Task-Oriented Training by a Personalized Electromyography-Driven Soft Robotic Hand in Chronic Stroke: A Randomized Controlled Trial.

BACKGROUND: Intensive task-oriented training has shown promise in enhancing distal motor function among patients with chronic stroke. A personalized electromyography (EMG)-driven soft robotic hand was developed to assist task-oriented object-manipulation training effectively. Objective. To compare the effectiveness of task-oriented training using the EMG-driven soft robotic hand. METHODS: A single-blinded, randomized controlled trial was conducted with 34 chronic stroke survivors. The subjects were randomly assigned to the Hand Task (HT) group (n = 17) or the control (CON) group (n = 17). The HT group received 45 minutes of task-oriented training by manipulating small objects with the robotic hand for 20 sessions, while the CON group received 45 minutes of hand-functional exercises without objects using the same robot. Fugl-Meyer assessment (FMA-UE), Action Research Arm Test (ARAT), Modified Ashworth Score (MAS), Box and Block test (BBT), Maximum Grip Strength, and active range of motion (AROM) of fingers were assessed at baseline, after intervention, and 3 months follow-up. The muscle co-contraction index (CI) was analyzed to evaluate the session-by-session variation of upper limb EMG patterns. RESULTS: The HT group showed more significant improvement in FMA-UE (wrist/hand, shoulder/elbow) compared to the CON group (P < .05). At 3-month follow-up, the HT group demonstrated significant improvements in FMA-UE, ARAT, BBT, MAS (finger), and AROMs (P < .05). The HT group exhibited a more significant decrease in muscle co-contractions compared to the CON group (P < .05). CONCLUSIONS: EMG-driven task-oriented training with the personalized soft robotic hand was a practical approach to improving motor function and muscle coordination. CLINICAL TRIAL REGISTRY NAME: Soft Robotic Hand System for Stroke Rehabilitation. CLINICAL TRIAL REGISTRATION-URL: https://clinicaltrials.gov/. UNIQUE IDENTIFIER: NCT03286309.

Unemployed, Immigrant, and Older Asian Workers in a U.S.-Based Job-Training Program: Their Experiences and Well-Being, and Strategies for Reaching This Important Population.

The Senior Community Service Employment Program (SCSEP) is a U.S.-based job-training program that serves unemployed workers aged 55 and older with incomes at or below 125% of the federal poverty level. While federal funds are set aside to serve Asian workers in SCSEP, little is known about their characteristics and experiences. In response, this pilot study aimed to document the health, well-being, and experiences of older Asian SCSEP participants in Massachusetts through the completion of a survey. Respondents (N = 39) ranged in age from 58 to 73 and identified as either Chinese (72%) or Vietnamese (28%). All were immigrants, and almost all spoke a language other than English at home. Most reported "good" health as well as financial difficulties. They also stated that their supervisors in their placements were supportive. On average, respondents noted moderate interest in searching for a paid job after exiting SCSEP, although more reported interest in searching for a volunteer role. Key to the success of this study was a robust collaboration with a local human services organization with strong ties to the Chinese and Vietnamese communities. The findings highlight the importance of this growing group of older workers.

The First Report of Candida Auris Infection in Vietnam.

Infection caused by Candida auris ha C. auris s rapidly become a global health threat. C. auris created a significant healthcare burden due to various complicating factors, including misidentification by commercial identification methods, potent antifungal resistance, high mortality rates and the possibility of nosocomial outbreaks through direct contact. In Vietnam, there are currently no clinical reports on C. auris infections. Here, we present four clinical cases of C. auris infections in the Department of Pulmonary Medicine of Cho Ray Hospital in southern Vietnam. Through this report, we aim to highlight the attention to the emergence of C. auris in Vietnam. Further research on C. auris infections is warranted, focusing on newly observed clinical characteristics present in all cases in this report, including hypoalbuminaemia and corticosteroid usage. Moreover, one case of resistance to amphotericin B has been identified, possibly due to prior exposure to this antifungal agent. LEARNING POINTS: Further research on Candida auris infections is warranted, focusing on newly observed clinical features present in all cases in this report, including hypoalbuminaemia and corticosteroid use during hospitalisation.While Candida auris remains susceptible to commonly used antifungal drugs, one case of resistance to amphotericin B has been documented, possibly due to prior exposure to this antifungal agent.

