bluuebunny/crossref_metadata_2025_split huggingface dataset:
Laser treatment for genitourinary syndrome of menopause
Authors: Phillips Christian , Hillard Timothy , Salvatore Stefano , Cardozo Linda , Toozs‐Hobson Philip ,   the Royal College of Obstetricians and Gynaecologists
Published: July 2022

Plain language summaryGenitourinary syndrome of menopause (GSM) is the term used to describe the group of symptoms including vaginal pain, vaginal dryness, itching, pain during sexual intercourse and fragile vaginal tissues as well as urinary symptoms including urinary frequency, urgency, incontinence, blood in the urine (haematuria) and recurrent urinary tract infections that occur due to a lack of the hormone estrogen.These symptoms can have a significant negative impact on psychosexual issues, sexual function and quality of life in postmenopausal women. Traditionally women have been treated with vaginal lubricants, vaginal moisturisers or low‐dose vaginal estrogens.Lasers have been used in the cosmetic industry for collagen remodelling and repair of the skin. Therefore, it has been suggested that laser therapy may be used on the vagina as an alternative treatment for GSM. A review of all the published studies assessing the safety and efficacy of laser therapy for GSM have shown promising beneficial results. The majority of studies to date have been small, short‐term, observational studies. However, there are randomised controlled trials underway. Laser treatment may be beneficial for the symptoms of GSM but until more robust evidence is available it should not be adopted into widespread practice, and should be used as part of a research study only.
“Statisticians are Particularly Attuned to the Beauty of Uncertainty”
Authors: Britten Anna 
Published: July 2022

Abstract
Data visualisation fans will need no introduction to David McCandless, data journalist and author of the bestselling books Information is Beautiful and Knowledge is Beautiful as well as, most recently, Beautiful News. He is also one of the media's most called-upon advocates for statistics as art, and tells Anna Britten about his process, data viz heroes and why communication is all about context
Thoracic myopericytoma in an older adult, rare but possible: A case report
Authors: Nigro Maria Concetta , Pirini Maria Giulia , Garelli Elena , Marchi Marina , Musto Alessandra , Pantaleo Maria Abbondanza , Solli Piergiorgio , Ardizzoni Andrea , Nannini Margherita 
Published: July 2022

AbstractMyopericytoma is a rare tumor generally arising from skin and soft tissues of extremities, trunk, head, and neck regions, rarely from visceral sites. An intrathoracic visceral localization may carry a broad differential diagnosis including primary lung, pleura and chest wall lesions, or metastatic lesions. To date, any radiological features have been recognized and diagnosis of myopericytoma with intrathoracic localization remains still challenging. Here, we describe the case of a subpleural lesion incidentally diagnosed in an older adult affected by gastric cancer. Radiological features did not allow a differential diagnosis between a benign lesion, a primary tumor, or a metastasis. After resection, the histological examination showed histopathological features congruent with the diagnosis of myopericytoma. This unusual presentation reflects the need to share clinical, radiological, and histopathological data about this uncommon but frequently misdiagnosed disease.
Immunomodulation by foods and microbes: Unravelling the molecular tango
Authors: Forde Brian , Yao Lu , Shaha Rupin , Murphy Sally , Lunjani Nonhlanhla , O'Mahony Liam 
Published: July 2022

AbstractMetabolic health and immune function are intimately connected via diet and the microbiota. Nearly 90% of all immune cells in the body are associated with the gastrointestinal tract and these immune cells are continuously exposed to a wide range of microbes and microbial‐derived compounds, with important systemic ramifications. Microbial dysbiosis has consistently been observed in patients with atopic dermatitis, food allergy and asthma and the molecular mechanisms linking changes in microbial populations with disease risk and disease endotypes are being intensively investigated. The discovery of novel bacterial metabolites that impact immune function is at the forefront of host‐microbe research. Co‐evolution of microbial communities within their hosts has resulted in intertwined metabolic pathways that affect physiological and pathological processes. However, recent dietary and lifestyle changes are thought to negatively influence interactions between microbes and their host. This review provides an overview of some of the critical metabolite‐receptor interactions that have been recently described, which may underpin the immunomodulatory effects of the microbiota, and are of relevance for allergy, asthma and infectious diseases.
Extracellular vesicles and microRNAs are altered in response to exercise, insulin sensitivity and overweight
Authors: Doncheva Atanaska Ivanova , Romero Silvana , Ramirez‐Garrastacho Manuel , Lee Sindre , Kolnes Kristoffer J. , Tangen Daniel Steensen , Olsen Thomas , Drevon Christian A. , Llorente Alicia , Dalen Knut Tomas , Hjorth Marit 
Published: July 2022

