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Kuang-Ming Liao,1 Chao-Ming Hung,2 Chin-Chung Shu,3,4 Ho-Sheng Lee,5 Yu-Feng Wei6,7 1Department of Internal Medicine, Chi Mei Medical Center, Chiali, Tainan, Taiwan; 2Department of Surgery, E-Da Cancer Hospital, Kaohsiung, Taiwan; 3Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; 4National Taiwan University College of Medicine, Taipei, Taiwan; 5Division of Chest Medicine, Department of Internal Medicine, E-Da Hospital, Kaohsiung, Taiwan; 6School of Medicine for International Students, College of Medicine, I-Shou University, Kaohsiung, Taiwan; 7Department of Internal Medicine, E-Da Cancer Hospital, Kaohsiung, TaiwanCorrespondence: Yu-Feng WeiDepartment of Internal Medicine, E-Da Hospital, No. 1, Yida Road, Jiao-su Village, Yan-chao District, Kaohsiung, 824, TaiwanTel +886-7-6150011Fax +886-7-6150927Email yufeng528@gmail.comBackground: Limited studies have focused on the impact of the coexistence of small cell lung cancer (SCLC) and chronic obstructive pulmonary disease (COPD). The study was to examine the impact of COPD on mortality in SCLC patients.Methods: We analyzed SCLC patients from the Taiwan Cancer Registry Database between January 1, 1997, and December 31, 2015. The COPD population was composed of patients with a COPD diagnosis before the diagnosis of SCLC. The control group was composed of randomly selected SCLC patients without COPD who were propensity score matched with those with concomitant COPD according to age, sex, index date, cancer staging and comorbidities at a 1:1 ratio.Results: Among 9425 SCLC patients in the database, eligible subjects were divided into the COPD group (n = 4235) and the non-COPD group (n = 2334). Compared to patients in the non-COPD group, the patients in the COPD group were older (71.4 versus 65.7 years, p< 0.0001), had a lower percentage of stage IV disease (60.1% versus 68.3%, p< 0.0001) and had more comorbidities. After matching, there were 1457 patients in each group. Older age, lower body mass index (BMI), and some comorbidities were associated with higher mortality, and comorbid COPD was associated with lower 1-year mortality in SCLC patients. Multivariate analysis identified older age, lower BMI, and concomitant congestive heart failure or diabetes as risk factors for OS.Conclusion: A diagnosis of COPD was associated with reduced 1-year mortality in SCLC patients, but no significant difference after 1-year in this population.Keywords: chronic obstructive pulmonary disease, small cell lung cancer

Background: Vitamin D deficiency is prevalent worldwide and associated with worse outcomes in various lung diseases. This study examines the association between vitamin D deficiency and pulmonary function in healthy young adults., Methods: This prospective cohort study (2017-2019) explored the impact of vitamin D deficiency on pulmonary function in a community-based young adult population. Pulmonary function was assessed via spirometry, with serum 25-hydroxyvitamin D [25(OH)D] and urinary copper levels quantified. Multivariate regression was used to estimate the relationship between vitamin D levels and lung function, with mediation analysis evaluating copper's role., Results: The study included 1034 participants, average age 33.45 years, 41.93 % male. The median 25(OH)D level was 19.20 ng/mL (Interquartile Range: 13.48-24.90 ng/mL). Over half (54.74 %) had 25(OH)D levels below 20 ng/mL. Higher 25(OH)D levels were associated with better forced vital capacity (FVC) and forced expiratory volume in one second (FEV₁). Trends suggested subgroup differences, but these were not statistically significant, indicating a consistent effect of 25(OH)D on pulmonary function across groups. SEM analysis suggested urinary copper as a mediator between 25(OH)D levels and FVC., Conclusion: Vitamin D deficiency is significantly associated with reduced pulmonary function in young adults in Taiwan., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper, (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Enzymatic reactions are essential for most cellular reactions and ubiquitous in living organisms. In the present study, we explore the pivotal role of the reverse reaction in enzymatic reactions. It is a powerful noise-buffering motif. By SSA (stochastic simulation algorithm), a remarkable 32% reduction of product CV (coefficient of variation) was observed. To better understand the causes, we split the upstream noise. The product CV reduction is more than 35% for the noise inherited from the enzyme but merely 6%-21% for that from the substrate. It implies that the system applies different strategies to different upstream noises. We identified two leading causes responsible for noise attenuation. A cell is well designed to control its intracellular noise, and to acquire wisdom from nature is always enjoyable., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Che-Chi Shu reports financial support was provided by National Science and Technology Council. Other authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Coherent control of molecular photodissociation through one-photon transitions has become a topic of interest in physical chemistry. Previous studies have shown that modulating the spectral phase of a single ultrafast laser pulse while keeping its spectral amplitude constant does not affect the dissociation yield of reactions originating from a pure eigenstate of the ground electronic state. Here, we explore the indirect photodissociation reaction of NaI molecules using theoretical and numerical methods. Our findings show that, in contrast to the outcomes achieved with negatively chirped pulses, time-dependent population of the eigenstates of the excited adiabatic potential induced by positively chirped laser pulses, acting as intermediates in the reaction, cannot be periodically restored to that caused by the unchirped pulse. This gives rise to an intriguing phenomenon: the sign of the pulse's chirp rate influences the distribution of dissociation fragments in coordinate and momentum space over extended periods. This work highlights the potential of using spectral-phase modulated pulses to manipulate indirect photodissociation reactions, offering a way to modify the transient photofragment distributions by controlling reaction intermediates.

Purpose: Mycobacterium abscessus complex (MABC) commonly causes lung disease (LD) and has a high treatment failure rate of around 50%. In this study, our objective is to investigate specific CT patterns for predicting treatment prognosis and monitoring treatment response, thus providing valuable insights for clinical physicians in the management of MABC-LD treatment., Methods: We retrospectively assessed 34 patients with MABC-LD treated between January 2015 and December 2020. CT scores for bronchiectasis, cellular bronchiolitis, consolidation, cavities, and nodules were measured at initiation and after treatment. The ability of the CT scores to predict treatment outcomes was analyzed in logistic regression analyses., Results: The CT scoring system had excellent inter-reader agreement (all intraclass correlation coefficients, > 0.82). The treatment failure (TF) group (17/34; 50%) had higher cavitation diameter (p = 0.049) and extension (p = 0.041) at initial CT and higher cavitation diameter (p = 0.049) and extension (p =0 .045), consolidation (p = 0.022), and total (p = 0.013) scores at follow-up CT than the treatment success (TS) group. The changes of total score and consolidation score (p = 0.049 and 0.024, respectively) increased in the TF group more than the TS group between the initial and follow-up CT. Multivariable logistic regression analysis showed initial cavitation extension, follow-up consolidation extension, and change in consolidation extension (adjusted odds ratio: 2.512, 2.495, and 9.094, respectively, per 1-point increase; all p < 0.05) were significant predictors of treatment failure., Conclusions: A high pre-treatment cavitation extension score and an increase in the consolidation extension score during treatment on CT could be alarm signs of treatment failure requiring tailor the treatment of MABC-LD carefully., (© 2024. The Author(s).)

