bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inédit. Le « passé amoureux d’Alban de Bricoule jusqu’à l’âge de quinze ans et demi » d’après les manuscrits des Garçons de Montherlant
Authors: Duroisin Pierre 
Published: January 2021

Les pages qu’on va lire nous plongeront dans les manuscrits des Garçons, ce roman que Montherlant porta en lui pendant près d’un demi-siècle et dont la version intégrale ne parut qu’en 1973, un an après sa mort. Cela dit, les manuscrits des Garçons tels qu’ils sont conservés à la Bibliothèque nationale de France comptent plus de mille deux cents folios. Ceux que nous avons retenus ne concernent que le « passé amoureux d’Alban de Bricoule – le héros du roman – jusqu’à ses quinze ans et demi », mais ils vont de 1929 aux années cinquante, nous donnant par là même une image fidèle de la méthode de l’écrivain : s’il était l’homme des pages écrites « toutes chaudes », Montherlant était aussi l’homme des pages travaillées et retravaillées jusqu’à ce qu’il en fût pleinement satisfait, l’artisan chez lui faisant bon ménage avec le créateur.
Quelques remarques sur la réécriture chez Montherlant : Mais aimons-nous ceux que nous aimons ? et Garder tout en composant tout
Authors: Coste Claude 
Published: January 2021

Dans Aimons-nous ceux que nous aimons ?, Montherlant revient sur deux œuvres de jeunesse qu’il réécrit partiellement ; il propose également un récit de rêve dont une première version paraît de façon posthume dans Garder tout en composant tout. Que signifie cette pratique récurrente de la réécriture ? Dans toute son œuvre, Montherlant cherche à rester maître de son image, conciliant la vérité de l’affect et les ruses de l’art.
Molecular basis of drug resistance to bedaquiline and delamanid in Mycobacterium tuberculosis
Authors: Perdigão João 
Published: January 2021

Aims & objectives:
Mycobacterium tuberculosis, the etiological agent of tuberculosis (TB), is amongst the most successful pathogens worldwide with a yearly incidence of approximately 10.0 million new cases and a death toll that is well above million people. Even though this is an ancient pathogen affecting humankind since its dawn, as a bacterial species it displays a very low mutation rate and shows a strictly clonal population structure owing to the lack of lateral gene transfer. This latter aspect imposes a limitation on the pathways by which drug resistance can emerge in this species: emergence of resistance must occur through de novo mutations affecting genes that are associated with the action mechanism of a given drug.

Methods:
The mutations and mechanisms leading to resistance to the drugs that are part of the frontline armamentarium have been extensively studied and the extent of its spectrum is relatively well understood. However, newer drugs such as bedaquiline and delamanid have been introduced to TB treatment in a very recent past. These were the first two drugs to become available in approximately 40 years and, as such, the toxicity and side effects associated with these drugs still pose several challenges.

Results:
Delamanid, a nitroimidazooxazole, is a pro-drug that requires metabolization to an intermediate metabolite that inhibits the synthesis of methoxy-mycolic acids and keto-mycolic acids. This activation step is mediated by the deazaflavin(F420)-dependent nitroreductase (Ddn) and it is the loss a function of this enzyme that constitutes the main mechanism of resistance acquisition to delamanid. Other gene products susceptible to mutagenesis and part of the F420 metabolism have been implicated in delamanid resistance (fbiABC and fgd1).

Conclusions:
Several genomic variants occurring in these genes have been reported yielding different resistant levels however, owing to the restricted usage of these drugs, many of these are reported from in vitro studies. The scenario portrayed by clinical strains is somewhat different and the mutational spectrum associated with resistance more limited. Besides covering the mechanisms of action and drug resistance this talk will discern between clinically relevant mutations vs those generated in vitro and the phylogenetic distribution of different polymorphisms in genes associated with resistance.
Screening of compounds containing aminobutanol and camphane moieties against mycobacterium tuberculosis clinical isolates of different genotypes
Authors: Vyazovaya Anna , Slavchev Ivaylo , Dogonadze Marine , Valcheva Violeta , Zaharieva Maya , Solovieva Natalia , Starkova Daria , Vasilieva Neliya , Narvskaya Olga , Mokrousov Igor , Zhuravlev Viacheslav , Dobrikov Georgi 
Published: January 2021

Aim and objectives:
Despite the availability of sufficiently effective treatment regimens, prevention and control, the widespread transmission and prevalence of resistant variants of Mycobacterium tuberculosis, which do not respond to any of the commercial drugs, remains a serious health problem for both developed and developing countries. Multidrug-resistant (MDR) strains present new threat to health security. This situation is of global concern due to increased human mobility, partly illegal and spontaneous. Patients infected with drug resistant strains are hard or impossible to be cured, and their treatment is more toxic and expensive. The urgent need of new antimycobacterial agents and development pathways is becoming more and more apparent.

