bluuebunny/crossref_metadata_2025 huggingface dataset:
The Impact of Various Anti-Osteoporosis Drugs on All-Cause Mortality After Hip Fractures: A Nationwide Population Study
Authors: Tai Ta-Wei , Hwang Jawl-Shan , Li Chia-Chun , Hsu Jason C. , Chang Chih-Wei , Wu Chih-Hsing
Published: June 2022

Anti-osteoporosis treatment following hip fractures may reduce the overall mortality rate. However, the effects of different drugs on mortality is still unclear. This population-based cohort study aimed to identify the degree of reduced mortality after various anti-osteoporosis regimens following hip fracture surgery. We conducted this cohort study to identify patients with newly diagnosed osteoporosis and hip fractures from 2009 to 2017 using the Taiwan National Health Insurance Research Database (NHIRD). The subsequent use of anti-osteoporosis medication following hip fracture surgery was collected and analyzed. National death registration records were retrieved to determine mortality. A total of 45,226 new cases of osteoporotic hip fracture were identified. Compared with patients who did not receive further treatment, patients who had ever used oral bisphosphonates (alendronate and risedronate, hazard ratio [HR] 0.81; 95% confidence interval [CI], 0.78–0.84), ibandronate (HR 0.76; 95% CI, 0.67–0.86), zoledronic acid (HR 0.70; 95% CI, 0.64–0.76), and denosumab (HR 0.64; 95% CI, 0.60–0.68) showed lower all-cause mortality rates. Patients treated with bisphosphonates had a lower mortality risk than those treated with selective estrogen receptor modulators (HR 0.81; 95% CI, 0.75–0.87). Patients treated with zoledronic acid showed a lower mortality risk than those treated with oral bisphosphonates (HR 0.89; 95% CI, 0.82–0.97). However, patients receiving denosumab and zoledronic acid did not show a significant difference in mortality (HR 0.94; 95% CI, 0.85–1.03). Different anti-osteoporosis treatments for postsurgical patients were associated with different levels of decline in mortality. Generally, longer durations of drug use were associated with lower mortality. © 2022 American Society for Bone and Mineral Research (ASBMR).
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

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 (<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

The 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

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 < 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 < 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

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

We 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

Background

Arctigenin (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.

Methods

Interleukin (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.

Results

ATG 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.

Conclusion

Arctigenin 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

Background

Having 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.

Methods

We 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.

Results

The 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.

Conclusion

Together, 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

Background

T‐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).

Methods

Th1/2/17 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.

Results

Th1 (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).

Conclusion

Th17 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

A 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

Quantifying 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

The 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

Precipitation 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.
Patellofemoral joint load and knee abduction/adduction moment are sensitive to variations in femoral version and individual muscle forces
Authors: Wheatley Benjamin B. , Chaclas Nathan A. , Seeley Mark A.
Published: June 2022

Torsional profiles of the lower limbs, such as femoral anteversion, can dictate gait and mobility, joint biomechanics and pain, and functional impairment. It currently remains unclear how the interactions between femoral anteversion, kinematics, and muscle activity patterns contribute to joint biomechanics and thus conditions such as knee pain. This study presents a computational modeling approach to investigating the interactions between femoral anteversion, muscle forces, and knee joint loads. We employed an optimal control approach to produce actuator and muscle‐driven simulations of the stance phase of gait for femoral anteversion angles ranging from −8° (retroversion) to 52° (anteversion) with a typically developing baseline of 12° of anteversion and implemented a Monte Carlo analysis for variations in lower limb muscle forces. While total patellofemoral joint load decreased with increasing femoral anteversion, patellofemoral joint load alignment worsened, and knee abduction/adduction magnitude increased with both positive and negative changes in femoral anteversion (p < 0.001). The rectus femoris muscle was found to greatly influence patellofemoral joint loads across all femoral anteversion alignments (R > 0.8, p < 0.001), and the medial gastrocnemius was found to greatly influence knee abduction/adduction moments for the extreme version cases (R > 0.74, p < 0.001). Along with the vastus lateralis, which decreased with increasing femoral anteversion (R = 0.89, p < 0.001), these muscles are prime candidates for future experimental and clinical efforts to address joint pain in individuals with extreme femoral version. These findings, along with future modeling efforts, could help clinicians better design treatment strategies for knee joint pain in populations with extreme femoral anteversion or retroversion.
Overview of the recent studies on high‐pressure impurity ices
Authors: Yoshimura Yukihiro
Published: June 2022

