bluuebunny/crossref_metadata_2025_split huggingface dataset:
Altered PBP4 and GdpP functions synergistically mediate MRSA-like high-level, broad-spectrum β-lactam resistance in
Staphylococcus aureus
Authors: Lai Li-Yin , Satishkumar Nidhi , Cardozo Sasha , Hemmadi Vijay , Marques Leonor B. , Huang Liusheng , Filipe Sergio R. , Pinho Mariana G. , Chambers Henry F. , Chatterjee Som S. 
Published: March 2024

ABSTRACT

Infections caused by
Staphylococcus aureus
are a leading cause of mortality worldwide.
S. aureus
infections caused by methicillin-resistant
Staphylococcus aureus
(MRSA) are particularly difficult to treat due to their resistance to next-generation β-lactams (NGBs) such as methicillin, nafcillin, and oxacillin. Resistance to NGBs, which is alternatively known as broad-spectrum β-lactam resistance, is classically mediated by PBP2a, a penicillin-binding protein encoded by
mecA
(or
mecC
) in MRSA. Thus, presence of
mec
genes among
S. aureus
spp. serves as the predictor of resistance to NGBs and facilitates determination of the proper therapeutic strategy for a staphylococcal infection. Although far less appreciated,
mecA
-deficient
S. aureus
strains can also exhibit NGB resistance. These strains, which are collectively termed as methicillin-resistant lacking
mec
(MRLM), are currently being identified in increasing numbers among natural resistant isolates of
S. aureus
. The mechanism/s through which MRLMs produce resistance to NGBs remains unknown. In this study, we demonstrate that mutations that alter PBP4 and GdpP functions, which are often present among MRLMs, can synergistically mediate resistance to NGBs. Furthermore, our results unravel that this novel mechanism potentially enables MRLMs to produce resistance toward NGBs at levels comparable to those of MRSAs. Our study provides a fresh new perspective about alternative mechanisms of NGB resistance, challenging our current overall understanding of high-level, broad-spectrum β-lactam resistance in
S. aureus
. It thus suggests reconsideration of the current approach toward diagnosis and treatment of β-lactam-resistant
S. aureus
infections.

IMPORTANCE

In
Staphylococcus aureus
, high-level, broad-spectrum resistance to β-lactams such as methicillin, also referred to as methicillin resistance, is largely attributed to
mecA
. This study demonstrates that
S. aureus
strains that lack
mecA
but contain mutations that functionally alter PBP4 and GdpP can also mediate high-level, broad-spectrum resistance to β-lactams. Resistance brought about by the synergistic action of functionally altered PBP4 and GdpP was phenotypically comparable to that displayed by
mecA
, as seen by increased bacterial survival in the presence of β-lactams. An analysis of mutations detected in naturally isolated strains of
S. aureus
revealed that a significant proportion of them had similar
pbp4
and
G
GDEF
d
omain
p
rotein containing
p
hosphodiesterase (
gdpP
) mutations, making this study clinically significant. This study not only identifies important players of non-classical mechanisms of β-lactam resistance but also indicates reconsideration of current clinical diagnosis and treatment protocols of
S. aureus
infections.
Draft genome sequence of a triple hybrid
Escherichia coli
strain isolated from a healthy donor feces
Authors: Ortega-Enríquez Judith Z. , Arenas-Hernández Margarita M. P. , Barrios-Villa Edwin 
Published: March 2024

ABSTRACT

Herein is reported the draft genome sequence of a triple hybrid
Escherichia coli
strain isolated from a healthy donor feces. The assembly is 5.2 Mbp, composed of 247 contigs, with a N
50
of 77, 241 bp, presenting a GC content of 50.8%.
Microscale advection governs microbial growth and oxygen consumption in macroporous aggregates
Authors: Shen Rachel , Borer Benedict , Ciccarese Davide , Salek M. Mehdi , Babbin Andrew R. 
Published: March 2024

