Longitudinal artificial intelligence-based deep learning models for diagnosis and prediction of the future occurrence of polyneuropathy in diabetes and prediabetes.

OBJECTIVE: The objective of this study was to develop artificial intelligence-based deep learning models and assess their potential utility and accuracy in diagnosing and predicting the future occurrence of diabetic distal sensorimotor polyneuropathy (DSPN) among individuals with type 2 diabetes mellitus (T2DM) and prediabetes. METHODS: In 394 patients (T2DM=300, Prediabetes=94), we developed a DSPN diagnostic and predictive model using Random Forest (RF)-based variable selection techniques, specifically incorporating the combined capabilities of the Clinical Toronto Neuropathy Score (TCNS) and nerve conduction study (NCS) to identify relevant variables. These important variables were then integrated into a deep learning framework comprising Convolutional Neural Networks (CNNs) and Long Short-Term Memory (LSTM) networks. To evaluate temporal predictive efficacy, patients were assessed at enrollment and one-year follow-up. RESULTS: RF-based variable selection identified key factors for diagnosing DSPN. Numbness scores, sensory test results (vibration), reflexes (knee, ankle), sural nerve attributes (sensory nerve action potential [SNAP] amplitude, nerve conduction velocity [NCV], latency), and peroneal/tibial motor NCV were candidate variables at baseline and over one year. Tibial compound motor action potential amplitudes were used for initial diagnosis, and ulnar SNAP amplitude for subsequent diagnoses. CNNs and LSTMs achieved impressive AUC values of 0.98 for DSPN diagnosis prediction, and 0.93 and 0.89 respectively for predicting the future occurrence of DSPN. RF techniques combined with two deep learning algorithms exhibited outstanding performance in diagnosing and predicting the future occurrence of DSPN. These algorithms have the potential to serve as surrogate measures, aiding clinicians in accurate diagnosis and future prediction of DSPN.

The Effects of Biologics on Hematologic Malignancy Development in Patients with Ankylosing Spondylitis, Psoriasis, or Psoriatic Arthritis: A National Cohort Study.

Biologics are used for ankylosing spondylitis (AS), psoriasis, and psoriatic arthritis (PsA) treatment. The association between biologics and the development of hematologic malignancies is controversial, and data on patients with AS, psoriasis, and PsA are scarce. This retrospective cohort study used data from 2010 to 2020 from Taiwan's National Health Insurance Research Database (NHIRD). Patients with AS, psoriasis, and PsA were divided into a biologics and non biologics group after 1:10 propensity score matching. The hematologic malignancy incidences and the time-/dose-dependent effects on biologics were analyzed by Poisson regression to evaluate the incidence rate ratio (IRR). Of the 4157 biologics users and 38,399 non biologics users included in the study, 10 and 72 persons developed hematologic malignancies, respectively. Biologics only significantly increased the risk of hematologic malignancies in non-Hodgkin's lymphoma (IRR: 2.48, 95% confidence interval (CI): 1.28-4.80). Different treatment patterns, types of biologics prescribed, cumulative defined daily doses, comorbidities, and comedications did not significantly affect hematologic malignancy development. A significantly increased risk was observed when biologics had been prescribed for 1-2 years (IRR: 2.95, 95% CI: 1.14-7.67). Clinical professionals should be aware of a patients' risk of hematologic malignancies during the second year of biologic treatment.

Dual-Energy Computed Tomography for Evaluation of Breast Cancer Follow-Ups: Comparison of Virtual Monoenergetic Images and Iodine-Map.

