bluuebunny/crossref_metadata_2025 huggingface dataset:
Sex‐Specific Neurotoxicity of Dietary Advanced Glycation End Products in APP/PS1 Mice and Protective Roles of Trehalose by Inhibiting Tau Phosphorylation via GSK‐3β‐TFEB
Authors: Zhou Huan‐Huan , Luo Lan , Zhai Xue‐Di , Chen Liangkai , Wang Guiping , Qin Li‐Qiang , Yu Zengli , Xin Li‐Li , Wan Zhongxiao
Published: October 2021

Scope

It remains unclear whether dietary advanced glycation end products (dAGEs)‐induced cognitive impairment is sex‐dependent. Trehalose may antagonize dAGEs‐induced neurotoxicity via glycogen synthase kinase‐3 beta (GSK3β)‐transcription factor EB (TFEB) signaling.

Methods and Results

The sex‐specific neurotoxicity of dAGEs and the protective role of trehalose are investigated both in vivo and in vitro. Both sexes of APP/PS1 mice are divided into three groups: that is, control, dAGEs, and dAGEs supplemented with trehalose. SHSY‐5Y cells incubated with AGE‐BSA and trehalose are also utilized. Dietary AGEs impair cognitive function only in female mice, which is restored by trehalose. Trehalose upregulates phosphorylated‐GSK3β serine9 (p‐GSK3β ser9), TFEB and transient receptor potential mucolipin 1, ADAM10, oligosaccharyl transferase‐48, estrogen receptor α and induces TFEB nuclear translocation in hippocampus, elevates IDE and ERβ in cortex, while reduces p‐tau ser396&404, CDK5, cathepsin B, and glial fibrillary acidic protein in hippocampus. Trehalose elevates p‐GSK3β ser9, induces TFEB nuclear translocation, consequently reverses AGE‐BSA‐induced tau phosphorylation in vitro.

Conclusions

Female mice are more susceptible to the deleterious effects of dAGEs on cognitive function, which may be owing to its regulation on ERβ. Trehalose can strongly reverse dAGEs‐induced tau phosphorylation by potentiating TFEB nuclear translocation via inhibiting GSK‐3β.
Increasing Post‐Digestive Solubility of Curcumin Is the Most Successful Strategy to Improve its Oral Bioavailability: A Randomized Cross‐Over Trial in Healthy Adults and In Vitro Bioaccessibility Experiments
Authors: Flory Sandra , Sus Nadine , Haas Kathrin , Jehle Sina , Kienhöfer Eva , Waehler Reinhard , Adler Günther , Venturelli Sascha , Frank Jan
Published: October 2021

Scope

Different mechanistic approaches to improve the low oral bioavailability of curcumin have been developed, but not yet directly compared in humans.

Methods and Results

In a randomized, double‐blind, cross‐over trial with 12 healthy adults, the 24 h pharmacokinetics of a single dose of 207 mg curcumin is compared from the following formulations: native, liposomes, with turmeric oils, with adjuvants (including piperine), submicron‐particles, phytosomes, γ‐cyclodextrin complexes, and micelles. No free, but only conjugated curcumin is detected in all subjects. Compared to native curcumin, a significant increase in the area under the plasma concentration–time curve is observed for micellar curcumin (57‐fold) and the curcumin‐γ‐cyclodextrin complex (30‐fold) only. In vitro digestive stability, solubility, and micellization efficiency of micellar curcumin (100%, 80%, and 55%) and curcumin‐γ‐cyclodextrin complex (73%, 33%, and 23%) are higher compared to all other formulations (<72%, <8%, and <4%). The transport efficiencies through Caco‐2 cell monolayers of curcumin from the digested mixed‐micellar fractions did not differ significantly.

Conclusion

The improved oral bioavailability of micellar curcumin, and to a lesser extent of γ‐cyclodextrin curcumin complexes, appears to be facilitated by increased post‐digestive stability and solubility, whereas strategies targeting post‐absorptive processes, including inhibition of biotransformation, appear ineffective.
Optimal subsidy design for shore power usage in ship berthing operations
Authors: Wang Shuaian , Qi Jingwen , Laporte Gilbert
Published: October 2021

Maritime transportation is the backbone of international trade but ships emit a large amount of air pollutants at ports. To encourage ships to use clean energy while berthing at port, subsidies are provided to ship operators that use clean energy and the subsidy amount is generally determined based on subjective judgment. We, therefore, examine the optimal subsidy design for government‐operated ports, aiming at balancing the environmental benefits and subsidy expenses. Considering the uncertainty of energy requirements by ships, we build a stochastic optimization model. Taking advantage of the problem structure, we convert the model into a deterministic one by applying sample average approximation and a binomial distribution. The model is then linearized and solved by CPLEX. A series of numerical experiments with realistic parameters are conducted to validate the model and useful managerial insights are obtained.
Viscoelastic and cyclic compaction response of prepregs tested under isothermal temperatures and various compaction speeds
Authors: Naresh Kakur , Khan Kamran Ahmed , Cantwell Wesley James , Umer Rehan
Published: October 2021

