misused with five adulterants including Chamaecyparis obtusa leaves (COL), Cupressus funebris leaves (CFL), Juniperus virginiana leaves (JVL), Sabina chinensis leaves (SCL), and Juniperus formosana leaves (JFL).

Objective

The purpose of this study was to distinguish POL (fresh leaves) from its five adulterants (fresh leaves).

Methods

The micromorphological features in terms of transection and microscopic characteristics of POL and adulterants were captured and compared using the an microscope. Both HPLC and TLC methods for the simultaneous determination of six bioactive flavonoids (myricitrin, isoquercitrin, quercitrin, amentoflavone, afzelin, and hinokiflavone) have been developed.

Results

There were significant differences in microscopic features of transverse section and powders. The TLC results suggested that the spots of myricitrin in POL were more obvious than those in the five adulterants. The contents of myricitrin and quercitrin, or the total content of flavonoids in POL, determined by HPLC, were significantly higher than those in the adulterants.

Conclusion

POL was successfully distinguished from its five adulterants by the comparison of morphology, microscopic characteristics, and chemical profiles.

Highlights

This research provides a comprehensive morphology, microscopic identification, TLC, and HPLC analysis for authenticating POL and its five adulterants.
Seamless phase II/III design: a useful strategy to reduce the sample size for dose optimization
Authors: Jiang Liyun , Yuan Ying
Published: May 2023

Background

The traditional more-is-better dose selection paradigm, originally developed for cytotoxic chemotherapeutics, can be problematic when applied to the development of novel molecularly targeted agents. Recognizing this issue, the US Food and Drug Administration initiated Project Optimus to reform the dose optimization and selection paradigm in oncology drug development, emphasizing the need for greater attention to benefit-risk considerations.

Methods

We identify different types of phase II/III dose-optimization designs, classified according to trial objectives and endpoint types. Through computer simulations, we examine their operating characteristics and discuss the relevant statistical and design considerations for effective dose optimization.

Results

Phase II/III dose-optimization designs are capable of controlling family-wise type I error rates and achieving appropriate statistical power with substantially smaller sample sizes than the conventional approach while also reducing the number of patients who experience toxicity. Depending on the design and scenario, the sample size savings range from 16.6% to 27.3%, with a mean savings of 22.1%.

Conclusions

Phase II/III dose-optimization designs offer an efficient way to reduce sample sizes for dose optimization and accelerate the development of targeted agents. However, because of interim dose selection, the phase II/III dose-optimization design presents logistical and operational challenges and requires careful planning and implementation to ensure trial integrity.
Risk of estrogen receptor–specific breast cancer by family history of estrogen receptor subtypes and other cancers
Authors: Wang Qiao-Li , Zhang Yuqi , Zeng Erwei , Grassmann Felix , He Wei , Czene Kamila
Published: May 2023

Background

The extent to which the risk of estrogen receptor (ER)–specific breast cancer is associated with ER status of breast cancer and other cancers among first-degree relatives is unclear.

Methods

This population-based cohort included 464 707 cancer-free women in Stockholm, Sweden, during 1978-2019. For ER-negative and ER-positive breast cancers, we estimated hazard ratios (HRs) associated with ER status of female first-degree relatives with breast cancer and of other cancers in all first-degree relatives. Associations between ER-negative and ER-positive status by family cancer history were estimated using logistic regression in a case-only design.

Results

Women with familial ER-positive breast cancer had 1.87 times (95% confidence interval [CI] = 1.77 to 1.97) higher risk of ER-positive subtype, whereas the corresponding hazard ratio for ER-negative was 2.54 (95% CI = 2.08 to 3.10) when having familial ER-negative breast cancer. The risk increased with an increasing number of female first-degree relatives having concordant subtypes and younger age at diagnosis (Ptrend <.001 for both). Nonbreast cancers among first-degree relatives were associated with both ER-positive (HR = 1.14, 95% CI = 1.10 to 1.17) and ER-negative (HR = 1.08, 95% CI = 1.01 to 1.16) breast cancers. Compared with women with ER-positive breast cancer, women with ER-negative breast cancer were more likely to have family history of liver (odds ratio [OR] = 1.33, 95% CI = 1.05 to 1.67), ovary (OR = 1.28, 95% CI = 1.01 to 1.61), and testicle cancer (OR = 1.79, 95% CI = 1.01 to 3.16) but less likely to have family history of endometrial cancer (OR = 0.77, 95% CI = 0.60 to 1.00) and leukemia (OR = 0.72, 95% CI = 0.56 to 0.91).

