Identification of bacterial determinants of tuberculosis infection and treatment outcomes: a phenogenomic analysis of clinical strains.

BACKGROUND: Bacterial diversity could contribute to the diversity of tuberculosis infection and treatment outcomes observed clinically, but the biological basis of this association is poorly understood. The aim of this study was to identify associations between phenogenomic variation in Mycobacterium tuberculosis and tuberculosis clinical features. METHODS: We developed a high-throughput platform to define phenotype-genotype relationships in M tuberculosis clinical isolates, which we tested on a set of 158 drug-sensitive M tuberculosis strains sampled from a large tuberculosis clinical study in Ho Chi Minh City, Viet Nam. We tagged the strains with unique genetic barcodes in multiplicate, allowing us to pool the strains for in-vitro competitive fitness assays across 16 host-relevant antibiotic and metabolic conditions. Relative fitness was quantified by deep sequencing, enumerating output barcode read counts relative to input normalised values. We performed a genome-wide association study to identify phylogenetically linked and monogenic mutations associated with the in-vitro fitness phenotypes. These genetic determinants were further associated with relevant clinical outcomes (cavitary disease and treatment failure) by calculating odds ratios (ORs) with binomial logistic regressions. We also assessed the population-level transmission of strains associated with cavitary disease and treatment failure using terminal branch length analysis of the phylogenetic data. FINDINGS: M tuberculosis clinical strains had diverse growth characteristics in host-like metabolic and drug conditions. These fitness phenotypes were highly heritable, and we identified monogenic and phylogenetically linked variants associated with the fitness phenotypes. These data enabled us to define two genetic features that were associated with clinical outcomes. First, mutations in Rv1339, a phosphodiesterase, which were associated with slow growth in glycerol, were further associated with treatment failure (OR 5·34, 95% CI 1·21-23·58, p=0·027). Second, we identified a phenotypically distinct slow-growing subclade of lineage 1 strains (L1.1.1.1) that was associated with cavitary disease (OR 2·49, 1·11-5·59, p=0·027) and treatment failure (OR 4·76, 1·53-14·78, p=0·0069), and which had shorter terminal branch lengths on the phylogenetic tree, suggesting increased transmission. INTERPRETATION: Slow growth under various antibiotic and metabolic conditions served as in-vitro intermediate phenotypes underlying the association between M tuberculosis monogenic and phylogenetically linked mutations and outcomes such as cavitary disease, treatment failure, and transmission potential. These data suggest that M tuberculosis growth regulation is an adaptive advantage for bacterial success in human populations, at least in some circumstances. These data further suggest markers for the underlying bacterial processes that contribute to these clinical outcomes. FUNDING: National Health and Medical Research Council/A∗STAR, National Institutes of Allergy and Infectious Diseases, National Institute of Child Health and Human Development, and the Wellcome Trust Fellowship in Public Health and Tropical Medicine.

Structural basis for the intracellular regulation of ferritin degradation.

The interaction between nuclear receptor coactivator 4 (NCOA4) and the iron storage protein ferritin is a crucial component of cellular iron homeostasis. The binding of NCOA4 to the FTH1 subunits of ferritin initiates ferritinophagy-a ferritin-specific autophagic pathway leading to the release of the iron stored inside ferritin. The dysregulation of NCOA4 is associated with several diseases, including neurodegenerative disorders and cancer, highlighting the NCOA4-ferritin interface as a prime target for drug development. Here, we present the cryo-EM structure of the NCOA4-FTH1 interface, resolving 16 amino acids of NCOA4 that are crucial for the interaction. The characterization of mutants, designed to modulate the NCOA4-FTH1 interaction, is used to validate the significance of the different features of the binding site. Our results explain the role of the large solvent-exposed hydrophobic patch found on the surface of FTH1 and pave the way for the rational development of ferritinophagy modulators.

Pyridostigmine to Reduce the duration of postoperative Ileus after Colorectal surgery (PyRICo-RCT): randomized clinical trial.

