bluuebunny/crossref_metadata_2025 huggingface dataset:
Silencing of PSMC2 inhibits development and metastasis of prostate cancer through regulating proliferation, apoptosis and migration
Authors: Chen Qingke , Fu Lingmin , Hu Jieping , Guo Guanghua , Xie An
Published: April 2021

Background

Prostate cancer is the most common malignant tumor of male genitourinary system, molecular mechanism of which is still not clear. PSMC2 (proteasome 26S subunit ATPase 2) is a key member of the 19S regulatory subunit of 26S proteasome, whose relationship with prostate cancer is rarely studied.

Methods

Here, expression of PSMC2 in tumor tissues or cells of prostate cancer was detected by qPCR, western blotting and immunohistochemical analysis. The effects of PSMC2 knockdown on cell proliferation, colony formation, cell migration, cell cycle and apoptosis were assessed by Celigo cell counting assay, colony formation assay, wound-healing assay, Transwell assay and flow cytometry, respectively. The influence of PSMC2 knockdown on tumor growth in vivo was evaluated by mice xenograft models.

Results

The results demonstrated that PSMC2 was upregulated in tumor tissues of prostate cancer and its high expression was significantly associated with advanced Gleason grade and higher Gleason score. Knockdown of PSMC2 could inhibited cell proliferation, colony formation and cell migration of prostate cancer cells, while promoting cell apoptosis and cell cycle arrest. The suppression of tumor growth in vivo by PSMC2 knockdown was also showed by using mice xenograft models. Moreover, the regulation of prostate cancer by PSMC2 may be mediated by Akt/Cyclin D1/CDK6 signaling pathway.

Conclusions

Therefore, our studies suggested that PSMC2 may act as a tumor promotor in the development and progression of prostate cancer, and could be considered as a novel therapeutic target for prostate cancer treatment.
Temporal trends in physical activity levels across more than a decade – a national physical activity surveillance system among Norwegian children and adolescents
Authors: Steene-Johannessen Jostein , Anderssen Sigmund Alfred , Kolle Elin , Hansen Bjørge Herman , Bratteteig Mari , Dalhaug Emilie Mass , Andersen Lars Bo , Nystad Wenche , Ekelund Ulf , Dalene Knut Eirik
Published: April 2021

Background

There is a scarcity of device measured data on temporal changes in physical activity (PA) in large population-based samples. The purpose of this study is to describe gender and age-group specific temporal trends in device measured PA between 2005, 2011 and 2018 by comparing three nationally representative samples of children and adolescents.

Methods

Norwegian children and adolescents (6, 9 and 15-year-olds) were invited to participate in 2005 (only 9- and 15-year-olds), 2011 and 2018 through cluster sampling (schools primary sampling units). A combined sample of 9500 individuals participated. Physical activity was assessed by hip worn accelerometers, with PA indices including overall PA (counts per minute), moderate-to-vigorous intensity PA (MVPA), and PA guideline adherence (achieving on average ≥ 60 min/day of moderate-to-vigorous PA). Random-effects linear regressions and logistic regressions adjusted for school-level clusters were used to analyse temporal trends.

Findings

In total, 8186 of the participating children and adolescents provided valid PA data. Proportions of sufficiently active 6-year-olds were almost identical in 2011 and 2018; boys 95% (95% CI: 92, 97) and 94% (95%CI: 92, 96) and girls 86% (95% CI: 83, 90) and 86% (95% CI: 82, 90). Proportions of sufficiently active 15-year-olds in 2005 and 2018 were 52% (95% CI: 46, 59) and 55% (95% CI: 48, 62) in boys, and 48% (95% CI: 42, 55) and 44% (95% CI: 37, 51) in girls, respectively, resulting from small differences in min/day of MVPA. Among 9-year-old boys and girls, proportions of sufficiently active declined between 2005 and 2018, from 90% (95% CI: 87, 93) to 84% (95% CI: 80, 87)) and 74% (95% CI: 69, 79) to 68% (95% CI: 64, 72), respectively. This resulted from 9.7 min/day less MVPA in boys (95% CI: − 14.8, − 4.7; p < 0.001) and 3.2 min/day less MVPA (95% CI: − 7.0, 0.7; p = 0.106) in girls.

Conclusions

PA levels have been fairly stable between 2005, 2011 and 2018 in Norwegian youth. However, the declining PA level among 9-year-old boys and the low proportion of 15-year-olds sufficiently active is concerning. To evaluate the effect of, and plan for new, PA promoting strategies, it is important to ensure more frequent, systematic, device-based monitoring of population-levels of PA.
Automatic identification of myopic maculopathy related imaging features in optic disc region via machine learning methods
Authors: Du Yuchen , Chen Qiuying , Fan Ying , Zhu Jianfeng , He Jiangnan , Zou Haidong , Sun Dazhen , Xin Bowen , Feng David , Fulham Michael , Wang Xiuying , Wang Lisheng , Xu Xun
Published: April 2021

Background

Myopic maculopathy (MM) is the most serious and irreversible complication of pathologic myopia, which is a major cause of visual impairment and blindness. Clinic proposed limited number of factors related to MM. To explore additional features strongly related with MM from optic disc region, we employ a machine learning based radiomics analysis method, which could explore and quantify more hidden or imperceptible MM-related features to the naked eyes and contribute to a more comprehensive understanding of MM and therefore may assist to distinguish the high-risk population in an early stage.

