Spatial and temporal-trend assessment of desertification-sensitive land using the desertification sensitivity index in the provincial Ninh Thuan, Vietnam.

Desertification is a specific land-degrading process, reducing soil productivity and potentially threatening global food security. Therefore, spatially and temporally identifying and mapping desertification-sensitive areas is essential for better management. The current study aimed to (1) assess spatial areas sensitive to desertification and (2) examine the changing tendency of the desertification-sensitive areas over the past 25 years in the provincial Ninh Thuan. The desertification sensitivity index (DSI) was computed based on the Medalus model using 10 quantitative parameters, grouped into the soil, climate, and vegetation quality indexes, computed for the years 1996, 2005, 2010, and 2016. GIS was used to map desertification-sensitive areas associated with five DSI classes. Results showed that classes II and III had the highest area percentage, followed by classes IV and V, and class I. The classes most sensitive to desertification (classes IV and V) covered around 13 to 17%, and classes II and III were 25 to 32% of the total study area, respectively. The coastal areas located in the southeastern parts were more sensitive to desertification than the other parts. Over the four examined periods, the areas of classes IV and V increased while those of classes II and I decreased. These indicated that the study province tended to increase in its desertification sensitivity with a severe increase in the coastal areas over the past 25 years. The key factors involved in these changes could be related the human activities and climate variation, which could be more serious in southeastern areas than in the other areas.

Physical activity across midlife and health-related quality of life in Australian women: A target trial emulation using a longitudinal cohort.

BACKGROUND: There is little long-term causal evidence on the effect of physical activity on health-related quality of life. This study aimed to examine the associations between longitudinal patterns of physical activity over 15 years and health-related quality of life in both the physical and mental health domains, in a cohort of middle-aged Australian women. METHODS AND FINDINGS: We used data collected at 3-year intervals (1998 to 2019) from 11,336 participants in the Australian Longitudinal Study on Women's Health (ALSWH) (1946 to 1951 birth cohort). Primary outcomes were the physical (PCS) and mental health component summary (MCS) scores (range from 0 to 100; higher scores indicate higher perceived physical/mental health) from the SF-36 in 2019 (when women aged 68 to 73 years). Using target trial emulation to imitate a randomized controlled trial (RCT), we tested 2 interventions: (1) meeting the World Health Organization (WHO) physical activity guidelines consistently throughout the 15-year "exposure period" (2001 to 2016; when women aged 50-55 to 65-70 years; physical activity assessed every 3 years); and (2) not meeting the guidelines at the beginning of the exposure period but starting to first meet the guidelines at age 55, 60, or 65; against the control of not meeting the guidelines throughout the exposure period. Analysis controlled for confounding using marginal structural models which were adjusted for sociodemographic and health variables and conditions. Consistent adherence to guidelines during the exposure period (PCS: 46.93 [99.5% confidence interval [CI]: 46.32, 47.54]) and first starting to meet the guidelines at age 55 (PCS: 46.96 [99.5% CI: 45.53, 48.40]) were associated with three-point higher PCS (mean score difference: 3.0 [99.5% CI: 1.8, 4.1] and 3.0 [99.5% CI:1.2, 4.8]) than consistent non-adherence (PCS: 43.90 [99.5% CI: 42.79, 45.01]). We found a similar pattern for most SF-36 subscales but no significant effects of the interventions on MCS. The main limitations of the study were that it may not account for all underlying health conditions and/or other unmeasured or insufficiently measured confounders, the use of self-reported physical activity and that findings may not be generalizable to all mid-age women. CONCLUSIONS: Results from the emulated RCT suggest women should be active throughout mid-age, ideally increasing activity levels to meet the guidelines by age 55, to gain the most benefits for physical health in later life.

A prediction model of abnormal acid reflux in gastroesophageal reflux disease.

