bluuebunny/crossref_metadata_2025_split huggingface dataset:
C‐peptide, glycaemic control, and diabetic complications in type 2 diabetes mellitus: A real‐world study
Authors: Huang Yajing , Wang Yahao , Liu Chuanfeng , Zhou Yue , Wang Xiang , Cheng Bingfei , Kui Che , Wang Yangang 
Published: November 2021

AbstractObjectiveTo explore the relationship between C‐peptide and glycaemic control rate and diabetic complications (microvascular complication and cerebral infarction) and provide evidence for stratified treatment of type 2 diabetes mellitus (T2DM)‐based C‐peptide.MethodThis is a cross‐sectional real‐world observational study. According to the inclusion and exclusion criteria, we studied 1377 patients with T2DM, grouped by fasting C‐peptide and HOMA‐IR. Blood samples were collected after fasting overnight. Logistic regression was used to analyse the relationship among fasting C‐peptide, HOMA‐IR, C2/C0 ratio (the ratio of 2 h postprandial C‐peptide to fasting C‐peptide), glycaemic control rate, and occurrence of diabetic complications. Restricted cubic spline (RCS) curves based on logistic regression were used to evaluate the relationship between C‐peptide, glycaemic control rate, and diabetic kidney disease (DKD).ResultsPatients were subdivided according to their fasting C‐peptide in 4 groups (Q1,Q2,Q3,Q4). Patients of group Q3 (1.71 ≤ C‐peptide < 2.51 ng/ml) showed the lowest incidence of DKD, diabetic retinopathy (DR), and rate of insulin absorption as welll as higher glycaemic control rate. Logistic regression shows that the probability of reaching glycemic control increased with higher levels of C‐peptide, compared with group Q1, after adjusting for age, gender, duration of diabetes, body mass index, systolic blood pressure, diastolic blood pressure, creatinine, low‐density lipoprotein, triglyceride, total cholesterol, and high‐density lipoprotein. RCS curve shows that, when C‐peptide is ≤2.68 ng/ml, the incidence of not reaching glycaemic control decreases with increasing C‐peptide. The possibility of not reaching glycaemic control decreased with increasing C2/C0, when C‐peptide is ≥1.71 ng/ml. RCS curve shows that the relationship between C‐peptide and DKD follows a U‐style curve. When C‐peptide is <2.84 ng/ml, the incidence of DKD decreased with increasing C‐peptide. With the increase in the C2/C0 ratio, the incidence of DKD, DR, and fatty liver did not decrease.ConclusionWhen C‐peptide is ≥ 1.71 and < 2.51 ng/ml, patients with T2DM had a higher glycemic control rate. Excessive C‐peptide plays different roles in DKD and DR; C‐peptide may promote the incidence of DKD but protects patients from DR. Higher C2/C0 ratio is important for reaching glycaemic control but cannot reduce the risk of DKD, DR, and fatty liver.
Biomarker‐based assessment of collagen cross‐linking identifies patients at risk of heart failure more likely to benefit from spironolactone effects on left atrial remodelling. Insights from the HOMAGE clinical trial
Authors: Ravassa Susana , López Begoña , Ferreira João Pedro , Girerd Nicolas , Bozec Erwan , Pellicori Pierpaolo , Mariottoni Beatrice , Cosmi Franco , Hazebroek Mark , Verdonschot Job A.J. , Cuthbert Joe , Petutschnigg Johannes , Moreno María U. , Heymans Stephane , Staessen Jan A. , Pieske Burkert , Edelmann Frank , Clark Andrew L. , Cleland John G.F. , Zannad Faiez , Díez Javier , González Arantxa ,   on behalf of the HOMAGE Trial Committees and Investigators
Published: November 2021

