bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessing industrial barriers of additively manufactured digital spare part implementation in the machine-building industry: a cross-organizational focus group interview study
Authors: Chekurov Sergei , Salmi Mika , Verboeket Victor , Puttonen Tuomas , Riipinen Tuomas , Vaajoki Antti
Published: January 2021

Purpose

Although additive manufacturing (AM) has been demonstrated to have significant potential in improving spare part delivery operations and has been adopted to a degree in the aviation and automotive industries, its use in spare part production is still limited in other fields due to a variety of implementation barriers. The purpose of this article is to assess the significance of previously reported barriers in the context of the machine-building industry.

Design/methodology/approach

Adoption barriers are identified from the literature and formulated as hypotheses, which are verified with a set of focus group interviews consisting of original equipment manufacturers (OEMs), AM service providers and quality inspection and insurance institutions. The results of the interviews are reported qualitatively, and the transcripts of the interviews are subjected to quantitative content analysis.

Findings

The article identifies distrust in quality, insufficient material and design knowledge among stakeholders and poor availability of design documentation on spare parts as the key barriers of adopting AM in the production of spare parts. The three key barriers are interconnected and training engineers to be proficient in design and material issues as well as producing high-quality design documentation will yield the highest increase in AM implementation in spare parts.

Originality/value

The article offers a unique approach as it investigates the subjective views of a cross-organizational group of industrial actors involved in the machine-building industry. The article contributes to the theory of digital spare parts by verifying and rejecting presented barriers of AM implementation and how they are interconnected.
What makes people engage in civic activism on social media?
Authors: Hong Hyehyun , Kim Yeuseung
Published: January 2021

Purpose

Given the profound impact of social media on civic activism, as demonstrated by the #BlackLivesMatter and #MeToo movements, the current study aimed to examine the factors that influence the public to engage in civic activism on social media platforms.

Design/methodology/approach

This study used the responses from 4,316 social media users who participated in the 2018 American Trends Survey (Wave 35) conducted by Pew Research Center. The dataset was analyzed using hierarchical regression.

Findings

The results suggest that respondents who were younger, female, White and liberal were more likely to participate in activism-related behaviors, such as using hashtags, changing profile pictures and participating in groups with shared interests in political and social issues. Respondents' engagement in online civic activism increased particularly when they had a strong motive for expressing and sharing their opinions. In contrast, external online political efficacy – the belief that social media influences policymaking and decision makers – was not significantly associated with activism engagement on social media.

Originality/value

This study identified key demographic characteristics of social media users who participate in online civic activism. In addition, the findings extend previous lines of inquiry by examining and assessing the impact of external online political efficacy and opinion expression motive. We conclude that individuals engage in civic activism on social media mainly because they find it important to express views on political and social issues and to find others who share these views, as opposed to thinking that social media can be used to exert influence on policy decisions.
Rare cases of PAMI syndrome in both father and son with the same missense mutation in PSTPIP1 gene and literature review
Authors: Huang Xiaowen , Xu Meinian , Dai Siqi , Wang Menglei , Zheng Huanxin , Zeng Kang , Li Li
Published: January 2021

PSTPIP1‐associated myeloid‐related proteinaemia inflammatory (PAMI) syndrome has been described as a rare and distinct clinical phenotype of PSTPIP1‐associated inflammatory diseases. We report PSTPIP1 mutation in both father and son who have leukopenia and acne‐like lesions. Through whole‐exome sequencing on blood DNA, it is found a heterozygous mutation of PSTPIP1 gene c.748G>A on the father and son. The diagnosis of PAMI is made based on DNA sequencing results and clinical characteristics of typical lesions, leukopenia, and the markedly increased serum S100A8/A9 (calprotectin).
Associations between testosterone and immune activity in alligators depend on bacteria species and temperature
Authors: LaVere Ashley A. , Hamlin Heather J. , Lowers Russell H. , Parrott Benjamin B. , Ezenwa Vanessa O.
Published: January 2021

The immunocompetence handicap hypothesis (ICHH) postulates that testosterone supports the development of secondary sexual traits while simultaneously suppressing immune function, creating a trade‐off between trait quality and pathogen vulnerability.

The nature of interactions between testosterone and immunity is complex. Conflicting patterns from the literature suggest that testosterone–immunity relationships are variable across immune measures and may be modified by factors both intrinsic and extrinsic to the organism.

In this study, we tested the ICHH in free‐ranging American alligators Alligator mississippiensis and examined how both intrinsic (steroid hormone levels) and extrinsic (temperature) factors modulate the relationship between testosterone and immunity. Specifically, we quantified the simultaneous effects of testosterone and dehydroepiandrosterone (DHEA) on microbial killing capacity of three bacteria species (Escherichia coli, Salmonella typhimurium and Klebsiella pneumoniae) at two challenge temperatures (15°C and 30°C).

We found that accounting for circulating levels of DHEA was important for predicting testosterone‐mediated effects on microbial killing capacity. We also found that testosterone‐mediated immunosuppression was dependent on temperature and bacteria species, with negative effects of testosterone present only for S. typhimurium at 15°C.

