Miracle-dz/UniFAR-FTUs huggingface dataset:
AFM Force Mapping Elucidates Pilus Deployment and Key Lifestyle-Dependent Surface Properties in Bdellovibrio bacteriovorus

Bdellovibrio bacteriovorus is known for predation of a wide variety of Gram-negative bacteria, making it of interest as an alternative or supplement to chemical antibiotics. However, a fraction of B. bacteriovorus follows a nonpredatory, “host-independent” (HI) life cycle. In this study, live predatory and HI B. bacteriovorus were captured on a surface and examined, in buffer, by collecting force maps using atomic force microscopy (AFM). The approach curves obtained on HI cells are similar to those on other Gram-negative cells, with a short nonlinear region followed by a linear region. In contrast, the approach curves obtained on predatory cells have a large nonlinear region, reflecting the unusual flexibility of the predatory cell. As the AFM tip is retracted, it shows virtually no adhesion to predatory B. bacteriovorus but has multiple adhesion events on HI cells and the 200–500+ nm region immediately surrounding them. Measured pull-off forces, pull-off distances, and effective spring constants are consistent with the multiple stretching events of Type IV pili, both on and especially adjacent to the cells. Exposure of the HI B. bacteriovorus to a pH-neutral 10% cranberry juice solution, which contains type A proanthocyanidins that are known to interfere with the adhesion of multiple types of pili, results in a substantial reduction in adhesion. Type IV pili are required for successful predation by B. bacteriovorus, but pili used in the predation process are located at the non-flagellated pole of the cell and can retract when not in use. Such pili are rarely observed under the conditions of this study, where the predator has not encountered a prey cell. In contrast, HI cells appear to have many pili distributed on and around the whole cell, presumably ready to be utilized for a variety of HI cell activities including attachment to surfaces.
Cerebrospinal Fluid HIV-1 Escape in Patients With Neurocognitive Symptoms: Pooled Data From a Neuro-HIV Platform and the NAMACO Study

Background: Despite modern antiretroviral therapy, human immunodeficiency virus-1 (HIV-1) ribonucleic acid (RNA) escape into the cerebrospinal fluid (CSF) may occur. We examined the prevalence of and factors associated with CSF HIV-1 escape among people living with HIV (PLWH) in Switzerland. Setting: The Neurocognitive Assessment in the Metabolic and Aging Cohort study is an ongoing, prospective, longitudinal, multicenter study within the Swiss HIV Cohort Study. The neuro-HIV platform is a multidisciplinary, single-day outpatient consultation at Lausanne University Hospital. Methods: We pooled data from the Neurocognitive Assessment in the Metabolic and Aging Cohort study and the neuro-HIV platform participants who underwent lumbar puncture between 2011 and 2019. Both patient groups had neurocognitive symptoms. Cerebrospinal fluid HIV-1 escape was defined as the presence of quantifiable CSF HIV-1 RNA when plasma HIV-1 RNA was suppressed or CSF HIV-1 RNA greater than plasma HIV-1 RNA when the latter was detectable. Results: Of 1166 PLWH assessed, 288 underwent lumbar puncture. Cerebrospinal fluid HIV-1 escape was observed in 25 PLWH (8.7%) of whom 19 (76%) had suppressed plasma HIV-1 RNA. Characteristics of PLWH were comparable whether they had CSF HIV-1 escape or not, including comorbidities, time since HIV diagnosis (15 vs 16 years, P = 0.9), median CD4 nadir (158.5/mm3 vs 171/mm3, P = 0.6), antiretroviral CSF penetration-effectiveness score (7 vs 7 points, P = 0.8), and neurocognitive diagnosis based on Frascati criteria and radiological findings. Conclusions: In this large pooled sample of PLWH with neurocognitive symptoms, CSF HIV-1 escape occurred in 8.7% of PLWH. People living with HIV with CSF HIV-1 escape presented no distinctive clinical or paraclinical characteristics. We conclude that lumbar puncture is unavoidable in confirming CSF HIV-1 escape.
Platelet‐rich plasma injections as a treatment for Achilles tendinopathy and plantar fasciitis in athletes

