bluuebunny/crossref_metadata_2025 huggingface dataset:
Heterosynaptic Plasticity Achieved by Highly Anisotropic Ionic Migration in Layered LixMoO3 for Neuromorphic Application
Authors: Qin Jing‐Kai , Zhu Bing‐Xuan , Wang Cong , Zhu Cheng‐Yi , Sun Ruo‐Yao , Zhen Liang , Chai Yang , Xu Cheng‐Yan
Published: September 2022

Heterosynaptic plasticity is important for the implementation of biological functions in an excitatory synapse. Although plenty of devices have been developed to emulate the synaptic behaviors, the capability of processing information with high heterosynaptic plasticity remains challenging. Herein, it is reported that the electrical conductance of Li+ ion pre‐intercalated MoO3 nanosheet (LixMoO3: 0 < x < 1) can be efficiently modulated, relying on the local phase transition associated with electric‐field‐driven ionic migration. The LixMoO3‐based in‐plane synaptic device exhibits attractive nonvolatile memory performance including high switching ratio (≈500) and long‐term retention of states (>4000 s). By combining experimental studies with theoretical calculations, the anisotropic in‐plane ionic migration in LixMoO3 is revealed, which is attributed to the dissimilarity of adiabatic barriers along different crystallographic directions. A multiterminal LixMoO3 memristor responses anisotropically to input spikes, and the slope of conductance change along a‐axis is almost 7 times larger than that along c‐axis, which contributes to the emulation of heterosynaptic plasticity required for neurobiological architecture. Additionally, the device can also fulfill the in‐memory Boolean logic operations naturally. This work demonstrates the great potentials of ionic migration to develop artificial synapses, highlighting its promising applications for future brain‐inspired computing systems.
Maize hybrid yield and physiological response to plant density across four decades in China
Authors: He Pin , Ding Xiangpeng , Bai Jing , Zhang Jiwang , Liu Peng , Ren Baizhao , Zhao Bin
Published: September 2022

The popularity of density‐tolerant maize (Zea mays L.) hybrids greatly increased the yield of maize hybrids in China in recent years. Clarifying trends in yield and plant density responses of agronomic characters of maize hybrids released in different years can provide theoretical and practical guidance for breeding high‐yield and density‐tolerant maize hybrids. The results showed grain yield (GY) of maize hybrids released in the 1970s and 1980s decreased with increased plant density. But GY of maize hybrids released in the 1990s and 2000s increased with a plant density increase. The GY gains from the low to high plant density plots were 86, 135, and 198 kg ha–1 per year, respectively. In all plant density treatments, yield and biomass of newer hybrids (2000s) were significantly higher than those of older hybrids (1970s). The leaf area index (LAI) of maize hybrids released in different years (1970s ∼ 2000s) increased with plant density, whereas the extinction coefficient decreased. Compared with the old hybrids, new hybrids have larger population sink capacity and stronger source supply ability, which is more prominent under high density. Population sink capacity is the main factor limiting maize yield. The key to maize hybrid improvement is to increase the population sink capacity. Breeders should continue to select for hybrids under stressful and high plant density conditions to increase seed setting rate and decrease empty ear rate of maize hybrids.
Smartphone use and willingness to adopt digital pest and disease management: Evidence from litchi growers in rural China
Authors: Cai Yi , Qi Wene , Yi Famin
Published: September 2022

This study uses a dataset covering 928 small litchi growers in southern China to investigate the determinants of farmers' willingness to adopt digital pest and disease management (DPDM), focusing on smartphone use. An endogenous switching probit model is employed to address potential selection bias. The result confirms the positive role of smartphone use on willingness to adopt DPDM. Age, education, health, wealth, cooperative membership, and credit access are also associated with farmers' willingness to adopt DPDM. Moreover, we find that the determinants of smartphone users' and nonusers' willingness to adopt DPDM are different. Finally, we propose a digital inclusion agenda to promote rural smartphone adoption and use in agriculture. [EconLit Citations: Q16, Q18].
Two‐dimensional Zn(II) coordination polymer and hydrogen bond‐mediated two‐dimensional Cu(II) network based on trans‐2‐aminocyclopentanecarboxylate
Authors: Yoo Sung Hyun , Gong Jintaek , Zhang Lianjin , Jeong Seoneun , Kim Jin , Lee Hee‐Seung
Published: September 2022

Coordination polymers from α‐amino acids are promising organic–inorganic hybrid composites with chirality and biocompatibility. However, coordination polymers from unnatural amino acids are rarely studied. Here, we report the transition metal complexes from an unnatural β‐amino acid, (1S,2S)‐2‐aminocyclopentanecarboxylic acid, affording two possible coordination modes from the conformationally rigid cyclopentane ring. X‐ray crystallographic analysis revealed that Zn(II) formed a two‐dimensional (2D) coordination polymer via N,O‐bridging mode. In contrast, Cu(II) formed a discrete complex via N,O‐chelating mode and then constructed a 2D supramolecular network stabilized by hydrogen bonding between water and the ligands.
Contrast‐enhanced ultrasound (CEUS) of benign and malignant renal tumors: Distinguishing CEUS features differ with tumor size
Authors: Zhu Jianing , Li Nan , Zhao Ping , Wang Yanjie , Song Qing , Song Luda , Li Qiuyang , Luo Yukun
Published: September 2022

Background

Contrast‐enhanced ultrasound (CEUS) is now a guideline‐recommended strategy for diagnosing renal lesions. Tumor size is related to the risk of the treatment and prognosis in renal tumors. Thus, we aim to analyze the CEUS features of solid renal tumors in relation to tumor size.

