Miracle-dz/UniFAR-FTUs huggingface dataset:
Iron and the heart: A paradigm shift from systemic to cardiomyocyte abnormalities

Iron is a key micronutrient for the human body and participates in biological processes, such as oxygen transport, storage, and utilization. Iron homeostasis plays a crucial role in the function of the heart and both iron deficiency and iron overload are harmful to the heart, which is partly mediated by increased oxidative stress. Iron enters the cardiomyocyte through the classic pathway, by binding to the transferrin 1 receptor (TfR1), but also through other routes: T‐type calcium channel (TTCC), divalent metal transporter 1 (DMT1), L‐type calcium channel (LTCC), Zrt‐, Irt‐like Proteins (ZIP) 8 and 14. Only one protein, ferroportin (FPN), extrudes iron from cardiomyocytes. Intracellular iron is utilized, stored bound to cytoplasmic ferritin or imported by mitochondria. This cardiomyocyte iron homeostasis is controlled by iron regulatory proteins (IRP). When the cellular iron level is low, expression of IRPs increases and they reduce expression of FPN, inhibiting iron efflux, reduce ferritin expression, inhibiting iron storage and augment expression of TfR1, increasing cellular iron availability. Such cellular iron homeostasis explains why the heart is very susceptible to iron overload: while cardiomyocytes possess redundant iron importing mechanisms, they are equipped with only one iron exporting protein, ferroportin. Furthermore, abnormalities of iron homeostasis have been found in heart failure and coronary artery disease, however, no clear picture is emerging yet in this area. If we better understand iron homeostasis in the cardiomyocyte, we may be able to develop better therapies for a variety of heart diseases to which abnormalities of iron homeostasis may contribute.
Signal amplification in flow cytometry using biotin tyramine.

BACKGROUND Catalysed reporter deposition (CARD) has been successfully used as a means of signal amplification in solid-phase immunoassays. The procedure relies on the use of horseradish peroxidase (HRP)-conjugated reagents--normally antibodies-in conjunction with substituted phenolic compounds such as biotin tyramine. The HRP catalyses deposition of biotin tyramine around the site of enzyme activity, and streptavidin-HRP can then be added to generate an amplified HRP signal. The possibility of using this technique for solution-phase amplifications has been suggested but not yet demonstrated. METHODS This paper describes the application of CARD to signal enhancement in flow cytometry. The specific examples described here are those of anti-human CD4 and anti-human CD36 antibodies binding to either human lymphocytes or mixed mononuclear cells. RESULTS Optimum biotin tyramine concentrations were evaluated, and a fivefold increase in signal was observed over standard detection of the anti-human CD4 antibody with anti-mouse-fluorescein isothiocyanate (FITC). In the example using the anti-CD36 antibody, the biotin tyramine treatment was repeated, resulting in an additional 2.5-fold signal amplification. CONCLUSIONS The technique described in this report provides a method of amplifying the signals achieved by standard flow cytometry detection reagents.
Induction of Oxidative DNA Damage in the Peri‐Infarct Region After Permanent Focal Cerebral Ischemia

Abstract: To address the role of oxidative DNA damage in focal cerebral ischemia lacking reperfusion, we investigated DNA base and strand damage in a rat model of permanent middle cerebral artery occlusion (MCAO). Contents of 8‐hydroxyl‐2′‐deoxyguanosine (8‐OHdG) and apurinic/apyrimidinic abasic sites (AP sites), hallmarks of oxidative DNA damage, were quantitatively measured in nuclear DNA extracts from brains obtained 4‐72 h after MCAO. DNA single‐ and double‐strand breaks were detected on coronal brain sections using in situ DNA polymerase I‐mediated biotin‐dATP nick‐translation (PANT) and terminal deoxynucleotidyl transferase‐mediated dUTP nick end‐labeling (TUNEL), respectively. Levels of 8‐OHdG and AP sites were markedly elevated 16‐72 h following MCAO in the frontal cortex, representing the peri‐infarct region, but levels did not significantly change within the ischemic core regions of the caudateputamen and parietal cortex. PANT‐ and TUNEL‐positive cells began to be detectable 4‐8 h following MCAO in the caudate‐putamen and parietal cortex and reached maximal levels at 72 h. PANT‐ and TUNEL‐positive cells were also detected 16‐72 h after MCAO in the lateral frontal cortex within the infarct border, where many cells also showed colocalization of DNA single‐strand breaks and DNA fragmentation. In contrast, levels of PANT‐positive cells alone were transiently increased (16 h after MCAO) in the medial frontal cortex, an area distant from the infarct zone. These data suggest that within peri‐infarct brain regions, oxidative injury to nuclear DNA in the form of base and strand damage may be a significant and contributory cause of secondary expansion of brain damage following permanent focal ischemia.
Use of Community Health Workers and Patient Navigators to Improve Cancer Outcomes Among Patients Served by Federally Qualified Health Centers: A Systematic Literature Review

