bluuebunny/crossref_metadata_2025_split huggingface dataset:
Implications of silver nanoparticles for H. pylori infection: modulation of CagA function and signaling
Authors: Hochvaldova Lucie , Posselt Gernot , Wessler Silja , Kvítek Libor , Panáček Aleš 
Published: June 2024

BackgroundHelicobacter pylori infection poses a significant health burden worldwide, and its virulence factor CagA plays a pivotal role in its pathogenesis.MethodsIn this study, the interaction between H. pylori-infected AGS cells and silver nanoparticles (AgNPs) was investigated, with a focus on the modulation of CagA-mediated responses, investigated by western blotting. Both, the dose-dependent efficacy against H. pylori (growth curves, CFU assay) and the impact of the nanoparticles on AGS cells (MTT assay) were elucidated.ResultsAGS cells infected with H. pylori displayed dramatic morphological changes, characterized by elongation and a migratory phenotype, attributed to CagA activity. Preincubation of H. pylori with AgNPs affected these morphological changes in a concentration-dependent manner, suggesting a correlation between AgNPs concentration and CagA function.ConclusionOur study highlights the nuanced interplay between host-pathogen interactions and the therapeutic potential of AgNPs in combating H. pylori infection and offers valuable insights into the multifaceted dynamics of CagA mediated responses.
Myelomodulatory treatments augment the therapeutic benefit of oncolytic viroimmunotherapy in murine models of malignant peripheral nerve sheath tumors
Authors: Paudel Siddhi N. , Hutzen Brian J. , Miller Katherine E. , Garfinkle Elizabeth A. R. , Chen Chun-Yu , Wang Pin-Yi , Glaspell Andrea M. , Currier Mark A. , Ringwalt Emily M. , Boon Louis , Mardis Elaine R. , Cairo Mitchell S. , Ratner Nancy , Dodd Rebecca D. , Cassady Kevin A. , Cripe Timothy P. 
Published: June 2024

IntroductionMalignant peripheral nerve sheath tumors (MPNST) pose a significant therapeutic challenge due to high recurrence rates after surgical resection and a largely ineffective response to traditional chemotherapy. An alternative treatment strategy is oncolytic viroimmunotherapy, which can elicit a durable and systemic antitumor immune response and is Food and Drug Administration (FDA)-approved for the treatment of melanoma. Unfortunately, only a subset of patients responds completely, underscoring the need to address barriers hindering viroimmunotherapy effectiveness. MethodsHere we investigated the therapeutic utility of targeting key components of the MPNST immunosuppressive microenvironment to enhance viroimmunotherapy’s antitumor efficacy in three murine models, one of which showed more immunogenic characteristics than the others. ResultsMyelomodulatory therapy with pexidartinib, a small molecule inhibitor of CSF1R tyrosine kinase, and the oncolytic herpes simplex virus T-VEC exhibited the most significant increase in median survival time in the highly immunogenic model. Additionally, targeting myeloid cells with the myelomodulatory therapy trabectedin, a small molecule activator of caspase-8 dependent apoptosis, augmented the survival benefit of T-VEC in a less immunogenic MPNST model. However, tumor regressions or shrinkages were not observed. Depletion experiments confirmed that the enhanced survival benefit relied on a T cell response. Furthermore, flow cytometry analysis following combination viroimmunotherapy revealed decreased M2 macrophages and myeloid-derived suppressor cells and increased tumor-specific gp70+ CD8 T cells within the tumor microenvironment. DiscussionIn summary, our findings provide compelling evidence for the potential to leverage viroimmunotherapy with myeloid cell targeting against MPNST and warrant further investigation.
Combining CD38 antibody with CD47 blockade is a promising strategy for treating hematologic malignancies expressing CD38
Authors: Li Song , Chen Dianze , Yang Yanan , Guo Huiqin , Liu Dandan , Sun Nana , Bai Xing , Wang Kaili , Li Tengfei , Li Guanghui , Yang Chunmei , Zhang Wei , Zhang Li , Zhao Gui , Peng Liang , Liu Sijin , Tu Xiaoping , Zhang Ruliang , Tian Wenzhi 
Published: June 2024

