bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Association of Cold Ambient Temperature With Fracture Risk and Mortality: National Data From Norway—A Norwegian Epidemiologic Osteoporosis Studies (NOREPOS) Study
Authors: Dahl Cecilie , Madsen Christian , Omsland Tone Kristin , Søgaard Anne-Johanne , Tunheim Ketil , Stigum Hein , Holvik Kristin , Meyer Haakon E. 
Published: June 2022

ABSTRACT
Norway is an elongated country with large variations in climate and duration of winter season. It is also a high-risk country for osteoporotic fractures, in particular hip fractures, which cause high mortality. Although most hip fractures occur indoors, there is a higher incidence of both forearm and hip fractures during wintertime, compared with summertime. In a nationwide longitudinal cohort study, we investigated whether cold ambient (outdoor) temperatures could be an underlying cause of this high incidence and mortality. Hospitalized/outpatient forearm fractures (International Classification of Diseases and Related Health Problems, 10th Revision [ICD-10] code S52) and hospitalized hip fractures (ICD-10 codes S72.0–S72.2) from 2008 to 2018 were retrieved from the Norwegian Patient Registry. Average monthly ambient temperatures (degrees Celsius, °C) from the years 2008 to 2018 were provided by the Norwegian Meteorological Institute and linked to the residential area of each inhabitant. Poisson models were fitted to estimate the association (incidence rate ratios [IRRs], 95% confidence intervals [CIs]) between temperature and monthly incidence of total number of forearm and hip fractures. Flexible parametric survival models (hazard ratios [HR], 95% CI) were used to estimate the association between temperature and post–hip fracture mortality, taking the population mortality into account. Monthly temperature ranged from −20.2°C to 22.0°C, with a median of −2.0°C in winter and 14.4°C in summer. At low temperatures (&lt;0°C) compared to ≥0°C, there was a 53% higher risk of forearm fracture (95% CI, 51%–55%) and 21% higher risk of hip fracture (95% CI, 19%–22%), adjusting for age, gender, calendar year, urbanization, residential region, elevation, and coastal proximity. When taking the population mortality into account, the post–hip fracture mortality in both men (HR 1.08; 95% CI, 1.02–1.13) and women (HR 1.09; 95% CI, 1.04–1.14) was still higher at cold temperatures. There was a higher risk of forearm and hip fractures, and an excess post–hip fracture mortality at cold ambient temperatures. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).
Osteoclasts and Macrophages—Their Role in Bone Marrow Cavity Formation During Mouse Embryonic Development
Authors: Tosun Benjamin , Wolff Lena Ingeborg , Houben Astrid , Nutt Stephen , Hartmann Christine 
Published: June 2022

ABSTRACTThe formation of the bone marrow cavity is a prerequisite for endochondral ossification. In reviews and textbooks, it is occasionally reported that osteoclasts are essential for bone marrow cavity formation removing hypertrophic chondrocytes. Mice lacking osteoclasts or having functionally defective osteoclasts have osteopetrotic bones, yet they still form a bone marrow cavity. Here, we investigated the role of osteoclasts and macrophages in bone marrow cavity formation during embryogenesis. Macrophages can assist osteoclasts in matrix removal by phagocytosing resorption byproducts. Rank-deficient mice, lacking osteoclasts, and Pu.1-deficient mice, lacking monocytes, macrophages, and osteoclasts, displayed a delay in bone marrow cavity formation and a lengthening of the zone of hypertrophic chondrocytes. F4/80-positive monocyte/macrophage numbers increased by about fourfold in the bone marrow cavity of E18.5 Rank-deficient mice. Based on lineage-tracing experiments, the majority of the excess F4/80 cells were derived from definitive hematopoietic precursors of the fetal liver. In long bones of both Rank−/− and Pu.1−/− specimens, Mmp9-positive cells were still present. In addition to monocytes, macrophages, and osteoclasts, Ctsb-positive septoclasts were lost in Pu.1−/− specimens. The mineralization pattern was altered in Rank−/− and Pu.1−/− specimens, revealing a significant rise in transverse-oriented mineralized structures. Taken together, our findings imply that early on during bone marrow cavity formation, osteoclasts facilitate the entry of blood vessels and later the turnover of hypertrophic chondrocytes, whereas macrophages appear to play no major role. Furthermore, the absence of septoclasts in Pu.1−/− specimens suggests that septoclasts are either derived from Pu.1-dependent precursors or require PU.1 activity for their differentiation. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).
Bone Turnover Markers Including Undercarboxylated Osteocalcin Are Associated With Mortality Risk in Older Men
Authors: Robertson Courtney L , Ghosh Gaurav , Fitzgerald Patrick , Hankey Graeme J , Levinger Itamar , Golledge Jonathan , Almeida Osvaldo P , Flicker Leon , Ebeling Peter R , Yeap Bu B 
Published: June 2022

