bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmacokinetics and safety of inhaled oxytocin compared with intramuscular oxytocin in women in the third stage of labour: A randomized open‐label study
Authors: Gajewska‐Knapik Katarzyna , Kumar Subramanya , Sutton‐Cole Amy , Palmer Kirsten R. , Cahn Anthony , Gibson Rachel A. , Kirkpatrick Carl , Parry Simon , Schneider Ian , Siederer Sarah , Stylianou Annie , Hacquoil Kimberley , Powell Marcy , Ellis Melissa , McIntosh Michelle P. , Lambert Pete 
Published: July 2023

AbstractAimsTo compare pharmacokinetics (PK) and safety of heat‐stable inhaled (IH) oxytocin with intramuscular (IM) oxytocin in women in third stage of labour (TSL), the primary endpoint being PK profiles of oxytocin IH and secondary endpoint of safety.MethodsA phase 1, randomized, cross‐over study was undertaken in 2 UK and 1 Australian centres. Subjects were recruited into 2 groups: Group 1, women in TSL; Group 2, nonpregnant women of childbearing potential (Cohort A, combined oral contraception; Cohort B, nonhormonal contraception). Participants were randomized 1:1 to: Group 1, oxytocin 10 IU (17 μg) IM or oxytocin 240 IU (400 μg) IH immediately after delivery; Group 2, oxytocin 5 IU (8.5 μg) intravenously and oxytocin 240 IU (400 μg) IH at 2 separate dosing sessions.ResultsParticipants were recruited between 23 November 2016 to 4 March 2019. In Group 1, 17 participants were randomized; received either IH (n = 9) or IM (n = 8) oxytocin. After IH and IM administration, most plasma oxytocin concentrations were below quantification limits (2 pg/mL). In Group 2 (n = 14), oxytocin IH concentrations remained quantifiable ≤3 h postdose. Adverse events were reported in both groups, with no deaths reported: Group 1, IH n = 3 (33%) and IM n = 2 (25%); Group 2, n = 14 (100%).ConclusionSafety profiles of oxytocin IH and IM were similar. However, PK profiles could not be established for oxytocin IH or IM in women in TSL, despite using a highly sensitive and specific assay.
Alpha‐synuclein fibrils amplified from multiple system atrophy and Parkinson's disease patient brain spread after intracerebral injection into mouse brain
Authors: Zhang Shuyu , Dauer Karina , Strohäker Timo , Tatenhorst Lars , Caldi Gomes Lucas , Mayer Simon , Jung Byung Chul , Kim Woojin S. , Lee Seung‐Jae , Becker Stefan , Liesche‐Starnecker Friederike , Zweckstetter Markus , Lingor Paul 
Published: July 2023

AbstractParkinson's disease (PD), multiple system atrophy (MSA), and dementia with Lewy bodies (DLB) are neurodegenerative disorders with alpha‐synuclein (α‐syn) aggregation pathology. Different strains of α‐syn with unique properties are suggested to cause distinct clinical and pathological manifestations resulting in PD, MSA, or DLB. To study individual α‐syn spreading patterns, we injected α‐syn fibrils amplified from brain homogenates of two MSA patients and two PD patients into the brains of C57BI6/J mice. Antibody staining against pS129‐α‐syn showed that α‐syn fibrils amplified from the brain homogenates of the four different patients caused different levels of α‐syn spreading. The strongest α‐syn pathology was triggered by α‐syn fibrils of one of the two MSA patients, followed by comparable pS129‐α‐syn induction by the second MSA and one PD patient material. Histological analysis using an antibody against Iba1 further showed that the formation of pS129‐α‐syn is associated with increased microglia activation. In contrast, no differences in dopaminergic neuron numbers or co‐localization of α‐syn in oligodendrocytes were observed between the different groups. Our data support the spreading of α‐syn pathology in MSA, while at the same time pointing to spreading heterogeneity between different patients potentially driven by individual patient immanent factors.
Combination therapy with hydrogen peroxide and irradiation promotes an abscopal effect in mouse models
Authors: Kemmotsu Naoya , Zhu Li , Nagasaki Joji , Otani Yoshihiro , Ueda Youki , Dansako Hiromichi , Fang Yue , Date Isao , Togashi Yosuke 
Published: July 2023