Determination of ITS1 haplotypes of Fritillariae Cirrhosae Bulbus by amplicon sequencing.

BACKGROUND: Fritillariae Cirrhosae Bulbus is an antitussive and expectorant Chinese medicinal material derived from the dried bulbs of six Fritillaria species. In the 2015 edition of the Chinese Pharmacopoeia, the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) is the officially listed method for their authenfication. Specifically, the ~ 300-bp ITS1 amplicon of only Fritillariae Cirrhosae Bulbus but not other Fritillaria species can be cleaved into two smaller fragments with restriction enzyme SmaI. Considering repeated reported cases of incomplete digestion of ITS1 amplicon, this study aims to investigate the possibility of heterogeneous ITS1 sequences contained in the Fritillariae Cirrhosae Bulbus. METHODS: In this study, ITS1 amplicons of Fritillaria Cirrhosae Bulbus and four other Fritillaria species were sequenced on Illumina platform. We utilised high-throughout amplicon sequencing to determine ITS1 haplotypes and their frequencies in Fritillaria genomes. RESULTS: Our results showed that all six botanical sources of Fritillariae Cirrhosae Bulbus indeed possess ITS1 haplotypes with no SmaI restriction site, and the average percentages of ITS1 reads containing SmaI restriction site ranged from 63.60% to 91.81%. CONCLUSION: Our findings suggest that the incomplete digestion in PCR-RFLP analysis of Fritillariae Cirrhosae Bulbus is caused by the presence of ITS1 haplotypes without SmaI restriction site due to intragenomic heterogeneity.

Methylation of histone H3 lysine 36 is a barrier for therapeutic interventions of head and neck squamous cell carcinoma.

Approximately 20% of head and neck squamous cell carcinomas (HNSCCs) exhibit reduced methylation on lysine 36 of histone H3 (H3K36me) due to mutations in histone methylase NSD1 or a lysine-to-methionine mutation in histone H3 (H3K36M). Whether such alterations of H3K36me can be exploited for therapeutic interventions is still unknown. Here, we show that HNSCC models expressing H3K36M can be divided into two groups: those that display aberrant accumulation of H3K27me3 and those that maintain steady levels of H3K27me3. The former group exhibits reduced proliferation, genome instability, and heightened sensitivity to genotoxic agents like PARP1/2 inhibitors. Conversely, H3K36M HNSCC models with constant H3K27me3 levels lack these characteristics unless H3K27me3 is elevated by DNA hypomethylating agents or inhibiting H3K27me3 demethylases KDM6A/B. Mechanistically, H3K36M reduces H3K36me by directly impeding the activities of the histone methyltransferase NSD3 and the histone demethylase LSD2. Notably, aberrant H3K27me3 levels induced by H3K36M expression are not a bona fide epigenetic mark because they require continuous expression of H3K36M to be inherited. Moreover, increased sensitivity to PARP1/2 inhibitors in H3K36M HNSCC models depends solely on elevated H3K27me3 levels and diminishing BRCA1- and FANCD2-dependent DNA repair. Finally, a PARP1/2 inhibitor alone reduces tumor burden in a H3K36M HNSCC xenograft model with elevated H3K27me3, whereas in a model with consistent H3K27me3, a combination of PARP1/2 inhibitors and agents that up-regulate H3K27me3 proves to be successful. These findings underscore the crucial balance between H3K36 and H3K27 methylation in maintaining genome instability, offering new therapeutic options for patients with H3K36me-deficient tumors.

Cytochrome oxidase I DNA barcodes of crocodilians meat selling in Hong Kong.

