bluuebunny/crossref_metadata_2025 huggingface dataset:
Altered prolactin and androgen receptors expression in companion rat benign mammary tumours
Authors: Vergneau‐Grosset Claire , Cluzel Caroline , Beauchamp Guy , Hubbard Neil E. , Paul‐Murphy Joanne , Paquet Marilène
Published: November 2020

Benign mammary tumours are among the most common tumours of companion rats (Rattus norvegicus domestica), as well as a major animal welfare concern and euthanasia. The first objective of this study was to evaluate the expression of oestrogen, progesterone, androgen, and prolactin receptors in neoplastic and normal mammary gland tissues and compare the expression of these receptors between groups. The second objective was to determine if the expression of these receptors in neoplastic mammary gland tissue correlates with overall survival and occurrence of an additional mass after initial mammary mass excision. The third objective was to determine if the expression of oestrogen, progesterone, androgen and prolactin receptors was associated with mammary tumor clinical parameters or with the age of the animals. Thirty‐two benign mammary tumours were collected from companion rats and submitted for immunohistochemistry staining of prolactin receptor, oestrogen receptor alpha (ERa), progesterone and androgen receptors (AR). Allred score were obtained for mammary tumours (n = 32) and surrounding normal mammary tissue (n = 20) when present. Prolactin receptor expression increased significantly with mammary gland tumorigenesis (P < .0001), while AR expression decreased with tumorigenesis (P < .0001). Lower expression of ERa in tumor stroma was associated with shorter survival (P = .02). Hormonal receptor expression was not significantly associated with age, mass diameter, location nor likelihood of additional mass development. Further studies should investigate the effects of prolactin antagonists in a prospective study involving companion rats with benign mammary tumours.
New Topoisomerase Inhibitors: Evaluating the Potency of Gepotidacin and Zoliflodacin in Fluoroquinolone-Resistant Escherichia coli upon
tolC
Inactivation and Differentiating Their Efflux Pump Substrate Nature
Authors: Schuster Sabine , Vavra Martina , Köser Raphael , Rossen John W. A. , Kern Winfried V.
Published: November 2020

Inactivating
tolC
in multidrug-resistant
Escherichia coli
with differing sequence types and quinolone resistance-determining mutations reveals remarkably potentiated activity of the first-in-class topoisomerase inhibitors gepotidacin and zoliflodacin. Differences between both structurally unrelated compounds in comparison to fluoroquinolones regarding the selectivity of
E. coli
RND (resistance-nodulation-cell division)-type transporters, efflux inhibitors, and AcrB porter domain mutations were demonstrated.
Virus Isoelectric Point Estimation: Theories and Methods
Authors: Heffron Joe , Mayer Brooke K.
Published: November 2020

Much of virus fate, both in the environment and in physical/chemical treatment, is dependent on electrostatic interactions. Developing an accurate means of predicting virion isoelectric point (pI) would help to understand and anticipate virus fate and transport, especially for viruses that are not readily propagated in the lab.
Defining the Mechanistic Correlates of Protection Conferred by Whole-Cell Vaccination against Pseudomonas aeruginosa Acute Murine Pneumonia
Authors: Sen-Kilic Emel , Blackwood Catherine B. , Huckaby Annalisa B. , Horspool Alexander M. , Weaver Kelly L. , Malkowski Aaron C. , Witt William T. , Bevere Justin R. , Damron F. Heath , Barbier Mariette
Published: November 2020

Pseudomonas aeruginosais a Gram-negative pathogen that causes severe pulmonary infections associated with high morbidity and mortality in immunocompromised patients. The development of a vaccine againstP. aeruginosacould help prevent infections caused by this highly antibiotic-resistant microorganism.
Identification of a Transcriptomic Network Underlying the Wrinkly and Smooth Phenotypes of Vibrio fischeri
Authors: Chavez-Dozal Alba , Soto William , Nishiguchi Michele K.
Published: November 2020

The wrinkly bacterial colony phenotype has been associated with increased squid host colonization in
V. fischeri
. The significance of our research is in identifying the genetic mechanisms that are responsible for heightened biofilm formation in
V. fischeri
.
The TLR3/IRF1/Type III IFN Axis Facilitates Antiviral Responses against Enterovirus Infections in the Intestine
Authors: Su Rui , Shereen Muhammad Adnan , Zeng Xiaofeng , Liang Yicong , Li Wen , Ruan Zhihui , Li Yongkui , Liu Weiyong , Liu Yingle , Wu Kailang , Luo Zhen , Wu Jianguo
Published: November 2020

Enterovirus infections are significant sources of human diseases and public health risks worldwide, but little is known about the mechanism of innate immune response in host intestine epithelial surface during the viral replication. We reported the epithelial immune response in cultured human normal and cancerous cells (IECs), mouse tissues, and human clinical intestine specimens following infection with enterovirus 71. The results mechanistically revealed type III interferons (IFN-λ1 and IFN-λ2/3), rather than type I interferons (IFN-α and IFN-β), as the dominant production through TLR3/IRF1 signaling upon multiple human enterovirus infection, including enterovirus 71 (EV71), coxsackievirus B3 (CVB3), and poliovirus 1 (PV1). IFN-λ subsequently induced antiviral activity against enterovirus replication
in vitro
and
in vivo.
These studies uncovered the role of the novel process of type III IFN production involved in the TLR3/IRF1 pathway in host intestine upon enterovirus infection, which highlighted a regulatory manner of antiviral defense in intestine during enterovirus infection.
Distinct Cytokine Profiles Correlate with Disease Severity and Outcome in Longitudinal Studies of Acute Hepatitis B Virus and Hepatitis D Virus Infection in Chimpanzees
Authors: Engle Ronald E. , De Battista Davide , Danoff Emily J. , Nguyen Hanh , Chen Zhaochun , Lusso Paolo , Purcell Robert H. , Farci Patrizia
Published: November 2020

