Miracle-dz/UniFAR-FTUs huggingface dataset:
Gene Fitness of Azotobacter vinelandii under Diazotrophic Growth

These results provide insights into the functional redundancy in A. vinelandii, while also providing a direct measure of fitness for specific genes associated with the process of BNF. These results will serve as a valuable reference tool in future studies to uncover the mechanisms that govern this process. ABSTRACT Azotobacter vinelandii is a nitrogen-fixing free-living soil microbe that has been studied for decades in relation to biological nitrogen fixation (BNF). It is highly amenable to genetic manipulation, helping to unravel the intricate importance of different proteins involved in the process of BNF, including the biosynthesis of cofactors that are essential to assembling the complex metal cofactors that catalyze the difficult reaction of nitrogen fixation. Additionally, A. vinelandii accomplishes this feat while growing as an obligate aerobe, differentiating it from many of the nitrogen-fixing bacteria that are associated with plant roots. The ability to function in the presence of oxygen makes A. vinelandii suitable for application in various potential biotechnological schemes. In this study, we employed transposon sequencing (Tn-seq) to measure the fitness defects associated with disruptions of various genes under nitrogen-fixing dependent growth, versus growth with extraneously provided urea as a nitrogen source. The results allowed us to probe the importance of more than 3,800 genes, revealing that many genes previously believed to be important, can be successfully disrupted without impacting cellular fitness. IMPORTANCE These results provide insights into the functional redundancy in A. vinelandii, while also providing a direct measure of fitness for specific genes associated with the process of BNF. These results will serve as a valuable reference tool in future studies to uncover the mechanisms that govern this process.
Deep significance clustering: a novel approach for identifying risk-stratified and predictive patient subgroups

Abstract Objective Deep significance clustering (DICE) is a self-supervised learning framework. DICE identifies clinically similar and risk-stratified subgroups that neither unsupervised clustering algorithms nor supervised risk prediction algorithms alone are guaranteed to generate. Materials and Methods Enabled by an optimization process that enforces statistical significance between the outcome and subgroup membership, DICE jointly trains 3 components, representation learning, clustering, and outcome prediction while providing interpretability to the deep representations. DICE also allows unseen patients to be predicted into trained subgroups for population-level risk stratification. We evaluated DICE using electronic health record datasets derived from 2 urban hospitals. Outcomes and patient cohorts used include discharge disposition to home among heart failure (HF) patients and acute kidney injury among COVID-19 (Cov-AKI) patients, respectively. Results Compared to baseline approaches including principal component analysis, DICE demonstrated superior performance in the cluster purity metrics: Silhouette score (0.48 for HF, 0.51 for Cov-AKI), Calinski-Harabasz index (212 for HF, 254 for Cov-AKI), and Davies-Bouldin index (0.86 for HF, 0.66 for Cov-AKI), and prediction metric: area under the Receiver operating characteristic (ROC) curve (0.83 for HF, 0.78 for Cov-AKI). Clinical evaluation of DICE-generated subgroups revealed more meaningful distributions of member characteristics across subgroups, and higher risk ratios between subgroups. Furthermore, DICE-generated subgroup membership alone was moderately predictive of outcomes. Discussion DICE addresses a gap in current machine learning approaches where predicted risk may not lead directly to actionable clinical steps. Conclusion DICE demonstrated the potential to apply in heterogeneous populations, where having the same quantitative risk does not equate with having a similar clinical profile.
Transcriptomic profiling in canines and humans reveals cancer specific gene modules and biological mechanisms common to both species

