bluuebunny/crossref_metadata_2025_split huggingface dataset:
Insulin receptor cleavage induced by estrogen impairs insulin signaling
Authors: Yuasa Tomoyuki , Takata Yasunori , Aki Nanako , Kunimi Kotaro , Satoh Miki , Nii Mari , Izumi Yoshihiko , Otoda Toshiki , Hashida Seiichi , Osawa Haruhiko , Aihara Ken-ichi 
Published: December 2021

IntroductionSoluble insulin receptor (sIR), which is the ectodomain of insulin receptor (IR), is present in human plasma. Plasma sIR levels are positively correlated with blood glucose levels and negatively correlated with insulin sensitivity. An in vitro model of IR cleavage shows that extracellular calpain 2 directly cleaves IR, which generates sIR, and sequential cleavage of the IRβ subunit by γ-secretase impairs insulin signaling in a glucose concentration-dependent manner. Nevertheless, sIR levels vary among subjects with normal glucose levels.Research design and methodsWe examined sIR levels of pregnant women throughout gestation. Using an in vitro model, we also investigated the molecular mechanisms of IR cleavage induced by estradiol.ResultsIn pregnant women, sIR levels were positively correlated with estrogen levels and significantly increased at late pregnancy independent of glucose levels. Using an in vitro model, estrogen elicited IR cleavage and impaired cellular insulin signaling. Estradiol-induced IR cleavage was inhibited by targeting of calpain 2 and γ-secretase. Estrogen exerted these biological effects via G protein-coupled estrogen receptor, and its selective ligand upregulated calpain 2 expression and promoted exosome secretion, which significantly increased extracellular calpain 2. Simultaneous stimulation of estrogen and high glucose levels had a synergic effect on IR cleavage. Metformin prevented calpain 2 release in exosomes and restored insulin signaling impaired by estrogen.ConclusionsEstradiol-induced IR cleavage causes cellular insulin resistance, and its molecular mechanisms are shared with those by high glucose levels. sIR levels at late pregnancy are significantly elevated along with estrogen levels. Therefore, estradiol-induced IR cleavage is preserved in pregnant women and could be part of the etiology of insulin resistance in gestational diabetes mellitus and overt diabetes during pregnancy.
Transfer in care and diabetes distress in young adults with type 1 diabetes mellitus
Authors: Sattoe Jane , Peeters Mariëlle , Bronner Madelon , van Staa AnneLoes 
Published: December 2021

IntroductionDiabetes distress (DD) is a serious problem in many people with diabetes and is associated with unfavorable clinical and psychosocial outcomes in children and adults. Little is known about DD in young adults (YAs) with type 1 diabetes mellitus (T1DM) who transferred to adult care. This study aimed to explore the differences between YAs with/without DD regarding transfer experiences, self-management and health-related quality of life (HRQoL).Research design and methodsCross-sectional online questionnaire completed by YAs with T1DM after transfer. DD was measured with the short-form Problem Areas in Diabetes scale. Descriptive analyses were followed by t-tests and χ2tests to explore differences between the groups with/without DD. Effect sizes were calculated.ResultsOf 164 respondents with mean age 22.7 (±1.56) years, 60.7% was female. The total sample scored low on DD (6.52±4.67; range: 0–17), but 57 (34.8%) had a score ≥8, indicating DD. YAs with DD felt less ready to transfer to adult care than those without DD and scored lower on alliance between pediatric and adult care and reception in adult care. They also reported poorer self-management skills and lower HRQoL in all domains of functioning.ConclusionsMore than one-third YAs experienced DD after transfer; this was associated with less favorable transition, self-management and psychosocial outcomes. Transfer in care seems to be a source of DD. Systematic screening on DD and attention for YAs’ worries is recommended in both pediatric and adult care.
Treatment-refractory ulcerative colitis responsive to indigo naturalis
Authors: Saiki Julie P , Andreasson Johan OL , Grimes Kevin V , Frumkin Lyn R , Sanjines Elvi , Davidson Matthew G , Park KT , Limketkai Berkeley 
Published: December 2021

