bluuebunny/crossref_metadata_2025 huggingface dataset:
Chitinase 3-like-1 contributes to acetaminophen-induced liver injury by promoting hepatic platelet recruitment
Authors: Shan Zhao , Li Leike , Atkins Constance Lynn , Wang Meng , Wen Yankai , Jeong Jongmin , Moreno Nicolas F , Feng Dechun , Gui Xun , Zhang Ningyan , Lee Chun Geun , Elias Jack A , Lee William M , Gao Bin , Lam Fong Wilson , An Zhiqiang , Ju Cynthia
Published: June 2021

Background:

Hepatic platelet accumulation contributes to acetaminophen (APAP)-induced liver injury (AILI). However, little is known about the molecular pathways involved in platelet recruitment to the liver and whether targeting such pathways could attenuate AILI.

Methods:

Mice were fasted overnight before intraperitoneally (i.p.) injected with APAP at a dose of 210 mg/kg for male mice and 325 mg/kg for female mice. Platelets adherent to Kupffer cells were determined in both mice and patients overdosed with APAP. The impact of α-chitinase 3-like-1 (α-Chi3l1) on alleviation of AILI was determined in a therapeutic setting, and liver injury was analyzed.

Results:

The present study unveiled a critical role of Chi3l1 in hepatic platelet recruitment during AILI. Increased Chi3l1 and platelets in the liver were observed in patients and mice overdosed with APAP. Compared to wild-type (WT) mice, Chil1-/- mice developed attenuated AILI with markedly reduced hepatic platelet accumulation. Mechanistic studies revealed that Chi3l1 signaled through CD44 on macrophages to induce podoplanin expression, which mediated platelet recruitment through C-type lectin-like receptor 2. Moreover, APAP treatment of Cd44-/- mice resulted in much lower numbers of hepatic platelets and liver injury than WT mice, a phenotype similar to that in Chil1-/- mice. Recombinant Chi3l1 could restore hepatic platelet accumulation and AILI in Chil1-/- mice, but not in Cd44-/- mice. Importantly, we generated anti-Chi3l1 monoclonal antibodies and demonstrated that they could effectively inhibit hepatic platelet accumulation and AILI.

Conclusions:

We uncovered the Chi3l1/CD44 axis as a critical pathway mediating APAP-induced hepatic platelet recruitment and tissue injury. We demonstrated the feasibility and potential of targeting Chi3l1 to treat AILI.

Funding:

ZS received funding from NSFC (32071129). FWL received funding from NIH (GM123261). ALFSG received funding from NIDDK (DK 058369). ZA received funding from CPRIT (RP150551 and RP190561) and the Welch Foundation (AU-0042–20030616). CJ received funding from NIH (DK122708, DK109574, DK121330, and DK122796) and support from a University of Texas System Translational STARs award. Portions of this work were supported with resources and the use of facilities of the Michael E. DeBakey VA Medical Center and funding from Department of Veterans Affairs I01 BX002551 (Equipment, Personnel, Supplies). The contents do not represent the views of the US Department of Veterans Affairs or the US Government.
Historicizing Comparative Literature in the Postcolonial Era
Authors: Tayim Constantin Sonkwé
Published: June 2021

This paper brings up the history of comparative literature from its beginning to the postcolonial era, discussing the challenges and controversies that have shaped the history of the discipline and practice. Drawing mainly upon Edward Said’s thought, but also other prominent theorists, the paper sketches the evolution of the concept of comparative literature on the one hand, and on the other hand, it shows through some recent examples of transnational and transcultural questions, how difficult it is in the contemporary context of Globalization to preserve the nation as a space and concept of reference for the writing of the history of literature, due to the very fact of the transformation of the nation and its contours in recent decades. It is also about showing that despite the circulation of worlds and the challenge of the nation’s rigid borders by the process of migration among others, the nation is not yet disqualified as a framework and substructure for literary production. It further discusses the relationship between literature and nation in the contemporary context as well as the issues of transnationality and world literariness, using two examples from France and Nigeria.
High throughput resource efficient reconfigurable interleaver for MIMO WLAN application
Authors: Upadhyaya Bijoy Kumar , Pramanik Pijush Kanti Dutta , Sanyal Salil Kumar
Published: June 2021

Demand for high-speed wireless broadband internet service is ever increasing. Multiple-input-multiple-output (MIMO) Wireless LAN (WLAN) is becoming a promising solution for such high-speed internet service requirements. This paper proposes a novel algorithm to efficiently model the address generation circuitry of the MIMO WLAN interleaver. The interleaver used in the MIMO WLAN transceiver has three permutation steps involving floor function whose hardware implementation is the most challenging task due to the absence of corresponding digital hardware. In this work, we propose an algorithm with a mathematical background for the address generator, eliminating the need for floor function. The algorithm is converted into digital hardware for implementation on the reconfigurable FPGA platform. Hardware structure for the complete interleaver, including the read address generator and memory module, is designed and modeled in VHDL using Xilinx Integrated Software Environment (ISE) utilizing embedded memory and DSP blocks of Spartan 6 FPGA. The functionality of the proposed algorithm is verified through exhaustive software simulation using ModelSim software. Hardware testing is carried out on Zynq 7000 FPGA using Virtual Input Output (VIO) and Integrated Logic Analyzer (ILA) core. Comparisons with few recent similar works, including the conventional Look-Up Table (LUT) based technique, show the superiority of our proposed design in terms of maximum improvement in operating frequency by 196.83%, maximum reduction in power consumption by 74.27%, and reduction of memory occupancy by 88.9%. In the case of throughput, our design can deliver 8.35 times higher compared to IEEE 802.11n requirement.
Methylmercury-induced cytotoxicity and oxidative biochemistry impairment in dental pulp stem cells: the first toxicological findings
Authors: Souza-Rodrigues Renata Duarte de , Puty Bruna , Bonfim Laís , Nogueira Lygia Sega , Nascimento Priscila Cunha , Bittencourt Leonardo Oliveira , Couto Roberta Souza D’Almeida , Barboza Carlos Augusto Galvão , de Oliveira Edivaldo Herculano Corrêa , Marques Marcia Martins , Lima Rafael Rodrigues
Published: June 2021