Studies performed in chimpanzees at the National Institutes of Health (NIH) demonstrated a significant difference in ALT levels during acute hepatitis of different viral etiologies, with a hierarchy in the extent of liver damage according to the infecting virus: the highest level was in HDV superinfection, followed by infection with a precore HBV mutant, HBV/HDV coinfection, and, lastly, wild-type HBV infection. Our study demonstrates that both the virus and host are important in disease pathogenesis and offers new insights into their roles. We found that distinct cytokine profiles were associated with disease severity and clinical outcome. In particular, resolution of classic acute hepatitis B (AHB) correlated with a predominant Th1 response, whereas HBV/HDV coinfection showed a predominant proinflammatory response. Severe AHB and HDV superinfection showed a restricted cytokine profile and no evidence of Th1 response. The lack of cytokines associated with adaptive T-cell responses toward the precore HBV mutant and HDV superinfection argues in favor of a direct cytopathic effect of these viruses.
Outcomes of corneal neurotisation using processed nerve allografts: a multicentre case series
Authors: Sweeney Adam R , Wang Margaret , Weller Christopher L , Burkat Cat , Kossler Andrea L. , Lee Bradford W , Yen Michael T
Published: November 2020

Background

Corneal neurotisation is a rapidly evolving procedure treating neurotrophic keratopathy. The variety of surgical techniques used and corresponding outcomes after corneal neurotisation are not well understood. This study describes the techniques and outcomes in the largest case series of corneal neurotisation using processed nerve allografts to date.

Methods

This is a retrospective case series of patients who underwent corneal neurotisation with human cadaveric processed nerve allografts. All patients had preoperative and postoperative description of best corrected visual acuity and measurement of corneal sensation. Comparative studies after stratification of techniques were performed.

Results

A total of 17 patients were identified. The cause of corneal anaesthesia was prior infection in eight cases, trigeminal nerve palsy in eight cases and ocular trauma in one case. There were no intraoperative or postoperative complications. Following neurotisation surgery, the time to first gain of corneal sensation and maximal gain of sensation occurred at a mean of 3.7 months (range 1–8 months) and 6.6 months (range 3–15 months), respectively. The mean preoperative and postoperative corneal sensation as measured by Cochet-Bonnet aesthesiometry was 0.36 cm (range 0–3.2 cm) and 4.42 cm (range 0–6 cm), respectively (p<0.01). Visual acuity was unchanged after neurotisation. There were no statistical differences in outcomes based on end-to-end versus end-to-side coaptations, donor nerve selection or laterality of donor nerve.

Conclusion

Corneal neurotisation with processed nerve allografts is a safe and effective procedure. This study provides further evidence for the use of processed nerve allografts for corneal neurotisation.
Prevalence and frequency of menstrual cycle symptoms are associated with availability to train and compete: a study of 6812 exercising women recruited using the Strava exercise app
Authors: Bruinvels Georgie , Goldsmith Esther , Blagrove Richard , Simpkin Andrew , Lewis Nathan , Morton Katie , Suppiah Ara , Rogers John P , Ackerman Kathryn E , Newell John , Pedlar Charles
Published: November 2020

Objectives

The menstrual cycle can affect sports participation and exercise performance. There are very few data on specific menstrual cycle symptoms (symptoms during various phases of the cycle, not only during menstruation) experienced by exercising women. We aimed to characterise the most common symptoms, as well as the number and frequency of symptoms, and evaluate whether menstrual cycle symptoms are associated with sporting outcomes.

Methods

6812 adult women of reproductive age (mean age: 38.3 (8.7) years) who were not using combined hormonal contraception were recruited via the Strava exercise app user database and completed a 39-part survey. Respondents were from seven geographical areas, and the questions were translated and localised to each region (Brazil, n=892; France, n=1355; Germany, n=839; Spain, n=834; UK and Ireland, n=1350; and USA, n=1542). The survey captured exercise behaviours, current menstrual status, presence and frequency of menstrual cycle symptoms, medication use for symptoms, perceived effects of the menstrual cycle on exercise and work behaviours, and history of hormonal contraception use. We propose a novel Menstrual Symptom index (MSi) based on the presence and frequency of 18 commonly reported symptoms (range 0–54, where 54 would correspond to all 18 symptoms each occurring very frequently).

Results

The most prevalent menstrual cycle symptoms were mood changes/anxiety (90.6%), tiredness/fatigue (86.2%), stomach cramps (84.2%) and breast pain/tenderness (83.1%). After controlling for body mass index, training volume and age, the MSi was associated with a greater likelihood of missing or changing training (OR=1.09 (CI 1.08 to 1.10); p≤0.05), missing a sporting event/competition (OR=1.07 (CI 1.06 to 1.08); p≤0.05), absenteeism from work/academia (OR=1.08 (CI 1.07 to 1.09); p≤0.05) and use of pain medication (OR=1.09 (CI 1.08 to 1.09); p≤0.05).

Conclusion

Menstrual cycle symptoms are very common in exercising women, and women report that these symptoms compromise their exercise participation and work capacity. The MSi needs to be formally validated (psychometrics); at present, it provides an easy way to quantify the frequency of menstrual cycle symptoms.
Injury incidence and burden in a youth elite football academy: a four-season prospective study of 551 players aged from under 9 to under 19 years
Authors: Materne Olivier , Chamari Karim , Farooq Abdulaziz , Weir Adam , Hölmich Per , Bahr Roald , Greig Matt , McNaughton Lars R
Published: November 2020

Objective

Investigate the incidence and burden of injuries by age group in youth football (soccer) academy players during four consecutive seasons.

