Miracle-dz/UniFAR-FTUs huggingface dataset:
The influence of direct and indirect fibroblast cell contact on human myogenic cell behaviour and gene expression in vitro.

Underpinning skeletal muscle plasticity is the interplay between many cell types, of which fibroblasts are emerging as potent players, both negatively in the development of fibrosis but also positively in stimulating muscle repair through enhancing myogenesis. The mechanisms behind this interaction however remain unknown. To investigate this, waste hamstring muscle tissue was obtained from 8 healthy young men undergoing reconstructive anterior cruciate ligament surgery and primary myoblasts and fibroblasts were isolated. Myoblasts were cultured alone or with fibroblasts, either in direct or indirect contact (separated by an insert with a permeable membrane). The myogenesis parameters proliferation, differentiation and fusion were determined from immunostained cells, while, in replicate samples, gene expression levels of GAPDH, Ki67, Pax7, MyoD, myogenin, myomaker, MHC IΒ, TCF7L2, COL1A1 and p16 were determined by RT-PCR. We found only trends for an influence of skeletal muscle fibroblasts on myogenic cell proliferation and differentiation. While greater mRNA levels of GAPDH, Pax7, MyoD, myogenin, and MHC IΒ were observed in myogenic cells in indirect contact with fibroblasts (insert) when compared to cells cultured alone, a similar effect of an empty insert was also observed. In conclusion we find very little influence of skeletal muscle fibroblasts on myoblasts derived from the same tissue, although it cannot be excluded that a different outcome would be seen under less optimal myogenic growth conditions.
Heterotrophic Aurantiochytrium sp. supplementation to layer diets sustainably increases the omega-3 concentration of eggs

ABSTRACT 1. The consumption of adequate amounts of the long-chain polyunsaturated omega-3 fatty acids (n-3 LC-PUFA) has been associated with beneficial effects on human health. Eggs are commonly consumed worldwide, and their omega-3 content can be easily altered by changing the diets of laying hens and so represent an important target for enrichment. 2. In this study, the effect of supplementing laying hens with DHA-rich, Aurantiochytrium limacinum at three different inclusion levels was investigated over a 24-week period. 3. Significant increases in egg DHA concentrations were observed after four weeks and were maintained for the duration of the 24-week study. The supplemented eggs in the current study had a DHA content of 82, 101, and 129 mg/yolk when supplemented with 0.25%, 0.5% and 1% treatments, respectively, which meets the EU criteria to be considered ‘high in omega-3ʹ. 4. Using the sustainably grown protist Aurantiochytrium limacinum to supplement layer diets increased the egg DHA concentration and decreased the n-6/n-3 ratio, improving the nutritional value of the eggs for human consumers.
Systematic review of toxicity removal by advanced wastewater treatment technologies via ozonation and activated carbon.

Upgrading wastewater treatment plants (WWTPs) with advanced technologies is one key strategy to reduce micropollutant emissions. Given the complex chemical composition of wastewater, toxicity is an integrative parameter to assess their removal performance. Thus, the goal of this systematic review is to evaluate how effective ozonation and activated carbon remove in vitro and in vivo toxicity. Out of 2464 publications, we extracted 46 relevant studies conducted at 22 pilot or full-scale WWTPs. We performed a quantitative and qualitative evaluation of in vitro (100 assays) and in vivo data (20 species), respectively. Data is more abundant on ozonation (573 data points) than on an activated carbon treatment (162 data points), and certain in vitro endpoints (especially estrogenicity) and in vivo models (e.g., daphnids) dominate. The literature shows that while a conventional treatment effectively removes toxicity, residual effects in the effluents may represent a risk to the receiving ecosystem based on effect-based trigger values. In general, an upgrade to ozonation or activated carbon treatment will significantly increase the toxicity removal with similar performance. Nevertheless, ozonation generates toxic transformation products that can be removed by a post-treatment. By assessing the growing body of effect-based studies, we identify sensitive and underrepresented endpoints and species, and provide guidance for future research.
Opposite microglial activation stages upon loss of PGRN or TREM2 result in reduced cerebral glucose metabolism

