Miracle-dz/UniFAR-FTUs huggingface dataset:
Reduction in Pseudomonas aeruginosa and Staphylococcus aureus biofilms from implant materials in a diffusion dominated environment

Antibiotic‐loaded calcium sulfate beads (CS‐B) are used to treat biofilm‐related periprosthetic joint infections (PJI). A previous study has shown that such beads are effective in reducing lawns biofilms grown on agar plates; however, the ability of CS‐B to eradicate biofilms grown on solid orthopedic material surfaces has not been investigated. We grew biofilms of bioluminescent strains of Pseudomonas aeruginosa Xen41 and a USA300 MRSA Staphylococcus aureus SAP231 on ultra‐high molecular weight polyethylene (PE), hydroxyapatite (HA), and 316L stainless steel (SS) coupons for three days under static growth conditions, with daily nutrient exchange. The coupons were rinsed with sterile phosphate buffered saline (PBS) to remove planktonic bacteria and placed in a petri dish, surrounded by four either antibiotic vancomycin and tobramycin loaded (CS‐BV+T) or unloaded beads (CS‐BU). A thin layer of agar was overlaid to simulate a periprosthetic infection where an implant abuts soft tissue and then incubated for 72 h. The amount of biofilm was measured by bioluminescence imaging (BLI) for activity and viable cell count (CFUs). Coupons exposed to CS‐BV+T showed a significant reduction in the amount of biofilm within 24 h, regardless of the bacterial strain or material type. The coupons exposed to control CS‐BU had no effect on bacteria over 72 h. Statement of Clinical Significance: Antibiotic‐loaded calcium sulfate beads (CS‐B) were effective in significantly reducing mature biofilms of P. aeruginosa and S. aureus from orthopedic relevant surfaces in our in vitro agar model. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:3081–3085, 2018.
Real‐time strategy video game experience and structural connectivity – A diffusion tensor imaging study

Experienced video game players exhibit superior performance in visuospatial cognition when compared to non‐players. However, very little is known about the relation between video game experience and structural brain plasticity. To address this issue, a direct comparison of the white matter brain structure in RTS (real time strategy) video game players (VGPs) and non‐players (NVGPs) was performed. We hypothesized that RTS experience can enhance connectivity within and between occipital and parietal regions, as these regions are likely to be involved in the spatial and visual abilities that are trained while playing RTS games. The possible influence of long‐term RTS game play experience on brain structural connections was investigated using diffusion tensor imaging (DTI) and a region of interest (ROI) approach in order to describe the experience‐related plasticity of white matter. Our results revealed significantly more total white matter connections between occipital and parietal areas and within occipital areas in RTS players compared to NVGPs. Additionally, the RTS group had an altered topological organization of their structural network, expressed in local efficiency within the occipito‐parietal subnetwork. Furthermore, the positive association between network metrics and time spent playing RTS games suggests a close relationship between extensive, long‐term RTS game play and neuroplastic changes. These results indicate that long‐term and extensive RTS game experience induces alterations along axons that link structures of the occipito‐parietal loop involved in spatial and visual processing.
Mechanical Loading of the Femoral Neck in Human Locomotion

Advancing age and reduced loading are associated with a reduction in bone formation. Conversely, loading increases periosteal apposition and may reduce remodeling imbalance and slow age‐related bone loss, an important outcome for the proximal femur, which is a common site of fracture. The ability to take advantage of bone's adaptive response to increase bone strength has been hampered by a lack of knowledge of which exercises and specific leg muscles load the superior femoral neck: a common region of microcrack initiation and progression following a sideways fall. We used an in vivo method of quantifying focal strains within the femoral neck in postmenopausal women during walking, stair ambulation, and jumping. Relative to walking, stair ambulation and jumping induced significantly higher strains in the anterior and superior aspects of the femoral neck, common regions of microcrack initiation and progression following a fall. The gluteus maximus, a hip extensor muscle, induced strains in the femoral neck during stair ambulation and jumping, in contrast to walking which induced strains via the iliopsoas, a hip flexor. The ground reaction force was closely associated with the level of strain during each task, providing a surrogate indicator of the potential for a given exercise to load the femoral neck. The gluteal muscles combined with an increased ground reaction force relative to walking induce high focal strains within the anterosuperior region of the femoral neck and therefore provide a target for exercise regimens designed to slow bone loss and maintain or improve microstructural strength. Model files used for calculating femoral neck strains are available at uitbl.mechse. illinois.edu/downloads © 2018 American Society for Bone and Mineral Research.
A new approach to hierarchical data analysis: Targeted maximum likelihood estimation for the causal effect of a cluster-level exposure

