Comparative analysis of tuberculin and defined antigen skin tests for detection of bovine tuberculosis in buffaloes (Bubalus bubalis) in Haryana state, India.

BACKGROUND: Bovine tuberculosis (bTB) is a chronic disease that results from infection with any member of the Mycobacterium tuberculosis complex. Infected animals are typically diagnosed with tuberculin-based intradermal skin tests according to World Organization of Animal Health which are presently in use. However, tuberculin is not suitable for use in BCG-vaccinated animals due to a high rate of false-positive reactions. Peptide-based defined skin test (DST) antigens have been identified using antigens (ESAT-6, CFP-10 and Rv3615c) which are absent from BCG, but their performance in buffaloes remains unknown. To assess the comparative performance of DST with the tuberculin-based single intradermal test (SIT) and the single intradermal comparative cervical test (SICCT), we screened 543 female buffaloes from 49 organized dairy farms in two districts of Haryana state in India. RESULTS: We found that 37 (7%), 4 (1%) and 18 (3%) buffaloes were reactors with the SIT, SICCT and DST tests, respectively. Of the 37 SIT reactors, four were positive with SICCT and 12 were positive with the DST. The results show that none of the animals tested positive with all three tests, and 6 DST positive animals were SIT negative. Together, a total of 43 animals were reactors with SIT, DST, or both, and the two assays showed moderate agreement (Cohen's Kappa 0.41; 95% Confidence Interval (CI): 0.23, 0.59). In contrast, only slight agreement (Cohen's Kappa 0.18; 95% CI: 0.02, 0.34) was observed between SIT and SICCT. Using a Bayesian latent class model, we estimated test specificities of 96.5% (95% CI, 92-99%), 99.7% (95% CI: 98-100%) and 99.0% (95% CI: 97-100%) for SIT, SICCT and DST, respectively, but considerably lower sensitivities of 58% (95% CI: 35-87%), 9% (95% CI: 3-21%), and 34% (95% CI: 18-55%) albeit with broad and overlapping credible intervals. CONCLUSION: Taken together, our investigation suggests that DST has a test specificity comparable with SICCT, and sensitivity intermediate between SIT and SICCT for the identification of buffaloes suspected of tuberculosis. Our study highlights an urgent need for future well-powered trials with detailed necropsy, with immunological and microbiological profiling of reactor and non-reactor animals to better define the underlying factors for the large observed discrepancies in assay performance, particularly between SIT and SICCT.

Comparing minimum inhibitory concentrations of amikacin for pulmonary Mycobacterium avium complex disease: An analysis of culture media differences.

Mycobacterium avium complex (MAC) is considered a paramount microbe, especially in East Asia, including Japan. The commonly used commercial Minimum Inhibitory Concentrations (MIC) assay using Middlebrook 7H9 (7H9) medium deviates from the latest Clinical and Laboratory Standards Institute (CLSI) guidelines. Alternatively, measurement with cation-adjusted Mueller-Hinton broth (CAMHB) that conforms to CLSI standards is not yet widely available. Following the approval and commercialization of amikacin liposome inhalation suspension (ALIS) in 2021, a more precise evaluation of amikacin (AMK) susceptibility in MAC is necessary for treatment decisions. In the present study, 33 sputum samples were extracted from 27 patients, and MICs of AMK were compared between the frequently used 7H9 and the recommended CAMHB of the isolated MAC strains. The history of exposure to aminoglycosides for each sample was also added as clinical information. The findings indicated that there was only an 18% concordance rate in MIC between the two media, with 19 samples (58%) indicating lower MICs in 7H9 relative to CAMHB. The 17 samples had a history of exposure to aminoglycosides for periods ranging from 1.5 to 28 months. Specifically, 10 samples were exposed to amikacin by inhalation and intravenous injection, and the remaining seven samples had a history of ALIS inhalation. Samples with a prior utilization of aminoglycosides were significantly predisposed to developing resistance to ALIS compared to those without such a history (P = 0.046). Physicians are encouraged to scrutinize the findings of susceptibility testing utilizing CLSI-endorsed MIC assay using CAMHB medium to ascertain the optimal therapeutic approach.