Microglia adopt numerous fates with homeostatic microglia (HM) and a microglial neurodegenerative phenotype (MGnD) representing two opposite ends. A number of variants in genes selectively expressed in microglia are associated with an increased risk for neurodegenerative diseases such as Alzheimer's disease (AD) and frontotemporal lobar degeneration (FTLD). Among these genes are progranulin (GRN) and the triggering receptor expressed on myeloid cells 2 (TREM2). Both cause neurodegeneration by mechanisms involving loss of function. We have now isolated microglia from Grn−/− mice and compared their transcriptomes to those of Trem2−/− mice. Surprisingly, while loss of Trem2 enhances the expression of genes associated with a homeostatic state, microglia derived from Grn−/− mice showed a reciprocal activation of the MGnD molecular signature and suppression of gene characteristic for HM. The opposite mRNA expression profiles are associated with divergent functional phenotypes. Although loss of TREM2 and progranulin resulted in opposite activation states and functional phenotypes of microglia, FDG (fluoro‐2‐deoxy‐d‐glucose)‐μPET of brain revealed reduced glucose metabolism in both conditions, suggesting that opposite microglial phenotypes result in similar wide spread brain dysfunction.
Mitophagy in Cancer: A Tale of Adaptation

In the past years, we have learnt that tumors co-evolve with their microenvironment, and that the active interaction between cancer cells and stromal cells plays a pivotal role in cancer initiation, progression and treatment response. Among the players involved, the pathways regulating mitochondrial functions have been shown to be crucial for both cancer and stromal cells. This is perhaps not surprising, considering that mitochondria in both cancerous and non-cancerous cells are decisive for vital metabolic and bioenergetic functions and to elicit cell death. The central part played by mitochondria also implies the existence of stringent mitochondrial quality control mechanisms, where a specialized autophagy pathway (mitophagy) ensures the selective removal of damaged or dysfunctional mitochondria. Although the molecular underpinnings of mitophagy regulation in mammalian cells remain incomplete, it is becoming clear that mitophagy pathways are intricately linked to the metabolic rewiring of cancer cells to support the high bioenergetic demand of the tumor. In this review, after a brief introduction of the main mitophagy regulators operating in mammalian cells, we discuss emerging cell autonomous roles of mitochondria quality control in cancer onset and progression. We also discuss the relevance of mitophagy in the cellular crosstalk with the tumor microenvironment and in anti-cancer therapy responses.
National Trends in Cessation Counseling, Prescription Medication Use, and Associated Costs Among US Adult Cigarette Smokers

Key Points Question What are the 10-year trends in the delivery of cigarette smoking cessation services for adult smokers in the United States? Findings In this cross-sectional study of 29 106 US adult smokers from 2006 to 2015, the proportion who reported receiving physician advice to quit smoking increased and the use of prescription cessation medication decreased with a corresponding reduction in expenditures. Lower rates of cessation services were observed in certain populations, including men, younger adults, uninsured individuals, racial/ethnic minority groups, and those without smoking-related comorbidities. Meaning The disparities in the delivery of known smoking cessation services among certain subgroups may be associated with higher smoking rates despite an all-time low prevalence of smoking, suggesting the call for a more targeted implementation of smoking cessation guidelines.
Amyloid Beta and Phosphorylated Tau-Induced Defective Autophagy and Mitophagy in Alzheimer’s Disease

