bluuebunny/crossref_metadata_2025 huggingface dataset:
A new ex vivo human model of osteoarthritis cartilage calcification
Authors: Faure Elodie , Wegrzyn Julien , Bernabei Ilaria , Falgayrac Guillaume , Bertheaume Nicolas , Pascart Tristan , Hugle Thomas , Busso Nathalie , Nasi Sonia
Published: January 2024

Objective

Cartilage pathologic calcification is a hallmark of osteoarthritis (OA). Here, we aimed to describe a new ex vivo human model to study the progression of cartilage calcification.

Method

Cartilage explants (n = 11), as well as primary chondrocytes (n = 3), were obtained from OA patients undergoing knee replacement. Explants and chondrocytes were cultured in control (NT) or calcification (CM) medium (supplemented with ascorbic acid and β-glycerophosphate). Calcification was evaluated by micro-CT scan at day 0 and 21 in explants, and by Alizarin red staining in chondrocyte monolayers. Raman spectrometry allowed characterization of the crystal type. Interleukin-6 (IL-6) secretion in explant and cell supernatants was measured by ELISA. Finally, matrix degradation was evaluated by Safranin-O staining of explant sections and by glycosaminoglycans (GAG) released in supernatants.

Results

Micro-CT scan showed calcifications in all explants at baseline (day 0), which in the CM group increased significantly in number and size after 21 days compared with the NT group. Raman spectrometry revealed that crystals were exclusively basic calcium phosphate crystals (carbonated hydroxyapatite) both in NT and CM. IL-6 secretion was significantly increased in calcifying conditions. Finally, CM significantly increased cartilage catabolism as assessed by decreased Safranin-O staining of tissue explants and increased GAG release in supernatants. CM effects (enhanced calcification, IL-6 secretion and proteoglycans turn-over) were recapitulated in vitro in OA chondrocytes.

Conclusions

We have described a new ex vivo human model of cartilage calcification that can summarize the triad of events seen during osteoarthritis progression, i.e. calcification, inflammation and cartilage degradation. This model will allow the identification of new anti-calcification compounds.
Stromal Keratitis Associated With Cytomegalovirus Anterior Uveitis
Authors: Pisitpayat Punyanuch , Mentreddy Akshay , Pekmezci Melike , Hwang David , Shantha Jessica , Benador-Shen Christine , Terry Merryl , Pothikamjorn Thananop , Gonzales John
Published: January 2024

Purpose:

Human cytomegalovirus (CMV) has commonly been reported as a cause of anterior uveitis and corneal endotheliitis. Unlike its other herpetic family members, herpes simplex virus and varicella zoster virus, involvement of the corneal stroma in CMV is uncommon. In this case series, we describe patients with CMV stromal keratitis.

Methods:

This was a retrospective chart review of patients seen at a tertiary referral center from 1999 to 2023 with stromal keratitis who tested positive for CMV by directed polymerase chain reaction of aqueous fluid or corneal tissue.

Results:

This series describes 5 patients, 4 of whom presented with anterior uveitis and stromal keratitis and were confirmed to be positive for CMV through the polymerase chain reaction of aqueous fluid. The fifth patient experienced recurrent corneal graft failures, with the most recent failed graft being positive for CMV based on immunohistochemical stains of the corneal stroma. The average age of patients was 62 years (range 36–80 years). Only 1 patient (20%) exhibited elevated intraocular pressure with stellate keratic precipitates at the initial presentation, whereas 3 other patients (60%) had a known history of glaucoma.

Conclusions:

Uveitis specialists are well aware of CMV as a cause of recurrent, hypertensive anterior uveitis but should also consider CMV in cases featuring stromal keratitis. The corneal endothelium may serve as a reservoir for both anterior uveitis and development of corneal stromal inflammation as demonstrated by the immunohistopathology exhibited in 1 case.
Helicobacter cinaedi Bacteremia in Children: A Case Report and Literature Review
Authors: Oren Itamar , Temper Violeta , Michael-Gayego Ayelet , Motro Yair , Volovelsky Oded , Moran-Gilad Jacob , Gordon Oren
Published: January 2024

Helicobacter cinaedi is known to cause invasive infections in immunocompromised adults. Here we report the first case of H. cinaedi bacteremia in a child with nephrotic syndrome. The patient presented with a mild transient febrile illness that resolved spontaneously. We discuss the diagnostic challenges associated with this case and the microbiologic approach, including genomic analysis. Furthermore, we review the current case together with all previous pediatric cases (n = 6). Notably, all cases involved neonates or otherwise immunocompromised individuals and were characterized by severe disease with complicated infections (eg, meningitis, cholangitis and arthritis). H. cinaedi bacteremia in children is associated with a wide spectrum of clinical presentations ranging from mild to life-threatening conditions. This bacterium may be difficult to diagnose and require specialized methods.
Back to the Future: Intravenous Fosfomycin is Safe and Effective for the Treatment of Complicated Infections in Children
Authors: Roversi Marco , Musolino Antonio , Di Giuseppe Martina , Tripiciano Costanza , Cursi Laura , Lancella Laura , Krzysztofiak Andrzej
Published: January 2024

Background:

Despite its broad spectrum and excellent safety profile, fosfomycin is still rarely used in pediatrics, with very limited experience from clinicians.

