bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multicenter performance evaluation of the Alinity m CMV assay for quantifying cytomegalovirus DNA in plasma samples
Authors: Lee Miae , Albert Eliseo , Wessels Els , Kim Soo-Kyung , Chung Hae-Sun , Giménez Estela , Vreeswijk Tom , Claas Eric C. J. , Tai Yan Chin , Reinhardt Birgit , Sasaki Mark M. , Navarro David 
Published: September 2023

ABSTRACT

Monitoring of cytomegalovirus (CMV) viral load is critical for informing treatment decisions in order to prevent the severe health consequences of CMV infection or reactivation of latent CMV in immunocompromised individuals. This first field evaluation examined the analytical and clinical performance of the Alinity m CMV assay. Analytical performance was assessed with a commercially available six-member panel, while the clinical performance evaluation compared the Alinity m CMV assay to the RealTi
m
e CMV assay and a laboratory-developed test (LDT) as the test of record at three large hospital-based clinical laboratories. Precision of the Alinity m CMV assay was demonstrated with total standard deviation (SD) between 0.08 and 0.28 Log IU/mL. A total of 457 plasma specimens were tested on the Alinity m CMV assay and compared to the test of record at each site (
n
= 304 with RealTi
m
e CMV and
n
= 153 with LDT CMV). The Alinity m CMV assay had excellent correlation (correlation coefficient
r
≥0.942) in comparison to the RealTi
m
e CMV or LDT CMV assays. The mean observed bias ranged from −0.03 to 0.34 Log IU/mL. Median onboard turnaround time of Alinity m CMV was less than 3 h. When the CMV assay is run on the Alinity m system, it has the capacity to shorten time to result and, therefore, to therapy.
A head-to-head comparison of three MALDI-TOF mass spectrometry systems with 16S rRNA gene sequencing
Authors: Dichtl Karl , Klugherz Isabel , Greimel Hanna , Luxner Josefa , Köberl Julian , Friedl Simone , Steinmetz Ivo , Leitner Eva 
Published: September 2023

ABSTRACT
Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) has revolutionized diagnostics in culture-based microbiology. Commonly used MALDI-TOF MS systems in clinical microbiology laboratories are MALDI Biotyper (Bruker Daltonics) and Vitek MS (bioMérieux), but recently the new EXS2600 (Zybio) has been launched. This study aimed to evaluate the performance of the three devices by comparing the results to 16S rRNA gene sequencing. A set of 356 previously collected difficult-to-identify bacteria was tested in parallel with the three systems. Only the direct smear method and simple formic acid extraction were applied. Valid results were achieved for 98.6%, 94.4%, and 93.3% of all isolates by MALDI Biotyper, EXS2600, and Vitek MS, respectively. Of all valid results, agreement with sequencing data was achieved in 98.9%, 98.5%, and 99.7% by MALDI Biotyper, EXS2600, and Vitek MS, respectively. Considering only the isolates with valid measurements at the single-species level, misidentification rates were 0%, 2.6%, and 1.1% for MALDI Biotyper, EXS2600, and Vitek MS, respectively. Apart from minor performance differences, our data demonstrate that the three systems provide comparable results and are suitable for use in medical diagnostic laboratories.
The morphogenic protein CopD controls the spatio-temporal dynamics of PBP1a and PBP2b in
Streptococcus pneumoniae
Authors: Lenoir Cassandra , Pelletier Anaïs , Manuse Sylvie , Millat Hugo , Ducret Adrien , Galinier Anne , Doan Thierry , Grangeasse Christophe 
Published: September 2023

