bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interferon lambda restricts herpes simplex virus skin disease by suppressing neutrophil-mediated pathology
Authors: Philip Drake T. , Goins Nigel M. , Catanzaro Nicholas J. , Misumi Ichiro , Whitmire Jason K. , Atkins Hannah M. , Lazear Helen M. 
Published: March 2024

ABSTRACT

Type III interferons (IFN-λ) are antiviral and immunomodulatory cytokines that have been best characterized in respiratory and gastrointestinal infections, but the effects of IFN-λ against skin infections have not been extensively investigated. We sought to define the skin-specific effects of IFN-λ against the highly prevalent human pathogen, herpes simplex virus (HSV). We infected mice lacking the IFN-λ receptor (
Ifnlr1
−/−
), both the IFN-λ and the IFN-α/β receptors (
Ifnar1
−/−
Ifnlr1
−/−
), or IFN-λ cytokines (
Ifnl2/3
−/−
) and found that IFN-λ restricts the severity of HSV-1 and HSV-2 skin lesions without affecting viral loads. We used RNAseq to define IFN-λ- and IFN-β-induced transcriptional responses in primary mouse keratinocytes. Using conditional knockout mice, we found that IFN-λ signaling in both keratinocytes and neutrophils was necessary to control HSV-1 skin lesion severity and that IFN-λ signaling in keratinocytes suppressed CXCL9-mediated neutrophil recruitment to the skin. Furthermore, depleting neutrophils or blocking CXCL9 protected against severe HSV-1 skin lesions in
Ifnlr1
−/−
mice. Altogether, our results suggest that IFN-λ plays an immunomodulatory role in the skin that restricts neutrophil-mediated pathology during HSV infection and suggests potential applications for IFN-λ in treating viral skin infections.

IMPORTANCE
Type III interferons (IFN-λ) have been shown to have antiviral and immunomodulatory effects at epithelial barriers such as the respiratory and gastrointestinal tracts, but their effects on the skin have not been extensively investigated. We used mice lacking IFN-λ signaling to investigate the skin-specific effects of IFN-λ against the herpes simplex virus (HSV), which targets epithelial tissues to cause cold sores and genital herpes. We found that IFN-λ limited the severity of HSV skin lesions without affecting viral load and that this protective effect required IFN-λ signaling in both keratinocytes and neutrophils. We found that IFN-λ signaling in keratinocytes suppressed neutrophil recruitment to the skin and that depleting neutrophils protected against severe HSV skin lesions in the absence of IFN-λ. Altogether, our results suggest that IFN-λ plays an immunomodulatory role in the skin that restricts neutrophil-mediated pathology during HSV infection and suggests potential applications for IFN-λ in treating viral skin infections.
How
P. aeruginosa
cells with diverse stator composition collectively swarm
Authors: de Anda Jaime , Kuchma Sherry L. , Webster Shanice S. , Boromand Arman , Lewis Kimberley A. , Lee Calvin K. , Contreras Maria , Medeiros Pereira Victor F. , Schmidt William , Hogan Deborah A. , O’Hern Corey S. , O’Toole George A. , Wong Gerard C. L. 
Published: March 2024

ABSTRACT

Swarming is a macroscopic phenomenon in which surface bacteria organize into a motile population. The flagellar motor that drives swarming in
Pseudomonas aeruginosa
is powered by stators MotAB and MotCD. Deletion of the MotCD stator eliminates swarming, whereas deletion of the MotAB stator enhances swarming. Interestingly, we measured a strongly asymmetric stator availability in the wild-type (WT) strain, with MotAB stators produced at an approximately 40-fold higher level than MotCD stators. However, utilization of MotCD stators in free swimming cells requires higher liquid viscosities, while MotAB stators are readily utilized at low viscosities. Importantly, we find that cells with MotCD stators are ~10× more likely to have an active motor compared to cells uses the MotAB stators. The spectrum of motility intermittency can either cooperatively shut down or promote flagellum motility in WT populations. In
P. aeruginosa
, transition from a static solid-like biofilm to a dynamic liquid-like swarm is not achieved at a single critical value of flagellum torque or stator fraction but is collectively controlled by diverse combinations of flagellum activities and motor intermittencies via dynamic stator utilization. Experimental and computational results indicate that the initiation or arrest of flagellum-driven swarming motility does not occur from individual fitness or motility performance but rather related to concepts from the “jamming transition” in active granular matter.

