Can the -CF3 Group Act as a Tight, Well-Defined Hydrogen Bond Acceptor? A Clear Crystallographic CF2-F···H-N+ Interaction Says Yes.

The CF3 group is well noted for being noninteractive with other functional groups. In this Note, we present a highly rigid model system containing a significant hydrogen bonding interaction between a charged N-H donor and a CF3 acceptor that challenges this accepted wisdom. Spectroscopic and single crystal X-ray crystallography data characterize this interaction, consistent with a weak to moderate hydrogen bond that would be difficult to observe in an intermolecular system.

Methods for measuring and valuing informal care: A systematic review and meta-analysis in stroke.

OBJECTIVES: To accurately capture informal care in healthcare evaluations, rigorous approaches are required to measure and value this important care component. In this systematic review and meta-analysis, we intended to summarize the current methods of measuring and valuing informal care costs in healthcare evaluations (full and partial healthcare evaluations, including cost of illness and cost analysis) in stroke. METHODS: A systematic search was conducted in Medline, Embase, EconLIT, and CINAHL. We used EndNote 20, Research Screener, and Covidence platforms for screening and data extraction. A meta-analysis was performed on informal care hours, and a sub-group meta-analysis was conducted based on stroke severity. RESULTS: A total of 31 articles were included in the qualitative synthesis. There was variation among the studies in the informal care measurement and valuation approaches. The meta-analysis of studies where data on informal care hours were available showed an estimate of informal care hours of 25.76 per week (95% Confidence interval [CI]: 13.36-38.16 with a high heterogeneity (I2=99.97%). The overall risk of bias in the studies was assessed as low. CONCLUSIONS: Standardizing the measurement and valuation of informal care costs is essential for improving the consistency and comparability of economic evaluations. Pilot studies that incorporate standardized informal care cost valuation methods can help identify any practical challenges and capture the impact of informal care more accurately.

Therapists' perspective on acceptance of robot-assisted physical rehabilitation in a middle-income country: a study from Vietnam.

Robot-assisted physical rehabilitation offers promising benefits for patients, yet its adoption among therapists remains a complex challenge. This study investigates the acceptance of robot-assisted physical rehabilitation technology among therapists in Vietnam, a middle-income country with a growing demand for rehabilitation services. Drawing on the Technology Acceptance Model 2 (TAM2) and the Theory of Planned Behaviour (TPB), an online survey and semi-structured interviews were conducted to explore therapists' attitudes and intentions towards using this technology. The results show that Vietnamese therapists recognised its potential benefits and expressed a willingness to use it. Although having similar acceptance patterns compared to developed regions, they demonstrated significantly higher levels of agreement across acceptance constructs. This may be attributed to factors such as the novelty effect, cultural perceptions of robots, and the high workload of therapists in Vietnam. Gender and location were found to influence two acceptance constructs-subjective norms and image, respectively-highlighting the need for tailored strategies in technology implementation. The study underscores the importance of considering socio-cultural factors in the adoption of technology and provides insights for enhancing the acceptance and effectiveness of robot-assisted physical rehabilitation in Vietnam. This contributes to the global understanding of therapist acceptance of technology in this field.

While robot-assisted physical rehabilitation offers promising benefits, there is limited understanding of therapist acceptance on a global scale, highlighting the need for more research in this area.This study in a middle-income country, Vietnam, reveals a generally positive view among therapists, but specific issues such as the novelty effect, cultural perceptions of robots, and high therapist workload impact acceptance levels, indicating the need for tailored strategies.Strategies for implementing robot-assisted physical rehabilitation should include addressing training needs, providing technological support, and considering sociocultural factors to enhance acceptance and effectiveness.

Lifestyle practices and associated factors among adults with hypertension: Conquering Hypertension in Vietnam-solutions at the grassroots level study.