Background

Methylmercury (MeHg) is a potent toxicant able to harm human health, and its main route of contamination is associated with the consumption of contaminated fish and other seafood. Moreover, dental amalgams are also associated with mercury release on human saliva and may contribute to the accumulation of systemic mercury. In this way, the oral cavity seems to be the primary location of exposure during MeHg contaminated food ingestion and dental procedures but there is a lack of literature about its effects on dental tissues and the impact of this toxicity on human health. In this way, this study aimed to analyze the effects of different doses of MeHg on human dental pulp stem cells after short-term exposure.

Methods

Dental pulp stem cells from human exfoliated deciduous teeth (SHED) were treated with 0.1, 2.5 and 5 µM of MeHg during 24 h. The MeHg effects were assessed by evaluating cell viability with Trypan blue exclusion assay. The metabolic viability was indirectly assessed by MTT reduction assay. In order to evaluate an indicative of antioxidant defense impairment, cells exposed to 0.1 and 5 µM MeHg were tested by measuring glutathione (GSH) level.

Results

It was observed that cell viability decreased significantly after exposure to 2.5 and 5 µM of MeHg, but the metabolic viability only decreased significantly at 5 µM MeHg exposure, accompanied by a significant decrease in GSH levels. These results suggest that an acute exposure of MeHg in concentrations higher than 2.5 µM has cytotoxic effects and reduction of antioxidant capacity on dental pulp stem cells.
nCov2019: an R package for studying the COVID-19 coronavirus pandemic
Authors: Wu Tianzhi , Hu Erqiang , Ge Xijin , Yu Guangchuang
Published: June 2021

Background

The global spreading of the COVID-19 coronavirus is still a serious public health challenge. Although there are a large number of public resources that provide statistics data, tools for retrospective historical data and convenient visualization are still valuable. To provide convenient access to data and visualization on the pandemic we developed an R package, nCov2019 (https://github.com/YuLab-SMU/nCov2019).

Methods

We collect stable and reliable data of COVID-19 cases from multiple authoritative and up-to-date sources, and aggregate the most recent and historical data for each country or even province. Medical progress information, including global vaccine development and therapeutics candidates, were also collected and can be directly accessed in our package. The nCov2019 package provides an R language interfaces and designed functions for data operation and presentation, a set of interfaces to fetch data subset intuitively, visualization methods, and a dashboard with no extra coding requirement for data exploration and interactive analysis.

Results

As of January 14, 2021, the global health crisis is still serious. The number of confirmed cases worldwide has reached 91,268,983. Following the USA, India has reached 10 million confirmed cases. Multiple peaks are observed in many countries. Under the efforts of researchers, 51 vaccines and 54 drugs are under development and 14 of these vaccines are already in the pre-clinical phase.

Discussion

The nCov2019 package provides detailed statistics data, visualization functions and the Shiny web application, which allows researchers to keep abreast of the latest epidemic spread overview.
First record of Trichinella in Leopardus guigna (Carnivora, Felidae) and Galictis cuja (Carnivora, Mustelidae): new hosts in Chile
Authors: Echeverry Diana Maritza , Henríquez AnaLía , Oyarzún-Ruiz Pablo , Silva-de la Fuente Maria Carolina , Ortega Rene , Sandoval Daniel , Landaeta-Aqueveque Carlos
Published: June 2021

Background

Trichinellosis is a zoonotic disease with a worldwide distribution. It is caused by several species of nematodes in the genus Trichinella. Trichinella spp. are transmitted through predation or carrion consumption and occur in domestic and sylvatic cycles. In humans trichinellosis occurs due to the consumption of raw or undercooked, infected meat and is mainly associated with the household slaughter of pigs or the consumption of game animals without veterinary inspection, a cultural practice that is difficult to resolve. Therefore, knowledge of this parasite’s reservoir is relevant for better implementing public health strategies. The aim of this study was to assess the presence of Trichinella sp. in several carnivore and omnivore vertebrates in central-southern Chile.

Methods

We collected muscle tissue from a total of 53 animals from 15 species and were digested to detect Trichinella larvae which were further identified to species level using molecular techniques.