AbstractExtracellular vesicles induced by exercise have emerged as potential mediators of tissue crosstalk. Extracellular vesicles and their cargo miRNAs have been linked to dysglycemia and obesity in animal models, but their role in humans is unclear.AimThe aim of the study was to characterize the miRNA content in plasma extracellular vesicle isolates after acute and long‐term exercise and to study associations between extracellular vesicle miRNAs, mRNA expression in skeletal muscle and adipose tissue, and cardiometabolic risk factors.MethodsSedentary men with or without dysglycemia and overweight underwent an acute bicycle test and a 12‐week exercise intervention with extensive metabolic phenotyping. Gene expression in m. vastus lateralis and subcutaneous adipose tissue was measured with RNA sequencing. Extracellular vesicles were purified from plasma with membrane affinity columns or size exclusion chromatography.ResultsExtracellular vesicle miRNA profiling revealed a transient increase in the number of miRNAs after acute exercise. We identified miRNAs, such as miR‐652‐3p, that were associated to insulin sensitivity and adiposity. By performing explorative association analyses, we identified two miRNAs, miR‐32‐5p and miR‐339‐3p, that were strongly correlated to an adipose tissue macrophage signature.ConclusionNumerous miRNAs in plasma extracellular vesicle isolates were increased by exercise, and several miRNAs correlated to insulin sensitivity and adiposity. Our findings warrant future studies to characterize exercise‐induced extracellular vesicles and cargo miRNA to clarify where exercise‐induced extracellular vesicles originate from, and to determine whether they influence metabolic health or exercise adaptation.
Dose escalations in phase I studies: Feasibility of interpreting blinded pharmacodynamic data
Authors: Hassing Gerardus J. , van Esdonk Michiel J. , van Westen Gerard J. P. , Cohen Adam F. , Burggraaf Jacobus , Gal Pim 
Published: July 2022

AimsDuring phase I study conduct, blinded data are reviewed to predict the safety of increasing the dose level. The aim of the present study was to describe the probability that effects are observed in blinded evaluations of data in a simulated phase I study design.MethodsAn application was created to simulate blinded pharmacological response curves over time for 6 common safety/efficacy measurements in phase I studies for 1 or 2 cohorts (6 active, 2 placebo per cohort). Effect sizes between 0 and 3 between‐measurement standard deviations (SDs) were simulated. Each set of simulated graphs contained the individual response and mean ± SD over time. Reviewers (n = 34) reviewed a median of 100 simulated datasets and indicated whether an effect was present.ResultsIncreasing effect sizes resulted in a higher chance of the effect being identified by the blinded reviewer. On average, 6% of effect sizes of 0.5 between‐measurement SD were correctly identified, increasing to 72% in 3.0 between‐measurement SD effect sizes. In contrast, on average 92–95% of simulations with no effect were correctly identified, with little effect of between‐measurement variability in single cohort simulations. Adding a dataset of a second cohort at half the simulated dose did not appear to improve the interpretation.ConclusionOur analysis showed that effect sizes <2× the between‐measurement SD of the investigated outcome frequently go unnoticed by blinded reviewers, indicating that the weight given to these blinded analyses in current phase I practice is inappropriate and should be re‐evaluated.
Low NUDT15 expression levels due to biallelic NUDT15 variants and 6‐mercaptopurine intolerance
Authors: Yoshida Masanori , Brown Scott A. , Moriyama Takaya , Nishii Rina , Tsujimoto Shin‐ichi , Yamada Yuji , Yoshida Kaoru , Shirai Ryota , Osumi Tomoo , Utano Tomoyuki , Fukano Reiji , Kudo Ko , Sakaguchi Kimiyoshi , Arakawa Yuki , Koh Katsuyoshi , Sekiguchi Masahiro , Sekimizu Masahiro , Miyamura Takako , Ishida Hisashi , Inukai Takeshi , Tomizawa Daisuke , Kiyokawa Nobutaka , Kato Motohiro , Yang Jun J. 
Published: July 2022