Methods

A total of 457 eyes (313 patients) were enrolled and were divided into severe MM group and without severe MM group. Radiomics analysis was applied to depict features significantly correlated with severe MM from optic disc region. Receiver Operating Characteristic were used to evaluate these features’ performance of classifying severe MM.

Results

Eight new MM-related image features were discovered from the optic disc region, which described the shapes, textural patterns and intensity distributions of optic disc region. Compared with clinically reported MM-related features, these newly discovered features exhibited better abilities on severe MM classification. And the mean values of most features were markedly changed between patients with peripapillary diffuse chorioretinal atrophy (PDCA) and macular diffuse chorioretinal atrophy (MDCA).

Conclusions

Machine learning and radiomics method are useful tools for mining more MM-related features from the optic disc region, by which complex or even hidden MM-related features can be discovered and decoded. In this paper, eight new MM-related image features were found, which would be useful for further quantitative study of MM-progression. As a nontrivial byproduct, marked changes between PDCA and MDCA was discovered by both new image features and clinic features.
HIV prevention at drug shops: awareness and attitudes among shop dispensers and young women about oral pre-exposure prophylaxis and the dapivirine ring in Shinyanga, Tanzania
Authors: Tubert Julia , Packel Laura , Hunter Lauren A. , Mfaume Rashid , Njau Prosper , Ramadhani Angela A. , Liu Jenny X. , McCoy Sandra I.
Published: April 2021

Background

HIV risk remains high among adolescent girls and young women (AGYW, ages 15–24) in Tanzania. Many AGYW experience stigma and provider bias at health facilities, deterring their use of HIV prevention services. Privately-owned drug shops, ubiquitous in many communities, may be an effective and accessible channel to deliver HIV prevention products to AGYW, including oral pre-exposure prophylaxis (PrEP) and the dapivirine vaginal ring.

Methods

In July–August 2019, we enrolled 26 drug shops in Shinyanga, Tanzania in an ongoing study to create “girl-friendly” drug shops where AGYW can access HIV self-testing and contraception. At baseline, all shop dispensers were given basic information about oral PrEP and the dapivirine ring and were asked about their interest in stocking each. During the next 3–5 months, we surveyed AGYW (n = 56) customers about their interest in oral PrEP and the ring.

Results

Among dispensers, the median age was 42 years and 77% were female. Overall, 42% of dispensers had heard of a medication for HIV prevention. Almost all dispensers reported some interest in stocking oral PrEP (92%) and the dapivirine ring (96%). Most (85%) reported they would provide oral PrEP to AGYW who requested it. Among AGYW customers, the median age was 17 years; 29% of AGYW were married or had a steady partner and 18% had children. Only 20% of AGYW had heard of a medication to prevent HIV, yet 64% and 43% expressed some interest in using oral PrEP and the dapivirine ring, respectively, after receiving information about the products. PrEP interest was higher among AGYW who were partnered and had children.

Conclusions

Despite low prior awareness of PrEP among shop dispensers and AGYW, we found high levels of interest in oral PrEP and the dapivirine ring in both groups. Community-based drug shops represent a promising strategy to make HIV prevention more accessible to AGYW.
Feasibility and effect of interactive telerehabilitation on balance in individuals with chronic stroke: a pilot study
Authors: Chen Shih-Ching , Lin Chueh-Ho , Su Sheng-Wen , Chang Yu-Tai , Lai Chien-Hung
Published: April 2021

Background

Stroke survivors need continuing exercise intervention to maintain functional status. This study assessed the feasibility and efficacy of an interactive telerehabilitation exergaming system to improve balance in individuals with chronic stroke, compared to conventional one-on-one rehabilitation.

Methods

In this prospective case–control pilot study, 30 Taiwanese individuals with chronic stroke were enrolled and randomly allocated to an experimental group and a control group. All participants received intervention 3 times per week for 4 weeks in the study hospital. The experiment group underwent telerehabilitation using a Kinect camera-based interactive telerehabilitation system in an independent room to simulate home environment. In contrast, the control group received conventional one-on-one physiotherapy in a dedicated rehabilitation area. The effectiveness of interactive telerehabilitation in improving balance in stroke survivors was evaluated by comparing outcomes between the two groups. The primary outcome was Berg Balance Scale (BBS) scores. Secondary outcomes were performance of the Timed Up and Go (TUG) test, Modified Falls Efficacy Scale, Motricity Index, and Functional Ambulation Category.

Results

Comparison of outcomes between experimental and control groups revealed no significant differences between groups at baseline and post-intervention for all outcome measures. However, BBS scores improved significantly in both groups (control group: p = 0.01, effect size = 0.49; experimental group: p = 0.01, effect size = 0.70). Completion times of TUG tests also improved significantly in the experimental group (p = 0.005, effect size = 0.70).

Conclusion

The Kinect camera-based interactive telerehabilitation system demonstrates superior or equal efficacy compared to conventional one-on-one physiotherapy for improving balance in individuals with chronic stroke.

Trial registrationClinicalTrials.gov. NCT03698357. Registered October 4, 2018, retrospectively registered.
Feelings of loneliness and mental health needs and services utilization among Chinese residents during the COVID-19 epidemic
Authors: Bao Li , Li Wen-Tian , Zhong Bao-Liang
Published: April 2021

Background

Due to the implementation of social distancing and quarantine measures, loneliness has been a major public health concern during the COVID-19 pandemic. However, few studies have examined loneliness in Chinese residents during the COVID-19 epidemic, as well as its associations with mental health needs and services utilization.