Differentiating tumor tissue from dense breast tissue can be difficult. Dual-energy CT (DECT) could be suitable for making diagnoses at breast cancer follow-ups. This study investigated the contrast in DECT images and iodine maps for patients with breast cancer being followed-up. Chest CT images captured in 2019 were collected. Five cases of metastatic breast cancer in the lungs were analyzed; the contrast-to-noise ratio (for breast tissue and muscle: CNRb and CNRm, respectively), tumor-to-breast mammary gland ratio (T/B), and tumor-to-muscle ratio (T/M) were calculated. For 84 cases of no metastasis, monochromatic spectral and iodine maps were obtained to compare differences under various breast densities using the K-means algorithm. The optimal T/B, T/M, and CNRb (related to mammary glands) were achieved for the 40-keV image. Conversely, CNRm (related to lungs) was better for higher energy. The optimal balance was achieved at 80 keV. T/B, T/M, and CNR were excellent for iodine maps, particularly for density > 25%. In conclusion, energy of 80 keV is the parameter most suitable for observing the breast and lungs simultaneously by using monochromatic spectral images. Adding iodine mapping can be appropriate when a patient's breast density is greater than 25%.

Optimization of Emulsification Conditions on Ethanol Extract of Taiwanese Green Propolis Using Polysorbate and Its Immunomodulatory Effects in Broilers.

Beeswax and resin are the main components of propolis, both of which are hydrophobic. The use of emulsifiers helps to improve the extraction of active propolis compounds and makes them more widely used. In this study, we investigated the optimal parameters for the emulsification of Taiwanese green propolis (TGP) using different polysorbates (polysorbate-20, polysorbate-60, and polysorbate-80) and evaluated the effects on the immunomodulatory response in broilers. The results showed that 4 mg/mL of TGP in combination with 2% polysorbate-60 at 60 °C for 60 min significantly decreased the undissolved particle size of ethanol extract of TGP during the emulsification. The bioactive compounds of TGP, the propolins (C, D, F, G, and H), were also detected after emulsification. Supplementation of emulsified TGP (eTGP) in the drinking water of broilers before and after vaccination significantly enhanced the antibody titer response to infectious bronchitis virus at 28 days of age. In the lipopolysaccharide-challenged model, supplementation of eTGP in the drinking water of broilers decreased pro-inflammatory gene expression and increased anti-inflammatory gene expression. These results together suggested that the polysorbate-60 could effectively emulsify the ethanol extract of TGP. Moreover, eTGP could be used as a vaccine adjuvant and an immunomodulator to improve the immune response of broilers.

Cerebral capillary blood flow upsurge during REM sleep is mediated by A2a receptors.

Sleep is generally viewed as a period of recovery, but how the supply of cerebral blood flow (CBF) changes across sleep/wake states has remained unclear. Here, we directly observe red blood cells (RBCs) within capillaries, where the actual substance exchange between the blood and neurons/glia occurs, by two-photon microscopy. Across multiple cortical areas, average capillary CBF is largely increased during rapid eye movement (REM) sleep, whereas it does not differ between periods of active wakefulness and non-REM sleep. Capillary RBC flow during REM sleep is further elevated following REM sleep deprivation, suggesting that capillary CBF reflects REM sleep pressure. At the molecular level, signaling via adenosine A2a receptors is crucial; in A2a-KO mice, capillary CBF upsurge during REM sleep is dampened, and effects of REM sleep pressure are abolished. These results provide evidence regarding the dynamics of capillary CBF across sleep/wake states and insights to the underlying mechanisms.

Synthetic dysmobility screen unveils an integrated STK40-YAP-MAPK system driving cell migration.

Integrating signals is essential for cell survival, leading to the concept of synthetic lethality. However, how signaling is integrated to control cell migration remains unclear. By conducting a "two-hit" screen, we revealed the synergistic reduction of cell migration when serine-threonine kinase 40 (STK40) and mitogen-activated protein kinase (MAPK) were simultaneously suppressed. Single-cell analyses showed that STK40 knockdown reduced cell motility and coordination by strengthening focal adhesion (FA) complexes. Furthermore, STK40 knockdown reduced the stability of yes-associated protein (YAP) and subsequently decreased YAP transported into the nucleus, while MAPK inhibition further weakened YAP activities in the nucleus to disturb FA remodeling. Together, we unveiled an integrated STK40-YAP-MAPK system regulating cell migration and introduced "synthetic dysmobility" as a novel strategy to collaboratively control cell migration.