Background: In bronchiectasis, nontuberculous mycobacteria (NTM) lung disease (NTM-LD) is a well-known coexisting infection. However, microorganism coisolates and clinical NTM-LD predictors are poorly studied., Methods: Patients with bronchiectasis diagnosed by means of computed tomography between January 2017 and June 2020 were screened, using the date of computed tomography as the index date. Those with a major bronchiectasis diagnosis in ≥2 follow-up visits after the index date were enrolled in the study, and NTM-LD occurrence and its association with pneumonia and hospitalization within 1 year were analyzed., Results: Of the 2717 participants, 79 (2.9%) had NTM-LD diagnosed. The factors associated with NTM-LD included hemoptysis, postinfectious bronchiectasis, a tree-in-bud score ≥2, a modified Reiff score ≥4, and chronic obstructive pulmonary disease (adjusted odds ratios, 1.80, 2.36, 1.78, 2.95, and 0.51, respectively). Compared with patients in the non-NTM group, those with NTM-LD had higher rates of hospitalization (15.9% vs 32.9%; P < .001) and pneumonia (9.8% vs 20.3%; P = .003). Pseudomonas aeruginosa was the most common microorganism in those with NTM-LD and those in the non-NTM group (10.1% vs 7.8%; P = .40). However, compared with those in the non-NTM group, Acinetobacter baumannii and Escherichia coli were more prevalent in patients with NTM-LD (0.7% vs 3.8% [ P = .03%] and 1.0% vs 3.8% [ P = .05], respectively)., Conclusions: Postinfectious bronchiectasis with hemoptysis, higher radiological involvement, and a tree-in-bud pattern were associated with NTM-LD risk. The rate of A baumannii and E coli coisolation was higher in bronchiectasis populations with NTM-LD., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: While all-cause mortality is reportedly increased in preserved ratio impaired spirometry (PRISm), no remedial efforts have been suggested., Aim: To study the ability of physical activity (PA) on reducing the morality increased in PRISm patients., Design: We prospectively enrolled a cohort of Taiwanese adults from 1994 to 2018 in a health surveillance program., Methods: Mortality risks of those who were inactive were compared against those meeting the current recommendation of 150 min/week of PA. Cox proportional hazards models were used for hazard ratios and life table method was for estimating loss of life expectancy., Results: A total of 461 183 adults were enrolled. Among them, one-seventh of the cohort (65 832 or 14.3%) had PRISm, and 53.1% were inactive. Those who were inactive with PRISm had 28% increased mortality from all-cause, 45% from cardiovascular diseases (CVDs) and 67% from respiratory disease, with a 3-year reduction in life expectancy (males, 3.72 and females, 2.93). In PRISm patients who met the exercise recommendation, excess mortality was reduced by two-third, both all-cause (from 28% to 9%) and CVD (from 45% to 15%)., Conclusion: PRISm involves a large portion of general population (14.3%) and shortens life expectancy by 3 years. More than half of the subjects were physically inactive, and adherence to 150 min/week of PA was associated with a two-third reduction of excess mortality from all cause and from CVD. Recommending PA among those with PRISm might be highly beneficial, although exercise alone may not eliminate all risks associated with PRISm., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Association of Physicians. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Tuberculosis (TB) remains prevalent worldwide, and anti-TB drugs are associated with drug-induced liver injury (DILI). Statins have pleiotropic effects which may decrease inflammation and achieve immunomodulation. However, few studies have investigated the pleiotropic effects of statins on the risk of DILI. The purpose of this study was to investigate whether statins prevent anti-tuberculosis DILI among active TB patients on standard anti-TB drug therapy., Methods: We conducted a hospital-based retrospective cohort study using claims data from the Integrated Medical Database of National Taiwan University Hospital (NTUH-iMD). Patients with a positive TB culture were included. The use of statins was defined as a daily equivalent dose >0.5 mg of pitavastatin. Deterioration in liver function was evaluated according to elevated liver enzyme levels. The primary and secondary endpoints were the DILI and the severe DILI. The prognostic value of statins was evaluated by Kaplan-Meier analysis, and Cox proportional hazards models., Results: A total of 1312 patients with a diagnosis of TB and receiving anti-TB treatment were included. During the study period, 193 patients had the DILI and 140 patients had the severe DILI. Kaplan-Meier analysis showed a significant difference between the usual statin users and controls in the DILI. In multivariable Cox proportional hazards analysis, statins showed a protective effect against the primary and secondary endpoints. In addition, the protective effect of statins showed a dose-response relationship against the DILI., Conclusion: Statin treatment had a protective effect against the risk of anti-TB DILI with a positive dose-response relationship., Competing Interests: Declaration of competing interest All authors declared no conflict of interests., (Copyright © 2024. Published by Elsevier B.V.)

Inorganic fullerene clusters have attracted widespread attention due to their highly symmetrical geometric structures and intrinsic electronic properties. However, cage-like clusters composed of heavy metal elements with high symmetry are rarely reported, and their synthesis is also highly challenging. In this study, we present the synthesis of a [K 2 (Bi@Pd 12 @Bi 20 )] 4- cluster that incorporates a {Bi 20 } cage with pseudo - I h symmetry, making it the largest main group metal cluster compound composed of the bismuth element to date. Magnetic characterization and theoretical calculations suggest that the spin state of the overall cluster is a quartet. Quantum chemical calculations reveal that the [Bi 20 ] 3- cluster has a similar electronic configuration to C 60 6- and the [Bi@Pd 12 @Bi 20 ] 6- cluster exhibits a unique open-shell aromatic character.

Background: It has been known that smoking and various lung diseases including lung cancer can cause lung function impairment. However, the impact of different types of lung function impairments, such as preserved ratio impaired spirometry (PRISm) and airflow obstruction (AO), on the incidence and mortality of lung cancer in both general and never-smoker populations remains unclear. We wished to examine the effect of lung function impairments on lung cancer risks., Methods: This was a retrospective cohort study (1 January 1994 to 31 December 2017) of individuals from a health surveillance programme in Taiwan who underwent baseline spirometry tests at the entry point. PRISm was defined as an FEV 1 /FVC (forced expiratory volume in 1 s/forced vital capacity) ratio >0.7 and FEV 1 <0.8, while AO was defined as an FEV 1 /FVC ratio <0.7. Cox proportional hazards models and cubic spline curves were used to examine the associations between lung function impairments and lung cancer risks., Results: The study included 461,183 individuals, of whom 14.3% had PRISm and 7.9% had AO. A total of 4038 cases of lung cancer and 3314 lung cancer-related deaths were identified during the 23 years of follow-up. Individuals with PRISm and AO exhibited a higher risk of lung cancer incidence and mortality compared with those with normal lung function. The adjusted HRs and 95% CIs were 1.14 (1.03 to 1.26) and 1.23 (1.10 to 1.37) in the overall cohort, and 1.08 (0.93 to 1.24), and 1.23 (1.05 to 1.45) in the never-smoker cohort. The risks of both developing and dying of lung cancer increased with the severity levels of lung function impairments and lower FEV 1 values., Conclusion: Impaired lung function is associated with increased risks of developing lung cancer and subsequent mortality. The study highlights the importance of considering lung function in lung cancer screening for better candidate selection., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: Non-tuberculous mycobacterial (NTM) lung disease (NTM-LD) prevalence is increasing worldwide. In this study, we aimed to evaluate the clinical significance of NTM pulmonary isolates (NTM-PI) and NTM-LD in patients with systemic autoimmune disease (SAD) who had a concurrent interstitial lung disease (ILD) diagnosis., Methods: We retrospectively identified patients with SAD who had a concurrent ILD diagnosis (SAD-ILD) and from whom clinically indicated sputum specimens were collected for NTM culture between 2003 and 2018 at a tertiary referral hospital. We analysed the prevalence and risk factors of NTM pulmonary isolates (NTM-PI; ≥1 positive culture) and NTM-LD (≥2 positive cultures)., Results: This study included 258 patients. Rheumatoid arthritis and Sjögren's syndrome were the most common SADs (32.2% and 26.7%, respectively). The NTM-negative subgroup had 204 patients (79.1%) and the NTM-PI subgroup had 54 patients (20.9%). In the NTM-PI subgroup, 33 patients had one NTM positive set of specimens (NTM 1+, 12.8% of the entire sample) and 21 had NTM-LD (8.1% of the entire sample). In a multivariable analysis, chronic kidney disease (CKD; adjusted odds ratio [aOR]: 3.10 [1.53, 6.29]) and chronic obstructive pulmonary disease (COPD; aOR: 2.59 [1.16, 5.78]) were significantly associated with NTM-PI. For NTM-LD, CKD (aOR: 2.79 [1.00, 7.76]) and COPD (aOR: 3.70 [1.23, 10.72]) remained significant risk factors., Conclusions: In patients with SAD-ILD, the NTM-PI and NTM-LD prevalence rates were 20.9% and 8.1%, respectively. COPD and CKD were independent risk factors of both NTM-PI and NTM-LD. Previous use of biological agents was associated with NTM-PI.