Platelet‐rich plasma (PRP) injections represent a growing interest in the use of biologic therapies for treatment of musculoskeletal injuries. One possible application of PRP is in the management of overuse injuries commonly experienced by athletes. The aim of this review is to evaluate and summarize existing evidence regarding the efficacy of PRP in the treatment of Achilles tendinopathy and plantar fasciitis in athletes. Although many lower quality single‐armed studies have demonstrated clinical improvement in athletes treated for Achilles tendinopathy with PRP, higher quality randomized controlled trials (RCTs) have shown no clear benefit in athletes. Existing data suggest PRP significantly improves clinical outcomes for plantar fasciitis in the general population, but very few studies and no RCTs are available that specifically analyze outcomes in athletic populations. More research is needed to evaluate how platelet concentration, leukocyte and erythrocyte presence, and sport type may interact to affect clinical outcomes in athletes.
PTEN mutation predicts unfavorable fertility preserving treatment outcome in the young patients with endometrioid endometrial cancer and atypical hyperplasia

Objective This study aimed to investigate the impact of molecular classification and PTEN, KRAS and PIK3CA gene mutation on the outcome of fertility-preserving treatment in the patients with endometrioid endometrial cancer (EEC) and endometrial atypical hyperplasia (EAH). Methods This is a single-center retrospective study. A total of 135 patients with EEC and EAH receiving fertility-preserving treatment and molecular classification were reviewed. The distribution of the four types of molecular classification was described. The impact of non-specific molecular profile (NSMP), mismatch repair-deficiency (MMRd), and PTEN, KRAS and PIK3CA gene mutation on the outcome of fertility-preserving treatment was analyzed. Results Of the patients analyzed, 86.7% (117/136) were classified as having NSMP; 14 (10.4%), MMRd; 1 (0.7%), POLEmut EAH; and 3 (2.2%), p53abn EEC. The patients having NSMP and MMRd achieved similar 16-, 32-, and 48-week complete response rates. The patients harboring tier I and tier II PTEN mutations (PTENmut-Clin) achieved lower cumulative 32-week CR rates than those with PTEN-others (without PTENmut-Clin) (22/47, 46.8% vs. 50/74, 67.6%; p=0.023; odds ratio=0.422; 95% confidence interval [CI]=0.199–0.896). Insulin-resistance (hazard ratio [HR]=0.435; 95% CI=0.269–0.702; p=0.001) and PTENmut-Clin (HR=0.535; 95% CI=0.324–0.885; p=0.015) were independent negative predictors for lower 32-week CR rates. Conclusion PTENmut-Clin is an independent risk factor for unfavorable fertility-preserving treatment outcomes in the patients with EEC and EAH. The patients with MMRd receiving fertility-preserving treatment achieved outcomes similar to those of the patients with NSMP. The molecular profiles might guide fertility-preserving treatment in the prognosis and clinical decisions.
Challenges Posed by the Banff Classification: Diagnosis and Treatment of Chronic Active T-Cell-Mediated Rejection

The three primary sites of acute T-cell-mediated rejection (TCMR) in transplanted kidneys are the tubular epithelial cells, interstitium, and the vascular endothelial cells. The pathology of acute lesions is characterized by inflammatory cell infiltration; the final diagnosis suggested by the Banff 2019 classification is guided by grading of tubulitis (the t score), interstitial inflammation (the i score), and endarteritis (the v score). Consistent major issues when using the Banff classification are the etiological classifications of interstitial fibrosis and tubular atrophy (IFTA). From 2015 to 2019, technological advances (i.e., genetic analysis in paraffin sections) increased our understanding of IFTA status in patients with smoldering acute TCMR and the roles played by inflammatory cell infiltration (the i-IFTA score) and tubulitis (the t-IFTA score) in IFTA. These two scores were introduced when establishing the diagnostic criteria for chronic active TCMR. Despite the increase in complexity and the lack of a consensus treatment for chronic active TCMR, the Banff classification may evolve as new techniques (i.e., genetic analysis in paraffin sections and deep learning of renal pathology) are introduced. The Banff conference proceeded as follows. First, lesions were defined. Next, working groups were established to better understand the lesions and to derive better classification methods. Finally, the new Banff classification was developed. This approach will continue to evolve; the Banff classification will become a very useful diagnostic standard. This paper overviews the history of TCMR diagnosis using the Banff classification, and the clinical importance, treatment, and prospects for acute and chronic active TCMR.
Incidence, prognostic factors and a nomogram of cervical cancer with distant organ metastasis: a SEER-based study