In the present short review, we briefly overview the history of ice polymorphism under high‐pressure and the recent progress on impurity ices (clathrate ice, salty ice, doped ice, empty ice, etc.), including our contributions due form high‐pressure Raman investigations to these research fields. In particular, the unique roles of impurities in ice, which are (1) acceleration of proton ordering at lower temperatures, (2) offering a clue to form new ice phases, and (3) phase transitions other than the original equilibrium stability region of pure H2O, ice are introduced. Then, as prospects, we address promising impacts on a new area of ice physics with the active use of impurities.
Astaxanthin absorption modulated antioxidant enzyme activity and targeted specific metabolic pathways in rats
Authors: Jia Zhe , Song Ru , Xu Yan , Liu Xinyan , Zhang Xiaoxia
Published: June 2022

BACKGROUND

Saponification contributed to an increase in the in vitro antioxidant activity of astaxanthin (Asta) extracts derived from Penaeus sinensis (Solenocera crassicornis) by‐products. However, the influence of non‐saponification (N‐Asta) and saponification Asta (S‐Asta) absorption on antioxidant activity in vivo was limited. The antioxidant properties of N‐Asta and S‐Asta were therefore compared in Sprague Dawley male rats after 6 h and 12 of absorption using biochemistry assays combined with an untargeted metabonomics strategy.

RESULTS

Non‐saponified Asta and S‐Asta showed similar digestive properties in a stimulated gastrointestinal tract. Increased glutathione content and decreased malondialdehyde content were measured in the liver tissues of N‐Asta and S‐Asta treated rats after 12 h of absorption. Absorption of N‐Asta increased liver total superoxide dismutase, glutathione peroxidase, and catalase activity. Treatment with S‐Asta up‐regulated NAD(P)H: quinine oxidoreductase‐1, and heme oxygenase‐1 expression was associated with the nuclear erythroid 2‐related factor 2/antioxidant responsive element pathway at the end of 12 h absorption. With partial least square‐discriminant analysis and metabolite heatmap profiles, the S‐Asta group was clearly separated from the N‐Asta group. The S‐Asta treatment also demonstrated stronger influences on plasma metabolites than the N‐Asta treatment. Both N‐Asta and S‐Asta absorption showed critical roles in the regulation of specific metabolites, and 15 potential biomarkers were identified in eight key pathways to separate these experimental groups after 12 h of absorption. However, an increased serotonin level was only detected in the S‐Asta group after 12 h absorption.

CONCLUSION

Absorption of N‐Asta and S‐Asta induced different antioxidant effects in normal rats, which were associated with metabolite changes. © 2022 Society of Chemical Industry.
Gastroprotective effects of Caragana ambigua stocks on ethanol‐induced gastric ulcer in rats supported by LC–MS/MS characterization of formononetin and biochanin A
Authors: Rubab Faryal , Ijaz Hira , Hussain Shah , Munir Ans , Stuppner Stefan , Jakschitz Thomas , Bonn Günther K , Ishtiaq Saiqa
Published: June 2022

BACKGROUND

Caragana ambigua has been the part of the dietary routines of the regional people in south‐west Pakistan and has traditionally been used for the treatment of diabetes there. There is an increased production of reactive oxygen species in diabetics, leading to gastrointestinal disorders. Natural antioxidants exhibit gastroprotective effects owing to their free‐radical scavenging action. C. ambigua possesses appreciable phenolic and flavonoid content; thus, it has the potential to protect against gastrointestinal disorders (e.g. gastric ulcer).

RESULTS

This study reports the anti‐ulcer potential of C. ambigua. Four different fractions (chloroform, ethyl acetate, butanol, and aqueous) of plant were compared against omeprazole. Ulcer index, ulcer inhibition percentage, gastric pH and volume, total acidity, gastric protein, gastric wall mucus, and histopathology of gastric walls of rats were assessed. All fractions exhibited a reduction in ulcer index and promotion of percentage of ulcer inhibition compared with the ulcer control group. Furthermore, the fractions revealed a significant (P < 0.001) diminution in gastric volume and total acidity with an increase in pH. Among the fractions investigated, the chloroform fraction unveiled the most promising anti‐ulcer activity, which is comparable to omeprazole. Liquid chromatography–tandem mass spectrometry screening of fractions revealed the presence of formononetin and biochanin A (isoflavones reported to have anti‐ulcer properties) in the chloroform fraction.

