Test Sequences Research Articles

Consider CUX1 variants in children with a variation of sex development: a case report and review of the literature

BackgroundThe Cut Homeobox 1 (CUX1) gene has been implicated in a number of developmental processes and has recently emerged as an important cause of developmental delay and impaired intellectual development. Individuals with variants in CUX1 have been described with a variety of co-morbidities including variations in sex development (VSD) although these features have not been closely documented.Case presentationThe proband is a 14-year-old male who presented with congenital complex hypospadias, neurodevelopmental differences, and subtle dysmorphism. A family history of neurodevelopmental differences and VSD was noted. Microarray testing and whole exome sequencing found the 46,XY proband had a large heterozygous in-frame deletion of exons 4–10 of the CUX1 gene.ConclusionsOur review of the literature has revealed that variants in CUX1 are associated with a range of VSD and suggest this gene should be considered in cases where a VSD is noted at birth, especially if there is a familial history of VSD and/or neurodevelopmental differences. Further work is required to fully investigate the role and regulation of CUX1 in sex development.

Complexity analysis of the VVenC versus VVC encoder

The joint video experts team (JVET) has recently finalized a next-generation open-source video codec, called versatile video coding (VVC). The new standard presents a higher gain in the run time and rate compressions. Based on the reference software (VTM, VVC Test Model) of VVC, an optimized encoder was developed these last years resulting in a fast and efficient encoder, called Fraunhofer versatile video encoder (VVenC). Based on the Bjontegaard methodology and the GPROF profiling tool, this paper presents a technical complexity analysis and comparison of both VVC and VVenC. The appropriate comparisons cover the percentage taken by each block in terms of processing time and the resulting whole encoding time. The peak signal-to-noise ratio (PSNR) and bit rate between VVC and VVenC encoders based on the common test conditions manual are also analyzed and compared. The profiling results show that the VVenC encoder presents a maximum gain of runtime and bit rate of 90% and 20% respectively in classes A and D test sequences, compared to the VVC encoder.

Phenotypic and genotypic analysis of 11 fetal cases with Bardet-Biedl syndrome.

To present the prenatal sonographic features and genomic spectrum of pregnancies with fetal Bardet-Biedl syndrome (BBS). This was a retrospective study of 11 cases with BBS diagnosed by prenatal ultrasound and confirmed by genetic testing. Clinical and laboratory data were collected and reviewed for these cases, including maternal demographics, prenatal sonographic findings, molecular testing sequencing results, and pregnancy outcomes. All cases had unremarkable first-trimester ultrasound scans without reporting limb malformations. All had second-trimester abnormal ultrasounds: postaxial polydactyly in nine cases (9/11), renal abnormalities in seven (7/11), reduced amniotic fluid volume in two (2/11), central nervous system anomalies in two (2/11), and ascites in three (3/11). Ten fetuses presented with at least two-system anomalies, and one (Case 11) presented with only postaxial polydactyly. Variants were detected in five genes, including BBS2, ARL6/BBS3, BBS7, CEP290/BBS14 and IFT74/BBS22. Ten pregnancies were terminated in the second trimester, while one continued to term. Enlarged hyperechogenic kidneys and postaxial polydactyly are the two most common sonographic features of fetal BBS. Prenatal diagnosis of BBS can be done with ultrasound and genetic testing although the diagnosis may be made in the second trimester.

Reflex Xpert MTB/XDR Testing of Residual Rifampicin-Resistant Specimens: A Clinical Laboratory-Based Diagnostic Accuracy and Feasibility Study in South Africa.