Methods:

We retrospectively reviewed the medical records of all children admitted to Bambino Gesù Children’s Hospital, IRCCS, Rome, Italy, and treated with fosfomycin for any serious infection. Children with immunodeficiency and oncologic diseases were excluded. Of each, we reported and analyzed demographic and clinical data.

Results:

The clinical charts of 20 patients were reviewed and analyzed. The mean age was 10.2 years. Most children were males (85%). Most patients treated had an osteo-articular infection (65%). In our sample, 7 patients (35%) had an underlying comorbidity. The causative agent was isolated in 14 cases (70%). All patients were treated with a combination of 2–3 antibiotics, including fosfomycin. The average duration of antibiotic treatment was 18 days. After treatment, 8 patients (40%) experienced a mild adverse reaction, possibly correlated with the administration of fosfomycin. All patients were discharged in good clinical condition.

Conclusions:

The present study reports on a sample of pediatric patients with complicated infections where administration of fosfomycin led to eradication of the disease with little or no side effects. Role of the underlying condition and concomitant medication in causing the reaction could not be ruled out. These data suggest that fosfomycin is an effective and safe antibiotic in the pediatric population, particularly for deep-seated infections sustained by multi-drug resistant pathogens.
Gaining experience in the provider role: Exploration of a novel simulation intervention to prepare nurse practitioner students to detect and manage skin cancer
Authors: Powers Kelly , Shue-McGuffin Katherine D.
Published: January 2024

Background:

The high prevalence and negative outcomes associated with skin cancer demand effective strategies to prepare nurse practitioner students to detect cancerous lesions and manage patient care. However, few studies have examined dermatologic simulations to prepare nurse practitioner students to detect and manage skin cancer.

Purpose:

An exploratory–descriptive qualitative approach was used to examine nurse practitioner students' experiences with simulations involving standardized patients wearing three-dimensional (3-D) prosthetic skin lesions, perceptions of ability to apply the simulations to clinical practice, and preferences for learning dermatologic care.

Methodology:

A convenience sample of 39 nurse practitioner students participated in simulations with standardized patients wearing 3-D skin lesions. Focus groups were conducted following simulation participation, and thematic analysis was performed by two researchers.

Results:

Four themes emerged: Simulation provides a safe place to practice, Dermatology should be an integral part of education, Realism makes a difference, and Improved confidence and preparation for practice.

Conclusions:

Simulations with standardized patients wearing 3-D skin lesion prosthetics provided students the opportunity to assess, diagnose, and manage the care of patients with cancerous skin lesions. Participants valued the realistic practice with dermatologic care and reported improved confidence and preparation for practice.

Implications:

Faculty can use simulations to provide experiential learning about the provider role in general and as it pertains to skin cancer care. Attention to realism is important to aid in building students' confidence and preparation for practice.
Establishment of Nomogram for Prediction of Hearing Preservation after Retrosigmoid Approach in Patients with Vestibular Schwannoma
Authors: Lu Qi , Guo Xiaoyan , Kou Ting , Chen Jiyue , Shen Weidong
Published: January 2024

Objective

To derive and validate a prognostic nomogram for the prediction of hearing preservation (HP) after retrosigmoid approach (RSA) in patients with vestibular schwannoma (VS) and further assist in clinical decision-making.

Study Design

Retrospective study.

Setting

Tertiary referral center.

Patients

A total of 111 patients diagnosed with VS with serviceable hearing from January 2013 to March 2023.

Interventions

All patients underwent surgery via RSA, and hearing outcomes were reviewed 2 weeks postoperatively.

Main Outcome Measures

Preoperative and postoperative hearing were analyzed and stratified according to the American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS).

Results

In multivariate analysis of the primary group, preoperative hearing, tumor size, and tumor origin were significantly related to postoperative HP (p = 0.029, p = 0.043, and p = 0.018, respectively). Factors derived from the multivariate analysis were all assembled into the nomogram. The receiver operating characteristic (ROC) curves showed good predictive accuracy of the nomogram model in both primary and validation groups with area under the ROC curve (AUC) values of 0.802 and 0.797, respectively.

Conclusion

Independent predictors of postoperative HP in patients with VS were selected to create the nomogram. The nomogram was able to stratify patients into different risk groups and assist in clinical decision making.
A Comparison of State-Specific Pediatric Emergency Medical Facility Recognition Programs, 2020
Authors: Boggs Krislyn M. , Voligny Emma , Auerbach Marc , Espinola Janice A. , Samuels-Kalow Margaret E. , Sullivan Ashley F. , Camargo Carlos A.
Published: January 2024

Objectives

Prior research suggests that the presence of state-specific pediatric emergency medical facility recognition programs (PFRPs) is associated with high emergency department (ED) pediatric readiness. The PFRPs aim to improve the quality of pediatric emergency care, but individual state programs differ. We aimed to describe the variation in PFRP characteristics and verification requirements and to describe the availability of pediatric emergency care coordinators (PECCs) in states with PFRPs.