BACKGROUND AND AIM: The measurement of esophageal acid exposure time (AET) using combined multichannel intraluminal impedance-pH (MII-pH) tests is the gold standard for diagnosing gastroesophageal reflux disease (GERD). However, this catheter-based 24-h test can cause considerable patient discomfort. Our aim is to identify factors affecting AET and to develop a scoring model for predicting AET abnormalities before conducting the MII-pH test. METHODS: Of the 366 patients who underwent MII-pH test at two facilities in Japan and Vietnam, 255 patients who also had esophagogastroduodenoscopy and high-resolution manometry were included in this study. Logistic regression analysis was conducted using risk factors for AET > 6% identified from a derivation cohort (n = 109). A scoring system predicting AET > 6% was then constructed and externally validated with a separate cohort (n = 146). RESULTS: Three variables were derived from the prediction model: male gender, Hill grades III-IV, and weak mean distal contractile integrals. Based on these scores, patients were classified into low (0 point), intermediate (1-3 points), and high (4 points) risk groups. The probabilities of having an AET > 6% were 6%, 34%, and 100% for these groups, respectively. A score of < 1 excluded patients with abnormal AET, with a negative predictive value of 93.8% in the derivation cohort and 80.0% in the validation cohort. CONCLUSIONS: We derived and externally validated a prediction model for abnormal AET. This system could assist in guiding the appropriate treatment strategies for GERD.

Digital Interventions to Understand and Mitigate Stress Response: Protocol for Process and Content Evaluation of a Cohort Study.

BACKGROUND: Staffing and resource shortages, especially during the COVID-19 pandemic, have increased stress levels among health care workers. Many health care workers have reported feeling unable to maintain the quality of care expected within their profession, which, at times, may lead to moral distress and moral injury. Currently, interventions for moral distress and moral injury are limited. OBJECTIVE: This study has the following aims: (1) to characterize and reduce stress and moral distress related to decision-making in morally complex situations using a virtual reality (VR) scenario and a didactic intervention; (2) to identify features contributing to mental health outcomes using wearable, physiological, and self-reported questionnaire data; and (3) to create a personal digital phenotype profile that characterizes stress and moral distress at the individual level. METHODS: This will be a single cohort, pre- and posttest study of 100 nursing professionals in Ontario, Canada. Participants will undergo a VR simulation that requires them to make morally complex decisions related to patient care, which will be administered before and after an educational video on techniques to mitigate distress. During the VR session, participants will complete questionnaires measuring their distress and moral distress, and physiological data (electrocardiogram, electrodermal activity, plethysmography, and respiration) will be collected to assess their stress response. In a subsequent 12-week follow-up period, participants will complete regular assessments measuring clinical outcomes, including distress, moral distress, anxiety, depression, and loneliness. A wearable device will also be used to collect continuous data for 2 weeks before, throughout, and for 12 weeks after the VR session. A pre-post comparison will be conducted to analyze the effects of the VR intervention, and machine learning will be used to create a personal digital phenotype profile for each participant using the physiological, wearable, and self-reported data. Finally, thematic analysis of post-VR debriefing sessions and exit interviews will examine reoccurring codes and overarching themes expressed across participants' experiences. RESULTS: The study was funded in 2022 and received research ethics board approval in April 2023. The study is ongoing. CONCLUSIONS: It is expected that the VR scenario will elicit stress and moral distress. Additionally, the didactic intervention is anticipated to improve understanding of and decrease feelings of stress and moral distress. Models of digital phenotypes developed and integrated with wearables could allow for the prediction of risk and the assessment of treatment responses in individuals experiencing moral distress in real-time and naturalistic contexts. This paradigm could also be used in other populations prone to moral distress and injury, such as military and public safety personnel. TRIAL REGISTRATION: ClinicalTrials.gov NCT05923398; https://clinicaltrials.gov/study/NCT05923398. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/54180.

Low HBV knowledge is associated with low HBV vaccination uptake in general adult population despite incentivization of HBV vaccination.

BACKGROUND: Hepatitis B virus (HBV) vaccination in Vietnamese adults remains low and unequally distributed. We conducted a study on HBV-naïve adults living in Ho Chi Minh City, Viet Nam, to determine barriers associated with HBV vaccination uptake after removing the financial barrier by providing free coupons for HBV vaccination. METHODS: After being screened for HBsAg, anti-HBs, and anti-HBc, 284 HBV-naïve study participants aged 18 and over (i.e., negative for HBsAg, anti-HBs, and anti-HBc total) were provided free 3-dose HBV vaccine coupons. Next, study participants' receipt of 1st, 2nd, and 3rd doses of HBV vaccine was documented at a pre-specified study healthcare facility, where HBV vaccines were distributed at no cost to the participants. Upon study entry, participants answered questionnaires on sociodemographics, knowledge of HBV and HBV vaccination, and related social and behavioral factors. The proportions of three doses of HBV vaccine uptake and their confidence intervals were analyzed. Associations of HBV vaccine initiation with exposures at study entry were evaluated using modified Poisson regression. RESULTS: 98.9% (281 of 284) of study participants had complete data and were included in the analysis. The proportion of participants obtaining the 1st, 2nd, and 3rd doses of HBV vaccine was 11.7% (95% Confidence Interval [95% CI] 8.0-15.5%), 10.7% (95%CI 7.1-14.3%), and 8.9% (95%CI 5.6-12.2%), respectively. On the other hand, participants were more likely to initiate the 1st dose if they had adequate knowledge of transmission (adjusted relative risk [aRR] = 2.58, 95% CI 1.12-5.92), adequate knowledge of severity (aRR = 6.75, 95%CI 3.38-13.48), and annual health-checking seeking behavior (aRR = 2.04, 95%CI 1.07-3.87). CONCLUSION: We documented a low HBV vaccination uptake despite incentivization. However, increased vaccine initiation was associated with better HBV knowledge and annual health check-up adherence. When considering expanding HBV vaccination to the general adult population, we should appreciate that HBV knowledge is an independent predictor of vaccine uptake.