Understanding relationships between spontaneous cancer in companion (pet) canines and humans can facilitate biomarker and drug development in both species. Towards this end we developed an experimental-bioinformatic protocol that analyzes canine transcriptomics data in the context of existing human data to evaluate comparative relevance of canine to human cancer. We used this protocol to characterize five canine cancers: melanoma, osteosarcoma, pulmonary carcinoma, B- and T-cell lymphoma, in 60 dogs. We applied an unsupervised, iterative clustering method that yielded five co-expression modules and found that each cancer exhibited a unique module expression profile. We constructed cancer models based on the co-expression modules and used the models to successfully classify the canine data. These canine-derived models also successfully classified human tumors representing the same cancers, indicating shared cancer biology between canines and humans. Annotation of the module genes identified cancer specific pathways relevant to cells-of-origin and tumor biology. For example, annotations associated with melanin production (PMEL, GPNMB, and BACE2), synthesis of bone material (COL5A2, COL6A3, and COL12A1), synthesis of pulmonary surfactant (CTSH, LPCAT1, and NAPSA), ribosomal proteins (RPL8, RPS7, and RPLP0), and epigenetic regulation (EDEM1, PTK2B, and JAK1) were unique to melanoma, osteosarcoma, pulmonary carcinoma, B- and T-cell lymphoma, respectively. In total, 152 biomarker candidates were selected from highly expressing modules for each cancer type. Many of these biomarker candidates are under-explored as drug discovery targets and warrant further study. The demonstrated transferability of classification models from canines to humans enforces the idea that tumor biology, biomarker targets, and associated therapeutics, discovered in canines, may translate to human medicine.
Role of pre-operative percutaneous embolization in orbital alveolar soft part sarcoma – An experience from a tertiary eye-care center

Purpose: To describe the clinic-radiological, pathological profile, and management outcomes of primary alveolar soft-part sarcoma (ASPS) of the orbit. Methods: A retrospective analysis of all histopathologically proven cases of orbital ASPS that presented between May 2016 and September 2019 was done. Data collected included demographics, clinical features, imaging characteristics, metastatic workup, management, and follow-up. Results: Five patients, of which four were males, presented to us during the study period. The mean age of presentation was 12.6 years (range 3–22 years). The most common presenting features were abaxial proptosis (n = 4) and diminished vision (n = 4). Imaging showed a well-defined orbital mass in all patients with internal flow voids in three. Preoperative percutaneous embolization with cyanoacrylate glue was done in these three patients owing to high vascularity. Four patients underwent complete tumor excision. One patient underwent exenteration. Histopathology showed polygonal tumor cells arranged in a pseudo-alveolar pattern and Periodic Acid-Schiff (PAS) positive crystals in the cytoplasm in all patients. One patient had systemic metastasis at presentation and developed a local recurrence after 3 months. No recurrence or metastasis was noted in the remaining four patients at a mean final follow-up of 11.2 months (range 5–15 months). Conclusion: ASPS is a rare orbital neoplasm that poses a diagnostic and therapeutic challenge. Imaging might show a soft-tissue tumor with high vascularity. Multidisciplinary management with interventional radiologists for preoperative embolization of vascular lesions helps minimize intraoperative bleeding and aids in complete tumor resection. A localized orbital disease carries a better prognosis.
The Association of Bullous Pemphigoid With Atopic Dermatitis and Allergic Rhinitis—A Population-Based Study

Background Although bullous pemphigoid (BP), atopic dermatitis (AD), and allergic rhinitis (AR) are associated with shared pathogenic mechanisms the epidemiological relationship between these conditions remains to be investigated. Objective To evaluate the bidirectional association of BP with AD and AR. Methods A population-based retrospective cohort study was performed comparing BP patients (n = 3924) with age-, sex-, and ethnicity-matched control subjects (n = 19,280), with respect to incident cases of AD and AR. A case-control design was additionally adopted to assess the odds of BP in individuals with a preexisting diagnosis of AD and AR. Results The odds of BP was increased after a preexisting diagnosis of AD (fully adjusted odds ratio, 1.76; 95% confidence interval [CI], 1.44–2.15; P < 0.001) and AR (fully adjusted odds ratio, 1.13; 95% CI, 1.01–1.28; P = 0.047). Patients with BP were at an increased risk of subsequent AD (fully adjusted hazard ratio, 2.00; 95% CI, 1.60–2.51; P < 0.001) but not AR (fully adjusted hazard ratio, 1.00; 95% CI, 0.83–1.20; P = 0.997). Compared with other patients with BP, those with BP and comorbid AD and AR were more frequently managed by adjuvant drugs and long-term systemic and topical corticosteroids and had decreased all-cause mortality. Conclusions A history of AD and AR confers susceptibility to the development of BP. Awareness of this association may be of help for physicians managing patients with these diseases.
Collocational knowledge in children: a comparison of English-speaking monolingual children, and children acquiring English as an Additional Language