Objective: Reports of tuberculosis (TB) during anticancer treatment with immune checkpoint inhibitors (ICIs) are increasing. However, it is not clear whether the use of ICIs is a significant risk factor for TB, including reactivation or latent TB infection (LTBI)., Methods: To determine the risk of TB reactivation in patients with lung cancer who use ICIs or tyrosine kinase inhibitors (TKIs), we conducted a retrospective study using a hospital-based cancer registry. In addition, we monitored patients with cancer using ICI or TKI in a multicenter prospective study to check the incidence of LTBI., Results: In the retrospective study, several demographic factors were imbalanced between the ICI and TKI groups: the ICI group was younger, had more males, exhibited more squamous cell carcinoma in histology rather than adenocarcinoma, had fewer EGFR mutations, and received more chemotherapy. Propensity score matching was used to control for confounding factors, and we found that the incidence of TB was higher among patients with lung cancer who received ICIs than among those who received TKIs (2298 vs 412 per 100 000 person-years, P = .0165). Through multivariable analysis, group (ICI vs TKI) was the independent risk factor for TB development (adjusted hazard ratio (aHR): 6.29, 95% CI, 1.23-32.09, P = .0269). In the prospective cohort, which included 72 patients receiving ICIs and 50 receiving TKIs, we found that the incidence of positive seroconversion of LTBI by interferon gamma release assay (IGRA) was significantly higher in patients receiving ICIs (18% vs 0%, aHR: 9.88, P = 0.035) under multivariable Cox regression., Conclusion: The use of ICIs may be linked to a higher likelihood of TB reactivation and LTBI than individuals solely receiving TKIs as anticancer therapy. Consequently, the implementation of a screening program for TB reactivation and LTBI among patients undergoing ICI treatment could prove advantageous by enabling early detection and prompt treatment of the infection., (© The Author(s) 2024. Published by Oxford University Press.)

Background: This study investigates the impact of nontuberculous mycobacterial lung disease (NTM-LD) on mortality and mechanical ventilation use in critically ill patients., Methods: We enrolled patients with NTM-LD or tuberculosis (TB) in intensive care units (ICU) and analysed their association with 30-day mortality and with mechanical ventilator-free survival (VFS) at 30 days after ICU admission., Results: A total of 5996 ICU-admitted patients were included, of which 541 (9.0 %) had TB and 173 (2.9 %) had NTM-LD. The overall 30-day mortality was 22.2 %. The patients with NTM-LD had an adjusted hazard ratio (aHR) of 1.49 (95 % CI, 1.06-2.05), and TB patients had an aHR of 2.33 (95 % CI, 1.68-3.24), compared to ICU patients with negative sputum mycobacterial culture by multivariable Cox proportional hazard (PH) regression. The aHR of age<65 years, obesity, idiopathic pulmonary fibrosis, end-stage kidney disease, active cancer and autoimmune disease and diagnosis of respiratory failure were also significantly positively associated with ICU 30-day mortality. In multivariable Cox PH regression for VFS at 30 days in patients requiring invasive mechanical ventilation, NTM-LD was negatively associated with VFS (aHR 0.71, 95 % CI: 0.56-0.92, p = 0.009), while TB showed no significant association. The diagnosis of respiratory failure itself predicted unfavourable outcome for 30-day mortality and a negative impact on VFS at 30 days., Conclusions: NTM-LD and TB were not uncommon in ICU and both were correlated with increasing 30-day mortality in ICU patients. NTM-LD was associated with a poorer outcome in terms of VFS at 30 days., Competing Interests: Declaration of competing interest All authors have reported that they have no financial or nonfinancial conflicts of interest related to this work., (Copyright © 2024. Published by Elsevier B.V.)

Regarding clinically-concerning non-standard initial anti-tuberculous (TB) regimens, few studies have examined their prevalence, risk factors and impacts. We recruited patients with drug susceptible TB and non-standard initial anti-TB regimens (NSTB group) and matched them with patients with standard initial regimens (STB group) in a 1:1 ratio. The risk factors and outcomes were analyzed. During the 11-year study period, we analyzed 50 (3.7%) patients with NSTB from a total set of 1337 patients with drug-susceptible TB. Pyrazinamide (60%) was the drug most commonly not prescribed in the NSTB group, followed by ethambutol (34%). Multivariable logistic regression identified independent risk factors as underlying eye disease (adjusted odds ratio [aOR]: 8.869; 95% CI 2.542-30.949; p = 0.001), gout/hyperuricemia (aOR: 4.012 [1.196-13.425]; p = 0.024), and liver disease (aOR: 12.790 [3.981-41.089]; p < 0.001). The NSTB group had longer treatment durations (281 ± 121 vs. 223 ± 63 days; p = 0.003) and more occurrences of treatment interruption (26% vs. 8%; p = 0.021) than the STB group. In conclusion, NSTB occurs in around 3.7% of patients and is associated with longer treatment and more treatment interruption. The risk factors might include underlying liver and eye diseases, and gout. Further studies to improve non-standard initial regimens and prevent negative outcomes are warranted., (© 2024. The Author(s).)

