Miracle-dz/UniFAR-FTUs huggingface dataset:
Superadditivity and Convex Optimization for Globally Optimal Cell Segmentation Using Deformable Shape Models

Cell nuclei segmentation is challenging due to shape variation and closely clustered or partially overlapping objects. Most previous methods are not globally optimal, limited to elliptical models, or are computationally expensive. In this work, we introduce a globally optimal approach based on deformable shape models and global energy minimization for cell nuclei segmentation and cluster splitting. We propose an implicit parameterization of deformable shape models and show that it leads to a convex energy. Convex energy minimization yields the global solution independently of the initialization, is fast, and robust. To jointly perform cell nuclei segmentation and cluster splitting, we developed a novel iterative global energy minimization method, which leverages the inherent property of superadditivity of the convex energy. This property exploits the lower bound of the energy of the union of the models and improves the computational efficiency. Our method provably determines a solution close to global optimality. In addition, we derive a closed-form solution of the proposed global minimization based on the superadditivity property for non-clustered cell nuclei. We evaluated our method using fluorescence microscopy images of five different cell types comprising various challenges, and performed a quantitative comparison with previous methods. Our method achieved state-of-the-art or improved performance.
Patients’ experiences with physical holding and mechanical restraint in the psychiatric care: an interview study

Abstract Background In the continuous work to reduce the use of coercion in psychiatric care, attention in Denmark has especially been directed towards mechanical restraint. While the use of mechanical restraint is currently decreasing, an increase in other types of coercion is observed (e.g. medication and hour-long episodes of physical holding). Physical holding has, in this cultural context, been considered less intrusive to a patient’s autonomy than the use of mechanical restraint. However, no study has yet compared the experiences of the patients on these two types of coercion in the same population. The objective of this study was to explore patients’ perspectives on physical holding and mechanical restraint, respectively. Methods Audio-recorded, semi-structured interviews following an interview guide were conducted with patients sharing their experiences with both types of coercion. The interviews were transcribed verbatim. The analytical approach was based on the principles of thematic content analysis. Results Nine informants were interviewed between September 2020 and April 2021. Four main themes were identified: experiences with physical holding, experiences with mechanical restraint, the effects of coercion on patients and their relation to mental health care, and improved mental health care. Conclusion It is inconclusive which type of restraint the patients preferred. This challenges the present hierarchy of coercive measures. To avoid coercion in the first place more communication and time with the patient are needed.
Studying the Effect of Long COVID-19 Infection on Sleep Quality Using Wearable Health Devices: Observational Study

Background Patients with COVID-19 have increased sleep disturbances and decreased sleep quality during and after the infection. The current published literature focuses mainly on qualitative analyses based on surveys and subjective measurements rather than quantitative data. Objective In this paper, we assessed the long-term effects of COVID-19 through sleep patterns from continuous signals collected via wearable wristbands. Methods Patients with a history of COVID-19 were compared to a control arm of individuals who never had COVID-19. Baseline demographics were collected for each subject. Linear correlations among the mean duration of each sleep phase and the mean daily biometrics were performed. The average duration for each subject’s total sleep time and sleep phases per night was calculated and compared between the 2 groups. Results This study includes 122 patients with COVID-19 and 588 controls (N=710). Total sleep time was positively correlated with respiratory rate (RR) and oxygen saturation (SpO2). Increased awake sleep phase was correlated with increased heart rate, decreased RR, heart rate variability (HRV), and SpO2. Increased light sleep time was correlated with increased RR and SpO2 in the group with COVID-19. Deep sleep duration was correlated with decreased heart rate as well as increased RR and SpO2. When comparing different sleep phases, patients with long COVID-19 had decreased light sleep (244, SD 67 vs 258, SD 67; P=.003) and decreased deep sleep time (123, SD 66 vs 128, SD 58; P=.02). Conclusions Regardless of the demographic background and symptom levels, patients with a history of COVID-19 infection demonstrated altered sleep architecture when compared to matched controls. The sleep of patients with COVID-19 was characterized by decreased total sleep and deep sleep.
Association of ABCG2 polymorphisms with susceptibility to anti-tuberculosis drug-induced hepatotoxicity in the Chinese population

