bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy and safety of intravenous chemotherapy during intensive treatment phase in patients with newly diagnosed pulmonary tuberculosis
Authors: Butova Tetyanas S , Butov Demytro O. 
Published: January 2021

Aims and objectives:
The purpose of our study was to examine the efficacy and safety of intravenous chemotherapy during intensive treatment phase in patients with newly diagnosed pulmonary tuberculosis (pulmonary TB).

Methods:
The study involved 92 patients with newly diagnosed pulmonary TB aged between 20 and 68. All patients with newly diagnosed pulmonary TB and chemosensitive tuberculosis were enrolled in the study. The patients were allocated to two groups. The first (control) group of 46 patients received standard chemotherapy orally. The second (main) group consisted of 46 patients who were prescribed isoniazid, rifampin, ethambutol by i.v. infusion, and pyrazinamide orally as a part of the standard treatment.

Results:
Symptoms of intoxication and chest manifestations in pulmonary TB patients from the second group were eliminated faster than the same symptoms in the group 1. In the group 2, the mycobacterial clearance in sputum smears was achieved more rapidly, and up to 2 months it was reached in 37 patients (80.43%), while in the control group in 25 patients (54.35%),p = 0.0066. Destruction healing and inflitrative change alleviation after 4 months was reached in 38 patients (82.61%) (in control group — 28 (60.87%), (p = 0.0192). No additional negative effects were detected when compared with the control group at any time.

Conclusions:
Thanks to i.v. chemotherapy, clinical manifestations of the in-patients with pulmonary TB were eliminated faster, severe side effects of anti-TB drugs were not noticed, time of bacterial clearance and healing of destruction was shorter, healing frequency of destructions increased and the of residual changes decreased.
Acquisition of Cross-Resistance to Bedaquiline and Clofazimine following Treatment for Tuberculosis in Pakistan
Authors: Ghodousi Arash , Rizvi Alamdar Hussain , Baloch Aurangzaib Quadir , Ghafoor Abdul , Khanzada Faisal Masood , Qadir Mehmood , Borroni Emanuele , Trovato Alberto , Tahseen Sabira , Cirillo Daniela Maria 
Published: January 2021

Aims and objectives:
In the present study, we report on the first seven cases of acquired bedaquiline and clofazimine resistance identified in Pakistan. The study was conducted within the framework of a retrospective surveillance project to monitor the acquisition of resistance to bedaquiline implemented by the National TB Reference Laboratory in Pakistan and TB Supranational Reference Laboratory.

Methods:
Seventy three sequential isolates from 31 drug-resistant-tuberculosis patients on bedaquiline-containing regimens were retrospectively tested for bedaquiline resistance by MIC testing in 7H11 medium, and for all isolates showing an increased MIC compared to the baseline isolate, further MIC testing for bedaquiline and clofazimine was conducted using the Bactec MGIT960 (BD, Franklin Lakes, NJ, USA). The H37Rv (ATCC 27294) strain was used as a susceptible control in MIC testing. Bedaquiline dry powder was supplied by Janssen-Pharmaceutica (Beerse, Belgium). WGS was carried out with the Illumina Nextera-XT DNA sample preparation kit to prepare paired-end libraries of 150-bp read length to sequence on an Illumina NextSeq platform. Data analysis and single nucleotide polymorphism (SNP) calling were performed using the MTBseq-Pipeline on low-frequency detection mode. Genes associated with resistance to bedaquiline and/or clofazimine (atpE, Rv0678, pepQ, and Rv1979c) were screened for mutations.

Results:
We studied 73 isolates from patients (n=31; 8 MDR, 16 pre-XDR, and 7 XDR) enrolled in bedaquiline-containing regimens. The sequential isolates tested included two strains from 22 patients, three from 7 patients, and four from 2 patients. All baseline strains included in the study were sensitive to bedaquiline. Seven patients developed an increase in bedaquiline MICs in 7H11 medium (range, 0.125 to >0.5mg·liter−1) during therapy, and six of them became resistant to bedaquiline according to the current critical concentration proposed for the drug. In all seven patients we detected genetic variants in Rv0678 that were not present at baseline isolates. Moreover in five out of seven patients the treatment was ultimately failed.

