bluuebunny/crossref_metadata_2025 huggingface dataset:
Shared decision-making for the management of small renal masses — development and acceptability testing of a novel patient decision aid
Authors: McAlpine Kristen , Breau Rodney H. , Stacey Dawn , Knee Christopher , Jewett Michael A.S. , Violette Philippe D. , Richard Patrick O. , Cagiannos Ilias , Morash Christopher , Lavallée Luke T.
Published: June 2020

Introduction: Shared decision-making incorporates patient’s values and preferences to achieve high-quality decisions. The objective of this study was to develop an acceptable patient decision aid to facilitate shared decision-making for the management of small renal masses (SRMs).

Methods: The International Patient Decision Aids Standards were used to guide an evidence-based development process. Management options included active surveillance, thermal ablation, partial nephrectomy, and radical nephrectomy. A literature review was performed to provide incidence rates for outcomes of each option. Once a prototype was complete, alpha-testing was performed using a 10-question survey to assess acceptability with patients, patient advocates, urologists, and methodological experts. The primary outcome was acceptability of the decision aid.

Results: A novel patient decision aid was created to facilitate shared decision-making for the management of SRMs. Acceptability testing was performed with 20 patients, 10 urologists, two patient advocates, and one methodological expert. Responders indicated the decision aid was appropriate in length (82%, 27 of 33), well-balanced (82%, 27 of 33), and had language that was easy to follow (94%, 31 of 33). All patient responders felt the decision aid would have been helpful during their consultation and would recommend the decision aid for future patients (100%, 20 of 20). Most urologists reported they intend to use the decision aid (90%, 9 of 10).

Conclusions: A novel patient decision aid was created to facilitate shared decision-making for management of SRMs. This clinical tool was acceptable with patients, patient advocates, and urologists and is freely available at: https://decisionaid.ohri.ca/decaids.html.
Physiological and Clinical Aspects of the Endocrinology of the Estrous Cycle and Pregnancy in Mares
Authors: Satué Katy , Carlos Gardon Juan
Published: June 2020

The use of advanced reproductive endocrinology can generate important economic benefits for equine breeding farms. Pregnancy in the mare involves considerable endocrine changes, which can be explained in part by the development of different structures such as embryonic vesicles, primary and secondary CL, endometrial cups and development of fetoplacental units. Both the pregnant mare and the fetus adapt to this development with unique mechanisms, such as alterations in the maternal endocrine metabolism and hormonal feedback. Since the ability to produce a viable foal is critical for the broodmare, the maintenance of the gestation implies almost a year of physiological effort. Therefore, the joint knowledge of basic reproductive science and current clinical endocrinology allows veterinarians and breeders to be better positioned to achieve their objectives. This chapter reviews normal and abnormal endocrine patterns during the equine estrual cycle, pregnancy. We also consider hormonal evaluation related to placentitis, abortions, recurrent pregnancy loss, and premature deliveries. Also, several aspects associated with endocrinological control of the reproductive cycle, ovulation, parturition, high-risk mare, and hormone supplementation will be developed.
An 11-Year-Old Boy Infected with COVID-19 with Presentation of Acute Liver Failure
Authors: Saeed Amir , Shorafa Eslam , Shahramian Iraj , Afshari Mahdi , Salahifard Mehrdad , Parooie Fateme
Published: June 2020

: Coronavirus disease 2019 (COVID-19) first emerged in Wuhan, China, in December 2019. Then, it spread to the whole world so that THE World Health Organization (WHO) declared a worldwide pandemic on March 11, 2020. Coronavirus disease 2019 is a novel and mysterious infectious disease that causes respiratory illness, multiorgan failure (MOF), and death. Although pediatric COVID-19 accounts for a small percentage of patients and is often milder than in adults, it can progress to severe disease in some cases. Liver involvement in COVID-19 and its severity have not been clearly investigated. In this paper, we present an 11-year-old boy admitted to a Pediatric Intensive Care Unit (PICU) with COVID-19 diagnosis in combination with elevated liver enzymes and bilirubin.
Long-Term Antithyroid Drug Treatment: Trends in Serum TSH and TSH Receptor Antibody Changes in Patients with Graves’ Disease
Authors: Okamura Ken , Bandai Sachiko , Fujikawa Megumi , Sato Kaori , Ikenoue Hiroshi , Kitazono Takanari
Published: June 2020

Objectives: Trends in serum thyroid-stimulating hormone (TSH) and TSH receptor antibody (TRAb) changes during antithyroid drug treatment, and long-term prognosis were evaluated in Graves’ hyperthyroidism (GD). Methods: In 609 GD patients initially treated with 15 mg of methyl-mercapto imidazole (MMI), the changes in serum TRAb and long-term prognosis were compared in the TSH-normalized group (A) and the TSH-suppressed group (B and C) during the initial 180 days of treatment. Results: Early responses to MMI during 180 days of treatment were as follows: 48 cases (7.9%) became hypothyroid with elevated TSH (A1), and 188 cases (30.9%) became euthyroid with normal TSH (A2). Among patients with continuously suppressed TSH, the free T4 (fT4) level was low in 31 cases (5.1%) (B1-inappropriately suppressed TSH), fT4 and fT3 were normal in 185 cases (30.4%) (B2), fT4 was normal, but fT3 remained high in 84 cases (13.8%) (B3), and fT4 remained high in 73 cases (12.0%) (C-refractory). Serum TRAb became negative after < 5 years then remained negative in 25% - 51% of the cases (smooth type), became negative after < 5 years then became positive again in 30% - 43% of the cases (fluctuating type), and remained positive after > 5 years in 10% - 42% of the cases (smoldering type). In total, remission occurred after 6.2 (3.0 - 10.4) years of treatment in 42%, possible remission on a small maintenance dosage of antithyroid drug occurred in 13%, and spontaneous hypothyroidism occurred in 4.4% of the cases. The smoldering type was more frequent in the B1 and C groups than in others, and remission was less frequent. The difference in the long-term prognosis depending on the early response to MMI disappeared after excluding the ablated patients. Without ablation, remission or spontaneous hypothyroidism could be expected in 60% - 75% of patients after tenacious treatment for > 10 years. Conclusions: Prolonged suppression of serum TSH may suggest active TRAb activity during treatment, and continuous TRAb positivity for more than 5 years suggests persistent GD activity.
Social Support Levels in Children with Type 1 Diabetes or Epilepsy
Authors: Korucu Elanur , Özyazıcıoğlu Nurcan , Atak Meryem , Manavoğlu Ceyhun
Published: June 2020