The crocodilians include true crocodiles, alligators, caimans, and gharial, and the trade of crocodilian products is regulated in accordance with the Convention of Wild Fauna and Flora (CITES). Hong Kong does not have her own wild crocodilians; thus, all crocodilians meat available is presumably imported with proper license. Here, we obtained a dataset of cytochrome oxidase I (COI) gene markers of 114 crocodilian meat samples (including frozen and dried crocodilian meat products) available in the contemporary market. We have also validated these barcodes in a phylogenetic approach with other data deposited on the GenBank, and detected 112 samples belonging to four crocodile species Crocodylus siamensis, C. porosus, C. niloticus and Alligator mississippiensis, and 2 samples belonging to snake Malayopython reticulatus. The dataset generated in this study will be useful for further studies including meat inspection, illegal trading, and enhancement of international and local legislations on illegal reptile importation.

Challenges in diagnosis and management of central airway obstruction: Case series.

Central airway obstruction often presents with respiratory symptoms identical to those of common respiratory diseases. Diagnosis of central airway obstruction is challenging in clinical practice, especially misdiagnosed as asthma or chronic obstructive pulmonary disease in case of "normal" chest X-ray. Here, we reported five central airway obstruction cases: the first and fourth cases misdiagnosed as asthma, the second masquerading as chronic obstructive pulmonary disease exacerbation, the third diagnosed incorrectly with non-resolving pneumonia, and the fifth misdiagnosed as chronic obstructive pulmonary disease. We then analyzed diagnostic clues potentially useful to differentiate central airway obstruction from asthma/chronic obstructive pulmonary disease. A multidisciplinary approach to manage central airway obstruction is essential, particularly selecting judiciously the method of respiratory support due to the high risk of completed airway collapse or obstruction during interventional period.

Evolutionary shift detection with ensemble variable selection.

Abrupt environmental changes can lead to evolutionary shifts in trait evolution. Identifying these shifts is an important step in understanding the evolutionary history of phenotypes. The detection performances of different methods are influenced by many factors, including different numbers of shifts, shift sizes, where a shift occurs on a tree, and the types of phylogenetic structure. Furthermore, the model assumptions are oversimplified, so are likely to be violated in real data, which could cause the methods to fail. We perform simulations to assess the effect of these factors on the performance of shift detection methods. To make the comparisons more complete, we also propose an ensemble variable selection method (R package ELPASO) and compare it with existing methods (R packages [Formula: see text]1ou and PhylogeneticEM). The performances of methods are highly dependent on the selection criterion. [Formula: see text]1ou+pBIC is usually the most conservative method and it performs well when signal sizes are large. [Formula: see text]1ou+BIC is the least conservative method and it performs well when signal sizes are small. The ensemble method provides more balanced choices between those two methods. Moreover, the performances of all methods are heavily impacted by measurement error, tree reconstruction error and shifts in variance.

Emerging treatments for corneal endothelium decompensation - a systematic review.

PURPOSE: Endothelial keratoplasty (EK) is the conventional treatment to improve visual acuity of corneal endothelium decompensation (CED) patients, with other therapies mainly for symptomatic relief. However, the shortage of corneal grafts and other limitations to EK urge the development of novel alternative treatments. In the last decade, novel options have been proposed, yet only a limited number of reviews have systematically reported on outcomes. Therefore, this systematic review evaluates the existing clinical evidence of novel surgical approaches for CED. METHOD: We identified 24 studies that illustrated the clinical observations of the surgical approaches in interest. We included Descemet stripping only (DSO), Descemet membrane transplantation (DMT) where Descement membrane alone instead of corneal endothelium with cells is transplanted, and cell-based therapy. RESULTS: In general, these therapies may provide visual outcomes comparable with EK under specific conditions. DSO and DMT target CED with relatively healthy peripheral corneal endothelium like Fuchs' corneal endothelial dystrophy, while cell-based therapy offers more versatile applications. Side effects of DSO would decrease with modifications to surgical techniques. Moreover, Rho-associated protein kinase inhibitor adjuvant therapy could enhance clinical results in DSO and cell-based therapy. CONCLUSION: Long-term controlled clinical trials with larger sample size on the therapies are needed. The simplicity of DSO and the high translational potential of cell-based therapy to treat CED of most etiologies made these two treatment strategies promising.

Methylation of histone H3 lysine 36 is a barrier for therapeutic interventions of head and neck squamous cell carcinoma.

