bluuebunny/crossref_metadata_2025_split huggingface dataset:
HOMA-IR Levels in US Youth Ages 12–18 Years From 1999–2018
Authors: Thaker Vidhu V , Deng Shuliang , Zhou Chuhan , West Brady , Si Yajuan , Fennoy Ilene 
Published: May 2021

Abstract
Introduction: The Homeostasis Model Assessment of insulin resistance (HOMA-IR) is a validated surrogate measure of insulin sensitivity and beta-cell function for epidemiological studies. Insulin resistance is closely associated with obesity and shares dysmetabolic state with other cardiometabolic risk factors. The aim of this study was to analyze the change in HOMA-IR levels in US youth from 1999 to 2018.
Methods: Serial cross-sectional data of fasting insulin and glucose levels measured in youth aged 12 to 18 years enrolled in National Health and Nutrition Examination Surveys representative of US population from 1999 to 2018 were used. Two-year survey cycles were combined to derive 4-year survey periods, and NHANES recommended adjustments were made for glucose and insulin levels for forward conversion to 2017–18 instrument levels. Median HOMA-IR was compared across the survey periods in subgroups by age, gender, race/ethnicity and levels of obesity. Association of HOMA-IR with selected cardiometabolic risk factors was assessed. Change of HOMA-IR levels were analyzed using design adjusted multivariable regression models, association of HOMA-IR with cardiometabolic risk factors was assessed and percentiles were derived.
Results: In an analysis of 5,541 youth, the unadjusted median HOMA-IR increased from 1.83 (95% CI 1.77–1.89) in 1999-02 to 2.41 (95% CI 2.29–2.54) in 2007–10 and has remained in this range till 2015–18. Youth with obesity (Body mass index &gt; 95th percentile or waist circumference &gt; 90th percentile), female gender, those of Hispanic and Black origin, and those aged 12–16 years had higher levels of HOMA-IR (p &lt;.001). While adjusting for age category, sex, race/ethnicity, obesity represented by waist circumference z-score with its quadratic term and interaction with gender, HOMA-IR increased by 26% (95% CI 15–37) in 2015–18 as compared to 1999-02. For waist-circumference z-score (WCZ) &gt; 1, the HOMA-IR levels were higher in boys compared to girls. The addition of total body fat from DXA scans in the model, when available, explained the variance related to gender, but not the interaction between gender and WCZ. No change was observed in the higher levels of HOMA-IR by ethnicity when high sensitivity CRP level as a measure of inflammation was added to the model. There was a positive association of HOMA-IR with triglycerides (29 %/unit, 95% CI 25–33), non-HDL cholesterol (8 %/unit, 95% CI 6–10), systolic blood pressure (2% /unit, 95% CI 1–2) and alanine transferase (11 %/unit, 95% CI 8–14) while controlling for age, sex, race/ethnicity, obesity and survey period. In youth with BMI between 5-85th percentile, HOMA-IR decreased with increase in age from 12 to 18 years.
Conclusions: HOMA-IR levels in US youth have increased since 1999-02 and may herald future cardiometabolic risks.
Reconsidering the Basal Proportion of Insulin Dose: Glycemic and Microvascular Outcomes in Type 1 Diabetes Mellitus
Authors: Pozos-Varela Francisco Javier , Mena-Ureta Tania Sofía , Lam-Chung César Ernesto , Ibarra-Salce Raúl , Martínez-Zavala Néstor , Janka-Zires Marcela , Almeda-Valdes Paloma 
Published: May 2021