The influence of attributes on community preferences regarding antibiotic treatment: evidence from a discrete choice model.

Antibiotic resistance (AR) rates in Vietnam are among the highest in Asia, and recent infections due to multi-drug resistance in the country have caused thousands of deaths each year. This study investigated a Vietnamese community's preferences for antibiotic treatment and its knowledge and attitudes regarding antibiotics. A discrete choice experiment-based survey was developed and administered to the population of interest. The respondents were given sociodemographic-, knowledge- and attitude-related items and 17 pairs of choice tasks. Two hypothetical options were included in each choice task. Latent class analysis was conducted to determine the differences among the respondents' preferences. Among 1,014 respondents, 805 (79.4%) gave valid questionnaires. A three-latent-class model with four covariates (age, healthcare-related education or career, occupation, and attitude classifications) was used in the analysis. All five attributes significantly influenced the respondents' decisions. The majority, including young employed respondents with non-healthcare-related work or education, found treatment failure more important. Older respondents who had healthcare-related education/careers and/or appropriate antibiotic use- and antibiotics resistance-related attitudes, regarded contribution to antibiotic resistance as an important attribute in selecting antibiotic treatments. Unemployed individuals with correct knowledge identified the cost of antibiotic treatment as the most essential decision-making factor. Findings suggest minimal antibiotic impact on resistance; only 7.83% view it as amajor concern. The respondents exhibited substantial preference heterogeneity, and the general Vietnamese public had poor knowledge of and attitudes toward antibiotic use and antibiotic resistance. This study emphasizes the need for individual responsibility for antibiotic resistance and appropriate antibiotic use.

Comparative Analysis of Antibiotic Resistance and Biofilm Characteristics of Two Major Enterococcus Species from Poultry Slaughterhouses in South Korea.

The spread of antibiotic-resistant Enterococcus in the poultry industry poses significant public health challenges due to multidrug resistance and biofilm formation. We investigated the antibiotic resistance profiles and biofilm characteristics of E. faecalis and E. faecium isolates from chicken meat in poultry slaughterhouses in South Korea. Ninety-six isolates (forty-eight each of E. faecalis and E. faecium) were collected between March and September 2022. Both species were analyzed using MALDI-TOF, PCR, antibiotic susceptibility testing, and biofilm assays. A high level of multidrug resistance was observed in E. faecalis (95.8%) and E. faecium (93.8%), with E. faecium exhibiting a broader range of resistance, particularly to linezolid (52.1%) and rifampicin (47.9%). All E. faecalis isolates formed biofilm in vitro, showing stronger biofilm formation than E. faecium with a significant difference (p < 0.001) in biofilm strength. Specific genes (cob, ccf, and sprE) were found to be correlated with biofilm strength. In E. faecium isolates, biofilm strength was correlated with resistance to linezolid and rifampicin, while a general correlation between antibiotic resistance and biofilm strength was not established. Through analysis, correlations were noted between antibiotics within the same class, while no general trends were evident in other analyzed factors. This study highlights the public health risks posed by multidrug-resistant enterococci collected from poultry slaughterhouses, emphasizing the complexity of the biofilm-resistance relationship and the need for enhanced control measures.

Subunit Communication within Dimeric SF1 DNA Helicases.

