Miracle-dz/UniFAR-FTUs huggingface dataset:
Comparison of Implant-Based Immediate Breast Reconstruction with and without Acellular Dermal Matrix

Background: Acellular dermal matrix is frequently used in implant-based breast reconstruction to cover the inferior aspect of the breast pocket. Its performance profile remains equivocal. The authors studied whether adding it in implant-based immediate breast reconstruction improved outcomes when compared with non–acellular dermal matrix reconstruction. Methods: Patients undergoing implant-based immediate breast reconstruction at a single academic medical center were evaluated. Aesthetic outcomes and postoperative complications were assessed and direct comparisons were made between acellular dermal matrix and non–acellular dermal matrix cohorts. Results: A total of 203 patients underwent 337 immediate expander-based breast reconstructions [with acellular dermal matrix, n = 208 (61.7 percent); without, n = 129 (38.3 percent)]. Patient characteristics, including age at time of reconstruction (mean, 49 ± 11 versus 47 ± 10 years) and body mass index (mean, 23 ± 5 versus 23 ± 3 kg/m2) were similar between groups (p > 0.05). Complications occurred in one-third of patients (33.5 percent). In univariate analyses, acellular dermal matrix use had fewer overall complications (odds ratio, 0.61; 95 percent CI, 0.38 to 0.97). The incidences of seroma/hematoma (p = 0.59), infection (p = 0.31), and wound complications (p = 0.26) did not differ. Aesthetic outcomes were higher in the acellular dermal matrix group. In multivariate logistic regression, acellular dermal matrix use was associated with less capsular contracture (odds ratio, 0.18; 95 percent CI, 0.08 to 0.43) and mechanical shift (odds ratio, 0.23; 95 percent CI, 0.06 to 0.78). Conclusions: Optimizing the inframammary fold with acellular dermal matrix creates a superior aesthetic result. Its use appears safe and is associated with less capsular contracture and mechanical shift and improvement in the inframammary fold appearance, without increasing postoperative complications. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.
Group Identification and Outgroup Attitudes in Four South African Ethnic Groups: A Multidimensional Approach

Although Sumner’s ethnocentrism hypothesis, which expects stronger group identification to be associated with more negative outgroup attitudes, has been widely accepted, empirical findings have been inconsistent. This research investigates the relationship of four dimensions of ethnocultural group identification previously proposed by Phinney, that is, salience, evaluation, attachment, and involvement, with attitudes to ethnic outgroups in four South African ethnocultural groups (Africans, Afrikaans Whites, English Whites, Indians). The findings supported the factorial independence of the four identification dimensions and indicated that only one, ethnocultural evaluation (ingroup attitudes), was systematically related to outgroup attitudes, but the association could be positive, negative, or zero. Both functionalist and similarity-dissimilarity approaches to intergroup relations seemed to provide plausible explanations for the pattern of relationships obtained between ingroup and outgroup attitudes.
Is there a similarity between DNA damage in adults with chronic alcoholism and community-dwelling healthy older adults?

AIMS Daily alcohol consumption and ageing have been linked with DNA damage, leading to the hypothesis that chronic alcoholism causes DNA damage similar to that which occurs with ageing. Likewise, it has been suggested that chronic alcoholism is the cause of accelerated or premature ageing. The objective of this study was to evaluate the frequency and magnitude of DNA damage among adults with chronic alcoholism and healthy older adults residing in Mexico City. METHODS A cross-sectional and comparative study was carried out in a sample of 53 chronic alcoholics of 25-44 years of age (without alcohol ingestion in the past 30 days) without additional diseases, 26 healthy subjects >or=60 years of age, and 25 healthy adults of 25-44 years of age without alcohol addiction, all residents of Mexico City during the past 10 years. DNA damage was evaluated by single-cell gel electrophoresis technique (Comet assay). RESULTS Our results showed a similar percentage of DNA damage between healthy elderly subjects and chronic alcoholics (62 vs 55%, P >0.05), although average DNA migration was greater in alcoholics than in the elderly (78.1 +/- 33.2 vs 58.6 +/- 26.2, P = 0.09). However, the percentage of subjects with more than six damaged cells was higher in the older adults subjects group than in the group chronic alcoholics (19 vs 35%, P = 0.16). CONCLUSIONS Data suggest that DNA damage is not similar in young subjects with chronic alcoholism that which occurs with ageing.
Denosumab for the prevention of skeletal complications in metastatic castration-resistant prostate cancer: comparison of skeletal-related events and symptomatic skeletal events