Methods

All injuries that caused time-loss or required medical attention (as per consensus definitions) were prospectively recorded in 551 youth football players from under 9 years to under 19 years. Injury incidence (II) and burden (IB) were calculated as number of injuries per squad season (s-s), as well as for type, location and age groups.

Results

A total of 2204 injuries were recorded. 40% (n=882) required medical attention and 60% (n=1322) caused time-loss. The total time-loss was 25 034 days. A squad of 25 players sustained an average of 30 time-loss injuries (TLI) per s-s with an IB of 574 days lost per s-s. Compared with the other age groups, U-16 players had the highest TLI incidence per s-s (95% CI lower-upper): II= 59 (52 to 67); IB=992 days; (963 to 1022) and U-18 players had the greatest burden per s-s: II= 42.1 (36.1 to 49.1); IB= 1408 days (1373 to 1444). Across the cohort of players, contusions (II=7.7/s-s), sprains (II=4.9/s-s) and growth-related injuries (II=4.3/s-s) were the most common TLI. Meniscus/cartilage injuries had the greatest injury severity (95% CI lower-upper): II= 0.4 (0.3 to 0.7), IB= 73 days (22 to 181). The burden (95% CI lower-upper) of physeal fractures (II= 0.8; 0.6 to 1.2; IB= 58 days; 33 to 78) was double than non-physeal fractures.

At this youth football academy, each squad of 25 players averaged 30 injuries per season which resulted in 574 days lost. The highest incidence of TLI occurred in under-16 players, while the highest IB occurred in under-18 players.
Venous thromboembolism in patients with COVID-19 and correlation with D-dimers: a single-centre experience
Authors: Khan Muhammad Ziaullah , Jamal Yousaf , Sutton Benjamin , Rauf Farrukh
Published: November 2020

Objective

To study the frequency of venous thromboembolism in hospitalised patients with COVID-19 and correlation with the D-dimers and thromboprophylaxis.

Design

Cross-sectional descriptive study.

Place and duration of study

Queen Elizabeth Hospital, 20 April 2020–13 May 2020.

Patients and methods

One hundred and seven (n=107) patients of PCR-confirmed COVID-19 pneumonia admitted to Queen Elizabeth Hospital, Birmingham, between 20 April 2020 and 13 May 2020 were included in the study using consecutive sampling. Data were collected using the Excel audit tool and included age, gender, weight, estimated eGFR, D-dimer values on admission, intensive care unit admission, presence of respiratory failure, imaging results for evaluation of venous thromboembolism (VTE) and anticoagulation received on admission. The data were entered in the SPSS (V.17) and were analysed. Data were summarised as means±SD, number or percentage as appropriate. A p value of less than 0.05 was considered significant.

Results

The frequency of VTE was found to be 11.2% in patients hospitalised with COVID-19 pneumonia. The mean D-dimers were 3322.24 ng/mL±9603 ng/mL with the values significantly higher for patients with VTE and those requiring intensive care unit admission. All of the seven patients (100%) with D-dimers value above 2000 ng/mL who underwent imaging were found to have VTE.

Conclusion

VTE is frequent in patients with COVID-19 pneumonia despite anticoagulation. A higher D-dimers value correlates well with the risk of VTE in these patients and further evaluation of such patients for VTE is necessary especially with D-dimers values above 2000 ng/mL.
Canadian College of Medical Geneticists (CCMG) points to consider: resuming genetic services in a pandemic—a summary
Authors: Chad Lauren , Dawson Angelika J , Goh Elaine Suk-Ying
Published: November 2020

The COVID-19 pandemic has disrupted the provision of genetic care in Canada. With the public health effort to flatten the curve, many clinics have moved to virtual care for select populations of patients while triaging and postponing others. As genetic services are asked to gradually resume, a roadmap is needed to ensure clinical care decisions for at-risk patients are transparent and equitable, that postponed care is resumed and that patients with or waiting for a genetic diagnosis are not disproportionately affected or abandoned.

The purpose of this document is to highlight the guiding ethical principles and stakeholder considerations in resuming genetic services to help guide the competing needs going forward of both limiting exposures while maintaining high-quality care. Considerations highlighted are (1) environment of practice, (2) nature of consult, (3) patient factors, (4) provider factors, and (5) laboratory factors. The intended users are those providing genetic care in a Canadian context with the recognition that there are clinic-specific and regional variations that will influence decision-making. While specific to the Canadian context, the ethical principles used to guide these decisions would be relevant for consideration in other jurisdictions.
Chapter 4 Depositional geometry at selected locations around the basin
Authors: Wilson A. O.
Published: November 2020

This chapter includes 11 cross-sections and one well log profile to show the depositional geometry and setting in specific areas around the basin: the Saudi Arabia outcrop belt; the Rimthan Arch; and the eastern and central areas of the intrashelf basin in Saudi Arabia, Bahrain, Qatar, Abu Dhabi and Oman. These cross-sections are used to demonstrate the similarity and degree of continuity of the upper Dhruma Formation, the Tuwaiq Mountain Formation, the source rock, the Hanifa, Jubaila–Arab and Arab–Hith formations and depositional sequences in these different locations in the basin. They show the manner in which the underlying platform formed, the rim developed, the source rock was deposited and the basin progressively filled. The blanket deposition of the Arab-D anhydrite was followed by the Arab-C to Arab-A and Hith carbonate and evaporite sequences. The cross-sections provide the framework used in subsequent chapters to make a series of facies maps and other interpretative diagrams and cross-sections that summarize and, for some intervals, revise the interpretation of the settings and geological events that formed the Arabian Intrashelf Basin.
The Diversity of Primates: From Biomedicine to Conservation Genomics
Authors: Orkin Joseph D. , Kuderna Lukas F.K. , Marques-Bonet Tomas
Published: November 2020