Approximately 20% of head and neck squamous cell carcinomas (HNSCC) exhibit reduced methylation on lysine 36 of histone H3 (H3K36me) due to mutations in histone methylase NSD1 or a lysine-to-methionine mutation in histone H3 (H3K36M). Whether such alterations of H3K36me can be exploited for therapeutic interventions is still unknown. Here, we show that HNSCC models expressing H3K36M can be divided into two groups: those that display aberrant accumulation of H3K27me3 and those that maintain steady levels of H3K27me3. The first group shows decreased proliferation, genome instability, and increased sensitivity to genotoxic agents, such as PARP1/2 inhibitors. In contrast, the H3K36M HNSCC models with steady H3K27me3 levels do not exhibit these characteristics unless H3K27me3 levels are elevated, either by DNA hypomethylating agents or by inhibiting the H3K27me3 demethylases KDM6A/B. Mechanistically, we found that H3K36M reduces H3K36me by directly impeding the activities of the histone methyltransferase NSD3 and the histone demethylase LSD2. Notably, we found that aberrant H3K27me3 levels induced by H3K36M expression is not a bona fide epigenetic mark in HNSCC since it requires continuous expression of H3K36M to be inherited. Moreover, increased sensitivity of H3K36M HNSCC models to PARP1/2 inhibitors solely depends on the increased H3K27me3 levels. Indeed, aberrantly high H3K27me3 levels decrease BRCA1 and FANCD2-dependent DNA repair, resulting in higher sensitivity to DNA breaks and replication stress. Finally, in support of our in vitro findings, a PARP1/2 inhibitor alone reduce tumor burden in a H3K36M HNSCC xenograft model with elevated H3K27me3, whereas in a H3K36M HNSCC xenograft model with consistent H3K27me3 levels, a combination of PARP1/2 inhibitors and agents that upregulate H3K27me3 proves to be successful. In conclusion, our findings underscore a delicate balance between H3K36 and H3K27 methylation, essential for maintaining genome stability. This equilibrium presents promising therapeutic opportunities for patients with H3K36me-deficient tumors.

The Role and Associated Factors of Liquid-Based Cytology of Bronchoalveolar Lavage Fluid in Lung Cancer Diagnosis: A Prospective Study.

Background Liquid-based cytology (LBC) has shown advantages over conventional smears (CS), but previous applications in bronchoalveolar lavage (BAL) fluid have produced inconsistent results. This study compared LBC and CS for diagnosing lung cancer using BAL fluid. Methodology A prospective study was conducted on 92 patients suspected of having lung cancer. All patients underwent bronchoscopy and had a final diagnosis confirmed by histopathology of lesions tissue through biopsy. The study aimed to assess the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the two cytological methods, in a pair-wise fashion. In addition, the study evaluated the correlation of factors, such as the volume of fluid used in LBC and bronchoscopy lesion morphology, with the sensitivity of LBC. Results The study involved 78 participants who were diagnosed with lung cancer. The sensitivity, specificity, PPV, and NPV of LBC were 25.7%, 100%, 100%, and 19.4%, respectively, whereas those of CS were 15.4%, 85.7%, 85.7%, and 15.4%, respectively. Although the sensitivity of LBC was higher than that of CS, the difference was not statistically significant (p=0.096, McNemar test). Furthermore, the median fluid volume performed during LBC in patients with positive results was significantly higher than in those with negative results (p=0.001, Mann-Whitney U test). Conclusions The application of LBC to BAL fluid has demonstrated similar and potentially superior diagnostic accuracy compared to CS in detecting lung cancer. It is recommended that further investigation be undertaken to examine the relationship between the volume of fluid utilized during the LBC process and its diagnostic accuracy to enhance its sensitivity.

Core gut microbes Cloacibacterium and Aeromonas associated with different gastropod species could be persistently transmitted across multiple generations.