Abstract Collocations, e.g., apples and pears, hard worker, constitute an important avenue of linguistic enquiry straddling both grammar and the lexicon. They are sensitive to language experience, with adult L2 learners and children learning English as an Additional Language (EAL) exhibiting poor collocational knowledge. The current study piloted a novel collocational assessment with children (mean age 6;3, 40 monolingual, 32 EAL). It investigated (1) the feasibility of a collocational assessment at this age, (2) whether collocational knowledge is associated with other language domains (receptive grammar and vocabulary), and (3) whether collocational knowledge is more affected than other domains. The assessment demonstrated good psychometric properties and was highly correlated with performance in other domains, indicating shared psycholinguistic mechanisms. Unlike adult counterparts, the EAL children performed equally poorly across domains. Given the role played by collocations in vocabulary development and reading, a focus on this domain may be beneficial for EAL children.
Determination of surgical outcomes with a novel formulation of intrastromal natamycin in recalcitrant fungal keratitis: A pilot study

Purpose: To evaluate the outcomes of water-soluble intrastromal natamycin (IS-NTM) as an adjunct therapy for recalcitrant fungal keratitis. Methods: This was a prospective interventional pilot study in the setting of a tertiary eye-care center. Twenty eyes of 20 consecutive patients with microbiologically proven recalcitrant fungal keratitis (ulcer size >2 mm, depth >50%, and not responding to topical NTM for 2 weeks) were recruited. The selected patients were injected with a novel composition of IS-NTM (10 ug/0.1 mL, soluble natamycin) prepared aseptically in the ocular pharmacology department. All the patients continued using topical NTM suspension 5% 4-hourly until the ulcer healed. Repeat injections were undertaken after 72 h depending on the clinical response and all the patients were followed till 6 months. Results: The mean age of the patients was 40.42 ± 10.09 years. The mean duration of the presentation was 20.8 ± 5.1 days. The most commonly isolated organisms were Aspergillus sp. (12/20, 60%) and Fusarium sp. (8/20, 40%). No patient had iatrogenic perforation or precipitate formation after IS-NTM injection. The overall cure rate with IS-NTM was 95% (19/20 patients). The number of patients who healed with the 1st, 2nd, and 3rd injection was 13, 5, and 1, respectively. One (5%) had no response to treatment and was subjected to penetrating keratoplasty. The average time taken for the resolution of the epithelial defect, stromal infiltrates, and hypopyon was 34 ± 5.2 days, 35.3 ± 6.4 days, and 15 ± 2.5 days. Healing with deep vascularization and cataract was noted in 6/19 eyes (31%) and 13/19 eyes (68.42%), respectively. Conclusion: Intrastromal injection of a novel formulation of NTM holds a promising role as adjunctive therapy to topical NTM in the management of recalcitrant filamentous fungal keratitis. The preliminary results are encouraging and further studies are required to validate the results.
Effects of pulmonary rehabilitation on diaphragm thickness and contractility in patients with chronic obstructive pulmonary disease