AimsThe HOMAGE randomized trial found that spironolactone reduced left atrial volume index (LAVI), E:A ratio, and a marker of collagen type I synthesis (procollagen type I C‐terminal propeptide) in patients at risk of heart failure (HF). Previous trials showed that patients with HF, preserved ejection fraction and low serum collagen type I C‐terminal telopeptide to matrix metalloproteinase‐1 ratio (CITP:MMP‐1), associated with high collagen cross‐linking, had less improvement in diastolic function with spironolactone. We evaluated the interaction between serum CITP:MMP‐1 and spironolactone on cardiac function in the HOMAGE trial.Methods and resultsPatients at risk of HF were randomized to spironolactone (n = 260) or not (n = 255). Blood sampling and echocardiography were done at baseline, one and nine months. CITP:MMP‐1 was used as an indirect measure of collagen cross‐linking. Higher baseline CITP:MMP‐1 (i.e. lower collagen cross‐linking) was associated with greater reductions in LAVI with spironolactone at both one (p = 0.003) and nine (p = 0.01) months, but no interaction was observed for E:A ratio. Spironolactone reduced LAVI after one and nine months only for those patients in the third tertile of CITP:MMP‐1 (estimated lowest collagen cross‐linking) [mean differencesspiro/control: −1.77 (95% confidence interval, CI −2.94 to −0.59) and −2.52 (95% CI −4.46 to −0.58) mL/m2; interaction pacross‐tertiles = 0.005; interaction pthird tertile = 0.008] with a similar trend for N‐terminal pro‐B‐type natriuretic peptide which was consistently reduced by spironolactone only in the lowest collagen cross‐linking tertile [mean differencesspiro/control: −0.47 (95% CI −0.66 to −0.28) and −0.31 (95% CI −0.59 to −0.04) ng/L; interaction pacross‐tertiles = 0.09; interaction pthird tertile < 0.001].ConclusionsThese findings suggest that, for patients at risk of HF, the effects of spironolactone on left atrial remodelling may be more prominent in patients with less collagen cross‐linking (indirectly assessed by serum CITP:MMP‐1).
Effect of n‐3 polyunsaturated fatty acid on bone health: A systematic review and meta‐analysis of randomized controlled trials
Authors: Dou Yuqi , Wang Ying , Chen Zekun , Yu Xue , Ma Defu 
Published: November 2021

AbstractBone metabolism is a complicated process, which involves bone modeling and remodeling. If this process is unbalanced, bone loss and resultant osteoporosis might occur. Recently, nutrition supplementations such as n‐3 polyunsaturated fatty acids (PUFAs) are considered to be used on improving the bone metabolism and reducing the risk of osteoporosis. To more precisely assess the effects of n‐3 PUFA supplementation on bone mass and clarify its potential mechanism, we have conducted a systematic review and meta‐analysis. Based on the strict inclusion and exclusion criteria, 12 articles were included in this meta‐analysis. The results in articles show that n‐3 PUFAs could slightly enhance the level of bone mineral density (BMD) (0.005 g/cm2; 95% CI, 0.000–0.010) (n = 7), which was the primary outcome for the research in comparison with the control group. In addition, the results also illustrate that the increasing effect on BMD (0.024 g/cm2; 95% CI, 0.020–0.028) became more significant for postmenopausal women. N‐3 PUFAs had no significance on the level of bone‐specific alkaline phosphatase (BALP) (−0.24 µg/L; 95% CI, −0.86 to 0.39) and osteocalcin (−0.63 μg/L; 95% CI, −1.84 to 0.57) (n = 5), which are the specific markers of bone formation. When compared with the eicosapentaenoic acid + docosahexaenoic acid supplementation, the supplementation form of α‐linolenic acid significantly increased the content of BALP (0.396 µg/L; 95% CI, 0.069–0.724). The effects of n‐3 PUFAs on bone resorption biomarkers containing type I collagen cross‐linked C‐terminal peptide (CTX) and type I collagen cross‐linked N‐terminal peptide (NTX) are considered and used in our study. Results indicated that participants who received n‐3 PUFAs significantly decreased the level of CTX in the human body (−0.367 μg/L; 95% CI, −0.726 to −0.007) (n = 4). However, there was no significant difference in NTX levels in humans after supplementation with n‐3 PUFA (−1.744 µg/L; 95% CI, −3.970–0.481) (n = 3). For postmenopausal women, it presented a significant decreasing level of CTX (−0.393 µg/L; 95% CI, −0.651 to −0.135) and NTX (−2.082 µg/L; 95% CI, −2.970 to −1.195) within their bodies. In conclusion, these findings suggested that n‐3 PUFAs might have a beneficial effect on bone health, especially for α‐linolenic acid supplementation form or for postmenopausal women.
Prediagnostic alterations in circulating bile acid profiles in the development of hepatocellular carcinoma
Authors: Stepien Magdalena , Lopez‐Nogueroles Marina , Lahoz Agustin , Kühn Tilman , Perlemuter Gabriel , Voican Cosmin , Ciocan Dragos , Boutron‐Ruault Marie‐Christine , Jansen Eugene , Viallon Vivian , Leitzmann Michael , Tjønneland Anne , Severi Gianluca , Mancini Francesca Romana , Dong Catherine , Kaaks Rudolf , Fortner Renee Turzanski , Bergmann Manuela M. , Boeing Heiner , Trichopoulou Antonia , Karakatsani Anna , Peppa Eleni , Palli Domenico , Krogh Vittorio , Tumino Rosario , Sacerdote Carlotta , Panico Salvatore , Bueno‐de‐Mesquita H. Bas , Skeie Guri , Merino Susana , Ros Raul Zamora , Sánchez Maria Jose , Amiano Pilar , Huerta Jose Mª , Barricarte Aurelio , Sjöberg Klas , Ohlsson Bodil , Nyström Hanna , Werner Marten , Perez‐Cornago Aurora , Schmidt Julie A. , Freisling Heinz , Scalbert Augustin , Weiderpass Elisabete , Christakoudi Sofia , Gunter Marc J. , Jenab Mazda 
Published: November 2021

