bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of WHO catalog of mutations and five WGS analysis tools for drug resistance prediction of
Mycobacterium tuberculosis
isolates from China
Authors: He Guiqing , Zheng Qingyong , Shi Jichan , Wu Lianpeng , Huang Bei , Yang Yang 
Published: June 2024

ABSTRACT

The continuous advancement of molecular diagnostic techniques, particularly whole-genome sequencing (WGS), has greatly facilitated the early diagnosis of drug-resistant tuberculosis patients. Nonetheless, the interpretation of results from various types of mutations in drug-resistant-associated genes has become the primary challenge in the field of molecular drug-resistance diagnostics. In this study, our primary objective is to evaluate the diagnosis accuracy of the World Health Organization (WHO) catalog of mutations and five WGS analysis tools (PhyResSE, Mykrobe, TB Profiler, Gen-TB, and SAM-TB) in drug resistance to 10 anti-
Mycobacterium tuberculosis
(MTB) drugs. We utilized the data of WGS collected between 2014 and 2017 in Zhejiang Province, consisting of 110 MTB isolates as detailed in our previous study. Based on phenotypic drug susceptibility testing (DST) results using the proportion method on Löwenstein-Jensen medium with antibiotics, we evaluated the predictive accuracy of genotypic DST obtained by these tools. The results revealed that the WHO catalog of mutations and five WGS analysis tools exhibit robust predictive capabilities concerning resistance to isoniazid, rifampicin, ethambutol, streptomycin, amikacin, kanamycin, and capreomycin. Notably, Mykrobe, SAM-TB, and TB Profiler demonstrate the most accurate predictions for resistance to pyrazinamide, prothionamide, and para-aminosalicylic acid, respectively. These findings are poised to significantly guide and influence future clinical treatment strategies and resistance monitoring protocols.

IMPORTANCE
Whole-genome sequencing (WGS) has the potential for the early diagnosis of drug-resistant tuberculosis. However, the interpretation of mutations of drug-resistant-associated genes represents a significant challenge as the amount and complexity of WGS data. We evaluated the accuracy of the World Health Organization catalog of mutations and five WGS analysis tools in predicting drug resistance to first-line and second-line anti-TB drugs. Our results offer clinicians guidance on selecting appropriate WGS analysis tools for predicting resistance to specific anti-TB drugs.
Comparative genomic sequencing to characterize
Mycoplasma pneumoniae
genome, typing, and drug resistance
Authors: Jiang Yue , Kang Hailong , Dou Haiwei , Guo Dongxing , Yuan Qing , Dong Lili , Du Zhenglin , Zhao Wenming , Xin Deli 
Published: June 2024

ABSTRACT

To analyze the characteristics of
Mycoplasma pneumoniae
as well as macrolide antibiotic resistance through whole-genome sequencing and comparative genomics. Thirteen clinical strains isolated from 2003 to 2019 were selected, 10 of which were resistant to erythromycin (MIC >64 µg/mL), including 8 P1-type I and 2 P1-type II. Three were sensitive (<1 µg/mL) and P1-type II. One resistant strain had an A→G point mutation at position 2064 in region V of the 23S rRNA, the others had it at position 2063, while the three sensitive strains had no mutation here. Genome assembly and comparative genome analysis revealed a high level of genome consistency within the P1 type, and the primary differences in genome sequences concentrated in the region encoding the P1 protein. In P1-type II strains, three specific gene mutations were identified: C162A and A430G in L4 gene and T1112G mutation in the CARDS gene. Clinical information showed seven cases were diagnosed with severe pneumonia, all of which were infected with drug-resistant strains. Notably, BS610A4 and CYM219A1 exhibited a gene multi-copy phenomenon and shared a conserved functional domain with the DUF31 protein family. Clinically, the patients had severe refractory pneumonia, with pleural effusion, necessitating treatment with glucocorticoids and bronchoalveolar lavage. The primary variations between strains occur among different P1-types, while there is a high level of genomic consistency within P1-types. Three mutation loci associated with specific types were identified, and no specific genetic alterations directly related to clinical presentation were observed.