Abstract The accumulation of endogenous hepatotoxin protoporphyrin IX (PPIX) in the liver was proposed to be a novel mechanism of anti-tuberculosis drug-induced hepatotoxicity (ATDH). ATP-binding cassette transporter G2 (ABCG2) plays an important role in modulating PPIX concentrations. This study aimed to explore the role of ABCG2 genetic polymorphisms in the risk of ATDH in Chinese patients. A 1:4 matched case–control study was performed among 202 ATDH cases and 808 controls. Conditional logistic regression model was used to estimate the association between genotypes and the risk of ATDH by odds ratios (ORs) with 95% confidence intervals (CIs). Male patients with CC genotype of rs2622605 had an increased risk of ATDH (adjusted OR = 1.615, 95% CI: 1.119–2.332, p = 0.011). The peak value of alkaline phosphatase (ALP) was significantly higher in male patients with CC genotype of rs2622605 than in those with TT + TC genotype during antituberculosis treatment (102.0 U/L vs. 98.0 U/L, p = 0.029). This is the first attempt to evaluate the association between ABCG2 genetic variants and the risk of ATDH. Based on the 1:4 matched case–control study, the polymorphism at rs2622605 in the ABCG2 gene may be associated with the susceptibility to ATDH in Chinese male patients.
Draft Genome Sequences of Nine Stenotrophomonas maltophilia Isolates from a Freshwater Catchment Area in Hong Kong

Stenotrophomonas maltophilia is a widely distributed, Gram-negative bacillus that is increasingly identified as a multidrug-resistant opportunistic pathogen of concern. Here, we report the draft genome sequences of nine strains that were isolated from a freshwater catchment area in Hong Kong, corresponding to four different monophyletic lineages within the species. ABSTRACT Stenotrophomonas maltophilia is a widely distributed, Gram-negative bacillus that is increasingly identified as a multidrug-resistant opportunistic pathogen of concern. Here, we report the draft genome sequences of nine strains that were isolated from a freshwater catchment area in Hong Kong, corresponding to four different monophyletic lineages within the species.
The Impact of Occlusion Therapy on Amblyopia Success Outcomes

ABSTRACT Purpose The recommended amount of occlusion therapy and amblyopia treatment success rates remains controversial. This study explores rates of occlusion therapy success and attempts to address limitations of previous literature. Methods A retrospective chart review was performed on patients with occlusion therapy outcomes from 2012 to 2019. Equal visual acuity (VA) or stable VA for three consecutive clinical visits, despite reported good compliance defined outcome VA. Results Results showed 90.3% of subjects obtained outcome distance VA of 0.3logMAR, 76% ≥0.3logMAR, 35% ≥0.2logMAR, and 6% ≥0.1logMAR in the amblyopic eye following treatment. Sixty-nine percent of the study population obtained equal vision following occlusion therapy. Only initial VA (amblyopic eye) and initial interocular visual optotype difference at distance predicted post-treatment success. Conclusion These results support the conclusion that occlusion therapy, both PTO and FTO, can be effective in treating amblyopia when good compliance is maintained based on parental reports of compliance. Additionally, as VA gain was higher than in previous literature, it is important to continue treatment until VA is equal or three consecutive cycles of stable VA are obtained to ensure maximum VA improvement.
New tree‐level temperature response curves document sensitivity of tree growth to high temperatures across a US‐wide climatic gradient

Temperature is a key climate indicator, whose distribution is expected to shift right in a warming world. However, the high‐temperature tolerance of trees is less widely understood than their drought tolerance, especially when it comes to sub‐lethal impacts of temperature on tree growth. I use a large data set of annual tree ring widths, combined with a flexible degree day model, to estimate the relationship between temperature and tree radial growth. I find that tree radial growth responds non‐linearly to temperature across many ecoregions of the United States: across temperate and/or dry ecoregions, spring–summer temperature increases are beneficial or mostly neutral for tree growth up to around 25–30°C in humid climates and 10–15°C in dry climates, beyond which temperature increases suppress growth. Thirty additional degree days above the optimal temperature breakpoint lead to an average decrease in tree ring width of around 1%–5%, depending on ecoregions, seasons, and inclusion or exclusion of temperature‐mediated drought impacts. High temperatures have legacy effects across a 5‐year horizon in dry ecoregions, but none in the temperate‐humid South‐East or among temperature‐sensitive trees. I find limited evidence that trees acclimatize to high temperatures within their lifetime: local variation in early exposure to high temperatures, which stems from local variation in the timing of tree birth, does not significantly impact the response to high temperatures, although temperature‐sensitive trees acquire some heightened sensitivity from early exposure. I also find some evidence that trees adapt to high temperatures in the long run: across humid ecoregions of the United States, high temperatures are 40% less harmful to tree growth, where their average incidence is one standard deviation above average. Overall, these results highlight the strength of a new methodology which, applied to representative tree ring data, could contribute to predicting forest carbon uptake potential and composition under global change.
Therapeutic Inhibition of Staphylococcus aureus ArlRS Two-Component Regulatory System Blocks Virulence