The World Health Organization-approved Xpert MTB/XDR test detects Mycobacterium tuberculosis and resistance to isoniazid, fluoroquinolones, ethionamide, and injectable drugs directly in specimens. This pragmatic, laboratory-based study assessed the diagnostic accuracy and feasibility of a reflex testing approach, where Xpert MTB/XDR was performed on residual specimens previously processed for Xpert MTB/RIF Ultra. Routine respiratory specimens, processed for Xpert MTB/RIF Ultra, were stored in sample reagent buffer at 2°C-8°C. If rifampicin resistant, the residual specimen was assessed for adequate volume (≥2 mL) and tested with Xpert MTB/XDR, with storage time recorded. A second specimen was used for routine and reference standard testing (culture and sequencing). Specimens (99% sputum) from 763 participants submitted to 2 large routine laboratories were included. Xpert MTB/XDR yielded valid resistance detection results in 639 (84%), compared with 507 (66%) for routine testing (difference [95% CI], 18% [13%-22%]). The median turnaround time for results was 23 hours for Xpert MTB/XDR and 15 days for routine testing. While 748 specimens (98%) were ≥2 mL, only 102 (13%) were stored for ≤4 hours. By the reference standard, 284 of 394 (72%) were isoniazid resistant, and 57 of 380 (15%) were fluroquinolone resistant. The sensitivities of Xpert MTB/XDR were 94% (95% CI, 91%-97%) for isoniazid and 91% (81%-97%) for fluoroquinolone resistance detection. The specificities were 98% (94%-100%) and 100% (98%-100%), respectively. Xpert MTB/XDR performed favorably compared with the reference, and the reflex testing approach increased results availability over routine testing, while dramatically decreasing turnaround time from weeks to hours. Laboratory workflow precluded testing within the manufacturer-recommended 4-hour storage time, but longer storage did not appear detrimental.

Narrative review on ethical and psychological issues raised by genetic and genomic testing in pediatric oncology care.

In pediatric oncology, genetic and genomic tests are proposed throughout the care pathway for many reasons (e.g., cancer characterization, identification of the most appropriate treatment, patient selection for clinical trials, identification of tissue/organ donors, or risk of relapse prediction). Despite the many different approaches (somatic or germline testing, targeted gene or genome sequencing), the implicated individuals are confronted with situations that may intersect and that are interesting to compare. No study has identified and analyzed the available works on these new practices in pediatric oncology. The aim of this narrative literature review was to describe the ethical and psychological perspectives of children with cancer, parents, and healthcare professionals when genetic or genomic testing is proposed as part of the cancer management. Eighteen articles met the inclusion criteria and were comprehensively coded using MAXQDA. Their analysis showed that concerning the subjective implications of genetic and genomic testing, the areas of ambivalence (desire of treatment, desire for knowledge, uncertainty, and guilt) reported by patients and their parents seem to mirror the healthcare professionals' concerns. The ethical and psychological issues about predisposition testing, long discussed in the context of hereditary retinoblastoma and Li-Fraumeni syndrome, represent a useful starting point for a wider discussion of a genetic and genomic testing pathway in pediatric oncology more broadly.

Co-existence of two plasmids harboring transferable resistance-nodulation-division pump gene cluster, tmexCD1-toprJ1, and colistin resistance gene mcr-8 in Klebsiella pneumoniae

BackgroundThe emergence of plasmid-mediated mobile colistin resistance (mcr) gene poses a great challenge to the clinical application of polymyxins. To date, mcr-1 to mcr-10 have been found in animals, humans, and the environment. Among them, mcr-8 was first identified in Klebsiella pneumoniae (K. pneumoniae) of swine origin, and then mcr-8.1 to mcr-8.5 were successively identified. Notably, K. pneumoniae is the major host of the mcr-8 gene in both animals and humans. This study aims to explore the characteristics of K. pneumoniae strains carrying the mcr-8 gene and tmexCD1-toprJ1 gene cluster and investigate the correlation between these two antibiotic resistance genes.MethodsThe isolates from the poultry farms and the surrounding villages were identified by mass spectrometer, and the strains positive for mcr-1 to mcr-10 were screened by polymerase chain reaction (PCR). The size of the plasmid and the antimicrobial resistance genes carried were confirmed by S1-nuclease pulsed-field gel electrophoresis (S1-PFGE) and Southern hybridization, and the transferability of the plasmid was verified by conjugation experiments. Antimicrobial susceptibility testing (AST) and whole genome sequencing (WGS) were used to characterize the strains.ResultsTwo K. pneumoniae isolates (KP26 and KP29) displaying polymyxin resistance were identified as mcr-8 gene carriers. Besides that, tigecycline-resistant gene cluster tmexCD1-toprJ1 was also found on the other plasmid which conferred strain resistance to tigecycline. Through epidemiological analysis, we found that the mcr-8 gene has dispersed globally, circulating in the human, animals, and the environment. Furthermore, our analysis suggests that the coexistence of mcr-8 and tmexCD1-toprJ1 on a single plasmid might evolved through plasmid recombination.ConclusionsAlthough the mcr-8 and tmexCD1-toprJ1 gene clusters in the two strains of K. pneumoniae in this study were on two different plasmids, they still pose a potential threat to public health, requiring close monitoring and further study.

