bluuebunny/crossref_metadata_2025_split huggingface dataset:
Perspectives of pharmacy employees on an inappropriate use of antimicrobials in Kathmandu, Nepal
Authors: Shrestha Nistha , Manandhar Sulochana , Maharjan Nhukesh , Twati Devina , Dongol Sabina , Basnyat Buddha , Baker Stephen , Karkey Abhilasha 
Published: August 2022

AbstractBackgroundUnregulated antimicrobial use is common in both hospital and community settings of low- and middle-income countries (LMICs). However, discrete data regarding the use/misuse of antimicrobials at pharmacies in LMICs are limited. This study was conducted to understand the knowledge, attitude, and practice of pharmacy employees on antimicrobial dispensing in Nepal.MethodsWe conducted a cross-sectional survey using a structured questionnaire on 801 pharmacy employees working in community and hospital pharmacies located in Lalitpur metropolitan city (LMC) of Kathmandu, Nepal between April 2017 and March 2019.ResultsNot all respondents replied to all questions asked. A majority (92%, 738/801) of respondents agreed that the demand for non-prescription antimicrobials was common. Sixty nine percent (437/635) of participants responded that they would ask of prescription before dispensing. Suspected respiratory tract infection was the most common reason demanding for non-prescription antimicrobials, identified by 68% (535/792) of respondents. Azithromycin was the most commonly prescribed and sold antimicrobials, as reported by 46%, (361/787) and 48% (377/779) of participants respectively. A majority (87%; 696/800) of respondents agreed on antimicrobial resistance (AMR) to be a global public health threat; 54% (429/796) perceived antimicrobial misuse to be an important driver of AMR, while only 39% (315/801) replied that judicious dispensing of antimicrobials can help curb AMR.ConclusionOur study revealed that the unfounded dispensing and use of antimicrobials is prevalent among pharmacies in Kathmandu, Nepal. This overreliance on antimicrobials, notably azithromycin, may escalated the burden of AMR. We identified several drivers of inappropriate antimicrobial dispensing practice in pharmacies, which will aid public health authorities in addressing these issues. Further studies considering the role of other stakeholders, such as physicians, veterinarians, general public, and policy makers are required to obtain a more holistic perspectives on the practices of antimicrobial use so to curb the extant AMR crisis.
Lipid metabolism dysfunction following symbiont elimination is linked to altered Kennedy pathway homeostasis
Authors: Attardo Geoffrey M. , Benoit Joshua B. , Michalkova Veronika , Kondragunta Alekhya , Baumann Aaron A. , Weiss Brian L. , Malacrida Anna , Scolari Francesca , Aksoy Serap 
Published: August 2022

AbstractLipid metabolism is critical for insect reproduction, especially for species that invest heavily into early developmental stages of their offspring. The role of symbiotic bacteria during this process is unknown but likely essential, especially in the case of obligate microbes that fulfill key biological functions in the host. Using a combined lipidomics, functional genomics and biochemical strategy, we examined the role of lipid metabolism in the interaction between the viviparous tsetse fly (Glossina morsitans morsitans) and its obligate endosymbiotic bacteria (Wigglesworthia glossinidia) during tsetse pregnancy. We observed increasedCTP:phosphocholine cytidylyltransferase(cct1) expression during pregnancy. This gene codes for the enzyme that functions as the rate limiting step in phosphatidylcholine biosynthesis in the Kennedy pathway which is critical for stored lipid metabolism and progeny development. Experimental removal ofWigglesworthiaimpaired lipid metabolism via disruption of the Kennedy pathway, yielding obese mothers whose developing progeny ultimately starve. Functional validation via experimentalcct1suppression revealed a phenotype similar to females lacking obligateWigglesworthiasymbionts. These results indicate that, inGlossina, symbiont-derived factors, likely B vitamins, are critical for proper function of both lipid biosynthesis and lipolysis. Loss of the symbiosis has a dramatic impact onGlossinafecundity, and may be broadly applicable to other insect systems, particularly to species that require symbiotic partners to maximize lipolysis and reproductive output.
DeDoc2 identifies and characterizes the hierarchy and dynamics of chromatin TAD-like domains in the single cells
Authors: Li Angsheng , Zeng Guangjie , Wang Haoyu , Li Xiao , Zhang Zhihua 
Published: August 2022