Conclusions

Risk of ER-specific breast cancer differs according to ER status of female first-degree relatives with breast cancer and some other cancers of first-degree relatives. This family history information should be considered in the individual risk prediction for ER subtypes.
Utility of ctDNA in predicting relapse in solid tumors after curative therapy: a meta-analysis
Authors: Mittal Abhenil , Molto Valiente Consolacion , Tamimi Faris , Di Iorio Massimo , Al-Showbaki Laith , Cescon David W , Amir Eitan
Published: May 2023

Background

Presence of circulating tumor DNA (ctDNA) is prognostic in solid tumors treated with curative intent. Studies have evaluated ctDNA at specific “landmark” or multiple “surveillance” time points. However, variable results have led to uncertainty about its clinical validity.

Methods

A PubMed search identified relevant studies evaluating ctDNA monitoring in solid tumors after curative intent therapy. Odds ratios for recurrence at both landmark and surveillance time points for each study were calculated and pooled in a meta-analysis using the Peto method. Pooled sensitivity and specificity weighted by individual study inverse variance were estimated and meta-regression using linear regression weighted by inverse variance was performed to explore associations between patient and tumor characteristics and the odds ratio for disease recurrence.

Results

Of 39 studies identified, 30 (1924 patients) and 24 studies (1516 patients) reported on landmark and surveillance time points, respectively. The pooled odds ratio for recurrence at landmark was 15.47 (95% confidence interval = 11.84 to 20.22) and at surveillance was 31.0 (95% confidence interval = 23.9 to 40.2). The pooled sensitivity for ctDNA at landmark and surveillance analyses was 58.3% and 82.2%, respectively. The corresponding specificities were 92% and 94.1%, respectively. Prognostic accuracy was lower with tumor agnostic panels and higher with longer time to landmark analysis, number of surveillance draws, and smoking history. Adjuvant chemotherapy negatively affected landmark specificity.

Conclusions

Although prognostic accuracy of ctDNA is high, it has low sensitivity, borderline high specificity, and therefore modest discriminatory accuracy, especially for landmark analyses. Adequately designed clinical trials with appropriate testing strategies and assay parameters are required to demonstrate clinical utility.
Central oral pulse granuloma: a case report of huge mandibular jaw lesion
Authors: Karimi Abbas , Derakhshan Samira , Aminishakib Pouyan , Saffar Hiva , Motlagh Kimia Hafezi
Published: May 2023

Oral pulse granuloma is a rare lesion of the oral cavity with unclear etiology. Some authors believe this lesion is a foreign body reaction to implanted food particles. In the oral cavity, most cases are found in the posterior regions of the mandible. The edentulous mandible was involved in 20 cases with oral pulse granuloma. In these cases, the premolar–molar site was the most common region. Here we present a case of a 70-year-old male with huge unilateral swelling of the mandible on the left side. This paper aims to present a case of oral pulse granuloma with wide extension, detailed clinicohistopathologic features with 2-year follow-up and a short review of reported cases.
The kinetic and magnetic energy budget of hub-filament systems during the gravitational fragmentation of molecular clouds
Authors: Camacho Vianey , Vázquez-Semadeni Enrique , Palau Aina , Zamora-Avilés Manuel
Published: May 2023

We present a numerical study of the balance between the gravitational (Eg), kinetic (Ek), and magnetic (Em) energies of structures within a hub-filament system in a simulation of the formation and global hierarchical collapse (GHC) of a giant molecular cloud. For structures defined by various density thresholds, and at different evolutionary stages, we investigate the scaling of the virial parameter, α, with mass M, and of the Larson ratio, ${\cal {L}}_{\rm v}\equiv \sigma _{\rm v}/R^{1/2}$, with column density Σ, where σv is the 1D velocity dispersion, and R is an effective radius. We also investigate these scalings for the corresponding magnetic parameters αm and ${\cal {L}}_{\rm {m}}$. Finally, we compare our numerical results with an observational sample of massive clumps. We find that: 1) αm and ${\cal {L}}_{\rm {m}}$ follow similar α–M and ${\cal {L}}$–Σ scalings as their kinetic counterparts, although the ratio Em/Ek decreases as |Eg| increases. 2) The largest objects, defined by the lowest thresholds, tend to appear gravitationally bound (and magnetically supercritical), while their internal substructures tend to appear unbound (and subcritical). This suggests that the latter are being compressed by the infall of their parent structures, and supports earlier suggestions that the measured mass-to-magnetic flux ratio μ decreases inwards in a centrally-peaked cloud under ideal MHD. 3) The scatter in the α–M and ${\cal {L}}$–Σ plots is reduced when Ek and Em are plotted directly against Eg, suggesting that the scatter is due to an ambiguity between mass and size. 4) The clumps in our GHC simulation follow the same trends as the observational sample of massive clumps in the ${\cal {L}}$–Σ and α–M diagrams. We conclude that the main controlling parameter of the energy budget in the structures is Eg, with the kinetic and magnetic energies being derived from it.
Resolving ambiguities in the inferred star formation histories of intense [O iii] emitters in the reionization Era
Authors: Laporte N , Ellis R S , Witten C E C , Roberts-Borsani G
Published: May 2023

