Genomic Insights from a Deeply Phenotyped Highly Consanguineous Neurodevelopmental Disorders Cohort.

PURPOSE: The genetic underpinning of neurodevelopmental disorders (NDDs) in diverse ethnic populations, especially those with high rates of consanguinity, remains largely unexplored. Here, we aim to elucidate genomic insight from 576 well phenotyped and highly consanguineous (16%) NDD cohort. METHODS: We employed chromosomal microarray (CMA; N:247), exome sequencing (ES; N:127), combined CMA and ES (N:202) and long-read genome sequencing to identify genetic etiology. Deep clinical multi-variate data was coupled with genomic variants for stratification analysis. RESULTS: Genetic diagnosis rates were 17% with CMA, 29.92% with ES, and 37.13% with combined CMA and ES. Notably, children of consanguineous parents showed a significantly higher diagnostic yield (p<0.01) compared to those from non-consanguineous parents. Among the ES-identified pathogenic variants, 36.19% (38/105) were novel, implicating 35 unique genes. Long-read sequencing of seizure participants unresolved by combined test identified expanded FMR1 trinucleotide repeats. Additionally, we identified two recurrent X-linked variants in the G6PD in 3.65% (12/329) of NDD participants. These variants were absent in large population control cohorts and cohort comprising neurodevelopmental and neuropsychiatric populations of European descendants, indicating a possible associated risk factor potentially resulting from ancient genetic drift. CONCLUSION: This study unveils unique clinical and genomic insights from a consanguinity rich Bangladeshi NDD cohort, highlighting a strong association of G6PD with NDD in this population.

Structural, morphological, dielectric, electric and magnetic properties of Ba 1 - x Dy 2 x / 3 Ti 0.98 Mn 0.02 O 3 ceramics for multifunctional applications.

Herein, the standard solid-state reaction process was employed to synthesize the polycrystalline Ba1-xDy2x/3Ti0.98Mn0.02O3 (x = 0.0000-0.0085) ceramics and each composition was sintered at 1200 °C for 3 h. The structural, morphological, electrical, and magnetic properties were carried out by the X-ray diffraction (XRD), field emission scanning electron microscopy (FESEM), impedance analyzer, and vibrating sample magnetometer (VSM) to investigate the influence of doping of Dy 3+ (low concentration) and Mn4+ in BaTiO3 simultaneously. The XRD study confirmed the formation of perovskite structure with tetragonal symmetry of the prepared solid solution. The magnitude of the porosity (P%) decreased from 13.22 to 9.49 with increasing content of Dy and x = 0.0080 sample showed the lowest value. The mean grain size was estimated in the micrometer range, with values ranging from 0.5713 to 0.1457 µm. The highest grain size determined for the x = 0.0070 sample was 0.5713 µm. The Brunauer-Emmett-Teller (BET) adsorption isotherm measurements were used to estimate the specific surface area; the result was 24.181 m2/g for x = 0.007 composition. For the compound with x = 0.0070 the maximum recorded dielectric constant was found to be 6 × 103 at 103 Hz. A relatively lower dielectric loss (<5 %) was observed. The Nyquist plot illustrated that only the grain boundary effect is significant for the conduction process in the studied compositions. The present solid solution revealed better magnetic results compared to other reported ceramics similar to the prepared constituents. The optimum value of saturation magnetization (0.371 emu/g) was obtained for x = 0.0080 composition. Among the synthesized Dy doped samples x = 0.0075 composition displayed a significant complex initial permeability ( µ i / ). An enhanced relative quality factor (RQF) was seen with increasing frequency and the highest relative quality factor was noticed (>100) for the x = 0.0075 sample at 108 Hz. The studied materials could be employed as an environmentally acceptable alternative to the hazardous lead (Pb)-based multiferroic substance.

Expanding deep phenotypic spectrum associated with atypical pathogenic structural variations overlapping 15q11-q13 imprinting region.

