bluuebunny/crossref_metadata_2025_split huggingface dataset:
Midgestation Leptin Infusion Induces Characteristics of Clinical Preeclampsia in Mice, Which Is Ablated by Endothelial Mineralocorticoid Receptor Deletion
Authors: Faulkner Jessica L. , Wright Derrian , Antonova Galina , Jaffe Iris Z. , Kennard Simone , Belin de Chantemèle Eric J. 
Published: June 2022

Background:
Patients with preeclampsia demonstrate increases in placental leptin production in midgestation, and an associated increase in late gestation plasma leptin levels. The consequences of mid-late gestation increases in leptin production in pregnancy is unknown. Our previous work indicates that leptin infusion induces endothelial dysfunction in nonpregnant female mice via leptin-mediated aldosterone production and endothelial mineralocorticoid receptor (ECMR) activation, which is ablated by ECMR deletion. Therefore, we hypothesized that leptin infusion in mid-gestation of pregnancy induces endothelial dysfunction and hypertension, hallmarks of clinical preeclampsia, which are prevented by ECMR deletion.

Methods:
Leptin was infused via miniosmotic pump (0.9 mg/kg per day) into timed-pregnant ECMR-intact (WT) and littermate-mice with ECMR deletion (KO) on gestation day (GD)11-18.

Results:

Leptin infusion decreased fetal weight and placental efficiency in WT mice compared with WT+vehicle. Radiotelemetry recording demonstrated that blood pressure increased in leptin-infused WT mice during infusion. Leptin infusion reduced endothelial-dependent relaxation responses to acetylcholine (ACh) in both resistance (second-order mesenteric) and conduit (aorta) vessels in WT pregnant mice. Leptin infusion increased placental ET-1 (endothelin-1) production evidenced by increased PPET-1 (preproendothelin-1) and ECE-1 (endothelin-converting enzyme-1) expressions in WT mice. Adrenal aldosterone synthase (
CYP11B2
) and angiotensin II type 1 receptor b (
AT1Rb
) expression increased with leptin infusion in pregnant WT mice. KO pregnant mice demonstrated protection from leptin-induced reductions in pup weight, placental efficiency, increased BP, and endothelial dysfunction.

Conclusions:
Collectively, these data indicate that leptin infusion in midgestation induces endothelial dysfunction, hypertension, and fetal growth restriction in pregnant mice, which is ablated by ECMR deletion.
Western and Central Tropical Pacific Rainfall Response to Climate Change: Sensitivity to Projected Sea Surface Temperature Patterns
Authors: Dutheil C. , Lengaigne M. , Vialard J. , Jullien S. , Menkes C. 
Published: June 2022

Abstract
Rainfall projections from the Coupled Model Intercomparison Project (CMIP) models are strongly tied to projected sea surface temperature (SST) spatial patterns through the “warmer-gets-wetter” mechanism. While these models consistently project an enhanced equatorial warming, they, however, indicate much more uncertain changes in zonal SST gradients. That translates into large uncertainties on rainfall projections. Here, we force an atmospheric model with synthetic SSTs whose zonal SST gradient changes span the range of CMIP5 uncertainties in the presence and in the absence of the robust equatorially enhanced warming. Our results confirm that projected rainfall changes are dominated by the effect of circulation changes, which are tied to SST through the “warmer-gets-wetter” mechanism. We show that SPCZ rainfall changes are entirely driven by the uncertain zonal SST gradient changes. The western equatorial Pacific rainfall increase is largely controlled by the robust enhanced equatorial warming for modest zonal SST gradient changes. However, for larger values, the effect of the zonal SST gradient change on rainfall projections becomes dominant due to nonlinear interactions with the enhanced equatorial warming. Overall, our study demonstrates that uncertainties in the zonal SST gradient changes strongly contribute to uncertainties in rainfall projections over both the South Pacific convergence zone and western equatorial Pacific. It is thus critical to reduce these uncertainties to produce more robust precipitation estimates.
Land–Atmosphere Interactions during GRAINEX: Planetary Boundary Layer Evolution in the Presence of Irrigation
Authors: Rappin E. D. , Mahmood R. , Nair U. S. , Pielke Sr. R. A. 
Published: June 2022

