TinyNS: Platform-Aware Neurosymbolic Auto Tiny Machine Learning.

Machine learning at the extreme edge has enabled a plethora of intelligent, time-critical, and remote applications. However, deploying interpretable artificial intelligence systems that can perform high-level symbolic reasoning and satisfy the underlying system rules and physics within the tight platform resource constraints is challenging. In this paper, we introduce TinyNS, the first platform-aware neurosymbolic architecture search framework for joint optimization of symbolic and neural operators. TinyNS provides recipes and parsers to automatically write microcontroller code for five types of neurosymbolic models, combining the context awareness and integrity of symbolic techniques with the robustness and performance of machine learning models. TinyNS uses a fast, gradient-free, black-box Bayesian optimizer over discontinuous, conditional, numeric, and categorical search spaces to find the best synergy of symbolic code and neural networks within the hardware resource budget. To guarantee deployability, TinyNS talks to the target hardware during the optimization process. We showcase the utility of TinyNS by deploying microcontroller-class neurosymbolic models through several case studies. In all use cases, TinyNS outperforms purely neural or purely symbolic approaches while guaranteeing execution on real hardware.

Lung Function Reference Equations for Indian Ethnic Groups Based on a Handheld Forced Oscillation Device for Age 9-19 Years.

OBJECTIVE: To develop regression equations to predict forced oscillation technique (FOT) parameters in Indian children and adolescents. METHODS: Lung function was assessed in a multigeographic cohort of residential school children using a portable FOT-based device (PulmoScan) and spirometry. FOT measurements were performed in 1497 study participants, aged 9-19 y, from 8 Indian districts. Bland-Altman analysis was performed for additional 32 adult subjects to compare the results of PulmoScan to a standard IOS device in an outpatient setting. Reference equations were developed for Rrs and Xrs from the data of healthy subjects with normal spirometry using multivariate regression model for Indo-European, Dravidian, and mixed ethnic groups. RESULTS: X5 (bias = 0.02) showed a better agreement than resistance parameters (R5 bias = 0.75, R20 bias = -0.22) in IOS/PulmoScan comparison. Anthropometric variables (age, height, and weight) were positively correlated with reactance (X5) and negatively with resistance parameters (R5, R10, R15, and R20), with most associations being stronger in boys. Final regression model considered ethnicity as a key determinant along with anthropometry. CONCLUSION: Multiethnic reference equations were developed for Indian children aged 9-19 y based on a novel handheld FOT device.

Utility of gastroscopy in the left lateral semi-recumbent position: A blood-free coup!

Background and study aims The utility of esophagogastroduodenoscopy (EGD) in the left lateral semi-recumbent position in the setting of acute upper gastrointestinal bleeding (UGIB) with a persistent fundal pool of blood for adequate visualization and effective endotherapy has not been studied. This study aimed to evaluate the feasibility, efficacy, and safety of this position in such settings. Patients and methods A prospective study of patients presenting with acute UGIB with an uncleared fundal pool of blood was conducted. All underwent EGD in the left lateral decubitus and secondary left lateral semi-recumbent positions. Outcomes in secondary position in terms of adequate visualization of the fundus, identification of new or additional sources of bleeding, and effectiveness of endotherapy were studied. Results We screened 860 patients and included 44 patients (5.11%) with a persistent fundal pool of blood. Endoscopy in the primary position revealed the source of bleeding in 37 of 44 patients (84%). The source of the bleeding was not identified in seven of 44 patients (16%). Endoscopy in the secondary position showed clearance of fundal pool in all 44 patients (100%). A new source of bleeding was identified in all seven patients (100%) and an additional source could be identified in another five patients (13.6%). Endotherapy was performed in the secondary position for all 44 patients with 100% technical success and 94% clinical success. Conclusions These data show that endotherapy in the left lateral semi-recumbent position is feasible, safe, and effective. It should be done when endoscopy in the left lateral decubitus position reveals a pool of blood in the fundus and there is inadequate visualization of the fundus.

Predictors of proximal migration of straight biliary plastic stents.