AbstractTopologically associating domains (TAD) are functional chromatin units with hierarchical structure. However, the existence, prevalence and dynamics of such hierarchy in single cells remain unexplored. Here, we report a new generation TAD-like domain (TLD) detection algorithm, named deDoc2, to decode the hierarchy of TLDs in single cells. With dynamic programming, deDoc2 seeks genome partitions with global minimal structure entropy for both whole and local contact matrix. Compared to state-of-the-art tools, deDoc2 can uniquely identify the hierarchy of TLDs in single cells, in addition to outperforming its competitors. By applying deDoc2, we showed that the hierarchy of TLDs in single cells is highly dynamic during cell cycle, as well as among human brain cortex cells, and that it is associated with cellular identity and functions. Thus, our results demonstrated the abundance of information potentially encoded by TLD hierarchy for functional regulation. The deDoc2 can be freely accessed at https://github.com/zengguangjie/deDoc2.
Synthetic fibrous hydrogels as a platform to decipher cell-matrix mechanical interactions
Authors: Yuan Hongbo , Liu Kaizheng , Cóndor Mar , Barrasa-Fano Jorge , Louis Boris , Vandaele Johannes , de Almeida Paula , Coucke Quinten , Chen Wen , Oosterwijk Egbert , Xing Chenfen , Van Oosterwyck Hans , Kouwer Paul H. J. , Rocha Susana 
Published: August 2022

AbstractThe interactions between cells and their direct environment are crucial for cell fate but biochemically and mechanically highly complex, and therefore, poorly understood. Despite recent advances that exposed the impact of a range of different factors, real progress remains challenging, since appropriate controllable matrices and quantitative analysis techniques that cover a range of time and length scales are unavailable. Here, we use a synthetic fibrous hydrogel with nonlinear mechanics to mimic and tailor the bi-directional cell-matrix interactions. Using advanced microscopy-based approaches, we acquire a comprehensive picture of how cellular traction forces, fiber remodeling, matrix stiffening, matrix properties and cellular behavior interact, highlighting for instance, the importance of a fibrous architecture and nonlinear mechanics of the matrix. Complete mapping of cell-matrix interactions at the cellular length scale provides indispensable information for the rational design of biomimetic materials to recreate realistic in vitro cell environments.
Context-Aware Technology Mapping in Genetic Design Automation
Authors: Engelmann Nicolai , Schwarz Tobias , Kubaczka Erik , Hochberger Christian , Koeppl Heinz 
Published: August 2022

AbstractGenetic design automation (GDA) tools hold promise to speed-up circuit design in synthetic biology. Their wide-spread adoption is hampered by their limited predictive power, resulting in frequent deviations between in-silico and in-vivo performance of a genetic circuit. Context-effects, i.e., the change in overall circuit functioning, due to the intracellular environment of the host and due to cross-talk among circuits components are believed to be a major source for the aforementioned deviations. Incorporating these effects in computational models of GDA tools is challenging but is expected to boost their predictive power, and hence, their deployment. Using fine-grained thermodynamic models of promoter activity we show in this work, how to account for two major components of cellular context effects: (i) Crosstalk due to limited specificity of used regulators and (ii) titration of circuit regulators to off-target binding sites on the host genome. We show, how we can compensate the incurred increase in computational complexity through dedicated branch-and-bound techniques during the technology mapping process. Using the synthesis of several combinational logic circuits based on Cello’s device library as a case study, we analyze the effect of different intensities and distributions of crosstalk on circuit performance and on the usability of a given device library.
Identifying climatic drivers of hybridization in Heuchereae (Saxifragaceae)
Authors: Folk R.A. , Gaynor M.L. , Engle-Wrye N.J. , O’Meara B.C. , Soltis P.S. , Soltis D.E. , Guralnick R.P. , Smith S.A. , Grady C.J. , Okuyama Y. 
Published: August 2022

