bluuebunny/crossref_metadata_2025_split huggingface dataset:
Successful endovascular treatment with a stent graft for chronic deep vein thrombosis with multiple arteriovenous fistulas: a case report
Authors: Kato Tamon , Fuke Megumi , Nagai Fumio , Nomi Hidetomo , Kanzaki Yusuke , Yui Hisanori , Maruyama Shusaku , Nagae Ayumu , Sakai Takahiro , Saigusa Tatsuya , Ebisawa Soichiro , Okada Ayako , Motoki Hirohiko , Kuwahara Koichiro 
Published: July 2022

Abstract
Background
Deep vein thrombosis with arteriovenous fistulas is rare, with few therapeutic options available for chronic-phase deep vein thrombosis. Moreover, the effectiveness of endovascular treatment for chronic-phase deep vein thrombosis with arteriovenous fistulas has not been established. We describe herein a case of successful endovascular treatment for chronic deep vein thrombosis with multiple arteriovenous fistulas.

Case presentation
We describe the case of a 72-year-old Asian woman who had begun experiencing left leg swelling and intermittent claudication 2 years prior. Enhanced computed tomography revealed left common iliac vein occlusion with vein-to-vein collateral formation and several arteriovenous fistulas. Angiography and ultrasound showed the arteriovenous fistulas to run from the common and internal iliac arteries to the external iliac and superficial femoral veins. We opted against surgical repair for the arteriovenous fistulas due to their complex nature and complicated morphology. Since her condition was progressive, endovascular treatment with a stent graft was performed for the deep vein thrombosis, after which her symptoms gradually improved. Four months following the procedure, enhanced computed tomography confirmed remarkable reduction of the vein-to-vein collaterals and arteriovenous fistulas.

Conclusions
In the present case, enhanced computed tomography with a stent graft was effective in improving symptoms. This strategy may therefore be a treatment option for intractable chronic deep vein thrombosis with arteriovenous fistulas.
Medications for preventing hypertensive disorders in high-risk pregnant women: a systematic review and network meta-analysis
Authors: Liabsuetrakul Tippawan , Yamamoto Yoshiko , Kongkamol Chanon , Ota Erika , Mori Rintaro , Noma Hisashi 
Published: July 2022

AbstractObjectivesTo determine the relative effectiveness of medications for preventing hypertensive disorders in high-risk pregnant women and to provide a ranking of medications using network meta-analysis.MethodsAll randomized controlled trials comparing the most commonly used medications to prevent hypertensive disorders in high-risk pregnant women that are nulliparity and pregnant women having family history of preeclampsia, history of pregnancy-induced hypertension in previous pregnancy, obstetric risks, or underlying medical diseases. We received the search results from the Cochrane Pregnancy and Childbirth’s Specialised Register of Controlled Trials, searched on 31st July 2020. At least two review authors independently selected the included studies and extracted the data and the methodological quality. The comparative risk ratios (RR) and 95% confidence intervals (CI) were analyzed using pairwise and network meta-analyses, and treatment rankings were estimated by the surface under the cumulative ranking curve for preventing preeclampsia (PE), gestational hypertension (GHT), and superimposed preeclampsia (SPE). Safety of the medications is also important for decision-making along with effectiveness which will be reported in a separate review.ResultsThis network meta-analysis included 83 randomized studies, involving 93,864 women across global regions. Three medications, either alone or in combination, probably prevented PE in high-risk pregnant women when compared with a placebo or no treatment from network analysis: antiplatelet agents with calcium (RR0.19, 95%CI0.04 to 0.86; 1 study; low-quality evidence), calcium (RR0.61, 95%CI0.47 to 0.80; 13 studies; moderate-quality evidence), antiplatelet agents (RR0.69, 95%CI0.57 to 0.82; 31 studies; moderate-quality evidence), and antioxidants (RR0.77, 95%CI0.63 to 0.93; 25 studies; moderate-quality evidence). Calcium probably prevented PE (RR0.63, 95%CI0.46 to 0.86; 11 studies; moderate-quality evidence) and GHT (RR0.89, 95%CI0.84 to 0.95; 8 studies; high-quality evidence) in nulliparous/primigravida women. Few included studies for the outcome of superimposed preeclampsia were found.ConclusionAntiplatelet agents, calcium, and their combinations were most effective medications for preventing hypertensive disorders in high-risk pregnant women when compared with a placebo or no treatment. Any high-risk characteristics for women are important in deciding the best medications. The qualities of evidence were mostly rated to be moderate.Systematic review registrationPROSPEROCRD42018096276
Maps are plans: re-evaluating territorial hermeneutics through Manuel de Solà-Morales’ project of description
Authors: Salgueiro Barrio Roi 
Published: July 2022