BACKGROUND/AIMS: Proximal biliary plastic stent migration (PSM) remains a challenging complication. The study aims at determining the PSM rate, retrieval outcomes and factors associated with PSM. METHODS: Endoscopy database was analyzed from January 2016 to January 2021 to identify 1137 patients, who underwent stent removal or repeat endoscopic retrograde cholangiopancreatography (ERCP). Demography, methods of stent retrieval, outcomes and complications were noted. Logistic regression was performed to determine risk factors for PSM. Propensity score matching was done in a 1:1 manner using age, sex, comorbidities and indication to assess endoscopy-related factors. Clinical trial registration done (CTRI/2022/02/040516). RESULTS: PSM was noted in 74 (6.5%) cases. Stent retrieval was successful in 94.59% (70/74) of cases. A balloon catheter (46/74) was commonly used. Technical failure was due to an impacted stent (2) and stent above the stricture (2). Complications were seen in 2.7% of cases. On multi-variate regression, sphincteroplasty at index ERCP (Odds ratio [OR] = 5.68, 95% confidence interval [CI] = 2.7-11.89), stent length < 10 cm (OR = 8.53, 95% CI = 3.2-22.47), 7-Fr stent (OR = 18.25, 95% CI = 6.5-50.64), dilated bile duct (mean diameter- 9.2 ± 3.94 mm) (OR = 0.384, 95% CI = 0.18-0.72) and delayed ERCP by > 3 months from index ERCP (OR = 15.28, 95% CI = 8.1-28.49). After performing propensity score matching for age, sex, comorbidities and indication to determine endoscopy-related factors, 7-Fr stent size (OR 3.495; 95% CI-1.23-9.93) and duration of indwelling stent for more than three months (OR-3.37; 95% CI-1.646-6.76) were significantly associated with proximal stent migration. CONCLUSION: Proximally migrated straight stents can be successfully retrieved using standard accessories. The use of 7-Fr size stent, stents indwelling for more than three months, sphincteroplasty at index ERCP, stent length < 10 cm and dilated bile duct were associated with increased risk of proximal migration of straight biliary plastic stents. After propensity score matching, the use of 7-Fr size stents and stent indwelling for over three months were endoscopy-related factors associated with proximal migration.

Screening of cardiovascular risk assessment accuracy of anthropometric indices in Indian children and adolescents.

Background: Body mass index (BMI) is the most popular anthropometric marker to define obesity and cardiometabolic risk. BMI is limited in its ability to discriminate central adiposity and other indices such as waist circumference (WC), and waist to height ratio (WHtR) could be a better choice. In this study, we aimed to evaluate the relative accuracy of these indices for the prediction of hypertension in Indian children and young adults. Methods: Anthropometric indices and blood pressure measurements were obtained in 2609 adolescent children and young adults (10-20 years) across a national residential school system. Z-scores were calculated for anthropometric parameters using the Box-Cox-Cole-Green method and World Health Organization (WHO) growth charts. Hypertension was defined using the sex, age and height specific cutoffs for systolic blood pressure. Receiver operator curve (ROC) analysis was performed to examine the predictive ability.  Results: Girls had higher BMI for age in our dataset (p < 0.001), along with higher odds for stunting (95% CI: 1.21 - 1.88) as well as central obesity (95% CI: 2.44 - 3.99). Hypertension was seen in 10.6% of the subjects, with higher age, and higher BMI or WHtR as the predictors. Prehypertension was higher in males (p <0.001). WHtR had acceptable but modest discrimination ability for hypertension (AUC > 0.6) in boys (AUC=0.62) and girls (AUC=0.66). Performance of BMI was better in boys (AUC = 0.67) but poor in girls (AUC = 0.55) Conclusion: WHtR was a better predictor of hypertension in Indian adolescent girls and could be used as an augmented parameter to BMI for a better assessment of cardiovascular risk.

TCL1A expression delineates biological and clinical variability in B-cell lymphoma.