AbstractBile acids (BAs) play different roles in cancer development. Some are carcinogenic and BA signaling is also involved in various metabolic, inflammatory and immune‐related processes. The liver is the primary site of BA synthesis. Liver dysfunction and microbiome compositional changes, such as during hepatocellular carcinoma (HCC) development, may modulate BA metabolism increasing concentration of carcinogenic BAs. Observations from prospective cohorts are sparse. We conducted a study (233 HCC case‐control pairs) nested within a large observational prospective cohort with blood samples taken at recruitment when healthy with follow‐up over time for later cancer development. A targeted metabolomics method was used to quantify 17 BAs (primary/secondary/tertiary; conjugated/unconjugated) in prediagnostic plasma. Odd ratios (OR) for HCC risk associations were calculated by multivariable conditional logistic regression models. Positive HCC risk associations were observed for the molar sum of all BAs (ORdoubling = 2.30, 95% confidence intervals [CI]: 1.76‐3.00), and choline‐ and taurine‐conjugated BAs. Relative concentrations of BAs showed positive HCC risk associations for glycoholic acid and most taurine‐conjugated BAs. We observe an association between increased HCC risk and higher levels of major circulating BAs, from several years prior to tumor diagnosis and after multivariable adjustment for confounders and liver functionality. Increase in BA concentration is accompanied by a shift in BA profile toward higher proportions of taurine‐conjugated BAs, indicating early alterations of BA metabolism with HCC development. Future studies are needed to assess BA profiles for improved stratification of patients at high HCC risk and to determine whether supplementation with certain BAs may ameliorate liver dysfunction.
Introduction of a Cys360Tyr Mutation in ANO5 Creates a Mouse Model for Gnathodiaphyseal Dysplasia
Authors: Li Hongyu , Wang Xiaoyu , Chen Erjun , Liu Xiu , Ma Xinrong , Miao Congcong , Tian Zhenchuan , Dong Rui , Hu Ying 
Published: November 2021