IMPORTANCE

It is now known that there exist multifactorial influences on swarming motility for
P. aeruginosa
, but it is not clear precisely why stator selection in the flagellum motor is so important. We show differential production and utilization of the stators. Moreover, we find the unanticipated result that the two motor configurations have significantly different motor intermittencies: the fraction of flagellum-active cells in a population on average with MotCD is active ~10× more often than with MotAB. What emerges from this complex landscape of stator utilization and resultant motor output is an intrinsically heterogeneous population of motile cells. We show how consequences of stator recruitment led to swarming motility and how the stators potentially relate to surface sensing circuitry.
Draft genome sequence of
Klebsiella pneumoniae
KLEB-33: a convergent biofilm hyperforming multiresistant strain belonging to the emerging ST16 lineage harboring multiple hypervirulence genes
Authors: Silva-Bea Sergio , García-Meniño Isidro , Rey Sonia , Romero Manuel , Fernández Javier , Hammerl Jens A. , Mora Azucena , Otero Ana 
Published: March 2024

ABSTRACT

The emergence of convergent
Klebsiella pneumoniae
strains showing multiresistance, characteristic of nosocomial pathotypes and hypervirulent traits typical of community-acquired isolates, makes them important models for studying
K. pneumoniae
pathogenesis. Here, we describe the convergent, multidrug-resistant KLEB-33 strain harboring several hypervirulence genes and make its genome available to the scientific community.
Human Vγ9Vδ2 T cells exhibit antifungal activity against
Aspergillus fumigatus
and other filamentous fungi
Authors: Koga Satoru , Takazono Takahiro , Namie Hodaka , Okuno Daisuke , Ito Yuya , Nakada Nana , Hirayama Tatsuro , Takeda Kazuaki , Ide Shotaro , Iwanaga Naoki , Tashiro Masato , Sakamoto Noriho , Watanabe Akira , Izumikawa Koichi , Yanagihara Katsunori , Tanaka Yoshimasa , Mukae Hiroshi 
Published: March 2024

ABSTRACT

Invasive aspergillosis (IA) and mucormycosis are life-threatening diseases, especially among immunocompromised patients. Drug-resistant
Aspergillus fumigatus
strains have been isolated worldwide, which can pose a serious clinical problem. As IA mainly occurs in patients with compromised immune systems, the ideal therapeutic approach should aim to bolster the immune system. In this study, we focused on Vγ9Vδ2 T cells that exhibit immune effector functions and examined the possibility of harnessing this unconventional T cell subset as a novel therapeutic modality for IA. A potent antifungal effect was observed when
A. fumigatus
(
Af293
) hyphae were challenged by Vγ9Vδ2 T cells derived from peripheral blood. In addition, Vγ9Vδ2 T cells exhibited antifungal activity against hyphae of all
Aspergillus
spp.,
Cunninghamella bertholletiae
, and
Rhizopus microsporus
but not against their conidia. Furthermore, Vγ9Vδ2 T cells also exhibited antifungal activity against azole-resistant
A. fumigatus
, indicating that Vγ9Vδ2 T cells could be used for treating drug-resistant
A. fumigatus
. The antifungal activity of Vγ9Vδ2 T cells depended on cell-to-cell contact with
A. fumigatus
hyphae, and degranulation characterized by CD107a mobilization seems essential for this activity against
A. fumigatus
. Vγ9Vδ2 T cells could be developed as a novel modality for treating IA or mucormycosis.

IMPORTANCE

Invasive aspergillosis (IA) and mucormycosis are often resistant to treatment with conventional antifungal agents and have a high mortality rate. Additionally, effective antifungal treatment is hindered by drug toxicity, given that both fungal and human cells are eukaryotic, and antifungal agents are also likely to act on human cells, resulting in adverse effects. Therefore, the development of novel therapeutic agents specifically targeting fungi is challenging. This study demonstrated the antifungal activity of Vγ9Vδ2 T cells against various
Aspergillus
spp. and several
Mucorales in vitro
and discussed the mechanism underlying their antifungal activity. We indicate that adoptive immunotherapy using Vγ9Vδ2 T cells may offer a new therapeutic approach to IA.
Organic Matter in the Ocean: Indicators of Biogeochemical Processes
Authors: Romankevich E. A. , Vetrov A. A. , Ulyantsev A. S. 
Published: March 2024