BackgroundCD38 and CD47 are expressed in many hematologic malignancies, including multiple myeloma (MM), B-cell non-Hodgkin lymphoma (NHL), B-cell acute lymphoblastic leukemia (ALL), and B-cell chronic lymphocytic leukemia (CLL). Here, we evaluated the antitumor activities of CD38/CD47 bispecific antibodies (BsAbs).MethodsFive suitable anti-CD38 antibodies for co-targeting CD47 and CD38 BsAb were developed using a 2 + 2 “mAb-trap” platform. The activity characteristics of the CD38/CD47 BsAbs were evaluated using in vitro and in vivo systems.ResultsUsing hybridoma screening technology, we obtained nine suitable anti-CD38 antibodies. All anti-CD38 antibodies bind to CD38+ tumor cells and kill tumor cells via antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP). Five anti-CD38 antibodies (4A8, 12C10, 26B4, 35G5, and 65A7) were selected for designing CD38/CD47 BsAbs (IMM5605) using a “mAb-trap” platform. BsAbs had higher affinity and binding activity to the CD38 target than those to the CD47 target, decreasing the potential on-target potential and off-tumor effects. The CD38/CD47 BsAbs did not bind to RBCs and did not induce RBC agglutination; thus, BsAbs had much lower blood toxicity. The CD38/CD47 BsAbs had a greater ability to block the CD47/SIRPα signal in CD38+/CD47+ tumor cells than IMM01 (SIRPα Fc fusion protein). Through Fc domain engineering, CD38/CD47 BsAbs were shown to kill tumors more effectively by inducing ADCC and ADCP. IMM5605–26B4 had the strongest inhibitory effect on cellular CD38 enzymatic activity. IMM5605–12C10 had the strongest ability to directly induce the apoptosis of tumor cells. The anti-CD38 antibody 26B4 combined with the SIRPα-Fc fusion proteins showed strong antitumor effects, which were better than any of the mono-therapeutic agents used alone in the NCI-H929 cell xenograft model. The CD38/CD47 BsAbs exhibited strong antitumor effects; specifically, IMM5605–12C10 efficiently eradicated all established tumors in all mice.ConclusionA panel of BsAbs targeting CD38 and CD47 developed based on the “mAb-tarp” platform showed potent tumor-killing ability in vitro and in vivo. As BsAbs had lower affinity for binding to CD47, higher affinity for binding to CD38, no affinity for binding to RBCs, and did not induce RBC agglutination, we concluded that CD38/CD47 BsAbs are safe and have a satisfactory tolerability profile.
Dynamic off-resonance correction improves functional image analysis in fMRI of awake behaving non-human primates
Authors: Shahdloo Mo , Khalighinejad Nima , Priestley Luke , Rushworth Matthew , Chiew Mark 
Published: June 2024

IntroductionUse of functional MRI in awake non-human primate (NHPs) has recently increased. Scanning animals while awake makes data collection possible in the absence of anesthetic modulation and with an extended range of possible experimental designs. Robust awake NHP imaging however is challenging due to the strong artifacts caused by time-varying off-resonance changes introduced by the animal's body motion. In this study, we sought to thoroughly investigate the effect of a newly proposed dynamic off-resonance correction method on brain activation estimates using extended awake NHP data.MethodsWe correct for dynamic B0 changes in reconstruction of highly accelerated simultaneous multi-slice EPI acquisitions by estimating and correcting for dynamic field perturbations. Functional MRI data were collected in four male rhesus monkeys performing a decision-making task in the scanner, and analyses of improvements in sensitivity and reliability were performed compared to conventional image reconstruction.ResultsApplying the correction resulted in reduced bias and improved temporal stability in the reconstructed time-series data. We found increased sensitivity to functional activation at the individual and group levels, as well as improved reliability of statistical parameter estimates.ConclusionsOur results show significant improvements in image fidelity using our proposed correction strategy, as well as greatly enhanced and more reliable activation estimates in GLM analyses.
Estrogen deficiency reduces maximal running capacity and affects serotonin levels differently in the hippocampus and nucleus accumbens in response to acute exercise
Authors: Lee Earric , Nissinen Tuuli A. , Ylä-Outinen Laura , Jalkanen Aaro , Karppinen Jari E. , Vieira-Potter Victoria Jeanne , Lipponen Arto , Karvinen Sira 
Published: June 2024

