Miracle-dz/UniFAR-FTUs huggingface dataset:
Consortium of Probiotics Attenuates Colonization of Clostridioides difficile

Clostridioides difficile infection (CDI) is increasing morbidity and mortality rates globally. Fecal microbiota transplantation (FMT), an effective therapy for eliminating Clostridioides difficile (C. difficile), cannot be used extensive due to a range of challenges. Probiotics thus constitutes a promising alternative therapy. In our study, we evaluated the effect of consortium of probiotics including five Lactobacilli strains and two Bifidobacterium strains on the colonization of toxigenic BI/NAP1/027 C. difficile in a mouse model. The results of 16S rRNA sequencing and targeted metabolomics showed the consortium of probiotics effectively decreased the colonization of C. difficile, changed the α- and β-diversity of the gut microbiota, decreased the primary bile acids, and increased the secondary bile acids. Spearman’s correlation showed that some of the OTUs such as Akkermansia, Bacteroides, Blautia et al. were positively correlated with C. difficile numbers and the primary bile acids, and negatively correlated with the secondary bile acids. However, some of the OTUs, such as Butyricicoccus, Ruminococcus, and Rikenellaceae, were negatively correlated with C. difficile copies and the primary bile acids, and positively correlated with the secondary bile acids. In summary, the consortium of probiotics effectively decreases the colonization of C. difficile, probably via alteration of gut microbiota and bile acids. Our probiotics mixture thus offers a promising FMT alternative.
Transcriptional Silencing of MCL-1 Through Cyclin-Dependent Kinase Inhibition in Acute Myeloid Leukemia

Acute myeloid leukemia (AML) is the most common adult acute leukemia. Survival remains poor, despite decades of scientific advances. Cytotoxic induction chemotherapy regimens are standard-of-care for most patients. Many investigations have highlighted the genomic heterogeneity of AML, and several new targeted therapeutic options have recently been approved. Additional novel therapies are showing promising clinical results and may rapidly transform the therapeutic landscape of AML. Despite the emerging clinical success of B-cell lymphoma (BCL)-2 targeting in AML and a large body of preclinical data supporting myeloid leukemia cell (MCL)-1 as an attractive therapeutic target for AML, MCL-1 targeting remains relatively unexplored, although novel MCL-1 inhibitors are under clinical investigation. Inhibitors of cyclin-dependent kinases (CDKs) involved in the regulation of transcription, CDK9 in particular, are being investigated in AML as a strategy to target MCL-1 indirectly. In this article, we review the basis for CDK inhibition in oncology with a focus on relevant preclinical mechanism-of-action studies of CDK9 inhibitors in the context of their therapeutic potential specifically in AML.
Breaking the Cybernetic Code: Understanding and Treating the Human Metacognitive Control System to Enhance Mental Health

The self-regulatory executive function (S-REF) model explains the role of strategic processes and metacognition in psychological disorder and was a major influence on the development of metacognitive therapy. The model identifies a universal style of perseverative negative processing termed the cognitive attentional syndrome (CAS), comprised of worry, rumination, and threat monitoring in the development of disorder. The CAS is linked to dysfunctional metacognitions that include beliefs and plans for regulating cognition. In this paper, I extend the theoretical foundations necessary to support further research on mechanisms linking metacognition to cognitive regulation and effective treatment. I propose a metacognitive control system (MCS) of the S-REF that can be usefully distinguished from cognition and is comprised of multiple structures, information, and processes. The MCS monitors and controls activity of the cognitive system and regulates the behavior of neural networks whose activities bias the way cognition is experienced. Metacognitive information involved in the regulation of on-line processing includes metacognitive beliefs, metacognitive procedural commands, and more transient cybernetic code. Separation of the cognitive and metacognitive systems and modeling their relationship presents major implications concerning what should be done in therapy and how it should be done. The paper concludes with an in-depth consideration of methods that strengthen the psychological basis of psychotherapy and aid in understanding and applying metacognitive therapy in particular. Finally, limitations of the model and implications for future research on self-awareness, self-regulation, and metacognition are discussed.
Intestinal Epithelial Cells Respond to Chronic Inflammation and Dysbiosis by Synthesizing H2O2