Abstract
Optimal glycemic control is required to lower the risk of complications in type 1 diabetes mellitus (T1DM). This can be achieved with multiple daily insulin injections (MDI) or with continuous subcutaneous insulin infusion (CSII). Most diabetes guidelines recommend a proportion of basal insulin (basal proportion of total insulin dose; %B/T) around 50% of the total daily dose (TDD), although there is scarce evidence that suggests that a lower %B/T is associated with lower HbA1c levels. Our objective was to evaluate the association of the %B/T with glycemic and microvascular outcomes. We included 132 T1DM adults of the Diabetes Clinic in a tertiary care center, 117 (88.6%) using MDI and 15 (11.4%) using CSII. Data from the medical records and insulin pumps software during outpatient visits were retrospectively collected. Individuals with end-stage renal disease, solid-organ transplant, pregnancy, and glucocorticoid use were excluded. A positive correlation between %B/T and HbA1c levels was found, r=0.26 (p=0.002). Three groups were analyzed according to the %B/T: ≤40%, 41–59% and ≥60%, observing differences in HbA1c concentrations: 7.1% (6.7–8.0%), 7.8% (7.2–9.1%) and 8.7% (7.6–10.2%), respectively (p=0.003). Regarding microvascular complications, the cases of nephropathy were 0 (0%), 23 (30.7%) and 18 (40%) across those groups (p=0.029) even though there was no difference in T1DM duration across groups. There were also no differences in body mass index, TDD, TDD/weight (units/kg/day), nor in the rates of retinopathy or neuropathy. Multiple regression analysis identified %B/T as an independent predictor of the HbA1c concentration. A difference in the rates of hypoglycemic episodes per month was found among individuals with a %B/T ≤50%: 2 (1–5) versus 6 (2.5–12) episodes per month in those having a higher %BT (p=0.002). There are limitations in our study, including the retrospective nature of the analysis, no data about meal content and a low usage of CGM (thus relying on variable self-monitoring of blood glucose). Therefore, we cannot asseverate that lowering the %B/T would improve glycemic and microvascular outcomes. Nevertheless, our findings indicate that the %B/T correlates with HbA1c levels and are consistent with those previously described. It also suggests a relationship with hypoglycemia and to the best of our knowledge, it is the first time that an association between %B/T and nephropathy has been noted.
Should Target Glucose Values Be Increased to Avoid Severe Hypoglycemia? Real-World Data Say “No.”
Authors: Welsh John , Dowd Robert , Price David A 
Published: May 2021

Abstract
Early studies such as the Diabetes Control and Complications Trial showed a strong inverse relationship between A1C and the risk of severe hypoglycemia in type 1 diabetes. This risk has historically limited insulin therapy intensification efforts, and some treatment guidelines (e.g., Rosenzweig et al., J Clin Endocrinol Metab 105:969, 2020) suggest that A1C values &lt;7% confer an increased risk of hypoglycemia. Nowadays, real-time continuous glucose monitoring (CGM) systems can flatten and attenuate the relationship between overall glucose control and hypoglycemia (Oliver et al., Diabetes Care 43:53, 2020). The glucose management indicator (GMI) is an estimate of A1C derived from the CGM system’s mean estimated glucose value (EGV) (Bergenstal et al., Diabetes Care 41:2275, 2018). We analyzed real-world evidence of the relationship between the GMI and exposure to hypoglycemia. Data were from an anonymized convenience sample of US-based users of the G6 CGM system (Dexcom, Inc., San Diego, CA) who used a mobile device to upload EGVs in the third quarter of 2020. Only data from people who had uploaded ≥80% of possible values were included. Each person’s GMI was calculated as GMI = 3.31 + (0.02392 × mean EGV [mg/dL]). Each person’s exposure to hypoglycemia was estimated as the percentage of EGVs &lt;70 mg/dL or &lt;54 mg/dL (%&lt;70 and %&lt;54, respectively). Patients were grouped into 6 categories according to GMI values &lt;6.5%, 6.5 to 6.9%, 7.0 to 7.4%, 7.5 to 7.9%, 8.0 to 8.4%, and ≥8.5%. Mean %&lt;70 mg/dL and %&lt;54 mg/dL were both inversely correlated with GMI, decreasing monotonically as the GMI category increased. GMI category, %&lt;70, and %&lt;54 are as follows: (&lt;6.5%: 5.27%, 1.13%); (6.5 to 6.9%: 2.84%, 0.59%); (7.0 to 7.4%: 1.95%, 0.41%); (7.5 to 7.9%: 1.46%, 0.31%); (8.0 to 8.4%: 1.14%, 0.25%); (≥8.5%: 0.69%, 0.17%). However, in all GMI categories except for the “&lt;6.5%” category, the extent of hypoglycemic exposure was below the consensus targets proposed by Battelino et al. (Diabetes Care 42:1593, 2019) of &lt;4% for EGVs &lt;70 mg/dL and &lt;1% for EGVs &lt;54 mg/dL. The approach of elevating A1C targets to reduce hypoglycemia risk is not supported by real-world evidence for CGM users who have GMI or A1C values ≥6.5%. CGM users can safely strive for A1C values &lt;7.0%.
Response to Twin Enabled Precision Treatment for Reversing Diabetes: An Initial Analysis at 4 Weeks of the Ongoing Randomised Controlled Trial
Authors: Shamanna Paramesh , Dharmalingam Mala , Vadavi Arun , Mohammed Jahangir , Poon Terrence , Thajudeen Mohamed , Keshavamurthy Ashok , Bhonsley Suchitra 
Published: May 2021