Methods

The present study was a cross-sectional survey during the COVID-19 outbreak in China. A total of 7741 adults were invited and completed an online self-administered questionnaire. The Chinese 12-item General Health Questionnaire was used to screen for common mental health problems, loneliness was measured with a single-item self-report question (“How often do you feel lonely in recent days?”), and two standardized questions were used to assess perceived needs for and use of mental health services.

Results

In total, 24.2 % of the participants felt lonely in recent days. Age of 16–29 years (OR = 1.36, P = 0.020), marital status of never-married (OR = 1.47, P < 0.001), marital status of “others” (re-married, co-habiting, separated, divorced, and widowed) (OR = 1.72, P < 0.001), having infected family members or close relatives (OR = 1.64, P = 0.026), and having infected colleagues, friends, or classmates (OR = 1.62, P < 0.001) were significant correlates of loneliness. Rates of mental health needs (17.4 % vs. 4.9 %, P < 0.001) and services utilization (2.7 % vs. 1.0 %, P < 0.001) were significantly higher in lonely than not lonely participants. After adjusting for socio-demographic and epidemic characteristics and common mental health problems, loneliness was still significantly associated with mental health needs (OR = 2.50, P < 0.001) and services utilization (OR = 1.62, P = 0.020).

Conclusions

Feelings of loneliness are prevalent among Chinese residents affected by the COVID-19 epidemic and the presence of loneliness is associated with high levels of mental health needs and greater services utilization. Effective measures aiming at preventing or reducing loneliness are potentially beneficial for the mental wellbeing of COVID-19-affected population and reducing the use of the limited mental health service resources during the COVID-19 pandemic.
Linalool odor‐induced analgesia is triggered by TRPA1-independent pathway in mice
Authors: Kashiwadani Hideki , Higa Yurina , Sugimura Mitsutaka , Kuwaki Tomoyuki
Published: April 2021

We had recently reported that linalool odor exposure induced significant analgesic effects in mice and that the effects were disappeared in olfactory-deprived mice in which the olfactory epithelium was damaged, thus indicating that the effects were triggered by chemical senses evoked by linalool odor exposure. However, the peripheral neuronal mechanisms, including linalool receptors that contribute toward triggering the linalool odor-induced analgesia, still remain unexplored. In vitro studies have shown that the transient receptor potential ankyrin 1 (TRPA1) responded to linalool, thus raising the possibility that TRPA1 expressed on the trigeminal nerve terminal detects linalool odor inhaled into the nostril and triggers the analgesic effects. To address this hypothesis, we measured the behavioral pain threshold for noxious mechanical stimulation in TRPA1-deficient mice. In contrast to our expectation, we found a significant increase in the threshold after linalool odor exposure in TRPA1-deficient mice, indicating the analgesic effects of linalool odor even in TRPA1-deficient mice. Furthermore, intranasal application of TRPA1 selective antagonist did not alter the analgesic effect of linalool odor. These results showed that the linalool odor-induced analgesia was triggered by a TRPA1-independent pathway in mice.
Evaluating diameter distribution series of small-leaved lime (Tilia cordata Mill.) in forest stands
Authors: Gabdelkhakov Aydar , Rakhmatullin Zagir , Martynova Maria , Fazlutdinov Ilyas , Mullagaleev Ilnur
Published: April 2021

Background

The paper provides studies on the structure of planted small-leaved lime (Tilia cordata Mill.) in the conditions of the Bashkir Cis-Urals. This work aimed to analyze their assortment by diameters and compile appropriate tables. This is the first study of lime for this region. The results of the study are based on data from 69 temporary sample plots. Stands are represented by trees of 11–79 years old, not affected by thinning. They belong to the I–III growth classes and the most common goutweed forests.

Results

It was found, that small-leaved limes have a specific structure—coefficient of diameter variation in stands decreases with a higher average diameter, reaching 26 and 16% at 28 cm with thin and dense initial planting, respectively. The variability of tree diameters is related to the average stand diameter and is due to the initial density of the grown plantations. Correlations between the coefficients of asymmetry and excess with age and the average diameter was revealed.

Conclusions

The verification of theoretically calculated frequencies of distribution series to empirically observed frequencies showed a discrepancy in 29 and 19% of the total number, respectively. For the remaining series of distributions, the scale and shape parameters of the Weibull function were modeled using the average, minimum and maximum diameters, standard deviation, coefficients of asymmetry and excess. This made it possible to develop stand tables for small-leaved limes depending on the average diameter.
Cyber-ethnography of cannabis marketing on social media
Authors: Jenkins Marina C. , Kelly Lauren , Binger Kole , Moreno Megan A.
Published: April 2021

Background

Since 2012, several states have legalized non-medical cannabis, and cannabis businesses have used social media as a primary form of marketing. There are concerns that social media cannabis exposure may reach underage viewers. Our objective was to identify how cannabis businesses cultivate an online presence and exert influence that may reach youth.

