bluuebunny/crossref_metadata_2025_split huggingface dataset:
A novel coli myophage and antibiotics synergistically inhibit the growth of the uropathogenic
E. coli
strain CFT073 in stoichiometric niches
Authors: Khunti Patiphan , Chantakorn Kittapart , Tantibhadrasapa Arishabhas , Htoo Htut Htut , Thiennimitr Parameth , Nonejuie Poochit , Chaikeeratisak Vorrapon 
Published: September 2023

ABSTRACT

Urinary tract infections are widespread bacterial infections affecting millions of people annually, with
Escherichia coli
being the most prevalent. Although phage therapy has recently gained interest as a promising alternative therapy for antibiotic-resistant bacteria, several studies have raised concerns regarding the evolution of phage resistance, making the therapy ineffective. In this study, we discover a novel coli myophage designated as Killian that targets
E. coli
strains, including the uropathogenic
E. coli
(UPEC) strain CFT073. It requires at least 20 minutes for 90% of its particles to adsorb to the host cells, undergoes subcellular activities for replication for 30 minutes, and eventually lyses the cells with a burst size of about 139 particles per cell. Additionally, Killian can withstand a wide variety of temperatures (4–50°C) and pHs (
4
–
10
). Genome analysis reveals that Killian’s genome consists of 169,905 base pairs with 35.5% GC content, encoding 276 open reading frames; of these, 209 are functionally annotated with no undesirable genes detected, highlighting its potential as an antibiotic alternative against UPEC. However, after an 8-hour phage treatment at high multiplicities of infection, bacterial density continuously increases, indicating an onset of bacterial growth revival. Thus, the combination study between the phage and three different antibiotics, including amikacin, ciprofloxacin, and piperacillin, was performed and showed that certain pairs of phage and antibiotics exhibited synergistic interactions in suppressing the bacterial growth revival. These findings suggest that Killian-antibiotic combinations are effective in inhibiting the growth of UPEC.

IMPORTANCE

Phage therapy has recently been in the spotlight as a viable alternative therapy for bacterial infections. However, several studies have raised concerns about the emergence of phage resistance that occurs during treatment, making the therapy not much effective. Here, we present the discovery of a novel
E. coli
myophage that, by itself, can effectively kill the uropathogenic
E. coli
, but the emergence of bacterial growth revival was detected during the treatment. Phage and antibiotics are then combined to improve the efficiency of the phage in suppressing the bacterial re-growth. This research would pave the way for the future development of phage-antibiotic cocktails for the sustainable use of phages for therapeutic purposes.
Lugdunin production and activity in
Staphylococcus lugdunensis
isolates are associated with its genotypes
Authors: Chang Shih-Cheng , Kao Cheng-Yen , Lin Lee-Chung , Hidrosollo Jazon Harl , Lu Jang-Jih 
Published: September 2023

ABSTRACT

Lugdunin produced by
Staphylococcus lugdunensis
has been shown to have broad inhibitory activity against Gram-positive bacteria; however, lugdunin activity among
S. lugdunensis
isolates and its association with different
agr
, SCC
mec
, and sequence types remain unclear. We used matrix-assisted laser desorption ionization-time-of-flight mass spectrometry to identify
S. lugdunensis
and collected 202
S
.
lugdunensis
samples for further assays. Agar spot tests were performed to characterize
S. lugdunensis
lugdunin production and activity. Multilocus sequence typing, SCC
mec,
and
agr
genotyping were performed on
S. lugdunensis
. In all, 91 S
taphylococcus aureus
strains with varying vancomycin susceptibilities were used to examine lugdunin activity in
S. lugdunensis
. In total, 48
S
.
lugdunensis
strains (23.8%) were found to be oxacillin-resistant
S. lugdunensis
(ORSL), whereas 154 (76.2%) were classified as oxacillin-sensitive
S. lugdunensis
(OSSL). Moreover, 16 (33.3%) ORSL and 35 (22.7%) OSSL strains showed antibacterial activity against
S. aureus
. Our data showed that most lugdunin-producing ORSL strains (14/48, 29.2%) were of ST3-SCC
mec
V-
agr
II genotypes, whereas most lugdunin-producing OSSL strains (15/154, 9.7%) were of ST3-
agr
II, followed by ST1-
agr
I (10/154, 6.5%). Our data also revealed that lugdunin exhibited weak inhibitory activity against the VISA ST239 isolate. In addition, we observed that ST239 VSSA was more resistant to lugdunin than ST5, ST59, and ST45 VSSA. Taken together, our data pioneered the epidemiology of lugdunin production in
S. lugdunensis
isolates and revealed its association with genotypes. However, further molecular and bioinformatics investigations are needed to elucidate the regulatory mechanisms of lugdunin production and activity.