Methods

The CEUS appearance of 156 pathologically diagnosed solid renal tumors were retrospectively analyzed. Three groups were stratified according to the tumor size (≤2 cm [group I], 2.1–4 cm [group II] and 4.1–7 cm [group III]). For each group, the features of wash‐in type, enhancement degree, enhancement homogeneity, and the presence of a pseudocapsule sign were compared between benign and malignant tumors.

Results

All 156 included lesions were detected by CEUS. The proportion of benign tumors in three size groups was 37.1%, 19.4%, and 20.4%, respectively. The proportion of malignant tumors was highest (80.6%) in group II, followed by group III (79.6%) and group I (62.9%). In group I, malignant and benign tumors differed significantly in the presence of a pseudocapsule sign (p = 0.015) and homogeneity (p = 0.007). In group II, the degree of enhancement differed (p = 0.02) between tumor types. In group III, the two tumor types differed in both the wash‐in pattern (p = 0.015) and enhancement degree (p = 0.024). The weighted and Cohen's kappa values for the concordance between inter‐observer agreement ranged from 0.31 (95% CI: 0.36–0.57) to 0.90 (95% CI: 0.77–1.00).

Conclusions

CEUS features of malignant and benign renal tumors change along with the tumor size. The use of CEUS features in the diagnosis of benign and malignant tumors requires consideration of tumor size.
Aberrantly expressed long noncoding RNAs as potential prognostic biomarkers in newly diagnosed multiple myeloma: A systemic review and meta‐analysis
Authors: Qin Jiading , Ke Bo , Liu Tingting , Kong Chunfang , Li Anna , Fu Huan , Jin Chenghao
Published: September 2022

Background

Numerous studies have manifested long noncoding RNAs (lncRNAs) as biomarkers to determine the prognosis of multiple myeloma (MM) patients. Nevertheless, the prognostic role of lncRNAs in MM is still ambiguous. Herein, we performed a meta‐analysis to evaluate the predictive value of aberrantly expressed lncRNAs in MM.

Methods

A systemic literature search was performed in PubMed, EMBASE, Cochrane, and Web of Science databases until October 9, 2021, and the protocol was registered in the PROSPERO database (CRD42021284364). Our study extracted the hazard ratios (HRs) and 95% confidence intervals (CIs) of overall survival (OS), progression‐free survival (PFS), or event‐free survival (EFS). Begg's and Egger's tests were employed to correct publication bias.

Result

Twenty‐six individual studies containing 3501 MM patients were enrolled in this study. The results showed that aberrant expression of lncRNAs was associated with poor OS and PFS of MM patients. The pooled HRs for univariate OS and PFS were 1.48 (95% CI = 1.17–1.88, p < 0.001) and 1.30 (95% CI = 1.18‐1.43, p < 0.001), respectively, whereas the pooled HRs for multivariate OS and PFS were 1.50 (95% CI = 1.16‐1.95, p < 0.001) and 1.59 (95% CI = 1.22‐2.07, p < 0.001), respectively. Subgroup analysis suggested that MALAT1, TCF7, NEAT1, and PVT1 upregulation were associated with poor OS (p < 0.05), PVT1, and TCF7 upregulation were implicated with worse PFS (p < 0.05), while only TCF7 overexpression was correlated with reduced EFS (p < 0.05). Moreover, the contour‐enhanced funnel plot demonstrated the reliability of our current conclusion, which was not affected by publication bias.

Conclusion

Aberrantly expressed particular lncRNAs are critical prognostic indicators in long‐term survival as well as promising biomarkers in progression‐free status. However, different cutoff values and dissimilar methods to assess lncRNA expression among studies may lead to heterogeneity.
Incorporation of liver chemistry score in predicting survival of liver‐involved advanced gastric cancer patients who received palliative chemotherapy
Authors: Feng Ying , Zhang Cheng , Wu Zhijun , Xu Hui , Zhang Xiaopeng , Feng Chong , Shao Jingyi , Xie Minmin , Yang Yahui , Zhang Yi , Ma Tai
Published: September 2022

Background

Gastric cancer liver metastasis (GCLM) patients usually accompany by abnormal serum liver function tests (LFTs) more or less; however, the prognostic value of LFTs is not fully understood. This study aimed to develop a liver chemistry score (LCS) based on LFTs and incorporate it into prognosis determination for GCLM patients who received palliative chemotherapy.

Methods

Data were derived from hospitalized GCLM patients in two general hospitals in China. LCS was generated based on the results of LFTs by LASSO regression. Cutoff value of the score was determined by restricted cubic spline. The score was then incorporated into Cox regression analysis to construct a predictive nomogram; the model was then evaluated internally and externally by AUC of time‐dependent receiver operating characteristic curves (ROC) and calibration curves.

Results

Three hundred and thirty‐six and 72 patients were included in development and validation cohort, respectively. LASSO regression analysis in development cohort finally reached a two‐parametric LCS calculated on AST and ALP levels as 0.03343515 × ln (AST, U/L) + 0.02687997 × ln (ALP, U/L), and 0.232 was set as optimal cutoff value. Patients in low (LCS < 0.232) or high (LCS ≥ 0.232) score group experienced different survival times; median OS was 13.54 (95% CI: 11.1–15.6) months in the low LCS group and 7.3 (6.6–9.3) months in the high LCS group (p < 0.001). A nomogram including LCS and other clinical parameters was constructed and showed superior performance than model not including LCS. AUC of 6‐month ROC improved from 0.647 (95% CI: 0.584–0.711) to 0.699 (0.638–0.759) in internal validation, and 0.837 (0.734–0.940) to 0.875 (0.784–0.966) in external validation.