AbstractApplications of molecular phylogenetic approaches have uncovered evidence of hybridization across numerous clades of life, yet the environmental factors responsible for driving opportunities for hybridization remain obscure. Verbal models implicating geographic range shifts that brought species together during the Pleistocene have often been invoked, but quantitative tests using paleoclimatic data are needed to validate these models. Here, we produce a phylogeny for Heuchereae, a clade of 15 genera and 83 species in Saxifragaceae, with complete sampling of recognized species, using 277 nuclear loci and nearly complete chloroplast genomes. We then employ an improved framework with a coalescent simulation approach to test and ultimately confirm previous hybridization hypotheses and identify one new intergeneric hybridization event. Focusing on the North American distribution of Heuchereae, we introduce and implement a newly developed approach to reconstruct potential past distributions for ancestral lineages across all species in the clade and across a paleoclimatic record extending from the late Pliocene. Time calibration based on both nuclear and chloroplast trees recovers a mid- to late-Pleistocene date for most inferred hybridization events, a timeframe concomitant with repeated geographic range restriction into overlapping refugia. Our results indicate an important role for past episodes of climate change, and the contrasting responses of species with differing ecological strategies, in generating novel patterns of range contact among plant communities and therefore new opportunities for hybridization.
La révolution de l’ADN: biocompatible and biosafe DNA data storage
Authors: Maes Alexandre , Le Peillet Jeanne , Julienne Achille , Blachon Clémence , Cornille Nicolas , Gibier Mariette , Arwani Erfane , Xu Zhou , Crozet Pierre , Lemaire Stéphane D. 
Published: August 2022

AbstractDNA data storage is an emerging technology that has the potential to replace bulky, fragile and energy-intensive current digital data storage media. Here, we report a storage strategy called DNA Drive, that organizes data on long double stranded replicative DNA molecules. The DNA Drive has unlimited storage capacity, and its encoding scheme ensures the biosafety of the process by limiting the potential of the DNA sequence to code for mRNA and proteins. Using our approach, we encoded two historical texts from the French Revolution, the Declaration of the Rights of Man and of the Citizen of 1789 and the Declaration of the Rights of Woman and of the Female Citizen published in 1791. In contrast to previous DNA storage strategies, the biocompatibility of the DNA Drive enables biological manipulation of the data including low cost copy.One-Sentence SummaryThe DNA Drive is a biosafe and biocompatible DNA data storage strategy with unlimited storage capacity.
Full structure/function analysis of all the pilin subunits in a type 4 pilus: a complex of minor pilins in Streptococcus sanguinis mediates binding to glycans
Authors: Shahin Meriam , Sheppard Devon , Raynaud Claire , Berry Jamie-Lee , Gurung Ishwori , Silva Lisete M. , Feizi Ten , Liu Yan , Pelicic Vladimir 
Published: August 2022

AbstractType 4 filaments (T4F) – of which type 4 pili (T4P) are the archetype – are a superfamily of filamentous nanomachines nearly ubiquitous in prokaryotes. T4F are polymers of one major pilin that also contain minor pilins whose roles are often poorly understood. Here, we complete the structure/function analysis of the full set of T4P pilins in the opportunistic pathogen Streptococcus sanguinis. We determined the structure of the minor pilin PilA, which is unexpectedly similar to one of the subunits of a tip-located complex of four minor pilins, widely conserved in T4F. We found that PilA interacts and dramatically stabilises the minor pilin PilC. We determined the structure of PilC, showing that it is a modular pilin with a lectin module binding a specific subset of glycans prevalent in the human glycome, the host of S. sanguinis. Altogether, our findings support a model whereby the minor pilins in S. sanguinis T4P form a tip-located complex promoting adhesion to various host receptors. Our findings have general implications for a group of minor pilins widely conserved in T4F.
Characterization of a novel estrogen- and progesterone-responsive endometrial cancer cell line: HCI-EC-23
Authors: Rush Craig M. , Blanchard Zannel , Polaski Jacob T. , Osborne Kyle S. , Osby Krystle , Vahrenkamp Jeffery M. , Yang Chieh-Hsiang , Lum David H. , Hagan Christy R. , Leslie Kimberly K. , Pufall Miles A. , Thiel Kristina W. , Gertz Jason 
Published: August 2022

