bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transmission-reducing and -enhancing monoclonal antibodies against
Plasmodium vivax
gamete surface protein Pvs48/45
Authors: Bansal Geetha P. , Araujo Maisa da Silva , Cao Yi , Shaffer Emily , Araujo Jessica Evangelista , Medeiros Jansen Fernandes , Hayashi Clifford , Vinetz Joseph , Kumar Nirbhay 
Published: January 2024

ABSTRACT

Gamete surface protein P48/45 has been shown to be important for male gamete fertility and a strong candidate for the development of a malaria transmission-blocking vaccine (TBV). However, TBV development for
Plasmodium vivax
homolog Pvs48/45 has been slow because of a number of challenges: availability of conformationally suitable recombinant protein; the lack of an
in vivo
challenge model; and the inability to produce
P. vivax
gametocytes in culture to test transmission-blocking activity of antibodies. To support ongoing efforts to develop Pvs48/45 as a potential vaccine candidate, we initiated efforts to develop much needed reagents to move the field forward. We generated monoclonal antibodies (mAbs) directed against Pvs48/45 and characterized putative functional domains in Pvs48/45 using recombinant fragments corresponding to domains D1–D3 and their biological functionality through
ex vivo
direct membrane feeding assays (DMFAs) using
P. vivax
parasites from patients in a field setting in Brazil. While some mAbs partially blocked oocyst development in the DMFA, one mAb caused a significant enhancement of the infectivity of gametocytes in the mosquitoes. Individual mAbs exhibiting blocking and enhancing activities recognized non-overlapping epitopes in Pvs48/45. Further characterization of precise epitopes recognized by transmission-reducing and -enhancing antibodies will be crucial to design an effective immunogen with optimum transmission-reducing potential.
Comparison of mouse models of microbial experience reveals differences in microbial diversity and response to vaccination
Authors: Sanders Autumn E. , Arnesen Henriette , Shepherd Frances K. , Putri Dira S. , Fiege Jessica K. , Pierson Mark J. , Roach Shanley N. , Carlsen Harald , Masopust David , Boysen Preben , Langlois Ryan A. 
Published: January 2024

ABSTRACT

Specific pathogen-free (SPF) laboratory mice dominate preclinical studies for immunology and vaccinology. Unfortunately, SPF mice often fail to accurately model human responses to vaccination and other immunological perturbations. Several groups have taken different approaches to introduce additional microbial experience to SPF mice to better model human immune experience. How these different models compare is unknown. Here, we directly compare three models: housing SPF mice in a microbe-rich barn-like environment (feralizing), adding wild-caught mice to the barn-like environment (fer-cohoused), or cohousing SPF mice with pet store mice in a barrier facility (pet-cohoused); the two latter representing different murine sources of microbial transmission. Pet-cohousing mice resulted in the greatest microbial exposure. Feralizing alone did not result in the transmission of any pathogens tested, while fer-cohousing resulted in the transmission of several picornaviruses. Murine astrovirus 2, the most common pathogen from pet store mice, was absent from the other two model systems. Previously, we had shown that pet-cohousing reduced the antibody response to vaccination compared with SPF mice. This was not recapitulated in either the feralized or fer-cohoused mice. These data indicate that not all dirty mouse models are equivalent in either microbial experience or immune responses to vaccination. These disparities suggest that more cross model comparisons are needed but also represent opportunities to uncover microbe combination-specific phenotypes and develop more refined experimental models. Given the breadth of microbes encountered by humans across the globe, multiple model systems may be needed to accurately recapitulate heterogenous human immune responses.

IMPORTANCE
Animal models are an essential tool for evaluating clinical interventions. Unfortunately, they can often fail to accurately predict outcomes when translated into humans. This failure is due in part to a lack of natural infections experienced by most laboratory animals. To improve the mouse model, we and others have exposed laboratory mice to microbes they would experience in the wild. Although these models have been growing in popularity, these different models have not been specifically compared. Here, we directly compare how three different models of microbial experience impact the immune response to influenza vaccination. We find that these models are not the same and that the degree of microbial exposure affects the magnitude of the response to vaccination. These results provide an opportunity for the field to continue comparing and contrasting these systems to determine which models best recapitulate different aspects of the human condition.
Quinalizarin as a potential antifungal drug for the treatment of
Candida albicans
fungal infection in cancer patients
Authors: Janeczko Monika , Kochanowicz Elżbieta , Górka Kamila , Skrzypek Tomasz 
Published: January 2024