BACKGROUND: Vietnam is experiencing an increasing prevalence of hypertension in its adult population. In addition to medical therapy, modifying adverse lifestyle practices is important for effective blood pressure control. There are limited data on unhealthy lifestyle practices in patients with chronic diseases, however, particularly among hypertensive patients living in rural Vietnam. Our study objectives were to examine the prevalence of unhealthy lifestyle practices and associated factors among rural Vietnamese adults with uncontrolled hypertension. METHODS: Data from the baseline survey of a cluster randomized trial among hypertensive Vietnamese adults (2017-2022) were utilized. Information on unhealthy lifestyle practices including smoking, excessive alcohol consumption, physical inactivity, and inadequate fruit and vegetable intake was collected from study participants. The primary study outcome was having ≥2 unhealthy lifestyle practices. A multivariable logistic regression model was used to examine factors associated with the primary study outcome. RESULTS: The mean age of the 671 patients was 67 years and 45.0% were men. Nearly three out of every four participants had one or fewer unhealthy practices, 24.0% had two, and 3.3% had three or all four unhealthy lifestyle practices. Men, individuals who did unpaid work or were unemployed, and individuals with hypertension level III were more likely to have ≥2 unhealthy lifestyle practices, whereas individuals with higher education were less likely to have ≥2 unhealthy lifestyle practices compared with respective comparison groups. CONCLUSIONS: We observed a high prevalence of unhealthy lifestyle practices among rural Vietnamese patients with uncontrolled hypertension. Several demographic factors were associated with a greater number of unhealthy lifestyle practices. Newer interventions and educational programs encouraging lifestyle modification practices are needed to control hypertension among adults living in rural settings of Vietnam.

Identifying measures for coverage of nutrition-sensitive social protection programs: Learnings from India.

Optimal child growth requires a combination of nutrition-specific and sensitive interventions in the first 1,000 days. There is limited guidance on how to measure the population-level coverage of nutrition-sensitive social protection (NSSP), which is designed with explicit nutrition goals and often provides food or cash transfers and co-coverage with nutrition and health intervention. In this study in India, we designed a questionnaire that captures seven core NSSP program elements (transfer type, size, modality, population, timing, provider, conditionalities), then used cognitive testing to refine the questionnaire, and then implemented the questions as part of a telephone survey. Cognitive testing indicated variability in understanding the terms used to specify NSSP programs, including the need to use regional program names. Respondents also had difficulty recalling the timing of the benefit receipt. We included the refined NSSP coverage questions in a phone-based survey with 6,627 mothers with children <2 years across six states. Coverage of subsidized food was 73% across all households. Women were more likely to report receiving food than cash transfers during pregnancy (89% vs. 60%) and during lactation (75% vs. 13%). Co-coverage of NSSP with nutrition and health interventions during pregnancy (16%) and early childhood (3%) was low. It was feasible to measure coverage of NSSP investments in these populations; however, further research is needed to comprehensively assess all the dimensions of the NSSP benefits, including benefit adequacy and the validity of these questions when administered in person and by phone.

Low-dose computed tomography scan and biopsy for assessing lung cancer prevalence and related factors in high-risk populations.

Background: Lung cancer is the second most diagnosed cancer and the leading cause of cancer death in 2020, representing approximately one in 10 (11.4 %) cancers diagnosed and one in 5 (18.0 %) deaths. There are currently very few studies evaluating the prevalence and related factors of lung cancer detected using low-dose CT scans. Objective: Evaluate the prevalence and related factors of lung cancer using low-dose CT scans in high-risk populations in Vietnam. Materials and methods: A cross-sectional analysis study of 169 high-risk patients was conducted to assess the lung cancer prevalence and related factors. Enrolled patients received a physical examination, low-dose computerized tomography scan, and biopsy if abnormalities were found through the CT scan. Univariable and Multivariable analysis through Odd Ratio (OR) to assess the related risk of lung cancer. Results: A total of 169 high-risk patients with a mean age of 62.93 ± 9.31 (years), and the majority were male (91.7 %). Of which 4 cases (2.37 %) were recorded with lung cancer, 3 cases of adenocarcinoma, and 1 case of squamous cell carcinoma. A history of smoking and Chronic Obstructive Pulmonary Disease (COPD) were associated with an increased risk of abnormalities on lung CT scans. Multivariate regression analysis revealed that smoking over 30 pack-years and COPD significantly increased the risk of abnormalities on lung CT scans, p < 0.05.100 % of lung cancer-detected cases were male and smoking ≥30 pack - years. Conclusion: The prevalence of lung cancer in the Vietnamese high-risk population was relatively high. Relative factors such as smoking ≥30 pack - years, and COPD had increased risk of CTscan abnormalities.

