bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antimalarial resistance risk in Mozambique detected by a novel quadruplex droplet digital PCR assay
Authors: Brown Noah , da Silva Clemente , Webb Caroline , Matias Daniela , Dias Brigite , Cancio Beatriz , Silva Miguel , Viegas Ruben , Salvador Crizolgo , Chivale Nordino , Luis Sonia , Arnaldo Paulo , Zulawinska Julia , Moore Christopher C. , Nogueira Fatima , Guler Jennifer L. 
Published: May 2024

ABSTRACT

While the
Plasmodium falciparum
malaria parasite continues to cause severe disease globally, Mozambique is disproportionally represented in malaria case totals. Acquisition of copy number variations (CNVs) in the parasite genome contributes to antimalarial drug resistance through overexpression of drug targets. Of interest, piperaquine resistance is associated with plasmepsin 2 and 3 CNVs (
pfpmp2
and
pfpmp3,
respectively), while CNVs in the multidrug efflux pump, multidrug resistance-1 (
pfmdr1
), increase resistance to amodiaquine and lumefantrine. These antimalarials are partner drugs in artemisinin combination therapies (ACTs) and therefore, CNV detection with accurate and efficient tools is necessary to track ACT resistance risk. Here, we evaluated ~300 clinically derived samples collected from three sites in Mozambique for resistance-associated CNVs. We developed a novel, medium-throughput, quadruplex droplet digital PCR (ddPCR) assay to simultaneously quantify the copy number of
pfpmp3, pfpmp2
, and
pfmdr1
loci in these clinical samples. By using DNA from laboratory parasite lines, we show that this nanodroplet-based method is capable of detecting picogram levels of parasite DNA, which facilitates its application for low yield and human host-contaminated clinical surveillance samples. Following ddPCR and the application of quality control standards, we detected CNVs in 13 of 229 high-quality samples (prevalence of 5.7%). Overall, our study revealed a low number of resistance CNVs present in the parasite population across all three collection sites, including various combinations of
pfmdr1
,
pfpmp2
, and
pfpmp3
CNVs. The potential for future ACT resistance across Mozambique emphasizes the need for continued molecular surveillance across the region.
Plasma and tissue concentrations of 2 g prophylactic cefazolin prior to lower extremity surgery
Authors: Eelsing Robin , Penning Diederick , Vos-van der Meer Marloes , Hodiamont Caspar J. , Mathôt Ron A. A. , Schepers Tim 
Published: May 2024

ABSTRACT

Surgical site infections (SSIs) are among the most clinically relevant complications and the use of prophylactic cefazolin is common practice. However, the knowledge about the pharmacological aspects of prophylactic cefazolin in the lower extremities remains limited. In this prospective cohort, a sub-study of the WIFI-2 randomized controlled trial, adults between 18 and 75 years of age who were scheduled for implant removal below the level of the knee and randomized for cefazolin, was included. A maximum of two venous plasma, target-site plasma, and target-site tissue samples were taken during surgery. The primary outcomes were the cefazolin concentrations in venous plasma, target-site plasma, and target-site tissue. A total of 27 patients [median (interquartile range) age, 42 (29–59) years; 17 (63%) male] with 138 samples were included in the study. A minimum of 6 weeks follow-up was available for all patients. The mean (SD) venous plasma, target-site plasma, and target-site tissue concentrations were 36 (13) µg/mL, 29 (13) µg/mL, and 28 (13) µg/g, respectively, and the cefazolin concentrations between the different locations of surgery did not differ significantly in both target-site plasma and target-site tissue (
P
= 0.822 and
P
= 0.840). In conclusion, 2 g of prophylactic cefazolin demonstrates adequacy in maintaining coverage for a duration of at least 80 minutes of surgery below the level of the knee, significantly surpassing the MIC
90
required to combat the most prevalent microorganisms. This study represents the first of its kind to assess cefazolin concentrations in the lower extremities by examining both plasma and tissue samples in this magnitude.
Soil fungal community has higher network stability than bacterial community in response to warming and nitrogen addition in a subtropical primary forest
Authors: Li Debao , Wu Chuansheng , Wu Jianping 
Published: May 2024