Abstract This study was to investigate the incidence, survival and prognostic factors of cervical cancer with distant organ metastasis, and to develop a nomogram to predict the prognosis of cervical cancer. We used the Surveillance, Epidemiology and End Results (SEER) database to screen patients diagnosed with cervical cancer from 2010 to 2014. The chi-squared test was used to analyse the differences in clinical characteristics, and we used Kaplan–Meier methods to perform survival analysis. Univariate and multivariate Cox proportional hazard regression models were used to estimate prognostic factors, and we developed a visual nomogram to judge the prognosis. We found that lung metastasis was the most common in cervical cancer patients with distant organ metastasis. Age, race, characteristics of the tumour, and therapy should be considered when analysing the prognosis of cervical cancer patients. The findings of this study may help clinicians to formulate individualised treatment strategies. Impact Statement What is already known on this subject? Distant organ metastasis of cervical cancer mainly involves lung, bone, liver and brain. Once it occurs, the survival and prognosis will be threatened seriously. What the results of this study add? 4176 patients were included, and lung metastasis was the most common in cervical cancer with distant organ metastasis (3.5%). Additionally, age, race, tumour grade, histological type, T-stage, N-stage, lung, liver and bone metastasis and the treatment mode are significantly related to the outcomes of cervical cancer patients. Furthermore, we developed a nomogram that could predict the probability of three-year and five-year OS. What the implications are of these findings for clinical practice and/or further research? The findings of this study may drive more and more studies focussing on the comprehensive prognostic assessment, diagnosis, and treatment of distant metastasis of cervical cancer. Besides, clinicians can utilise these findings to formulate individualised treatment strategies.
Method for experimental determination of Z dependence of impurity transport on JET

The prediction of impurity peaking in future fusion devices such as ITER necessitates the study of the dependence on Z of the impurity transport in present devices. In this paper we describe a novel technique to determine the transport of impurities with different atomic numbers independently. A technique has been developed that allows simultaneously the measurement of the transport of Ne and Ar in the same discharge while minimizing the systematic errors in the spectroscopic measurements. The reproduction of the charge-exchange measured densities, absolute vaccum ultra-violet line intensities and absolute soft x-ray intensity is achieved in an impurity transport simulation. The method used to estimate the errors on the transport coefficients of neon (Ne) and argon (Ar) is presented. In the plasma region where the diffusion and convection coefficients are determined for hybrid discharges, the transport of Ne and Ar is observed to exceed neoclassical predictions. In the same regions, the diffusion coefficients of both impurities are similar. The convection coefficients are also comparable for Ne and Ar. The peaking of Ne and Ar density profiles are comparable during the period where the intermittent slow reconnecting n = 1 mode is stable in these hybrid discharges.
Contributions of semantic and phonological working memory to narrative language independent of single word production: Evidence from acute stroke

ABSTRACT Neuropsychological case studies have provided evidence that individuals with semantic, but not phonological, working memory (WM) deficits have difficulty producing phrases containing several content words. These findings supported the claim of a phrasal scope of planning at the grammatical formulation stage of production, where semantic WM supports the maintenance of lexical-semantic representations as they are inserted into slots in phrasal constituents. Recent narrative production results for individuals at the acute stage of stroke supported the role for semantic WM in phrasal elaboration while suggesting a role for phonological WM at a subsequent phonological encoding stage in supporting fluent, rapid speech. In the present study, we employed a larger participant sample while controlling for single word production abilities at semantic and phonological levels. Results confirmed the relations between semantic WM and phrasal elaboration whereas the relation between phonological WM and speech rate was eliminated. There was, however, evidence that both impaired phonological retrieval and restricted phonological WM were related to the tendency to produce short, highly frequent words such as pronouns rather than longer, less frequent words. Future research is needed to address whether the results relating to phonological WM depend on damage specific to an output rather than an input phonological capacity.
RGS6 negatively regulates inhibitory G protein signaling in dopamine neurons and positively regulates binge‐like alcohol consumption in mice