Monomers of the Superfamily (SF) 1 helicases, E. coli Rep and UvrD, can translocate directionally along single stranded (ss) DNA, but must be activated to function as helicases. In the absence of accessory factors, helicase activity requires Rep and UvrD homo-dimerization. The ssDNA binding sites of SF1 helicases contain a conserved aromatic amino acid (Trp250 in Rep and Trp256 in UvrD) that stacks with the DNA bases. Here we show that mutation of this Trp to Ala eliminates helicase activity in both Rep and UvrD. Rep(W250A) and UvrD(W256A) can still dimerize, bind DNA, and monomers still retain ATP-dependent ssDNA translocase activity, although with ∼10-fold lower rates and lower processivities than wild type monomers. Although neither wtRep monomers nor Rep(W250A) monomers possess helicase activity by themselves, using both ensemble and single molecule methods, we show that helicase activity is achieved upon formation of a Rep(W250A)/wtRep hetero-dimer. An ATPase deficient Rep monomer is unable to activate a wtRep monomer indicating that ATPase activity is needed in both subunits of the Rep hetero-dimer. We find the same results with E. coli UvrD and its equivalent mutant (UvrD(W256A)). Importantly, Rep(W250A) is unable to activate a wtUvrD monomer and UvrD(W256A) is unable to activate a wtRep monomer indicating that specific dimer interactions are required for helicase activity. We also demonstrate subunit communication within the dimer by virtue of Trp fluorescence signals that only are present within the Rep dimer, but not the monomers. These results bear on proposed subunit switching mechanisms for dimeric helicase activity.

Enhanced photoreduction efficiency of Cr(VI) driven by visible light in a new Zr-based metal-organic framework modified by hydroxyl groups.

While metal-organic framework (MOF) photocatalysts have demonstrated a unique Cr(VI) photoreduction capability in recent decades, their performance is still insufficient for practical applications because of their low Cr(VI) uptake and poor visible light response. To cope with these drawbacks, a new OH-modified Zr-based MOF, termed HCMUE-1, was successfully prepared via a solvothermal method in this work. The complete characterization of HCMUE-1 was performed through various techniques, including powder X-ray diffraction (PXRD), Raman spectroscopy, Fourier transform infrared (FT-IR), thermogravimetric analysis and differential scanning calorimetry (TGA-DSC), scanning electron microscopy combined with energy-dispersive X-ray (SEM-EDX), and X-ray photoelectron spectroscopy (XPS). The obtained data exhibited the excellent Cr(VI) photoreduction efficiency of HCMUE-1, reaching up to 98% after 90 min and almost 100% after 120 min under visible light illumination in a low acidic medium. Noteworthily, HCMUE-1 retained the same Cr(VI) removal rate for at least seven cycles without considerable loss. Further experimental investigations demonstrated that the structural stability and surface morphology of HCMUE-1 were retained after photoreduction. Moreover, the photocatalytic reduction mechanism of Cr(VI) to Cr(III) was interpreted through a series of systematic experimental measurements. These results indicate that HCMUE-1 possesses potential as an efficient photocatalyst for reducing toxic Cr(VI) species from wastewater in real-life conditions.

UCL Throwing Injuries in Nonprofessional Baseball Players: A 14-Year Retrospective Study.

BACKGROUND: This study evaluated treatment modality (surgical vs nonoperative) of medial ulnar collateral ligament (UCL) injuries in nonprofessional throwing baseball athletes by comparing type, severity, and location of UCL injury. HYPOTHESIS: Baseball players with closed medial epicondyle physes and concomitant throwing-related UCL injury will be more likely to undergo surgical intervention than players with open medial epicondyle physes. STUDY DESIGN: Retrospective. LEVEL OF EVIDENCE: Level 5. METHODS: A total of 119 baseball players with a mean age of 16.9 ± 2.5 years (range, 11-25 years) were included in the study. Datapoints included sex, age at time of injury, severity, and location of UCL injury, growth plate status, operative versus conservative management, and concomitant flexor forearm injury. RESULTS: A total of 75 players were treated conservatively; 43 underwent UCL reconstruction (UCL-R), and 1 had an unknown treatment outcome. No significant difference was found for age related to treatment type, UCL-R (17.2 ± 2.2) versus conservative treatment (16.8 ± 2.6). Athletes with closed medial epicondylar growth plates were more likely to undergo UCL-R than athletes with open medial epicondylar growth plates (P = 0.02). There were no significant differences between UCL injury location (42 distal, 37 proximal, 18 combined tear locations, 11 complete tears, and 11 intact UCLs with inflammation) by treatment type (P = 0.09). There was a significant difference for UCL severity (11 complete tears, 96 partial tears) by treatment type (P = 0.03). CONCLUSION: Nonprofessional athletes with closed medial epicondylar growth plates and throwing-related UCL injuries were more likely to be treated surgically. Baseball athletes with partial tears, if skeletally immature, require further long-term evaluation. CLINICAL RELEVANCE: Continued knowledge gains in this area of throwing medicine will further improve our treatment algorithms in nonprofessional baseball players.