Viscoelastic compaction/relaxation and cyclic compaction studies of uncured prepregs are of importance to understand the process parameters, such as mold closing forces and speed and the clamping force required to maintain a given thickness during molding, and so forth, for many composites manufacturing processes, including compression molding. In this study, viscoelastic compaction/relaxation, and multi‐cycle‐compaction tests were performed on uncured glass/epoxy prepreg specimens at elevated temperatures and variable compaction speeds up to a target fiber volume fraction of 0.65. At low temperatures, the relaxation process was found to be less sensitive to compaction speed. At lower compaction speeds (e.g., 0.1 mm/min) and elevated temperatures, such as 90°C, higher maximum stresses, and resin bleed out were observed as compared to a relatively faster compaction speed of 1 mm/min. Specimens tested under multi‐cyclic‐compaction exhibited a lower final thickness, owing to cyclic hysteresis, which caused increased fiber nesting compared to that observed in stress relaxation tests. As a result, the percentage of permanent deformation is higher in the former case than in the viscoelastic compaction/relaxation tests. An investigation of the microstructure through X‐ray computed tomography aided voxel models of the cured specimens confirmed nesting of the fiber tows. Moreover, at a compaction speed of 0.1 mm/min, a decrease in thickness and an elongation of void sizes were also observed as the temperature increased.
Outcomes of laparoscopy‐assisted fetoscopic laser photocoagulation for twin–twin transfusion syndrome: An established alternative for inaccessible anterior placenta
Authors: Krispin Eyal , Nassr Ahmed A. , Espinoza Jimmy , Donepudi Roopali , Sun Raphael C. , Sanz‐Cortes Magda , Mostafaei Shayan , Belfort Michael A. , Shamshirsaz Alireza A.
Published: October 2021

Objective

To evaluate laparoscopy‐assisted fetoscopic laser photocoagulation (FLPC) of placental anastomoses in the treatment of twin‐to‐twin‐transfusion syndrome (TTTS).

Study Design

We performed a retrospective cohort study analyzing pregnancies complicated by TTTS who underwent FLPC in a single university‐affiliated tertiary medical‐center. Outcomes were compared between patients who received laparoscopy‐assisted FLPC (study group) and patients who underwent the conventional FLPC technique (control group). Baseline characteristics, sonographic findings, procedure details, and neonatal outcomes were compared between groups.

Results

The cohort included 278 women with 31 in the study group and 247 in the control group. Sonographic parameters, including fetal biometry and TTTS stage, were comparable between study groups. Gestational age at delivery did not differ between the groups (29.22 ± 4.55 weeks in the study group vs. 30.62 ± 4.3 weeks in the control group, p = 0.09). There were no differences in neonatal survival rates at birth and at 30 days between both groups. A subanalysis comparing the laparoscopy‐assisted group to only those patients with anterior placenta in the control group, showed a lower rate of incomplete Solomonization in the laparoscopy‐assisted study group (3.4% vs. 33%, p = 0.01).

Conclusion

Laparoscopy‐assisted FLPC is a reasonable and safe option that may be offered in cases of FLPC where an anterior placenta restricts adequate surgical access.
Reverse chemical ecology guides the screening for Grapholita molesta pheromone synergists
Authors: Liu Jiyuan , Zhou Tong , Li Chaoxia , Li Ruichi , Ye Xuan , Tian Zhen
Published: October 2021

BACKGROUND

Pheromone‐based management is a leading nonpesticidal strategy among integrated pest management options. Improving the potency of pheromone products by adding synergists would be a practical way to popularize pheromone‐based management as well as to reduce pesticide use.

RESULTS

Using reverse chemical ecology, synergists for Grapholita molesta sex pheromone were screened. Combined molecular docking and in vitro binding assay led to the determination of four potentially active odorants showing high affinity to G. molesta pheromone binding protein 2 (GmolPBP2). Thereafter, the high affinity between Codlemone and GmolPBP2 was further verified by exploration of GmolPBP2–Codlemone interactions. As the only sex pheromone synergist validated by both laboratory behavioral tests and field trapping, Codlemone was used to optimize commercial sex attractants currently used in G. molesta control. The recommended formulation [(Z)‐8‐dodecenyl acetate:(E)‐8‐dodecenyl acetate:Codlemone = 95:4:10] was found to trap about five to six times more G. molesta adults than the commercial sex attractant [(Z)‐8‐dodecenyl acetate:(E)‐8‐dodecenyl acetate: (Z)‐8‐dodecenol = 95:4:1].

CONCLUSION

Codlemone is an excellent pheromone synergist that can be potentially sensed by GmolPBP2, which can remarkably improve the potency of G. molesta sex attractants. It is believed that the introduction of reverse chemical ecology would increase the chance of discovering pheromone synergists, promoting the development of more efficacious pheromone products that can be used in controlling G. molesta and beyond. © 2021 Society of Chemical Industry.
Grid resolution dependency of land surface heterogeneity effects on boundary‐layer structure
Authors: Poll S. , Shrestha P. , Simmer C.
Published: October 2021

Land surface heterogeneity exerts a strong control on atmospheric boundary‐layer (ABL) evolution by spatially varying the distribution and partitioning of surface energy fluxes and triggering secondary circulations. The representation of this physical process in numerical weather prediction (NWP) models is especially affected in the terra incognita as the model grid resolution approaches the length‐scale of the largest eddies in the boundary layer. We explore these effects for a mesoscale strip‐like land surface inhomogeneity in land cover, soil moisture or a superposition of both embedded in an elsewhere homogeneous landscape. The study is conducted with the numerical weather prediction model ICON (ICOsahedral Nonhydrostatic), using the default operational level 2.5 Mellor–Yamada turbulence closure (MY) and a large‐eddy simulation (LES) configuration as a benchmark. While simulations with the default ABL scheme approach the LES reference when refining the spatial grid towards finer resolution, the model generates artificial circulations leading to ABL height oscillations when the horizontal grid resolution approaches the ABL height . The effect of these model‐induced circulations on the state of the boundary layer is even present with weak thermal heterogeneity under low background wind speed ( but diminishes with increasing background wind speed. The tuning of the asymptotic turbulent mixing length‐scale in the operational ABL scheme helps in reducing the amplitude of the oscillations, thereby reducing the artificially induced circulations due to thermal heterogeneity which might act as unintentional trigger for clouds and precipitation. Based on the tuned synthetic model data from sensitivity runs, we propose a new parametrization for a 2‐D as a function of , and , which is otherwise held as a constant in the ABL scheme.
X‐Ray Spectromicroscopy Investigation of Heterogeneous Sodiation in Hard Carbon Nanosheets with Vertically Oriented (002) Planes
Authors: Tan Xuehai , Jiang Keren , Zhai Shengli , Zhou Jigang , Wang Jian , Cadien Ken , Li Zhi
Published: October 2021