BACKGROUND: Postoperative ileus, driven by the cholinergic anti-inflammatory pathway, is the most common complication in patients undergoing colorectal surgery. By inhibiting acetylcholinesterase, pyridostigmine can potentially modulate the cholinergic anti-inflammatory pathway and accelerate gastrointestinal recovery. This study aimed to assess the efficacy of pyridostigmine in improving gastrointestinal recovery after colorectal surgery. METHODS: This double-blinded RCT enrolled adult patients undergoing elective colorectal surgery at two hospitals in South Australia. Patients were randomized to 60 mg oral pyridostigmine or placebo twice daily starting 6 h after surgery until the first passage of stool. The primary outcome was GI-2, a validated composite measure of time to first stool and tolerance of oral diet. Secondary outcomes included incidence of postoperative ileus (defined as GI-2 greater than 4 days), duration of hospital stay, and 30-day complications, evaluated by intention-to-treat univariate analysis. RESULTS: Of 130 patients recruited (mean(s.d.) age 58.4(16.4) years; 73 men, 56%), 65 were allocated to each arm. The median GI-2 was 1 day shorter with pyridostigmine compared with placebo (2 (i.q.r. 1-3) versus 3 (2-4) days; P = 0.015). However, there were no significant differences in postoperative ileus (17.2 versus 21.5%; P = 0.532) or duration of hospital stay (median 5 (i.q.r. 4-8.75) versus 5 (4-7.5) days; P = 0.921). Similarly, there were no significant differences in overall complications, anastomotic leak, cardiac complications, or patient-reported side effects. CONCLUSION: Pyridostigmine resulted in a quicker return of GI-2 and was well tolerated. Larger multicentre studies are required to determine the optimal dosing and evaluate the impact of pyridostigmine in different surgical settings. Registration number: ACTRN12621000530820 (https://anzctr.org.au).

Large-scale Deep Proteomic Analysis in Alzheimer's Disease Brain Regions Across Race and Ethnicity.

Introduction: Alzheimer's disease (AD) is the most prevalent neurodegenerative disease, yet our comprehension predominantly relies on studies within the non-Hispanic White (NHW) population. Here we aimed to provide comprehensive insights into the proteomic landscape of AD across diverse racial and ethnic groups. Methods: Dorsolateral prefrontal cortex (DLPFC) and superior temporal gyrus (STG) brain tissues were donated from multiple centers (Mayo Clinic, Emory University, Rush University, Mt. Sinai School of Medicine) and were harmonized through neuropathological evaluation, specifically adhering to the Braak staging and CERAD criteria. Among 1105 DLPFC tissue samples (998 unique individuals), 333 were from African American donors, 223 from Latino Americans, 529 from NHW donors, and the rest were from a mixed or unknown racial background. Among 280 STG tissue samples (244 unique individuals), 86 were African American, 76 Latino American, 116 NHW and the rest were mixed or unknown ethnicity. All tissues were uniformly homogenized and analyzed by tandem mass tag mass spectrometry (TMT-MS). Results: As a Quality control (QC) measure, proteins with more than 50% missing values were removed and iterative principal component analysis was conducted to remove outliers within brain regions. After QC, 9,180 and 9,734 proteins remained in the DLPC and STG proteome, respectively, of which approximately 9,000 proteins were shared between regions. Protein levels of microtubule-associated protein tau (MAPT) and amyloid-precursor protein (APP) demonstrated AD-related elevations in DLPFC tissues with a strong association with CERAD and Braak across racial groups. APOE4 protein levels in brain were highly concordant with APOE genotype of the individuals. Discussion: This comprehensive region resolved large-scale proteomic dataset provides a resource for the understanding of ethnoracial-specific protein differences in AD brain.

Association Between Prescription Drug Monitoring Program Use Mandate and Opioid Prescribing and Patient-Reported Outcomes After Surgery.