The assembly of a collection of gene-expression signatures of the major types of B-cell non-Hodgkin's lymphoma has identified increased T-cell leukemia/lymphoma 1A (TCL1) expression in multiple lymphoma types and cases, and has enabled the investigation of the functional and clinical importance of TCL1 expression. Specifically, Burkitt's lymphoma cases show a homogeneously strong expression of TCL1, whereas diffuse large B-cell lymphoma, follicular lymphoma, mantle cell lymphoma, chronic lymphocytic leukemia, nodal marginal zone lymphoma, and splenic marginal zone lymphoma display a striking variability in the intensity of TCL1 staining. This was validated in two independent series. A Gene-Set Enrichment Analysis of the genes correlated with TCL1A expression found that variation in the level of expression of TCL1A was significantly associated with some of the most important gene signatures recognizing B-cell lymphoma pathogenesis and heterogeneity, such as germinal center, B-cell receptor, NF-kappaB (and its target genes), death, MAP kinases, TNFR1, TOLL, and IL1R. Additionally, TCL1 expression was correlated with shorter time to treatment in chronic lymphocytic leukemia cases and shorter lymphoma-specific survival in mantle cell lymphoma series, thus indicating the clinical and biological significance of TCL1 expression, and suggesting TCL1A as a potential therapeutic target.

Somatic hypermutation signature in B-cell low-grade lymphomas.

BACKGROUND: Immunoglobulin gene somatic hypermutation is a biologically relevant and clinically useful prognostic factor in different types of low-grade B-cell lymphomas, including chronic lymphocytic leukemia, mantle cell lymphoma and splenic marginal zone lymphoma. DESIGN AND METHODS: With the aim of identifying surrogate markers of somatic hypermutation, a combined investigation of IgV(H) mutational status and expression profiles of 93 samples from patients with small B-cell lymphoma was performed. RESULTS: The analysis identified an somatic hypermutation signature of genes involved in the regulation of gene transcription, DNA repair and replication, and chromosome maintenance. Eight of these genes were subjected to protein analysis using tissue microarrays, for a set of 118 cases. We found a clear link between RAD51C and CDK7 protein expression and somatic hypermutation status, in that positive expression of either marker was significantly associated with a mutated status (p<0.003). We also found that positive expression of TFDP1 and POLA was significantly associated with ongoing somatic hypermutation (p<0.001). To assess the potential clinical applicability of these somatic hypermutation markers, we studied a series of cases of mantle cell lymphoma included in a tissue microarray. The expression of RCC1 and CDK7, separately and together, was found to be significantly associated with longer overall survival. CONCLUSIONS: An somatic hypermutation signature has been identified for different types of small B-cell lymphoma. This has a potential mechanistic and diagnostic value.

Clinical outcome study of crizotinib in immunohistochemistry-proven echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase fusion gene among Indian patients with adenocarcinoma lung.

AIMS: The anaplastic lymphoma kinase (ALK) Break Apart FISH Probe Kit and Ventana anti-ALK (D5F3) CDx immunohistochemistry (IHC) assay are the Food and Drug Administration-approved companion diagnostic for targeted therapy with the ALK inhibitor crizotinib in lung cancers. The aim of this study was to assess the efficacy and safety of twice daily crizotinib tablet (250 mg) in IHC-proven echinoderm microtubule-associated protein-like 4 (EML4)-ALK fusion gene among Indian patients with adenocarcinoma lung in the routine clinical practice. SUBJECTS AND METHODS: Patients with nonsmall cell lung cancer (NSCLC), adenocarcinoma histology, whose tumors were found to be positive for EML4-ALK fusion gene using IHC, were considered for this study. IHC analysis was performed using a Ventana automated immunostainer (Benchmark XT). Detection was performed using Optiview DAB detection and amplification kit. RESULTS: A total of 25 NSCLC adenocarcinoma patients were included in the study. There were 14 (56%) women and 10 (44%) men with a median age of 53 years. All patients had Stage IV disease at the time of initiation of crizotinib therapy. One patient achieved complete response and 20 achieved response rate (PR) for an overall PR of 84%. The median progression-free survival (PFS) was 11.8 months and median overall survival (OS) was 20.6 months. Two (8%) patients experienced severe hepatotoxicity requiring permanent discontinuation of crizotinib therapy. CONCLUSIONS: A very high PR, PFS, and OS achieved in our study population indicates that IHC can accurately identify EML4 ALK fusion gene mutations in lung adenocarcinoma patients who are responsive to ALK inhibitors such as crizotinib. IHC should be considered as a cost-effective alternative to FISH, especially in low-resource countries.

