bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phenotypic and genotypic characterization of virulence markers and antifungal susceptibility of oral Candida species from diabetic and non-diabetic hemodialysis patients
Authors: Mohammadi Faezeh , Charkhchian Maliheh , mirzadeh Monirsadat 
Published: May 2023

Abstract
Background
Patients with chronic kidney disease undergoing hemodialysis are often colonized by Candida species with high possibility of fungal infections. The purposes of this study were to determine the prevalence of Candida species, evaluate antifungal susceptibility profile, biofilm formation, proteinase and phospholipase activities, and the frequency of virulence genes in the Candida species isolated from the oral mucosa of hemodialysis diabetic (DM) and non-diabetic (non-DM) patients.

Methods
This study identified several species of Candida isolated from 69 DM and 58 non-DM patients on hemodialysis using phenotypic methods and PCR–RFLP technique. The identification of C. albicans and C. glabrata complex was performed by HWP1 gene and four oligonucleotides (UNI-5.8S, GLA-f, BRA-f, and NIV-f), respectively. Antifungal susceptibility to amphotericin B, fluconazole, itraconazole, voriconazole, and caspofungin was assessed according to CLSI M27-A3/S4. The biomass, metabolic activity of biofilm, proteinase (Prz), phospholipase (Pz), and molecular study for virulence genes were assessed using crystal violet, XTT assay, agar-based hydrolytic enzyme, and PCR technique, respectively.

Results
Candida prevalence was 44.9% with 47.8% and 41.4% among DM and non-DM patients, respectively (P = .045). The species identified were C. albicans (49.5%), C. glabrata (16.5%), C. tropicalis (12%), C. kefyr (8.8%), C. parapsilosis (6.6%), C. dubliniensis (3.3%), and C. lusitaniae (3.3%). The antifungal susceptibility profile showed that all Candida isolates were sensitive to amphotericin B, itraconazole, voriconazole, and caspofungin whereas fluconazole resistance was observed in 6.3% (MIC ≥ 64 μg/mL) of C. albicans and 6.6% of C. glabrata (MIC ≥ 64 μg/mL). The susceptible- dose-dependent rate was found in 10.5% of C. albicans. The Prz values of C. albicans ranged from 0.37 to 0.66 for the DM and 0.44–0.73 for the non-DM group (P < 0.05). The non-albicans Candida (NAC) species produced higher degree of biomass and metabolic activity compared to C. albicans (P < 0.05). Furthermore, significant (p < 0.05) correlations were detected between the biofilm formation with Prz values and fluconazole MICs. The most detected virulence factors were ALS3 and Sap5.

Conclusions
These results showed the importance of prevalence of NAC species in hemodialysis patients. Investigating antifungal susceptibility profile made a better understanding of the role of virulence markers in the pathogenesis of Candida strains.
The role of men’s forgiveness in marital satisfaction and coping strategies of infertile iranian women
Authors: Safari Samaneh , Hasanpoor-Azghady Seyedeh Batool , Amiri-Farahani Leila 
Published: May 2023

Abstract
Background
Infertility and its related problems create tensions in infertile women, which may lead to reduced marital satisfaction and the use of ineffective coping strategies. Considering the important role of forgiveness, marital satisfaction and effective coping strategies in the quality of life of infertile couples, and taking into account the growing number of Iranian infertile couples, this study was conducted to determine the relationship between men’s forgiveness, marital satisfaction, and coping strategies of infertile Iranian women.

Methods
This cross-sectional study included 200 Iranian infertile couples. The research environment was the most equipped infertility center in the west of Iran. Sampling was continuous. Data collection tools used included a self-generated demographic and fertility questionnaire, the Family Forgiveness Scale (FFS), the Index of Marital Satisfaction (IMS), and the Ways of Coping Questionnaire-revised (WOCQ-R).

Results
Husbands’ forgiveness had a significant direct relationship with the marital satisfaction of infertile women (r = -0.27, p < 0.001). However, there was no significant correlation between Husbands’ forgiveness, emotion-focused, and problem-focused coping of infertile women. Among the subscales of forgiveness, only the subscale of recognition had inversely correlated with the emotional coping of infertile women.