Methods

In mid-2020, we collected information about each PFRP from 3 sources: the state Emergency Medical Services for Children (EMSC) website, the EMSC Innovation and Improvement Center website, or via communication with the state's EMSC program manager. For each state with a PFRP, we documented program characteristics, including program start date, number of tiers, whether participation was required/optional, and requirements for verification.

Results

Overall, we identified 17 states with active PFRPs. Five states had only 1 tier or level of recognition whereas the others had multiple. All programs did require presence of a PECC for verification. However, some PRFPs with multiple verification tiers did not require presence of a PECC to achieve each level of verification. In states with PFRPs, EDs with higher total visit volumes, a separate pediatric ED area, located in the Northeast, and earlier program start date were all more likely to have a PECC.

Conclusions

There is variation in state PFRPs, although all prioritize the presence of a PECC. We encourage further research on the effect of different aspects of PFRPs on patient outcomes.
Gender-Affirming Mastectomy: Psychosocial and Surgical Outcomes in Transgender Adults
Authors: Bertrand AA , DeLong Michael R , McCleary Sean P , Nahabet Edward H , Slack Ginger C , DaLio Andrew L , Weimer Amy K , Kwan Lorna , Bernacki Jessica , Rudkin George H ,   the Plastic Surgery Research Group
Published: January 2024

BACKGROUND:

Limited literature exists examining the effects of gender-affirming mastectomy on transmasculine and nonbinary patients that is prospective and uses validated survey instruments.

STUDY DESIGN:

The psychosocial functioning of transmasculine and nonbinary patients was compared between patients who underwent gender-affirming mastectomy and those who had not yet undergone surgery. Participants were enrolled in a single-site, combined study of surgical and psychosocial outcomes, including a cross-sectional cohort of preoperative and postoperative patients, as well as separate prospective cohort. Participants completed the BREAST-Q psychosocial and sexual well-being modules, the BODY-Q satisfaction with chest and nipples modules, the Body Image Quality of Life Inventory, the Transgender Congruence Scale, the Patient Health Questionnaire-9, and the Generalized Anxiety Disorder-7 scale before and after surgery. We also examined how patient demographic factors correlated with postoperative surgical and psychosocial outcomes.

RESULTS:

A total of 111 transmasculine and nonbinary patients 18 to 63 years of age (mean ± SD 26.5 ± 8) underwent mastectomy and were included in the study. All were included in the cross-sectional cohort, and 20 were enrolled in the prospective cohort. More than one-third (34.2%) of patients were nonbinary. After surgery, psychosocial and sexual well-being, satisfaction, body image–related quality of life, and gender congruence were increased (p < 0.001) in both cohorts, and depression (p < 0.009 cross-sectional), and anxiety (p < 0.001 cross-sectional) were decreased. The most common adverse event was hypertrophic scarring, which occurred in 41 (36.9%) participants.

CONCLUSIONS:

In this study of transmasculine and nonbinary adults, gender-affirming mastectomy was followed by substantial improvements in psychosocial functioning.
Sorry we′re open, come in we're closed: different profiles in the perceived applicability of open science practices to completed research projects
Authors: Schneider Jürgen
Published: January 2024

Open science is an increasingly important topic for research, politics and funding agencies. However, the discourse on open science is heavily influenced by certain research fields and paradigms, leading to the risk of generalizing what counts as openness to other research fields, regardless of its applicability. In our paper, we provide evidence that researchers perceive different profiles in the potential to apply open science practices to their projects, making a one-size-fits-all approach unsuitable. In a pilot study, we first systematized the breadth of open science practices. The subsequent survey study examined the perceived applicability of 13 open science practices across completed research projects in a broad variety of research disciplines. We were able to identify four different profiles in the perceived applicability of open science practices. For researchers conducting qualitative-empirical research projects, comprehensively implementing the breadth of open science practices is tendentially not feasible. Further, research projects from some disciplines tended to fit a profile with little opportunity for public participation. Yet, disciplines and research paradigms appear not to be the key factors in predicting the perceived applicability of open science practices. Our findings underscore the case for considering project-related conditions when implementing open science practices. This has implications for the establishment of policies, guidelines and standards concerning open science.
Robotized unplugging of a cylindrical peg press-fitted into a cylindrical hole
Authors: Xu Shuihao , Pham Duc Truong , Su Shizhong
Published: January 2024

It is well accepted that remanufacturing, the returning of a product that has reached the end of its service life to its original condition, is economically and environmentally beneficial. Robotizing disassembly can make remanufacturing even more cost-effective by removing a substantial proportion of the labour costs associated with dismantling end-of-life products for subsequent processing. As unplugging of press-fitted components is a common operation in disassembly, it is appropriate to investigate how it can be robotized. This paper discusses an unplugging technique, twist-and-pull or twisting-pulling, to reduce the axial frictional resistance during the unplugging process and enable a robot to perform it easily. Through theoretical modelling, simulations, and experimental analysis, the paper explores the interaction between twisting, pulling and axial friction reduction during unplugging. Analysis of the experimental, simulation and theoretical results has confirmed that for a small radial interference, twist-and-pull reduces the axial friction and the maximum required unplugging force.
Imagination and idealism after the COVID-19 pandemic: the science of healthy ageing
Authors: Farrelly Colin
Published: January 2024

