A transcription factor atlas of directed differentiation.

Transcription factors (TFs) regulate gene programs, thereby controlling diverse cellular processes and cell states. To comprehensively understand TFs and the programs they control, we created a barcoded library of all annotated human TF splice isoforms (>3,500) and applied it to build a TF Atlas charting expression profiles of human embryonic stem cells (hESCs) overexpressing each TF at single-cell resolution. We mapped TF-induced expression profiles to reference cell types and validated candidate TFs for generation of diverse cell types, spanning all three germ layers and trophoblasts. Targeted screens with subsets of the library allowed us to create a tailored cellular disease model and integrate mRNA expression and chromatin accessibility data to identify downstream regulators. Finally, we characterized the effects of combinatorial TF overexpression by developing and validating a strategy for predicting combinations of TFs that produce target expression profiles matching reference cell types to accelerate cellular engineering efforts.

IL-17RA-signaling in Lgr5+ intestinal stem cells induces expression of transcription factor ATOH1 to promote secretory cell lineage commitment.

The Th17 cell-lineage-defining cytokine IL-17A contributes to host defense and inflammatory disease by coordinating multicellular immune responses. The IL-17 receptor (IL-17RA) is expressed by diverse intestinal cell types, and therapies targeting IL-17A induce adverse intestinal events, suggesting additional tissue-specific functions. Here, we used multiple conditional deletion models to identify a role for IL-17A in secretory epithelial cell differentiation in the gut. Paneth, tuft, goblet, and enteroendocrine cell numbers were dependent on IL-17A-mediated induction of the transcription factor ATOH1 in Lgr5+ intestinal epithelial stem cells. Although dispensable at steady state, IL-17RA signaling in ATOH1+ cells was required to regenerate secretory cells following injury. Finally, IL-17A stimulation of human-derived intestinal organoids that were locked into a cystic immature state induced ATOH1 expression and rescued secretory cell differentiation. Our data suggest that the cross talk between immune cells and stem cells regulates secretory cell lineage commitment and the integrity of the mucosa.

VISH-Pred: an ensemble of fine-tuned ESM models for protein toxicity prediction.

Peptide- and protein-based therapeutics are becoming a promising treatment regimen for myriad diseases. Toxicity of proteins is the primary hurdle for protein-based therapies. Thus, there is an urgent need for accurate in silico methods for determining toxic proteins to filter the pool of potential candidates. At the same time, it is imperative to precisely identify non-toxic proteins to expand the possibilities for protein-based biologics. To address this challenge, we proposed an ensemble framework, called VISH-Pred, comprising models built by fine-tuning ESM2 transformer models on a large, experimentally validated, curated dataset of protein and peptide toxicities. The primary steps in the VISH-Pred framework are to efficiently estimate protein toxicities taking just the protein sequence as input, employing an under sampling technique to handle the humongous class-imbalance in the data and learning representations from fine-tuned ESM2 protein language models which are then fed to machine learning techniques such as Lightgbm and XGBoost. The VISH-Pred framework is able to correctly identify both peptides/proteins with potential toxicity and non-toxic proteins, achieving a Matthews correlation coefficient of 0.737, 0.716 and 0.322 and F1-score of 0.759, 0.696 and 0.713 on three non-redundant blind tests, respectively, outperforming other methods by over $10\%$ on these quality metrics. Moreover, VISH-Pred achieved the best accuracy and area under receiver operating curve scores on these independent test sets, highlighting the robustness and generalization capability of the framework. By making VISH-Pred available as an easy-to-use web server, we expect it to serve as a valuable asset for future endeavors aimed at discerning the toxicity of peptides and enabling efficient protein-based therapeutics.

N4-acetylcytidine (ac4C) promotes mRNA localization to stress granules.