Conclusions

Liver chemistry score is useful in determining the prognosis of gastric cancer patients with liver metastasis and may be helpful to clinicians in decision‐making.
Risk factors for heightened COVID‐19‐Related anxiety among breast cancer patients
Authors: Shah Yash B. , Kjelstrom Stephanie , Martinez Diana , Leitenberger Adam , Manasseh Donna‐Marie , Bollmann‐Jenkins Melissa , Partridge Ann , Kaklamani Virginia , Chlebowski Rowen , Larson Sharon , Weiss Marisa
Published: September 2022

Background

The COVID‐19 pandemic has disrupted medical care, increased isolation, and exacerbated anxiety in breast cancer patients. Since March 2020, Breastcancer.org experienced a sustained surge in requested pandemic‐related information and support. To characterize the pandemic‐related experiences of breast cancer patients, we surveyed the Breastcancer.org Community early in the COVID‐19 era.

Methods

Breastcancer.org Community members were invited to complete an online questionnaire regarding their experience during the pandemic. Self‐reported data on demographics, comorbidities, care disruptions, anxiety, coping ability, telemedicine use, and satisfaction with care were collected. Results were analyzed using Stata 16.0 (Stata Corp., Inc).

Results

Included were 568 current and previous breast cancer patients, primarily with U.S. residence. Overall, 43.8% reported at least one comorbidity associated with severe COVID‐19 illness and 61.9% experienced care delays. Moderate to extreme anxiety about contracting COVID‐19 was reported by 36.5%, increasing with number of comorbidities (33.0% vs. 55.4%, p = 0.021), current breast cancer diagnosis (30.4% vs. 42.5%, p = 0.011), and poorer coping ability (15.5% vs. 53.9%, p < 0.0001). Moderate to extreme anxiety about cancer care disruptions was reported by 29.1%, increasing with current breast cancer diagnosis (19.1% vs. 38.9%, p < 0.0001), actual delayed care (18.9% vs. 35.3%, p < 0.0001), and poorer coping ability (13.1% vs. 57.7%, p < 0.0001). Most utilized telehealth and found it helpful, but also expressed increased anxiety and subjectively expressed that these were less preferable.

Conclusion

Early in the COVID‐19 pandemic, anxiety was reported by a large proportion of breast cancer patients, with increased prevalence in those with risk factors. Attention to mental health is critical, as emotional distress not only harms quality of life but may also compromise outcomes.
Impact of prior cancer history on survival of patients with hypopharyngeal cancer
Authors: Liang Qi‐Wei , Hong Shu‐Yi , Peng Liang , Liao Jing , Wen Wei‐Ping , Sun Wei
Published: September 2022

Background

The impact of prior cancer history on survival of hypopharyngeal cancer patients remains unknown. The present study assessed the impact of prior cancer history on survival of patients with hypopharyngeal cancer.

Methods

Patients with primary hypopharyngeal cancer diagnosed between 2004 and 2015 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Propensity score matching (PSM) was conducted to balance baseline characteristics. One‐to‐one PSM, Kaplan–Meier method, and log‐rank test were performed for survival analysis.

Results

We included 5017 patients with hypopharyngeal cancer. Prior cancer history had no significant impact on overall survival of hypopharyngeal cancer patients in comparison with those without prior cancer history (p = 0.845, after PSM). Subgroup analysis showed that prior cancer history had no significant effect on overall survival of hypopharyngeal cancer patients.

Conclusion

More hypopharyngeal cancer patients with prior cancer history should be considered for clinical trials. However, further prospective studies are needed.
Integrative community therapy for the promotion of mental health in adolescents: A quasi‐experimental study
Authors: Felipe Adriana Olimpia Barbosa , Alves Mariane Inaraí , de Andrade Maria Betânia Tinti , Bressan Vânia Regina , da Silva Moreira Denis
Published: September 2022

Background

The numerous transformations that occur during adolescence render this phase more susceptible to mental health issues, and it is therefore important to conduct studies assessing interventions aimed at promoting mental health among this population.

Aim

To evaluate the effects of integrative community therapy (ICT) on the mental health of adolescents.

Method

This is a quasi‐experimental pre‐ and post‐test study with a quantitative approach. The participants were 127 adolescents aged 12–17 years, attending a public school in the southern region of Minas Gerais, Brazil, who completed a participant characterisation questionnaire and the Strengths and Difficulties Questionnaire (SDQ). Ten ICT sessions were conducted for each group, with an average participation of 12 adolescents per group. The recommended guidelines of the Standards for Quality Improvement Reporting Excellence were used for the presentation of this study.

Results

In the pre‐intervention assessment, 70.1% of the adolescents presented a positive screening for mental health alteration. Females were more likely to present as borderline or abnormal based on the total SDQ score, and were more likely to report emotional and relationship issues with peers. It was evidenced that the ICT sessions contributed to a reduction in alterations in adolescent mental health in the domains of hyperactivity, emotional issues, conduct issues, relationship issues, and the total SDQ score.