OBJECTIVE: To evaluate changes in opioid prescribing and patient-reported outcomes after surgery following implementation of Michigan's prescription drug monitoring program (PDMP) use mandate in June 2018. BACKGROUND: Most states mandate clinicians to query prescription drug monitoring program (PDMP) databases before prescribing controlled substances. Whether these PDMP use mandates affect opioid prescribing and patient-reported outcomes after surgery is unclear, especially among patients with elevated "Narx" scores, a risk score for overdose death used in most PDMPs. METHODS: We conducted an interrupted time series analysis of a statewide surgical registry linked to Michigan's PDMP database. Analyses included adults undergoing general surgical procedures during January 2017-October 2019. Outcomes included monthly mean days supplied in dispensed opioid prescriptions (those filled within 3 days of discharge) and monthly mean scores for 3 patient-reported outcomes (pain in the week after surgery, care satisfaction, regret undergoing surgery). Segmented regression models were used to assess for level and slope changes in outcomes in June 2018. Analyses were repeated among patients with Narx scores ≥200, a threshold that defines the top quartile. RESULTS: Analyses included 21,897 patients. The mandate was associated with a -0.5 (95% CI: -0.8, -0.2) level decrease in mean days supplied in dispensed opioid prescriptions, but not with worsened patient-reported outcomes. Findings were similar among patients with Narx scores ≥200. CONCLUSIONS: Following implementation of Michigan's PDMP use mandate, the duration of opioid prescriptions decreased, but patient-reported outcomes did not worsen. Findings suggest PDMP use mandates may not be associated with worsened experience among general surgical patients.

Developing biomarker assays to accelerate tuberculosis drug development: defining target product profiles.

Drug development for tuberculosis is hindered by the methodological limitations in the definitions of patient outcomes, particularly the slow organism growth and difficulty in obtaining suitable and representative samples throughout the treatment. We developed target product profiles for biomarker assays suitable for early-phase and late-phase clinical drug trials by consulting subject-matter experts on the desirable performance and operational characteristics of such assays for monitoring of tuberculosis treatment in drug trials. Minimal and optimal criteria were defined for scope, intended use, pricing, performance, and operational characteristics of the biomarkers. Early-stage trial assays should accurately quantify the number of viable bacilli, whereas late-stage trial assays should match the number, predict relapse-free cure, and replace culture conversion endpoints. The operational criteria reflect the infrastructure and resources available for drug trials. The effective tools should define the sterilising activity of the drug and lower the probability of treatment failure or relapse in people with tuberculosis. The target product profiles outlined in this Review should guide and de-risk the development of biomarker-based assays suitable for phase 2 and 3 clinical drug trials.

Interactive network visualization of opioid crisis research: a tool for reinforcing data linkage skills for public health policy researchers.

Background: Public health policy researchers face a persistent challenge in identifying and integrating relevant data, particularly in the context of the U.S. opioid crisis, where a comprehensive approach is crucial. Purpose: To meet this new workforce demand health policy and health economics programs are increasingly introducing data analysis and data visualization skills. Such skills facilitate data integration and discovery by linking multiple resources. Common linking strategies include individual or aggregate level linking (e.g., patient identifiers) in primary clinical data and conceptual linking (e.g., healthcare workforce, state funding, burnout rates) in secondary data. Often, the combination of primary and secondary datasets is sought, requiring additional skills, for example, understanding metadata and constructing interlinkages. Methods: To help improve those skills, we developed a 2-step process using a scoping method to discover data and network visualization to interlink metadata. Results: We show how these new skills enable the discovery of relationships among data sources pertinent to public policy research related to the opioid overdose crisis and facilitate inquiry across heterogeneous data resources. In addition, our interactive network visualization introduces (1) a conceptual approach, drawing from recent systematic review studies and linked by the publications, and (2) an aggregate approach, constructed using publicly available datasets and linked through crosswalks. Conclusions: These novel metadata visualization techniques can be used as a teaching tool or a discovery method and can also be extended to other public policy domains.

The genetic landscape of a metabolic interaction.

