Miracle-dz/UniFAR-FTUs huggingface dataset:
Peritoneal microdialysis as a tool for detecting anastomotic leakage in patients after left-side colon and rectal resection. A systematic review

Abstract Objective: The objective was to evaluate peritoneal microdialysis in the detection of clinical anastomotic leakage after left-sided colon and rectal resection through a systematic review. Methods: A systematic review (PRISMA guidelines) based on a systematic search through PubMed, Cochrane Library, and EMBASE (1 February 2017) was performed. Methodological index of non-randomised studies score was selected to assess the methodological quality. Patient demographics and raw data for intraperitoneal microdialysis concentrations of glucose, lactate, glycerol and pyruvate for 5 d postoperative were obtained from the respective study groups. Results: Ten studies with a total of 128 patients were included. Thirty (23%) patients developed clinical anastomotic leakage. The area under the curve for intraperitoneal lactate concentration was significant higher in patients with anastomotic leakage (58.2; 95% CI 39.2, 77.2) compared with the no leakage group (41.0; 95% CI 35.2, 46.1; p = .007). Receiver operating characteristic curve analysis of the maximum measured lactate concentration demonstrated 25% sensitivity, 88% specificity and 74% accuracy for AL at a cut-off value of 9.8 mmol/L. The odds ratio for a 5 mmol/L increase in lactate in relation to the risk of AL was 2.9 (CI 1.1, 8.0). Conclusions: Increased intraperitoneal lactate concentration within the first 5 d postoperative was significantly associated with clinical anastomotic leakage, but with low predictive values. The microdialysis method is not yet ready for clinical implication before large prospective studies have defined cut off values for a biologic marker in the setting of a clear definitions of leakage.
Greater loss of mitochondrial function with ageing is associated with earlier onset of sarcopenia in C. elegans

Sarcopenia, the age-related decline of muscle, is a significant and growing public health burden. C. elegans, a model organism for investigating the mechanisms of ageing, also displays sarcopenia, but the underlying mechanism(s) remain elusive. Here, we use C. elegans natural scaling of lifespan in response to temperature to examine the relationship between mitochondrial content, mitochondrial function, and sarcopenia. Mitochondrial content and maximal mitochondrial ATP production rates (MAPR) display an inverse relationship to lifespan, while onset of MAPR decline displays a direct relationship. Muscle mitochondrial structure, sarcomere structure, and movement decline also display a direct relationship with longevity. Notably, the decline in mitochondrial network structure occurs earlier than sarcomere decline, and correlates more strongly with loss of movement, and scales with lifespan. These results suggest that mitochondrial function is critical in the ageing process and more robustly explains the onset and progression of sarcopenia than loss of sarcomere structure.
Association Between Lymph Node Ratio and Recurrence and Survival Outcomes in Patients With Oral Cavity Cancer