We often seek to estimate the impact of an exposure naturally occurring or randomly assigned at the cluster-level. For example, the literature on neighborhood determinants of health continues to grow. Likewise, community randomized trials are applied to learn about real-world implementation, sustainability, and population effects of interventions with proven individual-level efficacy. In these settings, individual-level outcomes are correlated due to shared cluster-level factors, including the exposure, as well as social or biological interactions between individuals. To flexibly and efficiently estimate the effect of a cluster-level exposure, we present two targeted maximum likelihood estimators (TMLEs). The first TMLE is developed under a non-parametric causal model, which allows for arbitrary interactions between individuals within a cluster. These interactions include direct transmission of the outcome (i.e. contagion) and influence of one individual’s covariates on another’s outcome (i.e. covariate interference). The second TMLE is developed under a causal sub-model assuming the cluster-level and individual-specific covariates are sufficient to control for confounding. Simulations compare the alternative estimators and illustrate the potential gains from pairing individual-level risk factors and outcomes during estimation, while avoiding unwarranted assumptions. Our results suggest that estimation under the sub-model can result in bias and misleading inference in an observational setting. Incorporating working assumptions during estimation is more robust than assuming they hold in the underlying causal model. We illustrate our approach with an application to HIV prevention and treatment.
Dynamic Regret of Strongly Adaptive Methods

To cope with changing environments, recent developments in online learning have introduced the concepts of adaptive regret and dynamic regret independently. In this paper, we illustrate an intrinsic connection between these two concepts by showing that the dynamic regret can be expressed in terms of the adaptive regret and the functional variation. This observation implies that strongly adaptive algorithms can be directly leveraged to minimize the dynamic regret. As a result, we present a series of strongly adaptive algorithms that have small dynamic regrets for convex functions, exponentially concave functions, and strongly convex functions, respectively. To the best of our knowledge, this is the first time that exponential concavity is utilized to upper bound the dynamic regret. Moreover, all of those adaptive algorithms do not need any prior knowledge of the functional variation, which is a significant advantage over previous specialized methods for minimizing dynamic regret.
Autoimmune cytopenias in chronic lymphocytic leukemia: a concise review and treatment recommendations

ABSTRACT Introduction: Chronic lymphocytic leukemia (CLL) is frequently complicated by cytopenias, either due to bone marrow infiltration or autoimmunity, resulting in autoimmune hemolytic anemia (AIHA), immune thrombocytopenia (ITP), pure red cell aplasia (PRCA), or autoimmune neutropenia (AIN). Morbidity due to autoimmune cytopenias (AIC) can be substantial; in addition, infection risk increases and pre-existing infections might deteriorate due to immunosuppressive medication. In the aging population, CLL occurs more frequently and AIC related to CLL represent a growing clinical challenge. Areas covered: This review summarizes current knowledge on pathophysiological mechanisms involved in AIC development and their prognostic significance. It provides diagnostic criteria and a treatment guideline for daily clinical practice, which includes the role of novel targeted agents. Expert commentary: The pathophysiology of AIC involves loss of self-tolerance, antigen presentation by malignant CLL cells, and autoantibody production through aberrant T- and B-cell function. The value of detecting autoantibodies via the direct antiglobulin test (DAT) is disputable, since a positive test does not imply overt hemolysis. Importantly, AIC should be distinguished from infiltrative cytopenias, because of prognostic and therapeutic consequences. Compared to chemotherapy, triggering AIC by targeted therapies is less common and, hence, these agents may be valuable as treatment for CLL-related immune cytopenias.
Cimetropium bromide does not improve polyp and adenoma detection during colonoscope withdrawal