BACKGROUND: The 15q11-q13 region is a genetic locus with genes subject to genomic imprinting, significantly influencing neurodevelopment. Genomic imprinting is an epigenetic phenomenon that causes differential gene expression based on the parent of origin. In most diploid organisms, gene expression typically involves an equal contribution from both maternal and paternal alleles, shaping the phenotype. Nevertheless, in mammals, including humans, mice, and marsupials, the functional equivalence of parental alleles is not universally maintained. Notably, during male and female gametogenesis, parental alleles may undergo differential marking or imprinting, thereby modifying gene expression without altering the underlying DNA sequence. Neurodevelopmental disorders, such as Prader-Willi syndrome (PWS) (resulting from the absence of paternally expressed genes in this region), Angelman syndrome (AS) (associated with the absence of the maternally expressed UBE3A gene), and 15q11-q13 duplication syndrome (resulting from the two common forms of duplications-either an extra isodicentric 15 chromosome or an interstitial 15 duplication), are the outcomes of genetic variations in this imprinting region. METHODS: Conducted a genomic study to identify the frequency of pathogenic variants impacting the 15q11-q13 region in an ethnically homogenous population from Bangladesh. Screened all known disorders from the DECIPHER database and identified variant enrichment within this cohort. Using the Horizon analysis platform, performed enrichment analysis, requiring at least >60% overlap between a copy number variation and a disorder breakpoint. Deep clinical phenotyping was carried out through multiple examination sessions to evaluate a range of clinical symptoms. RESULTS: This study included eight individuals with clinically suspected PWS/AS, all previously confirmed through chromosomal microarray analysis, which revealed chromosomal breakpoints within the 15q11-q13 region. Among this cohort, six cases (75%) exhibited variable lengths of deletions, whereas two cases (25%) showed duplications. These included one type 2 duplication, one larger atypical duplication, one shorter type 2 deletion, one larger type 1 deletion, and four cases with atypical deletions. Furthermore, thorough clinical assessments led to the diagnosis of four PWS patients, two AS patients, and two individuals with 15q11-q13 duplication syndrome. CONCLUSION: Our deep phenotypic observations identified a spectrum of clinical features that overlap and are unique to PWS, AS, and Dup15q syndromes. Our findings establish genotype-phenotype correlation for patients impacted by variable structural variations within the 15q11-q13 region.

Mutational spectrum and phenotypic variability of Duchenne muscular dystrophy and related disorders in a Bangladeshi population.

Duchenne muscular dystrophy (DMD) is a severe rare neuromuscular disorder caused by mutations in the X-linked dystrophin gene. Several mutations have been identified, yet the full mutational spectrum, and their phenotypic consequences, will require genotyping across different populations. To this end, we undertook the first detailed genotype and phenotype characterization of DMD in the Bangladeshi population. We investigated the rare mutational and phenotypic spectrum of the DMD gene in 36 DMD-suspected Bangladeshi participants using an economically affordable diagnostic strategy involving initial screening for exonic deletions in the DMD gene via multiplex PCR, followed by testing PCR-negative patients for mutations using whole exome sequencing. The deletion mapping identified two critical DMD gene hotspot regions (near proximal and distal ends, spanning exons 8-17 and exons 45-53, respectively) that comprised 95% (21/22) of the deletions for this population cohort. From our exome analysis, we detected two novel pathogenic hemizygous mutations in exons 21 and 42 of the DMD gene, and novel pathogenic recessive and loss of function variants in four additional genes: SGCD, DYSF, COL6A3, and DOK7. Our phenotypic analysis showed that DMD suspected participants presented diverse phenotypes according to the location of the mutation and which gene was impacted. Our study provides ethnicity specific new insights into both clinical and genetic aspects of DMD.

Carbapenem Resistance among Klebsiella pneumoniae in a Tertiary Care Hospital in Bangladesh.

Carbapenem-resistant K pneumoniae (CRKP) clinical isolates have spread widely now-a-days throughout the world. This study was designed to investigate the carbapenem resistance among Klebsiella pneumoniae and to see anitimicrobial susceptibility of these CRKP isolates to other antimicrobials in a tertiary care hospital in Bangladesh. K pneumoniae was detected by standard methods and various biochemical tests like Triple Sugar Iron (TSI) agar media, Simmons citrate agar media and Motility-Indole-Urea (MIU) agar media. Imipenem resistance was used as the indicator for carbapenem resistance. Agar dilution method was used to determine MIC of imipenem. CRKP were tested for their antimicrobial susceptibility by Kirby-Bauer modified disc-diffusion technique as per Clinical and Laboratory Standard Institute (CLSI) guidelines and United States Food and Drug Administration (FDA) guidelines. Total 75 K pneumoniae were isolated. Among the isolated K pneumoniae, 28(37.33%) were resistant to carbapenem. Most of the CRKP were recovered from intensive care unit. MIC of CRKP ranged from ≥32µg/ml to ≤4µg/ml. Most of the CRKP were resistant to other antimicrobials. Carbapenem resistance in K pneumoniae is increasing in Bangladesh, which is very alarming and we should give importance on standard guideline of antimicrobials use.