Adoption of sustainable farming practices in Vietnam: A discourse of the determining factors.

To delve into the intricacies of sustainable agricultural practices, our study investigates both the behavioral and non-behavioral factors influencing farmers' decision-making processes. Employing the New Ecological Model (NEP) to capture social factors, our research framework integrates insights from the sustainable livelihood framework, which delineates five crucial types of livelihood capital: (1) human capital, (2) natural capital, (3) financial capital, (4) physical capital, and (5) social capital. This comprehensive approach enables us to incorporate additional non-behavioral factors and their impacts on farmers' decisions. We underscore the pivotal role of farmers' decisions in fostering sustainable agriculture, aligning with seven of the Sustainable Development Goals (SDGs). Leveraging survey data collected from 303 Vietnamese farmers, we validate our research framework using two analytical models: Structural Equation Model (SEM) and binary logit analysis. Our findings underscore the significant influence of farmers' risk propensity and concerns regarding food safety and environmental conservation on the adoption of organic farming practices. Notably, farmers' level of knowledge emerges as a critical determinant shaping their inclination towards sustainable agriculture. The study underscores the importance of targeted educational initiatives and awareness campaigns, identifying key determinants such as proximity to green spaces and farm size in shaping farmers' choices towards sustainable practices.

Intramyelinic edema manifesting as central white matter diffusion restriction associated with brain contusion in pediatric patients.

In traumatic brain injury, white matter diffusion restriction can be an imaging manifestation of non-hemorrhagic axonal injury. In this article, a different pattern of widespread white matter diffusion restriction associated with ipsilateral cortical damage, all noted in pediatric and young adult TBI patients, is presented. Its atypical pattern of distribution and extensive scope on imaging suggest excitotoxicity and intramyelinic edema as possible underlying mechanisms.

Impact of leukemia-associated macrophages on the progression and therapy response of chronic lymphocytic leukemia.

The treatment landscape of chronic lymphocytic leukemia (CLL) has advanced remarkably over the past decade. The advent and approval of the BTK inhibitor ibrutinib and BCL-2 inhibitor venetoclax, as well as monoclonal anti-CD20 antibodies rituximab and obinutuzumab, have resulted in deep remissions and substantially improved survival outcomes for patients. However, CLL remains a complex disease with many patients still experiencing relapse and unsatisfactory treatment responses. CLL cells are highly dependent on their pro-leukemic tumor microenvironment (TME), which comprises different cellular and soluble factors. A large body of evidence suggests that CLL-associated macrophages shaped by leukemic cells play a pivotal role in maintaining CLL cell survival. In this review, we summarize the pro-survival interactions between CLL cells and macrophages, as well as the impact of the current first-line treatment agents, including ibrutinib, venetoclax, and CD20 antibodies on leukemia-associated macrophages.

Mapping the international health regulations monitoring and evaluation framework: an expert consultation, triangulation crosswalk and quantitative analysis.

The International Health Regulations Monitoring and Evaluation Framework (IHRMEF) includes four components regularly conducted by States Parties to measure the current status of International Health Regulations (IHR) 2005 core capacities and provide recommendations for strengthening these capacities. However, the four components are conducted independently of one another and have no systematic referral to each other before, during or after each process, despite being largely conducted by the same team, country and support organisations. This analysis sets out to identify ways in which IHRMEF components could work more synergistically to effectively measure the status of IHR core capacities, taking into account the country's priority risks. We developed a methodology to allow these independent components to communicate with each other, including expert consultation, a qualitative crosswalk analysis and a country-level quantitative analysis. The demonstrated results act as a proof of concept and illustrate a methodology to provide benefits across all four components before, during and after implementation.