Summary6‐Mercaptopurine (6‐MP) is widely used for the treatment of paediatric leukaemia and lymphoma. Recently, germline variants in the NUDT15 gene have been identified as one of the major genetic causes for 6‐MP–associated adverse effects such as myelosuppression. Patients with hypomorphic NUDT15 variants accumulate excessive levels of DNA‐incorporated thioguanine in white blood cells, resulting in severe myelosuppression. Although preclinical studies suggest that these variants may influence the protein stability of NUDT15, this has not been directly characterised in patients. In this study, we report the development of a series of novel monoclonal antibodies against NUDT15, using which we quantitatively assessed NUDT15 protein levels in 37 patients with acute lymphoblastic leukaemia treated with 6‐MP, using sandwich enzyme‐linked immunosorbent assay (ELISA). The NUDT15 genotype was highly correlated with its protein levels (p < 0.0001), with homozygous and compound heterozygous patients showing exceedingly low NUDT15 expression. There was a positive correlation between NUDT15 protein level and 6‐MP tolerance (r = 0.631, p < 0.0001). In conclusion, our results point to low NUDT15 protein abundance as the biochemical basis for NUDT15‐mediated 6‐MP intolerance, thus providing a phenotypic readout of inherited NUDT15 deficiency.
HINT1 neuropathy: Expanding the genotype and phenotype spectrum
Authors: Morel Victor , Campana‐Salort Emmanuelle , Boyer Amandine , Esselin Florence , Walther‐Louvier Ulrike , Querin Giorgia , Latour Philippe , Lia Anne‐Sophie , Magdelaine Corinne , Beze‐Beyrie Pierre , Behin Anthony , Delague Valérie , Levy Nicolas , Stojkovic Tanya , Attarian Shahram , Bonello‐Palot Nathalie 
Published: July 2022

AbstractInherited peripheral neuropathy (IPN) is a heterogeneous group of disorders due to pathogenic variation in more than 100 genes. In 2012, the first cases of IPN associated with HINT1 pathogenic variations were described in 33 families sharing the same phenotype characterized by an axonal neuropathy with neuromyotonia and autosomal recessive inheritance (NMAN: OMIM #137200). Histidine Triad Nucleotide Binding Protein 1 regulates transcription, cell‐cycle control, and is possibly involved in neuropsychiatric pathophysiology. Herein, we report seven French patients with NMAN identified by Next Generation Sequencing. We conducted a literature review and compared phenotypic and genotypic features with our cohort. We identified a new HINT1 pathogenic variation involved in NMAN: c.310G>C p.(Gly104Arg). This cohort is comparable with literature data regarding age of onset (7,4yo), neuronal involvement (sensorimotor 3/7 and motor pure 4/7), and skeletal abnormalities (scoliosis 3/7, feet anomalies 6/7). We expand the phenotypic spectrum of HINT1‐related neuropathy by describing neurodevelopmental or psychiatric features in six out of seven individuals such as generalized anxiety disorder (GAD), obsessive–compulsive disorder (OCD), mood disorder and attention deficit hyperactivity disorder (ADHD). However, only 3/128 previously described patients had neuropsychiatric symptomatology or neurodevelopmental disorder. These features could be part of HINT1‐related disease, and we should further study the clinical phenotype of the patients.
Determining a dosage threshold of drink‐driving enforcement operations: A systematic review
Authors: O'Hara Sharon E. , Paschall Mallie J. , Herd Denise A. 
Published: July 2022