ABSTRACT

Most microbial life on Earth is found in localized microenvironments that collectively exert a crucial role in maintaining ecosystem health and influencing global biogeochemical cycles. In many habitats such as biofilms in aquatic systems, bacterial flocs in activated sludge, periphyton mats, or particles sinking in the ocean, these microenvironments experience sporadic or continuous flow. Depending on their microscale structure, pores and channels through the microenvironments permit localized flow that shifts the relative importance of diffusive and advective mass transport. How this flow alters nutrient supply, facilitates waste removal, drives the emergence of different microbial niches, and impacts the overall function of the microenvironments remains unclear. Here, we quantify how pores through microenvironments that permit flow can elevate nutrient supply to the resident bacterial community using a microfluidic experimental system and gain further insights from coupled population-based and computational fluid dynamics simulations. We find that the microscale structure determines the relative contribution of advection vs diffusion, and even a modest flow through a pore in the range of 10 µm s
−1
can increase the carrying capacity of a microenvironment by 10%. Recognizing the fundamental role that microbial hotspots play in the Earth system, developing frameworks that predict how their heterogeneous morphology and potential interstitial flows change microbial function and collectively alter global scale fluxes is critical.

IMPORTANCE
Microbial life is a key driver of global biogeochemical cycles. Similar to the distribution of humans on Earth, they are often not homogeneously distributed in nature but occur in dense clusters that resemble microbial cities. Within and around these clusters, diffusion is often assumed as the sole mass-transfer process that dictates nutrient supply and waste removal. In many natural and engineered systems such as biofilms in aquatic environments, aggregates in bioremediation, or flocs in wastewater treatment plants, these clusters are exposed to flow that elevates mass transfer, a process that is often overlooked. In this study, we show that advective fluxes can increase the local growth of bacteria in a single microenvironment by up to 50% and shape their metabolism by disrupting localized anoxia or supplying nutrients at different rates. Collectively, advection-enhanced mass transport may thus regulate important biogeochemical transformations in both natural and engineered environments.
Rehydrated glass embayments record the cooling of a Yellowstone ignimbrite
Authors: Befus Kenneth S. , Thompson James O. , Allison Chelsea M. , Ruefer Anna C. , Manga Michael 
Published: March 2024

Abstract
Hydration fronts penetrate 50–135 μm into glassy rhyolite embayments hosted in quartz crystals from the Mesa Falls Tuff in the Yellowstone Plateau volcanic field. The hydration fronts occur as steep enrichments that reach 2.4 ± 0.6 wt% H2O at the embayment opening, representing much higher values than interior concentrations of 0.9 ± 0.2 wt% H2O. Molecular water accounts for most of the water enrichment. Water speciation indicates the hydration fronts comprise absorbed meteoric water that modified the original magmatic composition of the rhyolitic glass. We used finite difference diffusion models to demonstrate that glass rehydration was likely produced over a few decades as the ignimbrite cooled. Such temperatures and time scales are consistent with rare firsthand observations of decadal hydrothermal systems associated with cooling ignimbrites at Mount Pinatubo (Philippines) and the Valley of Ten Thousand Smokes (Alaska).
Okanogan lobe tunnel channels and subglacial floods into Moses Coulee, Channeled Scabland, northwestern United States
Authors: Gombiner Joel , Lesemann Jerome-Etienne 
Published: March 2024

Abstract
Outburst floods from glacial Lake Missoula largely explain erosion of the Channeled Scabland, a system of overfit, basaltic channels in Washington, northwestern United States. However, it is challenging to explain Missoula flood routing into Moses Coulee due to its topographic isolation from flood routes. To clarify flood pathways into Moses Coulee, we mapped channels that delineate a radial-anastomosing network connecting to Moses Coulee. Channels consist of coulee-like features eroded mainly in basalt. Channels climb adverse slopes and cross divides, and the network is draped with eskers and recessional moraines. These channel geometries and glacial landform associations suggest a tunnel channel network. Large channel dimensions and network anastomosis indicate formation in subglacial floods. The network connects to Moses Coulee with sufficient cross-sectional area to convey megafloods, hinting that subglacial floods may have been a significant source of Moses Coulee meltwater, in addition to possible diverted Missoula floods.
Investigation of renal perfusion and pathological changes in patients with acute kidney disease and tubulointerstitial nephritis using intravoxel incoherent motion and arterial spin labelling MRI: a prospective, observational study protocol
Authors: Liu Jiajia , Wang Rui , Qiu Jianxing , Su Tao 
Published: March 2024

