bluuebunny/crossref_metadata_2025 huggingface dataset:
Lithium‐Containing Biomaterials Stimulate Cartilage Repair through Bone Marrow Stromal Cells‐Derived Exosomal miR‐455‐3p and Histone H3 Acetylation
Authors: Liu Lu , Yu Fei , Chen Lei , Xia Lunguo , Wu Chengtie , Fang Bing
Published: January 2023

The repair of damaged cartilage still remains a great challenge in clinic. It is demonstrated that bone marrow stromal cells (BMSCs)‐chondrocytes communication is of great significance for cartilage repair. Moreover, BMSCs have been confirmed to enhance biological function of chondrocytes via exosome‐mediated paracrine pathway. Lithium‐containing scaffolds have been reported to effectively promote cartilage regeneration; however, whether lithium‐containing biomaterial could facilitate cartilage regeneration through regulating BMSCs‐derived exosomes has not been illustrated. In the study, the model lithium‐substituted bioglass ceramic (Li‐BGC) is selected and regulatory effects of BMSCs‐derived exosomes after Li‐BGC treatment (Li‐BGC‐Exo) are systemically evaluated. The data reveal that Li‐BGC‐Exo notably promotes chondrogenesis, which attributes to the upregulated exosomal miR‐455‐3p transfer, consequently leads to suppression of histone deacetylase 2 (HDAC2) and enhanced histone H3 acetylation in chondrocytes. Notably, BMSCs‐derived exosomes after LiCl treatment (LiCl‐Exo) exhibits the similar regulatory effect with Li‐BGC‐Exo, indicating that the pro‐chondrogenesis capability of them is mainly owing to the lithium ions. Furthermore, the in vivo study proves that LiCl‐Exo remarkably facilitates cartilage regeneration. The research may provide novel possibility for the intrinsic mechanism of chondrogenesis trigged by lithium‐containing biomaterials, and suggests that application of lithium‐containing scaffolds may be a promising strategy for cartilage regeneration.
Novel Titanium Implant: A 3D Multifunction Architecture with Charge‐Trapping and Piezoelectric Self‐Stimulation
Authors: Sun Lei , Chen Xuzhuo , Ma Kun , Chen Ruiguo , Mao Yi , Chao Rui , Wang Hui , Yu Bin , Wang Junfeng , Zhang Shanyong
Published: January 2023

Implant‐associated infection and inflammation are the main causes of implant failure, causing irreversible damage and significantly increasing clinical risks and economic losses. In this study, a 3D multifunctional architecture is constructed that consisted of hierarchical TiO2 nanotubes (NTs) and electrospun polyvinylidene fluoride nanofiber layers on the surface of a titanium implant. The movement of bacteria through the nanofiber layer is facilitated by its appropriate pore sizes and electrostatic interactions to reach the NT layer where the bacteria are killed by positive charge traps. In contrast, the macrophages tend to adhere to the nanofiber layer. The mechanical interactions between the macrophages and piezoelectric nanofibers generate a self‐stimulated electric field that regulated an anti‐inflammatory phenotype. This study provides a new method for multifunctional implant materials with antibacterial, piezoelectrically self‐stimulated anti‐inflammatory, and osteointegration properties that are driven by electrical stimulation.
Labeling Assembly of Hydrophilic Methionine into Nanoparticle for Mild‐Heat Mediated Immunometabolic Therapy
Authors: Zheng Xiao , Liu Ying , Zhang Tingting , Zhao Yuge , Liu Yiqiong , Zang Jie , Chong Gaowei , Li Yan , Yang Yushan , Yang Yan , Gu Jingjing , He Ruiqing , Liu Bingbing , Yin Weimin , Dong Haiqing , Li Yongyong
Published: January 2023

Methionine metabolism has a significant impact on T cells’ survival and activation even in comparison to arginine, a well‐documented amino acid in metabolic therapy. However, hydrophilic methionine is hardly delivered into TME due to difficult loading and rapid diffusion. Herein, the labeling assembly of methionine into nanoparticle is developed to overcome high hydrophilicity for mild‐heat mediated immunometabolic therapy. The strategy is to first label methionine with protocatechualdehyde (as the tag) via reversible Schiff‐base bond, and then drive nanoassembly of methionine (MPC@Fe) mediated by iron ions. In this fashion, a loading efficiency of 40% and assembly induced photothermal characteristics can be achieved. MPC@Fe can accumulate persistently in tumor up to 36 h due to tumor‐selective aggregation in acidic TME. A mild heat of 43 °C on tumor by light irradiation stimulated the immunogenic cell death and effectively generated CD8+ T cells. Notably, MPC@Fe assisted by mild heat promoted 4.2‐fold of tumor‐infiltrating INF‐γ+CD8+ T cells, leading to an inhibition ratio of 27.3‐fold versus the free methionine. Such labeling assembly provides a promising methionine delivery platform to realize mild heat mediated immunometabolic therapy, and is potentially extensible to other amino acids.
Ecology and age, but not genetic ancestry, predict fetal loss in a wild baboon hybrid zone
Authors: Fogel Arielle S. , Oduor Peter O. , Nyongesa Albert W. , Kimwele Charles N. , Alberts Susan C. , Archie Elizabeth A. , Tung Jenny
Published: January 2023

Objectives

Pregnancy failure represents a major fitness cost for any mammal, particularly those with slow life histories such as primates. Here, we quantified the risk of fetal loss in wild hybrid baboons, including genetic, ecological, and demographic sources of variance. We were particularly interested in testing the hypothesis that hybridization increases fetal loss rates. Such an effect would help explain how baboons may maintain genetic and phenotypic integrity despite interspecific gene flow.