Background: Studies on children and adolescents living with different chronic diseases show the importance of social support to face the disease. Social support affects the course of the disease in children with Type 1 Diabetes Mellitus (T1DM) or epilepsy. Objectives: This study was conducted to determine the level of social support of children with T1DM or epilepsy. Methods: The sample consisted of a total of 100 children aged 11 - 17, including 50 diabetes and 50 epilepsy patients. No sample calculation was made in the study. The study was completed with 100 children who met the inclusion criteria. The data of the study were collected by the researchers in the hospital environment between April and October 2017 using the Child Introductory Form and the Child-Adolescent Social Support Scale (CASSS). Results: Children with epilepsy had lower social support scores than children with T1DM when the scores of the children on the subscales of CASSS were examined. As the ages of all children participating in the study decreased, the obtained importance of social support scores increased. Conclusions: It may be proposed to know the social support levels of children with epilepsy or type 1 diabetes and plan nursing interventions to increase their awareness.
The Results of Uvulopalatopharyngoplasty in Patients with Moderate Obstructive Sleep Apnea Syndrome Having Cardiac Arrhythmias
Authors: Seyed Resuli Ali , Samur Hasan
Published: June 2020

Objectives: The goal of this practice was to explore whether the changes in arrhythmias after uvulopalatopharyngoplasty (UPPP) in patients with moderate obstructive sleep apnea syndrome (OSAS) who continued cardiac arrhythmias despite the use of antiarrhythmic drugs and those who could not tolerate the continuous positive airway pressure (CPAP) device. In addition, we evaluated the correlation between arrhythmias before and after UPPP. Methods: This retrospective study included patients who have OSAS and cardiac arrhythmias, between 2008 - 2017 by the cardiology clinic and consulted by the ear, nose, and throat (ENT) clinic. Thirty eight patients were selected and underwent UPPP operation. The rhythm Holter follow-ups of the patients in the 1st month before UPPP (pre-UPPP) and after UPPP (post-UPPP) 6th month were performed. The recordings were transferred to the computer and evaluated with the Holter program, then visually examined and the parasitic regions were excluded. Sinus bradycardia (SB), atrioventricular block (AVB), atrial premature beat (APB), supraventricular tachycardia (SVT), and ventricular extrasystole (VES) parameters were recorded for arrhythmia. Results: Statistically significant differences were observed in the changes in SB, AVB, APB, SVT and VE arrhythmia values in pre-UPPP and post-UPPP periods. Also, in one case the values of arrhythmia in the pre-UPPP period had a positive correlation with the values of the same arrhythmia in the post-UPPP period (P < 0.001). Conclusions: In this study, new information about the effects of UPPP which is one of OSAS treatment methods on cardiac arrhythmias is presented. According to our results, UPPP reduces the rate of SB, AVB, APB, SVT and VES arrhythmias in OSAS patients.
Structural Relationships Between Depression, Perceived Stress, Sleep Quality, and Quality of Life: Evidence from Iranian Elderly
Authors: Kamali Zarch Mahmoud , Sorbi Mohammad Hossein
Published: June 2020

Objectives: This study tested structural relationships between depression, perceived stress, sleep quality, and quality of life through path analysis. Methods: In this cross-sectional study, 360 elderly Iranian people were selected using multistage cluster sampling from April 2 to December 6, 2018. The instruments included a demographic form, the geriatric depression scale (GDS), the quality of life scale (QOLS), the perceived stress scale (PSC), and the Pittsburgh sleep quality index (PSQI). To analyze the data, the researchers used SPSS-21, LISREL-8.80, and the Sobel test. Results: The results showed that depression had a significant direct effect on sleep quality, but not on stress. The effect of depression and stress on the quality of life was found to be 45%. Further, depression, stress, and sleep quality had a significant direct effect on the quality of life. This could explain 85% of changes in the quality of life of the elderly. Moreover, depression with the mediating variable of sleep quality had an indirect effect on the quality of life. Conclusions: It can be concluded that providing conditions for a high quality of life level and a good sleep status can help to improve mental health in elderly people. However, further experimental and longitudinal research is needed in this respect, and it is necessary to study other mediating factors on quality of life in elderly
LE CYCLE DE JACK WATERMAN, OU LE GRAND ROMAN PULVÉRISÉ
Authors: Morency Jean
Published: June 2020