Importance Oral cavity squamous cell carcinoma (OCSCC) is associated with often-delayed clinical diagnosis, poor prognosis, and expensive therapeutic approaches. Prognostic accuracy is important in improving treatment outcomes of patients with this disease. Objectives To assess lymph node ratio (LNR) and other factors in estimating response to treatment and provide prognostic information helpful for clinical decision making. Design, Setting, and Participants A retrospective cohort study was conducted from January 1, 2000, to December 31, 2015, at an academic hospital in Denver, Colorado. Participants included 149 patients with primary OCSCC who received curative-intent surgery and/or postoperative adjuvant therapies. Analysis was performed from December 8, 2017, to August 15, 2018. Main Outcomes and Measures Overall survival (OS), disease-free survival (DFS), locoregional disease-free survival (LRDFS), and distant metastasis–free survival (DMDFS) adjusted for known prognostic risk factors, as well as correlation of LNR with other histopathologic prognostic factors. Results Of the 149 patients included in analysis, 105 were men (70.5%); the median age at diagnosis was 59 years (range, 28-88 years). Using the Kaplan-Meier method, the 5-year survival estimates for OS rate was 40.4% (95% CI, 31.3%-49.3%); DFS, 48.6% (95% CI, 38.6%-58.0%); LRDFS, 57.7% (95% CI, 46.6%-67.2%); and DMDFS, 74.7% (95% CI, 65.1%-82.0%). The median follow-up was 20 months for all patients and 34.5 months (range, 0-137 months) for surviving patients. Nonwhite race (hazard ratio [HR], 2.15; 95% CI, 1.22-3.81), T3-T4 category (HR, 1.99; 95% CI, 1.18-3.35), and LNR greater than 10% (HR, 2.71; 95% CI, 1.39-5.27) were associated with poorer OS. Nonwhite patients also had higher risk of locoregional failures (HR, 2.47; 95% CI, 1.28-4.79), whereas women were more likely to have distant metastasis (HR, 2.55; 95% CI, 1.14-5.71). Floor-of-mouth subsite had fewer locoregional recurrences than did other subsites (HR, 0.45, 95% CI, 0.21-0.99). An LNR greater than 10% independently was associated with worse OS (HR, 2.71; 95% CI, 1.39-5.27), DFS (HR, 2.48; 95% CI, 1.18-5.22), and DMDFS (HR, 6.05; 95% CI, 1.54-23.71). The LNR was associated with N-stage (Cramer V, 0.69; 95% CI, 0.58-0.78), extracapsular extension (Cramer V, 0.55; 95% CI, 0.44-0.66), lymphovascular invasion (Cramer V, 0.46; 95% CI, 0.27-0.61); number of excised lymph nodes (Cramer V, 0.24; 95% CI, 0.06-0.37), margin (Cramer V, 0.22; 95% CI, 0.05-0.38), and tumor thickness combined with depth of invasion (Cramer V, 0.25; 95% CI, 0.05-0.38). Conclusions and Relevance Locoregional treatment failure remained the predominant pattern of failure. An advanced pathologic stage and nonwhite race were found to be associated with worse outcomes. The findings from this study suggest that LNR is the most robust prognostic factor and appears to have implications for risk stratification in this disease.
3-min all-out effort on cycle ergometer is valid to estimate the anaerobic capacity by measurement of blood lactate and excess post-exercise oxygen consumption

Abstract The purpose of this study was to investigate the use of a single 3-min all-out maximal effort to estimate anaerobic capacity (AC) through the lactate and excess post-exercise oxygen consumption (EPOC) response methods (AC[La−]+EPOCfast) on a cycle ergometer. Eleven physically active men (age = 28.1 ± 4.0 yrs, height = 175.1 ± 4.2 cm, body mass = 74.8 ± 11.9 kg and ⩒O2max = 40.7 ± 7.3 mL kg−1 min−1), participated in the study and performed: i) five submaximal efforts, ii) a supramaximal effort at 115% of intensity of ⩒O2max, and iii) a 3-min all-out maximal effort. Anaerobic capacity was estimated using the supramaximal effort through conventional maximal accumulated oxygen deficit (MAOD) and also through the sum of oxygen equivalents from the glycolytic (fast component of excess post-exercise oxygen consumption) and phosphagen pathways (blood lactate accumulation) (AC[La−]+EPOCfast), while during the 3-min all-out maximal effort the anaerobic capacity was estimated using the AC[La−]+EPOCfast procedure. There were no significant differences between the three methods (p > 0.05). Additionally, the anaerobic capacity estimated during the 3-min all-out effort was significantly correlated with the MAOD (r = 0.74; p = 0.009) and AC[La−]+EPOCfast methods (r = 0.65; p = 0.029). Therefore, it is possible to conclude that the 3-min all-out effort is valid to estimate anaerobic capacity in physically active men during a single cycle ergometer effort.
Differential growth and shape formation in plant organs

Significance Plant leaves and flower petals in nature exhibit a wide variety of complex 3D shapes. Formation of these shapes has largely been studied from genetic and biomolecular viewpoints, overlooking contributions from biophysical factors such as mechanical stress and deformation. By means of computational simulations and quantitative analyses of the growth strains in live plant organs, we develop fundamental mechanistic insights into how nature invokes mechanics in the evolution of four commonly found shapes in plant organs by differential growth. We also demonstrate how these common shapes can be synthetically reproduced in hydrogel using this mechanistic understanding. Our study provides a broad scientific framework for rationalizing plant organ morphogenesis, but also provides pathways for generating bioinspired 3D architectures in soft materials. Morphogenesis is a phenomenon by which a wide variety of functional organs are formed in biological systems. In plants, morphogenesis is primarily driven by differential growth of tissues. Much effort has been devoted to identifying the role of genetic and biomolecular pathways in regulating cell division and cell expansion and in influencing shape formation in plant organs. However, general principles dictating how differential growth controls the formation of complex 3D shapes in plant leaves and flower petals remain largely unknown. Through quantitative measurements on live plant organs and detailed finite-element simulations, we show how the morphology of a growing leaf is determined by both the maximum value and the spatial distribution of growth strain. With this understanding, we develop a broad scientific framework for a morphological phase diagram that is capable of rationalizing four configurations commonly found in plant organs: twisting, helical twisting, saddle bending, and edge waving. We demonstrate the robustness of these findings and analyses by recourse to synthetic reproduction of all four configurations using controlled polymerization of a hydrogel. Our study points to potential approaches to innovative geometrical design and actuation in such applications as building architecture, soft robotics and flexible electronics.
Large Interruptions of GAA Repeat Expansion Mutations in Friedreich Ataxia Are Very Rare