CONCLUSION

This study establishes that C. ambigua possesses significant potential in reducing gastric ulcer progression. Formononetin and biochanin A are chiefly responsible for the stated bioactivity due to the fact that these compounds were solely present in the chloroform fraction. © 2022 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.
Application of albumin‐bilirubin grade and platelet count to indocyanine green‐based criteria for hepatectomy: Predicting impaired liver function and postoperative outcomes of hepatocellular carcinoma
Authors: Takamoto Takeshi , Nara Satoshi , Ban Daisuke , Nagashima Daisuke , Mizui Takahiro , Esaki Minoru , Shimada Kazuaki
Published: June 2022

Background

Applicability of the albumin‐bilirubin (ALBI) grade in preoperative decision‐making criteria based on the indocyanine green retention (ICG) test remains unclear. This study aimed to predict abnormal ICG values using standard blood tests and evaluate the impact on postoperative outcomes among patients undergoing hepatectomy for hepatocellular carcinoma (HCC).

Methods

Data on 949 consecutive HCC patients undergoing curative‐intent hepatectomy between 1996 and 2014 were retrospectively assessed. A nomogram using preoperative standard blood tests was created to predict abnormal ICGR15 (>15%).

Results

Three‐hundred nine patients had abnormal ICGR15. Predictors of abnormal ICGR15 included in the nomogram were: ALBI grade >1 (hazard ratio [HR]: 2.16, 95% confidence interval [CI]: 1.59–2.94), platelet count <130 000/mm3 (HR: 2.27, 95% CI: 1.68–3.08), aspartate aminotransferase >50 (IU/L) (HR: 1.90, 95% CI: 1.29–2.81), and viral hepatitis infection (HR: 1.46, 95% CI: 1.03–2.07). The nomogram named the PLT‐ALBI score was discriminative [C‐statistics: 0.719 (0.684–0.754)], and reliable (Hosmer‐Lemeshow Chi‐Square: 9.05, p = 0.338). The higher PLT‐ALBI score was associated with a more frequent incidence of clinically relevant posthepatectomy liver failure and poor overall survival.

Conclusions

The PLT‐ALBI score is applicable in distinguishing HCC patients with abnormal ICGR15. Patients with higher PLT‐ALBI score require more careful postoperative care, despite following the ICG criteria.
Quality of life following lobectomy versus total thyroidectomy is significantly related to hypothyroidism
Authors: Yaniv Dan , Vainer Igor , Amir Ido , Robenshtok Eyal , Hirsch Dania , Watt Torquil , Hilly Ohad , Shkedy Yotam , Shpitzer Thomas , Bachar Gideon , Feinmesser Raphael , Mizrachi Aviram
Published: June 2022

Objective

The aim of the present study was to investigate the differences in quality of life (QOL) following complete or partial thyroidectomy and with regard to thyroid hormone replacement (LT4) therapy.

Study Design

Patients who underwent thyroidectomy were asked to complete the validated thyroid‐specific ThyPRO QOL questionnaire at least 6 months following surgery.

Setting

Tertiary medical center.

Methods

Thyroid specific QOL questionnaire analysis.

Results

A total of 190 patients completed the ThyPRO questionnaire. Of them 89 patients had complete thyroidectomy and 101 patients had unilateral thyroid lobectomy. The total thyroidectomy group had significantly worse overall QOL self‐assessment score than the lobectomy patients (p < 0.0001). Patients receiving LT4 therapy regardless of the extent of surgery, reported worse QOL compared to patients not receiving LT4.

Conclusions

Quality of life following thyroid surgery is significantly related to hypothyroidism and the requirement for LT4 therapy, rather to the extent of surgery. The best QOL was reported in patients treated with lobectomy who did not require LT4 therapy.
Morphogenesis of Cell‐Shaped Assemblies via Heterotypic Assembly of Cyclic Triblock Peptides
Authors: Kim Hyoseok , Ko Sooho , Park Keunwan , Lim Yong‐beom
Published: June 2022

Despite the high prevalence and functional significance of nonregular assemblies in biology, little attention has been given to realize them in artificial systems. Here, the discovery of general principles underlying the formation of nonregular objects is described by chemical self‐assembly. The cell‐shaped assemblies (CSAs) are characterized by a main body comprising a nonregular vesicle and dendritically shaped spiky projections. The major mechanisms of CSA morphogenesis are: first, polycrystalline structures consisting of grains and grain boundaries induce the formation of nonregular objects by promoting nonuniform supramolecular crystal growth. Second, the fibrous nanostructures in 2D networks and in 1D bundles firmly support the main body and the spiky projections, respectively. This study also shows that there exist certain connections among entirely disparate entities, that is, organic supramolecular assemblies, inorganic materials, and cells regarding their fundamental principles of building block organizations. The principle behind the CSA formation can be applied to control the dynamic and mechanical properties of self‐assembled materials.
Ternary Memory Behavior of Carbazole‐Based Donor–Acceptor Polymer and CdS NPs Composites
Authors: Dou Feng , Zhao Xiaofeng , Gao Meng , He Zhaohua , Wang Shuao , Liu Hanzhou , Wang Shuhong , Wang Cheng
Published: June 2022