Hard carbon (HC) is a promising anode material for sodium‐ion batteries, but the performance remains unsatisfactory and the sodiation mechanism in HC is one of the most debated topics. Here, from self‐assembled cellulose nanocrystal sheets with crystallographic texture, unique HC nanosheets with vertically oriented (002) planes are fabricated and used as a model HC to investigate the sodiation mechanisms using synchrotron scanning transmission X‐ray microscopy (STXM) coupled with analytical transmission electron microscopy (TEM). The model HC simplifies the 3D sodiation in a typical HC particle into a 2D sodiation, which facilitates the visualization of phase transformation at different states of charge. The results for the first time unveil that the sodiation in HC initiates heterogeneously, with multiple propagation fronts proceeding simultaneously, eventually merging into larger aggregates. The spatial correlation between the preferential adsorption and nucleation sites suggests that the heterogeneous nucleation is driven by the local Na‐ion concentration, which is determined by defects or heteroatoms that have strong binding to Na ions. By identifying intercalation as the dominant sodium storage mechanism in the model HC, the findings highlight the importance of engineering the graphene layer orientation and the structural heterogeneity of edge sites to enhance the performances.
Constructing 3D Interconnected Si/SiOx/C Nanorings from Polyhedral Oligomeric Silsesquioxane
Authors: Lin Xieji , Chen Xinjian , Zhang Fan , Dong Yue , Chen Xiaohong , Li Ang , Song Huaihe
Published: October 2021

Polyhedral oligomeric silsesquioxane (POSS) is a family of organic/inorganic hybrid materials with specific molecular symmetry, and shows great potential in the structural design of nanomaterials. Here, a “bottom‐up” strategy is designed to fabricate 3D interconnected Si/SiOx/C nanorings (NRs) via AlCl3‐assisted aluminothermic reduction using dodecaphenyl cage silsesquioxane (T12‐Ph) as the building block. In this process, AlCl3 acts as both a liquid medium for reduction, and significantly as the catalyst to the cross‐linking of phenyl groups in T12‐Ph. The obtained Si/SiOx/C NRs exhibits uniform diameter of ≈165 nm and well distribution of C and Si elements. The unique ring‐like structure of Si/SiOx/C NRs makes it have great application potential in the field of lithium ion batteries. Notably, Si/SiOx/C NRs exhibits superior high‐rate capacity and good cycle stability when used as anode for LIBs. More excitingly, Si/SiOx/C NRs can deliver a high reversible capacity of 517.9 mA h g−1 at ultra‐low temperature of −70 °C, and the capacity retention as high as ≈50% of that at 25 °C. This work not only broadens structural design of carbon‐based nanomaterials but also provides more possibilities for the application of POSS.
Bimetallic‐MOF‐Derived Amorphous Zinc/Cobalt–Iron‐Based Hollow Nanowall Arrays via Ion Exchange for Highly Efficient Oxygen Evolution
Authors: Gu Zhengxiang , Wei Xuelian , Zhang Xiaoqin , Duan Zhengyu , Gu Zhongwei , Gong Qiyong , Luo Kui
Published: October 2021

Oxygen evolution reaction (OER) is critical for optimizing renewable energy systems, including metal–air batteries and water electrolysis. One major challenge for OER is to develop durable and cost‐effective electrocatalysts with high catalytic performance. Herein, a controllable ion‐exchange method to synthesize amorphous zinc/cobalt–iron hydroxide‐based hollow nanowall arrays (A‐Zn/Co–Fe HNAs) derived from bimetallic metal–organic frameworks (MOFs) on carbon cloth is reported. The amorphous characteristic enables the presented materials with more electrocatalytic sites and short diffusion paths for rapid access to the electrolyte, achieving efficient charge transfer for OER. The optimized nanostructure of A‐Zn/Co–Fe HNAs via tuning the amount of iron sulfate in the reaction solution delivers a low overpotential of 226 mV to reach a current density of 10 mA cm−2 with a small Tafel slope of 37.81 mV dec−1 while exhibiting high durability at varied current densities over 80 h. The remarkable electrochemical performance can be attributed to the synergistic effect from chemical elements of Zn, Co–Fe, and a robust hollow structure. This simple method of fabricating bimetallic‐MOF‐derived amorphous Zn/Co–Fe HNAs on carbon cloth can be applied as a practical platform for other OER electrocatalysts.
Permeable Conductors for Wearable and On‐Skin Electronics
Authors: Chen Fan , Huang Qiyao , Zheng Zijian
Published: October 2021