ABSTRACT
Osteocalcin in its undercarboxylated form (ucOC) may influence diabetes risk; however, its relationship with all-cause and cause-specific mortality is unclear. Whether other bone turnover markers (BTMs) are associated with mortality risk differently from ucOC also remains uncertain. Our aim was to determine associations of serum ucOC with all-cause and cause-specific mortality and compare these with the corresponding associations of serum total osteocalcin (TOC), procollagen type I N-propeptide (PINP), and collagen type 1 C-terminal cross-linked telopeptide (CTX) in older men. We conducted a prospective cohort study of 3871 community-dwelling men, aged 77.0 ± 3.6 years at baseline, followed for a median of 12.3 years. Exposure variables were ucOC, TOC, PINP, and CTX concentrations assayed in serum. Outcomes were incidence of all deaths and deaths due to cardiovascular disease (CVD) or cancer, ascertained using death registry data. Cox regression analyses adjusted for cardiovascular risk factors and prevalent CVD and for prevalent cancer in analyses of cancer-related mortality. Higher concentrations of ucOC, PINP, and CTX were associated with all-cause mortality (hazard ratio [HR] per 1 standard deviation increase: ucOC 1.12, 95% confidence interval [CI] 1.06–1.18, p &lt; 0.001; PINP HR = 1.06, 95% CI 1.01–1.11, p = 0.009; CTX HR = 1.13, 95% CI 1.08–1.19, p &lt; 0.001), but TOC was not associated. Similar results were found after excluding men with an incident fracture during follow-up. Higher ucOC and CTX were associated with CVD mortality (ucOC HR per 1 SD increase 1.13, 95% CI 1.05–1.22, p = 0.001; CTX HR = 1.12, 95% CI 1.04–1.20, p = 0.003), but this result was not significant in competing risks analysis. Higher CTX was also associated with cancer mortality (HR = 1.12, 95% CI 1.01–1.23, p = 0.024). In conclusion, in older men, higher bone turnover, assessed by BTMs including ucOC, is a biomarker for all-cause mortality risk. Undercarboxylated osteocalcin was a more informative biomarker for this outcome than TOC. Higher CTX was associated with all-cause and cancer-related mortality. Further evaluation of causality and potential underlying mechanisms is warranted. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).
Identifying Causes of Fracture Beyond Bone Mineral Density: Evidence From Human Genetics
Authors: Lu Tianyuan , Forgetta Vincenzo , Greenwood Celia M.T. , Richards J. Brent 
Published: June 2022

ABSTRACT
New therapies may help to prevent osteoporotic fractures other than through increasing bone mineral density (BMD). Because fracture risk has an important genetic component, we aim to identify loci increasing fracture risk that do not decrease BMD, using a recently-proposed structural equation model adapted to remove genetic influences of BMD on fracture risk. We used summary statistics of the largest genome-wide association studies (GWASs) for BMD and for fracture in these analyses. We next estimated the genetic correlation between the non-BMD or BMD-related genetic effects and other clinical risk factors for fracture. Last, based on white British participants in the UK Biobank, we conducted genetic risk score analyses to assess whether the aggregated genetic effects conferred increased major osteoporotic fracture risk. We found that only three loci affecting fracture risk exhibited genetic effects not mediated by BMD: SOST, CPED1-WNT16, and RSPO3, while these three loci simultaneously conferred BMD-related effects. No strong genetic associations between non-BMD or BMD-related effects and 16 clinical risk factors were observed. However, non-BMD effects might be genetic correlated with hip bone size. In the UK Biobank, a 1 standard deviation (1-SD) increase in the non-BMD genetic risk score conferred an odds ratio of 1.17 for incident major osteoporotic fracture, compared to 1.29 by a BMD-related genetic risk score. Our study suggests that the majority of common genetic predisposition toward fracture risk acts upon BMD. Although non-BMD genetic effects may exist, they are not strongly correlated with most traditional clinical risk factors. Risk loci harboring non-BMD genetic effects may influence other perspectives of bone quality, or confer effects that existing GWASs fail to capture, but they demonstrate weaker impact on fracture risk than BMD-related genetic effects. These findings suggest that most successful drug development programs for osteoporosis should focus on pathways identified through BMD-associated loci. © 2022 American Society for Bone and Mineral Research (ASBMR).
A re‐examination of analysts versus time‐series extrapolation of quarterly earnings: Superiority in accuracy and earning expectation proxy
Authors: Li Tao , Yu Ji , Liu Zenghui 
Published: June 2022

