bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adaptive responses of freshwater pearl mussels, Margaritifera margaritifera, to managed drawdowns
Authors: Curley Edward A.M. , Thomas Rhian , Adams Colin E. , Stephen Alastair 
Published: December 2021

Abstract

Alterations to water management practices, in response to a growing demand to maximize energy production from renewable sources, threaten to exacerbate anticipated future water shortages caused by severe drought episodes, brought on by climate change.
Across Scotland, many highly managed systems are inhabited by some of the last remaining reproductively viable populations of the freshwater pearl mussel, Margaritifera margaritifera. A lack of empirical evidence concerning mussel responses to alterations in flow is inhibiting the development of effective conservation management practices to prolonged drought.
This study addressed this knowledge gap by examining the response of M. margaritifera to controlled water level drawdowns in laboratory and field settings. Using a laboratory flume, the responses of M. margaritifera from two different populations (a regulated system versus an unregulated system) were compared across rates of drawdown and density treatments. An analogous field trial was undertaken to examine the responses of M. margaritifera in a regulated system, with a hydroelectric dam facilitating a controlled drawdown.
The study showed that M. margaritifera can detect alterations in flow depth, which culminate in the emersion of mussel beds, and respond by undertaking vertical and horizontal movements to mitigate the risk of prolonged aerial exposure. Results from the field trial corroborated findings from the flume experiments, with 80% of mussels shown to avoid emersion successfully by tracking receding water levels.
Findings from this study support the role of controlled drawdowns in regulated rivers to reduce mortalities associated with receding water levels during prolonged low‐flow episodes. Differences between populations in response highlight a need to adopt a context‐dependent approach to conservation efforts.
Design, synthesis, and biological evaluation of coumarin analogs as novel LSD1 inhibitors
Authors: Sun Yixiang , Lv Ruicheng , Wu Tianxiao , Zhang Xiangyu , Sun Yin , Yan Jiangkun , Zhang Ziheng , Zhao Dongmei , Cheng Maosheng 
Published: December 2021

AbstractThe abnormal expression of lysine‐specific histone demethylase 1 (LSD1) is associated with different cancer types, and it is increasingly recognized as a potential therapeutic target in oncology. Here, utilizing core hopping and conformational restriction strategies, we designed and synthesized a series of coumarin analogs that were shown to be potent LSD1 inhibitors in the enzyme assay. Furthermore, several potent compounds were selected to evaluate their antiproliferative activity on A549 cells and MGC‐803 cells with high expression of LSD1. Among them,YX10showed an anticlonogenic effect on A549 cells and MGC‐803 cells, with IC50values of 1.52 ± 0.16 and 0.98 ± 0.18 μM, respectively. Modeling suggested that the inhibitors would bind to the active site of the protein located around the key residues of Asp555 and Lys661. Meanwhile, a preliminary druggability evaluation showed that compoundYX10showed favorable liver microsomal and moderate plasma stability and weak inhibitory activity against cytochrome P450 isoforms at 10 μM. All the results indicated that compoundYX10could represent a promising lead compound for further development.
Targeting VEGFR‐2 by new quinoxaline derivatives: Design, synthesis, antiproliferative assay, apoptosis induction, and in silico studies
Authors: Alsaif Nawaf A. , Mahdy Hazem A. , Alanazi Mohammed M. , Obaidullah Ahmad J. , Alkahtani Hamad M. , Al‐Hossaini Abdullah M. , Al‐Mehizi Abdulrahman A. , Elwan Alaa , Taghour Mohammed S. 
Published: December 2021

AbstractTwelve new triazolo[4,3‐a]quinoxaline‐based compounds are reported as anticancer agents with potential effects against vascular endothelial growth factor receptor‐2 (VEGFR‐2), using sorafenib as a reference molecule. With sorafenib as the positive control, the antiproliferative effects of the synthesized compounds against MCF‐7 and HepG2 cells, as well as their VEGFR‐2‐inhibitory activities, were assessed. The most powerful VEGFR‐2 inhibitor was compound14a, which had an IC50value of 3.2 nM, which is very close to that of sorafenib (IC50 = 3.12 nM). Furthermore, compounds14cand15dshowed potential inhibitory activity against VEGFR‐2, with IC50values of 4.8 and 5.4 nM, respectively. Compound14acaused apoptosis in HepG2 cells and stopped the cell cycle at the G2/M phase. In HepG2 cells, it also increased the levels of the proteases caspase‐3 and caspase‐9, as well as the Bax/Bcl‐2 ratio. In silico ADMET (absorption, distribution, metabolism, excretion, and toxicity) and toxicity experiments revealed that the synthesized agents had acceptable drug‐likeness.
Use of multivariate distance measures for high‐dimensional data in tests for difference, superiority, equivalence and non‐inferiority
Authors: Kropf Siegfried , Antweiler Kai , Glimm Ekkehard 
Published: December 2021