AbstractHydrogen peroxide (H2O2) induces oxidative stress and cytotoxicity, and can be used for treating cancers in combination with radiotherapy. A product comprising H2O2 and sodium hyaluronate has been developed as a radiosensitizer. However, the effects of H2O2 on antitumor immunity remain unclear. To investigate the effects of H2O2, especially the abscopal effect when combined with radiotherapy (RT), we implanted murine tumor cells simultaneously in two locations in mouse models: the hind limb and back. H2O2 mixed with sodium hyaluronate was injected intratumorally, followed by irradiation only at the hind limb lesion. No treatment was administered to the back lesion. The H2O2/RT combination significantly reduced tumor growth at the noninjected/nonirradiated site in the back lesion, whereas H2O2 or RT individually did not reduce tumor growth. Flow cytometric analyses of the tumor‐draining lymph nodes in the injected/irradiated areas showed that the number of dendritic cells increased significantly with maturation in the H2O2/RT combination group. In addition, analyses of tumor‐infiltrating lymphocytes showed that the number of CD8+ (cluster of differentiation 8) T cells and the frequency of IFN‐γ+ (interferon gamma) CD8+ T cells were higher in the noninjected/nonirradiated tumors in the H2O2/RT group compared to those in the other groups. PD‐1 (programmed death receptor 1) blockade further increased the antitumor effect against noninjected/nonirradiated tumors in the H2O2/RT group. Intratumoral injection of H2O2 combined with RT therefore induces an abscopal effect by activating antitumor immunity, which can be further enhanced by PD‐1 blockade. These findings promote the development of H2O2/RT therapy combined with cancer immunotherapies, even for advanced cancers.
Enriched environment ameliorates fear memory impairments induced by sleep deprivation via inhibiting PIEZO1/calpain/autophagy signaling pathway in the basal forebrain
Authors: Zhang Zi‐qing , Lu Yan , Zhang Hao , Dong Su‐he , Wu Ya‐tong , Wang Si‐nian , Huang Ai‐hua , Jiang Qi‐sheng , Yin Shi‐min 
Published: July 2023

AbstractAimsTo verify the hypothesis that an enriched environment (EE) alleviates sleep deprivation‐induced fear memory impairment by modulating the basal forebrain (BF) PIEZO1/calpain/autophagy pathway.MethodsEight‐week‐old male mice were housed in a closed, isolated environment (CE) or an EE, before 6‐h total sleep deprivation. Changes in fear memory after sleep deprivation were observed using an inhibitory avoidance test. Alterations in BF PIEZO1/calpain/autophagy signaling were detected. The PIEZO1 agonist Yoda1 or inhibitor GsMTx4, the calpain inhibitor PD151746, and the autophagy inducer rapamycin or inhibitor 3‐MA were injected into the bilateral BF to investigate the pathways involved in the memory‐maintaining role of EE in sleep‐deprived mice.ResultsMice housed in EE performed better than CE mice in short‐ and long‐term fear memory tests after sleep deprivation. Sleep deprivation resulted in increased PIEZO1 expression, full‐length tropomyosin receptor kinase B (TrkB‐FL) degradation, and autophagy, as reflected by increased LC3 II/I ratio, enhanced p62 degradation, increased TFEB expression and nuclear translocation, and decreased TFEB phosphorylation. These molecular changes were partially reversed by EE treatment. Microinjection of Yoda1 or rapamycin into the bilateral basal forebrain induced excessive autophagy and eliminated the cognition‐protective effects of EE. Bilateral basal forebrain microinjection of GsMTx4, PD151746, or 3‐MA mimicked the cognitive protective and autophagy inhibitory effects of EE in sleep‐deprived mice.ConclusionsEE combats sleep deprivation‐induced fear memory impairments by inhibiting the BF PIEZO1/calpain/autophagy pathway.
Itch, sleep loss, depressive symptoms, fatigue, and productivity loss in patients with moderate‐to‐severe atopic dermatitis: Analyses of TREATgermany registry data
Authors: Birkner Thomas , Siegels Doreen , Heinrich Luise , Haufe Eva , Abraham Susanne , Heratizadeh Annice , Harder Inken , Bell Magnus , Fell Isabell , Worm Margitta , Handrick Christiane , Effendy Isaak , Asmussen Andrea , Kleinheinz Andreas , Homey Bernhard , Sticherling Michael , Hong‐Weldemann Sung‐Hei , Augustin Matthias , Weisshaar Elke , Schäkel Knut , Schaefer Thomas , Schwarz Beate , Wiemers Franca , Brücher Jens‐Joachim , Quist Sven , Wollenberg Andreas , Biedermann Tilo , Ertner Konstantin , von Kiedrowski Ralph , Werfel Thomas , Weidinger Stephan , Schmitt Jochen ,   and the TREATgermany Study Group
Published: July 2023