Construction of copy number variation landscape and characterization of associated genes in a Bangladeshi cohort of neurodevelopmental disorders.

Introduction: Copy number variations (CNVs) play a critical role in the pathogenesis of neurodevelopmental disorders (NDD) among children. In this study, we aim to identify clinically relevant CNVs, genes and their phenotypic characteristics in an ethnically underrepresented homogenous population of Bangladesh. Methods: We have conducted chromosomal microarray analysis (CMA) for 212 NDD patients with male to female ratio of 2.2:1.0 to identify rare CNVs. To identify candidate genes within the rare CNVs, gene constraint metrics [i.e., "Critical-Exon Genes (CEGs)"] were applied to the population data. Autism Diagnostic Observation Schedule-Second Edition (ADOS-2) was followed in a subset of 95 NDD patients to assess the severity of autism and all statistical tests were performed using the R package. Results: Of all the samples assayed, 12.26% (26/212) and 57.08% (121/212) patients carried pathogenic and variant of uncertain significance (VOUS) CNVs, respectively. While 2.83% (6/212) patients' pathogenic CNVs were found to be located in the subtelomeric regions. Further burden test identified females are significant carriers of pathogenic CNVs compared to males (OR = 4.2; p = 0.0007). We have observed an increased number of Loss of heterozygosity (LOH) within cases with 23.85% (26/109) consanguineous parents. Our analyses on imprinting genes show, 36 LOH variants disrupting 69 unique imprinted genes and classified these variants as VOUS. ADOS-2 subset shows severe social communication deficit (p = 0.014) and overall ASD symptoms severity (p = 0.026) among the patients carrying duplication CNV compared to the CNV negative group. Candidate gene analysis identified 153 unique CEGs in pathogenic CNVs and 31 in VOUS. Of the unique genes, 18 genes were found to be in smaller (<1 MB) focal CNVs in our NDD cohort and we identified PSMC3 gene as a strong candidate gene for Autism Spectrum Disorder (ASD). Moreover, we hypothesized that KMT2B gene duplication might be associated with intellectual disability. Conclusion: Our results show the utility of CMA for precise genetic diagnosis and its integration into the diagnosis, therapy and management of NDD patients.

Pre COVID-19 molecular epidemiology of respiratory syncytial virus (RSV) among children in Bangladesh.

Epidemiological data of specific respiratory pathogens from the pre-COVID-19 period are essential to determine the effects of the COVID-19 pandemic on other respiratory infections. In this study, we revealed the pre-COVID-19 molecular epidemiology of respiratory syncytial virus (RSV) among children in Bangladesh. We tested 3170 samples collected from 2008 to 2012 for a panel of respiratory viruses; RSV, human metapneumovirus (hMPV), human parainfluenza viruses (hPIV) 1, 2, 3, and adenovirus. Five hundred fifty-five samples (17.5 %) were positive for RSV, including 2.5% having co-infections with other viruses. Genotypic characterization of RSV showed that RSV-A (82%) contributed more acute respiratory infections than RSV-B (18%). Clinical features were similar with RSV-A and RSV-B infections. However, children with RSV-B were more likely to have upper respiratory infections (URI) (10% vs. 29%, p = 0.03). Among RSV-A cases, hospitalization was higher for ON1 cases (25%, ON1 vs. 8%, NA1, p = 0.04), whereas the recovery without a disability was higher among the NA1 cases (56%, ON1 vs. 88%, NA1, p = 0.02). The time to the most recent common ancestor (TMRCA) for RSV in Bangladesh was 1949 for RSV-A and 1944 for RSV-B. This study revealed the genotypic diversity and evolutionary relatedness of RSV strains in Bangladesh and provided pre-COVID molecular epidemiology data to understand better the COVID-19 impact on upcoming RSV epidemiology in Bangladesh.

The evolutionary footprint of influenza A subtype H3N2 strains in Bangladesh: implication of vaccine strain selection.