A case of AZOOR under immunomodulatory treatment.

To describe the clinical course and treatment response of a case of Acute Zonal Occult Outer Retinopathy (AZOOR). This is an observational case report. The examinations included ophthalmic examination, longitudinal multimodal imaging, visual field testing, electrophysiological recordings, serologic analyses and whole genome sequencing. In this report, the authors present the case of an otherwise healthy 33-year-old female with bilateral AZOOR manifestation. Other possible causes of the observed retinal lesions were ruled out by extensive diagnostic work-up. Treatment with oral prednisolone therapy led to temporal disease control but progression was observed after prednisolone discontinuation. A tapered oral prednisolone therapy in combination with adalimumab initiation prevented further progression for at least 21 months. Diagnosis of AZOOR is frequently complicated by the unspecific symptoms of the disease and significant number of differential diagnoses. Complete diagnostic work-up is important to rule out other etiologies. Due to the lack of randomized controlled trials, therapeutic decisions obligatorily rely on empiric treatment decisions in combination with frequent follow-up examinations.

Cendakimab in Patients With Moderate to Severe Atopic Dermatitis

Cendakimab selectively targets interleukin (IL)-13, a type 2 cytokine implicated in atopic dermatitis (AD) pathogenesis, by inhibiting binding to its receptors (IL13R-α1 and IL13R-α2). Proof-of-concept work in AD supports using cendakimab for type 2 inflammatory diseases. To evaluate the efficacy and safety of cendakimab compared with placebo in patients with moderate to severe AD. This phase 2, randomized, double-blind, placebo-controlled, parallel-group, dose-ranging clinical trial was conducted from May 2021 to November 2022. Adult patients with moderate to severe AD and inadequate response to topical medications were enrolled at 69 sites in 5 countries (US [n = 26], Japan [n = 17], Canada [n = 9], Poland [n = 9], and Czech Republic [n = 8]). Data were analyzed between April 25, 2023, and October 16, 2023. Patients were randomized (1:1:1:1) to receive subcutaneous cendakimab, 360 mg, every 2 weeks; 720 mg, every 2 weeks; 720 mg, once weekly; or placebo. Mean percentage change in Eczema Area and Severity Index scores from baseline to week 16. Hierarchical testing with multiplicity adjustment was performed for 720 mg, once weekly vs placebo, then 720 mg, every 2 weeks vs placebo, and then 360 mg, every 2 weeks vs placebo. Overall, 221 patients were randomized, and 220 received study drug (95 women [43%]; mean [SD] age, 37.7 [13.9] years; 720 mg, once weekly [54 (24%)]; 720 mg, every 2 weeks [55 (25%)]; 360 mg, every 2 weeks [55 (25%)]; placebo [56 (26%)]). The primary efficacy end point was met for cendakimab, 720 mg, once weekly vs placebo (-84.4 vs -62.7; P = .003) but missed statistical significance for 720 mg, every 2 weeks (-76.0 vs -62.7; P = .06). The treatment effect for 360 mg, every 2 weeks (-16.3; nominal P = .03 vs placebo) was comparable with 720 mg, once weekly (-21.8); however, significance was not claimed because the hierarchical testing sequence was interrupted. Of patients with treatment-emergent adverse events leading to discontinuation, 4 (7.4%) received 720 mg, once weekly; 2 (3.6%) 720 mg, every 2 weeks; 1 (1.8%) 360 mg, every 2 weeks; and 2 (3.6%) placebo. The results of this randomized clinical trial indicated that cendakimab was effective, generally safe, and well-tolerated in patients with moderate to severe AD. The primary end point was met with a significant reduction in Eczema Area and Severity Index scores with 720 mg, once weekly at week 16. Cendakimab demonstrated progressive AD improvement at all doses during 16 weeks of treatment. ClinicalTrials.gov Identifier: NCT04800315.