While much prior work has explored the constraints on protein sequence and evolution induced by physical protein-protein interactions, the sequence-level constraints emerging from non-binding functional interactions in metabolism remain unclear. To quantify how variation in the activity of one enzyme constrains the biochemical parameters and sequence of another, we focus on dihydrofolate reductase (DHFR) and thymidylate synthase (TYMS), a pair of enzymes catalyzing consecutive reactions in folate metabolism. We use deep mutational scanning to quantify the growth rate effect of 2696 DHFR single mutations in 3 TYMS backgrounds under conditions selected to emphasize biochemical epistasis. Our data are well-described by a relatively simple enzyme velocity to growth rate model that quantifies how metabolic context tunes enzyme mutational tolerance. Together our results reveal the structural distribution of epistasis in a metabolic enzyme and establish a foundation for the design of multi-enzyme systems.

Potential biological functions and future perspectives of sialylated milk oligosaccharides.

Sialyllactoses (SLs) primarily include sialylated human milk oligosaccharides (HMOs) and bovine milk oligosaccharides (BMOs). First, the safety assessment of 3'-sialyllactose (3'-SL) and 6'-sialyllactose (6'-SL) revealed low toxicity in various animal models and human participants. SLs constitute a unique milk component, highlighting the essential nutrients and bioactive components crucial for infant development, along with numerous associated health benefits for various diseases. This review explores the safety, biosynthesis, and potential biological effects of SLs, with a specific focus on their influence across various physiological systems, including the gastrointestinal system, immune disorders, rare genetic disorders (such as GNE myopathy), cancers, neurological disorders, cardiovascular diseases, diverse cancers, and viral infections, thus indicating their therapeutic potential.

Identifying Sources of Inter-hospital Variation in Episode Spending for Sepsis Care.

OBJECTIVE: To evaluate inter-hospital variation in 90-day total episode spending for sepsis, estimate the relative contributions of each component of spending, and identify drivers of spending across the distribution of episode spending on sepsis care. DATA SOURCES/STUDY SETTING: Medicare fee-for-service claims for beneficiaries (n=324,694) discharged from acute care hospitals for sepsis, defined by MS-DRG, between October 2014 and September 2018. RESEARCH DESIGN: Multiple linear regression with hospital-level fixed effects was used to identify average hospital differences in 90-day episode spending. Separate multiple linear regression and quantile regression models were used to evaluate drivers of spending across the episode spending distribution. RESULTS: The mean total episode spending among hospitals in the most expensive quartile was $30,500 compared with $23,150 for the least expensive hospitals (P<0.001). Postacute care spending among the most expensive hospitals was almost double that of least expensive hospitals ($7,045 vs. $3,742), accounting for 51% of the total difference in episode spending between the most expensive and least expensive hospitals. Female patients, patients with more comorbidities, urban hospitals, and BPCI-A-participating hospitals were associated with significantly increased episode spending, with the effect increasing at the right tail of the spending distribution. CONCLUSION: Inter-hospital variation in 90-day episode spending on sepsis care is driven primarily by differences in post-acute care spending.

HLA alleles associated with susceptibility and severity of the COVID-19 in Vietnamese.

The diversity of clinical manifestations in COVID-19 has been observed not only among individuals but also among various populations in globally. HLA molecules play a central role in physiology, protective immunity, and deleterious, disease-related autoimmune reactivity or overreaction. This study exploited the association between HLA frequencies and SARS-CoV-2 susceptibility and disease severity among the Vietnamese cohort (159 patients and 52 controls). A significant difference in frequency of both HLA class I and II in mild, moderate, and severe/fatal COVID-19 patients and negative exposure individuals - the controls were observed. Regarding SARS-CoV-2 sensitivity, HLA-A*03:01, 30:01, HLA-DQA1*01:02, DRB1*15:01, and DRB5*02:02 presented higher frequency in the control group compared with infected patients but DRB1 09:01 frequency was higher in infected patients. Regarding COVID-19 severity, HLA-F*01:01, 01:03 and DPA1*01:03 and 02:01, DPB1*04:01, DQA1*01:02, and DQB1*05:02 alleles were detected with higher frequency in severe patients but DOB*01:01, DRB1*05:01 and 09:01 had a significantly higher frequency in the mild group than remaining groups. Surprisingly, HLA-DQA1*01:02 and DRB1*09:01 alleles were identified with both inversely potential roles in protective function and severe risk. The obtained data herein will contribute to explore on the role of host genetic background in the pathology of COVID-19 disease.