AbstractDuring the late 1970s, Catalan architect Manuel de Solà-Morales focuses his research on understanding territory as an architectural construct. Influenced by post-war French urban geography and, especially, by the Italian debates about thecittà-territorioand Henri Lefebvre’s notion of total urbanization, Solà-Morales seeks to define methods of territorial analysis and description with the purpose of understanding how architecture can contribute to articulate an urbanized territory. The crucial piece of this intellectual quest is the research ‘La forma d’un país’ (‘The Shape of a Country’), an atlas in which the production of maps is simultaneously understood as an act of territorial description and territorial design. In Solà-Morales’ terminology: maps are already ‘plans’; their conception needs to move from the ‘literal’ to the ‘literary’. The goal of this article is to interrogate this cartographic project, by asking what its value is both within Solà-Morales broader theorization of territorial production, and for a contemporary understanding of the relations between architecture and territory.
Weighted Zernike defocus coefficient of treatment zone is a meaningful indicator for myopia control efficacy of Ortho-K lenses
Authors: Fan Yuzhuo , Li Yan , Wang Kai , Qu Jia , Zhao Mingwei 
Published: July 2022

Abstract
Background
The goal of this study was to reproduce a three-dimensional representation of corneal defocus characteristics after orthokeratology (Ortho-K) treatment via an indicator defined as the weighted Zernike defocus coefficient of the treatment zone (Cweighted defocus). This could be used to predict the effectiveness of Ortho-K treatment quantitatively in a timely manner after the one-month visit.

Methods
Seventy myopic children with axial length (AL) elongation after Ortho-K treatment (group A) and 63 myopic children with AL shortening after Ortho-K treatment (group B) were included in this one-year retrospective study. The proposed indicator was calculated by a customized MATLAB program. Multivariate binomial logistic regression and multivariate linear regression analyses were used to explore the association between AL change and the Cweighted defocus, age, sex, and other ocular biometric parameters.

Results
The 12-month AL change, age, pupil diameter, and vertical decentration of the Ortho-K lens were significantly different between the two groups. Multivariate logistic regression analysis showed that a larger Cweighted defocus (≥ 0.35 D/mm2) (OR: 0.224; 95% CI: 0.078–0.646; P = 0.006) was correlated with the emergence of AL shortening after orthokeratology treatment. A multivariate linear regression model showed that a greater Cweighted defocus was associated with slower 12-month AL elongation (β =  − 0.51, P = 0.001).

Conclusions
The Cweighted defocus is an effective predictive indicator of myopia control, and a larger Cweighted defocus may lead to slower elongation of AL. This meaningful indicator may help in the evaluation and adjustment of Ortho-K lens parameters in a timely manner and minimize the cost of clinical trial and error.
Ustekinumab during pregnancy and lactation: drug levels in maternal serum, cord blood, breast milk, and infant serum
Authors: Saito Jumpei , Kaneko Kayoko , Kawasaki Hiroyo , Hayakawa Takeshi , Yakuwa Naho , Suzuki Tomo , Sago Haruhiko , Yamatani Akimasa , Murashima Atsuko 
Published: July 2022

Abstract
Background
Patients with ulcerative colitis (UC) may be concerned about medication safety during preconception, pregnancy, and lactation, and they should be closely followed up to ensure that UC activity is controlled during the perinatal period. Reported information on the safety of ustekinumab during pregnancy and lactation is limited. In this case report, we examined the safety of ustekinumab in a fetus and breastfed infant with reference to drug concentrations in maternal serum, cord blood, breast milk, and infant serum.

Case presentation
A 36-year-old female who developed hematochezia and was diagnosed with ulcerative colitis at age 24 was pregnant with her first child. During pregnancy she was treated with subcutaneous bimonthly ustekinumab, at a dose of 90 mg, until 29 weeks of gestation. Her ulcerative colitis symptoms remained in remission. At 38 weeks of gestation she underwent cesarean section and delivered a healthy female infant weighing 3043 g and with no congenital malformations. The infant received routine vaccinations with no adverse events. Ustekinumab treatment was resumed at 7 weeks postpartum.
The ustekinumab concentration in maternal serum at 12 days after injection (30.7 weeks of gestation) was 7968.5 ng/mL, and it decreased to 106.1 ng/mL at 114 days after the last dose. In cord blood, the ustekinumab concentration was 1131.2 ng/mL at 65 days after the last dose; this was 2.5 times higher than that in the maternal serum, which was consistent with a previous report. Ustekinumab was detected in infant serum collected at 71 days after the last maternal dose (299.0 ng/mL), with rapid elimination from the infant’s body. In breast milk, the maximum ustekinumab concentrations were 13.6 ng/mL at 9 days after the last maternal dose, respectively. The ratio of the calculated areas under the time-concentration curves of ustekinumab in breast milk and maternal serum was 0.0008 (257.1/327632.7), which was comparable with a previous human study.