En s’appuyant sur les trois grandes tendances qui informent les romans de Poulin (l’américanité, la francité et la franco-américanité), cet article vise à mettre en lumière comment la pratique de la série et du cycle romanesques a guidé l’écrivain dans la construction de son oeuvre. Cette sérialité, qui est caractérisée par le paradoxe résidant entre l’ambition secrète du grand roman et la modestie apparente du discours romanesque, a accompagné l’élaboration de ce qu’on a appelé le cycle de Jack Waterman, qui regroupe les romans publiés dans le sillage de Volkswagen Blues. Toutes ces oeuvres expriment bien les apories qui sont constitutives du grand roman américain et plus largement encore franco-américain.
Le malaise professionnel des éducateurs spécialisés, entre mal-être et mal à être
Authors: Dugué Pierre
Published: June 2020

À l’heure actuelle, le malaise au travail des travailleurs sociaux et plus spécifiquement celui des éducateurs spécialisés s’avère devenir une problématique majeure et centrale. Comment pouvons-nous analyser l’apparition et l’installation de l’usure au travail des éducateurs spécialisés ? Les malaises exprimés ne seraient-ils pas des révélateurs d’une transformation identitaire professionnelle ? Quelles fonctions les plaintes et les ressentiments remplissent-ils d’un point de vue du processus de construction et de transaction identitaire ?
Habitual and ready positions in female table tennis players and their relation to the prevalence of back pain
Authors: Bańkosz Ziemowit , Barczyk-Pawelec Katarzyna
Published: June 2020

Background

The current body of knowledge shows that there is very little research into the occurrence and scale of asymmetry or postural defects in table tennis. It is interesting which regions of the spine are exposed to the greatest changes in the shape of its curvatures and whether the asymmetrical position of the shoulder and pelvic girdles in table tennis players changes when adopting the ready position. Consequently, can overload occur in certain parts of the spine and can the asymmetry deepen as a response of adopting this position? The reply to these questions may be an indication of the need for appropriate compensatory or corrective measures. Therefore, the aim of the study was to evaluate the effect of body position during play on the change in the shape of anterior–posterior spinal curvatures and trunk asymmetry in table tennis players.

Methods

To evaluate body posture the photogrammetric method based on the Moiré phenomenon with equipment by CQ electronic was applied. The study involved 22 female players practicing competitive table tennis (the age of 17 ± 4.5, with the average training experience of 7 ± 4.3 years, body mass of 47.8 ± 15.8, and body height of 161.2 ± 10.4). Each participant completed an author’s own questionnaire on spinal pain. The shape of curvatures in the sagittal and frontal plane was evaluated in the participant in the habitual standing position and in the table tennis ready position. Descriptive statistical analysis was performed and the significance of differences was tested using the Mann–Whitney U test.

Results and Conclusions

This study demonstrated the dominance of kyphotic body posture in table tennis players, which can be caused by many hours of using the ready position during playing. After adopting this position, there are significant differences in the angles of anterior and posterior spinal curvatures compared to the habitual posture. This may be the cause of overloads and pain complaints reported by the study participants. Adopting the ready position is also associated with an increase in asymmetry in the position (rotation) of the pelvis and spinous processes (frontal plane). Therefore, training programs should be extended with exercises that relieve the spine in the vertical line and exercises that improve symmetry of the work of the upper limbs, body trunk muscles and the pelvis.
Identification of SPRR3 as a novel diagnostic/prognostic biomarker for oral squamous cell carcinoma via RNA sequencing and bioinformatic analyses
Authors: Yu Lu , Yang Zongcheng , Liu Yingjiao , Liu Fen , Shang Wenjing , Shao Wei , Wang Yue , Xu Man , Wang Ya-nan , Fu Yue , Xu Xin
Published: June 2020

Oral squamous cell carcinoma (OSCC) has always been one of the most aggressive and invasive cancers among oral and maxillofacial malignancies. As the morbidity and mortality of the disease have increased year by year, the search for a promising diagnostic and prognostic biomarker for the disease is becoming increasingly urgent. Tumorous and adjacent tissues were collected from three OSCC sufferers and we obtained 229 differentially expressed genes (DEGs) between tumor and normal tissues via high-throughput RNA sequence. Function and pathway enrichment analyses for DEGs were conducted to find a correlation between tumorigenesis status and DEGs. Protein interaction network and molecular complex detection (MCODE) were constructed to detect core modules. Two modules were enriched in MCODE. The diagnostic and prognostic values of the candidate genes were analyzed, which provided evidence for the candidate genes as new tumor markers. Small Proline Rich Protein 3 (SPRR3), a potential tumor marker that may be useful for the diagnosis of OSCC, was screened out. The survival analysis showed that SPRR3 under expression predicted the poor prognosis of OSCC patients. Further experiments have also shown that the expression of SPRR3 decreased as the malignancy of OSCC increased. Therefore, we believe that SPRR3 could be used as a novel diagnostic and prognostic tumor marker.
Carbon Nanomaterials Applied for the Treatment of Inflammatory Diseases: Preclinical Evidence
Authors: Soltani Rym , Guo Shi , Bianco Alberto , Ménard‐Moyon Cécilia
Published: June 2020