IMPORTANCE

Mycoplasma pneumoniae
is an important pathogen of community-acquired pneumonia, and macrolide resistance brings difficulties to clinical treatment. We analyzed the characteristics of
M. pneumoniae
as well as macrolide antibiotic resistance through whole-genome sequencing and comparative genomics. The work addressed primary variations between strains that occur among different P1-types, while there is a high level of genomic consistency within P1-types. In P1-type II strains, three specific gene mutations were identified: C162A and A430G in L4 gene and T1112G mutation in the CARDS gene. All the strains isolated from severe pneumonia cases were drug-resistant, two of which exhibited a gene multi-copy phenomenon, sharing a conserved functional domain with the DUF31 protein family. Three mutation loci associated with specific types were identified, and no specific genetic alterations directly related to clinical presentation were observed.
Assessing a respiratory toxic infectious bronchitis virus (IBV) strain: isolation, identification, pathogenicity, and immunological failure insights
Authors: Liu Huixin , Wang Chenchen , He Yang , Wei Xiaofang , Cheng Junze , Yang Wenwen , Shi Kaichuang , Si Hongbin 
Published: June 2024

ABSTRACT

Infectious bronchitis virus (IBV) is caused by avian coronavirus and poses a global economic threat to the poultry industry. In 2023, a highly pathogenic IBV strain, IBV/CN/GD20230501, was isolated and identified from chickens vaccinated with IBV-M41 in Guangdong, China. This study comprehensively investigated the biological characteristics of the isolated IBV strain, including its genotype, whole genome sequence analysis of its S1 gene, pathogenicity, host immune response, and serum non-targeted metabolomics. Through the analysis of the S1 gene sequence, serum neutralization tests, and comparative genomics, it was proven that IBV/CN/GD20230501 belongs to the GI-I type of strain and is serotype II. One alanine residue in the S1 subunit of the isolated strain was mutated into serine, and some mutations were observed in the ORF1ab gene and the terminal region of the genome. Animal challenge experiments using the EID
50
and TCID
50
calculations showed that IBV/CN/GD20230501 possesses strong respiratory pathogenicity, with early and long-term shedding of viruses and rapid viral spread. Antibody detection indicated that chickens infected with IBV/CN/GD20230501 exhibited delayed expression of early innate immune genes, while those infected with M41 showed rapid gene induction and effective viral control. Metabolomics analysis demonstrated that this virus infection led to differential expression of 291 ions in chicken serum, mainly affecting the citric acid cycle (tricarboxylic acid cycle).

IMPORTANCE
This study identified an infectious bronchitis virus (IBV) strain isolated from vaccinated chickens in an immunized population that had certain sequence differences compared to IBV-M41, resulting in significantly enhanced pathogenicity and host defense. This strain has the potential to replace M41 as a more suitable challenge model for drug research. The non-targeted metabolomics analysis highlighting the citric acid cycle provides a new avenue for studying this highly virulent strain.
Use of an embolic protection device during carotid artery stenting is associated with lower periprocedural risk
Authors: Knappich Christoph , Bohmann Bianca , Kirchhoff Felix , Lohe Vanessa , Naher Shamsun , Kallmayer Michael , Eckstein Hans-Henning , Kuehnl Andreas 
Published: June 2024

ObjectiveTo investigate associations between individual embolic protection device (EPD) use and respective center policy with periprocedural outcomes after carotid artery stenting (CAS).MethodsThis analysis is based on the nationwide German statutory quality assurance database and was funded by Germany’s Federal Joint Committee Innovation Fund (G-BA Innovationsfonds, 01VSF19016 ISAR-IQ). According to their policy towards EPD use, hospitals were categorized asroutine EPD(>90%),selective EPD(10–90%), orsporadic EPD(<10%)centers. Primary study outcome was in-hospital stroke or death. Univariate and multivariate regression analyses were performed.ResultsOverall, 19 302 patients who had undergone CAS between 2013 and 2016 were included. The highest in-hospital stroke or death rate was found insporadic EPDcenters, followed byselectiveandroutine EPDcenters (3.1% vs 2.9% vs 1.8%; P<0.001). Across the whole cohort, EPD use was associated with a lower in-hospital stroke or death rate (OR=0.60; 95% CI 0.50 to 0.72). In the multivariate regression analysis, EPD use was independently associated with a lower in-hospital stroke rate (aOR=0.66; 95% CI 0.46 to 0.94). Regarding center policy,routine EPDcenters showed a significantly lower in-hospital mortality compared withsporadic EPDcenters (aOR=0.44; 95% CI 0.22 to 0.88).ConclusionsIn a contemporary real-world cohort with low risk of selection bias, EPD use was associated with a lower in-hospital risk of stroke. A center policy of routine EPD use was associated with lower mortality. These data support routine use of EPD during CAS to enhance patient safety.
Stent retriever versus aspiration based thrombectomy: impact on first pass reperfusion, procedure time, and clinical outcomes in large vessel occlusion. Nationwide registry based cohort study
Authors: Karlsson Adrian , Jood Katarina , Björkman-Burtscher Isabella , Rentzos Alexandros 
Published: June 2024