Detailed aggregate exposure analysis shows that exposure to fragrance ingredients in consumer products is low: Many orders of magnitude below thresholds of concern.

The Research Institute for Fragrance Materials (RIFM) and Creme Global Cremeglobal.com partnered to develop an aggregate exposure model for fragrance ingredients. The model provides a realistic estimate of the total exposure of fragrance ingredients to individuals across a population. The Threshold of Toxicological Concern (TTC) and Dermal Sensitization Threshold (DST) were used to demonstrate the magnitude of low exposure to fragrance materials. The total chronic systemic, inhalation, and dermal 95th percentile exposures on approximately 3000 fragrance ingredients in RIFM's inventory were compared to their respective TTC or DST. Additionally, representative fragrance ingredients were randomly selected and analyzed for exposure distribution by product type (i.e., cosmetic/personal care, household care, oral care, and air care) and route of exposure. It was found that 76 % of fragrance ingredients fall below their respective TTC limits when compared to 95th percentile systemic exposure, while 99 % are below inhalation TTC limits. The lowest 95th percentile aggregate exposure by product type was from household care products, then air care, and oral care products. The highest exposure was from personal care/cosmetic products. The volume of use for most fragrance ingredients (63 %) was <1 metric ton, estimating that environmental exposure to fragrance ingredients is likely low.

COVID-19 and Neurodevelopmental Delays in Early Childhood: A Longitudinal Analysis of Developmental Outcomes in Korean Children.

This study employed a longitudinal analysis to evaluate the association between the coronavirus disease 2019 pandemic and neurodevelopment by analyzing over 1.8 million children from the Korean Developmental Screening Test for Infants and Children included in South Korea's National Health Screening Program. We compared the developmental outcomes in five age groups-9-17 months, 18-29 months, 30-41 months, 42-53 months, and 54-65 months-between the pre-pandemic (2018-2019) and pandemic (2020-2021) periods. Significant increases in potential developmental delays were observed during the pandemic in communication, cognitive, social interaction, self-care, and fine motor skills across most age groups. All five age groups experienced notable disruptions in communication and fine motor skills. Children from socioeconomically disadvantaged backgrounds faced higher risks across all domains. These findings highlight the need for targeted interventions and continuous monitoring to support the developmental needs of children affected by pandemic-related disruptions.

DST-DETR: Image Dehazing RT-DETR for Safety Helmet Detection in Foggy Weather.

In foggy weather, outdoor safety helmet detection often suffers from low visibility and unclear objects, hindering optimal detector performance. Moreover, safety helmets typically appear as small objects at construction sites, prone to occlusion and difficult to distinguish from complex backgrounds, further exacerbating the detection challenge. Therefore, the real-time and precise detection of safety helmet usage among construction personnel, particularly in adverse weather conditions such as foggy weather, poses a significant challenge. To address this issue, this paper proposes the DST-DETR, a framework for foggy weather safety helmet detection. The DST-DETR framework comprises a dehazing module, PAOD-Net, and an object detection module, ST-DETR, for joint dehazing and detection. Initially, foggy images are restored within PAOD-Net, enhancing the AOD-Net model by introducing a novel convolutional module, PfConv, guided by the parameter-free average attention module (PfAAM). This module enables more focused attention on crucial features in lightweight models, therefore enhancing performance. Subsequently, the MS-SSIM + ℓ2 loss function is employed to bolster the model's robustness, making it adaptable to scenes with intricate backgrounds and variable fog densities. Next, within the object detection module, the ST-DETR model is designed to address small objects. By refining the RT-DETR model, its capability to detect small objects in low-quality images is enhanced. The core of this approach lies in utilizing the variant ResNet-18 as the backbone to make the network lightweight without sacrificing accuracy, followed by effectively integrating the small-object layer into the improved BiFPN neck structure, resulting in CCFF-BiFPN-P2. Various experiments were conducted to qualitatively and quantitatively compare our method with several state-of-the-art approaches, demonstrating its superiority. The results validate that the DST-DETR algorithm is better suited for foggy safety helmet detection tasks in construction scenarios.