Conclusion

Integrative community therapy was an effective intervention for reducing mental health alterations in adolescents. Worthy of note is the role of healthcare and education professionals in the promotion of adolescent health.
Synthesis of Mn(OH)(OCH3) as a Novel Precursor for 2D MnS‐Based Lithium‐ and Sodium‐Ion Battery Anode Materials**
Authors: Chen Xunjie , Zhang Menghui , Liu Zhiting , Cai Jianzhong , Fan Haosen , Cui Yuyan , Wu Zenan , Peng Feng
Published: September 2022

Manganese sulfides (MnS) are particularly appealing electrode candidates for lithium/sodium‐ion batteries, because of their low cost, wide availability, and environmental benignity. Herein, well‐defined Mn(OH)(OCH3) nanoflakes are synthesized for the first time, whereby two‐dimensional (2D) porous α‐MnS and its composite with N, S co‐doped carbon (α‐MnS@NSC) are produced via the topologic sulfurization of Mn(OH)(OCH3) or a Mn(OH)(OCH3)@polydopamine intermediate. The electrochemical lithium/sodium‐storage properties of α‐MnS are most likely governed by the conductivity, and thus can be significantly enhanced through integrating with conductive carbon coating. As a result, α‐MnS@NSC outperforms the bare α‐MnS and most of the reported MnS‐based anodes, demonstrating the high reversible capacities (1275 mA h g−1 at 0.2 A g−1 for LIBs and 581 mA h g−1 at 0.1 A g−1 for SIBs), great rate capability, and long cyclabilities. This work showcases both a novel strategy to fabricate 2D manganese‐based compounds and a preferred architecture for high performance lithium/sodium‐ion batteries.
Fe‐Catalyzed Electrochemical C−O Bond Cleavage of Ethers to Access Benzazoles from Ethers and o‐Substituted Anilines
Authors: Lai Yin‐Long , Yang Xiao , Wu Si‐Chao , Li Xi‐Yong , Gong Yao‐Xiong , Zhang Sheng‐Ling , Zhong Rui‐Min , Liao Jian‐Hua , Luo (Dr.) Jian‐Min
Published: September 2022

An efficient Fe‐catalyzed electrochemical synthesis of benzothiazoles from ethers with 2‐aminobenzenethiols has been developed through selective C−O bond cleavage of ethers under oxidant‐free conditions. A set of ethers have been converted to the corresponding 2‐aryl‐, 2‐heteroaryl‐, and 2‐alkyl‐substituted benzothiazoles in moderate to good yields. The method has also been successfully applied to generation of benzimidazoles and benzoxazoles with satisfactory yields and good functional group compatibility.
Transport phenomena with reactions in drug delivery: Towards a quantitative description
Authors: Qiu Xianjie , Neogi Parthasakha
Published: September 2022

A distributed system called a Krogh cylinder is used here to quantify the transport of a solute from the capillary into the extravascular tissue. The capillary network is broken down into cylindrical cells, each containing a capillary and an appropriate amount of extravascular tissue. The flow in the cylinder model has two‐dimensional velocities, which are in the axial and radial directions. All parameters of the system, together with the geometric ones, have been included in the model. For a given bioavailability, the uptakes of reactive and nonreactive solutes have been obtained. Very large or massive molecules have been considered. The diffusion in the tissue is found to be very low. Most of the drug uptake happens through convection, which is slowed down in the presence of a reaction. Further, this convection is entirely due to the flow out into the lymphatic system. For the case where a reaction takes place, local equilibrium is assumed, which both cuts down the computation times and provides good results in the case of reactive solutes. The full results of a distributed system have been obtained for the first time, and the mechanics of how the area‐under‐the‐curve can be used to calculate the actual solute uptake have been determined.
Prediction of critical total drawdown in sand production from gas wells: Machine learning approach
Authors: Alakbari Fahd Saeed , Mohyaldinn Mysara Eissa , Ayoub Mohammed Abdalla , Muhsan Ali Samer , Abdulkadir Said Jadid , Hussein Ibnelwaleed A. , Salih Abdullah Abduljabbar
Published: September 2022

Sand production is a critical issue in petroleum wells. The critical total drawdown (CTD) is an essential indicator of the onset of sand production. Although some models are available for CTD prediction, most of them are proven to lack accuracy or use commercial software. Furthermore, the previous correlations have not studied the trend analysis to verify the correct relationships between the parameters. Therefore, this study aims to build accurate and robust models for predicting CTD using response surface methodology (RSM) and support vector machine (SVM). The RSM is utilized to obtain the equation without using any software. The SVM model is an alternative method to predict the CTD with higher accuracy. This study used 23 datasets to develop the proposed models. The CTD is a strong function of the total vertical depth, cohesive strength, effective overburden vertical stress, and transit time with correlation coefficients (R) of 0.968, 0.963, 0.918, and −0.813. Different statistical methods, that is, analysis of variance (ANOVA), F‐statistics test, fit statistics, and diagnostics plots, have shown that the RSM correlation has high accuracy and is more robust than correlations reported in the literature. Moreover, trend analysis has proven that the proposed models ideally follow the correct trend. The RSM correlation decreased the average absolute percent relative error (AAPRE) by 12.7% compared to all published correlations' AAPRE of 22.6%–30.4%. The SVM model has shown the lowest AAPRE of 6.1%, with the highest R of 0.995. The effects of all independent variables on the CTD are displayed in three‐dimensional plots and showed significant interactions.
CO2 utilization in Eastern Canada: Sources, sites, and grid effects
Authors: Breuvart Emilie , Zeman Frank
Published: September 2022