Conclusions:
We documented cases failing therapy that developed specific mutations in Rv0678 and had increased MICs associated with cross-resistance to clofazimine during treatment. This study underlines the relevance of surveillance programs following the introduction of new drugs.
Effectiveness of intravenous isoniazid and ethambutol administration in patients with tuberculosis meningoencephalitis and HIV-infection
Authors: Butov Dmytro O. , Butova Tetyanas S 
Published: January 2021

Aims and objectives:
of our study was to investigate the effectiveness of intravenously (i/v) isoniazid (H) and ethambutol (E) administration in patients with new sputum positive drug-susceptible pulmonary tuberculosis (TB) with tuberculous meningoencephalitis (TM) and human immunodeficiency virus (HIV) co-infection in the intensive phase of treatment.

Methods:
Fifty-four patients with TB / TM and HIV co-infection were enrolled in this study. Group 1 included 23 patients treated with E and H i/v, while rifampicin and pyrazinamide were prescribed orally. Group 2 consisted of 31 patients treated with the first-line anti-TB drugs orally. Concentrations of H and E in blood serum were detected using a chromatographic method.

Results:
A significant improvement in clinical symptoms and X-ray signs in patients treated i/v with H and E was observed compared with group 2. Sputum Mycobacterium tuberculosis positivity was observed during the second month of treatment in 25.0 % of patients from group 1 and 76.1% of patients from the control group (p<0.01). In addition, 9 (39.1%) patients died up to six months when H and E were prescribed i/v compared with 22 (70.9%) in group 2 (p=0.02).

Conclusions:
In TB / TM with HIV, i/v H and E treatment was more effective than oral H and E treatment at 2 months of intensive treatment in sputum conversion as well as in clinical improvement, accompanied by significantly higher mean serum concentrations. In addition, the mortality rate was lower in i/v H and E treatment than oral.
Twenty Year Experience of Thoracic Surgery in a Tertiary Institute for Post TB Sequelae
Authors: Dewan Ravindra 
Published: January 2021

Aims & Objective:
Post TB sequelae like hemoptysis and recurrent chest infections are a source of lot of morbidity around the globe. Many of these patients present to thoracic surgeons and surgical intervention is able to offer significant relief in many of these patients.

Methods:
Retrospective analysis was carried out for cases operated upon for post TB seqalae in the period from March 1997 to December 2017 in the Thoracic Surgery Department of the National Institute of Tuberculosis and Respiratory Diseases, New Delhi, India. A total of 1325 cases of post TB sequelae were taken up for surgery Out of these, those operated upon primarily for troublesome hemoptysis were 1154 cases. 171 cases were taken up for surgery because they had for recurrent chest infections. Out of these, 558 had tubercular cavities or destroyed lungs, 213 had aspergilloma and post tubercular bronchiectasis was present in 554 cases. Procedures performed were pneumonectomy in 417 patients, lobectomy in 732, bilobectomy in 98, segmental and wedge resections in 16 and thoracoplasty in 62 cases.

Results:
A total of 60 deaths occurred in this series. There were 18 early and 42 late deaths. 7 patients died of hemorrhage, 4 of respiratory failure, 3 sudden deaths in postoperative period (possible cause-Cardiac arrhythmia or cardiac herniation) and 4 of sepsis. Bronchopleural fistula developed postoperatively in 88 cases, which was managed by tube thoracostomy, followed by thoracoplasty, if required. Other complications like wound infection, atelectasis and pneumonitis were quite manageable.

Conclusion:
Overall quite gratifying results are achieved if surgical intervention is offered in patients suffering from debilitating post TB symptoms in carefully selected and well prepared cases.
Value of serologic assay in diagnosis of COVID-19 among patients with negative molecular assay
Authors: Rezaei Mitra , Shiva Parvaneh Baghaei , Sadr Makan , Babamahmoodi Abdolreza , Marjani Majid 
Published: January 2021

Aims and objectives:
Due to the growing burden of coronavirus 2019 and considerable rate of RT-PCR false-negative results, a complementary diagnostic tool is necessary for the detection of active cases.

Methods:
This study was performed in Masih Daneshvari Hospital, Tehran, Iran, among admitted symptomatic cases clinically and radiologically suspected to COVID-19 and their first RT-PCR assay was negative. Results of second RT-PCR assay and serologic study were compared.

Results:
In the period of study 137 symptomatic patients with negative RT-PCR assay on the first sample were recruited. Second RT-PCR assay was positive for 45 (32.8%) of them. IgM and IgG antibodies against SARS-CoV-2 were positive in 83 (60.6%) and 86 (62.8%) of patients respectively. Finally, the serologic assay was diagnostic among 73% of patients and the yield of serology was higher after the first week of illness (p-value <0.001). The combination of RT-PCR and serology increased the diagnostic yield to 83.9%.