FRIZZLE PANICLE (FZP) regulates rice spikelets development through modulating cytokinin metabolism.

BACKGROUND: The number of grains per panicle is an important factor in determining rice yield. The DST-OsCKX2 module has been demonstrated to regulate panicle development in rice by controlling cytokinin content. However, to date, how the function of DST-OsCKX2 module is regulated during panicle development remains obscure. RESULT: In this study, the ABNORMAL PANICLE 1 (ABP1), a severely allele of FRIZZY PANICLE (FZP), exhibits abnormal spikelets morphology. We show that FZP can repress the expression of DST via directly binding to its promotor. Consistently, the expression level of OsCKX2 increased and the cytokinin content decreased in the fzp mutant, suggesting that the FZP acts upstream of the DST-OsCKX2 to maintain cytokinin homeostasis in the inflorescence meristem. CONCLUSIONS: Our results indicate that FZP plays an important role in regulating spikelet development and grain number through mediating cytokinin metabolism.

DST variants are responsible for neurogenic arthrogryposis multiplex congenita enlarging the spectrum of type VI hereditary sensory autonomic neuropathy.

Arthrogryposis multiplex congenita (AMC) is a developmental condition characterized by multiple joint contractures resulting from reduced or absent fetal movements. Through whole-exome sequencing combined with arrayCGH from DNA of a fetus presenting with early onset AMC, we identified biallelic loss of function variants in Dystonin (DST): a stop gain variant (NM_001144769.5:c.12208G > T:p.(Glu4070Ter)) on the neuronal isoform and a 175 kb microdeletion including exons 25-96 of this isoform on the other allele [NC_000006.11:g.(56212278_56323554)_(56499398_56507586)del]. Transmission electron microscopy of the sciatic nerve revealed abnormal morphology of the peripheral nerve with severe hypomyelination associated with dramatic reduction of fiber density which highlights the critical role of DST in peripheral nerve axonogenesis during development in human. Variants in the neuronal isoforms of DST cause hereditary sensory and autonomic neuropathy which has been reported in several unrelated families with highly variable age of onset from fetal to adult onset. Our data enlarge the disease mechanisms of neurogenic AMC.

Report on "The Second United Nations World Geospatial Information Congress (UN-WGIC) Pre-Event".

The United Nations Committee of Experts on Global Geospatial Information Management (GGIM) organises the World Geospatial Information Congress (UN-WGIC) once every four years bringing together member states of the UN-GGIM, experts in the field of Geospatial Technologies and its various application domains, commercial geospatial sector, academia, researchers and practitioners from across the globe. India is the proud host of the Second UN-WGIC scheduled for 10-14 October 2022 in Hyderabad, India. The Second UN-WGIC is organised by the United Nations and the Department of Science and Technology (DST), Government of India. Through a series of online virtual pre-events, DST intends to collect and collate various ideas and resource materials including applications and innovations in the field of Geospatial information generation to highlight the vibrant Indian Geospatial Ecosystem. One of the Pre events in India was held during 26th and 27th May, Co-ordinated by Prof. Biplab Biswas, Department of Geography, The University of Burdwan, Burdwan, West Bengal, India. The whole UN-WGIC pre-event was structured into-Inauguration; five technical sessions with presentations from various stakeholders like Government, Industry, Youth, Academics, others; and Conclusion with a detailed discussion over the nature, development and future trend of geospatial ecosystem in India and other countries.