In the last decade, graphene‐based nanomaterials and carbon dots have joined the family of carbon materials mainly composed of graphite, diamond, fullerene, and carbon nanotubes. Carbon nanomaterials have been widely exploited in various fields from electronics and materials science to nanomedicine. The studies on their effect on the immune system have revealed that they possess intrinsic anti‐inflammatory properties, reducing the production of proinflammatory cytokines and modulating immune cell maturation. In addition, their large specific surface area associated with high biocompatibility allows their use as carriers for the delivery of anti‐inflammatory agents. They can also contribute to the diagnosis of inflammatory diseases as biosensors for low‐limit detection and quantification of inflammation‐related biomarkers in body fluids and tissues allowing to monitor the concentration of drugs in urine and guide personalized drug usage. Finally, they are used as adsorbents for blood plasma purification in the clinical treatment of sepsis through efficient removal of certain cytokines. This review focuses on the intrinsic anti‐inflammatory properties of carbon nanomaterials. An overview is provided on their use as carriers of anti‐inflammatory drugs, as biosensors, and for blood purification in the context of inflammatory diseases. The potential of carbon nanomaterials for clinical translation is also critically discussed.
Smart Gold Nanostructures for Light Mediated Cancer Theranostics: Combining Optical Diagnostics with Photothermal Therapy
Authors: Tabish Tanveer A. , Dey Priyanka , Mosca Sara , Salimi Marzieh , Palombo Francesca , Matousek Pavel , Stone Nicholas
Published: June 2020

Nanotheranostics, which combines optical multiplexed disease detection with therapeutic monitoring in a single modality, has the potential to propel the field of nanomedicine toward genuine personalized medicine. Currently employed mainstream modalities using gold nanoparticles (AuNPs) in diagnosis and treatment are limited by a lack of specificity and potential issues associated with systemic toxicity. Light‐mediated nanotheranostics offers a relatively non‐invasive alternative for cancer diagnosis and treatment by using AuNPs of specific shapes and sizes that absorb near infrared (NIR) light, inducing plasmon resonance for enhanced tumor detection and generating localized heat for tumor ablation. Over the last decade, significant progress has been made in the field of nanotheranostics, however the main biological and translational barriers to nanotheranostics leading to a new paradigm in anti‐cancer nanomedicine stem from the molecular complexities of cancer and an incomplete mechanistic understanding of utilization of Au‐NPs in living systems. This work provides a comprehensive overview on the biological, physical and translational barriers facing the development of nanotheranostics. It will also summarise the recent advances in engineering specific AuNPs, their unique characteristics and, importantly, tunability to achieve the desired optical/photothermal properties.
Heavy‐Atom Tunneling Through Crossing Potential Energy Surfaces: Cyclization of a Triplet 2‐Formylarylnitrene to a Singlet 2,1‐Benzisoxazole
Authors: Nunes Cláudio M. , Viegas Luís P. , Wood Samuel A. , Roque José P. L. , McMahon Robert J. , Fausto Rui
Published: June 2020

Not long ago, the occurrence of quantum mechanical tunneling (QMT) chemistry involving atoms heavier than hydrogen was considered unreasonable. Contributing to the shift of this paradigm, we present here the discovery of a new and distinct heavy‐atom QMT reaction. Triplet syn‐2‐formyl‐3‐fluorophenylnitrene, generated in argon matrices by UV‐irradiation of an azide precursor, was found to spontaneously cyclize to singlet 4‐fluoro‐2,1‐benzisoxazole. Monitoring the transformation by IR spectroscopy, temperature‐independent rate constants (k≈1.4×10−3 s−1; half‐life of ≈8 min) were measured from 10 to 20 K. Computational estimated rate constants are in fair agreement with experimental values, providing evidence for a mechanism involving heavy‐atom QMT through crossing triplet to singlet potential energy surfaces. Moreover, the heavy‐atom QMT takes place with considerable displacement of the oxygen atom, which establishes a new limit for the heavier atom involved in a QMT reaction in cryogenic matrices.
Tetrazine Carbon Nanotubes for Pretargeted In Vivo “Click‐to‐Release” Bioorthogonal Tumour Imaging
Authors: Li He , Conde João , Guerreiro Ana , Bernardes Gonçalo J. L.
Published: June 2020

The bioorthogonal inverse‐electron‐demand Diels–Alder (IEDDA) cleavage reaction between tetrazine and trans‐cyclooctene (TCO) is a powerful way to control the release of bioactive agents and imaging probes. In this study, a pretargeted activation strategy using single‐walled carbon nanotubes (SWCNTs) that bear tetrazines (TZ@SWCNTs) and a TCO‐caged molecule was used to deliver active effector molecules. To optimize a turn‐on signal by using in vivo fluorescence imaging, we developed a new fluorogenic near‐infrared probe that can be activated by bioorthogonal chemistry and image tumours in mice by caging hemicyanine with TCO (tHCA). With our pretargeting strategy, we have shown selective doxorubicin prodrug activation and instantaneous fluorescence imaging in living cells. By combining a tHCA probe and a pretargeted bioorthogonal approach, real‐time, non‐invasive tumour visualization with a high target‐to‐background ratio was achieved in a xenograft mice tumour model. The combined advantages of enhanced stability, kinetics and biocompatibility, and the superior pharmacokinetics of tetrazine‐functionalised SWCNTs could allow application of targeted bioorthogonal decaging approaches with minimal off‐site activation of fluorophore/drug.
ECNU‐36: A Quasi‐Pure Polymorph CH Beta Silicate Composed of Hierarchical Nanosheet Crystals for Effective VOCs Adsorption
Authors: Jiao Meichen , Huang Ju , Xu Hao , Jiang Jingang , Guan Yejun , Ma Yanhang , Wu Peng
Published: June 2020