Conclusions:
This study showed that the serologic assay in parallel to RT-PCR may be useful as a complementary tool for diagnosis of COVID-19 among admitted cases.
Comparison of Two methods for precipitation Mycobacterium tuberculosis protein and Investigation of its protein profiles
Authors: Babaie Mahdi , Mosavari Nader , Ghaempanah Aram 
Published: January 2021

Aims and objectives:
Mycobacterium tuberculosis (Mtb) is a bacterium that causes tuberculosis (TB) in humans. tuberculoprotein are a widely used for detection of primary infection with Mtb. The production of tuberculoprotein is accompanied by some difficulties that require a series of modifications in the production and purification processes. In this study, we aimed to compare two methods for precipitation Mycobacterium tuberculosis tuberculoprotein and investigated its protein profiles.

Methods:
Mtb C strain grown in Löwenstein-Jensen and Dorset Henley liquid medium. Bacteria were inactivated by subjecting to 68°C for 90 min. After inactivation the culture was filtered and tuberculoprotein were precipitated by ammonium sulfate (AS) and Trichloroacetic acid (TCA). Protein concentrations were determined by using the Lowry protein assay. In finally, the approximate molecular weights in the purified fractions were determined by sodium dodecyl sulfate (SDS)-PAGE.

Results:
The results showed that concentration of extracted tuberculoprotein by AS precipitation method was lower than TCA method. SDS-PAGE pattern of proteins precipitation with TCA showed proteins with wide range of molecular weight but proteins precipitation with AS showed low molecular weight proteins.

Conclusions:
Finally the results of this study showed that optimum methods besides a novel approach of AS precipitation in production of tuberculoprotein are suitable and applicable.
Evaluation of Magnesium Oxide and Zinc Oxide Nanoparticles against Multi-drug-resistance Mycobacterium tuberculosis
Authors: kalurazi Tofigh Yaghubi , Jafari Alireza 
Published: January 2021

Aims and objectives:
The current study has evaluated the MICs and MBCs of ZnONPs, MgONPs, and MgONPs-ZnONPs against H37 Rv Mtb and MDR-Mtb.

Methods:
Mixture, magnesium oxide nanoparticles (NPs) and zinc oxide (MgONPs-ZnONPs) were prepared. The microplate alamar blue (MABA) assay and the proportion method were used to evaluate of anti-tubercular activity against MDR-MTB. MTT test was done to MgONPs-ZnONPs against Vero and HepG2 cell lines.

Results:
The MIC of MgONPs and ZnONPs were 0.195 and 0.468 μg.ml-1 against 104 of H37 Rv Mtb. As well, 0.166 μg.ml-1 of MgONPs-ZnONPs was able to inhibit 10-4 H37 Rv Mtb. The MIC of MgONPs against 104 concentrations of MDR-Mtb was 12.5 μg.ml-1 . The MIC of MgONPs/ZnONPs against 104 concentrations of MDR-Mtb reached to 0.664 μg.ml-1 . The MBC value of ZnONPs increased to 1.875 μg.ml-1 against 10-4 concentrations of MDR-Mtb. Testing showed that the MBCs of MgONPs/ZnONPs reached to 1.328 μg.ml-1 against 104 concentrations of MDR-Mtb. The IC50 against MDR-TB was 0.779 μg.ml-1 for ZnONPs and 0.883 μg.ml-1 for MgONPs-ZnONPs. The MgONPs-ZnONPs was not toxic to Vero cell lines however ZnONPs could inhibit the Vero and HepG2 cell lines.

Conclusion:
We found that ZnONPs and mixture MgONPs-ZnONPs not only have higher bactericide behavior but might have also synergistic effects against MDR-TB.
Evaluation of the accuracy of the microplate alamar blue assay and the proportion method for the prompt detection of Mycobacterium tuberculosis and susceptibility of multidrug-resistant Mycobacterium tuberculosis clinical isolates
Authors: Jafari Alireza , Taziki Masoomeh , Aski Hesamaddin shirzad , Mojtahedi Ali , Behnampour Nasser , Atarjalali Masoomeh , rafiei Elahe 
Published: January 2021

Aims and objectives:
Tuberculosis (TB) is estimated to have caused the deaths of 1 billion people in the last 200 years.

Methods:
In the first step, the microplate alamar blue assay (MABA) was used for the detection of seventy-eight clinical isolates from Golestan Regional Tuberculosis Reference Laboratory (GRTRL) and the results were compared with the proportion method. In second step, the MABA was used for the susceptibility testing of 35 clinical isolates and the results were compared with the proportion method.

