bluuebunny/crossref_metadata_2025_split huggingface dataset:
Substitution of mineral N fertilizers with organic wastes in two long‐term field experiments: Dynamics and drivers of crop yields
Authors: Chen Haotian , Levavasseur Florent , Houot Sabine 
Published: June 2024

AbstractOrganic wastes (OW) are rich in nutrients, and their recycling into agriculture can substitute chemical fertilizers. The level of substitution (partial with mineral fertilizer or exclusive with only OW), along with the method, amount, and timing of OW application, as well as the crop type, can impact crop productivity. The temporal dynamics of crop productivity after repeated applications of OW remain uncertain. Thus, two French long‐term field experiments (QualiAgro and PROspective, started in 1998 and 2000, respectively) were used to evaluate the effect of repeated OW applications on crop yield dynamics and investigate the potential driving factors affecting crop yields. Six different OW were applied: urban sewage sludge (SLU), green waste and SLU compost (GWS), biowaste compost (BIO), municipal solid waste compost (MSW), farmyard manure (FYM), and composted FYM (FYMC). The OW were applied every 2 years in QualiAgro (~4 t C ha−1) and PROspective (~1.7 t C ha−1). QualiAgro was studied under high and low mineral N conditions, while PROspective was examined with and without mineral N fertilization. The results indicated that at the QualiAgro site, a combination of OW and high mineral N treatments resulted in higher maize and wheat yields compared to the mineral N control, while the combination of OW and low mineral N reached the same maize and wheat yield as the mineral N control after 3 and 6 applications of OW, respectively. At the PROspective site, partially substituting mineral fertilizer with OW maintained maize yields but decreased wheat yields, while full substitution led to a decrease in both maize and wheat yields compared to the mineral N control. Results from the gradient boosting model (GBM) showed that soil total N rather than mineral N input was the primary driver of the relative maize yield, while mineral N fertilizer input was more critical for wheat during the second year. We conclude that the joined use of OW and mineral fertilizers is superior to using OW or mineral fertilizer alone for maintaining high yields and soil fertility. We further suggest that OW full substitution of mineral fertilizer may need to apply OW more frequently to meet the crop demands, and/or to use OW with higher N availability like digestates.
Government‐industrial‐research cooperation in virtual water strategy: A multi‐agent evolutionary game analysis
Authors: Zhi Yuan , Li Caiju , Liang Longyue , Hamilton Paul B. , Sun Yuanyuan , Xiong Debin 
Published: June 2024

AbstractThe virtual water strategy (VWS) is an effective tool to balance regional water resource endowments and guarantee water supply security. However, because of self‐interested games around VWS (human decision bias), there is a need for methods to maintain reliable cooperation between governments, virtual water (VW) enterprises and research institutions. This study builds a multi‐agent evolutionary game model to analyse the relationship of players and their impacts on VWS through changing decision mechanisms and the paths to enhance their confidence in cooperation. Considering differences in initial willingness to cooperate and changing factors affecting payoffs, an evolutionary game can produce changing stable equilibriums or stable cooperations, even if some players are reluctant to cooperate. Therefore, to promote the development of VWS, a multistep support mechanism can be built for the VW industry, which fosters model enterprises and optimizes the cooperation framework to stimulate research innovations at scientific institutions.
Type III interferon drives pathogenicity to
Staphylococcus aureus
via the airway epithelium
Authors: Pires Silvia , Kaiser Katherine , Parker Dane 
Published: June 2024

ABSTRACT

Type III interferon signaling contributes to the pathogenesis of the important human pathogen
Staphylococcus aureus
in the airway. Little is known of the cellular factors important in this response. Using
Ifnl2
-green fluorescent protein reporter mice combined with flow cytometry and cellular depletion strategies, we demonstrate that the alveolar macrophage is the primary producer of interferon lambda (IFN-λ) in response to
S. aureus
in the airway. Bone marrow chimeras showed reduced bacterial burden in IFN-λ receptor (IFNLR1)-deficient recipient mice, indicative that non-hematopoietic cells were important for pathogenesis, in addition to significant reductions in pulmonary inflammation. These observations were confirmed through the use of an airway epithelial-specific IFNLR knockout mouse. Our data suggest that upon entry to the airway,
S. aureus
activates alveolar macrophages to produce type III IFN that is subsequently sensed by the airway epithelium. Future steps will determine how signaling from the epithelium then exerts its influence on bacterial clearance. These results highlight the important, yet sometimes detrimental, role of type III IFN signaling during infection and the impact the airway epithelium plays during host–pathogen interactions.