Materials and Methods

We analyzed outcomes for 1020 pregnancies observed over 46 years in a natural yellow baboon‐anubis baboon hybrid zone. Fetal losses and live births were scored based on records of female reproductive state and the appearance of live neonates. We modeled the probability of fetal loss as a function of a female's genetic ancestry (the proportion of her genome estimated to be descended from anubis [vs. yellow] ancestors), age, number of previous fetal losses, dominance rank, group size, climate, and habitat quality using binomial mixed effects models.

Results

Female genetic ancestry did not predict fetal loss. Instead, the risk of fetal loss is elevated for very young and very old females. Fetal loss is most robustly predicted by ecological factors, including poor habitat quality prior to a home range shift and extreme heat during pregnancy.

Discussion

Our results suggest that gene flow between yellow and anubis baboons is not impeded by an increased risk of fetal loss for hybrid females. Instead, ecological conditions and female age are key determinants of this component of female reproductive success.
Gas/particle flow and pressure variation characteristics of Ende pulverized coal gasifier equipped with ejector
Authors: Song Minhang , Tang Di , Liu Xiaoying , Xu Yang
Published: January 2023

Ende pulverized coal gasifier (EPCG), as a typical representative of circulating fluidized bed gasifier, has been widely used in gasification field. The return conduit of EPCG is generally not equipped with a feedback control device (FCD), which tends to result in a low solid circulation rate (Gs) and high unburned combustibles in fly ash. To address these issues, a new technique using the ejector as the FCD was designed to provide a stable pressure barrier and improve solid circulation. Preliminary thermal experiments demonstrated the feasibility of improving the EPCG with injector system. Currently, the specific mechanisms that contribute to further optimize this technology have not been systematically studied. Considering the large impact of ejector operation on solid circulation rate and stability as well as syngas production, this work adopts a gas/particle 1:15 cold EPCG bench to investigate the gas/particle flow and pressure variation characteristics before and after ejector operation and under different working medium pressures (Pp). When the ejector operates at the design pressure Ps = 0.187 MPa, the outlet pressure of the return conduit is slightly larger than the furnace bottom pressure, thus preventing the reverse gas flow at the furnace bottom. The particle velocity and concentration distribution in the furnace are basically consistent with that without the ejector, showing a similar central spout region and near‐wall annulus flow region. As Pp increases from 0.04 to 0.24 MPa, the average particle velocity in the return conduit increases from 0.95 to 2.4 m/s, the particle concentration decreases from 0.088 to 0.051, and the solid circulation rate increases from 0.37 to 0.53 kg/h. The ejector outlet pressure gradually increases, the inlet pressure decreases, and the pressure barrier provided by the ejector rises from 1052 to 3640 Pa. When Pp is 0.12 MPa, the ratio of GN2/Gair is 0.91%, which can achieve the purpose of continuous and stable pressurization with a small amount of nitrogen.
Understanding glycidylation reaction for the formation of pure mono, diglycidyl and dual monomers as glycidyl methacrylate of vanillyl alcohol
Authors: Caillol Sylvain , Auvergne Rémi , Manseri Abdelatif , Boutevin Gilles , Boutevin Bernard , Grimaldi Marina , Balaguer Patrick
Published: January 2023

The mono epoxy methacrylate and the diepoxy of vanillyl alcohol (DGEVA) are products already known and reported in literature. However, their respective synthesis processes lead to mixtures of products and side‐products. Hence, the final reaction yields are low, mainly due to the purification steps. The mixture of by‐products obtained is due to the presence of phenol and methylol in raw vanillin. In this article, we have proposed selective synthesis methods avoiding the formation of these by‐products, which allows to consider the industrialization of these synthetic routes. Thanks to the difference in reactivity and the basicity of the catalysts used, we were able either to propose a two‐step synthesis of the mono‐epoxy vanilin, or to epoxidize the two hydroxyl groups to obtain the diepoxy in a single step. Finally, a toxicology study of pure vanillyl alcohol and pure DGEVA was carried out to demonstrate the interest of vanillyl alcohol as a potential substituent of bisphenol A.
Synthesis of five‐ring‐fused azepinone derivatives from bis‐isatins via sequential 6π‐electrocyclic ring closure, ring expansion, and dehydrogenation process
Authors: Lee Sangku , Lee Junseong , Kim Jae Nyoung
Published: January 2023

Five‐ring‐fused azepinone derivatives were synthesized serendipitously from bis‐isatins via sequential 6π‐electrocyclic ring closure, ring expansion, and dehydrogenation process in moderate yields (34%–47%). The reaction was carried out in diphenyl ether at 230 °C for 4–12 h under O2balloon atmosphere.
Synthesis, crystal structure, and photophysical properties of mononuclear and dinuclear palladium BODIPY chromophores
Authors: Gupta Gajendra , Lee Junseong , Lee Chang Yeon
Published: January 2023

Mononuclear and dinuclear palladium‐centered boron dipyrromethene (BODIPY) complexes, HBDPPdI and BDPPd2I2, respectively, were synthesized by the direct insertion of a palladium source into iodine‐substituted BODIPY chromophores. The molecular structures of both metal complexes were characterized using several analytical techniques, including single crystal x‐ray diffraction, to find that Pd(0) is coordinated directly to the ligand through a PdC bond facilitated by the insertion reaction. The photophysical properties of these complexes were also detailed.
Fatigue after COVID‐19 in non‐hospitalized patients according to sex
Authors: Mazurkiewicz Iwona , Chatys‐Bogacka Zaneta , Slowik Joanna , Klich‐Raczka Alicja , Fedyk‐Lukasik Malgorzata , Slowik Agnieszka , Wnuk Marcin , Drabik Leszek
Published: January 2023

Background

Limited evidence exists on sex differences in post‐COVID fatigue among non‐hospitalized patients. Therefore, aim of the study was to evaluate the course of chronic fatigue symptoms in non‐hospitalized subjects with the SARS‐CoV‐2 infection, according to sex.