Methods:
In this study, we synthesized new compounds containing 2-aminobutanol and camphane moieties and evaluated them with the reference strain and clinical M. tuberculosis isolates from a high-burden country, Russian Federation.

Results:
The isolates represented different clusters within clinically/epidemiologically important Beijing genotype (B0/W148, 94-32, Central Asian Outbreak, ancestral sublineage) and differed in phenotypic drug resistance (one extensively drug resistant, six multidrug resistant, two polyresistant, and two susceptible to all tested drugs). The most efficient compound showed a wide range of MIC that varied from 3.1 μg/ml (H37Rv, ancestral Beijing, most of B0/W148 isolates) to 100 μg/ml (other isolates).

Conclusions:
To conclude, this study highlighted a key importance of testing new anti-TB compounds not only with reference laboratory strain H37Rv that belongs to the phylogenetically marginal branch of M. tuberculosis, but on the clinical drug-resistant isolates circulating in the countries with high burden of MDR-TB.

Acknowledgements.
This study was supported by the Russian Science Foundation (grant 19-15-00028). Partial support was received from the Bulgarian National Science Fund (grant KP-06-H39-7).
Selective pressure diversity and phenotype-genotype correlation in clinical isolates of mycobacterium tuberculosis
Authors: Ushtanit Anastasia , Kulagina Elena , Lyubimova Alexandra , Borodulina Polina , Zimenkov Danila 
Published: January 2021

Aims and objectives:
Selection pressure, such as drug treatment or host microenvironment, drives the evolution of M. tuberculosis in vivo. The emergence of drug resistance by the accumulation of mutations leading to drug target modifications, drug transport or activation pathways inactivation, is the leading cause of treatment failure. Besides that, secondary mutations involved in bacterial adaptation, fitness-compensation, and resistance level were identified in the genome by microevolution studies.

Methods:
Whole-genome sequencing data of 2212 clinical isolates of M. tuberculosis with resistance data were downloaded from SRA. Identification of single nucleotide variations (SNVs) was performed using BWA-MEM and C-Sibelia scripts using AL123456.3 as reference. The SNVs database handling and calculations were performed with custom Python scripts. Fisher test analysis was performed as for individual mutations, also for mutation combinations. Pairs of mutations were joined using logical AND function. Thus, n^2/2 records were analyzed for correlation with resistance, where n – total number of mutations in the database. Resistance to the rifampicin, isoniazid, and ethionamide was analyzed.

Results:
A novel approach for GWAS was developed: we studied the correlation of simultaneous occurrence of mutations pairs and phenotypic resistance for all possible pairs. We identified several SNVs associated with resistance in combinations with other mutations, and its statistical significance was below the threshold when analyzed separately.

Conclusions:
Fisher exact test for mutation combinations allows for the identification of genetic determinants missed by conventional GWAS approach. Further evaluation of novel resistance determinants using other sets of clinical isolates data from various world regions is needed.

Acknowledgements
This study was supported by the Russian Foundation for Basic Research (project 20-015-00463).
Deadly bedfellows – Challenges of dual TB – COVID 19 infections in vulnerable settings in india
Authors: Mistry Nerges 
Published: January 2021

Aims and objectives:
Like a mistral, the SARS COVID2 virus has devastated the world in a span of 6 months infecting 29 million and leaving behalf a trail of one million dead. In its trajectory it has joined forces with another old but far more side-tracked airborne disease, tuberculosis. The synergy so far does not have a clear face even in vulnerable countries like India which face a “double whammy” of TB and COVID-19. One out of 3 TB patients in the world is Indian whereas India may outstrip the USA soon in the COVID affected count.

Methods:
Vulnerable settings in India do not have the luxury of social distancing. The strict lockdowns in vulnerable settings may paint different pictures depending on community behaviour. Ten people huddled for days in a 100 sq. ft room may perpetrate transmission of TB disease. Juxtaposed is the finding of a 60% drop in TB notification. The implications of this paradox will be discussed in the light of overcrowded living conditions, pollution and highly prevalent comorbidities like T2DM and HT.