Management of pediatric mandibular fractures using bioresorbable plating system - Efficacy, stability, and clinical outcomes: Our experiences and literature review.

AIMS: The purpose of this study was to determine the efficacy and stability of the biodegradable fixation system for treatment of mandible fractures in pediatric patients by measuring the bite force. METHODS: Sixty pediatric patients with mandibular fractures (36 males, 24 females) were included in this study. The 2.5-mm resorbable plates were adapted along Champy's line of ideal osteosynthesis and secured with four 2.5 mm diameter monocortical resorbable screws, 8 mm in length. All patients were followed for 10 months. Clinical parameters, such as soft tissue infection, nonunion, malunion, implant exposure, malocclusion, nerve injury, and bite force for stability, were prospectively assessed. RESULTS: Adequate fixation and primary bone healing was achieved in 100% of the cases. Six minor complications (10%) were observed: 2 soft tissue infections (3%), 1 plate dehiscence (2%), 1 malocclusion (2%), and 2 paresthesia (3%). CONCLUSION: 2.5-mm resorbable plating system along Champy's line of ideal osteosynthesis is a good treatment modality for mandible fractures in pediatric patients.

A unifying microenvironment model in follicular lymphoma: outcome is predicted by programmed death-1--positive, regulatory, cytotoxic, and helper T cells and macrophages.

PURPOSE: The microenvironment influences outcome in follicular lymphoma. Our hypothesis was that several immune cell subsets are important for disease outcome and their individual prognostic importance should be demonstrable in the same analysis and in competition with clinical factors. EXPERIMENTAL DESIGN: Seventy follicular lymphoma patients with extreme clinical outcome ("poor" and "good" cases) were selected in a population-based cohort of 197. None of the 37 good-outcome patients died from lymphoma, whereas all the 33 poor-outcome patients succumbed in

Functional signatures identified in B-cell non-Hodgkin lymphoma profiles.

Gene-expression profiling in B-cell lymphomas has provided crucial data on specific lymphoma types, which can contribute to the identification of essential lymphoma survival genes and pathways. In this study, the gene-expression profiling data of all major B-cell lymphoma types were analyzed by unsupervised clustering. The transcriptome classification so obtained, was explored using gene set enrichment analysis generating a heatmap for B-cell lymphoma that identifies common lymphoma survival mechanisms and potential therapeutic targets, recognizing sets of coregulated genes and functional pathways expressed in different lymphoma types. Some of the most relevant signatures (stroma, cell cycle, B-cell receptor (BCR)) are shared by multiple lymphoma types or subclasses. A specific attention was paid to the analysis of BCR and coregulated pathways, defining molecular heterogeneity within multiple B-cell lymphoma types.

Lentiviral (HIV)-based RNA interference screen in human B-cell receptor regulatory networks reveals MCL1-induced oncogenic pathways.

Aberrant inhibition of B-cell receptor (BCR)-induced programmed cell death pathways is frequently associated with the development of human auto-reactive B-cell lymphomas. Here, we integrated loss-of-function, genomic, and bioinformatics approaches for the identification of oncogenic mechanisms linked to the inhibition of BCR-induced clonal deletion pathways in human B-cell lymphomas. Lentiviral (HIV)-based RNA interference screen identified MCL1 as a key survival molecule linked to BCR signaling. Loss of MCL1 by RNA interference rendered human B-cell lymphomas sensitive to BCR-induced programmed cell death. Conversely, MCL1 overexpression blocked programmed cell death on BCR stimulation. To get insight into the mechanisms of MCL1-induced survival and transformation, we screened 41 000 human genes in a genome-wide gene expression profile analysis of MCL1-overexpressing B-cell lymphomas. Bioinformatic gene network reconstruction illustrated reprogramming of relevant oncoproteins within beta-catenin-T-cell factor signaling pathways induced by enforced MCL1 expression. Overall, our findings not only illustrate MCL1 as an aberrantly expressed reprogramming oncoprotein in follicular lymphomas but also highlight MCL1 as key therapeutic target.