Background: Endoscopic inspection of colonic mucosa is disturbed by colonic folds and peristalsis, which may result in missed polyps. Cimetropium bromide, an antispasmodic agent, inhibits peristalsis and colonic spasms, which may improve polyp detection. The purpose of this randomized, double-blind, placebo-controlled study was to investigate whether cimetropium bromide could improve polyp and adenoma detection in the colorectum and right colon. Methods: Patients undergoing screening or diagnostic colonoscopy were randomized to receive intravenous cimetropium bromide (5 mg) or placebo after cecal intubation. The primary outcomes were the number of polyps per patient (PPP) and adenomas per patient (APP); secondary outcomes were the polyp detection rate (PDR), adenoma detection rate (ADR), and advanced neoplasm detection rate (ANDR). Results: A total of 181 patients were analyzed; 91 patients received cimetropium bromide and 90 patients received placebo. Cimetropium bromide and placebo groups did not significantly differ in the PPP and APP for the colorectum (1.38 ± 1.58 vs 1.69 ± 2.28, P = .298; 0.96 ± 1.27 vs 1.11 ± 1.89, P = .517, respectively) and right colon (0.70 ± 0.95 vs 0.78 ± 1.21, P = .645; 0.47 ± 0.81 vs 0.51 ± 0.81, P = .757, respectively). Two groups also did not significantly differ in the PDR, ADR, and ANDR for the colorectum and right colon. Furthermore, there were no difference between groups in the PPP, APP, PDR, ADR, and ADNR in a sub-analysis of expert and non-expert endoscopists. Conclusions: Cimetropium bromide did not improve polyp and adenoma detection in the colorectum and right colon during colonoscope withdrawal, regardless of the expertness of the endoscopist. However, its use may be helpful in patients with active peristalsis or for beginning endoscopists during standard colonoscopy without a transparent cap.
Clinical, biochemical, and pathophysiological analysis of SLC34A1 mutations

Mutations in SLC34A1, encoding the proximal tubular sodium–phosphate transporter NaPi‐IIa, may cause a range of clinical phenotypes including infantile hypercalcemia, a proximal renal Fanconi syndrome, which are typically autosomal recessive, and hypophosphatemic nephrolithiasis, which may be an autosomal dominant trait. Here, we report two patients with mixed clinical phenotypes, both with metabolic acidosis, hyperphosphaturia, and renal stones. Patient A had a single heterozygous pathogenic missense mutation (p.I456N) in SLC34A1, consistent with the autosomal dominant pattern of renal stone disease in this family. Patient B, with an autosomal recessive pattern of disease, was compound heterozygous for SLC34A1 variants; a missense variant (p.R512C) together with a relatively common in‐frame deletion p.V91A97del7 (91del7). Xenopus oocyte and renal (HKC‐8) cell line transfection studies of the variants revealed limited cell surface localization, consistent with trafficking defects. Co‐expression of wild‐type and I456N and 91del7 appeared to cause intracellular retention in HKC‐8, whereas the R512C mutant had a less dominant effect. Expression in Xenopus oocytes failed to demonstrate a significant dominant negative effect for I456N and R512C; however, a negative impact of 91del7 on [32P]phosphate transport was found. In conclusion, we have investigated pathogenic alleles of SLC34A1 which contribute to both autosomal dominant and autosomal recessive renal stone disease.
Age alone is not a contraindication to kidney donation: Outcomes of donor nephrectomy in the elderly