Results:
For the MABA, the sensitivity was 100 (90.97-100), specificity was 74.36 (57.87-86.96), positive predictive value (PPV) was 79.59 (65.66-89.76), negative predictive value (NPV) was 100 (88.06-100). The concentrations of isoniazid (INH) and rifampicin (RMP) ranged from 1.0-0.01 μg.mL and 2.0-0.03 μg.mL, respectively. For the proportion method, the INH concentration was between 1.0-0.03 μg.mL and the RMP concentration was between 2.0-0.06 μg.mL. For the MABA to RMP, the sensitivity was 100 (89.11-100), specificity was 100 (29.24-100), PPV was 100 (89.11-100), NPV was 100 (29.24-100), and for the MABA to INH, the sensitivity was 84.38 (67.21-94.72), specificity was 66.67 (9.43-99.16), PPV was 96.43 (81.65-99.91), NPV was 28.57 (3.67-70.96).

Conclusion:
We found the high accuracy between the MABA-RMP and the proportion method. In fact, the rapid and low-cost MABA assay is inexpensive and alternative assays for the detection of RMP resistant tuberculosis in low-income countries.
Extra-pulmonary tuberculosis at Mustapha Hospital-University, Algiers, Algeria
Authors: Ziane H. , Seladji S. , Zordani F. , Hamlat A. , Tazir M. , Amhis W. 
Published: January 2021

Aims and objectives:
Extra-pulmonary tuberculosis (EPT) previously considered as rare would seems to be progressing thus constituting, at present, a real public health problem.

Methods:
Our study aims to determine frequency and characteristics of PET diagnosed in the medical microbiology department of CHU Mustapha (MMDCM), Algiers. A retrospective descriptive study was conducted over 3 years (2012, 2013 and 2014) identifying cases of PET diagnosed in the MMDCM.

Results:
From January 2012 to December 2014, 3529 samples were received at MMDCM and seeded in culture on Löwenstein -Jensen: 1814 from pulmonary origin and 1715 from extra-pulmonary sites. Of the 153 positive cultures, 74 were extra-pulmonary, ie 48.4%. Pleural tuberculosis was the most reported form (39%). Peritoneal and pericardial tuberculosis were also reported at 6.75% and 2.70% respectively. The neuro-meningeal, osteoarticular and lymph node forms accounted for 5.4%, 10.8% and 9.45%, respectively. We noted a slight predominance of women.

Conclusions:
The EPT rate determined during our study reflects the progress of this infection. There is also a diversity of clinical forms, which should encourage systematic bacteriological confirmation of suspected cases, to ensure regular and continuous monitoring.
Evaluation of the Xpert MTB/RIF test accuracy for rapid diagnosis of pulmonary tuberculosis in a tuberculosis endemic area
Authors: Mansoori Noormohamad , Arabmofrad Fateme , Pahlavanzadeh Bagher 
Published: January 2021

Aim and objectives:
Mycobacterium tuberculosis (MTB) is a causative agent of tuberculosis (TB) which remains as an endemic disease in Iran. One of the most significant steps for control of TB is the fast and accurate diagnosis of patients. Examination of sputum smears is the primary method for TB diagnosis, and the culture method remains as the gold standard. Recently, a molecular assay that named Xpert MTB/RIF assay (Xpert), was introduced for rapid diagnosis of TB. The aim of this study was to evaluate the performance of the Xpert assay for diagnosis of TB in Golestan province.

Methods:
The TB suspected cases which referred to Tuberculosis Reference laboratory, Gorgan, Iran, from March 2018 to February 2019 were included to this study. The sputum specimens were examined using smear microscopy after Ziehl–Neelsen staining and graded according to the International Union Against Tuberculosis and Lung Disease scale (scanty, 1+, 2+, 3+ and 4+). The Xpert analysis was performed according to the manufacturer's instructions and the provided semi-quantitative results for positive specimens (very low, low, medium and high) were documented. The specimens were cultured into Lowenstein-Jensen (LJ) culture media after decontamination by Petroff's method. Sensitivity and specificity of Xpert and smear microscopy were calculated using a culture as reference standard.

Results:
Of 102 presumptive TB cases, 17 (16.7%) had culture proven TB. The set of 16 (94·1%) culture-confirmed TB cases were equivalently detected using smear microscopy and Xpert. Compared to the culture method, specificity of Xpert and smear microscopy was 100% (85/85) and 97.6% (83/85), respectively. Both tests had a sensitivity of 94.1% (16/17). When the semi-quantitative results of Xpert were compared with smear microscopy, there was 92.3% agreement for specimens with medium/high results, with those that had 1+ to 3+ scales.