Results:
T-cell exhaustion in COVID-19 patients may increase susceptibility to TB and promote development of active TB in LTBI. Scarred lungs and pulmonary fibroses are sequalae of both diseases and could result in devastating disabilities. Modelling studies suggest a 6% increase in TB deaths overt extension of care pathways and treatment completion rates dropping to an abysmal 25%.

Conclusions:
Socio-financial and nutritional support to communities is an essential arm of mitigation. The COVID-19 pandemic at its best has also highlighted the importance of non-medical approaches of prevention especially in the realm of urban planning. The role of BCG, however ecological the evidence, is also a road worth exploring.
Are there any differences between genomic composition of clinical strains of mycobacterium tuberculosis with H37Rv?
Authors: Ahmadi Azam , Moghadasi Mona , Sadrnia Maryam , Arjomandzadegan Mohammad 
Published: January 2021

Aims & objectives:
The basis of antibiotic resistance in Mycobacterium tuberculosis (MTB), unlike Enterobacteriaceae, is the mutation in its chromosomal genes such as katG (Gene ID: 885638, causes isoniazid resistance) and rpoB (Gene ID: 888164, rifampin resistance). Evaluation of whole genome sequence of the standard strains of H37Rv in gene bank revealed the absence of integrons, plasmids and transposons. There are few reports on these genetic elements in clinical strains of MTB isolated from the patients. In this study, as a hypothesis based on the genetic composition differences between H37Rv and clinical isolates, and probably geographic differences between clinical strains genomic, we designed a study on a probably presence of a few genes in Iranian clinical strains.

Methods:
Previous studies of our research group showed that there is a new fragment in our clinical strains of MTB that was first recorded in the GenBank (Accession: MF279142.1). During extensive bioinformatics and gene bank (insilico) studies, it was found that this fragment might be a part of an integrase, belonging to a probably integron, plasmid, phage or transposon inside or outside the chromosome. Existence of its complete gene in different coding sequences was carefully investigated. A few genes including kleE, pmaB, sul, and suf, surrounding this fragment were amplified by using Mycobacterium abscessus plasmid and other non-tuberculosis mycobacteria as templets by PCR. Specific primers based on the aforementioned strains were designed. PCR reactions were optimized with various amplification programs. Bands were purified and were sequenced by ABI system apparatus. Sequencing results were analyzed by Mega, Chromas, and Basic Local Alignment Search Tool programs.

Results:
Bioinformatics analysis of sequencing results of purified 463bp amplicon revealed that the studied fragment was belonging to gene encoding dihydropterate synthase of Mycobacterium fortuitum but not in H37Rv and the other MTB strains in Gene Bank. It was confirmed that this new fragment there are in 30% of our clinical MTB strains.

Conclusion:
As the results, presence of a part of suf gene was reported for the first time in clinical isolates of Mycobacterium tuberculosis. Further experiences are under investigation to find the complete gene, and to examine whether it belongs to a larger genetic structure.
Phenotypic and genotypic resistance of drug-resistant mycobacterium tuberculosis isolates to first and second-line anti-TB drugs in iran
Authors: Kardan-Yamchi Jalil , Kazemian Hossein , Ghodousi Arash , Cirillo Daniela Maria , Douraghi Masoumeh , Abtahi Hamid Reza , Hamzelou Gholam-Reza , Amini Sirus , Feizabadi Mohammad Mehdi 
Published: January 2021

Aims and objectives:
Treatment of patients with drug-resistant tuberculosis is time-consuming and requires expensive drugs with more toxicity. Proper and timely identification of drug-resistant genotypes and determining the minimum inhibitory concentrations (MICs) alongside with the molecular basis of resistance can minimize the risk of further resistance development.

Methods:
Multidrug-resistant Mycobacterium tuberculosis (MDR-MTB) strains from different provinces were identified at Tehran Regional Reference Laboratory for Tuberculosis. Drug susceptibility testing for the first and second-line anti-TB drugs were performed and compared to the whole genome sequencing (WGS) results.

Results:
Simultaneous resistance to antibiotics included in each of the fluoroquinolones and second-line injectable drug families was observed in most of the MDR isolates. Sequencing was able to detect resistance to anti-TB drugs with a proper sensitivity. The most prevalent lineage among the Iranian MDR strains was Beijing.