With increasing organ demand, living kidney donation from older donors (>60‐years‐old) has become more common. Between 1975 and 2014, 3752 donor nephrectomies (DN) were performed at University of Minnesota; 167 (4.5%) were >60‐years‐old Short‐ and long‐term outcomes were compared between contemporaneous >60‐years‐old and <60‐years‐old donors. On univariate analysis, >60‐years‐old were more likely to have had prior abdominal surgery and hypertension; and less likely to smoke. Baseline estimated glomerular filtration rate (eGFR) was lower in >60‐years‐old (80 ± 16 vs 101 ± 26 mL/min/1.73 m2; P < .001). Intraoperative and postoperative complications were similar, except a higher prevalence of <30 day ileus (3% vs 7%; P = .021) and longer postoperative length of stay (LOS) (4.2 vs 4.6 days; P = .005). On multivariate analysis, <30 day ileus and LOS continued to be significantly greater for >60‐years‐old After >20 years post‐DN, systolic blood pressure was significantly higher among >60‐years‐old (142 vs 125 mm Hg; P < .001) and HTN was diagnosed earlier (9 vs 14 years). After donation, eGFR was significantly lower for >60‐years‐old but slope of eGFR and rates of end‐stage renal disease (ESRD) were not significantly different >20 years post‐DN. Thus, kidney donation among carefully selected >60‐years‐old poses minimal perioperative risks and no added risk of long‐term ESRD.
Adaptive voting aggregation for partial ballots in crowdsourcing

We evaluate rating aggregation methods for an online crowdsourcing platform, where users are allowed to submit partial ballots and change their votes over time. Our goal is to identify good content as accurately as possible, using a rating aggregation method that is difficult for users to manipulate. We modify Range voting, Borda count and Copeland’s method for partial ballots. We introduce a new method, which adapts to how users choose which items to rate. We evaluate all methods on synthetic data. If the synthetic agents submit top-truncated ballots, Borda count performs best, in the sense that it identifies the best content most often. If users submit randomly-censored partial ballots, then modified Range voting, Copeland’s method and User Preferences Ranking perform about equally well, and dramatically outperform Borda count. Our new adaptive method performs well across both conditions.
Bayesian Prediction of Future Street Scenes through Importance Sampling based Optimization

For autonomous agents to successfully operate in the real world, anticipation of future events and states of their environment is a key competence. This problem can be formalized as a sequence prediction problem, where a number of observations are used to predict the sequence into the future. However, real-world scenarios demand a model of uncertainty of such predictions, as future states become increasingly uncertain and multi-modal -- in particular on long time horizons. This makes modelling and learning challenging. We cast state of the art semantic segmentation and future prediction models based on deep learning into a Bayesian formulation that in turn allows for a full Bayesian treatment of the prediction problem. We present a new sampling scheme for this model that draws from the success of variational autoencoders by incorporating a recognition network. In the experiments we show that our model outperforms prior work in accuracy of the predicted segmentation and provides calibrated probabilities that also better capture the multi-modal aspects of possible future states of street scenes.
Prevention of Clinically-relevant Postoperative Pancreatic Fistula After Pancreticoduodenectomy.

1. Markar SR, Mackenzie H, Lagergren P, et al. Surgeon age in relation to prognosis after esophageal cancer resection. Ann Surg. 2017. doi: 10.1097/ SLA.0000000000002260. [Epub ahead of print]. 2. Yun YH, Kim YA, Min YH, et al. The influence of hospital volume and surgical treatment delay on long-term survival after cancer surgery. Ann Oncol. 2012;23:2731–2737. 3. Liu CJ, Chou YJ, Teng CJ, et al. Association of surgeon volume and hospital volume with the outcome of patients receiving definitive surgery for colorectal cancer: a nationwide population-based study. Cancer. 2015;121:2782–2790. 4. Derogar M, Sadr-Azodi O, Johar A, et al. Hospital and surgeon volume in relation to survival after esophageal cancer surgery in a population-based study. J Clin Oncol. 2013;31:551–557. 5. Neumayer LA, Gawande AA, Wang J, et al. Proficiency of surgeons in inguinal hernia repair: effect of experience and age. Ann Surg. 2005;242:344– 348. 6. Liang Y, Wu L, Wang X, et al. The positive impact of surgeon specialization on survival for gastric cancer patients after surgery with curative intent. Gastric Cancer. 2015;18:859–867. 7. Li P, Huang CM, Lin JX, et al. A preoperatively predictive difficulty scoring system for laparoscopic spleen-preserving splenic hilar lymph node dissection for gastric cancer: experience from a large-scale single center. Surg Endosc. 2016;30:4092–4101. 8. Martinez A, Ngo C, Leblanc E, et al. Surgical complexity impact on survival after complete cytoreductive surgery for advanced ovarian cancer. Ann Surg Oncol. 2016;23:2515–2521.
Transdifferentiation of human gingival mesenchymal stem cells into functional keratinocytes by Acalypha indica in three‐dimensional microenvironment