ABSTRACT

This study aims to analyze the antifungal properties of quinalizarin, a plant-derived compound with proven anticancer effects. Quinalizarin exhibited antifungal activity against opportunistic pathogenic
Candida
species and
Geotrichum capitatum
. The treatment with this anthraquinone reduced hyphal growth, inhibited biofilm formation, and damaged mature
Candida albicans
biofilms. Real-time RT-PCR revealed that quinalizarin downregulated the expression of hyphae-related and biofilm-specific genes. The flow cytometry method used in the study showed that both apoptosis and necrosis were the physiological mechanisms of quinalizarin-induced
C. albicans
cell death, depending on the dose of the antifungal agent. A further study revealed an increase in the levels of intracellular reactive oxygen species and alterations in mitochondrial membrane potential after treatment with quinalizarin. Finally, quinalizarin was found to have low toxicity in a hemolytic test using human erythrocytes. In conclusion, we have identified quinalizarin as a potential antifungal compound.

IMPORTANCE
This article is a study to determine the antifungal activity of quinalizarin (1,2,5,8-tetrahydroxyanthraquinone). Quinalizarin has potential antitumor properties and is effective in different types of tumor cells. The aim of the present study was to prove that quinalizarin can be used simultaneously in the treatment of cancer and in the treatment of intercurrent fungal infections. Quinalizarin was identified as a novel antifungal compound with low toxicity. These results may contribute to the development of a new drug with dual activity in the treatment of cancer-associated candidiasis.
Estimating the ratio of fatal to non-fatal overdoses involving all drugs, all opioids, synthetic opioids, heroin or stimulants, USA, 2010–2020
Authors: Casillas Shannon M , Pickens Cassandra M , Tanz Lauren J , Vivolo-Kantor Alana M 
Published: January 2024

IntroductionUS drug overdose deaths are at historic levels. For every fatal drug overdose, there are many more non-fatal; however, minimal nationally representative data exist on trends in the ratio of fatal to non-fatal drug overdoses and how this differs by drug type.MethodsData from the Centers for Disease Control and Prevention’s National Vital Statistics System were used to assess the number of fatal overdoses; data from the Healthcare Cost and Utilization Project Nationwide Emergency Department Sample database were used to estimate the number of non-fatal overdoses treated in emergency departments. Counts of fatal and non-fatal overdoses by drug type (all drug, all opioid, synthetic opioid, heroin, stimulant, and opioid and stimulant polysubstance) were calculated from 2010 to 2020 (for non-fatal synthetic opioid-involved overdoses, from 2016 to 2020 only). Trends in overdose counts and the ratio of fatal to non-fatal overdoses were assessed.ResultsOn average, counts of fatal overdoses increased quarterly among all drug types, and non-fatal overdoses increased among most drug types. Over the 11-year period, the greatest average quarterly percent change (AQPC) in fatal overdose counts was among synthetic opioid-involved overdoses (AQPC: 7.1%; 95% CI: 6.0 to 8.2) and for non-fatal overdoses was among heroin-involved overdoses (AQPC: 4.3%; 95% CI: 3.9 to 4.8). During 2010‒2020, there was approximately 1 fatal overdose per 15 non-fatal. The ratio of fatal to non-fatal drug overdoses increased among every drug type except heroin; ratio increases were driven by greater relative increases in fatal overdoses compared with non-fatal.ConclusionsAssessment of the ratio of fatal to non-fatal drug overdoses can be used to understand the lethality of different drugs and inform response and prevention efforts.
Association of a gene-expression subtype to outcome and treatment response in patients with recurrent/metastatic head and neck squamous cell carcinoma treated with nivolumab
Authors: Serafini Mara Serena , Cavalieri Stefano , Licitra Lisa , Pistore Federico , Lenoci Deborah , Canevari Silvana , Airoldi Mario , Cossu Rocca Maria , Strojan Primoz , Kuhar Cvetka Grasic , Merlano Marco , Perrone Federica , Vingiani Andrea , Denaro Nerina , Perri Francesco , Argiris Athanassios , Gurizzan Cristina , Ghi Maria Grazia , Cassano Alessandra , Allegrini Giacomo , Bossi Paolo , De Cecco Loris 
Published: January 2024

