bluuebunny/crossref_metadata_2025 huggingface dataset:
A Regional Approach to Hospital-Based Violence Intervention Programs Through LOV
Authors: Mueller Kristen L. , Chapman-Kramer Kateri , Cooper Benjamin P. , Kaser Taylor , Mancini Michael , Moran Vicki , Vogel Matthew , Foraker Randi E. , Anwuri Victoria
Published: March 2023

Context:

Community violence is an underaddressed public health threat. Hospital-based violence intervention programs (HVIPs) have been used to address the root causes of violence and prevent reinjury.

Objective:

In this article, we describe the methodology of the St Louis Region-wide HVIP, Life Outside Violence (LOV) program, and provide preliminary process outcomes.

Design:

Life Outside Violence mentors intervene following a violent injury to decrease risk of subsequent victimization and achieve goals unique to each participant by providing therapeutic counseling and case management services to patients and their families.

Participants and Setting:

Eligible patients are victims of violent injury between the ages of 8 and 24 years, who are residents of St Louis, Missouri, and present for care at a LOV partner adult or pediatric level I trauma hospital.

Intervention:

Enrolled participants receive program services for 6 to 12 months and complete an individual treatment plan.

Main Outcome Measures:

In this article, we report LOV operational methodology, as well as process metrics, including program enrollment, graduation, and qualitative data on program implementation.

Results:

From August 15, 2018, through April 30, 2022, 1750 LOV-eligible violently injured patients presented to a partner hospital, 349 were approached for program enrollment, and 206 consented to enroll in the program. During this pilot phase, 91 participants graduated from the LOV program and have process output data available for analysis.

Conclusions:

Life Outside Violence has been implemented into clinical practice as the first HVIP to influence across an entire region through partnership with multiple university and hospital systems. It is our hope that methods shared in this article will serve as a primer for organizations hoping to implement and expand HVIPs to interrupt community violence at the regional level.
Mapping the Central Sulcus Extraoperatively Using Stereoelectroencephalography: A New Application of an Established Method
Authors: Kheder Ammar , Al-Ramadhani Ruba , Bhalla Sonam , Dickey Adam , Alwaki Abdulrahman , Chern Joshua , Pederson Nigel , Gedela Satyanarayana
Published: March 2023

Purpose:

Central sulcus localization is undertaken intraoperatively with subdural electrodes through a phase reversal technique using somatosensory evoked potentials from sensorimotor cortices. Extraoperative central sulcus localization using stereoelectroencephalography has not been described previously.

Methods:

Six pediatric patients (aged 12–18 years, 50% females) were investigated with stereoelectroencephalography. Peripheral median and posterior tibial nerve stimulation were performed while recording somatosensory evoked potentials from stereoelectroencephalography electrodes.

Results:

Central sulcus was successfully localized by this novel method, and this was further supplemented by cortical stimulation data.

Conclusions:

This is the first report of somatosensory evoked potentials gained using stereoelectroencephalography in primary motor and sensory cortices. This can further supplement other data for safe surgical resection in the eloquent cortex.
Qipengyuania spongiae sp. nov., isolated from marine sponge Cinachyrella kuekenthali
Authors: Zhang Mimi , Song Qianqian , Sang Jin , Li Zhiyong
Published: March 2023

A novel bacterial strain, designated as PHS-Z21T, was isolated from the marine sponge Cinachyrella kuekenthali collected from PG Dave’s Rock, Philippines. Cells of PHS-Z21T are Gram-stain-negative, non-motile, pale-yellow-pigmented, short rods. PHS-Z21T is able to grow at 10–40 ℃ (optimum, 30 ℃), pH 5.5–9.0 (optimum, pH 8.5) and with 3–9 % (w/v) NaCl (optimum, 4 %). Its 16S rRNA gene sequence shows 98.6 % similarity to

Qipengyuania nanhaisediminis

CGMCC 1.7715T, 98.5 % similarity to

Qipengyuania vulgaris

022-2-10T and 98.4 % similarity to

Qipengyuania flava

SW-46T, respectively. The phylogenetic tree based on 16S rRNA gene sequences reveals that PHS-Z21T is clustered with

Q. flava

SW-46T. The total genome of PHS-Z21T is approximately 2 932 896 bp in size with a DNA G+C content of 64.7 %. The average nucleotide identity (ANI) and digital DNA–DNA hybridization (dDDH) values among PHS-Z21T and other type strains are 70.0–77.3 % (ANIb), 83.3–86.8 % (ANIm) and 13.0–26.9 % (dDDH), respectively. The dDDH and ANI values are below the standard cutoff criteria for delineating bacterial species. Percentage of conserved proteins (POCP) values between the genome of strain PHS-Z21T and those of members of the genera

Qipengyuania

,

Erythrobacter

,

Altererythrobacter

and

Alteriqipengyuania

were 62.0–74.5 %, 55.8–63.2 %, 60.7–66.9 % and 63.9–66.8%, respectively, while the AAI values were 68.4–74.3 %, 63.8–65.9 %, 66.3–68.3 % and 64.7–66.9%, respectively. The major fatty acids of PHS-Z21T are composed of summed feature 8 (C18 : 1ω7c and/or C18 : 1ω6c), C18 : 1ω7c 11-methyl, C16 : 0 and summed feature 3 (C16 : 1ω7c and/or C16 : 1ω6c). The polar lipids of PHS-Z21T mainly consist of diphosphatidylglycerol, glycolipid, phosphatidylcholine, phosphatidylethanolamine, phosphatidylglycerol and glycophospholipid. The respiratory lipoquinone was identified as Q-10. On the basis of the phenotypic and phylogenetic data, strain PHS-Z21T represents a novel species of the genus