Factors affecting highly pathogenic avian influenza vaccination practices at poultry farms in Tra Vinh, Vietnam.

Background: The increased number of cases of highly pathogenic avian influenza (HPAI) as a zoonosis has raised concerns in terms of poultry and human health. Farmers' preventive practices are an effective way of reducing zoonosis. However, this practice may have been affected by many factors, including production behaviors, awareness, and farmers' perceptions of farmers toward zoonosis. Aim: This study was conducted on 166 poultry farms in Tra Vinh Province with 14,894 poultry heads to determine the socioeconomic profiles and production characteristics of poultry farms and analyze the effect of these factors on HPAI vaccination practices. Methods: Respondents were selected from lists provided by government officers. Descriptive statistics were used to describe all variables, and factors affecting HPAI vaccination practices were analyzed using binary regression analysis. Results: The results showed that most farmers raised poultry with other livestock using the free-range method, which is a semi-intensive system. The primary objectives of poultry farming are meat sales and augmenting household consumption, with farmers primarily raising chicks produced on their farms. The implementation of the vaccine was less than 50% on the surveyed farms, with a small number of farmers administering an HPAI booster dose. However, only 6% of the farmers confirmed that their livestock had been exposed to HPAI. In addition, HPAI vaccination and booster dose practices significantly increased when farmers had 4-6 family members and received HPAI prevention training. Moreover, increased poultry numbers have led to increased vaccination rates and the implementation of booster doses for poultry. The study also reported that the vaccination rate decreased when poultry was used for household consumption. Conclusion: Sociodemographic characteristics and production behaviors can affect the implementation of HPAI vaccination on small poultry farms.

Stakeholder perspectives following implementation of Vietnam's first speech-language pathology degrees: recommendations for future curriculum development.

PURPOSE: To investigate perspectives of multiple stakeholders involved in development and delivery of Vietnam's first speech-language pathology degrees and derive recommendations for future degrees in Vietnam and other Majority World countries. METHODS: An exploratory-descriptive qualitative research design using focus groups and individual semi-structured interviews in the preferred language (English or Vietnamese) was used, with 70 participants from five stakeholder groups: project managers, students, academic educators, placement supervisors and interpreters. Transcriptions were analysed using thematic network analysis. RESULTS: Analysis identified five organising themes: (1) People enjoyed working with/learning from others; (2) Benefits from/to stakeholders; (3) The pandemic impacted program delivery and learning; (4) Practical challenges; (5) Preparation with flexibility required for success and sustainability. From the five organising themes, one synthesising global theme was developed, conveying that satisfying international collaborations require preparation, support, high quality interpreting, and management of challenges. CONCLUSIONS: Recommendations highlight the need for preparation, collaboration, support to manage challenges, flexibility, recognition for placement supervisors and high-quality interpreting. The recommendations are of relevance to other organisations engaged in development of professional degrees in Majority World countries. Future research would benefit from a critical investigation of the diverse perspectives of stakeholders involved in the development and implementation of international curricula.

Many Majority World countries are seeking to develop university degrees to build a workforce of speech-language pathologists to provide services to people with communication and swallowing disabilitiesCollaborative relationships, flexibility, and delineation of roles and commitments are vital to partnership successConceptualisation of rehabilitation services in cross-cultural contexts must privilege the knowledge, experiences and preferences of local partnersLocal capacity building will support training programs and rehabilitation services that are sustainable and culturally relevant.

Functional outcomes following anterior resection for colorectal cancer: a needs assessment and proposal of a nurse-led remote management algorithm.