IntroductionAcute kidney injury (AKI) is a critical condition with a complex aetiology and different outcomes, where haemodynamic dysfunction, renal hypoperfusion and inflammation serve as key contributors to its development and progression. Early and accurate diagnosis is vital for initiating targeted treatments like fluid resuscitation, vasoactive agents or steroid therapy, which are essential for improving patient outcomes. Intravoxel incoherent motion (IVIM) MRI assesses both capillary perfusion and tissue water diffusion, while arterial spin labelling (ASL) MRI measures renal blood flow without the need for contrast. Research on combined use of IVIM and ASL MRI in patients with AKI is rare. This study aims to investigate the MRI characteristics of IVIM and ASL in patients with tubulointerstitial nephritis (TIN) and to explore their relationship with pathological findings and renal recovery.Methods and analysisSingle-centre, prospective, observational cohort study of 30 patients with biopsy-proven TIN. Participants will undergo renal IVIM and ASL MRI within 7 days post-biopsy. The pathological assessments of active and chronic tubulointerstitial injuries will be semiscored using modified Banff criteria. The estimated glomerular filtration rate (eGFR) during follow-up and prevalence of chronic kidney disease at 3 and 6 months will be reported. An eGFR below 45 mL/min is considered a poor renal outcome.Ethics and disseminationThe study has been reviewed and approved by the Ethics Committee of Peking University First Hospital and written informed consent will be obtained from all participants (2022Y503). The study results will be disseminated through publication in a relevant peer-reviewed journal and presentation at academic meetings to increase awareness and share findings with the scientific community.
Innovative services in home health nursing: a scoping review protocol
Authors: Eshghi Fateme , Pourgholam Nima , Kianian Toktam , Kashani Maryam , Azami Masoomeh 
Published: March 2024

IntroductionAdvances in the use of technology in home health nursing (HHN) not only can facilitate the delivery of home care but can also influence the entire healthcare system. Additionally, it can contribute to the individual autonomy in the area of health. The aim of this scoping review protocol is to identify, describe and map the types of innovative services and their delivery approaches in the HHN structure worldwide.Methods and analysisThe main question of the research is as follows: what are different types of innovative services and their delivery approaches in the HHN structure around the world? The Joanna Briggs Institute (JBI) method for scoping reviews will guide the conducting this scoping review, and the participants, concept and context framework will be used as eligibility criteria. MEDLINE databases via PubMed, Embase, Cochrane Library, Scopus, Web of Science, Science Direct, Persian scientific databases and grey literature will be searched prior to May 2024 to include eligible studies, without any language restrictions. To be included, studies will be reviewed by two independent reviewers. A data extraction form developed for the study purpose will be used to extract the data relevant to the review questions. Data analysis will be performed based on each innovative service and answering the subquestions about it. According to the concepts of interest, the results will be analysed and presented using tables, figures, images and a narrative summary.Ethics and disseminationThis study will not involve human or animal participants. Data will be sourced from the published literature. To be published, the results of the study will be submitted to an international peer-reviewed, open-access journal as well as scientific meetings on HHN and innovative services research.
Hidden hunger in patients with type 2 diabetes (T2D) and its effect on glycaemic control: a protocol for systematic review and meta-analysis
Authors: Mangal Daya Krishan , Gautam Diksha , Pandey Anuj Kumar , Shaikh Nida , Mishra Sidharth Sekhar , Tolani Himanshu , Sonnathi Yeshwanth , Gupta Shiv Dutt , Sharma Kamlesh Chand , Prasad Jagdish , Tewari Rajeev , Anwar Fahmina 
Published: March 2024