Staphylococcus aureus is a common cause of severe infections, and its widespread antibiotic resistance necessitates search for alternative therapies, such as inhibition of virulence. As S. aureus produces multiple individual virulence factors, inhibition of an entire regulatory system might provide better effects than targeting each virulence factor separately. ABSTRACT Staphylococcus aureus is a common cause of severe infections, and its widespread antibiotic resistance necessitates search for alternative therapies, such as inhibition of virulence. As S. aureus produces multiple individual virulence factors, inhibition of an entire regulatory system might provide better effects than targeting each virulence factor separately. Herein, we describe two novel inhibitors of S. aureus two-component regulatory system ArlRS: 3,4’-dimethoxyflavone and homopterocarpin. Unlike other putative ArlRS inhibitors previously identified, these two compounds were effective and specific. In vitro kinase assays indicated that 3,4’-dimethoxyflavone directly inhibits ArlS autophosphorylation, while homopterocarpin did not exhibit such effect, suggesting that two inhibitors work through distinct mechanisms. Application of the inhibitors to methicillin-resistant S. aureus (MRSA) in vitro blocked ArlRS signaling, inducing an abnormal gene expression pattern that was reflected in changes at the protein level, enhanced sensitivity to oxacillin, and led to the loss of numerous cellular virulence traits, including the ability to clump, adhere to host ligands, and evade innate immunity. The pleiotropic antivirulence effect of inhibiting a single regulatory system resulted in a marked therapeutic potential, demonstrated by the ability of inhibitors to decrease severity of MRSA infection in mice. Altogether, this study demonstrated the feasibility of ArlRS inhibition as anti-S. aureus treatment, and identified new lead compounds for therapeutic development.
Parallel Evolution towards Increased Motility in Long-Term Cultures of Escherichia coli, Even Though Motility was Not Required for Long-Term Survival

Understanding how bacteria adapt in long-term cultures aids in both better treatment options for bacterial infections and gives insight into the mechanisms involved in bacterial evolution. In the past, it has been difficult to study these organisms in their natural environments. ABSTRACT Escherichia coli can survive for long periods in batch culture in the laboratory, where they experience a stressful and heterogeneous environment. During this incubation, E. coli acquires mutations that are selected in response to this environment, ultimately leading to evolved populations that are better adapted to these complex conditions, which can lead to a better understanding of evolutionary mechanisms. Mutations in regulatory genes often play a role in adapting to heterogeneous environments. To identify such mutations, we examined transcriptional differences during log phase growth in unaged cells compared to those that had been aged for 10 days and regrown. We identified expression changes in genes involved in motility and chemotaxis after adaptation to long-term cultures. We hypothesized that aged populations would also have phenotypic changes in motility and that motility may play a role in survival and adaptation to long-term cultures. While aged populations did show an increase in motility, this increase was not essential for survival in long-term cultures. We identified mutations in the regulatory gene sspA and other genes that may contribute to the observed differences in motility. Taken together, these data provide an overall picture of the role of mutations in regulatory genes for adaptation while underscoring that all changes that occur during evolution in stressful environments are not necessarily adaptive. IMPORTANCE Understanding how bacteria adapt in long-term cultures aids in both better treatment options for bacterial infections and gives insight into the mechanisms involved in bacterial evolution. In the past, it has been difficult to study these organisms in their natural environments. By using experimental evolution in heterogeneous and stressful laboratory conditions, we can more closely mimic natural environments and examine evolutionary mechanisms. One way to observe these mechanisms is to look at transcriptomic and genomic data from cells adapted to these complex conditions. Here, we found that although aged cells increase motility, this increase is not essential for survival in these conditions. These data emphasize that not all changes that occur due to evolutionary processes are adaptive, but these observations could still lead to hypotheses about the causative mutations. The information gained here allow us to make inferences about general mechanisms underlying phenotypic changes due to evolution.
Factors associated with lifetime suicide attempts: findings from the bipolar disorder course and outcome study from India (BiD-CoIN study)

Abstract Aim To evaluate the risk factors associated with lifetime suicide attempts in bipolar disorder (BD) patients. Methodology 773 BD patients with a duration of illness of at least ten years, currently in clinical remission, were evaluated for suicidal attempts in their lifetime. Those with and without lifetime suicide attempt(s) were compared for various demographic and clinical risk factors. Results 242 (31.3%) patients had a history of at least one lifetime suicide attempt. Compared to those without lifetime suicide attempts, those with suicidal attempts were less educated, were more often females, spent more time in episodes, and had a significantly more number of total episodes (in the lifetime, first five years of illness, and per year of illness), had significantly more number of total depressive episodes (in the lifetime, first five years of illness, and per year of illness), spent more time in depressive episodes, had more severe depressive episodes, more often had depression as the first episode in the lifetime, spent more time in mania/hypomania/mixed episodes, had higher residual depressive and manic symptoms, more often had rapid cycling affective disorder pattern in the lifetime, use of cannabis in dependence pattern, had poorer insight into their illness and had a higher level of disability (especially in three out of the four domains of Indian disability evaluation assessment scale). Conclusions About one-third of the patients with BD have at least one-lifetime suicidal attempt, and those with suicide attempts usually have a poorer course of illness.
Essential Roles of Ribonucleotide Reductases under DNA Damage and Replication Stresses in Cryptococcus neoformans