Background/aim Studies are showing that pulmonary rehabilitation (PR) increases diaphragmatic excursion by decreasing hyperinflation in patients with chronic obstructive pulmonary disease (COPD). However, there is a lack of knowledge about its effects on the diaphragm thickness (dt) and contractility. This study aims to evaluate the dt and contractility before and after PR in patients with COPD. Materials and methods All subjects participated in an out-patient PR of 6 weeks and 3 sessions per week prospectively. Dyspnea severity, the disease-specific quality of life (St. Georges Respiratory Questionnaire-SGRQ), pulmonary function tests (PFT), exercise capacity, the dt at the end of the expiration and at maximal inspiration (B-mode ultrasound) were evaluated at baseline and after PR. Results A total of 34 patients with a mean age and FEV1 61.05 ± 8.22 years and 57.9 ± 20.4% predicted respectively showed improvements in exercise capacity and some items of PFT and SGRQ. Diaphragmatic thickness at the end of the expiration also significantly improved regardless of the disease severity and was positively correlated with functional performance. The 6-weeks of PR didn’t result in a significant difference in diaphragm contractility. Conclusion The 6-weeks of PR resulted in a significant increase in dt without a significant difference in diaphragm contractility.
A model of head direction and landmark coding in complex environments

Environmental information is required to stabilize estimates of head direction (HD) based on angular path integration. However, it is unclear how this happens in real-world (visually complex) environments. We present a computational model of how visual feedback can stabilize HD information in environments that contain multiple cues of varying stability and directional specificity. We show how combinations of feature-specific visual inputs can generate a stable unimodal landmark bearing signal, even in the presence of multiple cues and ambiguous directional specificity. This signal is associated with the retrosplenial HD signal (inherited from thalamic HD cells) and conveys feedback to the subcortical HD circuitry. The model predicts neurons with a unimodal encoding of the egocentric orientation of the array of landmarks, rather than any one particular landmark. The relationship between these abstract landmark bearing neurons and head direction cells is reminiscent of the relationship between place cells and grid cells. Their unimodal encoding is formed from visual inputs via a modified version of Oja’s Subspace Algorithm. The rule allows the landmark bearing signal to disconnect from directionally unstable or ephemeral cues, incorporate newly added stable cues, support orientation across many different environments (high memory capacity), and is consistent with recent empirical findings on bidirectional HD firing reported in the retrosplenial cortex. Our account of visual feedback for HD stabilization provides a novel perspective on neural mechanisms of spatial navigation within richer sensory environments, and makes experimentally testable predictions.
The readability of official public health information on COVID‐19

The information needs of people with lower health literacy or from culturally and linguistically diverse backgrounds have received limited attention during the coronavirus disease 2019 (COVID19) pandemic. In one study, the complexity of most governmentproduced COVID19 information in Australia and overseas exceeded the recommended grade 8 reading level, making it too difficult for general audiences, let alone people with lower health literacy.1 We therefore compared the complexity (readability, understandability, actionability) of Australian and overseas COVID19 vaccination information with that of other COVID19related information (physical distancing, mask wearing), including “easy read” resources developed in Australia and New Zealand.
A lipoprotein allosterically activates the CwlD amidase during Clostridioides difficile spore formation

Spore-forming pathogens like Clostridioides difficile depend on germination to initiate infection. During gemination, spores must degrade their cortex layer, which is a thick, protective layer of modified peptidoglycan. Cortex degradation depends on the presence of the spore-specific peptidoglycan modification, muramic-∂-lactam (MAL), which is specifically recognized by cortex lytic enzymes. In C. difficile, MAL production depends on the CwlD amidase and its binding partner, the GerS lipoprotein. To gain insight into how GerS regulates CwlD activity, we solved the crystal structure of the CwlD:GerS complex. In this structure, a GerS homodimer is bound to two CwlD monomers such that the CwlD active sites are exposed. Although CwlD structurally resembles amidase_3 family members, we found that CwlD does not bind Zn2+ stably on its own, unlike previously characterized amidase_3 enzymes. Instead, GerS binding to CwlD promotes CwlD binding to Zn2+, which is required for its catalytic mechanism. Thus, in determining the first structure of an amidase bound to its regulator, we reveal stabilization of Zn2+ co-factor binding as a novel mechanism for regulating bacterial amidase activity. Our results further suggest that allosteric regulation by binding partners may be a more widespread mode for regulating bacterial amidase activity than previously thought.
Health professionals' perceptions of maggot debridement therapy.