Qipengyuania

, for which the name Qipengyuania spongiae sp. nov. is proposed. The type strain is PHS-Z21T (=MCCC 1K07849T=KCTC 92590T).
Brevibacillus humidisoli sp. nov., a moderately thermoalkaliphilic and halotolerant species isolated from riverside soil
Authors: Lee Jae Ha , Shin You Me , Ra Jun Sik , Kim Seung Bum
Published: March 2023

A Gram-stain-positive, aerobic, rod-shaped, motile, and endospore-forming bacterial strain designated MMS20-4M-10-YT was isolated from riverside soil and subjected to taxonomic characterization. Strain MMS20-4M-10-YT was moderately thermophilic, alkaliphilic and halotolerant, as the strain grew at 25–50 °C (optimum, 45 °C), at pH 7.0–10.0 (optimum, pH 8.0) and in the presence of 0–6 % NaCl (optimum, 0 %). Analysis of 16S rRNA gene sequences indicated that MMS20-4M-10-YT fell into a phylogenetic cluster belonging to the genus

Brevibacillus

. Strain MMS20-4M-10-YT showed the highest 16S rRNA gene sequence similarity to

Brevibacillus marinus

SCSIO 07484T (96.7 %). Based on the reults of orthologous average nucleotide identity analysis, MMS20-4M-10-YT was again mostly related to

B. marinus

SCSIO 07484T with 78.0 % identity, which also shared the highest average nucleotide identity of 68.0 %. In contrast, the digital DNA–DNA relatedness analysis indicated that Aneureibacillus migulanus DSM 2895T was the closest species with 29.5 % similarity. The genome-based analyses indicated that all compared species showed low genomic relatedness with MMS20-4M-10-YT. The major fatty acids of the strain were anteiso-C15 : 0, iso-C15 : 0, iso-C16 : 0 and iso-C17 : 0, the major respiratory quinone was MK-7, the diagnostic polar lipids were phosphatidyl-N-methylethanolamine, diphosphatidylglycerol, phosphatidylethanolamine and phosphatidylglycerol, and diagnostic cell-wall diamino acid was meso-diaminopimelic acid, which was consistent with the general chemotaxonomic features of the genus. The total length of the genome was 4.91 Mbp and the DNA G+C content was 51.8 mol%. Based on both phenotypic and phylogenetic evidence, strain MMS20-4M-10-YT should be classified as representing a novel species of the genus

Brevibacillus

, for which a name Brevibacillus humidisoli sp. nov. (type strain=MMS20-4M-10-YT=KCTC 43333T=LMG 32359T) is proposed.
Learning to fake it: limited responses and fabricated references provided by ChatGPT for medical questions
Authors: Gravel Jocelyn , D’Amours-Gravel Madeleine , Osmanlliu Esli
Published: March 2023

Background

ChatGPT have gained public notoriety and recently supported manuscript preparation. Our objective was to evaluate the quality of the answers and the references provided by ChatGPT for medical questions.

Methods

Three researchers asked ChatGPT a total of 20 medical questions and prompted it to provide the corresponding references. The responses were evaluated for quality of content by medical experts using a verbal numeric scale going from 0 to 100%. These experts were the corresponding author of the 20 articles from where the medical questions were derived. We planned to evaluate three references per response for their pertinence, but this was amended based on preliminary results showing that most references provided by ChatGPT were fabricated.

Results

ChatGPT provided responses varying between 53 and 244 words long and reported two to seven references per answer. Seventeen of the 20 invited raters provided feedback. The raters reported limited quality of the responses with a median score of 60% (1stand 3rdquartile: 50% and 85%). Additionally, they identified major (n=5) and minor (n=7) factual errors among the 17 evaluated responses. Of the 59 references evaluated, 41 (69%) were fabricated, though they appeared real. Most fabricated citations used names of authors with previous relevant publications, a title that seemed pertinent and a credible journal format.

Interpretation

When asked multiple medical questions, ChatGPT provided answers of limited quality for scientific publication. More importantly, ChatGPT provided deceptively real references. Users of ChatGPT should pay particular attention to the references provided before integration into medical manuscripts.
Long-Term Outcomes After Transcatheter Aortic Valve Replacement: Meta-Analysis of Kaplan-Meier-Derived Individual Patient Data
Authors: Shimamura Junichi , Takemoto Sho , Fukuhara Shinichi , Miyamoto Yoshihisa , Yokoyama Yujiro , Takagi Hisato , Kampaktsis Polydoros N , Kolte Dhaval , Grubb Kendra J , Kuno Toshiki , Latib Azeem
Published: March 2023

Background

Transcatheter aortic valve replacement (TAVR) is as an alternative treatment to surgical AVR, but the long-term outcomes of TAVR remain unclear. This study aimed to analyze long-term outcomes following TAVR using meta-analysis.

Methods

A literature search was performed with MEDLINE, EMBASE, Cochrane Library, Web of Science, and Google Scholar through December 2022; studies reporting clinical outcomes of TAVR with follow-up periods of ≥ 8 years were included. The outcomes of interest were overall survival and/or freedom from structural valve deterioration (SVD). Surgical risk was assessed with the Society of Thoracic Surgeons (STS) predicted risk of mortality (PROM) score. A subgroup analysis was conducted for intermediate-/high-surgical risk patients only.