Conclusion
The placental transfer and breast milk secretion of ustekinumab in our case were comparable with previous reports. Use of ustekinumab during pregnancy and lactation was feasible in this case. Further research is needed to clarify the safety of ustekinumab during pregnancy and lactation.
Single transcription factor efficiently leads human induced pluripotent stem cells to functional microglia
Authors: Sonn Iki , Honda-Ozaki Fumiko , Yoshimatsu Sho , Morimoto Satoru , Watanabe Hirotaka , Okano Hideyuki 
Published: July 2022

Abstract
Background
Microglia are innate immune cells that are the only residential macrophages in the central nervous system. They play vital physiological roles in the adult brain and during development. Microglia are particularly in the spotlight because many genetic risk factors recently identified for neurodegenerative diseases are largely expressed in microglia. Rare polymorphisms in these risk alleles lead to abnormal activity of microglia under traumatic or disease conditions.

Methods
In the present study, to investigate the multifaceted functions of human microglia, we established a novel robust protocol to generate microglia from human induced pluripotent stem cells (hiPSCs) using a combination of cytokines and small chemicals essential for microglia ontogeny. Moreover, we highly enhanced the microglial differentiation efficiency by forcing the expression of PU.1, a crucial transcription factor for microglial development, during posterior mesoderm differentiation.

Results
By our novel method, we demonstrated the generation of a greater number of hiPSC-derived microglia (hiMGLs, approximately 120-folds) than the prior methods (at most 40-folds). Over 90% of the hiMGLs expressed microglia-specific markers, such as CX3CR1 and IBA-1. Whole-transcriptome analysis revealed that these hiMGLs are similar to human primary microglia but differ from monocytes/macrophages. Furthermore, the specific physiological functions of microglia were confirmed through indices of lipopolysaccharide responsiveness, phagocytotic ability, and inflammasome formation. By co-culturing these hiMGLs with mouse primary neurons, we demonstrated that hiMGLs can regulate the activity and maturation of neurons.

Conclusions
In this study, our new simple, rapid, and highly efficient method for generating microglia from hiPSCs will prove useful for future investigations on microglia in both physiological and disease conditions, as well as for drug discovery.
Electrocardiographic features in SCN5A mutation-positive patients with Brugada and early repolarization syndromes: a systematic review and meta-analysis
Authors: Radford Danny , Chou Oscar Hou In , Bazoukis George , Letsas Konstantinos , Liu Tong , Tse Gary , Lee Sharen 
Published: July 2022

Abstract
Background
Early repolarization syndrome (ERS) and Brugada syndrome (BrS) are both J-wave syndromes. Both can involve mutations in the SCN5A gene but may exhibit distinct electrocardiographic (ECG) differences. The aim of this systematic review and meta-analysis is to investigate possible differences in ECG markers between SCN5A-positive patients with ERS and BrS.

Methods
PubMed and Embase were searched from their inception to 20 October 2021 for human studies containing the search terms “SCN5A” and “variant” and “early repolarization” or “Brugada”, with no language restrictions. Continuous variables were expressed as mean±standard deviation. PR interval, QRS duration, QTc and heart rate from the included studies were pooled to calculate a mean for each variable amongst BrS and ERS patients. A two-tailed Student’s t test was then performed to for comparisons.

Results
A total of 328 studies were identified. After full-text screening, 12 studies met our inclusion criteria and were included in this present study. One hundred and four ERS patients (mean age 30.86±14.45) and 2000 BrS patients (mean age 36.17±11.39) were studied. Our meta-analysis found that ERS patients had shorter QRS duration (90.40±9.97 vs. 114.79±20.10, P = 0.0001) and shorter corrected QT intervals (QTc) with borderline significance (393.63±40.04 vs. 416.82±37.43, P = 0.052). By contrast, no significant differences in baseline heart rate (65.15±18.78 vs. 76.06±18.78, P = 0.068) or PR intervals (197.40±34.69 vs. 191.88±35.08, P = 0.621) were observed between ERS and BrS patients.