IMPORTANCE

Lugdunin is active against both methicillin-resistant
Staphylococcus aureus
and vancomycin-resistant enterococci by dissipating their membrane potential. However, the association of lugdunin activity with the genotypes of
Staphylococcus lugdunensis
has not been addressed. Here, we show the high prevalence of lugdunin-producing strains among ST1 (83.3%), ST2 (66.7%), and ST3 (53.3%)
S. lugdunensis
. Moreover, we identified the antibacterial activity of lugdunin-producing strains against VISA and hVISA. These results shed light on the potential application of lugdunin for the treatment of drug-resistant pathogens.
Insight into the drug-resistant characteristics and genetic diversity of multidrug-resistant
Mycobacterium tuberculosis
in China
Authors: Song Zexuan , Liu Chunfa , He Wencong , Pei Shaojun , Liu Dongxin , Cao Xiaolong , Wang Yiting , He Ping , Zhao Bing , Ou Xichao , Xia Hui , Wang Shengfen , Zhao Yanlin 
Published: September 2023

ABSTRACT

Multidrug-resistant tuberculosis (MDR-TB) has a severe impact on public health. To investigate the drug-resistant profile, compensatory mutations and genetic variations among MDR-TB isolates, a total of 546 MDR-TB isolates from China underwent drug-susceptibility testing and whole genome sequencing for further analysis. The results showed that our isolates have a high rate of fluoroquinolone resistance (45.60%, 249/546) and a low proportion of conferring resistance to bedaquiline, clofazimine, linezolid, and delamanid. The majority of MDR-TB isolates (77.66%, 424/546) belong to Lineage 2.2.1, followed by Lineage 4.5 (6.41%, 35/546), and the Lineage 2 isolates have a strong association with pre-XDR/XDR-TB (
P
< 0.05) in our study. Epidemic success analysis using time-scaled haplotypic density (THD) showed that clustered isolates outperformed non-clustered isolates. Compensatory mutations happened in
rpoA
,
rpoC,
and non-RRDR of
rpoB
genes, which were found more frequently in clusters and were associated with the increase of THD index, suggesting that increased bacterial fitness was associated with MDR-TB transmission. In addition, the variants in resistance associated genes in MDR isolates are mainly focused on single nucleotide polymorphism mutations, and only a few genes have indel variants, such as
katG
,
ethA
. We also found some genes underwent indel variation correlated with the lineage and sub-lineage of isolates, suggesting the selective evolution of different lineage isolates. Thus, this analysis of the characterization and genetic diversity of MDR isolates would be helpful in developing effective strategies for treatment regimens and tailoring public interventions.

IMPORTANCE

Multidrug-resistant tuberculosis (MDR-TB) is a serious obstacle to tuberculosis prevention and control in China. This study provides insight into the drug-resistant characteristics of MDR combined with phenotypic drug-susceptibility testing and whole genome sequencing. The compensatory mutations and epidemic success analysis were analyzed by time-scaled haplotypic density (THD) method, suggesting clustered isolates and compensatory mutations are associated with MDR-TB transmission. In addition, the insertion and deletion variants happened in some genes, which are associated with the lineage and sub-lineage of isolates, such as the
mpt64
gene. This study offered a valuable reference and increased understanding of MDR-TB in China, which could be crucial for achieving the objective of precision medicine in the prevention and treatment of MDR-TB.
Nifuratel reduces
Salmonella
survival in macrophages by extracellular and intracellular antibacterial activity
Authors: Xie Tian , Liu Guifeng , Ma Jiayi , Wang Yaonan , Gao Ran , Geng Shizhong , Jiao Xinan , Barrow Paul 
Published: September 2023