Conclusion
The results showed that the higher the forgiveness of husbands, the higher the marital satisfaction of infertile women. Also, with the increase of husbands’ forgiveness in the recognition subscale, the use of emotion-focused coping decreased in infertile women. Based on the results with empowering the husbands of infertile women with forgiveness skills, it is possible to take a step towards marital satisfaction and thus improve the quality of life of infertile women.
Differentiation between fetal and postnatal iron deficiency in altering brain substrates of cognitive control in pre-adolescence
Authors: Hua Mengdi , Shi Donglin , Xu Wenwen , Zhu Liuyan , Hao Xiaoxin , Zhu Bingquan , Shu Qiang , Lozoff Betsy , Geng Fengji , Shao Jie 
Published: May 2023

Abstract
Background
Early iron deficiency (ID) is a common risk factor for poorer neurodevelopment, limiting children’s potential and contributing to global burden. However, it is unclear how early ID alters the substrate of brain functions supporting high-order cognitive abilities and whether the timing of early ID matters in terms of long-term brain development. This study aimed to examine the effects of ID during fetal or early postnatal periods on brain activities supporting proactive and reactive cognitive control in pre-adolescent children.

Methods
Participants were part of a longitudinal cohort enrolled at birth in southeastern China between December 2008 and November 2011. Between July 2019 and October 2021, 115 children aged 8–11 years were invited to participate in this neuroimaging study. Final analyses included 71 children: 20 with fetal ID, 24 with ID at 9 months (postnatal ID), and 27 iron-sufficient at birth and 9 months. Participants performed a computer-based behavioral task in a Magnetic Resonance Imaging scanner to measure proactive and reactive cognitive control. Outcome measures included accuracy, reaction times, and brain activity. Linear mixed modeling and the 3dlme command in Analysis of Functional NeuroImages (AFNI) were separately used to analyze behavioral performance and neuroimaging data.

Results
Faster responses in proactive vs. reactive conditions indicated that all groups could use proactive or reactive cognitive control according to contextual demands. However, the fetal ID group was lower in general accuracy than the other 2 groups. Per the demands of cues and targets, the iron-sufficient group showed greater activation of wide brain regions in proactive vs. reactive conditions. In contrast, such condition differences were reversed in the postnatal ID group. Condition differences in brain activation, shown in postnatal ID and iron-sufficient groups, were not found in the fetal ID group. This group specifically showed greater activation of brain regions in the reward pathway in proactive vs. reactive conditions.

Conclusions
Early ID was associated with altered brain functions supporting proactive and reactive cognitive control in childhood. Alterations differed between fetal and postnatal ID groups. The findings imply that iron supplement alone is insufficient to prevent persisting brain alterations associated with early ID. Intervention strategies in addition to the iron supplement should consider ID timing.
Pulmonary magnetic resonance-guided online adaptive radiotherapy of locally advanced non-small-cell lung cancer: the PUMA trial
Authors: Regnery Sebastian , de Colle Chiara , Eze Chukwuka , Corradini Stefanie , Thieke Christian , Sedlaczek Oliver , Schlemmer Heinz-Peter , Dinkel Julien , Seith Ferdinand , Kopp-Schneider Annette , Gillmann Clarissa , Renkamp C. Katharina , Landry Guillaume , Thorwarth Daniela , Zips Daniel , Belka Claus , Jäkel Oliver , Debus Jürgen , Hörner-Rieber Juliane 
Published: May 2023