Upon DNA replication or damage stresses, it is critical to provide proper levels of deoxynucleotide triphosphates (dNTPs) and activate DNA repair machinery. Ribonucleotide reductases (RNRs), which are composed of large and small subunits, are required for synthesizing dNTP. ABSTRACT A balance in the deoxyribonucleotide (dNTPs) intracellular concentration is critical for the DNA replication and repair processes. In the model yeast Saccharomyces cerevisiae, the Mec1-Rad53-Dun1 kinase cascade mainly regulates the ribonucleotide reductase (RNR) gene expression during DNA replication and DNA damage stress. However, the RNR regulatory mechanisms in basidiomycete fungi during DNA replication and damage stress remain elusive. Here, we observed that in C. neoformans, RNR1 (large RNR subunit) and RNR21 (one small RNR subunit) were required for cell viability, but not RNR22 (another small RNR subunit). RNR22 overexpression compensated for the lethality of RNR21 suppression. In contrast to the regulatory mechanisms of RNRs in S. cerevisiae, Rad53 and Chk1 kinases cooperatively or divergently controlled RNR1 and RNR21 expression under DNA damage and DNA replication stress. In particular, this study revealed that Chk1 mainly regulated RNR1 expression during DNA replication stress, whereas Rad53, rather than Chk1, played a significant role in controlling the expression of RNR21 during DNA damage stress. Furthermore, the expression of RNR22, not but RNR1 and RNR21, was suppressed by the Ssn6-Tup1 complex during DNA replication stress. Notably, we observed that RNR1 expression was mainly regulated by Mbs1, whereas RNR21 expression was cooperatively controlled by Mbs1 and Bdr1 as downstream factors of Rad53 and Chk1 during DNA replication and damage stress. Collectively, the regulation of RNRs in C. neoformans has both evolutionarily conserved and divergent features in DNA replication and DNA damage stress, compared with other yeasts. IMPORTANCE Upon DNA replication or damage stresses, it is critical to provide proper levels of deoxynucleotide triphosphates (dNTPs) and activate DNA repair machinery. Ribonucleotide reductases (RNRs), which are composed of large and small subunits, are required for synthesizing dNTP. An imbalance in the intracellular concentration of dNTPs caused by the perturbation of RNR results in a reduction in DNA repair fidelity. Despite the importance of their roles, functions and regulations of RNR have not been elucidated in the basidiomycete fungi. In this study, we found that the roles of RNR1, RNR21, and RNR22 genes encoding RNR subunits in the viability of C. neoformans. Furthermore, their expression levels are divergently regulated by the Rad53-Chk1 pathway and the Ssn6-Tup1 complex in response to DNA replication and damage stresses. Therefore, this study provides insight into the regulatory mechanisms of RNR genes to DNA replication and damage stresses in basidiomycete fungi.
Apr 27, 2021 The “Rapid’Salmonella” Method: Estimation of the Limit of Detection for Salmonella Strains Typhimurium and Enteritidis Isolated from

As a part of evaluation the surveillance system of Salmonella in frozen imported poultry meat into Jordan, we conducted a study to estimate the limit of detection (LOD 50% and LOD 95% ) of Salmonella Typhimurium and Salmonella Enteritidis based on chromogenic media of Rapid’ Salmonella method. Salmonella -free chicken meat samples was inoculated with 1 to 100 CFU of 11 wild strains that originated from frozen imported poultry meat and 2 reference strains. In the experiment, the observed lowest concentration for Salmonella Typhimurium and Salmonella Enteritidis using Rapid’ Salmonella method were from 1 to 50 CFU/25 g. Based on these results, probability of detection (POD) curve was estimated according to the model described in EN ISO 16140-4. From the estimated POD functions, the LOD 50% and LOD 95% was determined for the Rapid’ Salmonella method. The LOD 50% of the different strains varied from 0.9 to 21.2 CFU/25 g. The two reference strains and 9 wild strains had a LOD 50% less than 2 CFU/25 g, one wild strain of Salmonella Enteritidis had a LOD 50% of 6.8 CFU/25 g and another one had a LOD 50% of 21.2 CFU/25 g. The majority of Salmonella strains has a LOD 50% of 1-4 CFU/25 g in poultry meat, but also that there are some Salmonella strains which will first be detected at 10 CFU/25 g and higher.