bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of diagnostic ultrasound with cRGD-microbubbles on simultaneous detection and treatment of atherosclerotic plaque in ApoE−/− mice
Authors: Guo Shengcun , Zhang Shengye , Chen Kui , Chen Xi , Hu Fudong
Published: July 2022

Background

Atherosclerotic vulnerable plaque is the leading cause of acute fatal cardiovascular events. Thus, early rapid identification and appropriate treatment of atherosclerotic plaque maybe can prevent fatal cardiovascular events. However, few non–invasive molecular imaging techniques are currently available for the simultaneous detection and targeted treatment of atherosclerotic plaques. We hypothesized that diagnostic ultrasound (DU) combined with cyclic Arg-Gly-Asp-modified microbubbles (MBR) could provide targeted imaging and dissolution of activated platelets to identify advanced atherosclerotic plaques and improve plaque instability.

Methods

Three mouse models, apolipoprotein E-deficient mice on a hypercholesterolemic diet (HCD) or normal chow diet and wild-type mice on an HCD were used. The most appropriate ultrasonic mechanical index (MI) was determined based on the expression of GP IIb/IIIa in sham, DU alone and DUMBR-treated groups at MI values of 0.5, 1.5, and 1.9. The video intensity (VI) values, activated platelets and plaque instability were analyzed by ultrasound molecular imaging, scanning electron microscopy and histopathological methods.

Results

We found that the VI values of ultrasound molecular imaging of MBR were positively correlated with plaque GP IIb/IIIa expression, vulnerability index and necrotic center / fiber cap ratio. 24 h after treatment at different MIs, compared with those of the other groups, both the VI values and GP IIb/IIIa expression were significantly reduced in MI 1.5 and MI 1.9 DUMBR-treated groups. The plaque vulnerability index and necrotic center / fiber cap ratio were significantly decreased in MI 1.5-treated group, which may be due to targeted dissolution of activated platelets, with a reduction in von Willebrand factor expression.

Conclusion

DUMBR targeting GP IIb/IIIa receptors could rapidly detect advanced atherosclerotic plaques and simultaneously give targeted therapy by dissolving activated and aggregated platelets. This technology may represent a novel approach for the simultaneous identification and treatment of atherosclerotic plaques.
A method to advance adolescent sexual health research: Automated algorithm finds sexual history documentation
Authors: Robertson Caryn , Mukherjee Gargi , Gooding Holly , Kandaswamy Swaminathan , Orenstein Evan
Published: July 2022

Background:

We aimed to develop and validate a rule-based Natural Language Processing (NLP) algorithm to detect sexual history documentation and its five key components [partners, practices, past history of sexually transmitted infections (STIs), protection from STIs, and prevention of pregnancy] among adolescent encounters in the pediatric emergency and inpatient settings.

Methods

We iteratively designed a NLP algorithm using pediatric emergency department (ED) provider notes from adolescent ED visits with specific abdominal or genitourinary (GU) chief complaints. The algorithm is composed of regular expressions identifying commonly used phrases in sexual history documentation. We validated this algorithm with inpatient admission notes for adolescents. We calculated the sensitivity, specificity, negative predictive value, positive predictive value, and F1 score of the tool in each environment using manual chart review as the gold standard.

Results

In the ED test cohort with abdominal or GU complaints, 97/179 (54%) provider notes had a sexual history documented, and the NLP algorithm correctly classified each note. In the inpatient validation cohort, 97/321 (30%) admission notes included a sexual history, and the NLP algorithm had 100% sensitivity and 98.2% specificity. The algorithm demonstrated >97% sensitivity and specificity in both settings for detection of elements of a high quality sexual history including protection used and contraception. Type of sexual practice and STI testing offered were also detected with >97% sensitivity and specificity in the ED test cohort with slightly lower performance in the inpatient validation cohort.

Conclusion

This NLP algorithm automatically detects the presence of sexual history documentation and its key components in ED and inpatient settings.
Evidence for metabolic diversity in Meso-Neoproterozoic stromatolites (Vazante Group, Brazil)
Authors: Callefo Flavia , Ricardi-Branco Fresia , Alves Forancelli Pacheco Mírian Liza , Cardoso Alexandre Ribeiro , Noffke Nora , de Carvalho Teixeira Verônica , Neckel Itamar Tomio , Maldanis Lara , Bullock Emma , Bower Dina , Moreira Silva Adalene , Ferreira Sanchez Dario , Rodrigues Fabio , Galante Douglas
Published: July 2022