Lenvatinib Induces AKT/NF-κB Inactivation, Apoptosis Signal Transduction and Growth Inhibition of Non-small Cell Lung Cancer In Vivo.

BACKGROUND/AIM: Non-small cell lung cancer (NSCLC) is the most common type of lung cancer with poor prognosis. Lenvatinib is a multi-kinase inhibitor that has the potential to suppress tumor progression. Our previous study suggested that lenvatinib induces cytotoxicity and apoptosis in CL-1-5-F4 cells in vitro. However, whether lenvatinib suppresses NSCLC progression in vivo remains unclear. MATERIALS AND METHODS: Tumor growth inhibition and normal tissue toxicity evaluation following lenvatinib treatment were performed on CL-1-5-F4-bearing mice. RESULTS: Tumor growth calculated by caliper and living cell intensity decreased by lenvatinib treatment as analysed by bioluminescence imaging. Phosphorylation of AKT, NF-κB, and NF-κB downstream proteins involved in tumor progression were reduced by lenvatinib in the tumor tissue. No pathological changes were found in the liver, kidney, and spleen after lenvatinib treatment. CONCLUSION: Induction of apoptosis and suppression of AKT/NF-κB were associated with lenvatinib-induced inhibition of the progression of NSCLC in vivo.

Copine-7 is required for REM sleep regulation following cage change or water immersion and restraint stress in mice.

Sleep is affected by the environment. In rodents, changes in the amount of rapid eye movement sleep (REMS) can precede those of other sleep/wake stages. The molecular mechanism underlying the dynamic regulation of REMS remains poorly understood. Here, we focused on the sublaterodorsal nucleus (SLD), located in the pontine tegmental area, which plays a crucial role in the regulation of REMS. We searched for genes selectively expressed in the SLD and identified copine-7 (Cpne7), whose involvement in sleep was totally unknown. We generated Cpne7-Cre knock-in mice, which enabled both the knockout (KO) of Cpne7 and the genetic labeling of Cpne7-expressing cells. While Cpne7-KO mice exhibited normal sleep under basal conditions, the amount of REMS in Cpne7-KO mice was larger compared to wildtype mice following cage change or water immersion and restraint stress, both of which are conditions that acutely reduce REMS. Thus, it was suggested that copine-7 is involved in negatively regulating REMS under certain conditions. In addition, chemogenetically activating Cpne7-expressing neurons in the SLD reduced the amount of REMS, suggesting that these neurons negatively regulate REMS. These results identify copine-7 and Cpne7-expressing neurons in the SLD as candidate molecular or neuronal components of the regulatory system that controls REMS.

Variation in global distribution, population structures, and demographic history for four Trichiurus cutlassfishes.