Stress granules are an integral part of the stress response that are formed from non-translating mRNAs aggregated with proteins. While much is known about stress granules, the factors that drive their mRNA localization are incompletely described. Modification of mRNA can alter the properties of the nucleobases and affect processes such as translation, splicing and localization of individual transcripts. Here, we show that the RNA modification N4-acetylcytidine (ac4C) on mRNA associates with transcripts enriched in stress granules and that stress granule localized transcripts with ac4C are specifically translationally regulated. We also show that ac4C on mRNA can mediate localization of the protein NOP58 to stress granules. Our results suggest that acetylation of mRNA regulates localization of both stress-sensitive transcripts and RNA-binding proteins to stress granules and adds to our understanding of the molecular mechanisms responsible for stress granule formation.

Regulation of Notch signaling by non-muscle myosin II Zipper in Drosophila.

The Notch pathway is an evolutionarily conserved signaling system that is intricately regulated at multiple levels and it influences different aspects of development. In an effort to identify novel components involved in Notch signaling and its regulation, we carried out protein interaction screens which identified non-muscle myosin II Zipper (Zip) as an interacting partner of Notch. Physical interaction between Notch and Zip was further validated by co-immunoprecipitation studies. Immunocytochemical analyses revealed that Notch and Zip co-localize within same cytoplasmic compartment. Different alleles of zip also showed strong genetic interactions with Notch pathway components. Downregulation of Zip resulted in wing phenotypes that were reminiscent of Notch loss-of-function phenotypes and a perturbed expression of Notch downstream targets, Cut and Deadpan. Further, synergistic interaction between Notch and Zip resulted in highly ectopic expression of these Notch targets. Activated Notch-induced tumorous phenotype of larval tissues was enhanced by over-expression of Zip. Notch-Zip synergy resulted in the activation of JNK pathway that consequently lead to MMP activation and proliferation. Taken together, our results suggest that Zip may play an important role in regulation of Notch signaling.

Navigating portal hypertension: Unlocking safe passage to healthy pregnancy in EHPVO.

BACKGROUND AND AIMS: Pregnancy is associated with hyperdynamic circulatory state and increased risk of portal hypertension related complications in patients with extra-hepatic portal vein obstruction (EHPVO). We aim to study the impact of EHPVO on pregnancy-related outcomes with focus on subset of patients with UGIB (upper GI bleed). METHODS: Retrospective analysis of obstetric, maternal and neonatal outcomes of patients with EHPVO registered between January 2006 and December 2022. Forty-five patients were included. Forty-five healthy females with low-risk pregnancies formed the control group. RESULTS: Adverse obstetric and neonatal outcomes were comparable between EHPVO and control group (22% vs. 28.6%; p > .05; low birth weight/ small for gestational age 17.8% vs. 36%, p = .0918 and 14.2% vs. 10%, p = .5698 respectively). Adverse outcomes were similar in patients with and without history of UGIB (26.3% vs. 19.4%, p = .0814; 17.8% vs. 36%, p = .0918; 14.2% vs. 10%, p = .5698). There was no maternal mortality in both the groups. A total of 7% pregnancies in EHPVO patients were complicated by ascites. CONCLUSIONS: EHPVO pregnancies have successful obstetric and neonatal outcomes with adequate management of portal hypertension.

Clinical, immunological and molecular profiles of DOCK8 deficiency in six patients from a tertiary care centre in North India.

BACKGROUND: Dedicator of cytokinesis protein 8 (DOCK8) deficiency is an autosomal recessive form of combined immunodeficiency. This rare disorder is characterized by an increased predisposition to allergy, autoimmunity and malignancies. OBJECTIVES: To analyse clinical, immunological and molecular profiles of patients with DOCK8 deficiency. METHODS: Clinic records of all patients attending the primary immunodeficiency clinic from 2018 to 2021 were reviewed. Six patients from five families were found to have DOCK8 deficiency. RESULTS: Median age at diagnosis was 7.5 years (range 2-13), with a male/female ratio of 5 : 1. Among the six patients, recurrent eczematous skin lesions were the predominant cutaneous manifestation, present in five patients (83%). Warts and molluscum contagiosum were evident in two patients (33%) and one patient (16%), respectively. Two patients had recalcitrant prurigo nodularis lesions and two had epidermodysplasia verruciformis-like lesions. Food allergies and asthma were reported by one patient each. Of the six patients, recurrent sinopulmonary infections were detected in five (83%). Epstein-Barr virus-driven non-Hodgkin lymphoma with liver metastases was the only case of malignancy, in a 4-year-old boy. IgE was elevated in all patients. Lymphopenia and eosinophilia were observed in three patients (50%) and five patients (83.3%), respectively. Genetic analysis showed DOCK8 pathogenic variants in all patients: homozygous deletion mutations in two patients, compound heterozygous deletion mutations in one, and homozygous nonsense mutations in two. A novel pathogenic homozygous missense variant in the DOCK8 gene was identified in one patient. CONCLUSIONS: DOCK8 deficiency should be considered as a possibility in any patient with early onset eczema, cutaneous viral infections and increased predisposition to allergy, autoimmunity and malignancy.