IntroductionEstrogen deficiency is associated with unfavorable changes in body composition and metabolic health. While physical activity ameliorates several of the negative effects, loss of ovarian function is associated with decreased physical activity levels. It has been proposed that the changes in brain neurochemical levels and /or impaired skeletal muscle function may underlie this phenomenon.MethodsWe studied the effect of estrogen deficiency induced via ovariectomy (OVX) in female Wistar rats (n = 64). Rats underwent either sham or OVX surgery and were allocated thereafter into four groups matched for body mass and maximal running capacity: sham/control, sham/max, OVX/control, and OVX/max, of which the max groups had maximal running test before euthanasia to induce acute response to exercise. Metabolism, spontaneous activity, and maximal running capacity were measured before (PRE) and after (POST) the surgeries. Three months following the surgery, rats were euthanized, and blood and tissue samples harvested. Proteins were analyzed from gastrocnemius muscle and retroperitoneal adipose tissue via Western blot. Brain neurochemical markers were measured from nucleus accumbens (NA) and hippocampus (HC) using ultra-high performance liquid chromatography.ResultsOVX had lower basal energy expenditure and higher body mass and retroperitoneal adipose tissue mass compared with sham group (p ≤ 0.005). OVX reduced maximal running capacity by 17% (p = 0.005) with no changes in muscle mass or phosphorylated form of regulatory light chain (pRLC) in gastrocnemius muscle. OVX was associated with lower serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA) level in the NA compared with sham (p = 0.007). In response to acute exercise, OVX was associated with low serotonin level in the HC and high level in the NA (p ≤ 0.024).DiscussionOur results highlight that OVX reduces maximal running capacity and affects the response of brain neurochemical levels to acute exercise in a brain region-specific manner. These results may offer mechanistic insight into why OVX reduces willingness to exercise.
Pharmacokinetics, safety, and efficacy of Fuqi Guben Gao in the treatment of kidney-yang deficiency syndrome: a randomized, double-blind phase I trial
Authors: Cao Wei-Yi , Liu Jun-Yu , Sun Min , Wang Jing-Kun , Lu Fang , Yang Qiao-Ning , Zhang Wan-Tong , Zi Ming-Jie , Zhang Bai-E , Liu Hong-Bin , Wang Shu-Ge , Wu Yi , Wu Rong-Zu , Wu Wen-Di , Li Rui , Zhu Zhao-Yun , Gao Rui 
Published: June 2024

Introduction: Fuqi Guben Gao (FQGBG) is a botanical drug formulation composed of FuZi (FZ; Aconitum carmichaelii Debeaux [Ranunculaceae; Aconiti radix cocta]), Wolfberry (Lycium barbarum L. [Solanaceae; Lycii fructus]), and Cinnamon (Neolitsea cassia (L.) Kosterm. [Lauraceae; Cinnamomi cortex]). It has been used to clinically treat nocturia caused by kidney-yang deficiency syndrome (KYDS) for over 30 years and warms kidney yang. However, the pharmacological mechanism and the safety of FQGBG in humans require further exploration and evaluation.Methods: We investigated the efficacy of FQGBG in reducing urination and improving immune organ damage in two kinds of KYDS model rats (hydrocortisone-induced model and natural aging model), and evaluated the safety of different oral FQGBG doses through pharmacokinetic (PK) parameters, metabonomics, and occurrence of adverse reactions in healthy Chinese participants in a randomized, double-blind, placebo-controlled, single ascending dose clinical trial. Forty-two participants were allocated to six cohorts with FQGBG doses of 12.5, 25, 50, 75, 100, and 125 g. The PKs of FQGBG in plasma were determined using a fully validated LC-MS/MS method.Results: FQGBG significantly and rapidly improved the symptoms of increased urination in both two KYDS model rats and significantly resisted the adrenal atrophy in hydrocortisone-induced KYDS model rats. No apparent increase in adverse events was observed with dose escalation. Major adverse drug reactions included toothache, thirst, heat sensation, gum pain, diarrhea, abdominal distension, T-wave changes, and elevated creatinine levels. The PK results showed a higher exposure level of benzoylhypaconine (BHA) than benzoylmesaconine (BMA) and a shorter half-life of BMA than BHA. Toxic diester alkaloids, aconitine, mesaconitine, and hypaconitine were below the lower quantitative limit. Drug-induced metabolite markers primarily included lysophosphatidylcholines, fatty acids, phenylalanine, and arginine metabolites; no safety-related metabolite changes were observed.Conclusion: Under the investigated dosing regimen, FQGBG was safe. The efficacy mechanism of FQGBG in treating nocturia caused by KYDS may be related to the improvement of the hypothalamus-pituitary-adrenal axis function and increased energy metabolism.Clinical Trial Registration:https://www.chictr.org.cn/showproj.html?proj=26934, identifier ChiCTR1800015840.
Distribution of self-reported borderline personality disorder traits symptoms in a large-scale clinical population
Authors: Lin Yong , Guo ZiLei , Zhou Yong , Wei YanYan , Xu LiHua , Tang XiaoChen , Wang Zixuan , Hu YeGang , Wang JiJun , Mei Yi , Wu HaiSu , Luo YanLi , Zhang TianHong 
Published: June 2024

