bluuebunny/crossref_metadata_2025_split huggingface dataset:
A microbiota–root–shoot circuit favours Arabidopsis growth over defence under suboptimal light
Authors: Hou Shiji , Thiergart Thorsten , Vannier Nathan , Mesny Fantin , Ziegler Jörg , Pickel Brigitte , Hacquard Stéphane 
Published: July 2021

AbstractBidirectional root–shoot signalling is probably key in orchestrating stress responses and ensuring plant survival. Here, we show that Arabidopsis thaliana responses to microbial root commensals and light are interconnected along a microbiota–root–shoot axis. Microbiota and light manipulation experiments in a gnotobiotic plant system reveal that low photosynthetically active radiation perceived by leaves induces long-distance modulation of root bacterial communities but not fungal or oomycete communities. Reciprocally, microbial commensals alleviate plant growth deficiency under low photosynthetically active radiation. This growth rescue was associated with reduced microbiota-induced aboveground defence responses and altered resistance to foliar pathogens compared with the control light condition. Inspection of a set of A. thaliana mutants reveals that this microbiota- and light-dependent growth–defence trade-off is directly explained by belowground bacterial community composition and requires the host transcriptional regulator MYC2. Our work indicates that aboveground stress responses in plants can be modulated by signals from microbial root commensals.
Systemic immune reaction in axillary lymph nodes adds to tumor-infiltrating lymphocytes in triple-negative breast cancer prognostication
Authors: Liu Fangfang , Hardiman Thomas , Wu Kailiang , Quist Jelmar , Gazinska Patrycja , Ng Tony , Purushotham Arnie , Salgado Roberto , Guo Xiaojing , Pinder Sarah E. , Grigoriadis Anita 
Published: July 2021

AbstractThe level of stromal tumor-infiltrating lymphocytes (sTILs) in triple-negative (TNBC) and HER2-positive breast cancers convey prognostic information. The importance of systemic immunity to local immunity is unknown in breast cancer. We previously demonstrated that histological alterations in axillary lymph nodes (LNs) carry clinical relevance. Here, we capture local immune responses by scoring TILs at the primary tumor and systemic immune responses by recording the formation of secondary follicles, also known as germinal centers, in 2,857 cancer-free and involved axillary LNs on haematoxylin and eosin (H&E) stained sections from a retrospective cohort of 161 LN-positive triple-negative and HER2-positive breast cancer patients. Our data demonstrate that the number of germinal center formations across all cancer-free LNs, similar to high levels of TILs, is associated with a good prognosis in low TILs TNBC. This highlights the importance of assessing both primary and LN immune responses for prognostication and for future breast cancer research.
Evaluation of overall survival and barriers to surgery for patients with breast cancer treated without surgery: a National Cancer Database analysis
Authors: Boyce-Fappiano D. , Bedrosian I. , Shen Y. , Lin H. , Gjyshi O. , Yoder A. , Shaitelman S. F. , Woodward W. A. 
Published: July 2021

AbstractSurgery remains the foundation of curative therapy for non-metastatic breast cancer, but many patients do not undergo surgery. Evidence is limited regarding this population. We sought to assess factors associated with lack of surgery and overall survival (OS) in patients not receiving breast cancer surgery. Retrospective cohort study of patients in the US National Cancer Database treated in 2004–2016. The dataset comprised 2,696,734 patients; excluding patients with unknown surgical status or stage IV, cT0, cTx, or pIS, metastatic or recurrent disease resulted in 1,192,294 patients for analysis. Chi-square and Wilcoxon rank-sum tests were used to assess differences between groups. OS was analyzed using the Kaplan–Meier method with a Cox proportional hazards model performed to assess associated factors. In total 50,626 (4.3%) did not undergo surgery. Black race, age >50 years, lower income, uninsured or public insurance, and lower education were more prevalent in the non-surgical cohort; this group was also more likely to have more comorbidities, higher disease stage, and more aggressive disease biology. Only 3,689 non-surgical patients (7.3%) received radiation therapy (RT). Median OS time for the non-surgical patients was 58 months (3-year and 5-year OS rates 63% and 49%). Median OS times were longer for patients who received chemotherapy (80 vs 50 (no-chemo) months) and RT (85 vs 56 (no-RT) months). On multivariate analysis, age, race, income, insurance status, comorbidity score, disease stage, tumor subtype, treatment facility type and location, and receipt of RT were associated with OS. On subgroup analysis, receipt of chemotherapy improved OS for patients with triple negative (HR 0.66, 95% CI 0.59–0.75, P < 0.001) and HER2+ (HR 0.74, 95% CI 0.65–0.84, P < 0.001) subgroups while RT improved OS for ER+ (HR 0.72, 95% CI 0.64–0.82, P < 0.001) and favorable-disease (ER+, early-stage, age >60) (HR 0.61, 95% CI 0.45–0.83, P = 0.002) subgroups. Approximately 4% of women with breast cancer do not undergo surgery, particularly those with more aggressive disease and lower socioeconomic status. Despite its benefits, RT was underutilized. This study provides a benchmark of survival outcomes for patients who do not undergo surgery and highlights a potential role for use of RT.
Accurate long-range forecasting of COVID-19 mortality in the USA
Authors: Ramazi Pouria , Haratian Arezoo , Meghdadi Maryam , Mari Oriyad Arash , Lewis Mark A. , Maleki Zeinab , Vega Roberto , Wang Hao , Wishart David S. , Greiner Russell 
Published: July 2021