Data shown are the first of each SRE/SSE event type (radiation to bone, fracture, or surgery to bone, or spinal cord compression) without considering when the other event types first occurred. For SSE, the incidence of symptomatic pathologic fractures and symptomatic spinal cord compression is shown. For SRE, the incidence of pathologic fractures and spinal cord compression is shown. For first and subsequent skeletal events, regardless of whether assessed as SRE or SSE, only events occurring ≥21 days after the previous event were counted, and if multiple event types occurred on the same day, only one event was counted based on the following priority order (based on severity): (i) spinal cord compression, (ii) surgery to bone, (iii) fracture, and (iv) radiation to bone. For these reasons, some first and subsequent events may not have been counted, resulting in a lower incidence than first skeletal events (e.g. 15 versus 24 surgery to bone events assessed as SSE). co rr ig en du m corrigendum Annals of Oncology 26: 1274, 2015 doi:10.1093/annonc/mdv155
Online Stochastic Optimization in the Large: Application to Kidney Exchange

Kidneys are the most prevalent organ transplants, but demand dwarfs supply. Kidney exchanges enable willing but incompatible donor-patient pairs to swap donors. These swaps can include cycles longer than two pairs as well, and chains triggered by altruistic donors. Current kidney exchanges address clearing (deciding who gets kidneys from whom) as an offline problem: they optimize the current batch. In reality, clearing is an online problem where patient-donor pairs and altruistic donors appear and expire over time. In this paper, we study trajectory-based online stochastic optimization algorithms (which use a recent scalable optimal offline solver as a subroutine) for this. We identify tradeoffs in these algorithms between different parameters. We also uncover the need to set the batch size that the algorithms consider an atomic unit. We develop an experimental methodology for setting these parameters, and conduct experiments on real and generated data. We adapt the REGRETS algorithm of Bent and van Hentenryck for the setting. We then develop a better algorithm. We also show that the AMSAA algorithm of Mercier and van Hentenryck does not scale to the nationwide level. Our best online algorithm saves significantly more lives than the current practice of solving each batch separately.
Nonlinear Dynamic Modelling of Platelet Aggregation via Microfluidic Devices

The recent application of new microfluidic technologies and methods has facilitated significant progress in the understanding of the fundamental mechanisms governing blood platelet function and how these parameters affect pathological thrombus formation. In-line with these new bioengineering approaches, the application of nonlinear dynamic systems analysis holds particular potential to extend our understanding of the complex interplay between mechanical and biochemical factors that underlie this complex biological phenomenon. In this paper we propose a simple mathematical model of the main dynamics of platelet aggregation/disaggregation observed experimentally in a novel microfluidic device that approximates a severe arterial stenosis. We apply dynamic systems theory (system identification) to explore the dynamics of the biomechanical platelet aggregation response to a range of shear stress rates, inhibiting blood-born chemical pathways of platelet activation (ADP, TXA2, and thrombin). We demonstrate that the proposed model is able to replicate experimental results with low variation, and suggest that the reduced set of model parameters has the potential to be used as a simplified way to evaluate the biomechanical dynamics of platelet aggregation. The proposed model has application to the development of automatic controllers within the context of microfluidic systems that may show great utility in the clinical assessment of platelet hyperfunction.
Predicting patients' exposure to cyclosporin