AbstractTests based on pairwise distance measures for multivariate sample vectors are common in ecological studies but are usually restricted to two‐sided tests for differences. In this paper, we investigate extensions to tests for superiority, equivalence and non‐inferiority.
Descriptive versus general praise with and without edibles for acquisition in young children
Authors: Kamana Bertilde U. , Dozier Claudia L. , Foley Elizabeth A. , Hubbs Amber N. 
Published: December 2021

AbstractPrevious research comparing the effects of descriptive and general praise on the acquisition of skills has yielded mixed outcomes. We attempted to replicate extend previous research by (a) isolating the effects of the different types of praise for acquisition of skills in eight preschool children and (b) determining child preference for the different types of praise. However, only two participants consistently acquired target skills (with negligible differences across the different types of praise); six of the eight participants did not consistently acquire target skills with either type of praise. Therefore, we added edibles to increase the efficacy of praise for these six participants. Results showed that all six participants acquired more skills when edibles were added. Furthermore, two of the six participants for whom we added edibles showed acquisition under particular conditions after a history with edibles. Results of the preference evaluation showed idiosyncratic outcomes across the seven participants with whom it was conducted.
Rational hinge engineering of carboxylic acid reductase from Mycobacterium smegmatis enhances its catalytic efficiency in biocatalysis
Authors: Wang Liuzhu , Sun Yangyang , Diao Shiqing , Jiang Shuiqin , Wang Hualei , Wei Dongzhi 
Published: December 2021

AbstractBackground: Carboxylic acid reductases (CARs) represent useful tools for the production of aldehydes from ubiquitous organic carboxylic acids. However, the low catalytic efficiency of these enzymes hampers their application.Methods: Herein, a CAR originating from Mycobacterium smegmatis was redesigned through rational hinge engineering to enhance the catalytic efficiency.Results: Based on the unique domain architecture of CARs and their superfamily, a mutagenesis library of the hinge region was designed. The best mutant R505I/N506K showed a 6.57‐fold improved catalytic efficiency. Molecular dynamics simulations showed the increased catalytic efficiency was due to the strong binding of the acyl‐AMP complex with it. Meanwhile, the ε‐nitrogen atom of Lys610 frequently interacted with the ribose‐ring oxygen atom of the complex, the distance (d1) between them represents a great indicator for that. The d1 value was used as a nimble indicator to evaluate unexplored mutants of that region for enhanced activity by in silico mutational experiments. Overall, eight mutants were identified to show higher enhanced activity compared with wild‐type enzyme and R505F/N506G showed the highest catalytic efficiency.Conclusion: Altogether, the two‐step strategy used here provided useful references for the engineering of CARs and other similar multiple‐domain enzymes.
An undergraduate laboratory experiment with real‐world applications: Utilizing templateless polymerase chain reaction and real‐time polymerase chain reaction to test for SARS‐CoV‐2 RNA
Authors: Crane Julia , Page Shallee T. 
Published: December 2021

AbstractWe present a course‐embedded undergraduate research module that involves real‐time polymerase chain reaction testing for the presence of SARS‐CoV‐2 in environmental samples. A positive control RNA was constructed and two RNA extraction methods were compared and a range of primers were available to compare. Using a combination of published protocols, we assembled a successful project that illustrated a topical exercise similar to real‐world assay development. The exercise is aimed at upper‐level undergraduates and requires 3 weeks of laboratory periods. The students were able to design and test experimental protocols, while learning about RNA detection. This project could be utilized in upper‐level classes including molecular biology, biochemistry, biotechnology, or for independent research projects.
Demoralisation and its link with depression, psychological adjustment and suicidality among cancer patients: A network psychometrics approach
Authors: Bobevski Irene , Kissane David W. , Vehling Sigrun , Mehnert‐Theuerkauf Anja , Belvederi Murri Martino , Grassi Luigi 
Published: December 2021