We report here the synthesis and characterization of two endohedral Zintl-ion clusters, [Fe 4 Sn 18 ] 4- and [Fe 4 Pb 18 ] 4- , which contain rhombic Fe 4 cores. The Fe-Fe bond lengths are all below 2.5 Å, distinctly shorter than in the corresponding Cu clusters, indicating the presence of Fe-Fe bonding. Subtle differences in the structure of the Fe 4 core between the two clusters suggest that the change in tetrel element causes a change in electronic ground state, with a very short Fe-Fe bond length of 2.328 Å present across the diagonal of the rhombus in the lead case., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Background: Chronic airway diseases have been associated with an increased risk of tuberculosis (TB); however, data in patients with bronchiectasis is limited. Statins have been shown to exhibit anti-inflammatory effects by modulating the inflammatory response. This study investigated whether statin treatment could reduce the risk of TB in patients with bronchiectasis., Methods: We conducted a retrospective cohort study using a nationwide population database of patients with bronchiectasis who did or did not receive statin treatment. The defined daily dose (DDD) of statin, current or past statin user and statin exposure time were measured for the impact of statin use. The primary outcome was the incidence of new-onset TB. Considering of potential immortal time bias due to stain exposure time, Cox regression models with time-dependent covariates were employed to estimate HRs with 95% CIs for TB incidence among patients with bronchiectasis., Results: Patients with bronchiectasis receiving statin treatment had a decreased risk of TB. After adjusting for age, sex, income, comorbidities and Charlson Comorbidity Index, statin users had a 0.59-fold lower risk of TB incidence compared with non-statin users (95% CI 0.40 to 0.88; p=0.0087). Additionally, compared with non-statin users, statin treatment was a protective factor against TB in users with a cumulative DDD greater than 180 per year, with an HR of 0.32 (95% CI 0.12 to 0.87; p=0.0255)., Conclusions: Statin treatment demonstrated a dose-dependent protective effect and was associated with a reduced risk of TB in patients with bronchiectasis. These findings suggest that statins may play a role in lowering TB risk by modulating airway inflammation in this patient population., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

BACKGROUND: The importance of early intravenous (IV) antibiotic use for Mycobacterium abscessus complex lung diseases (MABC-LD) treatment remains unknown. METHODS: A retrospective multi-centre observational study was conducted in Taiwan. Patients who were diagnosed with and received treatment for MABC-LD from January 2007 to April 2021 were included. Treatment outcome was defined as modified microbiological cure of MABC-LD. RESULTS: Of the 89 enrolled patients, 34 (38.2%) received IV antibiotics as part of the treatment regimen. The median time to IV initiation was 1 day (IQR 1???49); 24 (70.6%) of these patients received IV agents within 4 weeks, defined as early-use. Forty-two (47.2%) patients achieved modified microbiological cure. In the multivariable logistic analysis, early IV antibiotic use was an independent factor associated with modified microbiological cure (aOR 5.32, 95% CI 1.66???17.00), whereas high radiological score (aOR 0.86, 95% CI 0.73???1.00) demonstrated negative association. CONCLUSIONS: In the present study, early use of effective IV antibiotic was prescribed in a low percentage (27%) for MABC-LD. By contrast, early IV antibiotic use was correlated with higher microbiological cure than were late or non-use. Future larger and prospective studies are needed to validate the association.

Objectives: Persistent growth of Mycobacterium abscessus complex (MABC) in the respiratory system is not uncommon and may indicate continuous infection of MABC lung disease (MABC-LD), but its prevalence, risk factors, and clinical impact have not been investigated., Methods: The present study was conducted in two medical centers in northern Taiwan. We enrolled patients with MABC-LD and investigated the prevalence and predictors of persistent culture positivity (MABC-PP). Furthermore, we analyzed the association between MABC-PP and radiographic or clinical progression., Results: Among 189 patients with MABC-LD, 58 were in the MABC-PP group. Independent predictors for MABC-PP included an increasing radiographic score and highest acid-fast stain (AFS) of strong positivity (3-4+) at initial diagnosis (compared with negative AFS). MABC-PP and highest AFS were independently associated with MABC-LD progression by the multivariable analysis model. The adjusted hazard ratio increased to 3.56 when the two independent factors existed., Conclusions: MABC-PP accounted for 30.7% and was predicted by initial AFS grade and radiographic score. Patients with MABC-PP, and highest AFS grade might have disease progression., Competing Interests: Declaration of Competing Interest All authors declare no conflict of interest., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose: The treatment advantage of guideline-based therapy (GBT) in Mycobacterium avium complex lung disease (MAC-LD) is well-known. However, GBT is not always feasible. The aim of the study was to analyze the relationship of treatment regimens and duration with outcomes., Materials and Methods: This study screened patients with MAC-LD from Jan 2011 to Dec 2020 and enrolled those who received treatment. The treatment regimens were categorized to triple therapy (three active drugs) and non-triple therapy. The favorable outcomes included microbiological cure or clinical cure if no microbiologic persistence., Results: A total of 106 patients with MAC-LD were enrolled. Among them, 88 subjects (83 %) received triple therapy, 58 (54.7 %) had MAC treatment >12 months, and 66 (62.3 %) had favorable outcomes. Patients receiving triple therapy (90.9 % vs. 67.5 %, p = 0.008) and treatment >12 months (62.1 % vs. 42.5 %, p = 0.07) had higher proportion of favorable outcomes than unfavorable outcomes. Multivariable logistic regression analysis showed that age >65, comorbidities of COPD and prior tuberculosis, low hemoglobin, and high MAC burden were independent risk factors of unfavorable outcome. In contrast, triple therapy (OR: 0.018, 95 % CI: 0.04-0.78, p = 0.022) and treatment duration >12 months (OR: 0.20, 95 % CI: 0.055-0.69, p = 0.012) were protective factors against unfavorable outcome., Conclusions: Triple therapy including GBT, and treatment more than 12 months achieved more favorable outcome. Maintenance of triple therapy, but not reducing the number of active drugs, might be an acceptable alternative of GBT., Competing Interests: Conflicts of interest All of the authors declare no conflict of interest., (Copyright © 2023. Published by Elsevier B.V.)

The role of gut microbiota in host defense against nontuberculous mycobacterial lung disease (NTM-LD) was poorly understood. Here, we showed significant gut microbiota dysbiosis in patients with NTM-LD. Reduced abundance of Prevotella copri was significantly associated with NTM-LD and its disease severity. Compromised TLR2 activation activity in feces and plasma in the NTM-LD patients was highlighted. In the antibiotics-treated mice as a study model, gut microbiota dysbiosis with reduction of TLR2 activation activity in feces, sera, and lung tissue occurred. Transcriptomic analysis demonstrated immunocompromised in lung which were closely associated with increased NTM-LD susceptibility. Oral administration of P. copri or its capsular polysaccharides enhanced TLR2 signaling, restored immune response, and ameliorated NTM-LD susceptibility. Our data highlighted the association of gut microbiota dysbiosis, systematically compromised immunity and NTM-LD development. TLR2 activation by P. copri or its capsular polysaccharides might help prevent NTM-LD.

We present a theoretical investigation into the coherent control of photodissociation reactions in halomethanes, specifically focusing on CH 2 BrCl by manipulating the spectral phase of a single femtosecond laser pulse. We examine the photodissociation of CH 2 BrCl under an ultrashort pulse with a quadratic spectral phase and reveal the sensitivity of both the total dissociation probability and the resulting radical products (Br+CH 2 Cl and Cl+CH 2 Br) to chirp rates. To gain insights into the underlying mechanism, we calculate the population distributions of excited vibrational states in the ground electronic state, demonstrating the occurrence of resonance Raman scattering (RRS) in the strong-field limit regime. By utilizing chirped pulses, we show that this RRS phenomenon can be suppressed and even eliminated through quantum destructive interference. This highlights the high sensitivity of photodissociation into Cl+CH 2 Br to the spectral phase, showcasing a phenomenon that goes beyond the traditional one-photon photodissociation of isolated molecules in the weak-field limit regime. These findings emphasize the importance of coherent control in the exploration and utilization of photodissociation in polyatomic molecules, paving the way for new advancements in chemical physics and femtochemistry.