DIFFERENTIATED CHOICE OF POSTERIOR METHODS OF DISCONNECTION OF ANATOMICAL COMPONENTS OF THE ABDOMINAL WALL IN COMBINATION WITH ALLOPLASTY IN POSTOPERATIVE VENTRAL HERNIAS OF GIANT SIZE.

OBJECTIVE: The aim: The aim of the article is to increase the effectiveness of the treatment of postoperative ventral hernias of giant size by a differentiated approach to the selection of the posterior technique of dissection of the anatomical components of the anterior abdominal wall in combination with alloplasty. PATIENTS AND METHODS: Materials and methods: An analysis of the surgical treatment of 312 patients with giant postoperative ventral hernias (PVH). The main group consisted of 232 patients who underwent a differentiated approach to the selection of component separation in combination with alloplasty, taking into account intra-ab¬dominal pressure (IAP) when simulating hernioplasty during surgery. In the second control group (80 patients), surgical treatment of PVH of giant sizes was performed using only the posterior Carbonell technique. RESULTS: Results: In 78 patients of the 1st subgroup, IAP was 9.1±1.2 mm Hg. the posterior technique of separating anatomical components according to Carbonell was performed in combination with sublay alloplasty. In 80 patients of the II subgroup with IAP from 11.1 to 14.1±1.2 mm Hg - the TAR technique was performed with sublay alloplasty. In 74 patients of III subgroups with IAP from 16 to 20.1±1.2 mm Hg, performed the TAR technique, we improved in combination with IPOM alloplasty. CONCLUSION: Conclusions: An increase in the effectiveness of surgical treatment was achieved in patients of subgroup I, reducing the probability of intra-abdominal hypertension to 5.1% versus 11.2%, in patients of subgroup II to 5% versus 11.2%, and in patients of subgroup III to 1.4% versus 11.2% of the control group.

Stereoselective Plasmonic Interaction in Peptide-tethered Photopolymerizable Diacetylenes Doped with Chiral Gold Nanoparticles.

Designing polymeric systems with ultra-high optical activity is instrumental in the pursuit of smart artificial chiroptical materials, including the fundamental understanding of structure/property relations. Herein, we report a diacetylene (DA) moiety flanked by chiral D- and L-FF dipeptide methyl esters that exhibits efficient topochemical photopolymerization in the solid phase to furnish polydiacetylene (PDA) with desired control over the chiroptical properties. The doping of the achiral gold nanoparticles provides plasmonic interaction with the PDAs to render asymmetric shape to the circular dichroism bands. With the judicious design of the chiral amino acid ligand appended to the AuNPs, we demonstrate the first example of selective chiral amplification mediated by stereo-structural matching of the polymer-plasmonic AuNP hybrid pairs. Such ordered self-assembly aided by topochemical polymerization in peptide-tethered PDA provides a smart strategy to produce soft responsive materials for applications in chiral photonics.

Pathogenic DST sequence variants result in either epidermolysis bullosa simplex (EBS) or hereditary sensory and autonomic neuropathy type 6 (HSAN-VI).

DST encodes bullous pemphigoid antigen-1 (BPAG1), a protein with eight tissue-specific isoforms expressed in the skin, muscle, brain and nerves. Accordingly, mutations in this gene are associated with epidermolysis bullosa simplex (EBS) and hereditary sensory and autonomic neuropathy type 6 (HSAN-VI). The genotypic spectrum is attested to by 19 distinct mutations but genotype-phenotype correlation for both disorders is not well established. In this study, we performed next-generation sequencing (NGS) on two families with different phenotypic presentations, one foetus (P1) with musculoskeletal and neurological malformations established by prenatal ultrasound and family history, and a 15-year-old female patient (P2) with skin blistering. P1 had a novel homozygous nonsense mutation, DST: NM_001144769, c.3805C>T, p.R1269* within a region of genetic homozygosity (ROH). This mutation resides within the plakin domain of BPAG1 and ablates all isoforms of this protein, leading to novel extracutaneous phenotypes consistent with HSAN-VI in P1. P2 had a recurrent homozygous mutation DST: NM_001723.7, c.3370C>T, p.Gln1124* that presented with giant, trauma-induced skin blisters without extracutaneous involvement. This mutation is located within the coiled-coil domain present in the skin isoform of DST, BPGA1-e, associated with EBS. In summary, we report two families with pathogenic DST variants and expand the spectrum of DST genotype and phenotypes.