BACKGROUND: Studies on the gut microbiota of animals have largely focused on vertebrates. The transmission modes of commensal intestinal bacteria in mammals have been well studied. However, in gastropods, the relationship between gut microbiota and hosts is still poorly understood. To gain a better understanding of the composition of gut microbes and their transmission routes in gastropods, a large-scale and long-term experiment on the dynamics and transmission modes of gut microbiota was conducted on freshwater snails. RESULTS: We analyzed 244 microbial samples from the digestive tracts of freshwater gastropods and identified Proteobacteria and Bacteroidetes as dominant gut microbes. Aeromonas, Cloacibacterium, and Cetobacterium were identified as core microbes in the guts, accounting for over 50% of the total sequences. Furthermore, both core bacteria Aeromonas and Cloacibacterium, were shared among 7 gastropod species and played an important role in determining the gut microbial community types of both wild and cultured gastropods. Analysis of the gut microbiota at the population level, including wild gastropods and their offspring, indicated that a proportion of gut microbes could be consistently vertically transmitted inheritance, while the majority of the gut microbes resulted from horizontal transmission. Comparing cultured snails to their wild counterparts, we observed an increasing trend in the proportion of shared microbes and a decreasing trend in the number of unique microbes among wild gastropods and their offspring reared in a cultured environment. Core gut microbes, Aeromonas and Cloacibacterium, remained persistent and dispersed from wild snails to their offspring across multiple generations. Interestingly, under cultured environments, the gut microbiota in wild gastropods could only be maintained for up to 2 generations before converging with that of cultured snails. The difference observed in gut bacterial metabolism functions was associated with this transition. Our study also demonstrated that the gut microbial compositions in gastropods are influenced by developmental stages and revealed the presence of Aeromonas and Cloacibacterium throughout the life cycle in gastropods. Based on the dynamics of core gut microbes, it may be possible to predict the health status of gastropods during their adaptation to new environments. Additionally, gut microbial metabolic functions were found to be associated with the adaptive evolution of gastropods from wild to cultured environments. CONCLUSIONS: Our findings provide novel insights into the dynamic processes of gut microbiota colonization in gastropod mollusks and unveil the modes of microbial transmission within their guts. Video Abstract.

The genome of the deep-sea anemone Actinernus sp. contains a mega-array of ANTP-class homeobox genes.

Members of the phylum Cnidaria include sea anemones, corals and jellyfish, and have successfully colonized both marine and freshwater habitats throughout the world. The understanding of how cnidarians adapt to extreme environments such as the dark, high-pressure deep-sea habitat has been hindered by the lack of genomic information. Here, we report the first chromosome-level deep-sea cnidarian genome, of the anemone Actinernus sp., which was 1.39 Gbp in length and contained 44 970 gene models including 14 806 tRNA genes and 30 164 protein-coding genes. Analyses of homeobox genes revealed the longest chromosome hosts a mega-array of Hox cluster, HoxL, NK cluster and NKL homeobox genes; until now, such an array has only been hypothesized to have existed in ancient ancestral genomes. In addition to this striking arrangement of homeobox genes, analyses of microRNAs revealed cnidarian-specific complements that are distinctive for nested clades of these animals, presumably reflecting the progressive evolution of the gene regulatory networks in which they are embedded. Also, compared with other sea anemones, circadian rhythm genes were lost in Actinernus sp., which likely reflects adaptation to living in the dark. This high-quality genome of a deep-sea cnidarian thus reveals some of the likely molecular adaptations of this ecologically important group of metazoans to the extreme deep-sea environment. It also deepens our understanding of the evolution of genome content and organization of animals in general and cnidarians in particular, specifically from the viewpoint of key developmental control genes like the homeobox-encoding genes, where we find an array of genes that until now has only been hypothesized to have existed in the ancient ancestor that pre-dated both the cnidarians and bilaterians.

Amorphous RuO2 Catalyst for Medium Size Carboxylic Acid to Alkane Dimer Selective Kolbe Electrolysis in an Aqueous Environment.