SummaryBackgroundTREATgermany is a multicenter registry including patients with moderate‐to‐severe atopic dermatitis (AD) from currently 74 study centers (university clinics, hospitals and practices) in Germany. As of August 31, 2021, 1,230 adult patients were enrolled.MethodsIn TREATgermany, patients and physicians fill in questionnaires pertaining to symptoms, disease severity, quality of life, depressiveness, and fatigue. In particular, limitations in work performance are assessed using the Work Limitations Questionnaire (WLQ). To assess associations between occupational performance/work limitations and symptoms, correlations and regression models were calculated.ResultsThe examined sample of 228 employed patients reported an average of 6% at‐work productivity loss within the past two weeks prior to enrolment in the registry. The WLQ productivity loss score was moderately associated with itch (r = 0.32) and sleep loss (r = 0.39) and strongly associated with depressive symptoms (r = 0.68) and fatigue (r = 0.60).ConclusionsThe analyses of the registry data show that moderate‐to‐severe atopic dermatitis has a negative impact on the work productivity of the patients. The analyses further point out the relevant associations between work productivity, depressive symptoms, and fatigue highlighting the disease burden caused by the psychological components of AD.
Prognosis in stage II melanoma of the head and neck depends on the histological subtype
Authors: Jasper Sophie , Keim Ulrike , Leiter Ulrike , Amaral Teresa , Flatz Lukas , Forschner Andrea 
Published: July 2023

SummaryBackground and objectivesThe melanoma guideline is mainly based on the AJCC stage. There is no difference according to histological subtypes such as superficial spreading melanoma (SSM), lentigo maligna melanoma (LMM) or nodular malignant melanoma (NM). We aimed to evaluate whether patients with LMM have a different clinical course from patients with SSM/NM. This is particularly important as adjuvant anti‐PD‐1 therapy is approved for stage IIB and IIC melanoma.Patients and methodsData were extracted from the Central Registry of Malignant Melanoma. Only patients with LMM, SSM, and NM of the head and neck with primary diagnosis between 01/01/2000 and 12/31/2019 were included. Progression‐free survival (PFS), melanoma‐specific survival (MSS), and pattern of metastases were analyzed for the LMM group compared to SSM/NM.ResultsThe LMM cohort (n = 902) had significantly better MSS than the SSM/NM cohort (n = 604). There was no difference in PFS. The 5‐year MSS of the stage II LMM cohort was 88.5% (95% CI 81.4‐95.6) compared to 79.7% (95% CI 72.8‐86.6) in the stage II SSM/NM cohort.ConclusionIt does not appear appropriate to use adjuvant therapy in stage II LMM patients to the same extent as in patients with SSM/NM.
Insights of tricuspid regurgitation mechanisms in patients with right ventricular apical pacing by three‐dimensional echocardiography
Authors: Chango‐Azanza Diego Xavier , Munin Martin , Sanchez Gustavo , Raggio Ignacio , Pelayo Maria Eugenia , Garro Hugo , Arevalo Mario , Carbajales Justo , Makhoul Silvia , Ronderos Ricardo 
Published: July 2023

AbstractObjectiveDevice lead‐induced tricuspid regurgitation (LITR) mechanisms are well‐defined by 3D transthoracic echocardiography (3D‐TTE). There is a lack of data on the Latin‐American population. The objective of this study was to describe the prevalence of several mechanisms and insights in patients with permanent right ventricular (RV) implanted devices by 3D‐TTE examination.MethodsWe performed a cross‐sectional analysis of 101 patients with permanent cardiac devices such as pacemakers or defibrillators. 3D‐TTE was obtained on all patients in RV‐focused apical views to perform a complete tricuspid valve (TV) evaluation: leaflets, subvalvular apparatus, precise lead location, and functional assessment to evaluate possible mechanisms of tricuspid regurgitation (TR).ResultsIn a total of 101 patients, the leads did not interfere with TV function in 53 p. (59%), while LITR was observed in 38 (41%) patients. Adherent, impinging, entangled, and mixed lead‐induced mechanisms were observed. Time in years since device implantation was significantly higher in patients with LITR.ConclusionsLITR was present in a high proportion of our population. LITR is the result of damage to the TV as well as its subvalvular apparatus due to the fibrotic and inflammatory response over time when leads are situated in unfavorable locations.
Electoral proximity, political violence, and personal wellbeing: An experimental analysis in West Africa
Authors: Doces John A. 
Published: July 2023