IntroductionBorderline Personality Disorder (BPD) traits play a crucial role in the prognosis of psychiatric disorders, as well as in assessing risks associated with negativity and impulsivity. However, there is a lack of data regarding the distribution characteristics of BPD traits and symptoms within clinical populations.MethodsA total of 3015 participants (1321 males, 1694 females) were consecutively sampled from outpatients at the psychiatric and psycho-counseling clinics at the Shanghai Mental Health Center. BPD symptoms were assessed using a self-reported personality diagnostic questionnaire. Having BPD traits is defined as having five or more positive items in self-reported BPD characteristics. Participants were stratified into male and female groups, age groups, and diagnostic groups (schizophrenia, mood disorders, anxiety disorders). Exploratory factor analysis using principal components analysis was conducted. Three factors were identified: “F1: Affective Instability and Impulsivity”, “F2: Interpersonal Unstable and Extreme Reactions”, and “F3: Identity Disturbance”.ResultsAmong 3015 participants, 45.9% of the patients self-reported BPD traits. Comparing of male and female patients, there was no statistically significant difference in the occurrence rate of BPD traits (χ2 = 1.835, p=0.176). However, in terms of symptoms, female patients reported more symptoms than male patients. Female patients also exhibited more pronounced features on F2 compared to male patients (t =-1.972, p=0.049). There is a general decrease in BPD traits, symptoms, and factors with increasing age. Specifically, the proportion of positive BPD traits is approximately halved before the age of 30 and decreases to around one-third after the age of 30. BPD traits were most common in the Mood Disorders group at 55.7%, followed by the Anxiety Disorders group at 44.4%, and Schizophrenia group at 41.5% (χ2 = 38.084, p&lt;0.001).DiscussionOur study revealed the pervasive presence of BPD traits and symptoms among psychiatric outpatients, exhibiting distinctive distributions across gender, age, and diagnostic categories. These findings emphasize the significance of identifying and addressing BPD pathology in the clinical care of psychiatric outpatients.
Litigation in access to universal health coverage for children and adolescents in Brazil
Authors: Coelho Tavares da Silva Suely , Tavares da Silva Paulo Henrique , Antão de Medeiros Robson , Barbosa do Nascimento Vânia 
Published: June 2024

BackgroundBrazil’s Unified Health System (SUS) ensures universal, equitable, and excellent quality health coverage for all. The broad right to health, supported by the Constitution, has led to excessive litigation in the public sector. This has negatively impacted the financial stability of SUS, created inequality in children and adolescents’ access to healthcare, and affected communication between the healthcare system and the judiciary. The enactment of Law Number 13.655 on 25 April 2018, proposed significant changes in judicial decisions. This study aimed to investigate decision-making changes in health litigation involving children and adolescents following the implementation of the new normative model.MethodsThe study is cross-sectional, analyzing 3753 national judgment documents from all State Courts of Brazil, available on their respective websites from 2014 to 2020. It compares regional legal decisions before and after the promulgation of Law Number 13.655/2018. Data tabulation, statistical analysis, textual analysis, coding, and counting of significant units in the collected documents were performed. The results of data cross-referencing are presented in tables and diagrams.ResultsThe majority (96.86%) of legal claims (3635 cases) received partial or total provision of what was prescribed by the physician. The Judiciary predominantly handled these cases individually. The analysis indicates that the decisions made did not adhere to the norms established in 2018.ConclusionRegional heterogeneity in health litigation was observed, and there was no significant variability in decisions during the studied period, even after the implementation of the new normative paradigm in 2018. Technical-scientific support was undervalued by the magistrates. Prioritizing litigants undermines equity in access to Universal Health Coverage for children and adolescents.
Prevention method preferences and factors influencing hypothetical choice among women in South Africa: a survey exploring opportunities for a multipurpose prevention technology implant
Authors: Martin Catherine E. , Kutywayo Alison , Mataboge Paballo , Chidumwa Glory , Mthimkhulu Nqaba , Bothma Rutendo , Mullick Saiqa 
Published: June 2024