Deciphering the evolution of ecological interactions among the metabolic types during the early diversification of life on Earth is crucial for our understanding of the ancient biosphere. The stromatolites from the genus Conophyton cylindricus represent a datum for the Proterozoic (Meso to Neoproterozoic) on Earth. Their typical conical shape has been considered a result of a competition between microorganisms for space, light and nutrients. Well-preserved records of this genus from the “Paleontological Site of Cabeludo”, Vazante Group, São Francisco Craton (Southern Brazil) present in situ fossilized biofilms, containing preserved carbonaceous matter. Petrographic and geochemical analyses revealed an alternation between mineral laminae (light grey laminae) and fossilized biofilms (dark grey laminae). The dark grey laminae comprise three different biofilms recording a stratified microstructure of microbial communities. These three biofilms composing the dark grey laminae tend to be organized in a specific pattern that repeats through the stromatolite vertical section. Iron and manganese are distributed differently along the dark and light grey laminae; X-ray absorption and luminescence data showed possible different areas with authigenic iron and iron provided from diagenetic infiltration. Cryptocrystalline apatite in the lowermost biofilms in each dark grey laminae may suggest past metabolic activity of sulfide-oxidizing bacteria. These findings suggest that the microorganisms reached a complex metabolic diversification in order to maintain an equilibrium situation between the three different biofilms along the vertical section of the structures, thus benefiting the whole microbial community. This means that the stromatolites from the Conophyton genus may have formed as a result of a greater complexity of interactions between microorganisms, and not only from competition between photosynthesizers.
Numerical Simulation Analysis of Mechanical Properties on Rock Brittle–Ductility Transformation Under Different Loading Rates
Authors: Tian Zhichao , Tang Chunan , Yu Chaoyun , Liu Yejiao , Chen Shijiang , Jin Yun
Published: July 2022

At present, a large number of physical tests and numerical simulations have been carried out to study the effect of confining pressure on rock deformation mechanism, and some achievements have been achieved; however, the mechanism of rock deformation in actual mine engineering needs to be further studied, for example, rock-burst is actually a unilateral unloading process of rock mass, and this process can not be completed by physical test. RFPA3D was used to simulate the brittle–ductility transformation mechanical properties of rock under different confining pressures in this paper. The damage constitutive equation of rock was derived from continuum damage mechanics; the damage coefficients of different rocks were determined based on the numerical results of stress acoustic emission, so the correctness of rock damage constitutive equation was verified. According to the derived brittle–ductility damage equation and the fitting results of ductility cumulative damage data, it was found that the development trend of rock brittleness stage was almost the same, and the extended separation occurred after entering ductility stage. The larger the Poisson’s ratio was, the longer the ductility stage was. The smaller the Poisson’s ratio was, the shorter the ductility stage was, but the larger the bearing capacity was. At the late loading stage, the ductility cumulative damage of rock showed a linear upward trend, the bearing capacity sharply decreased, the rock stability failure occurred, and the ductility damage coefficient increased gradually. The study on the brittle–ductile mechanical properties of rocks can help to deep mine’s rock-burst prediction and prevention and has significant engineering significance.
Experimental and analytical investigation on frost heave characteristics of coarse-grained soils under closed and open systems
Authors: Huang Wanjun , Mao Xuesong , Wu Qian , Zhao Shichen , Zhang Jianxun
Published: July 2022

Coarse-grained soil is widely used in the seasonal frozen soil region as subgrade filler. However, substantial frost heave has been observed in coarse filler in high-speed railway embankments. To investigate the frost heave characteristics of the coarse-grained soil in a deep seasonal frozen soil zone, indoor tests were carried out under water supply and no water supply conditions. The effect of water, fineness, and temperature on frost heave behavior is studied experimentally. The relationship between the freezing rate and frost heave of coarse-grained soils was analyzed. The results show that the freezing process of the filler can be divided into the rapid cooling stage, phase transition stage, slow freezing stage, and freezing stability stage. In the closed system, the increase of the fine-grained soil does not affect the cooling process, while the moisture content significantly affects the whole process. In the opened system, both the fine-grained soil content and the ambient temperature affect the cooling process. When the ambient temperature decreased from −5°C to −15°C, the duration of the phase transition stage decreased by almost 17 h, whereas when the fine-grained soil content increased from 2.7 to 16%, the duration of the phase transition stage increased by only 5 h. In both opened and closed systems, the development of the frost heave is closely related to the cooling process. Approximately 95% of frost heave occurs during the phase transition stage and slow freezing stage. Frost heave develops most rapidly in the phase transition stage, with approximately 85% of the frost heave amount occurring in this stage.
A Cambrian fossil from the Chengjiang fauna sharing characteristics with gilled lobopodians, opabiniids and radiodonts
Authors: Liu Jianni , Dunlop Jason A. , Steiner Michael , Shu Degan
Published: July 2022

Parvibellus atavus gen. et sp. nov. from the Early Cambrian Chengjiang fauna of China is a small fossil having a distinct cephalic region bearing a pair of lateral projections and a circular, ventral mouth. The trunk bears eleven pairs of probably flap-like appendages and a short pair of terminal projections. This character combination is unique for the Chengjiang biota. A circular ventral mouth is seen in Radiodonta and in some of the gilled lobopodians which are thought to be among the radiodont’s closest relatives. P. atavus, gilled lobopodians, opabiniids, and radiodonts also share the putative character of flap-like appendages along the trunk. However, the new fossil differs from radiodonts and gilled lobopodians by the absence of enlarged and/or raptorial frontal appendages. It also differs from gilled lobopodians by lacking in ventral lobopod limbs and from radiodonts by lacking in stalked eyes. It provisionally resolves as a sister-group to a clade containing the gilled lobopodians, opabiniids, and radiodonts, and could potentially be part of an early radiation of the nektonic lower stem—Euarthropoda.
Pottery Use and Starchy Foods During the Shuangdun Culture (ca.7.3–6.8 Ka BP) in the Middle Catchment of the Huai River, China
Authors: Li Weiya , Luo Wuhong , Yao Ling , Xuan Huali , Yi Wenwen , Tian Weixin , Zhang Dailing , Sun Yajie , Kan Xuhang , Zhang Juzhong
Published: July 2022