BackgroundImmune checkpoint inhibitors have been approved and currently used in the clinical management of recurrent and metastatic head and neck squamous cell carcinoma (R/M HNSCC) patients. The reported benefit in clinical trials is variable and heterogeneous. Our study aims at exploring and comparing the predictive role of gene-expression signatures with classical biomarkers for immunotherapy-treated R/M HNSCC patients in a multicentric phase IIIb trial.MethodsClinical data were prospectively collected in Nivactor tiral (single-arm, open-label, multicenter, phase IIIb clinical trial in platinum-refractory HNSCC treated with nivolumab). Findings were validated in an external independent cohort of immune-treated HNSCC patients, divided in long-term and short-term survivors (overall survival >18 and <6 months since the start of immunotherapy, respectively). Pretreatment tumor tissue specimen from immunotherapy-treated R/M HNSCC patients was used for PD-L1 (Tumor Proportion Score; Combined Positive Score (CPS)) and Tumor Mutational Burden (Oncopanel TSO500) evaluation and gene expression profiling; classical biomarkers and immune signatures (retrieved from literature) were challenged in the NIVACTOR dataset.ResultsCluster-6 (Cl6) stratification of NIVACTOR cases in high score (n=16, 20%) and low score (n=64, 80%) demonstrated a statistically significant and clinically meaningful improvement in overall survival in the high-score cases (p=0.00028; HR=4.34, 95% CI 1.84 to 10.22) and discriminative ability reached area under the curve (AUC)=0.785 (95% CI 0.603 to 0.967). The association of high-score Cl6 with better outcome was also confirmed in: (1) NIVACTOR progression-free survival (p=4.93E-05; HR=3.71, 95% CI 1.92 to 7.18) and objective-response-rate (AUC=0.785; 95% CI 0.603 to 0.967); (2) long survivors versus short survivors (p=0.00544). In multivariate Cox regression analysis, Cl6 was independent from Eastern Cooperative Oncology Group performance status, PDL1-CPS, and primary tumor site.ConclusionsThese data highlight the presence of underlying biological differences able to predict survival and response following treatment with immunotherapy in platinum-refractory R/M HNSCC that could have translational implications improving treatment selection.Trial registration numberEudraCT Number: 2017-000562-30.
Mosaic RASopathies concept: different skin lesions, same systemic manifestations?
Authors: Morren Marie-Anne , Fodstad Heidi , Brems Hilde , Bedoni Nicola , Guenova Emmanuella , Jacot-Guillarmod Martine , Busiah Kanetee , Giuliano Fabienne , Gilliet Michel , Atallah Isis 
Published: January 2024

BackgroundCutaneous epidermal nevi are genotypically diverse mosaic disorders. Pathogenic hotspot variants inHRAS,KRAS, and less frequently, NRASandBRAFmay cause isolated keratinocytic epidermal nevi and sebaceous nevi or several different syndromes when associated with extracutaneous anomalies. Therefore, some authors suggest the concept of mosaic RASopathies to group these different disorders.MethodsIn this paper, we describe three new cases of syndromic epidermal nevi caused by mosaicHRASvariants: one associating an extensive keratinocytic epidermal nevus with hypomastia, another with extensive mucosal involvement and a third combining a small sebaceous nevus with seizures and intellectual deficiency. Moreover, we performed extensive literature of all cases of syndromic epidermal nevi and related disorders with confirmed pathogenic postzygotic variants inHRAS, KRAS, NRASorBRAF.ResultsMost patients presented with bone, ophthalmological or neurological anomalies. Rhabdomyosarcoma, urothelial cell carcinoma and pubertas praecox are also repeatedly reported.KRASpathogenic variants are involved in 50% of the cases, especially in sebaceous nevi, oculoectodermal syndrome and encephalocraniocutaneous lipomatosis. They are frequently associated with eye and brain anomalies. Pathogenic variants inHRASare rather present in syndromic keratinocytic epidermal nevi and phacomatosis pigmentokeratotica.ConclusionThis review delineates genotype/phenotype correlations of syndromic epidermal nevi with somaticRASandBRAFpathogenic variants and may help improve their follow-up.
Thromboembolic and bleeding events after valvular intervention in patients with atrial fibrillation
Authors: Skogseid Ebba-Louise , Batra Gorav , Westerbergh Johan , Held Claes , Christersson Christina 
Published: January 2024