BackgroundIndigo naturalis (IN) is an herbal medicine that has been used for ulcerative colitis with an unclear mechanism of action. Indigo and indirubin, its main constituents, are ligands of the aryl hydrocarbon receptor (AhR). We assessed the safety, efficacy, and colon AhR activity of IN given orally to patients with treatment-refractory ulcerative colitis. The role of AhR in IN benefit was further evaluated with an AhR antagonist in a murine colitis model.MethodsThis open-label, dose-escalation study sequentially treated 11 patients with ulcerative colitis with either IN 500 mg/day or 1.5 g/day for 8 weeks, followed by a 4-week non-treatment period. The primary efficacy endpoint was clinical response at week 8, assessed by total Mayo score. Secondary endpoints included clinical remission, Ulcerative Colitis Endoscopic Index of Severity, quality of life, and colon AhR activity measured by cytochrome P450 1A1 (CYP1A1) RNA expression.ResultsTen of 11 (91%) patients, including 8/9 (89%) with moderate-to-severe disease, achieved a clinical response. Among these 10 patients, all had failed treatment with 5-aminosalicylic acid, 8 patients with a tumour necrosis factor (TNF)-alpha inhibitor, and 6 patients with TNF-alpha inhibitor and vedolizumab. Five patients were corticosteroid dependent. Clinical response was observed in all five patients who had been recommended for colectomy. Three patients achieved clinical remission. All patients experienced improved endoscopic severity and quality of life. Four weeks after treatment completion, six patients had worsened partial Mayo scores. Four patients progressed to colectomy after study completion. Colon CYP1A1 RNA expression increased 12 557-fold at week 8 among six patients evaluated. No patient discontinued IN due to an adverse event. Concomitant administration of 3-methoxy-4-nitroflavone, an AhR antagonist, in a murine colitis model abrogated the benefit of IN.ConclusionIN is a potentially effective therapy for patients with treatment-refractory ulcerative colitis. This benefit is likely through AhR activation.Trial registration numberNCT02442960.
Development and validation pathways of artificial intelligence tools evaluated in randomised clinical trials
Authors: Siontis George C M , Sweda Romy , Noseworthy Peter A , Friedman Paul A , Siontis Konstantinos C , Patel Chirag J 
Published: December 2021

ObjectiveGiven the complexities of testing the translational capability of new artificial intelligence (AI) tools, we aimed to map the pathways of training/validation/testing in development process and external validation of AI tools evaluated in dedicated randomised controlled trials (AI-RCTs).MethodsWe searched for peer-reviewed protocols and completed AI-RCTs evaluating the clinical effectiveness of AI tools and identified development and validation studies of AI tools. We collected detailed information, and evaluated patterns of development and external validation of AI tools.ResultsWe found 23 AI-RCTs evaluating the clinical impact of 18 unique AI tools (2009–2021). Standard-of-care interventions were used in the control arms in all but one AI-RCT. Investigators did not provide access to the software code of the AI tool in any of the studies. Considering the primary outcome, the results were in favour of the AI intervention in 82% of the completed AI-RCTs (14 out of 17). We identified significant variation in the patterns of development, external validation and clinical evaluation approaches among different AI tools. A published development study was found only for 10 of the 18 AI tools. Median time from the publication of a development study to the respective AI-RCT was 1.4 years (IQR 0.2–2.2).ConclusionsWe found significant variation in the patterns of development and validation for AI tools before their evaluation in dedicated AI-RCTs. Published peer-reviewed protocols and completed AI-RCTs were also heterogeneous in design and reporting. Upcoming guidelines providing guidance for the development and clinical translation process aim to improve these aspects.
Effect of a cervical collar on head and neck acceleration profiles during emergency spinal immobilisation and extrication procedures in elite football (soccer) players: protocol for a randomised, controlled cross-over trial
Authors: Callaghan Michael J , Hughes Tom , Davin John , Hayes Russell , Hough Neil , Torpey Daniel , Perry David , Dawson Sam , Murray Eoghan , Jones Richard K 
Published: December 2021