ABSTRACT

Global change factors are known to strongly affect soil microbial community function and composition. However, as of yet, the effects of warming and increased anthropogenic nitrogen deposition on soil microbial network complexity and stability are still unclear. Here, we examined the effects of experimental warming (3°C above ambient soil temperature) and nitrogen addition (5 g N m
−2
year
−1
) on the complexity and stability of the soil microbial network in a subtropical primary forest. Compared to the control, warming increased |negative cohesion|:positive cohesion by 7% and decreased network vulnerability by 5%; nitrogen addition decreased |negative cohesion|:positive cohesion by 10% and increased network vulnerability by 11%. Warming and decreased soil moisture acted as strong filtering factors that led to higher bacterial network stability. Nitrogen addition reduced bacterial network stability by inhibiting soil respiration and increasing resource availability. Neither warming nor nitrogen addition changed fungal network complexity and stability. These findings suggest that the fungal community is more tolerant than the bacterial community to climate warming and nitrogen addition. The link between bacterial network stability and microbial community functional potential was significantly impacted by nitrogen addition and warming, while the response of soil microbial network stability to climate warming and nitrogen deposition may be independent of its complexity. Our findings demonstrate that changes in microbial network structure are crucial to ecosystem management and to predict the ecological consequences of global change in the future.

IMPORTANCE
Soil microbes play a very important role in maintaining the function and health of forest ecosystems. Unfortunately, global change factors are profoundly affecting soil microbial structure and function. In this study, we found that climate warming promoted bacterial network stability and nitrogen deposition decreased bacterial network stability. Changes in bacterial network stability had strong effects on bacterial community functional potentials linked to metabolism, nitrogen cycling, and carbon cycling, which would change the biogeochemical cycle in primary forests.
Critical analysis of polycyclic tetramate macrolactam biosynthetic gene cluster phylogeny and functional diversity
Authors: Harper Christopher P. , Day Anna , Tsingos Maya , Ding Edward , Zeng Elizabeth , Stumpf Spencer D. , Qi Yunci , Robinson Adam , Greif Jennifer , Blodgett Joshua A. V. 
Published: May 2024

ABSTRACT

Polycyclic tetramate macrolactams (PTMs) are bioactive natural products commonly associated with certain actinobacterial and proteobacterial lineages. These molecules have been the subject of numerous structure-activity investigations since the 1970s. New members continue to be pursued in wild and engineered bacterial strains, and advances in PTM biosynthesis suggest their outwardly simplistic biosynthetic gene clusters (BGCs) belie unexpected product complexity. To address the origins of this complexity and understand its influence on PTM discovery, we engaged in a combination of bioinformatics to systematically classify PTM BGCs and PTM-targeted metabolomics to compare the products of select BGC types. By comparing groups of producers and BGC mutants, we exposed knowledge gaps that complicate bioinformatics-driven product predictions. In sum, we provide new insights into the evolution of PTM BGCs while systematically accounting for the PTMs discovered thus far. The combined computational and metabologenomic findings presented here should prove useful for guiding future discovery.

IMPORTANCE

Polycyclic tetramate macrolactam (PTM) pathways are frequently found within the genomes of biotechnologically important bacteria, including
Streptomyces
and
Lysobacter
spp
.
Their molecular products are typically bioactive, having substantial agricultural and therapeutic interest. Leveraging bacterial genomics for the discovery of new related molecules is thus desirable, but drawing accurate structural predictions from bioinformatics alone remains challenging. This difficulty stems from a combination of previously underappreciated biosynthetic complexity and remaining knowledge gaps, compounded by a stream of yet-uncharacterized PTM biosynthetic loci gleaned from recently sequenced bacterial genomes. We engaged in the following study to create a useful framework for cataloging historic PTM clusters, identifying new cluster variations, and tracing evolutionary paths for these molecules. Our data suggest new PTM chemistry remains discoverable in nature. However, our metabolomic and mutational analyses emphasize the practical limitations of genomics-based discovery by exposing hidden complexity.
COVID-19 therapeutics
Authors: Focosi Daniele , Franchini Massimo , Maggi Fabrizio , Shoham Shmuel 
Published: May 2024