In February each year, World Health Organization (WHO) recommends candidate vaccine viruses for the forthcoming northern hemisphere (NH) season; however, the influenza season in the temperate zone of NH begins in October. During egg- or cell culture-propagation, the vaccine viruses become too old to confer the highest match with the latest strains, impacting vaccine effectiveness. Therefore, an alternative strategy like mRNA-based vaccine using the most recent strains should be considered. We analyzed influenza A subtype H3N2 strains circulating in NH during the last 10 years (2009-2020). Phylogenetic analysis revealed multiple clades of influenza strains circulating every season, which had substantial mismatches with WHO-recommended vaccine strains. The clustering pattern suggests that influenza A subtype H3N2 strains are not fixed to the specific geographical region but circulate globally in the same season. By analyzing 39 seasons from eight NH countries with the highest vaccine coverage, we also provide evidence that the influenza A, subtype H3N2 strains from South and Southeast Asia, including Bangladesh, had the highest genetic proximity to the NH strains. Furthermore, insilico analysis showed minimal effect on the Bangladeshi HA protein structure, indicating the stability of Bangladeshi strains. Therefore, we propose that Bangladeshi influenza strains represent genetic makeup that may better fit and serve as the most suitable candidate vaccine viruses for the forthcoming NH season.

Prevalence of Colistin Resistance in Klebsiella pneumoniae Isolated from a Tertiary Care Hospital in Bangladesh and Molecular Characterization of Colistin Resistance Genes among Them by Polymerase Chain Reaction and Sequencing.

Resistance to colistin, the last resort of treatment for multidrug resistant organisms has increased now-a-days. This cross-sectional study was conducted in the Department of Microbiology of Dhaka Medical College, Dhaka, Bangladesh, from July 2016 to June 2017 and was designed to investigate the colistin resistance profile along with the genetic background of colistin resistance among Klebsiella pneumoniae in a tertiary care hospital in Bangladesh. K. pneumoniae was detected by colony morphology on culture media and various biochemical tests. Agar dilution method was used to determine MIC of colistin. PCR was done for detection of colistin resistance genes and sequencing of the amplified mgr B gene products was done. Total 75(23.73%) K. pneumoniae were isolated. Among the isolated K. pneumoniae, 8(10.67%) were resistant to colistin. MIC of colistin of resistant isolates ranged from ≥64µg/ml to ≤4µg/ml. Out of 8 colistin resistant K. pneumoniae, 4(50.00%) were positive for mgr B gene and 3(37.50%) were positive for pho Q gene. Colistin resistance in K. pneumoniae is increasing in Bangladesh, which is very alarming and we should give importance on standard guideline of antimicrobials use.

Analyzing single cell transcriptome data from severe COVID-19 patients.

We describe the protocol for identifying COVID-19 severity specific cell types and their regulatory marker genes using single-cell transcriptomics data. We construct COVID-19 comorbid disease-associated gene list using multiple databases and literature resources. Next, we identify specific cell type where comorbid genes are upregulated. We further characterize the identified cell type using gene enrichment analysis. We detect upregulation of marker gene restricted to severe COVID-19 cell type and validate our findings using in silico, in vivo, and in vitro cellular models. For complete details on the use and execution of this protocol, please refer to Nassir et al. (2021b).

Performance evaluation of micro lens arrays: Improvement of light intensity and efficiency of white organic light emitting diodes.

This paper proposes a unique method to improve light intensity and efficiency of white organic light emitting diodes (OLEDs) by engraving micro lens arrays (MLAs) on the outer face of the substrate layer. The addition of MLAs on the substrate layer improves the light intensity and external quantum efficiency (EQE) of the OLEDs. The basic OLED model achieved an EQE of 14.45% for the effective refractive index (ERI) of 1.86. The spherical and elliptical (planoconvex and planoconcave) MLAs were incorporated on the outer face of the substrate layer to increase the EQE of the OLEDs. The maximum EQE of 17.30% was obtained for Convex-1 (elliptical planoconvex) MLA engraved OLED where the ERI was 1.70. In addition, Convex-1 MLA engraved OLED showed an improvement of 3.8 times on the peak electroluminescence (EL) light intensity compared to basic OLED. Therefore, Convex-1 MLA incorporated OLED can be considered as a potential white OLED because of its excellent light distribution and intensity profile.