The microbes in the gastrointestinal tract are separated from the host by a single layer of intestinal epithelial cells (IECs) that plays pivotal roles in maintaining homeostasis by absorbing nutrients and providing a physical and immunological barrier to potential pathogens. Preservation of homeostasis requires the crosstalk between the epithelium and the microbial environment. One epithelial-driven innate immune mechanism that participates in host-microbe communication involves the release of reactive oxygen species (ROS), such as hydrogen peroxide (H2O2), toward the lumen. Phagocytes produce high amounts of ROS which is critical for microbicidal functions; the functional contribution of epithelial ROS, however, has been hindered by the lack of methodologies to reliably quantify extracellular release of ROS. Here, we used a modified Amplex Red assay to investigate the inflammatory and microbial regulation of IEC-generated H2O2 and the potential role of Duox2, a NADPH oxidase that is an important source of H2O2. We found that colonoids respond to interferon-γ and flagellin by enhancing production of H2O2 in a Duox2-mediated fashion. To extend these findings, we analyzed ex vivo production of H2O2 by IECs after acute and chronic inflammation, as well as after exposure to dysbiotic microbiota. While acute inflammation did not induce a significant increase in epithelial-driven H2O2, chronic inflammation caused IECs to release higher levels of H2O2. Furthermore, colonization of germ-free mice with dysbiotic microbiota from mice or patients with IBD resulted in increased H2O2 production compared with healthy controls. Collectively, these data suggest that IECs are capable of H2O2 production during chronic inflammation and dysbiotic states. Our results provide insight into luminal production of H2O2 by IECs as a read-out of innate defense by the mucosa.
Optimization of the k2′ Parameter Estimation for the Pharmacokinetic Modeling of Dynamic PIB PET Scans Using SRTM2

Background: This study explores different approaches for estimating the clearance rate of reference tissue (k2') parameter, used for pharmacokinetic modelling using the simplified reference tissue model 2 (SRMT2) and its effect on the binding potential (BPnd) of 11C-labelled Pittsburgh Compound B (PIB) PET scans. Methods: Thirty subjects underwent a dynamic PIB PET scan and were classified as PIB positive (+) or negative (-). Thirteen regions were defined from where to estimate k2': whole masked imagebrain, eight anatomical based on the Hammer’s atlas, one SPM voxel-based comparison between groups, and three using different BPnd(SRTM) thresholds. Results: The different approaches resulted in distinct k2' estimations. The median value of the estimated k2' across all subjects was of 0.057. In general, PIB+ subjects presented smaller k2' estimates than this median, and PIB-, larger. Furthermore, only grey matter and SPMthreshold and white matter methods resulted in non-significant bigger differences between groups in the k2' estimations. A sensitivity analysis was done by fixing k2' to a range of values and assessing the effects on BPnd(SRTM2), and a non-linear relationship between the parameters was observed. Furthermore, Tthreshold approaches yielded the best correlation between BPnd(SRTM) and BPnd(SRTM2) for both groups (R²=0.85 for PIB+, and R²=0.88 for PIB-). Lastly, sensitivity analysis shows that overestimating k2' values resulted in less bias in the BPnd(SRTM2) estimates. Conclusion: Results suggested that setting a threshold on BPnd(SRTM) might be the best method for estimating k2' in voxel-based modelling approaches, while the use of a white matter region of interest might be a better option for volume of interest-based analysis.
Weddell-Scotia Confluence Effect on the Iron Distribution in Waters Surrounding the South Shetland (Antarctic Peninsula) and South Orkney (Scotia Sea) Islands During the Austral Summer in 2007 and 2008

An oceanographic survey around the South Shetland Islands (SSI) and the South Orkney Islands (SOI) was conducted during January 2007 and February 2008, respectively, as part of the United States Antarctic Marine Living Resources program ecosystems surveys. At 27 stations, concentrations of dissolved labile (DFe) and total acid leachable (unfiltered, TaLFe) iron (Fe) were measured in the upper 200 m (including coastal and oceanic waters) to better resolve the factors limiting primary production in these regions. Northwest of the SSI, a region influenced by Drake Passage waters, mean DFe (~0.26 nM) and TaLFe (~1.02 nM) concentrations were the lowest, whereas intermediate concentrations for both DFe and TaLFe were measured in the Bransfield Strait. Around Elephant Island, over and off the continental shelf, Fe concentrations differed between the west and the east margins. DFe and TaLFe concentrations further support the argument that the effect of the Shackleton Transverse Ridge is a crucial structure affecting both the Fe and the chlorophyll distributions in this region. The waters around the SOI had DFe concentrations higher than those in the SSI, with the area north of the South Scotia Ridge (60oS), having the highest DFe (0.54 nM) concentrations and the waters in Powell Basin having the lowest DFe (1.17 nM) and TaLFe (4.51 nM) and concentrations. These spatial patterns of Fe suggest that there are different Fe inputs from shelf waters near the Antarctic Slope Front. The overall TaLFe:DFe ratios, used as indicator for understanding the relative distance of Fe sources, were lower around the SOI compared to those in the SSI, suggesting that the Fe source for SOI waters was more distant. The spatial patterns between Fe and chlorophyll-a concentrations in relation to the hydrography, highlight the complexity and variability of the oceanographic processes in the region. These results improve the knowledge on the Fe sources and inputs in the less known SOI waters during the austral summer, and they further support the importance of advective processes from the Fe-rich waters that flow from the eastern margin of the Antarctic Peninsula into the Weddell-Scotia Confluence.
Temperature Modulates Sex-Biased Gene Expression in the Gametophytes of the Kelp Saccharina latissima