AbstractMost endometrial cancers express the hormone receptor estrogen receptor alpha (ER) and are driven by excess estrogen signaling. However, evaluation of the estrogen response in endometrial cancer cells has been limited by the availability of hormonally responsivein vitromodels, with one cell line, Ishikawa, being used in most studies. Here, we describe a novel, adherent endometrioid endometrial cancer (EEC) cell line model, HCI-EC-23. We show that HCI-EC-23 retains ER expression and that ER functionally responds to estrogen induction over a range of passages. We also demonstrate that this cell line retains paradoxical activation of ER by tamoxifen, which is also observed in Ishikawa and is consistent with clinical data. The mutational landscape shows that HCI-EC-23 is mutated at many of the commonly altered genes in EEC, has relatively few copy-number alterations, and is microsatellite instable high (MSI-high).In vitroproliferation of HCI-EC-23 is strongly reduced upon combination estrogen and progesterone treatment. HCI-EC-23 exhibits strong estrogen dependence for tumor growthin vivoand tumor size is reduced by combination estrogen and progesterone treatment. Molecular characterization of estrogen induction in HCI-EC-23 revealed hundreds of estrogen-responsive genes that significantly overlapped with those regulated in Ishikawa. Analysis of ER genome binding identified similar patterns in HCI-EC-23 and Ishikawa, although ER exhibited more bound sites in Ishikawa. This study demonstrates that HCI-EC-23 is an estrogen- and progesterone-responsive cell line model that can be used to study the hormonal aspects of endometrial cancer.
SnFFPE-Seq: towards scalable single nucleus RNA-Seq of formalin-fixed paraffin-embedded (FFPE) tissue
Authors: Chung Hattie , Melnikov Alexandre , McCabe Cristin , Drokhlyansky Eugene , Van Wittenberghe Nicholas , Magee Emma M. , Waldman Julia , Spira Avrum , Chen Fei , Mazzilli Sarah , Rozenblatt-Rosen Orit , Regev Aviv 
Published: August 2022

AbstractProfiling cellular heterogeneity in formalin-fixed paraffin-embedded (FFPE) tissues is key to characterizing clinical specimens for biomarkers, therapeutic targets, and drug responses. Here, we optimize methods for isolating intact nuclei and single nucleus RNA-Seq from FFPE tissues in the mouse brain, and demonstrate a pilot application to a human clinical specimen of lung adenocarcinoma. Our method opens the way to broad applications of snRNA-Seq to archival tissues, including clinical samples.
Gut Microbiome Signatures of Yorkshire Terrier Enteropathy during Disease and Remission
Authors: Doulidis Pavlos G. , Galler Alexandra I. , Hausmann Bela , Berry David , Rodríguez-Rojas Alexandro , Burgener Iwan A. 
Published: August 2022

AbstractThe role of the gut microbiome in developing Inflammatory Bowel Disease (IBD) in humans and dogs has received attention in recent years. Evidence suggests that IBD is associated with alterations in gut microbial composition, but further research is needed in veterinary medicine. The impact of IBD treatment on the gut microbiome needs to be better understood, especially in a breed-specific form of IBD in Yorkshire Terriers known as Yorkshire Terrier Enteropathy (YTE). This study aimed to investigate the difference in gut microbiome composition between YTE dogs during disease and remission and healthy Yorkshire Terriers. Our results showed a significant increase in specific taxa such asClostridium sensu stricto1,Escherichia-Shigella, andStreptococcus, and a decrease inBacteroides, Prevotella, Alloprevotella, andPhascolarctobacteriumin YTE dogs compared to healthy controls. No significant difference was found between the microbiome of dogs in remission and those with active disease, suggesting that the gut microbiome is affected beyond clinical recovery.
The rate of spontaneous mutations in yeast deficient for MutSβ function
Authors: Plavskin Yevgeniy , de Biase Maria Stella , Schwarz Roland F , Siegal Mark L. 
Published: August 2022

AbstractMutations in simple sequence repeat loci underlie many inherited disorders in humans, and are increasingly recognized as important determinants of natural phenotypic variation. In eukaryotes, mutations in these sequences are primarily repaired by the MutSβ mismatch repair complex. To better understand the role of this complex in mismatch repair and the determinants of simple sequence repeat mutation predisposition, we performed mutation accumulation in yeast strains with abrogated MutSβ function. We demonstrate that mutations in simple sequence repeat loci in the absence of mismatch repair are primarily deletions. We also show that mutations accumulate at drastically different rates in short (<8 bp) and longer repeat loci. These data lend support to a model in which the mismatch repair complex is responsible for repair primarily in longer simple sequence repeats.
Extreme sensitivity of fitness to environmental conditions; lessons from #1BigBatch
Authors: Kinsler  , Schmidlin  , Newell  , Eder  , Apodaca  , Lam  , Petrov  , Geiler-Samerotte  
Published: August 2022