Until now, the field of primate genomics has focused on two major themes: understanding human evolution and advancing biomedical research. We propose that it is now time for a third theme to receive attention: conservation genomics. As a result of anthropogenic effects, the majority of primate species have become threatened with extinction. A more robust primate conservation genomics will allow for genetically informed population management. Thanks to a steady decline in the cost of sequencing, it has now become feasible to sequence whole primate genomes at the population level. Furthermore, technological advances in noninvasive genomic methods have made it possible to acquire genome-scale data from noninvasive biomaterials. Here, we review recent advances in the analysis of primate diversity, with a focus on genomic data sets across the radiation.
Methylation of histone 4’s lysine 20: a critical analysis of the state of the field
Authors: Corvalan Adriana Z. , Coller Hilary A.
Published: November 2020

Chromatin is a highly dynamic structure whose plasticity is achieved through multiple processes including the posttranslational modification of histone tails. Histone modifications function through the recruitment of nonhistone proteins to chromatin and thus have the potential to influence many fundamental biological processes. Here, we focus on the function and regulation of lysine 20 of histone H4 (H4K20) methylation in multiple biological processes including DNA repair, cell cycle regulation, and DNA replication. The purpose of this review is to highlight recent studies that elucidate the functions associated with each of the methylation states of H4K20, their modifying enzymes, and their protein readers. Based on our current knowledge of H4K20 methylation, we critically analyze the data supporting these functions and outline questions for future research.
Incidence of Endophthalmitis after Intravitreal Anti-Vascular Endothelial Growth Factor Injections in an Operating Room in China
Authors: Chen Yanyun , Wei Wenbin , Vavvas Demetrios G. , Zhang Feng , She Haicheng , Zhou Haiying , Li Lei , Huang Yao , Ntentakis Dimitrios P. , Shi Xiangyu
Published: November 2020

Purpose. To evaluate the rate of presumed endophthalmitis (EO) after intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections performed in an operating room (OR) under sterile conditions in mainland China. Methods. Retrospective single-center study between September 2012 and December 2017 at Beijing Tongren Eye Center, Beijing, China. Intravitreal injection database was reviewed. All anti-VEGF injections were performed using a standardized sterile technique in an OR. Injection protocols included antibiotics for 3 days pre-injection, topical 5% povidone-iodine rinsing before the procedure, and post-injection antibiotics for 3 days. Results. A total of 37,830 intravitreal injections were performed at Beijing Tongren Eye Center. Three cases were managed as presumed EO (0.0079%). Positive cultures were documented in 2 of 3 cases. EO incidence following ranibizumab and conbercept administration was 0.0088% (3 in 33,930) and 0% (0 in 3,900), respectively. No significant difference was detected between the two drugs (

P
=
0.745

). Conclusions. Very low EO rates were seen in mainland China using a standardized sterile technique in an OR. However, EO could not be completely avoided.
Ship Velocity Estimation in Airborne Along-Track Interferometric SAR Imagery Based on the Fractional Fourier Transform
Authors: Chen Chao , Li Yan , Huang Kuihua , Long Yonghong , Zhang Linlin , Ouyang Kewei
Published: November 2020

Synthetic aperture radar (SAR) was originally exploited to image stationary scenes. However, it is important to derive target information of velocity for many applications. The fractional Fourier transform (FrFT) is a generalization of the classical Fourier transform and is well-known as a useful tool to estimate the chirp rate of linear frequency-modulated (LFM) signals. Motion compensation is critical to moving target imaging. It is difficult for us to obtain the actual motion parameters in real scenarios. Based on the moving target echo model in airborne along-track interferometric SAR (ATI-SAR) and expression of the ATI phase, a method is proposed to estimate the ship velocity by combining the ATI phase with FrFT. First, we use the FrFT to evaluate the chirp rate of the moving target echo. Then, we construct an equation to estimate the ship velocity using the chirp rate estimation, peak response time, and ATI phase. Finally, the simulation experiments are used to validate the effectiveness of the proposed method.
Chrysophanol Alleviates Metabolic Syndrome by Activating the SIRT6/AMPK Signaling Pathway in Brown Adipocytes
Authors: Liu Xueying , Yang Zehong , Li Huixuan , Luo Wen , Duan Wentao , Zhang Junmei , Zhu Zhangzhi , Liu Min , Li Saimei , Xin Xiaoyi , Wu Haoxiang , Xian Shaoxiang , Liu Meijing , Liu Changhui , Shen Chuangpeng
Published: November 2020