Early JWST spectroscopic campaigns have confirmed the presence of strong [O iii] line-emitting galaxies in the redshift interval 7 < z < 9. Although deduced earlier from Spitzer photometry as an indicative of young stellar populations, some studies suggested the relevant photometric excesses attributed to [O iii] emission could, in part, be due to Balmer breaks arising from older stars. We demonstrate that this is likely the case by exploiting medium-band near-infrared JWST photometry in the Hubble Ultra Deep Field. We locate a sample of six galaxies with redshifts 8.2<z <8.6 for which the relevant medium-band filters enables us to separate the contributions of [O iii] emission and a Balmer break, thereby breaking earlier degeneracies of interpretation. The technique is particularly valuable since it provides photometric redshifts whose precision, $\Delta \, z\simeq \, \pm 0.08$, approaches that of spectroscopic campaigns now underway with JWST. Although some sources are young, a third of our sample have prominent Balmer breaks consistent with stellar ages of ≥150 Myr. Our results indicate that even intense [O iii] emitters experienced episodes of earlier star formation to z ∼10 and beyond, as is now being independently deduced from direct detection of the progenitors of similar systems.
New-onset of eosinophilic granulomatosis with polyangiitis without eosinophilia and eosinophilic infiltration under benralizumab treatment: A case report
Authors: Yonezawa Haruka , Ohmura Shin-ichiro , Ohkubo Yusuke , Otsuki Yoshiro , Miyamoto Toshiaki
Published: May 2023

Eosinophilic granulomatosis with polyangiitis (EGPA) is a small- to medium-vessel necrotising vasculitis and eosinophilic inflammation. Mepolizumab, an anti-interleukin-5 (IL-5) monoclonal antibody has been approved in Japan since 2018 for refractory EGPA treatment. Benralizumab, an anti-IL-5 receptor monoclonal antibody, also has been reported to reduce the glucocorticoid dose in patients with refractory EGPA. On the other hand, several investigators have demonstrated new-onset EGPA under biologics, and it is unclear whether this treatment for severe allergic diseases can prevent the development of EGPA. Herein, we report a case of new-onset EGPA under benralizumab treatment. The patient had fever, weight loss, muscle pain, and paraesthesia, the serum eosinophil count was 0/μL, and the biopsy showed necrotizing vasculitis without eosinophilic infiltration. She was diagnosed as having EGPA and treated with high-dose glucocorticoid and intravenous cyclophosphamide, with a good response. Our case report indicates that anti-IL-5 agents may mask the development of EGPA and clinicians should be aware of the development of EGPA during anti-IL-5 agents.
Extensive ischaemic colitis–like colonic lesions in eosinophilic granulomatosis with polyangiitis
Authors: Ueda Yoshitaka , Shimada Kota
Published: May 2023

Eosinophilic granulomatosis with polyangiitis is a rare, immune-mediated, multisystemic disorder belonging to the group of antineutrophil cytoplasmic antibody-associated vasculitides. Gastrointestinal symptoms are relatively common in patients with eosinophilic granulomatosis with polyangiitis, reportedly occurring in ∼22.3% of cases. Vasculitic necrotising lesions normally occur in the intestinal tract, and in the present case, the colonic lesions were remarkably severe and extensive. Pulse steroid therapy combined with cyclophosphamide improved the patient’s condition without any serious complications, such as intestinal perforation.
Inclusion, Diversity, Access, and Equity in Infectious Diseases Fellowship Training: Tools for Program Directors
Authors: Luther Vera P , Barsoumian Alice E , Konold Victoria J L , Vijayan Tara , Balba Gayle , Benson Constance , Blackburn Brian , Cariello Paloma , Perloff Sarah , Razonable Raymund , Acharya Kartikey , Azar Marwan M , Bhanot Nitin , Blyth Dana , Butt Saira , Casanas Beata , Chow Brian , Cleveland Kerry , Cutrell James B , Doshi Saumil , Finkel Diana , Graber Christopher J , Hazra Aniruddha , Hochberg Natasha S , James Scott H , Kaltsas Anna , Kodiyanplakkal Rosy Priya L , Lee Mikyung , Marcos Luis , Mena Lora Alfredo J , Moore Christopher C , Nnedu Obinna , Osorio Georgina , Paras Molly L , Reece Rebecca , Salas Natalie Mariam , Sanasi-Bhola Kamla , Schultz Sara , Serpa Jose A , Shnekendorf Rachel , Weisenberg Scott , Wooten Darcy , Zuckerman Richard A , Melia Michael , Chirch Lisa M
Published: May 2023