Abstract Introduction: In the United States, disparities in cancer screening, morbidity, and mortality are well documented, and often are related to race/ethnicity and socioeconomic indicators including income, education, and healthcare access. Public health approaches that address social determinants of health have the greatest potential public health benefit, and can positively impact health disparities. As public health interventions, community health workers (CHWs), and patient navigators (PNs) work to address disparities and improve cancer outcomes through education, connecting patients to and navigating them through the healthcare system, supporting patient adherence to screening and diagnostic services, and providing social support and linkages to financial and community resources. Clinical settings, such as federally qualified health centers (FQHCs) are mandated to provide care to medically underserved communities, and thus are also valuable in the effort to address health disparities. We conducted a systematic literature review to identify studies of cancer-related CHW/PN interventions in FQHCs, and to describe the components and characteristics of those interventions in order to guide future intervention development and evaluation. Method: We searched five databases for peer-reviewed CHW/PN intervention studies conducted in partnership with FQHCs with a focus on cancer, carried out in the United States, and published in English between January 1990 and December 2013. Results: We identified 24 articles, all reporting positive outcomes of CHW/PNs interventions in FQHCs. CHW/PN interventions most commonly promoted breast, cervical, or colorectal cancer screening and/or referral for diagnostic resolution. Studies were supported largely through federal funding. Partnerships with academic institutions and community-based organizations provided support and helped develop capacity among FQHC clinic leadership and community members. Discussion: Both the FQHC system and CHW/PNs were borne from the need to address persistent, complex health disparities among medically underserved communities. Our findings support the effectiveness of CHW/PN programs to improve completion and timeliness of breast, cervical, and colorectal cancer screening in FQHCs, and highlight intervention components useful to design and sustainability.
Computerized Medical Imaging and Graphics

Automatic pancreas segmentation in 3D radiological scans is a critical, yet challenging task. As a pre-requisite for computer-aided diagnosis (CADx) systems, accurate pancreas segmentation could generate both quantitative and qualitative information towards establishing the severity of a condition, and thus provide additional guidance for therapy planning. Since the pancreas is an organ of high inter-patient anatomical variability, previous segmentation approaches report lower quantitative accuracy scores in comparison to abdominal organs such as the liver or kidneys. This paper presents a novel approach for automatic pancreas segmentation in magnetic resonance imaging (MRI) and computer tomography (CT) scans. This method exploits 3D segmentation that, when coupled with geometrical and morphological characteristics of abdominal tissue, classiﬁes distinct contours in tight pixel-range proximity as “pan-creas” or “non-pancreas”. There are three main stages to this approach: (1) identify a major pancreas region and apply contrast enhancement to differentiate between pancreatic and surrounding tissue; (2) perform 3D segmentation via continuous max-ﬂow and min-cuts approach, structured forest edge detection, and a training dataset of annotated pancreata; (3) eliminate non-pancreatic contours from resultant segmentation via morphological operations on area, structure and connectivity between distinct contours. The proposed method is evaluated on a dataset containing 82 CT image volumes, achieving mean Dice Similarity coefﬁcient (DSC) of 79.3 ± 4.4%. Two MRI datasets containing 216 and 132 image volumes are evaluated, achieving mean DSC 79.6 ± 5.7% and 81.6 ± 5.1% respectively. This approach is statistically stable, reﬂected by lower metrics in standard deviation in comparison to state-of-the-art approaches.
Enteral vs. parenteral nutrition in septic shock: are they equivalent?