Generating field-free (non-stationary) orientation of molecules in space has been a longstanding goal in the field of quantum control of molecular rotation, which has significant applications in physical chemistry, chemical physics, strong-field physics, and quantum information science. In this Perspective, we review and examine several representative control schemes developed in recent years and implemented in theoretical and experimental areas for generating field-free orientation of molecules. By conducting numerical simulations of different control schemes on the same molecular system, we demonstrate that quantum coherent control, specifically targeting a limited number of the lowest-lying rotational levels to achieve an optimal superposition, can result in a high degree of orientation. To this end, we provide an overview of our latest developed analytical method, which enables the precise design of terahertz field parameters through resonant excitation. This design approach facilitates the attainment of desired field-free orientations by optimizing the amplitudes and phases of rotational wave functions for the selected rotational levels. Finally, we outlook the significance of such progress in multiple frontier research fields, highlighting its potential applications in ultracold physics, quantum computation, quantum simulation, and quantum metrology.

The endohedral Zintl-ion cluster [Fe 3 Sn 18 ] 4- contains a linear Fe 3 core with short Fe-Fe bond lengths of 2.4300(9) Å. The ground state is a septet, with significant σ and π contributions to the Fe-Fe bonds. The Sn 18 cage is made up of two partially fused Sn 9 fragments, and is structurally intermediate between [Ni 2 CdSn 18 ] 6- , where the fragments are clearly separated and [Pd 2 Sn 18 ] 4- , where they are completely fused. It therefore represents an intermediate stage in cluster growth. Analysis of the electronic structure suggests that the presence of the linear Fe-Fe-Fe unit is an important factor in directing reactions towards fusion of the two Sn 9 units rather than the alternative of oligomerization via exo bond formation., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Objectives: Histological scoring remains the gold-standard for quantifying post-traumatic osteoarthritis (ptOA) in animal models, allowing concurrent evaluation of numerous joint tissues. Available systems require scoring multiple sections/joint making analysis laborious and expensive. We investigated if a single section allowed equivalent quantitation of pathology in different joint tissues and disease stages, in three ptOA models., Method: Male 10-12-week-old C57BL/6 mice underwent surgical medial-meniscal-destabilization, anterior-cruciate-ligament (ACL) transection, non-invasive-ACL-rupture, or served as sham-surgical, non-invasive-ACL-strain, or naïve/non-operated controls. Mice (n = 12/group) were harvested 1-, 4-, 8-, and 16-week post-intervention. Serial sagittal toluidine-blue/fast-green stained sections of the medial-femoro-tibial joint (n = 7/joint, 84 µm apart) underwent blinded scoring of 40 histology-outcomes. We evaluated agreement between single-slide versus entire slide-set maximum or median scores (weighted-kappa), and sensitivity/specificity of single-slide versus median/maximum to detect OA pathology., Results: A single optimal mid-sagittal section showed excellent agreement with median (weighted-kappa 0.960) and maximum (weighted-kappa 0.926) scores. Agreement for individual histology-outcomes was high with only 19/240 median and 15/240 maximum scores having a weighted-kappa ≤0.4, the majority of these (16/19 and 11/15) in control groups. Statistically-significant histology-outcome differences between ptOA models and their controls detected with the entire slide-set were reliably reproduced using a single slide (sensitivity >93.15%, specificity >93.10%). The majority of false-negatives with single-slide scoring were meniscal and subchondral bone histology-outcomes (89%) and occurred in weeks 1-4 post-injury (84%)., Conclusion: A single mid-sagittal slide reduced the time needed to score diverse histopathological changes by 87% without compromising the sensitivity or specificity of the analysis, across a variety of ptOA models and time-points., Competing Interests: Declaration of Competing Interest The authors declare no competing interests for the work presented in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: The coexistence of lung cancer and tuberculosis is not rare. Rifamycin plays a pivotal role in anti-tuberculosis therapy. However, its potential impact on the liver metabolism of oncology drugs raises concerns. We performed this study to explore whether Rifamycin affects the survival of patients with tuberculosis and lung cancer., Methods: Drawing from the Taiwan National Health Insurance Research Database, we identified patients diagnosed with concurrent lung cancer and tuberculosis between 2000 and 2014. Patients were categorized based on whether they underwent rifamycin-inclusive or rifamycin-exempt anti-tuberculosis therapy. Subsequently, we paired them at a 1:1 ratio and evaluated the mortality risk over a two-year span., Results: Out of the study participants, 1558 (81.4%) received rifamycin-based anti-tuberculosis therapy, while 356 (18.6%) underwent a rifamycin-free regimen. Analysis revealed no marked variance in the biennial mortality rate between the groups (adjusted hazard ratio: 1.33, 95% confidence interval 0.93-1.90, p = 0.1238). When focusing on the matched sets comprising 127 individuals in each group, the data did not indicate a significant link between rifamycin and a heightened two-year mortality risk (adjusted hazard ratio: 1.00, 95% confidence interval 0.86-1.18, p = 0.9538)., Conclusions: For individuals with concomitant lung cancer and tuberculosis, rifamycin's administration did not adversely influence two-year survival. Thus, rifamycin-containing anti-TB regimens should be prescribed for the indicated patients.