Abstract
Introduction: Technology enabled precision nutrition, a combination of macro, micro and biota nutrients, along with Continuous Glucose Monitoring (CGM) have been demonstrated to be a key for reversal of diabetes.
Methods: We conducted an initial analysis (n=23) of the ongoing randomized controlled trial of Twin Precision Treatment (TPT): a novel whole-body digital twin enabled precision treatment for reversing diabetes. The clinical and the biochemical parameters were evaluated as the longitudinal follow up at the first follow up visit at 4 weeks. The target sample size is 300 with an estimated duration of 5 years. Descriptive statistics were used
Results: 8/23 (35%) patients achieved the intended outcome of reversal of HbA1c and off any anti-diabetic medications. There was a statistically significant improvement in HbA1c % (8.5 ± 1.6 to 6.8 ± 0.66; p&lt;0.0001), Fasting Blood Glucose mg/dL (FBS) (151 ± 44 to 98 ± 18; p&lt;0.0001), HOMA2-IR (1.7 ± 0.64 to 1 ± 0.45; p=0.0001), HOMA2-Beta (53 ± 28 to 86 ± 38; p=0.0013), Systolic BP (129 ± 11 to 120 ± 11; p=0.008) and serum albumin g/dL (4.5 ± 0.21 to 4.2 ± 0.31; p=0.0042). The baseline values for the other parameters including body weight, waist circumference, Diastolic BP, Alanine transaminase (ALT), Gamma-glutamyl transferase (GGT), eGFR, WBC, Platelet, Globulin, ESR, demonstrated a clinically relevant, superior change
Discussion: The initial analysis for the prospectively designed trial reveals a remarkable improvement in the clinical and the biochemical parameters that would determine the complete and the prolonged remission of diabetes. The initial results are an early indicator for the translation of the scientific rationale for the technological intervention, through digital twin technology, powered by Internet of Things (IoT) and Artificial Intelligence (AI), as a modality to enable reversal of diabetes into an achievable outcome that would be durable. The impactful glycemic control appears to have positive meaningful metabolic health consequences
Trial Registration: The trial has been prospectively registered in Clinical Trial Registry – India: Reference no. CTRI/2020/08/027072 on August 10, 2020
Artemisinin and the Derivatives Play Novel Role in Treatment for Graves’ Orbitopathy as Conventional Antimalarials
Authors: Guo Yan , Li Yanbing 
Published: May 2021