Pattern of disease expression in SLE patients with antiphospholipid antibodies: data from Indian Systemic Lupus Erythematosus Inception cohort (INSPIRE).

Antiphospholipid antibodies (APLA) are present in one-third of systemic lupus erythematosus (SLE) patients, and they are associated with both criteria and non-criteria manifestations. We studied the prevalence, clinical associations, and impact on mortality of APLA in SLE patients from India. Among the Indian SLE inception cohort (INSPIRE), patients who had data on all five routinely performed APLAs [lupus anticoagulant (LA), IgG and IgM anticardiolipin antibody (aCL) and anti-ß2-glycoprotein I(ß2GPI)] at enrolment were selected. Patients were divided into four categories based on the presence/absence of APLA associated manifestations and presence/absence of the APLA viz SLE-APS, SLE-APLA, SLE: events but no APLA, and SLE: no events, no APLA (reference group). 1035 SLE patients at least 1 APLA antibody was detected in 372 (35.9%). LA was present in 206 (19.9%), aCL in 126 (12.2%) and ß2-GPI in 178 (17.2%). There were 88 thrombotic events in 83 patients (8.0%); 73 (82.9%) being arterial; APLA positivity was present in 37 (44.6%) [AOR 1.70 (1.054, 2.76)]. SLE-APS patients were younger and had higher mortality [AOR 4.11 (1.51, 11.3)], neuropsychiatric and hematologic disease. SLE-APLA also had a higher mortality rate [AOR 2.94 (1.06, 8.22)] than the reference group. The mortality was highest in the subset of patients with thrombotic events in the presence of APLA [AOR 7.67 (1.25, 46.9)]. The mere presence of APLA also conferred higher mortality even in the absence of thrombotic events [AOR 3.51 (1.43, 8.63)]. Hematologic manifestations (36.1%) were the most common non-criteria-manifestation. One-third of SLE patients have APLA and its presence is associated with non-criteria hematologic manifestations, arterial thrombosis and higher mortality rate.

Formulation and Characterization of Soybean Oil-in-Water Emulsions Stabilized Using Gelatinized Starch Dispersions from Plant Sources.

Consumers are concerned about employing green processing technologies and natural ingredients in different manufacturing sectors to achieve a "clean label" standard for products and minimize the hazardous impact of chemical ingredients on human health and the environment. In this study, we investigated the effects of gelatinized starch dispersions (GSDs) prepared from six plant sources (indica and japonica rice, wheat, corn, potatoes, and sweet potatoes) on the formulation and stability of oil-in-water (O/W) emulsions. The effect of gelatinization temperature and time conditions of 85-90 °C for 20 min on the interfacial tension of the two phases was observed. Emulsification was performed using a primary homogenization condition of 10,000 rpm for 5 min, followed by high-pressure homogenization at 100 MPa for five cycles. The effects of higher oil weight fractions (15-25% w/w) and storage stability at different temperatures for four weeks were also evaluated. The interfacial tension of all starch GSDs with soybean oil decreased compared with the interfacial tension between soybean oil and water as a control. The largest interfacial tension reduction was observed for the GSD from indica rice. Microstructural analysis indicated that the GSDs stabilized the O/W emulsion by coating oil droplets. Emulsions formulated using a GSD from indica rice were stable during four weeks of storage with a volume mean diameter (d4,3) of ~1 µm, minimal viscosity change, and a negative ζ-potential.