Results

Eleven studies including 5,458 patients were identified and analyzed. The mean age was 82.0 ± 6.5 years, and mean STS PROM score ranged from 2.9 to 10.6%. Survival rate at 5 and 10 years was 47.7% ± 1.4% and 12.1 ± 2.0%. Five studies including 1,509 patients were analyzed for SVD. Freedom from SVD at 5 and 8 years was 95.5 ± 0.7% and 84.9 ± 3.1%. Similar results for survival and SVD were noted in the subgroup analysis of intermediate-/high-risk patients.

Conclusions

Following TAVR, approximately 88% of patients died within 10 years, whereas 85% were free from SVD at 8 years. These date suggest that baseline patient demographic have the greatest impact on survival, and SVD does not seem to have a prognostic impact in this population. Further investigations on longer-term outcomes of younger and lower-risk patients are warranted.

What is new?

-

Meta-analysis of time-to-event data was performed to assess long-term outcomes following transcatheter aortic valve replacement in a large population.

-

Six studies, including 4,910 patients with follow-up periods of more than 20 years were identified and analyzed.

-

Nearly 88% of patients who underwent transcatheter aortic valve replacement died within 10 years, while 85% remained free from structural valve deterioration at 8 years.

Perspective Statement What are the clinical implications?

-

This meta-analysis demonstrated excellent freedom from structural valve deterioration in intermediate- to high elderly risk patients.

-

Baseline patient characteristics correlated with high mortality at 10 years.

-

Further investigation into the outcomes in younger and lower-risk populations is imperative to evaluate the future expanded indications for transcatheter aortic valve replacement.
Her6 and Prox1 are novel regulators of photoreceptor regeneration in the zebrafish retina
Authors: Veen Kellie , Krylov Aaron , Yu Shuguang , He Jie , Boyd Patrick , Hyde David R. , Mantamadiotis Theo , Cheng Louise Y , Jusuf Patricia R
Published: March 2023

Damage to light-sensing photoreceptors (PRs) occurs in highly prevalent retinal diseases. As humans cannot regenerate new PRs, these diseases often lead to irreversible blindness. Intriguingly, animals, such as the zebrafish, have the ability to regenerate PRs efficiently and restore functional vision. Upon injury, mature Müller glia (MG) undergo reprogramming to adopt a stem cell-like state. This process is similar to cellular dedifferentiation, and results in the generation of progenitor cells, which, in turn, proliferate and differentiate to replace lost retinal neurons. In this study, we tested whether factors involved in dedifferentiation ofDrosophilaCNS are implicated in the regenerative response in the zebrafish retina. We found thathairy-related 6(her6) negatively regulates of PR production by regulating the rate of cell divisions in the MG-derived progenitors.prospero homeobox 1(prox1) is expressed in differentiated PRs, and likely promotes PR differentiation through phase separation. Interestingly, upon Her6 downregulation, Prox1 is precociously upregulated in the PRs, to promote PR differentiation; conversely, loss of Prox1 also induces a downregulation of Her6. Together, we identified two novel candidates of PR regeneration that cross regulate each other, and may be exploited to promote human retinal regeneration and vision recovery.
DRPBind: prediction of DNA, RNA and protein binding residues in intrinsically disordered protein sequences
Authors: Sharma Ronesh , Tsunoda Tatsuhiko , Sharma Alok
Published: March 2023

DRPbind predicts three components: deoxyribonucleic acid (DNA) binding, ribonucleic acid (RNA) binding and protein-binding residues of query protein sequences. DRPbind utilizes independent sources of information encoded for each component predictor and relies on the information-rich profiles of protein evolutionary-based features, protein physicochemical-based features, and protein structural-based features. DRPbind employs protein profile-based features extracted from the bigrams of PSSM and HMM profiles. It also extracts features from physicochemical and structural attributes. DRPbind takes primary protein sequences as input, and through the Support Vector Machine (SVM) classifier, it provides the binding prediction. DRPbind is optimized based on a specific binding type and shown superior performance in terms of simultaneously predicting the DNA-binding, RNA-binding and protein-binding residues. The source code is available at https://github.com/roneshsharma/DNA-RNA-Protein-Binding/wiki
Metabolic dynamics of the coral-algal symbiosis from fertilization to settlement identify critical coral energetic vulnerabilities
Authors: Huffmyer Ariana Snow , Wong Kevin H , Becker Danielle M , Strand Emma , Mass Tali , Putnam Hollie M
Published: March 2023