Abstract
The article presents informative organogeochemical indicators used in oceanology to characterize biogeochemical processes. A classification based on data on suspended particulate matter, plankton, benthos, bottom sediments, and sea, river, and pore water has been developed. Clusters have been identified that include the elemental and isotopic composition of organic matter (OM), the group composition of lipids, aliphatic and alicyclic hydrocarbons, higher alcohols, macromolecular acids and ketones, isoprenoids, lignin and its structural monomers, and PAHs. The most informative indices are considered, which make it possible to assess the genesis of the original OM, the degree of its transformation, sources, and the ratio of aquatic and terrigenous components. These indices reflect the influx of riverine and aeolian material and permafrost thawing and make it possible to reconstruct the temperature of river waters and coastal upwellings. They significantly complement biooceanological, lithological, and geochemical studies and expand the biogeochemical methodology for studying the carbon cycle.
Trends of hospitalisation among new admission inpatients with oesophagogastric variceal bleeding in cirrhosis from 2014 to 2019 in the Affiliated Hospital of Southwest Medical University: a single-centre time-series analysis
Authors: Peng Jieyu , Zeng Xinyi , Huang Shu , Zhang Han , Xia Huifang , Zou Kang , Zhang Wei , Shi Xiaomin , Shi Lei , Zhong Xiaolin , Lü Muhan , Peng Yan , Tang Xiaowei 
Published: March 2024

ObjectivesThis study aimed to assess the internal law and time trend of hospitalisation for oesophagogastric variceal bleeding (EGVB) in cirrhosis and develop an effective model to predict the trend of hospitalisation time.DesignWe used a time series covering 72 months to analyse the hospitalisation for EGVB in cirrhosis. The number of inpatients in the first 60 months was used as the training set to establish the autoregressive integrated moving average (ARIMA) model, and the number over the next 12 months was used as the test set to predict and observe their fitting effect.Setting and dataCase data of patients with EGVB between January 2014 and December 2019 were collected from the Affiliated Hospital of Southwest Medical University.Outcome measuresThe number of monthly hospitalised patients with EGVB in our hospital.ResultsA total of 877 patients were included in the analysis. The proportion of EGVB in patients with cirrhosis was 73% among men and 27% among women. The peak age at hospitalisation was 40–60 years. The incidence of EGVB varied seasonally with two peaks from January to February and October to November, while the lowest number was observed between April and August. Time-series analysis showed that the number of inpatients with EGVB in our hospital increased annually. The sequence after the first-order difference was a stationary series (augmented Dickey-Fuller test p=0.02). ARIMA (0,1,0) (0,1,1)12with a minimum Akaike Information Criterion value of 260.18 could fit the time trend of EGVB inpatients and had a good short-term prediction effect. The root mean square error and mean absolute error were 2.4347 and 1.9017, respectively.ConclusionsThe number of hospitalised patients with EGVB at our hospital is increasing annually, with seasonal changes. The ARIMA model has a good prediction effect on the number of hospitalised patients with EGVB in cirrhosis.
Preparing occupational therapy students for practice in rural areas: a scoping review protocol
Authors: Hayes Karen , Dos Santos Vagner , Boyd Nerida , Connelly Bronwyn , Lustig Kim 
Published: March 2024

IntroductionDespite greater needs in rural areas, occupational therapists are maldistributed to urban spaces which limits service access and health outcomes for rural people and communities. Preparation of students for rural practice may improve rural workforce recruitment and retention; however, the range and scope of preparation strategies employed by education providers are unclear. This scoping review aims to understand and describe the range of strategies education services use to prepare occupational therapy students for rural practice across the globe.Methods and analysisThe study will include all publications about strategies used to prepare occupational therapy students for future rural practice, prior to enrolment, during the programme or on graduation.MEDLINE (Ovid),Emcare (Ovid),APA PsychInfo (Ovid),CINAHL (EBSCOhost),Health Source: Nursing/Academic(EBSCOHost),Educational Resources Information Centre (ERIC),Open Access Theses and Dissertations (OATD), andScientific Electronic Library Online (SciELO)databases will be systematically searched in English, Spanish, French and Portuguese languages. Citations will be screened by two or more independent researchers against inclusion criteria and data extracted from included publications using a customised extraction tool. Frequency counts will be provided for study type, student location and sociodemographics, and the timing/educational strategy. The extracted data will be analysed using a matrix framework and presented in diagrammatic/tabular form and accompanied by a narrative summary which will describe how the results relate to the reviews’ questions.Ethics and disseminationThis study will not involve human/animal subjects and does not require ethics approval. Results will be disseminated to relevant groups in peer-reviewed journal(s) and at relevant occupational therapy, higher education and/or rural health conferences. Results will also be translated and shared in blogs/social media to support access for non-research audiences and shared with other regional universities to influence curriculum design.
Thiamine as adjunctive therapy for diabetic ketoacidosis (DKAT) trial protocol and statistical analysis plan: a prospective, single-centre, double-blind, randomised, placebo-controlled clinical trial in the USA
Authors: Vine Jacob , Mehta Shivani , Balaji Lakshman , Berg Katherine M , Berlin Noa , Liu Xiaowen , Ngo Long , Shea Meredith , Moskowitz Ari , Donnino Michael W , Grossestreuer Anne V 
Published: March 2024

