bluuebunny/crossref_metadata_2025 huggingface dataset:
Maize productivity response to combined tillage and mulching in coastal saline zones
Authors: Zhang Jishi , Bian Qianqian , Miao Qi , Jiang Xilong , Wang Yunhong , Wang Hongye , Cui Zhenling
Published: November 2021

Soil salinization is threatening sustainable crop production in coastal saline regions. An integrated approach with combined tillage and mulching may be more successful than sole management practice (e.g., rotary tillage) for reducing soil salinity and improving crop productivity in coastal saline zones. We conducted a 3‐yr field experiment in maize (Zea mays L.) in the Yellow River Delta. We used four treatments: (a) rotary tillage to 15 cm (RT) (local farmers’ practice), (b) deep tillage to 25‐to‐30‐cm depth followed by RT (DT), (c) flat planting with the application of plastic mulch after DT (DM), and (d) ridge‐furrow planting together with plastic mulching after DT (DMF). These treatments were intended to improve soil properties and maize productivity, while increasing net returns. Grain yields were significantly increased by 18.5–20.9% under DMF and DM, nitrogen partial factor productivity (PFPN) by 18.5–20.8%, and net returns by US$103–124 ha–1, compared with RT. Grain yields with DMF and DM were also improved by 12.7–15.0%, PFPN by 12.8–15.0%, and net returns by $ 39–60 ha–1, compared with DT. Compared with RT, soil electrical conductivity (EC) and Na+ concentration with DMF and DM were reduced by 16.2–75.4% and 19.0–78.2%; EC and Na+ concentration were also reduced by 6.41–64.4% and 11.1–53.7%, compared with DT. These results demonstrate that combined tillage and mulching is an efficient integrated management approach for improving soil properties, promoting maize productivity, and increasing financial benefits in coastal saline zones.
Survey Regarding Gastrointestinal Stoma Construction and Closure in Japan
Authors: Ando Yoshiko , Takahashi Arata , Fujii Makoto , Hasegawa Hiroshi , Kimura Toshimoto , Yamamoto Hiroyuki , Tajima Tetsuya , Nishiguchi Yukio , Kakeji Yoshihiro , Miyata Hiroaki , Kitagawa Yuko
Published: November 2021

Background and Aim

In Japan, the actual number of stoma constructions and stoma closures is not known. The aim of this study was to conduct a survey to determine the number of gastrointestinal stoma constructions and closures in Japan.

Methods

Enrolled participants comprised patients undergoing selected gastrointestinal surgeries who were recorded in the National Clinical Database. This database uses the “Common Items for Gastrointestinal Surgeons.” These procedures were formulated by the Japanese Society of Gastroenterological Surgery during 2013–2018.

Results

According to the National Clinical Database, a total of 154,323 gastrointestinal stomas were constructed between January 1, 2013 and December 31, 2018. By procedure, there were 78,723 cases of stoma construction, 39,653 of abdominoperineal resection, 2470 total pelvic exenteration procedures, and 33,572 Hartmann's procedures. The ratio of stoma closures to stoma constructions increased annually in patients under 70 y of age but not in older patients. Approximately 35% of total colectomies, 60% of proctocolectomies, and 20% of low anterior resections were accompanied by stoma construction. The number of patients with rectal cancer who underwent colostomy increased gradually during the study period and the number who underwent stoma construction increased among older patients.

Conclusion

The number of cases of gastrointestinal stoma construction has increased gradually in Japan, and the proportion of older patients is increasing each year. The purposes and surgical techniques for stoma construction are diverse and are expected to increase in Japan, a super‐aged society.
From heatmaps to structured explanations of image classifiers
Authors: Fuxin Li , Qi Zhongang , Khorram Saeed , Shitole Vivswan , Tadepalli Prasad , Kahng Minsuk , Fern Alan
Published: November 2021

This paper summarizes our endeavors in the past few years in terms of explaining image classifiers, with the aim of including negative results and insights we have gained. The paper starts with describing the explainable neural network (XNN), which attempts to extract and visualize several high‐level concepts purely from the deep network, without relying on human linguistic concepts. This helps users understand network classifications that are less intuitive and substantially improves user performance on a difficult fine‐grained classification task of discriminating among different species of seagulls. Realizing that an important missing piece is a reliable heatmap visualization tool, we have developed integrated‐gradient optimized saliency (I‐GOS) and iGOS++ utilizing integrated gradients to avoid local optima in heatmap generation, which improved the performance across all resolutions. During the development of those visualizations, we realized that for a significant number of images, the classifier has multiple different paths to reach a confident prediction. This has led to our recent development of structured attention graphs, an approach that utilizes beam search to locate multiple coarse heatmaps for a single image, and compactly visualizes a set of heatmaps by capturing how different combinations of image regions impact the confidence of a classifier. Through the research process, we have learned much about insights in building deep network explanations, the existence and frequency of multiple explanations, and various tricks of the trade that make explanations work. In this paper, we attempt to share those insights and opinions with the readers with the hope that some of them will be informative for future researchers on explainable deep learning.
Identification and functional study of FOXC1 variants in Chinese families with glaucoma
Authors: Wang Xinyao , Liu Xiangyuan , Li Yuying , Yang Bo , Sun Xuejiao , Yang Peng , Zhong Zilin , Chen Jianjun
Published: November 2021