Conclusion
BrS patients with positive SCN5A mutations exhibited prolonged QRS, indicating conduction abnormalities, whereas ERS patients with positive SCN5A mutations showed normal QRS. By contrast, whilst QTc intervals were longer in BrS than in ERS SCN5A positive patients, they were within normal limits. Further studies are needed to examine the implications of these findings for arrhythmic risk stratification.
Clove Oil Endorsed Transdermal Flux of Dronedarone Hydrochloride Loaded Bilosomal Nanogel: Factorial Design, In vitro Evaluation and Ex vivo Permeation
Authors: Teaima Mahmoud H. , Alsofany Jihad Mahmoud , El-Nabarawi Mohamed A. 
Published: July 2022

AbstractThe goal of this study was to develop a bilosomal gel formulation to enhance transdermal permeability of dronedarone hyrdrochloride (DRN) which suffers from poor oral absorption and limited bioavailability. To overcome this obstacle, bilosomes were successfully prepared using 23full-factorial design. Span®40, cholesterol, sodium deoxycholate (bile salt), clove oil (permeability enhancer), and either Tween® 60 or Tween® 80 (edge activator) were used in bilosome preparation by ethanol injection method. In this design, independent variables were X1, edge activator type; X2, edge activator amount (mg); and X3, permeability enhancer concentration (% w/v). Optimal formula (B2) of the highest desirability of (0.776) demonstrated minimum vesicle size (VS) of 312.4 ± 24.42 nm, maximum absolute value of zeta potential (ZP) − 36.17 ± 2.57 mV, maximum entrapment efficiency (EE %) of 80.95 ± 3.01%, maximum deformability Index (DI) of 8.24 ± 1.26 g and maximum drug flux after 12 h (J12) of 21.23 ± 1.54 µg/cm2h upon ex vivo permeation study. After 12 h, 70.29 ± 6.46% of DRN was released from B2. TEM identification of B2 showed spherical shaped nanosized vesicles which were physically stable for 3 months at different temperatures. B2 was incorporated into carboxymethylcellulose gel base for easiness of dermal application. B2 gel demonstrated good physical properties, non-Newtonian psuedoplastic flow, and enhanced release (57.0 ± 8.68% of DRN compared to only 13.3 ± 1.2% released from drug suspension after 12 h) and enhanced skin permeation.Graphical abstract
GLP-1 Receptor Blockade Reduces Stimulated Insulin Secretion in Fasted Subjects With Low Circulating GLP-1
Authors: Gray Sarah M , Hoselton Andrew L , Krishna Radha , Slentz Cris A , D’Alessio David A 
Published: July 2022

Abstract

Context
Glucagon-like peptide 1 (GLP-1), an insulinotropic peptide released into the circulation from intestinal enteroendocrine cells, is considered a hormonal mediator of insulin secretion. However, the physiological actions of circulating GLP-1 have been questioned because of the short half-life of the active peptide. Moreover, there is mounting evidence for localized, intra-islet mediation of GLP-1 receptor (GLP-1r) signaling including a role for islet dipeptidyl-peptidase 4 (DPP4).

Objective
To determine whether GLP-1r signaling contributes to insulin secretion in the absence of enteral stimulation and increased plasma levels, and whether this is affected by DPP4.

Methods
Single-site study conducted at an academic medical center of 20 nondiabetic subjects and 13 subjects with type 2 diabetes. This was a crossover study in which subjects received either a DPP4 inhibitor (DPP4i; sitagliptin) or placebo on 2 separate days. On each day they received a bolus of intravenous (IV) arginine during sequential 60-minute infusions of the GLP-1r blocker exendin[9-39] (Ex-9) and saline. The main outcome measures were arginine-stimulated secretion of C-Peptide (C-PArg) and insulin (InsArg).

Results
Plasma GLP-1 remained at fasting levels throughout the experiments and IV arginine stimulated both α- and β-cell secretion in all subjects. Ex-9 infusion reduced C-PArg in both the diabetic and nondiabetic groups by ~14% (P &lt; .03 for both groups). Sitagliptin lowered baseline glycemia but did not affect the primary measures of insulin secretion. However, a significant interaction between sitagliptin and Ex-9 suggested more GLP-1r activation with DPP4i treatment in subjects with diabetes.