IMPORTANCE

The contribution of type III interferon signaling to the control of bacterial infections is largely unknown. We have previously demonstrated that it contributes to the pathogenesis of acute
Staphylococcus aureus
respiratory infection. In this report, we document the importance of two cell types that underpin this pathogenesis. We demonstrate that the alveolar macrophage is the cell that is responsible for the production of type III interferon and that this molecule is sensed by airway epithelial cells, which impacts both bacterial clearance and induction of inflammation. This work sheds light on the first two aspects of this important pathogenic cascade.
Unsaturated fatty acid perturbation combats emerging triazole antifungal resistance in the human fungal pathogen
Aspergillus fumigatus
Authors: Gutierrez-Perez Cecilia , Puerner Charles , Jones Jane T. , Vellanki Sandeep , Vesely Elisa M. , Xatse Mark A. , Viera Andre F. C. , Olsen Carissa P. , Attiku Keren O. , Cardinale Steven , Kwasny Steven M. , G-Dayanandan Narendran , Opperman Timothy J. , Cramer Robert A. 
Published: June 2024

ABSTRACT

Contemporary antifungal therapies utilized to treat filamentous fungal infections are inhibited by intrinsic and emerging drug resistance. Consequently, there is an urgent need to develop novel antifungal compounds that are effective against drug-resistant filamentous fungi. Here, we utilized an
Aspergillus fumigatus
cell-based high-throughput screen to identify small molecules with antifungal activity that also potentiated triazole activity. The screen identified 16 hits with promising activity against
A. fumigatus
. A nonspirocyclic piperidine, herein named MBX-7591, exhibited synergy with triazole antifungal drugs and activity against pan-azole-resistant
A. fumigatus
isolates. MBX-7591 has additional potent activity against
Rhizopus
species and CO
2
-dependent activity against
Cryptococcus neoformans
. Chemical, genetic, and biochemical mode of action analyses revealed that MBX-7591 increases cell membrane saturation by decreasing oleic acid content. MBX-7591 has low toxicity
in vivo
and shows good efficacy in decreasing fungal burden in a murine model of invasive pulmonary aspergillosis. Taken together, our results suggest MBX-7591 is a promising hit with a novel mode of action for further antifungal drug development to combat the rising incidence of triazole-resistant filamentous fungal infections.

IMPORTANCE

The incidence of infections caused by fungi continues to increase with advances in medical therapies. Unfortunately, antifungal drug development has not kept pace with the incidence and importance of fungal infections, with only three major classes of antifungal drugs currently available for use in the clinic. Filamentous fungi, also called molds, are particularly recalcitrant to contemporary antifungal therapies. Here, a recently developed
Aspergillus fumigatus
cell reporter strain was utilized to conduct a high-throughput screen to identify small molecules with antifungal activity. An emphasis was placed on small molecules that potentiated the activity of contemporary triazole antifungals and led to the discovery of MBX-7591. MBX-7591 potentiates triazole activity against drug-resistant molds such as
A. fumigatus
and has activity against Mucorales fungi. MBX-7591’s mode of action involves inhibiting the conversion of saturated to unsaturated fatty acids, thereby impacting fungal membrane integrity. MBX-7591 is a novel small molecule with antifungal activity poised for lead development.
Identification of a conserved B-cell epitope on the capsid protein of porcine circovirus type 4
Authors: Fang Zheng , Sun Mingxia , Cai Xuehui , An Tongqing , Tu Yabin , Wang Haiwei 
Published: June 2024