ABSTRACT

Penicillin-binding proteins (PBPs) are key to the assembly of peptidoglycan, the major component of the bacterial cell wall. Although several PBP-specific regulatory proteins have been identified in different species, little is known about how the activity of PBPs is controlled and coordinated during the cell cycle. In this study, we characterize the unknown function protein Spr1400 and demonstrate its regulatory function on two PBPs in
Streptococcus pneumoniae
. For that, we use a combination of technics ranging from bacterial genetics and protein biochemistry to microscopy imaging. First, we show that pneumococcal Spr1400 localizes late to the cell division septum. Furthermore, deletion of
spr1400
results in wider cells. Using co-immunoprecipitation and bacterial two hybrid (B2H), we observe that Spr1400 interacts with two PBPs, the class A PBP PBP1a and the class B PBP PBP2b, which are required for cell elongation. Microscale thermophoresis combined with B2H further reveals that these interactions occur through their transmembrane domains. We also show that Spr1400 co-localizes with PBP1a and PBP2b throughout the cell cycle. Strikingly, deletion of
spr1400
alters the dynamics of PBP1a and PBP2b. Indeed, the two PBPs persist longer at the division site and localize later at the division site of daughter cells. Collectively, these data demonstrate that Spr1400, thus named CopD for
c
oordinator
o
f
P
BP1a and 2b
d
ynamics, is a spatio-temporal regulator of PBP1a and PBP2b required for pneumococcal morphogenesis.

IMPORTANCE

Penicillin-binding proteins (PBPs) are essential for proper bacterial cell division and morphogenesis. The genome of
Streptococcus pneumoniae
encodes for two class B PBPs (PBP2x and 2b), which are required for the assembly of the peptidoglycan framework and three class A PBPs (PBP1a, 1b and 2a), which remodel the peptidoglycan mesh during cell division. Therefore, their activities should be finely regulated in space and time to generate the pneumococcal ovoid cell shape. To date, two proteins, CozE and MacP, are known to regulate the function of PBP1a and PBP2a, respectively. In this study, we describe a novel regulator (CopD) that acts on both PBP1a and PBP2b. These findings provide valuable information for understanding bacterial cell division. Furthermore, knowing that ß-lactam antibiotic resistance often arises from PBP mutations, the characterization of such a regulator represents a promising opportunity to develop new strategies to resensitize resistant strains.
VirB, a key transcriptional regulator of
Shigella
virulence, requires a CTP ligand for its regulatory activities
Authors: Gerson Taylor M. , Ott Audrey M. , Karney Monika M. A. , Socea Jillian N. , Ginete Daren R. , Iyer Lakshminarayan M. , Aravind L. , Gary Ronald K. , Wing Helen J. 
Published: September 2023

ABSTRACT

The VirB protein, encoded by the large virulence plasmid of
Shigella
spp., is a key transcriptional regulator of virulence genes. Without
virB
,
Shigella
cells are avirulent. On the virulence plasmid, VirB functions to offset transcriptional silencing mediated by the nucleoid structuring protein, H-NS, which binds and sequesters AT-rich DNA, making it inaccessible for gene expression. Thus, gaining a mechanistic understanding of how VirB counters H-NS-mediated silencing is of considerable interest. VirB is unusual in that it does not resemble classic transcription factors. Instead, its closest relatives are found in the ParB superfamily, where the best-characterized members function in faithful DNA segregation before cell division. Here, we show that VirB is a fast-evolving member of this superfamily and report for the first time that the VirB protein binds a highly unusual ligand, CTP. VirB binds this nucleoside triphosphate preferentially and with specificity. Based on alignments with members of the ParB family, we identify amino acids of VirB likely to bind CTP. Substitutions in these residues disrupt several well-documented activities of VirB, including its anti-silencing activity, its ability to generate a Congo red positive phenotype, and the ability of the VirB protein to form foci in the bacterial cytoplasm when fused to GFP. Although stably produced, our CTP binding mutants do not bind DNA
in vivo
, likely explaining these phenotypes. Thus, this work is the first to show that VirB is a bona fide CTP-binding protein, links
Shigella
virulence phenotypes to the nucleoside triphosphate CTP, and provides novel insight into VirB-CTP-DNA interactions.