Our results highlight the context dependency of interactions between testosterone and immunity, and illustrate the importance of evaluating the ICHH in natural systems to identify key intrinsic and extrinsic factors modulating testosterone‐immunity trade‐offs.

A free Plain Language Summary can be found within the Supporting Information of this article.
Tumor LAG‐3 and NY‐ESO‐1 expression predict durable clinical benefits of immune checkpoint inhibitors in advanced non‐small cell lung cancer
Authors: Jung Eun Hee , Jang Hee Ryeong , Kim Se Hyun , Suh Koung Jin , Kim Yu Jung , Lee Ju‐Hyun , Chung Jin‐Haeng , Kim Miso , Keam Bhumsuk , Kim Tae Min , Kim Dong‐Wan , Heo Dae Seog , Lee Jong Seok
Published: January 2021

Background

Immune checkpoint inhibitors (ICIs) are an established treatment for non‐small cell lung cancer (NSCLC) that have demonstrated durable clinical benefits (DCBs). Previous studies have suggested NY‐ESO‐1 and LAG‐3 to be surrogate markers of ICI responses in NSCLC; therefore, we explored the predictive value of their expression in NSCLC.

Methods

We retrospectively reviewed the records of 38 patients with advanced NSCLC treated with anti‐PD‐1 monoclonal antibodies from 2013 to 2016 at Seoul National University Hospital and Seoul National University Bundang Hospital after failed platinum‐based chemotherapy. Tumor tissues from each patient were subjected to immunohistochemical analysis to determine NY‐ESO‐1, LAG‐3, and PD‐L1 expression, whose ability to predict progression‐free survival (PFS) and overall survival (OS) was then analyzed alongside their positive (PPV) and negative (NPV) predictive values.

Results

NY‐ESO‐1 or LAG‐3 expression was detected in all tumor samples from patients with high PD‐L1 expression and was significantly associated with favorable outcomes, unlike PD‐L1 expression. Patients with both NY‐ESO‐1‐ and LAG‐3‐expressing tumors had a high DCB rate and those with triple‐positive PD‐L1, LAG‐3, and NY‐ESO expression had a superior median OS and PFS than those with triple‐negative expression. Furthermore, LAG‐3 and NY‐ESO‐1 co‐expression was an independent predictor of both PFS and OS, while LAG‐3 displayed a good NPV.

Conclusions

Patients with NSCLC who co‐express NY‐ESO‐1 or LAG‐3 with PD‐L1 exhibit greater DCBs and improved long‐term survival following anti‐PD‐1 therapy. Moreover, NY‐ESO‐1 and LAG‐3 could be novel predictive biomarkers of survival and should be considered in the future use of ICIs.
Financial Reporting Quality and Investors' Divergence of Opinion*
Authors: Silva Diogo , Cerqueira António
Published: January 2021

The main purpose of this study is to analyze the association of financial reporting quality and investors' divergence of opinion. We focus on UK firms listed on the London Stock Exchange. Divergence of opinion is measured by two proxies based on unexpected trading volume and by dispersion in analysts' forecasts made one and two years ahead. Previous literature shows that the amount of firms' disclosure is negatively associated with the dispersion in analysts' forecasts. The results obtained in our study show that the quality of the disclosure is negatively associated with divergence of opinion, whether it is proxied by measures of unexpected trading volume or dispersion in analysts' forecasts. Financial reporting quality affects divergence of opinion not only in the months that immediately follow the disclosure of the reports but in the whole year that follows.
Self‐obtained vaginal swabs are not inferior to provider‐performed endocervical sampling for emergency department diagnosis of Neisseria gonorrhoeae and Chlamydia trachomatis
Authors: Chinnock Brian , Yore Mackensie , Mason Jessica , Kremer Mallory , Farshidpour Leyla , Lopez Diana , Castaneda Jannet
Published: January 2021

Objective

Provider‐performed endocervical sampling (PPES) in the diagnosis of Neisseria gonorrhoeae (NG) and Chlamydia trachomatis (CT) may be difficult to perform in a busy emergency department (ED) due to patient preference, availability of the pelvic examination room, or provider availability. Our objective was to assess if self‐obtained vaginal swabs (SOVS) were noninferior to PPES in the ED diagnosis of NG/CT using a rapid nucleic acid amplification test (NAAT).

Methods

We conducted a prospective observational cohort study in a single ED. Participants were adult female English‐ and Spanish‐speaking patients in whom the ED provider felt that NG/CT testing was warranted. Each patient had SOVS and PPES performed. For SOVS, a research associate reviewed a one‐page handout describing the procedure but gave no other assistance. Patients answered survey questions regarding acceptability of SOVS and symptomatology. We established a minimum sensitivity of 90% for SOVS to be considered clinically noninferior to standard PPES.