SUMMARY
Since the emergence of COVID-19 in 2020, an unprecedented range of therapeutic options has been studied and deployed. Healthcare providers have multiple treatment approaches to choose from, but efficacy of those approaches often remains controversial or compromised by viral evolution. Uncertainties still persist regarding the best therapies for high-risk patients, and the drug pipeline is suffering fatigue and shortage of funding. In this article, we review the antiviral activity, mechanism of action, pharmacokinetics, and safety of COVID-19 antiviral therapies. Additionally, we summarize the evidence from randomized controlled trials on efficacy and safety of the various COVID-19 antivirals and discuss unmet needs which should be addressed.
Lipid A modification of colistin-resistant
Klebsiella pneumoniae
does not alter innate immune response in a mouse model of pneumonia
Authors: Bhushan Gitanjali , Castano Victor , Wong Fok Lung Tania , Chandler Courtney , McConville Thomas H. , Ernst Robert K. , Prince Alice S. , Ahn Danielle 
Published: May 2024

ABSTRACT

Polymyxin resistance in carbapenem-resistant
Klebsiella pneumoniae
bacteria is associated with high morbidity and mortality in vulnerable populations throughout the world. Ineffective antimicrobial activity by these last resort therapeutics can occur by transfer of
mcr-1
, a plasmid-mediated resistance gene, causing modification of the lipid A portion of lipopolysaccharide (LPS) and disruption of the interactions between polymyxins and lipid A. Whether this modification alters the innate host immune response or carries a high fitness cost in the bacteria is not well established. To investigate this, we studied infection with
K. pneumoniae
(KP) ATCC 13883 harboring either the
mcr-1
plasmid (p
mcr-1
) or the vector control (pBCSK) ATCC 13883. Bacterial fitness characteristics of
mcr-1
acquisition were evaluated. Differentiated human monocytes (THP-1s) were stimulated with KP bacterial strains or purified LPS from both parent isolates and isolates harboring
mcr-1
. Cell culture supernatants were analyzed for cytokine production. A bacterial pneumonia model in WT C57/BL6J mice was used to monitor immune cell recruitment, cytokine induction, and bacterial clearance in the bronchoalveolar lavage fluid (BALF). Isolates harboring
mcr-1
had increased colistin MIC compared to the parent isolates but did not alter bacterial fitness. Few differences in cytokines were observed with purified LPS from
mcr-1
expressing bacteria
in vitro
. However, in a mouse pneumonia model, no bacterial clearance defect was observed between p
mcr-1
-harboring KP and parent isolates. Consistently, no differences in cytokine production or immune cell recruitment in the BALF were observed, suggesting that other mechanisms outweigh the effect of these lipid A mutations in LPS.
Final closure of the Paleo-Tethys Ocean: Insights from Triassic granitoids in the central Qiangtang area, northern Tibetan Plateau
Authors: Zhai Qingguo , Hu Peiyuan , Liu Yiming , Tang Yue , Lee Haoyang 
Published: May 2024