BACKGROUND: Species-specific information on distribution and demographic patterns provides important implications for conservation and fisheries management. However, such information is often lacking for morphologically-similar species, which may lead to biases in the assessments of these species and even decrease effort towards sustainable management. Here, we aimed to uncover the distribution range, population structure and demographic history for four exploited Trichiurus cutlassfishes using genetics. These cutlassfishes contribute substantial global fisheries catch, with a high proportion of catch harvested from the NW Pacific. METHODS: We chose the widely available mitochondrial 16S ribosomal RNA (16S) as the genetic marker for cutlassfishes. We compiled the 16S sequence data from both the GenBank and a survey of trawler catch samples along the NW Pacific coasts 22-39°N. Genealogical relationships within each species was visualized with haplotype networks and potential population differentiations were further evaluated with AMOVA. Demographic histories were estimated using neutrality test, mismatch analysis, and the Bayesian skyline plot. The reconstructed phylogenetic trees were used to delimit and estimate the divergence time of species and included populations. RESULTS: In each of two cosmopolitan species, T. lepturus and T. nanhaiensis, we observed distinct populations along the coasts of warm oceans; such population differentiation might result from historical geographic barriers in the Pleistocene. In the NW Pacific, four Trichiurus species vary in their distribution habitats, which reflect differential ecological niches among these species. The small-sized T. brevis are primarily found in nearshore habitats; the warm-affiliated T. nanhaiensis are present along the path of the Kuroshio Current; the cold-affiliated T. japonicus spatially diverged from the widely-distributed T. lepturus, with the latter mainly occupy in warmer regions. Despite these differences, a single well-mixing fish stock, thus one management unit, was identified in each of the four species, presumably due to expansion of their population sizes predated the Last Glacial Maximum and a lack of distribution barrier. The most dominant T. japonicus, which have at least one magnitude higher effective population size than the others, show a unique abrupt size expansion event at 75 to 50-kilo years ago when the low sea level occurred during the ice age. MAIN CONCLUSIONS: The demographic history revealed by our genetic analyses advances understanding of the current distribution and population structure for these congeneric species. Moreover, the uncovered population structure provides insight into the assessment and management of these species. Such information complements contemporary knowledge about these species and enables us to forecast their ability to resist future environmental and anthropogenic disturbances.

Anticancer Efficacy and Mechanism of Amentoflavone for Sensitizing Oral Squamous Cell Carcinoma to Cisplatin.

BACKGROUND/AIM: Nuclear factor kappa B (NF-κB) inactivation and apoptosis activation have been shown to enhance the anticancer effect of cisplatin in oral squamous cell carcinoma (OSCC). Amentoflavone may suppress NF-κB activity and trigger apoptosis in different types of cancer. The aim of this study was to investigate the anticancer effect and mechanism of amentoflavone in combination with cisplatin in OSCC. MATERIALS AND METHODS: We investigated the combination effect and mechanism of amentoflavone and cisplatin via cell viability analysis, flow cytometry-based apoptosis analyses, transwell migration/invasion assay, immunofluorescence staining and western blotting assay. RESULTS: Both amentoflavone and QNZ (NF-κB inhibitor) significantly increased cisplatin-induced cytotoxicity. Amentoflavone reduced cisplatin-triggered NF-κB activity and enhanced cisplatin-induced intrinsic caspase-dependent and independent apoptotic pathways. Moreover, amentoflavone augments cisplatin-suppressed invasion and migration ability of OSCC cells. CONCLUSION: Inactivation of NF-κB and induction of apoptosis through intrinsic caspase-dependent and independent apoptotic pathways are associated with amentoflavone enhanced anti-OSCC efficacy of cisplatin.

The In Vivo Radiosensitizing Effect of Magnolol on Tumor Growth of Hepatocellular Carcinoma.

BACKGROUND/AIM: Radiation (RT) induced ERK/NF-κB in hepatocellular carcinoma (HCC) has been reported in our previous works; it weakens the toxicity of RT or triggers a radioresistance effect. Thus, combining RT with a suitable NF-κB inhibitor may sensitize HCC to RT. Magnolol, a bioactive compound, was known to have anti-inflammatory and anti-tumor functions. Here, we aimed to investigate whether magnolol may enhance anti-HCC efficacy of RT in vivo. MATERIALS AND METHODS: We established a Hep3B bearing mouse to evaluate the efficacy of the combination treatment of magnolol and RT. RESULTS: Most significantly, tumor volume and tumor weight inhibition was found in the combination group. Tumor immunohistochemistry staining also illustrated the suppression of RT-induced ERK/NF-κB-related proteins expression by magnolol. In addition, intrinsic apoptosis-related proteins, such as caspase-3 and -9, were markedly increased in the combination group. CONCLUSION: Magnolol may effectively enhance anti-HCC ability of RT by downregulating the expression of ERK/NF-κB-related proteins and increasing the expression of apoptosis-related proteins.