When immobilisation after a cervical spine or head injury is required, the role of the rigid cervical collar is unclear and controversial. There is a need for further studies investigating the use of a rigid cervical collar when head and neck trauma occurs in sport. This study will compare present practice (immobilisation with a cervical collar) to the same procedure without a collar during a simulated spinal immobilisation and extraction scenario from the field of play to the side-line in football (soccer). It will use a prospective cohort within-subjects cross over randomised, controlled trial design. Healthy participants will assume the role of players with a head or neck injury. Clinical practitioners will perform the immobilisation and extrication procedure according to current clinical guidelines. Three dimensional linear and angular acceleration profiles of the head and torso will be measured and the time taken to complete the procedure. The interventions will be a ‘cervical collar’ or ‘no collar’ in random order. Data from the IMUs will be transferred wirelessly to a computer for analysis. Accordingly, within-subject differences between each condition (collar vs no collar) will be assessed with parametric or non-parametric inferential statistics. Statistical significance will be set at p<0.05.Trial registration number:ISRCTN16515969
Tumor-associated macrophages induced spheroid formation by CCL18-ZEB1-M-CSF feedback loop to promote transcoelomic metastasis of ovarian cancer
Authors: Long Lingli , Hu Yue , Long Tengfei , Lu Xiaofang , Tuo Ying , Li Yubing , Wang Min , Ke Zunfu 
Published: December 2021

BackgroundOvarian cancer (OvCa)-tumor-associated macrophages (TAMs) spheroids are abundantly present within ascites of high malignant patients. This study investigated the mutual interaction of OvCa cells and TAMs in the spheroids.MethodsThree-dimensional coculture system and transwell coculture system were created to mimic the OvCa and TAMs in spheroids and in disassociated state. Transwell-migration assay and scratch wound healing assay were used to measure the invasive and migratory capacity. Western blot, quantitative reverse transcription-PCR and immunostaining were used to measure the mesenchymal and epithelial markers. Flow cytometry was used to assess the polarization of TAMs. Also, the differential gene expression profile of OvCa cells and OvCa cells from spheroids were tested by RNA-sequence. Finally, the ovarian mice models were constructed by intraperitoneal injection of ID8 or OvCa-TAMs spheroids.ResultsOur results indicated that the formation of OvCa-TAMs spheroids was positive related to the malignancy of OvCa cells. M2-TAMs induced the epithelial-mesenchymal transition of OvCa cells by releasing chemokine (C-C motif) ligand 18 (CCL18) in the spheroids. While, CCL18 induced macrophage colony-stimulating factor (M-CSF) transcription in OvCa cells through zinc finger E-box-binding homeobox 1 (ZEB1). This study further indicated that M-CSF secreted by OvCa cells drived the polarization of M2-TAMs. Therefore, a CCL18-ZEB1-M-CSF interacting loop between OvCa cells and TAMs in the spheroids was identified. Moreover, with blocking the expression of ZEB1 in the OvCa cell, the formation of OvCa-TAMs spheroids was impeded. In the ovarian mice models, the formation of OvCa-TAMs spheroids in the ascites was promoted by overexpressing of ZEB1 in OvCa cells, which resulted in faster and earlier transcoelomic metastasis.ConclusionThese findings suggested that the formation of OvCa-TAMs spheroids resulted in aggressive phenotype of OvCa cells, as a specific feedback loop CCL18-ZEB1-M-CSF in it. Inhibition of ZEB1 reduced OvCa-TAMs spheroids in the ascites, impeding the transcoelomic metastasis and improving the outcome of ovarian patients.
LLDAS is an attainable treat-to-target goal in childhood-onset SLE
Authors: Wahadat Mohamed Javad , van den Berg Lotte , Timmermans Demi , van Rijswijk Kevin , van Dijk-Hummelman Annette , Bakx Susan , Verkaaik Marleen , Versnel Marjan A , Kamphuis Sylvia 
Published: December 2021