Methods

We chose a cyber-ethnographic approach to explore cannabis retailers on social media. We searched cannabis retailers with Facebook and Instagram presence from Alaska, Oregon, Colorado, and Washington, and identified 28 social media business profiles. One year of content was evaluated from each profile. In-depth, observational field notes were collected from researchers immersed in data collection on business profiles. Field notes were analyzed to uncover common themes associated with social media cannabis marketing.

Results

A total of 14 businesses were evaluated across both Facebook and Instagram, resulting in 14 sets of combined field notes. A major theme was Normalization of Cannabis, involving both Broad Appeal and Specific Targeting.

Conclusions

It is concerning that Normalization of Cannabis by cannabis businesses may increase cannabis acceptability among youth. In a digital world where the majority of youth are spending time online, it is important for policymakers to examine additional restrictions for cannabis businesses marketing through social media.
Association between clinical parameters and size of three-dimensionally reconstructed anatomical abnormalities in patients with lateral epicondylitis: a cross-sectional study
Authors: Hong Seok Woo , Kang Jeong-Hyun , Park Jin Hun , Kim Ji Na , Park Hee Jin , Kim Eugene
Published: April 2021

Background

The association of the severity of clinical symptoms and level of functional performance with the degree of magnetic resonance imaging abnormalities in patients with lateral epicondylitis has not been fully elucidated. This study aimed to investigate the association between the degree of anatomical abnormalities by evaluating three-dimensional magnetic resonance imaging models of the common extensor tendon and clinical parameters in patients with lateral epicondylitis.

Materials and methods

A total of 61 patients (24 men and 37 women) with lateral epicondylitis were included in this study. 3-Tesla magnetic resonance imaging was performed for all patients, and clinical parameters, including pain visual analog scale score, Quick Disabilities of Arm, Shoulder and Hand questionnaire score, elbow range of motion, and demographic factors, were evaluated. The proportion of lesion volume of common extensor tendon was adopted for three-dimensional model analysis. To determine the factors associated with clinical parameters, univariate, and multivariate linear regression analyses were performed.

Results

The proportion of lesion volume of common extensor tendon was not associated with clinical parameters. Gender and muscle edema were independently associated with pain visual analog scale scores. However, demographic factors and magnetic resonance imaging abnormalities were not associated with the Quick Disabilities of Arm, Shoulder, and Hand questionnaire score or elbow range of motion.

Conclusions

The three-dimensional volumetric lesion size of common extensor tendon was not associated with clinical symptoms and functional performance in patients with lateral epicondylitis. The clinical parameters of lateral epicondylitis may be influenced by several factors.
Patient and caregiver experiences of living with acute hepatic porphyria in the UK: a mixed-methods study
Authors: Gill Liz , Burrell Sue , Chamberlayne John , Lombardelli Stephen , Mora Jordanna , Mason Nicola , Schurer Marieke , Merkel Madeline , Meninger Stephen , Ko John J.
Published: April 2021

Background

This study used quantitative and qualitative research methods to analyze how acute hepatic porphyria (AHP) affects patients with varying annualized porphyria attack rates. The overall impact of AHP on patients and caregivers, including their quality of life, was explored. The nature and treatment of acute attacks, experiences of long-term heme arginate treatment and access to other appropriate treatment, and the extent of and treatment for chronic symptoms were also investigated within this study.

Methods

Patient and caregiver data were collected via an online survey of members of the British Porphyria Association, followed by an optional 1-h telephone interview.

Results

Thirty-eight patients and 10 caregivers responded to the survey. Of those, 10 patients and three caregivers completed follow-up interviews. Overall, 19 patients (50%) had experienced an acute attack within the previous 2 years, and the severity and types of symptoms experienced during or between acute attacks varied considerably. There were no clear definitions among patients for ‘mild’ or ‘severe’ attacks. Treatments and treatment settings used to manage attacks also varied. Following unsatisfactory care experiences at hospitals, some patients reported avoiding further hospital services for later attacks. Therefore, using settings of care as a measure of attack severity should be avoided. Ninety-four percent of patients also experienced chronic symptoms, which were as varied as acute attacks. Pain was the predominant chronic symptom and was managed with opioids in severe cases. Regardless of AAR, porphyria heavily impacted the daily lives of patients and caregivers. Although patients experiencing frequent attacks generally endured a greater impact on their daily life, patients with less frequent attacks also experienced impacts on all domains (social, leisure activities, relationship with family, relationships, psychological wellbeing, finances, employment, and study). Caregivers were most affected in the finance, relationships with family, and employment domains, and just over half of the caregivers reported a moderate impact on their psychological wellbeing.

Conclusions/implications

The burden of illness with AHP is high across all patients, regardless of frequency of attacks, and AHP negatively affects patients and caregivers alike.
Mitochondrial complex I abnormalities is associated with tau and clinical symptoms in mild Alzheimer’s disease
Authors: Terada Tatsuhiro , Therriault Joseph , Kang Min Su Peter , Savard Melissa , Pascoal Tharick Ali , Lussier Firoza , Tissot Cecile , Wang Yi-Ting , Benedet Andrea , Matsudaira Takashi , Bunai Tomoyasu , Obi Tomokazu , Tsukada Hideo , Ouchi Yasuomi , Rosa-Neto Pedro
Published: April 2021

Background

Mitochondrial electron transport chain abnormalities have been reported in postmortem pathological specimens of Alzheimer’s disease (AD). However, it remains unclear how amyloid and tau are associated with mitochondrial dysfunction in vivo. The purpose of this study is to assess the local relationships between mitochondrial dysfunction and AD pathophysiology in mild AD using the novel mitochondrial complex I PET imaging agent [18F]BCPP-EF.