Alzheimer’s disease (AD) is a progressive neurodegenerative disease characterized by memory loss and multiple cognitive impairments. Several decades of intense research have revealed that multiple cellular changes are implicated in the development and progression of AD, including mitochondrial damage, synaptic dysfunction, amyloid beta (Aβ) formation and accumulation, hyperphosphorylated tau (P-Tau) formation and accumulation, deregulated microRNAs, synaptic damage, and neuronal loss in patients with AD. Among these, mitochondrial dysfunction and synaptic damage are early events in the disease process. Recent research also revealed that Aβ and P-Tau-induced defective autophagy and mitophagy are prominent events in AD pathogenesis. Age-dependent increased levels of Aβ and P-Tau reduced levels of several autophagy and mitophagy proteins. In addition, abnormal interactions between (1) Aβ and mitochondrial fission protein Drp1; (2) P-Tau and Drp1; and (3) Aβ and PINK1/parkin lead to an inability to clear damaged mitochondria and other cellular debris from neurons. These events occur selectively in affected AD neurons. The purpose of our article is to highlight recent developments of a Aβ and P-Tau-induced defective autophagy and mitophagy in AD. This article also summarizes several aspects of mitochondrial dysfunction, including abnormal mitochondrial dynamics (increased fission and reduced fusion), defective mitochondrial biogenesis, reduced ATP, increased free radicals and lipid peroxidation, and decreased cytochrome c oxidase (COX) activity and calcium dyshomeostasis in AD pathogenesis. Our article also discusses how reduced levels of Drp1, Aβ, and P-Tau can enhance the clearance of damaged mitochondria and other cellular debris by autophagy and mitophagy mechanisms.
Small amounts of involuntary muscle activity reduce passive joint range of motion.

When assessing passive joint range of motion in neurological conditions, concomitant involuntary muscle activity is generally regarded small enough to ignore. This assumption is untested. If false, many clinical and laboratory studies that rely on these assessments may be in error. We determined to what extent small amounts of involuntary muscle activity limit passive range of motion in thirty able-bodied adults. Subjects were seated with the knee flexed 90° and the ankle in neutral, and predicted maximal plantarflexion torque was determined using twitch interpolation. Next, with the knee flexed 90° or fully extended, the soleus muscle was continuously electrically stimulated to generate 1, 2.5, 5, 7.5 and 10% of predicted maximal torque, in random order, while the ankle was passively dorsiflexed to a torque of 9 Nm by a blinded investigator. A trial without stimulation was also performed. Ankle dorsiflexion torque-angle curves were obtained at each percent of predicted maximal torque. On average (mean, 95% CI), each 1% increase in plantarflexion torque decreases ankle range of motion by 2.4° (2.0 to 2.7°; knee flexed 90°) and 2.3° (2.0 to 2.5°; knee fully extended). Thus, 5% of involuntary plantarflexion torque, the amount usually considered small enough to ignore, decreases dorsiflexion range of motion by ~12°. Our results indicate that even small amounts of involuntary muscle activity will bias measures of passive range, and hinder the differential diagnosis and treatment of neural and non-neural mechanisms of contracture.
Sensory Axon Growth Requires Spatiotemporal Integration of CaSR and TrkB Signaling

Neural circuit development involves the coordinated growth and guidance of axons. During this process, axons encounter many different cues, but how these cues are integrated and translated into growth is poorly understood. In this study, we report that receptor signaling does not follow a linear path but changes dependent on developmental stage and coreceptors involved. Using developing chicken embryos of both sexes, our data show that calcium-sensing receptor (CaSR), a G-protein-coupled receptor important for regulating calcium homeostasis, regulates neurite growth in two distinct ways. First, when signaling in isolation, CaSR promotes growth through the PI3-kinase-Akt pathway. At later developmental stages, CaSR enhances tropomyosin receptor kinase B (TrkB)/BDNF-mediated neurite growth. This enhancement is facilitated through a switch in the signaling cascade downstream of CaSR (i.e., from the PI3-kinase-Akt pathway to activation of GSK3α Tyr279). TrkB and CaSR colocalize within late endosomes, cotraffic and coactivate GSK3, which serves as a shared signaling node for both receptors. Our study provides evidence that two unrelated receptors can integrate their individual signaling cascades toward a nonadditive effect and thus control neurite growth during development. SIGNIFICANCE STATEMENT This work highlights the effect of receptor coactivation and signal integration in a developmental setting. During embryonic development, neurites grow toward their targets guided by cues in the extracellular environment. These cues are sensed by receptors at the surface that trigger intracellular signaling events modulating the cytoskeleton. Emerging evidence suggests that the effects of guidance cues are diversified, therefore expanding the number of responses. Here, we show that two unrelated receptors can change the downstream signaling cascade and regulate neuronal growth through a shared signaling node. In addition to unraveling a novel signaling pathway in neurite growth, this research stresses the importance of receptor coactivation and signal integration during development of the nervous system.
Analysis of prognostic variables among patients with locally advanced head and neck cancer treated with late chemo-intensification protocol: impact of nodal density and total tumor volume.