Study on the clinical and electrophysiological characteristics of nerve function in myasthenia gravis patients in Vietnam.

Background: In Vietnam, there is limited research on the role of nerve conduction in myasthenia gravis and its association with clinical features. Objective: This study aims to describe the electrophysiological features in patients with myasthenia gravis. Methods: This descriptive study was conducted from September 2019 to December 2021. The study included 33 myasthenia gravis patients who sought medical consultation or received inpatient treatment during this period. The Myasthenia Gravis Foundation of America classifies myasthenia gravis into five groups: I, IIa, IIb, IIIa, IIIb, IVa, IVb, and V. Notably, Group I involves pure ocular weakness, whereas Group a primarily impacts limb and axial muscles, and Group b mainly affects bulbar and respiratory muscles. Results: The study revealed that motor and sensory nerve conduction in the upper and lower limbs were within normal limits for the patient group under evaluation. Repetitive nerve stimulation testing at a frequency of 3 Hz showed positive results in 66.7% of myasthenia gravis patients. Myasthenia gravis patients displayed distinct clinical symptoms, with ptosis being the most common (87.9%). Myasthenia Gravis Foundation of America classification indicated the highest proportion in subgroup IIa (24.2%), with myasthenia gravis predominating in limb and axial muscles (Group a) observed in 51.5% of cases. Needle electromyography showed no abnormalities in myasthenia gravis patients. There was an association between acetylcholine receptor antibody titers and the results of the 3 Hz repetitive nerve stimulation test in myasthenia gravis patients, with a significance of p = 0.002. Conclusion: Nerve conduction studies should be performed in patients with suspected neuromuscular disorders to aid in differential diagnosis and definitive diagnosis of myasthenia gravis.

Cryo-EM confirms a common fibril fold in the heart of four patients with ATTRwt amyloidosis.

ATTR amyloidosis results from the conversion of transthyretin into amyloid fibrils that deposit in tissues causing organ failure and death. This conversion is facilitated by mutations in ATTRv amyloidosis, or aging in ATTRwt amyloidosis. ATTRv amyloidosis exhibits extreme phenotypic variability, whereas ATTRwt amyloidosis presentation is consistent and predictable. Previously, we found an unprecedented structural variability in cardiac amyloid fibrils from polyneuropathic ATTRv-I84S patients. In contrast, cardiac fibrils from five genotypically-different patients with cardiomyopathy or mixed phenotypes are structurally homogeneous. To understand fibril structure's impact on phenotype, it is necessary to study the fibrils from multiple patients sharing genotype and phenotype. Here we show the cryo-electron microscopy structures of fibrils extracted from four cardiomyopathic ATTRwt amyloidosis patients. Our study confirms that they share identical conformations with minimal structural variability, consistent with their homogenous clinical presentation. Our study contributes to the understanding of ATTR amyloidosis biopathology and calls for further studies.

Predicting Cardiotoxicity of Molecules Using Attention-Based Graph Neural Networks.

In drug discovery, the search for new and effective medications is often hindered by concerns about toxicity. Numerous promising molecules fail to pass the later phases of drug development due to strict toxicity assessments. This challenge significantly increases the cost, time, and human effort needed to discover new therapeutic molecules. Additionally, a considerable number of drugs already on the market have been withdrawn or re-evaluated because of their unwanted side effects. Among the various types of toxicity, drug-induced heart damage is a severe adverse effect commonly associated with several medications, especially those used in cancer treatments. Although a number of computational approaches have been proposed to identify the cardiotoxicity of molecules, the performance and interpretability of the existing approaches are limited. In our study, we proposed a more effective computational framework to predict the cardiotoxicity of molecules using an attention-based graph neural network. Experimental results indicated that the proposed framework outperformed the other methods. The stability of the model was also confirmed by our experiments. To assist researchers in evaluating the cardiotoxicity of molecules, we have developed an easy-to-use online web server that incorporates our model.