Multi‐level memory can greatly improve information density, so it has been widely studied. In this study, a carbazole‐based donor–acceptor polymer poly[2,7‐9‐(heptadecan‐9‐yl)‐9H‐carbazole‐alt‐7H‐benzimidazo[2,1‐a]benz[de]isoquinolin‐7‐one] (PCz‐BB) is synthesized, which exhibits flash‐type ternary memory behavior. Further, CdS nanoparticles (NPs) are embedded into the prepared polymer to enhance the storage performance. The current–voltage (I–V) characteristics of memory devices based on PCz‐BB:CdS composites and the effect of the embedding ratio of CdS NPs on the memory devices are studied. It is verified that the ON2/ON1/OFF current ratios of the devices at low CdS embedding concentrations are improved, and the threshold voltages are also reduced. The memory device based on the optimal embedding concentration (3 wt% CdS) exhibits a high ON2/ON1/OFF current ratio of 18631:72:1, a low threshold voltage of −0.40/−1.20 V, and excellent stability. The mechanism of resistive switching is explained by the theory of charge traps and conductive filaments. This work provides a new avenue for high‐performance multi‐level organic electrical storage materials.
Fluorescence Resonance Energy Transfer Measurements in Polymer Science: A Review
Authors: Valdez Sara , Robertson Mark , Qiang Zhe
Published: June 2022

Fluorescence resonance energy transfer (FRET) is a non‐invasive characterization method for studying molecular structures and dynamics, providing high spatial resolution at nanometer scale. Over the past decades, FRET‐based measurements are developed and widely implemented in synthetic polymer systems for understanding and detecting a variety of nanoscale phenomena, enabling significant advances in polymer science. In this review, the basic principles of fluorescence and FRET are briefly discussed. Several representative research areas are highlighted, where FRET spectroscopy and imaging can be employed to reveal polymer morphology and kinetics. These examples include understanding polymer micelle formation and stability, detecting guest molecule release from polymer host, characterizing supramolecular assembly, imaging composite interfaces, and determining polymer chain conformations and their diffusion kinetics. Finally, a perspective on the opportunities of FRET‐based measurements is provided for further allowing their greater contributions in this exciting area.
In vivo visualization of fluorescence reflecting CDK4 activity in a breast cancer mouse model
Authors: Gao Yi‐Yang , Yang Rui‐Qin , Lou Kang‐Liang , Dang Yong‐Ying , Dong Yuan‐Yuan , He Yue‐Yang , Huang Wen‐He , Chen Min , Zhang Guo‐Jun
Published: June 2022

The CDK4/6‐Rb axis is a crucial target of cancer therapy and several selective inhibitors of it have been approved for clinical application. However, current therapeutic efficacy evaluation mostly relies on anatomical imaging, which cannot directly reflect changes in drug targets, leading to a delay in the selection of optimal treatment. In this study, we constructed a novel fluorescent probe, CPP30‐Lipo/CDKACT4, for real‐time monitoring of CDK4 activity and the therapeutic efficacy of its inhibitor in HR+/HER2– breast cancer. CPP30‐Lipo/CDKACT4 exhibited good optical stability and targetability. The signal of the probe in living cells decreased after CDK4 knockdown or palbociclib treatment. Moreover, the fluorescence intensity of the tumors after 7 days of palbociclib treatment was significantly lower than that before treatment, while no significant change in tumor diameter was observed under magnetic resonance imaging. Overall, we developed an innovative fluorescent probe that can monitor CDK4 activity and the early therapeutic response to CDK4 inhibitors in living cells and in vivo. It may provide a new strategy for evaluating antitumor therapeutic efficacy in a clinical context and for drug development.
Clinical Features, Neuroimaging, and Levodopa‐Responsiveness in Holmes' Tremor: A Video‐Based Case‐Series with a Review of the Literature
Authors: Mishra Anumeha , Pandey Sanjay
Published: June 2022

Background

Holmes' tremor (HT) is a low‐frequency tremor characterized by a combination of rest, posture, and action components. We are reporting the clinical features, neuroimaging findings, and levodopa responsiveness in 12 patients with HT.