The use of rice and millet has been uncovered at a few archaeological sites associated with the Shuangdun Culture (ca. 7.3–6.8 ka BP) in the middle catchment of the Huai River, China. Nevertheless, the consumption of rice, millet, and other types of plant foods at other contemporaneous sites in the same region still needs supporting information from more case studies. This article examines pottery sherds (n = 21) excavated from another representative Shuangdun Culture site at Houjiazhai with starch grain analysis. Varied types of pottery vessels contain starch remains from rice (Oryza sativa), foxtail millet (Setaria italica), broomcorn millet (Panicum miliaceum), Job’s tears (Coix lacryma-jobi), Triticeae, roots of snake gourd (Trichosanthes kirilowii), lotus root (Nelumbo nucifera), Chinese yam (Dioscorea panthainca), lily bulbs (Lilium sp.), acorns (Quercus sp.), and beans (Vigna sp. or/and Vicia sp.). Further quantitative analysis of the starch data indicates that cereals, including rice and millet, were predominantly consumed in the pottery vessels. Changes and continuities of culinary practices are also present at Houjiazhai, which are reflected in the different pottery assemblages as well as the utilized plant species in different occupation phases at the site. Combining previous studies, this article also reveals the differences and similarities of the past population in choosing their plant food resources during the period of Shuangdun Culture in the middle catchment of the Huai River, China.
Impact of new undercrossing tunnel excavation on the stability of the existing tunnel
Authors: Zhu Qingli , Ding Yanping
Published: July 2022

The rapidly expanding transportation hub system in China has driven a large number of track and highway engineering projects nationwide, resulting in increasing interchanges of highway and railway tunnels year on year. The mutual impact between new and existing tunnels is one of the most important topics in geotechnical engineering. Constructed undercrossing, an existing highway tunnel is commonly seen in new railway tunnel projects. The new railway tunnel excavation will affect the stability and safety of the existing highway tunnel. Our study takes the newly built Huilongwan Railway Tunnel section undercrossing the existing Longzhouwan Highway Tunnel, one of the East Ring Line Projects of Chongqing Railway Terminal, as the object. This article simulated the displacement changes and structural deformation pattern of the existing highway tunnel caused by the excavation of the new railway tunnel with finite element analysis software and compared them with on-site measurements one by one to clarify the impact of new railway tunnel excavation on the stability of the existing highway tunnel. The result proved that the non-blasting excavation with a three-step temporary invert method could ensure the safety of the existing highway tunnel.
Teaching Preschoolers Theory of Mind Skills With Mobile Games
Authors: Nikolayev Mariya , Evmenova Anya S. , Reich Stephanie M. , Clark Kevin A. , Burns M. Susan
Published: July 2022

This single-case research study examined whether interactive touch screen apps enriched with Theory of Mind (ToM)—enhancing language would promote ToM skills in preschoolers. Six typically developing girls between the ages of 46- and 52- months participated in multiple sessions across the three phases of the study: In baseline, participants played games without voice-overs; in the original treatment phase, participants played games with embedded voice-overs; finally, in the modified treatment phase, participants first played games with embedded voice-overs, then engaged in the researcher-led conversation. All sessions across the three phases concluded with ToM assessments: two measures based on a continuous scale. The first measure included three tasks targeting earlier-developing ToM skills (diverse desires, diverse beliefs, and knowledge access), and the other measure had two tasks that assessed a later-developing ToM competency, false belief understanding. Results showed that apps with ToM-embedded language improved children’s earlier-developing ToM skills (i.e., understanding that people can have different desires, beliefs, and knowledge access) in the phase where an adult-led conversation also followed voice-over-enriched app play. Apps with ToM-embedded language without a follow-up discussion were only marginally effective in promoting the earlier-emerging ToM skills. Across the conditions, apps were not effective in promoting children’s later-developing ToM skills—false belief understanding. Our findings indicate that incorporating ToM conducive language in mobile apps can promote ToM development in preschoolers, especially when supplemented by an adult-led conversation.
Content and Language Integrated Scientific Modelling: A Novel Approach to Model Learning
Authors: Roth Tamara , Scharfenberg Franz-Josef , Bogner Franz X.
Published: July 2022

The relevance of English language competencies in authentic, discipline-specific contexts at school is increasingly acknowledged outside of English-speaking countries. Since any understanding of complex scientific problems requires the combination of scientific literacy with other competencies, such as scientific modelling, the appropriate application of Content and Language Integrated Learning (CLIL) is of great importance. The present study focuses on an established, hands-on outreach genetic education module on DNA structure, which it extends with a bilingual adaption to examine the influence of non-CLIL and CLIL learning on students’ scientific modelling skills and model understanding. When comparing non-CLIL learners (n = 149) and CLIL learners (n = 316), the former received higher scores in the assessment of model-related self-evaluation sheets and built better models. We also found that non-CLIL learners achieved better temporary knowledge of “DNA as a model” scores and, for model evaluation, were more reflective in determining similarities and differences between their hand-crafted model and a commercial DNA school model. However, CLIL learners performed better in comparing their model sketches with their hand-crafted models. They also used different approaches to develop models and conceptualize integral components of models, as reflected in their advanced model understanding. We conclude that CLIL influences modelling qualities on different levels, by fostering modelling practice, and in particular, model understanding.
Transfer of training among non-traditional students in higher education: Testing the theory of planned behavior
Authors: Gegenfurtner Andreas , Testers Laurent
Published: July 2022