Drugs of abuse, including alcohol, increase dopamine in the mesocorticolimbic system via actions on dopamine neurons in the ventral tegmental area (VTA). Increased dopamine transmission can activate inhibitory G protein signalling pathways in VTA dopamine neurons, including those controlled by GABAB and D2 receptors. Members of the R7 subfamily of regulator of G protein signalling (RGS) proteins can regulate inhibitory G protein signalling, but their influence on VTA dopamine neurons is unclear. Here, we investigated the influence of RGS6, an R7 RGS family memberthat has been implicated in the regulation of alcohol consumption in mice, on inhibitory G protein signalling in VTA dopamine neurons.
The effect of ball possession on physical and technical performance in UEFA Champions league matches

ABSTRACT This study aimed to examine the effects of low-percentage ball possession teams (LPBPT) and high-percentage ball possession teams (HPBPT) on the physical and technical performance of UEFA Champions League (UCL) players. All data were obtained from group stage matches of UCL during the 2020/21 season using a semi-automatic optical tracking system. Linear mixed model was fitted with contextual variables as covariates. Wide midfielders and forwards in LPBPT covered more total distance, low-intensity running, and achieved greater average speed than in HPBPT (all large effect sizes [ES]). Central defenders and fullbacks covered more high-intensity running (small ES), while CMs covered more sprinting (medium ES) in HPBPT than in LPBPT. Players on all playing positions produced greater number of passes and successful passes in HPBPT than in LPBPT (large ES), except forwards who produced more passes in LPBPT than in HPBPT (small ES). Both physical and technical performance were highly dependent on ball possession percentages, with evident position-specific changes, indicating that the effect of ball possession is highly position-dependent. These findings provide information for soccer coaches on physical and technical demands across teams with varying percentage ball possession, which could be used to individualise training programs based on playing style and position.
Staphylococcus aureus binding to Seraph® 100 Microbind® Affinity Filter: Effects of surface protein expression and treatment duration

Introduction Extracorporeal blood purification systems represent a promising alternative for treatment of blood stream infections with multiresistant bacteria. Objectives The aim of this study was to analyse the binding activity of S. aureus to Seraph affinity filters based on heparin coated beads and to identify effectors influencing this binding activity. Results To test the binding activity, we used gfp-expressing S. aureus Newman strains inoculated either in 0.9% NaCl or in blood plasma and determined the number of unbound bacteria by FACS analyses after passing through Seraph affinity filters. The binding activity of S. aureus was clearly impaired in human plasma: while a percent removal of 42% was observed in 0.9% NaCl (p-value 0.0472) using Seraph mini columns, a percent removal of only 10% was achieved in human plasma (p-value 0.0934). The different composition of surface proteins in S. aureus caused by the loss of SarA, SigB, Lgt, and SaeS had no significant influence on its binding activity. In a clinically relevant approach using the Seraph® 100 Microbind® Affinity Filter and 1000 ml of human blood plasma from four different donors, the duration of treatment was shown to have a critical effect on the rate of bacterial reduction. Within the first four hours, the number of bacteria decreased continuously and the reduction in bacteria reached statistical significance after two hours of treatment (percentage reduction 64%, p-value 0.01165). The final reduction after four hours of treatment was close to 90% and is dependent on donor. The capacity of Seraph® 100 for S. aureus in human plasma was approximately 5 x 108 cells. Conclusions The Seraph affinity filter, based on heparin-coated beads, is a highly efficient method for reducing S. aureus in human blood plasma, with efficiency dependent on blood plasma composition and treatment duration.
Turbulent line momentum puffs