Friedreich ataxia is a multi-system autosomal recessive inherited disorder primarily caused by homozygous GAA repeat expansion mutations within intron 1 of the frataxin gene. The resulting deficiency of frataxin protein leads to progressive mitochondrial dysfunction, oxidative stress, and cell death, with the main affected sites being the large sensory neurons of the dorsal root ganglia and the dentate nucleus of the cerebellum. The GAA repeat expansions may be pure (GAA)n in sequence or may be interrupted with regions of non-GAA sequence. To our knowledge, there has been no large-scale study of FRDA patient DNA samples to determine the frequency of large interruptions in GAA repeat expansions. Therefore, we have investigated a panel of 245 Friedreich ataxia patient and carrier DNA samples using GAA repeat PCR amplification and MboII restriction enzyme digestion. We demonstrate that the vast majority (97.8%) of Friedreich ataxia GAA repeat expansion samples do not contain significant sequence changes that would result in abnormal MboII digestion profiles, indicating that they are primarily pure GAA repeats. These results show for the first time that large interruptions in the GAA repeats are very rare.
Long-term follow-up of patients with myasthenia gravis treated with low-dose rituximab

Myasthenia gravis (MG) is a disease of the neuromuscular junction, usually caused by an autoimmune process associated with antibodies against the acetylcholine receptor (AChR) or muscle-specific kinase (MuSK). Rituximab (RTX), a monoclonal antibody targeting CD20, has emerged as a potential treatment in the management of MG, in particular for MuSK positive patients.1 2 Most (80%) patients received 375 mg/m2 of RTX per week for 4 weeks, with lower doses being infrequently reported. We previously reported on our experience with low-dose RTX in the treatment of MG3 and now report our long-term experience from an enlarged cohort. We identified retrospectively all patients with MG treated with RTX between May 2006 and July 2017 in South East Queensland, Australia. Cases were identified via review of pharmacy and hospital records as well as by direct contact with the treating neurologists. The clinical states of patients were scored using the Myasthenia Gravis Association of America (MGFA) Clinical Research Standards. Disease severity and concurrent therapies were documented through review of medical records (Timepoints: Diagnosis, RTX treatment, 3-monthly for the first year, annually thereafter). Wilcoxon ranked test was used to assess difference in steroid doses. ### Patient characteristics A total of 38 patients were treated (AChR: 28 patients (74%, female:male (F:M)=18:10), MuSK: six patients (16%, F:M=4:2), antibody negative four patients (10%, all female)). The mean age at initial treatment was 51.5 (range 22–87 years) with mean disease duration prior to …
An Empirical Analysis of Popular Press Claims Regarding Linguistic Change in President Donald J. Trump

Linguistic features of a person’s speech can change over time. It has been proposed that characteristics in the speech of President Donald J. Trump (DJT) have changed across time, though this claim has been based on subjective and anecdotal reports. A previous study of speech by Presidents of the United States identified an increase in the use of conversational fillers and non-specific nouns, and lower unique word counts, in the speech of President Ronald W. Reagan, but not in the speech of President George H.W. Bush. To empirically test claims of a systematic change in speech by DJT, we applied the same analysis by transcribing and analyzing publicly available Fox News interviews with DJT between 2011 and 2017. A regression analysis revealed a significant increase in the use of filler words by DJT over time. There was no significant change in numbers of unique words. The observed rise in filler words was significantly greater than filler-word change in President George H.W. Bush, and was not significantly different from the rise previously found in the speech of President Ronald W. Reagan. Identifying the reason for this linguistic change is not possible from speech samples alone, and the variables index linguistic change rather than being validated measures of change in cognitive ability. Nonetheless, features of the data such as the trajectory starting years before announcement of candidacy rule-out several potential explanations. To summarize, we find statistical evidence to support suggestions that speech by DJT has changed over time.
PPP3CB contributes to poor prognosis through activating nuclear factor of activated T‐cells signaling in neuroblastoma