The Infectious Diseases Society of America (IDSA) has set clear priorities in recent years to promote inclusion, diversity, access, and equity (IDA&E) in infectious disease (ID) clinical practice, medical education, and research. The IDSA IDA&E Task Force was launched in 2018 to ensure implementation of these principles. The IDSA Training Program Directors Committee met in 2021 and discussed IDA&E best practices as they pertain to the education of ID fellows. Committee members sought to develop specific goals and strategies related to recruitment, clinical training, didactics, and faculty development. This article represents a presentation of ideas brought forth at the meeting in those spheres and is meant to serve as a reference document for ID training program directors seeking guidance in this area.
Evaluating Demographic Representation in Clinical Trials: Use of the Adaptive Coronavirus Disease 2019 Treatment Trial (ACTT) as a Test Case
Authors: Ortega-Villa Ana M , Hynes Noreen A , Levine Corri B , Yang Katherine , Wiley Zanthia , Jilg Nikolaus , Wang Jing , Whitaker Jennifer A , Colombo Christopher J , Nayak Seema U , Kim Hannah Jang , Iovine Nicole M , Ince Dilek , Cohen Stuart H , Langer Adam J , Wortham Jonathan M , Atmar Robert L , El Sahly Hana M , Jain Mamta K , Mehta Aneesh K , Wolfe Cameron R , Gomez Carlos A , Beresnev Tatiana , Mularski Richard A , Paules Catharine I , Kalil Andre C , Branche Angela R , Luetkemeyer Annie , Zingman Barry S , Voell Jocelyn , Whitaker Michael , Harkins Michelle S , Davey Richard T , Grossberg Robert , George Sarah L , Tapson Victor , Short William R , Ghazaryan Varduhi , Benson Constance A , Dodd Lori E , Sweeney Daniel A , Tomashek Kay M
Published: May 2023

Background

Clinical trials initiated during emerging infectious disease outbreaks must quickly enroll participants to identify treatments to reduce morbidity and mortality. This may be at odds with enrolling a representative study population, especially when the population affected is undefined.

Methods

We evaluated the utility of the Centers for Disease Control and Prevention’s COVID-19–Associated Hospitalization Surveillance Network (COVID-NET), the COVID-19 Case Surveillance System (CCSS), and 2020 United States (US) Census data to determine demographic representation in the 4 stages of the Adaptive COVID-19 Treatment Trial (ACTT). We compared the cumulative proportion of participants by sex, race, ethnicity, and age enrolled at US ACTT sites, with respective 95% confidence intervals, to the reference data in forest plots.

Results

US ACTT sites enrolled 3509 adults hospitalized with COVID-19. When compared with COVID-NET, ACTT enrolled a similar or higher proportion of Hispanic/Latino and White participants depending on the stage, and a similar proportion of African American participants in all stages. In contrast, ACTT enrolled a higher proportion of these groups when compared with US Census and CCSS. The proportion of participants aged ≥65 years was either similar or lower than COVID-NET and higher than CCSS and the US Census. The proportion of females enrolled in ACTT was lower than the proportion of females in the reference datasets.

Conclusions

Although surveillance data of hospitalized cases may not be available early in an outbreak, they are a better comparator than US Census data and surveillance of all cases, which may not reflect the population affected and at higher risk of severe disease.
Temporal associations between use of psychoactive substances and somatic symptoms in the daily lives of people with fibromyalgia
Authors: Kuzu Duygu , Valentine Thomas R , Kratz Anna L
Published: May 2023

Objective

Consumption of psychoactive substances—alcohol, nicotine, caffeine, opioids, and cannabis—is common among people with fibromyalgia. Associations between the use of substances and somatic symptoms could reflect efforts to cope with symptoms, aggravation or alleviation of symptoms after the use of substances, or a combination of these. To date, no study has provided insight into temporal associations between the consumption of psychoactive substances and fluctuations in somatic symptoms. We explored whether changes in ratings of pain and fatigue (mental and physical) predicted the later use of psychoactive substances or vice versa (substance use predicting later change in symptoms).

Design

Micro-longitudinal design.

Setting/subjects

Fifty adults (88% female, 86% White, mean age of 44.9 years) with fibromyalgia.

Methods

Participants completed ecological momentary assessments of substance use, pain intensity, and physical/mental fatigue 5 times per day for 8 days.

Results

Results of multilevel models indicated that momentary increases in fatigue showed a consistent association with greater odds of later use of psychoactive substances, whereas momentary increases in pain were related to lower odds of later cannabis and nicotine use and higher odds of later alcohol use. Only nicotine use predicted later mental fatigue.