Cases

The majority of the patients were male (11/12). Dystonia was observed in 10 patients and the remaining two patients had head tremor, a “forme‐fruste” of cervical dystonia. The underlying etiologies were vascular (n = 8), head trauma (n = 2), and tumor resection (n = 2). Neuroimaging showed isolated involvement of the midbrain in four, thalamus in two, and basal ganglia and cerebellum in one patient each. A combination of the lesion (thalamus and cerebellum = 2; cerebellopontine angle = 1, and cortical/subcortical = 1) was present in four patients. Levodopa responsiveness was seen in 75% of patients including one with levodopa‐induced dyskinesia.

Literature Review

Of 139 patients from 49 studies, levodopa was tried in 123 patients. Improvement with levodopa was seen in 71 patients (57.72%). No improvement with levodopa was observed in 33 patients (26.82%) and details regarding therapeutic response were unavailable in 19 patients (15.44%).

Conclusions

Dystonia is an important clinical manifestation of HT. Levodopa responsiveness seen in the majority of the patients is consistent with the hypothesis that nigrostriatal pathway damage is crucial for the pathophysiology of HT.
Geste Antagoniste Effects on Motor Performance in Dystonia—A Kinematic Study
Authors: Newby Rachel , Muhamed Siti , Alty Jane , Cosgrove Jeremy , Jamieson Stuart , Smith Stephen , Kempster Peter
Published: June 2022

Background

The kinematic effects of gestes have not previously been studied. The mechanism(s) by which these sensory tricks modify dystonic movement is not well understood.

Objectives

A kinematic investigation of the geste phenomenon in patients with dystonia.

Methods

Twenty‐three patients with dystonia associated with a geste were studied. Twenty‐nine healthy controls also participated. Fifteen seconds of finger tapping was recorded by electromagnetic sensors, and the task was repeated with geste. Separable motor components were extracted using a custom‐written MATLAB script. Performance with and without geste was compared using Wilcoxon signed ranks testing.

Results

Speed and fluency of finger tapping is impaired in dystonia. When patients executed their geste, speed of movement (amplitude × frequency) increased (P < 0.0001), and halts decreased (P = 0.007).

Conclusions

That gestes improve not only dystonic muscle contraction but also the efficiency of voluntary movement suggests a broad influence at the premotor control stage.
End‐user satisfaction with Hurricane Dorian information in Atlantic Canada
Authors: Silver Amber , Finnis Joel , Behlendorf Brandon , Reid‐Musson Emily
Published: June 2022

Both Environment and Climate Change Canada (ECCC) and the National Oceanic and Atmospheric Administration have focused significant time and resources towards improving their forecast products. However, weather prediction remains an imperfect science, and as such, it is not unusual for meteorologists to prioritize accuracy over consistency or vice versa. There is considerable debate within the literature about whether (and how) inaccuracies and/or inconsistencies in forecasting will affect end‐user trust in future warnings. Hurricane Dorian presented the opportunity to explore the intersection between these concepts as its messaging was at times both inaccurate (e.g., then‐President Donald J. Trump indicated the storm would directly affect the state of Alabama) and inconsistent (i.e., both the storm's forecasted intensity and track changed over time). Two research projects were undertaken in Atlantic Canada: the first utilized semi‐structured interviews to examine the ways that ECCC meteorologists (n = 6) perceived the needs of their end‐users during the storm. There was considerable concern that changes in the storm's forecasted track and intensity would negatively influence public response. The second project utilized a large sample questionnaire (n = 1218) to examine ways that end‐users searched for, shared, and responded to storm‐related information. Despite changes in the storm's track and intensity as it approached Atlantic Canada, as well as the international news coverage of Sharpiegate, respondents overwhelmingly agreed that the storm was well forecasted and its impacts were well predicted. The implications for this (seemingly) contradictory response are explored in the context of probabilistic forecast potential.
CMMSE: Analysis of order reduction when Lawson methods integrate nonlinear initial boundary value problems
Authors: Cano Begoña , Reguera Nuria
Published: June 2022

In this paper a thorough analysis is carried out of the type of order reduction that Lawson methods exhibit when used to integrate nonlinear initial boundary value problems. In particular, we focus on nonlinear reaction‐diffusion problems, and therefore, this study is important in a large number of practical applications modeled by this type of nonlinear equations. A theoretical study of the local and global error of the total discretization of the problem is carried out, taking into account both, the error coming from the space discretization and that due to the integration in time. These results are also corroborated by the numerical experiments performed in this paper.