Chrysophanol, a primary active ingredient of Cassia mimosoides Linn or Rhei radix et rhizoma, has various pharmacological properties, including anticancer, antidiabetic, and anti-inflammatory, as well as blood lipid regulation. However, whether chrysophanol can mitigate obesity, and its underlying mechanisms remains unclear. This study investigated whether chrysophanol effects energy metabolism in high-fat diet- (HFD-) induced obese mice and fat-specific Sirtuin 6- (SIRT6-) knockout (FKO) mice, targeting the SIRT6/AMPK signaling pathway in brown and white fat tissue. Our results showed that chrysophanol can effectively inhibit lipid accumulation in vitro and reduce mice’s body weight, improve insulin sensitivity and reduced fat content of mice, and induce energy consumption in HFD-induced obese mice by activating the SIRT6/AMPK pathway. However, a treatment with OSS-128167, an SIRT6 inhibitor, or si-SIRT6, SIRT6 target specific small interfering RNA, in vitro blocked chrysophanol inhibition of lipid accumulation. Similar results were obtained when blocking the AMPK pathway. Moreover, in the HFD-induced obese model with SIRT6 FKO mice, histological analysis and genetic test results showed that chrysophanol treatment did not reduce lipid droplets and upregulated the uncoupling protein 1 (UCP1) expression. Rather, it upregulated the expression of thermogenic genes and activated white fat breakdown by inducing phosphorylation of adenosine 5

′

-monophosphate- (AMP-) activated protein kinase (AMPK), both in vitro and in vivo. OSS-128167 or si-SIRT6 blocked chrysophanol’s upregulation of peroxisome proliferator-activated receptor-γ coactivator-1α (Pgc-1α) and Ucp1 expression. In conclusion, this study demonstrated that chrysophanol can activate brown fat through the SIRT6/AMPK pathway and increase energy consumption, insulin sensitivity, and heat production, thereby alleviating obesity and metabolic disorders.
Hematologic Chaos in Lupus Flare: A Case of Fulminant and Simultaneous Antiphospholipid, Anti-ADAMTS13, and Red Blood Cell Autoantibodies
Authors: Al-Mondhiry Jafar , Chen Caroline Y. , Rosove Michael H.
Published: November 2020

Systemic lupus erythematosus may present with several distinct autoimmune phenomena simultaneously. We report a patient presenting with three serious hematologic disorders: thrombotic thrombocytopenic purpura, catastrophic antiphospholipid syndrome, and warm-type IgG red cell autoantibodies. The case is an example of the complex clinical nature of lupus and the importance of accurately identifying individual complications in order to optimize management.
On Topological Descriptors of Certain Metal-Organic Frameworks
Authors: Xu Peng , Azeem Mehran , Izhar Muhammad Mubashir , Shah Syed Mazhar , Binyamin Muhammad Ahsan , Aslam Adnan
Published: November 2020

Topological indices are numerical numbers that represent the topology of a molecule and are calculated from the graphical depiction of the molecule. The importance of topological indices is due to their use as descriptors in QSPR/QSAR modeling. QSPRs (quantitative structure-property relationships) and QSARs (quantitative structure-activity relationships) are mathematical correlations between a specified molecular property or biological activity and one or more physicochemical and/or molecular structural properties. In this paper, we give explicit expressions of some degree-based topological indices of two classes of metal-organic frameworks (MOFs), namely, butylated hydroxytoluene- (BHT-) based metal-organic (

M
=
Co

, Fe, Mn, Cr) (MBHT) frameworks and

M

1

TPyP
−

M

2

(TPyP = 

5,10,15,20

-tetrakis(4-pyridyl)porphyrin and

M

1

,

M

2

 = Fe and Co) MOFs.
Impact Characteristics and Fatigue Life Analysis of Multi-Wire Recoil Spring for Guns
Authors: Wei Zhifang , Zhang Xiaolian , Hu Yecang , Cheng Yangyang
Published: November 2020

Recoil spring is a key part in automatic or semi-automatic weapons re-entry mechanism. Because the stranded wire helical spring (SWHS) has longer fatigue life than an ordinary single-wire cylindrically helical spring, it is often used as a recoil spring in various weapons. Due to the lack of in-depth research on the dynamic characteristics of the current multi-wire recoil spring in recoil and re-entry processes, the fatigue life analysis of the current multi-wire recoil spring usually only considers uniform loading and does not consider dynamic impact loads, which cannot meet modern design requirements. Therefore, this paper proposes a research method for fatigue life prediction analysis of multi-wire recoil spring. Firstly, based on the secondary development of UG, a three-wire recoil spring parameterized model for a gun is established. Secondly, ABAQUS is used to carry out a finite element analysis of its dynamic response characteristics under impact, and experimental verification is performed. Then, based on the stress-time history curve of the dangerous position obtained by finite element analysis, the rain flow counting method is used to obtain the fatigue stress spectrum of recoil spring. Finally, according to the Miner fatigue cumulative damage theory, the fatigue life prediction of the recoil spring based on the S-N curve of the material is compared with experimental results. The research results show that the recoil spring has obvious transient characteristics during the impact of the bolt carrier. The impact velocity is far greater than the propagation speed of the stress wave in the recoil spring, which easily causes the spring coils to squeeze each other. The maximum stress occurs at the fixed end of the spring. And the mean fatigue curve (50% survival rate) is used to predict the life of the recoil spring. The calculation result is 8.6% different from the experiment value, which proves that the method has certain reliability.
Case Series of Chronic Inflammatory Rheumatic Disease Patients Infected by Coronavirus Disease 2019 (COVID-19)
Authors: Tiendrébéogo Wendlassida Joëlle Stéphanie , Kaboré Fulgence , Diendéré Eric Arnaud , Ouedraogo Dieu-Donné
Published: November 2020

Coronavirus disease 2019 (COVID-19) is a viral infection that appeared in December 2019. The risk of infection seems to be increased in chronic inflammatory rheumatic diseases due to both immune disturbances related to the disease and treatment. In this case report, we describe the clinical features of 5 rheumatic immune disease patients with the concomitant presence of COVID-19. Among these patients, 3 had rheumatoid arthritis and 2 had systemic lupus erythematosus. Patients’ age ranged between 38 and 63 years. Only one patient (SLE) had a severe subtype of COVID-19. All the patients were cured of COVID-19 and were subsequently discharged.
Photovoltaic and Charge Trapping Characteristics of Screen-Printed Monocrystalline Silicon Solar Cells with Molybdenum Oxides as Hole-Selective Layers by H2/Ar Plasma Pretreatment
Authors: Cheng Chin-Lung , Liu Chi-Chung , Hsu Chih-Chieh
Published: November 2020