Conclusion

Findings highlight the importance of individualized interventions for symptom management or problems related to the use of psychoactive substances. We observed that although somatic symptoms predicted later use of substances, use of substances did not show appreciable effects with regard to alleviating somatic symptoms in people with fibromyalgia.
Seeing What is Representative
Authors: Esponda Ignacio , Oprea Ryan , Yuksel Sevgi
Published: May 2023

We provide evidence for a bias that we call “representative signal distortion” (RSD), which is particularly relevant to settings of statistical discrimination. Experimental subjects distort their evaluation of new evidence on individual group members and interpret such information to be more representative of the group to which the individual belongs (relative to a reference group) than it really is. This produces a discriminatory gap in the evaluation of members of the two groups. Because it is driven by representativeness, the bias (and the discriminatory gap) disappears when subjects are prevented from contrasting different groups; because it is a bias in the interpretation of information, it disappears when subjects receive information before learning of the individual’s group. We show that this bias can be easily estimated from appropriately constructed data sets and can be distinguished from previously documented inferential biases in the literature. Importantly, we document how removing the bias produces a kind of free lunch in reducing discrimination, making it possible to significantly reduce discrimination without lowering accuracy of inferences.
Investigation of liver-targeted peripheral focused ultrasound stimulation (pFUS) and its effect on glucose homeostasis and insulin resistance in type 2 diabetes mellitus: a proof of concept, phase 1 trial
Authors: Ashe J , Graf J , Madhavan R , Wallace K , Cotero V , Abate S , Pandey R K , Herzog R , Porindla S N , Shoudy D , Fan Y , Kao T -J , Puleo C
Published: May 2023

Background

Mechanical waves produced by ultrasound pulses have been shown to activate mechanosensitive ion channels and modulate peripheral nerves. However, while peripheral ultrasound neuromodulation has been demonstrated in vitro and in pre-clinical models, there have been few reports of clinical tests.

Aim

We modified a diagnostic imaging system for ultrasound neuromodulation in human subjects. We report the first safety and feasibility outcomes in subjects with type 2 diabetes (T2D) mellitus and discuss these outcomes in relation to previous pre-clinical results.

Design

The study was performed as an open label feasibility study to assess the effects of hepatic ultrasound (targeted to the porta hepatis) on glucometabolic parameters in subjects with T2D. Stimulation (peripheral focused ultrasound stimulation treatment) was performed for 3 days (i.e. 15 min per day), preceded by a baseline examination and followed by a 2-week observation period.

Methods

Multiple metabolic assays were employed including measures of fasting glucose and insulin, insulin resistance and glucose metabolism. The safety and tolerability were also assessed by monitoring adverse events, changes in vital signs, electrocardiogram parameters and clinical laboratory measures.

Results and conclusion

We report post-pFUS trends in several outcomes that were consistent with previous pre-clinical findings. Fasting insulin was lowered, resulting in a reduction of HOMA-IR scores (P-value 0.01; corrected Wilcoxon signed-rank test). Additional safety and exploratory markers demonstrated no device-related adverse impact of pFUS. Our findings demonstrate that pFUS represents a promising new treatment modality that could be used as a non-pharmaceutical adjunct or even alternative to current drug treatments in diabetes.
Morphological classification of radio galaxies with Wasserstein generative adversarial network-supported augmentation
Authors: Rustige Lennart , Kummer Janis , Griese Florian , Borras Kerstin , Brüggen Marcus , Connor Patrick L S , Gaede Frank , Kasieczka Gregor , Knopp Tobias , Schleper Peter
Published: May 2023

Machine learning techniques that perform morphological classification of astronomical sources often suffer from a scarcity of labelled training data. Here, we focus on the case of supervised deep learning models for the morphological classification of radio galaxies, which is particularly topical for the forthcoming large radio surveys. We demonstrate the use of generative models, specifically Wasserstein generative adversarial networks (wGANs), to generate data for different classes of radio galaxies. Further, we study the impact of augmenting the training data with images from our wGAN on three different classification architectures. We find that this technique makes it possible to improve models for the morphological classification of radio galaxies. A simple fully connected neural network benefits most from including generated images into the training set, with a considerable improvement of its classification accuracy. In addition, we find it is more difficult to improve complex classifiers. The classification performance of a convolutional neural network can be improved slightly. However, this is not the case for a vision transformer.
Does international R&D cooperation under institutional agreements have a greater impact than those without agreements?
Authors: Feitosa Paulo Henrique Assis , Salles-Filho Sergio , Bin Adriana , Juk Yohanna , Colugnati Fernando Antonio Basile
Published: May 2023

Funding agencies (FAs) have increasingly engaged in international cooperation agreements (ICAs) to encourage world-class research and achieve more promising outcomes in the context of increasing competition for research resources. While the benefits of International Research Collaboration are largely supported by literature, less attention was paid to the influence of ICA on scientific and technological outputs. We employed a quasi-experimental evaluation with a comparison between funding for international collaboration carried under ICA (treatment) and funding for international collaboration not carried under ICA (control). The sample was collected from the database of the São Paulo Research Foundation (FAPESP) between 1990 and 2018. We have found that ICA has a positive and significant impact on the quality of scientific production measured by the number of citations, h-index, and the number of national and international papers co-authorship. However, no significant difference was found in terms of scholarly and technological outputs.
Biosynthesis of cannabigerol and cannabigerolic acid: the gateways to further cannabinoid production
Authors: Kearsey Lewis J , Yan Cunyu , Prandi Nicole , Toogood Helen S , Takano Eriko , Scrutton Nigel S
Published: May 2023