The catalytic transformation of biomass-derived volatile carboxylic acids in an aqueous environment is crucial to developing a sustainable biorefinery. To date, Kolbe electrolysis remains arguably the most effective means to convert energy-diluted aliphatic carboxylic acids (carboxylate) to alkane for biofuel production. This paper reports the use of a structurally disordered amorphous RuO2 (a-RuO2 ) that is synthesized facilely in a hydrothermal method. The a-RuO2 is highly effective towards electrocatalytic oxidative decarboxylation of hexanoic acid and is able to produce the Kolbe product, decane, with a yield 5.4 times greater than that of commercial RuO2 . A systematic study of the reaction temperature, current intensity, and electrolyte concentration reveals the enhanced Kolbe product yield is attributable to the more efficient oxidation of the carboxylate anions for the alkane dimer formation. Our work showcases a new design idea for establishing an efficient electrocatalysts for decarboxylation coupling reaction, providing a new electrocatalyst candidate for Kolbe electrolysis.

MLK4 promotes glucose metabolism in lung adenocarcinoma through CREB-mediated activation of phosphoenolpyruvate carboxykinase and is regulated by KLF5.

MLK4, a member of the mitogen-activated protein kinase kinase kinase (MAP3K) family, has been implicated in cancer progression. However, its role in lung adenocarcinoma has not been characterized. Here, we showed that MLK4 was overexpressed in a significant subset of lung adenocarcinoma, associated with a worse prognosis, and exerted an oncogenic function in vitro and in vivo. Bioinformatics analyses of clinical datasets identified phosphoenolpyruvate carboxykinase 1 (PCK1) as a novel target of MLK4. We validated that MLK4 regulated PCK1 expression at transcriptional level, by phosphorylating the transcription factor CREB, which in turn mediated PCK1 expression. We further demonstrated that PCK1 is an oncogenic factor in lung adenocarcinoma. Given the importance of PCK1 in the regulation of cellular metabolism, we next deciphered the metabolic effects of MLK4. Metabolic and mass spectrometry analyses showed that MLK4 knockdown led to significant reduction of glycolysis and decreased levels of glycolytic pathway metabolites including phosphoenolpyruvate and lactate. Finally, the promoter analysis of MLK4 unravelled a binding site of transcription factor KLF5, which in turn, positively regulated MLK4 expression in lung adenocarcinoma. In summary, we have revealed a KLF5-MLK4-PCK1 signalling pathway involved in lung tumorigenesis and established an unusual link between MAP3K signalling and cancer metabolism.

Loss of function of GATA3 regulates FRA1 and c-FOS to activate EMT and promote mammary tumorigenesis and metastasis.

Basal-like breast cancers (BLBCs) are among the most aggressive cancers, partly due to their enrichment of cancer stem cells (CSCs). Breast CSCs can be generated from luminal-type cancer cells via epithelial-mesenchymal transition (EMT). GATA3 maintains luminal cell fate, and its expression is lost or reduced in BLBCs. However, deletion of Gata3 in mice or cells results in early lethality or proliferative defects. It is unknown how loss-of-function of GATA3 regulates EMT and CSCs in breast cancer. We report here that haploid loss of Gata3 in mice lacking p18Ink4c, a cell cycle inhibitor, up-regulates Fra1, an AP-1 family protein that promotes mesenchymal traits, and downregulates c-Fos, another AP-1 family protein that maintains epithelial fate, leading to activation of EMT and promotion of mammary tumor initiation and metastasis. Depletion of Gata3 in luminal tumor cells similarly regulates Fra1 and c-Fos in activation of EMT. GATA3 binds to FOSL1 (encoding FRA1) and FOS (encoding c-FOS) loci to repress FOSL1 and activate FOS transcription. Deletion of Fra1 or reconstitution of Gata3, but not reconstitution of c-Fos, in Gata3 deficient tumor cells inhibits EMT, preventing tumorigenesis and/or metastasis. In human breast cancers, GATA3 expression is negatively correlated with FRA1 and positively correlated with c-FOS. Low GATA3 and FOS, but high FOSL1, are characteristics of BLBCs. Together, these data provide the first genetic evidence indicating that loss of function of GATA3 in mammary tumor cells activates FOSL1 to promote mesenchymal traits and CSC function, while concurrently repressing FOS to lose epithelial features. We demonstrate that FRA1 is required for the activation of EMT in GATA3 deficient tumorigenesis and metastasis.

SPADE4: Sparsity and Delay Embedding Based Forecasting of Epidemics.