A quasi‐pure CH polymorph of microporous zeolite beta, named ECNU‐36, was obtained as a highly crystalline silicate using 1,5‐bis(tetramethylimidazolium) hydroxide as organic structure‐directing agent (OSDA) in fluoride media. An appropriate concentration of free fluoride in the synthetic mother liquor was crucial to purify the CH‐phase. The framework structure of ECNU‐36 consists of polymorph CH (>95 %) and polymorph B, elucidated by a combination of PXRD data, DIFFaX simulation, EDT, and HRTEM techniques. For the first time, the framework structure of beta CH polymorph was directly confirmed and solved using electron diffraction data. The pure‐silica ECNU‐36 showed an unusual crystal morphology, composed of stacked nanosheets, with typical 17 nm thickness and exposed {100} facets, which exhibited attractive adsorption performance for hydrocarbons and aromatics.
Template‐Directed Copying of RNA by Non‐enzymatic Ligation
Authors: Zhou Lijun , O'Flaherty Derek K. , Szostak Jack W.
Published: June 2020

The non‐enzymatic replication of the primordial genetic material is thought to have enabled the evolution of early forms of RNA‐based life. However, the replication of oligonucleotides long enough to encode catalytic functions is problematic due to the low efficiency of template copying with mononucleotides. We show that template‐directed ligation can assemble long RNAs from shorter oligonucleotides, which would be easier to replicate. The rate of ligation can be greatly enhanced by employing a 3′‐amino group at the 3′‐end of each oligonucleotide, in combination with an N‐alkyl imidazole organocatalyst. These modifications enable the copying of RNA templates by the multistep ligation of tetranucleotide building blocks, as well as the assembly of long oligonucleotides using short splint oligonucleotides. We also demonstrate the formation of long oligonucleotides inside model prebiotic vesicles, which suggests a potential route to the assembly of artificial cells capable of evolution.
Biocatalysis: Enzymatic Synthesis for Industrial Applications
Authors: Wu Shuke , Snajdrova Radka , Moore Jeffrey C. , Baldenius Kai , Bornscheuer Uwe T.
Published: June 2020

Biocatalysis has found numerous applications in various fields as an alternative to chemical catalysis. The use of enzymes in organic synthesis, especially to make chiral compounds for pharmaceuticals as well for the flavors and fragrance industry, are the most prominent examples. In addition, biocatalysts are used on a large scale to make specialty and even bulk chemicals. This review intends to give illustrative examples in this field with a special focus on scalable chemical production using enzymes. It also discusses the opportunities and limitations of enzymatic syntheses using distinct examples and provides an outlook on emerging enzyme classes.
Intermarriage of Halide Perovskites and Metal‐Organic Framework Crystals
Authors: Hou Jingwei , Wang Zhiliang , Chen Peng , Chen Vicki , Cheetham Anthony K. , Wang Lianzhou
Published: June 2020

This Review examines how the intermarriage of perovskite and metal‐organic framework crystals brings new paradigms for material design and functionality. The strategic combination of halide perovskites and metal–organic frameworks (MOFs) has generated a new family of porous composite materials that will enable new applications, including optoelectronic, catalysis, sensing, and data encryption. This Review surveys the current progress of this exciting new area. Fundamental aspects, including perovskite nucleation and growth, heterojunction electron–hole transfer, electronic structure, and luminescence within confined spaces, are highlighted, with suggestions of approaches by which guest confinement within MOFs can be synthetically designed. We further address the underlying principles and discuss the new insights and tools for the manipulation of these composite materials for the development of synthetic microporous semiconducting composites, as well as new strategies for host–guest interfacial engineering.
Sox genes in Agasicles hygrophila (Coleoptera: Chrysomelidae) are involved in ovarian development and oogenesis
Authors: Dong Wan‐Ying , Wang Yao , Zhou Zhong‐Shi , Guo Jian‐Ying
Published: June 2020

The alligator weed flea beetle, Agasicles hygrophila is a monophagous natural enemy of the invasive alligator weed Alternanthera philoxeroides. Oogenesis plays a vital role in the process of individual development and population continuation of oviparous insects. Sox is an ancient and ubiquitous metazoan gene family that plays a key regulatory role in various physiological processes, including oogenesis, which is closely related to fecundity. In this study, two Sox genes AhDichaete and AhSox3 were cloned and characterized, and then the expression profiles of AhDichaete and AhSox3 were qualified by a quantitative reverse transcription‐polymerase chain reaction. The result showed that these two Sox genes were expressed significantly higher in ovary, especially in the adult developmental stage. Furthermore, the functions of AhDichaete and AhSox3 in A. hygrophila females were studied using RNA interference (RNAi). Fewer offsprings were produced when AhDichaete and AhSox3 RNAi females mated with wild‐type males. Moreover, dsAhSox3 injection reduced the hatching rate of eggs but injection with dsAhDichaete did not. Further study of the reproductive system of AhDichaete and AhSox3 RNAi females showed that yolk protein deposition reduction in the ovarioles, then the expression of vitellogenin gene AhVg2 in ovaries was decreased. These results indicate that AhDichaete and AhSox3 play an important regulatory role in the process of ovarian development and oogenesis by affecting yolk synthesis in the ovary of A. hygrophila.
New applications of squalene synthase inhibitors: Membrane cholesterol as a therapeutic target
Authors: Kourounakis Angeliki P. , Bavavea Eugenia
Published: June 2020