AbstractThe phrase “survival of the fittest” has become an iconic descriptor of how natural selection works. And yet, precisely measuring fitness, even for single-celled microbial populations growing in controlled laboratory conditions, remains a challenge. While numerous methods exist to perform these measurements, including recently developed methods utilizing DNA barcoding, all methods seem limited in their precision to differentiate strains with small fitness differences. This limit on precision is relevant in many fields, including the field of experimental evolution. In this study, we hone in on the factors that contribute to noisy fitness measurements and suggest solutions to avoid certain sources of noise. Surprisingly, even when common sources of technical noise are controlled for, we find that fitness measurements are still very noisy. Our data suggest that subtle environmental differences among replicates create substantial variation across fitness measurements. We conclude by providing best practices for obtaining precise fitness measurements and by discussing how these measurements should be interpreted given their extreme context dependence. This work was inspired by the scientific community who followed us and gave us tips as we live-tweeted a high-replicate fitness measurement experiment at #1BigBatch.
Long-term NAD+ supplementation prevents the progression of age-related hearing loss in mice
Authors: Okur Mustafa N. , Kimura Risako , Sahbaz Burcin Duan , Manor Uri , Patel Jaimin , Andrade Leo , Puligilla Kala , Croteau Deborah L. , Bohr Vilhelm A. 
Published: August 2022

ABSTRACTAge-related hearing loss (ARHL) is the most common sensory disability associated with human aging. Yet, there are no approved measures for preventing or treating this debilitating condition. With its slow progression, continuous and safe approaches are critical for ARHL treatment. Nicotinamide Riboside (NR), a NAD+ precursor, is well tolerated even for long-term use and is already shown effective in various disease models including Alzheimer’s and Parkinson’s Disease. It has also been beneficial against noise induced hearing loss and in hearing loss associated with premature aging. However, its beneficial impact on ARHL is not known. Using two different wild-type mouse strains, we show that long-term NR administration prevents the progression of ARHL. Through transcriptomic and biochemical analysis, we find that NR administration restores age-associated reduction in cochlear NAD+ levels, upregulates biological pathways associated with synaptic transmission and PPAR signaling, and reduces the number of orphan ribbon synapses between afferent auditory neurons and inner hair cells. We also find that NR targets a novel pathway of lipid droplets in the cochlea by inducing the expression of CIDEC and PLIN1 proteins that are downstream of PPAR signaling and are key for lipid droplet growth. Taken together, our results demonstrate the therapeutic potential of NR treatment for ARHL and provide novel insights into its mechanism of action.
Disclosure of Gender Identity among Transgender Individuals to Healthcare Professionals in China: An Online Cross-sectional Study
Authors: Chauma Shamen Susan , Wan Chengsong , Dong Willa , Fu Xuezhen , Tucker Joseph D , Marley Gift , Tang Weiming 
Published: August 2022

ABSTRACTPurposeCulture and stigma-relevant issues discourage transgender (TG) individuals in China from disclosing their gender identities. This limits their access to transgender competent health services. This study evaluates the factors associated with gender identity disclosure to health professionals among transgender individuals in China.MethodsA cross-sectional study was conducted in nine cities across mainland China from December 2019 to June 2020 among transgender individuals. Participants completed questions covering socio-demographic information, HIV/STI testing, sexual behaviors, and access to medical and mental health services.ResultsOverall, 277 (85.5%) out of 324 transgender individuals were eligible to participate in the study. The mean age was 29±8 years old. Among them, 78% (192/277) had ever disclosed their gender identity to others, and 56% (155/277) had disclosed their gender identity to health professionals. 79.4% had ever tested for HIV (with an HIV prevalence of 9.1%), 47.3% had tested for other STIs, 42.6% had used hormone therapy, and 9.4% had undergone gender-affirming surgery. Results from the multivariable logistic regression demonstrated that compared to non-disclosers, disclosers were more likely to have tested for STIs (aOR=1.94, 95%CI: 1.12-3.39). Hormone intervention therapy (aOR=2.81, 95%CI: 1.56-5.05) and Pre-Exposure Prophylaxis (PrEP) use (aOR= 3.51, 95%CI: 1.12-10.97) were associated with gender identity disclosure to health professionals.ConclusionsLow rates of gender identity disclosure to health professionals among transgender people may reflect fear of stigma and outing, suggesting the need for more trans-inclusive environments. More research is needed to understand the importance of disclosure in improving transgender health services.SummaryA study among transgender individuals in nine cities across mainland China found that gender identity disclosers to health care professionals were more likely to test for STIs than nondisclosures.