ObjectivesTo study whether clinical remission (CR) and Low Lupus Disease Activity State (LLDAS) are achievable goals in childhood-onset SLE.MethodsData on medication use and disease activity were prospectively collected. LLDAS was defined as Safety of Estrogen in Lupus Erythematosus National Assesment-SLE disease Activity Index (SELENA-SLEDAI) ≤4 with zero scores for renal, Central Nervous System (CNS), serositis, vasculitis and constitutional components, no increase in any SLEDAI component since the previous visit, PGA ≤1, and prednisone dose ≤7.5 mg/day. CR on treatment (Tx) was defined as a Physician Global Assessment <0.5, SELENA-SLEDAI=0, with prednisone ≤5 mg/day and maintenance treatment with immunosuppressives. CR off Tx was the same but without prednisone or other immunosuppressive usage.Results51 patients (700 visits) were included. Within 3 months after diagnosis, 94.1% of children were treated with hydroxychloroquine and 60.8% with prednisone. Prednisone dosage decreased from a median of 0.74 mg/kg/day at diagnosis to 0.44 mg/kg/day at 3 months and 0.16 mg/kg/day at 6 months after diagnosis. Use of mycophenolate mofetil increased from 25.5% to 56.9% within 6 months after diagnosis. All children achieved LLDAS (median 186 days) and 72.5% remained in LLDAS >50% of time. 52.9% children achieved CR on Tx, and only 21.6% children achieved CR off Tx.ConclusionsLLDAS is an attainable treat-to-target goal in contrast to CR on and off Tx. Even more, LLDAS can be reached with limited use of corticosteroids with early introduction of immunosuppressives.
Gradient flow and holography from a local Wilsonian cutoff
Authors: Ellwanger Ulrich 
Published: December 2021

AbstractWe consider the vacuum partition function of a 4d scalar QFT in a curved background as function of bare marginal and relevant couplings. A local UV cutoff $$\Lambda (x)$$

Λ
(
x
)

transforming under Weyl rescalings allows to construct Weyl invariant kinetic terms including Wilsonian cutoff functions. The local cutoff can be absorbed completely by a rescaling of the metric and the bare couplings. The vacuum partition function satisfies consistency conditions which follow from the Abelian nature of local redefinitions of the cutoff, and which differ from Weyl rescalings. These imply a gradient flow for beta functions describing the cutoff dependence of rescaled bare couplings. The consistency conditions allow to satisfy all but one Hamiltonian constraints required for a holographic description of the flow of bare couplings with the cutoff.
f(T) cosmology with nonzero curvature
Authors: Paliathanasis Andronikos 
Published: December 2021

We investigate exact and analytic solutions in [Formula: see text] gravity within the context of a Friedmann–Lemaître–Robertson–Walker background space with nonzero spatial curvature. For the power-law theory [Formula: see text] we find that the field equations admit an exact solution with a linear scalar factor for negative and positive spatial curvature. That Milne-like solution is asymptotic behavior for the scale factor near the initial singularity for the model [Formula: see text]. The analytic solution for that specific theory is presented in terms of Painlevé series for [Formula: see text]. Moreover, from the value of the resonances of the Painlevé series we conclude that the Milne-like solution is always unstable while for large values of the independent parameter, the field equations provide an expanding universe with a de Sitter expansion of a positive cosmological constant. Finally, the presence of the cosmological term [Formula: see text] in the studied [Formula: see text] model plays no role in the general behavior of the cosmological solution and the universe immerge in a de Sitter expansion either when the cosmological constant term [Formula: see text] in the [Formula: see text] model vanishes.
Scientific Method in Late-Antique Paganism: The (Rational) Empiricism of al-Filāḥa l-nabaṭiyya (The Nabatean Agriculture)
Authors: van Dalen Elaine 
Published: December 2021

Abstract
The reputation of the late-antique or early Islamic al-Filāḥa l-nabaṭiyya (The Nabatean Agriculture) as an esoteric forgery has recently begun to shift and its value as a source for the study of early-Islamic or late-antique Near Eastern paganism has been restored. This article contributes to a further reinterpretation of the work by elucidating its value for the history of late-antique and early Islamic science. It argues that the work distinguishes between the epistemological categories of the rational and the marvelous and critically approaches both based on a rational empiricism which it shares with contemporary disciplines such as medicine and astrology. The concepts of experience (taǧriba) and reason (qiyās) are central to al-Filāḥa l-nabaṭiyya’s epistemology, and the work relies on observation and experiments, combined with methods of deductive and analogical reasoning to obtain applied botanical and agricultural knowledge. Al-Filāḥa l-nabaṭiyya also contains competing views regarding prophecy and astrological knowledge which are illustrative of epistemological debates within Pagan late-antique scholarship.
“They Call Them Antiḳa”. Ottoman Travellers in Italy and the Idea of Antiquities in the Early Tanzimat Period
Authors: Berardi Luca 
Published: December 2021