The time evolution of a line puff—a turbulent element with momentum—is studied by numerical simulation of the flow and mixing using a two-equation turbulence model, and by experimental measurements of the scalar concentration field in an advected line puff. The numerical solution reveals a distinct double-vortex flow with a loss of initial impulse due to pressure interaction, and mixing at the front of the puff. The added mass coefficient associated with the loss of impulse is found to be approximately 1. The computed flow and puff characteristics support the concept of self-similarity beyond a dimensionless time of 25–30. The predicted puff flow features and mixing rates are well-supported by experimental observations.
Suspension dynamics: moving beyond steady

Abstract The dynamics of flowing, concentrated suspensions of non-colloidal particles continues to surprise, despite decades of work and the widespread importance of suspension transport properties to industrial processes and natural phenomena. Blanc, Lemaire & Peters (J. Fluid Mech., 2014, vol. 746, R4) report a striking example. They probed the time-dependent dynamics of concentrated suspensions of rigid and neutrally buoyant spheres by simultaneously measuring the oscillatory rheology and the sedimentation rate of a falling ball. The sedimentation velocity of the ball through the suspension depends strongly on the frequency of oscillation, though the rheology was found to be independent of frequency. The results demonstrate the complexities of suspension flows and highlight opportunities for improving models by exploring suspension dynamics and rheology over a wide range of conditions, beyond steady and unidirectional ones.
Spatial variation of the gut microbiome in response to long-term metformin treatment in high-fat diet-induced type 2 diabetes mouse model of both sexes

ABSTRACT Antidiabetic drug metformin alters the gut microbiome composition in the context of type 2 diabetes and other diseases; however, its effects have been mainly studied using fecal samples, which offer limited information about the intestinal site-specific effects of this drug. Our study aimed to characterize the spatial variation of the gut microbiome in response to metformin treatment by using a high-fat diet-induced type 2 diabetes mouse model of both sexes. Four intestinal parts, each at the luminal and mucosal layer level, were analyzed in this study by performing 16S rRNA sequencing covering six variable regions (V1-V6) of the gene and thus allowing to obtain in-depth information about the microbiome composition. We identified significant differences in gut microbiome diversity in each of the intestinal parts regarding the alpha and beta diversities. Metformin treatment altered the abundance of different genera in all studied intestinal sites, with the most pronounced effect in the small intestine, where Lactococcus increased remarkably. The abundance of Lactobacillus was substantially lower in male mice compared to female mice in all locations, in addition to an enrichment of opportunistic pathogens. Diet type and intestinal layer had significant effects on microbiome composition at each of the sites studied. We observed a different effect of metformin treatment on the analyzed subsets, indicating the multiple dimensions of metformin’s effect on the gut microbiome.
Kras oncogene ablation prevents resistance in advanced lung adenocarcinomas

KRASG12C inhibitors have revolutionized the clinical management of patients with KRASG12C-mutant lung adenocarcinoma. However, patient exposure to these inhibitors leads to the rapid onset of resistance. In this study, we have used genetically engineered mice to compare the therapeutic efficacy and the emergence of tumor resistance between genetic ablation of mutant Kras expression and pharmacological inhibition of oncogenic KRAS activity. Whereas Kras ablation induces massive tumor regression and prevents the appearance of resistant cells in vivo, treatment of KrasG12C/Trp53-driven lung adenocarcinomas with sotorasib, a selective KRASG12C inhibitor, caused a limited antitumor response similar to that observed in the clinic, including the rapid onset of resistance. Unlike in human tumors, we did not observe mutations in components of the RAS-signaling pathways. Instead, sotorasib-resistant tumors displayed amplification of the mutant Kras allele and activation of xenobiotic metabolism pathways, suggesting that reduction of the on-target activity of KRASG12C inhibitors is the main mechanism responsible for the onset of resistance. In sum, our results suggest that resistance to KRAS inhibitors could be prevented by achieving a more robust inhibition of KRAS signaling mimicking the results obtained upon Kras ablation.