Achieving net zero carbon dioxide (CO2) emissions will require the cessation of fossil fuel emissions into the atmosphere, yet the need for ‘fuel’ and energy storage will remain. One solution could be a carbon‐based fuel system where CO2 of biogenic origin is converted to fuels using hydrogen generated by electrolysis powered by renewable energy sources. Methane has value as an initial target given its prevalence in biogas, use in home heating and in electricity generation. Sources of CO2 in Eastern Canada are dominated by the iron and steel, cement, and aluminium industries, all of which have biogenic fuel options. Collecting all of the potentially biogenic CO2 would displace 75% of current natural gas use and require a 50% increase in generating capacity. Initial efforts could site a carbon capture, utilization, and storage facility near Montreal, QC, with other large‐scale facilities near Hamilton, ON, and Lac St‐Jean, QC. These facilities would be grid connected and expected to operate ~6200 h annually. The most high‐frequency electrolysis events would be 10 h of run time and 2 h of idle time. These periods would peak during the equinox months and be at a minimum during the winter solstice. These operational assumptions will all be subject to the increased variability caused by anthropogenic climate change and increased renewable generation on the grid. A closed‐loop carbon‐based fuel system would require an equivalent price of $250 per tonne CO2.
Effects of Ti Doping on TaFeSb Half‐Heuslers Estimated by a Single Parabolic Band Model
Authors: Park Hyunjin , Kim Sang‐il , Lee Kiyoung , Seo Won‐Seon , Kim Hyun‐Sik
Published: September 2022

Recent discovery of new p‐type Ta1‐xTixFeSb‐based half‐Heusler thermoelectric alloy has drawn much attention due to its high thermoelectric performance, zT of ∼1.52 near 970 K. However, the electronic band parameters of TaFeSb nor Ti‐doped TaFeSb have not been studied so far. Here we report the band parameters of Ta1‐xTixFeSb (x=0–0.16) calculated by the Single Parabolic Band model. Ti doping (x=0.12) both increases the density‐of‐states effective mass and non‐degenerate mobility by 27 and 29 times compared to those of the pristine TaFeSb (x=0). This simultaneous increase results in weighted mobility improvement by a factor of 4000 with Ti doping of x=0.12. Based on the estimated weighted mobility and the lattice thermal conductivity, the 300 K zT of Ta0.88Ti0.12FeSb (x=0.12) can be further increased by 10% once the carrier concentration is appropriately tuned.
Pharmacokinetics and Bioequivalence of 2 Safinamide Tablets in Healthy Chinese Volunteers Under Fasting and Fed Conditions
Authors: Li Xin , Wen Jing , Liu Yujie , Xu Bing , Li Yuan , Li You , Zhang Ping , Li Xianjing
Published: September 2022

To assess the bioequivalence of a generic safinamide tablet (test) vs a brand‐name safinamide tablet (reference) and effects of food on the pharmacokinetics of safinamide in healthy Chinese subjects, a single‐center, single‐dose, randomized, open‐label, 2‐preparation, 2‐period study with a 15‐day washout period was undertaken. A total of 56 healthy subjects were recruited in this study (fasting, n = 28; fed, n = 28). A single dose of a 100‐mg test or reference safinamide tablet was administered to each subject in a randomized sequence. Blood samples were obtained at 5 minutes before drug administration and during the 120 hours after dosing. The safinamide concentration in plasma was determined by high‐performance liquid chromatography–tandem mass spectrometry. Pharmacokinetic parameters were analyzed with noncompartmental methods. Safety was also monitored. The major pharmacokinetic parameters including maximum plasma drug concentration, area under plasma concentration‐time curve (AUC) from zero to time t (AUC0‐t), and AUC from time 0 to infinity (AUC0‐∞) were similar between the test and reference tablets under fasting and fed conditions. The 90% CIs of the test/reference ratios of log‐transformed maximum plasma drug concentration, AUC from zero to time t, and AUC from time 0 to infinity all fell within the equivalence interval (80.0%‐125%) whether under fasting condition or fed condition. In conclusion, the 2 formulations of safinamide tablets were bioequivalent and well tolerated under both fasting and fed conditions in healthy Chinese volunteers. High‐fat food delayed the absorption of safinamide but did not affect the final bioavailability.
Phosphorous NMR Analysis and Activity of Chiral BINAP‐Silver Complexes
Authors: Plevová Kristína , Prieto Pabon Laura Juliana , Gaysinski Marc , Poulain‐Martini Sophie , Michelet Véronique
Published: September 2022

Chiral Ag‐atropisomeric ligand species were studied in solution at different temperatures by 31P‐NMR spectroscopy. The analysis and understanding of key parameters in Ag‐BINAP complexes were considered in the context of an enantioselective transformation. An efficient silver‐catalyzed intramolecular [4+2] cycloaddition reaction of amide‐1,6‐enyne provided an enantiomerically enriched tricyclic compound using simple reagents and under mild reaction conditions.
Studying Telmisartan Plasma Exposure, Kidney Distribution, Receptor Occupancy, and Response in Patients With Type 2 Diabetes Using [11C]Telmisartan
Authors: van der Hoek Sjoukje , Mulder Douwe J. , Willemsen Antoon T.M. , Visser Ton , Heeres Andre , Slart Riemer H.J.A. , Elsinga Philip H. , Heerspink Hiddo J.L. , Stevens Jasper
Published: September 2022