Cannabinoids are a therapeutically valuable class of secondary metabolites with a vast number of substituents. The native cannabinoid biosynthetic pathway of Cannabis sativa generates cannabigerolic acid (CBGA), the common substrate to multiple cannabinoid synthases. The bioactive decarboxylated analog of this compound, cannabigerol (CBG), represents an alternate gateway into the cannabinoid space as a substrate either to non-canonical cannabinoid synthase homologs or to synthetic chemical reactions. Herein, we describe the identification and repurposing of aromatic prenyltransferase (AtaPT), which when coupled with native enzymes of C. sativa can form an Escherichia coli production system for CBGA in cell lysates and CBG in whole cells. Engineering of AtaPT, guided by structural analysis, was performed to enhance its kinetics toward CBGA production for subsequent use in a proof-of-concept lysate system. For the first time, we show a synthetic biology platform for CBG biosynthesis in E. coli cells by employing AtaPT under an optimized microbial system. Our results have therefore set the foundation for sustainable production of well-researched and rarer cannabinoids in an E. coli chassis.

Graphical Abstract
Evolution of anelloviruses from a circovirus-like ancestor through gradual augmentation of the jelly-roll capsid protein
Authors: Butkovic Anamarija , Kraberger Simona , Smeele Zoe , Martin Darren P , Schmidlin Kara , Fontenele Rafaela S , Shero Michelle R , Beltran Roxanne S , Kirkham Amy L , Aleamotu’a Maketalena , Burns Jennifer M , Koonin Eugene V , Varsani Arvind , Krupovic Mart
Published: May 2023

Anelloviruses are highly prevalent in diverse mammals, including humans, but so far have not been linked to any disease and are considered to be part of the ‘healthy virome’. These viruses have small circular single-stranded DNA (ssDNA) genomes and encode several proteins with no detectable sequence similarity to proteins of other known viruses. Thus, anelloviruses are the only family of eukaryotic ssDNA viruses currently not included in the realm Monodnaviria. To gain insights into the provenance of these enigmatic viruses, we sequenced more than 250 complete genomes of anelloviruses from nasal and vaginal swab samples of Weddell seal (Leptonychotes weddellii) from Antarctica and a fecal sample of grizzly bear (Ursus arctos horribilis) from the USA and performed a comprehensive family-wide analysis of the signature anellovirus protein ORF1. Using state-of-the-art remote sequence similarity detection approaches and structural modeling with AlphaFold2, we show that ORF1 orthologs from all Anelloviridae genera adopt a jelly-roll fold typical of viral capsid proteins (CPs), establishing an evolutionary link to other eukaryotic ssDNA viruses, specifically, circoviruses. However, unlike CPs of other ssDNA viruses, ORF1 encoded by anelloviruses from different genera display remarkable variation in size, due to insertions into the jelly-roll domain. In particular, the insertion between β-strands H and I forms a projection domain predicted to face away from the capsid surface and function at the interface of virus–host interactions. Consistent with this prediction and supported by recent experimental evidence, the outermost region of the projection domain is a mutational hotspot, where rapid evolution was likely precipitated by the host immune system. Collectively, our findings further expand the known diversity of anelloviruses and explain how anellovirus ORF1 proteins likely diverged from canonical jelly-roll CPs through gradual augmentation of the projection domain. We suggest assigning Anelloviridae to a new phylum, ‘Commensaviricota’, and including it into the kingdom Shotokuvirae (realm Monodnaviria), alongside Cressdnaviricota and Cossaviricota.
Control of Mandibular Width With 3D Printed Occlusal Splint in Children With Multiple Mandibular Fractures
Authors: Wu Benxing , Lv Kun
Published: May 2023

Background:

The fracture of mandibular symphysis combined with bilateral condylar fractures often leads to changes in the width of the mandible, which significantly widens the face of the child. Therefore, it is necessary to reposition the mandible through accurate adduction.

Methods:

To ensure that the mandible can be accurately repositioned, a 3D printed occlusal splint was used. Bilateral maxillomandibular fixation screws were implanted. The 3D printed occlusal splint was located on the maxillary dentition and fixed to the maxillomandibular fixation screws with wire loops. The reference basis for adduction is to make the mandibular dentition located in the occlusal splint. The absorbable plate was contoured according to the restored model and fixed at the fracture site. The 3D printed occlusal splint was retained in the maxillary dentition for two months.