IMPORTANCE

Shigella
species cause bacillary dysentery, the second leading cause of diarrheal deaths worldwide. There is a pressing need to identify novel molecular drug targets.
Shigella
virulence phenotypes are controlled by the transcriptional regulator, VirB. We show that VirB belongs to a fast-evolving, plasmid-borne clade of the ParB superfamily, which has diverged from versions with a distinct cellular role—DNA partitioning. We report that, like classic members of the ParB family, VirB binds a highly unusual ligand, CTP. Mutants predicted to be defective in CTP binding are compromised in a variety of virulence attributes controlled by VirB, likely because these mutants cannot engage DNA. This study (i) reveals that VirB binds CTP, (ii) provides a link between VirB-CTP interactions and
Shigella
virulence phenotypes, (iii) provides new insight into VirB-CTP-DNA interactions, and (iv) broadens our understanding of the ParB superfamily, a group of bacterial proteins that play critical roles in many bacteria.
GraS signaling in
Staphylococcus aureus
is regulated by a single D35 residue in the extracellular loop
Authors: Cho Junho , Manna Adhar C. , Snelling Helah S. , Cheung Ambrose L. 
Published: September 2023

ABSTRACT

Bacterial two-component systems are crucial features of bacterial pathogens such as methicillin-resistant
Staphylococcus aureus
to overcome environmental and antimicrobial stresses by activating regulons to interfere with the bactericidal mechanisms. GraRS is a unique subset of two-component systems belonging to the intramembrane-sensing histidine kinase family (IM-HK) and is responsible for resistance to cationic host defense peptides. However, the precise manner by which the short 9-residue extracellular loop of the membrane sensor GraS detects the antimicrobial peptides and transduces the signal is not comprehensively understood. Here, we show that a single point mutation (D35A) in the extracellular loop of GraS blocked activation of GraRS, but this effect was also abrogated with
graS
mutations in the N-terminal transmembrane segments without any accompanying effect on GraS protein expression. Additionally, mutations in H120 and T172 in the dimerization/histidine phosphotransfer (DHp) domain of GraS increased activation without any accompanying enhancement in dimerization, likely due to disruption of the H120-T172 interaction that restricts rotational movements of the DHp helices since swapping H120 and T172 did not alter GraS activation. Notably, the enhancing effects of H120 and T172 mutations were abolished with a D35 mutation, highlighting the pivotal role of D35 in the 9-residue extracellular loop of GraS in GraR phosphorylation. In summary, our study delivers the significance of the D35 in the extracellular loop of GraS and ensuing changes in the N-terminal transmembrane helices as a model to illustrate signaling in the IM-HK subset of two-component regulatory systems.

IMPORTANCE

Methicillin-resistant
Staphylococcus aureus
(MRSA) is a human pathogen capable of infecting skin, blood, internal organs, and artificial medical devices. Generally, personal hygiene and a robust immune system can limit the spread of this pathogen; however, MRSA possesses an assortment of phenotypic tools to survive the hostile host environment including host defense peptides. More specifically,
S. aureus
utilizes two-component systems to sense noxious environmental cues to respond to harmful environmental elements. Our study focused on a two-component system called GraRS that
S. aureus
deploys against host defense peptides. We showed that one single residue in the extracellular loop of GraS and the adjacent membrane segment controlled the activation of GraRS, indicating the importance of a well-tuned-charged residue in the extracellular loop of GraS for sensing activity.
Westward underthrusting of thick North American crust: The dominant thickening process that built the Cordilleran orogenic plateau
Authors: Long Sean P. 
Published: September 2023

Abstract
Quantification of the crustal thickening processes that construct orogenic plateaus is essential for interpreting their genesis. In the North American Cordillera, a 2.75–3.5-km-elevation, 200–250-km-wide plateau was constructed to the west of the Cretaceous–Paleogene Sevier fold-and-thrust belt (SFTB). The SFTB deformed a Mesoproterozoic to Mesozoic sedimentary package that thickened westward from a 2–3-km-thick platform section that was deposited above the ~40-km-thick craton to a 15–25-km-thick continental margin section that was deposited above middle to lower crust that had been significantly thinned during Neoproterozoic rifting. Shortening in the SFTB translated this thick sedimentary package as much as 265 km eastward, which resulted in the relative westward underthrusting of an equivalent length of thick cratonic basement beneath the hinterland region. Measurement of components of thickening with respect to the initial and final crustal thickness above and below the basal thrust décollement demonstrates that thickening accommodated by underthrusting outweighed thickening in the overlying SFTB by a factor of 1.5–3 and was likely the dominant thickening mechanism that constructed the broad hinterland plateau. In eastern Nevada, the reconstructed western edge of the underthrusted craton underlies the western limit of 2.75–3.5 km paleoelevations, which supports this interpretation. This analysis provides an important case study for underthrusting as a first-order thickening process in fold-and-thrust systems that deform sedimentary packages with a high pre-orogenic taper.
The 2022 Summer record-breaking heatwave and health information-seeking behaviours: an infodemiology study in Mainland China
Authors: Li Zhiwei , Fan Yinguang , Su Hong , Xu Zhiwei , Ho Hung Chak , Zheng Hao , Tao Junwen , Zhang Yunquan , Hu Kejia , Hossain Mohammad Zahid , Zhao Qi , Huang Cunrui , Cheng Jian 
Published: September 2023