A review on green approaches utilizing phytochemicals in the synthesis of vanadium nano particles and their applications.

In the modern era, inorganic nanoparticles have received profound attention as they possess boundless applications in various fields. Among these, vanadium-based nanoparticles (VNPs) are highly remarkable due to their inherent physiological and biological properties with many therapeutic and other applications, such as drug delivery systems for diseases like cancer, environmental remediation, energy storage, energy conversion, and photocatalysis. Moreover, physically, and chemically synthesized VNPs are very versatile, however, these synthesis routes cause concern to health and the environment due to the highly savage reaction conditions, using highly toxic and harsh chemicals, which compel the researchers to develop an eco-friendly, greener, and sustainable route for synthesis. In this outlook, to avoid the innumerable limitations, a bio approach is used over chemical and physical methods. This present review emphasis on the role of various biological components in the synthesis, especially Phyto-molecules that acts as capping and reducing agent, and solvent system for the nanoparticles synthesis. Furthermore, the influence of various factors on the biogenic synthesized nanoparticles has also been discussed. Finally, potential applications of as-synthesized VNPs, principally as an antimicrobial agent and their role as a nanomedicine, energy applications as a supercapacitor, and photocatalytic agents, have been discussed.

Assessment of Nursing Staff's Knowledge, Attitude and Practice Regarding Oral Hygiene Care in Intensive Care Unit Patients: A Multicenter Cross-sectional Study.

Background: Oral care is one of the fundamental nursing care procedures used to decrease oral colonization, dental plaque, respiratory infections, patient stay, and cost. The importance of good oral hygiene for patients in intensive care units (ICUs) is well recognized, however, the most effective way to achieve good oral care in the ICU is unclear. Therefore, the aim of this study was to assess the knowledge, attitude, and practice of nursing professionals regarding oral healthcare in ICUs among various medical institutes across India. Materials and methods: A questionnaire-based multicentric cross-sectional survey was conducted among registered nursing professionals employed at ICUs of three government tertiary healthcare centers (THC) of India: THC-I, THC-II, and THC-III located in the eastern and northern parts of India between February 2022 and July 2022. Results: A total of 150 nurses completed the questionnaire form (response rate: 62.5%) comprised of 49 (32.7%) males and 101 (67.3%) females with a mean age of 35.69 ± 7.7 years. Nursing officers' knowledge surpassed that of staff nurses regarding the duration of toothbrushing (p = 0.033). Among interinstitutional comparisons, THC-I nurses showed the greatest knowledge regarding the duration of toothbrushing and the mechanism of preventing saliva accumulation to reduce microbial growth (p = 0.013 and p = 0.003, respectively). Based on total work experience, participants were segregated into three groups: Group I (<7 years), group II (7.1-13.9 years), and group III (>14 years). Group II surpassed the knowledge of denture removal during sleep, cleaning after every meal, and storing in personalized air-tight containers (p = 0.001 and p = 0.036, respectively). The majority from group II recommended plain saline as the material for oral hygiene maintenance in ICU patients (p = 0.008). Group III predominantly practiced the ideal handwashing technique pre- and post-patient contact which was statistically significant (p = 0.001). Conclusion: This study observed that a knowledge gap exists among the nurses of the three institutes across India pertaining to the oral hygiene care of ICU patients. Nurse's education and implementation of the proper oral hygiene measures for intubated patients in ICU setup is an essential need. How to cite this article: Kumar S, Singh B, Mahuli AV, Kumar S, Singh A, Jha AK. Assessment of Nursing Staff's Knowledge, Attitude and Practice Regarding Oral Hygiene Care in Intensive Care Unit Patients: A Multicenter Cross-sectional Study. Indian J Crit Care Med 2024;28(1):48-57.

Natural history of portal vein thrombosis in cirrhosis: A systematic review with meta-analysis.