Methods

Patients and staff from the University Hospital in Krakow anonymously and retrospectively completed neuropsychological questionnaire that included eight symptoms of chronic fatigue syndrome. The presence of these symptoms was assessed before COVID‐19 and 0–4, 4–12, and >12 weeks postinfection. The inclusion criteria were as follows: age 18 or more years, >12 weeks since the onset of the SARS‐CoV‐2 infection, and diagnosis confirmed by the RT‐PCR from anasopharyngeal swab.

Results

We included 303 patients (79.53% women, 47.52% medical personnel) assessed retrospectively after a median of 30 (interquartile range: 23–35) weeks since the onset of symptoms. A higher prevalence of at least one chronic fatigue symptom was found in females in all time intervals after the onset of COVID‐19 compared to males (p < .036). Women, compared to men, more often experienced persistent fatigue, not caused by effort and persisting after rest (for <4 weeks, odds ratio [OR] = 2.31, 95% confidence interval [CI]: 1.13–4.73; for 4–12 weeks, OR = 1.95, 95% CI: 1.06–3.61), non‐restorative sleep (for <4 weeks, OR = 2.17, 95% CI: 1.23–3.81; for >12 weeks, OR = 1.95, 95% CI: 1.03–3.71), and sore throat (for <4 weeks, OR = 1.97, 95% CI: 1.03–3.78; for 4–12 weeks, OR = 2.76, 95% CI: 1.05–7.27). Sex differences in headache, arthralgia, and prolonged postexercise fatigue were observed only during the first 4 weeks (OR = 2.59, 95% CI: 1.45–4.60, OR = 2.97, 95% CI: 1.02–8.64, and OR = 1.87, 95% CI: 1.01–3.51, respectively). There were no differences between women and men in myalgia and self‐reported lymph node enlargement.

Conclusions

The course of post‐COVID fatigue differs significantly between sexes in non‐hospitalized individuals with COVID‐19, with women more often suffering from persistent fatigue, not caused by effort and persisting after rest, non‐restorative sleep, and sore throat.
Comparison of characteristics and outcomes of young‐onset versus average onset pancreatico‐biliary adenocarcinoma
Authors: Jayakrishnan Thejus , Nair Kanika G. , Kamath Suneel D. , Wei Wei , Estfan Bassam N. , Krishnamurthi Smitha S. , Khorana Alok A.
Published: January 2023

Background

Young‐onset gastrointestinal malignancies appear to be increasing in incidence. There are limited data on young‐onset pancreaticobiliary adenocarcinoma (YO‐PBA).

Methods

The study comprised patients with PBA (pancreatic adenocarcinoma, intra‐, and extra‐hepatic cholangiocarcinoma) and included in the National Cancer Database (NCDB) between 2004 and 2017. YO‐PBA was defined as a diagnosis at age less than 50 years. Logistic regression to assess factors associated with YO‐PBA status, and cox proportional hazards modeling to associate relevant factors with overall survival was performed.

Results

The study cohort comprised 360,764 patients, with 20,822 (5.8%) YO‐PBA. YO‐PBA was associated with (p‐values<0.0001 for all): male sex (6.3% YO‐male out of all male patients vs. 5.2% YO‐female, OR 1.29, 95% CI 1.25–1.33), Black race (7.9% YO‐Black vs. 5.0% YO‐White, OR 1.72, 95% CI 1.64–1.80), lower income (6.4% YO‐lowest household income based group vs. 5.5% highest, OR 1.08, 95% CI 1.03–1.13). YO‐PBA were more likely to present with stage‐IV disease (6.4% YO‐Stage IV of all stage IV vs. 5.4% YO‐Stage I–III, OR 1.25, 95% CI 1.21–1.29 p‐value < 0.0001). Factors associated with overall survival (OS) in non‐operable patients included—sex ‐ male vs. female, HR 1.12 (95% CI 1.08–1.15); race ‐ Black vs. White, HR 1.23 (95% CI 1.06–1.42); income group ‐ lowest vs. highest, HR 1.33 (95% CI 1.27–1.39), and treatment center type ‐ academic vs. nonacademic center, HR 0.87 (95% CI 0.85–0.90).

Conclusions

Socioeconomic factors significantly impact incidence and outcomes for young‐onset pancreaticobiliary adenocarcinoma (YO‐PBA). More work is needed to help understand the mechanisms involved while addressing the disparities.
Phase 1 dose escalation study of FGFR4 inhibitor in combination with pembrolizumab in advanced solid tumors patients
Authors: Xu Jianming , Cui Jiuwei , Jiang Haiping , Zeng Yan , Cong Xiuyu
Published: January 2023

Objective

Inhibition of fibroblast growth factor (FGF) 19‐FGF Receptor 4 (FGFR4) signaling demonstrates potent anticancer activity. EVER4010001 is a highly selective FGFR4 inhibitor and pembrolizumab is approved for the treatment of several solid tumors. This study determined the maximum tolerated dose (MTD), recommended Phase 2 dose (RP2D), pharmacokinetics, safety, and preliminary efficacy of EVER4010001 plus pembrolizumab in patients with advanced solid tumors.