AIM: With the rise of structured, remote follow-up of colorectal cancers, there is the potential risk of underdiagnosing and undermanaging low anterior resection syndrome (LARS). This cohort study aims to determine the rate of LARS and its patterns of care, with the aim of generating a risk-stratified management algorithm that can be employed for nurse-led follow-up. METHOD: Patients who underwent elective anterior resection for the management of colorectal cancer between 1 January 2017 and 31 December 2021 were sent quality-of-life questionnaires (EORTC-QLQ-CR29 and LARS score) and surveyed for LARS symptoms and management utilized. RESULTS: Out of 70 patients who completed questionnaires, 71.4% had LARS and 42.9% had major LARS. The international Delphi consensus definition identified more patients (n = 50) with LARS than the LARS score (n = 41). Tumours located <8 cm from the anal verge, ULAR, and temporary stoma were predictive of major LARS on univariate analysis. However, only temporary stoma was predictive for LARS (OR 7.89 (1.15-53.95), P = 0.035) and majors LARS (8.14 (1.79-37.01), P = 0.007) on multivariate analysis. Forty-four percent of patients with LARS did not have input from any health professional for this condition. Consultation with specialist allied health and/or colorectal surgeons ranged from 4% to 22%. CONCLUSIONS: Our study highlights that with the current remote follow-up system focused on cancer outcomes a significant proportion of patients with LARS are overlooked, resulting in the underutilization of relevant health professionals and management options. We propose a nurse-led management algorithm to address this issue while still minimizing surgical outpatient load.

Bridging the Gap: Multi-Omics Profiling of Brain Tissue in Alzheimer's Disease and Older Controls in Multi-Ethnic Populations.

INTRODUCTION: Multi-omics studies in Alzheimer's disease (AD) revealed many potential disease pathways and therapeutic targets. Despite their promise of precision medicine, these studies lacked African Americans (AA) and Latin Americans (LA), who are disproportionately affected by AD. METHODS: To bridge this gap, Accelerating Medicines Partnership in AD (AMP-AD) expanded brain multi-omics profiling to multi-ethnic donors. RESULTS: We generated multi-omics data and curated and harmonized phenotypic data from AA (n=306), LA (n=326), or AA and LA (n=4) brain donors plus Non-Hispanic White (n=252) and other (n=20) ethnic groups, to establish a foundational dataset enriched for AA and LA participants. This study describes the data available to the research community, including transcriptome from three brain regions, whole genome sequence, and proteome measures. DISCUSSION: Inclusion of traditionally underrepresented groups in multi-omics studies is essential to discover the full spectrum of precision medicine targets that will be pertinent to all populations affected with AD.

CB1 Receptor Negative Allosteric Modulators as a Potential Tool to Reverse Cannabinoid Toxicity.

While the opioid crisis has justifiably occupied news headlines, emergency rooms are seeing many thousands of visits for another cause: cannabinoid toxicity. This is partly due to the spread of cheap and extremely potent synthetic cannabinoids that can cause serious neurological and cardiovascular complications-and deaths-every year. While an opioid overdose can be reversed by naloxone, there is no analogous treatment for cannabis toxicity. Without an antidote, doctors rely on sedatives, with their own risks, or 'waiting it out' to treat these patients. We have shown that the canonical synthetic 'designer' cannabinoids are highly potent CB1 receptor agonists and, as a result, competitive antagonists may struggle to rapidly reverse an overdose due to synthetic cannabinoids. Negative allosteric modulators (NAMs) have the potential to attenuate the effects of synthetic cannabinoids without having to directly compete for binding. We tested a group of CB1 NAMs for their ability to reverse the effects of the canonical synthetic designer cannabinoid JWH018 in vitro in a neuronal model of endogenous cannabinoid signaling and also in vivo. We tested ABD1085, RTICBM189, and PSNCBAM1 in autaptic hippocampal neurons that endogenously express a retrograde CB1-dependent circuit that inhibits neurotransmission. We found that all of these compounds blocked/reversed JWH018, though some proved more potent than others. We then tested whether these compounds could block the effects of JWH018 in vivo, using a test of nociception in mice. We found that only two of these compounds-RTICBM189 and PSNCBAM1-blocked JWH018 when applied in advance. The in vitro potency of a compound did not predict its in vivo potency. PSNCBAM1 proved to be the more potent of the compounds and also reversed the effects of JWH018 when applied afterward, a condition that more closely mimics an overdose situation. Lastly, we found that PSNCBAM1 did not elicit withdrawal after chronic JWH018 treatment. In summary, CB1 NAMs can, in principle, reverse the effects of the canonical synthetic designer cannabinoid JWH018 both in vitro and in vivo, without inducing withdrawal. These findings suggest a novel pharmacological approach to at last provide a tool to counter cannabinoid toxicity.