Methods

Thirty-two amyloid and tau positive mild stage AD dementia patients (mean age ± SD: 71.1 ± 8.3 years) underwent a series of PET measurements with [18F]BCPP-EF mitochondrial function, [11C]PBB3 for tau deposition, and [11C] PiB for amyloid deposition. Age-matched normal control subjects were also recruited. Inter and intrasubject comparisons of levels of mitochondrial complex I activity, amyloid and tau deposition were performed.

Results

The [18F]BCPP-EF uptake was significantly lower in the medial temporal area, highlighting the importance of the mitochondrial involvement in AD pathology. [11C]PBB3 uptake was greater in the temporo-parietal regions in AD. Region of interest analysis in the Braak stage I-II region showed significant negative correlation between [18F]BCPP-EF SUVR and [11C]PBB3 BPND(R = 0.2679,p = 0.04), but not [11C] PiB SUVR.

Conclusions

Our results indicated that mitochondrial complex I is closely associated with tau load evaluated by [11C]PBB3, which might suffer in the presence of its off-target binding. The absence of association between mitochondrial complex I dysfunction with amyloid load suggests that mitochondrial dysfunction in the trans-entorhinal and entorhinal region is a reflection of neuronal injury occurring in the brain of mild AD.
Comparative preventive efficacy of ProHeart® 12, Heartgard® Plus and Interceptor® Plus against a macrocyclic lactone-resistant strain (JYD-34) of heartworm (Dirofilaria immitis) in dogs
Authors: McTier Tom L. , Holzmer Susan , Kryda Kristina , Mahabir Sean , McCall John W. , Trombley Jami , Maeder Steven J.
Published: April 2021

Background

The current studies compared ProHeart®12, Heartgard®Plus and Interceptor®Plus for preventive efficacy against JYD-34, a macrocyclic lactone (ML)-resistant strain ofDirofilaria immitisin dogs.

Methods

In two studies, each using 24 adult beagles, dogs were allocated to four treatment groups (n = 6): placebo-treated control; ProHeart 12 as per label (0.5 mg/kg moxidectin); Heartgard Plus (HGP) as per label (minimum 6 µg/kg ivermectin); and Interceptor Plus (INP) as per label (minimum 0.5 mg/kg milbemycin oxime). In both studies, ProHeart 12 was administered as a single subcutaneous dose on day 0, and HGP and INP were administered orally on days 0, 30, 60, 90, 120 and 150. In Studies 1 and 2, dogs were inoculated with 50 third-stage heartworm larvae (JYD-34 strain) on days −30 and 165, respectively. In Study 2, treatment for both HGP and INP was continued on days 180, 210, 240, 270, 300 and 330. Adult heartworm recoveries were performed on day 185 in Study 1 and on day 360 in Study 2.

Results

In Studies 1 and 2, all placebo-treated dogs developed adult heartworm infections (geometric mean, 29.9 and 34.9 worms/dog, respectively). A single dose of ProHeart 12 was 100% effective in preventing the development of adult JYD-34 heartworms when treatment was initiated 30 days after heartworm inoculation, while six consecutive monthly doses of HGP and INP were only 10.5% and 14.6% effective, respectively. The mean worm count for the ProHeart 12-treated group was significantly lower (P < 0.0001) than that for the placebo control, HGP- and INP-treated groups. In Study 2, the dogs treated with ProHeart 12 had an efficacy of 98.3%. All dogs treated with HGP and INP for 12 consecutive months had adult heartworms with efficacies of 37.7% and 34.9%, respectively. The mean worm count for the ProHeart 12-treated dogs was significantly lower (P < 0.0001) than those for the control group, HGP- and INP-treated groups.

Conclusions

A single administration of ProHeart 12 was 98–100% effective in preventing the development of the ML-resistant JYD-34 heartworm strain and was significantly better than multiple consecutive monthly doses of either Heartgard Plus or Interceptor Plus in both studies.

Graphical Abstract
Design of sparse arrays via deep learning for enhanced DOA estimation
Authors: Wandale Steven , Ichige Koichi
Published: April 2021

This paper introduces an enhanced deep learning-based (DL) antenna selection approach for optimum sparse linear array selection for direction-of-arrival (DOA) estimation applications. Generally, the antenna selection problem yields a combination of subarrays as a solution. Previous DL-based methods designated these subarrays as classes to fit the problem into a classification problem to which a convolutional neural network (CNN) is employed to solve it. However, these methods sample the combination set randomly to reduce computational cost related to the generation of training data, and it often leads to sub-optimal solutions due to ill-sampling issues. Hence, in this paper, we propose an improved DL-based method by constraining the combination set to retain the hole-free subarrays to enhance the method’s performance and sparse subarrays rendered. Numerical examples show that the proposed method yields sparser subarrays with better beampattern properties and improved DOA estimation performance than conventional DL techniques.
Lyapunov-type inequalities for differential equation with Caputo–Hadamard fractional derivative under multipoint boundary conditions
Authors: Wang Youyu , Wu Yuhan , Cao Zheng
Published: April 2021