Abstract The introduction of a new formulation of cyclosporin, Neoral, has reduced pharmacokinetic variability and it may be possible to simplify area‐under‐curve (AUC) measurements using a limited sampling strategy. We have examined the timing of blood samples necessary to obtain accurate AUC predictions for cyclosporin using limited data from stable renal transplant patients dosed twice daily with Neoral. Best subset regression of blood concentration profile data obtained from ten patients at steady state indicated that two samples, timed at 2 and 8 h post‐dose, accounted for 97 % of the variance in AUC. The accuracy of this prediction was tested using profile data collected in a further 36 patients on three occasions separated by 4 and 44 weeks. Using the regression, AUC = 1.96 × [2 h] + 11.5 × [8 h] + 355.2, the mean (95 % CI) prediction errors of the three occasions were 1.7 % (‐ 2.1–5.4 %), 3.3 % (‐ 2.6–9.2 %) and 0.4 % (‐ 3.4–4.2 %). Data are presented that suggest AUC monitoring with a single blood sample could be feasible in a clinical setting.
Impact of training volume and intensity on RBC-NOS/NO pathway and endurance capacity.

BACKGROUND Acute exercise increases red blood cell-nitric oxide synthase (RBC-NOS) activation and RBC deformability but the effect of regular training remains unclear. OBJECTIVE To detect the chronic effect of enduring moderate and high intensity training on the RBC-NOS/NO pathway and to detect a relation between RBC deformability and endurance capacity. METHODS 38 healthy male subjects were randomly assigned to one of three training groups: High Volume Training (HVT; 120-140 beats per minute (bpm)), High Intensity Training (HIT; 160-180 bpm) and Moderate Intensity Training (MIT; 140-160 bpm). Blood parameters, maximum oxygen capacity (VO2 max), RBC deformability, RBC nitrite level and RBC-NOS activation were measured after venous blood sampling at rest pre (T0) and after six weeks of training (T1). RESULTS RBC-NOS activation, RBC nitrite concentration and RBC deformability were significantly increased at T1 in the HIT group. Parameters were unaltered in MIT and HVT. Maximum oxygen uptake was only significantly increased in the HIT group and regression analysis revealed positive regression between VO2 max and RBC deformability. CONCLUSIONS High intensity training was the only training programme that sustainably affected RBC-NOS dependent NO production and performance capacity. HIT therefore represents a time efficient training program resulting in improved RBC function potentially improving physical condition.
TRIM27 Negatively Regulates NOD2 by Ubiquitination and Proteasomal Degradation

NOD2, the nucleotide-binding domain and leucine-rich repeat containing gene family (NLR) member 2 is involved in mediating antimicrobial responses. Dysfunctional NOD2 activity can lead to severe inflammatory disorders, but the regulation of NOD2 is still poorly understood. Recently, proteins of the tripartite motif (TRIM) protein family have emerged as regulators of innate immune responses by acting as E3 ubiquitin ligases. We identified TRIM27 as a new specific binding partner for NOD2. We show that NOD2 physically interacts with TRIM27 via the nucleotide-binding domain, and that NOD2 activation enhances this interaction. Dependent on functional TRIM27, ectopically expressed NOD2 is ubiquitinated with K48-linked ubiquitin chains followed by proteasomal degradation. Accordingly, TRIM27 affects NOD2-mediated pro-inflammatory responses. NOD2 mutations are linked to susceptibility to Crohn's disease. We found that TRIM27 expression is increased in Crohn's disease patients, underscoring a physiological role of TRIM27 in regulating NOD2 signaling. In HeLa cells, TRIM27 is partially localized in the nucleus. We revealed that ectopically expressed NOD2 can shuttle to the nucleus in a Walker A dependent manner, suggesting that NOD2 and TRIM27 might functionally cooperate in the nucleus. We conclude that TRIM27 negatively regulates NOD2-mediated signaling by degradation of NOD2 and suggest that TRIM27 could be a new target for therapeutic intervention in NOD2-associated diseases.
Long-term assessment of the risk of spread in primary late-onset focal dystonia