Squalene synthase (SQS) inhibitors, mostly known as antihyperlipidemic agents for controlling blood cholesterol levels, have been increasingly used to study alterations of the cholesterol content in cell membranes. As such, SQS inhibitors have been demonstrated to control cellular activities related to cancer cell proliferation and migration, neuron degeneration, and parasite growth. While the mechanisms behind the effects of cellular cholesterol are still being revealed in detail, the evidence for SQS as a therapeutic target for several seemingly unrelated diseases is increasing. SQS inhibitors may be the next promising candidates targeting the three remaining primary therapeutic areas, beyond cardiovascular disease, which still need to be addressed; their application as anticancer, antimicrobial, and antineurodegenerative agents appears promising for new drug discovery projects underway.
Development of a prediction model with serum tumor markers to assess tumor metastasis in lung cancer
Authors: Wang Jiasi , Chu Yanpeng , Li Jie , Zeng Fanwei , Wu Min , Wang Tingjie , Sun Liangli , Chen Qianlai , Wang Pingxi , Zhang Xiuqin , Zeng Fanxin
Published: June 2020

Background

This study aimed to explore the possibility of serum tumor markers (TMs) combinations in assessing tumor metastasis in patients with lung cancer.

Methods

We performed a retrospective analysis of 541 patients diagnosed with lung cancer between January 2016 and December 2017 at the Pneumology Department of Dazhou Central Hospital. Serum carcinoembryonic antigen (CEA), carbohydrate antigen (CA)125, CA153, CA199, CA724, cytokeratin 19 fragment (CYFRA), and neuron‐specific enolase (NSE) levels were quantified in each patient at the time of lung cancer diagnosis. Metastasis was confirmed by computed tomography, and/or positron emission tomography, and/or surgery or other necessary methods. Receiver operating characteristic (ROC) curves and calibration curves were used to evaluate the performance of the model.

Results

Of the 541 patients eligible for final analysis, 253 were detected with metastasis and 288 were detected without metastasis. Compared with those in nonmetastatic patients, the serum CEA, CA125, CA199, CA153, CYFRA, and NSE levels were notably higher in metastatic patients (P < .05). The ROC curve demonstrated that the CEA‐CA125‐CA199‐CA153‐CYFRA‐NSE‐CA724 combination based on the cut‐off value had an optimal area under the curve and specificity in assessing tumor metastasis. The decision tree model is a convenient and valuable tool for guiding the appropriate application of our model to assess metastasis in lung cancer patients.

Conclusions

Our study suggested that the nomogram of the regression model is valuable for assessing tumor metastasis in newly diagnosed lung cancer patients before traditional standard methods are used. These findings could aid in the evaluation of metastasis in the clinic.
Recent survival trends in diffuse large B‐cell lymphoma––Have we made any progress beyond rituximab?
Authors: Epperla Narendranath , Vaughn John L. , Othus Megan , Hallack Abrahao , Costa Luciano J.
Published: June 2020

Background

Population‐based studies previously showed an improvement in overall survival (OS) for patients with diffuse large B‐cell lymphoma (DLBCL) who received chemoimmunotherapy with rituximab. However, there is limited data (especially at the population level) that show a similar trend in OS improvement, in the most recent time period. We hypothesized that survival for DLBCL patients diagnosed in the United States has continued to improve in recent years and intended to measure outcome improvements.

Methods

Using the SEER‐18 registries, we compared the incidence and relative survival rates (RSRs) of DLBCL patients between 2002‐2007 and 2008‐2013 (availability of novel agents, broader use of autologous hematopoietic cell transplantation and improvement in supportive care). Multivariable Cox regression models were used to assess associations between the year of diagnosis and OS while controlling for age, gender, stage, and ethnicity.

Results

There were a total of 53 439 patients with DLBCL who were diagnosed between 2002 and 2013. Of these, 25 810 were diagnosed during time period‐1 and 27 629 diagnosed during time period‐2. There was a slight decline in incidence of DLBCL (time period‐1 vs time period‐2), 7.75 (95% CI = 7.66‐7.84) vs 7.43 (95% CI = 7.34‐7.52) cases per 100 000 persons, respectively (P < .0001). Overall, there was a modest improvement in DLBCL RSRs, with 5‐year RSR improving from 61% (time period‐1) to 64% (time period‐2) and the improvement was noted across all subsets of patients. On multivariable analysis, patients diagnosed in time period‐2 had lower mortality relative to time period‐1 (HR = 0.87, 95% CI = 0.85‐0.89).

Conclusions

Our study shows an improvement in the outcomes of DLBCL patients beyond the introduction of rituximab, although the magnitude of improvement is small. It will be interesting to see the impact of chimeric antigen receptor‐T cell therapy translating to population‐level survival in the next 5 years.
Detecting Cysteine in Bioimaging with a Near‐Infrared Probe Based on a Novel Fluorescence Quenching Mechanism
Authors: Tao Yuanfang , Ji Xin , Zhang Jian , Jin Yue , Wang Nannan , Si Yubing , Zhao Weili
Published: June 2020

Near‐infrared (NIR) fluorescent probes are very significant for detecting cysteine in biological systems. Herein, we report a highly selective and sensitive NIR turn‐on fluorescent probe (BDP‐NIR) based on BODIPY with large Stokes shift (105 nm) for detecting Cys. We clarified the sensing mechanism based on the different thiol‐induced SNAr substitution/rearrangement reaction of the probe with cysteine and homocysteine/glutathione, which leads to the corresponding amino‐ and thiol‐BODIPY dyes with distinct photophysical properties. Moreover, a novel mechanism of fluorescence quenching was demonstrated by density functional theory calculation. The reason for the fluorescence quenching of the probe might be intersystem crossing (from singlet to triplet excited state). Moreover, BDP‐NIR had a high linear dynamic range of 0–500 μM, which was promising for detecting cysteine quantificationally. Significantly, BDP‐NIR was capable of sensing endogenous cysteine in living cells and in vivo.
Endocrine markers of puberty timing and antisocial behaviour in girls and boys
Authors: Michielsen Philip Jules Simon , Roza Sabine Judith , van Marle Hjalmar Johan Carel
Published: June 2020

Background

Early puberty is associated with higher than average risk of antisocial behaviour, both in girls and boys. Most studies of such association, however, have focused on psychosocial mediating and moderating factors. Few refer to coterminous hormonal measures.