OBJECTIVE The aim of the present study was to define the prognostic impact of nodal density (ND) and total tumor volume along with many other tumor, treatment and patient related variables using the late chemo-intensification treatment regimen with conventionally fractionated radiotherapy (70 Gy/7 weeks). METHODS A total of 74 patients with Stage III and IV biopsy proven squamous cell carcinoma of oropharynx, hypopharynx and larynx were treated with this regimen. ND and total tumor volume was measured on high resolution CT scans for all the patients. Chemotherapy consisted of continuous infusion of 5 FU at 350 mg/m(2)/day and cisplatin as 1 h infusion at 10 mg/m(2)/day on days 1-5 of week 6 and 7 of radiotherapy. RESULTS Grade III mucositis was present in 48 (64.9%) patients. Overall complete response rate was 77%. At 28 months, locoregional relapse-free survival (LRFS), overall survival (OS) and distant metastases-free survival (DMFS) was 70.8%, 66.9% and 81.9%, respectively. In the final multivariate Cox-regression model tumor stage, ND, primary site and nodal stage were independent variables predicting for LRFS. Similarly AJCC group staging, ND and total treatment volume were found to have significant impact, independently over LRFS. CONCLUSIONS There is tremendous variation in terms of ND and total tumor volume within AJCC nodal staging and tumor staging, respectively. ND had significant impact over LRFS and OS. Future phase III trial may need stratification on the basis of these variables.
ICEROSS — a consensus view: A questionnaire survey of the use of ICEROSS in the United Kingdom

The management of the individual with a trans-tibial amputation has been strongly influenced by the increasing use of the ICEROSS socket system over recent years. Despite this growth in clinical experience, there has been very little research into its place in current prosthetic practice, and prescribing activity is largely determined by personal experience. In order to formulate the current consensus view on the use of ICEROSS, questionnaires were sent to 42 doctors and 43 senior prosthetists around the UK. The influence of 38 different factors on prescribing activity was assessed using a grading system (ranging from “primary indication” to “absolute contraindication”). An 85% response rate was achieved and no significant differences in response between the two professional groups were identified. Those factors considered by most to be positive indications for using ICEROSS were “pistoning”, “shear-sensitive skin / split-skin grafts”, “patient unsuccessful with supracondylar (s/c) or cuff suspension” and “insufficient suspension due to change in type or level of activity”. Those considered by most to be absolute contra-indications were “ulceration / unhealed scars”, “poor patient hygiene” and “poor patient commitment to prosthetic rehabilitation”. This consensus of opinion is in keeping with the results of the few published audits of ICEROSS usage. There was a lack of consensus, however, about the use of ICEROSS in some situations, including skin complications. Whilst some consensus does exist about the use of ICEROSS, the results of this survey indicate significant variations in clinical practice which serve to illustrate the urgent need for data from prospective clinical trials.
Trial of labor versus elective repeat cesarean delivery in twin pregnancies after a previous cesarean delivery-A systematic review and meta-analysis.

OBJECTIVE To perform a systematic review of success rates of trial of labor after cesarean (TOLAC) and maternal and neonatal outcomes in twin pregnancy versus elective repeat cesarean delivery (ERCD). METHODS We searched MEDLINE, EMBASE, and Web of Science from data inception to May 2018 with no language or regional restrictions, to identify all studies that compared twin TOLAC and ERCD for maternal and/or neonatal outcomes. The Newcastle-Ottawa Scale was used to assess the methodological quality of the included studies. We assessed the pooled relative risk and mean difference using a random-effects model. The pooled event rates for successful VBAC, cesarean delivery for twin B after vaginal delivery of twin A, and uterine rupture were determined. RESULTS Of the 841 citations identified, 10 were eligible for analysis (2336 TOLAC cases and 5763 ERCD cases). The pooled event rates for successful VBAC and uterine rupture during TOLAC were 72.2% (95% CI 59.7%-83.2%) and 0.87% (95% CI 0.51%-1.31%), respectively. TOLAC was associated with a significantly higher risk of neonatal death (RR 3.02 [95% CI 1.07-8.54]) with no significant differences in mean gestational age at birth, NICU admission rates, or 5-minute Apgar <7. Although the risk for maternal infectious morbidity was significantly lower with TOLAC (RR 0.48 [95% CI 0.25-0.90]), risks of uterine dehiscence, blood transfusions, and hysterectomy were comparable. CONCLUSIONS Twin TOLAC is associated with a relatively high rate of successful vaginal delivery and a low risk of uterine rupture. The finding of higher neonatal mortality rates may be influenced by prematurity, but requires further investigation.
Expression of Poly (Adenosine Diphosphate-Ribose) Polymerase and p53 in Epithelial Ovarian Cancer and Their Role in Prognosis and Disease Outcome