On 5 May 2023, the World Health Organization declared that COVID-19 no longer constituted a public health emergency of international concern. Medical science must now consider how it ought to recalibrate its imagination and idealism in a post-COVID-19 pandemic world. The fact that
advanced age
was the largest risk factor for COVID-19 mortality and serious illness, as well as for the most prevalent chronic diseases, reveals the urgency and significance of shifting the focus from mitigating each specific pathology risk, one at a time, to targeting biological ageing itself. In his 1910 JAMA Address entitled ‘Imagination and Idealism in the Medical Sciences', Christian Herter made an important distinction between two ways imagination and idealism can be invoked in the medical sciences: (i) humanitarian medicine, which emphasizes the obvious and direct paths of ameliorating human suffering; and (ii) a curiosity-oriented approach which explores pure science and the experimental laboratory. The latter examines the indirect ways of winning, in Herter's words, ‘the citadel’ of health promotion. Herter's reflections on these two contrasting approaches to medicine have significance for both the COVID-19 pandemic and the aspiration to promote the ideal of healthy ageing in the post-COVID-19 pandemic era.
The effect of body size and inbreeding on cancer mortality in breeds of the domestic dog: a test of the multi-stage model of carcinogenesis
Authors: Nunney Leonard
Published: January 2024

Cancer is a leading cause of death in domestic dogs. Deaths due to cancer vary widely among breeds, providing an opportunity for testing the multi-stage model of carcinogenesis. This model underpins evolutionary and basic studies of cancer suppression and predicts a linear increase in cancer with breed size, an expectation complicated by bigger breeds having a shorter lifespan (decreasing risk). Using three independent datasets, the weight and lifespan of breeds provided a good fit of lifetime cancer mortality to the multi-stage model, the fit suggesting many canine cancers are initiated by four driver mutations. Of 85 breeds in more than one dataset, only flat-coated retriever showed significantly elevated cancer mortality, with Scottish terrier, Bernese mountain dog and bullmastiff also showing notable risk (greater than 50% over expected). Analysis of breed clades suggested terriers experience elevated cancer mortality. There was no evidence that the lower mass-specific metabolic rate of larger breeds reduced cancer risk. Residuals indicated increased breed inbreeding shortened expected lifespan, but had no overall effect on cancer mortality. The results provide a baseline for identifying increased breed risk for specific cancers and demonstrate that, unless selection promotes increased cancer suppression, the evolution of larger longer-lived animals leads to a predictable increased cancer risk.
Extreme lower jaw elongation in a placoderm reflects high disparity and modularity in early vertebrate evolution
Authors: Jobbins Melina , Rücklin Martin , Sánchez Villagra Marcelo R. , Lelièvre Hervé , Grogan Eileen , Szrek Piotr , Klug Christian
Published: January 2024

Jaws are a key vertebrate feature that arose early in our evolution. Placoderms are among the first jawed vertebrates; their fossils yield essential knowledge about the early diversification of gnathostome feeding strategies, diets and modularity. Modularity can be expressed through disproportional lengths of lower and upper jaws as in swordfish or halfbeaks.
Alienacanthus malkowskii
is an arthrodire from the Famennian of Morocco and Poland, whose most remarkable feature is its lower jaw, which is twice as long as the skull. This is the oldest record of such extreme jaw elongation and modularity in vertebrates. The gnathal plates of
Alienacanthus
possess sharp, posteriorly recurved teeth that continue anterior of the occlusion in the inferognathals. The dentition suggests a catching and trapping live prey function, and the jaw occlusion is unique among placoderms. This armoured ‘fish’ expands the morphological and ecological diversity during one of the first radiations of jawed vertebrates with a combination of features so far unrecorded for arthrodires.
Experimental studies on snaking in 3D-printed cylindrical shells under axial compression using photogrammetry
Authors: Ravulapalli V. , Raju G. , Narayanamurthy V.
Published: January 2024

The buckling instability of cylindrical shells under axial compression has been one of the most renowned problems in structural engineering for several decades. Many pioneering works in the twentieth century have provided insights into understanding the shells’ infamous imperfection sensitivity and led to reliability-based designs. However, a recent surge in numerical studies of the snaking phenomenon explores the development of a localized stable post-buckling mode in axially compressed cylindrical shells. Hitherto, none of the experimental studies report on the evolution of azimuthal snaking. In this work, experimental studies are carried out with the objective of revealing the snaking phenomenon. The axial compression experiments are performed on 3D-printed shells made of thermoplastic polyurethane (TPU). The work’s novelty lies in the usage of TPU shells for slowing down the propagation of circumferential dimples and making it feasible to capture them using photogrammetry. Despite the match between the experimental and numerical mode shapes, the experiments reveal multiple routes for the snaking sequence. Furthermore, mode transitions such as reduction in circumferential wave number and transformation of symmetric mode into an asymmetric one are observed. These experimental results provide insights into the localized phenomenon of snaking and validate numerical solutions.
Quantitative functional imaging of the pigeon brain: implications for the evolution of avian powered flight
Authors: Balanoff Amy , Ferrer Elizabeth , Saleh Lemise , Gignac Paul M. , Gold M. Eugenia L. , Marugán-Lobón Jesús , Norell Mark , Ouellette David , Salerno Michael , Watanabe Akinobu , Wei Shouyi , Bever Gabriel , Vaska Paul
Published: January 2024