The angiotensin receptor blocker telmisartan slows progression of kidney disease in patients with type 2 diabetes (T2D), yet many patients remain at high risk for progressive kidney function loss. The underlying mechanisms for this response variation might be attributed to differences in angiotensin‐1 receptor occupancy (RO), resulting from individual variation in plasma drug exposure, tissue drug exposure, and receptor availability. Therefore, we first assessed the relationship between plasma telmisartan exposure and urinary‐albumin‐to‐creatinine‐ratio (UACR) in 10 patients with T2D and albuminuria (mean age 66 years, median UACR 297 mg/g) after 4 weeks treatment with 80 mg telmisartan once daily. Increasing telmisartan exposure associated with a larger reduction in UACR (Pearson correlation coefficient (PCC) = −0.64, P = 0.046, median change UACR: −40.1%, 95% confidence interval (CI): −22.9 to −77.4%, mean telmisartan area under the curve (AUC) = 2927.1 ng·hour/mL, 95% CI: 723.0 to 6501.6 ng·hour/mL). Subsequently, we assessed the relation among plasma telmisartan exposure, kidney distribution, and angiotensin‐1 RO in five patients with T2D (mean age 60 years, median UACR 72 mg/g) in a separate positron emission tomography imaging study with [11C]Telmisartan. Individual plasma telmisartan exposure correlated with telmisartan distribution to the kidneys (PCC = 0.976, P = 0.024). A meaningful RO could be calculated in three patients receiving 120 mg oral telmisartan, and although high exposure seems related to higher RO, with AUC0–last of 31, 840, and 274 ng·hour/mL and corresponding RO values 5.5%, 44%, and 59%, this was not significant (P = 0.64). Together these results indicate, for the first time, a relationship among interindividual differences in plasma exposure, kidney tissue distribution, RO, and ultimately UACR response after telmisartan administration.
Salivary Areca and tobacco alkaloids for bioverification in the Betel Nut Intervention Trial
Authors: Franke Adrian A. , Li Xingnan , Herzog Thaddeus A. , Paulino Yvette C. , Badowski Grazyna , Wilkens Lynne R. , Lai Jennifer F.
Published: September 2022

Background

The Betel Nut Intervention Trial (BENIT) is the first known randomized controlled intervention trial designed to help minority Pacific Islanders in Guam and Saipan quit chewing the carcinogenic Areca catechu nut (AN). We report the BENIT's saliva bioverification results against the self‐reported chewing status (“quitter” or “chewer”) at day 22 follow‐up.

Material and Methods

AN‐specific (arecoline, arecaidine, guvacoline, and guvacine) and tobacco‐specific (nicotine, cotinine, and hydroxycotinine) alkaloids were analyzed in saliva from 176 BENIT participants by an established and sensitive liquid chromatography mass spectrometry‐based assay.

Results

The combined four AN alkaloid levels decreased from baseline in quitters (n = 50) and chewers (n = 108) by 32% and 9%, respectively. In quitters, decreases were significant for arecoline (p = 0.044)—the most prominent AN alkaloid, along with arecaidine (p = 0.042) and nicotine (p = 0.011). In chewers, decreases were significant only for hydroxycotinine (p = 0.004). Similar results were obtained when quitters and chewers were stratified by treatment arm.

Discussion

Salivary AN alkaloid levels generally agreed with self‐reported chewing status, which suggests the former can be used to verify the latter.

Conclusion

Our results can help to objectively evaluate compliance and program effectiveness in AN cessation programs.
Glypican‐6 and Glypican‐4 stimulate embryonic stomach growth by regulating Hedgehog and noncanonical Wnt signaling
Authors: Shi Wen , Filmus Jorge
Published: September 2022

Background

Glypicans are a family of proteoglycans that play important roles in embryonic morphogenesis. The mammalian genome contains six glypicans (GPC1 to GPC6). GPC6 and GPC4 are the pair of glypicans that show the highest degree of homology within the family. GPC6‐null embryos display bone abnormalities and severely shortened intestines.

Results

We show that GPC6‐null embryos display significantly smaller stomachs, and that Hedgehog and noncanonical Wnt signaling are dysregulated in GPC6‐null stomachs. Like GPC6, GPC4 is expressed by the developing stomach. However, GPC4‐null embryos have normal stomachs. To investigate whether GPC6 and GPC4 display functional overlap in the developing stomach, we crossed GPC4‐null mice with GPC6 conditional mutants in which the expression of this glypican is severely reduced in the stomach. Notably, we found that the compound mutants display stomachs that are smaller than those of the GPC6 conditional mutants. We also found that this functional overlap between GPC6 and GPC4 is mediated by the noncanonical Wnt pathway.

Conclusion

This study demonstrates that GPC6 stimulates the growth of the embryonic stomach via Wnt and Hh signaling. In addition, we uncovered a Wnt‐mediated functional overlap between GPC6 and GPC4 in the developing stomach.
Ventricular anisotropic deformation and contractile function of the developing heart of zebrafish in vivo
Authors: Salehin Nabid , Teranikar Tanveer , Lee Juhyun , Chuong Cheng‐Jen
Published: September 2022

Background

The developing zebrafish ventricle generates higher intraventricular pressure (IVP) with increasing stroke volume and cardiac output at different developmental stages to meet the metabolic demands of the rapidly growing embryo (Salehin et al. Ann Biomed Eng, 2021;49(9): 2080‐2093). To understand the changing role of the developing embryonic heart, we studied its biomechanical characteristics during in vivo cardiac cycles. By combining changes in wall strains and IVP measurements, we assessed ventricular wall stiffness during diastolic filling and the ensuing systolic IVP‐generation capacity during 3‐, 4‐, and 5‐day post fertilization (dpf). We further examined the anisotropy of wall deformation, in different regions within the ventricle, throughout a complete cardiac cycle.

Results

We found the ventricular walls grow increasingly stiff during diastolic filling with a corresponding increase in IVP‐generation capacity from 3‐ to 4‐ and 5‐dpf groups. In addition, we found the corresponding increasing level of anisotropic wall deformation through cardiac cycles that favor the latitudinal direction, with the most pronounced found in the equatorial region of the ventricle.