Results

We detected Trichinella larvae in Leopardus guigna (Felidae) and Galictis cuja (Mustelidae). We identified the larvae collected from L. guigna as Trichinella spiralis, but we were unable to molecularly characterize the larvae from G. cuja. This is the first record of Trichinella in a native mustelid of South America and the first record of T. spiralis in L. guigna. This study identified two novel hosts; however, further work is needed to identify the role that these and other hosts play in the cycle of Trichinella in Chile.
Management of Breast AbscessbyOpen Drainage with Primary Closure versus Standard Incision and Drainage- ARandomised Trial
Authors: Raj Monish , Arya Satyavrat , Chejara Raj Kumar , Chaudhary Rohit , Mani Vignesh
Published: June 2021

Introduction: Breast abscess is a localised collection of purulent material within the breast, which can be a complication of mastitis. In women of reproductive age, these are predominantly lactational but non-lactational abscesses are also seen in premenopausal women. Abscesses generally require drainage in conjunction with antibiotics. For the treatment of breast abscesses, surgical incision and drainage are usually carried out under general anaesthesia, as a traditional method. Aim: To compare conventional incision and drainage versus open drainage with primary closure with negative suction drain modalities of treatment of breast abscess in terms of different aspects including duration and quality of healing, number of dressings required, length of hospitalisation, postoperative complications. Materials and Methods: The present study was a randomised study conducted in the Department of General Surgery, Vardhaman Mahavir Medical College and Safdarjung Hospital, New Delhi, India. There were 30 patients in group A undergoing open drainage with primary closure with negative suction drain and 30 patients in group B undergoing conventional incision and drainage. They were evaluated for the study period of 18 months, between October 2018 and April 2020. The data collected were analysed with Statistical Package for the Social Sciences (SPSS) version 17.0. Results: The incidence of breast abscess was more common in age group of 21-30 years with right side affected more than left side. Both the surgical procedures were comparable with each other in terms of incidence of recurrence. The primary closure group fared better with less incidence of postoperative pain (duration of analgesics requirement 2.40 vs 5.43 days), reduced hospital stay (3.63 vs 6.67 days) and dressings requirement was also less (2.33 vs 12.27 days) compared to standard incision and drainage drainage which were statistically significant. Conclusion: Hence, it can be concluded that open drainage with primary closure with negative suction drain placement can be considered as a safe and effective alternative to the standard incision and drainage in patients with breast abscess.
Structural and functional characterization of a plant alpha‐actinin
Authors: Persson Karina , Backman Lars
Published: June 2021

The Australian tree malletwood (Rhodamnia argentea) is unique. The genome of malletwood is the only known plant genome that contains a gene coding for an α‐actinin‐like protein. Several organisms predating the animal‐plant bifurcation express an α‐actinin or α‐actinin‐like protein. Therefore, it appears that plants in general, but not malletwood, have lost the α‐actinin or α‐actinin‐like gene during evolution. In order to characterize its structure and function, we synthesized the gene and expressed the recombinant R. argentea protein. The results clearly show that this protein has all properties of genuine α‐actinin. The N‐terminal actin‐binding domain (ABD), with two calponin homology motifs, is very similar to the ABD of any α‐actinin. The C‐terminal calmodulin‐like domain, as well as the intervening rod domain, are also similar to the corresponding regions in other α‐actinins. The R. argentea α‐actinin‐like protein dimerises in solution and thereby can cross‐link actin filaments. Based on these results, we believe the R. argentea protein represents a genuine α‐actinin, making R. argentea unique in the plant world.
H
awkins,
F
rancis
B
isset
Authors: Armitage Peter
Published: June 2021

A prolific author in the fields of industrial medicine and public health, Hawkins wrote the first book on medical statistics in English in 1829. The book now has only curiosity value, but it was influential in the use of hospital records and in the insertion of cause of death in registration documents.
Micro‐Randomized Trial
Authors: Xu Gongjun , Wu Zhenke , Murphy Susan A.
Published: June 2021

This article reviews the micro‐randomized trial, an experimental design developed to support mobile intervention development in modern mobile health applications. The article first gives an introduction to mobile health and the motivation for the micro‐randomized trial and then describes the design of micro‐randomized trials, including an overview of the data analysis and an example.
Proximal Methods for Penalized Regression
Authors: Chi Eric C.
Published: June 2021

This brief entry covers two important proximal methods for computing regression coefficients in nonsmoothly penalized regression. We use the lasso to illustrate each.
Does QBank participation impact in‐training examination performance?
Authors: Walter Lauren A. , Khoury Charles A. , DeLaney Matthew C. , Thompson Maxwell A. , Rushing Courtney , Edwards Andrew R.
Published: June 2021

Background

Performance on the annual in‐training examination (ITE) for emergency medicine (EM) residents has been shown to correlate with performance on the American Board of Emergency Medicine (ABEM) qualifying examination. As such, significant planning is often committed to ITE preparation, from an individual resident and a residency program perspective. Online specialty‐specific question banks (QBanks) represent a popular medium for ITE preparation; however, the impact of QBanks on ITE performance is unclear. We sought to assess the impact of QBank participation on EM resident ITE performance.

Methods

ITE and QBank performance results were collated over 2 academic years, 2019 and 2020, from a 3‐year EM residency program. The QBank was provided as a self‐study option in 2019 and incorporated as a mandatory component of the curriculum in 2020. ITE raw scores and percentile rank for training level scores were compared with performance on the QBank, including QBank average performance score as well as number of QBank questions completed. The Pearson correlation coefficient was used to measure association between ITE performance and QBank correlates. Additional descriptive demographics, to include gender, PGY level, and USMLE step 1 and 2 scores were also considered.