The evolution of flight is a rare event in vertebrate history, and one that demands functional integration across multiple anatomical/physiological systems. The neuroanatomical basis for such integration and the role that brain evolution assumes in behavioural transformations remain poorly understood. We make progress by (i) generating a positron emission tomography (PET)-based map of brain activity for pigeons during rest and flight, (ii) using these maps in a functional analysis of the brain during flight, and (iii) interpreting these data within a macroevolutionary context shaped by non-avian dinosaurs. Although neural activity is generally conserved from rest to flight, we found significant increases in the cerebellum as a whole and optic flow pathways. Conserved activity suggests processing of self-movement and image stabilization are critical when a bird takes to the air, while increased visual and cerebellar activity reflects the importance of integrating multimodal sensory information for flight-related movements. A derived cerebellar capability likely arose at the base of maniraptoran dinosaurs, where volumetric expansion and possible folding directly preceded paravian flight. These data represent an important step toward establishing how the brain of modern birds supports their unique behavioural repertoire and provide novel insights into the neurobiology of the bird-like dinosaurs that first achieved powered flight.
Ecological generalism and physiology mediate fish biogeographic ranges under ocean warming
Authors: Hayes Chloe , Mitchell Angus , Mellin Camille , Booth David J. , Ravasi Timothy , Nagelkerken Ivan
Published: January 2024

Climate-driven species redistributions are facilitated by niche modifications that increase a species's chances of establishment in novel communities. It is well understood how range-extending species adjust individual niche traits when entering novel environments, yet whether modification of ecological niche traits collectively alters the pace of range extensions or contractions remains unknown. We quantified habitat niche, abundance, physiological performance and cellular defence/damage of range-extending coral reef fishes and coexisting local temperate fishes along a 2000 km latitudinal gradient. We also assessed their dietary and behavioural niches, and establishment potential, to understand whether ecological generalism facilitates successful range extension of coral reef fishes. The coral reef fish that increased all ecological niches, showed stronger establishment, increased physiological performance and cellular damage, but decreased cellular defence at their cold-range edge, whereas tropical species that showed unmodified ecological niches showed lower establishment. One temperate species showed decreased abundance, habitat niche width and body condition, but increased cellular defence, cellular damage and energy reserves at their warm-trailing range, while other temperate species showed contrasting responses. Therefore, ecological generalists might be more successful than ecological specialists during the initial stages of climate change, with increasing future warming strengthening this pattern by physiologically benefitting tropical generalists but disadvantaging temperate specialists.
Highly resolved genome assembly and comparative transcriptome profiling reveal genes related to developmental stages of tapeworm
Ligula intestinalis
Authors: Nazarizadeh Masoud , Nováková Milena , Drábková Marie , Catchen Julian , Olson Peter D. , Štefka Jan
Published: January 2024

Ligula intestinalis
(Cestoda: Diphyllobothriidae) is an emerging model organism for studies on parasite population biology and host–parasite interactions. However, a well-resolved genome and catalogue of its gene content has not been previously developed. Here, we present the first genome assembly of
L. intestinalis
, based on Oxford Nanopore Technologies, Illumina and Omni-C sequencing methodologies. We use transcriptome profiling to compare plerocercoid larvae and adult worms and identify differentially expressed genes (DEGs) associated with these life stages. The genome assembly is 775.3 mega (M)bp in size, with scaffold N50 value of 118 Mbp and encodes 27 256 predicted protein-coding sequences. Over 60% of the genome consists of repetitive sequences. Synteny analyses showed that the 10 largest scaffolds representing 75% of the genome display high correspondence to full chromosomes of cyclophyllidean tapeworms. Mapping RNA-seq data to the new reference genome, we identified 3922 differentially expressed genes in adults compared with plerocercoids. Gene ontology analyses revealed over-represented genes involved in reproductive development of the adult stage (e.g. sperm production) and significantly enriched DEGs associated with immune evasion of plerocercoids in their fish host. This study provides the first insights into the molecular biology of
L. intestinalis
and provides the most highly contiguous assembly to date of a diphyllobothriid tapeworm useful for population and comparative genomic investigations of parasitic flatworms.
Cleaning Up Our Disinfectants: Usage of antimicrobial biocides in direct-to-consumer products in Australia
Authors: Nunez Charles , Bamert Rebecca , Lambert Karen , Short Francesca
Published: January 2024