Quantitative evaluation of breast density using a dual-energy technique on a digital breast tomosynthesis system.

PURPOSE: Although breast density is considered a strong risk factor of breast cancer, its quantitative assessment is difficult. To investigate a quantitative method of measuring breast density using dual-energy mammographic imaging with central digital breast tomosynthesis in physically uniform and nonuniform phantoms. MATERIAL AND METHODS: The dual-energy imaging unit used a tungsten anode and silver filter with 30 kVp for high-energy images and 20 kVp for low-energy images. Uniform glandular-equivalent phantoms were used to calibrate a dual-energy based decomposition algorithm. The first study used uniform breast phantoms which ranged in thicknesses from 20 to 70 mm, in 10-mm increments, and which provided 30%, 50%, and 70% of breast density. The second study used uniform phantoms ranging from 10% to 90% of breast density. The third study used non-uniform phantoms (at an average density of 50%) with a thickness which ranged from 20 to 90 mm, in 10-mm increments. RESULTS: The root mean square error of breast density measurements was 2.64-3.34% for the uniform, variable thickness phantoms, 4.17% for the uniform, variable density phantoms, and 4.49% for the nonuniform, variable thickness phantoms. CONCLUSION: The dual-energy technique could be used to measure breast density with a margin of error of < 10% using digital breast tomosynthesis.

Mechanism and pathways underlying the self-sensitized photodegradation of methotrexate under simulated solar irradiation.

Methotrexate, a chemotherapeutic agent, was found to undergo self-sensitized photodegradation in aqueous environments. As the initial concentration increased, methotrexate was able to enhance its own direct photolysis reaction not only in DI but also in natural waters. The methotrexate degradation rate increased through the production of singlet oxygen (1O2), the triplet excited state of methotrexate (3MTX*), and the triplet excited state of the pteridine structure (3PT*) from the phototransformation byproducts. At low methotrexate concentrations (<20 ppb), 1O2 played an important role, whereas at higher methotrexate concentrations (>2000 ppb), the presence of oxygen decreased the overall methotrexate degradation rate by physically quenching 3MTX* and 3PT*. The cleavage of the CN bond resulted in a significant amount of byproducts: pteridine derivatives and N-(4-aminobenzoyl)-l-glutamic acid (yields: 13.5 ± 0.6% and 32.3 ± 2.2% for 10 ppm and 500 ppb MTX, respectively). The reactivity of the phototransformation byproducts and the substructures of methotrexate were investigated to help elucidate the proposed self-sensitized pathways. The results indicated that methotrexate as well as compounds containing a pteridine structure will generate pteridine byproducts during photodegradation and 3PT* is the primary triplet excited species that can cause self-sensitized photodegradation.

Feasibility and Characterization Mortar Blended with High-Amount Basic Oxygen Furnace Slag.

Basic oxygen furnace slag (BOFS) was ground to three levels of fineness as a replacement for cement at weight proportions of 10, 30, 50, and 70 wt.%. Fineness and weight proportion were shown to have significant effects on the flowability and setting time of the mortars. The expansion of BOFS mortars increased with an increase in the proportion of cement replaced, thereby exacerbating the effects of cracking. Optimal mechanical properties were achieved when 10 wt.% of the cement was replaced using BOFS with fineness of 10,000 cm²/g. The compressive strength of BOFS mortar is similar to that of ordinary Portland mortar, which makes BOFS suitable for the partial replacement of cement as a supplementary cementitious material. Scanning electron microscopy results revealed that the reaction of CaO with H2O results in the formation of C⁻S⁻H colloids, whereas the reaction of SiO2 with Al2O3 produces C⁻A⁻S⁻H colloids. The use of BOFS as a partial replacement for Portland cement could make a tremendous contribution to the steel industry and help to lower CO2 emissions.