Conclusions

From 3‐ to 4‐ and 5‐dpf groups, the ventricular wall myocardium undergoes increasing level of anisotropic deformation. This, in combination with the increasing wall stiffness and IVP‐generation capacity, allows the developing heart to effectively pump blood to meet the rapidly growing embryo's needs.
Seabirds subsidize terrestrial food webs and coral reefs in a tropical rat‐invaded archipelago
Authors: Linhares Bruno de Andrade , Bugoni Leandro
Published: September 2022

Allochthonous resource fluxes mediated by organisms crossing ecosystem boundaries may be essential for supporting the structure and function of resource‐limited environments, such as tropical islands and surrounding coral reefs. However, invasive species, such as black rats, thrive on tropical islands and disrupt the natural pathways of nutrient subsidies by reducing seabird colonies. Here, we used stable isotopes of nitrogen and carbon to examine the role of seabirds in subsidizing the terrestrial food webs and adjacent coral reefs in the Abrolhos Archipelago, Southwest Atlantic Ocean. By sampling invasive rats and multiple ecosystem compartments (soil, plants, grasshoppers, tarantulas, and lizards) within and outside seabird colonies, we showed that seabird subsidies led to an overall enrichment in 15N across the food web on islands. However, contrary to other studies, δ15N values were consistently lower within the seabird colonies, suggesting that a higher seabird presence might produce a localized depletion in 15N in small islands influenced by seabirds. In contrast, the nitrogen content (%N) in plants and soils was higher inside the colonies, corresponding to a higher effect of seabirds at the base of the trophic web. Among consumers, lizards and invasive rats seemed to obtain allochthonous resources from subsidized terrestrial organisms outside the colony. Inside the colony, however, they showed a more direct consumption of marine matter, suggesting that subsidies benefit these native and invasive animals both directly and indirectly. Nonetheless, in coral reefs, scleractinian corals assimilated seabird‐derived nitrogen only around the two smaller and lower‐elevation islands, as demonstrated by the substantially higher δ15N values in relation to the reference areas. This provides evidence that island morphology may influence the incorporation of seabird nutrients in coral reefs around rat‐invaded islands, likely because guano lixiviation toward seawater is facilitated in small and low‐elevation terrains. Overall, these results showed that seabirds affected small islands across all trophic levels within and outside colonies and that these effects spread outward to coral reefs, evidencing resiliency of seabird subsidies even within a rat‐invaded archipelago. Because rats are consumers of seabird chicks and eggs, however, rat eradication could potentially benefit the terrestrial and nearshore ecosystems through increased subsides carried by seabirds.
Feast or famine: How is global change affecting forage supply for Yellowstone's ungulate herds?
Authors: Frank Douglas A. , Becklin Katie M. , Penner Jacob F. , Lindsay K. Alice , Geremia Chris J.
Published: September 2022

The ecological integrity of US national parks and other protected areas are under threat in the Anthropocene. For Yellowstone National Park (YNP), the impacts that global change has already had on the park's capacity to sustain its large migratory herds of wild ungulates is incompletely understood. Here we examine how two understudied components of global change, the historical increase in atmospheric CO2 and the spread of nonnative, invasive plant species, may have altered the capacity of YNP to provide forage for ungulates over the last 200‐plus years. We performed two experiments: (1) a growth chamber study that determined the growth rates of important invasive and native YNP grasses that are forages for ungulates under preindustrial (280 ppm) versus modern (410 ppm) CO2 levels and (2) a field study that compared the effect of defoliation (clipping) on the shoot growth of invasive and native mesic grassland plants under ambient CO2 conditions in 2019. The growth chamber experiment revealed that modern CO2 increased the growth rates of both invasive and native grasses, and invasive grasses grew faster regardless of CO2 conditions. The field results showed a continuum of positive to negative responses of shoot growth to defoliation, with a subgroup of invasive species responding most positively. Altogether the results indicated that the historical increase in CO2 and the spread of invasive species, some of which were planted to provide forage for ungulates in the early and mid‐1900s, have likely increased the capacity of forage production in YNP. However, rising CO2 has also resulted in regional warming and increased aridity in YNP, which will likely reduce grassland productivity. The challenge for global change biologists and park managers is to determine how competing components of global change have already affected and will increasingly affect forage dynamics and the sustainability of Yellowstone's iconic ungulate herds in the Anthropocene.
Temporal shifts in avian phenology across the circannual cycle in a rapidly changing climate: A global meta‐analysis
Authors: Romano Andrea , Garamszegi László Zsolt , Rubolini Diego , Ambrosini Roberto
Published: September 2022

The alteration of the timing of biological events is one of the best documented effects of climate change, with overwhelming evidence across taxa. Many studies have investigated the phenology of consumers, especially birds. However, most of these studies have focused on specific phenophases, whereas a global analysis of avian phenological trends during recent climate change across different phases of the circannual cycle is still lacking. Here, we performed a comprehensive meta‐analytic synthesis of the phenological responses (temporal shifts in days year−1) of birds across different phenophases (prebreeding migration, breeding, and postbreeding migration) by summarizing more than 5500 time series from 684 species from five continents during 1811–2018. Our results confirm that avian taxa have advanced prebreeding migration and breeding by ~2–3 days per decade, whereas no significant temporal changes in the timing of postbreeding migration were documented. Advancement in the timing of prebreeding migration and breeding strongly depended on migratory behavior, with the advance being the weakest for long‐distance migrants and the strongest for resident species. Diet generalists and primary consumers tended to advance prebreeding migration timing more than species with different dietary specializations. Increasing body size resulted in a larger advancement in the onset (but not in the mean date) of prebreeding migration and breeding, whereas phenological advances were larger in the northern than in the southern hemisphere. Our synthesis, covering most of the world, highlighted previously unappreciated patterns in avian phenological shifts over time, suggesting that specific life‐history or ecological traits may drive different responses to climate change.
Effects of Drying Conditions on the Content of Biologically Active Compounds in Winter Camelina Sativa Seeds
Authors: Gawrysiak‐Witulska Marzena , Siger Aleksander , Grygier Anna , Rusinek Robert , Gancarz Marek
Published: September 2022