ABSTRACT
Gnathodiaphyseal dysplasia (GDD) is a rare autosomal dominant genetic disease characterized by the osteosclerosis of tubular bones and the formation of cemento-osseous lesions in mandibles. Although genetic mutations for GDD have been identified in the ANO5/TMEM16E gene, the cellular and molecular mechanisms behind the pathogenesis of GDD remain unclear. Here, we generated the first knock-in mouse model for GDD with the expression of human mutation p.Cys360Tyr in ANO5. Homozygous Ano5 knock-in mice (Ano5KI/KI) replicated GDD-like skeletal features, including massive jawbones, bowing tibia, bone fragility, sclerosis, and cortical thickening of the femoral and tibial diaphysis. Serum alkaline phosphatase (ALP) levels were elevated in Ano5KI/KI mice as in GDD patients with p.Cys360Tyr mutation. Calvaria-derived Ano5KI/KI osteoblast cultures showed increased osteoblastogenesis, including hypermineralized bone matrix and enhanced bone formation-related factors expression. Interestingly, Ano5KI/KI bone marrow-derived macrophage cultures showed decreased osteoclastogenesis, and Ano5KI/KI osteoclasts exhibited disrupted actin ring formation, which may be associated with some signaling pathways. In conclusion, this new mouse model may facilitate elucidation of the pathogenesis of GDD and shed more light on its treatment. © 2021 American Society for Bone and Mineral Research (ASBMR).
Comparison of Bougainvillea spectabilis and Bougainvillea glabra species inhibited in Pakistan based on microscopic studies: Light microscope and scanning electron microscope
Authors: Shaheen Shabnum , Khan Muhammad Asaf , Naeem Muhammad Afzal , Shahid Muhammad Naveed , Jaffer Mehwish , Mukhtar Hanan 
Published: November 2021

AbstractThe anatomical variations of two plants from the Nyctaginaceae family, Bougainvillea spectabilis and Bougainvillea glabra, were studied using light and scanning electron microscopy methods in this work. Bougainvillea is a dicotyledonous with defensive traits that can withstand extreme (hot and dry) settings; according to the findings, crystal inclusions in cells, woody spines, and an abnormal development pattern are all features that help them survive against predators and are unique to this species. The Bougainvillea plant's leaves are arranged in simple pattern, alternate to each other along stem having an undulate leaves edge and an oval form. The xylem and phloem, palisade, parenchyma midrib, spongy mesophyll, raphide crystal bundles, and trichomes were all visible when bracts and leaves were transversally sectioned and dyed with toluidine blue O (TBO). The presence of crystals was confirmed by a detailed examination of the transverse leaves by using bright‐field and cross‐polarizing microscopy. Dissecting microscopic examination showed that all the leaves revealed leaves venation pattern that had midvein, lateral veins areoles, and trichomes. Although trichomes have been identified on both sides, a closer look at a cleaned leaf dyed with TBO showed multicellular abundant trichomes on adaxial surface. Stomata complexes were typically found on the abaxial surface of the leaf according to epidermal peels. Present studies also showed that on adaxial side, stomata were lesser in number or were absent and also showed that the morphologies of the pavement cells on the adaxial and abaxial sides of the leaf differed.
Palyno‐morphological attributes of some selected plant species of family Asteraceae from district Dera Ismail Khan, KPK, Pakistan
Authors: Gul Farheen , Malik Khafsa , Qureshi Rahmatullah , Ahmad Mushtaq , Ansari Lubna , Zafar Muhammad , Hussain Sabtain , Khalid Sidra , Imran Muhammad , Rashid Neelam 
Published: November 2021