AimTo assess outcomes after cardiac surgery with biological valve replacement, valve repair or transcatheter aortic valve implantation (TAVI) in patients with atrial fibrillation (AF) in accordance with oral anticoagulant (OAC) treatment.MethodsAll patients in Sweden undergoing valvular intervention with AF were included. Associations between OAC exposure and cardiovascular (CV) events (composite of CV death, ischaemic stroke or systemic embolism) and major bleeding were investigated using Cox regression analysis. The analysis was separated in time periods of 0–3 and 3–12 months after discharge.Results4730 patients were included in the first time period, 54.0% had received a surgical biological valve prosthesis, 23.8% valve repair and 22.2% TAVI. Exposure to warfarin (comparator) was 62.3%, to non-vitamin K antagonist oral anticoagulants (NOACs) 10.0% and to no OAC 27.7%. NOAC exposure was associated with similar risk of the composite CV outcome and major bleeding from 0 to 3 months. No OAC was associated with increased risk of the composite CV outcome (HR 1.71; 95% CI 1.26 to 2.32) and similar risk of major bleeding. Further analysis of the bioprosthetic valve replacement subgroup indicated increased risk of CV death when exposed to NOAC (HR 2.58; 95% CI 1.15 to 5.78) and no OAC (HR 2.82; 95% CI 1.65 to 4.82) compared with warfarin from 0 to 3 months. No differences were seen between 3 and 12 months.ConclusionIn this registry-based cohort study of patients with AF with severe valvular heart disease undergoing various valvular interventions, NOAC appears to be comparable with warfarin regarding efficacy and safety. Patients not receiving OAC had higher risk of CV events. NOAC was associated with increased CV death compared with warfarin in the surgical bioprosthetic valve replacement subgroup, illustrating the importance of being cautious when extrapolating data from one patient group to another. Further studies comparing NOAC and warfarin in the early postoperative phase are warranted, especially following surgical bioprosthetic valve replacement.
Iliopsoas plane block does not improve pain after primary total hip arthroplasty in the presence of multimodal analgesia: a single institution randomized controlled trial
Authors: Kim Ji Yeong , Lee Jong Seok , Kim Ji Young , Yoon Eun Jang , Lee Wootaek , Lee Seungyeon , Kim Do-Hyeong 
Published: January 2024

BackgroundThe clinical analgesic efficacy of iliopsoas plane block remains a subject of discussion. This study aimed to assess the analgesic efficacy of iliopsoas plane block under general anesthesia using multimodal analgesia.MethodsFifty-six adult patients who underwent elective primary hip arthroplasty were enrolled. Patients were randomized to receive either a single-shot iliopsoas plane block (10 mL 0.75% ropivacaine with 1:200 000 epinephrine) or a sham block (10 mL normal saline). All patients received general anesthesia, multimodal analgesia (preoperative buprenorphine patch, 5 µg/h), intraoperative intravenous dexamethasone (8 mg) and nefopam (20 mg), and round-the-clock acetaminophen and celecoxib. The primary outcome was the numeric rating scale pain score at rest 6 hour after surgery.ResultsIliopsoas plane block did not have a notable advantage over the sham block in terms of pain relief at rest, as assessed by the numeric rating scale score, 6 hour after total hip arthroplasty (iliopsoas plane block: median, 4.0; IQR, 2.0–5.8; sham: median, 5.5; IQR, 2.3–6.8; median difference, −1.0; 95% CI −2.0 to 0.0; p≥0.999). Linear mixed model analysis showed no differences in pain scores, opioid consumption, quadriceps strength, or quality of recovery between the groups.ConclusionsIliopsoas plane block did not improve postoperative analgesia following total hip arthroplasty under general anesthesia with a multimodal analgesic regimen. The blockade of sensory femoral branches supplying the anterior hip capsule using iliopsoas plane block may not yield additional benefits concerning patient outcomes in the aforementioned clinical context.Trial registration numberNCT05212038,https://clinicaltrials.gov/ct2/show/NCT05212038
Additive value of superficial parasternal intercostal plane block and serratus anterior plane block in lung transplantation surgery: a retrospective exploratory study
Authors: Azem Karam , Fein Shai , Zribi Benjamin , Iluz-Freundlich Daniel , Neuman Ido , Livne Michal Y , Kaplan Omer , Aranbitski Roussana , Heesen Philip , Statlender Liran , Gorfil Dan , Barac Yaron , Peysakhovich Yuri , Mangoubi Eitan 
Published: January 2024