Potential efficacy of digital polymerase chain reaction for non-invasive prenatal screening of autosomal aneuploidies: a systematic review and meta-analysis

BackgroundDigital Polymerase Chain Reaction (dPCR) presents a promising approach for quantifying DNA and analyzing copy number variants, particularly in non-invasive prenatal testing. This method offers a streamlined and time-efficient procedure in contrast to the widely used next-generation sequencing for non-invasive prenatal testing. Studies have reported encouraging results for dPCR in detecting fetal autosomal aneuploidies. Consequently, this systematic review aimed to evaluate the effectiveness of dPCR in screening for trisomy 21, 18, and 13.MethodsA systematic search was conducted in PubMed, Web of Sciences, and Embase for relevant articles published up to December 30, 2023. The Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) was utilized for the quality assessment of the included articles. Furthermore, a bivariate random-effect regression model was used to conduct a meta-analysis on the utility of dPCR for trisomy 21 screening.ResultsA total of 9 articles were included in this review, with all of them assessing the utility of dPCR in trisomy 21 screening, and 2 and 1 studies conducting additional analysis on the screening abilities of dPCR for trisomy 18 and 13, respectively. A bivariate random-effects model calculated pooled sensitivity and specificity with a 95% confidence interval (CI). Meta-analysis of 6 studies comparing trisomy-21 screening with karyotyping demonstrated dPCR's pooled sensitivity of 98% [95% CI: 94 -100] and specificity of 99% [95% CI: 99 -100]. While conducting a meta-analysis for trisomy 13 and 18 proved impractical, reported values for sensitivity and specificity were favorable.ConclusionsThese findings suggest that dPCR holds promise as an effective tool for non-invasive prenatal testing, presenting a less time-consuming and intricate alternative to next-generation sequencing. However, further research is necessary to evaluate dPCR's applicability in clinical settings and to delineate its specific advantages over next-generation sequencing. This study contributes valuable insights into the potential of dPCR for enhancing prenatal screening methodologies.Trial registrationThe protocol of this study was registered in the International Prospective Register of Systematic Reviews (PROSPERO) on 7/3/2024, with a registration code of CRD42024517523.

Multishot laser damage of multilayer dielectric mirrors in the near-infrared subpicosecond regime

The laser damage resistance of dielectric components of high-power laser facilities to laser irradiation depends significantly on the irradiation sequence. In the short pulse (fs) regime, it is known that continuous irradiation of these components leads to a reduction in the damage threshold, reflecting a laser fatigue effect. Conversely, in the long pulse (ns) regime, progressive irradiation of these components leads to an increase in the damage threshold, reflecting a laser conditioning effect. In this article, we experimentally evaluate the competition between the effects of laser fatigue and laser conditioning for multilayer dielectric components irradiated in the subpicosecond pulse regime in the infrared (∼1µm) through different test sequences. For this purpose, we implemented an original test sequence derived from an S-on-1 type protocol, which consists of irradiating the component until damage. By repeating this sequence at different set points, it was possible to estimate the progressive reduction in damage threshold with the number of laser irradiations and to compare it with that observed during the fluence ramps. Particular attention was also paid to the precise knowledge of the test beam irradiating the component, as a dependence of the beam surface on the test set point was highlighted.

Evolutionary accumulation of FKS1 mutations from clinical echinocandin-resistant Candida auris

Introduction: Drug resistance to echinocandins, first-line drugs used to treat Candida auris infection, is rapidly emerging. However, the accumulation of mutations in genes other than FKS1 (before an isolate develops to resistance via FKS1 mutations), remains poorly understood. Methods Four clinical cases and 29 isolates associated with the incremental process of echinocandin resistance were collected and analyzed using antifungal drug susceptibility testing and genome sequencing to assess the evolution of echinocandin resistance. Findings: Six echinocandin minimum inhibitory concentration (MIC)-elevated C. auris strains and seven resistant strains were isolated from the urinary system of patients receiving echinocandin treatment. Meanwhile, phylogenetic analyses illustrated that the echinocandin-resistant strains were closely related to other strains in the same patient. Genomic data revealed that the echinocandin-resistant strains had FKS1 mutations. Furthermore, three categories (ECN-S/E/R) of non-synonymous mutant SNP genes (such as RBR3, IFF6, MKC1, MPH1, RAD2, and MYO1) in C. auris appeared to be associated with the three-stage-evolutionary model of echinocandin resistance in C. glabrata: cell wall stress, drug adaptation, and genetic escape (FKS mutation). Interpretation: Echinocandin-resistant C. auris undergoes spatial and temporal phase changes closely related to echinocandin exposure, particularly in the urinary system. These findings suggest that FKS1 mutations mediate an evolutionary accumulation of echinocandin resistance followed by modulation of chromosome remodeling and DNA repair processes that ultimately lead to FKS1 hot spot mutations and the development of drug resistance. This study provides an in-depth exploration of the molecular pathways involved in the evolution of Candida auris echinocandin resistance.