Climate change accelerates coral reef decline and jeopardizes recruitment essential for ecosystem recovery. Adult corals rely on a vital nutritional exchange with their symbiotic algae (Symbiodiniaceae), but the dynamics and sensitivity of this reliance from fertilization to recruitment are understudied. We investigated the physiological, metabolomic, and transcriptomic changes across 13 developmental stages ofMontipora capitata, a coral in Hawaii that inherits symbionts from parent to egg. We found that embryonic development depends on maternally provisioned mRNAs and lipids, with a rapid shift to symbiont-derived nutrition in swimming larvae. Symbiont density and photosynthesis peak once swimming to fuel pelagic larval dispersal. In contrast, respiratory demand increases significantly during metamorphosis, settlement, and calcification, reflecting this energy-intensive morphological reorganization. Symbiont ontogenetic proliferation is driven by symbiont ammonium assimilation with little evidence of nitrogen metabolism in the coral host. As development progresses, the host enhances nitrogen sequestration, regulating symbiont populations, and ensuring the transfer of fixed carbon to support metamorphosis, with both metabolomic and transcriptomic indicators of increased carbohydrate availability. Although algal symbiont communities remained stable, bacterial communities shifted with ontogeny, associated with holobiont metabolic reorganization. Our study reveals extensive metabolic changes during development, increasingly reliant on symbiont nutrition. Metamorphosis and settlement emerge as the most critical periods of energetic vulnerability to projected climate scenarios that destabilize symbiosis. This highly detailed elucidation of symbiotic nutritional exchange relative to sensitive early life stages provides essential knowledge for understanding and forecasting nutritional symbiosis integration, and specifically, coral survival and recruitment in a future of climate change.
THE RHODOEXPLORER PLATFORM FOR RED ALGAL GENOMICS AND WHOLE GENOME ASSEMBLIES FOR SEVERAL GRACILARIA SPECIES
Authors: Lipinska Agnieszka P. , Krueger-Hadfield Stacy A. , Godfroy Olivier , Dittami Simon , Ayres-Ostrock Lígia , Bonthond Guido , Brillet-Guéguen Loraine , Coelho Susana , Corre Erwan , Cossard Guillaume , Destombe Christophe , Epperlein Paul , Faugeron Sylvain , Ficko-Blean Elizabeth , Beltrán Jessica , Lavaut Emma , Bars Arthur Le , Marchi Fabiana , Mauger Stéphane , Michel Gurvan , Potin Philippe , Scornet Delphine , Sotka Erik E. , Weinberger Florian , Cabral de Oliveira Mariana , Guillemin Marie-Laure , Plastino Estela M. , Valero Myriam
Published: March 2023

Macroalgal (seaweed) genomic resources are generally lacking as compared to other eukaryotic taxa, and this is particularly true in the red algae (Rhodophyta). Understanding red algal genomes is critical to understanding eukaryotic evolution given that red algal genes are spread across eukaryotic lineages from secondary endosymbiosis and red algae diverged early in the Archaeplastids. The Gracilariales are highly diverse and widely distributed order whose species can serve as ecosystem engineers in intertidal habitats, including several notorious introduced species. The genusGracilariais cultivated worldwide, in part for its production of agar and other bioactive compounds with downstream pharmaceutical and industrial applications. This genus is also emerging as a model for algal evolutionary ecology. Here, we report new whole genome assemblies for two species (G. chilensisandG. gracilis), a draft genome assembly ofG. caudata, and genome annotation of the previously publishedG. vermiculophyllagenome. To facilitate accessibility and comparative analysis, we integrated these data in a newly created web-based portal dedicated to red algal genomics (https://rhodoexplorer.sb-roscoff.fr). These genomes will provide a resource for understanding algal biology and, more broadly, eukaryotic evolution.
Early acting inbreeding depression can evolve as an inbreeding avoidance mechanism
Authors: Brandvain Yaniv J , Thomson Lia , Pyhajarvi Tanja
Published: March 2023

Despite the potential for mechanical, developmental and/or chemical mechanisms to prevent self-fertilization, incidental self-fertilization is inevitable in many predominantly outcrossing species. In such cases, inbreeding can compromise individual fitness. Unquestionably, much of this inbreeding depression is maladaptive. However, we show that when reproductive compensation allows for the replacement of inviable embryos lost early in development, selection can favor deleterious recessive variants that induce "self-sacrificial" death of inbred embryos. Our theoretical results provide numerous testable predictions which could challenge the assumption that inbreeding depression is always maladaptive. Our work is applicable any species that cannot fully avoid inbreeding, exhibits substantial inbreeding depression, and has the potential to compensate embryos lost early in development. In addition to its general applicability our theory suggests that self-sacrificial variants might be responsible for the remarkably low realized selfing rates of gymnosperms with high primary selfing rates, as gymnosperms exhibit strong inbreeding depression, have effective reproductive compensation mechanisms, and cannot evolve chemical self-incompatibility.
Transmembrane Stem Factor Nanodiscs Enhanced Revascularization in a Hind Limb Ischemia Model in Diabetic, Hyperlipidemic Rabbits
Authors: Takematsu Eri , Massidda Miles , Howe Gretchen , Goldman Julia , Felli Patricia , Mei Lei , Callahan Gregory , Sligar Andrew D , Smalling Richard , Baker Aaron B.
Published: March 2023

Therapies to revascularize ischemic tissue have long been a goal for the treatment of vascular disease and other disorders. Therapies using stem cell factor (SCF), also known as a c-Kit ligand, had great promise for treating ischemia for myocardial infarct and stroke, however clinical development for SCF was stopped due to toxic side effects including mast cell activation in patients. We recently developed a novel therapy using a transmembrane form of SCF (tmSCF) delivered in lipid nanodiscs. In previous studies, we demonstrated tmSCF nanodiscs were able to induce revascularization of ischemia limbs in mice and did not activate mast cells. To advance this therapeutic towards clinical application, we tested this therapy in an advanced model of hindlimb ischemia in rabbits with hyperlipidemia and diabetes. This model has therapeutic resistance to angiogenic therapies and maintains long term deficits in recovery from ischemic injury. We treated rabbits with local treatment with tmSCF nanodiscs or control solution delivered locally from an alginate gel delivered into the ischemic limb of the rabbits. After eight weeks, we found significantly higher vascularity in the tmSCF nanodisc-treated group in comparison to alginate treated control as quantified through angiography. Histological analysis also showed a significantly higher number of small and large blood vessels in the ischemic muscles of the tmSCF nanodisc treated group. Importantly, we did not observe inflammation or mast cell activation in the rabbits. Overall, this study supports the therapeutic potential of tmSCF nanodiscs for treating peripheral ischemia.
Ultra-flexible endovascular probes for brain recording through micron-scale vasculature
Authors: Zhang Anqi , Mandeville Emiri T. , Xu Lijun , Stary Creed M. , Lo Eng H. , Lieber Charles M.
Published: March 2023