AbstractIssuesPolicy enforcement is crucial to achieve impacts on alcohol‐related harm. It is not clear what level of enforcement intensity or ‘dosage’ is necessary for addressing drink driving and related harms. Given competing enforcement demands and agencies' resource constraints, understanding how much enforcement is sufficient to deter drink driving is critical.ApproachThis systematic literature review followed Preferred Reporting Items for Systematic Review and Meta‐Analysis Protocols (PRISMA) guidelines to examine research about dosage effects of enforcement and related visibility on drink‐driving outcomes, including motor vehicle crashes and fatalities. Risk of bias was assessed using the Cochrane Collaboration Effective Practice and Organization of Care tool and the JBI checklist.Key FindingsThe 21 studies that met the inclusion criteria for this review differed in measures of enforcement dosage and outcomes, making it difficult to synthesise results across studies and draw conclusions about a threshold or optimal level of enforcement. Although most included studies found that sustained enforcement was associated with reductions in drink driving or related harms, only two studies tested an optimal dosage. Due to study design limitations, a substantial percentage of these studies must be considered with caution.ImplicationsAdditional research with rigorous study designs with appropriate controls is needed to determine an optimal high visibility enforcement dosage level to help law enforcement agencies make realistic decisions about allocating enforcement resources to address drink driving.ConclusionConsistent evidence about a drink‐driving enforcement dosage threshold is lacking, partly due to an insufficient number of well‐designed studies. Addressing challenges of conducting rigorous studies in community settings is crucial.
Floristic homogenization as a result of the introduction of exotic species in China
Authors: Qian Hong , Qian Shenhua 
Published: July 2022

AbstractAimThe introduction of exotic plants can both increase (homogenize) and decrease (differentiate) floristic similarity between areas. We have a poor understanding of the degree to which plant species introductions tend to homogenize or differentiate floras, and relevant studies covering large spatial extent are scarce. China has been heavily invaded by exotic plants. Here, we analyse a comprehensive dataset of vascular plants to determine whether the introduction of exotic plant species has homogenized or differentiated species composition in regions across China.LocationChina.MethodsWe calculated the Jaccard index and Simpson index of similarity for each pair of province‐level regions for native and exotic species separately and jointly, and calculated a homogenization index for each pair of regional floras. We correlated species richness of native and exotic plants to climatic factors, and correlated the Jaccard index and Simpson index to geographic and climatic distances. We used variation partitioning analysis to determine the relative importance of geographic and climatic distances on species turnover. We also examined the effect of human population density on florisitic similarity of exotic species.ResultsWe found that the geographic range of each species was, on average, larger for exotics than for natives; floristic similarity between regions was greater for exotics than for natives; the vast majority of pairwise regional floras have been homogenized; the introduction of exotic species has caused stronger biotic homogenization for pairwise floras with greater dissimilarity in their species composition; geographic distributions of exotic and native species were determined by different sets of climatic factors; and distributions of exotic species were determined by climatic factors more strongly, compared to those of native species. Human population density had a moderate effect on florisitic similarity of exotic species.Main conclusionsThe introduction of exotic plant species has homogenized regional floras across China. Because strong international trades between China and other countries and dramatic development of transportation systems are continuing in China, which help spread of exotic species, we predict that exotic species will continue to spread and will strengthen biotic homogenization in China.
Sulfur cycling at natural hydrocarbon and sulfur seeps in Santa Paula Creek, CA
Authors: Aronson Heidi S. , Monteverde Danielle R. , Barnes Ben Davis , Johnson Brooke R. , Zawaski Mike J. , Speth Daan R. , Wang Xingchen Tony , Wu Fenfang , Webb Samuel M. , Trower Elizabeth J. , Magyar John S. , Sessions Alex L. , Orphan Victoria J. ,   Geobiology Course 2017,   Geobiology Course 2018, Fischer Woodward W. 
Published: July 2022

AbstractBiogeochemical cycling of sulfur is relatively understudied in terrestrial environments compared to marine environments. However, the comparative ease of access, observation, and sampling of terrestrial settings can expand our understanding of organisms and processes important in the modern sulfur cycle. Furthermore, these sites may allow for the discovery of useful process analogs for ancient sulfur‐metabolizing microbial communities at times in Earth's past when atmospheric O2 concentrations were lower and sulfide was more prevalent in Earth surface environments. We identified a new site at Santa Paula Creek (SPC) in Ventura County, CA—a remarkable freshwater, gravel‐bedded mountain stream charged with a range of oxidized and reduced sulfur species and heavy hydrocarbons from the emergence of subsurface fluids within the underlying sulfur‐ and organic‐rich Miocene‐age Monterey Formation. SPC hosts a suite of morphologically distinct microbial biofacies that form in association with the naturally occurring hydrocarbon seeps and sulfur springs. We characterized the geology, stream geochemistry, and microbial facies and diversity of the Santa Paula Creek ecosystem. Using geochemical analyses and 16S rRNA gene sequencing, we found that SPC supports a dynamic sulfur cycle that is largely driven by sulfide‐oxidizing microbial taxa, with contributions from smaller populations of sulfate‐reducing and sulfur‐disproportionating taxa. This preliminary characterization of SPC revealed an intriguing site in which to study geological and geochemical controls on microbial community composition and to expand our understanding of sulfur cycling in terrestrial environments.
Antibacterial activity and mechanism of ginger extract against Ralstonia solanacearum
Authors: Zhang Lingling , Qin Manli , Yin Junliang , Liu Xuli , Zhou Jie , Zhu Yongxing , Liu Yiqing 
Published: July 2022