AbstractBackgroundDemoralisation is a clinically significant problem among cancer patients with a prevalence of 13%–18%. It is defined by difficulty in adjusting to a stressor, wherein the person feels trapped in their predicament and experiences helplessness, hopelessness, loss of confidence and loss of meaning in life. Demoralisation has a strong link with the desire for hastened death and suicidal ideation among the medically ill. This study explored whether a group of symptoms could be identified, distinct from depression, but consistent with adjustment difficulties with demoralisation and linked to ideation of death and suicide.MethodsExploratory Graph Analysis, a network psychometrics technique, was conducted on a large German study of 1529 cancer patients. Demoralisation was measured with the Demoralisation Scale II and depressive symptoms with the PHQ‐9.ResultsA network of symptoms, with four stable communities, was identified: 1. Loss of hope and meaning; 2. Non‐specific emotionality; 3. Entrapment; 4. Depressive symptoms. The first three communities were clearly distinct from the PHQ‐9 depressive symptoms, except for suicidality and fear of failure. Community 1, Loss of hope and meaning, had the strongest association with thoughts of death and suicide. Hopelessness, loss of role in life, tiredness, pointlessness and feeling trapped were the most central symptoms in the network.ConclusionsCommunities 1 to 3 are consistent with poor coping without anhedonia and other classic depression symptoms, but linked to suicidal ideation. For people facing the existential threat of cancer, this may indicate poor psychological adjustment to the stressors of their illness.
Survival outcomes of combined hepatocellular‐cholangiocarcinoma compared with intrahepatic cholangiocarcinoma: A SEER population‐based cohort study
Authors: Yang Zhen , Shi Guangjun 
Published: December 2021

AbstractBackgroundCombined hepatocellular‐cholangiocarcinoma (CHC) is a heterogeneous group of primary liver cancers characterized by the coexistence of both hepatic and biliary cellular contents. The aim of this study was to compare CHC and intrahepatic cholangiocarcinoma (ICC) and investigate the treatment and survival of patients with CHC.MethodsData on CHC and ICC, including clinicopathological characteristics, treatments, and survival outcomes were extracted from the SEER database between 2004 and 2016. Univariate and multivariate analyses of all data were performed to identify the risk factors associated with survival outcomes. The overall survival (OS) rates of CHC patients who underwent hepatic resection (HR) or liver transplantation (LT) were also assessed before and after propensity score matching.ResultsA total of 1066 consecutive patients who had been diagnosed with CHC (n = 286) or ICC (n = 780) were identified. The mean age of the CHC cohort was 60.8±10.7 years old. Among the CHC group, a large proportion of the patients were men and of White ethnicity (73.1% and 71.3%, respectively). The majority of tumors were poorly differentiated (37.8%), while the most common AJCC stage at presentation was stage I (31.4%). Multivariable analysis of all CHC patients revealed that only tumor size, M1 stage, AJCC stage IIIC, AJCC stage IV, surgery, and chemotherapy were significantly associated with OS. The OS was comparable with the ICC in the initial 36 months and better in the subsequent follow‐up after treatment. Surgery was associated with better survival outcomes, whether in the early or advanced stages. Regarding the specific types of surgery, the OS rates were similar in selected patients following HR or LT.ConclusionIn patients with CHC, surgical intervention resulted in better long‐term survival outcomes than nonsurgical treatments. The OS rate of CHC patients compared with that of ICC patients was discriminated before and after a 3‐year follow‐up.
Synthesis and Evaluation of Novel Quinazolinone Derivatives as Potential Anti‐HCC Agents
Authors: Qiu Jingying , Zou Yueting , Liu Qingchuan , Jiang Chunyu , Zhou Qingqing , Li Shuqiong , Chen Wang , Li Zheng , Gu Xiaoke 
Published: December 2021

AbstractHepatocellular carcinoma (HCC), a common malignancy worldwide, has a high mortality rate and limited effective therapeutic options. In this work, a series of quinazolinone compounds (6a–t and 7a–i) were synthesized as potential anti‐HCC agents. Among them, compound 7b more potently inhibited HepG2, HUH7 and SK‐Hep‐1 cells proliferation than classical anti‐HCC drug sorafenib, indicating its potential anti‐HCC effect. Interestingly, 7b could dose‐dependently decrease Cyclin D1 and CDK2 levels, and increase p21 protein expression, thus inducing HepG2 cells cycle arrest at G0/G1 phase. In addition, 7b also displayed potent apoptosis‐induced effect on HepG2 cells by interfering Bad, Bax, Bcl‐2 and Bcl‐xl proteins expression. Notably, 7b could efficiently block the activity of PI3K pathway by dose‐dependently reducing the phosphorylation of PI3K (Y607) and AKT (S473). Moreover, predicted ADME properties indicated that 7b possessed a good pharmacokinetic profile. Collectively, compound 7b might be a promising lead to the development of novel therapeutic agents towards HCC.
Novel method for detecting and quantifying residual bran and germ tissues in refined maize grits
Authors: Rocha‐Villarreal Verónica , Serna‐Saldívar Sergio O. , García‐Lara Silverio 
Published: December 2021