AbstractWe document findings that earning extrapolation based on seasonal random trend (SRT) model is not inferior to analysts’ quarterly earnings forecasts, which contradicts the belief that analysts are superior to time‐series models. Our findings suggest that while the frequency of analysts beating SRT extrapolations is greater than 50%, the marginal accuracy improvement is weak. Analysts’ forecasts contain larger absolute forecast error and significant pessimistic bias than SRT extrapolation. Prior studies attribute the superiority of analysts’ forecasts in proxying for earnings expectation to its higher accuracy. Given that the SRT extrapolations have lower average forecast error, we explore whether market participants use them to develop earnings expectations. Our findings indicate that the market anchors to analysts’ forecasts and treats SRT extrapolations as supplemental.
Arctigenin inhibits apoptosis, extracellular matrix degradation, and inflammation in human nucleus pulposus cells by up‐regulating miR‐483‐3p
Authors: Ji Zhe , Guo Rui , Ma Zhigang , Li Hongwei 
Published: June 2022

AbstractBackgroundArctigenin (ATG) is the active ingredient of the Chinese herbal medicine Arctium lappa, with anti‐inflammatory and antioxidant effects. Excessive inflammation and cell apoptosis are important causes of intervertebral disc degeneration (IDD). Hence, this study probed into the possible role of ATG in IDD.MethodsInterleukin (IL)‐1β (10 ng/ml) was adopted to induce human nucleus pulposus cells (HNPCs) as a cell model for IDD. The effects of different concentrations of ATG (0, 2, 5, 10, 20, 50 μmol/L) on the viability of HNPCs and effects of ATG (10, 50 μmol/L) on the viability of IL‐1β‐induced HNPCs were detected by cell counting kit‐8 (CCK‐8). After IL‐1β‐induced HNPCs were transfected with miR‐483‐3p inhibitor and/or treated with ATG, cell viability and apoptosis were determined by CCK‐8 and flow cytometry; the expressions of miR‐483‐3p, extracellular matrix (ECM)‐related genes, and inflammation‐related genes were measured by quantitative real time polymerase chain reaction (qRT‐PCR), and expressions of ECM/apoptosis/NF‐κB pathway‐related proteins were quantified by Western blot.ResultsATG had no significant effect on the viability of HNPCs but could promote the viability of IL‐1β‐induced HNPCs. ATG inhibited apoptosis, ECM degradation, inflammation, and activation of NF‐κB pathway in HNPCs induced by IL‐1β, but promoted the expression of miR‐483‐3p. MiR‐483‐3p inhibitor reversed the above‐mentioned regulatory effects of ATG.ConclusionArctigenin suppresses apoptosis, ECM degradation, inflammation, and NF‐κB pathway activation in HNPCs by up‐regulating miR‐483‐3p.
RNA demethylase ALKBH5 regulates hypopharyngeal squamous cell carcinoma ferroptosis by posttranscriptionally activating NFE2L2/NRF2 in an m6A‐IGF2BP2‐dependent manner
Authors: Ye Jing , Chen Xiaozhen , Jiang Xiaohua , Dong Zhihuai , Hu Sunhong , Xiao Mang 
Published: June 2022

AbstractBackgroundHaving emerged as the most abundant posttranscriptional internal mRNA modification in eukaryotes, N6‐methyladenosine (m6A) has attracted tremendous scientific interest in recent years. However, the functional importance of the m6A methylation machinery in ferroptosis regulation in hypopharyngeal squamous cell carcinoma (HPSCC) remains unclear.MethodsWe herein performed bioinformatic analysis, cell biological analyses, transcriptome‐wide m6A sequencing (m6A‐seq, MeRIP‐seq), RNA sequencing (RNA‐seq), and RNA immunoprecipitation sequencing (RIP‐seq), followed by m6A dot blot, MeRIP‐qPCR, RIP‐qPCR, and dual‐luciferase reporter assays.ResultsThe results revealed that ALKBH5‐mediated m6A demethylation led to the posttranscriptional inhibition of NFE2L2/NRF2, which is crucial for the regulation of antioxidant molecules in cells, at two m6A residues in the 3′‐UTR. Knocking down ALKBH5 subsequently increased the expression of NFE2L2/NRF2 and increased the resistance of HPSCC cells to ferroptosis. In addition, m6A‐mediated NFE2L2/NRF2 stabilization was dependent on the m6A reader IGF2BP2. We suggest that ALKBH5 dysregulates NFE2L2/NRF2 expression in HPSCC through an m6A‐IGF2BP2‐dependent mechanism.ConclusionTogether, these results have revealed an association between the ALKBH5‐NFE2L2/NRF2 axis and ferroptosis, providing insight into the functional importance of reversible mRNA m6A methylation and its modulators in HPSCC.
Longitudinal change of Th1, Th2, and Th17 cells and their relationship between cognitive impairment, stroke recurrence, and mortality among acute ischemic stroke patients
Authors: Yu Shijian , Cui Wei , Han Jingfeng , Chen Jiawei , Tao Weiping 
Published: June 2022