Methods

This Phase 1, multicenter, open‐label study enrolled 19 Asian–Chinese patients (57.9% male: median age 58 years) with advanced solid tumors. For “3+3” dose escalation, 3–6 patients received treatment at each dose level (EVER4010001 40, 60, 80, or 100 mg twice daily [BID] plus pembrolizumab 200 mg every 3 weeks).

Results

At the data cutoff (August 12, 2021), no dose‐limiting toxicities (DLTs) were reported at 40 mg–80 mg. At 100 mg, 2 (40.0%) patients had 3 DLTs within the 28‐day DLT observation period after first administration. Median time to peak EVER4010001 concentration (Tmax) was 0.55–1.03 hours. Mean terminal EVER4010001 half‐life (T1/2) was 4.00–4.92 hours. The area under the concentration‐time curve (AUC0–t) and maximum observed concentration (Cmax) ranged from 2370.87–5475.77 hour*ng/ml and 606.07–1348.86 ng/ml, respectively. The most common EVER4010001‐related treatment‐emergent adverse events were diarrhea (94.7%), increased aspartate aminotransferase (57.9%), and increased alanine aminotransferase (47.4%).

Conclusion

Eighty milligrams BID was the MTD and RP2D for EVER4010001 plus pembrolizumab. Efficacy results were promising, and no new safety risks were reported, justifying the Phase 2 portion of this study.
A study of preferred and natural memory colours across different ethnic groups
Authors: Cao Mingkai , Luo Ming Ronnier , Lu Yan , Xaio Kaida
Published: January 2023

A psychophysical experiment was carried out to specify the preferred and natural memory colours corresponding to 24 familiar objects on mobile displays. These objects were selected to cover a large colour gamut in CIELAB space. One hundred and six observers from five different ethnic groups participated. Forty‐nine colours for each object were rendered three‐dimensionally to cover a large colour range. The results showed inter‐observer variations are small between different ethnic groups, about 1.4 and 1.3 CIEDE2000 colour difference units for naturalness and preference, respectively. Comparing the preference and the naturalness colour centres, the preferred colours are brighter and more colourful than naturalness colours, by 1 and 2 units in L* and C*ab attributes, respectively. Both sets of data show a great hue consistency. The results showed that different ethnic groups agreed well on the objects studied. It was found that the best‐agreed objects are strawberry, green apple, tomato, corn and purple grape, and the worst‐agreed objects are blueberry, broccoli, smurf, green pepper and blue sky.
Atorvastatin Metabolite Pattern in Skeletal Muscle and Blood from Patients with Coronary Heart Disease and Statin‐Associated Muscle Symptoms
Authors: Lauritzen Trine , Munkhaugen John , Peersen Kari , Kristiansen Oscar , Sverre Elise , Nebauer Shane D. , Villseth Maja , Andersen Anders M. , Svarstad Anja Camilla , Jensen Elena Prunés , Bergan Stein , Husebye Einar , Vethe Nils Tore
Published: January 2023

Self‐perceived statin‐associated muscle symptoms (SAMS) are prevalent, but only a minority is drug‐dependent. Diagnostic biomarkers are not yet identified. The local statin exposure in skeletal muscle tissue may correlate to the adverse effects. We aimed to determine whether atorvastatin metabolites in blood reflect the corresponding metabolite levels in skeletal muscle, and whether genetic variants of statin transporters modulate this relationship. We also addressed atorvastatin metabolites as potential objective biomarkers of SAMS. Muscle symptoms were examined in patients with coronary disease and self‐perceived SAMS during 7 weeks of double‐blinded treatment with atorvastatin 40 mg/day and placebo in randomized order. A subset of 12 patients individually identified with more muscle symptoms on atorvastatin than placebo (confirmed SAMS) and 15 patients with no difference in muscle symptom intensity (non‐SAMS) attended the present follow‐up study. All received 7 weeks of treatment with atorvastatin 40 mg/day followed by 8 weeks without statins. Biopsies from the quadriceps muscle and blood plasma were collected after each treatment period. Strong correlations (rho > 0.7) between muscle and blood plasma concentrations were found for most atorvastatin metabolites. The impact of the SLCO1B1 c.521T>C (rs4149056) gene variant on atorvastatin's systemic pharmacokinetics was translated into muscle tissue. The SLCO2B1 c.395G>A (rs12422149) variant did not modulate the accumulation of atorvastatin metabolites in muscle tissue. Atorvastatin pharmacokinetics in patients with confirmed SAMS were not different from patients with non‐SAMS. In conclusion, atorvastatin metabolite levels in skeletal muscle and plasma are strongly correlated, implying that plasma measurements are suitable proxies of atorvastatin exposure in muscle tissue. The relationship between atorvastatin metabolites in plasma and SAMS deserves further investigation.
The efficacy and safety of a duckbill‐type anti‐reflux metal stent as the initial metal stent for distal malignant biliary obstruction in unresectable pancreatic cancer
Authors: Takeda Tsuyoshi , Sasaki Takashi , Yamada Yuto , Okamoto Takeshi , Mie Takafumi , Furukawa Takaaki , Kasuga Akiyoshi , Matsuyama Masato , Ozaka Masato , Sasahira Naoki
Published: January 2023

Background

The usefulness of duckbill‐type anti‐reflux metal stent (DMS) in self‐expandable metal stent‐naïve pancreatic cancer (PC) patients has not been well‐studied. This study aimed to evaluate the efficacy and safety of DMS in such patients.

Methods

We analyzed consecutive patients with unresectable PC who received a covered metal stent (CMS) as the initial self‐expandable metal stent at our institution. Technical success, functional success, causes of recurrent biliary obstruction (RBO), time to RBO (TRBO), adverse events (AEs), and reintervention rates were compared between DMS and conventional CMS (c‐CMS).