Abstract
This paper analyzed observations from the Great Plains Irrigation Experiment (GRAINEX) to better understand land–atmosphere (L–A) interactions and PBL evolution. This study is focused on a day when the largest forcing on the boundary layer originated from the land surface/land use. To examine these impacts, we also applied the Weather Research and Forecasting (WRF) Model. Results from the observations show that compared to nonirrigated areas, air temperature, wind speed, and PBL height (PBLH) were lower while dewpoint temperature and latent heat flux were higher over irrigated areas. Findings suggest that entrainment layer drying and differences in energy partitioning over irrigated and nonirrigated areas played an important role in PBL evolution. In the final hours of the day, the PBL collapsed faster over nonirrigated areas compared to irrigated. The WRF Model simulations agree with these observations. They also show that the extent of irrigation [expressed as irrigation fraction (IF)] in an area impacts L–A response. Under ∼60% IF, the latent heat flux and mixing ratio reach their highest value while temperature and PBLH are at their lowest, and sensible heat flux is near its lowest value. Results are reversed for ∼2% IF. It is concluded that irrigation notably impacts L–A interactions and PBL evolution.
An Accurate Wind Retrieval Method Based on Observing Hydrogen Balloons with Multi-Theodolite Measurements
Authors: Zhou Jie , Gao Hang , Wang Xuesong , Li Jianbing 
Published: June 2022

Abstract
The hydrogen balloon is widely used for wind sensing by tracking it with optical theodolites. The traditional theodolite observation (single- and double-theodolite) methods assume that the balloon is a perfect tracer of the background wind and it rises with a constant speed during the whole observation period, but these assumptions may not hold well in complex wind circumstances. In this paper, an accurate wind field retrieval method based on multi-theodolite measurement is proposed. The extended Kalman filter algorithm is used to filter the angle data observed by the theodolites in order to accurately estimate the trajectory of the balloon, and the motion equation is used to correct the velocity difference between the background wind and the balloon. As a result, not only the horizontal velocity but also the vertical velocity can be accurately retrieved by this method. Numerical simulation and field experiments show that the multi-theodolite observation method excels the traditional single-theodolite method, and the velocity errors can be reduced by even more than 40% in comparison with the single-theodolite method for complex wind cases.

Significanace Statement
In the meteorological community, hydrogen balloon tracking is a widely used wind retrieval method, but the accuracy is limited, especially under complex wind conditions. In this paper, a new method based on tracking the hydrogen balloon with multi-theodolite is proposed, which uses the extended Kalman filter and the motion equation to get an accurate estimation of the balloon’s velocity and fix the inertia effect of balloon, respectively. Simulation and field experiment show that the new method can reduce the velocity error by more than 40% compared with the traditional method.
Extracellular protein kinase A and G are potential biomarkers of some inflammation-associated disorders
Authors: Wu Yan , Ye Jun , Zhao Chunhui , Pang Ji , Li Yueying , Lin Xinyue 
Published: June 2022

Introduction Protein kinase A (PKA) and protein kinase G (PKG) are the main downstream effectors of second messengers cAMP and cGMP, which play important roles in physiological and pathological processes. Recently, there are two findings: one is PKA catalytic subunits α (PKACα) and PKG II can be secreted, the other is that the two secretory protein kinases are associated with the progression of tumors. Previous data also demonstrate that the two kinases, as signal cascades, involved in inflammation-associated disorders. However, it remains unclear whether the secreted PKACα or PKG II could serve as diagnostic biomarkers for inflammation-associated disorders. Methods The serum from suffered coronary disease, diabetes, rheumatoid arthritis, and schizophrenia were collected. The serum PKACα and PKG II were detected by ELISA. All the patients were consent informed. Results Our results showed that the serum PKACα and PKG II had obvious changes in coronary disease, rheumatoid arthritis, schizophrenia patients. However, the trends was opposite, especially in rheumatoid arthritis. Conclusions Serum PKACα and PKG II could serve as potentially diagnostic biomarkers for some inflammation-associated disorders, such as coronary disease, rheumatoid arthritis, and schizophrenia.
Gene network analysis reveals candidate genes related with the hair follicle development in sheep
Authors: He Junmin , Zhao Bingru , Huang Xixia , Fu Xuefeng , Liu Guifen , Tian Yuezhen , Wu Cuiling , Mao Jingyi , Liu Jing , Gun Shuangbao , Tian Kechuan 
Published: June 2022

Abstract
Background
Merino sheep are the most famous fine wool sheep in the world. They have high wool production and excellent wool quality and have attracted worldwide attention. The fleece of the Merino sheep is composed predominantly of wool fibers grown from secondary wool follicles. Therefore, it is necessary to study the development of hair follicles to understand the mechanism of wool production. The hair follicle is a complex biological system involved in a dynamic process governed by gene regulation. The hair follicle development process is very complex and poorly understood. The purpose of our research is to identify candidate genes related to hair follicle development, provide a theoretical molecular breeding basis for the cultivation of fine wool sheep, and provide a reference for the problems of hair loss and alopecia areata that affect human beings.