MRI-Based Inner Ear Assessment and Cochlin Tomoprotein-Based Evaluation of Perilymphatic Fistula in Patients with Sudden Hearing Loss.

To study the correlation between positive cochlin tomoprotein testing (CTP), magnetic resonance (MR) imaging, and the auditory and vestibular function amongst patients with sudden hearing loss. Prospective case series. We prospectively examined eight patients who presented with sudden hearing loss (>60 dB) with or without vertigo or tinnitus. We performed an ELISA-based CTP detection test using middle ear lavage samples. In addition to the CTP examination, a magnetic resonance imaging (MRI) examination was performed using different sequences (T1 and a T1 sequence with a contrast medium (CM), a T2 sequence, 4 h delayed intravenous gadolinium-enhanced three-dimensional fluid-attenuated inversion recovery (3D FLAIR)). All patients with sudden hearing loss (>60 dB) presented a non-specific contrast enhancement in the cochlea and vestibulum on the affected side on delayed 3D-FLAIR MRI. Four patients had a positive CTP test, suggesting a perilymphatic fistula (PLF). However, no specific MRI signal for a PLF was observed. Using multimodal diagnostic measures, such as CTP testing and different MRI sequences, no correlation could be found in patients with a PLF.

SARS-CoV-2 Variants and COVID-19 in Bangladesh-Lessons Learned.

The coronavirus infectious disease-2019 (COVID-19) in Bangladesh is a paradigm for how one of the most densely populated countries in the world, with 1270 people per square kilometer, managed to cope with the COVID-19 pandemic under extraordinary circumstances. This review highlights the SARS-CoV-2 variants in Bangladesh and the timeline of their detection in the context of the global experience with the management of vaccination and natural SARS-CoV-2 infection. The motivation to overcome the COVID-19 vaccine dilemma and track Bangladeshi SARS-CoV-2 sub-variants underscores the potential for a low-income country to excel in international medical science, despite having stressed health care services and limited availability of resources for SARS-CoV-2 testing and gene sequencing.

MNSS: Neural Supersampling Framework for Real-Time Rendering on Mobile Devices.

Although neural supersampling has achieved great success in various applications for improving image quality, it is still difficult to apply it to a wide range of real-time rendering applications due to the high computational power demand. Most existing methods are computationally expensive and require high-performance hardware, preventing their use on platforms with limited hardware, such as smartphones. To this end, we propose a new supersampling framework for real-time rendering applications to reconstruct a high-quality image out of a low-resolution one, which is sufficiently lightweight to run on smartphones within a real-time budget. Our model takes as input the renderer-generated low resolution content and produces high resolution and anti-aliased results. To maximize sampling efficiency, we propose using an alternate sub-pixel sample pattern during the rasterization process. This allows us to create a relatively small reconstruction model while maintaining high image quality. By accumulating new samples into a high-resolution history buffer, an efficient history check and re-usage scheme is introduced to improve temporal stability. To our knowledge, this is the first research in pushing real-time neural supersampling on mobile devices. Due to the absence of training data, we present a new dataset containing 57 training and test sequences from three game scenes. Furthermore, based on the rendered motion vectors and a visual perception study, we introduce a new metric called inter-frame structural similarity (IF-SSIM) to quantitatively measure the temporal stability of rendered videos. Extensive evaluations demonstrate that our supersampling model outperforms existing or alternative solutions in both performance and temporal stability.

Design and implementation of deep learning-based object detection and tracking system

Many human tracking methods by deep learning rely on powerful computing resources. For embedded platforms with limited resources, efficient use of resources is a priority. In this paper, we design an object detection and tracking system based on deep learning methods. We propose an efficient system with software and hardware design. We apply the framework of Vitis AI and its Deep Learning Processing Unit using a hardware/software co-design approach. This approach capitalizes on a higher-level acceleration design framework, where the convolutional models can be updated more flexibly and rapidly. This design approach not only provides a fast design flow but also has good performance in terms of throughput. We facilitate the design and accelerate the object detection model YOLO v3 to achieve higher throughput and energy efficiency. Our tracking method achieves a 1.27x improvement in processing speed with the addition of a single-object tracker. Our proposed human tracking methods can achieve better performance than the others in precision with the same test sequences.