Comparative Analysis of Hindgut Microbiota Variation in Protaetia brevitarsis Larvae across Diverse Farms.

Protaetia brevitarsis larvae are farm-raised for food, are used in traditional East Asian medicine, and convert organic waste into biofertilizers. Here, the comparative analysis of the gut microbiota of third-instar larvae obtained from five different farms was investigated using 16S rRNA microbial profiling. Species richness, evenness, and diversity results using α-diversity analysis (observed species, Chao1, Shannon, Simpson) were similar between farms, except for those between the TO and KO farms. ß-diversity was significantly different in distribution and relative abundance between farms (PERMANOVA, pseudo-F = 13.20, p = 0.001). At the phylum level, Bacillota, Bacteroidota, Actinomycetota, and Pseudomonadota were the most dominant, accounting for 73-88% of the hindgut microbial community. At the genus level, Tuberibacillus, Proteiniphilum, Desulfovibrio, Luoshenia, and Thermoactinomyces were the most abundant. Although oak sawdust was the main feed component, there were large variations in distribution and relative abundance across farms at the phylum and genus levels. Venn diagram and linear discriminant analysis effect size analyses revealed large variations in the hindgut microbial communities of P. brevitarsis larvae between farms. These results suggest environmental factors were more important than feed ingredients or genetic predisposition for the establishment of the intestinal microbiota of P. brevitarsis larvae. These findings serve as reference data to understand the intestinal microbiota of P. brevitarsis larvae.

Development and Implementation of a Stress Monitoring Paradigm Using Virtual Reality Simulation During the COVID-19 Pandemic.

Healthcare providers, particularly during the COVID-19 crisis, have been forced to make difficult decisions and have reported acting in ways that are contrary to their moral values, integrity, and professional commitments, given the constraints in their work environments. Those actions and decisions may lead to healthcare providers' moral suffering and distress. This work outlines the development of the Moral Distress Virtual Reality Simulator (Moral Distress VRS) to research stress and moral distress among healthcare workers during the COVID-19 pandemic. The Moral Distress VRS was developed based on the agile methodology framework, with three simultaneous development streams. It followed a two-week sprint cycle, ending with meetings with stakeholders and subject matter experts, whereby the project requirements, scope, and features were revised, and feedback was provided on the prototypes until reaching the final prototype that was deployed for in-person study sessions. The final prototype had two user interfaces (UIs), one for the participant and one for the researcher, with voice narration and customizable character models wearing medical personal protective equipment, and followed a tree-based dialogue scenario, outputting a video recording of the session. The virtual environment replicated an ICU nursing station and a fully equipped patient room. We present the development process that guided this project, how different teams worked together and in parallel, and detail the decisions and outcomes in creating each major component within a limited deadline. Finally, we list the most significant challenges and difficulties faced and recommendations on how to solve them.

Genetic Characterization and Phylogeographic Analysis of the First H13N6 Avian Influenza Virus Isolated from Vega Gull in South Korea.

Avian influenza virus (AIV) is a pathogen with zoonotic and pandemic potential. Migratory birds are natural reservoirs of all known subtypes of AIVs, except for H17N10 and H18N11, and they have been implicated in previous highly pathogenic avian influenza outbreaks worldwide. This study identified and characterized the first isolate of the H13N6 subtype from a Vega gull (Larus vegae mongolicus) in South Korea. The amino acid sequence of hemagglutinin gene showed a low pathogenic AIV subtype and various amino acid substitutions were found in the sequence compared to the reference sequence and known H13 isolates. High sequence homology with other H13N6 isolates was found in HA, NA, PB1, and PA genes, but not for PB2, NP, M, and NS genes. Interestingly, various point amino acid mutations were found on all gene segments, and some are linked to an increased binding to human-type receptors, resistance to antivirals, and virulence. Evolutionary and phylogenetic analyses showed that all gene segments are gull-adapted, with a phylogeographic origin of mostly Eurasian, except for PB2, PA, and M. Findings from this study support the evidence that reassortment of AIVs continuously occurs in nature, and migratory birds are vital in the intercontinental spread of avian influenza viruses.

O-GlcNAc forces an α-synuclein amyloid strain with notably diminished seeding and pathology.