The moisture content of Camelina sativa seeds has to be maintained at 7–12% during storage in order to preserve their quality. If seeds with higher moisture contents are to be stored, they first need to be dried. This study presents the effects of high‐temperature drying (at 40, 60, 80, 100, 120, and 140 °C) of C. sativa seeds on the technological usefulness (expressed as the acid value) and bioactive compound content (as polyenoic fatty acid, vitamin‐E active compounds, and phytosterols). It is shown that drying temperature significantly affects levels of bioactive compounds. Losses of phytosterols reached a maximum of 24% (for temperatures in the 80–140 °C range), while losses of tocopherols range from 2–11%, depending on cultivar. A change in the percentage composition of polyenoic acids is observed upon air drying at 100–140 °C. It is recommended not to exceed 60 °C when drying C. sativa seeds, in order to guarantee that high‐quality cold‐pressed oil with high levels of bioactive compounds is obtained.

Practical application: The seeds of Camelina sativa, like other oilseeds, require appropriate storage after harvesting in order to maintain continuity of production. Maintaining the high seed quality during storage requires drying them after harvesting to a moisture content of 7–12%. Drying conditions have a significant effect on seed quality, expressed as acid number, and also affect the levels of bioactive compounds (such as polyene fatty acids, tocopherols, plastochromanol‐8, and phytosterols) in the oil. Information on optimum drying conditions will contribute to the availability of high‐quality camelina oils produced by small local manufacturers.
Changes in Emulsifying and Physical Properties of Shrimp Oil/Soybean Oil‐in‐Water Emulsion Stabilized by Fish Myofibrillar Protein during the Storage
Authors: Rajasekaran Bharathipriya , Singh Avtar , Zhang Bin , Hong Hui , Benjakul Soottawat
Published: September 2022

Properties of shrimp oil/soybean oil (30:70)‐in‐water emulsion stabilized using fish myofibrillar protein (FMP) at different concentrations (15, 30, and 45 mg mL−1) are investigated. When FMP concentration increases, emulsion activity index decreases (p < 0.05). Conversely, emulsion stability index, adsorbed protein, and interfacial protein contents are augmented (p < 0.05). During storage of 15 days, emulsion added with FMP at 45 mg mL−1 (FMP‐45) has the highest turbidity, zeta potential, viscosity, and viscoelastic properties (G′ and G″) than the others (p < 0.05). Emulsions show shear‐thinning and non‐Newtonian behavior. The emulsion added with FMP at 15 and 30 mg mL−1 (FMP‐15 and FMP‐30, respectively) has dominant viscous properties (G′ < G″), whereas FMP‐45 shows elastic gel‐like behavior (G′ > G″) (p < 0.05). Lower droplet size (d32 and d43), polydispersity index (PDI), flocculation (Fi), and coalescence (Ci) are observe in FMP‐45 (p < 0.05). Microstructure reveals smaller droplet size and smaller increase in droplet size of FMP‐45 after storage. Overall, all emulsions remain stable with no obvious phase separation throughout the storage. Confocal laser scanning microscopic  images show that increase in FMP concentration can yield monodisperse emulsion. Therefore, fish myofibrillar protein exhibits excellent emulsifying property and stability for shrimp/soybean oils‐in‐water emulsion.

Practical Applications: Oil from shrimp hepatopancreas, a byproduct from hepatopancreas free whole shrimp, is well known for their health benefits. It can be used to produce functional food emulsion such as mayonnaise. The use of fish myofibrillar protein is proven to be a potential emulsifier, which can improve emulsifying properties. The obtained emulsion is stable without no phase separation during the extended storage. This finding can be beneficial for food industries to produce food emulsion rich in high quality protein and polyunsaturated fatty acid. Also, hepatopancreas can be fully exploited.
A Long‐Lasting Skin Protectant Based on CG‐101, a Deep Eutectic Solvent Comprising Choline and Geranic Acid
Authors: Shevachman Marina , Mandal Abhirup , Gelston Kevin , Mitragotri Samir , Joshi Nitin
Published: September 2022

The COVID‐19 public health crisis has spotlighted the need to improve global hygiene and sanitization. In addition to causing staggering rates of transmission and fatality, COVID‐19 has severely impacted the quality of life and mental health of global citizens. The World Health Organization (WHO) and Centers for Disease Control and Prevention (CDC) encourage hand hygiene as the first defense against the spread of infection, yet frequent handwashing is often impractical. Widely used ethanol‐based hand sanitizers provide immediate protection against pathogens on the skin, albeit short‐lived, due to their rapid evaporation. Herein, a novel, long‐lasting skin protectant formulated with biocompatible ionic liquid/deep eutectic solvents prepared using generally recognized as safe materials – choline and geranic acid (CG‐101, 5% w/w) – is described. In vitro studies demonstrated that CG‐101 inactivates bacteria and the human coronavirus, hCoV229E, for 4 h after application. Two human clinical studies demonstrate that CG‐101 does not cause skin irritation or sensitization, and a single application of CG‐101 gel imparts skin protection against microbes for significantly longer than conventional 70% ethanol‐based hand sanitizers. These data are the first to indicate that CG‐101 may be a better alternative to alcohol‐based hand sanitizers for long‐term skin protection against infectious diseases.