This study aimed to identify the disease‐causing gene of three Chinese families with glaucoma. Whole exome sequencing was performed on the probands and detected three different variants (c.405C>A (p.Cys135Ter), c.851G>T (p.Ser284Ile), and c.392C>T (p.Ser131Leu)) in FOXC1 as a causative gene of glaucoma, and Sanger sequencing was performed for verification and cosegregation analysis. Three in silico tools all predicted these two missense variants to be probably disease‐causing. Western blot analysis, immunofluorescence, and dual‐luciferase assay were further used to evaluate the effect of FOXC1 missense variants, and demonstrated that the two variants resulted in decreased transactivation activity of FOXC1 although the variants had no effect on the protein amount and the nucleus subcellar localization of FOXC1 compared with the wild type, which implies that both of two variants may be probably pathogenic. In this study, we reported two novel FOXC1 variants as well as a reported variant and the phenotypes associated to these variants, which expands the spectrum and relevant phenotypes of FOXC1 variants. Additionally, the functional analysis of FOXC1 variants provides further insight into the possible pathogenesis of anterior segment anomaly related to FOXC1.
Advances in assessment of hypermobility‐related disorders
Authors: Simmonds Jane V.
Published: November 2021

There has been increasing recognition in recent years of the prevalence and impact of symptoms which extend beyond the musculoskeletal system on the lives of people with hypermobility‐related disorders. This has led researchers to develop more comprehensive assessment tools to help direct and monitor treatment. This article presents some of the latest assessment and diagnostic developments and their implications for practice from a physical therapy perspective.
Fascial thickness and stiffness in hypermobile Ehlers‐Danlos syndrome
Authors: Wang Tina J. , Stecco Antonio
Published: November 2021

There is a high prevalence of myofascial pain in people with hypermobile Ehlers‐Danlos Syndrome (hEDS). The fascial origin of pain may correspond to changes in the extracellular matrix. The objective of this study was to investigate structural changes in fascia in hEDS. A series of 65 patients were examined prospectively—26 with hEDS, and 39 subjects with chronic neck, knee, or back pain without hEDS. The deep fascia of the sternocleidomastoid, iliotibial tract, and iliac fascia were examined with B‐mode ultrasound and strain elastography, and the thicknesses were measured. Stiffness (strain index) was measured semi‐quantitatively using elastography comparing fascia to muscle. Differences between groups were compared using one‐way analysis of variance. hEDS subjects had a higher mean thickness in the deep fascia of the sternocleidomastoid compared with non‐hEDS subjects. There was no significant difference in thickness of the iliac fascia and iliotibial tract between groups. Non‐hEDS subjects with pain had a higher strain index (more softening of the fascia with relative stiffening of the muscle) compared with hEDS subjects and non‐hEDS subjects without back or knee pain. In myofascial pain, softening of the fascia may occur from increase in extracellular matrix content and relative increase in stiffness of the muscle; this change is not as pronounced in hEDS.
miR‐146b Protects the Perinatal Brain against Microglia‐Induced Hypomyelination
Authors: Bokobza Cindy , Joshi Pooja , Schang Anne‐Laure , Csaba Zsolt , Faivre Valérie , Montané Amélie , Galland Anne , Benmamar‐Badel Anouk , Bosher Emmanuelle , Lebon Sophie , Schwendimann Leslie , Mani Shyamala , Dournaud Pascal , Besson Valerie , Fleiss Bobbi , Gressens Pierre , Van Steenwinckel Juliette
Published: November 2021

Objectives

In the premature newborn, perinatal inflammation mediated by microglia contributes significantly to neurodevelopmental injuries including white matter injury (WMI). Brain inflammation alters development through neuroinflammatory processes mediated by activation of homeostatic microglia toward a pro‐inflammatory and neurotoxic phenotype. Investigating immune regulators of microglial activation is crucial to find effective strategies to prevent and treat WMI.

Methods

Ex vivo microglial cultures and a mouse model of WMI induced by perinatal inflammation (interleukin‐1‐beta [IL‐1β] and postnatal days 1–5) were used to uncover and elucidate the role of microRNA‐146b‐5p in microglial activation and WMI.

Results

A specific reduction in vivo in microglia of Dicer, a protein required for microRNAs maturation, reduces pro‐inflammatory activation of microglia and prevents hypomyelination in our model of WMI. Microglial miRNome analysis in the WMI model identified miRNA‐146b‐5p as a candidate modulator of microglial activation. Ex vivo microglial cell culture treated with the pro‐inflammatory stimulus lipopolysaccharide (LPS) led to overexpression of immunomodulatory miRNA‐146b‐5p but its drastic reduction in the microglial extracellular vesicles (EVs). To increase miRNA‐146b‐5p expression, we used a 3DNA nanocarrier to deliver synthetic miRNA‐146b‐5p specifically to microglia. Enhancing microglial miRNA‐146b‐5p overexpression significantly decreased LPS‐induced activation, downregulated IRAK1, and restored miRNA‐146b‐5p levels in EVs. In our WMI model, 3DNA miRNA‐146b‐5p treatment significantly prevented microglial activation, hypomyelination, and cognitive defect induced by perinatal inflammation.