IntroductionDiabetic ketoacidosis (DKA) is a potentially life-threatening diabetic complication. Despite the high prevalence of DKA and the substantial associated healthcare burden, limited research on strategies to improve outcomes currently exists.Thiamine (vitamin B1) is a cofactor of pyruvate dehydrogenase, which plays a key role in aerobic glucose metabolism. Thiamine deficiency is common in patients with DKA, resulting in a shift to anaerobic metabolism and hyperlactatemia, which can prolong and complicate recovery. Therefore, we hypothesise that thiamine administration will improve aerobic metabolism and lead to faster resolution of acidemia in patients with DKA.Methods and analysisIn this single centre, double-blind, randomised, placebo-controlled, parallel group interventional trial, 100 patients admitted to the hospital with DKA will be randomised to receive either intravenous thiamine (200 mg in 50 mL 0.9% saline) or placebo (0.9% saline identical in appearance and volume) two times per day for 2 days. The primary outcome will be the change in bicarbonate level over 24 hours as compared between the two treatment groups. Additional secondary outcomes include the change over time in anion gap, lactate levels, oxygen consumption by circulating mononuclear cells, intensive care unit and hospital length-of-stay and hospital resource usage when comparing the two study arms.Ethics and disseminationThis trial was approved by the Committee on Clinical Investigations, the institutional review board of Beth Israel Deaconess Medical Center (protocol number 2018P000475). Findings will be disseminated through peer-reviewed publications and professional conference presentations.Trial registration numberNCT03717896; clinicaltrials.gov.
What role does community-based health insurance play in the utilisation of health services among households in Ethiopia? A community-based comparative cross-sectional study
Authors: Terefa Dufera Rikitu , Geta Edosa Tesfaye , Shama Adisu Tafari , Desisa Adisu Ewunetu 
Published: March 2024

ObjectiveIn Ethiopia, despite increased health service coverage, health service utilisation remains very low. However, evidence on the level of health service utilisation between insured and non-insured households in the study area was scanty. Therefore, this study aimed to assess health service utilisation and its predictors among insured and non-insured households of community-based health insurance in the East Wallaga Zone, Oromia region, Ethiopia, in 2022.MethodsA community-based comparative cross-sectional study was employed. Data were collected using semi-structured interviewer-administered pretested questionnaire by face-to-face interviewing of heads of the households or spouse from 1 January 2022 to 30 January 2022, on 900 (450 insured and 450 non-insured). Epi-Data V.3.1 and Statistical Package for Social Science V.26 were used for data entry and analysis, respectively. The association between dependent (health service utilisation) and independent variables was analysed first using binary logistic regression. Multivariable logistic regression was used to identify potential predictor variables at a p<0.05.ResultsAbout 60.5% (95% CI 55.7% to 64.8%) of insured households had used health services compared with 45.9% (95% CI 41.4% to 50.9%) of non-insured households in the last 6 months. Family health status (Adjusted Odd Ratio (AOR) and 95% CI=2.74 (1.37 to 5.45), AOR and 95% CI=1.62 (1.01 to 3.14)); family with chronic disease (AOR and 95% CI=8.33 (5.11 to 13.57), AOR and 95% CI=4.90 (2.48 to 9.67)); perceived availability of drugs (AOR and 95% CI=0.34 (0.15 to 0.79), AOR and 95% CI=3.97 (1.69 to 9.34)); perceived transportation cost (AOR and 95% CI=0.44 (0.21 to 0.90), AOR and 95% CI=1.71 (1.00 to 2.93)); participated in indigenous community insurance (AOR and 95% CI=3.82 (1.96 to 7.45), AOR and 95% CI=0.13 (0.06 to 0.29)) and >10 km travel distance from nearby health facilities (AOR and 95% CI=1.52 (1.02 to 2.60), AOR and 95% CI=8.37 (4.54 to 15.45)) among insured and non-insured households, respectively, were predictors of health service utilisation.ConclusionInsured households were more likely to utilise health services compared with non-insured households. Family health status, family with chronic disease, perceived availability of drugs, perceived transportation cost, participation in indigenous community insurance and >10 km travel were predictors of health service utilisation among insured and non-insured households. Hence, the greatest emphasis should be given to enhancing enrolment in the community-based health insurance scheme to achieve universal health coverage.
Should intermittent pneumatic compression devices be standard therapy for the prevention of venous thromboembolic events in major surgery? Protocol for a randomised clinical trial (IMPOSTERS)
Authors: Lott Natalie , Douglas Jeanene Lizbeth , Magnusson Monique , Gani Jonathan , Reeves Penny , Connah David , Organ Nicole , Oldmeadow Chris , Attia John , Smith Stephen Ridley 
Published: March 2024