Photovoltaic characteristics of screen-printed monocrystalline silicon solar cells (SPSSCs) with molybdenum oxide (MoO

x

) as hole-selective layers (HSLs) were demonstrated. A H2/Ar plasma pretreatment (PPT) was incorporated into a MoO

x

/p-Si(100) interface, which shows the expected quality in terms of passivation. Moreover, the charge trapping characteristics of the MoO

x

/p-Si(100) interface were presented. The PPT parameters, including power, treated time, flow ratio of H2/Ar, and temperature, were investigated. The experimental results indicate that the Si-H bond with a relatively high intensity was demonstrated for the H2/Ar PPT. The achievement of a conversion efficiency (CE) improvement of more than 1.2% absolute from 18.3% to 19.5% for SPSSCs with H2/Ar PPT was explored. The promoted mechanism was attributed to the reduction of the interface trap density caused by the large number of Si-H bonds at the silicon substrate and MoO

x

interface.
Radix Scutellariae Ameliorates Stress-Induced Depressive-Like Behaviors via Protecting Neurons through the TGFβ3-Smad2/3-Nedd9 Signaling Pathway
Authors: Zhao Fan , Zhang Chenyiyu , Xiao Dong , Zhang Weihua , Zhou Liping , Gu Simeng , Qu Rong
Published: November 2020

Chronic stress can impair hippocampal neurogenesis, increase neuronal apoptosis, and cause depressive-like behaviors. Our previous studies found that Radix Scutellariae (RS) can rescue the stress-induced neuronal injury, but the mechanism is not clear. Here, we continued to investigate the underlying antidepressant mechanisms of the RS extract. A 7-week chronic unpredictable mild stress (CUMS) procedure was used to establish a murine depression model. 0.75 g/kg or 1.5 g/kg RS was administered daily to the mice during the last 4 weeks. Depressive-like behaviors were evaluated by the sucrose preference test (SPT), forced swimming test (FST), open field test (OFT), and tail suspension test (TST). The neuroprotective effect of RS was evaluated with the expression of hippocampal neuron-related markers and apoptosis-associated proteins by Nissl staining, immunohistochemistry, and western blot. Transforming growth factor-β3 (TGFβ3) pathway-related proteins were detected by western blot. Results showed that RS could ameliorate depressive-like behaviors, increase the expression of the antiapoptotic protein B-cell lymphoma 2 (BCL-2), reduce the expression of the proapoptotic protein BCL-2-associated X (BAX), and increase the number of doublecortin- (DCX-), microtubule-associated protein 2- (MAP2-), and neuronal nucleus- (NeuN-) positive cells in the hippocampus. Moreover, RS could reverse the CUMS-induced decrease of TGFβ3 protein, promote the phosphorylation of SMAD2/3, and increase the expression of downstream NEDD9 protein. These results suggest that RS could exert antidepressant effects via protecting neurons. And the molecular mechanism might be related to the regulation of the TGFβ3-SMAD2/3-NEDD9 pathway.
Randomized Phase II and Biomarker Study of Pembrolizumab plus Bevacizumab versus Pembrolizumab Alone for Patients with Recurrent Glioblastoma
Authors: Nayak Lakshmi , Molinaro Annette M. , Peters Katherine , Clarke Jennifer L. , Jordan Justin T. , de Groot John , Nghiemphu Leia , Kaley Thomas , Colman Howard , McCluskey Christine , Gaffey Sarah , Smith Timothy R. , Cote David J. , Severgnini Mariano , Yearley Jennifer H. , Zhao Qing , Blumenschein Wendy M. , Duda Dan G. , Muzikansky Alona , Jain Rakesh K. , Wen Patrick Y. , Reardon David A.
Published: November 2020

Purpose:

VEGF is upregulated in glioblastoma and may contribute to immunosuppression. We performed a phase II study of pembrolizumab alone or with bevacizumab in recurrent glioblastoma.

Patients and Methods:

Eighty bevacizumab-naïve patients with recurrent glioblastoma were randomized to pembrolizumab with bevacizumab (cohort A, n = 50) or pembrolizumab monotherapy (cohort B, n = 30). The primary endpoint was 6-month progression-free survival (PFS-6). Assessed biomarkers included evaluation of tumor programmed death-ligand 1 expression, tumor-infiltrating lymphocyte density, immune activation gene expression signature, and plasma cytokines. The neurologic assessment in neuro-oncology (NANO) scale was used to prospectively assess neurologic function.

Results:

Pembrolizumab alone or with bevacizumab was well tolerated but of limited benefit. For cohort A, PFS-6 was 26.0% [95% confidence interval (CI), 16.3–41.5], median overall survival (OS) was 8.8 months (95% CI, 7.7–14.2), objective response rate (ORR) was 20%, and median duration of response was 48 weeks. For cohort B, PFS-6 was 6.7% (95% CI, 1.7–25.4), median OS was 10.3 months (95% CI, 8.5–12.5), and ORR was 0%. Tumor immune markers were not associated with OS, but worsened OS correlated with baseline dexamethasone use and increased posttherapy plasma VEGF (cohort A) and mutant IDH1, unmethylated MGMT, and increased baseline PlGF and sVEGFR1 levels (cohort B). The NANO scale contributed to overall outcome assessment.