Results and Discussion:

Postoperative computed tomography showed that the mandible had been adducted according to the preoperative design. Two months of follow-up showed that the child's facial development, mouth opening type, occlusion, and range of motion were good. It is especially suitable for children with mandibular symphyseal fractures accompanied by bilateral condylar fractures.
Meaning of the Skulls Depicted in Emblem Books of the 17th Century
Authors: Hwang Se Won , Tukeshov Sultan K , Hwang Kun
Published: May 2023

The aim of this study is to elucidate the meaning of the skulls depicted in emblem books of the 17th century. Three emblem books of the 17th century were reviewed and analyzed: (1) Rollenhagen emblem: Gabrielis Rollenhagii Selectorum emblematum centuria secunda (1613), (2) Quarles’ emblems; illustrations engraved by William Marshall and others (1635), and (3) Wither’s emblem: A collection of emblemes, ancient and moderne: quickened with metricall illustrations, both morall and divine: and disposed into lotteries (1635). Among the 100 illustrations in Rollenhagen’s book, 4 (4.0%) had skulls. Among the 76 illustrations in Quarles’ book, 6 (7.9%) had skulls. Among the 256 illustrations in Wither’s book, 12 (4.7%) had skulls. Thereafter, 22 (5.1%) of 432 illustrations had skulls. Four emblems in Rollenhagen’s book were exactly identical to those in Wither’s book. Therefore, 18 emblems (6 Quarles’ emblem, 12 Wither’s emblem) were analyzed. The most frequent meaning of skulls in 18 emblems was death (12, 66.7%), followed by resurrection (2, 11.2%). Other meanings were grief, the brevity of life, vanity of love, and pain, respectively (1 each). The most frequent of the theme of the emblems, which included skulls, was ‘Memento mori’ (remember death, 6, 33.3%), followed by an earnest desire for salvation or resurrection (3, 16.7%), and importance of knowledge or learning (2, 11.1%). Since these emblem books were published after Vesalius’ Fabrica (1543), the drawing of the bones of the arm and legs had anatomic correlations. However, skulls were not sufficiently precise, showing each part of the facial bones.
The Effectiveness of Releasing the Lower Lateral Cartilage Through Intranasal Z-plasty Incision on the Vestibular Web During Secondary Correction of Nasal Deformities in Complete Unilateral Cleft Lip and Palate
Authors: Jeon Sungmi , Kim Yung Hoon , Kim Byung Jun , Kim Sukwha , Chung Jee Hyeok
Published: May 2023

The primary goal in the secondary correction of unilateral cleft lip nose deformity is to achieve symmetry of the nose and nostril. This study aimed to investigate the efficacy of freeing the lower lateral cartilage from the pyriform ligament through an intranasal Z-plasty incision on the vestibular web in adult patients with complete unilateral cleft lip and palate. Thirty-six patients with complete unilateral cleft lip and palate, who underwent open rhinoplasty between August 2014 and December 2021, were identified retrospectively. Five parameters for nose form and nostril symmetry were measured on basal views through 2-dimensional photographic analysis. The patients were divided into subgroups with or without septoplasty. Cleft-to-non-cleft ratios between the Z (13 patients) and non-Z groups (23 patients) were compared using the Mann-Whitney U test. The mean follow-up was 12.9 months (6–31 mo). In the Z group, there were significant differences between the preoperative and postoperative values for nostril angulation, regardless of septoplasty (all P<0.05). Despite septoplasty, significant differences in the postoperative changes in nostril angulation were found between the Z and non-Z groups (all P<0.05). Intranasal Z-plasty on the plica vestibularis is an effective technique for releasing the lower lateral cartilage, improving the nostril asymmetry in cleft lip nose deformity.
Untangling an insect virome from its endogenous viral elements
Authors: Rozo-Lopez Paula , Brewer William , Käfer Simon , Martin McKayla M. , Parker Benjamin J.
Published: May 2023

Abstract

Insects are an important reservoir of viral biodiversity, but the vast majority of viruses associated with insects have not been discovered. Recent studies have therefore employed high-throughput sequencing of RNA, which has led to rapid advances in our understanding of insect viral diversity. However, insect genomes frequently contain transcribed endogenous viral elements with significant homology to exogenous viruses, complicating the use of RNAseq for viral discovery. In this study, we use a multi-pronged sequencing approach to study the virome of an important agricultural pest and prolific vector of plant pathogens, the potato aphidMacrosiphum euphorbiae. We first used rRNA-reduced RNAseq to characterize the bacteria and viruses found in individual insects. We then characterized the frequency of a heritable Flavivirus and an Ambidensovirus in our population. We next generated a quality draft genome assembly forM. euphorbiaeusing Illumina-corrected Nanopore sequencing. This analysis showed that the Ambidensovirus, previously described from an RNAseq viral screen, is not a exogenous virus and instead is a transcribed endogenous viral element in theM. euphorbiaegenome. Our study generates key insight into an important agricultural pest and highlights a widespread challenge for the study of viral diversity using RNAseq.
Tumor-specific neutrophils originating from meninges promote glioblastoma
Authors: Zhao Jiarui , Wu Di , Liu Jiaqi , Zhang Yang , Cao Penghui , Li Chunzhao , Wu Shixuan , Li Mengyuan , Cui Yiwen , Sun Yiwen , Yang Ence , Ji Nan , Yang Jing , Chen Jian
Published: May 2023