AbstractThe current study aimed to investigate the palyno‐morphological features of Asteraceous species from District Dera Ismail Khan, Khyber Pakhtunkhwa, Pakistan. A total of 13 species were collected, pressed, identified, and examined by using light and scanning electron microscopy. Both qualitative and quantitative pollen characters were observed, that is, equatorial and polar diameter, number of pores and colpi, exine thickness, exine sculpturing, pollen shape, and P/E ratio. Pollen shapes observed in studied taxa were spheroidal, suboblate, oblate‐spheroidal, and lophate‐spheroidal. The aperturation patterns of pollens vary from tricolporate to tetracolporate. The maximum polar and equatorial diameter of 75–100 (87.5 ± 13.6) μm and 87.5–117.5 (102.5 ± 16.4) μm, respectively, was recorded in Echinops echinatus, while minimum polar and equatorial diameter of 20–22.5 (21 ± 1.36) μm and 22.5–25 (23.5 ± 1.36) μm, respectively, was recorded in Aster subulatus. Six types of exine sculpturing patterns were observed; echinate, micro‐echinate, echinate‐microreticulate, microreticulate, echinate‐perforate, and scabrate. Maximum exine thickness of 8.75 μm was recorded in E. echinatus and minimum of 1.25 μm in Launaea mucronata. The pollen morphology has valuable significance in understanding the taxonomy of different plant groups and plays a central role in the correct identification and classification of Asteraceous flora at species, generic, and tribe levels.
Quantifying Bone Marrow Fat Fraction and Iron by MRI for Distinguishing Aplastic Anemia from Myelodysplastic Syndromes
Authors: Zeng Zhaolong , Ma Xiangzheng , Guo Yifan , Ye Baodong , Xu Maosheng , Wang Wei 
Published: November 2021

ROIs were manually drawn at the level containing the largest section of the left posterior superior ilium (A, B, D, E). The zoomed version of the ROIs showed in the upper left corner. (A, D) FF value of AA and MDS is 86.98% and 25.84%, respectively. (B, E) Iron content from R2*image is 117.91 and 147.98/second. (C, F) Histologic sections images of AA and MDS. Compared with MDS group (F), the number of fat cells (black arrow) in the AA group (C) was increased by Zeng et al. (1754–1760)
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Meta‐Analysis of Apparent Diffusion Coefficient in Pediatric Medulloblastoma, Ependymoma, and Pilocytic Astrocytoma
Authors: Dury Richard J. , Lourdusamy Anbarasu , Macarthur Donald C. , Peet Andrew C. , Auer Dorothee P. , Grundy Richard G. , Dineen Robert A. 
Published: November 2021

BackgroundMedulloblastoma, ependymoma, and pilocytic astrocytoma are common pediatric posterior fossa tumors. These tumors show overlapping characteristics on conventional MRI scans, making diagnosis difficult.PurposeTo investigate whether apparent diffusion coefficient (ADC) values differ between tumor types and to identify optimum cut‐off values to accurately classify the tumors using different performance metrics.Study typeSystematic review and meta‐analysis.SubjectsSeven studies reporting ADC in pediatric posterior fossa tumors (115 medulloblastoma, 68 ependymoma, and 86 pilocytic astrocytoma) were included following PubMed and ScienceDirect searches.Sequence and Field StrengthDiffusion weighted imaging (DWI) was performed on 1.5 and 3 T across multiple institution and vendors.AssessmentThe combined mean and standard deviation of ADC were calculated for each tumor type using a random‐effects model, and the effect size was calculated using Hedge's g.Statistical TestsSensitivity/specificity, weighted classification accuracy, balanced classification accuracy. A P value < 0.05 was considered statistically significant, and a Hedge's g value of >1.2 was considered to represent a large difference.ResultsThe mean (± standard deviation) ADCs of medulloblastoma, ependymoma, and pilocytic astrocytoma were 0.76 ± 0.16, 1.10 ± 0.10, and 1.49 ± 0.16 mm2/sec × 10−3. To maximize sensitivity and specificity using the mean ADC, the cut‐off was found to be 0.96 mm2/sec × 10−3 for medulloblastoma and ependymoma and 1.26 mm2/sec × 10−3 for ependymoma and pilocytic astrocytoma. The meta‐analysis showed significantly different ADC distributions for the three posterior fossa tumors. The cut‐off values changed markedly (up to 7%) based on the performance metric used and the prevalence of the tumor types.Data ConclusionThere were significant differences in ADC between tumor types. However, it should be noted that only summary statistics from each study were analyzed and there were differences in how regions of interest were defined between studies.Evidence Level1Technical EfficacyStage 3
MRI‐Based Multiple Instance Convolutional Neural Network for Increased Accuracy in the Differentiation of Borderline and Malignant Epithelial Ovarian Tumors
Authors: Jian Junming , Li Yong'ai , Xia Wei , He Zhang , Zhang Rui , Li Haiming , Zhao Xingyu , Zhao Shuhui , Zhang Jiayi , Cai Songqi , Wu Xiaodong , Gao Xin , Qiang Jinwei 
Published: November 2021