AbstractBackgroundPatients with locally-advanced non-small-cell lung cancer (LA-NSCLC) are often ineligible for surgery, so that definitive chemoradiotherapy (CRT) represents the treatment of choice. Nevertheless, long-term tumor control is often not achieved. Intensification of radiotherapy (RT) to improve locoregional tumor control is limited by the detrimental effect of higher radiation exposure of thoracic organs-at-risk (OAR). This narrow therapeutic ratio may be expanded by exploiting the advantages of magnetic resonance (MR) linear accelerators, mainly the online adaptation of the treatment plan to the current anatomy based on daily acquired MR images. However, MR-guidance is both labor-intensive and increases treatment times, which raises the question of its clinical feasibility to treat LA-NSCLC. Therefore, the PUMA trial was designed as a prospective, multicenter phase I trial to demonstrate the clinical feasibility of MR-guided online adaptive RT in LA-NSCLC.MethodsThirty patients with LA-NSCLC in stage III A-C will be accrued at three German university hospitals to receive MR-guided online adaptive RT at two different MR-linac systems (MRIdian Linac®, View Ray Inc. and Elekta Unity®, Elekta AB) with concurrent chemotherapy. Conventionally fractioned RT with isotoxic dose escalation up to 70 Gy is applied. Online plan adaptation is performed once weekly or in case of major anatomical changes. Patients are followed-up by thoracic CT- and MR-imaging for 24 months after treatment. The primary endpoint is twofold: (1) successfully completed online adapted fractions, (2) on-table time. Main secondary endpoints include adaptation frequency, toxicity, local tumor control, progression-free and overall survival.DiscussionPUMA aims to demonstrate the clinical feasibility of MR-guided online adaptive RT of LA-NSCLC. If successful, PUMA will be followed by a clinical phase II trial that further investigates the clinical benefits of this approach. Moreover, PUMA is part of a large multidisciplinary project to develop MR-guidance techniques.Trial registrationClinicalTrials.gov:NCT05237453.
Health-related quality of life in patients with Kashin–Beck disease is lower than in those with osteoarthritis: a cross-sectional study
Authors: Jin Zhankui , Wu Xueyuan , Sun Zhengming , Chen Ming , Yang Bo , Dong Xianghui , Liu Shizhang , Chang Yanhai , Xu Cuixiang , Yi Zhi , Ling Ming 
Published: May 2023

Abstract
Background
Kashin–Beck disease (KBD) is an endemic deformable bone and joint disease, which affects the quality of life (QOL) of patients. We conducted a cross-sectional study of the QOL of KBD patients by a new KBD quality of life (KBDQOL) questionnaire.

Methods
A total of 252 KBD patients and 248 OA patients came from Northwest China, and 260 healthy people living in the same area as KBD and osteoarthritis (OA) patients served as the controls. KBDQOL questionnaire was used to evaluate the QOL of all objects.

Results
The average scores for physical functions, activity limitations, support of society, mental health and general health were significantly lower in KBD patients than that in OA patients and healthy people except for economics. Monofactor analysis showed that age, height, weight status, education level and grade of KBD had a significant effect on KBDQOL score. Multivariate analysis showed that grade of KBD was the influencing factor of physical function score; gender, age, height, grade of KBD and duration of symptoms were the influencing factors of activity restriction score; age and grade of KBD were factors affecting the general health score.

Conclusion
The QOL of KBD patients was significantly lower than that of OA patients and healthy people. The KBDQOL questionnaire may be a promising tool for assessing the QOL of KBD patients.
Irbesartan overcomes gemcitabine resistance in pancreatic cancer by suppressing stemness and iron metabolism via inhibition of the Hippo/YAP1/c-Jun axis
Authors: Zhou Tianxing , Xie Yongjie , Hou Xupeng , Bai Weiwei , Li Xueyang , Liu Ziyun , Man Quan , Sun Jingyan , Fu Danqi , Yan Jingrui , Zhang Zhaoyu , Wang Yifei , Wang Hongwei , Jiang Wenna , Gao Song , Zhao Tiansuo , Chang Antao , Wang Xiuchao , Sun Hongxia , Zhang Xiufeng , Yang Shengyu , Huang Chongbiao , Hao Jihui , Liu Jing 
Published: May 2023

Abstract
Background
Chemoresistance is the main reason for the poor prognosis of pancreatic ductal adenocarcinoma (PDAC). Thus, there is an urgent need to screen out new targets and compounds to reverse chemotherapeutic resistance.

Methods
We established a bio-bank of human PDAC organoid models, covering a representative range of PDAC tumor subtypes. We screened a library of 1304 FDA-approved compounds to identify candidates efficiently overcoming chemotherapy resistance. The effects of the compounds were evaluated with a CellTiter-Glo-3D assay, organoid apoptosis assay and in vivo patient-derived xenograft (PDX), patient-derived organoid (PDO) and LSL-KrasG12D/+; LSL-Trp53R172H/+; Pdx1-Cre (KPC) genetically engineered mouse models. RNA-sequencing, genome editing, sphere formation assays, iron assays and luciferase assays were conducted to elucidate the mechanism.