BackgroundFirst pass reperfusion (FPR), defined as near complete reperfusion (extended Treatment in Cerebral Ischemia (eTICI) score 2c/3) in a single attempt without rescue therapy has been proposed as a quality metric. However, it remains unclear if the thrombectomy method influences clinical outcome and FPR rate. This study evaluates whether stent retriever and aspiration based thrombectomy differ in FPR rate, technical and clinical outcomes in FPR, and multiple pass reperfusion (MPR).MethodsThis retrospective, nationwide, multicenter registry study included consecutive patients with proximal anterior or posterior circulation stroke, treated between 2018 and 2021 in Sweden. Outcome measures were FPR rate, procedure time, early neurological improvement (≥4 points on National Institutes of Health Stroke Scale (NIHSS) or a score of 0–1 at 24 hours), favorable functional outcome (modified Rankin Scale score of 0–2 or no decline at 90 days), and mortality at 90 days.ResultsOf 3309 patients (median age 75, median NIHSS 16), 1990 underwent stent retriever and 1319 aspiration based thrombectomy as the firstline method. No difference in FPR rate was observed. Aspiration based thrombectomy showed a shorter procedure time in the FPR group (crude OR (cOR) 6.4 min (95% CI 3.4 to 9.3), adjusted OR (aOR) 8.7 min (95% CI 1.8 to 15.6)) and MPR group (cOR 9.7 min (95% CI 4.0 to 15.4), aOR 17.4 min (95% CI 9.6 to 25.2)), and association with early neurological improvement (cOR 1.21 (95% CI 1.03 to 1.42), aOR 1.40 (95% CI 1.18 to 1.67)) and favorable functional outcome (aOR 1.22 (95% CI 1.01 to 1.47)).ConclusionsOur findings suggest that aspiration based thrombectomy was associated with a shorter procedure time and better clinical outcomes than treatment with a stent retriever. No difference was found in FPR rate.
Tirofiban versus aspirin to prevent in-stent thrombosis after emergent carotid artery stenting in acute ischemic stroke
Authors: Medina-Rodriguez Manuel , Villagran Diego , Luque-Ambrosiani Antonio Cristobal , Cabezas-Rodríguez Juan Antonio , Ainz-Gómez Leire , Baena Palomino Pablo , Pardo-Galiana Blanca , Zamora Aynara , de Albóniga-Chindurza Asier , Aguilar-Perez Marta , González Alejandro , Moniche Francisco , Zapata-Arriaza Elena 
Published: June 2024