BACKGROUND Maggot debridement therapy (MDT), or the use of maggots in dead tissue removal, has been shown to be beneficial in wound healing. Yet MDT in the US is often only used once conventional debridement methods have failed. METHOD In this study, nine health professionals, experienced in MDT, were interviewed in order to identify and analyse the perceived societal barriers to MDT acceptance and usage in the US. RESULTS Through qualitative analysis, using the grounded theory framework, this study found that among those interviewed, insurance reimbursement restrictions and stigmatisation of medicinal maggots were the factors driving resistance to MDT use. CONCLUSION Specifically, the 'yuck' factor and the perception of MDT as an 'ancient' modality contributed towards MDT stigma; in addition, lack of outpatient insurance coverage deterred MDT use. These findings provide useful information regarding the perceptual and systemic barriers that prevent greater acceptance of MDT. Ultimately, these barriers must be understood if we are to facilitate MDT implementation and improve MDT usage in the future.
Comparison of transcriptional profiles of Treponema pallidum during experimental infection of rabbits and in vitro culture: Highly similar, yet different

Treponema pallidum ssp. pallidum, the causative agent of syphilis, can now be cultured continuously in vitro utilizing a tissue culture system, and the multiplication rates are similar to those obtained in experimental infection of rabbits. In this study, the RNA transcript profiles of the T. pallidum Nichols during in vitro culture and rabbit infection were compared to examine whether gene expression patterns differed in these two environments. To this end, RNA preparations were converted to cDNA and subjected to RNA-seq using high throughput Illumina sequencing; reverse transcriptase quantitative PCR was also performed on selected genes for validation of results. The transcript profiles in the in vivo and in vitro environments were remarkably similar, exhibiting a high degree of concordance overall. However, transcript levels of 94 genes (9%) out of the 1,063 predicted genes in the T. pallidum genome were significantly different during rabbit infection versus in vitro culture, varying by up to 8-fold in the two environments. Genes that exhibited significantly higher transcript levels during rabbit infection included those encoding multiple ribosomal proteins, several prominent membrane proteins, glycolysis-associated enzymes, replication initiator DnaA, rubredoxin, thioredoxin, two putative regulatory proteins, and proteins associated with solute transport. In vitro cultured T. pallidum had higher transcript levels of DNA repair proteins, cofactor synthesis enzymes, and several hypothetical proteins. The overall concordance of the transcript profiles may indicate that these environments are highly similar in terms of their effects on T. pallidum physiology and growth, and may also reflect a relatively low level of transcriptional regulation in this reduced genome organism.
Endoplasmic reticulum stress promotes HBV production by enhancing use of the autophagosome/multivesicular body axis

HBV infection has been reported to trigger endoplasmic reticulum (ER) stress and initiate autophagy. However, how ER stress and autophagy influence HBV production remains elusive. Here, we studied the effect of tunicamycin (TM), an N‐glycosylation inhibitor and ER stress inducer, on HBV replication and secretion and examined the underlying mechanisms.
A KG-Enhanced Multi-Graph Neural Network for Attentive Herb Recommendation

Traditional Chinese Medicine (TCM) has the longest clinical history in Asia and contributes a lot to health maintenance worldwide. An essential step during the TCM diagnostic process is syndrome induction, which comprehensively analyzes the symptoms and generates an overall summary of the symptoms. Given a set of symptoms, the existing herb recommenders aim to generate the corresponding herbs as a treatment by inducing the implicit syndrome representations based on TCM prescriptions. As different symptoms have various importance during the comprehensive consideration, we argue that treating the co-occurred symptoms equally to do syndrome induction in the previous studies will lead to the coarse-grained syndrome representation. In this paper, we bring the attention mechanism to model the syndrome induction process. Given a set of symptoms, we leverage an attention network to discriminate the symptom importance and adaptively fuse the symptom embeddings. Besides, we introduce a TCM knowledge graph to enrich the input corpus and improve the quality of representation learning. Further, we build a KG-enhanced Multi-Graph Neural Network architecture, which performs the attentive propagation to combine node feature and graph structural information. Extensive experimental results on two TCM data sets show that our proposed model has the outstanding performance over the state-of-the-arts.