PURPOSE OF REVIEW The current review focuses on recent clinical evidence and updated guideline recommendations on the benefits of enteral vs. parenteral nutrition in adult critically ill patients with (septic) shock. RECENT FINDIGS The largest multicenter randomized-controlled trial showed that the route of nutrient supply was unimportant for 28-day and 90-day mortality, infectious morbidity and length of stay in mechanically ventilated patients with shock. The enteral route, however, was associated with lower macronutrient intake and significantly higher frequency of hypoglycemia and moderate-to-severe gastrointestinal complications. Integrating these findings into recent meta-analyses confirmed that the route per se has no effect on mortality and that interactions with (infectious) morbidity are inconsistent or questionable. SUMMARY The strong paradigm of favoring the enteral over the parenteral route in critically ill patients has been challenged. As a consequence, updated guidelines recommend withholding enteral nutrition in patients with uncontrolled shock. It is still unclear, however, whether parenteral nutrition is advantageous in patients with shock although benefits are conceivable in light of less gastrointestinal complications. Thus far, no guideline has addressed indications for parenteral nutrition in these patients. By considering recent scientific evidence, specific guideline recommendations, and expert opinions, we present a clinical algorithm that may facilitate decision-making when feeding critically ill patients with shock.
Golgi α-mannosidase II cleaves two sugars sequentially in the same catalytic site

Golgi α-mannosidase II (GMII) is a key glycosyl hydrolase in the N-linked glycosylation pathway. It catalyzes the removal of two different mannosyl linkages of GlcNAcMan5GlcNAc2, which is the committed step in complex N-glycan synthesis. Inhibition of this enzyme has shown promise in certain cancers in both laboratory and clinical settings. Here we present the high-resolution crystal structure of a nucleophile mutant of Drosophila melanogaster GMII (dGMII) bound to its natural oligosaccharide substrate and an oligosaccharide precursor as well as the structure of the unliganded mutant. These structures allow us to identify three sugar-binding subsites within the larger active site cleft. Our results allow for the formulation of the complete catalytic process of dGMII, which involves a specific order of bond cleavage, and a major substrate rearrangement in the active site. This process is likely conserved for all GMII enzymes—but not in the structurally related lysosomal mannosidase—and will form the basis for the design of specific inhibitors against GMII.
CRISPR/Cas9‐mediated knockout of the eye pigmentation gene white leads to alterations in colour of head spots in the oriental fruit fly, Bactrocera dorsalis

The intensely studied white gene is widely used as a genetic marker in Drosophila melanogaster. Here, we cloned and characterized the white gene in an important pest of the fruit industry, Bactrocera dorsalis, to understand its functional role in pigmentation. We obtained BdWhite knockout strains, based on the wild‐type strain, using the CRISPR/Cas9 genome editing system, and found that mutants lost pigmentation in the compound eye and their black head spots. We then examined differences in the expression levels of genes associated with melanin pigmentation between mutants and the wild‐type strain using quantitative reverse transcription PCR. We found that transcription levels of the Bd‐yellow1 were lower in the head of mutants than in the wild‐type strain, and there were no significant differences in expression of the other six genes between mutants and the wild type. Since yellow is critical for melanin biosynthesis (Heinze et al., Scientific Reports. 2017;7:4582), the lower levels of expression of Bd‐yellow1 in mutants led to reduced dark pigmentation in head spots. Our results provide the first evidence, to our knowledge, that white may play a functional role in cuticle pigmentation by affecting the expression of yellow.
Association of Intraoperative Ventilator Management With Postoperative Oxygenation, Pulmonary Complications, and Mortality.