AbstractThe need for improved models that can accurately predict COVID-19 dynamics is vital to managing the pandemic and its consequences. We use machine learning techniques to design an adaptive learner that, based on epidemiological data available at any given time, produces a model that accurately forecasts the number of reported COVID-19 deaths and cases in the United States, up to 10 weeks into the future with a mean absolute percentage error of 9%. In addition to being the most accurate long-range COVID predictor so far developed, it captures the observed periodicity in daily reported numbers. Its effectiveness is based on three design features: (1) producing different model parameters to predict the number of COVID deaths (and cases) from each time and for a given number of weeks into the future, (2) systematically searching over the available covariates and their historical values to find an effective combination, and (3) training the model using “last-fold partitioning”, where each proposed model is validated on only the last instance of the training dataset, rather than being cross-validated. Assessments against many other published COVID predictors show that this predictor is 19–48% more accurate.
A scaffolded approach to unearth potential antibacterial components from epicarp of Malaysian Nephelium lappaceum L.
Authors: Asghar Ali , Tan Yong Chiang , Zahoor Mohammad , Zainal Abidin Syafiq Asnawi , Yow Yoon-Yen , Khan Ezzat , Lahiri Chandrajit 
Published: July 2021

AbstractThe emergence and spread of antimicrobial resistance have been of serious concern to human health and the management of bacterial infectious diseases. Effective treatment of these diseases requires the development of novel therapeutics, preferably free of side effects. In this regard, natural products are frequently conceived to be potential alternative sources for novel antibacterial compounds. Herein, we have evaluated the antibacterial activity of the epicarp extracts of the Malaysian cultivar of yellow rambutan fruit (Nephelium lappaceum L.) against six pathogens namely, Bacillus subtilis, methicillin-resistant Staphylococcus aureus (MRSA), Streptococcus pyogenes, Pseudomonas aeruginosa, Klebsiella pneumoniae and Salmonella enterica. Among a series of solvent extracts, fractions of ethyl acetate and acetone have revealed significant activity towards all tested strains. Chemical profiling of these fractions, via HPLC, LC–MS and GC–MS, has generated a library of potentially bioactive compounds. Downstream virtual screening, pharmacological prediction, and receptor-ligand molecular dynamics simulation have eventually unveiled novel potential antibacterial compounds, which can be extracted for medicinal use. We report compounds like catechin, eplerenone and oritin-4-beta-ol to be computationally inhibiting the ATP-binding domain of the chaperone, DnaK of P. aeruginosa and MRSA. Thus, our work follows the objective to propose new antimicrobials capable of perforating the barrier of resistance posed by both the gram positives and the negatives.
Association between thyroid cysts and hypertension by atherosclerosis status: a cross-sectional study
Authors: Shimizu Yuji , Kawashiri Shin-Ya , Noguchi Yuko , Nagata Yasuhiro , Maeda Takahiro , Hayashida Naomi 
Published: July 2021

