Miracle-dz/UniFAR-FTUs huggingface dataset:
A tale of two phage tails: Engineering the host range of bacteriophages infecting Clostridioides difficile

Clostridioides difficile infection (CDI) is a leading cause of antibiotic-associated diarrhoea across the globe. Although treatable with a restricted number of antibiotics, the emergence of resistant variants and high relapse rates necessitate alternative countermeasures. Phage therapy represents an attractive option. However, its implementation is handicapped by the narrow host specificity of the C. difficile bacteriophages isolated to date. One strategy to rationally expand phage host range would be to make appropriate modifications to the phage receptor binding protein (RBP). Here, we identify the tail fibre as the RBP of two Myoviridae phages, ΦCD1801 and ΦCD2301, which were previously isolated and propagated using the C. difficile strains CD1801 (RT078) and CD2301 (RT014), respectively. Contrary to studies into reprogramming the host ranges of phage of other bacterial other species, exchanging the tail fibre genes (tcf/tfp) alone between the two phage was insufficient to change host specificity. Rather, alterations to host range were dependent their exchange together with a putative chaperone encoded by hyp, localised adjacent to the tail fibre gene. Capitalising on this discovery, CRISPR/Cas9 was used to change the host range of one phage to that of the other by swapping the respective tcf/tfp and hyp genes. Significantly, one of the resulting mutants, surpassed both parental phages in terms of host range and efficiency of infection. This is the first time that genome engineering has successfully expanded the host range of a C. difficile phage, a prerequisite for implementing phage for the treatment of CDI. Importance Alternatives to antibiotics for treating Clostridioides difficile infection (CDI) are urgently required. Phage therapy presents an attractive option as it has the potential to clear the infection with minimal microbiome disruption and eliminate the possibility of recurrence. However, the C. difficile bacteriophages isolated to date have highly restricted host ranges. Moreover, rational strategies to alter specificity have till now been precluded as the identity of the phage receptor binding proteins involved was largely unknown. Here, we demonstrated that tail fibre proteins and an associated putative chaperone determine the host range of two Myoviridae phage. This enabled the alteration of specificity through CRISPR-mediated genome editing and the creation of a phage derivative with a host range and infection efficiency exceeding that of the parental phages. This is the first time that the host range of a C. difficile phage has been successfully expanded through rational genome engineering.
BioKG: a comprehensive, large-scale biomedical knowledge graph for AI-powered, data-driven biomedical research

To cope with the rapid growth of scientific publications and data in biomedical research, knowledge graphs (KGs) have emerged as a powerful data structure for integrating large volumes of heterogeneous data to facilitate accurate and efficient information retrieval and automated knowledge discovery (AKD). However, transforming unstructured content from scientific literature into KGs has remained a significant challenge, with previous methods unable to achieve human-level accuracy. In this study, we utilized an information extraction pipeline that won first place in the LitCoin NLP Challenge to construct a large-scale KG using all PubMed abstracts. The quality of the large-scale information extraction rivals that of human expert annotations, signaling a new era of automatic, high-quality database construction from literature. Our extracted information markedly surpasses the amount of content in manually curated public databases. To enhance the KG’s comprehensiveness, we integrated relation data from 40 public databases and relation information inferred from high-throughput genomics data. The comprehensive KG enabled rigorous performance evaluation of AKD, which was infeasible in previous studies. We designed an interpretable, probabilistic-based inference method to identify indirect causal relations and achieved unprecedented results for drug target identification and drug repurposing. Taking lung cancer as an example, we found that 40% of drug targets reported in literature could have been predicted by our algorithm about 15 years ago in a retrospective study, demonstrating that substantial acceleration in scientific discovery could be achieved through automated hypotheses generation and timely dissemination. A cloud-based platform (https://www.biokde.com) was developed for academic users to freely access this rich structured data and associated tools.
Phages Produce Persisters