ABSTRACT

Porcine circovirus type 4 (PCV4), a recently identified circovirus, is prevalent in numerous provinces in China, as well as in South Korea, Thailand, and Europe. PCV4 virus rescued from an infectious clone showed pathogenicity, suggesting the economic impact of PCV4. However, there remains a lack of understanding regarding the immunogenicity and epitopes of PCV4. This study generated a monoclonal antibody (MAb) 1D8 by immunizing mice with PCV4 virus-like particles (VLPs). Subsequently, the epitope recognized by the MAb 1D8 was identified by truncated protein expression and alanine scanning mutagenesis analysis. Results showed that the
225
PKQG
228
located at the C-terminus of the PCV4 Cap protein is the minimal motif binding to the MAb. Homology modeling analysis and immunoelectron microscopy revealed that the epitope extends beyond the outer surface of the PCV4 VLP. Moreover, the epitope is highly conserved among PCV4 strains and does not react with other PCVs. Together, the MAb 1D8 recognized epitope shows potential for detecting PCV4. These findings significantly contribute to the design of antigens for PCV4 detection and control strategies.

IMPORTANCE
Porcine circovirus type 4 (PCV4) is a novel circovirus. Although PCV4 has been identified in several countries, including China, Korea, Thailand, and Spain, no vaccine is available. Given the potential pathogenic effects of PCV4 on pigs, PCV4 could threaten the global pig farming industry, highlighting the urgency for further investigation. Thus, epitopes of PCV4 remain to be determined. Our finding of a conserved epitope significantly advances vaccine development and pathogen detection.
Lactobacillus acidophilus
protects against
Corynebacterium pseudotuberculosis
infection by regulating the autophagy of macrophages and maintaining gut microbiota homeostasis in C57BL/6 mice
Authors: Li Dengliang , Jiang Yuecai , Cui Zhanding , Ma Mengzhen , Zhu Fang , Li Guanhua , Yang Haoyue , Li Shaofei , Zhang Tianliang , Chen Dekun , Ma Wentao 
Published: June 2024

ABSTRACT

Corynebacterium pseudotuberculosis
(
C. p
), a facultative intracellular bacterium, is an important zoonotic pathogen that causes abscesses and pyogenic granulomas. The relationship between gut microbiota and host health or diseases has received increasing attention. However, the role of gut microbiota in the process of
C. p
infection is still unclear. In this study, we established a
C. p
infection model in C57BL/6 mice and examined the impact of preemptive oral administration
Lactobacillus acidophilus
(
L. acidophilus
) on infection. Our findings revealed that
C. p
infection led to pronounced pathological alterations in the liver and kidneys, characterized by abscess formation, intense inflammatory responses, and bacterial overload. Remarkably, these deleterious effects were greatly relieved by oral administration of
L. acidophilus
before infection with
C. p
. Additionally, we further found that during
C. p
infection, peritoneal macrophages (PMs) of mice orally administered with
L. acidophilus
accumulated more rapidly at sites of infection. Furthermore, our results showed that PMs from mice with oral
L. acidophilus
administration showed a stronger
C. p
clearance effect, and this was mediated by high expression of LC3-II protein. Meanwhile, oral administration of
L. acidophilus
protected the gut microbiota disorder in C57BL/6 mice caused by
C. p
infection. In summary, our study demonstrates that oral administration of
L. acidophilus
confers effective protection against
C. p
infection in C57BL/6 mice by modulating macrophage autophagy, thereby augmenting bacterial clearance and preserving gut microbiota and function stability. These findings position
L. acidophilus
as a viable probiotic candidate for the clinical prevention of
C. p
infection.

IMPORTANCE

Corynebacterium pseudotuberculosis
(C.
p
) is known to induce a range of chronic diseases in both animals and humans. Currently, clinical treatment for C.
p
infection mainly relies on antibiotic therapy or surgical intervention. However, excessive use of antibiotics may increase the risk of drug-resistant strains, and the effectiveness of treatment remains unsatisfactory. Furthermore, surgical procedures do not completely eradicate pathogens and can easily cause environmental pollution. Probiotic interventions are receiving increasing attention for improving the body’s immune system and maintaining health. In this study, we established a C.
p
infection model in C57BL/6 mice to explore the impact of
Lactobacillus
acidophilus during C.
p
infection. Our results showed that
L. acidophilus
effectively protected against C.
p
infection by regulating the autophagy of macrophages and maintaining intestinal microbiota homeostasis. This study may provide a new strategy for the prevention of C.
p
infection.
Caesarean section for a primipara with Guillain-Barré syndrome under combined spinal epidural anaesthesia
Authors: Okahara Shoko , Bowe Ross , Wong Patricia , Johnson Mark 
Published: June 2024