Conclusions:

Pembrolizumab was ineffective as monotherapy and with bevacizumab for recurrent glioblastoma. The infrequent radiographic responses to combinatorial therapy were durable. Tumor immune biomarkers did not predict outcome. Baseline dexamethasone use and tumor MGMT warrant further study as potential biomarkers in glioblastoma immunotherapy trials.
Regulation of CEACAM5 and Therapeutic Efficacy of an Anti-CEACAM5–SN38 Antibody–drug Conjugate in Neuroendocrine Prostate Cancer
Authors: DeLucia Diana C. , Cardillo Thomas M. , Ang Lisa , Labrecque Mark P. , Zhang Ailin , Hopkins James E. , De Sarkar Navonil , Coleman Ilsa , da Costa Rui M. Gil , Corey Eva , True Lawrence D. , Haffner Michael C. , Schweizer Michael T. , Morrissey Colm , Nelson Peter S. , Lee John K.
Published: November 2020

Purpose:

Neuroendocrine prostate cancer (NEPC) is an aggressive form of castration-resistant prostate cancer (CRPC) for which effective therapies are lacking. We previously identified carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) as a promising NEPC cell surface antigen. Here we investigated the scope of CEACAM5 expression in end-stage prostate cancer, the basis for CEACAM5 enrichment in NEPC, and the therapeutic potential of the CEACAM5 antibody–drug conjugate labetuzumab govitecan in prostate cancer.

Experimental Design:

The expression of CEACAM5 and other clinically relevant antigens was characterized by multiplex immunofluorescence of a tissue microarray comprising metastatic tumors from 34 lethal metastatic CRPC (mCRPC) cases. A genetically defined neuroendocrine transdifferentiation assay of prostate cancer was developed to evaluate mechanisms of CEACAM5 regulation in NEPC. The specificity and efficacy of labetuzumab govitecan was determined in CEACAM5+ prostate cancer cell lines and patient-derived xenografts models.

Results:

CEACAM5 expression was enriched in NEPC compared with other mCRPC subtypes and minimally overlapped with prostate-specific membrane antigen, prostate stem cell antigen, and trophoblast cell surface antigen 2 expression. We focused on a correlation between the expression of the pioneer transcription factor ASCL1 and CEACAM5 to determine that ASCL1 can drive neuroendocrine reprogramming of prostate cancer which is associated with increased chromatin accessibility of the CEACAM5 core promoter and CEACAM5 expression. Labetuzumab govitecan induced DNA damage in CEACAM5+ prostate cancer cell lines and marked antitumor responses in CEACAM5+ CRPC xenograft models including chemotherapy-resistant NEPC.

Conclusions:

Our findings provide insights into the scope and regulation of CEACAM5 expression in prostate cancer and strong support for clinical studies of labetuzumab govitecan for NEPC.
Cognitive Function Is a Prognostic Factor for Mortality of Nursing Home Residents during a 3-Year Observational Period
Authors: Pytka Dorota , Czarkowska-Paczek Bozena
Published: November 2020

Introduction: Assessing cognitive function could help to provide appropriate care for nursing home residents. The aim of the study was to identify the factors affecting cognitive function in nursing home residents in Poland and assess how it influenced the mortality rate during a 3-year observational period. Methods: This study included 202 elderly individuals from a nursing home in 2015. The investigation included examination of cognitive function using the MMSE and bioelectrical impedance analysis. Collected data included sex, age, blood pressure (BP), heart rate, number of comorbidities, years spent in the nursing home, educational level, and cigarette-smoking. Results: The mean MMSE score was 21.36 ± 6.35, which was negatively correlated with age and diastolic BP (p = 0.001 and p = 0.024, respectively) and positively correlated with body mass, BMI, fat-free mass, fat, muscle mass, and education level (p = 0.004, p = 0.004, p = 002, p = 0.049, p = 0.005, and p ˂ 0.001, respectively). Patients who died during the observational period had lower MMSE scores than those who survived (23.34 ± 5.68 vs. 20.16 ± 6.45; p < 0.001). Smokers had better MMSE results than nonsmokers (23.34 ± 5.98 vs. 20.08 ± 4.94; p < 0.001). Discussion: Polish nursing home residents had mild cognitive impairment depending on their age, sex, educational level, and nutritional status. Lower MMSE score was a prognostic factor for mortality in the 3-year observational period.
A Simple Method to Avoid Bile Duct Injury during Percutaneous Radiofrequency Ablation Therapy for Hepatocellular Carcinoma
Authors: Takashima Hidetaka , Moriguchi Michihisa , Hayashi Natsuko , Ikeda Kyohei , Ogiso Kiyoshi , Yokomizo Chihiro , Uejima Hirokazu , Itoh Tadashi , Tomioka Hideo , Mizuno Shigeto , Shimizu Seiji , Yasui Koichiroh , Itoh Yoshito
Published: November 2020

Hepatocellular carcinoma represents a major global health burden. Its treatment is often complicated by the anatomical location of tumors, which can lead to adverse outcomes. Radiofrequency ablation has recently gained attention as a safe method for treating hepatocellular carcinoma, but only in tumors that are not adjacent to bile ducts. Here, we report a new method for cooling the bile duct during radiofrequency ablation therapy, in which the outer jacket of an elastor needle was fixed and flash-cooled with chilled saline. This method was applied in a patient with hepatocellular carcinoma tumors near the main bile duct. The patient underwent successful radiofrequency ablation with bile duct cooling. The advantages of this method include low medical cost, simpler securing of nonexpanded bile ducts, and simultaneous removal upon termination of the radiofrequency ablation therapy. Bile duct complications associated with radiofrequency ablation typically have delayed onset. Computed tomography examination 2 months after treatment showed no bile duct injury in this case.
Cardiovascular Risk Factors, Cognitive Dysfunction, and Mild Cognitive Impairment
Authors: Vintimilla Raul , Balasubramanian Kishore , Hall James , Johnson Leigh , O’Bryant Sid
Published: November 2020