Root hydraulic properties: An exploration of their variability across scales.

Root hydraulic properties are key physiological traits that determine the capacity of root systems to take up water, at a specific evaporative demand. They can strongly vary among species, cultivars or even within the same genotype, but a systematic analysis of their variation across plant functional types (PFTs) is still missing. Here, we reviewed published empirical studies on root hydraulic properties at the segment-, individual root-, or root system scale and determined its variability and the main factors contributing to it. This corresponded to a total of 241 published studies, comprising 213 species, including woody and herbaceous vegetation. We observed an extremely large range of variation (of orders of magnitude) in root hydraulic properties, but this was not caused by systematic differences among PFTs. Rather, the (combined) effect of factors such as root system age, driving force used for measurement, or stress treatments shaped the results. We found a significant decrease in root hydraulic properties under stress conditions (drought and aquaporin inhibition, p < .001) and a significant effect of the driving force used for measurement (hydrostatic or osmotic gradients, p < .001). Furthermore, whole root system conductance increased significantly with root system age across several crop species (p < .01), causing very large variation in the data (>2 orders of magnitude). Interestingly, this relationship showed an asymptotic shape, with a steep increase during the first days of growth and a flattening out at later stages of development. We confirmed this dynamic through simulations using a state-of-the-art computational model of water flow in the root system for a variety of crop species, suggesting common patterns across studies and species. These findings provide better understanding of the main causes of root hydraulic properties variations observed across empirical studies. They also open the door to better representation of hydraulic processes across multiple plant functional types and at large scales. All data collected in our analysis has been aggregated into an open access database (https://roothydraulic-properties.shinyapps.io/database/), fostering scientific exchange.

Does the education level of the CEO and CFO affect the profitability of real estate and construction companies? Evidence from Vietnam.

This article aims to determine the level and trend of the impact of the educational level of CEOs and CFOs on the profitability of real estate and construction companies in Vietnam. Because Vietnam is an emerging economy, insights into the profitability of this market will be lessons learned for other economies with similar characteristics. This quantitative study is based on secondary data collected from audited financial statements, annual reports of 123 Vietnamese real estate and construction companies, and macroeconomic data. Pool OLS, Fixed effect and Random effect regression models and the Hausman test are used to find the appropriate model. The study uses GLS regression to overcome heteroscedasticity and autocorrelation and uses the generalized method of moments (GMM) to overcome endogeneity. We find that the profitability of listed construction and real estate companies with highly educated CEOs is no higher than that of other companies. Furthermore, companies whose CFOs have master's or doctorate degrees are less likely to be profitable. Other findings confirm the heterogeneous effects of operating efficiency, economic growth rate, and financial leverage on different profitability measures. The study also proves that company age, firm size, net working capital, liquidity ratio and inflation rate do not affect profitability.

Synthesis of MnFe2O4/activated carbon derived from durian shell waste for removal of indole in water: Optimization, modelling, and mechanism.

While durian shell is often discharged into landfills, this waste can be a potential and zero-cost raw material to synthesize carbon-based adsorbents with purposes of saving costs and minimizing environmental contamination. Indole (IDO) is one of serious organic pollutants that influence aquatic species and human health; hence, the necessity for IDO removal is worth considering. Here, we synthesized a magnetic composite, denoted MFOAC, based on activated carbon (AC) derived from durian shell waste supported by MnFe2O4 (MFO) to adsorb IDO in water. MFOAC showed a microporous structure, along with a high surface area and pore volume, at 518.9 m2/g, and 0.106 cm3/g, respectively. Optimization of factors affecting the IDO removal of MFOAC were implemented by Box-Behnken design and response surface methodology. Adsorption kinetics and isotherms suggested a suitable model for MFOAC to remove IDO. MFOAC was recyclable with 3 cycles. Main interactions involving in the IDO adsorption mechanism onto MFOAC were clarified, including pore filling, n-π interaction, π-π interaction, Yoshida H-bonding, H-bonding.