Background: We investigated the impacts of the standard treatment durations of and adherence to standard anti-tuberculous therapy (ATT) on recurrence after the successful completion of tuberculosis (TB) treatment., Methods: We recruited patients with TB who had received treatment for six or nine months from the 2008-2017 databases of the Taiwanese National Health Insurance Research Database. Treatment duration and adherence to standard ATT were analyzed for their impacts on recurrence within two years. Complete adherence to standard ATT was defined as daily use of ethambutol, isoniazid, pyrazinamide, and rifampin for the first two months, and daily use of isoniazid and rifampin for the first six months., Results: A total of 33,298 TB patients with new-onset TB were identified and classified into two groups by treatment duration: six months (n = 25,849, 77.63%) and nine months (n = 7449). Sex and age distributions varied between the groups. Treatment duration did not affect TB recurrence within two years (adjusted hazard ratio (AHR): 1.18, 95% confidence interval (C.I.) [0.96-1.44], p = 0.1156). Multivariable logistic regression showed that incomplete adherence to standard anti-tuberculous therapy (80-89% and 90-99% standard anti-TB therapy, AHR: 1.57, 95% C.I. [1.26-1.95], and 1.63, 95% C.I. [1.26-2.06], respectively, p < 0.0001) increased TB recurrence. In addition, male sex, older age, and comorbidity with diabetes mellitus or chronic obstructive pulmonary disease were independent risk factors for TB recurrence within two years., Conclusions: TB recurrence was 1.54% within two years under a DOT era. TB treatment durations of six or nine months did not affect TB recurrence within two years after completion of TB treatment, but incomplete adherence to standard anti-tuberculous therapy might increase the TB recurrence rate., Competing Interests: Declaration of Competing Interest All authors have no competing interests to declare., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Type 2 diabetes mellitus (DM) is a risk factor for mycobacterial pulmonary infections (MPI), including tuberculosis (TB) and nontuberculous mycobacterial lung disease (NTM-LD). Dipeptidyl peptidase IV inhibitor (DPP4i), a common DM medication, has an immune-modulation effect that raises concerns about developing MPI. However, there is scarce research on the topic., Methods: This retrospective study was conducted in a tertiary-referral center in Taiwan from 2009 to 2016. Patients with type 2 DM who were receiving any DM medication were enrolled. TB and NTM-LD were defined by microbiological criteria. We analyzed the risk of MPI in DPP4i users using Cox proportional hazard regression with adjusted inverse probability of treatment weighting., Results: A total of 9963 patients were included. Among them, 3931 were classified as DPP4i users, and 6032 patients were DPP4i nonusers. DPP4i users had no increase in incidences of MPI (604 vs. 768 per 100,000 person-years, p = 0.776), NTM-LD (174 vs. 255 per 100,000 person-years, p = 0.228), and TB (542 vs. 449 per 100,000 person-years, p = 0.663) relative to those of DPP4i nonusers. After adjustment, the adjusted hazard ratios for MPI (aHR: 1.07, 95% CI: 0.79-1.45), TB (aHR: 1.15, 95% CI: 0.81-1.64) and NTM-LD (aHR: 0.85, 95% CI: 0.49-1.47) were not significantly increased relative to those of nonusers. The subgroup analysis also showed that DPP4i use did not increase the risk of MPI in different DM severities and comorbidities., Conclusions: According to our large cohort study, DPP4i use is safe for patients with type 2 DM and might not increase the risk of MPI., Competing Interests: Declaration of Competing Interest No conflict of interest to declare., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Solid organ transplant recipients have an increased risk of tuberculosis (TB). Due to the use of immunosuppressants, the incidence of TB among solid organ transplant recipients has been consistently reported to be higher than that among the general population. TB frequently develops within the first year after transplantation when a high level of immunosuppression is maintained. Extrapulmonary TB and disseminated TB account for a substantial proportion of TB among solid organ transplant recipients. Treatment of TB among recipients is complicated by the drug-drug interactions between anti-TB drugs and immunosuppressants. TB is associated with an increased risk of graft rejection, graft failure and mortality. Detection and management of latent TB infection among solid organ transplant candidates and recipients have been recommended. However, strategy to mitigate the risk of TB among solid organ transplant recipients has not yet been established in Taiwan. To address the challenges of TB among solid organ transplant recipients, a working group of the Transplantation Society of Taiwan was established. The working group searched literatures on TB among solid organ transplant recipients as well as guidelines and recommendations, and proposed interventions to strengthen TB prevention and care among solid organ transplant recipients., Competing Interests: Declaration of competing interest The authors have no conflicts of interest relevant to this article., (Copyright © 2023. Published by Elsevier B.V.)

Introduction: Bacillus Calmette-Guérin (BCG) vaccination has been reported to be protective against latent tuberculosis infection (LTBI) in the general population. The aim of this study was to investigate the protective effect of BCG vaccination against LTBI in adult patients with end-stage renal disease (ESRD) and renal transplants., Methods: Patients aged ≥ 20 years with ESRD who received hemodialysis (HD), peritoneal dialysis (PD) or kidney transplant were enrolled from January 2012 to December 2019 at a medical center and a regional hemodialysis center. Patients with active tuberculosis (TB), previously treated TB, active immunosuppressant therapy or human immunodeficiency virus infection were excluded. LTBI status was determined by QuantiFERON-TB Gold In-tube (QFT-GIT)., Results: After the exclusion of indeterminate results of QFT-GIT, 517 participants were enrolled and 97 (18.8%) were identified as having LTBI. Participants with LTBI were older (55.1 ± 11.4 vs. 48.5 ± 14.6 years, p < 0.001) and had a significantly higher proportion receiving HD than those without LTBI (70.1% vs. 56.7%, p = 0.001). The percentage with BCG scars was higher in the non-LTBI group than in the LTBI group (94.8% vs. 81.4%, p < 0.001), whereas the neutrophil-to-lymphocyte ratio (NLR) (≥ 2.68) was significantly higher in the LTBI group (62.8% vs. 45.5%, p = 0.02). By multivariate logistic regression analysis, presence of BCG scar and high NLR were independent protective factors against LTBI [adjusted OR: 0.19 (0.063-0.58, p = 0.001) and 0.50 (0.28-0.89, p = 0.02)]., Conclusion: The prevalence of LTBI was as high as 18.8% in patients with end-stage kidney disease or kidney transplant. BCG vaccination and high NLR might have protective effects against LTBI in patients with renal failure or transplant., (© 2023. The Author(s).)

Background: Mycobacterium avium complex lung disease (MAC-LD) preferentially occurs in postmenopausal women and may have immune exhaustion involving the programmed cell death 1 (PD-1) pathway. It is still unknown whether sex-specific associations between susceptibility to MAC-LD and programmed cell death 1 gene (PDCD1) polymorphisms exist., Methods: Adult patients with MAC-LD (n = 152) and controls (n = 167) were included at 2 medical centers in Taiwan. Five single-nucleotide polymorphisms in PDCD1 genes were genotyped, and their associations with MAC-LD and soluble PD-1 protein were analyzed, especially in sex subgroups., Results: PDCD1 rs2227982 polymorphism was associated with increased risk of MAC-LD in women (adjusted odds ratio for AA vs AG vs GG, 2.205 [95% confidence interval, 1.108-4.389]; P = .02), and the rs10204525 TT genotype was associated with low risk in men (TT vs TC and CC, 0.396 [.176-.890]; P = .02). Compared with men with rs10204525 TT, women with rs2227982 AG and with AA had 2.7- and 5.0-fold increased risks, respectively. Soluble PD-1 levels were lower in the female subgroup with rs2227982 AG and AA than in the remainder (median level [interquartile range], 46.7 [33.7-71.5] pg/mL vs 66.2 [48.6-101.5] pg/mL; P < .001)., Conclusions: PDCD1 genetic polymorphisms were associated with the risk of MAC-LD in a sex-specific pattern, possibly through regulation of PD-1 expression., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Bioflocculants have received more and more attention as alternatives to chemical flocculants because of their innocuousness, environmental friendliness, and high effectiveness. This study aims to investigate various factors that influence the performance of the novel bioflocculant produced by Bacillus thuringiensis (BF-TWB10) and analyze its adsorption kinetics to optimize its flocculation performance for real applications. The best-fit kinetic model was pseudo-second order with R 2  = 0.999. The effects of pretreatment temperature, pH, and the presence of cations on flocculation were assessed. Further investigations of flocculation, including zeta potential analysis and particle size analysis, were also conducted. Thermal pretreatment of BF-TWB10 or the presence of divalent cations could stimulate the decolorization efficiency of the bioflocculant. BF-TWB10 manifested outstanding dye removal performances with over 90% for all tested anionic dyes at pH 2 and 3. Its decolorization efficiency on anionic dyes decreased with the increase of pH values. Zeta potential analysis revealed that the electrostatic repulsion between anionic dyes decreased after the addition of BT-TWB10 and further diminished by adjusting the reaction mixture to pH 2 before flocculation, suggesting the occurrence of adsorption bridging and charge neutralization. These findings proposed that BF-TWB10 might be a promising bioflocculant for the removal of dyes in textile wastewater. PRACTITIONER POINTS: Bioflocculant BF-TWB10 shows outstanding performance in flocculation. Adsorption process follows pseudo-second-order kinetic model. Flocculation process is pH-responsive. High-temperature pretreatment or divalent cations enhance its flocculation performance. The analyses suggest the occurrence of charge neutralization and adsorption bridging., (© 2023 Water Environment Federation.)