BackgroundAdequate pain control following lung transplantation (LTx) surgery is paramount. Thoracic epidural analgesia (TEA) is the gold standard; however, the potential use of extracorporeal membrane oxygenation (ECMO) and consequent anticoagulation therapy raises safety concerns, prompting clinicians to seek safer alternatives. The utility of thoracic wall blocks in general thoracic surgery is well established; however, their role in the context of LTx has been poorly investigated.MethodsIn this retrospective exploratory study, we assessed the effect of adding a superficial parasternal intercostal plane (sPIP) block and serratus anterior plane (SAP) block to standard anesthetic and analgesic care on tracheal extubation rates, pain scores and opioid consumption until 72 hours postoperatively in LTx.ResultsSixty patients were included in the analysis; 35 received the standard anesthetic and analgesic care (control group), and 25 received sPIP and SAP blocks in addition to the standard anesthetic and analgesic care (intervention group). We observed higher tracheal extubation rates in the intervention group at 8 hours postoperatively (16.0% vs 0.0%, p=0.03). This was also shown after adjusting for known prognostic factors (OR 1.18; 95% CI 1.04 to 1.33, p=0.02). Furthermore, we noted a lower opioid consumption measured by morphine milligram equivalents at 24 hours in the intervention group (median 405 (IQR 300–490) vs 266 (IQR 168–366), p=0.02). This was also found after adjusting for known prognostic factors (β −118; 95% CI −221 to 14, p=0.03).ConclusionsPIP and SAP blocks are safe regional analgesic techniques in LTx involving ECMO and clamshell incision. They are associated with faster tracheal extubation and lower opioid consumption. These techniques should be considered when TEA is not appropriate. Further high-quality studies are warranted to confirm these findings.
Differences in the association between epidural analgesia and length of stay by surgery type: an observational study
Authors: Patel Anuj B , Kerins Gerard J , Sites Brian D , Duprat Chloe Nadine M , Davis Matthew 
Published: January 2024

IntroductionDespite a decline in the use of thoracic epidural analgesia related in part to concerns for delayed discharge, it is unknown whether changes in length of stay (LOS) associated with epidural analgesia vary by surgery type. Therefore, we determined the degree to which the association between epidural analgesia (vs no epidural) and LOS differed by surgery type.MethodsWe conducted an observational study using data from 1747 patients who had either non-emergent open abdominal, thoracic, or vascular surgery at a single tertiary academic hospital. The primary outcome was hospital LOS and the incidence of a prolonged hospital LOS defined as 21 days or longer. Secondary endpoints included escalation of care, 30-day all-cause readmission, and reason for epidural not being placed. The association between epidural status and dichotomous endpoints was examined using logistic regression.ResultsAmong the 1747 patients, 85.7% (1499) received epidural analgesia. 78% (1364) underwent abdominal, 11.5% (200) thoracic, and 10.5% (183) vascular surgeries. After adjustment for differences, receiving epidural analgesia (vs no epidural) was associated with a 45% reduction in the likelihood of a prolonged LOS (p<0.05). This relationship varied by surgery type: abdominal (OR 0.42, 95% CI 0.23 to 0.79, p<0.001), vascular (OR 1.66, 95% CI 0.17 to 16.1, p=0.14), and thoracic (OR 1.07, 95% CI 0.20 to 5.70, p=0.93). Among abdominal surgical patients, epidural analgesia was associated with a median decrease in LOS by 1.4 days and a 37% reduction in the likelihood of 30-day readmission (adjusted OR 0.63, 0.41 to 0.97, p<0.05). Among thoracic surgical patients, epidural analgesia was associated with a median increase in LOS by 3.2 days.ConclusionsThe relationship between epidural analgesia and LOS appears to be different among different surgical populations.