Serratia marcescens Burden in a Neonatal Intensive Care Unit: Colonization Rate, Clinical Infections and Strain Relatedness

Background: Serratia marcescens (S. marcescens) is an environmentally associated organism known for causing healthcare associated infections and outbreaks in neonatal intensive care units (NICUs). The colonization or infection rates in NICU settings remain uncertain. This study aims to evaluate the rate of baseline colonization and clinical infection and relatedness of S. marcescens isolates. Methods: Prospective surveillance of rectal colonization and clinical infection of S. marcescens was conducted on patients admitted to the NICU at Mount Sinai Hospital in Toronto, Ontario, from March 1, 2023, to September 30, 2023. The NICU is a 57 bed unit with all private rooms. Monthly point prevalence assessments by rectal screening were performed, alongside active surveillance for clinical infections associated with S. marcesens. Isolates from screening or clinical samples underwent assessment for relatedness using pulse field gel electrophoresis (PFGE). Results: Over the 7 month study period, 12 different patients (5.4%) were colonized/infected with S. marcescens. Among these, 10 patients (4.5%) were identified through rectal screening (316 rectal swabs were collected from 224 patients) and two patients (0.9%) exhibited positive clinical specimens (urine and endotracheal aspirate) in association with pyelonephritis and ventilator-associated pneumonia, respectively. Of the two clinical cases, one case showed a negative preceding rectal swab and the other detected through a clinical sample before the point prevalence date. The age at which a positive S. marcescens swab or positive clinical specimen was identified ranged from 4 to 66 days (median=18 days, IQR 5-38.8) (Figure 1). Sixty seven infants had repeated screening. Three out of 67 (4.5%) were colonized with S. marcescens, the timing and sequence of positive and negative testing are presented in Figure 2. Females demonstrated a higher positivity rate compared to males [9.1% (9/99) vs 2.4% (3/125), p=0.04, respectively]. PFGE analysis of all 12 (100%) isolates revealed a polyclonal pattern. Most cases were detected from March to May in 9/12 cases (75%). Ten different strains were identified. Notably, two strains demonstrated clusters of two cases each, one during March and the other during May (Figure 3). No mortality was reported among the cases. Conclusions: The study highlights the polyclonal nature of S. marcesens and raises questions about the utility of point prevalence in anticipating clinical cases or patient-to-patient transmission, especially in patients with clinical infection where there were no preceding positive screening tests.

Drug-Resistant Profiles and Genetic Diversity of Mycobacterium Tuberculosis Revealed by Whole-Genome Sequencing in Hinggan League of Inner Mongolia, China.

Tuberculosis remains a major public health concern in China, with varying prevalence and drug resistance profiles across regions. This study explores the genetic diversity and drug-resistant profiles of MTB strains in Hinggan League, a high TB burden in Inner Mongolia, China. This population-based retrospective study, encompassing all culture-positive TB cases from Jun. 2021 to Jun. 2023 in Hinggan League. Drug resistant profiles and genetic diversity of MTB strains were assessed using phenotypic drug susceptibility testing and whole-genome sequencing. Risk factors associated with drug resistance were analyzed using univariate and multivariate logistic regression models. A total of 211 MTB strains were recovered successfully and included into final analysis. Lineage 2.2.1 (88.6%, 187/211) was the dominant sub-lineage, followed by lineage 4.5 (7.1%, 15/211) and lineage 4.4 (4.3%, 9/211). MTB strains exhibited the highest resistance rates to isoniazid (16.1%, 34/211), followed by rifampicin (10.0, 21/211). In addition, the MTB strains also showed relatively high rates of resistance against new and repurposed anti-TB drugs, with resistant rates of 2.4% (5/211) to delamanid and 1.9% (4/211) to bedaquiline. Overall, 25.6% (54/211) of MTB strains were DR-TB, and 14 MTB strains met the definition of MDR-TB, including 7 strains of simple-MDR-TB, 5 of pre-XDR-TB, and 2 of XDR-TB. Genetic analysis revealed that the dominant mutations of isoniazid-, rifampin-, ethambutol-, levofloxacin-/moxifloxacin-, and ethionamide- resistance were katG_Ser315Thr(46.4%), rpoB_Ser450Leu (47.4%), embB_Met306Val (25.0%), gyrA_Asp94Ala (40.0%), and fabG1_c15t (42.9%), respectively. Previously treated patients (AOR = 2.015, 95% CI: 1.052-4.210) and male patients (AOR = 3.858, 95% CI: 1.416-10.511) were identified as independent risk factors associated with DR-TB. Our study offers crucial insights into the genetic diversity and drug-resistant profiles of TB strains circulating in Hinggan League. These findings are valuable for DR-TB surveillance and for guiding treatment regimens and public health interventions in the region.