The role of conformational heterogeneity in regulating the apoptotic activity of BAX protein.

While activation of BAX is required for initiating mitochondria-mediated apoptosis, the underlying mechanisms remain unsettled. We studied conformations of BAX protein using pressure- and temperature-resolved ESR techniques and obtained the thermodynamic properties of the conformations. We show that inactive BAX is structurally heterogeneous and exists in equilibrium between two major populations of the conformations, UM and UM', of which the former is thermodynamically favored at room temperature. An increase in the population of UM', induced by either pressure or point mutations of BAX, renders BAX susceptible to oligomerization, which leads to cell death. This study uncovers the biological significance of BAX conformations and shows that the pro-apoptotic activity of BAX can be triggered by altering the equilibrium between the two states. It suggests that therapeutic intervention may focus on shifting the balance in the conformational heterogeneity.

Investigation of an optimized scanning protocol for the dentomaxillofacial region using 320-slice multidetector computed tomography.

OBJECTIVES: To propose an imaging protocol that provides satisfactory image quality for oral examination while minimizing radiation dosage using 320-slice multidetector CT (MDCT). METHODS: An anthropomorphic head phantom was scanned using 320 MDCT with protocols combining different scanning modes: volume scanning (whole or local) vs helical scanning (80- or 64-slice detectors); tube voltage settings (80 kVp, 120 kVp and 135 kVp); and tube current settings (60 mA, 80 mA, 100 mA and 120 mA). A total of six anatomical bone structures and three anatomical soft-tissue structures were assessed using quantitative and qualitative analysis in the three orthographic planes (axial, sagittal and coronal). A figure of merit (FOM) was used to determine the optimal imaging protocol in terms of tube voltage, tube current and scanning mode. RESULTS: The 80-kVp setting had the worst quantitative and qualitative results (both p < 0.001) compared with the 135-kVp and 120-kVp settings, especially for soft-tissue structures. A significant difference was noted for the scores obtained using a tube current between 120 mA and 60 mA by quantitative analysis, but not by qualitative analysis. Volume scans using either whole or local modes had a significantly higher FOM than helical scanning of 80 or 64 slices. CONCLUSIONS: In 320 MDCT, a protocol using 135 kVp, 80 mA and the volume-scanning mode (whole or local) offers adequate visualization of both soft-tissue and bone structures while keeping the radiation dose as low as possible. This may therefore be considered a first choice among a wide selection of scanning protocols for dentomaxillofacial CT.

Acquisition of Mycobacterium abscessus among ventilator-dependent patients in Taiwan chronic respiratory care facilities.

AIM: To investigate the acquisition of Mycobacterium abscessus among ventilator-dependent patients. MATERIALS & METHODS: We prospectively recruited ventilator-dependent patients in five respiratory care wards (RCWs). Respiratory specimens were cultured for mycobacteria on day 1 (D1), 3 months (M3) and 6 months (M6) after enrollment. RESULTS: 72 patients had cultures taken at all three time points. The proportion of patients with a culture positive for M. abscessus increased from 15.3% (11/72) on D1 to 30.6% (22/72) at M3 and 38.9% (28/72) at M6. Two M. abscessus subspecies abscessus isolates obtained from different patients had identical randomly amplified polymorphic DNA patterns. Being in RCW D and advanced age were significantly associated with initial cultures positivity. CONCLUSION: Our study reveals that acquisition of M. abscessus was common among ventilator-dependent patients.

Local bone quality affects the outcome of prosthetic total knee arthroplasty.