Bacteria primarily encounter stress, and, arguably, their greatest threats are phages. It is often assumed that those bacteria that escape phage attack have mutated; however, another possibility is that a subpopulation forms the dormant persister state, in a manner similar to that demonstrated for bacterial cells undergoing nutritive, oxidative, and antibiotic stress. Persister cells do not undergo mutation and survive lethal conditions by ceasing growth transiently. Slower growth and dormancy play a key physiological role as they allow host phage defense systems more time to clear the phage infection. Here we investigated how bacteria survive lytic phage infection by isolating surviving cells from the plaques of T2, T4, and lambda (cI mutant) virulent phages. We found that bacteria in plaques can escape phage attack both by mutation (i.e., become resistant) and without mutation (i.e., become persistent). Specifically, whereas T4-resistant and lambda-resistant bacteria with over a 100,000-fold less sensitivity were isolated from plaques with obvious genetic mutations (e.g., causing mucoidy), cells were also found after T2 infection that undergo no significant mutation, retain wild-type phage sensitivity, and survive lethal doses of antibiotics. Corroborating this, adding T2 phage to persister cells resulted in 137,000-fold more survival compared to that of addition to exponentially-growing cells. Phage treatments with Klebsiella pneumonia and Pseudomonas aeruginosa also generated persister cells. Hence, along with resistant strains, bacteria also form persister cells during phage infection.
Drosophila Bchs overexpression recapitulates human WDFY3 neurodevelopmental phenotypes with implications for glial cell involvement in altered head circumference

The autophagy adaptor WDFY3 is linked to neurodevelopmental delay and altered brain size. Loss-of-function variants are associated with an increased brain size in both humans and mice. We thus, hypothesized that the microcephaly observed in some of the patients may be related to a gain-of-function of the WDFY3 gene product. While the role of WDFY3 loss-of-function has been studied extensively in neurons, little is known about the effects of WDFY3 overexpression in different neural cell types. We utilized a Drosophila melanogaster overexpression model to investigate the effect of the WDFY3 ortholog Bchs (blue cheese) on development, CNS size, and gene expression profiles. Glial and neuronal overexpression of Bchs impaired CNS development, locomotion and autophagy. Glial overexpression of Bchs also altered CNS size significantly. We identified 79 genes that were differentially expressed and overlapped in flies that overexpress Bchs in glial and neuronal cells, respectively. Additionally, upon neuronal Bchs overexpression differentially expressed genes clustered in gene ontology categories associated with autophagy and mitochondria. Our data indicate that WDFY3/Bchs overexpression in both neurons and glial cells results in impaired neural development, which corresponds to symptoms observed in WDFY3-related neurodevelopmental delay.
Cockayne syndrome patient iPSC-derived brain organoids and neurospheres show early transcriptional dysregulation of biological processes associated with brain development and metabolism

Cockayne syndrome is a rare hereditary autosomal recessive disorder characterized by diverse neurological afflictions. However, little is known about the cerebral development in CS patients. We generated neurospheres and cerebral organoids utilizing Cockayne Syndrome B Protein (CSB) deficient induced pluripotent stem cells derived from two patients with distinct severity levels of CS and healthy controls. The transcriptome of both developmental timepoints was explored using RNA-Seq and bioinformatic analysis to identify dysregulated biological processes common to both CS patients in comparison to control. CSB-deficient neurospheres displayed upregulation of VEGFA-VEGFR2 signaling pathway, Vesicle-Mediated transport and head development. CSB-deficient cerebral organoids exhibited downregulation of brain development, neuron projection development and synaptic signalling. We further identified upregulation of Steroid Biosynthesis as common to both timepoints, in particular upregulation of the Cholesterol Biosynthesis branch. Our results provide insights into the neurodevelopmental dysregulation in CS patients and strengthen the theory, that CS is not only a neurodegenerative, but also a neurodevelopmental disorder.
Transformational Planning for Autonomous Household Robots Using Libraries of Robust and Flexible Plans (Transformationsplanen für autonome Haushaltsroboter mit Hilfe einer Bibliothek von robusten und flexiblen Plänen)