Abstract
Context: Graves’ orbitopathy (GO) an autoimmune disease in orbit, characterized with proptosis due to excessive proliferation, adipogenesis, fibrosis and hyaluronan secretion of orbital fibroblasts (OFs). OFs is potential to be a target for proptosis. But there are few effective therapies. Objectives: Our present purpose was to evaluate the effects of artemisinin (ARS) and the derivatives dihydroartemisinin (DHA), artesunate (ART) on OFs from GO patients in vitro. Design/Setting/Participants: OFs isolated from patients with GO (n = 10) were allowed to proliferate in the proliferation medium (PM); differentiate into adipocytes in the differentiation medium (DM) or differentiate into myofibroblast stimulated by TGF-β (10ng/ml); or produce hyaluronan stimulated by IL-1β (5ng/ml). Different dosages of ARS and the derivatives were administered in the above conditions. Main Outcome Measures: CCK-8 was used to assessed cell viability of OFs, EdU incorporation and flow cytometry were conducted to assess cellular proliferation. Adipogenesis was determined by Western blot and Oil Red O staining. Hyaluronan was quantified by ELISA. Fibrosis was assessed using Western blot. Results: ARS in concentrations lower than 100 μM, DHA &lt; 20 μM and ART &lt; 10 μM are nontoxic for OFs. Cellular proliferation of GO-OFs was halted by ARS and its derivatives at the maximum nontoxic dosage. ARS and its derivatives exerted an inhibitory action on adipogenesis of OFs in a concentration-dependent manner.
Moreover, hyaluronan secretion was obviously decreased by ARS and its derivatives. Intriguingly, fibrosis markers were also decreased by the antimalarias in a dosage-dependent way. Conclusions: We elucidated the efficacies of ARS and its derivatives on proliferation, adipogenesis, fibrosis and hyaluronan production of OFs, supporting that ARS-based antimalarials play potential role as a novel therapy for GO from a perspective of in-vitro study.
Bisphenol A and S, but Not F, Alter Oxidative Stress Levels in Spermatozoa
Authors: Nguyen Mimi , Sabry Reem , St. John ., Elizabeth J , Favetta Laura A 
Published: May 2021

Abstract
Exposures to endocrine disrupting compounds (EDCs) have been linked to male reproductive dysfunction. The increase in prevalence of male infertility to date has been correlated with the widespread use of bisphenols, particularly bisphenol A and its analogs. Current literature suggests that exposure to EDCs is associated with abnormalities in spermatogenesis, as well as reduced sperm motility and morphology. At this time, the mechanism for bisphenols’ action in spermatozoa is still unknown, though it has been proposed that bisphenols alter sperm parameters by affecting their oxidative stress pathways. The aim of this project is to elucidate whether BPA and its analogs affect oxidative stress levels inducing decreased sperm quality and fertilization capability. An in vitro bovine model was used as the most appropriate translational model to humans. Motile spermatozoa were separated using Percoll gradient centrifugation of frozen-thawed sperm and a pilot experiment was conducted in a time-dependent manner to establish the ideal incubation time of 4 hours. Sperm was then incubated in five treatment groups: control, vehicle (0.01% ethanol), BPA, BPS, and BPF, at the physiological relevant dose of 0.05 mg/ml in 0.01% ethanol. Key reactive oxygen species (ROS) scavenger genes (superoxide mutase 1 [SOD1], superoxide mutase 2 [SOD2], catalase [CAT], glutathione peroxidase 1 [GPX1], glutathione peroxidase 4 [GPX4]) were quantified at the RNA level using qPCR. Of the five genes examined: BPA, BPS, and BPF exposure significantly decreased GPX4 expression (p&lt;0.05) compared to control and vehicle groups. BPA and BPS exposure significantly increased SOD1 expression compared to BPF, control, and vehicle (p&lt;0.05). No significant differences were found in GPX1 after bisphenols’ exposure. SOD2 and CAT expression was not detectable in all five groups suggesting a lack of expression in bovine sperm. Future investigations will involve experiments at the protein level and quantifying total ROS levels. Additionally, sperm morphology was evaluated using Spermac stain. Preliminary results indicate an increased number of abnormal spermatozoa with notably tail defects after 4 hours of bisphenols exposure. These initial findings support BPA and BPS’s ability to alter oxidative stress pathways in sperm via changes in antioxidant enzymes but suggest that BPF likely acts through different mechanisms. Overall, this research aims to understand the effects of bisphenols on male fertility to improve male factors during assisted reproductive biotechnologies.
Hyperthermia as a Steroidogenic Inhibitor of Adrenodortical Cells, an Adrenal Sparing Treatment for Primary Aldosteronism?
Authors: Donlon Padraig T , Mullen Nathan , Warde Kate , O’Shea Paula M , O’Halloran Martin , Prakash Punit , Dennedy Michael Conall 
Published: May 2021