Results
We analyzed mRNAs data in skin tissues of 18 Merino sheep at four embryonic days (E65, E85, E105 and E135) and two postnatal days (P7 and P30). G1 to G6 represent hair follicles developmental at six stages (i.e. E65 to P30). We identified 7879 differentially expressed genes (DEGs) and 12623 novel DEGs, revealed different expression patterns of these DEGs at six stages of hair follicle development, and demonstrated their complex interactions. DEGs with stage-specific expression were significantly enriched in epidermal differentiation and development, hair follicle development and hair follicle morphogenesis and were enriched in many pathways related to hair follicle development. The key genes (LAMA5, WNT10A, KRT25, SOSTDC1, ZDHHC21, FZD1, BMP7, LRP4, TGFβ2, TMEM79, SOX10, ITGB4, KRT14, ITGA6, and GLI2) affecting hair follicle morphogenesis were identified by network analysis.

Conclusion
This study provides a new reference for the molecular basis of hair follicle development and lays a foundation for further improving sheep hair follicle breeding. Candidate genes related to hair follicular development were found, which provided a theoretical basis for molecular breeding for the culture of fine wool sheep. These results are a valuable resource for biological investigations of fleece evolution in animals.
Outcomes from a mechanistic biomarker multi-arm and randomised study of liposomal MTP-PE (Mifamurtide) in metastatic and/or recurrent osteosarcoma (EuroSarc-Memos trial)
Authors: Barnes David J. , Dutton Peter , Bruland Øyvind , Gelderblom Hans , Faleti Ade , Bühnemann Claudia , van Maldegem Annemiek , Johnson Hannah , Poulton Lisa , Love Sharon , Tiemeier Gesa , van Beelen Els , Herbschleb Karin , Haddon Caroline , Billingham Lucinda , Bradley Kevin , Ferrari Stefano , Palmerini Emanuela , Picci Piero , Dirksen Uta , Strauss Sandra J. , Hogendoorn Pancras C. W. , Buddingh Emmeline , Blay Jean-Yves , Cleton-Jansen Anne Marie , Hassan Andrew Bassim 
Published: June 2022

AbstractThe phase III clinical study of adjuvant liposomal muramyl tripeptide (MTP-PE) in resected high-grade osteosarcoma (OS) documented positive results that have been translated into regulatory approval, supporting initial promise for innate immune therapies in OS. There remains, however, no new approved treatment such as MTP-PE for either metastatic or recurrent OS. Whilst the addition of different agents, including liposomal MTP-PE, to surgery for metastatic or recurrent high-grade osteosarcoma has tried to improve response rates, a mechanistic hiatus exists in terms of a detailed understanding the therapeutic strategies required in advanced disease. Here we report a Bayesian designed multi-arm, multi-centre, open-label phase II study with randomisation in patients with metastatic and/or recurrent OS, designed to investigate how patients with OS might respond to liposomal MTP-PE, either given alone or in combination with ifosfamide. Despite the trial closing because of poor recruitment within the allocated funding period, with no objective responses in eight patients, we report the design and feasibility outcomes for patients registered into the trial. We demonstrate the feasibility of the Bayesian design, European collaboration, tissue collection with genomic analysis and serum cytokine characterisation. Further mechanistic investigation of liposomal MTP-PE alone and in combination with other agents remains warranted in metastatic OS.
The impact of social determinants of health on early childhood development: a qualitative context analysis in Iran
Authors: Atashbahar Omolbanin , Sari Ali Akbari , Takian Amirhossein , Olyaeemanesh Alireza , Mohamadi Efat , Barakati Sayyed Hamed 
Published: June 2022

Abstract
Background
Social determinants have a significant impact on children’s development and their abilities and capacities, especially in early childhood. They can bring about inequity in living conditions of children and, as a result, lead to differences in various dimensions of development including the social, psychological, cognitive and emotional aspects. We aimed to identify and analyze the social determinants of Early Childhood Development (ECD) in Iran and provide policy implications to improve this social context.