Implantable neuroelectronic interfaces have enabled significant advances in both fundamental research and treatment of neurological diseases, yet traditional intracranial depth electrodes require invasive surgery to place and can disrupt the neural networks during implantation. To address these limitations, we have developed an ultra-small and flexible endovascular neural probe that can be implanted into small 100-micron scale blood vessels in the brains of rodents without damaging the brain or vasculature. The structure and mechanical properties of the flexible probes were designed to meet the key constraints for implantation into tortuous blood vessels inaccessible with existing techniques.In vivoelectrophysiology recording of local field potentials and single-unit spikes has been selectively achieved in the cortex and the olfactory bulb. Histology analysis of the tissue interface showed minimal immune response and long-term stability. This platform technology can be readily extended as both research tools and medical devices for the detection and intervention of neurological diseases.
Intramuscular Versus Intravenous SARS-CoV-2 Neutralizing Antibody Sotrovimab for Treatment of COVID-19 (COMET-TAIL): A Randomized Non-inferiority Clinical Trial
Authors: Shapiro Adrienne E. , Sarkis Elias , Acloque Jude , Free Almena , Gonzalez-Rojas Yaneicy , Hussain Rubaba , Juarez Erick , Moya Jaynier , Parikh Naval , Inman David , Cebrik Deborah , Nader Ahmed , Noormohamed Nadia , Wang Qianwen , Skingsley Andrew , Austin Daren , Peppercorn Amanda , Agostini Maria L. , Parra Sergio , Chow Sophia , Mogalian Erik , Pang Phillip S. , Hong David K. , Sager Jennifer E. , Yeh Wendy W. , Alexander Elizabeth L. , Gaffney Leah A. , Kohli Anita
Published: March 2023

Background

Convenient administration of coronavirus disease 2019 (COVID-19) treatment in community settings is desirable. Sotrovimab is a pan-sarbecovirus dual-action monoclonal antibody formulated for intravenous (IV) or intramuscular (IM) administration for early treatment of mild/moderate COVID-19.

Methods

This phase 3, randomized, multicenter, open-label study tested non-inferiority of IM to IV administration using a 3.5% absolute non-inferiority margin. From June to August 2021, patients aged ≥12 years with COVID-19, not hospitalized or receiving supplemental oxygen, and at high risk for progression were randomized 1:1:1 to a single 500-mg IV sotrovimab infusion or 500-mg or 250-mg IM sotrovimab injection. The primary composite endpoint was progression to all-cause hospitalization for >24 hours for acute management of illness or all-cause death through day 29.

Results

Sotrovimab 500 mg IM was non-inferior to 500 mg IV: 10/376 (2.7%) participants in the sotrovimab 500-mg IM group versus 5/378 (1.3%) in the sotrovimab 500-mg IV group met the primary endpoint (absolute adjusted risk difference: 1.06% [95% confidence interval [CI]: −1.15%, 3.26%]). The CI upper limit was lower than the prespecified non-inferiority margin of 3.5%. 250-mg IM group enrollment was discontinued early because a greater proportion of hospitalizations was seen in that group versus the 500-mg groups. Serious adverse events occurred in <1% to 2% of participants across groups. Four participants experienced serious disease related events and died (500 mg IM: 2/393 [<1%]; 250 mg IM: 2/195 [1%]).

Conclusions

Sotrovimab 500-mg IM injection was well tolerated and non-inferior to IV administration. IM administration could expand outpatient treatment access for COVID-19.

Registration

ClinicalTrials.govIdentifier:NCT04913675

Key Points

Sotrovimab 500-mg IM was non-inferior to sotrovimab 500-mg IV for treatment of mild/moderate COVID-19 in high-risk patients, measured by all-cause hospitalization >24h or death through day 29, and was well-tolerated. Sotrovimab IM should provide easier outpatient access to COVID-19 treatment.
Ultra-Rapid and Specific Gelation of Collagen Molecules for Transparent and Tough Gels by Transition Metal Complexation
Authors: Suezawa Tomoyuki , Sasaki Naoko , Assan Nazgul , Uetake Yuta , Onuma Kunishige , Sakurai Hidehiro , Katayama Ryohei , Inoue Masahiro , Matsusaki Michiya
Published: March 2023

Collagen is one of the main components of tumor stromal tissues with a high elastic modulus, but there have been limitations when attempting to fabricate a tough collagen gel with cells like a cancer stroma. Here, we demonstrate the rapid and specific formation of collagen gels with high transparency and high elastic modulus by transition metal complexation within minutes. Transition metal ions such as K2PtCl4exhibited rapid gelation due to the formation of a cross-linked network of the collagen triple-helix by Pt– O and/or Pt–N bonds. Interestingly, type I to IV collagens showed rapid gelation, while other extracellular matrices and DNA did not exhibit this phenomenon, suggesting the importance of intermolecular interaction in a rigid triple-helix structure. Live imaging of colon cancer organoids in three-dimensional culture indicated a collective migration property with modulating high elastic modulus, suggesting activation for metastasis progress. This technology that facilitates deep-live observation and mechanical stiffness adjustment will be useful as a new class of scaffolds.