IntroductionHeatwave is a major global health concern. Many countries including China suffered a record-breaking heatwave during the summer of 2022, which may have a significant effect on population health or health information-seeking behaviours but is yet to be examined.MethodsWe derived health information-seeking data from the Baidu search engine (similar to Google search engine). The data included city-specific daily search queries (also referred to Baidu Search Index) for heat-sensitive diseases from 2021 to 2022, including heatstroke, hospital visits, cardiovascular diseases and diabetes, respiratory diseases, mental health and urological diseases. For each city, the record-breaking heatwave days in 2022 were matched to days in the same calendar month in 2021.ResultsThe 2022 record-breaking heatwave hit most cities (83.64%) in Mainland China. The average heatwave duration was 13 days and the maximum temperature was 3.60°C higher than that in 2021 (p<0.05). We observed increased population behaviours of seeking information on respiratory diseases (RR=1.014, 95% CI: 1.008 to 1.020), urological diseases (RR=1.011, 95% CI: 1.006 to 1.016) and heatstroke (RR=1.026, 95% CI: 1.016 to 1.036) associated with the heatwave intensity in 2022 (per 1°C increase). The heatwave duration in 2022 (per 1 day increase) was also associated with an increase in seeking information on cardiovascular diseases and diabetes (RR=1.003, 95% CI: 1.002 to 1.004), urological diseases (RR=1.005, 95% CI: 1.002 to 1.008), mental health (RR=1.009, 95% CI: 1.006 to 1.012) and heatstroke (RR=1.038, 95% CI: 1.032 to 1.043). However, there were substantial geographical variations in the effect of the 2022 heatwave intensity and duration on health information-seeking behaviours.ConclusionThis infodemiology study suggests that the 2022 summer unprecedented heatwave in Mainland China has significantly increased population demand for health-related information, especially for heatstroke, urological diseases and mental health. Population-based research of real-time disease data is urgently needed to estimate the negative health impact of the exceptional heatwave in Mainland China and elsewhere.
Adult mortality trends in Matlab, Bangladesh: an analysis of cause-specific risks
Authors: Ahmed Ali , Nahian Mahin Al , Rahman Md Mahabubur , Alam Nurul , Nahar Quamrun , Streatfield Peter Kim , Haider M Moinuddin , Rahman Mizanur 
Published: September 2023

ObjectiveWith socioeconomic development, improvement in preventing and curing infectious diseases, and increased exposure to non-communicable diseases (NCDs) risk factors (eg, overweight/obesity, sedentary lifestyle), the majority of adult deaths in Bangladesh in recent years are due to NCDs. This study examines trends in cause-specific mortality risks using data from the Matlab Health and Demographic Surveillance System (HDSS).Design, settings and participantsWe conducted a follow-up study from 2003 to 2017 using data from Matlab HDSS, which covers a rural population of 0.24 million (in 2018) in Chandpur, Bangladesh. HDSS assessed the causes of all deaths using verbal autopsy and classified the causes using the 10th revision of the International Statistical Classification of Diseases. We examined 19 327 deaths involving 2 279 237 person-years.MethodsWe calculated annual cause-specific mortality rates and estimated adjusted proportional HRs using a Cox proportional hazards model.ResultsAll-cause mortality risk declined over the study period among people aged 15 and older, but the risk from stroke increased, and from heart disease and cancers remained unchanged. These causes were more common among middle-aged and older people and thus bore the most burden. Mortality from causes other than NCDs—namely, infectious and respiratory diseases, injuries, endocrine disorders and others—declined yet still constituted over 30% of all deaths. Thus, the overall mortality decline was associated with the decline of causes other than NCDs. Mortality risk sharply increased with age. Men had higher mortality than women from heart disease, cancers and other causes, but not from stroke. Lower household wealth quintile people have higher mortality than higher household wealth quintile people, non-Muslims than Muslims.ConclusionDeaths from stroke, heart disease and cancers were either on the rise or remained unchanged, but other causes declined continuously from 2003 to 2017. Immediate strengthening of the preventive and curative healthcare systems for NCDs management is a burning need.
Quality of care from the perspective of people obtaining abortion: a qualitative study in four countries
Authors: Baum Sarah E , Jacobson Laura , Ramirez Ana Maria , Katz Anna , Grosso Belen , Bercu Chiara , Pearson Erin , Gebrehanna Ewenat , Chakraborty Nirali M , Dirisu Osasuyi , Chowdhury Rezwana , Zurbriggen Ruth , Filippa Sofia , Tabassum Tanzila , Gerdts Caitlin 
Published: September 2023