Abstract
Introduction: Primary Aldosteronism (PA) is the commonest secondary cause of hypertension. Mainstay therapy, adrenalectomy resects both hypersecreting and adjacent normal tissue. It is therefore only suitable for patients with unilateral disease (40% cases), whom are surgical candidates. Thermal therapy presents a plausible minimally invasive therapeutic, to target and disrupt hypersecreting adrenal nodules in primary aldosteronism, while also preserving adjacent normal adrenal cortex.
Methodology: Adrenocortical cell lines (H295R and HAC15) were treated with hyperthermia using a water bath at temperatures between 37-650C for 15 minutes. Cell death and apoptosis were analysed immediately, 24 hours, and 48 hours post hyperthermia using Annexin V / Propidium Iodide (PI) (flow cytometry), and Calcein / PI imaging techniques. Steroidogenic potential was also analysed post hyperthermia by (i) measuring cytosolic calcium flux in response to angiotensin II (ANGII) using Flou-4 staining (flow cytometry); (ii) measurement of steroidogenic enzyme expression (RT-PCR); (iii) by measurement of cortisol and aldosterone in cell supernatants (chemiluminescent assays). Cells were also stimulated with forskolin for steroid enzyme and output assays.
Results: Hyperthermia induced mainly necrotic cell death not apoptotic. Percentage cell death was significantly increased from 500C-65 0C (95.41+/- 5.74% versus control 9.17+/- 3.01%, p&lt;0.0001). Cytosolic calcium changes in response to ANGII were lowered from 550C-650C in H295R (-36.33+/-7.06 Ca+ Response versus control 10.67+/- 1.76 Ca+ Response, p&lt;0.001) and from 450C-650C in HAC15 (-43.33+/-12.36 Ca+ Response versus control 4.43+/-1.57 Ca+ Response, p&lt;0.002), intracellular stored calcium was also diminished with increased hyperthermia exposures in both cell lines. CYP11B1 (-31.6+/-2.8 ααCt versus control, p&lt;0.0001), CYP11B2 (-11.3+/-4.9 ααCt versus control, p&lt;0.0001), and HSD3B2 (-42+/-9.8 ααCt versus control, p&lt;0.0001) enzyme gene expression was decreased following 450C for 15 minutes in HAC15 cells while only CYP11B2 (-9.3+/-2.5 ααCt versus control, p&lt;0.0001), and HSD3B2 (-15+/-1.3 ααCt versus control, p&lt;0.0001) enzyme gene expression was decreased in H295R cells. Steroid output was also shown to be impaired at 450C for 15 minutes (22.35+/- 4.49 nmol/L versus control 117.7+/- 25 nmol/L, p&lt;0.0001).
Conclusion: Hyperthermic therapy delivered at sublethal temperatures and exposure times inhibits steroidogenesis. Inhibiting steroidogenesis by applying targeted thermal therapy to functional adrenocortical nodules represents a novel adrenal sparing approach to definitive management of primary aldosteronism.
АКТУАЛЬНЫЕ ПРОБЛЕМЫ ФИНАНСИРОВАНИЯ ЗДРАВООХРАНЕНИЯ С УЧЕТОМ ОПЫТА РЕСПУБЛИКИ БАШКОРТОСТАН
Authors: Ermolenko Tatyana V. , Bikkinin Irek A. 
Published: May 2021