AbstractOur recent studies indicate that thyroid cysts have clinical implications. Thyroid cysts could have a positive effect on the supply of thyroid hormones. Both hyperthyroidism and hypothyroidism cause hypertension. Hypothyroidism, but not hyperthyroidism, is a risk factor for atherosclerosis. Therefore, thyroid cysts could be associated with hypertension, and atherosclerosis might influence the association between thyroid cysts and hypertension. To evaluate the clinical significance of thyroid cysts, a cross-sectional study was conducted with 1801 Japanese aged 40–74 years. Thyroid cysts were significantly positively associated with hypertension in participants without atherosclerosis. However, there was a significant inverse association in those with atherosclerosis. The potential confounding factor adjusted odd ratios and 95% confidence intervals (95% CIs) were 1.49 (95% CI 1.17–1.90) for participants without atherosclerosis and 0.49 (95% CI 0.24–0.98) for those with atherosclerosis. The present study demonstrates that thyroid cysts have clinical implications because thyroid cysts support thyroid hormone activity. Our findings provide sufficient evidence to develop a risk assessment for hypertension for the general population, even though further research is required.
Secret messaging with endogenous chemistry
Authors: Kennedy Eamonn , Geiser Joseph , Arcadia Christopher E. , Weber Peter M. , Rose Christopher , Rubenstein Brenda M. , Rosenstein Jacob K. 
Published: July 2021

AbstractData encoded in molecules offers opportunities for secret messaging and extreme information density. Here, we explore how the same chemical and physical dimensions used to encode molecular information can expose molecular messages to detection and manipulation. To address these vulnerabilities, we write data using an object’s pre-existing surface chemistry in ways that are indistinguishable from the original substrate. While it is simple to embed chemical information onto common objects (covers) using routine steganographic permutation, chemically embedded covers are found to be resistant to detection by sophisticated analytical tools. Using Turbo codes for efficient digital error correction, we demonstrate recovery of secret keys hidden in the pre-existing chemistry of American one dollar bills. These demonstrations highlight ways to improve security in other molecular domains, and show how the chemical fingerprints of common objects can be harnessed for data storage and communication.
Genome-wide CRISPR/Cas9 screening in human iPS derived cardiomyocytes uncovers novel mediators of doxorubicin cardiotoxicity
Authors: Sapp Valerie , Aguirre Aitor , Mainkar Gayatri , Ding Jeffrey , Adler Eric , Liao Ronglih , Sharma Sonia , Jain Mohit 
Published: July 2021

AbstractHuman induced pluripotent stem (iPS) cell technologies coupled with genetic engineering now facilitate the study of the molecular underpinnings of disease in relevant human cell types. Application of CRISPR/Cas9-based approaches for genome-scale functional screening in iPS-derived cells, however, has been limited by technical constraints, including inefficient transduction in pooled format, loss of library representation, and poor cellular differentiation. Herein, we present optimized approaches for whole-genome CRISPR/Cas9 based screening in human iPS derived cardiomyocytes with near genome-wide representation at both the iPS and differentiated cell stages. As proof-of-concept, we perform a screen to investigate mechanisms underlying doxorubicin mediated cell death in iPS derived cardiomyocytes. We identified two poorly characterized, human-specific transporters (SLCO1A2, SLCO1B3) whose loss of function protects against doxorubicin-cardiotoxicity, but does not affect cell death in cancer cells. This study provides a technical framework for genome-wide functional screening in iPS derived cells and identifies new targets to mitigate doxorubicin-cardiotoxicity in humans.
Assessing the post-treatment therapeutic effect of pinaverium in irritable bowel syndrome: a randomized controlled trial
Authors: Zheng Liang , Lu Weimin , Xiao Qi , Lai Yaoliang , Fan Heng , Sun Yuling , Huang Dawei , Wang Yuanyuan , Li Zhen , Jiang Zhengyan , Liu Xingxing , Zhang Lijuan , Zuo Dongmei , Shou Zhexing , Tang Qing , Huang Huisuo , Yang Yongqiang , Tang Zongxiang , Xiao Jun 
Published: July 2021