A primigravida in mid 30s presented to hospital at 30+2 weeks gestation, due to progressive neurological symptoms including ascending limb weakness and paraesthesia bilaterally as well as dysphagia, facial weakness and dysphasia.The patient was diagnosed with Guillain-Barré syndrome after physical examination and electromyography, which showed a patchy demyelinating sensorimotor polyneuropathy. The patient underwent a 5-day course of intravenous immunoglobulin, beginning the day after admission. Markers of severity including forced vital capacity improved thereafter until delivery.With limited evidence favouring one particular anaesthetic technique in parturients with Guillain-Barré syndrome, combined spinal epidural anaesthesia was preferred over general anaesthesia in order to avoid the potential for prolonged intubation postoperatively and to allow careful titration of neuraxial blockade. Delivery by caesarean section at 34+1 weeks due to pre-eclampsia was uncomplicated. Thereafter the patient’s condition deteriorated, requiring a further 5-day course of intravenous immunoglobulin with symptoms gradually improving over a 6-month admission.
Impella versus VA-ECMO for the treatment of patients with cardiogenic shock: the Impella Network Project – observational study protocol for cost-effectiveness and budget impact analyses
Authors: Ardito Vittoria , Rognoni Carla , Pieri Marina , Barbone Alessandro , Briguori Carlo , Cigala Emanuele , Gerosa Gino , Iannaccone Mario , Loforte Antonio , Marini Marco , Montalto Andrea , Oreglia Jacopo , Pacini Davide , Pennacchi Mauro , Pestrichella Vincenzo , Porto Italo , Stefano Pierluigi , Tarantini Giuseppe , Valente Serafina , Vandoni Pietro , Tarricone Rosanna , Scandroglio Anna Mara 
Published: June 2024

IntroductionThe treatment of patients with cardiogenic shock (CS) encompasses several health technologies including Impella pumps and venoarterial extracorporeal membrane oxygenation (VA-ECMO). However, while they are widely used in clinical practice, information on resource use and quality of life (QoL) associated with these devices is scarce. The aim of this study is, therefore, to collect and comparatively assess clinical and socioeconomic data of Impella versus VA-ECMO for the treatment of patients with severe CS, to ultimately conduct both a cost-effectiveness (CEA) and budget impact (BIA) analyses.Methods and analysisThis is a prospective plus retrospective, multicentre study conducted under the scientific coordination of the Center for Research on Health and Social Care Management of SDA Bocconi School of Management and clinical coordination of Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) San Raffaele Scientific Institute in Milan. The Impella Network stemmed for the purposes of this study and comprises 17 Italian clinical centres from Northern to Southern Regions in Italy. The Italian network qualifies as a subgroup of the international Impella Cardiac Surgery Registry. Patients with CS treated with Impella pumps (CP, 5.0 or 5.5) will be prospectively recruited, and information on clinical outcomes, resource use and QoL collected. Economic data will be retrospectively matched with data from comparable patients treated with VA-ECMO. Both CEA and BIA will be conducted adopting the societal perspective in Italy. This study will contribute to generate new socioeconomic evidence to inform future coverage decisions.Ethics and disseminationAs of May 2024, most of the clinical centres submitted the documentation to their ethical committee (N=13; 76%), six centres received ethical approval and two centres started to enrol patients. Study results will be published in peer-reviewed publications and disseminated through conference presentations.
Study protocol on the efficacy of exergames-acceptance and commitment therapy program for the treatment of major depressive disorder: comparison with acceptance and commitment therapy alone and treatment-as-usual in a multicentre randomised controlled trial
Authors: Zhang Bingyu , Deng Hongdu , Ren Jinli , Legrand Fabien D , Ahmad Yusof Hazwani , Zhang Ruiling , Leong Bin Abdullah Mohammad Farris Iman 
Published: June 2024