Background: Primary late-onset focal dystonias may spread over time to adjacent body regions, but differences in the risk of spread over time among the various focal forms and the influence of age at dystonia onset on the risk of spread are not well established. Methods: Patients presenting with primary late-onset focal blepharospasm (BSP, n = 124), cervical dystonia (CD, n = 73) and focal hand dystonia (FHD, n = 24) with 10 years or more of disease duration (mean ± SD, 15.3 (SD 4.9) years) were included in the study. The relationship between demographic/clinical variables and spread of dystonia was assessed by Kaplan–Meier survival curves and Cox proportional hazard regression models. Results: Patients starting with BSP, CD and FHD had similar age, sex and disease duration. Age at dystonia onset, age at initial spread and the risk of initial spread were significantly higher, whereas time elapsing from onset to initial spread was significantly lower in the BSP group than in those with onset in the neck or in the upper extremities. Conversely, these parameters were similar in the CD and FHD groups. The greater risk of spread in the BSP group was mainly evident in the first 5 years of history; thereafter, it declined and became similar to that of patients with CD/FHD. The difference in the risk of initial spread by site of onset was partly confounded by age at dystonia onset. Site of and age at dystonia onset, and age at first spread, were not significant predictors of the risk of a second spread. Conclusion: This study adds new insights into the phenomenon of spread of primary late-onset focal dystonia and provides the framework for future studies aimed at an indepth investigation of the mechanism(s) of spread.
Randomized comparison of effectiveness of unimodal opioid analgesia with multimodal analgesia in post–cesarean section pain management

Background Postoperative pain leads to patient discomfort, decreased level of satisfaction, prolonged recovery, and higher health costs. Acute pain control therefore improves the overall quality of life in patients undergoing cesarean section. Pain relief is a fundamental human right, but there is no gold standard for post–cesarean section pain management. Objective To compare the efficacy of pentazocine and tramadol used in unimodal and multimodal (in combination with piroxicam) approach, in the management of post–cesarean section pain. Materials and methods This study employed a random allocation design to compare the effectiveness of intramuscular pentazocine (60 mg) or tramadol (100 mg) as single analgesic agent and in combination with daily intramuscular piroxicam 20 mg, for the management of post–cesarean section pain during the immediate 12 hours after surgery. The primary outcome measure was control of postoperative pain, while the secondary outcome measures were the analgesic agent onset of action, duration of action, patient satisfaction, and maternal and neonatal adverse outcomes. Data obtained were entered into a predesigned sheet and analyzed with the Statistical Package for Social Sciences version 17. Means ± standard deviation (SD) were calculated for the quantitative variables, and the difference between two independent groups was compared using unpaired Student’s t-test. The level of significance was set at 0.05. Results A total of 120 patients were equally and randomly allocated to four study groups – two that received unimodal analgesia (the pentazocine group and the tramadol group) and two that received multimodal analgesia (the pentazocine-piroxicam group and the tramadol-piroxicam group). Among the unimodal groups, tramadol had a faster onset of action, but pentazocine had a longer duration of action and provided better control of pain. Among the multimodal groups, the combination of pentazocine with piroxicam was superior to the tramadol with piroxicam combination, and it was also more effective than pentazocine alone. Conclusion The multimodal approach of combining pentazocine with piroxicam is a safe, effective, and an acceptable mode of analgesia for post–cesarean section pain management, especially in a resource-constrained setting.
Social networks and Internet connectivity effects

This paper explores the impact of communication media and the Internet on connectivity between people. Results from a series of social network studies of media use are used as background for exploration of these impacts. These studies explored the use of all available media among members of an academic research group and among distance learners. Asking about media use as well as about the strength of the tie between communicating pairs revealed that those more strongly tied used more media to communicate than weak ties, and that media use within groups conformed to a unidimensional scale, showing a configuration of different tiers of media use supporting social networks of different ties strengths. These results lead to a number of implications regarding media and Internet connectivity, including: how media use can be added to characteristics of social network ties; how introducing a medium can create latent tie connectivity among group members that provides the technical means for activating weak ties, and also how a change in a medium can disrupt existing weak tie networks; how the tiers of media use also suggest that certain media support different kinds of information flow; and the importance of organization-level decisions about what media to provide and promote. The paper concludes with a discussion of implications for Internet effects.
Exceptions to Generics: Where Vagueness, Context Dependence and Modality Interact