Osteoporosis and osteoarthritis commonly coexist in the elderly. In patients undergoing prosthetic total knee arthroplasty (TKA), the bone quality around the knee joint may affect the safety of prosthetic implantation and consequently satisfaction with the surgical outcome. We recruited 50 postmenopausal women undergoing TKA for primary osteoarthritis; 43 completed the study protocol. The bone quality parameters of the operated knee, including bone mineral density assessed using dual-energy X-ray absorptiometry and microarchitecture variables assessed using micro-computed tomography, were determined. Surgical outcomes were assessed according to immediate (<1 week) postoperative pain quantified using the visual analog scale and knee function quantified using the Knee Injury and Osteoarthritis Outcome Score (KOOS) at 2 and 6 months postoperatively. The influence of bone quality parameters on surgical outcomes was analyzed using simple and multiple regression analyses. Volumetric bone mineral density (R(2) = 0.187-0.234, p < 0.01), the structural model index (R(2) = 0.103-0.181, p < 0.05), and trabecular separation (R(2) = 0.289-0.424, p < 0.05) were significantly associated with postoperative pain and improvement according to the KOOS. In conclusion, local bone quality, including mineral content and microarchitecture, affects the surgical outcome of TKA.

Identification of Weissella species by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.

Although some Weissella species play beneficial roles in food fermentation and in probiotic products, others such as Weissella confusa are emerging Gram-positive pathogens in immunocompromised hosts. Weissella species are difficult to identify by conventional biochemical methods and commercial automated systems and are easily misidentified as Lactobacillus and Leuconostoc species. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) is increasingly being used for bacterial identification. Little, however, is known about the effectiveness of MALDI-TOF MS in identifying clinical isolates of Weissella to the species level. In this study, we evaluated whether the MALDI-TOF MS Bruker Biotyper system could accurately identify a total of 20 W. confusa and 2 W. cibaria blood isolates that had been confirmed by 16s rRNA sequencing analysis. The MALDI-TOF Biotyper system yielded no reliable identification results based on the current reference spectra for the two species (all score values <1.7). New W. confusa spectra were created by randomly selecting 3 W. confusa isolates and external validation was performed by testing the remaining 17 W. confusa isolates using the new spectra. The new main spectra projection (MSP) yielded reliable score values of >2 for all isolates with the exception of one (score value, 1.963). Our results showed that the MSPs in the current database are not sufficient for correctly identifying W. confusa or W. cibaria. Further studies including more Weissella isolates are warranted to further validate the performance of MALDI-TOF in identifying Weissella species.

Plasma Biomarkers Can Predict Treatment Response in Tuberculosis Patients: A Prospective Observational Study.

Despite numerous studies, there has been little progress in the use of biomarkers for predicting treatment response in patients with tuberculosis (TB). Patients with culture-confirmed pulmonary TB between 2010 and 2014 were prospectively recruited. Blood samples were taken upon diagnosis and 2 months after the start of standard anti-TB treatment. A pilot study utilizing measurement of TB-antigen-stimulated cytokines was conducted to select potential biomarkers for further testing. Outcome was defined as persistent culture positivity at 2 months into treatment. Of 167 enrolled patients, 26 had persistent culture positivity. RANTES, IL-22, MMP-8, IL-18, MIG, and Granzyme A were selected as potential biomarkers. For predicting persistent culture positivity, receiver-operating characteristics (ROC) analysis showed that initial RANTES (AUC: 0.725 [0.624-0.827]) and 2-month MMP-8 (AUC: 0.632 [0.512-0.713]) had good discriminative ability. Using a logistic regression model, low initial RANTES level (< 440 pg/mL), initial smear positivity, and high 2-month MMP-8 level (> 3000 pg/mL) were associated with persistent culture positivity. Low initial RANTES level and initial smear positivity had a positive predictive value of 60% (12/20) for persistent culture positivity, compared with 4% (3/75) among patients with high RANTES level and smear negativity upon diagnosis. In the 72 patients with either low RANTES/smear negativity or high RANTES/smear positivity upon diagnosis, the 2-month MMP-8 level had a positive and negative predictive value of 24 and 94%, respectively, for 2-month culture status. Aside from an initial sputum smear status, serum RANTES level at diagnosis and MMP-8 level at 2 months of treatment may be used to stratify risk for culture persistence.