AbstractBackground and ObjectivesMaize is dry‐milled to generate fine grits by separating the germ and bran fractions from the starchy endosperm. The removal without affecting the aleurone layer of these two components, rich in fiber and fat, is critical because their presence impacts the yield, quality, and stability of the final product during storage. However, there is a lack of adequate methods to directly detect or quantify these bran and germ residues. This study developed a fast and effective method to identify and quantify the pericarp, aleurone layer, and germ residues in refined maize grits.FindingsThe heat treatment allowed the clear visualization of germ residues in grits, whereas staining effectively identified bran and aleurone residues. The additional use of a color association algorithm enabled the detection and quantification of bran (0%–0.49%) and germ (1.63%–3.39%) areas in the six grit samples.ConclusionThe method developed can be used to quickly and accurately determine grit purity and enhance the quality assessment of refined grits; thereby, providing useful insights for decision making, quality control, and optimization of the milling process.Significance and NoveltyThis study developed a quick and inexpensive detection method that uses a combination of heat, dyes, and a scanner to directly identify germ, pericarp, and aleurone residues in refined maize grits.
Safe clinical technique for increasing the occlusal vertical dimension in case of erosive wear and missing teeth
Authors: D’Arcangelo Camillo , Vadini Mirco , Buonvivere Matteo , De Angelis Francesco 
Published: December 2021

AbstractA safe method to increase the occlusal vertical dimension (OVD) in patients with mild temporomandibular symptoms (such as tenderness upon palpation) is described. After a temporomandibular joint magnetic resonance (MR), an OVD increase was sought, pursuing pure rotational movement without condyle displacement. Prior to definitive rehabilitation, an additional MR confirmed steady and healthy condyle‐disc‐fossa relationships.
A prenatal case of lissencephaly with cerebellar hypoplasia: New mutation in RELN gene
Authors: Balza Claire , Garofalo Giulia , Cos Teresa , Désir Julie , Kang Xin , Keymolen Kathelijn , Soblet Julie , Van Berkel Kim , Vilain Catheline , Ben Abbou Wafa , Cassart Marie 
Published: December 2021

AbstractReelinopathies cause a distinctive lissencephaly type associated with cerebellar hypoplasia. To help further management, we wanted to report here the first prenatal diagnosis due to a homozygous inherited reelinopathy.
Treatment of Morgellons disease with doxycycline
Authors: Zhang Jeff F. , Gopalakrishnan Keerthy , Molloy Daniel J. 
Published: December 2021

AbstractMorgellons disease (MD) is a rare dermatopathy characterized by nonspecific symptoms and the production of multicolored fibers and granular tissue from diffuse skin ulcerations which are described as being either pruritic or painful. The etiology of MD is currently unknown; previous studies have suggested both psychiatric and infectious causes, with increasing interest over the previous decade in elaborating a possible pathogenesis for the disease secondary to infection by Borrelia species. We report a middle‐aged Caucasian female who developed symptoms of MD in the days following exposure to a tick bite after spending an afternoon hiking through a wooded area. She was subsequently treated with a course of Doxycycline and found on two‐week follow‐up to have complete remission of her symptoms. This case report further supports the theory for an infectious etiology of MD and encourages future studies into its pathophysiology.
Jejunal hemorrhage due to hemolymphangioma successfully detected and controlled by double‐balloon enteroscopy
Authors: Ito Yuki , Osuga Tatsuya , Kawasaki Kentaro , Ikura Yoshihiro 
Published: December 2021

AbstractLymphangiomas are benign, often subclinical, neoplasms, which can develop in the digestive tracts. Hemorrhagic jejunal tumors are relatively rare and diagnostic challenge. We report herein a case of hemorrhagic jejunal hemolymphangioma successfully diagnosed and treated by double‐balloon enteroscopy.
Endovascular snare retrieval of an Angio‐Seal causing acute limb ischemia
Authors: Busch Lucas , Stern Manuel , Wolff Georg , Kelm Malte 
Published: December 2021