BACKGROUND "Lung-protective ventilation" describes a ventilation strategy involving low tidal volumes (VTs) and/or low driving pressure/plateau pressure and has been associated with improved outcomes after mechanical ventilation. We evaluated the association between intraoperative ventilation parameters (including positive end-expiratory pressure [PEEP], driving pressure, and VT) and 3 postoperative outcomes: (1) PaO2/fractional inspired oxygen tension (FIO2), (2) postoperative pulmonary complications, and (3) 30-day mortality. METHODS We retrospectively analyzed adult patients who underwent major noncardiac surgery and remained intubated postoperatively from 2006 to 2015 at a single US center. Using multivariable regressions, we studied associations between intraoperative ventilator settings and lowest postoperative PaO2/FIO2 while intubated, pulmonary complications identified from discharge diagnoses, and in-hospital 30-day mortality. RESULTS Among a cohort of 2096 cases, the median PEEP was 5 cm H2O (interquartile range = 4-6), median delivered VT was 520 mL (interquartile range = 460-580), and median driving pressure was 15 cm H2O (13-19). After multivariable adjustment, intraoperative median PEEP (linear regression estimate [B] = -6.04; 95% CI, -8.22 to -3.87; P < .001), median FIO2 (B = -0.30; 95% CI, -0.50 to -0.10; P = .003), and hours with driving pressure >16 cm H2O (B = -5.40; 95% CI, -7.2 to -4.2; P < .001) were associated with decreased postoperative PaO2/FIO2. Higher postoperative PaO2/FIO2 ratios were associated with a decreased risk of pulmonary complications (adjusted odds ratio for each 100 mm Hg = 0.495; 95% CI, 0.331-0.740; P = .001, model C-statistic of 0.852) and mortality (adjusted odds ratio = 0.495; 95% CI, 0.366-0.606; P < .001, model C-statistic of 0.820). Intraoperative time with VT >500 mL was also associated with an increased likelihood of developing a postoperative pulmonary complication (adjusted odds ratio = 1.06/hour; 95% CI, 1.00-1.20; P = .042). CONCLUSIONS In patients requiring postoperative intubation after noncardiac surgery, increased median FIO2, increased median PEEP, and increased time duration with elevated driving pressure predict lower postoperative PaO2/FIO2. Intraoperative duration of VT >500 mL was independently associated with increased postoperative pulmonary complications. Lower postoperative PaO2/FIO2 ratios were independently associated with pulmonary complications and mortality. Our findings suggest that postoperative PaO2/FIO2 may be a potential target for future prospective trials investigating the impact of specific ventilation strategies for reducing ventilator-induced pulmonary injury.
Assessment of mental health and psycho-social support pilot program’s effect on intended stigmatizing behavior at the Saftawi Health Center, Gaza: a cross-sectional study

Abstract Background: In the midst of a global refugee crisis, addressing mental health is critical for refugee health care delivery. Understanding efficacy of mental health interventions is more important than ever. Aims: In this study, we aim to assess the efficacy of comprehensive mental health and psychosocial support services for refugees in Gaza by comparing intended stigmatizing behavior toward mental health disorders between two health centers (HCs)(Saftawi and Nasser). Methods: One year after these services by the United Nations Relief and Works Agency (UNRWA) for Palestine Refugees in the Near East were implemented at Saftawi HC, a randomly selected sample of HC patrons (n = 205) from Saftawi, and a comparable number from a control HC (n = 203 at Nasser) completed the Reported and Intended Behavior Scale (RIBS) regarding stigma towards mental illnesses. Multivariable linear regressions were used to determine the impact of these services in the HC on attitudes against mental health. Results: Saftawi respondents endorsed significantly less intended stigmatizing behavior compared to Nasser respondents (p < 0.001). Multivariable analysis demonstrated significantly less intended stigmatizing behavior at Saftawi compared to Nasser (p < 0.01) while controlling for demographic covariables. Conclusions: UNRWA primary care services and education implemented for refugees in Gaza was associated with reduced stigmatizing behavior toward mental health, which can help guide efficacious mental health care interventions within the Palestine refugee community and in other simiilar communities.
Mass spectrometry based quantitative proteomics and integrative network analysis accentuates modulating roles of annexin‐1 in mammary tumorigenesis