Results

A total of 69 patients were included (DMS: 28, c‐CMS: 41). Technical success, functional success, and AEs were similar between groups. Tumor ingrowth was more common in the DMS group (18% vs. 0%, p = 0.009), while non‐occlusion cholangitis tended to be more common in the c‐CMS group (0% vs. 15%, p = 0.074). Median time to RBO was similar between groups (276 vs. 273 days, p = 0.915). The anti‐reflux valve of DMS was found torn in 56% of patients. Endoscopic reintervention was successful in all cases, despite failed stent removal in 88% of patients in the DMS group.

Conclusions

DMS was not associated with longer time to RBO compared to c‐CMS in self‐expandable metal stent‐naïve patients.
Seismic analysis of 3D train–wheel–bridge–bearing systems: Modeling
Authors: Li Hong‐Wei , Xu Zhao‐Dong , Gomez Daniel , Dyke Shirley J. , Ni Yi‐Qing , Wang You‐Wu
Published: January 2023

Bearing effects have not been deeply investigated in the dynamic analysis of a train–bridge coupled system subjected to earthquake motions, and existing studies on base isolation of railway bridges have typically not considered the running train. To fill these gaps, this paper develops the numerical model of a three‐dimensional train–wheel–bridge–bearing (TWBB) system for seismic analysis. The substructuring method is implemented to separate the TWBB system into the train, wheel–rail, bridge and bearing subsystems, and couple them using state‐space representations. The complete model of the TWBB system has three main features: fewer degrees of freedom (DOF) than traditional finite element methods, applicability to different types of bearings, and simplicity as no iterations in the simulation are required. Therefore, the proposed procedure demonstrates that the TWBB model is an efficient and flexible representation to obtain and predict realistic demands for engineering purposes.
Inference in difference‐in‐differences: How much should we trust in independent clusters?
Authors: Ferman Bruno
Published: January 2023

We analyze the challenges for inference in difference‐in‐differences (DID) when there is spatial correlation. We present novel theoretical insights and empirical evidence on the settings in which ignoring spatial correlation should lead to more or less distortions in DID applications. We show that details, such as the time frame used in the estimation, the choice of the treated and control groups, and the choice of the estimator, are key determinants of distortions due to spatial correlation. We also analyze the feasibility and trade‐offs involved in a series of alternatives to take spatial correlation into account. Given that, we provide relevant recommendations for applied researchers on how to mitigate and assess the possibility of inference distortions due to spatial correlation.
Optical coherence tomography angiography with adaptive multi‐time interval
Authors: He Bin , Zhang Yuxin , Meng Zhe , He Zhijun , Wang Chengming , Chen Zhenyu , Yin Zichen , Hu Zhangwei , Shi Yejiong , Zhang Ning , Zhang Wenxin , Wang Guihuai , Xue Ping
Published: January 2023

Optical coherence tomography angiography (OCTA) can provide in vivo three‐dimensional microvasculature information of bio‐tissues, but it is sensitive to motion and time‐consuming. To overcome these limitations, we propose an adaptive multiple time interval correlation mapping OCTA with a time‐efficient scanning protocol and motion compensation algorithms. A spectral‐domain OCT with a center wavelength of 850 nm, A‐scan rate of 120 kHz and spatial resolution of 4.1 μm (axial) × 6.9 μm (lateral) is built to reconstruct the microvascular networks in the human arm. By adaptive optimization of the weights of different time interval B‐scan angiograms, our novel OCTA technique achieves better performance with a visible vascular density increase of ~67% and a signal‐to‐noise ratio enhancement of ~11.6%.
Energy transfer between Si nanocrystals and protoporphyrin molecules as a function of distance, orientation and size
Authors: Koliogiorgos Athanasios , Polcar Tomas , Rezek Bohuslav
Published: January 2023

The interaction between protoporphyrin molecules (donor) and Si nanocrystals (acceptor) up to 2.5 nm for varying distances and orientations is studied by DFT, semi‐empirical and TDDFT methods. Simulations show an effect on electronic structure, indicative of electron charge transfer in parallel orientation and small distances and nonelectron energy transfer for different orientations and larger distances. An absorption‐emission spectral overlap is observed. The calculations of coupling and energy transfer rates show a distance dependence typical of fluorescence resonance energy transfer (FRET) in the long range, while in the short and ultra‐short range the distance dependence indicates electron transfer in addition to FRET. The Si NCs with the smallest size yield larger couplings than the larger nanocrystals. The PPIX/Si NC coupling was enhanced by adding a plasmon nanoparticle as a bridge in the donor‐acceptor system. Results using Au nanoparticles show increased energy transfer rates up to 104 and lower distance dependence.
Clinical genetic counseling and translation considerations for polygenic scores in personalized risk assessments: A Practice Resource from the National Society of Genetic Counselors
Authors: Wand Hannah , Kalia Sarah S. , Helm Benjamin M. , Suckiel Sabrina A. , Brockman Deanna , Vriesen Natalie , Goudar Ranjit K. , Austin Jehannine , Yanes Tatiane
Published: January 2023

Polygenic scores (PGS) are primed for use in personalized risk assessments for common, complex conditions and population health screening. Although there is growing evidence supporting the clinical validity of these scores in certain diseases, presently, there is no consensus on best practices for constructing PGS or demonstrated clinical utility in practice. Despite these evidence gaps, individuals can access their PGS information through commercial entities, research programs, and clinical programs. This prompts the immediate need for educational resources for clinicians encountering PGS information in clinical practice. This practice resource is intended to increase genetic counselors' and other healthcare providers' understanding and comfort with PGS used in personalized risk assessments. Drawing on best practices in clinical genomics, we discuss the unique considerations for polygenic‐based (1) testing, (2) clinical genetic counseling, and (3) translation to population health services. This practice resource outlines the emerging uses of PGS, as well as the critical limitations of this technology that need to be addressed before wide‐scale implementation.
Explaining obesity disparities by urbanicity, 2006 to 2016: A decomposition analysis
Authors: Zang Emma , Flores Morales Josefina , Luo Liying , Baid Drishti
Published: January 2023

Objective

A large, and potentially growing, disparity in obesity prevalence exists between large central metros and less urban United States counties. This study examines its key predictors.