Interpretations

These findings support that miRNA‐146b‐5p is a major regulator of microglia phenotype and could be targeted to reduce the incidence and the severity of perinatal brain injuries and their long‐term consequences. ANN NEUROL 2022;91:48–65
Can the Union of Prodrug Therapy and Nanomedicine Lead to Better Cancer Management?
Authors: Muthiah Giredhar , Jaiswal Amit
Published: November 2021

Prodrug‐mediated and nanomedicine‐mediated therapies stand at the forefront of cancer management today. However, a lot of recent research efforts have been focused on identifying novel strategies in treating tumor by combining the techniques and attributes of both prodrug‐mediated and nanomedicine‐mediated therapies into distinct prodrug‐based‐nanomedicine‐mediated (ProNaMed) therapies. Many of these amalgamated therapies exhibit augmented and sometimes synergistic antitumor effects which are engendered by the complementary and cooperative activities of the prodrugs and the nanostructures involved. Herein, the distinctive as well as overlapping features of prodrug‐mediated and nanomedicine‐mediated therapies with a few examples are expounded. Then, as some of the general trends observed in combined ProNaMed therapies are explored, the strategies used in such therapies along with some recent research examples and their respective therapeutic outcomes are discussed. Further, light is shed on the diverse manifestations of augmented antitumor effects and chemotherapeutic ameliorations which are noticeably materialized in many of the ProNaMed therapies. Fundamental insights are offered on why pursuing ProNaMed strategies may offer us better therapeutic solutions over isolated prodrug‐ or nanomedicine‐based strategies for tumor management.
CO‐Tolerant PEMFC Anodes Enabled by Synergistic Catalysis between Iridium Single‐Atom Sites and Nanoparticles
Authors: Yang Xiaolong , Wang Ying , Wang Xian , Mei Bingbao , Luo Ergui , Li Yang , Meng Qinglei , Jin Zhao , Jiang Zheng , Liu Changpeng , Ge Junjie , Xing Wei
Published: November 2021

Proton‐exchange membrane fuel cells (PEMFCs) are limited by their extreme sensitivity to trace‐level CO impurities, thus setting a strict requirement for H2purity and excluding the possibility to directly use cheap crude hydrogen as fuel. Herein, we report a proof‐of‐concept study, in which a novel catalyst comprising both Ir particles and Ir single‐atom sites (IrNP@IrSA‐N‐C) addresses the CO poisoning issue. The Ir single‐atom sites are found not only to be good CO oxidizing sites, but also excel in scavenging the CO molecules adsorbed on Ir particles in close proximity, thereby enabling the Ir particles to reserve partial active sites towards H2oxidation. The interplay between Ir nanoparticles and Ir single‐atom centers confers the catalyst with both excellent H2oxidation activity (1.19 W cm−2) and excellent CO electro‐oxidation activity (85 mW cm−2) in PEMFCs; the catalyst also tolerates CO in H2/CO mixture gas at a level that is two times better than that of the current best PtRu/C catalyst.
Rapid, Ordered Polymerization of Crystalline Semiconducting Covalent Triazine Frameworks
Authors: Sun Tian , Liang Yan , Xu Yuxi
Published: November 2021

The rapid synthesis of crystalline covalent triazine frameworks (CTFs) and exploration of the polymerization mechanism are highly desired for the research of crystalline porous polymers, but have not yet been reported. Herein, we demonstrate a scalable microwave‐assisted synthetic strategy to successfully prepare a series of highly crystalline and semiconducting CTFs within 20 minutes for the first time. By in situ imaging and time‐dependent characterization, we proposed an ordered two‐dimensional (2D) polymerization mechanism for crystalline CTFs, in which the monomers rapidly polymerize into periodic 2D molecular sheets within 10 s and then grow into more ordered framework structures. Photocatalytic study of CTF with different crystallinity revealed that large crystalline domain could significantly improve the photocatalytic performance. Single‐layer and few‐layer crystalline 2D triazine polymer nanosheets could be obtained through simple ball‐milling exfoliation of the bulk layered CTFs and exhibit nearly fivefold improved photocatalytic hydrogen evolution rate up to 7971 μmol g−1 h−1.
Harbour porpoise (Phocoena phocoena) presence is reduced during tidal turbine operation
Authors: Palmer Laura , Gillespie Douglas , MacAulay Jamie D. J. , Sparling Carol E. , Russell Debbie J. F. , Hastie Gordon D.
Published: November 2021

Uptake of tidal turbine technology to generate renewable energy has been partly limited by poor understanding of ecological impacts, including the potential for collisions between cetaceans and rotating turbine blades. To address this concern, it is necessary to identify whether cetaceans behaviourally respond to operating turbines.

A turbine in Scotland was instrumented with hydrophones to detect cetacean vocalizations. A generalized additive model was used to investigate temporal variability in harbour porpoise presence close to the turbine. As there were incidentally periods when the turbine was not operating, it was possible to determine the effect of blade rotation, whilst accounting for the potentially confounding effect of tidal flow.

Harbour porpoise presence varied intra‐annually, diurnally and with tidal state. Peak presence occurred during winter (September–February), at night and at high flow speeds on the flood tide.

Porpoises exhibited significant avoidance of the tidal turbine when it was operating; avoidance increased with flow speed, whereby mean porpoise presence was reduced by up to 78% (95% CIs, 51%, 91%) on the flood tide and up to 64% (95% CI, 3%, 91%) on the ebb tide.

The temporal variability in encounter rate in the present study highlights that collision risk assessments assuming static densities probably fail to capture the temporal variability of collision risk. Future studies should conduct long‐term baseline monitoring to derive encounter rates at larger spatio‐temporal scales and as a reference from which to measure change in habitat use. It is also critical that the generality of the avoidance rates presented here is assessed for other sites, turbine types, array sizes and cetacean species. As the tidal industry expands, it will be important to reconcile the benefits of avoidance responses from a collision risk perspective with potential chronic effects of displacement from, or barriers between, important habitats.
Using upper thermal limits of Lampsilis bracteata (Texas fatmucket) from the North Llano and San Saba rivers, Texas to inform water management practices in the Edwards Plateau
Authors: Goldsmith Amanda , Khan Jennifer M. , Robertson Clinton R. , Lopez Roel , Randklev Charles R.
Published: November 2021

Overexploitation of freshwater resources coupled with climate change can affect the flow and temperature regimes in rivers, which can be catastrophic for aquatic biota. The San Saba and Llano rivers, located in central Texas, are experiencing low flows and stream dewatering owing to over‐allocation. Both systems harbour imperilled species, including Lampsilis bracteata, Texas fatmucket, which has been proposed for listing under the US Endangered Species Act. It is suspected that elevated water temperatures are a contributing factor in its decline.