Teaser

Transparent collagen gels with tunable mechanical properties allow deep-live observation of cells cultured in a tough environment like our bodies.
A difference in larval mosquito size allows a biocontrol agent to target the invasive species
Authors: Russell Marie C.
Published: March 2023

As the global temperature rises in the coming decades,Aedes albopictusis expected to invade and establish in South East England, whereCulex pipiensis currently the most common native mosquito species. Biocontrol measures that use local cyclopoid copepods againstAe. albopictusmay be compromised if the copepods prefer alternateCx. pipiensprey. In this study, we assessed the predation efficiency ofMegacyclops viridiscopepods against FrenchAe. albopictuslarvae and larvae that hatched from egg rafts ofCx. pipienscollected in South East England. The experiments were conducted at 15°C and 25°C, which are representative of present and future summer temperatures in South East England.Ae. albopictuslarvae that survived the course of the experiment in the predator-absent controls were significantly smaller thanCx. pipienslarvae that survived in the absence of predation. The background mortality ofCx. pipienslarvae increased with the ten-degree increase in temperature, and the smaller size of survivingCx. pipienslarvae at 25°C, relative to survivors at 15°C, suggests that largerCx. pipienslarvae were more likely to die at the higher temperature setting. Across all experimental treatments, the ratio of copepod body length to mean prey length, based on larval lengths of survivors from the corresponding predator-absent controls, was a significant predictor of predation efficiency. Adding temperature setting to the predation efficiency model as a predictor did not improve model fit. Within the mixed prey treatments, the predation efficiency ofM. viridiswas 34.5 percentage points higher againstAe. albopictusprey than againstCx. pipiensprey. The higher predation efficiency thatM. viridisexhibited against invasiveAe. albopictusprey, likely due to the smaller size of these larvae, supports the future use ofM. viridisas a biocontrol agent in the UK.
Prophage maintenance is determined by environment-dependent selective sweeps rather than mutational availability
Authors: Bailey Zachary M. , Igler Claudia , Wendling Carolin C.
Published: March 2023

Prophages, viral sequences integrated into bacterial genomes, can be beneficial and costly. Despite the risk of prophage activation and subsequent bacterial death, active prophages are present in most bacterial genomes. However, our understanding of the selective forces that maintain prophages in bacterial populations is limited. Combining experimental evolution with stochastic modelling, we show that prophage maintenance and loss are primarily determined by environmental conditions that alter the net fitness effect of a prophage. When prophages are too costly, they are rapidly lost through environment-specific sequences of selective sweeps. Conflicting selection pressures that select against the prophage but for a prophage-encoded accessory gene can maintain prophages. The dynamics of prophage maintenance additionally depends on the sociality of this accessory gene. Non-cooperative genes maintain prophages at higher frequencies than cooperative genes, which can protect phage-free ‘cheaters’ that may emerge if prophage costs outweigh their benefits. Our simulations suggest that environmental variation plays a larger role than mutation rates in determining prophage maintenance. These findings highlight the complexity of selection pressures that act on mobile genetic elements and challenge our understanding of the role of environmental factors relative to random chance events in shaping the evolutionary trajectory of bacterial populations.
A cortical surface template for human neuroscience
Authors: Feilong Ma , Jiahui Guo , Gobbini M. Ida , Haxby James V.
Published: March 2023

Neuroimaging data analysis relies on normalization to standard anatomical templates to resolve macroanatomical differences across brains. Existing human cortical surface templates sample locations unevenly because of distortions introduced by inflation of the folded cortex into a standard shape. Here we present the onavg template, which affords uniform sampling of the cortex. We created the onavg template based on openly-available high-quality structural scans of 1,031 brains—25 times more than existing cortical templates. We optimized the vertex locations based on cortical anatomy, achieving an even distribution. We observed consistently higher multivariate pattern classification accuracies and representational geometry inter-subject correlations based on onavg than on other templates, and onavg only needs 3⁄4 as much data to achieve the same performance compared to other templates. The optimized sampling also reduces CPU time across algorithms by 1.3%–22.4% due to less variation in the number of vertices in each searchlight.
Cell-type specific EWAS identifies genes involved in HIV pathogenesis and oncogenesis among people with HIV infection
Authors: Zhang Xinyu , Hu Ying , Vandenhoudt Ral E. , Yan Chunhua , Marconi Vincent C , Cohen Mardge H. , Justice Amy C , Aouizerat Bradley E , Xu Ke
Published: March 2023