AbstractVascular complications (VCs) remain an important source of morbidity and mortality following percutaneous arterial catheterization. Vascular closure devices are popular and frequently used, but sometimes cause vessel occlusions that may require vascular surgery or complex endovascular procedures. In this case report, we describe the endovascular retrieval of an embolized Angio‐Seal device causing acute limb ischemia in a severely diseased 75‐year‐old female patient. This case highlights the endovascular technique using a snare catheter and adds another example to the growing evidence of an endovascular approach to manage vascular access site complications in comorbid patients at risk.
Portrait of a Family of Highly Stabilizing and Selective Guanine Quadruplex Platinum(II)‐Based Binders
Authors: Miron Caitlin E. , Chen Mickey , Mergny Jean‐Louis , Petitjean Anne 
Published: December 2021

AbstractThe long‐standing history of platinum coordination complexes in nucleic acid recognition attests to the unique suitability of such species for therapeutic applications. Here, we report the synthetic exploration and development of a family of di‐imine ligands, and their platinum(II) complexes, elaborated on a 3‐(2‐pyridyl)‐[1,2,4]triazolo[4,3‐a]pyridine platform which, in its unsubstituted form, has recently been shown to display exceptional capabilities for guanine quadruplex (G4) targeting. The identification of facile, high‐yielding synthetic methods for the derivatization of this platform for the incorporation of additional sites of interactions with guanine quadruplex loops and grooves, along with the optimization of platinum(II) complexation methods, are discussed. Gratifyingly, preliminary biophysical screening of this novel family of binders validates all but one family members as robust G4 binders and highlights enhanced selectivity for quadruplex versus duplex DNA compared to the parent compound. These results bear promise for practical developments based on this platform.
Discovery of Kalmane Diterpenoids as Potent Analgesics from the Flowers of Rhododendron dauricum
Authors: Feng Yuanyuan , Zha Suqin , Gao Biao , Zhang Hanqi , Jin Pengfei , Zheng Guijuan , Ma Yilin , Yao Guangmin 
Published: December 2021

Comprehensive SummaryKalmane diterpenoids, featuring a 5/8/5/5 tetracyclic carbon skeleton, are very rare in nature. The flowers of Rhododendron dauricum L. (Ericaceae) were phytochemically investigated for the first time, leading to the isolation of eight kalmane diterpenoids (1—8) including four new ones, named rhodokalmanols A—D (1—4). The structures of 1—8 were elucidated by comprehensive spectroscopic methods and 13C NMR‐DP4+ analysis, and the absolute configurations of 1, 2, 4, and 5 were defined by single‐crystal X‐ray diffraction analysis with Cu Kα radiation. Rhodokalmanol A (1) represents the first 5,8‐epoxykalmane diterpenoid and also the first kalm‐15(16)‐ene diterpenoid. Rhodokalmanols B—D (2—4) are the first examples of kalm‐7(8)‐ene, kalm‐16(17)‐ene, and 8α‐methoxykalmane diterpenoids, respectively. All the isolated kalmane diterpenoids 1—8 exhibited significant analgesic effects, and rhodokalmanol C (3) and kalmanol (8) expressed more potent analgesic activity than morphine at doses of 0.2 and 0.04 mg/kg. The preliminary structure‐activity relationships of kalmane diterpenoids as potent analgesics are discussed.
Study on fracture behavior of molars based on three‐dimensional high‐precision computerized tomography scanning and numerical simulation
Authors: Feng Xianhui , Kou Wen , Liu Hongyuan , Gong Bin , Tang Chun'an 
Published: December 2021

AbstractA series of three‐dimensional (3D) numerical simulations are conducted to investigate the gradual failure process of molars in this study. The real morphology and internal mesoscopic structure of a whole tooth are implemented into the numerical simulations through computerized tomography scanning, digital image processing, and 3D matrix mapping. The failure process of the whole tooth subject to compressions including crack initiation, crack propagation, and final failure pattern is reproduced using 3D realistic failure process analysis (RFPA3D) method. It is concluded that a series of microcracks are gradually initiated, nucleated, and subsequently interconnect to form macroscopic cracks when the teeth are under over‐compressions. The propagation of the macroscopic cracks results in the formation of fracture surfaces and penetrating cracks, which are essential signs and manifestations of the tooth failure. Moreover, the simulations reveal that, the material heterogeneity is a critical factor that affects the mechanical properties and fracture modes of the teeth, which vary from crown fractures to crown‐root fractures and root fractures depending on different homogeneity indices.