Conclusion
GLP-1r activation contributes to β-cell secretion in diabetic and nondiabetic people during α-cell activation, but in the absence of increased circulating GLP-1. These results are compatible with regulation of β-cells by paracrine signals from α-cells. This process may be affected by DPP4 inhibition.
Distinctions in PCOS Induced by Letrozole Vs Dehydroepiandrosterone With High-fat Diet in Mouse Model
Authors: Poojary Pooja Suresh , Nayak Guruprasad , Panchanan Gangotri , Rao Arpitha , Kundapur Sanjna Das , Kalthur Sneha Guruprasad , Mutalik Srinivas , Adiga Satish Kumar , Zhao Yulian , Bakkum-Gamez Jamie , Chang Alice Y , DeStephano Christopher , Sherman Mark , Kannan Nagarajan , Kalthur Guruprasad 
Published: July 2022

Abstract
Polycystic ovarian syndrome (PCOS) is a complex health condition associated with metabolic disturbances and infertility. Recent data suggest that the prevalence of PCOS is increasing among women globally, although the etiology of these trends is undefined. Consequently, preclinical models that better reflect the biology of PCOS are urgently needed to facilitate research that can lead to the discovery of prevention strategies or improved management. The existing animal models have several limitations as they do not reflect all the PCOS features metabolically and/or phenotypically. Therefore, there is no clear consensus on the use of appropriate animal model and selection of the most appropriate PCOS-inducing agent. To that end, we have established a Swiss albino mouse model of PCOS based on 3 weeks of daily treatment with letrozole (50 μg/day; intraperitoneal) and dehydroepiandrosterone (DHEA, 6 mg/100 g body weight; subcutaneous) in 5-week-old female mice fed on normal or high-fat diet (HFD). Mice were regularly assessed for body weight, blood glucose, and estrous cycle. Three weeks after drug administration, mice were sacrificed and assessed for blood-based metabolic parameters as well as ovarian function. Our results indicate that DHEA combined with HFD produces changes mimicking those of clinical PCOS, including elevated serum testosterone and luteinizing hormone, dyslipidemia, poor ovarian microenvironment, and development of multiple ovarian cysts, recapitulating cardinal features of PCOS. In comparison, normal diet and/or letrozole produced fewer features of PCOS. The data from the experimental models presented here can improve our understanding of PCOS, a growing concern in women’s health.
Nuclear localization of histamine receptor 2 in primary human lymphatic endothelial cells
Authors: Pal Sarit , Gashev Anatoliy , Roy Debarshi 
Published: July 2022

ABSTRACT
Histamine exerts its physiological functions through its four receptor subtypes. In this work, we report the subcellular localization of histamine receptor 2 (H2R), a G protein-coupled receptor (GPCR), which is expressed in a wide variety of cell and tissue types. A growing number of GPCRs have been shown to be localized in the nucleus and contribute toward transcriptional regulation. In this study, for the first time, we demonstrate the nuclear localization of H2R in lymphatic endothelial cells. In the presence of its ligand, we show significant upregulation of H2R nuclear translocation kinetics. Using fluorescently tagged histamine, we explored H2R-histamine binding interaction, which exhibits a critical role in this translocation event. Altogether, our results highlight the previously unrecognized nuclear localization pattern of H2R. At the same time, H2R as a GPCR imparts many unresolved questions, such as the functional relevance of this localization, and whether H2R can contribute directly to transcriptional regulation and can affect lymphatic specific gene expression. H2R blockers are commonly used medications that recently have shown significant side effects. Therefore, it is imperative to understand the precise molecular mechanism of H2R biology. In this aspect, our present data shed new light on the unexplored H2R signaling mechanisms.
This article has an associated First Person interview with the first author of the paper.
Symbiosis of disciplines: how can developmental biologists join conservationists in sustaining and restoring earth's biodiversity?
Authors: Gilbert Scott F. , Hadfield Michael G. 
Published: July 2022

ABSTRACTWhat can developmental biology contribute toward mitigating the consequences of anthropogenic assaults on the environment and climate change? In this Spotlight article, we advocate a developmental biology that takes seriously Lynn Margulis' claim that ‘the environment is part of the body’. We believe this to be a pre-condition for developmental biology playing important roles in conservation and environmental restoration. We need to forge a developmental biology of the holobiont – the multi-genomic physiologically integrated organism that is also a functional biome. To this end, we highlight how developmental biology needs to explore more deeply the interactions between developing organisms, and their chemical, physical and biotic environments.