BackgroundSeveral antithrombotic treatments during emergent carotid artery stenting (eCAS) have been proposed, but an appropriate protocol to balance risk–benefit is not well known.ObjectiveTo investigate the efficacy and safety of tirofiban compared with aspirin in patients with acute ischemic stroke undergoing eCAS.MethodsWe conducted a retrospective single-center study of the prospective ARTISTA Registry, including patients with atherosclerotic internal carotid artery occlusion treated with eCAS. Two groups, according to antiplatelet drug, were studied: aspirin (250–500 mg single-dose) versus tirofiban (500 μg bolus+200 μg/h). Primary outcomes were the rate of in-stent thrombosis and symptomatic intracranial hemorrhage (sICH) within the first 24 hours.ResultsDuring the period 2019–2023, 181 patients were included, 103 received aspirin, 78 tirofiban; 149 (82.3%) had tandem lesions. The primary efficacy outcome occurred in 9 (9.4%) in the aspirin group, as compared with 1 (1.3%) in the tirofiban group (adjusted odds ratio (aOR)=0.11, 95% CI 0.01 to 0.98; P=0.048). The primary safety outcome was detected in 12 (11.7%) in the aspirin group, as compared with 2 (2.6%) in the tirofiban group (aOR=0.16, 95% CI 0.03 to 0.87; P=0.034). The tirofiban group presented a lower risk of parenchymal hemorrhage (18 (17.4%) vs 4 (5.2%), aOR=0.27, 95% CI 0.09 to 0.88; P=0.029) and an increased rate of excellent recanalization (expanded Treatment in Cerebral Infarction (eTICI) 2c–3) (50 (48.5%) vs 54 (69.2%); aOR=2.15, 95% CI 1.12 to 4.13; P=0.02). There were no differences in functional outcomes or mortality at 3 months.ConclusionsPeriprocedural antithrombotic therapy with tirofiban was associated with a lower risk of in-stent thrombosis and sICH at 24 hours from eCAS compared with aspirin. Prospective randomized clinical trials are needed to confirm our results.
Association between heavy alcohol consumption and cryptogenic ischaemic stroke in young adults: a case–control study
Authors: Martinez-Majander Nicolas , Kutal Shakar , Ylikotila Pauli , Yesilot Nilufer , Tulkki Lauri , Zedde Marialuisa , Sarkanen Tomi , Junttola Ulla , Nordanstig Annika , Fromm Annette , Ryliskiene Kristina , Licenik Radim , Ferdinand Phillip , Jatuzis Dalius , Kõrv Liisa , Kõrv Janika , Pezzini Alessandro , Tuohinen Suvi , Sinisalo Juha , Lehto Mika , Gerdts Eva , Ryödi Essi , Autere Jaana , Hedman Marja , Fonseca Ana Catarina , Waje-Andreassen Ulrike , von Sarnowski Bettina , Redfors Petra , Sairanen Tiina , Tatlisumak Turgut , Roine Risto O , Huhtakangas Juha , Numminen Heikki , Jäkälä Pekka , Putaala Jukka 
Published: June 2024

BackgroundThe underlying risk factors for young-onset cryptogenic ischaemic stroke (CIS) remain unclear. This multicentre study aimed to explore the association between heavy alcohol consumption and CIS with subgroup analyses stratified by sex and age.MethodsAltogether, 540 patients aged 18–49 years (median age 41; 47.2% women) with a recent CIS and 540 sex-matched and age-matched stroke-free controls were included. Heavy alcohol consumption was defined as >7 (women) and >14 (men) units per week or at least an average of two times per month ≥5 (women) and ≥7 (men) units per instance (binge drinking). A conditional logistic regression adjusting for age, sex, education, hypertension, cardiovascular diseases, diabetes, hypercholesterolaemia, current smoking, obesity, diet and physical inactivity was used to assess the independent association between alcohol consumption and CIS.ResultsPatients were twice as more often heavy alcohol users compared with controls (13.7% vs 6.7%, p<0.001), were more likely to have hypertension and they were more often current smokers, overweight and physically inactive. In the entire study population, heavy alcohol consumption was independently associated with CIS (adjusted OR 2.11; 95% CI 1.22 to 3.63). In sex-specific analysis, heavy alcohol consumption was associated with CIS in men (2.72; 95% CI 1.25 to 5.92), but not in women (1.56; 95% CI 0.71 to 3.41). When exploring the association with binge drinking alone, a significant association was shown in the entire cohort (2.43; 95% CI 1.31 to 4.53) and in men (3.36; 95% CI 1.44 to 7.84), but not in women.ConclusionsHeavy alcohol consumption, particularly binge drinking, appears to be an independent risk factor in young men with CIS.
Flavor asymmetry of light sea quarks in proton: a light-front spectator model
Authors: Choudhary Poonam , Chakrabarti Dipankar , Mondal Chandan 
Published: June 2024

AbstractWe formulate a light-front spectator model for the proton that incorporates the presence of light sea quarks. In this particular model, the sea quarks are seen as active partons, whereas the remaining components of the proton are treated as spectators. The proposed model relies on the formulation of the light-front wave function constructed by the soft wall AdS/QCD. The model wave functions are parameterized by fitting the unpolarized parton distribution functions of light sea quarks from the CTEQ18 global analysis. We then employ the light-front wave functions to obtain the sea quarks generalized parton distribution functions, transverse momentum dependent parton distributions, and their asymmetries, which are accessible in the upcoming Electron-Ion-Colliders. We investigate sea quarks’ spin and orbital angular momentum contributions to the proton spin.
PTP4A2 Promotes Glioblastoma Progression and Macrophage Polarization under Microenvironmental Pressure
Authors: Chouleur Tiffanie , Emanuelli Andrea , Souleyreau Wilfried , Derieppe Marie-Alix , Leboucq Téo , Hardy Serge , Mathivet Thomas , Tremblay Michel L. , Bikfalvi Andreas 
Published: June 2024