This thesis investigates the problem of competently accomplishing everyday manipulation activities for autonomous robots as a plan-based control problem. We propose TRANER (TRAnsformational PlanNER) as a plan transformation system for the optimization of everyday activities. TRANER advances the state-of-the-art in three important ways. First, it extends concurrent reactive plan representation to support the specification of robust and transformable plans. Second, it proposes a library of general and flexible plans for a household robot. Third, it provides a suite of general transformation rules that are capable of improving the course of activities in important and novel ways. Comprehensive and extensive experiments in a realistic simulation environment show that transformational planning enables robots to substantially improve their performance by tailoring their course of activity to their tasks, environments, and capabilities.
NFTeller: Dual-centric Visual Analytics for Assessing Market Performance of NFT Collectibles

Non-fungible tokens (NFTs) have recently gained widespread popularity as an alternative investment. However, the lack of assessment criteria has caused intense volatility in NFT marketplaces. Identifying attributes impacting the market performance of NFT collectibles is crucial but challenging due to the massive amount of heterogeneous and multi-modal data in NFT transactions, e.g., social media texts, numerical trading data, and images. To address this challenge, we introduce an interactive dual-centric visual analytics system, NFTeller, to facilitate users’ analysis. First, we collaborate with five domain experts to distill static and dynamic impact attributes and collect relevant data. Next, we derive six analysis tasks and develop NFTeller to present the evolution of NFT transactions and correlate NFTs’ market performance with impact attributes. Notably, we create an augmented chord diagram with a radial stacked bar chart to explore intersections between NFT collection projects and whale accounts. Finally, we conduct three case studies and interview domain experts to evaluate the effectiveness and usability of this system. As such, we gain in-depth insights into assessing NFT collectibles and detecting opportune moments for investment.
Effect of poultry manure and/or inorganic fertilizer on the yield of shallot [Allium cepa var. aggergatum (G. Don)]

The study was carried out to determine the optimum levels of poultry manure, inorganic fertilizer and their combined effect on yield of shallots grown on sandy Anloga soils in Ghana. Treatments comprised a 4x3 factorial combination of poultry manure at 0, 10, 20 and 40 tons/ha and three levels of NPK 15-15-15 fertilizer at 0, 300 and 600 kg ha - 1 in a randomised complete block design with four replications. A combination of 40 tons/ha of poultry manure with 300 kg/ha and 6000 kg/ha of NPK 15-15-15 fertilizer increased plant height, number of leaves per plant and number of plantlets per plant. Although application of inorganic fertilizer alone or in combination with poultry manure significantly increased bulb yield, there was a decrease in dry matter content. Sole application of 40 tons/ha gave the highest bulb yield. Our results demonstrate that farmers in the Anloga district of Ghana can rely on organic matter alone applied at 40 tons/ha for shallot production.
A mechanism for prime-realignment during influenza A virus replication

The influenza A virus genome consists of eight segments of single-stranded RNA. These segments are replicated and transcribed by a viral RNA-dependent RNA polymerase (RdRp) that is made up of the influenza virus proteins PB1, PB2 and PA. To copy the viral RNA (vRNA) genome segments and the complementary RNA (cRNA) segments, the replicative intermediate of viral replication, the RdRp must use two promoters and two different de novo initiation mechanisms. On the vRNA promoter, the RdRp initiates on the 3’ terminus, while on the cRNA promoter the RdRp initiates internally and subsequently realigns the nascent vRNA product to ensure that the template is copied in full. In particular the latter process, which is also used by other RNA viruses, is not understood. Here we provide mechanistic insight into prime-realignment during influenza virus replication and show that it is controlled by the priming loop and a helix-loop-helix motif of the PB1 subunit of the RdRp. Overall, these observations advance our understanding of how the influenza A virus initiates viral replication and amplifies the genome correctly. Importance Influenza A viruses cause severe disease in humans and are considered a major threat to our economy and health. The viruses replicate and transcribe their genome using an enzyme called the RNA polymerases. To ensure that the genome is amplified faithfully and abundant viral mRNAs are made for viral protein synthesis, the RNA polymerase must work correctly. In this report, we provide insight into the mechanism that the RNA polymerase employs to ensure that the viral genome is copied correctly.
Practice of Epidemiology The Impact of Different CD4 Cell-Count Monitoring and Switching Strategies on Mortality in HIV-Infected African Adults on Antiretroviral Therapy: An Application of Dynamic Marginal Structural Models