BACKGROUND AND AIM: Progression of liver disease in cirrhosis is associated with an increased incidence of portal vein thrombosis (PVT) in cirrhosis. However, evidence suggests that spontaneous recanalization of PVT may occur even without anti-thrombotic therapy. Thus, the present meta-analysis was conducted to study the natural history of PVT in cirrhosis, facilitating decisions regarding anticoagulation. METHODS: Three electronic databases were searched from 2000 to August 2022 for studies reporting the outcome of PVT in cirrhotics without anticoagulation. The pooled proportions with their 95% confidence intervals (CIs) were calculated using a random-effect model. RESULTS: A total of 26 studies (n = 1441) were included in the final analysis. Progression of PVT on follow-up was seen in 22.2% (95% CI 16.1-28.4), while 77.7% (95% CI 71.6-83.9) remained non-progressive (improved or stable). The most common outcome was a stable PVT with a pooled event rate of 44.6% (95% CI 34.4-54.7). The pooled rates of regression and complete recanalization of PVT in cirrhotics were 29.3% (95% CI 20.9-37.7) and 10.4% (95% CI 5.0-15.8), respectively. On follow-up after improvement, pooled recurrence rate of PVT was 24.0% (95% CI 14.7-33.4). MELD score, and presence of ascites had a negative association, while a longer follow-up duration had positive association with PVT regression. CONCLUSION: Approximately 25% of the cases of PVT in cirrhosis are progressive, 30% cases improve, and 45% remain stable. Future studies are needed to analyze the predictors of spontaneous regression.

Altered m6A RNA methylation contributes to hippocampal memory deficits in Huntington's disease mice.

N6-methyladenosine (m6A) regulates many aspects of RNA metabolism and is involved in learning and memory processes. Yet, the impact of a dysregulation of post-transcriptional m6A editing on synaptic impairments in neurodegenerative disorders remains unknown. Here we investigated the m6A methylation pattern in the hippocampus of Huntington's disease (HD) mice and the potential role of the m6A RNA modification in HD cognitive symptomatology. m6A modifications were evaluated in HD mice subjected to a hippocampal cognitive training task through m6A immunoprecipitation sequencing (MeRIP-seq) and the relative levels of m6A-modifying proteins (FTO and METTL14) by subcellular fractionation and Western blot analysis. Stereotaxic CA1 hippocampal delivery of AAV-shFTO was performed to investigate the effect of RNA m6A dysregulation in HD memory deficits. Our results reveal a m6A hypermethylation in relevant HD and synaptic related genes in the hippocampal transcriptome of Hdh+/Q111 mice. Conversely, m6A is aberrantly regulated in an experience-dependent manner in the HD hippocampus leading to demethylation of important components of synapse organization. Notably, the levels of RNA demethylase (FTO) and methyltransferase (METTL14) were modulated after training in the hippocampus of WT mice but not in Hdh+/Q111 mice. Finally, inhibition of FTO expression in the hippocampal CA1 region restored memory disturbances in symptomatic Hdh+/Q111 mice. Altogether, our results suggest that a differential RNA methylation landscape contributes to HD cognitive symptoms and uncover a role of m6A as a novel hallmark of HD.

Assessment of portal system hemodynamics for the prediction of portal vein thrombosis in cirrhosis-A systematic review and meta-analysis.