In supermarkets and chemists worldwide, consumers are faced with an array of antimicrobial domestic cleaning and personal hygiene products purporting to kill germs and keep people safe. Many of these proven active ingredients (biocides) encourage the development of antimicrobial resistance (AMR) in microbes and microbial populations, in turn increasing the likelihood of AMR infections. In order to understand and address the selective pressure towards AMR posed by the unrestricted use of biocides, it is necessary to understand which biocides are most frequently found in consumer products and the current regulatory framework that governs their use. In this research we survey the biocidal active ingredients in the major categories of cleaning and personal care products available from supermarkets and pharmacies in Australia, and comment on the regulations that dictate how these products are tested and marketed. Benzalkonium chloride and ethanol were the two most prevalent antimicrobial biocides in this study, while triclosan, which is banned in several jurisdictions, was found in a small number of products. In Australia, many antimicrobial consumer products are regulated for efficacy and safety under the Therapeutic Goods Act, but the potential to drive microbial adaptation and AMR is not considered. Overall this survey underscores the broad use and light regulation of antimicrobial biocides in products available to the general public in Australia, and provides an information resource to inform further research and stewardship efforts.
Evaluating the effect and mechanism of Yiqi Huayu Jiedu decoction combined with FLOT regimen neoadjuvant chemotherapy for the patients with locally advanced gastric cancer: protocol for a prospective, double-arm, randomized controlled clinical trial
Authors: Zou Kun , Zhang Pei-Chan , Luo Chun-Yang , Wang Rui , Xu Shuo , Xiang Chun-Jie , Huan Xiang-Kun , Yao Wen-Chao , Li Xiu-Yuan , Zhang Jun-Feng , Liu Shen-Lin , Wu Zhen-Feng
Published: January 2024

Background

Neoadjuvant chemotherapy plays a vital role in the treatment of advanced gastric cancer, however, optimizing its effectiveness remains an important research focus. Traditional Chinese medicine (TCM), a promising adjunctive therapy, has shown enhanced clinical outcomes when combined with postoperative adjuvant chemotherapy. Therefore, this study is designed to evaluate the clinical efficacy of Yiqi Huayu Jiedu decoction combined with neoadjuvant chemotherapy FLOT in the treatment of advanced gastric cancer.

Methods

This study is a prospective, double-arm, randomized controlled trial. It involves a total of 260 patients diagnosed with advanced gastric cancer, who will be randomly assigned to two groups - a TCM treatment group and a control group, each comprising 130 patients. All patients will receive standard FLOT chemotherapy, and patients in the TCM treatment group will additionally receive traditional Chinese medicine treatment with Yiqi Huayu Jiedu decoction. After four cycles of chemotherapy, gastric cancer D2 radical surgery will be performed. The primary objective is to evaluate the postoperative pathological response rate of the tumor. The secondary objectives include evaluating the perioperative nutritional status, the efficacy of traditional Chinese medicine syndrome, and adverse events associated with both chemotherapy and surgery.

Discussion

Currently, no trials have investigated the impact of traditional Chinese medicine in combination with neoadjuvant chemotherapy on the preoperative treatment in patients with advanced gastric cancer.

Accordingly, it is imperative to conduct this prospective study to evaluate the clinical efficacy and safety of this regimen, meanwhile providing high-level clinical evidence for traditional Chinese medicine combined with neoadjuvant chemotherapy and introducing an innovative regimen for preoperative comprehensive treatment of gastric cancer.

Trial registration

ChiCTR2300072742
Hurdles to Horizontal Gene Transfer: Synonymous variation determines antibiotic resistance phenotype across species
Authors: Finnegan Michael , Rose Caroline J , Hamet Jeanne , Prat Benjamin , Bedhomme Stéphanie
Published: January 2024

Evidence that synonymous mutations and synonymous gene variants have fitness effects have accumulated recently. Since horizontal gene transfer represents a change in the genome of expression of the transferred gene, we hypothesized that the codon usage preferences of a horizontally transferred gene could determine the conferred fitness advantage or disadvantage, condition the immediate success of the transfer and in the longer term orient transfers.

To test this hypothesis, we characterized resistance levels of synonymous variants of a gentamicin resistance gene, inserted into a broad-host range plasmid and transformed into three different bacterial speciesEscherichia coli, Acinetobacter baylyi and Pseudomonas aeruginosa.We revealed a strong species effect, explained in part by differences in plasmid copy number between host species. Importantly, the relative levels of resistance conferred by each synonymous variant were not conserved across species, indicating that these phenotypic effects are due to differing compatibility between the transferred variants and the receiver bacterial genomes. This species-variant interaction confirms that the codon composition of a gene can be a determinant of post-horizontal gene transfer success. However, the similarity in codon usage between the synonymous variants and the host genome only explained the phenotypic differences between variants in one species,P. aeruginosa. Further investigations of the effects of local codon usage, translation bottlenecks and internal Shine-Dalgarno sequences did not reveal common universal mechanisms across our three bacterial species and point to multiple paths leading from the synonymous sequence to phenotype and a species-specific sensitivity to these different paths.
The MKK3 MAPK cascade integrates temperature and after-ripening signals to modulate seed germination
Authors: Otani Masahiko , Tojo Ryo , Regnard Sarah , Zheng Lipeng , Hoshi Takumi , Ohmori Suzuha , Tachibana Natsuki , Sano Tomohiro , Koshimizu Shizuka , Ichimura Kazuya , Colcombet Jean , Kawakami Naoto
Published: January 2024