Methods
In a qualitative study, data were collected through semi-structured interviews with 40 experts from October 2017 to June 2018. Based on Leichter’s (1979) framework and using the deductive approach, two independent researchers conducted the data analysis. We used MAXQDA.11 software for data management.

Results
We identified challenges related to ECD context in the form of 8 themes and 22 subthemes in 4 analytical categories relevant to the social determinants of ECD including: Structural factors (economic factors: 6 subthemes, political factors: 2 subthemes), Socio-cultural factors (the socio-cultural setting of society: 6 subthemes, the socio-cultural setting of family: 4 subthemes), Environmental or International factors (the role of international organizations: 1 subtheme, political sanctions: 1 subtheme), and Situational factors (genetic factors: 1 subtheme, the phenomenon of air pollution: 1 subtheme). We could identify 24 policy recommendations to improve the existing ECD context from the interviews and literature.

Conclusion
With regard to the challenges related to the social determinants of ECD, such as increasing social harms, decreasing social capital, lack of public awareness, increasing socio-economic inequities, economic instability, which can lead to the abuse and neglect of children or unfair differences in their growth and development, the following policy-making options are proposed: focusing on equity from early years in policies and programs, creating integration between policies and programs from different sectors, prioritizing children in the welfare umbrella, empowering families, raising community awareness, and expanding services and support for families, specially the deprived families subject to special subsidies.
Characterization of a prognostic model for lung squamous cell carcinoma based on eight stemness index-related genes
Authors: Jiang Wenfa , Xie Ning , Xu Chenyang 
Published: June 2022

Abstract
Background
Cancer stem cells (CSCs) are implicated in cancer progression, chemoresistance, and poor prognosis; thus, they may be promising therapeutic targets. In this study, we aimed to investigate the prognostic application of differentially expressed CSC-related genes in lung squamous cell carcinoma (LUSC).

Methods
The mRNA stemness index (mRNAsi)-related differentially expressed genes (DEGs) in tumors were identified and further categorized by LASSO Cox regression analysis and 1,000-fold cross-validation, followed by the construction of a prognostic score model for risk stratification. The fractions of tumor-infiltrating immune cells and immune checkpoint genes were analyzed in different risk groups.

Results
We found 404 mRNAsi-related DEGs in LUSC, 77 of which were significantly associated with overall survival. An eight-gene prognostic signature (PPP1R27, TLX2, ANKLE1, TIGD3, AMH, KCNK3, FLRT3, and PPBP) was identified and used to construct a risk score model. The TCGA set was dichotomized into two risk groups that differed significantly (p = 0.00057) in terms of overall survival time (1, 3, 5-year AUC = 0.830, 0.749, and 0.749, respectively). The model performed well in two independent GEO datasets (p = 0.029, 0.033; 1-year AUC = 0747, 0.783; 3-year AUC = 0.746, 0.737; 5-year AUC = 0.706, 0.723). Low-risk patients had markedly increased numbers of CD8+ T cells and M1 macrophages and downregulated immune checkpoint genes compared to the corresponding values in high-risk patients (p < 0.05).

Conclusion
A stemness-related prognostic model based on eight prognostic genes in LUSC was developed and validated. The results of this study would have prognostic and therapeutic implications.
Factors associated with low back pain in patients with lumbar spinal stenosis: a cross-sectional study
Authors: Ogon Izaya , Teramoto Atsushi , Takashima Hiroyuki , Terashima Yoshinori , Yoshimoto Mitsunori , Emori Makoto , Iba Kousuke , Takebayashi Tsuneo , Yamashita Toshihiko 
Published: June 2022

Abstract
Background
Low back pain (LBP) is a major symptom of symptomatic lumbar spinal stenosis (SLSS). It is important to assess LBP in patients with SLSS to develop better treatment. This study aimed to analyse the factors associated with LBP in patients with SLSS.

Methods
This cross-sectional study included consecutive patients with SLSS aged between 51 and 79 years who had symptoms in one or both the legs, with and without LBP. The participants were classified into two groups: the high group (LBP visual analogue scale [VAS] score ≥ 30 mm) and the low group (LBP VAS score < 30 mm). We performed multiple logistic regression analysis with the high and low groups as dependent variables, and a receiver operating characteristic (ROC) analysis.