AbstractBackgroundT‐helper (Th) cells regulate immunity and inflammation, and modulate cognitive impairment in both cardio‐cerebrovascular and neurological diseases. This study aimed to explore the correlation of longitudinal change of Th1/2/17 cells with cognitive impairment and prognosis in acute ischemic stroke (AIS).MethodsTh1/2/17 cells were detected by flow cytometry in peripheral blood samples from 150 AIS patients at admission (baseline), Day (D)1, D3, and D7 after admission, and from 30 controls. Mini‐Mental State Examination (MMSE) score among AIS patients at discharge was assessed. Stroke recurrence and mortality were evaluated.ResultsTh1 (p = 0.013) and Th17 cells (p < 0.001) but not Th2 cells (p = 0.105) were elevated in AIS patients versus controls. Th1 cells (p = 0.027) and Th17 cells (p < 0.001) but not Th2 cells (p = 0.227) were positively correlated with NIHSS score in AIS patients. Furthermore, Th1 and Th17 cells elevated from baseline to D3 and then decreased on D7 after AIS onset, while Th2 cells illustrated an opposite trend (all p < 0.001). Th17 cells on D1 (p = 0.011), D3 (p = 0.014), and D7 (p < 0.001) were correlated with lower MMSE score, and their levels on D3 (p = 0.033) and D7 (p = 0.004) were related to elevated cognitive impairment. Th1 and Th2 cells were not related to cognitive function (all p > 0.05). Additionally, Th17 cells at baseline, D1, D3, and D7 (all p < 0.05) were increased in recurrent patients versus non‐recurrent patients, and in survived patients versus dead patients, but Th1 or Th2 cells did not vary (all p > 0.05).ConclusionTh17 cells correlate with increased cognitive impairment, stroke recurrence, and mortality among AIS patients.
Facile synthesis and antimicrobial activity of bis(fused 4H‐pyrans) incorporating piperazine as novel hybrid molecules: Michael's addition approach
Authors: Salem Mostafa E. , Fares Ibrahim M. Z. , Ghozlan Said A. S. , Abdel‐Aziz Marwa M. , Abdelhamid Ismail A. , Elwahy Ahmed H. M. 
Published: June 2022

AbstractA new series of bis(4H‐chromene), bis (pyrano[3,2‐c]chromene), and bis (pyrano[2,3‐c]pyrazole) each linked to the piperazine core via ether linkages was synthesized. The target compounds are probably formed through a three‐component reaction involving two equivalents of each malononitrile and the corresponding active methylene compounds, such as dimedone, 4‐hydroxycoumarine, or 5‐methyl‐2,4‐dihydro‐3H‐pyrazol‐3‐one. Several spectral methods and elemental analyses were used to deduce the chemical structures of the novel compounds. Furthermore, all synthesized compounds were tested for antimicrobial activity, which revealed promising inhibitory results against a variety of multidrug‐resistant microbial strains. These findings were compared to those obtained in the in silico molecular docking study. The docking results improved the activity of new derivatives as potentially effective antimicrobial agents.
Information entropy‐based projection of temperature variability under the warming trend in China
Authors: Sun Meiping , Zhang Haiyan , Yao Xiaojun , Zhang Mingjun , Xing Qiaofeng 
Published: June 2022