Abstract
The geodynamic evolution during the closure of the Paleo-Tethys Ocean in the Tibetan Plateau remains to be fully understood. The Longmu Co–Shuanghu suture zone in the northern Tibetan Plateau has usually been considered to represent the main ocean basin of the Paleo-Tethys Ocean, so it plays a key role in understanding the evolution of the Paleo-Tethys Ocean. In this study, we focused on the Gacuo and Bensong batholiths on the north and south sides of the Longmu Co–Shuanghu suture zone, respectively. We conducted detailed zircon geochronology and whole-rock geochemical and Sr-Nd isotopic analyses, as well as zircon Hf isotope studies. Zircon U-Pb dating indicates that the Gacuo batholith was formed ca. 223–209 Ma, and the age of the Bensong batholith is ca. 213–203 Ma. The Gacuo batholith is mainly composed of I-type granitoids, which are most likely attributed to partial melting of ancient sedimentary materials of the North Qiangtang terrane with a mixture of ~0%–30% amounts of mantle-derived components. In contrast, the Bensong batholith has granitoids of A-type affinity, and it was probably generated by partial melting of Mesoproterozoic crust of the South Qiangtang terrane with limited mantle contribution (&lt;5%). Finally, we suggest that the Gacuo batholith was probably generated by the break-off of the oceanic slab beneath the North Qiangtang terrane, while the Bensong batholith was related to a possible lithospheric delamination process of the South Qiangtang terrane after continental collision. Therefore, the Gacuo and Bensong batholiths both developed in a postcollisional tectonic setting, and they recorded the evolutionary process of the subduction and closure of the Paleo-Tethys Ocean during the Late Triassic.
Stakeholder perspectives on contributors to delayed and inaccurate diagnosis of cardiovascular disease and their implications for digital health technologies: a UK-based qualitative study
Authors: Abdullayev Kamilla , Gorvett Olivia , Sochiera Anna , Laidlaw Lynn , Chico Timothy , Manktelow Matthew , Buckley Oliver , Condell Joan , Van Arkel Richard , Diaz Vanessa , Matcham Faith 
Published: May 2024

ObjectiveThe aim of this study is to understand stakeholder experiences of diagnosis of cardiovascular disease (CVD) to support the development of technological solutions that meet current needs. Specifically, we aimed to identify challenges in the process of diagnosing CVD, to identify discrepancies between patient and clinician experiences of CVD diagnosis, and to identify the requirements of future health technology solutions intended to improve CVD diagnosis.DesignSemistructured focus groups and one-to-one interviews to generate qualitative data that were subjected to thematic analysis.ParticipantsUK-based individuals (N=32) with lived experience of diagnosis of CVD (n=23) and clinicians with experience in diagnosing CVD (n=9).ResultsWe identified four key themes related to delayed or inaccurate diagnosis of CVD: symptom interpretation, patient characteristics, patient–clinician interactions and systemic challenges. Subthemes from each are discussed in depth. Challenges related to time and communication were greatest for both stakeholder groups; however, there were differences in other areas, for example, patient experiences highlighted difficulties with the psychological aspects of diagnosis and interpreting ambiguous symptoms, while clinicians emphasised the role of individual patient differences and the lack of rapport in contributing to delays or inaccurate diagnosis.ConclusionsOur findings highlight key considerations when developing digital technologies that seek to improve the efficiency and accuracy of diagnosis of CVD.
Characteristics of first-time users of the nursing small-scale multifunctional home care service: a pooled cross-sectional study using Japanese long-term care insurance claims data from 2012 to 2019
Authors: Morioka Noriko , Kashiwagi Masayo , Kashiwagi Kimikazu , Abe Kazuhiro , Miyawaki Atsushi 
Published: May 2024

ObjectivesIn April 2012, the Japanese government launched a new nursing service called the nursing small-scale multifunctional home care (NSMHC) to meet the nursing care demands of individuals with moderate-to-severe activities of daily living (ADLs) dysfunction and who require medical care, thereby allowing them to continue living in the community. We aimed to preliminarily analyse the characteristics of first-time users of NSMHC service.DesignThis pooled cross-sectional study used the Japanese long-term care insurance (LTCI) claims data from the users’ first use of NSMHC (from April 2012 to December 2019).SettingNSMHC includes nursing home visits, home care, daycare, overnight stays and medical treatment.ParticipantsThe study population included LTCI beneficiaries who received their first long-term care requirement certification in Japan from April 2012 onwards, died between April 2012 and December 2019, and used any LTCI service at least once.ResultsAmong the 836 563 individuals who used any LTCI service at least once, 3957 (0.47%) used NSMHC. We analysed 3634 individuals without any missing data regarding long-term care requirement certification. Most individuals were aged 80 years or older, with 64.3% requiring care level 3 or above, indicating complete assistance with ADLs. Regarding ADLs in individuals with dementia, 70.6% were at level 2 or below, indicating they can live almost independently even with dementia. A large proportion of NSMHC users availed the service approximately 6 months before death, with no prior use of any LTCI services; they continued using the service for around 4 months, although some people continued to use NSMHC until their month of death.ConclusionsUsing individual data on nationwide LTCI, we described the characteristics of first-time users of NSMHC among those who died within 7.5 years from the first certification of care needs. Further studies are needed to investigate the effect of NSMHC use on user outcomes.
Does living alone influence fall risk among Swiss older adults aged 60+? A pooled observational analysis of three RCTs on fall prevention
Authors: Braendle Kilian , Egli Andreas , Bischoff-Ferrari Heike , Freystaetter Gregor 
Published: May 2024