Highly adsorptive removal of ciprofloxacin and E. coli inactivation using amino acid tryptophan modified nano-gibbsite.

Adsorption of essential amino acid, Tryptophan (Tryp) on synthesized gibbsite nanoparticles and their applications in eliminating of antibiotic ciprofloxacin (CFX) and bacteria Escherichia coli (E. coli) in aqueous solution. Nano-gibbsite which was successfully fabricated, was characterized by XRD, TEM-SAED, FT-IR, SEM-EDX and zeta potential measurements. The selected parameters for Tryp adsorption on nano-gibbsite to form biomaterial, Tryp/gibbsite were pH 11, gibbsite dosage 20 mg/mL and 1400 mg/L Tryp. The optimum conditions for CFX removal using Tryp/gibbsite were adsorption time 60 min, pH 5, and 20 mg/mL Tryp/gibbsite dosage. The CFX removal significantly raised from 63 to 90% when using Tryp/gibbsite. The Freundlich and pseudo-second-order models achieved the best fits for CFX adsorption isotherm and kinetic on Tryp/gibbsite, respectively. The amount of CFX increased with increasing ionic strength, suggesting that both electrostatic and non-electrostatic interactions were important. After four reused time, CFX removal was greater than 66%, demonstrating that Tryp/gibbsite is reusable with high performance in removing CFX. The application in bacterial activity in term of E. coli reached greater than 98% that was the best material for bacteria inactivation. The present study reveals that Tryp/gibbsite is an excellent bio-material for removing CFX and E. coli.

Antibodies Targeting Human or Mouse VSIG4 Repolarize Tumor-Associated Macrophages Providing the Potential of Potent and Specific Clinical Anti-Tumor Response Induced across Multiple Cancer Types.

V-set immunoglobulin domain-containing 4 (VSIG4) is a B7 family protein with known roles as a C3 fragment complement receptor involved in pathogen clearance and a negative regulator of T cell activation by an undetermined mechanism. VSIG4 expression is specific for tumor-associated and select tissue-resident macrophages. Increased expression of VSIG4 has been associated with worse survival in multiple cancer indications. Based upon computational analysis of transcript data across thousands of tumor and normal tissue samples, we hypothesized that VSIG4 has an important role in promoting M2-like immune suppressive macrophages and that targeting VSIG4 could relieve VSIG4-mediated macrophage suppression by repolarizing tumor-associated macrophages (TAMs) to an inflammatory phenotype. We have also observed a cancer-specific pattern of VSIG4 isoform distribution, implying a change in the functional regulation in cancer. Through a series of in vitro, in vivo, and ex vivo assays we demonstrate that anti-VSIG4 antibodies repolarize M2 macrophages and induce an immune response culminating in T cell activation. Anti-VSIG4 antibodies induce pro-inflammatory cytokines in M-CSF plus IL-10-driven human monocyte-derived M2c macrophages. Across patient-derived tumor samples from multiple tumor types, anti-VSIG4 treatment resulted in the upregulation of cytokines associated with TAM repolarization and T cell activation and chemokines involved in immune cell recruitment. VSIG4 blockade is also efficacious in a syngeneic mouse model as monotherapy as it enhances efficacy in combination with anti-PD-1, and the effect is dependent on the systemic availability of CD8+ T cells. Thus, VSIG4 represents a promising new target capable of triggering an anti-cancer response via multiple key immune mechanisms.

The Roles of NOTCH3 p.R544C and Thrombophilia Genes in Vietnamese Patients With Ischemic Stroke: Study Involving a Hierarchical Cluster Analysis.