This study tested the predictive validity of Ajzen’s theory of planned behavior with a sample of 182 non-traditional students in higher education to develop our understanding of non-traditional students’ intentions to transfer trained knowledge and skills from university courses to the workplace. After completing their courses, a survey measured behavioral, normative, and control beliefs, transfer attitudes, perceived social norms, transfer self-efficacy, and transfer intentions. One year later, a follow-up survey measured transfer of training. Partial least squares-based structural equation modeling (PLS-SEM) revealed that behavioral beliefs were positively associated with transfer attitudes, normative beliefs were positively associated with social norms, and control beliefs were positively associated with self-efficacy. Transfer attitudes and transfer self-efficacy predicted transfer intentions. Social norms, however, were non-significantly associated with intentions. Transfer intentions and transfer self-efficacy predicted transfer 1 year after training. These findings are discussed in terms of their predictive validity of Ajzen’s theory and their educational implications for non-traditional students enrolled in higher education programs.
Differential self-reported COVID-19 impacts among U.S. secondary teachers by race/ethnicity
Authors: McCauley Erin Josephine , Cooperstock Alexandra
Published: July 2022

The COVID-19 pandemic created drastic changes for public education in the United States, including the role and responsibilities of educators. This study explores the self-reported psycho-social implications of COVID-19 among U.S. secondary teachers who are white, Black, Indigenous, and people of color. Using a national survey (n = 1,478) fielded between October 2020 and March 2021, we capture teachers’ self-reported level of concern, life change, impact on thinking, and impact on teaching ability due to the COVID-19 pandemic. While teachers who are Black, Indigenous, and people of color report higher levels of concern and daily life change stemming from COVID-19, they report lower impacts on their teaching ability relative to their white peers. These findings are consistent with racial/ethnic disparities in COVID-19 case rates and mortality and highlight the resiliency of the U.S. secondary teachers who are Black, Indigenous, and people of color.
Intrauterine Device Use: A New Frontier for Behavioral Neuroendocrinology
Authors: Beltz Adriene M. , Demidenko Michael I. , Chaku Natasha , Klump Kelly L. , Joseph Jane E.
Published: July 2022

Intrauterine devices (IUDs) are the most-used reversible contraceptive method for women in the world, but little is known about their potential modulation of brain function, cognition, and behavior. This is disconcerting because research on other hormonal contraceptives, especially oral contraceptives (OCs), increasingly shows that exogenous sex hormones have behavioral neuroendocrine consequences, especially for gendered cognition, including spatial skills. Effects are small and nuanced, however, partially reflecting heterogeneity. The goal of this paper is to introduce IUD use as a new frontier for basic and applied research, and to offer key considerations for studying it, emphasizing the importance of multimodal investigations and person-specific analyses. The feasibility and utility of studying IUD users is illustrated by: scanning women who completed a functional magnetic resonance imaging mental rotations task; taking an individualized approach to mapping functional connectivity during the task using network analyses containing connections common across participants and unique to individual women, focusing on brain regions in putative mental rotations and default mode networks; and linking metrics of brain connectivity from the individualized networks to both mental rotations task performance and circulating hormone levels. IUD users provide a promising natural experiment for the interplay between exogenous and endogenous sex hormones, and they are likely qualitatively different from OC users with whom they are often grouped in hormonal contraceptive research. This paper underscores how future research on IUD users can advance basic neuroendocrinological knowledge and women’s health.
NTCP Deficiency Affects the Levels of Circulating Bile Acids and Induces Osteoporosis
Authors: Yang Fangji , Xu Wenxiong , Wu Lina , Yang Luo , Zhu Shu , Wang Lu , Wu Wenbin , Zhang Yuzhen , Chong Yutian , Peng Liang
Published: July 2022

Background

The p.Ser267Phe mutation in the SLC10A1 gene can cause NTCP deficiency. However, the full clinical presentation of p.Ser267Phe homozygous individuals and its long-term consequences remain unclear. Hence, in the present study, we characterized the phenotypic characteristics of NTCP deficiency and evaluated its long-term prognosis.

Methods

Ten NTCP p.Ser267Phe homozygous individuals were recruited and a comprehensive medical evaluation with a 5-year follow-up observation was performed. The phenotypic characteristics of NTCP deficiency were also demonstrated using an NTCP-global knockout mouse model.

Results

During the 5-year follow-up observation of 10 NTCP p.Ser267Phe homozygous adults, we found that the most common phenotypic features of NTCP deficiency in adults were hypercholanemia, vitamin D deficiency, bone loss, and gallbladder abnormalities. The profile of bile acids (BAs) in the serum was significantly altered in these individuals and marked by both elevated proportion and concentration of primary and conjugated BAs. Moreover, the NTCP deficiency led to increased levels of serum BAs, decreased levels of vitamin D, and aggravated the osteoporotic phenotype induced by estrogen withdrawal in mice.