The booming development of wearable and on‐skin electronics has driven increased interest in flexible and stretchable conductors, which serve as the indispensable building blocks for these electronic devices. However, conductors for such soft electronics are mostly fabricated with impermeable elastic thin films, which not only affect the long‐term wearing comfort but also limit the device's multifunctionality. In recent years, permeable conductors, conducting materials that are fabricated based on breathable materials and structures with deformability, have shown great promise for applications in wearable and skin‐mountable electronics. Herein, a specific perspective on the development of permeable conductors that can simultaneously display conductivity, flexibility or stretchability, and permeability to air, moisture, and liquid is provided. Key design considerations of permeable conductors, as well as the state‐of‐the‐art strategies to endow flexible and stretchable conductors with permeability, are discussed. Finally, key challenges and future directions of permeable conductors and electronic devices are discussed along with the analysis of possible solutions.
Long non‐coding RNA LINC00514 promotes the proliferation and invasion through the miR‐708‐5p/HOXB3 axis in cervical squamous cell carcinoma
Authors: Liu Xiaoying , Shen Xin , Zhang Jing
Published: October 2021

Long non‐coding RNA (lncRNA) LINC00514 is a cancer‐related lncRNA that has been proven to be implicated in the progression of several cancers. However, the biological function of LINC00514 in cervical squamous cell carcinoma (CSCC) remains unclear. Thus, we aimed to identify the LINC00514 expression profile in CSCC and determine its exact mechanism. Our results showed that the expression of LINC00514 was up‐regulated in human CSCC tissues and cell lines. Knockdown of LINC00514 significantly inhibited the proliferation and invasion of CSCC cells, as well as suppressed tumorigenesis of CSCC in vivo. In addition, LINC00514 was found to work as a miRNA sponge for miR‐708‐5p and suppressed the expression of miR‐708‐5p in CSCC cells. Homeobox B3 (HOXB3) was found to be a target gene of miR‐708‐5p. Rescue assays demonstrated that miR‐708‐5p inhibitor attenuated the effects of LINC00514 knockdown on cell proliferation and invasion in CSCC cells. In addition, overexpression of HOXB3 reversed the inhibitory effects of miR‐708‐5p mimics on cell proliferation and invasion. Taken together, our findings for the first time elucidated that lncRNA LINC00514 promotes the proliferation and invasion through the miR‐708‐5p/HOXB3 axis in CSCC. Thus, LINC00514/miR‐708‐5p/HOXB3 axis might be a promising therapeutic target for the treatment of CSCC.
Involvement of miRNAs in response to oxidative stress induced by the steroidal glycoalkaloid α‐solanine in hepatocellular carcinoma cells
Authors: Gouhar Shaimaa A. , Abo‐elfadl Mahmoud T. , Gamal‐Eldeen Amira M. , El‐Daly Sherien M.
Published: October 2021

Background

α‐Solanine is a natural toxic glycoalkaloid produced in some species of the Solanaceae family with antiproliferative activity in various cancers.

Objective

This study aimed to investigate the effect of α‐solanine on the oxidative stress status in human hepatocellular carcinoma HepG2 cells and to evaluate its influence on microRNAs (miRNAs) associated with oxidative stress and NF‐κB regulation.

Methods

The prooxidant effect of α‐solanine was tested by the decay rate of the fluorescent probe, β‐phycoerythrin, and by measuring malondialdehyde, reduced Glutathione, catalase, and superoxide dismutase following treatment of HepG2 cells with low doses of α‐solanine. Immunocytochemical techniques were used to detect mitochondrial membrane potential (ΔΨm) and NF‐κB protein. The gene expression of NF‐κB and miRNAs was evaluated by real‐time PCR.

Results

α‐Solanine is a prooxidant that causes a rapid decay in the fluorescence intensity of β‐phycoerythrin. It induces oxidative stress‐related alterations such as increased lipid peroxidation and reduced antioxidant markers. Oxidative stress induced by α‐solanine was mediated by decreased ΔΨm, increased NF‐κB expression, upregulation of miRNAs that control oxidative stress by regulating the NF‐κB pathway, and downregulation of oncogenic miRNAs that inhibit the NF‐κB pathway.

Conclusion

α‐Solanine‐induced oxidative stress is mediated by alterations in the NF‐κB pathway with a detected crosstalk between α‐solanine treatment and the expression of oxidative stress‐responsive miRNAs.
Gastrointestinal bleeding and endoscopic findings in critically and non‐critically ill patients with corona virus disease 2019 (COVID‐19): Results from Lean European Open Survey on SARS‐CoV‐2 (LEOSS) and COKA registries
Authors: Zellmer Stephan , Hanses Frank , Muzalyova Anna , Classen Johanna , Braun Georg , Piepel Christiane , Erber Johanna , Pilgram Lisa , Walter Lorenz , Göpel Siri , Wille Kai , Hower Martin , Rüthrich Maria Madeleine , Rupp Jan , Degenhardt Christian , Voigt Ingo , Borgmann Stefan , Stecher Melanie , Jakob Carolin , Dhillon Christine , Messmann Helmut , Ebigbo Alanna , Römmele Christoph ,   the LEOSS study group
Published: October 2021

Background

Corona virus disease 2019 (COVID‐19) patients are at increased risk for thromboembolic events. It is unclear whether the risk for gastrointestinal (GI) bleeding is also increased.

Methods

We considered 4128 COVID‐19 patients enrolled in the Lean European Open Survey on SARS‐CoV‐2 (LEOSS) registry. The association between occurrence of GI bleeding and comorbidities as well as medication were examined. In addition, 1216 patients from COKA registry were analyzed focusing on endoscopy diagnostic findings.