IntroductionHidden hunger or micronutrient deficiencies are quite common in many parts of the world, particularly in the countries of sub-Saharan Africa and South Asia. Micronutrient deficiencies may impact insulin signalling pathways and glucose metabolism, potentially accelerating the onset and development of type 2 diabetes (T2D). This review aims to estimate the prevalence of multiple micronutrient deficiencies among patients with T2D and assess the effect of their deficiency on glycaemic control.MethodologyThe review follows the Cochrane Handbook and PRISMA 2020 guidelines. It includes all eligible studies reporting the prevalence of micronutrient deficiencies and their effect on glycaemic control in T2D patients. We would undertake a comprehensive literature search across databases: PubMed, Scopus, EMBASE, LILACS, ProQuest, Google Scholar and grey literature, and identify the studies meeting the inclusion criteria. We would perform data extraction using a prepiloted data extraction sheet and record relevant study characteristics and outcomes.AnalysisData will be analysed using JBI Sumari software and R software. Pooled prevalence/incidence of micronutrient deficiency will be estimated, and variance will be stabilised using logit transformation and a double-arcsine transformation of the data. The OR and risk ratio of glycaemic control among T2D cases with and without micronutrient deficiency will be estimated using the ‘rma’ function under the ‘meta’ and ‘metafor’ packages.The study findings will have implications for diabetes management strategies and may inform interventions targeting improved glycaemic control through addressing micronutrient deficiencies.Ethics and disseminationThis systematic review will be based on the scientific information available in the public domain; therefore, ethics approval is not required. We will share the study findings at national and international conferences and submit them for publication in relevant scientific journals.PROSPERO registration numberCRD42023439780.
Skeletal muscle relaxants as adjunctive pain control following cardiothoracic surgery: a systematic review protocol
Authors: Kabir Shadman , Whaley Quinn , Fernandez Melissa , Murphy Travis W 
Published: March 2024

IntroductionMultimodal pain control following cardiothoracic surgery remains a focus in international guidelines. We hypothesise that non-depolarising skeletal muscle relaxants can prove to be a useful adjunct for this population.Methods/analysisThis systematic review will focus on human adult studies of pain control using muscle relaxants within 1 week following cardiac and thoracic surgery available in PubMed, Cochrane Central, Web of Science and EMBASE. Target studies will have a primary focus on measured effects on quality of pain control and reduction in opioid usage. Studies that include non-depolarising skeletal muscle relaxants given during cardiothoracic surgery or in the week after will be included. Study selection will be in keeping with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Procedures and agents used will be analysed together, and a meta-analysis will be conducted then compared with current therapies recommended in international practice guidelines.Ethics and disseminationFormal ethical approval will not be required as primary data will not be collected. The results will be disseminated through peer-reviewed publication, conference presentation and lay press.PROSPERO registration numberCRD42023397917.
Efficacy and safety of natural killer cells injection combined with XELOX chemotherapy in postoperative patients with stage III colorectal cancer in China: a prospective randomised controlled clinical trial study protocol
Authors: Geng Shan , Yu Xingrui , Yu Shaohong 
Published: March 2024

BackgroundColorectal cancer (CRC) is the second most frequently diagnosed cancer and the fifth leading cause of cancer-related death in China. However, resistance to multiple chemotherapeutics after surgery leads to failure of the main therapy to CRC. Natural killer (NK) cells are innate cytotoxic lymphocytes that exhibit strong cytotoxic activity against tumour cells. NK cell-based therapy, either alone or in combination with chemotherapy, has achieved favourable results and holds promise for addressing recurrence and metastasis in CRC patients after surgery.Methods and analysisThis is a prospective, randomised controlled clinical trial to evaluate efficacy and safety of interleukin 2 activated NK cells injection combined with XELOX (capecitabine plus oxaliplatin)-based chemotherapy for postoperative CRC patients. Participants will be randomly divided into treatment group and control group, and every group includes 40 patients. The treatment group will also receive NK cells (5×109) with+XELOX-based chemotherapy, while the control group will receive only XELOX-based chemotherapy. This treatment will be repeated for eight cycles (6 months). The follow-up period lasts about 3 years, during which CEA, CA19-9, CA125, enhancement CT and colonoscopy will be conducted. The primary endpoints of this study are progression-free survival and overall survival, while the secondary endpoint is safety (number and severity of adverse events). Additionally, we aim to identify cancer stem cells in peripheral blood and predictive biomarkers (cytokines secreted by NK cells and activated markers of NK cells) that indicate patients who achieve an effective response.Ethics and disseminationThe study has been approved by the Clinical Research Ethics Committee of our hospital (approval number 2023LLSC006) and the Chinese Clinical Trials. It will be conducted in accordance with the Declaration of Helsinki. Written informed consent will be obtained from all participants. The study findings will be submitted to peer-reviewed journals for publication.Trial registration numberChinese Clinical Trials Registry (ChiCTR2300075861).
Association between osteoarthritis and cardiovascular disease in elderly in Japan: an administrative claims database analysis
Authors: Uematsu Takuya , Nojiri Shuko , Ishijima Muneaki , Nishizaki Yuji 
Published: March 2024