AbstractIrritable bowel syndrome (IBS) is the most common gastrointestinal disorder significantly decreasing patients’ lives of quality and placing huge economic burden on our society. Existing studies indicated that the therapeutic effects maintained for a period of time after the treatments were discontinued. It is clinically important to assess these post-treatment therapeutic effects (PTTE), which prevent IBS from relapsing. To assess the PTTE in pinaverium treatment and obtain high-quality evidence to justify the use of PTTE for long-term IBS management, we performed this controlled, double blind study on patients with IBS who were randomized to pinaverium 50 mg (n = 132) or placebo (n = 132), three times daily, for 4 weeks, and were followed up for 57 weeks after the treatments. The primary endpoints were abdominal pain and stool consistency. The secondary endpoints were pain frequency and stool frequency. The tertiary endpoints were global overall symptom and adverse events. Three days after pinaverium was discontinued, endpoints rebounded only 23.2–42.8% (P < 0.015 cf. placebo). The PTTE (P < 0.05 cf. placebo) lasted 9–17 weeks, which is similar to other antispasmodics with a 15-week treatment in striking contrast to ≥ 1 year PTTE in cognitive behavior therapy and < 1 week PTTE in serotonin antagonist treatment indicating that PTTE length markedly depends on the medication class used for the treatment and less depends on treatment length. After 17 weeks, the stage could be considered as an IBS natural history [no significant differences between pinaverium and placebo (all endpoints’ P’s > 0.05)], during which an average of 51.5–56.4% of patients (pool pinaverium and placebo data together) had IBS symptoms. These results provide clinical insights into efficient and cost-effective management of refractory IBS, and lend support to the IBS management that the selection of a therapy should consider both its effectiveness during treatment and its PTTE after the treatment.Trial registration number: NCT02330029 (16/08/2016).
A bacteriocin-based treatment option for Staphylococcus haemolyticus biofilms
Authors: Kranjec Christian , Kristensen Sofie S. , Bartkiewicz Karolina T. , Brønner Mikkel , Cavanagh Jorunn P. , Srikantam Aparna , Mathiesen Geir , Diep Dzung B. 
Published: July 2021

AbstractBacteriocins are ribosomally-synthesized antimicrobial peptides, showing great potential as novel treatment options for multidrug-resistant pathogens. In this study, we designed a novel hybrid bacteriocin, Hybrid 1 (H1), by combing the N-terminal part and the C-terminal part of the related bacteriocins enterocin K1 (K1) and enterocin EJ97 (EJ97), respectively. Like the parental bacteriocins, H1 used the membrane-bound protease RseP as receptor, however, it differed from the others in the inhibition spectrum. Most notably, H1 showed a superior antimicrobial effect towards Staphylococcus haemolyticus—an important nosocomial pathogen. To avoid strain-dependency, we further evaluated H1 against 27 clinical and commensal S. haemolyticus strains, with H1 indeed showing high activity towards all strains. To curtail the rise of resistant mutants and further explore the potential of H1 as a therapeutic agent, we designed a bacteriocin-based formulation where H1 was used in combination with the broad-spectrum bacteriocins micrococcin P1 and garvicin KS. Unlike the individual bacteriocins, the three-component combination was highly effective against planktonic cells and completely eradicated biofilm-associated S. haemolyticus cells in vitro. Most importantly, the formulation efficiently prevented development of resistant mutants as well. These findings indicate the potential of a bacteriocins-based formulation as a treatment option for S. haemolyticus.
Sex-related differences in response to masseteric injections of glutamate and nerve growth factor in healthy human participants
Authors: Alhilou Abdelrahman M. , Shimada Akiko , Svensson Camilla I. , Svensson Peter , Ernberg Malin , Cairns Brian E. , Christidis Nikolaos 
Published: July 2021

AbstractThe neurophysiological mechanisms underlying NGF-induced masseter muscle sensitization and sex-related differences in its effect are not well understood in humans. Therefore, this longitudinal cohort study aimed to investigate the effect of NGF injection on the density and expression of substance P, NMDA-receptors and NGF by the nerve fibers in the human masseter muscle, to correlate expression with pain characteristics, and to determine any possible sex-related differences in these effects of NGF. The magnitude of NGF-induced mechanical sensitization and pain during oral function was significantly greater in women than in men (P < 0.050). Significant positive correlations were found between nerve fiber expression of NMDA-receptors and peak pain intensity (rs = 0.620, P = 0.048), and expression of NMDA-receptors by putative nociceptors and change in temporal summation pain after glutamate injection (rs = 0.561, P = 0.003). In women, there was a significant inverse relationship between the degree of NGF-induced mechanical sensitization and the change in nerve fiber expression of NMDA-receptors alone (rs = − 0.659, P = 0.013), and in combination with NGF (rs = − 0.764, P = 0.001). In conclusion, women displayed a greater magnitude of NGF-induced mechanical sensitization that also was associated with nerve fibers expression of NMDA-receptors, when compared to men. The present findings suggest that, in women, increased peripheral NMDA-receptor expression could be associated with masseter muscle pain sensitivity.
High-resolution particle separation by inertial focusing in high aspect ratio curved microfluidics
Authors: Cruz Javier , Hjort Klas 
Published: July 2021