A novel variant in the dystonin gene causing hereditary sensory autonomic neuropathy type VI in a male infant: Case report and literature review.

The DST gene is located on chromosome 6p and encodes for a large protein. Alternative splicing of this protein produces the neuronal (a1-a3), muscular (b1-b3), and epithelial (e) isoforms. Hereditary sensory and autonomic neuropathy (HSAN) type VI is a rare autosomal recessive disorder due to mutations affecting the a2 isoform. We present a case of HSAN-VI in a male neonate born to consanguineous parents. Genome sequencing revealed a novel homozygous variant (DST_c.1118C > T; p.Pro373Leu) inherited from both parents. This case further expands the phenotype and genotype of this rare syndrome.

Implementation of a dermal sensitization threshold (DST) concept for risk assessment: structure-based DST and in vitro data-based DST.

Skin sensitization resulting in allergic contact dermatitis represents an important toxicological endpoint as part of safety assessments. When available substance-specific sensitization data are inadequate, the dermal sensitization threshold (DST) concept has been proposed to set a skin exposure threshold to provide no appreciable risk of skin sensitization. Structure-based DSTs, which include non-reactive, reactive, and high potency category (HPC) DSTs, can be applied to substances with an identified chemical structures. An in vitro data-based "mixture DST" can be applied to mixtures based on data from in vitro test methods, such as KeratinoSens™ and the human Cell Line Activation Test. The purpose of this review article is to discuss the practical use of DSTs for conducting sound sensitization risk assessments to assure the safety of consumer products. To this end, several improvements are discussed in this review. For application of structure-based DSTs, an overall structural classification workflow was developed to exclude the possibility that "HPC but non-reactive" chemicals are misclassified as "non-reactive", because such chemicals should be classified as HPC chemicals considering that HPC rules have been based on the chemical structure of high potency sensitizers. Besides that, an extended application of the mixture DST principle to mixtures that either is cytotoxic or evaluated as positive was proposed. On a final note, we also developed workflows that integrate structure-based and in vitro-based mixture DST. The proposed workflows enable the application of the appropriate DST, which serves as a point of departure in the quantitative sensitization risk assessment.

Overnight 1 mg dexamethasone suppression test and 24 h urine free cortisol-accuracy and pitfalls when screening for Cushing's syndrome.

Diagnosis of Cushing's syndrome (CS) is often delayed due to variable clinical features and its rarity. Simple and accurate screening tests are required to enhance screening for hypercortisolism. Both overnight 1 mg dexamethasone suppression test (DST) and urinary free cortisol (UFC) demonstrate high sensitivity and specificity for the diagnosis of CS. However, each test has its own distinctive features, making it preferable in specific clinical conditions. This review will discuss the pitfalls for each of those tests.

Updating the Dermal Sensitisation Thresholds using an expanded dataset and an in silico expert system.

The Dermal Sensitisation Thresholds (DST) are Thresholds of Toxicological Concern, which can be used to justify exposure-based waiving when conducting a skin sensitisation risk assessment. This study aimed to update the published DST values by expanding the size of the Local Lymph Node Assay dataset upon which they are based, whilst assigning chemical reactivity using an in silico expert system (Derek Nexus). The potency values within the expanded dataset fitted a similar gamma distribution to that observed for the original dataset. Derek Nexus was used to classify the sensitisation activity of the 1152 chemicals in the expanded dataset and to predict which chemicals belonged to a High Potency Category (HPC). This two-step classification led to three updated thresholds: a non-reactive DST of 710 µg/cm2 (based on 79 sensitisers), a reactive (non-HPC) DST of 73 µg/cm2 (based on 331 sensitisers) and an HPC DST of 1.0 µg/cm2 (based on 146 sensitisers). Despite the dataset containing twice as many sensitisers, these values are similar to the previously published thresholds, highlighting their robustness and increasing confidence in their use. By classifying reactivity in silico the updated DSTs can be applied within a skin sensitisation risk assessment in a reproducible, scalable and accessible manner.