Results

Sixty‐two sets (30 residents in 2019, 32 residents in 2020) of ITE performance data and QBank correlates were included. Overall, raw ITE scores and number of QBank questions completed were found to have a significant, positive correlation, (r(60) = 0.34, p < 0.05); correlation was stronger for 2019 (r[28] = 0.39, p < 0.05) compared to 2020 (r[30] =0.25, p = 0.16). Overall, ITE percentile rank for training level scores were also found to have a significant, positive correlation with number of QBank questions completed (r(60) = 0.35, p < 0.05); correlation was again stronger for 2019 (r(28) = 0.42, p < 0.05) compared to 2020 (r(30) = 0.29, p = 0.12). Finally, ITE percentile rank for training level correlated positively with QBank average performance (as a percentage), albeit weakly, and was not found to be significant overall (r[60] = 0.20, p = 0.16); in this instance, 2019 did not show a correlation (r[28] =0.12, p = 0.54); however, 2020 did (r[30] =0.55, p < 0.05). Academic year 2020 raw ITE scores also demonstrated a significant correlation with QBank average performance (r[30] = 0.66, p < 0.0001) while 2019 did not (r[28] = 0.08, p = 0.68).

Conclusion

Participation and engagement in a QBank are associated with improved EM resident performance on the ABEM ITE. Utilization of a QBank may be an effective mode of ITE preparation for EM residents.
“Intolerance of uncertainty” mediates the relationship between social profile and anxiety in both Williams syndrome and autism
Authors: South Mikle , Hanley Mary , Normansell‐Mossa Karys , Russell Nicholas C. C. , Cawthorne Thomas , Riby Deborah M.
Published: June 2021

Anxiety is the most significant mental health concern for both Williams syndrome (WS) and autism. Whilst WS and autism are characterized by some syndrome‐specific social differences, less is known about cross‐syndrome profiles of anxiety symptoms. Previous research has shown that Intolerance of Uncertainty (IU) is a core mechanism of anxiety maintenance for clinically anxious populations and for autistic children, adolescents, and adults. The only published study in this area for WS has shown some similar patterns—with an added emphasis on the role of sensory sensitivities—in a sample of older teens and adults (mean age = 24), with the authors highlighting the need for younger samples to consider developmental influences. Here we report a cross‐syndrome, cross‐sectional mediation analyses of children diagnosed with WS or autism, including data from parent surveys of 90 children with WS (n = 48) or autism (n = 42). Group differences showed higher trait levels on all measures for the autism group. Importantly, the relationship between social profile and anxiety was fully mediated by IU level for both groups. This suggests possible similar core mechanisms underlying anxiety in these conditions, and the possibility of generalized intervention approaches especially related to managing distress related to uncertainty in multiple contexts.

Lay Summary

Autism and Williams Syndrome share some similarities in social profile and also in anxiety traits, but there are also some key differences as well. Comparing them side‐by‐side at the same time improved identification of ways to reduce feelings of anxiety. We found that the intolerance of uncertainty affected the relationship between social profile and anxiety in the same way for young children diagnosed with autism or Williams syndrome, meaning that intervention approaches could be similar for both.
‘In‐tuition’ problems: Consider rulings on students’ breach‐of‐contract claims
Authors: Lyerly Eric
Published: June 2021

Students and parents have initiated a flood of lawsuits against colleges and universities due to the sudden, unexpected shift to remote learning during the pandemic. There have been hundreds of such cases to date, many of them class‐action lawsuits. However, the thrust of the claims remains largely the same in that plaintiffs demand tuition refunds from their college or university under a breach‐of‐contract theory. Plaintiffs allege virtual learning served as an inferior substitute for the in‐person instruction promised in institutions’ handbooks, catalogs, and literature.
Minimizing the hidden dangers of cholecystectomy in vascular Ehlers‐Danlos syndrome through a multidisciplinary approach
Authors: Crane Jasmine , Lam Stephen , Kiam Jian Shen , Kumar Bhaskar
Published: June 2021

Ehlers‐Danlos syndrome, specifically EDS4, can be a dangerous condition. Clinicians should be aware of this when referring such patients for any interventional procedure. An MDT approach should be adopted to help plan perioperative treatment and care.
Mediastinal cystic teratoma misdiagnosed as pleural tuberculosis: A case report and review of 53 cases revealed by pleural effusion
Authors: Katoto Patrick D. M. C. , Byamungu Liliane N.
Published: June 2021

Mediastinal teratoma (MT) can be misdiagnosed for a long period and revealed by fatal pleural effusion at any age. In high burden tuberculosis settings, it is important to consider MT for extra‐pulmonary tuberculosis not responding to medical treatment.
Pedunculated hepatic focal nodular hyperplasia: A case report and review of the literature
Authors: Ben Ismail Imen , Zenaidi Hakim , Jouini Raja , Rebii Saber , Zoghlami Ayoub
Published: June 2021

Focal nodular hyperplasia (FNH) is a common asymptomatic benign hepatic tumor encountered in middle‐aged women. However, pedunculated FNH is exceedingly rare and more frequently associated with complications. That is why surgical management is mandatory in this form.
Delayed diagnosis of avoidant/restrictive food intake disorder and autism spectrum disorder in a 14‐year‐old boy
Authors: Rajendram Rageen , Psihogios Maria , Toulany Alene
Published: June 2021

Psychiatric comorbidities are common among individuals with ARFID and may contribute to a failure to establish an accurate diagnosis, delayed diagnosis, and poor long‐term prognosis, especially among children and adolescents.
Spontaneous thrombosis of a giant common hepatic artery aneurysm—A case report
Authors: Piachas Athanasios , Stavride Eliza , Lazaridis Ioannis , Tigkiropoulos Konstantinos
Published: June 2021

Splachnic aneurysms (hepatic artery aneurysms) are a rare entity ranging from atypical symptoms to devastating rupture.
Steakhouse syndrome
Authors: Shikino Kiyoshi , Ikusaka Masatomi
Published: June 2021