Single-cell transcriptome identifies FCGR3B upregulated subtype of alveolar macrophages in patients with critical COVID-19.

Understanding host cell heterogeneity is critical for unraveling disease mechanism. Utilizing large-scale single-cell transcriptomics, we analyzed multiple tissue specimens from patients with life-threatening COVID-19 pneumonia, compared with healthy controls. We identified a subtype of monocyte-derived alveolar macrophages (MoAMs) where genes associated with severe COVID-19 comorbidities are significantly upregulated in bronchoalveolar lavage fluid of critical cases. FCGR3B consistently demarcated MoAM subset in different samples from severe COVID-19 cohorts and in CCL3L1-upregulated cells from nasopharyngeal swabs. In silico findings were validated by upregulation of FCGR3B in nasopharyngeal swabs of severe ICU COVID-19 cases, particularly in older patients and those with comorbidities. Additional lines of evidence from transcriptomic data and in vivo of severe COVID-19 cases suggest that FCGR3B may identify a specific subtype of MoAM in patients with severe COVID-19 that may present a novel biomarker for screening and prognosis, as well as a potential therapeutic target.

Epidemiology and genetic characterization of human sapovirus among hospitalized acute diarrhea patients in Bangladesh, 2012-2015.

Human sapovirus, which causes acute gastroenteritis, is not well studied and poorly understood. This study aims to investigate the contribution of sapovirus in diarrhea, their clinical association, and genotypic diversity. Fecal specimens (n = 871) were randomly selected from diarrheal patients who attended International Centre for Diarrhoeal Disease Research, Bangladesh hospital in Dhaka, Bangladesh during January 2012-December 2015 and tested for the presence of sapovirus RNA using real-time polymerase chain reaction. Sapovirus RNA was identified in 2.3% (n = 20) of the samples. Seventy-five percent of the sapovirus positive cases were coinfected with other pathogens, such as rotavirus, norovirus, enterotoxigenic Escherichia coli, adenovirus, Shigella spp., and Vibrio cholerae. A vast genetic diversity was observed among sapovirus with at least seven common genotypes (GI.1, GI.2, GI.7, GII.1, GII.4, GII.6, and GIV), and a new genotype GII.NA1. Some of the GI.1 strains detected were similar to GI.4 in the polymerase region sequence and were confirmed as recombinant strains. Our findings suggest that the overall contribution of sapovirus in hospitalized diarrheal illness is low but highlight enormous genetic diversity.

The prevalence and determinants of postpartum depression (PPD) symptomatology among facility delivered mothers of Dhaka city.

BACKGROUND: Postpartum depression (PPD) is among the top mental health issues and affects children's health and cognitive development. This study aimed to identify the prevalence of PPD symptomatology and possible determinants among facility delivered mothers of Dhaka city. METHOD: A cross-sectional study was conducted among 291 mothers within the 12 months of postpartum during January to May 2019. RESULTS: The prevalence of PPD symptomatology was 29.9 % among postpartum mothers. Multiple adjusted odds ratios of stepwise logistic regression analyses revealed, mothers age more than 30 years (AOR = 2.56:95 %CI = 1.21-5.39), being a mother for the first time (AOR = 2.08:95 %CI = 1.09-3.96), lost job or couldn't able to do paid work due to pregnancy (AOR = 2.60:95 %CI = 1.25-5.43), hypertension history (AOR = 2.48:95 %CI = 1.20-5.10), neonatal complication (AOR = 2.04:95 %CI = 1.05-3.95), and rare or no support from husband (AOR = 4.12:95 %CI = 2.14-7.95) were identified as significant predictors of PPD. However, having a household income of more than 50,000 Bangladeshi Taka per month (AOR = 0.36:95 %CI = 0.17-0.76) and passing less sedentary hours (AOR = 0.41:95 % CI = 0.23-0.75) were protective factors for PPD. CONCLUSION: Our study has revealed a relatively high prevalence of PPD symptomatology; therefore, mental health counseling and proper management of cases are essential for bettering mothers and the next generation.

Early Assessment Window for Predicting Breast Cancer Neoadjuvant Therapy using Biomarkers, Ultrasound, and Diffuse Optical Tomography.