Results
A total of 80 patients with LSS were included (35 men and 45 women; mean age 64.5 years), with 47 and 30 patients in the high and low groups, respectively. Multivariate logistic regression analysis revealed that the sagittal vertical axis (SVA; + 10 mm; odds ratio, 1.331; 95% confidence interval, 1.051 − 1.660) and pelvic incidence-lumbar lordosis (PI-LL; + 1°; odds ratio, 1.065; 95% confidence interval, 1.019–1.168) were significantly associated with LBP. A receiver operating characteristic analysis revealed cut-off values of 47.0 mm of SVA and 30.5° of PI-LL, respectively.

Conclusion
Our results indicated that SVA and PI-LL were significant predictors for LBP in SLSS. It is suggested that these parameters should be taken into consideration when assessing LBP in patients with SLSS.
Robot and mechanical testing of a specialist manual toothbrush for cleaning efficacy and improved force control
Authors: Acherkouk Amina , Götze Marco , Kiesow Andreas , Ramakrishnan Anantha , Sarembe Sandra , Lang Tomas , Gaengler Peter 
Published: June 2022

Abstract
Background
Toothbrushes require flexibility to access all dental surfaces and remove plaque effectively, but they should also aim to prevent or limit overbrushing and consequent damage to teeth and gums. In two studies, the physical properties and cleaning performance of specialist test toothbrushes with flexible necks were compared to a reference rigid-necked toothbrush.

Methods
In Study 1, a universal testing machine (Instron E 10,000) with a specially designed setup was used to test the deflection behaviour of toothbrush head and neck. Untufted toothbrushes were fixed in a custom holder and force was applied to the head while the deflection was measured. In Study 2, one control and five test toothbrushes were assessed using a robot system to simulate the cleaning of artificial plaque from defined surfaces of artificial replicated human teeth in a model oral cavity (typodonts).

Results
Study 1 showed that the flexible-neck toothbrush deflected 2 to 2.5 times more than the rigid-neck reference toothbrush when same force was applied to the toothbrush head. Study 2 revealed that all five test toothbrushes showed statistically superior simulated plaque removal to the reference toothbrush. This superiority was observed for all test toothbrushes employing horizontal and rotating brushing action (all p = 0.001) but only three of the five toothbrushes when vertical brushing was employed (all p = 0.001). Cleaning efficacy of the test toothbrushes was demonstrated both interdentally and at the gumline locations. The Complete Protection toothbrush showed the most effective cleaning performance followed by the Repair and Protect and Rapid Relief toothbrushes.

Conclusion
The addition of a flexible-neck component to the toothbrush designs helped to reduce stiffness and may allow more effective cleaning compared to rigid designs with controlled force distribution on the teeth and gums. This may help to provide plaque control at all potential risk areas in an in vitro robot model and could support good oral hygiene in-use.
The gap in life expectancy and lifespan inequality between Iran and neighbour countries: the contributions of avoidable causes of death
Authors: Allel Kasim , Hajizadeh Mohammad , Kiadaliri Ali 
Published: June 2022

Abstract
Background
Healthcare system and intersectoral public health policies play a crucial role in improving population health and reducing health inequalities. This study aimed to quantify their impact, operationalized as avoidable deaths, on the gap in life expectancy (LE) and lifespan inequality (LI) between Iran and three neighbour countries viz., Turkey, Qatar, and Kuwait in 2015–2016.

Methods
Annual data on population and causes of deaths by age and sex for Iran and three neighbour countries were obtained from the World Health Organization mortality database for the period 2015–2016. A recently developed list by the OECD/Eurostat was used to identify avoidable causes of death (with an upper age limit of 75). The cross-country gaps in LE and LI (measured by standard deviation) were decomposed by age and cause of death using a continuous-change model.

Results
Iranian males and females had the second lowest and lowest LE, respectively, compared with their counterparts in the neighbour countries. On the other hand, the highest LIs in both sexes (by 2.3 to 4.5 years in males and 1.1 to 3.3 years in females) were observed in Iran. Avoidable causes contributed substantially to the LE and LI gap in both sexes with injuries and maternal/infant mortality represented the greatest contributions to the disadvantages in Iranian males and females, respectively.

Conclusions
Higher mortality rates in young Iranians led to a double burden of inequality –shorter LE and greater uncertainty at timing of death. Strengthening intersectoral public health policies and healthcare quality targeted at averting premature deaths, especially from injuries among younger people, can mitigate this double burden.