IntroductionVenous thromboembolism (VTE) is a recognised postsurgical risk. Current prevention methods involve low molecular weight heparin (LMWH), graduated compression stockings (GCS), and intermittent pneumatic compression devices (IPCDs). Australian guidelines, commonly adopted by surgeons, recommend LMWH with GCS and/or IPCDs. IPCDs pose clinical risks, increase care burden, are poorly tolerated, and are costly single-use plastic items. Utilising only LMWH and GCS, without IPCDs, could be more practical, patient-friendly, and cost-effective, with added environmental benefits.MethodsThis is a multicentre, prospective, two-arm randomised controlled non-inferiority trial at five New South Wales (NSW) hospitals, in Australia. We propose to randomise 4130 participants in a 1:1 ratio between arm A: LMWH+GCS+IPCDs (n=2065) or arm B: LMWH+GCS (n=2065). The primary outcome of interest is symptomatic VTE (deep vein thrombosis/pulmonary embolism) identified at the day 30 phone follow-up (FU), confirmed by ultrasound or imaging. Radiologists interpreting the lower-extremity ultrasonography will be blinded to intervention allocation. Secondary outcomes are quality of life at baseline, days 30 and 90 FU using the 5-level European Quality of Life Score, compliance and adverse events with IPCDs, GCS, and LMWH, as well as healthcare costs (from the perspective of the patient and the hospital), and all-cause mortality. The trial has 90% power to detect a 2% non-inferiority margin to detect a reduction rate of VTE from 4% to 2%.Ethics and disseminationThis study has been approved by the Hunter New England Human Research Ethics Committee (2022/ETH02276) protocol V.10, 13 July 2023. Study findings will be presented at local and national conferences and in scientific research journals.Trial registration numberANZCTR12622001527752
Breastfeeding assessment and management instruments: a scoping review protocol
Authors: Souza Joyce Wadna Rodrigues , Silva Janiny Lima , Câmara Saionara Maria Aires 
Published: March 2024

IntroductionDifferent aspects are involved in the breastfeeding process that may vary according to the target population, postpartum phase and evaluation scenario. The identification of such instruments, their constructs and applicability in health services will contribute to the understanding of the most relevant aspects and dissemination of tools that can be implemented in the necessary spaces to promote breast feeding. This article describes a review protocol to map the assessment and management instruments applied to breast feeding in the puerperal period existing in the literature.Methods and analysisThis is a protocol of a scoping review that follows the methodological recommendations of the Joanna Briggs Institute (JBI). In March 2024, a search will be carried out in the databases Medical Literature Analysis and Retrieval System Online—Medline (PubMed), Latin American and Caribbean Health Science Literature—Lilacs (BVS), Cochrane Library and Embase (CAPES). Peer-reviewed studies that address instruments for evaluating the breastfeeding process during the puerperium will be included, regardless of year of publication or language. The selection of studies and data extraction will be done by peers and disagreements will be resolved by a third researcher. The selection will be made through the Rayann platform (https://www.rayyan.ai/). Data extraction and synthesis will be performed by pairs, using a semistructured instrument, based on the model available in the JBI manual. The studies will be summarised according to the postpartum period in which the instrument was used (immediate, remote or late postpartum) and their constructs, domains and contexts of utilisation will be identified.Ethics and disseminationEthical approval is not necessary for this scoping review. The results of the review will be shared through publications in peer-reviewed journals, at relevant scientific conferences and seminars and meetings with maternal and child healthcare providers.Study registrationThis study was registered with Open Science Framework registry (osf.io/f4hz8) on 27 April 2023.