ABSTRACT

Salmonella
are intracellular bacterial pathogens for which, as with many of the other
Enterobacteriaceae
, antibiotic resistance is becoming an increasing problem. New antibiotics are being sought as recommended by the World Health Organization and other international institutions. These must be able to penetrate macrophages, and infect the major host cells and the
Salmonella
-containing vacuole. This study reports screening a small library of Food and Drug Administration (FDA)-approved drugs for their antibacterial effect in macrophages infected with a rapid-multiplying mutant of
Salmonella
Enteritidis. The most effective drug that was least toxic for macrophages was Nifuratel, a nitrofuran antibiotic already in use for parasitic infections. In mice, it provided 60% protection after oral infection with a lethal
S
. Enteritidis dose with reduced bacterial numbers in the tissues. It was effective against different serovars, including multidrug-resistant strains of
Salmonella
Typhimurium, and in macrophages from different host species and against
Listeria monocytogenes
and
Shigella flexneri
. It reduced IL-10 and STAT3 production in infected macrophages which should increase the inflammatory response against
Salmonella
.

IMPORTANCE

Salmonella
can keep long-term persistence in host's macrophages to evade cellular immune defense and antibiotic attack and exit in some condition and reinfect to cause salmonellosis again. In addition to multidrug resistance, this infection circle causes
Salmonella
clearance difficult in the host, and so there is a great need for new antibacterial agents that reduce intramacrophage
Salmonella
survival to block endogenous
Salmonella
reinfection.
First Data on Vertical Particle Fluxes and Environmental Conditions in the Northern Segment of the Mohns Ridge, Norwegian Sea
Authors: Klyuvitkin A. A. , Kravchishina M. D. , Novigatsky A. N. , Politova N. V. , Bulokhov A. V. , Gulev S. K. 
Published: September 2023

AbstractContinuous two-year studies of particle fluxes and associated environmental parameters in the axial zone of the Arctic segment of the Mid-Atlantic Ridge at the junction of the Mohns and Knipovich ridges (Norwegian Sea) have been carried out for the first time. Sediment traps were deployed from the R/VAkademik Mstislav Keldyshin June 2019 in the northeastern part of the Mohns Ridge with revision in August 2020 and lifting in July 2021. It is shown that the sedimentation of particles in the study area was affected by the global transport of water masses in the northeasterly direction, with Atlantic waters in the subsurface layer and water masses of Arctic origin recirculating deeper in the subsurface. A weak positive temperature trend at a depth of more than 2500 m (0.02°C over two years) is detected. The bimodal vertical distribution of fluxes and changes in the composition of sinking particles corresponded to the pattern of sediment recycling in the ocean. The annual course of fluxes in the subsurface layer is determined by the activity of Si-concentrating and calcifying plankton, while the maximum bloom period is also manifested in the deep layer. At the same time, the main significant source of the flux deeper than 2000 m is the supply of lithogenic matter from the near-bottom nepheloid layer.
Prognostic significance of melanogenesis pathway and its association with the ultrastructural characterisation of melanosomes in uveal melanoma
Authors: Jha Jayanti , Singh Mithalesh Kumar , Singh Lata , Pushker Neelam , Meel Rachna , Lomi Neiwete , Bakhshi Sameer , Nag Tapas Chandra , Chosdol Kunzang , Sen Seema , Kashyap Seema 
Published: September 2023

BackgroundPigmentation could be a relevant prognostic factor in uveal melanoma (UM) development. Microphthalmia-associated transcription factor (MITF) regulates melanin synthesis by activating tyrosinase-related protein 2 (TYRP2) and silver protein (SILV) that induce the melanogenesis pathway. Although their oncogenic potential has been observed in various malignancies but has not been investigated in UM Asian population. Our aim is to study the ultrastructure of melanosomes and the prognostic significance of pigmentation markers such as TYRP2, MITF and SILV in UM.MethodsTransmission electron microscopy was performed to compare the ultrastructure of melanosomes in the normal choroid and UM cases. Immunoexpression of TYRP2, SILV and MITF was analysed in 82 UM samples. The mRNA expression level of all genes was measured in 70 UM cases. A statistical correlation was performed to determine the prognostic significance of all markers.ResultsPremelanosomes and mature melanosomes undergoing dedifferentiation were observed in high-pigmented UM cases as compared with low-pigmented UM cases. Seventy per cent of UM cases showed high SILV expression while TYRP2 and MITF expression was present in 58% and 56% of cases, respectively. At the mRNA level, upregulation of TYRP2, SILV and MITF markers was seen in around 50% of UM cases, which was statistically significant with high pigmentation. Reduced metastatic-free survival was statistically significant with the MITF protein expression.ConclusionOur results demonstrated that ultrastructural changes in melanosomes and high expression of TYRP2, MITF and SILV could dysregulate the melanogenesis pathway and might be responsible for the aggressive behaviour of UM.
Suboptimal gestational weight gain and neonatal outcomes in low and middle income countries: individual participant data meta-analysis
Authors: Perumal Nandita , Wang Dongqing , Darling Anne Marie , Liu Enju , Wang Molin , Ahmed Tahmeed , Christian Parul , Dewey Kathryn G , Kac Gilberto , Kennedy Stephen H , Subramoney Vishak , Briggs Brittany , Fawzi Wafaie W 
Published: September 2023