Objectives: The present study sought to evaluate the contribution of cardiovascular risk factors to cognitive functioning in a sample of Mexican Americans diagnosed with mild cognitive impairment (MCI). Methods: Hypertension, diabetes, dyslipidemia, and obesity were diagnosed based on self-report and/or standardized procedures. Cognitive function was measured with MMSE, Logical Memory I and II, Trail A & B, FAS, animal naming, and digit span tests. Independent samples t tests and two-way ANOVAs were conducted for analyses, adjusting for relevant covariates. We studied 100 Mexican Americans (65 female) with MCI, ages 50–86, from a longitudinal study of cognitive aging conducted at the University of North Texas Health Science Center. Results: A difference between subjects with and without obesity and memory scores was shown by t tests. Two-way ANOVAs detected an association between the coexistence of hypertension and diabetes with language measures, diabetes and dyslipidemia with executive function, and diabetes and obesity with memory and language measures. Conclusions: This study provides additional evidence about the link between cardiovascular risk factors and cognitive dysfunction in MCI subjects, and also demonstrated that comorbid risk factors increased the degree of cognitive deficit in many areas, which may indicate a higher risk of developing dementia.
Erythromelanosis Follicularis Faciei et Colli: A Case Report in a Caucasian Male and Brief Review of the Literature
Authors: Thielmann Carl Maximilian , Sondermann Wiebke
Published: November 2020

Erythromelanosis follicularis faciei et colli, a rare condition of unknown etiology, was first described by Kitamura et al. from Japan in 1960. It is characterized by a triad consisting of well-demarcated erythema, hyperpigmentation, and follicular papules. We report the case of a 50-year-old Caucasian male, who had asymptomatic symmetrical facial lesions since the age of 42. His family history was unremarkable. Published erythromelanosis follicularis faciei et colli cases of the last 10 years are summarized in this report to demonstrate the variability and differences in the clinical presentation of this uncommon diagnosis.
Epidemiology, Clinical Characteristics, and Visual Outcomes of Patients with Intraocular Foreign Bodies in Southwest China: A 10-Year Review
Authors: Chang Tiancong , Zhang Yun , Liu Ling , Zhang Keren , Zhang Xinyu , Wang Miao , Zeng Yue , Zhang Meixia
Published: November 2020

Introduction: Intraocular foreign bodies (IOFBs) are a serious subset of open-globe injury that can result in visual loss. This study analyzed the epidemiology, clinical characteristics, and visual outcomes of patients with IOFBs in Southwest China. Methods: This retrospective study comprised 1,176 patients with the primary diagnosis of IOFBs who resided in Sichuan Province over a 10-year period. All data were collected from medical records and analyzed statistically. Results: The annual incidence for IOFBs was 0.14 per 100,000 (95% confidence interval 0.12–0.16 per 100,000) people in Southwest China. In that period, IOFBs accounted for 22.3% of all open-globe injuries. Working-age male patients accounted for 79.1% of all IOFBs patients and there had significant differences in age distributions between genders (p < 0.001). Metallic IOFBs were the most common (74.6%) IOFB, but there were significant differences in the materials of IOFBs between adults and children of different age-groups (p < 0.001). At discharge, 277 (23.6%) patients had increased visual acuity (VA) and 95 (8.0%) had no light perception. Initial VA <20/200 (odds ratio [OR], 5.5; p < 0.001), increasing wound size (OR, 1.3; p = 0.004), IOFBs in the posterior segment (OR, 2.6; p = 0.002) and existing complications (traumatic cataract, endophthalmitis, retinal detachment, or retinal break) were independent risk factors for final VA <20/200. Conclusion: The incidence of IOFBs in Southwest China differed from global statistics. Adults and children had different clinical characteristics. Thus, their prevention strategies should be different.
Brolucizumab: A Newly Developed Anti-VEGF Molecule for the Treatment of Neovascular Age-Related Macular Degeneration
Authors: Tadayoni Ramin , Sararols Laura , Weissgerber Georges , Verma Rohini , Clemens Andreas , Holz Frank G.
Published: November 2020

Background: Despite the success of anti-vascular endothelial growth factors (anti-VEGFs), currently, there is a need for highly effective compounds that can alleviate the burden of managing neovascular age-related macular degeneration (nAMD). Purpose: To review the milestones in the molecular and clinical development of brolucizumab, the first single-chain antibody fragment (scFv) designed specifically for intraocular use in humans. Methods: In this article, we summarize the preclinical and current clinical evidence of brolucizumab administration with an overview of the other treatment regimens and additional indications under investigation. Results: The unique molecular design of brolucizumab led to a low molecular weight of only 26 kDa, allowing for a concentrated molar dose of 1 intravitreal injection compared with other anti-VEGF agents. Phase I and II clinical trial outcomes validated the efficacy of brolucizumab in the treatment of nAMD with signals of a more durable treatment effect. The pivotal phase III trials, HAWK and HARRIER, which included a total of 1,817 patients, established that brolucizumab can be administered every 3 months while maintaining disease control. Conclusions: The preclinical and clinical data on brolucizumab provide evidence of sustained disease control with longer injection intervals, thus potentially reducing the treatment burden in patients with nAMD.