Predicting the evolution of diseases is challenging, especially when the data availability is scarce and incomplete. The most popular tools for modelling and predicting infectious disease epidemics are compartmental models. They stratify the population into compartments according to health status and model the dynamics of these compartments using dynamical systems. However, these predefined systems may not capture the true dynamics of the epidemic due to the complexity of the disease transmission and human interactions. In order to overcome this drawback, we propose Sparsity and Delay Embedding based Forecasting (SPADE4) for predicting epidemics. SPADE4 predicts the future trajectory of an observable variable without the knowledge of the other variables or the underlying system. We use random features model with sparse regression to handle the data scarcity issue and employ Takens' delay embedding theorem to capture the nature of the underlying system from the observed variable. We show that our approach outperforms compartmental models when applied to both simulated and real data.

When can we reconstruct the ancestral state? Beyond Brownian motion.

Reconstructing the ancestral state of a group of species helps answer many important questions in evolutionary biology. Therefore, it is crucial to understand when we can estimate the ancestral state accurately. Previous works provide a necessary and sufficient condition, called the big bang condition, for the existence of an accurate reconstruction method under discrete trait evolution models and the Brownian motion model. In this paper, we extend this result to a wide range of continuous trait evolution models. In particular, we consider a general setting where continuous traits evolve along the tree according to stochastic processes that satisfy some regularity conditions. We verify these conditions for popular continuous trait evolution models including Ornstein-Uhlenbeck, reflected Brownian Motion, bounded Brownian Motion, and Cox-Ingersoll-Ross.

Current microfluidic platforms for reverse engineering of cornea.

According to the World Health Organization, corneal blindness constitutes 5.1% of global blindness population. Surgical outcomes have been improved significantly in the treatment of corneal blindness. However, corneal transplantation is limited by global shortage of donor tissue, prompting researchers to explore alternative therapies such as novel ocular pharmaceutics to delay corneal disease progression. Animal models are commonly adopted for investigating pharmacokinetics of ocular drugs. However, this approach is limited by physiological differences in the eye between animals and human, ethical issues and poor bench-to-bedside translatability. Cornea-on-a-chip (CoC) microfluidic platforms have gained great attention as one of the advanced in vitro strategies for constructing physiologically representative corneal models. With significant improvements in tissue engineering technology, CoC integrates corneal cells with microfluidics to recapitulate human corneal microenvironment for the study of corneal pathophysiological changes and evaluation of ocular drugs. Such model, in complement to animal studies, can potentially accelerate translational research, in particular the pre-clinical screening of ophthalmic medication, driving clinical treatment advancement for corneal diseases. This review provides an overview of engineered CoC platforms with respect to their merits, applications, and technical challenges. Emerging directions in CoC technology are also proposed for further investigations, to accentuate preclinical obstacles in corneal research.

Post-COVID-19 Pulmonary Alveolar Proteinosis Treated Successfully with Whole Lung Lavage: A Rare Case Report.

Pulmonary alveolar proteinosis (PAP) is an uncommon disease and its diagnosis remains challenging. During the COVID-19 pandemic, it has been difficult to distinguish between PAP and post-COVID-19 pulmonary sequelae. Here we present a case of a 44-year-old male patient who experienced exertional dyspnea after recovering from COVID-19. He was initially diagnosed with post-COVID-19 syndrome and treated with systemic corticosteroid without improvement. Chest computed tomography (CT) showed crazy-paving pattern with ground-glass opacities. Fibreoptic bronchoscopy with bronchial lavage fluid (BLF) analysis confirmed the final diagnosis of PAP. The patient underwent left lung lavage in combination with conventional therapy and experienced significant improvement in his respiratory condition and overall health during follow-up. Hence, PAP could occur after a COVID-19 infection. This case highlights the importance of considering PAP as a potential diagnosis in patients with persistent respiratory symptoms after COVID-19. The high suspicion indicators of PAP revealed by chest-CT and BLF may be a key to differentiating PAP from post-COVID-19 pulmonary sequelae. Moreover, it is plausible that SARS-CoV-2 plays a role in the development of proteinosis, either by inducing a flare-up or by directly causing the condition.