The upper thermal tolerances of glochidia and juvenile life stages were evaluated within each river. Mussels were acclimated to 27°C and tested across a range of temperatures (30–39°C) in 24 h (glochidia) and 96 h (juveniles) laboratory tests. The resulting tolerances were related to in situ water temperature and discharge using a uniform continuous above‐threshold analysis.

In the Llano, the 24 h LT50 (lethal temperature resulting in 50% mortality) was 31.8°C (95% CI 31.5–32.1°C), whereas the 96 h LT50 was 32.4°C (95% CI 32.1–32.7°C). In the San Saba, the 24 h LT50 was 34.7°C (95% CI 34.5–35.0°C), whereas the 96 h LT50 was 32.5°C (95% CI 32.2–32.9°C). LT50 thresholds were not exceeded for L. bracteata within the San Saba, but LT05 (lethal temperature resulting in 5% mortality) thresholds were exceeded. Water temperature loggers were lost in the Llano River as a result of a large flood; however, samples reported by the Texas Commission on Environmental Quality show that the LT05 and LT50 for both glochidia and juveniles were exceeded.

Findings from this study indicate that thermal tolerances of L. bracteata vary by population and that low flows may be contributing to its decline. Our approach is non‐species and region specific, which means that the methods presented should help managers and conservationists evaluate whether reduced water quantity and elevated temperatures are exerting impacts on aquatic species within their region.
Cribra orbitalia is correlated with the meningo‐orbital foramen and is vascular and developmental in nature
Authors: Zdilla Matthew J. , Nestor Nicholas S. , Rothschild Bruce M. , Lambert H. Wayne
Published: November 2021

Cribra orbitalia is a phenomenon with interdisciplinary interest. However, the etiology of cribra orbitalia remains unclear. Recently, the appearance of cribra orbitalia was identified as vascular in nature. This study assessed the relationship between anatomical variation of vasculature, as determined by the presence of meningo‐orbital foramina, and the presence of cribra orbitalia in 178 orbits. Cribra orbitalia was identified in 27.5% (49:178) of orbits (22.7%, 35:154 adult orbits and 58.3%, 14:24 subadult orbits) and meningo‐orbital foramina were identified in 65.8% (100:152) of orbits. Among the 150 total intact adult orbits (i.e., orbital roof and posterior orbits both intact), cribra orbitalia was found in 35 (23.3%). Of these 35 occurrences of cribra orbitalia, 32 (91.4%) had the concurrent finding of a meningo‐orbital foramen. However, in the absence of the meningo‐orbital foramen, cribra orbitalia was only found in three sides out of the total sample of intact orbits (3:150; 2.0%). Fisher's exact test revealed that the presence of cribra orbitalia and the meningo‐orbital foramen were statistically dependent variables (p = .0002). Visual evidence corroborated statistical findings—vascular impressions joined cribra orbitalia to meningo‐orbital foramina. This study identifies that individuals who possess a meningo‐orbital foramen are anatomically predisposed to developing cribra orbitalia. Conversely, cribra orbitalia is unlikely to occur in an individual who does not possess a meningo‐orbital foramen. Thus, the antecedent of cribra orbitalia is both vascular and developmental in nature. This report represents an important advancement in the understanding of cribra orbitalia—there is an anatomical predisposition to the development of cribra orbitalia.
A turn off–on fluorometric and paper‐based colorimetric dual‐mode sensor for isoniazid detection
Authors: Azizi Neda , Hallaj Tooba , Samadi Naser
Published: November 2021

In the present study, cobalt oxyhydroxide (CoOOH) nanosheets were applied for establishing a dual fluorometric and smartphone‐paper‐based colorimetric method to detect isoniazid. CoOOH nanosheets quenched the fluorescence emission of sulfur and nitrogen co‐doped carbon dots (S,N‐CDs) due to inner filter effect (IFE). The quenched fluorescence intensity of S,N‐CDs restored in the presence of isoniazid due to destroying CoOOH nanosheets by this drug. Moreover, with adding isoniazid the solution color of CoOOH nanosheets altered from brownish yellow to pale yellow. We exploited these facts to design a turn off–on fluorometric and paper‐based colorimetric sensor for isoniazid measurement at the range 0.5–5 and 5–100 μM with detection limits of 0.28 μM and 4.0 μM, respectively. The introduced dual sensor was used for pharmaceutical, environmental and biological analysis of isoniazid with satisfactory results. The paper‐based colorimetric sensor can be applied for isoniazid portable monitoring using a smartphone as a detector or even the naked eye.
A novel near‐infrared fluorescence probe for detecting and imaging Hg2+ in living cells
Authors: Liang Fanghui , Xu Longbin , Jin Danhong , Dong Lidan , Lin Shourui , Huang Rui , Song Daqian , Ma Pinyi
Published: November 2021