In this work, we establish Lyapunov-type inequalities for the fractional boundary value problems with Caputo–Hadamard fractional derivative subject to multipoint and integral boundary conditions. As far as we know, there is no literature that has studied these problems.
Histological verification of the treatment effect of tirabrutinib for relapsed/refractory primary central nervous system lymphoma
Authors: Okita Yoshiko , Kano-Fujiwara Rieko , Nakatsuka Shin-Ichi , Honma Keiichiro , Kinoshita Manabu
Published: April 2021

Tirabrutinib (ONO/GS-4059; Ono Pharmaceutical) is a newly developed drug that selectively and irreversibly inhibits Bruton’s tyrosine kinase (BTK) and has been approved in Japan for treating relapsed/refractory primary central nervous system lymphoma (PCNSL). However, its therapeutic effect is yet to be verified at the pathological level in human patients. A 64-year-old patient with recurrent PCNSL enrolled in the phase I/II clinical trial of tirabrutinib, a second-generation BTK inhibitor designed for treating relapsed/refractory PCNSL. The left cerebellum lesions on magnetic resonance imaging disappeared one month after tirabrutinib treatment. The patient died because of suspected pneumocystis pneumonia and acute exacerbation of interstitial pneumonia 43 days after starting tirabrutinib. An autopsy confirmed no viable tumor cells in the entire brain, including the left cerebellum lesion, confirming complete obliteration of tumor cells by tirabrutinib. This letter pathologically confirms the effect of tirabrutinib on relapsed/refractory PCNSL for the first time in humans.

Trial registration: JapicCTI-173646. Registered 14 July 2017, https://www.clinicaltrials.jp/cti-user/trial/ShowDirect.jsp?japicId=JapicCTI-173646.
“Breaking down the wall” patients` and families` experience of multifamily therapy for young adult women with severe eating disorders
Authors: Brinchmann Berit Støre , Krvavac Sanja
Published: April 2021

Background

This paper addresses patients` and families` experience of multifamily therapy (MFT) for young adults (18–22) with an eating disorder (ED). EDs are serious illnesses leading to lowered quality of life for the patient and their family. The Regional Centre for Eating Disorders (RESSP) at Nordland Hospital in Bodø, Norway has developed an adjunct psychotherapeutic approach for the treatment of young adult patients with severe EDs. The patient’s family members take part in the multifamily therapy (MFT) group programme.

Methods

The aim of the study was to explore patients` and families` experience of MFT for young adult women with severe EDs. A Grounded Theory (GT) approach was used. Data were collected by field observations in two MFT groups, qualitative group interviews and qualitative individual interviews with patients and their family members. Data were analysed using the constant comparative method. The data analysis consisted of open and selective coding and memo writing.

Results

Two main categories were identified: ‘Connectedness and recognition’ and ‘Opening up and sharing`.MFT was described as a space for recognition within which it was possible to speak of things happening in the family with others with similar difficulties. It felt good and freeing, but also painful, to meet others with similar experiences. The participants had in common a considerable loneliness because it is difficult for outsiders to grasp what it is like in a home dominated by an ED. The meeting with other families created an underlying safety. The participants received help to distinguish between realistic and unrealistic concerns and learned about openness and communication in relation to their daughter. Some women with EDs said that MFT was most important for the parents but also had been good for them as things had become better at home.

Conclusion

The participants reported that their family had become better at talking to each other after having been in MFT. As a result, they were able to speak more openly about difficult things and share feelings. This gave rise to increased understanding. The study shows that MFT was found to be valuable and important. Never before had these families had such an opportunity, something so directly tailored to them. MFT for adults can be developed further and used in other groups, such as those concerning other chronic illnesses.
Blocking microglial activation of reactive astrocytes is neuroprotective in models of Alzheimer’s disease
Authors: Park Jong-Sung , Kam Tae-In , Lee Saebom , Park Hyejin , Oh Yumin , Kwon Seung-Hwan , Song Jae-Jin , Kim Donghoon , Kim Hyunhee , Jhaldiyal Aanishaa , Na Dong Hee , Lee Kang Choon , Park Eun Ji , Pomper Martin G. , Pletnikova Olga , Troncoso Juan C. , Ko Han Seok , Dawson Valina L. , Dawson Ted M. , Lee Seulki
Published: April 2021

Alzheimer’s disease (AD) is the most common cause of age-related dementia. Increasing evidence suggests that neuroinflammation mediated by microglia and astrocytes contributes to disease progression and severity in AD and other neurodegenerative disorders. During AD progression, resident microglia undergo proinflammatory activation, resulting in an increased capacity to convert resting astrocytes to reactive astrocytes. Therefore, microglia are a major therapeutic target for AD and blocking microglia-astrocyte activation could limit neurodegeneration in AD. Here we report that NLY01, an engineered exedin-4, glucagon-like peptide-1 receptor (GLP-1R) agonist, selectively blocks β-amyloid (Aβ)-induced activation of microglia through GLP-1R activation and inhibits the formation of reactive astrocytes as well as preserves neurons in AD models. In two transgenic AD mouse models (5xFAD and 3xTg-AD), repeated subcutaneous administration of NLY01 blocked microglia-mediated reactive astrocyte conversion and preserved neuronal viability, resulting in improved spatial learning and memory. Our study indicates that the GLP-1 pathway plays a critical role in microglia-reactive astrocyte associated neuroinflammation in AD and the effects of NLY01 are primarily mediated through a direct action on Aβ-induced GLP-1R+ microglia, contributing to the inhibition of astrocyte reactivity. These results show that targeting upregulated GLP-1R in microglia is a viable therapy for AD and other neurodegenerative disorders.
China and the steppe: technological study of precious metalwork from Xigoupan Tomb 2 (4th–3rd c. BCE) in the Ordos region, Inner Mongolia
Authors: Liu Yan , Li Rui , Yang Junchang , Liu Ruiliang , Zhao Guoxing , Tan Panpan
Published: April 2021