Results
High-throughput drug screening of chemotherapy-resistant PDOs identified irbesartan, an angiotensin ‖ type 1 (AT1) receptor antagonist, which could synergistically enhance the ability of chemotherapy to kill PDAC cells. In vitro and in vivo validation using PDO, PDX and KPC mouse models showed that irbesartan efficiently sensitized PDAC tumors to chemotherapy. Mechanistically, we found that irbesartan decreased c-Jun expression by inhibiting the Hippo/YAP1 pathway and further overcame chemotherapy resistance in PDAC. We also explored c-Jun, a potential target of irbesartan, which can transcriptionally upregulate the expression of key genes involved in stemness maintenance (SOX9/SOX2/OCT4) and iron metabolism (FTH1/FTL/TFRC). More importantly, we observed that PDAC patients with high levels of c-Jun expression demonstrated poor responses to the current standard chemotherapy regimen (gemcitabine plus nab-paclitaxel). Moreover, patients with PDAC had significant survival benefits from treatment with irbesartan plus a standard chemotherapy regimen in two-center retrospective clinical cohorts and patients with high c-Jun expression exhibited a better response to combination chemotherapy.

Conclusions
Irbesartan could be used in combination with chemotherapy to improve the therapeutic efficacy in PDAC patients with high levels of c-Jun expression. Irbesartan effectively inhibited chemotherapy resistance by suppressing the Hippo/YAP1/c-Jun/stemness/iron metabolism axis. Based on our findings, we are designing an investigator-initiated phase II clinical trial on the efficacy and safety of irbesartan plus a standard gemcitabine/nab-paclitaxel regimen in the treatment of patients with advanced III/IV staged PDAC and are hopeful that we will observe patient benefits.
Heterogeneity in the definition of delirium in ICUs and association with the intervention effect in randomized controlled trials: a meta-epidemiological study
Authors: Collet Lucie , Lanore Aymeric , Alaterre Camille , Constantin Jean-Michel , Martin Guillaume L. , Caille Agnès , James Arthur , Dechartres Agnès 
Published: May 2023

Abstract
Purpose
To evaluate the heterogeneity in the definition of delirium in randomized controlled trials (RCTs) included in meta-analyses of delirium in intensive care units (ICUs) and to explore whether intervention effect depends on the definition used.

Methods
We searched PubMed for meta-analyses including RCTs evaluating prevention or treatment strategies of delirium in ICU. The definition of delirium was collected from RCTs and classified as validated (DSM criteria, CAM-ICU, ICDSC, NEECHAM, DRS-R98) or non-validated (non-validated scales, set of symptoms, physician appreciation or not reported). We conducted a meta-epidemiological analysis to compare intervention effects between trials using or not a validated definition by a two-step method as primary analysis and a multilevel model as secondary analysis. A ratio of odds ratios (ROR) < 1 indicated larger intervention effects in trials using a non-validated definition.

Results
Of 149 RCTs (41 meta-analyses), 109 (73.1%) used a validated definition and 40 (26.8%) did not (including 31 [20.8%] not reporting the definition). The primary analysis of 7 meta-analyses (30 RCTs) found no significant difference in intervention effects between trials using a validated definition and the others (ROR = 0.54, 95% CI 0.27–1.08), whereas the secondary multilevel analysis including 12 meta-analyses (67 RCTs) found significantly larger effects for trials using a non-validated versus a validated definition (ROR = 0.36, 95% CI 0.21–0.62).

Conclusion
The definition of delirium was heterogeneous across RCTs, with one-fifth not reporting how they evaluated delirium. We did not find a significant association with intervention effect in the primary analysis. The secondary analysis including more studies revealed significantly larger intervention effects in trials using a non-validated versus a validated definition.
Development of a hookworm egg hatching assay to determine the ovicidal effects of anthelminthics
Authors: Easland Erin , Biendl Stefan , Keiser Jennifer 
Published: May 2023

Abstract
Background
Few anthelminthics are currently available, manifesting the urgent need for new treatment options. In vitro profiling of current anthelminthics against larval and adult stage helminths displayed varying effects on closely related worm species and between life stages of the same species. Conversely, limited research has been performed on the egg stage of human hookworms, and the effects of investigational compounds on the egg stage are not routinely assessed.

Methods
We profiled the development and hatching of Heligmosomoides polygyrus, Ancylostoma duodenale and Necator americanus eggs isolated from rodent faeces in liquid media with various nutrient levels, osmolar concentrations, and acidities in dependence on incubation temperature and light exposure. Incubation conditions were optimised to allow the study of drug effect on immature and embryonated eggs. We analysed concentration-effect relationships of commercially available anthelminthics over 72 h.