Abstract

Phosphatase of regenerating liver 2 (also known as PTP4A2) has been linked to cancer progression. Still, its exact role in glioblastoma (GBM), the most aggressive type of primary brain tumor, remains elusive. In this study, we report that pharmacologic treatment using JMS-053, a pan–phosphatase of regenerating liver inhibitor, inhibits GBM cell viability and spheroid growth. We also show that PTP4A2 is associated with a poor prognosis in gliomas, and its expression correlates with GBM aggressiveness. Using a GBM orthotopic xenograft model, we show that PTP4A2 overexpression promotes tumor growth and reduces mouse survival. Furthermore, PTP4A2 deletion leads to increased apoptosis and proinflammatory signals. Using a syngeneic GBM model, we show that depletion of PTP4A2 reduces tumor growth and induces a shift in the tumor microenvironment (TME) toward an immunosuppressive state. In vitro assays show that cell proliferation is not affected in PTP4A2-deficient or -overexpressing cells, highlighting the importance of the microenvironment in PTP4A2 functions. Collectively, our results indicate that PTP4A2 promotes GBM growth in response to microenvironmental pressure and support the rationale for targeting PTP4A2 as a therapeutic strategy against GBM.

Significance:
High levels of PTP4A2 are associated with poor outcomes in patients with glioma and in mouse models. PTP4A2 depletion increases apoptosis and proinflammatory signals in GBM xenograft models, significantly impacts tumor growth, and rewires the TME in an immunocompetent host. PTP4A2 effects in GBM are dependent on the presence of the TME.
The Tumor Microbiome Reacts to Hypoxia and Can Influence Response to Radiation Treatment in Colorectal Cancer
Authors: Benej Martin , Hoyd Rebecca , Kreamer McKenzie , Wheeler Caroline E. , Grencewicz Dennis J. , Choueiry Fouad , Chan Carlos H.F. , Zakharia Yousef , Ma Qin , Dodd Rebecca D. , Ulrich Cornelia M. , Hardikar Sheetal , Churchman Michelle L. , Tarhini Ahmad A. , Robinson Lary A. , Singer Eric A. , Ikeguchi Alexandra P. , McCarter Martin D. , Tinoco Gabriel , Husain Marium , Jin Ning , Tan Aik C. , Osman Afaf E.G. , Eljilany Islam , Riedlinger Gregory , Schneider Bryan P. , Benejova Katarina , Kery Martin , Papandreou Ioanna , Zhu Jiangjiang , Denko Nicholas , Spakowicz Daniel ,   for the exORIEN Consortium
Published: June 2024

Abstract

Tumor hypoxia has been shown to predict poor patient outcomes in several cancer types, partially because it reduces radiation’s ability to kill cells. We hypothesized that some of the clinical effects of hypoxia could also be due to its impact on the tumor microbiome. Therefore, we examined the RNA sequencing data from the Oncology Research Information Exchange Network database of patients with colorectal cancer treated with radiotherapy. We identified microbial RNAs for each tumor and related them to the hypoxic gene expression scores calculated from host mRNA. Our analysis showed that the hypoxia expression score predicted poor patient outcomes and identified tumors enriched with certain microbes such as Fusobacterium nucleatum. The presence of other microbes, such as Fusobacterium canifelinum, predicted poor patient outcomes, suggesting a potential interaction between hypoxia, the microbiome, and radiation response. To experimentally investigate this concept, we implanted CT26 colorectal cancer cells into immune-competent BALB/c and immune-deficient athymic nude mice. After growth, in which tumors passively acquired microbes from the gastrointestinal tract, we harvested tumors, extracted nucleic acids, and sequenced host and microbial RNAs. We stratified tumors based on their hypoxia score and performed a metatranscriptomic analysis of microbial gene expression. In addition to hypoxia-tropic and -phobic microbial populations, analysis of microbial gene expression at the strain level showed expression differences based on the hypoxia score. Thus, hypoxia gene expression scores seem to associate with different microbial populations and elicit an adaptive transcriptional response in intratumoral microbes, potentially influencing clinical outcomes.

Significance:
Tumor hypoxia reduces radiotherapy efficacy. In this study, we explored whether some of the clinical effects of hypoxia could be due to interaction with the tumor microbiome. Hypoxic gene expression scores associated with certain microbes and elicited an adaptive transcriptional response in others that could contribute to poor clinical outcomes.