Saccharina latissima is an economically and ecologically relevant kelp species in Europe and North America. In kelps, the sexuality is expressed during the haploid life stage and the microscopic gametophytes exhibit significant sexual dimorphism. To understand the sex-dependent impact of temperature on the gametophyte stage, we analyzed for the first time, gene expression profiles of male and female gametophytes at three different temperatures (4°C, 12°C and 20°C) characteristic for the species distribution range by using RNA-sequencing. We identified several differentially expressed genes between sexes; while female biased genes were enriched in general metabolism and energy production, male biased genes function within cell cycle and signaling. In our study, temperature modulated sex-biased gene expression, with only a small percentage of differentially expressed genes consistently male (7%) or female-biased (12%) at the three temperatures. Female gametophytes responded stronger to higher temperatures than males, suggesting that males are more heat tolerant. Differences between S. latissimaand other brown algal gender-dependent gene expression might mirror the different evolutionary and ecological contexts. Genomic information on kelp gametophyte is still scarce and thus this study adds to our knowledge on sex differences in abiotic stress responses in macroalgae at the transcriptomic level.
Mr Imaging of Chronic Alcoholism

We evaluated the brain lesions of patients with chronic alcoholism (n = 34) in comparison with age- and sex-matched controls (n = 40) by MR imaging. T1-weighted sagittal and axial images and T2-weighted axial images were obtained with a 0.5 T superconducting MR unit. Various brain measurements were then performed, and the presence of regions of abnormal signal intensity was also compared between the two groups. The brain measurements revealed significant cerebral atrophy (characterized by lateral and 3rd ventricular dilatation, and widening of the interhemispheric fissure) as well as significant cerebellar atrophy (represented by 4th ventricular dilatation) in the alcoholic group. These changes were more prominent in patients in their fifties and sixties than in those aged in the thirties and forties. Focal hypointense lesions were observed in 20.6% of the alcoholics and in 5% of the controls (p < 0.01), while focal hyperintense lesions were observed in 61.8% of the alcoholics and in 20% of the controls (p < 0.001). The severity of these MR findings correlated well with the age of the patients. These observations suggest that alcohol is an important promotor of brain aging.
Computed Tomography of the Brain in Cases with Venous Vasculitis Compared with an Age-Matched Reference Group

Patients with a particular, steroid-sensitive headache and often characteristic pathology at orbital phlebography, have been suggested to suffer from venous vasculitis. Fifty such patients were examined with computed tomography (CT) of the brain. The findings were compared with those of an age-matched reference group selected at random to represent normal subjects. The CT examinations were analyzed with respect to size of lateral ventricles and signs of atrophy. In both groups, there was a significant increase of atrophy with age. There was also a significantly higher degree of atrophy in the patient group as compared with the reference group. The findings indicate that the supposedly underlying venous vasculitis is related to early aging and atrophy of the brain.
Ultrasound Guided Needle Biopsy of Brain Tumors Using an Automatic Sampling Instrument

All ultrasound (US) guided needle biopsies of brain tumors performed during an 8-year period were reviewed. Tissue samples were obtained in 112 of 115 biopsy procedures, and a histologic diagnosis was established in 99 cases (88.4%). The rate of major complications was 8.0%. The mortality is similar as in reports on stereotactic and CT-guided biopsy procedures while the morbidity is higher in our material. There are no large series available on US guided intracranial biopsy with adequate reports of complications. A modified biopsy technique is introduced here using a cutting needle and an automatic sampling instrument. The modified technique, which has been used in all cases since 1985, yielded diagnostic material in 91.5%. This method consistently provides a tissue core which is essential for a confident histopathologic diagnosis.
Predictors of radiological sequelae of pulmonary tuberculosis