Aim

The aim of this review is to consider the role of hormonal markers as potential mediating or moderating factors between puberty timing and antisocial behaviour.

Method

A systematic literature search was conducted searching Medline, Embase, Web of Science, Scopus, Psycinfo, Cochrane and Google Scholar.

Results

Just eight studies were found to fit criteria, all cross‐sectional. Measurements were too heterogeneous to allow meta‐analysis. The most consistent associations found were between adrenal hormones—both androgens and cortisol—which were associated with early adrenarche and antisocial behaviours in girls and later adrenarche and antisocial behaviour in boys.

Conclusions

The findings from our review suggest that longitudinal studies to test bidirectional hormone–behaviour associations with early or late puberty would be worthwhile. In view of the interactive processes between hypothalamic–pituitary–adrenal and hypothalamic–pituitary–gonadal axes, integrated consideration of the hormonal end products is recommended.
Graphitic‐shell encapsulated FeNi alloy/nitride nanocrystals on biomass‐derived N‐doped carbon as an efficient electrocatalyst for rechargeable Zn‐air battery
Authors: Wu Mingjie , Zhang Gaixia , Hu Yongfeng , Wang Jian , Sun Tianxiao , Regier Tom , Qiao Jinli , Sun Shuhui
Published: June 2020

Oxygen reduction/evolution reactions (ORR/OERs) catalysts play a key role in the metal‐air battery and water‐splitting process. Herein, we developed a facile template‐free method to fabricate a new type of non–noble metal‐based hybrid catalyst which consists of binary FeNi alloy/nitride nanocrystals with graphitic‐shell and biomass‐derived N‐doped carbon (NC) (FexNiyN@C/NC). This novel nanostructure exhibits superior performance for ORR/OER, which can be attributed to the strong interactions between the graphitic‐shell encapsulated FeNi alloy/nitride nanocrystals and the N‐doped porous carbon substrate. The X‐ray absorption spectroscopy technique was employed to reveal the underlying mechanisms for the excellent performance. The assembled Zn‐air battery device exhibits outstanding charging/discharging performance and cycling stability, indicating the great potential of this type of novel catalysts.
Transition Metal Promoted Cascade Heterocycle Synthesis through C−H Functionalization
Authors: Baccalini Alessio , Faita Giuseppe , Zanoni Giuseppe , Maiti Debabrata
Published: June 2020

Sequential, domino and tandem reactions could be defined as a sequence of synthetic transformations that occur one after the other, in the same reaction flask. This Review highlights recent advances at the overlap of two worlds: transition‐metal mediated C−H activation as a trigger of cascade reaction, for the heterocycles synthesis. To shed some light on this intricate “middle‐earth”, focus was put on the reaction mechanism rather than the type of metal or the chronological order of the reaction. The aim is to separate, and then highlight, the true domino reactions initiated by C−H activation, compared to other examples of C−H functionalization for heterocycle syntheses.
Phosphorus‐Containing Dibenzonaphthanthrenes: Electronic Fine Tuning of Polycyclic Aromatic Hydrocarbons through Organophosphorus Chemistry
Authors: Ascherl Johannes D. R. , Neiß Christian , Vogel Alexander , Graf Jürgen , Rominger Frank , Oeser Thomas , Hampel Frank , Görling Andreas , Kivala Milan
Published: June 2020

A concise synthetic route towards a new family of phosphorus‐containing polycyclic aromatic hydrocarbons starting from the versatile acridophosphine has been established. The structural and optoelectronic properties of these compounds were efficiently modulated through derivatization of the phosphorus center. X‐ray crystallographic analysis, UV/Vis spectroscopic, and electrochemical studies supported by DFT calculations identified the considerable potential of these scaffolds for the development of organophosphorus functional materials with tailored properties upon further functionalization.
Understanding the Effect of Hydroxypropyl‐β‐Cyclodextrin on Fenebrutinib Absorption in an Itraconazole–Fenebrutinib Drug–Drug Interaction Study
Authors: Durk Matthew R. , Jones Nicholas S. , Liu Jia , Nagapudi Karthik , Mao Chen , Plise Emile G. , Wong Susan , Chen Jacob Z. , Chen Yuan , Chinn Leslie W. , Chiang Po‐Chang
Published: June 2020