BACKGROUND: The pathogenesis of portal vein thrombosis (PVT) in cirrhosis is multifactorial, with altered hemodynamics being proposed as a possible contributor. The present systematic review was conducted to study the role of assessment of portal hemodynamics for the prediction of PVT in patients with cirrhosis. METHODS: Three databases (Medline, Embase, and Scopus) were searched from inception to February 2023 for studies comparing portal venous system parameters in patients with cirrhosis developing PVT with those not. Results were presented as mean difference (MD) or odds ratio (OR) with their 95% confidence intervals (CIs). RESULTS: A total of 31 studies (patients with cirrhosis: 19 studies, patients with cirrhosis undergoing splenectomy: 12 studies) were included. On pooling the data from multivariable analyses of the included studies, a larger portal vein diameter was a significant predictor of PVT in patients with cirrhosis without or with splenectomy with OR 1.74 (1.12-2.69) and OR 1.55 (1.26-1.92), respectively. On the other hand, a lower portal vein velocity (PVV) was a significant predictor of PVT in cirrhotics without or with splenectomy with OR 0.93 (0.91-0.96) and OR 0.71 (0.61-0.83), respectively. A PVV of <15 cm/s was the most commonly used cut-off for the prediction of PVT. Patients developing PVT also had a significantly higher splenic length, thickness, and splenic vein velocity. CONCLUSION: The assessment of portal hemodynamic parameters at baseline evaluation in patients with cirrhosis may predict the development of PVT. Further studies are required to determine the optimal cut-offs for various parameters.

Evaluation of active tactile sensibility in a single-tooth implant opposing a natural tooth with either an immediate or delayed functional loading protocol: A parallel design clinical study.

STATEMENT OF PROBLEM: High primary stability makes immediate loading more predictable, but immediately loaded implants are subjected to higher stresses and strains during the healing phase than implants that are left to heal for 3 months. Whether an earlier sensory-motor phenomenon with an immediate loading protocol helps to reduce the risk of overloading at the implant-bone interface is unclear. PURPOSE: The purpose of this concurrent parallel design clinical study was to evaluate and compare active tactile sensibility for a single-tooth implant opposing a natural tooth in the mandibular posterior region with either a delayed or immediate functional loading -protocol. MATERIAL AND METHODS: In this parallel group randomized trial, 2 test groups were formed: the DL group comprised 20 participants with the delayed loading protocol (loading after 3 months), and the IL group comprised 20 participants with the immediate loading protocol (loading within 2 days). Natural tooth-to-tooth contact on the side contralateral to the implant site (split mouth) in both test groups was used as a control to evaluate active tactile sensibility, which was evaluated in the test and control sites of both groups by using interocclusal articulating foils of varying thickness in maximum intercuspation. Active tactile sensibility was compared between the DL and IL groups at 3 and 6 months of follow-up. The nonparametric Mann-Whitney test was used for intergroup comparisons (P=.05). RESULTS: A significant difference was found for 8-µm- and 12-µm-thick articulating foil at 3 months and for 8-µm-thick foil at 6 months (P<.05), indicating a difference in active tactile sensibility between the DL and IL groups. No implant failure was recorded in this short clinical study. CONCLUSIONS: An immediate loading protocol can be performed in implants with sufficient primary stability. Upon loading, the IL group has shown more active tactile perception than the DL group.

Regulation of Notch signaling by the chromatin-modeling protein Hat-trick.

Notch signaling plays a pleiotropic role in a variety of cellular processes, including cell fate determination, differentiation, proliferation and apoptosis. The increasingly complex regulatory mechanisms of Notch signaling account for the many functions of Notch during development. Using a yeast two-hybrid screen, we identified the Drosophila DNA-binding protein Hat-trick (Htk) to be an interacting partner of Notch-intracellular domain (Notch-ICD); their physical interaction was further validated by co-immunoprecipitation experiments. htk genetically interacts with Notch pathway components in trans-heterozygous combinations. Loss of htk function in htk mutant somatic clones resulted in the downregulation of Notch targets, whereas its overexpression caused ectopic expression of Notch targets, without affecting the level of the Notch protein. In the present study, immunocytochemical analyses demonstrate that Htk and overexpressed Notch-ICD colocalize in the same nuclear compartment. Here, we also show that Htk cooperates with Notch-ICD and Suppressor of Hairless to form an activation complex and binds to the regulatory sequences of Notch downstream targets such as Enhancer of Split complex genes, to direct their expression. Together, our results suggest a novel mode of regulation of Notch signaling by the chromatin-modeling protein Htk.

Paper and thread as media for the frugal detection of urinary tract infections (UTIs).