Fluorescence imaging, as one of the important means of biological lesion analysis, is widely used in medical analysis. To improve detection specificity, near‐infrared emission fluorescent probes have been developed. Sensitive and selective near‐infrared (NIR) fluorescent probes for Hg2+, which is a heavy metal ion harmful to human health, are urgently needed to investigate the physiological toxicity of Hg2+. The NIR fluorophore based on the traditional structure of rhodamine was prepared by introducing anthocyanin functional groups, and a rhodamine spiro ring structure was constructed to recognize Hg2+ (CCS–Hg). The probe CCS–Hg demonstrated good selectivity and high detection sensitivity for Hg2+ and the most likely mechanism was verified through theoretical calculations. We applied the probe CCS–Hg in the examination of Hg2+ distribution in living cells by NIR fluorescence imaging. This work provides a promising molecular tool for studying the toxicological effects of mercury ions in cell.
Clusterin, paraoxonase 1, and myeloperoxidase alterations induce high‐density lipoproteins dysfunction and contribute to peripheral artery disease; aggravation by type 2 diabetes mellitus
Authors: Sanda Gabriela M. , Toma Laura , Barbalata Teodora , Moraru Oriana E. , Niculescu Loredan S. , Sima Anca V. , Stancu Camelia S.
Published: November 2021

Peripheral artery disease (PAD) is an atherosclerotic disorder affecting arteries of the lower limbs, the major risk factors including dyslipidemia and diabetes mellitus (DM). We aimed to identify alterations of the proteins in high‐density lipoproteins (HDL) associated with HDL dysfunction in PAD patients. HDL2 and HDL3 were isolated from plasma of PAD patients with/without DM (PAD‐DM/PAD) and healthy subjects (N). Apolipoprotein AI (ApoAI), ApoAII, ApoCIII, clusterin (CLU), paraoxonase 1 (PON1), myeloperoxidase (MPO), and ceruloplasmin (CP) were measured in HDL2/HDL3 and plasma. Oxidation and glycation of the analyzed proteins were assessed as malondialdehyde‐protein adducts (MDA) and advanced glycation end‐products (AGE), respectively. The anti‐inflammatory effect of HDL3 was estimated as its potential to reduce monocyte adhesion to tumor necrosis factor α‐activated endothelial cells. We show that in PAD patients compared to N subjects: (i) HDL2 presented increased levels of MDA‐PON1, AGE‐PON1, AGE‐ApoAI, ApoAII, ApoCIII, and CP levels, and decreased PON1 levels; (ii) HDL3 had increased levels of MDA‐ and AGE‐CLU and ‐ApoAI, MDA‐PON1, ApoCIII, CLU, MPO, CP, and reduced PON1 levels. All these alterations were exacerbated by DM. These changes were more pronounced in HDL3, which had reduced anti‐inflammatory potential in PAD and became pro‐inflammatory in PAD‐DM. In PAD patients' plasma, CLU levels and MPO specific activity increased, while PON1 specific activity decreased. In conclusion, HDL function is altered in PAD patients due to multiple modifications of associated proteins that are aggravated by DM. Plasma CLU, MPO, and PON1 could constitute indicators of HDL dysfunction and contribute to risk stratification in PAD patients.
Characterization of hydrodynamics and volumetric power input in microtiter plates for the scale‐up of downstream operations
Authors: Montes‐Serrano Ignacio , Satzer Peter , Jungbauer Alois , Dürauer Astrid
Published: November 2021

Parameter estimation for scale‐up of downstream operations from microtiter plates (MTPs) is mostly done empirically because engineering correlations between microplates and stirred tank reactors (STRs) are not yet available. It is challenging to change the operation mode from shaken MTPs to large‐scale STRs. For the scale‐up of STRs, volumetric power input is well‐established although it is unclear whether this parameter can be used to transfer the operations from MTPs. We determine the volumetric power input in MTPs via the temperature increase caused by the motion of the liquid. The hydrodynamics in MTPs are studied with computational fluid dynamics (CFD). Mixing is investigated in 96‐, 24‐, and 6‐well MTPs to cover different geometries, filling volumes, shaking diameters, and shaking frequencies. All CFD simulations are validated by experimental results, which now allows prediction of the volumetric power input and hydrodynamics at various conditions in MTPs without the need for further experiments. We provide a map of the power input achievable in MTPs. Based on this map, from knowing about large‐scale conditions, adequate microscale conditions can be adjusted for process development. This enables the direct scale‐up of downstream unit operations from MTPs to STRs.
Fragmentation method for assigning oxidation numbers in organic and bioorganic compounds
Authors: Yuen Pong Kau , Lau Cheng Man Diana
Published: November 2021

Oxidation number (ON) is taught as an electron‐counting concept for redox reactions in chemistry curriculum. The molecular formula method, the Lewis formula method, and the structural formula method have all been used to determine ON. However, the task of assigning ON still poses problems for some teachers and students. This paper explores a new method, the fragmentation method, which is a visual approach for counting the individual ON of any atom according to its structural formula. The critical step is to break the carbon‐heteroatom bond into organic fragments and inorganic fragments. The individual ON of carbon atoms and heteroatoms can be determined by the bond cleavages in the organic and biological compounds. The mean ON of carbons can be calculated by the arithmetic mean of all individual ON of carbons in a molecule or molecular ion. The step‐by‐step operating procedures and examples are provided. When comparing corresponding molecules in organic conversions, the change of individual ON of atoms can be used as a tool for determining the number of transferred electrons. Furthermore, a reaction site can be identified by their changes of individual ON, chemical composition, and bond order in metabolic redox reactions.
Mobile electrophoresis kit for high school students: Scientific practices with innovation
Authors: Maurye Praveen , Basu Arpita , Jana Chayna , Devi Manoharmayum Shaya , Kumari Kavita , Naskar Malay
Published: November 2021