Cyclodextrins are widely used pharmaceutical excipients, particularly for insoluble compounds dosed orally, such as the oral solution of itraconazole, which is frequently used in clinical drug–drug interaction studies to inhibit cytochrome P450 3A. Since cyclodextrins act by forming inclusion complexes with their coformulated drug, they could have an unintended consequence of affecting absorption if they form a strong complex with the potential victim drug in an itraconazole drug–drug interaction study. This observation was made in a drug–drug interaction study with the Bruton’s tyrosine kinase (BTK) inhibitor fenebrutinib and itraconazole, in which, relative to the control group, the expected increase in fenebrutinib maximum plasma concentration (Cmax) was not observed in the itraconazole group, and a delay in time to reach maximum plasma concentration (Tmax) was observed in the itraconazole group. The in vitro binding constant between fenebrutinib and hydroxypropyl‐β‐cyclodextrin was determined to be 2 × 105 M−1, and the apparent permeability of fenebrutinib across a Madin‐Darby canine kidney cell monolayer decreased in a cyclodextrin concentration‐dependent manner. This observation was confirmed in vivo, in a pentagastrin‐pretreated dog model, in which fenebrutinib was administered with or without cyclodextrin; a reduction in Cmax, a prolonged Tmax, and increased fenebrutinib recovery in feces replicated the previous observation in healthy volunteers and supported the hypothesis that complexation with cyclodextrin decreased rate and extent of fenebrutinib absorption. Physiologically‐based pharmacokinetic modeling was used to translate the in vitro effect of cyclodextrin on fenebrutinib apparent permeability to the in vivo effect on absorption, which was then confirmed using the in vivo dog pharmacokinetic data.
Global Frequencies of Clinically Important HLA Alleles and Their Implications For the Cost‐Effectiveness of Preemptive Pharmacogenetic Testing
Authors: Zhou Yitian , Krebs Kristi , Milani Lili , Lauschke Volker M.
Published: June 2020

Immune‐mediated drug hypersensitivity reactions are an important source of iatrogenic morbidity and mortality. Human leukocyte antigen (HLA)‐B*57:01, HLA‐B*15:02, HLA‐A*31:01, and HLA‐B*58:01 constitute established risk factors and preemptive genotyping of these HLA alleles in patients prior to the initiation of abacavir, carbamazepine, and allopurinol‐based therapies can prevent toxicity and improve patient outcomes. However, the cost‐effectiveness of preemptive HLA testing has only been evaluated in the United States and few countries in Europe and Asia. In this study, we consolidated HLA genotypes from 3.5–6.4 million individuals across up to 74 countries and modeled the country‐specific cost‐effectiveness of genetic testing. We find major ethnogeographic differences in risk allele prevalence, which translated into pronounced differences in the number of patients needed to test to prevent one case of severe hypersensitivity reactions between countries and populations. At incremental cost‐effectiveness ratio thresholds of $40,000, testing of HLA‐B*57:01 in patients initiating abacavir was cost‐effective in the majority of countries with potential exceptions of East Asia, Saudi Arabia, Ghana, and Zimbabwe. For carbamazepine, preemptive genotyping of HLA‐B*15:02 is only cost‐effective across most of East and South Asia, whereas HLA‐A*31:01 testing is likely to be cost‐effective globally. Testing of HLA‐B*58:01 is more likely to be cost‐effective throughout Africa and Asia compared with Europe and the Americas. We anticipate that this data set can serve as an important resource for clinicians and health economists to guide clinical decision making and inform public healthcare strategies.
Developing Drugs for Tissue‐Agnostic Indications: A Paradigm Shift in Leveraging Cancer Biology for Precision Medicine
Authors: Seligson Nathan D. , Knepper Todd C. , Ragg Susanne , Walko Christine M.
Published: June 2020

Targeted therapies have reshaped the landscape of the development of cancer therapeutics. Recent biomarker‐driven, tissue‐agnostic clinical trials represent a significant paradigm shift in precision cancer medicine. Despite their growth in preclinical and clinical studies, to date only a few biomarker‐driven, tissue‐agnostic indications have seen approval by the US Food and Drug Administration (FDA). These approvals include pembrolizumab in microsatellite instability‐high or mismatch repair deficient solid tumors, as well as both larotrectinib and entrectinib in NTRK fusion‐positive tumors. Complex cancer biology, clinical trial design, and identification of resistance mechanisms represent some of the challenges that future tissue‐agnostic therapies have to overcome. In this Review, we present a brief history of the development of tissue‐agnostic therapies, comparing the similarities in the approval of pembrolizumab, larotrectinib, and entrectinib for tissue‐agnostic indications. We also explore the future of tissue‐agnostic cancer therapeutics while identifying important challenges for the future that drugs targeting tissue‐agnostic indications will face.
Strategies for Testing Intervention Matching Schemes in Cancer
Authors: Schork Nicholas J. , Goetz Laura H. , Lowey James , Trent Jeffrey
Published: June 2020

Personalized medicine, or the tailoring of health interventions to an individual's nuanced and often unique genetic, biochemical, physiological, behavioral, and/or exposure profile, is seen by many as a biological necessity given the great heterogeneity of pathogenic processes underlying most diseases. However, testing and ultimately proving the benefit of strategies or algorithms connecting the mechanisms of action of specific interventions to patient pathophysiological profiles (referred to here as “intervention matching schemes” (IMS)) is complex for many reasons. We argue that IMS are likely to be pervasive, if not ubiquitous, in future health care, but raise important questions about their broad deployment and the contexts within which their utility can be proven. For example, one could question the need to, the efficiency associated with, and the reliability of, strategies for comparing competing or perhaps complementary IMS. We briefly summarize some of the more salient issues surrounding the vetting of IMS in cancer contexts and argue that IMS are at the foundation of many modern clinical trials and intervention strategies, such as basket, umbrella, and adaptive trials. In addition, IMS are at the heart of proposed “rapid learning systems” in hospitals, and implicit in cell replacement strategies, such as cytotoxic T‐cell therapies targeting patient‐specific neo‐antigen profiles. We also consider the need for sensitivity to issues surrounding the deployment of IMS and comment on directions for future research.