Results

A cumulative number of 97 patients (1.8%) with GI bleeding were identified in the LEOSS registry and COKA registry. Of 4128 patients from the LEOSS registry, 66 patients (1.6%) had a GI bleeding. The rate of GI bleeding in patients with intensive care unit (ICU) admission was 4.5%. The use of therapeutic dose of anticoagulants showed a significant association with the increased incidence of bleeding in the critical phase of disease. The Charlson comorbidity index and the COVID‐19 severity index were significantly higher in the group of patients with GI bleeding than in the group of patients without GI bleeding (5.83 (SD = 2.93) vs. 3.66 (SD = 3.06), p < 0.01 and 3.26 (SD = 1.69) vs. 2.33 (SD = 1.53), p < 0.01, respectively). In the COKA registry 31 patients (2.5%) developed a GI bleeding. Of these, the source of bleeding was identified in upper GI tract in 21 patients (67.7%) with ulcer as the most frequent bleeding source (25.8%, n = 8) followed by gastroesophageal reflux (16.1%, n = 5). In three patients (9.7%) GI bleeding source was located in lower GI tract caused mainly by diverticular bleeding (6.5%, n = 2). In seven patients (22.6%) the bleeding localization remained unknown.

Conclusion

Consistent with previous research, comorbidities and disease severity correlate with the incidence of GI bleeding. Also, therapeutic anticoagulation seems to be associated with a higher risk of GI bleeding. Overall, the risk of GI bleeding seems not to be increased in COVID‐19 patients.
Particulate and drug-induced toxicity assessed in novel quadruple cell human primary hepatic disease models of steatosis and pre-fibrotic NASH
Authors: Kermanizadeh Ali , Valli Jessica , Sanchez Katarzyna , Hutter Simon , Pawlowska Agnieszka , Whyte Graeme , Moritz Wolfgang , Stone Vicki
Published: October 2021

In an effort to replace, reduce and refine animal experimentation, there is an unmet need to advance current in vitro models that offer features with physiological relevance and enhanced predictivity of in vivo toxicological output. Hepatic toxicology is key following chemical, drug and nanomaterials (NMs) exposure, as the liver is vital in metabolic detoxification of chemicals as well as being a major site of xenobiotic accumulation (i.e., low solubility particulates). With the ever-increasing production of NMs, there is a necessity to evaluate the probability of consequential adverse effects, not only in health but also in clinically asymptomatic liver, as part of risk stratification strategies. In this study, two unique disease initiation and maintenance protocols were developed and utilised to mimic steatosis and pre-fibrotic NASH in scaffold-free 3D liver microtissues (MT) composed of primary human hepatocytes, hepatic stellate cells, Kupffer cells and sinusoidal endothelial cells. The characterized diseased MT were utilized for the toxicological assessment of a panel of xenobiotics. Highlights from the study included: 1. Clear experimental evidence for the pre-existing liver disease is important in the augmentation of xenobiotic-induced hepatotoxicity and 2. NMs are able to activate stellate cells. The data demonstrated that pre-existing disease is vital in the intensification of xenobiotic-induced liver damage. Therefore, it is imperative that all stages of the wide spectrum of liver disease are incorporated in risk assessment strategies. This is of significant consequence, as a substantial number of the general population suffer from sub-clinical liver injury without any apparent or diagnosed manifestations.
The role of Raman spectroscopy in biopharmaceuticals from development to manufacturing
Authors: Esmonde-White Karen A. , Cuellar Maryann , Lewis Ian R.
Published: October 2021

Biopharmaceuticals have revolutionized the field of medicine in the types of active ingredient molecules and treatable indications. Adoption of Quality by Design and Process Analytical Technology (PAT) frameworks has helped the biopharmaceutical field to realize consistent product quality, process intensification, and real-time control. As part of the PAT strategy, Raman spectroscopy offers many benefits and is used successfully in bioprocessing from single-cell analysis to cGMP process control. Since first introduced in 2011 for industrial bioprocessing applications, Raman has become a first-choice PAT for monitoring and controlling upstream bioprocesses because it facilitates advanced process control and enables consistent process quality. This paper will discuss new frontiers in extending these successes in upstream from scale-down to commercial manufacturing. New reports concerning the use of Raman spectroscopy in the basic science of single cells and downstream process monitoring illustrate industrial recognition of Raman’s value throughout a biopharmaceutical product’s lifecycle. Finally, we draw upon a nearly 90-year history in biological Raman spectroscopy to provide the basis for laboratory and in-line measurements of protein quality, including higher-order structure and composition modifications, to support formulation development.

Graphical abstract
LDA measurements in a one-sided ribbed square channel at Reynolds numbers of 50,000 and 100,000
Authors: Ruck Sebastian , Arbeiter Frederik
Published: October 2021

Laser Doppler anemometry (LDA) measurements in the fully developed turbulent flow through a one-sided rib-roughened square channel with a rib-height-to-channel-height ratio of $$k/H = 0.0667$$

k
/
H
=
0.0667

and a rib-pitch-to-rib-height ratio of $$p/k = 9$$

p
/
k
=
9

were carried out at Reynolds numbers (based on the channel height H and the mean bulk velocity $$u_B$$

u
B

) of $${Re}_H = 5.0 \cdot 10^4$$

Re

H

=
5.0
·

10
4

and $$1.0 \cdot 10^5$$

1.0
·

10
5

. Mean velocities, Reynolds normal, and shear stresses were determined. The first- and second-order statistical moments of the velocity differed slightly between both Reynolds numbers when normalized by the bulk velocity and the channel height. Deviations were attributed to a minor elongation increase in the large recirculation region behind the rib with increasing Reynolds numbers. The crucial role of turbulent diffusion was reflected in the non-coincidence of the maximum primary mean shear and the Reynolds normal stress as well as outward drifts of the Reynolds stress peaks along the rib crest. Turbulent diffusion contributed significantly to the turbulence kinetic energy (TKE) budget near the rib crest and within the separated shear layer, while mean convection made a remarkable contribution only at the rib leading edge. The detailed first- and second-order moments provide a basis for the validation of computational methods and turbulence models.