Обеспечение населения доступной и качественной медицинской помощью и финансирование системы здравоохранения приобрели особую актуальность. В статье приведен исторический анализ норм права, устанавливающих источники финансирования здравоохранения, а также анализ действующего порядка финансового обеспечения системы здравоохранения и трудностей, с которыми столкнулась медицинское обслуживание РФ в наши дни. В работе сформированы предложения по путям решения существующих проблем, в целях совершенствования медицинского обслуживания населения, повышения эффективности порядка финансирования деятельности медицинских учреждений, в том числе и образовательных, в целях развития медицинской науки, подготовки квалифицированного медицинского персонала.
Цель. Изучить особенности становления финансирования системы здравоохранения в Российской Федерации, а также проанализировать современные проблемы, стоящие перед здравоохранением России, вытекающие из недостаточного его обеспечения.
Материалы и методы. Проанализированы источники права устанавливающие порядок финансового обеспечения системы здравоохранения, начиная от времен Древней Руси до наших дней. Расходы федерального бюджета с 2017 по 2019 год на нужды системы здравоохранения сравнивались с расходами по другим статьям функциональной классификации. Полученные данные обработаны методами непараметрической статистики. Количественные признаки представлены в виде таблицы.
Результаты. Ежегодно выделяемый бюджет на нужды здравоохранения составлял не более 2.5 % ВВП. В связи с текущим финансированием здравоохранения сложились некоторые проблемы: дефицит квалифицированных медицинских работников, недостаточная мотивация студентов к продолжению профессиональной медицинской деятельности, несогласованность порядка финансового обеспечения между регионами, уровень российской фармацевтики не соответствует современным требованиям.
Заключение. Таким образом, проблема недостаточного финансирования здравоохранения является актуальной и свидетельствует о необходимости разработки мероприятий, направленных на стабилизацию состояния системы здравоохранения, модернизации ее в будущем в целях обеспечения населения страны доступным и качественным медицинским обслуживанием.
Soziopragmatik von unser bei Rufnamen im Westmitteldeutschen.
Authors: Werth Alexander 
Published: May 2021

Speakers of Western Central German dialects frequently use the first person plural form of the possessive article unser with proper names (e. g. us Dietmar ‘our Dietmar’). But conditions of use are so far totally unclear. This paper focuses on form and use of unser with proper names in Moselle Franconian dialects. The findings are based on interviews. They show that unser is primarily used to refer to blood relatives. However, consanguinity is a necessary, but not sufficient, condition for unser. In particular, its use is triggered by social closeness and the assumption of responsibility by the speaker.
Algorithm optimization of cross-interfaces computed tomography into full field
Authors: Ling Chen , Chen Haiyan , Gao Yu , Wu Yue 
Published: May 2021

Tomographic approaches in confined space require advanced imaging algorithms that can properly consider the refractive distortion as the imaging rays pass through the optical wall. Our previous work established an algorithm (cross-interfaces computed tomography, CICT) and practically solved tomographic problems in confined space. However, critical restriction was found in CICT, which is that images simulated at small azimuth angles are contaminated with noticeable signal loss and become unusable. Based on this recognition, this work has developed an improved tomography approach, namely, full-field cross-interfaces computed tomography (FCICT), to extend the available view angles to all perspectives. The key to this approach involves the 3D domain discretization using voxel parallelepipeds instead of traditional voxel layers to establish the ray-tracing relationship between imaging planes and the measurement domain. The imaging process of FCICT is first validated by quantitatively comparing the grid imaging locations in measured and simulated projections of a calibration plate. By evenly distributing the view angles in the whole azimuth angle range, the FCICT reconstruction is then numerically validated by reconstructing a simulated double-cone flame phantom. The reconstruction presents a high correlation coefficient of

∼

98

%

with the original phantom. Finally, the FCICT is employed to reconstruct an ethylene-air premixed flame. Comparisons show that re-projections generated by the FCICT reconstruction are in accordance with measured flame images, with the mean correlation coefficients of more than 95%.