Glioma is one of the most aggressive human cancers with limited therapeutic options. Though research has extensively examined immune components in those malignant tumors, the pathophysiological mechanism establishing their immunosuppressive microenvironment remains incompletely characterized. In this study, we report for the first time the unique presence of tumor-specific neutrophils (TSNs) in human glioblastoma (GBM) tumors. This newly defined neutrophil subtype exhibits the high expression of several immunosuppressive genes (e.g., CD274 and IDO1) and is strongly correlated with glioma grades and poor prognosis of patients. TSNs with comparable gene signatures are similarly present in the tumors but not bone marrow or spleen of mouse glioma models. Blockage of TSN recruitment by eitherCxcl1-knockout in glioma cells orCxcr2-deletion in host mice significantly enhances antitumor immunity and inhibits tumor progression. Surprisingly, we further identify the meninges as the key extratumoral source of generating TSNs in both human GBM patients and mouse glioma models. These results have elucidated a novel mechanism of neutrophils designating the tumor immune microenvironment and the essential link of meningeal immunity to glioma.
An evolutionary mechanism to assimilate new nutrient sensors into the mTORC1 pathway
Authors: Liu Grace Y. , Jouandin Patrick , Bahng Raymond E. , Perrimon Norbert , Sabatini David M.
Published: May 2023

Animals must sense and respond to nutrient availability in their local niche. This task is coordinated in part by the mTOR complex 1 (mTORC1) pathway, which regulates growth and metabolism in response to nutrients1-5. In mammals, mTORC1 senses specific amino acids through specialized sensors that act through the upstream GATOR1/2 signaling hub6-8. To reconcile the conserved architecture of the mTORC1 pathway with the diversity of environments that animals can occupy, we hypothesized that the pathway might maintain plasticity by evolving distinct nutrient sensors in different metazoan phyla1,9,10. Whether such customization occurs— and how the mTORC1 pathway might capture new nutrient inputs—is not known. Here, we identify theDrosophila melanogasterprotein Unmet expectations (Unmet, formerly CG11596) as a species-restricted nutrient sensor and trace its incorporation into the mTORC1 pathway. Upon methionine starvation, Unmet binds to the fly GATOR2 complex to inhibit dTORC1.S-adenosylmethionine (SAM), a proxy for methionine availability, directly relieves this inhibition. Unmet expression is elevated in the ovary, a methionine-sensitive niche11, and flies lacking Unmet fail to maintain the integrity of the female germline under methionine restriction. By monitoring the evolutionary history of the Unmet-GATOR2 interaction, we show that the GATOR2 complex evolved rapidly in Dipterans to recruit and repurpose an independent methyltransferase as a SAM sensor. Thus, the modular architecture of the mTORC1 pathway allows it to co-opt preexisting enzymes and expand its nutrient sensing capabilities, revealing a mechanism for conferring evolvability on an otherwise highly conserved system.
splicekit: a comprehensive toolkit for splicing analysis from short-read RNA-seq
Authors: Rot Gregor , Wehling Arne , Schmucki Roland , Berntenis Nikolaos , Zhang Jitao David , Ebeling Martin
Published: May 2023

Motivation

Analysis of alternative splicing using short-read RNA-seq data is a complex process that involves several steps: alignment of reads to the reference genome, identification of alternatively spliced features, motif discovery, analysis of RNA-protein binding near donor and acceptor splice sites, and exploratory data visualization.

Results

We introducesplicekit, a python package that provides a comprehensive set of tools for conducting splicing analysis.

Availability and implementation

https://github.com/bedapub/splicekitand over PyPI.
Ongoing convergent evolution of a selfing syndrome threatens plant-pollinator interactions
Authors: Acoca-Pidolle Samson , Gauthier Perrine , Devresse Louis , Deverge Merdrignac Antoine , Pons Virginie , Cheptou Pierre-Olivier
Published: May 2023

Plant-pollinator interactions evolved early in the angiosperm radiation. Ongoing environmental changes are however leading to pollinator declines that may cause pollen limitation to plants and change the evolutionary pressures shaping plant mating systems.

We used resurrection ecology methodology to contrast ancestors and contemporary descendants in four natural populations of the field pansy (Viola arvensis) in the Paris region (France), a depauperate pollinator environment. We combine population genetics analysis, phenotypic measurements and behavioural tests on a common garden experiment.

Population genetics analysis reveals 27% increase in realized selfing rates in the field during this period. We documented trait evolution towards smaller and less conspicuous corollas, reduced nectar production and reduced attractiveness to bumblebees, with these trait shifts convergent across the four studied populations.

We demonstrate the rapid evolution of a selfing syndrome in the four studied plant populations, associated with a weakening of the interactions with pollinators over the last three decades. This study demonstrates that plant mating systems can evolve rapidly in natural populations in the face of ongoing environmental changes. The rapid evolution towards a selfing syndrome may in turn further accelerate pollinator declines, in an eco-evolutionary feedback loop with broader implications to natural ecosystems.