In Steakhouse syndrome, computed tomography revealed circumferential esophageal wall thickening and a mass in the esophageal lumen, which could be mistaken as esophageal cancer.
Orbital mass and hairy kidney as characteristics of Erdheim‐Chester disease
Authors: Yamamoto Koichiro , Oka Kosuke , Hasegawa Kou , Otsuka Fumio
Published: June 2021

Erdheim‐Chester disease (ECD) is a rare non‐Langerhans cell histiocytosis, involving multiple organs. We report a case of ECD with typical features of an orbital mass and "hairy kidneys," whose recognition can lead to early diagnosis and treatment.
Anesthetic management of a patient with Freeman‐Sheldon syndrome undergoing oral surgery: A case report
Authors: Sato (Boku) Aiji , Sento Yoshiki , Hasegawa Tatsuya , Tsutsumi Kosuke , Kamimura Yuji , So MinHye , Kako Eisuke , Sobue Kazuya
Published: June 2021

In the anesthetic management in this case was how to manage the patient without causing respiratory depression and respiratory muscle fatigue.
Highly Selective Carbon‐Supported Boron for Oxidative Dehydrogenation of Propane
Authors: Mark Lesli O. , Dorn Rick W. , McDermott William P. , Agbi Theodore O. , Altvater Natalie R. , Jansen Jacob , Lebrón‐Rodríguez Edgard A. , Cendejas Melissa C. , Rossini Aaron J. , Hermans Ive
Published: June 2021

Bulk boron materials, such as hexagonal boron nitride (h‐BN), are highly selective catalysts for the oxidative dehydrogenation of propane (ODHP). Previous attempts to improve the productivity of these systems involved the immobilization of boron on silica and resulted in less selective catalysts. Here, we report that acid‐treated, activated carbon‐supported boron prepared via incipient wetness impregnation with boric acid (B/OAC) exhibits equal propylene selectivity and improved productivity (kgpropylene kgcat−1 hr−1) as compared to h‐BN. Characterization of the fresh and spent catalysts with infrared, Raman, X‐ray photoelectron, and solid‐state NMR spectroscopies reveals the presence of oxidized/hydrolyzed boron that is clustered on the surface of the support.
Polyzwitterions Functionalized Nafion Barrier Toward High Performance Lithium‐Sulfur Batteries
Authors: Hao Yu , Xing Yingjie , Kong Haijuan , Jiao Yucong
Published: June 2021

Lithium‐sulfur (Li−S) batteries have emerged to be the next generation energy storage batteries due to their high theoretical capacity and low cost. Nevertheless, the growth of lithium dendrites and the notorious shuttle effects of lithium polysulfides (LiPS) during electrochemical reactions hinder the further application of Li−S batteries. Herein, a novel imidazolium‐type polyzwitterions functionalized Nafion barrier was successfully prepared by grafting the zwitterion 3‐(1‐vinyl‐3‐imidazolio) propanesulfonate onto Nafion. The polyzwitterions can promote the lithium salts dissociation to fast ion distribution, and guide Li+ uniform nucleation for effective dendrite inhibition. In addition, with the strong interaction between the imidazole rings and LiPS, the polyzwitterions functionalized separator can capture LiPS thus suppressing the shuttle effects during Li−S battery cycling. Consequently, the symmetrical Li cell with polyzwitterions can provide superior cycling stability over 1200 h with no dendrite formation at a high current density of 3 mA cm−2. The polyzwitterions enhanced Li−S battery can deliver a reversible specific capacity of 460 mA h g−1 at 1 C for over 500 cycles, demonstrating a great promise in the development of high efficiency and high safety Li−S batteries.
Patient‐reported pain severity and health‐related quality of life in patients with multiple myeloma in real world clinical practice
Authors: Ludwig Heinz , Bailey Abigail Lucy , Marongiu Andrea , Khela Keerun , Milligan Gary , Carlson Katherine Brewer , Rider Alex , Seesaghur Anouchka
Published: June 2021

Background

The association between patient self‐reported pain severity and health‐related quality‐of‐life (HRQoL) is poorly understood.

Aims

This real‐world study of symptomatic multiple myeloma (MM) patients sought to determine how pain severity from a single question asked during routine clinical consultation was associated with HRQoL.

Methods and results

Point‐in‐time data on HRQoL of 330 patients with MM (median age 70 years) receiving anti‐myeloma therapy in Germany and Italy from November 2017 through February 2018 were analyzed. HRQoL was assessed using validated questionnaires (Work Productivity and Activity Impairment [WPAI], European Organization for Research and Treatment of Cancer Quality of Life Questionnaire ‐C30 and ‐MY20). Physical pain severity was assessed during clinical consultation by a single question, asking patients to describe their pain as “no pain,” “mild,” “moderate,” or “severe.” Associations between patient‐reported pain severity and HRQoL scores were assessed by analysis of variance or χ2 tests. Ninety‐six of the 330 patients (29.1%) reported moderate to severe pain. Increase in pain severity, from “no” to “severe” pain, was associated with significantly decreased overall HRQoL (mean score 70.2 to 33.3); significant decreases in levels of physical (82.7 to 35.1), social (81.1 to 44.4), emotional (78.1 to 48.3), and role functioning (79.5 to 38.9); and increased levels of WPAI usual activity impairment (35.4 to 71.4), and fatigue burden (26.0 to 68.9) (all p < .001).