Epigenome-wide association studies (EWAS) of heterogenous blood cells have identified CpG sites associated with chronic HIV infection, which offer limited knowledge of cell-type specific methylation patterns associated with HIV infection. Applying a computational deconvolution method validated by capture bisulfite DNA methylation sequencing, we conducted a cell type-based EWAS and identified differentially methylated CpG sites specific for chronic HIV infection among five immune cell types in blood: CD4+ T-cells, CD8+ T-cells, B cells, Natural Killer (NK) cells, and monocytes in two independent cohorts (Ntotal=1,134). Differentially methylated CpG sites for HIV-infection were highly concordant between the two cohorts. Cell-type level meta-EWAS revealed distinct patterns of HIV-associated differential CpG methylation, where 67% of CpG sites were unique to individual cell types (false discovery rate, FDR <0.05). CD4+ T-cells had the largest number of HIV-associated CpG sites (N=1,472) compared to any other cell type. Genes harboring statistically significant CpG sites are involved in immunity and HIV pathogenesis (e.g.CX3CR1in CD4+ T-cells,CCR7in B cells,IL12Rin NK cells,LCKin monocytes). More importantly, HIV-associated CpG sites were overrepresented for hallmark genes involved in cancer pathology (FDR<0.05) (e.g.BCL family, PRDM16, PDCD1LGD, ESR1, DNMT3A, NOTCH2). HIV-associated CpG sites were enriched among genes involved in HIV pathogenesis and oncogenesis such as Kras-signaling, interferon-α and −γ, TNF-α, inflammatory, and apoptotic pathways. Our findings are novel, uncovering cell-type specific modifications in the host epigenome for people with HIV that contribute to the growing body of evidence regarding pathogen-induced epigenetic oncogenicity, specifically on HIV and its comorbidity with cancers.
Dimension-agnostic and granularity-based spatially variable gene identification
Authors: Wang Juexin , Li Jinpu , Kramer Skyler T , Su Li , Chang Yuzhou , Xu Chunhui , Ma Qin , Xu Dong
Published: March 2023

Identifying spatially variable genes (SVGs) is critical in linking molecular cell functions with tissue phenotypes. Spatially resolved transcriptomics captures cellular-level gene expression with corresponding spatial coordinates in two or three dimensions and can be used to infer SVGs effectively. However, current computational methods may not achieve reliable results and often cannot handle three-dimensional spatial transcriptomic data. Here we introduce BSP (big-small patch), a spatial granularity-guided and non-parametric model to identify SVGs from two or three-dimensional spatial transcriptomics data in a fast and robust manner. This new method has been extensively tested in simulations, demonstrating superior accuracy, robustness, and high efficiency. BSP is further validated by substantiated biological discoveries in cancer, neural science, rheumatoid arthritis, and kidney studies with various types of spatial transcriptomics technologies.
Integrating long-read RNA sequencing improves locus-specific quantification of transposable element expression
Authors: Lee Sojung , Barbour Jayne A. , Tam Yee Man , Yang Haocheng , Huang Yuanhua , Wong Jason W. H.
Published: March 2023

Transposable elements (TEs) can influence human diseases by disrupting genome integrity, yet their quantification has been challenging due to the repetitive nature of these sequences across the genome. We developed LocusMasterTE, a method that integrates long-read with short-read RNA-seq to increase the accuracy of TE expression quantification. By incorporating fractional transcript per million (TPM) values from long-read sequencing data into an expectation-maximization (EM) algorithm, LocusMasterTE reassigns multi-mapped reads, enhancing accuracy in short-read-based TE quantification. Validated with simulated and human datasets, LocusMasterTE holds promise for revealing new insights into TE functions through precise quantification.
Proximity Proteome Analysis Reveals Novel TREM2 Interactors in the ER-Mitochondria Interface of Human Microglia
Authors: Kwak Chulhwan , Finan Gina M. , Park Yu Rim , Garg Anjali , Harari Oscar , Mun Ji Young , Rhee Hyun-Woo , Kim Tae-Wan
Published: March 2023

Triggering receptor expressed on myeloid cells 2 (TREM2) plays a central role in microglial biology and the pathogenesis of Alzheimer’s disease (AD). Besides DNAX-activating protein 12 (DAP12), a communal adaptor for TREM2 and many other receptors, other cellular interactors of TREM2 remain largely elusive. We employed a ‘proximity labeling’ approach using a biotin ligase, TurboID, for mapping protein–protein interactions in live mammalian cells. We discovered novel TREM2-proximal proteins with diverse functions, including those localized to the Mitochondria-ER contact sites (MERCs), a dynamic subcellular ‘hub’ implicated in a number of crucial cell physiology such as lipid metabolism. TREM2 deficiency alters the thickness (inter-organelle distance) of MERCs, a structural parameter of metabolic state, in microglia derived from human induced pluripotent stem cells. Our TurboID-based TREM2 interactome study suggest novel roles for TREM2 in the structural plasticity of the MERCs, raising the possibility that dysregulation of MERC-related TREM2 functions contribute to AD pathobiology.
Lightweight Fine-tuning a Pretrained Protein Language Model for Protein Secondary Structure Prediction
Authors: Yang Wei , Liu Chun , Li Zheng
Published: March 2023

Pretrained large-scale protein language models, such as ESM-1b and ProtTrans, are becoming the fundamental infrastructure for various protein-related biological modeling tasks. Existing works use mainly pretrained protein language models in feature extraction. However, the knowledge contained in the embedding features directly extracted from a pretrained model is task-agnostic. To obtain task-specific feature representations, a reasonable approach is to fine-tune a pretrained model based on labeled datasets from downstream tasks. To this end, we investigate the fine-tuning of a given pretrained protein language model for protein secondary structure prediction tasks. Specifically, we propose a novel end-to-end protein secondary structure prediction framework involving the lightweight fine-tuning of a pretrained model. The framework first introduces a few new parameters for each transformer block in the pretrained model, then updates only the newly introduced parameters, and then keeps the original pretrained parameters fixed during training. Extensive experiments on seven test sets, namely, CASP12, CASP13, CASP14, CB433, CB634, TEST2016, and TEST2018, show that the proposed framework outperforms existing predictors and achieves new state-of-the-art prediction performance. Furthermore, we also experimentally demonstrate that lightweight fine-tuning significantly outperforms full model fine-tuning and feature extraction in enabling models to predict secondary structures. Further analysis indicates that only a few top transformer blocks need to introduce new parameters, while skipping many lower transformer blocks has little impact on the prediction accuracy of secondary structures.
Transient demographic dynamics of recovering fish populations shaped by past climate variability, harvest, and management
Authors: Goto Daisuke
Published: March 2023