Gel electrophoresis (GE) is the most preferred and adapted technique for the separation and identification of biological molecules like proteins/peptides and nucleic acids from diverse types of organisms. All over the world, researchers, educators, and students aspiring to work in biochemistry and molecular biology disciplines use the polyacrylamide gel electrophoresis (PAGE) technique for resolving proteins/nucleic acids for understanding the structure and function of any cell. A simple PAGE technique requires a wide range of chemicals/reagents along with a well‐equipped and well‐spaced laboratory. We have developed a compact and impeccable mobile electrophoresis kit suitable for any vertically oriented PAGE technique. This comprehensive and portable laboratory set‐up provides the complete advantages of safety, cost‐efficiency, space management, and utility to the researchers for high‐throughput research. All new equipment of the mobile electrophoresis kit is fabricated using inexpensive and off‐the‐rack components. Overall performance of the mobile kit was verified through a practical exercises executed by high school students with positive outcomes.
The metabolite profiling of 3,4‐dicaffeoylquinic acid in Sprague–Dawley rats using ultra‐high performance liquid chromatography equipped with linear ion trap‐Orbitrap MS
Authors: Zhao Yuanyuan , Ren Yiran , Liu Zhenqing , Wang Zijian , Liu Ying
Published: November 2021

3,4‐Dicaffeoylquinic acid (3,4‐DiCQA) is a dicaffeoylquinic acid that possesses antioxidant, anti‐inflammatory, antibacterial, antiviral, anticancer, hypoglycemic, hypotensive, and hepatoprotective activities. This study developed a rapid and reliable method using ultra‐high performance liquid chromatography equipped with linear ion trap‐Orbitrap MS to identify the metabolites of 3,4‐DiCQA in rat plasma, urine, feces, and tissues. The metabolic profile of 3,4‐DiCQA was determined after an oral administration of 200 mg/kg to rats. A strategy of full scan‐parent ions list acquisition coupled to diagnostic product ion analysis for screening and identification of target metabolites was used. A total of 67 metabolites, combined with accurate mass measurement, diagnostic ions, neutral losses, and reference standards, were observed and characterized for the first time. The results indicated that hydrolysis, methylation, hydrogenation, hydration, dehydroxylation, dehydrogenation, sulfate conjugation, and glucuronide conjugation were the major metabolic reactions of 3,4‐DiCQA in vivo.
Highly sensitive quantification of pemetrexed in human plasma using UPLC‐MS/MS to support microdosing studies
Authors: van Ewijk‐Beneken Kolmer Eleonora W. J. , Teulen Marga J. A. , Boosman Rene J. , de Rouw Nikki , Burgers Jacobus A. , ter Heine Rob
Published: November 2021

Pemetrexed is an antifolate drug approved for the treatment of non‐small‐cell lung cancer and mesothelioma. Assessing pemetrexed pharmacokinetics after administration of a microdose (100 μg) may facilitate drug–drug interaction and dose individualization studies with cytotoxic drugs, without causing harm to patients. Therefore, a highly sensitive bioanalytical assay is required.

A reversed‐phase ultra‐high performance liquid chromatography method was developed to determine pemetrexed concentrations in human ethylenediaminetetraacetic acid–plasma after microdosing. [13C5]‐Pemetrexed was used as the internal standard. The sample preparation involved solid‐phase extraction from plasma. Detection was performed using MS/MS in a total run time of 9.5 min.

The assay was validated over the concentration range of 0.0250–25.0 μg/L pemetrexed. The average accuracies for the assay in plasma were 96.5 and 96.5%, and the within‐day and between‐day precision in coefficients of variations was <8.8%. Extraction recovery was 59 ± 1 and 55 ± 5% for pemetrexed and its internal standard. Processed plasma samples were stable for 2 days in a cooled autosampler at 10°C.

The assay was successfully applied in a pharmacokinetic curve, which was obtained as a part of an ongoing clinical microdosing study.
Value of screening and follow‐up brain MRI scans in patients with metastatic melanoma
Authors: Eggen Annemarie C. , Wind Thijs T. , Bosma Ingeborg , Kramer Miranda C. A. , van Laar Peter Jan , van der Weide Hiska L. , Hospers Geke A. P. , Jalving Mathilde
Published: November 2021

Background

Novel treatments make long‐term survival possible for subsets of patients with melanoma brain metastases. Brain magnetic resonance imaging (MRI) may aid in early detection of brain metastases and inform treatment decisions. This study aimed to determine the impact of screening MRI scans in patients with metastatic melanoma and follow‐up MRI scans in patients with melanoma brain metastases.

Methods

This retrospective cohort study included patients diagnosed with metastatic melanoma or melanoma brain metastases between June 2015 and January 2018. The impact of screening MRI scans was evaluated in the first 2 years after metastatic melanoma diagnosis. The impact of follow‐up MRI scans was examined in the first year after brain metastases diagnosis. The number of MRI scans, scan indications, scan outcomes, and changes in treatment strategy were analyzed.

Results

In total, 116 patients had no brain metastases at the time of the metastatic melanoma diagnosis. Twenty‐eight of these patients (24%) were subsequently diagnosed with brain metastases. Screening MRI scans detected the brain metastases in 11/28 patients (39%), of which 8 were asymptomatic at diagnosis. In the 96 patients with melanoma brain metastases, treatment strategy changed after 75/168 follow‐up MRI scans (45%). In patients treated with immune checkpoint inhibitors, the number of treatment changes after follow‐up MRI scans was lower when patients had been treated longer.