Methods

Using a rich county‐year data set spanning 2006 to 2016, the authors conducted a Gelbach decomposition to examine the relative importance of demographic, socioeconomic, environmental, and behavioral factors in shaping the baseline obesity gap and the growth rate over time between large central metros and other counties.

Results

Predictors included in this model explain almost the entire obesity gap between large central metros and other counties in the baseline year but can explain only ~32% of the growing gap. At baseline, demographic predictors explain more than half the obesity gap, and socioeconomic and behavioral predictors explain the other half. Behavioral and socioeconomic predictors explain more than half the growing gap over time whereas controlling for environmental and demographic predictors decreases the obesity gap by urbanicity over time.

Conclusions

Results suggest policy makers should prioritize interventions targeting health behaviors of residents in non‐large central metros to slow the growth of the obesity gap between large central metros and other counties. However, to fundamentally eliminate the obesity gap, in addition to improving health behaviors, policies addressing socioeconomic inequalities are needed.
Structural design optimization of CFRP/Al hybrid co‐cured high‐speed flywheel with the particle swarm optimization algorithm
Authors: Zhong Bingfu , Li Junli , Cai Xiaojiang , Chen Tao , An Qinglong , Chen Ming
Published: January 2023

With the development of CFRP materials and co‐cured structure, CFRP/Al hybrid co‐cured materials have been widely used for high‐speed energy storage flywheels. Therefore, it has become a hot research topic, which is to design a CFRP/Al hybrid co‐cured flywheel with a reasonable structure. In this paper, a particle swarm optimization algorithm is presented for improving the energy storage density to optimize the structure of the CFRP/Al hybrid co‐cured high‐speed flywheel. First, the stress and structural analysis of the flywheel are carried out based on energy storage. The inner‐radius‐to‐outer‐radius and the radial wall thickness h are chosen as the objective function because the and h are the factors which influence the energy storage density of the flywheel. Based the Tsai‐Hill criterion, the assembly interference t is the constraint condition which is the factor to meet the stress of design requirements. Then, the mathematical model of the flywheel is established by the objective function and the restriction with the particle swarm optimization algorithm (PSO). Finally, a specific CFRP/Al hybrid co‐cured flywheel is presented for the structural optimization with PSO by improving the energy storage density. In addition, the optimized flywheel is carried out to examine the static and dynamic requirements by the finite element method. The results indicate the PSO can be effectively used to optimize the structure of the CFRP/Al hybrid co‐cured high‐speed flywheel.
A bibliography of the literature on process capability indices (PCIs): 2010–2021, Part II: Multivariate PCI‐ and functional PCI‐related papers, special applications, software packages, and omitted papers
Authors: Yum Bong‐Jin
Published: January 2023

This is the second part of the bibliography on process capability indices (PCIs) for the period 2010–2021, and includes multivariate and functional PCI‐related papers, special applications, software packages, and papers omitted in the author's previous bibliography.
Denica 2.0 and Tactical Management Information System (TMIS)
Authors: Van Thuyne Gilles , Uvin Tom , Petrevska Nechkoska Renata , Poels Geert
Published: January 2023

Middle managers are often operating in complex and fast-moving environments, resulting in having to deal with enormous challenges in a short span of time, maneuvering diverse and numerous “givens” and aiming to achieve specific goals. These challenges are very diverse and require support tailored to the needs and characteristics of middle management. Due to the lack of tailored tools, middle managers often use methods that were originally designed for strategic or operational management, which they then adapt as best as possible to fit their tactical management needs. We thus see middle managers as the prototype of managers that have tactical management responsibilities, even though tactical management issues are also faced by executive, operational, and project managers. In a fast-changing world, heavily impacted by globalization and digitization, adaptability is one of the most essential characteristics of a middle manager. However, because of the lack of methods and systems tailored specifically to the tactical management level, middle managers are often not sufficiently supported to be able to deal with numerous givens, unpredictability, and a dynamic, turbulent, and complex environment. Hence, they lack proper support for being adaptable.
Risk factors for incomplete resection with pharyngeal endoscopic submucosal dissection and long-term prognosis after resection
Authors: Sakaguchi Yoshiki , Saito Yuki , Ando Mizuo , Yoshida Masafumi , Fukuoka Osamu , Kobayashi Kenya , Kubota Dai , Ohki Daisuke , Mizutani Hiroya , Niimi Keiko , Tsuji Yosuke , Fujishiro Mitsuhiro , Yamasoba Tatsuya
Published: January 2023

Background

Advances in endoscopic imaging technology have led to an increase in detection of superficial pharyngeal squamous carcinoma. Endoscopic submucosal dissection (ESD) has been reported to be effective for the treatment of these lesions, however there is still insufficient evidence on the long-term results of pharyngeal ESD.

Methods

This is a single-center retrospective study of all cases of superficial pharyngeal cancer that underwent ESD as primary treatment between January 2010 and May 2022. A total of 83 lesions in 63 patients were analyzed.