Background: Lung cancer is one of the leading causes of cancer death worldwide, and tuberculosis (TB) is a common pre-existing disease. However, there is scarce literature studying the mortality risk in patients with prior TB and subsequent lung cancer., Methods: We recruited lung cancer patients from the Taiwan Cancer Registry from 2011 to 2015 and classified them into two groups according to presence or absence of prior TB. We then matched them in a ratio of 1:4 using the exact matching approach. The mortality risk within 3 years after diagnosis of lung cancer was analyzed and compared between these two groups., Results: During the study period, 43,472 patients with lung cancer were recruited, and of these, 1,211 (2.79%) patients had prior TB. After matching, this cohort included 5,935 patients with lung cancer in two groups: patients with prior TB before lung cancer ( n  = 1,187) and those without ( n  = 4,748). After controlling for demographic factors and comorbidities, the patients with prior TB had increased adjusted hazard ratios of 1.13 (95% CI: 1.04-1.23) and 1.11 (1.02-1.21) for all-cause and cancer-specific 3-year mortality, respectively, compared to the lung cancer patients without prior TB. Duration between TB and lung cancer (<1 year vs. 1-3 years vs. >3 years) had no differences for mortality risk., Conclusion: In the present study, 2.79% patients with lung cancer had prior TB, which was associated with higher 3-year mortality after they developed lung cancer. The mortality risk with prior TB did not decrease even if >3 years passed before diagnosis of lung cancer., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Liao, Lee, Wu, Shu and Ho.)

Rationale: Nontuberculous mycobacterial (NTM) diseases are difficult-to-treat infections, especially in lung transplant (LTx) candidates. Currently, there is a paucity of recommendations on the management of NTM infections in LTx, focusing on Mycobacterium avium complex (MAC), M. abscessus and M. kansasii ., Methods: Pulmonologists, infectious disease specialists, LTx surgeons and Delphi experts with expertise in NTM were recruited. A patient representative was also invited. Three questionnaires comprising questions with multiple response statements were distributed to panellists. Delphi methodology with a Likert scale of 11 points (5 to -5) was applied to define the agreement between experts. Responses from the first two questionnaires were collated to develop a final questionnaire. The consensus was described as a median rating >4 or <-4 indicating for or against the given statement. After the last round of questionnaires, a cumulative report was generated., Results: Panellists recommend performing sputum cultures and a chest computed tomography scan for NTM screening in LTx candidates. Panellists recommend against absolute contraindication to LTx even with multiple positive sputum cultures for MAC, M. abscessus or M. kansasii. Panellists recommend MAC patients on antimicrobial treatment and culture negative can be listed for LTx without further delay. Panellists recommend 6 months of culture-negative for M. kansasii , but 12 months of further treatment from the time of culture-negative for M. abscessus before listing for LTx., Conclusion: This NTM LTx study consensus statement provides essential recommendations for NTM management in LTx and can be utilised as an expert opinion while awaiting evidence-based contributions., Competing Interests: Conflict of interest: H. Asif, A. Ohsumi, J. Philley, A. Emtiazjoo, T. Hirama, C-C. Shu, F. Silveira, V. Poulin, M. Nagao, P-R. Burgel, S. Hays, T. Kawasaki, C. Dela Cruz, S. Aliberti, T. Nakajima, S. Ruoss, T.K. Marras and G.I. Snell have no conflict to report. F.F. Rahaghi has received research grants, paid to his institution, from Mallinckrodt, outside the submitted work; and payment or honoraria for lectures, presentations, consultation fee events from United Therapeutics, Mallinckrodt and Actelion Pharma, outside the submitted work. P. Rizzuto has received research grants, paid to his institution, from Insmed, regarding the submitted work. T. Aksamit has received payment or honoraria for lectures, presentations, consultation fee events from Advanced Respiratory, Inc., outside the submitted work. A.W. Baker has received research grants, paid to his institution, from NIH/NIAID, Insmed and CDC's Prevention Epicenters Program outside the submitted work. K. Winthrop has received restricted research grants, paid to his institution, from E.R Squibb & Sons, Regeneron Pharm and Gentech, outside the submitted work; and payment or honoraria for lectures, presentations, consultation fee events from Insmed, AbbVie, Eli Lilly and WhiteHall, outside the submitted work. M. Mirsaeidi has received research grants, paid to his institution, from Boehringer Ingelheim, Ashvattha and Mallinckrodt, outside the submitted work., (Copyright ©The authors 2023.)

Background: Tuberculosis (TB) is one of the leading causes of death worldwide and a major cause of ill health. Without treatment, the mortality rate of TB is approximately 50%; with treatment, most patients with TB can be cured. However, anti-TB drug treatments may result in many adverse effects. Therefore, it is important to detect and predict these adverse effects early. Our study aimed to build models using an artificial intelligence/machine learning approach to predict acute hepatitis, acute respiratory failure, and mortality after TB treatment., Materials and Methods: Adult patients (age ≥ 20 years) who had a TB diagnosis and received treatment from January 2004 to December 2021 were enrolled in the present study. Thirty-six feature variables were used to develop the predictive models with AI. The data were randomly stratified into a training dataset for model building (70%) and a testing dataset for model validation (30%). These algorithms included XGBoost, random forest, MLP, light GBM, logistic regression, and SVM., Results: A total of 2248 TB patients in Chi Mei Medical Center were included in the study; 71.7% were males, and the other 28.3% were females. The mean age was 67.7 ± 16.4 years. The results showed that our models using the six AI algorithms all had a high area under the receiver operating characteristic curve (AUC) in predicting acute hepatitis, respiratory failure, and mortality, and the AUCs ranged from 0.920 to 0.766, 0.884 to 0.797, and 0.834 to 0.737, respectively., Conclusions: Our AI models were good predictors and can provide clinicians with a valuable tool to detect the adverse prognosis in TB patients early.