Conclusion(s)

Screening MRI scans aid in early detection of melanoma brain metastases, and follow‐up MRI scans inform treatment strategy. In patients with brain metastases responding to immune checkpoint inhibitors, treatment changes were less frequently observed after follow‐up MRI scans. These results can inform the development of brain imaging protocols for patients with immune checkpoint inhibitor sensitive tumors.
Tumor stemness and immune infiltration synergistically predict response of radiotherapy or immunotherapy and relapse in lung adenocarcinoma
Authors: Shi Hongjie , Han Linzhi , Zhao Jinping , Wang Kaijie , Xu Ming , Shi Jiajun , Dong Zhe
Published: November 2021

Cancer stem cells (CSCs) have been shown to accelerate tumor recurrence, radiotherapy, and chemotherapy resistance. Immunotherapy is a powerful anticancer treatment that can significantly prolong the overall survival of patients with lung adenocarcinoma (LUAD). However, little is known about the function of genes related to tumor stemness and immune infiltration in LUAD. After integrating the tumor stemness index based on mRNA expression (mRNAsi), immune score, mRNA expression, and clinical information from the TCGA database, we screened 380 tumor stemness and immune (TSI)‐related genes and constructed a five TSI‐specific‐gene (CPS1, CCR2, NT5E, ANLN, and ABCC2) signature (TSISig) using a machine learning method. Survival analysis indicated that TSISig could stably predict the prognosis of patients with LUAD. Comparison of mRNAsi and immune score between high‐ and low‐TSISig groups suggested that TSISig characterized tumor stemness and immune infiltration. In addition, enrichment of immune subpopulations showed that the low‐TSISig group held more immune subpopulations. GSEA revealed that TSISig had a strong association with the cell cycle and human immune response. Further analysis revealed that TSISig not only had a good predictive ability for prognosis but could also serve as an excellent predictor of tumor recurrence and response to radiotherapy and immunotherapy in LUAD patients. TSISig might regulate the development of LUAD by coordinating tumor stemness and immune infiltration. Finally, a connectivity map (CMap) analysis demonstrated that the HDAC inhibitor could target TSISig.
Association between somatic RET mutations and clinical and genetic characteristics in patients with metastatic colorectal cancer
Authors: Yang Yuan‐Zhong , Hu Wan‐Ming , Xia Liang‐Ping , He Wen‐Zhuo
Published: November 2021

Background

Rearranged during transfection (RET) is a targetable oncogene. RET fusions have been reported in patients with metastatic colorectal cancer (mCRC). However, RET mutations in mCRC are less studied. Here, we aimed to characterize the clinical, pathological, and molecular landscape of RET‐mutated mCRC.

Methods

Five hundred and eighty‐two patients were included in this study. Next‐generation sequencing was performed to detect RET mutations and calculate tumor mutation burden (TMB). We compared the clinical, pathological, and molecular characteristics of mCRC cases with tumors that harbored somatic RET mutations (N = 16, 2.7%) or had wild‐type RET (N = 566, 97.3%).

Results

Males comprised the absolute majority of cases with RET mutations (15/16 [93.8%]) compared to their fraction among cases with wild‐type RET (339/566 [59.9%]). Furthermore, all patients with RET mutations were younger than 60 years (16/16 [100%]), whereas such patients were less predominant in the group with wild‐type RET (379/566 [67.0%]). Individuals with tumors positive for RET mutations more frequently exhibited mucinous histology (5/16 [31.2%] vs. 55/566 [9.7%]), exhibited a lower incidence of liver metastasis (4/16 [25.0%] vs. 335/566 [59.2%]), and higher incidence of peritoneal metastasis (9/16 [56.2%] vs.161/566 [28.4%]), expressed wild‐type TP53 (8/16 [50.0%] vs.120/566 [21.2%]), and showed an increased frequency of MSI‐high (6/16 [37.5%] vs. 18/566 [3.2%]). In those with microsatellite‐stable mCRC, patients with RET mutations had a higher median TMB than patients with wild‐type RET (9.4 vs. 6.7 mutations/Mb, respectively, p = 0.001). The median progression‐free survival was similar in individuals with mutated and wild‐type RET on the oxaliplatin‐based regimen (7.1 vs. 8.7 months, p = 0.516).

Conclusions

Our study suggests that cases with RET mutations represent a separate mCRC subtype. Further studies are needed to evaluate the efficacy of RET inhibitors in mCRC patients with RET mutations.
Secondary Metabolites from the Fresh Leaves of Pinus yunnanensis Franch
Authors: Liu Di , Du Kai‐Cheng , Wang An‐Dong , Meng Da‐Li , Li Jian Lin
Published: November 2021

Fifteen metabolites, including two flavonols (1–2), three lignans (3–5), and ten diterpenoids (6–15), were isolated from the leaves of Pinus yunnanensis. Among them, flavanonol (1) were identified as undescribed flavonol derivative with natural rarely B‐ring fission lactone. Massive spectroscopic methods, the DP4+ probabilities and CD/ECD calculations were applied to establish the structure of component 1. Among these compounds, taxifolin (2) showed potent cytotoxicity, having IC50 values from 21.33 to 45.48 μg/mL, it also showed broad antibacterial activity against human pathogens with MIC values from 32 to 64 μg/mL.
K+ Transport in Perfluorosulfonic Acid Membranes and Its Influence on Membrane Resistance in CO2 Electrolysis
Authors: Vetter Kim‐Marie , Härtl Jamie , Reinisch David , Reichbauer Thomas , Martić Nemanja , Hinrichsen Kai‐Olaf , Schmid Günter
Published: November 2021