AbstractDoes the threat of political violence affect wellbeing? We argue that political violence induced by elections reduces wellbeing as it provokes emotional reactions like anxiety and fear. There is a lingering effect from political violence that reemerges with new rounds of elections, and that reduces wellbeing. To test this claim, we employ an experimental analysis in Côte d'Ivoire. We motivate political violence via a treatment about the 2020 election, and the proximity of the 2020 election. We find that each has a negative effect on wellbeing. In Côte d'Ivoire, we also consider the direct effect of political violence on wellbeing, and find that it is inversely associated with wellbeing. Finally, we extend the analysis of election proximity to Nigeria during the 2023 election. The results here show that proximity is (i) inversely associated with wellbeing and (ii) that it is directly associated with the expectation of political violence. In all cases, political violence lowers self‐assessed wellbeing. We argue that this effect is likely to be greater for women than men, but find that it is generally true for the latter. We conclude the paper with considerations about its generalizability, ideas for future research, and policy implications.
Treatment of extracapsular fractures of the mandibular condylar process: A retrospective evaluation of 377 cases
Authors: Maurer Michael , Klaes Tabea , Meier Johannes K. , Gottsauner Josef Maximilian , Taxis Jürgen , Schuderer Johannes , Reichert Torsten E. , Ettl Tobias 
Published: July 2023

AbstractBackground/AimMandibular condylar fractures represent 25%–35% of all mandibular fractures. Despite profound research, there is still a controverse debate about treating these fractures conservatively or by open reduction and internal fixation (ORIF).The aim of this study is to analyse the outcome after open and closed treatment of extracapsular mandibular condyle fractures regarding general characteristics, post‐treatment malocclusion, facial nerve palsy (FNP), maximum mouth opening (MMO) and parotid complications.MethodsA retrospective cohort of 377 fractures (350 open, 27 closed treatment) was reviewed by reference to clinical and radiological pre‐ and postoperative documentation. Follow‐up period was 12 months. Pearsons' chi‐square‐test, correlations, Kruskal–Wallis test and t‐test were carried out for statistical analysis.ResultsThe dominant type of fracture was type II in Spiessl and Schroll classification (50.1%). In the open treated fractures, the most common approach was retromandibular transparotid (91.7%). Post‐treatment malocclusion occurred in 18.0% and was significantly increased in bilateral fractures (p = .039), in luxation fractures (p = .016) and in patients with full dentition (p = .004). After open reduction and internal fixation (ORIF), temporary FNP was documented in 7.1% whereas a permanent paresis occurred in 1.7%. FNP was significantly associated with high fractures (p = .001), comminution (p = .028) and increased duration of surgery (p = .040). Parotid complications were significantly associated with revision surgery (p = .009). Post‐treatment reduction of MMO mainly occurred in female patients (p < .001) as well as in patients with bilateral fractures (p < .001), high fractures (p = .030) and concomitant mandibular (p = .001) and midfacial fractures (p = .009).ConclusionMalocclusion seems to be the most frequent long‐term complication after open reduction and osteosynthesis of extracapsular mandibular condyle fractures. We suggest ORIF by a transparotid approach to be an appropriate treatment with a low complication rate regarding especially FNP for extracapsular fractures of the mandibular condyle.
Vitamin D deficiency and genetic polymorphisms of vitamin D‐associated genes in Parkinson's disease
Authors: Pal Randrita , Choudhury Supriyo , Kumar Hrishikesh , Dey Sanjit , Das Nilansu , Basu Barnali Ray 
Published: July 2023