Results
Rapid embryonation and hatching were observed at room temperature with and without light exposure without nutrient supplementation in a wide range of acidities. Hookworms hatched optimally at room temperature in PBS achieving > 75% hatching over 34 h. Developmental delays were seen when eggs were stored at 4 °C with no effect on viability. Similar delays were also seen with increased osmolar concentrations resulting in decreased viability. Benzimidazole anthelminthics effectively reduced the viability and prevented hatching of hookworm eggs, with albendazole and thiabendazole eliciting particularly potent effects at EC50 values below 1 µM. Macrolide anthelminthics as well as emodepside, oxantel pamoate, and pyrantel pamoate were inactive while monepantel, levamisole, and tribendimidine displayed varied potencies among the hookworm species.

Conclusion
The presented egg-hatching assay will complement ongoing anthelminthic drug discovery and allow a full characterisation of drug activity against all life stages. In the development and application of the egg-hatching assay, good accordance was observed between the three hookworm species evaluated. Marketed anthelminthics show differences of drug action compared to larval and adult stages highlighting the importance of profiling drug activity against all life stages.

Graphical Abstract
The impact of epigenetic landscape on ovarian cells in infertile older women undergoing IVF procedures
Authors: Sgueglia Giulia , Longobardi Salvatore , Valerio Domenico , Campitiello Maria Rosaria , Colacurci Nicola , Di Pietro Cinzia , Battaglia Rosalia , D’Hooghe Thomas , Altucci Lucia , Dell’Aversana Carmela 
Published: May 2023

AbstractThe constant decline in fertility and older reproductive age is the major cause of low clinical pregnancy rates in industrialised countries. Epigenetic mechanisms impact on proper embryonic development in women undergoing in vitro fertilisation (IVF) protocols. Here, we describe the main epigenetic modifications that may influence female reproduction and could affect IVF success.
Graphical Abstract
Harmonised culture procedures minimise but do not eliminate mesenchymal stromal cell donor and tissue variability in a decentralised multicentre manufacturing approach
Authors: Calcat-i-Cervera Sandra , Rendra Erika , Scaccia Eleonora , Amadeo Francesco , Hanson Vivien , Wilm Bettina , Murray Patricia , O’Brien Timothy , Taylor Arthur , Bieback Karen 
Published: May 2023

AbstractBackgroundMesenchymal stromal cells (MSCs), commonly sourced from adipose tissue, bone marrow and umbilical cord, have been widely used in many medical conditions due to their therapeutic potential. Yet, the still limited understanding of the underlying mechanisms of action hampers clinical translation. Clinical potency can vary considerably depending on tissue source, donor attributes, but importantly, also culture conditions. Lack of standard procedures hinders inter-study comparability and delays the progression of the field. The aim of this study was A- to assess the impact on MSC characteristics when different laboratories, performed analysis on the same MSC material using harmonised culture conditions and B- to understand source-specific differences.MethodsThree independent institutions performed a head-to-head comparison of human-derived adipose (A-), bone marrow (BM-), and umbilical cord (UC-) MSCs using harmonised culture conditions. In each centre, cells from one specific tissue source were isolated and later distributed across the network to assess their biological properties, including cell expansion, immune phenotype, and tri-lineage differentiation (part A). To assess tissue-specific function, angiogenic and immunomodulatory properties and the in vivo biodistribution were compared in one expert lab (part B).ResultsBy implementing a harmonised manufacturing workflow, we obtained largely reproducible results across three independent laboratories in part A of our study. Unique growth patterns and differentiation potential were observed for each tissue source, with similar trends observed between centres. Immune phenotyping verified expression of typical MSC surface markers and absence of contaminating surface markers. Depending on the established protocols in the different laboratories, quantitative data varied slightly. Functional experiments in part B concluded that conditioned media from BM-MSCs significantly enhanced tubulogenesis and endothelial migration in vitro. In contrast, immunomodulatory studies reported superior immunosuppressive abilities for A-MSCs. Biodistribution studies in healthy mice showed lung entrapment after administration of all three types of MSCs, with a significantly faster clearance of BM-MSCs.ConclusionThese results show the heterogeneous behaviour and regenerative properties of MSCs as a reflection of intrinsic tissue-origin properties while providing evidence that the use of harmonised culture procedures can reduce but do not eliminate inter-lab and operator differences.