Gingival tissue is reportedly a promising, easily accessible, abundant resource of mesenchymal stem cells (MSC) for use in various tissue engineering strategies. Human gingival MSC (HGMSCs) were successfully isolated from gingival tissue and characterized. To analyze in a two‐dimensional form, HGMSCs were cultured with basal medium and induced with 25 µg/ml of Acalypha indica. Quantitative real‐time polymerase chain reaction (qPCR) and western blot analysis showed the presence of keratinocyte‐specific markers, including cytokeratin‐5 and involucrin. To further assess its capability for stratification akin to human keratinocytes, HGMSCs were encapsulated in a HyStem®‐HP Cell Culture Scaffold Kit and cultured in the presence of A. indica. Calcein AM staining indicated that the HyStem®‐HP Scaffold Kit has excellent biocompatibility. Immunofluorescence and qPCR analysis revealed the presence of keratinocyte‐specific markers. The study concluded that the three‐dimensional microenvironment is a novel method for inducing epidermal differentiation of HGMSCs to engineer epidermal substitutes with the help of A. indica, which provides an alternative strategy for skin tissue engineering.
Long-term spatiotemporal stability and dynamic changes in helminth infracommunities of spiny mice (Acomys dimidiatus) in St. Katherine's Protectorate, Sinai, Egypt

Abstract The importance of parasites as a selective force in host evolution is a topic of current interest. However, short-term ecological studies of host–parasite systems, on which such studies are usually based, provide only snap-shots of what may be dynamic systems. We report here on four surveys, carried out over a period of 12 years, of helminths of spiny mice (Acomys dimidiatus), the numerically dominant rodents inhabiting dry montane wadis in the Sinai Peninsula. With host age (age-dependent effects on prevalence and abundance were prominent) and sex (female bias in abundance in helminth diversity and in several taxa including Cestoda) taken into consideration, we focus on the relative importance of temporal and spatial effects on helminth infracommunities. We show that site of capture is the major determinant of prevalence and abundance of species (and higher taxa) contributing to helminth community structure, the only exceptions being Streptopharaus spp. and Dentostomella kuntzi. We provide evidence that most (notably the Spiruroidea, Protospirura muricola, Mastophorus muris and Gongylonema aegypti, but with exceptions among the Oxyuroidae, e.g. Syphacia minuta), show elements of temporal-site stability, with a rank order of measures among sites remaining similar over successive surveys. Hence, there are some elements of predictability in these systems.
The GBA p.Trp378Gly mutation is a probable French‐Canadian founder mutation causing Gaucher disease and synucleinopathies

Biallelic GBA mutations cause Gaucher disease (GD), and heterozygous carriers are at risk for synucleinopathies. No founder GBA mutations in French‐Canadians are known. GBA was fully sequenced using targeted next generation and Sanger sequencing in French‐Canadian Parkinson disease (PD) patients (n = 436), rapid eye movement (REM)‐sleep behavior disorder (RBD) patients (n = 189) and controls (n = 891). Haplotype, identity‐by‐descent (IBD) and principal component analyses (PCA) were performed using single nucleotide polymorphism‐chip data. Data on GD patients from Toronto and Montreal were collected from patients' files. A GBA p.Trp378Gly mutation was identified in two RBD and four PD patients (1% of all patients combined), and not in controls. The two RBD patients had converted to DLB within 3 years of their diagnosis. Haplotype, IBD and PCA analysis demonstrated that this mutation is from a single founder. Out of 167 GD patients screened, 15 (9.0%) carried the p.Trp378Gly mutation, all in trans with p.Asn370Ser. Three (20%) of the GD patients with the p.Trp378Gly mutation had developed Parkinsonism, and 11 patients had family history of PD. The p.Trp378Gly mutation is the first French‐Canadian founder GBA mutation to be described, which leads to synucleinopathies and to GD type 1 when in compound heterozygosity with p.Asn370Ser.