BACKGROUND: The etiology of ischemic stroke is multifactorial. Several gene mutations have been identified as leading causes of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), a hereditary disease that causes stroke and other neurological symptoms. OBJECTIVE: We aimed to identify the variants of NOTCH3 and thrombophilia genes, and their complex interactions with other factors. METHODS: We conducted a hierarchical cluster analysis (HCA) on the data of 100 patients diagnosed with ischemic stroke. The variants of NOTCH3 and thrombophilia genes were identified by polymerase chain reaction with confronting 2-pair primers and real-time polymerase chain reaction. The overall preclinical characteristics, cumulative cutpoint values, and factors associated with these somatic mutations were analyzed in unidimensional and multidimensional scaling models. RESULTS: We identified the following optimal cutpoints: creatinine, 83.67 (SD 9.19) µmol/L; age, 54 (SD 5) years; prothrombin (PT) time, 13.25 (SD 0.17) seconds; and international normalized ratio (INR), 1.02 (SD 0.03). Using the Nagelkerke method, cutpoint 50% values of the Glasgow Coma Scale score; modified Rankin scale score; and National Institutes of Health Stroke Scale scores at admission, after 24 hours, and at discharge were 12.77, 2.86 (SD 1.21), 9.83 (SD 2.85), 7.29 (SD 2.04), and 6.85 (SD 2.90), respectively. CONCLUSIONS: The variants of MTHFR (C677T and A1298C) and NOTCH3 p.R544C may influence the stroke severity under specific conditions of PT, creatinine, INR, and BMI, with risk ratios of 4.8 (95% CI 1.53-15.04) and 3.13 (95% CI 1.60-6.11), respectively (Pfisher<.05). It is interesting that although there are many genes linked to increased atrial fibrillation risk, not all of them are associated with ischemic stroke risk. With the detection of stroke risk loci, more information can be gained on their impacts and interconnections, especially in young patients.

Structural and mechanistic insights into a lysosomal membrane enzyme HGSNAT involved in Sanfilippo syndrome.

Heparan sulfate (HS) is degraded in lysosome by a series of glycosidases. Before the glycosidases can act, the terminal glucosamine of HS must be acetylated by the integral lysosomal membrane enzyme heparan-α-glucosaminide N-acetyltransferase (HGSNAT). Mutations of HGSNAT cause HS accumulation and consequently mucopolysaccharidosis IIIC, a devastating lysosomal storage disease characterized by progressive neurological deterioration and early death where no treatment is available. HGSNAT catalyzes a unique transmembrane acetylation reaction where the acetyl group of cytosolic acetyl-CoA is transported across the lysosomal membrane and attached to HS in one reaction. However, the reaction mechanism remains elusive. Here we report six cryo-EM structures of HGSNAT along the reaction pathway. These structures reveal a dimer arrangement and a unique structural fold, which enables the elucidation of the reaction mechanism. We find that a central pore within each monomer traverses the membrane and controls access of cytosolic acetyl-CoA to the active site at its luminal mouth where glucosamine binds. A histidine-aspartic acid catalytic dyad catalyzes the transfer reaction via a ternary complex mechanism. Furthermore, the structures allow the mapping of disease-causing variants and reveal their potential impact on the function, thus creating a framework to guide structure-based drug discovery efforts.

The Relationship of Preterm and Small for Gestational Age with Child Cognition During School-Age Years.

BACKGROUND: Children born preterm and/or small for gestational age (SGA) are at increased risk of poor cognitive outcomes, particularly in low and middle-income countries (LMICs). OBJECTIVES: This study aimed to examine the cognitive and academic deficits during the school-age years in children born preterm or SGA compared with those in children born term adequate for gestational age (AGA) in rural Vietnam. METHODS: Children born to women in a preconception micronutrient supplementation trial in Vietnam were classified into 3 groups: preterm AGA (n =138), term SGA (n =169), and term AGA (n = 1134). Cognitive abilities were assessed using the Wechsler Intelligence Scale for Children, measuring 4 domains [verbal comprehension index (VCI), perceptual reasoning index (PRI), working memory index (WMI), and processing speed index (PSI) scores] and full-scale intelligence quotient (FSIQ) at 6-7 and 10-11 y. Academic achievement was assessed with mathematic and language tests. Analysis of variance and multiple regression models were used to analyze differences in cognitive function and academic achievement at 6-7 and 10-11 y by birth phenotypes. RESULTS: Compared with term AGA children, those born SGA had lower cognitive scores at both 6-7 y (VCI, -2.3; PRI, -3.7; PSI -2.1; and FSIQ, -2.9) and 10-11 y (VCI, -3.7; PRI, -3.5; WMI, -2.7; PSI, -1.9; and FSIQ, -3.9). Children born SGA also had poorer academic achievement with lower language (5.3) and mathematic (2.5) scores. Adjustments for maternal factors and home environment attenuated the associations, but the differences in VCI, PRI, FSIQ, and language at 10-11 y remained significant. There were no differences in cognitive function and academic achievement between children born preterm and AGA. CONCLUSIONS: Our findings highlight the enduring association of birth phenotype on cognitive functioning and academic achievement during the school years, despite adjustments for maternal education and family environment. Further research is needed to implement effective interventions to improve birth outcomes and optimize child health and development in LMICs. The trial was registered at clinicaltrials.gov as NCT01665378 (URL: https://clinicaltrials.gov/ct2/show/NCT01665378).