Conclusions

Both mice and humans with NTCP deficiency presented hypercholanemia and were more prone to vitamin D deficiency and aggravated osteoporotic phenotype. Therefore, we recommend monitoring the levels of BAs and vitamin D, bone density, and abdominal ultrasounds in individuals with NTCP deficiency.
Inter-Network Brain Functional Connectivity in Adolescents Assigned Female at Birth Who Experience Gender Dysphoria
Authors: Skorska Malvina N. , Lobaugh Nancy J. , Lombardo Michael V. , van Bruggen Nina , Chavez Sofia , Thurston Lindsey T. , Aitken Madison , Zucker Kenneth J. , Chakravarty M. Mallar , Lai Meng-Chuan , VanderLaan Doug P.
Published: July 2022

Gender dysphoria (GD) is characterized by distress due to an incongruence between experienced gender and sex assigned at birth. Brain functional connectivity in adolescents who experience GD may be associated with experienced gender (vs. assigned sex) and/or brain networks implicated in own-body perception. Furthermore, sexual orientation may be related to brain functional organization given commonalities in developmental mechanisms proposed to underpin GD and same-sex attractions. Here, we applied group independent component analysis to resting-state functional magnetic resonance imaging (rs-fMRI) BOLD timeseries data to estimate inter-network (i.e., between independent components) timeseries correlations, representing functional connectivity, in 17 GD adolescents assigned female at birth (AFAB) not receiving gender-affirming hormone therapy, 17 cisgender girls, and 15 cisgender boys (ages 12-17 years). Sexual orientation was represented by degree of androphilia-gynephilia and sexual attractions strength. Multivariate partial least squares analyses found that functional connectivity differed among cisgender boys, cisgender girls, and GD AFAB, with the largest difference between cisgender boys and GD AFAB. Regarding sexual orientation and age, the brain’s intrinsic functional organization of GD AFAB was both similar to and different from cisgender girls, and both differed from cisgender boys. The pattern of group differences and the networks involved aligned with the hypothesis that brain functional organization is different among GD AFAB (vs. cisgender) adolescents, and certain aspects of this organization relate to brain areas implicated in own-body perception and self-referential thinking. Overall, brain functional organization of GD AFAB was generally more similar to that of cisgender girls than cisgender boys.
New insights on hyperglycemia in 17-hydroxylase/17,20-lyase deficiency
Authors: Xu Lingling , Lu Lin , Tong Anli , Chen Shi , Li Wei , Zhang Huabing , Ping Fan , Li Yuxiu
Published: July 2022

Objective

The adrenal glands of patients with 17-hydroxylase/17,20-lyase deficiency (17OHD) synthesize excessive 11-deoxycorticosterone(DOC) and progesterone, and produce less amount of sex steroid production. Mineralocorticoids and sex hormones play an important role in regulating glucose homeostasis. This study aimed to describe the glucose metabolism in 17OHD patients diagnosed at Peking Union Medical College Hospital (PUMCH).

Design/methods

A total of 69 patients diagnosed with 17OHD after adolescence in PUMCH from 1995 to June in 2021. Among them 23 patients underwent a 3-hours oral glucose tolerance test (3hOGTT) after being diagnosed with 17OHD. Insulin response in patients with normal glucose tolerance (NGT) were further compared between the study two groups with different kalemia status. Another 19 patients were followed up to 30 years and older. All clinical data were obtained from the hospital information system of PUMCH.

Results

Baseline: (1) The average body mass index(BMI) of all patients at baseline was 20.3 ± 3.7kg/m2. Twenty-three patients underwent 3hOGTT, of whom three were diagnosed with diabetes mellitus, and one with impaired glucose tolerance (IGT). Positive correlation between the ratio of progesterone to upper limit of normal range (P times) and hyperglycaemia was exist(r=0.707, P=0.005). (2) In 19 NGT patients, the insulin concentrations at 0 minute, results of the homeostasis model assessment for β-cell function and insulin resistance were lower in the hypokalaemia group than in the normal kalemia group(7.0(5.8-13.2) vs 12.4(8.9-14.9) μIU/ml, P=0.017; 115.5(88.2-240.9) vs 253.1(177.2-305.8), P=0.048; 1.54(1.17-2.61) vs 2.47(1.91-2.98), P=0.022, respectively). Follow-up: Four patients had IGT, while seven patients had diabetes mellitus. Of the 19 patients,11 had hyperglycaemia. P times was significantly higher(7.6(5.0-11.0) vs 3.75(2.2-5.3), P=0.008) in hyperglycemia group than in the normal glucose group.

Conclusions

Abnormal glucose metabolism was common in 17OHD patients, which was possibly associated with hypokalaemia and high progesterone levels. Routine monitoring on glucose metabolism in 17OHD patient should be conducted.
Effect of Body Surface Area on Severe Osteoporotic Fractures: A Study of Osteoporosis in Changsha China
Authors: Wu Xi-Yu , Li Hong-Li , Shen Yi , Tan Li-Hua , Yuan Ling-Qing , Dai Ru-Chun , Zhang Hong , Peng Yi-Qun , Xie Zhong-Jian , Sheng Zhi-Feng
Published: July 2022