This paper deals with the exceptions-tolerance property of generic sentences with indefinite singular and bare plural subjects (IS and BP generics, respectively) and with the way this property is connected to some well-known observations about felicity differences between the two types of generics (e.g. Lawler's 1973, Madrigals are popular vs. #A madrigal is popular). I show that whereas both IS and BP generics tolerate exceptional and contextually irrelevant individuals and situations in a strikingly similar way, which indicates the existence of a basically equivalent tolerance mechanism, there is also a difference between them, unnoticed so far, which concerns the degree to which the properties of the legitimate exceptions can be characterized in advance. Following claims in Greenberg (2003), I argue that both this newly observed difference as well as the traditional felicity differences result from an underlying contrast in the type of 'non-accidentalness' expressed by the two types of generic sentences, and more formally, in the accessibility relations that their generic quantifier (Gen) is compatible with. To capture the new difference in tolerance of exceptions, I develop an improved version of the exceptions-tolerance mechanism for generic sentences suggested in Kadmon & Landman (1993), namely, a restriction on the set of individuals and situations quantified by Gen, which is partially vague to two different degrees using supervaluationist methods. The different degrees of vagueness in this restriction are shown to be systematically dependent on the two types of accessibility relations that IS and BP generics are compatible with, which are redefined as precise and vague restrictions on the generic quantification over worlds.
Cataract-Causing Mutation of Human Connexin 46 Impairs Gap Junction, but Increases Hemichannel Function and Cell Death

Connexin channels play a critical role in maintaining metabolic homeostasis and transparency of the lens. Mutations in connexin genes are linked to congenital cataracts in humans. The G143R missense mutation on connexin (Cx) 46 was recently reported to be associated with congenital Coppock cataracts. Here, we showed that the G143R mutation decreased Cx46 gap junctional coupling in a dominant negative manner; however, it significantly increased gap junctional plaques. The G143R mutant also increased hemichannel activity, inversely correlated with the level of Cx46 protein on the cell surface. The interaction between cytoplasmic loop domain and C-terminus has been shown to be involved in gating of connexin channels. Interestingly, the G143R mutation enhanced the interaction between intracellular loop and Cx46. Furthermore, this mutation decreased cell viability and the resistance of the cells to oxidative stress, primarily due to the increased hemichannel function. Together, these results suggest that mutation of this highly conserved residue on the cytoplasmic loop domain of Cx46 enhances its interaction with the C-terminus, resulting in a reduction of gap junction channel function, but increased hemichannel function. This combination leads to the development of human congenital cataracts.
The Lateral Membrane Organization and Dynamics of Myelin Proteins PLP and MBP Are Dictated by Distinct Galactolipids and the Extracellular Matrix

In the central nervous system, lipid-protein interactions are pivotal for myelin maintenance, as these interactions regulate protein transport to the myelin membrane as well as the molecular organization within the sheath. To improve our understanding of the fundamental properties of myelin, we focused here on the lateral membrane organization and dynamics of peripheral membrane protein 18.5-kDa myelin basic protein (MBP) and transmembrane protein proteolipid protein (PLP) as a function of the typical myelin lipids galactosylceramide (GalC), and sulfatide, and exogenous factors such as the extracellular matrix proteins laminin-2 and fibronectin, employing an oligodendrocyte cell line, selectively expressing the desired galactolipids. The dynamics of MBP were monitored by z-scan point fluorescence correlation spectroscopy (FCS) and raster image correlation spectroscopy (RICS), while PLP dynamics in living cells were investigated by circular scanning FCS. The data revealed that on an inert substrate the diffusion rate of 18.5-kDa MBP increased in GalC-expressing cells, while the diffusion coefficient of PLP was decreased in sulfatide-containing cells. Similarly, when cells were grown on myelination-promoting laminin-2, the lateral diffusion coefficient of PLP was decreased in sulfatide-containing cells. In contrast, PLP's diffusion rate increased substantially when these cells were grown on myelination-inhibiting fibronectin. Additional biochemical analyses revealed that the observed differences in lateral diffusion coefficients of both proteins can be explained by differences in their biophysical, i.e., galactolipid environment, specifically with regard to their association with lipid rafts. Given the persistence of pathological fibronectin aggregates in multiple sclerosis lesions, this fundamental insight into the nature and dynamics of lipid-protein interactions will be instrumental in developing myelin regenerative strategies.