The relationship between bisphenol A and phthalates with precocious puberty in Vietnamese children.

OBJECTIVES: This study is aimed to explore the correlation between bisphenol A (BPA) and phthalates, including diethylhexylphthalate (DEHP) and dibutylphthalate (DBP), and precocious puberty (PP). METHODS: A case-control study was conducted in Ho Chi Minh City, Vietnam, from November 2021 to April 2022, involving 250 children, with 124 of them diagnosed with PP and 126 serving as controls. We assessed the levels of urinary BPA, DEHP, and DBP in all participants and examined their association with the risk of PP. RESULTS: BPA was detected in 11.3 % of PP cases but was not found in any individuals in the control group (p<0.001). Diethylhexylphthalate metabolite (MEHP) was not detected in any of the samples. Positive urinary results for dibutylphthalate metabolite (MBP) were observed in 8.1 % of PP cases and 2.4 % in the control group, with an odds ratio of 3.6 (95 % confidence interval: 0.97-13.4, p=0.03). CONCLUSIONS: The PP group exhibited a higher prevalence of positive urinary BPA and DBP levels compared to the control group.

Research upon Cu-Doping Contents in TiO2 Nanoparticles Incorporated onto Cellulose Nanofibers for Dye Removal and Self-Cleaning Applications.

Cu-doping contents in the TiO2 lattice structure were studied to show the effects on the crystal structure, morphology, and photocatalytic activity of TiO2 nanoparticles and thus composite cellulosic nanofibrous membranes. Pristine and copper-doped TiO2 nanoparticles were synthesized using the sol-gel technique, a wet chemical method with the advantages of low synthesizing temperature, uniform nanosize distribution, and purity. The as-synthesized semiconductor nanoparticles were first tested with the dye removal process and then impregnated onto electrospun cellulose nanofibers (CL nanofibers) to acquire modified nanofibers with self-cleaning properties. The as-prepared composite CL nanofibers consisting of doped and undoped TiO2 nanoparticles were characterized by various techniques, such as field emission scanning electron microscopy, transmission electron microscopy, UV-vis, X-ray diffraction, Fourier transform infrared spectroscopy, and tensile tests. The copper-doped TiO2 molar ratio in the nanocomposite was found to possess a pronounced impact on the dye removal and self-cleaning effects under the visible light spectrum, whereas TiO2 is highly effective under specific UV-light irradiation. Optical measurements and dye decomposition showed that the Cu-doped TiO2 nanocomposite was optimized at a 1% molar ratio by the copper-doping concentration regarding dye removal and self-cleaning applications under the visible light range.

Effects of a large-scale alcohol ban on population-level alcohol intake, weight, blood pressure, blood glucose, and domestic violence in India: a quasi-experimental population-based study.