Conclusion:
The rapid and accurate laboratory diagnosis of TB is one of the most important steps for TB control programs. In this study, the Xpert was effectively used to early and accurate diagnosis of TB in the study area. In the other hand, correlation between the Xpert semi-quantitative results and smear microscopy showed that Xpert could help in evaluation of patient's transmission potential.
Genome Research for Asian Tuberculosis (GReAT)
Authors: Satoshi Mitarai , Yoshira Murase , Tomotada Iwamoto 
Published: January 2021

Aims and objectives:
To establish a Mycobacterium tuberculosis genome database in collaboration with Asian countries, and to utilise the data for genotypic drug susceptibility and testing molecular epidemiology

Methods:
M. tuberculosis isolates collected in each participating country based on drug resistance and/or prevalence survey was collected as bacteria or genomic DNA, and whole genome sequencing was performed using Illumina sequencers. As a meta-data, the minimum inhibitory concentration (MIC) and conventional drug susceptibility testing (DST) data were collected for each isolate.

Results:
Approximately 5,000 genome data has been collected from Japan, China, Korea, Taiwan, Philippines, Vietnam, and Mongolia. Approximately 75% of isolates belonged to lineage 2.2.1. Base on the MIC and mutations/indels data, some confident mutations/indels were identified. With the data, the sensitivity of genetic DST for pyrazinamide was increased from 60.1% to 97.2% without losing specificity.

Conclusions:
Genome database will be a basis of genotypic DST and molecular epidemiology. However, the confidence of meta-data including MIC and other clinical information will be the key factor of genome database. In addition, genome data solution programme/software will be of great importance.
Advancing host-directed therapy for tuberculosis/MDR-TB
Authors: Meda Nikhila , Sriram Dharmarajan 
Published: January 2021

Aim and Objective:
Previous studies reported the implications of host-immune cell signalling pathways contributing towards survival of mycobacteria. Among the few, abrogation of PI3K-AKT-mTOR pathway has been shown to impact bacterial viability in macrophages. However, the intricate molecular mechanisms associated with such outcome at the juncture of host-pathogen interaction remain elusive.

Methods:
We have used novel AKT inhibitor against MTB infected macrophage and tested its survivability and its molecular mechanism of killing inside macrophage.

Result:
In the present work mouse peritoneal macrophages infected with pathogenic strain of M.tb (H37Rv) exhibited increased phosphorylation of AKT. Interestingly, suppression of AKT activity by a novel small molecule inhibitor during mycobacterial infection promoted phagolysosome fusion, apoptosis and autophagy, altogether contributing towards reduction in bacterial count in vitro. At the molecular level, we noticed that, small molecule inhibitor to AKT treatment deciphered the requirement of phosphorylation of AS160, Bad and mTOR by phosphorylated AKT in infected macrophages. Additionally, inhibition of phosphorylated AKT hampered nuclear translocation of NF-kB resulting in decreased cytokine expression.

Conclusion:
Taken together, our inhibitor can be utilized as an adjunctive therapy, as it shows high efficacy in decreasing bacterial count in combination with standard drugs to TB and also prevent the development of antibiotic resistance as host pathways are being targeted.
Surgical or homemade masks and medical clothing for inactivation of SARS-CoV-2 (COVID-19)
Authors: Ghanavi Rozhina , Nadji Seyed Alireza , Farnia Poopak , Ghanavi Jalaledin 
Published: January 2021

Aims &Objective:
SARS-CoV-2 spreads when you cough, sneeze, talk, sing, laugh, or breathe out rapidly. Therefore, to protect the individuals or health-care workers, the WHO and CDC have given their standard precautions to use the different types of masks depending on the load of SARS-CoV-2 in their working area. We made a mask that not only protect ourselves from SARS-CoV-2 through respiration, but also give us a protection through inactivation of attached SARS-CoV-2.

Methods:
The spray made by modified molecule of macrocycle (Ghanavi, United States patent; 10147951). The clothing was sprayed and after using in contaminated area was observed under scanning electron microscopy. The virus load was counted using RTPCR.

Result:
the Load of virus showed reduction up to 64 fold (94%) in sprayed clothing. The inactivation of COVID-19 were observed under scanning electron microscopy

Conclusions:
By this technology, the spread and transmission of virus from contaminated to clean area can be reduced or controlled.