Conclusion

Higher pain severity, based on a single self‐report question, was associated with poorer HRQoL in patients with MM, thereby supporting the clinical relevance of directly asking patients to self‐evaluate their pain severity.
Reducing Non‐Radiative Voltage Losses by Methylation of Push–Pull Molecular Donors in Organic Solar Cells
Authors: Baisinger Lukasz , Andrés Castán José María , Simón Marqués Pablo , Londi Giacomo , Göhler Clemens , Deibel Carsten , Beljonne David , Cabanetos Clément , Blanchard Philippe , Benduhn Johannes , Spoltore Donato , Leo Karl
Published: June 2021

Organic solar cells are approaching power conversion efficiencies of other thin‐film technologies. However, in order to become truly market competitive, the still substantial voltage losses need to be reduced. Here, the synthesis and characterization of four novel arylamine‐based push‐pull molecular donors was described, two of them exhibiting a methyl group at the para‐position of the external phenyl ring of the arylamine block. Assessing the charge‐transfer state properties and the effects of methylation on the open‐circuit voltage of the device showed that devices based on methylated versions of the molecular donors exhibited reduced voltage losses due to decreased non‐radiative recombination. Modelling suggested that methylation resulted in a tighter interaction between donor and acceptor molecules, turning into a larger oscillator strength to the charge‐transfer states, thereby ensuing reduced non‐radiative decay rates.
Routing protocols & unmanned aerial vehicles autonomous localization in flying networks
Authors: Khan Inam Ullah , Shah Syed Bilal Hussain , Wang Lei , Aziz Muhammad Adnan , Stephan Thompson , Kumar Neeraj
Published: June 2021

Nowadays, as the world is transformed because of the interconnectivity, there we see several issues regarding security which is supposed to be one of the biggest problems for the concept of smart cities. In future, aerial vehicles can be merged with smart cities to enhance the interoperability among internet of things (IoT) devices. Routing protocols plays an important role when flying vehicles communicate with one another. Reinforcing connection in flying ad hoc networks using routing protocols is the optimal way to reduce end‐to‐end delay. However, utilizing flying networks with the deployment of routing techniques is a very difficult task to tackle the dynamic pattern of aerial vehicles. Internet of flying vehicles is the emerging area which is still in the evolutionary process; however, the interconnectivity can be efficiently formulated by applying security algorithms for improving signal power. In unmanned aerial vehicles (UAVs), every node will have some specific location, direction, speed, velocity, and acceleration which will identify and relate information about mobility model. This paper proposes a novel routing technique, which is the extension of AntHocNet due to mobile characteristics; it is termed as flying nature inspired algorithm. Also a case study is conducted to improve the signal power using modeled learning approach called decision tree. Experimental simulations are managed on network simulators that prove the proposed work efficiency.
A profile of brain reserve in adults at genetic risk of Alzheimer's disease
Authors: Coughlan Gillian , Zhukovsky Peter , Voineskos Aristotle , Grady Cheryl
Published: June 2021

Introduction

The apolipoprotein E (APOE) ε4 allele is the greatest genetic risk factor for Alzheimer's disease (AD). Our aim was to identify the structural brain measures that mitigate the negative effect of APOE ε4 on cognition, which would have implications for AD diagnosis and treatment trial selection.

Methods

A total of 742 older adults (mean age: 70.1 ± 8.7 years) were stratified by APOE status and classified as cognitively normal (CDR 0) or with very mild dementia (CDR 0.5). Regional brain volume and cognitive performance were measured.

Results

There were significant interactions between APOE and CDR on the left precuneus and on bilateral superior frontal volumes. These regions were preserved in CDR‐0 ε3/ε4 and ε4/ε4 carriers but were reduced in CDR‐0.5 ε3/ε4 and ε4/ε4 carriers, compared to their respective ε3/ε3 counterparts. Educational attainment predicted greater brain reserve.

Discussion

This pattern of preserved brain structure in cognitively normal ε4 carriers with comprised medial temporal volume is consistent with the theory of brain reserve.
Management‐mediated predation rate in the caribou–moose–wolf system: spatial configuration of logging activities matters
Authors: Vanlandeghem Virginie , Drapeau Pierre , Prima Marie‐Caroline , St‐Laurent Martin‐Hugues , Fortin Daniel
Published: June 2021

Landscape complexity can determine the population dynamics of interacting predators and prey. Yet, management plans are commonly developed from aspatial predictive models. This oversight may result in unexpected outcomes or the loss of opportunities to make spatial interventions that would increase a plan's effectiveness. The management of the threatened woodland caribou (Rangifer tarandus caribou), boreal population, provides an example of such shortcomings when using an aspatial approach. Currently, the most influential management recommendation is to maintain at least 65% of undisturbed forests in areas occupied by caribou populations, regardless of the spatial configuration of the forest cover. Using a spatially explicit individual‐based model (IBM), we evaluated the effects of the spatial configuration of cuts and roads on the mortality of boreal caribou living in sympatry with wolves (Canis lupus) and moose (Alces alces), an apparent competitor. Starting with a real forest landscape, we created forest management scenarios of the specific spatial distribution of cuts (mosaic, small, or large agglomeration) with increasing disturbance levels. We then ran the IBM with simulated agents, representing individuals of the three species, moving according to movement rules determined from radio‐collared individuals. We found that movement responses to land cover types and roads differed among species. For example, caribou and moose generally avoided areas close to roads, contrary to wolves. Those differences influenced the mortality of caribou agents, which not only depended on the levels of disturbance but also depended on the spatial distribution of cuts and roads. After controlling for disturbance level, wolves were more successful when forest management required an extensive road network resulting in relatively high habitat fragmentation. Caribou agents experienced lower mortality in landscapes with low densities of road and disturbance‐related edges. The effect remained much stronger, however, for the level than the spatial configuration of human disturbances. Still, our IBM demonstrated how landscape management could be used to manipulate species interactions, with the intent of either increasing or decreasing predation rates on specific populations, depending on management goals.
Proactive inhibition is not modified by deep brain stimulation for Parkinson's disease: An electrical neuroimaging study
Authors: De Pretto Michael , Mouthon Michael , Debove Ines , Pollo Claudio , Schüpbach Michael , Spierer Lucas , Accolla Ettore A.
Published: June 2021