Graphic abstract
Health problems associated with single, multiple, and the frequency of months of objectively measured long working hours: a cohort study by the National Institute of Occupational Safety and Health, Japan
Authors: Ochiai Yuko , Takahashi Masaya , Matsuo Tomoaki , Sasaki Takeshi , Sato Yuki , Fukasawa Kenji , Araki Tsuyoshi , Otsuka Yasumasa
Published: October 2021

Purpose

We aimed to examine the prospective associations of monthly working hours measured in a month, the 6-month averaged hours, and the frequency of long working hours (≥ 205 h/month) during the past 6 months with health indicators.

Methods

This study included 6,806 Japanese company workers (response rate = 86.6%). Data on the workers’ monthly attendance during the second half of fiscal year 2016 and annual health checkups in fiscal years 2016 and 2017 were collected. We evaluated the association of the above three types of monthly working hours with subsequent health checkup data in fiscal year 2017. We adjusted for the corresponding data in fiscal year 2016.

Results

Multivariate logistic regression analyses revealed significant associations between monthly working hours and workers’ systolic and diastolic blood pressure as well as aspartate aminotransferase, alanine aminotransferase, low-density lipoprotein cholesterol (LDL), and triglyceride levels. However, the associations were not consistent between months. The average monthly working hours were significantly associated with higher LDL levels for the 220–240 h/mo group (OR: 1.49, 95%CI: 1.07–2.08) and lower triglyceride levels for the < 140 h/mo group (OR: 0.15, 95%CI: 0.03–0.77), compared to the 140–180 h/mo group. The frequency of long working hours was significantly associated with higher LDL levels.

Conclusions

Working hours over several months produced various associations with health indicators compared to those measured in a single month. Our present data suggest that the effects of average or frequency of long working hours during the past 6 months are likely to appear in LDL levels.
Upper and lower respiratory airway complaints among female veterinary staff
Authors: Hoffmeyer F. , Beine A. , Lotz A. , Kleinmüller O. , Nöllenheidt C. , Zahradnik E. , Nienhaus A. , Raulf M.
Published: October 2021

Objective

Working with animals is characterized by exposure to particulate, biological or chemical matter, and respiratory complaints are common. The aim of our cross-sectional study was to assess the prevalence of respiratory symptoms and diagnoses among veterinary staff.

Methods

Participants working in veterinary practices were examined and a detailed questionnaire was used to collect data. IgE tests to common and animal allergens were performed to specify sensitization. Associations with respiratory outcomes were analysed using logistic regression models while controlling for potential confounders.

Results

Atopy was seen in 31% of the 109 female participants. Symptoms of rhinoconjunctivitis were the most frequent complaints (n = 92; 84%). In 18% the diagnosis was confirmed by physicians. Symptoms of upper and lower airways were highly correlated and an asthma diagnosis was confirmed in 11% of participants. Modelling revealed that sensitization against cats/dogs was a significant risk factor for respiratory symptoms of upper [odds ratio (OR) 4.61; 95% confidence interval (CI) 1.13–18.81] and lower airways (OR 5.14; 95% CI 1.25–21.13), physician-confirmed rhinoconjunctivitis (OR 13.43; 95% CI 1.69–106.5) and asthma (OR 9.02; 95% CI 1.16–70.39) in assistant staff of small-animal practices.

Conclusions

In several cases, rhinoconjunctivitis worsened after entering the profession. Atopy and specific sensitization to cats/dogs were risk factors for health impairments. Thus, to implement preventive measures, veterinary practice staff should be educated that upper respiratory tract symptoms are not harmless and should be diagnosed and treated early.
Ultrastructure and functional morphology of the dorsal organs in Scoloplos armiger (Annelida, Sedentaria, Orbiniida)
Authors: Buhre Jana Sophia , Purschke Günter
Published: October 2021

Annelids and particularly polychaetes possess a great variety of sensory organs and respond to numerous sensory stimuli. Although eyes and nuchal organs are comparatively well studied, the so-called dorsal organs are among the lesser-known sense organs in aquatic annelids. Moreover, they are known to be restricted to only two out of approximately 80 families of polychaetes—Orbiniidae and Spionidae—which are not closely related. These organs have been regarded as segmentally repeated nuchal organs in the latter taxon, but in Orbiniidae, data are lacking, although it is known that the organs occur almost along the entire trunk except for the anterior-most segments. Furthermore, although the nuchal organ ultrastructure is known to be comparatively uniform for many polychaete species, a comparative investigation has not been conducted in Orbiniidae. To bridge this data gap, we examined an intertidal population of the widely distributed species Scoloplos armiger. Although not completely identical, nuchal and dorsal organs show a high degree of correspondence in the examined specimens. Moreover, both organs correspond to the general structure of nuchal organs. They comprise ciliated supportive cells and bipolar receptor cells and are innervated directly from the brain. The supportive cells form subcuticular spaces and olfactory chambers apically protected by specialized microvilli that house the sensory processes—cilia and microvilli—of the monociliated receptor cells. Therefore, it can be concluded that nuchal and dorsal organs are also identical in Orbiniidae. However, despite general correspondence with spionids, convergent evolution in the two taxa appears to be the most parsimonious interpretation.
Disparities in telehealth use: How should the supportive care community respond?
Authors: Dixit Niharika , Van Sebille Ysabella , Crawford Gregory B. , Ginex Pamela K. , Ortega Paz Fernandez , Chan Raymond J.
Published: October 2021