PURPOSE: The purpose of the study was to assess the utility of tumor biomarkers, ultrasound (US) and US-guided diffuse optical tomography (DOT) in early prediction of breast cancer response to neoadjuvant therapy (NAT). METHODS: This prospective HIPAA compliant study was approved by the institutional review board. Forty one patients were imaged with US and US-guided DOT prior to NAT, at completion of the first three treatment cycles, and prior to definitive surgery from February 2017 to January 2020. Miller-Payne grading was used to assess pathologic response. Receiver operating characteristic curves (ROCs) were derived from logistic regression using independent variables, including: tumor biomarkers, US maximum diameter, percentage reduction of the diameter (%US), pretreatment maximum total hemoglobin concentration (HbT) and percentage reduction in HbT (%HbT) at different treatment time points. Resulting ROCs were compared using area under the curve (AUC). Statistical significance was tested using two-sided two-sample student t-test with P < 0.05 considered statistically significant. Logistic regression was used for ROC analysis. RESULTS: Thirty-eight patients (mean age = 47, range 24-71 years) successfully completed the study, including 15 HER2 + of which 11 were ER + ; 12 ER + or PR + /HER2-, and 11 triple negative. The combination of HER2 and ER biomarkers, %HbT at the end of cycle 1 (EOC1) and %US (EOC1) provided the best early prediction, AUC = 0.941 (95% CI 0.869-1.0). Similarly an AUC of 0.910 (95% CI 0.810-1.0) with %US (EOC1) and %HbT (EOC1) can be achieved independent of HER2 and ER status. The most accurate prediction, AUC = 0.974 (95% CI 0.933-1.0), was achieved with %US at EOC1 and %HbT (EOC3) independent of biomarker status. CONCLUSION: The combined use of tumor HER2 and ER status, US, and US-guided DOT may provide accurate prediction of NAT response as early as the completion of the first treatment cycle. CLINICAL TRIAL REGISTRATION NUMBER: NCT02891681. https://clinicaltrials.gov/ct2/show/NCT02891681 , Registration time: September 7, 2016.

Assessing Rectal Cancer Treatment Response Using Coregistered Endorectal Photoacoustic and US Imaging Paired with Deep Learning.

Background Conventional radiologic modalities perform poorly in the radiated rectum and are often unable to differentiate residual cancer from treatment scarring. Purpose To report the development and initial patient study of an imaging system comprising an endorectal coregistered photoacoustic (PA) microscopy (PAM) and US system paired with a convolution neural network (CNN) to assess the rectal cancer treatment response. Materials and Methods In this prospective study (ClinicalTrials.gov identifier NCT04339374), participants completed radiation and chemotherapy from September 2019 to September 2020 and images were obtained with the PAM/US system prior to surgery. Another group's colorectal specimens were studied ex vivo. The PAM/US system consisted of an endorectal imaging probe, a 1064-nm laser, and one US ring transducer. The PAM CNN and US CNN models were trained and validated to distinguish normal from malignant colorectal tissue using ex vivo and in vivo patient data. The PAM CNN and US CNN were then tested using additional in vivo patient data that had not been seen by the CNNs during training and validation. Results Twenty-two patients' ex vivo specimens and five patients' in vivo images (a total of 2693 US regions of interest [ROIs] and 2208 PA ROIs) were used for CNN training and validation. Data from five additional patients were used for testing. A total of 32 participants (mean age, 60 years; range, 35-89 years) were evaluated. Unique PAM imaging markers of the complete tumor response were found, specifically including recovery of normal submucosal vascular architecture within the treated tumor bed. The PAM CNN model captured this recovery process and correctly differentiated these changes from the residual tumor. The imaging system remained highly capable of differentiating tumor from normal tissue, achieving an area under the receiver operating characteristic curve of 0.98 (95% CI: 0.98, 0.99) for data from five participants. By comparison, the US CNN had an area under the receiver operating characteristic curve of 0.71 (95% CI: 0.70, 0.73). Conclusion An endorectal coregistered photoacoustic microscopy/US system paired with a convolutional neural network model showed high diagnostic performance in assessing the rectal cancer treatment response and demonstrated potential for optimizing posttreatment management. © RSNA, 2021 Supplemental material is available for this article. See also the editorial by Klibanov in this issue.

Effect and correction of optode coupling errors in breast imaging using diffuse optical tomography.