Clinical vertebral fractures and femoral neck fractures are severe osteoporotic fractures that increase morbidity and mortality. Anthropometric variables are associated with an increased risk of osteoporotic fractures, but it is not clear whether body surface area (BSA) has an effect on clinically severe osteoporotic fractures. The study included total of 3,694 cases of clinical vertebral fractures and femoral neck fractures (2,670 females and 1,024 males) and 3,694 controls without fractures who were matched with the cases by sex and age. There was a significant positive correlation between BSA and bone mineral density (BMD) in female and male fracture patients (females: r = 0.430–0.471, P < 0.001; males: r = 0.338–0.414, P < 0.001). There was a significant systematic increase in BMD in both genders at various skeletal sites, grouped by BSA quartile. The osteoporosis rates of the lumbar spine (97.9%), femoral neck (92.4%) and total hip (87.1%) in the female Q1 group were significantly higher than those in the Q4 group (P < 0.001), which were 80.0%, 57.9% and 36.9%, respectively, in the Q4 group; the osteoporosis rates of the lumbar spine, femoral neck, and total hip were 53.9%, 59.4%, and 36.3% in the male Q1 group, and 15.2%, 21.9%, and 7.03% in the Q4 group, which were significantly lower than those in the Q1 group (P < 0.001). In age-adjusted Cox regression models, the risk of fracture in the remaining three groups (Q2, Q3, and Q4) for weight, BMI, and BSA for both genders, compared with the highest quartile (Q1 by descending quartile stratification) were significantly higher. In models adjusted for age and BMD, only men in the BSA Q3 (HR = 1.55, 95% CI = 1.09–2.19) and BSA Q4 groups (HR = 1.41, 95% CI = 1.05–1.87) had significantly higher fracture risks. In models adjusted for age, height, weight, BMI, and BSA, low BMD was the greatest fracture risks for both sexes. Our results showed that BSA was closely related to BMD, prevalence of osteoporosis, and fracture risk, and that a decline in BSA may be a new potential risk factor for osteoporotic fractures in Chinese men.
Targeted Deletion of the Claudin12 Gene in Mice Increases Articular Cartilage and Inhibits Chondrocyte Differentiation
Authors: Xing Weirong , Pourteymoor Sheila , Chen Yian , Mohan Subburaman
Published: July 2022

To study the role of Claudin (CLDN)12 in bone, we developed mice with a targeted deletion of exon2 in the Cldn12 gene for skeletal phenotype analysis. Micro-CT analysis of the secondary spongiosa of distal femurs of mice with targeted disruption of the Cldn12 gene and control littermates showed no significant genotype-specific differences in either cortical or trabecular bone parameters for either gender in 13-week-old mice. Immunohistochemistry revealed that while CLDN12 was expressed in both differentiating chondrocytes and osteoblasts of the secondary spongiosa of 3-week-old wild-type mice, its expression was restricted to differentiating chondrocytes in the articular cartilage and growth plate in adult mice. Articular cartilage area at the knee were increased by 47% in Cldn12 knockout (KO) mice compared to control littermates. Micro-CT analyses found that while the trabecular number was increased by 9% and the trabecular spacing was reduced by 9% in the femoral epiphysis of Cldn12 KO mice, neither bone volume nor bone volume adjusted for tissue volume was different between the two genotypes. The expression levels of Clusterin, Lubricin and Mmp13 were increased by 56%, 46%, and 129%, respectively, in primary articular chondrocytes derived from KO compared to control mice. Our data indicate that targeted deletion of the Cldn12 gene in mice increases articular cartilage, in part, by promoting articular chondrocyte phenotype.
Restoration of euthyroidism with levothyroxine: implications of etiology of hypothyroidism and the degree of residual endogenous thyroid function
Authors: Jonklaas Jacqueline
Published: July 2022

There are many thyroid-related factors that combine with non-thyroid-related factors in order to affect the patient response to treatment of hypothyroidism, in terms of their satisfaction with therapy. Some of the thyroid-derived factors include the etiology of the hypothyroidism and the amount of residual thyroid function that the patient retains. These two factors may be intertwined and affected by a third influence, the presence of thyroid peroxidase antibodies. The downstream consequences of the interactions between these three factors may influence both free thyroxine and free triiodothyronine levels, TSH concentrations, and various thyroid biomarkers. Evidence of the widespread importance of thyroid hormones can be inferred from the multiple genes that are regulated, with their regulation affecting multiple serum biomarkers. Thyroid biomarkers may extend from various well-known serum markers such as lipids and sex hormone-binding globulin to serum levels of thyroid hormone metabolites. Moreover, the interplay between thyroid hormones and biomarkers and their relative ratios may be different depending on the hypothyroidism etiology and degree of residual thyroid function. The ultimate significance of these relationships and their effect on determining patient-reported outcomes, quality of life, and patient satisfaction is, as yet, poorly understood. However, identification of better biomarkers of thyroid function would advance the field. These biomarkers could be studied and correlated with patient-reported outcomes in future prospective studies comparing the impact of various thyroid hormone therapies.
REG1A and RUNX3 Are Potential Biomarkers for Predicting the Risk of Diabetic Kidney Disease
Authors: Wang Xinyu , Wu Han , Yang Guangyan , Xiang Jiaqing , Xiong Lijiao , Zhao Li , Liao Tingfeng , Zhao Xinyue , Kang Lin , Yang Shu , Liang Zhen
Published: July 2022