Telehealth use has increased in the setting of the COVID-19 pandemic. However, there are disparities in telehealth use based on age, income, race/ethnicity, low health, digital literacy, and limited English proficiency. There are multilevel barriers to telehealth use at the patient, health systems, telehealth portal, and policy levels. To ensure equity in telehealth services and to leverage these services to maximize the reach of health care services, concerted efforts are needed to design telehealth tools and workflows. It should include reimbursement for staff training, patient education, and technical support needed for telehealth use. Furthermore, ongoing monitoring and responsive modifications in the use of telehealth services are needed to promote telehealth equity.
Blink reflex in newly diagnosed and treated patients with Wilson’s disease
Authors: Bembenek Jan P. , Kiryluk Karolina , Inglot Ewa , Litwin Tomasz , Smoliński Łukasz , Członkowska Anna
Published: October 2021

Abnormal blink reflex (BR) results mainly from the dysfunction of reticular brainstem pathways and is one of the features of degenerative brain disorders. We aimed to investigate whether patients with Wilson’s disease (WD) have abnormal BR. This was a prospective, observational, single-center study. BR was assessed in accordance with generally accepted standards in 44 newly diagnosed treatment-naïve and 66 treated patients with WD. Any abnormal parameters in BR were observed in 45.5% treatment-naïve patients and 37.9% treated patients (p = 0.429). We also did not observe significant differences in BR parameters and frequency of abnormal findings between treated and treatment naïve patients. Abnormal findings in any of the BR parameters were more frequent in patients with neurological vs. non-neurological presentation (57.5 vs. 28.6%, p = 0.002), present vs. absent Kayser–Fleischer ring (73 vs. 21.5%, p < 0.001), and typical vs. no typical WD abnormalities in brain MRI (50% vs. 24.4%, p = 0.009). In addition, longer median R1 and R2 latencies, both ipsilateral and contralateral, were significantly more frequent in neurological than non-neurological WD patients, those with Kayser–Fleischer rings, and those with abnormal MRI findings typical of WD. Our results confirm frequent BR abnormalities in WD, which may be explained by the pathological influence of copper deposits in the circuit linking the basal ganglia, cerebellum and brainstem.
Understanding patient-reported knowledge of hernia surgery: a quantitative study
Authors: Jiménez D. Rosselló , López-Cano M. , Gonçalves V. Rodrigues , Tremolosa M. Verdaguer , Serra J. Saludes , Bravo-Salva A. , Rodríguez J. A. Pereira
Published: October 2021

Purpose

The objective of this study was to gather information on patient-reported knowledge (PRK) in the field of hernia surgery.

Methods

A prospective quantitative study was designed to explore different aspects of PRK and opinions regarding hernia surgery. Patients referred for the first time to a surgical service with a presumed diagnosis of hernia and eventual hernia repair were eligible, and those who gave consent completed a simple self-assessment questionnaire before the clinical visit.

Results

The study population included 449 patients (72.8% men, mean age 61.5). Twenty (4.5%) patients did not have hernia on physical examination. The patient’s perceived health status was “neither bad nor good” or “good” in 56.6% of cases. Also, more patients considered that hernia repair would be an easy procedure (35.1%) rather than a difficult one (9.8%). Although patients were referred by their family physicians, 32 (7.1%) answered negatively to the question of coming to the visit to assess the presence of a hernia. The most important reason of the medical visit was to receive medical advice (77.7%), to be operated on as soon as possible (40.1%) or to be included in the surgical waiting list (35.9%). Also, 46.1% of the patients considered that they should undergo a hernia repair and 56.8% that surgery will be a definitive solution.

Conclusion

PRK of patients referred for the first time to an abdominal wall surgery unit with a presumed diagnosis of hernia was quite limited and there is still a long way towards improving knowledge of hernia surgery.
Open data products-A framework for creating valuable analysis ready data
Authors: Arribas-Bel Dani , Green Mark , Rowe Francisco , Singleton Alex
Published: October 2021

This paper develops the notion of “open data product”. We define an open data product as the open result of the processes through which a variety of data (open and not) are turned into accessible information through a service, infrastructure, analytics or a combination of all of them, where each step of development is designed to promote open principles. Open data products are born out of a (data) need and add value beyond simply publishing existing datasets. We argue that the process of adding value should adhere to the principles of open (geographic) data science, ensuring openness, transparency and reproducibility. We also contend that outreach, in the form of active communication and dissemination through dashboards, software and publication are key to engage end-users and ensure societal impact. Open data products have major benefits. First, they enable insights from highly sensitive, controlled and/or secure data which may not be accessible otherwise. Second, they can expand the use of commercial and administrative data for the public good leveraging on their high temporal frequency and geographic granularity. We also contend that there is a compelling need for open data products as we experience the current data revolution. New, emerging data sources are unprecedented in temporal frequency and geographical resolution, but they are large, unstructured, fragmented and often hard to access due to privacy and confidentiality concerns. By transforming raw (open or “closed”) data into ready to use open data products, new dimensions of human geographical processes can be captured and analysed, as we illustrate with existing examples. We conclude by arguing that several parallels exist between the role that open source software played in enabling research on spatial analysis in the 90 s and early 2000s, and the opportunities that open data products offer to unlock the potential of new forms of (geo-)data.
Juvenile idiopathic arthritis-associated uveitis in the era of biological therapy: how the disease changed in more than 20 years of observation in a tertiary referral center in Rome (Italy)
Authors: Del Giudice E. , Simio C. , Scala A. , Di Coste A. , La Torre G. , Spadea L. , Lubrano R. , Duse M. , Paroli M. P.
Published: October 2021

Objectives

To describe the ophthalmological characteristics in a Juvenile idiopathic arthritis (JIA) cohort and to evaluate how therapeutic advances have changed the course of the uveitis.