ObjectiveThis qualitative study aimed to identify person-centred domains that would contribute to the definition and measurement of abortion quality of care based on the perceptions, experiences and priorities of people seeking abortion.MethodsWe conducted interviews with people seeking abortion aged 15–41 who obtained care in Argentina, Bangladesh, Ethiopia or Nigeria. Participants were recruited from hospitals, clinics, pharmacies, call centres and accompaniment models. We conducted thematic analysis and quantified key domains of quality identified by the participants.ResultsWe identified six themes that contributed to high-quality abortion care from the clients’ perspective, with particular focus on interpersonal dynamics. These themes emerged as participants described their abortion experience, reflected on their interactions with providers and defined good and bad care. The six themes included (1) kindness and respect, (2) information exchange, (3) emotional support, (4) attentive care throughout the process, (5) privacy and confidentiality and (6) prepared for and able to cope with pain.ConclusionsPeople seeking abortion across multiple country contexts and among various care models have confirmed the importance of interpersonal care in quality. These findings provide guidance on six priority areas which could be used to sharpen the definition of abortion quality, improve measurement, and design interventions to improve quality.
Does the advertisement in Swiss pharmacy windows rest on evidence-based medicine? An observational study
Authors: Känzig Tanja , Potterat Melisa , Corpataux Thibault , Ackermann Simone Daniele , Chaix Edouard , Gibilisco Andrea , Portmann Aurelia , Roberts Judith , Schaller Amandine , Wenger Nicolas , Wolffers Oliver , Beguelin Charles , Genne Daniel 
Published: September 2023

ObjectivesThe aim of the study was to analyse the proportion of evidence-based medication displayed in pharmacies and compare it between the different linguistic regions of the country, at different times of the year to determine the amount of proven effective medications indirectly recommended to the public in different parts of Switzerland.DesignThis is an observational study conducted by medical doctors in the department of internal medicine at the Spitalzentrum Biel, Switzerland.SettingThe observation took place from July 2019 to May 2020. From a total of 1800 pharmacies in Switzerland, 68 different pharmacies were selected across the 3 main linguistic regions and the medication on display in their windows were examined 4 times a year regarding their efficacy. The displays of medication with or without evidence-based efficacy were described using absolute numbers and proportions and compared between the different linguistic regions at different seasons using χ2.ParticipantsThere were no human or animal participants involved in this study.Primary and secondary outcome measuresThe primary outcome is the proportion of medication displayed in pharmacy windows with a proven effectiveness in medical literature. The secondary outcome was the variability of the primary outcome over time (seasonal changes), over the different linguistic regions of Switzerland and between chains and privately owned pharmacies.ResultsWe examined 970 medications and found that over the whole year, there is a high proportion of non-evidence-based drugs (56,9%) displayed in pharmacies. Swiss German cantons display significantly more non-evidence-based medications in winter. We found no statistical difference for other seasons or between chains and privately owned pharmacies.ConclusionPharmacies in Switzerland tend to display significantly more non-evidence-based drugs, thus indirectly recommending them to the public. In a time of necessary expansion of self-medication by the population, this could incite consumers to buy drugs without proven effectiveness.