Technology employed by the ancient goldsmiths is traceable through archaeometallurgy. Using non-destructive analytical methods, namely, a 3D digital microscopy and a scanning electron microscopy with energy dispersive spectrometer (SEM–EDS), we investigated the manufacturing techniques and chemical composition of gold and silver artefacts recovered from Tomb 2 (M2), the richest find from Xigoupan cemetery (fourth-third century BCE) in the northern part of Jungar Banner, Inner Mongolia. The present research contributes to a better understanding of the inventive nature of precious metal working industry in early China (eighth-third century BCE). First, cultural interchange was evidenced in the metalwork examined, notably as being closely linked to techniques emerging from the Eurasian steppes. In Xigoupan M2, the ornamentation of sheet works in the Scytho-Siberian animal style was seen to be clearly influenced by the central Asian steppe goldsmithing practice, while certain cast items were typical of the Chinese tradition. Second, our analysis reveals that the gold appliqués with raised animal figures that were previously thought to be repoussé work have actually been made with double-sided carving. We consider such a new technology as one of local inventions that was inspired by methods arriving from the central Asian steppes. In addition, our analysis of elemental composition reveals that the gold artefacts found in Xigoupan M2 to be made of natural gold, while the horse harness ornament is made of pure silver. These results, combined with the study of the existing data pertaining to comparable examples, attest to the shared craftsmanship in prestige metal production across the northern Chinese states, especially with regard to the pre-imperial period Qin workshop.
Effects of local neighbourhood diversity on crown structure and productivity of individual trees in mature mixed-species forests
Authors: Georgi Louis , Kunz Matthias , Fichtner Andreas , Reich Karl Friedrich , Bienert Anne , Maas Hans-Gerd , von Oheimb Goddert
Published: April 2021

Background

Species-specific genotypic features, local neighbourhood interactions and resource supply strongly influence the tree stature and growth rate. In mixed-species forests, diversity-mediated biomass allocation has been suggested to be a fundamental mechanism underlying the positive biodiversity-productivity relationships. Empirical evidence, however, is rare about the impact of local neighbourhood diversity on tree characteristics analysed at a very high level of detail. To address this issue we analysed these effects on the individual-tree crown architecture and tree productivity in a mature mixed forest in northern Germany.

Methods

Our analysis considers multiple target tree species across a local neighbourhood species richness gradient ranging from 1 to 4. We applied terrestrial laser scanning to quantify a large number of individual mature trees (N = 920) at very high accuracy. We evaluated two different neighbour inclusion approaches by analysing both a fixed radius selection procedure and a selection based on overlapping crowns.

Results and conclusions

We show that local neighbourhood species diversity significantly increases crown dimension and wood volume of target trees. Moreover, we found a size-dependency of diversity effects on tree productivity (basal area and wood volume increment) with positive effects for large-sized trees (diameter at breast height (DBH) > 40 cm) and negative effects for small-sized (DBH < 40 cm) trees. In our analysis, the neighbour inclusion approach has a significant impact on the outcome. For scientific studies and the validation of growth models we recommend a neighbour selection by overlapping crowns, because this seems to be the relevant scale at which local neighbourhood interactions occur. Because local neighbourhood diversity promotes individual-tree productivity in mature European mixed-species forests, we conclude that a small-scale species mixture should be considered in management plans.
The educational power of humor on student engagement in online learning environments
Authors: Erdoğdu Fatih , Çakıroğlu Ünal
Published: April 2021

The primary goal of the study is to investigate the effect of the usage of humor on behavioral, emotional, and cognitive engagement in online learning. Humorous elements were integrated into the online learning components. The mixed-method study was conducted over 14 weeks with the participation of 74 university students in an online university course. As a result, elements of humor can be integrated into materials for attention grabbing, recalling, feedback, and humor breaks. A diversity of humorous elements created a significant difference and improved behavioral engagement for course materials, discussions, and assignments. However, humorous elements did not contribute to the behavioral engagement for quizzes. It was additionally observed for emotional engagement that the use of humor created a significant difference and improved emotional engagement. As for cognitive engagement, a positive influence of the usage of humorous elements in course materials, discussions and assignments was observed.
Introduction
Authors: Rosenthal Adam R.
Published: April 2021

Beginning in 2008, with the French publication of volume 1 of The Beast and the Sovereign, Éditions Galilée, the University of Chicago Press, and an international editorial team initiated the process of editing, publishing, and translating, in reverse chronological order, the complete seminars of Jacques Derrida. These seminars, given variously at the Sorbonne, the École normale supérieure, the École des hautes études en sciences sociales, Johns Hopkins University, Yale University, the University of California, Irvine, the New School for Social Research, the Cardozo Law School, and New York University, encompass material presented as early as 1959 and as late as 2003.With Derrida’s death in 2004, the seminar publications —projected to continue well into the 2050s — became the principal source of all Derrida’s future, posthumous publications, now under the direction of Katie Chenoweth, director of the Bibliothèque Derrida series at the French publishing house Éditions du Seuil. This special issue of Poetics Today addresses two questions that are raised by this enterprise: First, how does the publication, mediatization, and mass dissemination of Derrida’s teaching transform his corpus? Second, how does this corpus already speak to, anticipate, and preprogram the virtualization, translation, and transmission of the space of “the seminar”？
Growth as related to the Cell Cycle in Single-cell Cultures of Tetrahymena piriformis1
Authors: Zeuthen Erik
Published: April 2021