Results

The en bloc resection rate was 100%, and R0 resection rate was 59.0%, with an adverse event rate of 6.0%. During a mean observation period of 1134 days, there were 0 cases of disease-specific metastasis or death. However, the 5-year cumulative incidence of metachronous head and neck cancer after resection was 27.1% and the 5-year overall survival and 10-year overall survival after pharyngeal ESD were 87.0% and 69.6%, respectively. Of the 34 cases with non-R0 resection, local recurrence occurred in 8.8%. Location of lesion (p = 0.011), disparity between demarcation of the lesion with NBI and iodine staining (p = 0.026), and non-effective laryngeal elevation (p = 0.080) were risk factors for non-R0 resection.

Conclusion

Pharyngeal ESD is effective and safe. Further studies are needed to improve and standardize indications and strategies for pharyngeal ESD.
GTP energy dependence of endocytosis and autophagy in the aging brain and Alzheimer’s disease
Authors: Martínez Ricardo A. Santana , Pinky Priyanka D. , Harlan Benjamin A. , Brewer Gregory J.
Published: January 2023

Increased interest in the aging and Alzheimer’s disease (AD)-related impairments in autophagy in the brain raise important questions about regulation and treatment. Since many steps in endocytosis and autophagy depend on GTPases, new measures of cellular GTP levels are needed to evaluate energy regulation in aging and AD. The recent development of ratiometric GTP sensors (GEVALS) and findings that GTP levels are not homogenous inside cells raise new issues of regulation of GTPases by the local availability of GTP. In this review, we highlight the metabolism of GTP in relation to the Rab GTPases involved in formation of early endosomes, late endosomes, and lysosomal transport to execute the autophagic degradation of damaged cargo. Specific GTPases control macroautophagy (mitophagy), microautophagy, and chaperone-mediated autophagy (CMA). By inference, local GTP levels would control autophagy, if not in excess. Additional levels of control are imposed by the redox state of the cell, including thioredoxin involvement. Throughout this review, we emphasize the age-related changes that could contribute to deficits in GTP and AD. We conclude with prospects for boosting GTP levels and reversing age-related oxidative redox shift to restore autophagy. Therefore, GTP levels could regulate the numerous GTPases involved in endocytosis, autophagy, and vesicular trafficking. In aging, metabolic adaptation to a sedentary lifestyle could impair mitochondrial function generating less GTP and redox energy for healthy management of amyloid and tau proteostasis, synaptic function, and inflammation.
Process analyses of friction drilling using the Smoothed Particle Galerkin method
Authors: Stockburger Eugen , Zhang Wanmu , Wester Hendrik , Rosenbusch Daniel , Behrens Bernd-Arno
Published: January 2023

As a cost-effective hole production technique, friction drilling is widely used in industrial and automotive manufacturing. Compared with the traditional bolted connection, it enables the fastening of thin metal sheets and thin-walled tubular profiles. Friction drilling results in higher thread length and joint strength, thus better fulfilling the demand for lightweight structures. However, in the numerical simulation of friction drilling, the traditional finite element method encounters difficulties caused by the extreme deformation and complex failure of the material. A large number of elements are usually deleted due to the failure criterion, which significantly reduces the solution accuracy. The development of meshless methods over the past 20 years has alleviated this problem. Especially the Smoothed Particle Galerkin (SPG) method proposed in recent years and incorporating a bond-based failure mechanism has been shown to be advantageous in material separation simulations. It does not require element removal and can continuously evolve each particle's information such as strain and stress after the material failure. Therefore, the SPG method was used in this research for the simulation of frictional drilling of HX220 sheet metal. First the particle distance and the friction coefficient were varied to investigate the applicability of the SPG method to the friction drilling process. Predicted and experimental results were compared and found to be in high agreement. Furthermore, the influence of input parameters, such as sheet thickness, feed rate and rotational speed, on axial force as well as torque of the tool and the surface temperature of the workpiece during friction drilling was investigated numerically.
Interaction of Factors Determining Critical Power
Authors: Goulding Richie P. , Marwood Simon
Published: January 2023

The physiological determinants of high-intensity exercise tolerance are important for both elite human performance and morbidity, mortality and disease in clinical settings. The asymptote of the hyperbolic relation between external power and time to task failure, critical power, represents the threshold intensity above which systemic and intramuscular metabolic homeostasis can no longer be maintained. After ~ 60 years of research into the phenomenon of critical power, a clear understanding of its physiological determinants has emerged. The purpose of the present review is to critically examine this contemporary evidence in order to explain the physiological underpinnings of critical power. Evidence demonstrating that alterations in convective and diffusive oxygen delivery can impact upon critical power is first addressed. Subsequently, evidence is considered that shows that rates of muscle oxygen utilisation, inferred via the kinetics of pulmonary oxygen consumption, can influence critical power. The data reveal a clear picture that alterations in the rates of flux along every step of the oxygen transport and utilisation pathways influence critical power. It is also clear that critical power is influenced by motor unit recruitment patterns. On this basis, it is proposed that convective and diffusive oxygen delivery act in concert with muscle oxygen utilisation rates to determine the intracellular metabolic milieu and state of fatigue within the myocytes. This interacts with exercising muscle mass and motor unit recruitment patterns to ultimately determine critical power.
Academic Freedom as a Defensive Right
Authors: Stachowiak-Kudła Monika , Westa Sina , Santos Botelho Catarina , Bartha Ildikó
Published: January 2023