Purpose: In patients with pulmonary tuberculosis, clinical factors that are associated with poor radiological outcome have not been adequately addressed in the medical literature. The aim of this study was to explore some of these factors in patients admitted to a large chest hospital in Saudi Arabia with pulmonary tuberculosis. Material and Methods: Chest radiographs of 1080 patients with pulmonary tuberculosis were reviewed. Post-treatment residual changes were classified from 1 to 5 according to the severity of these changes. Data analysis was done by tabulating these classes against different variables that were likely to influence the final radiological appearance at the end of the treatment period. Results: Near-complete or complete clearance of chest radiography (Class 1) was seen in 43.5% of patients <20 years old compared to 30.3% in patients >40 years old (p<0.05). The latter group also had significantly higher rate of pleural thickening (9.4% vs. 3.6%), higher rate of fibronodular densities (24.9% vs. 19.5%) and higher rate of persistent cavitation (18.3% vs. 11.9%). Females had a significantly lower rate of chest radiography clearance (30.5%) than males (41.4%). Patients with a duration of respiratory symptoms of <4 weeks had 45.2% Class 1 radiography compared to 24.6% for those with longer duration of symptoms (>8 weeks). Chest radiography clearance was more frequent (51.6%) in patients with good compliance with drug therapy compared to those with poor compliance (18.8%). Persistent cavitation (Class 5) was seen in 30.4% of cases with a past history of tuberculosis and in only 14% of cases with no such history. Conclusion: Old age, female gender, long duration of symptoms (delayed diagnosis), poor compliance with treatment and positive history of tuberculosis were associated with poor radiological outcome.
Scintigraphic Evaluation of Traumatic Splenic Lesions in Children

Ninety-eight children with recent blunt abdominal trauma which initially evoked clinical suspicion of splenic injury were examined with colloid scintigraphy of the spleen and the liver using multiple imaging views and with abdominal survey. Nineteen children were, in addition, examined with tomographic scintigraphy. The clinical findings and the course of the disorder were reanalysed. Scintigraphy indicated splenic injury in 56 children and hepatic injury in another 5 children. The left lateral and the left oblique were the optimum imaging views for detecting splenic ruptures. Tomographic scintigraphy did not improve the diagnostic yield. Abdominal survey failed to indicate almost every second case of splenic rupture and provided no additional information of significance. The clinical review agreed with the scintigraphic diagnosis of splenic lesions but, in addition, it suggested possible splenic lesions in another 10 children with normal scintigraphy. This discrepancy cannot be explained as surgery was not employed; the occurrence of splenic lesions too small to become detectable at scintigraphy or to provoke clinically evident symptoms may be supposed.
Viscosity of Some Contemporary Contrast Media before and after Mixing with Whole Blood

The viscosity of 7 contrast media was measured using a rotational viscometer. When solutions with similar iodine concentrations were compared, the highest viscosities were found for the nonionic dimers iodixanol and iotrolan, the lowest for diatrizoate, iopamidol, and iopromide, and intermediate values for iohexol and ioxaglate. The viscosity of iohexol and ioxaglate was found to vary linearly with temperature and quadratically with concentration. Whole-blood viscosity was measured for 5 subjects at high and low shear rates before and after mixing with contrast media in various proportions. Low-shear viscosity was found to decrease and high-shear viscosity to increase with contrast medium concentration. It is concluded that the contrast media currently used may affect blood rheology less than previous agents, despite their higher viscosity.
Improving performance and security of indirect memory references on speculative execution machines

Indirect memory references hobble efficient and secure execution on current processor architectures. Traditional hardware techniques such as caches and speculative execution are ineffective on demanding workloads, such as in-memory databases, machine learning, and graph analytics. While terabytes of DRAM are now available in public cloud machines, indirect memory references in large working sets often incur the full penalty of a random DRAM access. Furthermore, caches and speculative execution enable the recently discovered Spectre family of side-channel attacks, which allow untrusted neighbors in a public cloud to steal secrets. In this thesis, we introduce complementary software and hardware techniques to improve the performance of caches and speculative execution, and to block the largest attack class with low overhead. Milk is our C++ extension to improve data cache locality. Milk’s programming model preserves parallel program semantics and maps well to the Bulk-Synchronous Parallel (BSP) theoretical model. Within a BSP superstep, which may encompass billions of memory references, Milk captures the temporal and spatial locality of ideal infinite caches on real hardware and provides up to 4x speedup. Cimple is our domain specific language (DSL) to improve the effectiveness of speculative execution in discovering instruction level parallelism and memory level parallelism. Improving memory parallelism on current CPUs allows up to ten memory references in parallel to reduce the effective DRAM latency. Speculative execution is constrained by branch predictor effectiveness and can only uncover independent accesses within the hardware limits of instruction windows (up to 100 instructions). With Cimple, interleaved co-routines expose instruction and memory level parallelism close to ideal hardware with unlimited instruction windows and perfect predictors. On in-memory database index data structures, Cimple achieves up to 6x speedup. DAWG is our secure cache architecture that prevents leaks via measuring the cache effects of speculative indirect memory references. Unlike performance isolation mechanisms such as Intel’s Cache Allocation Technology (CAT), DAWG blocks both speculative and non-speculative side-channels by isolating cache protection domains. DAWG incurs no overhead over CAT for isolation in public clouds. DAWG also enables OS isolation with efficient sharing and communication via caches, e.g., in system calls. Thesis Supervisor: Saman Amarasinghe Title: Professor of Electrical Engineering and Computer Science