Conclusions:
Mutations in drug resistance-related genes were mostly in accordance with the phenotypic drug susceptibility testing results. Drug-resistant tuberculosis can be identified quickly using molecular techniques. However, genetic background of resistance for some antibiotics were remained for more investigation.
Detection of Mycobacterium bovis in goat milk samples by loop-mediated isothermal amplification
Authors: Rocha Rosana Valeria , Macias Analía , Magnano Gabriel , Sticotti Erika , Mació Mauro , Schneider Manuel , Bigi Fabiana , Trangoni Marcos , Sioya Bernardo , Eirin María Emilia , Zumárraga Martín José 
Published: January 2021

Aims &Objective:
Mycobacterium bovis is the causative agent of bovine tuberculosis. It is also a pathogen for other animals such as goats and humans. Molecular methods are applied to detect members of the M. tuberculosis complex in different clinical samples as milk. The Loop-Mediated Isothermal Amplification (LAMP) proceeds at a constant temperature using a strand displacement reaction. LAMP does not require a thermal cycler. It is characterized by its efficiency, rapidity, high yield of final product, robustness, sensitivity and specificity. The primers are specifically designed to recognize 6 distinct regions on the target gene. The amplified product can be detected by naked eye as a white precipitate or a color change of the reaction solution.: To detect species of the Mycobacterium tuberculosis complex in goat milk samples by IS6110-LAMP

Methods:
Twenty goat milk samples from animals reacting to the tuberculin test were studied by IS6110-LAMP, Touch-Down (TD) IS6110 and Rv2807 PCR. These goats had been slaughtered, their organs and milk cultured. The isolates obtained were typed by spoligotyping. DNA extraction was performed using 500uL of milk sample. It was incubated with sodium dodecyl sulfate / proteinase K and treated twice with phenol:chloroform:isoamylic alcohol and once with chloroform:isoamylic alcohol. Then NaCl was added and DNA was precipitated with isopropanol and washed with ethanol. The remaining ethanol was evaporated and the pellet resuspended in water. IS6110-LAMP reaction was performed in a 25uL volume containing Bst DNA polymerase, betaine, magnesium sulfate, dNTPs, and primers (F3, B3, FIP, BIP, LF, LR). SYBR Gold solution was added inside of the cup of the tubes that were incubated at 63°C during one hour. After that the tubes were shacked and a yellowish color indicated a positive reaction.

Results:
While 17/20 goats were confirmed by bacteriology, no isolates were obtained from milk culture. The 17 isolates were further confirmed as M. bovis by spoligotyping. Neither NTM nor Nocordia sp. templates amplified by IS6110-LAMP. The 40 % (8/20) of the samples were IS6110-LAMP positive. There was only one discordant result between IS6110-LAMP, TD-Rv2807 and TD-IS6110.

Conclusion:
IS6110-LAMP is a useful tool to detect species of the M. tuberculosis complex in goat milk samples that could be implemented in laboratories with low technological complexity.
Alarming rates of attrition among tuberculosis patients in public-private facilities in Lahore, Pakistan
Authors: Khan Basharat J. , Kumar Ajay MV , Stewart Alex , Selvaraj Kalaiselvi , Khan Nasir , Fatima Razia , Samad Zia 
Published: January 2021

Aims and objectives:
All public-private mix (PPM) facilities caring for tuberculosis (TB) patients in Lahore city, Pakistan, under four models: PPM1 (general practitioners), PPM2 (non-governmental organizations), PPM3 (private hospitals) and PPM4 (others).

Methods:
This was a retrospective cohort study reviewing existing program records. Poisson regression was used to identify factors associated with outcomes. Data collection, variables and sources: The data were extracted from the TB laboratory registers and TB treatment registers maintained in the PPM facilities. The variables included type of PPM model, laboratory serial number, patient's name, age, sex, date of diagnosis and treatment start, smear grade, type of TB and treatment outcome. The data were collected using a structured proforma. Two electronic databases were created.

Results:
The two databases were then electronically matched for Results: Of 2473 patients diagnosed, 1590 (64%) were lost to follow-up before treatment. This was higher among males (68%) and the elderly (79%), and lower among 'high positives' (smear grading 2+ or 3+, 53%) and in the PPM1 model (34%). Of 883 patients started on treatment, 165 (19%) had unfavorable outcomes: 8% LTFU, 5% treatment failure, 3% died and 3% not evaluated. Previously treated patients (34%) and children (44%) had the worst outcomes.