Mediator complex subunit MED25 physically interacts with DST to regulate spikelet number in rice.

Grain number is a flexible trait and contributes significantly to grain yield. In rice, the zinc finger transcription factor DROUGHT AND SALT TOLERANCE (DST) controls grain number by directly regulating cytokinin oxidase/dehydrogenase 2 (OsCKX2) expression. Although specific upstream regulators of the DST-OsCKX2 module have been identified, the mechanism employed by DST to regulate the expression of OsCKX2 remains unclear. Here, we demonstrate that DST-interacting protein 1 (DIP1), known as Mediator subunit OsMED25, acts as an interacting coactivator of DST. Phenotypic analyses revealed that OsMED25-RNAi and the osmed25 mutant plants exhibited enlarged panicles, with enhanced branching and spikelet number, similar to the dst mutant. Genetic analysis indicated that OsMED25 acts in the same pathway as the DST-OsCKX2 module to regulate spikelet number per panicle. Further biochemical analysis showed that OsMED25 physically interacts with DST at the promoter region of OsCKX2, and then recruits RNA polymerase II (Pol II) to activate OsCKX2 transcription. Thus, OsMED25 was involved in the communication between DST and Pol II general transcriptional machinery to regulate spikelet number. In general, our findings reveal a novel function of OsMED25 in DST-OsCKX2 modulated transcriptional regulation, thus enhancing our understanding of the regulatory mechanism underlying DST-OsCKX2-mediated spikelet number.

Magnetic Resonance Imaging findings in pregnancy related neurological complications.

OBJECTIVE: To describe the various neurological complications that occur in pregnancy and puerperium using magnetic resonance imaging as the diagnostic tool. METHODS: The prospective study was conducted at the Radiology Department of Lady Reading Hospital, Peshawar, Pakistan, from June 2018 to June 2019, and comprised pregnant and puerperium patients presenting with neurological symptoms who were referred for magnetic resonance imaging. Clinical records of the patients were reviewed for risk factors and neurological symptomatology. Imaging was done using a 1.5Tesla machine. Departmental routine imaging protocols for magnetic resonance imaging brain and magnetic resonance venography were used. Data was analysed using SPSS 23. RESULTS: There were 60 pregnant women with a mean age of 25.85±5.1 years (range: 17-40 years). Magnetic resonance imaging showed posterior reversible encephalopathy syndrome in 20(33.3%) patients and haemorrhagic infarct in 18(30%), while 9(15%) were found to be normal. Magnetic resonance venography exhibited dural sinus thrombosis in 19(31.7%) patients. CONCLUSIONS: Magnetic resonance imaging was found to play a vital role in early diagnosis of pregnancy-related neurological complications.

Drug resistance patterns, treatment outcomes and factors affecting unfavourable treatment outcomes among extensively drug resistant tuberculosis patients in Pakistan; a multicentre record review.