AbstractQuantifying the predictability of temperature in the future is a priority to inform policy and adaptation planning. Based on information entropy theory, this study uses global climate models within the Coupled Model Intercomparison Project Phase 6 (CMIP6) to project spatiotemporal changes and variability of temperature in China in the 21st century under different shared socio‐economic pathway scenarios (SSP2‐4.5 and SSP5‐8.5). Results show that the multimodel ensembled values can accurately capture the spatiotemporal pattern of temperature in China. The warming rates of annual mean temperature in China under SSP2‐4.5, SSP5‐8.5 scenarios are 0.42 and 0.61°C·decade−1 in the near‐term (2021–2050), 0.20 and 0.87°C·decade−1 in the long‐term (2071–2100), respectively. Warming is found to be the greatest in winter. Northeast, northwest, and the first region of southwest are anticipated to increase particularly rapidly, with larger increases than the rest of China. The intrayear variability of temperature (the variability of monthly mean temperature within the year or different seasons) in China shows obvious latitudinal differences. The variability of monthly mean temperature exhibits a decreasing trend in parts of northeast and the first region of southwest, and an increasing trend in northwest and parts of north. This is mainly resultant from the variability of monthly mean temperatures within spring and autumn. And this trend is more significant under the SSP5‐8.5 scenario than that under the SSP2‐4.5 scenario. The interannual variability of temperature (the variability of annual or seasonal mean temperature) in China shows significant regional difference, and two obvious regions with extreme variability (northeast and the first region of southwest). The trend of variability increases and then decreases under the SSP2‐4.5 scenario, whereas it keeps increasing under the SSP5‐8.5 scenario. This study helps to understand the spatiotemporal characteristics of temperature variability in China in the 21st century.
Anthropogenic influence on extreme temperature changes over the mid–high latitudes of Asia
Authors: Jiang Wenhao , Chen Huopo , Shi Zuoqiao 
Published: June 2022

AbstractThe influence of anthropogenic (ANT) activity and the other external factors on extreme temperature changes over the mid–high latitudes of Asia are analysed using the different forcing simulations from the Coupled Model Intercomparison Project Phase 6 (CMIP6) models. The optimal fingerprinting technique and the probability ratio (PR) are employed to detect and quantify the influences of the external forcings on extreme temperature changes, which include annual maximum daily maximum temperature (TXx) and annual minimum daily minimum (TNn) temperature. Results indicate that TXx and TNn have increased from 1979 to 2014, and the simulations from historical (anthropogenic plus natural; ALL), greenhouse gas (GHG), and anthropogenic (ANT) experiments reasonably reproduce the spatiotemporal characteristics of extreme temperatures. Based on the optimal fingerprinting method, the impact of ANT forcing, in which GHG forcing is critical, can be detected in the changes of warm extremes and cold extremes. ANT and NAT forcings are separately detectable for warm extremes. GHG forcing can be separated from other ANT forcings for cold extremes but not warm extremes. Furthermore, the analysis applying the PR method shows that the probability of observed warm extremes that occur once in 20 years over the mid–high latitudes of Asia has risen by approximately three times owing to the anthropogenic influence, whereas the cold extremes became once in 50 years. Briefly, the increased anthropogenic activity has exacerbated the warm extremes and soothed the cold extremes over the mid–high latitudes of Asia during the past decades.
Future changes in the transitions of monthly‐to‐seasonal precipitation extremes over the Midwest in Coupled Model Intercomparison Project Phase 6 models
Authors: Chen Liang , Ford Trent W. 
Published: June 2022

AbstractPrecipitation extremes present significant risks to Midwest agriculture, water resources, and natural ecosystems. Recently, there is growing attention to the transitions of precipitation extremes, or shifts between heavy precipitation and drought, due to their profound environmental and socio‐economic impacts. Changes in Midwest precipitation extremes and transitions between extremes over the past few decades have been documented; however, their future changes are still unknown. In this study, we estimate the projected changes in transitions of precipitation extremes in the Midwest based on 17 CMIP6 models. Two Standardized Precipitation Index (SPI) based metrics, intra‐annual variability and transitions, are used to quantify the magnitude, duration, and frequency of variability and transitions between wet and dry extremes. Compared with the observation‐based precipitation datasets, the multimodel ensemble median of CMIP6 can reasonably represent the spatial patterns of SPI extremes and transitions. Climate projections show significantly intensified wet extremes across the Midwest by the end of the century, with a greater increase over the northern Midwest and the Great Lakes region. The short‐term SPI also shows intensified dry extremes over the western half of the Midwest. Consequently, there is a significant increase in the magnitude of intra‐annual variability in most areas. Projections also suggest more frequent and rapid transitions between the wet and dry extremes, especially over the Great Lakes region and northern Midwest. Seasonally, more frequent transitions from a wet spring to a dry summer (or from a dry fall to a wet winter/spring) are projected to occur; and generally, the wet and dry conditions between the transitions are projected to be more intense compared to the historical period. Furthermore, the intensified precipitation extremes and accelerated transitions are greatly alleviated under a lower emission scenario, implying that future changes in hydroclimate extremes, and impacts thereof, in the Midwest are sensitive to climate change mitigation.