Abstract

Objective
To estimate the associations between gestational weight gain (GWG) during pregnancy and neonatal outcomes in low and middle income countries.

Design
Individual participant data meta-analysis.

Setting
Prospective pregnancy studies from 24 low and middle income countries.

Main outcome measures
Nine neonatal outcomes related to timing (preterm birth) and anthropometry (weight, length, and head circumference) at birth, stillbirths, and neonatal death.

Analysis methods
A systematic search was conducted in PubMed, Embase, and Web of Science which identified 53 prospective pregnancy studies published after the year 2000 with data on GWG, timing and anthropometry at birth, and neonatal mortality. GWG adequacy was defined as the ratio of the observed maternal weight gain over the recommended weight gain based on the Institute of Medicine body mass index specific guidelines, which are derived from data in high income settings, and the INTERGROWTH-21st GWG standards. Study specific estimates, adjusted for confounders, were generated and then pooled using random effects meta-analysis models. Maternal age and body mass index before pregnancy were examined as potential modifiers of the associations between GWG adequacy and neonatal outcomes.

Results

Overall, 55% of participants had severely inadequate (<70%) or moderately inadequate (70% to <90%) GWG, 22% had adequate GWG (90-125%), and 23% had excessive GWG (≥125%). Severely inadequate GWG was associated with a higher risk of low birthweight (adjusted relative risk 1.62, 95% confidence interval 1.51 to 1.72; 48 studies, 93 337 participants; τ
2
=0.006), small for gestational age (1.44, 1.36 to 1.54; 51 studies, 93 191 participants; τ
2
=0.016), short for gestational age (1.47, 1.29 to 1.69; 40 studies, 83 827 participants; τ
2
=0.074), and microcephaly (1.57, 1.31 to 1.88; 31 studies, 80 046 participants; τ
2
=0.145) compared with adequate GWG. Excessive GWG was associated with a higher risk of preterm birth (1.22, 1.13 to 1.31; 48 studies, 103 762 participants; τ
2
=0.008), large for gestational age (1.44, 1.33 to 1.57; 47 studies, 90 044 participants; τ
2
=0.009), and macrosomia (1.52, 1.33 to 1.73; 29 studies, 68 138 participants; τ
2
=0) compared with adequate GWG. The direction and magnitude of the associations between GWG adequacy and several neonatal outcomes were modified by maternal age and body mass index before pregnancy.

Conclusions
Inadequate and excessive GWG are associated with a higher risk of adverse neonatal outcomes across settings. Interventions to promote optimal GWG during pregnancy are likely to reduce the burden of adverse neonatal outcomes, however further research is needed to assess optimal ranges of GWG based on data from low and middle income countries.
Efficacy and safety of an inactivated virus-particle vaccine for SARS-CoV-2, BIV1-CovIran: randomised, placebo controlled, double blind, multicentre, phase 3 clinical trial
Authors: Mohraz Minoo , Vahdat Katayoun , Ghamari Seyyed-Hadi , Abbasi-Kangevari Mohsen , Ghasemi Erfan , Ghabdian Yasaman , Rezaei Negar , Pouya Maryam Amini , Abdoli Asghar , Malekpour Mohammad-Reza , Koohgir Keyvan , Saeedi Moghaddam Sahar , Tabarsi Payam , Moghadami Mohsen , Khorvash Farzin , Khodashahi Rozita , Salehi Mohammadreza , Hosseini Hamed 
Published: September 2023

Abstract

Objective
To report the efficacy, safety, and exploratory immunogenicity findings of two 5 µg doses of the BIV1-CovIran vaccine.