Background: Extensively drug resistant tuberculosis (XDR-TB) is considered as a major threat to global health. This study aimed to analyse the treatment outcomes and identify the factors significantly associated with unfavourable treatment outcomes among XDR-TB patients. Methods: We conducted a retrospective observational study at 10 Programmatic Management Units of the National Tuberculosis Control Program of Pakistan. The Electronic Nominal Recording Reporting System records were used to collect data of all eligible XDR-TB patients registered at the study sites between March 2012 and August 2018. Treatment outcomes were analysed as per the standard criteria. Factors associated with unfavourable treatment outcomes were analysed by using multivariate binary logistic regression analysis. Results: Out of the total 184 patients, 59 (32.1%) completed their treatment successfully. Whereby, 83 patients (45.1%) died, 24 (13%) had treatment failure, and 11 (6%) were lost to follow-up. Treatment outcomes were not evaluated in 7 (3.8%) patients. Factors significantly associated with unfavourable treatment outcomes included; conventional therapy with bedaquiline, unfavourable interim treatment outcomes and occurrence of adverse drug events (negative association). Conclusion: Treatment success rate in the study cohort was sub-optimal (i.e., <75%). The poor success rate and high mortality are concerning, and requires immediate attention of the program managers and clinicians.

[Clinical Characteristics of Nontuberculous Mycobacterium Infection Cases in Sichuan, China in 2016-2021: A Retrospective Study].

Objective: To study the distribution of nontuberculous mycobacterium (NTM) strains, clinical characteristics and drug sensitivity data of NTM infections so as to provide support for the prevention and treatment of diseases caused by NTM infection in Sichuan. Methods: The clinical data of NTM infection cases treated at the Public Health Clinical Center of Chengdu between July 2016 and July 2021 were collected and the characteristics of the infections were retrospectively reviewed. Results: There were differences in sex, age and underlying diseases among the NTM infection cases in Sichuan. Specifically, young and middle-aged men aged between 20 and 40 were susceptible to AIDS, older men aged over 60 were susceptible to lung diseases, and middle-aged and older women over 40 were susceptible to bronchiectasis. Respiratory tract was the main route of NTM infection. The dominant strain in Sichuan was M. chelonae/ abscessus. The drug resistance rate of M. avium and M. chelonae/ abscessus were relatively higher. Conclusion: For NTM infection patients with different demographic characteristics and underlying diseases, the NTM infection sites, strains, and drug resistance are also different. Definite etiological diagnosis is essential to the treatment of NTM infection. We should highlight the importance of adopting individualized treatment for different NTM infections.

Design of Multidrug-Resistant Tuberculosis Treatment Regimens Based on DNA Sequencing.

BACKGROUND: Comprehensive and reliable drug susceptibility testing (DST) is urgently needed to provide adequate treatment regimens for patients with multidrug-resistant/rifampicin-resistant tuberculosis (MDR/RR-TB). We determined whether next-generation sequencing (NGS) analysis of Mycobacterium tuberculosis complex isolates and genes implicated in drug resistance can guide the design of effective MDR/RR-TB treatment regimens. METHODS: NGS-based genomic DST predictions of M. tuberculosis complex isolates from MDR/RR-TB patients admitted to a TB reference center in Germany between 1 January 2015 and 30 April 2019 were compared with phenotypic DST results of mycobacteria growth indicator tubes (MGIT). Standardized treatment algorithms were applied to design individualized therapies based on either genomic or phenotypic DST results, and discrepancies were further evaluated by determination of minimal inhibitory drug concentrations (MICs) using Sensititre MYCOTBI and UKMYC microtiter plates. RESULTS: In 70 patients with MDR/RR-TB, agreement among 1048 pairwise comparisons of genomic and phenotypic DST was 86.3%; 76 (7.2%) results were discordant, and 68 (6.5%) could not be evaluated due to the presence of polymorphisms with yet unknown implications for drug resistance. Importantly, 549 of 561 (97.9%) predictions of drug susceptibility were phenotypically confirmed in MGIT, and 27 of 64 (42.2%) false-positive results were linked to previously described mutations mediating a low or moderate MIC increase. Virtually all drugs (99.0%) used in combination therapies that were inferred from genomic DST were confirmed to be susceptible by phenotypic DST. CONCLUSIONS: NGS-based genomic DST can reliably guide the design of effective MDR/RR-TB treatment regimens.