BackgroundThe prevalence of major depressive disorder (MDD) is on the rise globally, and the use of antidepressant medications for its treatment does not usually result in full remission. However, the combination of physical exercise and psychotherapy for the treatment of MDD increase the rate of full remission among patients. This three-armed, parallel-group, double-blinded randomised controlled trial (RCT) aims to assess and compare the effects between the combination of exergame and acceptance and commitment therapy (e-ACT) programme, ACT only and treatment-as-usual (TAU) control groups on the severity of depression and anxiety symptoms, the degree of experiential avoidance and quality of life (QoL) and the serum levels of depression biomarkers (such as brain-derived neurotrophic factor, C-reactive protein and vascular endothelial growth factor) among patients with MDD across three time points.Methods and analysisThis RCT will recruit 126 patients with MDD who will be randomised using stratified permuted block randomisation into three groups, which are the combined e-ACT programme, ACT-only and TAU control groups in a 1:1:1 allocation ratio. The participants in the e-ACT and ACT-only intervention groups will undergo once a week intervention sessions for 8 weeks. Assessments will be carried out through three time points, such as the pre-intervention assessment (t0), assessment immediately after completion of the intervention at 8 weeks (t1) and assessment at 24 weeks after completion of the intervention (t2). During each assessment, the primary outcome to be assessed includes the severity of depression symptoms, while the secondary outcomes to be assessed are the severity of anxiety symptoms, experiential avoidance, QoL and depression biomarkers.Ethics and disseminationApproval of this study was obtained from the Human Research Ethics Committee of Universiti Sains Malaysia (USM/JEPeM/PP/23050420). The findings of the study will be published in academic peer-reviewed journals.Trial registration numberNCT05812001(ClinicalTrials.gov). Registered on 12 April 2023.
Norepinephrine weaning guided by the Hypotension Prediction Index in vasoplegic shock after cardiac surgery: protocol for a single-centre, open-label randomised controlled trial – the NORAHPI study
Authors: Beyls Christophe , Lefebvre Thomas , Mollet Nicolas , Boussault Annabelle , Meynier Jonathan , Abou-Arab Osama , Mahjoub Yazine 
Published: June 2024

IntroductionNorepinephrine (NE) is the first-line recommended vasopressor for restoring mean arterial pressure (MAP) in vasoplegic syndrome (vs) following cardiac surgery with cardiopulmonary bypass. However, solely focusing on target MAP values can lead to acute hypotension episodes during NE weaning. The Hypotension Prediction Index (HPI) is a machine learning algorithm embedded in the Acumen IQ device, capable of detecting hypotensive episodes before their clinical manifestation. This study evaluates the clinical benefits of an NE weaning strategy guided by the HPI.Material and analysisThe Norahpi trial is a prospective, open-label, single-centre study that randomises 142 patients. Inclusion criteria encompass adult patients scheduled for on-pump cardiac surgery with postsurgical NE administration for vs patient randomisation occurs once they achieve haemodynamic stability (MAP>65 mm Hg) for at least 4 hours on NE. Patients will be allocated to the intervention group (n=71) or the control group (n=71). In the intervention group, the NE weaning protocol is based on MAP>65 mmHg and HPI<80 and solely on MAP>65 mm Hg in the control group. Successful NE weaning is defined as achieving NE weaning within 72 hours of inclusion. An intention-to-treat analysis will be performed. The primary endpoint will compare the duration of NE administration between the two groups. The secondary endpoints will include the prevalence, frequency and time of arterial hypotensive events monitored by the Acumen IQ device. Additionally, we will assess cumulative diuresis, the total dose of NE, and the number of protocol weaning failures. We also aim to evaluate the occurrence of postoperative complications, the length of stay and all-cause mortality at 30 days.Ethics and disseminationEthical approval has been secured from the Institutional Review Board (IRB) at the University Hospital of Amiens (IRB-ID:2023-A01058-37). The findings will be shared through peer-reviewed publications and presentations at national and international conferences.Trial registration numberNCT05922982.