Ensuring the proper implementation of academic freedom can be difficult both for policymakers and university authorities. Hence, great emphasis should be given to the defensive function of academic freedom. In this paper, we analyse the legal regulations and the jurisprudence of the constitutional courts of Germany, Hungary, Poland, Portugal, and Spain. We identify who is the holder of academic freedom, how the defensive function of academic freedom works and what academic activities are being protected. The study shows that individual countries emphasise slightly different aspects of the defensive function of academic freedom but remain unanimous on the essence of this function. As academic freedom is not defined unequivocally in most constitutions and legal frameworks, constitutional courts play a significant role in shaping its defensive function.
The Determinants of Non-compliance on Rabies Vaccination in North-West Peninsular Malaysia
Authors: Mohammad Basir Mohammad Fazrul , Mohd Hairon Suhaily , Tengku Ismail Tengku Alina , Che’ Muda Che Muzaini , Abdul Halim Hamizar Iqbal
Published: January 2023

Introduction

Rabies post-exposure vaccination (Rabies PEV) remains the most fundamental prevention of human Rabies if administered in a timely and appropriate manner. The study was aimed to determine the proportion and determinants of non-compliance on Rabies PEV among dog bite patients in Perlis, Malaysia from July 2015 to June 2020.

Methods

A retrospective cohort study was conducted using Perlis Rabid Potential Animal Bite Registry data. Independent variables and compliance status were obtained from the registry. Logistic regression analysis was utilized on 507 dog bite patients.

Results

Most of dog bite patients were age group of 46–60 years old (23.1%), male (61.3%), Chinese (49.5%), seeking treatment less than 24 h after the exposure (78.3%), category two of exposure (76.3%) and bitten on lower extremities (57.8%) by an owned dog (58.4%). Only 19.5% were non-compliance to Rabies PEV. Siamese had significantly two-timed (AOR: 2.00; 95% CI 1.06, 3.76) odd higher to become non-compliance. Being bitten during 3rd (AOR: 0.27; 95% CI 0.12, 0.59), 4th (AOR: 0.24; 95% CI 0.11, 0.52) and 5th (AOR: 0.20; 95% CI 0.09, 0.44) year of the outbreak had significantly lower odds to non-comply with Rabies PEV.

Conclusion

19.5% of dog bite patients still did not comply with the Rabies PEV series. Siamese would likely to non-comply whereas bitten on the 3rd, 4th and 5th years of outbreak less tendency to non-comply. Continuous health promotion to the public in the various languages despite outbreak status are ongoing to improve the perception of risk and benefit toward compliance of Rabies PEV.
Measuring clinical outcomes of highly multiplex molecular diagnostics for respiratory infections: A systematic review and conceptual framework
Authors: Timbrook Tristan T. , Wigmosta Tara B. , Hemmert Rachael B. , Dimas Jonathan B. , Krause Alexander , Spinali Sébastien , Thelen Meghan , Tongio Isabelle , Tissier Jean-Louis
Published: January 2023

Objectives:

To review methodologies and outcomes reporting among these studies and to develop a conceptual framework of outcomes to assist in guiding studies and production of clinical metrics.

Data sources:

PubMed and Embase from January 1, 2012, thru December 1, 2021.

Study eligibility criteria:

Studies evaluating highly multiplex molecular respiratory diagnostics and their impact on either clinical or economic outcomes.

Methods:

A systematic literature review (SLR) of methodologies and outcomes reporting was performed. A qualitative synthesis of identified SLRs and associated primary studies was conducted to develop conceptual framework for outcomes.

Results:

Ultimately, 4 systemic literature reviews and their 12 associated primary studies were selected for review. Most primary studies included patient outcomes focusing on antimicrobial exposure changes such as antibiotic (80%) and antiviral use (50%) or occupancy changes such as hospital length of stay (60%). Economic outcomes were infrequently reported, and societal outcomes, such as antibiotic resistance impact, were absent from the reviewed literature. Qualitative evidence synthesis of reported outcomes yielded a conceptual framework of outcomes to include operational, patient, economic, and societal domains.

Conclusions:

Our review highlights the significant heterogeneity in outcomes reporting among clinical impact studies for highly multiplex molecular respiratory diagnostics. Furthermore, we developed a conceptual framework of outcomes domains that may act as a guide to improve considerations in outcomes selection and reporting when evaluating clinical impact of these tests. These improvements may be important in synthesizing the evidence for informing clinical decision making, guidelines, and financial reimbursement.
Vibration induced by active nematics
Authors: Saghatchi Roozbeh , Yildiz Mehmet
Published: January 2023

Active elements in active nematics can impose forces on immersed bodies and move them accordingly. We numerically investigate the vibrational motion of a cantilever beam placed in active nematics. The continuous energy transfer from vortices to the beam results in beam oscillation, whose direction and amplitude depend on the vortex strength, size and position. Referring to the kinetic-energy spectrum, we indicate that both the large- and small-scale vortices are the primary mechanism for the energy transfer between the fluid and beam, leading to the beam oscillatory motion, with the contribution from the large-scale vortices being higher. We investigate the effect of fluid properties such as activity, viscosity and elastic constant on the oscillation frequency. We show that the intensification of the activity increases peak frequency, and there is a linear correlation between the peak frequency and activity. We further demonstrate the reciprocal relationship between viscosity and peak frequency. Subsequently, we relate the increase and decrease in the peak frequency to the energy injection/dissipation by activity/viscosity. Moreover, we reveal the negligibly small dependency of beam peak frequency on the elastic constant and discuss free energy's role in accounting for this behaviour. The findings clearly demonstrate that active fluids can impose an oscillatory motion on flexible bodies, which might be used as a novel method for measuring the critical properties of active nematics.