We previously identified a gain‐of‐function mutation in PPP3CB in a neuroblastoma (NB) with MYCN amplification. Here we investigated the functional and clinical role of PPP3CB in NB. High PPP3CB expression was an independent indicator predicting poor prognosis of NB. Overexpression of wildtype or mutated PPP3CB (PPP3CBmut) promoted cell growth, but PPP3CB knockdown decreased cell growth in NB cells. Forced expressions of PPP3CB and PPP3CBmut activated NFAT2 and NFAT4 transcription factors and inhibited GSK3β activity, resulting in the increase in the expressions of c‐Myc, MYCN, and β‐catenin, which were downregulated in response to PPP3CB knockdown. Treatment with calcineurin inhibitor cyclosporin A (CsA) or FK506 suppressed cell proliferation and induced apoptotic cell death in both MYCN‐amplified and MYCN‐non‐amplified NB cell lines. Expression of PPP3CB protein was decreased in response to two calcineurin inhibitors. c‐Myc, MYCN, and β‐catenin were downregulated at the mRNA and protein levels in CsA or FK506‐treated NB cells. Our data indicate that elevated expression of PPP3CB and the expression of its constitutively active mutant contribute to the aggressive behavior of NB tumors and therefore suggest that inhibition of calcineurin activity might have therapeutic potential for high‐risk NB.
Understanding a Deep Machine Listening Model Through Feature Inversion

Methods for interpreting machine learning models can help one understand their global and/or local behaviours, and thereby improve them. In this work, we apply a global analysis method to a machine listening model, which essentially inverts the features generated in a model back into an interpretable form like a sonogram. We demonstrate this method for a state-of-the-art singing voice detection model. We train up-convolutional neural networks to in-vert the feature generated at each layer of the model. The results suggest that the deepest fully connected layer of the model does not preserve temporal and harmonic structures, but that the inverted features from the deepest convolutional layer do. Moreover, a qualitative analysis of a large number of inputs suggests that the deepest layer in the model learns a decision function as the information it preserves depends on the class label associated with an input.
From Labeled to Unlabeled Data - On the Data Challenge in Automatic Drum Transcription

Automatic Drum Transcription (ADT), like many other music information retrieval tasks, has made progress in the past years through the integration of machine learning and audio signal processing techniques. However, with the increasing popularity of data-hungry approaches such as deep learning, the insufﬁcient amount of data becomes more and more a challenge that concerns the generality of the resulting models and the validity of the evaluation. To address this challenge in ADT, this paper ﬁrst examines the existing labeled datasets and how representative they are of the research problem. Next, possibilities of using unlabeled data to improve general ADT systems are explored. Speciﬁcally, two paradigms that harness information from unlabeled data, namely feature learning and student-teacher learning, are applied to two major types of ADT systems. All systems are evaluated on four different drum datasets. The results highlight the necessity of more and larger annotated datasets and indicate the feasibility of exploiting unlabeled data for improving ADT systems.
High-Dose Rifamycins Enable Shorter Oral Treatment in a Murine Model of Mycobacterium ulcerans Disease