In predictable contexts, motor inhibitory control can be deployed before the actual need for response suppression. The brain functional underpinnings of proactive inhibition, and notably the role of basal ganglia, are not entirely identified. We investigated the effects of deep brain stimulation of the subthalamic nucleus or internal globus pallidus on proactive inhibition in patients with Parkinson's disease. They completed a cued go/no‐go proactive inhibition task ON and (unilateral) OFF stimulation while EEG was recorded. We found no behavioural effect of either subthalamic nucleus or internal globus pallidus deep brain stimulation on proactive inhibition, despite a general improvement of motor performance with subthalamic nucleus stimulation. In the non‐operated and subthalamic nucleus group, we identified periods of topographic EEG modulation by the level of proactive inhibition. In the subthalamic nucleus group, source estimation analysis suggested the initial involvement of bilateral frontal and occipital areas, followed by a right lateralized fronto‐basal network, and finally of right premotor and left parietal regions. Our results confirm the overall preservation of proactive inhibition capacities in both subthalamic nucleus and internal globus pallidus deep brain stimulation, and suggest a partly segregated network for proactive inhibition, with a preferential recruitment of the indirect pathway.
Hypoxia‐Inducible Exosomes Facilitate Liver‐Tropic Premetastatic Niche in Colorectal Cancer
Authors: Sun Hao , Meng Qingtao , Shi Chengyu , Yang Hongbao , Li Xiaobo , Wu Shenshen , Familiari Giuseppe , Relucenti Michela , Aschner Michael , Wang Xuehao , Chen Rui
Published: June 2021

Background and Aims

Liver metastasis is a frequent occurrence in patients with colorectal cancer (CRC), with 15%‐25% of CRC patients having liver metastases at the time of initial diagnosis. Specifically, some regional‐stage patients with mild symptoms (stage 1 or 2) will also advance to liver metastases rapidly, even if the CRC lesion in situ is resected in time. Nevertheless, the precise mechanism of liver metastasis is still unclear.

Approach and Results

Fresh tumor tissues from patients with CRC, adjacent noncancerous tissues, and colorectal adenoma tissues were subjected to microarray analysis to identify differentially expressed microRNA. Exosomes from human serum and cell culture medium were separated, quantitated, and verified by transmission electronic microscopy and Zetasizer Nano. Luciferase reporter assay, real‐time quantitative PCR, western blot, immunoprecipitation, chromatin and re‐chromatin immunoprecipitation, migration and invasion assay, PDX mouse model, flow cytometry, immunohistochemistry, and immunofluorescence staining were employed to explore the regulation among CRC liver metastases, immunosuppression, and cell adhesion. In this study, we demonstrated that the hypoxic microenvironment in primary CRC lesions boosted exosome release, selectively initiated favorable premetastatic niche formation in the liver but not in other organs. Mechanistically, Kupffer cells (KCs) can phagocytose exosomes containing highly expressed miR‐135a‐5p from the blood circulation into the liver. Exosomal miR‐135a‐5p initiated the large tumor suppressor kinase 2–yes‐associated protein–matrix metalloproteinase 7 axis to promote the occurrence of CRC liver metastasis, and cluster of differentiation 30–TNF receptor–associated factor 2–p65–mediated immunosuppression signaling also contributed to this process.

Conclusions

Hypoxia‐induced exosomal miR‐135a‐5p correlates with the development, clinical severity, and prognosis of CRC liver metastases through the premetastatic niche; and our findings revealed that miR‐135a‐5p might be a promising target in halting CRC liver metastases.
Exploratory composite endpoint demonstrates benefit of trilaciclib across multiple clinically meaningful components of myeloprotection in patients with small cell lung cancer
Authors: Dómine Gómez Manuel , Csőszi Tibor , Jaal Jana , Kudaba Iveta , Nikolov Krasimir , Radosavljevic Davorin , Xiao Jie , Horton Janet K. , Malik Rajesh K. , Subramanian Janakiraman
Published: June 2021

Chemotherapy‐induced myelosuppression is an acute, dose‐limiting toxicity of chemotherapy regimens used in the treatment of extensive‐stage small cell lung cancer (ES‐SCLC). Trilaciclib protects haematopoietic stem and progenitor cells from chemotherapy‐induced damage (myeloprotection). To assess the totality of the myeloprotective benefits of trilaciclib, including analysis of several clinically relevant but low‐frequency events, an exploratory composite endpoint comprising five major adverse haematological events (MAHE) was prospectively defined: all‐cause hospitalisations, all‐cause chemotherapy dose reductions, febrile neutropenia (FN), prolonged severe neutropenia (SN) and red blood cell (RBC) transfusions on/after Week 5. MAHE and its individual components were assessed in three randomised, double‐blind, placebo‐controlled Phase 2 trials in patients receiving a platinum/etoposide or topotecan‐containing chemotherapy regimen for ES‐SCLC and in data pooled from the three trials. A total of 242 patients were randomised across the three trials (trilaciclib, n = 123; placebo, n = 119). In the individual trials and the pooled analysis, administering trilaciclib prior to chemotherapy resulted in a statistically significant reduction in the cumulative incidence of MAHE compared to placebo. In the pooled analysis, the cumulative incidences of all‐cause chemotherapy dose reductions, FN, prolonged SN and RBC transfusions on/after Week 5 were significantly reduced with trilaciclib vs placebo; however, no significant difference was observed in rates of all‐cause hospitalisations. Additionally, compared to placebo, trilaciclib significantly extended the amount of time patients remained free of MAHE. These data support the myeloprotective benefits of trilaciclib and its ability to improve the overall safety profile of myelosuppressive chemotherapy regimens used to treat patients with ES‐SCLC.
Phase I clinical trial of HC‐1119: A deuterated form of enzalutamide
Authors: Li Xiaoyu , Cheng Ke , Li Xinghai , Zhou Yuwen , Liu Jiyan , Zeng Hao , Chen Yuanwei , Liu Xiao , Zhang Ying , Wang Yongsheng , Bi Feng , Zheng Li
Published: June 2021