ObjectivesFalling and living alone have been identified as public health challenges in an ageing society. Our study investigates whether living alone influences fall risk in community-dwelling older adults in Switzerland.Design and methodsSecondary analysis of three randomised controlled trials investigating how different doses of vitamin D and an exercise programme may influence the risk of further falls in people 60+ at risk of falling. We used logistic regression to examine the association between living alone and the odds of becoming a faller, and negative binomial regression to examine the association between living alone and the rate of falls. We assessed both any falls and falls with injury. All analyses were adjusted for sex, body mass index, age, grip strength, comorbidities, use of walking aids, mental health, trial and treatment group. Predefined subgroups were by sex and age.ResultsAmong 494 participants (63% women; mean age was 74.7±7.5 years) 643 falls were recorded over 936.5 person-years, including 402 injurious falls. Living alone was associated with a 1.76-fold higher odds of becoming a faller (OR (95% CI)=1.76 (1.11 to 2.79)). While the odds did not differ by sex, older age above the median age of 74.6 years increased the odds to 2.19-fold (OR (95% CI)=2.19 (1.11 to 4.32)). The rate of total or injurious falls did not differ by living status.ConclusionsCommunity-dwelling older adults living alone have a higher odds of becoming a faller. The increased odds is similar for men and women but accentuated with higher age.Trial registration numbersZDPT:NCT01017354, NFP53:NCT00133640, OA:NCT00599807.
Effect of HIV and substance use disorder comorbidity on the placenta, fetal and maternal health outcomes: systematic review and meta-analysis protocol
Authors: Sorato Mende Mensa , Alemu Tsegaye , Toma Alemayehu , Paulos Getahun , Mekonnen Shewangizaw 
Published: May 2024

BackgroundSubstance use disorders and HIV infection have a bidirectional relationship. People who use illicit drugs are at increased risk of contracting HIV/AIDS, and people living with HIV/AIDS are at increased risk of using substances due to disease-related complications like depression and HIV-associated dementia. There is no adequate evidence on the effect of HIV/AIDS and substance use disorder comorbidity-related effects on placental, fetal, maternal and neonatal outcomes globally.Methods and analysisWe will search articles written in the English language until 30 January 2024, from PubMed/Medline, Cochrane Library, Embase, Scopus, Web of Sciences, SUMsearch2, Turning Research Into Practice database and Google Scholar. A systematic search strategy involving AND/OR Boolean Operators will retrieve information from these databases and search engines. Qualitative and quantitative analysis methods will be used to report the effect of HIV/AIDS and substance use disorders on placental, fetal and maternal composite outcomes. Descriptive statistics like pooled prevalence mean and SD will be used for qualitative analysis. However, quantitative analysis outcomes will be done by using Comprehensive Meta-Analysis Software for studies that are combinable. The individual study effects and the weighted mean difference will be reported in a forest plot. In addition to this, the presence of multiple morbidities like diabetes, chronic kidney disease and maternal haemoglobin level could affect placental growth, fetal growth and development, abortion, stillbirth, HIV transmission and composite maternal outcomes. Therefore, subgroup analysis will be done for pregnant women with multiple morbidities.Ethics and disseminationSince systematic review and meta-analysis will be conducted by using published literature, ethical approval is not required. The results will be presented in conferences and published in peer-reviewed journals.PROSPERO registration numberCRD42023478360.