Background : Lung cancer increases the risk for pulmonary tuberculosis (PTB). The risk factors for newly diagnosed PTB are not known in lung cancer. This study analyzed risk factors of new-onset PTB among lung cancer patients in Taiwan. Methods : Taiwan's National Health Insurance Research Database and Taiwan Cancer Registry were used to define PTB and lung cancer patients between 2007 and 2015. Considering that mortality was a competing risk event during the cancer treatment, Fine and Gray method was performed to estimate the possible risk factors for PTB among lung cancer patients. Results : A total of 1,335 patients had PTB after lung cancer. The incidence of PTB increased with patients' raising age. Males had 1.7-fold (95% CI: 1.5-2.0) risk of PTB compared with females. Patients aged between 60-69 years (HR: 1.4; 95% CI: 1.1-1.8) and those ≥70 years (HR: 1.9; 95% CI: 1.5-2.4) had higher PTB risk than those aged under 50 years. Patients with history of pneumoconiosis and patients who received the treatments of surgery and chemotherapy also had significant increasing risk of PTB. Conclusion : Screening for PTB may be important among lung cancer patients with the aforementioned risk factors., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Introduction: Fall from ladders is increasingly identified as a significant cause of injury and mortality, yet large-scale research into ladder fall outcomes and trends is limited., Objectives: To explore the nature and severity of injuries resulting from ladder falls and to determine predictors of Injury Severity Score (ISS) and 6-month mortality., Methods: Data were obtained from the New South Wales (NSW) Trauma Registry, Admitted Patient Data Collection and Registry of Births, Deaths, and Marriages on patients aged 15 and over who had major trauma from a ladder fall and were admitted to hospital between January 1st, 2012, and July 31st, 2019. Data linkage and descriptive statistics were carried out alongside bivariate and multivariable regression analysis., Results: 963 patients injured after ladder falls were identified. The mean age was 61.9 years (SD 14.2), 91.0% were male, and 489 (50.8%) were born in Australia. The height of fall was between one and five meters in 827 (86.2%) patients, and the place of fall was home and residential places in 27.5%. The most common body areas injured were the head (26.5%), spine (21.2%) and thorax (20.6%), and the median injury severity score was 17. The median length of stay of patients' in-hospital and intensive care unit was six days and two days, respectively. Six months post-discharge mortality was 6.4%. The unadjusted association between the presence of comorbidities or socio-economic class and ISS or mortality was not statistically significant. Increasing ISS was found to be associated with increasing age (Estimate (Est), 15.2; 95% Confidence Interval (CI), 12.3-18.1) and a fall height greater than five metres (Est, 5.8; CI, 3.2-8.4). Mortality was found to be associated with increasing age (Odds ratio (OR), 1.06; CI, 1.03-1.08) and increasing ISS (OR, 1.19; CI, 1.15-1.24)., Conclusion: People presenting to the hospital after falling from a ladder were predominately male, aged over 60 and had fallen in a residential setting. Increasing age and fall height are associated with more severe injuries., Competing Interests: Declaration of Competing Interest None to declare., (Crown Copyright © 2022. Published by Elsevier Ltd. All rights reserved.)

We present a combined analytical and numerical study for coherent terahertz control of a single molecular polariton, formed by strongly coupling two rotational states of a molecule with a single-mode cavity. Compared to the bare molecules driven by a single terahertz pulse, the presence of a cavity strongly modifies the postpulse orientation of the polariton, making it difficult to obtain its maximal degree of orientation. To solve this challenging problem toward achieving complete quantum coherent control, we derive an analytical solution of a pulse-driven quantum Jaynes-Cummings model by expanding the wave function into entangled states and constructing an effective Hamiltonian. We utilize it to design a composite terahertz pulse and obtain the maximum degree of orientation of the polariton by exploiting photon blockade effects. This Letter offers a new strategy to study rotational dynamics in the strong-coupling regime and provides a method for complete quantum coherent control of a single molecular polariton. It, therefore, has direct applications in polariton chemistry and molecular polaritonics for exploring novel quantum optical phenomena.

The ability to observe quantum coherence and interference is crucial for understanding quantum effects in nonlinear optical spectroscopy and is of fundamental interest in quantum mechanics. Here, we present an experimental study combined with theoretical analysis and numerical simulations to identify the underlying process behind the rotational revivals induced by a pair of time-delayed ultrafast femtosecond laser pulses for air molecules under ambient conditions. Our time-resolved two-dimensional alignment measurements confirm that one-step non-resonant Raman transitions from initial states of mixed molecules play a dominant role, showing a signature of weak-field-induced rotational revivals. Furthermore, we demonstrate that such rotational revival spectra can simultaneously measure the entire pure rotational Raman spectra and observe the quantum interference between two transition pathways from a given initial state. This work provides a powerful tool to observe, control, and identify the rotational dynamics of mixed molecular samples under weak-field excitations.

We examined gene expression with DNA switching between two states, active and inactive. Subpopulations emerge from mechanisms that do not arise from trivial transcriptional heterogeneity. Although the RNA demonstrates a unimodal distribution, dimerization intriguingly causes protein bimodality. No control loop or deterministic bistability are present. In such a situation, increasing the degradation rate of the protein does not lead to bimodality. The bimodality is achieved through the interplay between the protein monomer and the formation of protein dimer. We applied Stochastic Simulation Algorithm (SSA) and found that cells spontaneously change states at the protein level. While sweeping parameters, decreasing the rate constant of dimerization severely impairs the bimodality. We also examined the influence of DNA switching. To have bimodality, the system requires a proper ratio of DNA in the active state to the inactive state. In addition to bimodality of the monomer, tetramerization also causes the bimodality of the dimer., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Our previous study identified that the Mycobacterium abscessus subsp. abscessus T28 sequevar does not fully represent inducible macrolide resistance. Thus, we initiated a correlation study between genotypes and phenotypes. In total, 75 isolates from patients with skin and soft tissue infections were enrolled in the study. These strains were tested against 11 antimycobacterial agents using Sensitire RAPMYCO plates and the CLSI-recommended broth microdilution method. In order to analyze erm (41) and partial hsp65 , rpoB , secA1 , and rrl genes, bacterial genomic DNA was extracted from bacteria. The MEGA X software was used for phylogenetic analyses. The most active agents against most M. abscessus species were amikacin and tigecycline. Clarithromycin was effective toward M. abscessus subsp. massiliense and nearly all M. abscessus subsp. abscessus C28 sequevars. Two varieties of M. abscessus subsp. abscessus T28 sequevars did not represent inducible macrolide resistance. Most M. abscessus species showed intermediate susceptibility to cefoxitin and imipenem. Six additional agents were less effective against M. abscessus species. Following phylogenetic analyses, two outliers of M. abscessus subsp. abscessus T28 sequevars seem to represent no inducible macrolide resistance. In addition, we discovered genetic mosaicism of hsp65 , rpoB , and secA1 in M. abscessus species was common. T28 sequevars of M. abscessus subsp. abscessus do not fully represent inducible macrolide resistance. The outlier of erm (41) phylogeny of the M. abscessus subsp. abscessus T28 sequevar is possibly due to macrolide susceptibility. Evaluation of the antimicrobial susceptibility of M. abscessus species is a reliable tool for assisting physicians in selecting the most effective antimycobacterial agent(s). IMPORTANCE Macrolides are the mainstays of the antimycobacterial regimens against Mycobacterium abscessus species (formerly Mycobacterium abscessus complex). erm (41) confers inducible macrolide resistance for M. abscessus subsp. bolletii strains, and the majority of M. abscessus subsp. abscessus T28 sequevars. Furthermore, the acquired macrolide resistance of M. abscessus species is due to a point mutation in rrl . However, not all M. abscessus subsp. abscessus T28 sequevars have inducible macrolide resistance. Exploration of the mechanism of macrolide resistance requires an understanding of genetic diversity. The genetic mosaicism of the erm (41), rpoB , hsp65 , and secA1 genes within three subspecies of M. abscessus species is not uncommon. The T28 sequevar of erm (41) confers inducible macrolide resistance to the genetic mosaic strain. The development of new anti-M. abscessus species infection overcoming inducible macrolide resistance and/or acquired macrolide resistance is a crucial issue.