Diabetic kidney disease (DKD) is the leading cause of end-stage renal disease. Clinical features are traditionally used to predict DKD, yet with low diagnostic efficacy. Most of the recent biomarkers used to predict DKD are based on transcriptomics and metabolomics; however, they also should be used in combination with many other predictive indicators. The purpose of this study was thus to identify a simplified class of blood biomarkers capable of predicting the risk of developing DKD. The Gene Expression Omnibus database was screened for DKD biomarkers, and differentially expressed genes (DEGs) in human blood and kidney were identified via gene expression analysis and the Least Absolute Shrinkage and Selection Operator regression. A comparison of the area under the curve (AUC) profiles on multiple receiver operating characteristic curves of the DEGs in DKD and other renal diseases revealed that REG1A and RUNX3 had the highest specificity for DKD diagnosis. The AUCs of the combined expression of REG1A and RUNX3 in kidney (AUC = 0.929) and blood samples (AUC = 0.917) of DKD patients were similar to each other. The AUC of blood samples from DKD patients and healthy individuals obtained for external validation further demonstrated that REG1A combined with RUNX3 had significant diagnostic efficacy (AUC=0.948). REG1A and RUNX3 expression levels were found to be positively and negatively correlated with urinary albumin creatinine ratio and estimated glomerular filtration rate, respectively. Kaplan-Meier curves also revealed the potential of REG1A and RUNX3 for predicting the risk of DKD. In conclusion, REG1A and RUNX3 may serve as biomarkers for predicting the risk of developing DKD.
New Insights Into the Evolution of Corticotropin-Releasing Hormone Family With a Special Focus on Teleosts
Authors: Maugars Gersende , Mauvois Xavier , Martin Patrick , Aroua Salima , Rousseau Karine , Dufour Sylvie
Published: July 2022

Corticotropin-releasing hormone (CRH) was discovered for its role as a brain neurohormone controlling the corticotropic axis in vertebrates. An additional crh gene, crh2, paralog of crh (crh1), and likely resulting from the second round (2R) of vertebrate whole genome duplication (WGD), was identified in a holocephalan chondrichthyan, in basal mammals, various sauropsids and a non-teleost actinopterygian holostean. It was suggested that crh2 has been recurrently lost in some vertebrate groups including teleosts. We further investigated the fate of crh1 and crh2 in vertebrates with a special focus on teleosts. Phylogenetic and synteny analyses showed the presence of duplicated crh1 paralogs, crh1a and crh1b, in most teleosts, resulting from the teleost-specific WGD (3R). Crh1b is conserved in all teleosts studied, while crh1a has been lost independently in some species. Additional crh1 paralogs are present in carps and salmonids, resulting from specific WGD in these lineages. We identified crh2 gene in additional vertebrate groups such as chondrichthyan elasmobranchs, sarcopterygians including dipnoans and amphibians, and basal actinoperygians, Polypteridae and Chondrostei. We also revealed the presence of crh2 in teleosts, including elopomorphs, osteoglossomorphs, clupeiforms, and ostariophysians, while it would have been lost in Euteleostei along with some other groups. To get some insights on the functional evolution of the crh paralogs, we compared their primary and 3D structure, and by qPCR their tissue distribution, in two representative species, the European eel, which possesses three crh paralogs (crh1a, crh1b, crh2), and the Atlantic salmon, which possesses four crh paralogs of the crh1-type. All peptides conserved the structural characteristics of human CRH. Eel crh1b and both salmon crh1b genes were mainly expressed in the brain, supporting the major role of crh1b paralogs in controlling the corticotropic axis in teleosts. In contrast, crh1a paralogs were mainly expressed in peripheral tissues such as muscle and heart, in eel and salmon, reflecting a striking subfunctionalization between crh1a and b paralogs. Eel crh2 was weakly expressed in the brain and peripheral tissues. These results revisit the repertoire of crh in teleosts and highlight functional divergences that may have contributed to the differential conservation of various crh paralogs in teleosts.
Clinical Features and Management of Suboptimal Ovarian Response During in vitro Fertilization and Embryo Transfer: Analysis Based on a Retrospective Cohort Study
Authors: Yan Yizhi , Qu Ruomu , Ma Xiaodong , Qin Siyuan , Chen Lixue , Ni Xiaoxiao , Yang Rui , Wang Ying , Li Rong , Qiao Jie
Published: July 2022

Background

Based on dynamic changes of indicators during controlled ovarian hyperstimulation and of clinical outcomes of suboptimal ovarian response with different protocols, this study aimed to summarize the clinical characteristics of SOR and provide clinical recommendations.

Methods

Data of 125 patients with SOR and 125 controls who had undergone appropriate protocols for in vitro fertilization-embryo transfer were collected from a single medical center from January 2017 to January 2019. Basic clinical indexes, including age, BMI, antral-follicle count, infertility time, basic follicle-stimulating hormone, luteinizing hormone, LH/FSH ratio, estradiol, progesterone, testosterone, androstenedione, prolactin, anti-Mullerian hormone, and thyroid stimulating hormone levels, were analyzed using T-test. Dynamic indexes during COH, including amount and days of gonadotropin, sex hormone levels, and number of large/medium/small follicles at specified time periods, were analyzed using T-test and joint diagnosis analysis with ROC curves. Indexes of laboratory and clinical indicators were analyzed using the chi-square test.