In Africa, antiretroviral therapy (ART) is delivered with limited laboratory monitoring, often none. In 2003 – 2004, investigators in the Development of Antiretroviral Therapy in Africa (DART) Trial randomized persons initiating ART in Uganda and Zimbabwe to either laboratory and clinical monitoring (LCM) or clinically driven monitoring (CDM). CD4 cell counts were measured every 12 weeks in both groups but were only returned to treating clinicians for man-agement in the LCM group. Follow-up continued through 2008. In observational analyses, dynamic marginal structural models on pooled randomized groups were used to estimate survival under different monitoring-frequencyand clinical/immunological switching strategies. Assumptions included no direct effect of randomized group on mortality or confounders and no unmeasured confounders which influenced treatment switch and mortality or treatment switch and time-dependent covariates. After 48 weeks of first-line ART, 2,946 individuals contributed 11,351 person-years of follow-up, 625 switches, and 179 deaths. The estimated survival probability after a further 240 weeks for post-48-week switch at the first CD4 cell count less than 100 cells/mm 3 or non- Candida World Health Organization stage 4 event (with CD4 count <250) was 0.96 (95% confidence interval (CI): 0.94, 0.97) with 12-weekly CD4 testing, 0.96 (95% CI: 0.95, 0.97) with 24-weekly CD4 testing, 0.95 (95% CI: 0.93, 0.96) with a single CD4 test at 48 weeks (baseline), and 0.92 (95% CI: 0.91, 0.94) with no CD4 testing. Comparing randomized groups by 48-week CD4 count, the mortality risk associated with CDM versus LCM was greater in persons with CD4 counts of <100 (hazard ratio = 2.4, 95% CI: 1.3, 4.3) than in those with CD4 counts of ≥ 100 (hazard ratio = 1.1, 95% CI: 0.8, 1.7; interaction P = 0.04). These findings support a benefit from identifying patients immunologically failing first-line ART at 48 weeks.
BURGLARY DETECTION IN THE RESIDENTIAL AREAS USING YOLO AND SSD ONE-STAGE DETECTION ALGORITHM: A COMPARATIVE PERSPECTIVE

Deep learning facts are becoming increasingly important and popular. It is a significant factor in object detection. Moreover, object detection, one of the most critical and challenging parts of deep learning, is mainly used in people's everyday lives in areas like video surveillance and self-driving cars. This research is to identify and detect burglars in residential areas. To get a complete and deep understanding of the primary development status of the object (burglary) detection system, we started by looking at the existing algorithms for detection models and setting up our dataset. This paper explains how single-shot multibox detectors and Yolo use deep-learning algorithms to find burglars in residential areas. This research evaluates the deep learning approach for cutting-edge burglary detection systems. This research paper compares two algorithms of one-stage object detection, i.e., you only look once, and single-shot multibox detectors to determine which algorithm is the most effective and fastest. In this comparison, we used the datasets for each algorithm to look at how well they worked, where they were weak, and where they were strong. Based on the results, it says that in the testing environment, Yolo does better than SSD.
Non-Macrophage-Tropic Human Immunodeﬁciency Virus Type 1 R5 Envelopes Predominate in Blood, Lymph Nodes, and Semen: Implications for Transmission and Pathogenesis