There is some evidence that synthesis in single cells of Tetrahymena occurs with very nearly constant rate when traced from one division to the next. Overall exponential growth over a number of cell cycles may be the statistical result of the fact that centres—of which each one is in control of synthetic processes occurring with constant rates—multiply by discrete doublings, i.e. exponentially, in close relation with the process of cell division. While this doubling occurs there may be a provisional block to further increase in respiratory rate. In the post-exponential growth-phase cells may differentiate and some may grow too big for their synthetic machinery, as—after a lag—it becomes reactivated upon transfer to fresh nutrient medium. For this reason overall exponential growth over a number of cell cycles may pertain only to a fraction of the cell with which the experiment was started.
Growth and Degeneration of the Pronephric System ofRana temporaria
Authors: Fox H.
Published: April 2021

Growth and degeneration of various components of the pronephric system of R. temporaria were investigated qualitatively and quantitatively in a series of stages ranging from 29 to 54, i.e. stages equivalent to those for R. dalmatina (Cambar & Marrot, 1954). All pronephric components except individual cell volume increase up to stage 47 (specimen 33 mm. long), and the first signs of degeneration are recognizable at stage 49, i.e. the stage preceding that at which the animal possesses an externally visible left forelimb. Progressive degeneration of the pronephros and duct continues until stage 54 (the animal having just metamorphosed), by which stage the organ has almost disappeared. The glomus likewise degenerates pari passu with the pronephros, but between stages 29 (specimens 9 mm. long) and 47 (specimens 33 mm. long) it barely changes in size and shape.
The Use of Sex Chromatin in Identifying Embryonic and Maternal Tissues in the Placenta: New Observations on the Haemochorial Nature of the Cat Placenta
Authors: Zhemkova Z. P.
Published: April 2021

Histological investigation of the cat placenta at various stages of development has led to the conclusion that it belongs to the haemochorial type. Study of the sex chromatin bodies in the nuclei of the so-called ‘endothelial’ and ‘decidual’ cells in the cat placentae of male foetuses has shown that these cells are derived from the embryo and are trophoblastic. The results of the study of the sex chromatin bodies have confirmed the data of the histological investigation. Consequently the cat placenta should be considered as haemochorial, and not syndesmo-, vaso-, or endotheliochorial.
The Culture in vitro of Urogenital Organs of Pleurodeles waltlii
Authors: Foote Charles L. , Foote Florence M.
Published: April 2021

The trunk portions of Pleurodeles waltlii, stages 37–38, were grown in groups of 4 in chick vitelline membranes in organ cultures for 57 days. Growth and differentiation of urogenital structures and nervous tissues occurred, including some cells thought to be primordial germ cells. Trunks of larvae placed directly on culture medium were less well differentiated and less well maintained.

Larval gonads containing young germ cells or gonads with immature germ cells from adult P. waltlii were well maintained in organ culture for 21 days. Spermatozoa and meiotic stages in expiants of mature testes became dis-organized and necrotic. Immature gonads of P. waltlii are better maintained in organ culture than gonads of the other species of amphibians studied to date.
Stillbirths from Adrenal Demedullated Mice Subjected to Chronic Stress Throughout Gestation
Authors: Caldwell Donald F.
Published: April 2021

The role of the maternal adrenal medulla on frequency of stillbirths from chronic stress administered throughout gestation was investigated in CF/1 mice. Evidence showing a decreased frequency of stillbirths in adrenal demedullated mice compared to normals is presented. Mechanisms are discussed whereby the medullary hormones epinephrine and norepinephrine may affect prenatal development during maternal stress.
The Influence of the Uterine Environment on the Development of Mouse Eggs
Authors: Kirby D. R. S.
Published: April 2021

Oviducal segmented eggs of the mouse, when transferred beneath the kidney capsule, give rise to trophoblast and extra-embryonic membranes only. Uterine blastocysts transferred to a similar position develop into embryos. Mouse eggs prevented from entering the uterus develop into blastocysts that are morphologically normal. These tube-locked blastocysts, however, that have been denied the uterine environment, do not develop into embryos when transferred to the kidney. -day-old tube-locked blastocysts develop into normal embryos if restored to the uterus. Eggs retained in the oviduct for days, although they appear normal, do not subsequently develop when transferred to the uterus. Oviducal, pre-blastocyst-stage eggs, transferred for a time to the uterus prior to transplantation to the kidney, develop into trophoblast and extra-embryonic membranes only. It is concluded that a blastocyst, to realize totipotency, must be subjected to the uterine environment to days after copulation. The substance producing this effect is termed the ‘uterine factor’. The action of the ‘uterine factor’ and the egg’s limited period of competence to react to it are discussed. A comparison between the potency of tubal mouse eggs and the tubal eggs of other mammals is made.