ObjectiveTo investigate whether osteoarthritis (OA) is a risk factor for cardiovascular disease (CVD); whether there are differences concerning ischaemic heart disease (IHD), congestive heart failure (CHF) and stroke; and whether there are differences between OA sites (hips, knees and hand) in predicting CVD onset.DesignPopulation-based matched case–control study.SettingHealth insurance claims data among Japanese patients.ParticipantsJapanese patients aged ≥65 years with newly diagnosed CVD and hospitalised between January 2015 and December 2020 (cases) and age-matched and sex-matched 1:1 individuals (controls).Main outcome measuresA conditional logistic regression model was used to estimate the adjusted ORs and their 95% CIs for CVD, IHD, CHF and stroke risk, adjusting for covariates.ResultsA total of 79 296 patients were included, with respect to CVD (39 648 patients with newly diagnosed CVD and 39 648 controls). After adjustment for covariates, the exposure odds of knee OA (KOA), hip OA (HipOA) and hand OA (HandOA) for CVD were 1.192 (95% CI 1.115 to 1.274), 1.057 (95% CI 0.919 to 1.215) and 1.035 (95% CI 0.684 to 1.566), respectively, showing an association only for KOA. The exposure odds of KOA, HipOA and HandOA for IHD were 1.187 (95% CI 1.086 to 1.297), 1.078 (95% CI 0.891 to 1.306) and 1.099 (95% CI 0.677 to 1.784), respectively. The exposure odds of KOA, HipOA and HandOA for stroke were 1.221 (95% CI 1.099 to 1.356), 0.918 (95% CI 0.723 to 1.165) and 1.169 (95% CI 0.635 to 2.151), respectively. Similar to CVD, only KOA was associated with both. For CHF, neither KOA nor HipOA and HandOA were associated with CHF development.ConclusionThis study confirms the association of KOA with CVD, particularly IHD and stroke, in the Japanese population. The finding that patients with KOA have a higher CVD risk can potentially assist in guiding future treatment strategies.
Effectiveness and cost-effectiveness of a sustainable obesity prevention programme for preschool children delivered at scale ‘HENRY’ (Health, Exercise, Nutrition for the Really Young): protocol for the HENRY III cluster randomised controlled trial
Authors: Bryant Maria , Burton Wendy , Collinson Michelle , Martin Adam , Copsey Bethan , Groves-Williams Dawn , Foster Alexis , Willis Thomas A , Garnett Philip , O'Cathain Alicia 
Published: March 2024

IntroductionOne-fifth of children start school already overweight or living with obesity, with rates disproportionately impacting those living in the most deprived areas. Social, environmental and biological factors contribute to excess weight gain and programmes delivered in early years settings aim to support families to navigate these in order to prevent obesity. One of these programmes (Health, Exercise and Nutrition for the Really Young, HENRY) has been delivered in UK community venues (hereon named ‘centres’) in high deprivation areas since 2008 and aims to help families to provide a healthy start for their preschool children. We aim to establish the effectiveness and cost-effectiveness of HENRY, including its potential role from a wider systems perspective.Methods and analysisThis is a multicentre, open-labelled, two-group, prospective, cluster randomised controlled trial, with cost-effectiveness analysis, systems-based process evaluation and internal pilot. Primary analysis will compare body mass index (BMI) z-score at 12 months in children (n=984) whose parents have attended HENRY to those who have not attended. Secondary outcomes include parent and staff BMI and waist circumference, parenting efficacy, feeding, eating habits, quality of life, resource use and medium term (3 years) BMI z-scores (child and siblings). 82 centres in ~14 local authority areas will be randomised (1:1) to receive HENRY or continue with standard practice. Intention-to-treat analysis will compare outcomes using mixed effects linear regression. Economic evaluation will estimate a within-trial calculation of cost-per unit change in BMI z-score and longer-term trajectories to determine lifelong cost savings (long-term outcomes). A systems process evaluation will explore whether (and how) implementation of HENRY impacts (and is impacted by) the early years obesity system. An established parent advisory group will support delivery and dissemination.Ethics and disseminationEthical approval has been granted by the University of York, Health Sciences’ Research Governance Committee (HSRGC/2022/537/E). Dissemination includes policy reports, community resources, social media and academic outputs.Trial registration numberISRCTN16529380.