In CO2 electroreduction it is common to use cation exchange membranes in combination with high‐molar electrolytes. In a model polymer electrolyte membrane (PEM) water electrolysis setup, which mimics CO2 electrolysis in a mixed (modemix) and in a separate electrolyte mode (modesep), this study investigates how K+‐sulfonate interactions increase membrane resistance dependent on the electrolyte concentration. K+‐based electrolytes (KHCO3, K2SO4) are used instead of ultrapure water in the PEM‐model electrolyzer. At 1.0 M KHCO3, the membrane resistance is increased by 1.7 Ω cm2 (cathode side only) to 4.2 Ω cm2 (modemix), causing a significant voltage increase that needs to be invested for K+ transport over a PFSA membrane. We quantify the underlying ionic interactions to 527–545 mV and observed a further effect, namely a space‐charge limitation expressed by a strongly increased voltage, occurring in the case of K+ overload when lacking hopping centers for cation transport. Beginning at ca. 300 mA/cm2, the current density gets high enough to drive K+ back to the cathode side and low enough to prevent large resistive contributions and K+ overload. Along with thermodynamic considerations and pH‐induced intrinsic operational contributions, the membrane resistance was found to have a significant impact contributing to the total cell voltage Vtotal and proved that current research towards green and scalable CO2 electrolysis is on a promising way towards broad application.
Flexibility Control of Two‐Dimensional Coordination Polymers by Crystal Morphology: Water Adsorption and Thermal Expansion
Authors: Ohtani Ryo , Yoshino Haruka , Yanagisawa Junichi , Ohtsu Hiroyoshi , Hashizume Daisuke , Hijikata Yuh , Pirillo Jenny , Sadakiyo Masaaki , Kato Kenichi , Shudo Yuta , Hayami Shinya , Le Ouay Benjamin , Ohba Masaaki
Published: November 2021

Layer flexibility in two‐dimensional coordination polymers (2D‐CPs) contributes to several functional materials as it results in anisotropic structural response to external stimuli. Chemical modification is a common technique for modifying layer structures. This study demonstrates that crystal morphology of a cyanide‐bridged 2D‐CP of type [Mn(salen)]2[ReN(CN)4] (1) consisting of flexible undulating layers significantly impacts the layer configuration and assembly. Nanoplates of 1 showed an in‐plane contraction of layers with a longer interlayer distance compared to the micrometer‐sized rod‐type particles. These effects by crystal morphology on the structure of the 2D‐CP impacted the structural flexibility, resulting in dual‐functional changes: the enhancement of the sensitivity of structural transformation to water adsorption and modification of anisotropic thermal expansion of 1. Moreover, the nanoplates incorporated new adsorption sites within the layers, resulting in the uptake of an additional water molecule compared to the micrometer‐sized rods.
Efficient Process for Batch Analysis
Authors: Schmidt Benedikt , Tan Ruomu , Li Nuo , Hollender Martin , Gärtler Marco
Published: November 2021

Identification of quality issues in batch production is relevant for stable and successful production. The identification of systematic quality issues and the identification of root causes is complex and challenging. Powerful multivariate statistical methods exist to perform batch analysis, yet their application is difficult due to data diversity and complexity in model training. Here, insights from data analysis projects on four batch plants are presented and real world challenges are reviewed. This leads to a semi‐automatic process for more efficient batch analysis overcoming the mentioned tedious tasks.
Hot Electron‐induced Electrochemiluminescence with Dimethyl Silicone Oil Coated Electrode for the Determination of Puerarin
Authors: Xue Yuan , Xia Yong , Han Yanchao , Peng Chao , Li Jing , Wang Erkang
Published: November 2021

The development of the hot electron‐induced cathodic electrochemiluminescence (HECL) often accompanied with the advance in the electrode materials and instruments. In this work, dimethyl silicone oil was employed as the coating layer for initiating the HECL. The insulating layer was obtained by simple drop casting and subsequent polishing, which could withstand high voltage and meet the requirement of HECL. With the as‐prepared interface, the quantitative detection of puerarin in the aqueous solution was achieved based on the quenching effect on the SO4⋅−.
Stable and Efficient Graded MA0.83Cs0.17Pb(I0.83Br0.17)3 Alloy Thin Film‐Based Inverted‐Type Perovskite Solar Cells
Authors: Chang Sheng Hsiung , Cheng Kai-Ren , Chandel Anjali , Wu Jia-Ren , Shen Ji-Lin , Chen Sheng-Hui
Published: November 2021

The surface morphologies, crystallinities, and excitonic characteristics of MAxCs1−xPb(IxBr1−x)3 thin films deposited on top of the P3CT‐Na/ITO/glass substrates are investigated by using the atomic‐force microscopic images, absorbance spectra, grazing incidence X‐ray diffraction patterns, photoluminescence (PL) spectra, and Raman scattering spectra. The P3CT‐Na‐based perovskite solar cell shows a stable and efficient maximum power density curve due to the formation of a graded MA0.83Cs0.17Pb(I0.83Br0.17)3 alloy thin film which is confirmed by using the surface‐sensitive PL and Raman scattering spectra. The highest power conversion efficiency (PCE) of the P3CT‐Na‐based MA0.83Cs0.17Pb(I0.83Br0.17)3 solar cells is 15.93% mainly due to the high fill factor of 79.4%. Besides, the PCE of the nonencapsulated solar cell slowly decreases to a moderate value (10.48%) within 157 days under an uncontrolled environment (55–60 relative humidity%) at room temperatures (22–25 °C).