AbstractThe ability to focus, separate and concentrate specific targets in a fluid is essential for the analysis of complex samples such as biological fluids, where a myriad of different particles may be present. Inertial focusing is a very promising technology for such tasks, and specially a recently presented variant, inertial focusing in High Aspect Ratio Curved systems (HARC systems), where the systems are easily engineered and focus the targets together in a stable position over a wide range of particle sizes and flow rates. However, although convenient for laser interrogation and concentration, by focusing all particles together, HARC systems lose an essential feature of inertial focusing: the possibility of particle separation by size. Within this work, we report that HARC systems not only do have the capacity to separate particles but can do so with extremely high resolution, which we demonstrate for particles with a size difference down to 80 nm. In addition to the concept for particle separation, a model considering the main flow, the secondary flow and a simplified expression for the lift force in HARC microchannels was developed and proven accurate for the prediction of the performance of the systems. The concept was also demonstrated experimentally with three different sub-micron particles (0.79, 0.92 and 1.0 µm in diameter) in silicon-glass microchannels, where the resolution in the separation could be modulated by the radius of the channel. With the capacity to focus sub-micron particles and to separate them with high resolution, we believe that inertial focusing in HARC systems is a technology with the potential to facilitate the analysis of complex fluid samples containing bioparticles like bacteria, viruses or eukaryotic organelles.
Association of body mass index and maternal age with first stage duration of labour
Authors: Lundborg Louise , Liu Xingrong , Åberg Katarina , Sandström Anna , Tilden Ellen L. , Stephansson Olof , Ahlberg Mia 
Published: July 2021

AbstractTo evaluate associations between early-pregnancy body mass index (BMI) and active first stage labour duration, accounting for possible interaction with maternal age, we conducted a cohort study of women with spontaneous onset of labour allocated to Robson group 1. Quantile regression analysis was performed to estimate first stage labour duration between BMI categories in two maternal age subgroups (more and less than 30 years). Results show that obesity (BMI > 30) among younger women (< 30 years) increased the median labour duration of first stage by 30 min compared with normal weight women (BMI < 25), and time difference estimated at the 90th quantile was more than 1 h. Active first stage labour time differences between obese and normal weight women was modified by maternal age. In conclusion: (a) obesity is associated with longer duration of first stage of labour, and (b) maternal age is an effect modifier for this association. This novel finding of an effect modification between BMI and maternal age contributes to the body of evidence that supports a more individualized approach when describing labour duration.
Metagenomic analysis of a throat swab sample collected in China on a patient infected with Varicella Zoster Virus
Authors: Guo Hong , Rivailler Pierre , Wang Jiangxia , Wang Huanyu , Xu Wenbo , Xu Songtao , Xu Hongmei , Hu Ruiping 
Published: July 2021

AbstractVaricella Zoster Virus (VZV) is endemic worldwide, causing varicella in children and zoster upon reactivation in adults. This study concerned a metagenomic analysis of a throat swab sample collected in China, on a young patient suffering from Systemic Lupus Erythematosus (SLE) and diagnosed with varicella. The complete genome sequence of a VZV strain of clade 2 has been generated. Clade 2 strains are the most prevalent in Asian countries. A comparison of 223 VZV genomes identified 77 clade specific markers, 20 of them specific to clade 2. The metagenomic analysis also identified sequences covering most of the genome of the bacteria Schaalia odontolytica also known as Actinomyces odontolyticus. VZV infection and bacterial infection in the context of SLE is further discussed. Even though the patient presented only mild symptoms, this study is a reminder that vaccination against VZV is critical to avoid severe complications like bacterial superinfection or even death in the case of immunodeficiency.