Urinary tract infections (UTIs) make up a significant proportion of the global burden of disease in vulnerable groups and tend to substantially impair the quality of life of those affected, making timely detection of UTIs a priority for public health. However, economic and societal barriers drastically reduce accessibility of traditional lab-based testing methods for critical patient groups in low-resource areas, negatively affecting their overall healthcare outcomes. As a result, cellulose-based materials such as paper and thread have garnered significant interest among researchers as substrates for so-called frugal analytical devices which leverage the material's portability and adaptability for facile and reproducible diagnoses of UTIs. Although the field may be only in its infancy, strategies aimed at commercial penetration can appreciably increase access to more healthcare options for at-risk people. In this review, we catalogue recent advances in devices that use cellulose-based materials as the primary housing or medium for UTI detection and chart out trends in the field. We also explore different modalities employed for detection, with particular emphasis on their ability to be ported onto discreet casings such as sanitary products.

Association of SNP (rs1042579) in thrombomodulin gene and plasma thrombomodulin level in North Indian children with Kawasaki disease.

BACKGROUND: Kawasaki disease (KD) is the commonest systemic vasculitis in children. It predisposes to development of coronary artery abnormalities (CAAs). Thrombomodulin (THBD) gene polymorphism rs1042579 is associated with high risk of cerebrovascular diseases. However, association of THBD polymorphism (rs1042579) and plasma thrombomodulin (TM) levels with susceptibility to KD and CAAs remains unclear. METHODS AND RESULTS: Polymorphism in THBD gene (rs1042579) was analysed in 50 KD patients and 50 age, gender and ethnicity matched controls using Sanger sequencing. Plasma TM levels were measured by ELISA. RESULTS: Mean plasma TM level (± SD) in KD patients was 2549.41 (± 853.18) pg/ml and in controls was 2298.03 (± 869.14) pg/ml; p = 0.042. Mean plasma TM levels in CC genotype was 2299.98 (± 834.88) pg/ml and in CT/TT genotype was 2837.96 (± 857.14) pg/ml; p = 0.005. Genotyping data did not reveal significant differences in patients with KD as compared to controls (p = 0.25), and in KD patients with and without CAAs (p = 0.407). Odds of finding T allele in cases were 2.07 times greater than in controls (p = 0.093). CONCLUSIONS: This is the first study from India, and second in the world, that investigates association of THBD gene polymorphism with KD. This is also the first study to assess plasma TM levels in KD patients. Our data show that plasma TM levels were significantly higher in KD patients with CT/TT genotypes. Further, the polymorphism rs1042579 at exon 1 of THBD gene was found to be more common in KD patients than in controls although the difference was not statistically significant.

A Machine-Learning Based Approach for Predicting Older Adults' Adherence to Technology-Based Cognitive Training.

Adequate adherence is a necessary condition for success with any intervention, including for computerized cognitive training designed to mitigate age-related cognitive decline. Tailored prompting systems offer promise for promoting adherence and facilitating intervention success. However, developing adherence support systems capable of just-in-time adaptive reminders requires understanding the factors that predict adherence, particularly an imminent adherence lapse. In this study we built machine learning models to predict participants' adherence at different levels (overall and weekly) using data collected from a previous cognitive training intervention. We then built machine learning models to predict adherence using a variety of baseline measures (demographic, attitudinal, and cognitive ability variables), as well as deep learning models to predict the next week's adherence using variables derived from training interactions in the previous week. Logistic regression models with selected baseline variables were able to predict overall adherence with moderate accuracy (AUROC: 0.71), while some recurrent neural network models were able to predict weekly adherence with high accuracy (AUROC: 0.84-0.86) based on daily interactions. Analysis of the post hoc explanation of machine learning models revealed that general self-efficacy, objective memory measures, and technology self-efficacy were most predictive of participants' overall adherence, while time of training, sessions played, and game outcomes were predictive of the next week's adherence. Machine-learning based approaches revealed that both individual difference characteristics and previous intervention interactions provide useful information for predicting adherence, and these insights can provide initial clues as to who to target with adherence support strategies and when to provide support. This information will inform the development of a technology-based, just-in-time adherence support systems.