Human immunodeﬁciency virus type 1 (HIV-1) R5 isolates that predominantly use CCR5 as a coreceptor are frequently described as macrophage tropic. Here, we compare macrophage tropism conferred by HIV-1 R5 envelopes that were derived directly by PCR from patient tissue. This approach avoids potentially selective culture protocols used in virus isolation. Envelopes were ampliﬁed (i) from blood and semen of adult patients and (ii) from plasma of pediatric patients. The phenotypes of these envelopes were compared to those conferred by an extended panel of envelopes derived from brain and lymph node that we reported previously. Our results show that R5 envelopes vary by up to 1,000-fold in their capacity to confer infection of primary macrophages. Highly macrophage-tropic envelopes were predominate in brain but were infrequent in semen, blood, and lymph node samples. We also conﬁrmed that the presence of N283 in the C2 CD4 binding site of gp120 is associated with HIV-1 envelopes from the brain but absent from macrophage-tropic envelopes ampliﬁed from blood and semen. Finally, we compared infection of macrophages, CD4 (cid:1) T cells, and peripheral blood mononuclear cells (PBMCs) conferred by macrophage-tropic and non-macrophage-tropic envelopes in the context of full-length replication competent viral clones. Non-macrophage-tropic envelopes conferred low-level infection of macrophages yet infected CD4 (cid:1) T cells and PBMCs as efﬁciently as highly macrophage-tropic brain envelopes. The lack of macrophage tropism for the majority of the envelopes ampliﬁed from lymph node, blood, and semen is striking and contrasts with the current consensus that R5 primary isolates are generally macrophage tropic. The extensive variation in R5 tropism reported here is likely to have an important impact on pathogenesis and on the capacity of HIV-1 to transmit.
PHENOTYPIC CHARACTERIZATION OF CARBAPENEM RESISTANT ESCHERICHIA COLI AND KLEBSIELLA PNEUMONIAE AT A TERTIARY CARE HOSPITAL IN INDORE, INDIA

Background: Carbapenem is one of the last resort antibiotics used for infections caused by multidrug-resistant Enterobacteriaceae. But Enterobacteriaceae can produce the enzyme carbapenemase and become carbapenem resistant. The presence of carbapenemase can be detected by using methods like the Carba-NP test and the modified carbapenem inactivation method (mCIM). The aim of the study was to detect carbapenemase production in Escherichia coli and Klebsiella pneumoniae isolates by the CarbaNP and modified carbapenem inactivation method (mCIM). Materials and Methods: Fifty dry human radii were collected from the Department of Anatomy at Rajah Muthiah Medical College, Chidambaram, and Government Erode Medical College, Perundurai, for this study. The number, position, and direction of the foramen were observed in each bone. Result: A total of 156 Escherichia coli and Klebsiella pneumoniae isolates which were detected for carbapenem resistance by the Kirby Bauer disc diffusion method were subjected to CarbaNP and mCIM tests. The positivity for mCIM was slightly higher (94.88 %) when compared with the Carba NP test (91.02%). The results of the present study did not reveal any statistical difference in the detection of carbapenemase production by both methods. (p-value> 0.05). Conclusion: The Carba NP and mCIM tests were equally effective in detection of the carbapenamase production.
The Impact of Social Media Discourse on Market Reactions to Data Breach Announcements: An Empirical Analysis Opleiding Informatica & Economie

This study investigates the role of social media engagement preceding data breach announcements and its impact on market reactions. We posits two hypotheses: (1) social media discourse about a firm increases before a data breach announcement, suggesting potential impression management efforts; (2) such increased discourse tempers the negative effect of the announcement on cumulative abnormal returns and thus the market reaction. An empirical of data breach announcements and corresponding Twitter activity confirms both hypotheses. It shows a significant surge in daily tweets about the firms 11 to 2 days prior to the announcements compared to a baseline of daily tweets, indicating the potential use of strategic impression management by the firms. Moreover, a rise in pre-announcement social media discourse is associated with less negative market reactions, unveiling a crucial link between social media engagement and financial implications of data breaches. This research underlines the importance of proactive social media strategies for firms managing data breaches and provides valuable insights