Buruli ulcer (BU), caused by Mycobacterium ulcerans, is a neglected tropical skin and soft tissue infection that is associated with disability and social stigma. The mainstay of BU treatment is an 8-week course of rifampin (RIF) at 10 mg/kg of body weight and 150 mg/kg streptomycin (STR). ABSTRACT Buruli ulcer (BU), caused by Mycobacterium ulcerans, is a neglected tropical skin and soft tissue infection that is associated with disability and social stigma. The mainstay of BU treatment is an 8-week course of rifampin (RIF) at 10 mg/kg of body weight and 150 mg/kg streptomycin (STR). Recently, the injectable STR has been shown to be replaceable with oral clarithromycin (CLR) for smaller lesions for the last 4 weeks of treatment. A shorter, all-oral, highly efficient regimen for BU is needed, as the long treatment duration and indirect costs currently burden patients and health systems. Increasing the dose of RIF or replacing it with the more potent rifamycin drug rifapentine (RPT) could provide such a regimen. Here, we performed a dose-ranging experiment of RIF and RPT in combination with CLR over 4 weeks of treatment in a mouse model of M. ulcerans disease. A clear dose-dependent effect of RIF on both clinical and microbiological outcomes was found, with no ceiling effect observed with tested doses up to 40 mg/kg. RPT-containing regimens were more effective on M. ulcerans. All RPT-containing regimens achieved culture negativity after only 4 weeks, while only the regimen with the highest RIF dose (40 mg/kg) did so. We conclude that there is dose-dependent efficacy of both RIF and RPT and that a ceiling effect is not reached with the current standard regimen used in the clinic. A regimen based on higher rifamycin doses than are currently being evaluated against tuberculosis in clinical trials could shorten and improve therapy of Buruli ulcer.
Programming of CD8 T Cell Quantity and Polyfunctionality by Direct IL-1 Signals

IL-1, generally considered an amplifier of adaptive immune responses, has been proposed for use as adjuvant during immunization with weak immunogens. However, its effects on memory T cell function remain largely undefined. Using the murine model of acute viral infection, in this paper, we show that in addition to augmenting the size of the Ag-specific pool, IL-1 signals act directly on CD8 T cells to promote the quality of effector and memory responses. Ablation of IL-1R1 or MyD88 signaling in T cells led to functional impairment; both the ability to produce multiple cytokines on a per cell basis (polyfunctionality) and the potential for recall proliferation in response to antigenic restimulation were compromised. IL-1 supplementation during priming augmented the expansion of Ag-specific CD8 T cells through the MyD88–IRAK1/4 axis, resulting in a larger memory pool capable of robust secondary expansion in response to rechallange. Together, these findings demonstrate a critical role of the IL-1–MyD88 axis in programming the quantity and quality of memory CD8 T cell responses and support the notion that IL-1 supplementation may be exploited to enhance adoptive T cell therapies against cancers and chronic infections.
Mesenchymal Stem Cell–Derived Small Extracellular Vesicles Promote Neuroprotection in a Genetic DBA/2J Mouse Model of Glaucoma

Purpose To determine if bone marrow-derived stem cell (BMSC) small extracellular vesicles (sEV) promote retinal ganglion cell (RGC) neuroprotection in the genetic DBA/2J mouse model of glaucoma for 12 months. Methods BMSC sEV and control fibroblast-derived sEV were intravitreally injected into 3-month-old DBA/2J mice once a month for 9 months. IOP and positive scotopic threshold responses were measured from 3 months: IOP was measured monthly and positive scotopic threshold responses were measured every 3 months. RGC neuroprotection was determined in wholemounts stained with RNA binding protein with multiple splicing (RBPMS), whereas axonal damage was assessed using paraphenylenediamine staining. Results As expected, DBA/2J mice developed chronic ocular hypertension beginning at 6 months. The delivery of BMSC sEV, but not fibroblast sEV, provided significant neuroprotective effects for RBPMS+ RGC while significantly reducing the number of degenerating axons seen in the optic nerve. BMSC sEV significantly preserved RGC function in 6-month-old mice, but provided no benefit at 9 and 12 months. Conclusions BMSC sEV are an effective neuroprotective treatment in a chronic model of ocular hypertension for 1 year, preserving RGC numbers and protecting against axonal degeneration.
Brain Networks Reorganization During Maturation and Healthy Aging-Emphases for Resilience

Maturation and aging are important life periods that are linked to drastic brain reorganization processes which are essential for mental health. However, the development of generalized theories for delimiting physiological and pathological brain remodeling through life periods linked to healthy states and resilience on one side or mental dysfunction on the other remains a challenge. Furthermore, important processes of preservation and compensation of brain function occur continuously in the cerebral brain networks and drive physiological responses to life events. Here, we review research on brain reorganization processes across the lifespan, demonstrating brain circuits remodeling at the structural and functional level that support mental health and are parallelized by physiological trajectories during maturation and healthy aging. We show evidence that aberrations leading to mental disorders result from the specific alterations of cerebral networks and their pathological dynamics leading to distinct excitability patterns. We discuss how these series of large-scale responses of brain circuits can be viewed as protective or malfunctioning mechanisms for the maintenance of mental health and resilience.