Design
Randomised, placebo controlled, double blind, multicentre, phase 3 clinical trial.

Setting
In six cities of Iran, including Bushehr, Isfahan, Karaj, Mashhad, Shiraz, and Tehran. The first vaccine or placebo injection of the first participant was on 16 May 2021 in Tehran. The last vaccine or placebo injection of the last participant occurred on 15 July 2021 in Isfahan.

Participants
20 000 participants aged 18-75 years were randomly assigned to the intervention or placebo groups with a ratio of 2:1.

Intervention
5 µg vaccine or placebo with the interval of 28 days.

Main outcome measures
Vaccine efficacy for a 90 day follow-up period, safety and explanatory immunogenicity assessment, and variant detection during the trial.

Results
20 000 participants were recruited and randomly assigned to receive BIV1-CovIran (n=13 335 (66.7%)) or placebo (n=6665 (33.3%)). Participants' mean age was 38.3 (standard deviation 11.2) years, and 6913 (34.6%) were female. Among vaccinated participants that had covid-19 reported during the follow-up (median 83 days), 758 (5.9%) had symptoms, 144 (1.1%) had severe infection, and seven (0.1%) were critical. Among participants who received placebo during the follow-up, 688 (10.7%) had symptoms, 221 (3.4%) had severe infection, and 19 (0.3%) were critical. Overall efficacy was 50.2% (95% confidence interval 44.7% to 55.0%) against symptomatic covid-19, 70.5% (63.7% to 76.1%) against severe disease, and 83.1% (61.2% to 93.5%) against critical cases. Two deaths were reported in the efficacy population in the placebo group, no deaths were from the intervention group. During follow-up, 41 922 adverse events were reported: 28 782 (68.7%) were adverse reactions, of which 19 363 (67.3%) were in the intervention group. Most adverse reactions were mild or moderate in severity (grade 1 or 2) and self-limiting. No serious adverse events were related to the injections. For variant investigation, of 119 participants positive for the SARS-CoV-2 variant, 106 (89.1%) were positive for the delta variant.

Conclusions
A two dose regimen of the BIV1-CovIran vaccine conferred efficacy of 50.2% against symptomatic covid-19, 70.5% against severe disease, and 83.1% against critical disease. Vaccination was well tolerated, with no safety concerns raised.

Trial registration
Iranian Registry of Clinical Trials, IRCT20201202049567N3.

Funding
Shifa-Pharmed Industrial Group.
Association between urban–rural location and prevalence of type 2 diabetes and impaired fasting glucose in West Africa: a cross–sectional population–based epidemiological study
Authors: Issaka Ayuba , Stevenson Christopher , Paradies Yin , Houehanou Yessito Corine N , Bosu William K , Kiwallo Jean Baptiste , Wesseh Chea Sanford , Houinato Dismand Stephan , Nazoum Diarra J P , Cameron Adrian J 
Published: September 2023

ObjectivesWe investigated the association between urban/rural location and both type 2 diabetes mellitus (T2DM) and pre-diabetes among populations of five West African countries.DesignCross-sectional studies, using the WHO Stepwise (STEPs) survey data.SettingNational representative data of both urban and rural areas from Benin, Burkina Faso, Ghana, Liberia and Mali.ParticipantsAdults comprising 15 468 participants (6774 men and 8746 women; 7663 urban and 7805 rural residents) aged between 25 and 64 years.ResultsThe age and sex-adjusted prevalence of T2DM was 6.2% for urban areas and 2.5% for rural areas. The prevalence of impaired fasting glucose (IFG) was 6.6% for urban areas, and 3.0% for rural areas. No differences by sex were observed. The crude relative risk (RR) and 95% CI of T2DM and IFG in urban compared with rural areas were 2.69 (1.85 to 3.91) and 2.37 (1.53 to 3.66), respectively. This reduced to RR: 2.03, 95% CI (1.34 to 3.08) and RR: 2.04, 95% CI (1.27 to 3.28), respectively, after adjusting for covariables.ConclusionThe prevalence of both T2DM and IFG was more than two times as high in urban areas compared with rural areas in West Africa. Behavioural risk factors are common among urban populations, with ongoing urbanisation expected to drive increases in the prevalence of T2DM. These results could guide planning for T2DM screening, preventive strategies and resource allocation in West Africa.