Current Practices in Genetic Testing for Prostate Cancer: The Indian Scenario.

Despite genetic testing being recommended by international guidelines for the selection of targeted therapy for prostate cancer (PCa), limited data are available on genetic testing for PCa in India. The objective is to understand the current genetic testing practice pattern for PCa in India. A panel of 9 experts developed and validated a premeeting online questionnaire comprising 12 objective questions. The questionnaire was circulated from February 2022 to May 2022 among medical oncologists and uro-oncologists across pan-India, followed by response collection over 3 months. Descriptive statistics were used to summarize results and concluding statements were formulated on current genetic testing practice patterns for PCa. A total of 103 responses were received. Genetic testing was advised by 35.9% of the participants in <5% of patients with PCa. Patients with a family history of PCa (88.3%) were most commonly referred for genetic testing. Nearly half (50.2%) of the participants routinely tested for homologous recombination repair (HRR) genes; 52% used blood and tissue as the most preferred specimen for performing genetic testing and 44.7% followed the testing sequence of tumor tissue followed by blood. Major barriers to genetic testing were affordability and scarcity of genetic counselors, while a major change could be brought by making it cost-effective and improving access to medication. We observed a lower prescription frequency of genetic testing for the HRR gene across pan-India. Improving the quality and access to genetic testing and the availability of cost-effective-targeted therapies will aid in delivering personalized care to patients with metastatic PCa.

Frontiers in Operations: Optimal Genetic Testing of Families

Problem definition: Through the laws of inheritance, knowing an individual’s genetic status informs disease risk for family members, but current protocols for deciding whom to genetically test only consider one person at a time rather than design an optimal testing plan for the entire family. Methodology/results: We develop a Markov decision process framework for maximizing the net benefits of genetic testing that integrates a Bayesian network of genetic statuses, with a functional representation of cost-effectiveness. Our model provides a contingent sequence of family members to test one at a time, that is, a plan that dynamically incorporates new test results, revealed sequentially at random, to decide who next to test. In the general case, we show that optimal stopping follows a structure with two-sided thresholds, previously known only for individual testing. Although the optimal testing sequence, in general, is contingent on the family test results, in the special case of sibling-only tests we can identify this sequence a priori. Our numerical case study, which was conducted in a realistic BRCA1/2 testing setting, demonstrates that an optimal policy significantly improves cost-effectiveness over existing policies. Thus, our framework offers a promising and powerful new approach to genetic testing. Managerial implications: In an optimal policy, prioritizing testing family members who might otherwise not have been tested can lead to an overall improvement in familial health value, surpassing even the most cost-effective existing protocols. From a management perspective, healthcare organizations and insurance companies can potentially save costs by implementing this approach for such families. History: This paper has been accepted in the Manufacturing &amp; Service Operations Management Frontiers in Operations Initiative. Funding: D. Adelman is grateful for financial support from Booth School of Business. Supplemental Material: The online appendix is available at https://doi.org/10.1287/msom.2023.0057 .

Achieving Long-Term Stability of Partial Nitrification and Autotrophic Denitrification in an MABR via Sulfide Dosing.

While partial nitrification (PN) has the potential to reduce energy for aeration, it has proven to be unstable when treating low-strength wastewater. This study introduces an innovative combined strategy incorporating a low rate of oxygen supply, pH control, and sulfide addition to selectively inhibit nitrite-oxidizing bacteria (NOB). This strategy led to a stable PN in a laboratory-scale membrane aerated biofilm reactor (MABR). Over a period of 260 days, the nitrite accumulation ratio exceeded 60% when treating synthetic sewage containing 50 mg NH4+-N/L. Through in situ activity testing and high-throughput sequencing, the combined strategy led to low levels of nitrite-oxidation activity (<5.5 mg N/m2 h), Nitrospira species (relative abundance <1%), and transcription of nitrite-oxidation genes (undetectable). The addition of sulfide led to simultaneous PN and autotrophic denitrification in the single-stage MABR, resulting in over 60% total inorganic nitrogen removal. Sulfur-based autotrophic denitrification consumed nitrite and inhibited NOB conversion of nitrite to nitrate. The combined strategy has potential to be applied in large-scale sewage treatment and deserves further exploration.