PARP, poly (adenosine diphosphate-ribose) polymerase, is a damage-sensing protein, which is essential for the repair of DNA single-strand breaks. PARP and p53 function synergistically in repairing DNA damage and suppressing chromosomal rearrangements. The aim of this study was to determine the expression of PARP and p53 in epithelial ovarian cancer (EOC) and to correlate their expression with clinicopathologic characteristics. PARP and p53 were evaluated using immunohistochemistry applied on a tissue microarray of 189 EOC and their expressions were correlated to clinicopathologic variables, including the age of diagnosis, stage, grade, histologic type, optimal debulking, progression-free survival, and overall survival (OS). PARP and p53 expressions were shown in 61% and 54% of cases, respectively. PARP-positive tumors are more likely to have higher grade (P=0.03) and complete response to initial first-line chemotherapy (P=0.009). Patients with positive p53 staining are more likely to be at the advanced stage disease (P=0.004). Finally, there were no significant associations between PARP and p53 expression and no differences in progression-free survival and OS for PARP or p53 expressions. The overexpression of PARP and p53 in high grade, and advanced stage tumors indicated that these 2 markers might serve as an indicator of aggressive disease behavior. Additional studies are warranted to evaluate the role of PARP and PARP inhibitors in the setting of adjuvant chemotherapy.
Distribution of Triatomine (Hemiptera: Reduviidae) Vectors of Chagas Disease in the State of Hidalgo, Mexico

ABSTRACT: Chagas disease represents a significant public health problem in Mexico. In the state of Hidalgo, studies on the presence of triatomines are scarce and restricted to a few locations. To determine the risk of transmission in the state of Hidalgo and stratify the vector potential, the distribution of Triatominae was surveyed from 2015 to 2016 in collaboration with primary health care services and local communities. A total of 570 specimens was collected in 278 houses in 25 municipalities. The species of Triatominae detected were T. dimidiata with 391 samples, T. mexicana with 159 samples, T. gerstaeckeri with 17 samples, and T. barberi with three samples. The samples were collected in domestic and peridomestic areas. The general index of natural infection was 9.8%. Indices of colonization and crowding were determined for species and municipality and results were variable.
Prenatal Weight Gain Advice: An Examination of the Recent Prenatal Weight Gain Recommendations of the Institute of Medicine

The Institute of Medicine (IOM) recently published new guidelines for maternal weight gain during pregnancy. Using data collected at Moffitt Hospital, University of California at San Francisco, we examined the associations between maternal weight gain outside the recommendations of the IOM and three pregnancy outcomes (small for gestational age [SGA] infants, large for gestational age [LGA] infants, and cesarean delivery). These analyses were repeated using population-specific weight gain ranges derived from a subgroup of women in this cohort with healthy pregnancy outcomes. The purpose of the study was to compare the national guidelines of the IOM with hospital standards. Both the recommendations of the IOM and the hospital ranges were associated with fewer SGA infants, LGA infants, and cesarean deliveries. The overall associations were similar for the population-derived and national ranges. Although the IOM ranges should be examined in other populations and with other birth outcomes, our results validated their recommendations. Maternal weight gain within the IOM recommendations reduced the risk of the outcomes studied; furthermore, these ranges performed as well as those derived from the target population.