Abstract
During the nineteenth century, the Ottoman fashion of looking at archaeological relics, present in large quantities in the territories of the Empire, deeply changed. This paper examines the reports of three Ottoman travellers who visited European countries in the early Tanzimat period. They introduced a new conceptualization of antiquities that stemmed from the direct observation of ancient monuments and museums in Italian cities. My argument is that the experience of travelling in Italy was one of the factors that contributed to shaping the new perception of antiquities that was emerging among the Ottoman elite.
An Emblematic Case in the Kingdom of Iraq: the Jewish Commander in Charge of the Baghdad Arsenal, Yamen Yousef, from Integration in Nation-Building to Exclusion
Authors: Nissan Ephraim 
Published: December 2021

Abstract
This article illustrates aspects of modern Iraqi history, being concerned with the life and career of Yamen Yousef (Yāmēn Yūsif, Hebrew name: Yāmīn Ṣiyyōn [ben] Yōsēf [ben] Nissīm), an officer in the army of the Kingdom of Iraq, who was the commander in charge of the Baghdad Royal Arsenal in the 1930s, and earlier on had been one of the three young officers made to proclaim Iraq’s first king during the coronation ceremony. That up to the late 1930s he was commander in charge of the Baghdad Royal Arsenal is in retrospect surprising (and that late in that decade a false charge was made against him by the far right is unsurprising), in consideration of rising animosity towards his ethno-religious identity. This came to a breaking point when he resigned, thus reverting from the acquired status of a career in the service of the state, to private bourgeoisie: this was happening in the first decade of full independence, when Jewish civil servants were being dismissed in their droves, after having been co-opted into the process of nation-building, owing to their educational qualifications giving them for a while an advantage. This study contributes novel data and facets that enable a fairly novel, and certainly more nuanced view of intercommunal relations in Iraq from late Ottoman times throughout the Hashemite monarchy (and beyond).
Certain Women Directors: US Independent Filmmakers in the World
Authors: White Patricia 
Published: December 2021

Abstract
This article analyzes the work of Chloé Zhao and its reception in order to explore the role of female auteurs in 21st century world cinema. By comparing Zhao to Kelly Reichardt, another US director acclaimed internationally for distinctive works of US regional realism, the essay argues that US independent women directors critique American cultural hegemony and the global dominance of Hollywood both through the subject matter and formal structures of their films and through their positioning within the discourse of world cinema auteurism. After analyzing the authorial personae of both directors as constructed in their films and press reception, the essay offers close readings of Reichardt’s Certain Women and Zhao’s The Rider, both set in the US West, with specific attention to the perspectives of central Native American characters. The readings demonstrate how the filmmakers use realism to locate a singular, gendered authorial perspective on the world.
The Double-Edged ECtHR Lăcătuş Judgment on Criminalisation of Begging: Da Mihi Elimo Sinam Propter Amorem Dei
Authors: Ganty Sarah 
Published: December 2021

Judgment: European Court of Human Rights, Lăcătuş v Switzerland 14065/15 (ECtHR, 19 January 2021), Judgment (Merits and Just Satisfaction)
Section of the Court: Chamber (Third Section)
Applicable Convention Rights: Article 8 echr (Right to respect for private and family life) – Violation
Primary Legal Issues: Did Switzerland violate Article 8 echr by imposing a fine and subsequent imprisonment for five days for non-payment on a poor and vulnerable Roma woman for unintrusive begging?
Link to Case: <http://hudoc.echr.coe.int/eng?i=001-207377>
Anthoceros subtilis and A. telaganus (Anthocerotaceae): two new records for America from the hornwort flora of Mexico
Authors: IBARRA-MORALES ARIADNA 
Published: December 2021

In a recent trip to southern Mexico, Anthoceros subtilis and A. telaganus were recorded for the first time in Mexico and the American continent. Several previous records of A. subtilis were from Asia and one from Africa, and A. telaganus is known only from Indonesia. The new range extension of these two species is reported and the species are described and illustrated.
Mexican populations of A. subtilis are characterized by small brown spores (26–42 μm), similar ornamentation on proximal and distal spore surfaces with papillate to tuberculate projections. Anthoceros telaganus is characterized by larger black spores (32–53 μm) with a smooth strip along the trilete mark on the proximal surface. Molecular genetic sequencing is needed to test whether Asian and American populations of these morphologically similar but geographically disjunct taxa are conspecific.