AbstractParkinson's disease (PD) and vitamin D share a unique link as vitamin D deficiency (VDD) prevails in PD. Thus, an in‐depth understanding of vitamin D biology in PD might be crucial for therapeutic strategies emphasising vitamin D. Specifically, explicating the effect of VDD and genetic polymorphisms of vitamin D‐associated genes in PD, like VDR (vitamin D receptor) or GC (vitamin D binding protein) may aid the process along with polymorphisms of vitamin D metabolising genes (e.g., CYP2R1 and CYP27A1) in PD. Literature review of single nucleotide polymorphisms (SNPs) related to vitamin D levels [GC (GC1‐rs7041 and GC2‐rs4588), CYP2R1, CYP24A1 and CYP27B1] and vitamin D function [VDR (FokI ‐ rs2228570 and rs10735810; ApaI ‐ rs7976091, rs7975232BsmI and rs1544410; and TaqI ‐ rs731236)] was conducted to explore their relationship with PD severity globally. VDR‐FokI polymorphism was reported to be significantly associated with PD in Hungarian, Chinese and Japanese populations, whereas VDR‐ApaI polymorphism was found to affect PD in the Iranian population. However, VDR‐TaqI and BsmI polymorphisms had no significant association with PD severity. Conversely, GC1 polymorphisms reportedly affected vitamin D levels without influencing the disease severity. CYP2R1 (excluding rs1993116) was also reportedly linked to clinical manifestations of PD. Genetic polymorphisms might cause VDD despite enough sunlight exposure and vitamin D‐rich food intake, enhancing inflammation, there by influencing PD pathophysiology. Knowledge of the polymorphisms associated with VDD appears promising for developing precision vitamin D‐dosing therapeutic strategies against PD.
Understanding of refugees in management studies and implications for future research on workplace integration
Authors: Pesch Robin , Ipek Ebru 
Published: July 2023

AbstractDue to the ongoing refugee crises, refugees and their workplace integration have attracted the attention of management scholars. The understanding of refugees varies and often lacks clarity in this emerging research. In analyzing how management scholars define the term “refugee,” detailing their approaches to heterogeneous refugee populations and outlining their assumptions about refugees' coping agency, this literature review provides a structured analysis of the emerging field's collective knowledge and theorization. We propose detailed implications to enhance the understanding of refugees in management research and show future avenues for research.
BERTuit: Understanding Spanish language in Twitter with transformers
Authors: Huertas‐Tato Javier , Martín Alejandro , Camacho David 
Published: July 2023

AbstractThe appearance of complex attention‐based language models such as BERT, RoBERTa or GPT‐3 has allowed to address highly complex tasks in a plethora of scenarios. However, when applied to specific domains, these models encounter considerable difficulties. This is the case of Social Networks such as Twitter, an ever‐changing stream of information written with informal and complex language, where each message requires careful evaluation to be understood even by humans given the important role that context plays. Addressing tasks in this domain through Natural Language Processing involves severe challenges. When powerful state‐of‐the‐art multilingual language models are applied to this scenario, language specific nuances get lost in translation. To face these challenges we present BERTuit, the largest transformer proposed so far for Spanish language, pre‐trained on a massive dataset of 230 M Spanish tweets using RoBERTa optimization. Our motivation is to provide a powerful resource to better understand Spanish Twitter and to be used on applications focused on this social network, with special emphasis on solutions devoted to tackle the spreading of misinformation in this platform. BERTuit is evaluated on several tasks and compared against M‐BERT, XLM‐RoBERTa and XLM‐T, very competitive multilingual transformers. The utility of our approach is shown with applications, in this case: an unsupervised methodology to visualize groups of hoaxes; and supervised profiling of authors spreading disinformation.
Paclitaxel alters melanogenesis and causes pigmentation in the skin of gynecological cancer patients
Authors: Montero Paula , Sanz Celia , Pérez‐Fidalgo Jose Alejandro , Pérez‐Leal Martín , Milara Javier , Cortijo Julio 
Published: July 2023

AbstractBackgroundPaclitaxel (PTX) is a microtubule‐stabilizing antineoplastic that has been shown to damage healthy tissues like the skin. Hyperpigmentation can be found among the adverse effects caused by PTX, but the literature is limited and the mechanisms driving PTX‐induced pigmentary alterations are unknown.ObjectivesThis study aimed to describe the pigmentary alterations caused by PTX and to determine the effects of PTX on melanocytes.MethodsPigmentary skin alterations were measured in 20 gynecological cancer patients under PTX treatment by using specific probes, which determine the melanin index and the pigmentation level. Melanocytes were incubated with paclitaxel to analyze melanogenesis markers gene expression, melanin content, and transcription factors activation.ResultsPaclitaxel induced alterations in the skin pigmentation with no visible clinical manifestations. Gynecological cancer patients under paclitaxel treatment had an increase in the melanin index and pigmentation levels. In vitro, PTX exposure to melanocytes increased the expression of melanogenesis markers, melanin content, and induced activation of ERK and MITF.ConclusionsThe results suggest that PTX alters pigmentation in patients with no clinically visible manifestations, and these alterations might be driven by its capacity to stimulate melanogenesis on melanocytes through the MITF activation pathway.