Conclusion:
Pre-treatment LTFU was alarmingly high and requires urgent attention, including the development and institution of mechanisms for patient tracking using information and mobile phone technology, and making TB notification mandatory in the private sector.
Non-tuberculosis Mycobacteria (NTM) and the issue of false-reactors in tuberculination of cattle, an iranian observation
Authors: Nader Mosavari , Keyvan Tadayon , Rouhollah Keshavarz , Reza Arefpajohi , Mehdi Dehghanpour , Shojaat Dashtipour 
Published: January 2021

The genus Mycobacterium comprises a broad spectrum of obligate microorganisms most notably the M. tuberculosis complex bacteria; potentially-pathogenic or opportunistic species gathered under the common name of M. avium-intracellulare complex, and finally saprophytic mycobacteria. In cattle farming, Mycobacterium bovis (M. bovis) is considered as the principle cause for bovine tuberculosis (bTB). Nevertheless, non-tuberculosis mycobacteria (NTM) are potential pathogens that are increasingly reported to interfere with contemporary intradermal tuberculin tests in veterinary medicine.
Therefore, these neglected mycobacteria are capable to make hurdles for bTB diagnosis. In the Iranian environment, the extent and importance of this phenomenon in regard with the public health and economical aspects is just underestimated.
This work was therefore intended to isolate and characterize the mycobacterial organisms potentially involved in causing positive reactions in tuberculination of Iranian cattle.
Abattoir meat inspection and laboratory microbiological investigation of slaughtered heifers from a 2,000-head Simental cattle farm with 10% of the herd positive tuberculin reactors, failed to provide any evidence of M. bovis infection. No mycobacteria was detected in bacterial culture of specimens from feedstuff, water or even the visiting feral rodents of the farm. When the farm workers were included in assessments, 22 individuals were found tuberculin-positive with 5 of them also smear-positive in their sputa assessment.
Molecular identification of the five isolates from workers through sequencing of the 16SrRNA proved their identity as Mycobacterium thermoresistibile (Mth). Removing of the carrier workers from the farm vicinity, successfully ended the issue of the constantly-positive tuberculin test in the herd with no return of the problem until now.
We are convinced further investigations are essential in search for interference extent and importance of NTM species in cattle tuberculination scheme in Iran.
Mycobacterium tuberculosis strain diversity and non Tuberculous Mycobacteria isolates in the West and Central Africa
Authors: Thumamo Pokam Benjamin D. , Yeboah-Manu D. , Lawson L. , Guemdjom P. W. , Teyim P. M. , Okonu R. E. , Asuquo Anne E. 
Published: January 2021

Aims and objectives:
The prevalence of pulmonary tuberculosis as well as Non Tuberculous Mycobacteria (NTM), has been on the increase worldwide. In order to improve the control of the disease, genotyping and drug susceptibility of Mycobacterium tuberculosis complex (MTBC) are important. This study sought to determine drug susceptibility and genetic diversity of MTBC as well as NTM in three West/Central African countries.

Methods:
A collection of 503 isolates (158 from Cameroon, 202 from Nigeria and 143 from Ghana) obtained from culture using either Lowenstein–Jensen medium, Middlebrook 7H9 Broth and/or Xpert MTB/RIF were included in the study and some isolates tested for drug susceptibility using the proportion method, BACTEC MGIT 960 or Line Probe Assay (LPA). Isolates were further subjected to IS6110 typing, large sequence polymorphisms, and spoligotyping. All IS6110-negative strains suspected as NTM were tested using hsp65 gene amplification, DNA sequencing and blast analysis.

Results:
The Cameroon family was the most prevalent genetic strain [128/202 (63.4%) in Nigeria, 54/150 (36%) in Cameroon and 27/119 (22.7%) in Ghana] and SIT 61 the largest cluster with 111/202 (55%) and 43/150 (27%) isolates in Nigeria and Cameroon respectively. Multidrug resistance (MDR) was observed in 29/202 (14.4%) cases in Nigeria, and HIV positivity [37/202 (18.3%) patients] was associated with rifampicin 9/37 (24.3%) resistance (p=0.012), as well as gender (p=0.009). In Cameroon, 13/147 (8.8 %) were resistant to rifampicin (RIF), with 6 (46.2%) of the 13 RIF resistant isolates associated with UgandaI sublineage (p=0.0007). Other sublineages such as Haarlem, Ghana, West African 1 were recorded in the three countries. NTMs isolates included M. colombiense, M. engbaekii, M. intracellulare strain, M. gordonae, M. fortuitum, M. paraense and Nocardia veteran.

Conclusion:
Neglected NTM timely diagnosis should be reinforced in the study area. Drug resistance in TB/HIV co-infected patients and its association with a sublineage calls for a surveillance strategy to curb its expansion in the west/central Africa.