Temperature is a major environmental cue for seed germination. The permissive temperature range for germination is narrow in dormant seeds and expands during after-ripening. Quantitative trait loci analyses of pre-harvest sprouting in cereals have revealed that MKK3, a mitogen-activated protein kinase (MAPK) cascade protein, is a negative regulator of grain dormancy. Here we show that the MAPKKK19/20-MKK3-MPK1/2/7/14 cascade modulates germination temperature range in Arabidopsis seeds by elevating germinability of the seeds at sub- and supra-optimal temperatures. The expression ofMAPKKK19andMAPKKK20is regulated by an unidentified temperature sensing and signaling mechanism the sensitivity of which is modulated during after-ripening of the seeds, and MPK7 is activated at the permissive temperature for germination regulated by expression levels ofMAPKKK19/20. Activation of the MKK3 cascade represses abscisic acid (ABA) biosynthesis enzyme gene expression, and induces expression of ABA catabolic enzyme and gibberellic acid biosynthesis enzyme genes, resulting in expansion of the germinable temperature range. Our data demonstrate that the MKK3 cascade integrates temperature and after-ripening signals to germination processes including phytohormone metabolism.
PTF-Vāc:Ab-initiodiscovery of plant transcription factors binding sites using explainable and generative deep co-learning encoders-decoders
Authors: Gupta Sagar , Jyoti  , Bhati Umesh , Kesarwani Veerbhan , Sharma Akanksha , Shankar Ravi
Published: January 2024

Discovery of transcription factors (TFs) binding sites (TFBS) and their motifs in plants pose significant challenges due to high cross-species variability. The interaction between TFs and their binding sites is highly specific and context dependent. Most of the existing TFBS finding tools are not accurate enough to discover these binding sites in plants. They fail to capture the cross-species variability, interdependence between TF structure and its TFBS, and context specificity of binding. Since they are coupled to predefined TF specific model/matrix, they are highly vulnerable towards the volume and quality of data provided to build the motifs. All these software make a presumption that the user input would be specific to any particular TF which renders them of very limited uses. This all makes them hardly of any use for purposes like genomic annotations of newly sequenced species. Here, we report an explainable Deep Encoders-Decoders generative system, PTF-Vāc, founded on a universal model of deep co-learning on variability in binding sites and TF structure, PTFSpot, making it completely free from the bottlenecks mentioned above. It has successfully decoupled the process of TFBS discovery from the prior step of motif finding and requirement of TF specific motif models. Due to the universal model for TF:DNA interactions as its guide, it can discover the binding motifs in total independence from data volume, species and TF specific models. PTF-Vāc can accurately detect even the binding motifs for never seen before TF families and species, and can be used to define credible motifs from its TFBS report.
Genetic Dynamics of Mustang and Feral Horse Populations in the Western United States
Authors: Cothran E. Gus , Khanshour Anas , Funk Stephan , Conant Eleanore , Juras Rytis , Davis Brian W.
Published: January 2024

The history and population dynamics of feral horse and wild mustang population in the Western United States has led to diverse populations of disparate ancestry. These iconic populations are currently managed by the Bureau of Land Management (BLM) and their genetic history is of great interest for both management and conservation purposes. We examined population genetic parameters using 12 well established microsatellite loci in nearly 8,500 horses representing 235 populations sampled across more than 20 years. Samples were collected by BLM or by members of other management agencies from 10 states. Genetic variability and genetic resemblance to domestic horse breeds using multiple methods were estimated. A wide range of variation levels were observed across the populations. In general, within-population variability was slightly lower than what has been found in domestic horse breeds, but still retains diversity. As expected, levels of population variation correlated to census size. Several populations were sampled longitudinally with intervals between sampling of about 5 years. For these longitudinal samples, there was no trend towards an increase or decline in diversity, indicating consistent management practices. Relationships between populations and domestic breeds ranged from close association to one or two specific breeds to extreme divergence of the feral horses to all breeds examined. Reasons for divergence are mainly related to the founding of the population and subsequent demographic history. Overall, there was a slight tendency for geographically close feral populations to be more similar to each other than to more distant populations. The results of this study show the feral horse populations in the western US have a considerable variation, though management practices can strongly influence variability levels.
Predicting protein functions using positive-unlabeled ranking with ontology-based priors
Authors: Zhapa-Camacho Fernando , Tang Zhenwei , Kulmanov Maxat , Hoehndorf Robert
Published: January 2024

Automated protein function prediction is a crucial and widely studied problem in bioinformatics. Computationally, protein function is a multilabel classification problem where only positive samples are defined and there is a large number of unlabeled annotations. Most existing methods rely on the assumption that the unlabeled set of protein function annotations are negatives, inducing thefalse negativeissue, where potential positive samples are trained as negatives. We introduce a novel approach named PU-GO, wherein we address function prediction as a positive-unlabeled ranking problem. We apply empirical risk minimization, i.e., we minimize the classification risk of a classifier where class priors are obtained from the Gene Ontology hierarchical structure. We show that our approach is more robust than other state-of-the-art methods on similarity-based and time-based benchmark datasets. Data and code are available athttps://github.com/bio-ontology-research-group/PU-GO.
Mitochondrial DNA analysis in ayu (Plecoglossus altivelis) raises a urgent conservation need for its southernmost population
Authors: Ha Linh Manh , Tran Hau Duc , Takeshima Hirohiko , Iguchi Kei’ichiro
Published: January 2024