Background: Globally, alcohol consumption is a leading risk factor for deaths and disability and a causal factor in over 200 diseases, injuries, and health conditions. In April 2016, the manufacture, transport, sale, and consumption of alcohol was banned in Bihar, a populous Indian state. We sought to estimate the impacts of this ban on health outcomes and domestic violence. Methods: Data from the Indian National Family Health Surveys (2005-06, 2015-16, 2019-21), Annual Health Survey (2013), and District Level Household Survey (2012), were used to conduct difference-in-differences (DID) analysis, comparing Bihar (n = 10,733 men, n = 88,188 women) and neighbouring states (n = 38,674 men, n = 284,820 women) before and after the ban. Outcomes included frequent (daily or weekly) alcohol consumption, underweight, obesity, hypertension, diabetes, and intimate partner violence. A triple difference model adding male-female interaction to the DID model was also estimated. Attributable averted cases were calculated to estimate the impact of the ban. Findings: Across all models, the ban led to reduced frequent alcohol consumption (DID: -7.1 percentage points (pp) (95% CI -9.6pp, -4.6pp), lower overweight/obesity (-5.6pp (-8.9, -2.2) among males, and reduced experiences of emotional (-4.8pp (-8.2pp, -1.4pp) and sexual (-5.5pp (-8.7pp, -2.3pp) violence among females. The ban prevented approximately 2.4 million cases of daily/weekly alcohol consumption and 1.8 million cases of overweight/obesity among males, and 2.1 million cases of intimate partner violence among females. Interpretation: Strict alcohol regulation policies may yield significant population level health benefits for frequent drinkers and many victims of intimate partner violence. Funding: No funding was received for this work.

Artificial Intelligence Methods for the Argenta Classification of Deformational Plagiocephaly to Predict Severity and Treatment Recommendation.

INTRODUCTION: Deformational plagiocephaly (DP) can be classified into 5 severity types using the Argenta scale (AS). Patients with type III or higher require referral to craniofacial surgery for management. Primary care pediatricians (PCPs) are often the first to encounter patients with DP, but current screening methods are subjective, increasing the risk of bias, especially for clinicians with little exposure to this population. The authors propose the use of artificial intelligence (AI) to classify patients with DP using the AS and to make recommendations for referral to craniofacial surgery. METHODS: Vertex photographs were obtained for patients diagnosed with unilateral DP from 2019 to 2020. Using the photographs, an AI program was created to characterize the head contour of these infants into 3 groups based on the AS. The program was trained using photographs from patients whose DP severity was confirmed clinically by craniofacial surgeons. To assess the accuracy of the software, the AS predicted by the program was compared with the clinical diagnosis. RESULTS: Nineteen patients were assessed by the AI software. All 3 patients with type I DP were correctly classified by the program (100%). In addition, 4 patients with type II were correctly identified (67%), and 7 were correctly classified as type III or greater (70%). CONCLUSIONS: Using vertex photographs and AI, the authors were able to objectively classify patients with DP based on the AS. If converted into a smartphone application, the program could be helpful to PCPs in remote or low-resource settings, allowing them to objectively determine which patients require referral to craniofacial surgery.

Toward high-resolution modeling of small molecule-ion channel interactions.

Ion channels are critical drug targets for a range of pathologies, such as epilepsy, pain, itch, autoimmunity, and cardiac arrhythmias. To develop effective and safe therapeutics, it is necessary to design small molecules with high potency and selectivity for specific ion channel subtypes. There has been increasing implementation of structure-guided drug design for the development of small molecules targeting ion channels. We evaluated the performance of two RosettaLigand docking methods, RosettaLigand and GALigandDock, on the structures of known ligand-cation channel complexes. Ligands were docked to voltage-gated sodium (NaV), voltage-gated calcium (CaV), and transient receptor potential vanilloid (TRPV) channel families. For each test case, RosettaLigand and GALigandDock methods frequently sampled a ligand-binding pose within a root mean square deviation (RMSD) of 1-2 Å relative to the experimental ligand coordinates. However, RosettaLigand and GALigandDock scoring functions cannot consistently identify experimental ligand coordinates as top-scoring models. Our study reveals that the proper scoring criteria for RosettaLigand and GALigandDock modeling of ligand-ion channel complexes should be assessed on a case-by-case basis using sufficient ligand and receptor interface sampling, knowledge about state-specific interactions of the ion channel, and inherent receptor site flexibility that could influence ligand binding.