Large-scale commercial harvesting and climate-induced fluctuations in ocean properties shape the dynamics of marine populations as interdependent drivers at varied timescales. Selective removals of larger, older members of a population can distort its demographic structure, eroding resilience to fluctuations in habitat conditions and thus amplifying volatility in transient dynamics. Through the implementation of stricter management measures, many historically depleted fish stocks began showing signs of recovery in recent decades. But these interventions coincided with accelerated changes in the oceans triggered by increasingly warmer, more variable climates. Applying multilevel models to annual estimates of demographic metrics of 38 stocks comprising 11 species across seven ecoregions in the northeast Atlantic Ocean, this study explores how time-varying local and regional climates contributed to the transient dynamics of recovering populations exposed to variable fishing pressures moderated by management actions. Analyses reveal that progressive reductions in fishing pressure and shifting climate conditions nonlinearly shaped rebuilding patterns of the stocks through restorations of maternal demographic structure (reversing age truncation) and reproductive capacity. As the survival rate and demographic structure of reproductive fish improved, transient growth became less sensitive to variability in recruitment and juvenile survival and more to that in adult survival. As the biomass of reproductive fish rose, recruitment success also became increasingly regulated by density-dependent processes involving higher numbers of older fish. When reductions in fishing pressure were insufficient or delayed, however, stocks became further depleted, with more eroded demographic structures. Although warmer local climates in spawning seasons promoted recruitment success in some ecoregions, changing climates in recent decades began adversely affecting reproductive performances overall, amplifying sensitivities to recruitment variability. These shared patterns underscore the value of demographic transients in developing robust strategies for managing marine resources. Such strategies could form the foundation for effective applications of adaptive measures resilient to future environmental change.
Chromosome-aware phylogenomics of Assassin Bugs (Hemiptera: Reduvioidea) elucidates ancient gene conflict
Authors: Knyshov Alexander , Gordon Eric R. L. , Masonick Paul K. , Castillo Stephanie , Forero Dimitri , Hoey-Chamberlain Rochelle , Hwang Wei Song , Johnson Kevin P. , Lemmon Alan R. , Lemmon Emily Moriarty , Standring Samantha , Zhang Junxia , Weirauch Christiane
Published: March 2023

Though the phylogenetic signal of loci on sex chromosomes can differ from those on autosomes, chromosomal-level genome assemblies for non-vertebrates are still relatively scarce and conservation of chromosomal gene content across deep phylogenetic scales has therefore remained largely unexplored. We here assemble a uniquely large and diverse set of samples (17 Anchored Hybrid Enrichment [AHE], 24 RNA-Seq, and 70 whole-genome sequencing [WGS] samples of variable depth) for the medically important assassin bugs (Reduvioidea). We assess the performance of genes based on multiple features (e.g., nucleotide vs. amino acid, nuclear vs. mitochondrial, and autosomal vs. X chromosomal) and employ different methods (concatenation and coalescence analyses) to reconstruct the unresolved phylogeny of this diverse (∼7,000 spp.) and old (>180 MYA) group. Our results show that genes on the X chromosome are more likely to have discordant phylogenies than those on autosomes. We find that the X chromosome conflict is driven by high gene substitution rates that impact accuracy of phylogenetic inference. However, gene tree clustering showed strong conflict even after discounting variable third codon positions. Alternative topologies were not particularly enriched for sex chromosome loci, but spread across the genome. We conclude that binning genes to autosomal or sex chromosomes may result in a more accurate picture of the complex evolutionary history of a clade.
Cell targeting and immunostimulatory properties of a novel Fcγ-receptor independent agonistic anti-CD40 antibody in rhesus macaques
Authors: Yan Xianglei , Ols Sebastian , Cerveira Rodrigo Arcoverde , Lenart Klara , Hellgren Fredrika , Ye Kewei , Cagigi Alberto , Buggert Marcus , Nimmerjahn Falk , Højen Jesper Falkesgaard , Parera Daniel , Pessara Ulrich , Fischer Stephan , Loré Karin
Published: March 2023

Targeting CD40 by agonistic antibodies used as vaccine adjuvants or for cancer immunotherapy is a strategy to stimulate immune responses. The majority of studied agonistic anti-human CD40 antibodies require crosslinking of their Fc region to inhibitory FcγRIIb to induce immune stimulation although this has been associated with toxicity in previous studies. Here we introduce an agonistic anti-human CD40 monoclonal IgG1 antibody (MAB273) unique in its specificity to the CD40L binding site of CD40 but devoid of Fcγ-receptor binding, we demonstrate rapid binding of MAB273 to B cells and dendritic cells resulting in strong activationin vitroon human cells andin vivoin rhesus macaques. Dissemination of fluorescently labeled MAB273 after subcutaneous administration was found predominantly at the site of injection and specific draining lymph nodes. Phenotypic cell differentiation and upregulation of genes associated with immune activation were found in the targeted tissues. Antigen-specific T cell responses were enhanced by MAB273 when given in a prime-boost regimen and for boosting low preexisting responses. MAB273 may therefore be a promising immunostimulatory adjuvant that warrants future testing for therapeutic and prophylactic vaccination strategies.