Annexin‐1 (ANXA1) is known to be involved in important cellular processes and implicated in cancer. Our previous study showed its roles in cell migration and DNA‐damage response processes in breast cancer initiation. In order to understand its roles in tumorigenesis, we extended our studies to analyze tumors derived from polyomavirus middle T‐antigen ANXA1 heterozygous (ANXA1+/−) and ANXA1 null (ANXA1−/−) mice. We performed quantitative comparison of ANXA1+/− and ANXA1−/− tumors employing reductive dimethyl labeling quantitative proteomics. We observed 253 differentially expressed proteins (DEPs) with high statistical significance among over 5000 quantified proteins. Combinatorial use of pathway and network‐based computational analyses of the DEPs revealed that ANXA1 primarily modulates processes related to cytoskeletal remodeling and immune responses in these mammary tumors. Of particular note, ANXA1−/− tumor showed reduced expression of a known epithelial‐to‐mesenchymal transition (EMT) marker vimentin, as well as myosin light‐chain kinase, which has been reported to induce Rho‐kinase mediated assembly of stress fibers known to be implicated in EMT. Integrative network analysis of established interactome of ANXA1 alongside with DEPs further highlights the involvement of ANXA1 in EMT. Functional role of ANXA1 in tumorigenesis was established in invasion assay where knocking down ANXA1 in murine mammary tumor cell line 168FARN showed lower invasive capability. Altogether, this study emphasizes that ANXA1 plays modulating roles contributing to invasion–metastasis in mammary tumorigenesis, distinctive to its roles in cancer initiation.
The recent increase in contraceptive discontinuation in Egypt

Abstract This study sought to establish whether recent changes in discontinuation of contractive use and switching in Egypt can be considered an important cause of the unexpected increase in overall fertility and slight fall in contraceptive prevalence in the country. The analysis was based on calendar data from the 2008 and 2014 Egyptian DHS. Single/multiple decrement life tables were built to calculate contraceptive discontinuation rates and examine these by reasons for discontinuation focusing on three methods: IUDs, pills and injectables. The unit of the analysis was ‘segment of use’, defined as a continuous period of use/non-use of a contraceptive method (in months). It was found that over the period 2008–2014 the rise in the ‘all method’ discontinuation rate was mainly due to the shift away from IUDs to hormonal methods, which have higher discontinuation rates. Segments of use were more likely to be discontinued for ‘method/service-related’ reasons than for ‘reduced need’ reasons. This was due to an increase in contraceptive failure and side-effect/health concerns. Also, ‘the desire to get pregnant’ increased to become the second highest reason-specific discontinuation rate. This has coincided with a recent increase in ideal family size in Egypt. About half of the women who reported discontinuing for reasons related to method/services switched to another method, while the rest became subject to the risk of an unintended pregnancy. The rate of switching, rather than stopping use, increased for IUDs, remained the same for pills and increased slightly for injectables, indicating an improvement in switching behaviour. However, a marked high percentage of switchers moved to less-effective methods. If these issues are not addressed, many women in Egypt have an unmet need for contraception, leading to an increase in unintended pregnancies. Specific interventions that would greatly benefit the family planning programme in Egypt include improvement in counselling at the time of IUD insertion and removal and the reduction in failure rates for hormonal methods.
Fine‐scale genetic structure of two carabid species with contrasted levels of habitat specialization

Using microsatellite markers, we compared the genetic structure of populations of two carabid species, one described as a generalist (commonly found in forest and in open habitats) and the other known as a forest specialist. Both species were sampled in the same forest plots, which were separated from each other by either open or forested areas. At the local scale considered (13.6 km separating the most distant plots), genetic differentiation was substantial for both species studied, but populations of the forest specialist Carabus punctatoauratus appeared to be more spatially structured than those of C. nemoralis. Isolation by distance analyses showed that nonforested areas are partial barriers to gene flow for both species studied, although more clearly for the forest specialist. Between and within forests, dispersal capacity of the generalist C. nemoralis was shown to be higher than that of the specialist C. punctatoauratus.