Methods

Analysis of a retrospective cohort study of consecutive JIA pediatric patients including JIA-associated uveitis (JIA-U) and comparison with a previous study in the same uveitis center assessed before the wide-spread of biological therapy.

Results

The total of 49 JIA patients were analyzed, of whom 18 JIA-U, compared with a JIA-U past cohort of 66 patients. Systemic corticosteroids were used significantly less in the current JIA-U group (p = 0.008) than in the past one. JIA-U present cohort was on therapy more frequently with conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) than the past group (p = 0.039), mostly treated with methotrexate (93.3%). Furthermore, a larger use of biologic disease-modifying anti-rheumatic drugs (bDMARDs) was described in the current JIA-U group (p = 0.005) also associated with csDMARDs (p = 0.003). Adalimumab was used more (72.7%) in the present JIA-U cohort compared to a larger treatment with infliximab (61.5%) in the past (p = 0.005). Higher number of uveitis recurrences was observed in the previous cohort compared to the current one (p = 0.005). Fewer complications were described in this study than in the previous: posterior synechiae (p = 0.007), cataract (p < 0.001), band keratopathy (p < 0.001), and elevated intraocular pressure (IOP) (p = 0.047).

Conclusion

Current therapies reduced the uveitis recurrences and ocular complications including cataract due also to the lower use of corticosteroids. The new close collaboration with the pediatric rheumatologic center in the same University has contributed to the care improvement and decrease of uveitis complications.
Pharmacokinetic/Pharmacodynamic Modeling of a Cell-Penetrating Peptide Phosphorodiamidate Morpholino Oligomer in mdx Mice
Authors: Mukashyaka Marie Claire , Wu Chia-Ling , Ha Kristin , Zhang Jianbo , Wood Jenna , Foley Samantha , Mastis Bryan , Jungels Nino , Sun Huadong , Shadid Mohammad , Harriman Shawn , Hadcock John R.
Published: October 2021

Purpose

Peptide-conjugated phosphorodiamidate morpholino oligomers (PPMOs) have shown promise in treating Duchenne muscular dystrophy (DMD). We evaluated a semi-mechanistic pharmacokinetic (PK) and pharmacodynamic (PD) model to capture the relationship between plasma and muscle tissue exposure/response in mdx mice treated by mouse surrogate PPMO.

Methods

A single or repeated (every 4 weeks for 20 weeks) intravenous PPMO dose was administered to mdx mice (n = 6/timepoint). A PK/PD model was built to characterize data via sequential modeling. A 2-compartment model was used to describe plasma PK. A simultaneous tissue PK/PD model was subsequently developed: 2-compartment model to describe muscle PK; linked to an indirect response model describing stimulation of synthesis of skipped transcript, which was in turn linked to stimulation of synthesis of dystrophin protein expression.

Results

Model performance assessment via goodness-of-fit plots, visual predictive checks, and accurate parameter estimation indicated robust fits of plasma PK and muscle PK/PD data. The model estimated a PPMO tissue half-life of 5 days—a useful parameter in determining the longevity of PPMOs in tissue and their limited accumulation after multiple doses. Additionally, the model successfully described dystrophin expression after single dosing and associated protein accumulation after multiple dosing (increasing ~ twofold accumulation from the first to last dose).

Conclusions

This first PK/PD model of a PPMO in a DMD disease model will help characterize and predict the time course of PK/PD biomarkers in mdx mice. Furthermore, the model framework can be used to develop clinical PK/PD models and can be extended to other exon-skipping therapies and species.
‘At first I was overwhelmed, but then—I have to say—I did almost enjoy it’. Psychological needs satisfaction and vitality of student teachers during the first Covid-19 lockdown
Authors: Carmignola Matteo , Martinek Daniela , Hagenauer Gerda
Published: October 2021

According to Self-Determination Theory, the satisfaction of the three basic psychological needs (BPN) is crucial for optimal personal and academic development, as well as well-being, which is associated with the perceived vitality. These dimensions can be fostered or hindered by contextual factors within the work, study and personal environment. During the first COVID-19 lockdown, most social contexts for student teachers were substantially altered, for which we hypothesised negative outcomes with regards to perceived basic needs satisfaction and vitality. To investigate changes in needs satisfaction and subjective vitality during distance learning, this research applied an explanatory sequential mixed-methods design combining a quantitative and qualitative study. For the quantitative study, two surveys were conducted; the first before the lockdown (N = 161) and the second after the lockdown (N = 146). The purpose of these surveys was to test the interrelations between need satisfaction, frustration and vitality before and during the distance learning by implementing a SEM-based mediation analysis. In addition, we elaborated on significant and unexpected findings of the quantitative study by interviewing 14 other student teachers, allowing for an in-depth and contextualised understanding of the psychological changes in and the triggering factors of the ‘corona-lockdown’. Results stress the relevance of physical activity and time spent outdoors for the perception of vitality which was supported by a more flexible time structure during distance learning. For the context of distance learning, this research emphasises the relevance of BPN also in the context of online-based learning where higher levels of interaction with fellow students and lecturers, a clear course structure and formative feedback proved to be essential for motivational and achievement-related outcomes.