The central-marginal hypothesis predicts that genetic diversity decreases and genetic differentiation increases toward the species distribution margin. We analyzed the mitochondrial DNA control region of ayu (Plecoglossus altivelis) collected from different localities, including central and marginal populations, to test the hypothesis. The results show that the ayu populations at southern marginal habitats (Tien Yen River in Vietnam and Yakugachi River in Amami-oshima Island) displayed low genetic diversity (Haplotype diversity,H= 0.52 and 0.67; Nucleotide diversity,Pi= 0.01 and 0.006, respectively) and significantly differed from the central populations (p< 0.001), consistent with the central-marginal hypothesis. However, ayu populations at the center of their distribution range (Shinano River in Honsyu and Hamoji River in Sado Island) and the northern marginal habitats (Yoichi River in Hokkaido and Aonae River in Okushiri Island) exhibited high genetic diversity (H= 1 for all rivers;Pi= 0.024–0.029). The genetic differences between the populations at the center and the northern marginal habitats were insignificant (p> 0.05). This study showed that in ayu, the central-marginal hypothesis is valid in the southern direction but not in the northern direction. Urgent conservation is needed for the genetically distinct population in the degraded southern habitat with severely low genetic diversity.
The impact of ligand-induced oligomer dissociation on enzyme diffusion, directly observed at the single-molecule level
Authors: Yancheva Yulia D. , Kaya Saniye G. , Belyy Alexander , Fraaije Marco W. , Tych Katarzyna M.
Published: January 2024

The existence of the phenomenon of enhanced enzyme diffusion (EED) has been a topic of debate in recent literature. One proposed mechanism to explain the origin of EED is oligomeric enzyme dissociation. We use mass photometry (MP), a label-free single-molecule technique, to investigate the dependence of the oligomeric states of several enzymes on their ligands. The studied enzymes of interest are catalase, aldolase, alkaline phosphatase and vanillyl-alcohol oxidase (VAO). We compared the ratios of oligomeric states in the presence and absence of substrate as well as different substrate and inhibitor concentrations. Catalase and aldolase were found to dissociate into smaller oligomers in the presence of their substrates, independently of inhibition, while for alkaline phosphatase and VAO, different behaviors were observed. Thus, we have identified a possible mechanism which explains the previously observed diffusion enhancementin vitro. This enhancement may occur due to the dissociation of oligomers through ligand binding.
Possible roles of phytochemicals with bioactive properties in the prevention of and recovery from COVID-19
Authors: Koyama Sachiko , Shields Vonnie D.C. , Heinbockel Thomas , Joseph Paule V. , Adhikari Poonam , Kaur Rishemjit , Kumar Ritesh , Alizadeh Rafieh , Bhutani Surabhi , Calcinoni Orietta , Mucignat-Caretta Carla , Chen Jingguo , Cooper Keiland W. , Das Subha R. , Domínguez Paloma Rohlfs , Guàrdia Maria Dolors , Klyuchnikova Maria A. , Laktionova Tatiana K. , Mori Eri , Namjoo Zeinab , Nguyen Ha , Özdener Mehmet Hakan , Parsa Shima , Poyraz Elif Özdener , Strub Daniel Jan , Taghizadeh-Hesary Farzad , Ueha Rumi , Voznessenskaya Vera V.
Published: January 2024

Purpose

There have been large geographical differences in the infection and death rates of COVID-19. Foods and beverages containing high amounts of phytochemicals with bioactive properties were suggested to prevent contracting, to limit the severity of, and to facilitate recovery from COVID-19. The goal of our study was to determine the correlation of the type of foods/beverages people consumed and the risk reduction of contracting COVID-19 and the recovery from COVID-19.

Methods

We developed an online survey that asked the participants whether they contracted COVID-19, their symptoms, time to recover, and their frequency of eating various types of foods/beverages. The survey was first developed in English and then translated into 10 different languages.

Results

The participants who did not contract COVID-19 consumed vegetables, herbs/spices, and fermented foods/beverages significantly more than the participants who contracted COVID-19 and those who were not tested but became sick most likely from COVID-19. The geographic location of participants corresponded with the language of the survey, except for the English version, thus, nine out of the 10 language versions represented a country. Among the six countries (India, Iran, Italy, Japan, Russia, Spain) with over one hundred participants, we found that in India and Japan the people who contracted COVID-19 showed significantly shorter recovery time, and greater daily intake of vegetables, herbs/spices, and fermented foods/beverages was associated with faster recovery.

Conclusion

Our results suggest that phytochemical compounds included in the vegetables may have contributed in not only preventing contraction of COVID-19, but also accelerating their recovery. (249 words; EJN limit is 250 words)