Results

For the SOR group, BMI, duration time, and dosage of gonadotropin used for SOR were significantly higher. In the ultra-long/long group, ROC curve analysis showed that the LH/FSH ratio and BMI yielded cutoff values of 0.61 and 21.35 kg/m2, respectively. A combined diagnosis of the two indexes showed higher sensitivity (90%) and specificity (59%). In the GnRH-ant group, ROC curve analysis showed an LH level, an LH/FSH ratio on COH day 2, and BMI yielded cutoff values of 2.47 IU/L, 0.57, and 23.95 kg/m2, respectively. Combining the two indexes with BMI, both showed increased sensitivity (77%) and specificity (72% and 74%). The estradiol level and progesterone level during the late follicular stage in SOR patients were significantly lower than those in control patients for both protocol groups. At each monitoring time, delayed follicular development was observed. The live-birth rate in fresh cycles of the ultra-long/long group and the live-birth rate in cumulative cycles of the antagonist group in the SOR group were lower than those in the control group.

Conclusion

SOR had adverse effects on clinical outcome. We provide some threshold values of basic LH/FSH ratio, BMI, COH day 2 LH, counts of follicles, and levels of estradiol/progesterone to be taken as reference to assist the early recognition of SOR.
Correlates of Glycemic Control Among Patients With Type 2 Diabetes in Eastern Ethiopia: A Hospital-Based Cross-Sectional Study
Authors: Letta Shiferaw , Aga Fekadu , Yadeta Tesfaye Assebe , Geda Biftu , Dessie Yadeta
Published: July 2022

Introduction

Even though optimal blood glucose control reduces the risk of diabetes-related complications, many patients with type 2 diabetes (T2D) fail to achieve it for a variety of reasons. In the study area, there was a paucity of evidence regarding correlates of glycemic control. Therefore, this study aimed to find out the correlates of glycemic control among patients with T2D in Eastern Ethiopia.

Methods

A cross-sectional study was conducted among 879 adult patients with T2D on follow-up at two public hospitals in Harar. Data were collected through interviews, physical measurements, and record reviews. The level of glycemic control was determined from three consecutive fasting plasma glucose (FPG) measurements. A mean value of FPG measurements falling in the normal range (80–130 mg/dl) was considered as optimal glycemic control; otherwise, a mean FPG level that is below or above the normal range (<80 mg/dl or >130 mg/dl) was defined as suboptimal glycemic control. Descriptive statistics were used to summarize the data, while a linear regression model was used to find out the correlates of glycemic control. A beta coefficient and a 95% CI reported associations. The statistical significance was declared at a p-value ≤0.05.

Results

The mean age of the patients with T2D was 52.7 ( ± 13.3) years. The mean FPG level was 172 ± 56 mg/dl. Suboptimal glycemic control was found in 76% (95% CI: 73.41, 79.04) of patients with T2D. In a multivariable linear regression, khat chewing (β = 6.12; 95% CI: 1.55, 8.69), triglycerides (β = 0.56; 95% CI: 0.41.48, 0.65), comorbidity (β = 5.29; 95% CI: 1.39, 9.13), and poor level of self-care practices (β = 5.43; 95% CI: 1.41, 6.46) showed a significant correlation with glycemic control.

Conclusions

This study found that about three-fourths of patients with T2D had suboptimal glycemic control. Khat chewing, comorbidity, and poor level of self-care practices were independently correlated with glycemic control. Thus, suppressing glycemic levels through appropriate treatment and strict diabetes self-care practices including avoidance of Khat chewing is a useful approach to attaining glycemic target that subsequently reduces cardiovascular risks.
A Risk Stratification Model for Metastatic Lymph Nodes of Papillary Thyroid Cancer: A Retrospective Study Based on Sonographic Features
Authors: Ni Xiaofeng , Xu Shangyan , Zhan Weiwei , Zhou Wei
Published: July 2022

Background

Papillary thyroid carcinoma (PTC) has a high probability of cervical lymph node (LN) metastasis. The aim of the study was to develop an ultrasound risk stratification model to standardize the diagnosis of metastatic LNs of PTC.

Methods

Patients with suspicious thyroid nodules who underwent US examination and US guided fine-needle aspiration for cervical LNs were retrospectively collected. Univariate and multivariate logistic regression analyses were performed to assess the independent risk factor of metastatic LNs. According to the OR value of correlated indicators in logistic regression analysis, a risk stratification model was established.

Results

A total of 653 LNs were included. The independent risk factors of metastatic LNs were long-axis diameter/short-axis ≤ 2 (OR=1.644), absence of hilum (OR=1.894), hyperechogenicity (OR=5.375), calcifications (OR=6.201), cystic change (OR=71.818), and abnormal flow (OR=3.811) (P<0.05 for all). The risk stratification model and malignancy rate were as follows: 0-2 points, malignancy rate of 10.61%, low suspicion; 3-5 points, malignancy rate of 50.49%, intermediate suspicion, ≥6 points, malignancy rate of 84.81%, high suspicion. The area under the receiver operating characteristic curve for the model was 0.827 (95% CI 0.795-0.859).

Conclusions

Our established risk stratification model can effectively evaluate metastatic LNs in the patients with suspicious thyroid nodules, and it might provide a new strategy choice for clinical practice.