In diffuse optical tomography (DOT) and spectroscopy (DOS) using handheld probes, tissue curvature can cause bad fiber-to-tissue contact. Understanding and minimizing image artifacts caused by these coupling errors would significantly improve DOT and DOS image quality. In this work, we utilized Monte Carlo simulations and experiments with gelatin-Intralipid phantoms to systematically study the influence of source or detector (optode) coupling errors. Optode coupling errors can increase the amplitude and decrease the phase of the measured diffuse reflectance, creating artifacts in the reconstructed absorption maps, such as hot spots on the edges. We propose an outlier removal algorithm that can correct these image artifacts, and we demonstrate its performance using simulations, phantom experiments, and breast patient data acquired with bad probe contact due to a dense or small breast. Further, we designed and implemented a new resistance-type thin-film force sensor array that provides real-time optode coupling feedback and guides the outlier removal to minimize optode coupling errors. Our approaches and study results have significant implications for reducing image artifacts arising from handheld probes, which are commonly used with mobile and wearable DOT and DOS devices.

Whole exome sequencing uncovered highly penetrant recessive mutations for a spectrum of rare genetic pediatric diseases in Bangladesh.

Collectively, rare genetic diseases affect a significant number of individuals worldwide. In this study, we have conducted whole-exome sequencing (WES) and identified underlying pathogenic or likely pathogenic variants in five children with rare genetic diseases. We present evidence for disease-causing autosomal recessive variants in a range of disease-associated genes such as DHH-associated 46,XY gonadal dysgenesis (GD) or 46,XY sex reversal 7, GNPTAB-associated mucolipidosis II alpha/beta (ML II), BBS1-associated Bardet-Biedl Syndrome (BBS), SURF1-associated Leigh Syndrome (LS) and AP4B1-associated spastic paraplegia-47 (SPG47) in unrelated affected members from Bangladesh. Our analysis pipeline detected three homozygous mutations, including a novel c. 863 G > C (p.Pro288Arg) variant in DHH, and two compound heterozygous variants, including two novel variants: c.2972dupT (p.Met991Ilefs*) in GNPTAB and c.229 G > C (p.Gly77Arg) in SURF1. All mutations were validated by Sanger sequencing. Collectively, this study adds to the genetic heterogeneity of rare genetic diseases and is the first report elucidating the genetic profile of (consanguineous and nonconsanguineous) rare genetic diseases in the Bangladesh population.

An Exploration of Physical and Phenotypic Characteristics of Bangladeshi Children with Autism Spectrum Disorder.

This study explored the physical and clinical phenotype of Bangladeshi children with autism spectrum disorder (ASD). A totally of 283 children who were referred for screening and administered Module 1 of the Autism Diagnostic Observation Schedule (ADOS) were included. Overall, 209 met the ADOS algorithmic cutoff for ASD. A trend for greater weight and head circumference was observed in children with ASD versus non-ASD. Head circumference was significantly (p < 0.03) larger in ASD males compared with non-ASD males. A trend was also observed for symptom severity, higher in females than males (p = 0.068), with further analyses demonstrating that social reciprocity (p < 0.014) and functional play (p < 0.03) were significantly more impaired in ASD females than males. The findings help understand sex differences in ASD.

Role of blood oxygenation saturation in ovarian cancer diagnosis using multi-spectral photoacoustic tomography.

In photoacoustic tomography (PAT), a tunable laser typically illuminates the tissue at multiple wavelengths, and the received photoacoustic waves are used to form functional images of relative total haemoglobin (rHbT) and blood oxygenation saturation (%sO2 ). Due to measurement errors, the estimation of these parameters can be challenging, especially in clinical studies. In this study, we use a multi-pixel method to smooth the measurements before calculating rHbT and %sO2 . We first perform phantom studies using blood tubes of calibrated %sO2 to evaluate the accuracy of our %sO2 estimation. We conclude by presenting diagnostic results from PAT of 33 patients with 51 ovarian masses imaged by our co-registered PAT and ultrasound system. The ovarian masses were divided into malignant and benign/normal groups. Functional maps of rHbT and %sO2 and their histograms as well as spectral features were calculated using the PAT data from all ovaries in these two groups. Support vector machine models were trained on different combinations of the significant features. The area under ROC (AUC) of 0.93 (0.95%CI: 0.90-0.96) on the testing data set was achieved by combining mean %sO2 , a spectral feature, and the score of the study radiologist.