Amyloid-forming proteins such α-synuclein and tau, which are implicated in Alzheimer's and Parkinson's disease, can form different fibril structures or strains with distinct toxic properties, seeding activities and pathology. Understanding the determinants contributing to the formation of different amyloid features could open new avenues for developing disease-specific diagnostics and therapies. Here we report that O-GlcNAc modification of α-synuclein monomers results in the formation of amyloid fibril with distinct core structure, as revealed by cryogenic electron microscopy, and diminished seeding activity in seeding-based neuronal and rodent models of Parkinson's disease. Although the mechanisms underpinning the seeding neutralization activity of the O-GlcNAc-modified fibrils remain unclear, our in vitro mechanistic studies indicate that heat shock proteins interactions with O-GlcNAc fibril inhibit their seeding activity, suggesting that the O-GlcNAc modification may alter the interactome of the α-synuclein fibrils in ways that lead to reduce seeding activity in vivo. Our results show that posttranslational modifications, such as O-GlcNAc modification, of α-synuclein are key determinants of α-synuclein amyloid strains and pathogenicity.

Analyzing the correlation between protein expression and sequence-related features of mRNA and protein in Escherichia coli K-12 MG1655 model.

It was necessary to have a tool that could predict the amount of protein and optimize the gene sequences to produce recombinant proteins efficiently. The Transim model published by Tuller et al. in 2018 can calculate the translation rate in E. coli using features on the mRNA sequence, achieving a Spearman correlation with the amount of protein per mRNA of 0.36 when tested on the dataset of operons' first genes in E. coli K-12 MG1655 genome. However, this Spearman correlation was not high, and the model did not fully consider the features of mRNA and protein sequences. Therefore, to enhance the prediction capability, our study firstly tried expanding the testing dataset, adding genes inside the operon, and using the microarray of the mRNA expression data set, thereby helping to improve the correlation of translation rate with the amount of protein with more than 0.42. Next, the applicability of 6 traditional machine learning models to calculate a "new translation rate" was examined using initiation rate and elongation rate as inputs. The result showed that the SVR algorithm had the most correlated new translation rates, with Spearman correlation improving to R = 0.6699 with protein level output and to R = 0.6536 with protein level per mRNA. Finally, the study investigated the degree of improvement when combining more features with the new translation rates. The results showed that the model's predictive ability to produce a protein per mRNA reached R = 0.6660 when using six features, while the correlation of this model's final translation rate to protein level was up to R = 0.6729. This demonstrated the model's capability to predict protein expression of a gene, rather than being limited to predicting expression by an mRNA and showed the model's potential for development into gene expression predicting tools.

Development and validation of algorithms for identifying lines of therapy in multiple myeloma using real-world data.

Aim: To validate algorithms based on electronic health data to identify composition of lines of therapy (LOT) in multiple myeloma (MM). Materials & methods: This study used available electronic health data for selected adults within Henry Ford Health (Michigan, USA) newly diagnosed with MM in 2006-2017. Algorithm performance in this population was verified via chart review. As with prior oncology studies, good performance was defined as positive predictive value (PPV) ≥75%. Results: Accuracy for identifying LOT1 (N = 133) was 85.0%. For the most frequent regimens, accuracy was 92.5-97.7%, PPV 80.6-93.8%, sensitivity 88.2-89.3% and specificity 94.3-99.1%. Algorithm performance decreased in subsequent LOTs, with decreasing sample sizes. Only 19.5% of patients received maintenance therapy during LOT1. Accuracy for identifying maintenance therapy was 85.7%; PPV for the most common maintenance therapy was 73.3%. Conclusion: Algorithms performed well in identifying LOT1 - especially more commonly used regimens - and slightly less well in identifying maintenance therapy therein.

Electronic health data helps us understand treatment in the 'real world'. The data has great value in cancer if we can identify the drugs patients get. Yet this is hard in multiple myeloma (MM), where treatment is complex. Algorithms (set of decision rules) to identify drugs can help here. We tested an existing algorithm for identifying 'lines of therapy' (LOT) given to patients with MM. Each LOT included one or more drugs for MM. We also developed and tested a new algorithm for 'maintenance therapy'. This is a treatment given to help maintain the response to the main MM treatment. We tested how well the algorithms identified MM treatments in electronic health data. This data came from Henry Ford Health, a healthcare system in Michigan, USA. Treatments were confirmed by cancer specialists who reviewed medical charts. The LOT algorithm was good at finding the first LOT patients. The maintenance algorithm did a fair job of identifying the most used therapy. Our algorithms could help researchers study the real-world treatment of MM.