Abstract

Aims
The current study aimed to determine the chemical compositions of ginger extract (GE) and to assess the antibacterial activities of GE against the ginger bacterial wilt pathogen Ralstonia solanacearum and to screen their mechanisms of action.

Methods and Results
A total of 393 compounds were identified by using ultra-performance liquid chromatography and tandem-mass spectrometry. The antibacterial test indicated that GE had strong antibacterial activity against R. solanacearum and that the bactericidal effect exhibited a dose-dependent manner. The minimum inhibitory concentration and minimum bactericidal concentration of R. solanacearum were 3.91 and 125 mg/ml, respectively. The cell membrane permeability and integrity of R. solanacearum were destroyed by GE, resulting in cell content leakage, such as electrolytes, nucleic acids, proteins, extracellular adenosine triphosphate and exopoly saccharides. In addition, the activity of cellular succinate dehydrogenase and alkaline phosphatase of R. solanacearum decreased gradually with an increase in the GE concentration. Scanning electron microscopy analysis revealed that GE treatment changed the morphology of the R. solanacearum cells. Further experiments demonstrated that GE delayed or slowed the occurrence of bacterial wilt on ginger.

Conclusions
GE has a significant antibacterial effect on R. solanacearum, and the antibacterial effect is concentration dependent. The GE treatments changed the morphology, destroyed membrane permeability and integrity, reduced key enzyme activity and inhibit the synthesis of the virulence factor EPS of R. solanacearum. GE significantly controlled the bacterial wilt of ginger during infection.

Significance and Impact of the Study
This research provides insight into the antimicrobial mechanism of GE against R. solanacearum, which will open a new application field for GE.
An improved, simple and field-deployable CRISPR-Cas12a assay for the detection of SARS-CoV-2
Authors: Misra Chitra S. , Rangu Shyam S. , Phulsundar Ravindra D. , Bindal Gargi , Singh Mandeep , Shashidhar Ravindranath , Saha Tushar K. , Rao Akkipeddi V. S. S. N. , Rath Devashish 
Published: July 2022

Abstract

Aims
The RT-PCR is the most popular confirmatory test for SARS-CoV-2. It is sensitive, but high instrumentation cost makes it difficult for use outside routine clinical setup. This has necessitated the development of alternative methods such as CRISPR-based DETECTR method which uses lateral flow technology. Although accurate and sensitive, this method is limited by complex steps and recurrent cost of high-quality lateral flow strips. The main goal of this study was to improve the Cas12a-based SARS-CoV-2 DETECTR method and develop a portable and field-deployable system to reduce the recurring consumable cost.

Methods and results
Specific regions of N and E genes from SARS-CoV-2 virus and human RNase P (internal control) were reverse transcribed (RT) and amplified by loop-mediated isothermal amplification (LAMP). The amplified products were detected by a Cas12a-based trans-cleavage reaction that generated a fluorescent signal which could be easily visualized by naked eye. Detection of internal control, RNase P gene was improved and optimized by redesigning RT-LAMP primers. A number of steps were reduced by combining the reagents related to the detection of Cas12a trans-cleavage reaction into a single ready-to-use mix. A portable, cost-effective battery-operated instrument, CRISPR-CUBE was developed to run the assay and visualize the outcome. The method and instrument were validated using both contrived and patient samples.

Conclusions
The simplified CRISPR-based SARS-CoV-2 detection and instrument developed in this study, along with improved design for internal control detection allows for easier, more definitive viral detection requiring only reagents, consumables and the battery operable CRISPR-CUBE.

Significance and impact of study
Significant improvement in Cas12 method, coupled with simple visualization of end point makes the method and instrument deployable at the point-of-care (POC) for SARS-CoV-2 detection, without any recurrent cost for the lateral flow strips which is used in other POC methods.