IntroductionSouth African women bear an intersecting burden of HIV, sexually transmitted infections (STIs) and unintended pregnancy. Multipurpose prevention technologies (MPTs) are a class of products that address multiple needs and have the potential to improve uptake and use of prevention products.MethodsAnalysing survey data from 703 HIV-negative women 18–40 years in three provinces in South Africa, collected between July and November 2022, this study explores their preferences for prevention methods and factors influencing choice of hypothetical prevention methods, including MPTs. Descriptive statistics and multinomial regression analyses were conducted to determine prevention method preferences and factors associated with choosing a pill, injectable or MPT-implant type prevention method.ResultsMost women wanted to prevent HIV, STIs and pregnancy. The most important factors when choosing a prevention product were whether it provided dual and long-term protection and if side effects were manageable. If choosing only one method, half of women would choose any MPT-implant and a quarter each would choose a pill or an injectable method, with method choices differing by population group.DiscussionPrevention method choices were influenced by sexual-behavioural factors and current and prior contraceptive method use. Providing a choice of prevention methods and a population specific approach to new method development and introduction with access to accurate information could enhance their ability to fill a gap in prevention needs.
Ultrasound-guided approach to surgery for nodal recurrence following lateral neck dissection for differentiated thyroid carcinoma. A single institution experience
Authors: Pacilli Mario , Pavone Giovanna , Quazzico Andrea , Fersini Alberto , Ambrosi Antonio , Tartaglia Nicola 
Published: June 2024

IntroductionTotal thyroidectomy (TT) and central neck dissection (CND) had a significant effect on the reduction of local recurrence compared with TT alone. Lateral Neck Dissection (LND) was performed in all the cases with therapeutic intent. The suspicion of nodal recurrence is provided by the appearance of one or more enlarged nodes in the central and/or laterocervical compartment during the follow up period.MethodsFrom January 2018 to November 2023, 16 patients at the University General Surgery unit of the Polyclinic of Foggia underwent reoperation due to nodal recurrence after previously undergoing total thyroidectomy with central and lateral cervical dissection.ResultsAll surgical interventions were approached with intraoperative ultrasound performed by the operating surgeon. In all cases, ultrasound identification of the suspicious lymph node led to histological confirmation of malignancy. In only two cases it was necessary to carry out an extemporaneous intraoperative histological examination. No complications were recorded during the operations.ConclusionsSurgical reintervention in patients with nodal recurrence is challenging and requires an assessment by members of the interdisciplinary team. The ideal method should be economically convenient, easy to practice, with a quick learning curve, easily reproducible, and safe for patients. Intraoperative, ultrasound-guided, is a safe and effective technique. It facilitates tumor localization and removal, especially in patients requiring re-operative neck surgery.
Sequential Fermentation in Red Wine cv. Babić Production: The Influence of Torulaspora delbrueckii and Lachancea thermotolerans Yeasts on the Aromatic and Sensory Profile
Authors: Ivić Stipe , Jeromel Ana , Kozina Bernard , Prusina Tihomir , Budić-Leto Irena , Boban Ana , Vasilj Višnja , Jagatić Korenika Ana-Marija 
Published: June 2024

This research aimed to analyze the impact of two different non-Saccharomyces yeast species on the aromatic profile of red wines made from the cv. Babić (Vitis vinifera L.) red grape variety. The grapes were obtained from two positions in the Middle and South of Dalmatia. This study compared a control treatment with the Saccharomyces cerevisiae (Sc) strain as a type of sequential inoculation treatment with Lachancea thermotolerans (Lt x Sc) and Torulaspora delbrueckii (Td x Sc). The focus was on the basic wine parameters and volatile aromatic compound concentrations determined using the SPME-Arrow-GC/MS method. The results revealed significant differences in cis-linalool oxide, geraniol, neric acid, and nerol, which contribute to the sensory profile with floral and rose-like aromas; some ethyl esters, such as ethyl furoate, ethyl hexanoate, ethyl lactate, ethyl 2-hydroxy-3-methylbutanoate, ethyl 3-hydroxy butanoate, diethyl glutarate, and diethyl succinate, contribute to the aromatic profile with fruity, buttery, overripe, or aging aromas. A sensory evaluation of wines confirmed that Td x Sc treatments exhibited particularly positive aromatic properties together with a more intense fullness, harmony, aftertaste, and overall impression.