The purpose of our study was to investigate the safety, pharmacokinetics (PK), and initial antitumor efficacy of HC‐1119 in patients with metastatic castration‐resistant prostate cancer (mCRPC). Eligible mCRPC patients were included in our study (NCT 03774056) with two parts. Part A was a dose escalation study in which patients received a dose escalation of HC‐1119 (40, 80, 160 and 200 mg/day). Part B was a dose expansion study in which patients received HC‐1119 at the dose of 80 and 160 mg. Safety assessment and pharmacokinetic samplings were performed for all patients at the given time points; preliminary tumor response was also assessed. Twenty‐four patients were enrolled in part A and 19 patients in part B, respectively. HC‐1119 was safe, well tolerated and no dose‐limiting toxicity was observed. Fatigue was the most common treatment‐related adverse event and no seizures were observed. At the dose levels of 40, 80 and 160 mg, the AUC and Cmax of HC‐1119 in plasma increased almost dose‐proportionally at the steady state in mCRPC patients. Maximum prostate‐specific antigen (PSA) response rates (≥50% reduction from the baseline) in dose escalation and dose expansion cohorts were 77% and 75%, respectively; the overall disease control rate (22 patients available for imaging analysis) was 72.7%, with PR in 4 patients, SD in 12 patients and PD in 6 patients; the 2‐year overall survival rate in patients from Part B was 56.8%. HC‐1119 was safe, well tolerated and efficacious and HC‐1119 at 80 mg/day is recommended for further studies.
Mass spectrometry‐based urinary metabolomics for exploring the treatment effects of Radix ginseng‐Schisandra chinensis herb pair on Alzheimer's disease in rats
Authors: Wang Aimin , Pi Zifeng , Liu Shu , Zheng Zhong , Liu Zhiqiang , Song Fengrui
Published: June 2021

Herb pairs are the unique combinations of two relatively fixed herbs, intrinsically convey the basic idea of traditional Chinese medicine prescriptions. The compatibility of Radix ginseng and Schisandra chinensis has been used in traditional Chinese medicine for treating Alzheimer's disease for many years. However, there are few studies on Radix ginseng‐Schisandra chinensis herb pair, and the underlying action mechanism is still unclear. In this study, the mechanism of Radix ginseng‐Schisandra chinensis herb pair on Alzheimer's disease was investigated by using the mass spectrometry‐based urinary metabolomics method. Sixteen urinary endogenous metabolites were identified as potential biomarkers. Meanwhile, 10 biomarkers were quantified with tandem mass spectrometry. The study result showed that the brain pathologic symptoms of model rats were improved and the potential biomarkers were adjusted backward significantly after the herb pair administration. The metabolic pathways linked to the herb pair‐regulated endogenous biomarkers included phenylalanine and tyrosine metabolism, tryptophan metabolism, purine metabolism, and so on. The above metabolic pathways reflected that Radix ginseng‐Schisandra chinensis herb pair mainly regulates abnormal energy metabolism, reduces inflammation, and regulates gut microbiota and neurotransmitters in the treatment of Alzheimer's disease.
Recent developments in Lablab purpureus genomics: A focus on drought stress tolerance and use of genomic resources to develop stress‐resilient varieties
Authors: Missanga Julius S. , Venkataramana Pavithravani B. , Ndakidemi Patrick A.
Published: June 2021

Drought is a major climatic challenge that contributes significantly to the decline of food productivity. One of the strategies to overcome this challenge is the use of drought‐tolerant crops with a wide range of benefits. Lablab is a leguminous crop that has been showing high promise to drought tolerance. It is reported to have higher drought resilience compared with the commonly cultivated legumes such as common beans and cowpeas. Because of its great genetic diversity, Lablab can withstand high temperature and low rainfall, unlike other related crops. On top of that, it is grown for multitudes of purposes including food, forages, conservation agriculture, and improved soil fertility. To enhance its production and benefits during the present effects of climate change, it is crucial to develop improved varieties that would overcome the challenge of drought stress. In the past years, there have been several reviews on Lablab based on origin, domestication, characterization, utilization, germplasm conservation, some cultivation constraints, and conventional breeding with limitations on the genomic exploitation of the crop for drought tolerance. Conventional breeding is the major breeding technique for many Lablab cultivars. The integration of genomic, physiological, biochemical, and molecular approaches would be required to develop drought‐tolerant cultivars of Lablab. In this review, we discuss recent developments in Lablab genomics with a focus on drought stress tolerance and the use of genomic resources to develop stress‐resilient varieties.