BackgroundPreoperative differentiation of borderline from malignant epithelial ovarian tumors (BEOT vs. MEOT) is challenging and can significantly impact surgical management.PurposeTo develop a multiple instance convolutional neural network (MICNN) that can differentiate BEOT from MEOT, and to compare its diagnostic performance with that of radiologists.Study TypeRetrospective study of eight clinical centers.SubjectsBetween January 2010 and June 2018, a total of 501 women (mean age, 48.93 ± 14.05 years) with histopathologically confirmed BEOT (N = 165) or MEOT (N = 336) were divided into the training (N = 342) and validation cohorts (N = 159).Field Strength/SequenceThree axial sequences from 1.5 or 3 T scanner were used: fast spin echo T2‐weighted imaging with fat saturation (T2WI FS), echo planar diffusion‐weighted imaging, and 2D volumetric interpolated breath‐hold examination of contrast‐enhanced T1‐weighted imaging (CE‐T1WI) with FS.AssessmentThree monoparametric MICNN models were built based on T2WI FS, apparent diffusion coefficient map, and CE‐T1WI. Based on these monoparametric models, we constructed an early multiparametric (EMP) model and a late multiparametric (LMP) model using early and late information fusion methods, respectively. The diagnostic performance of the models was evaluated using the receiver operating characteristic (ROC) curve and compared to the performance of six radiologists with varying levels of experience.Statistical TestsWe used DeLong test, chi‐square test, Mann–Whitney U‐test, and t‐test, with significance level of 0.05.ResultsBoth EMP and LMP models differentiated BEOT from MEOT, with an area under the ROC curve (AUC) of 0.855 (95% CI, 0.795–0.915) and 0.884 (95% CI, 0.831–0.938), respectively. The AUC of the LMP model was significantly higher than the radiologists' pooled AUC (0.884 vs. 0.797).Data ConclusionThe developed MICNN models can effectively differentiate BEOT from MEOT and the diagnostic performances (AUCs) were more superior than that of the radiologists' assessments.Level of Evidence3Technical Efficacy Stage2
Inter‐comparison of historical simulation and future projections of rainfall and temperature by CMIP5 and CMIP6 GCMs over Egypt
Authors: Hamed Mohammed Magdy , Nashwan Mohamed Salem , Shahid Shamsuddin 
Published: November 2021

AbstractThe global climate models (GCMs) performances of the recently released Coupled Model Intercomparison Project phase 6 (CMIP6) compared to its predecessor, CMIP5, are evaluated to anticipate the expected changes in climate over Egypt. Thirteen GCMs and their multi‐model ensemble (MME) of both CMIPs were used for this purpose. The future projections were compared for two radiative concentration pathways (RCP 4.5 and 8.5) and two shared socio‐economic pathways (SSP 2–4.5 and 5–8.5). The results revealed improvement in most CMIP6 models in replicating historical rainfall, maximum temperature (Tmax), and minimum temperature (Tmin) climatology over Egypt. The MME of the CMIPs revealed that both could reproduce Egypt's spatial distribution and seasonal climate variability. However, the bias in CMIP5 was higher than that for CMIP6. The uncertainties in simulating seasonal variability of rainfall and temperatures were lower for CMIP6 compared to CMIP5. The future projection of rainfall using CMIP6 MME revealed a higher reduction of precipitation (10–26 mm) in the economically crucial northern region than that estimated using CMIP5 (0–17 mm), compared to 133.5 mm rainfall in the base period. CMIP6 also projected a 0.74–1.63°C more rise in Tmax and Tmin compared to CMIP5 by the end of the century. The study indicates more aggravated scenarios of climate changes in Egypt than anticipated earlier, using the CMIP5 models. Therefore, Egypt needs to streamline the existing adaptation and mitigation measures to account for climate projections.