Results

A total of 533 patients completed enrollment and answered survey questions, 515 of whom had laboratory results for both SOVS and PPES. There were 86 patients with a positive result: 29 with NG, 47 with CT, and 10 with coinfection. SOVS had a sensitivity of 95% (95% confidence interval = 88% to 99%) for the detection of NG/CT when compared to PPES. SOVS were felt to be an acceptable collection method in 93% of patients and 75% preferred SOVS to PPES.

Conclusion

SOVS are noninferior to PPES in NG/CT diagnosis using a rapid NAAT in ED patients and surveys indicate high patient acceptability.
Physiological and psychological effects of ambient noise in operating room on medical staff
Authors: Gülşen Muaz , Aydıngülü Nursevim , Arslan Sevban
Published: January 2021

Background

The study was conducted to assess operating room noise levels and to investigate its effects on medical staff.

Methods

Single‐blind study. This study was conducted with 92 medical staff working in 11 operating rooms of a university hospital. Data was collected using a personal information form and sound level measuring devices. Sound measurements were made 3 days a week in the morning and in the afternoon, twice a day and lasted 15 min each. Mean values of the measurements in each room were collected and recommended maximum values for operating rooms (35 dB during daytime) by the World Health Organization were set as a reference point.

Results

The highest noise level was measured in orthopaedic (67.5 dB), and the lowest in gynaecology room (55.5 dB). Daily mean noise level of all operating rooms was 60.90 dB. Noise disturbance score measured with Visual Analogue Scale was 6.66 ± 1.84. Of the medical staff, 84.8% were physiologically, 93.5% psychologically, and 82.6% both physiologically and psychologically affected. Of those affected physiologically, 51.1% experienced fatigue, and 33.7% headache, and of those affected psychologically, 43.5% experienced inattentiveness, 34.8% agitation and 15.2% restlessness. Only 4.34% reported not being affected by the noise.

Conclusion

Operating room noise levels were higher than normal limits set by the World Health Organization, which affected the medical staff both physiologically and psychologically. Since experienced negativities may reduce medical staff's motivation and increase error making, making arrangements to control noise levels is recommended.
Is abdominal hysterectomy still the surgery of choice in sub‐Saharan Africa?
Authors: Rudnicki Martin , Shayo Benjamin C. , Mchome Bariki
Published: January 2021

A trend toward minimally invasive surgery is increasing worldwide. However, reports on the extent and the role of vaginal or laparoscopic hysterectomy in benign gynecologic surgery in sub‐Saharan Africa are scarce. Our commentary aims to highlight the existing gaps and potential barriers to implementation of vaginal or laparoscopic hysterectomy and suggests how to introduce and expand minimally invasive gynecologic surgery in this region. Little documentation exists in the literature to account for the role of minimally invasive surgery in the sub‐Saharan Africa. Hysterectomy for benign reasons is commonly performed by the abdominal approach. This approach is accompanied by significant complications, prolonged hospitalization, and longer recovery duration. Our commentary highlights the importance of investigating region‐specific barriers to the practice of minimally invasive gynecologic surgery in sub‐Saharan Africa.
The structural and comparative analysis of intravitreal dexamethasone implant (Ozurdex) and anti‐VEGF injection in branched retinal vein occlusion patients by optical coherence tomography angiography images quantitation
Authors: Park JinHeung
Published: January 2021

Purpose

To evaluate and compare the structural changes of retinal vasculature after intravitreal dexamethasone implant (Ozurdex) and anti‐vascular endothelial growth factor (anti‐VEGF) injection in branched retinal vein occlusion (BRVO) patients by optical coherence tomography angiography (OCTA) images quantitation.

Methods

We retrospectively analyzed thirty‐nine patients with unilateral BRVO. Subjects were divided into two groups according to treatment agent, Ozurdex (n = 18) and anti‐VEGF (n = 21). Swept Source (SS) OCT and OCTA were performed, and images were analyzed quantitatively by using ImageJ software. Intravitreal implant and injections were performed following a pro re nata (PRN) regimen. Anti‐VEGF agent was chosen between bevacizumab, ranibizumab and aflibercept.

Results

In independent two‐sample t‐test, the vessel reperfusion was more significant in intravitreal Ozurdex implant group than anti‐VEGF injection group in choriocapillaris slab of angiography mode (p = 0.013). Positive change of particles number was more prominent in intravitreal anti‐VEGF injection group than intravitreal Ozurdex implant group in outer retina slab of En‐face mode (p = 0.039). ETDRS density map (p = 0.632) and other angiography slabs; superficial (p = 0.200), deep (p = 0.199) and outer retina (p = 0.210) showed no significant difference in two treatment groups.

Conclusions

Quantitative analysis of OCTA images using ImageJ software showed that intravitreal Ozurdex implant seems to be better treatment than anti‐VAGF injection for BRVO in the aspect of retinal vascular reperfusion.
Macular changes after silicone oil or gas tamponade for uncomplicated retinal detachment using swept source OCT and OCT‐Angiography
Authors: Braham Imene Zhioua , El Amri Hatem , Boukari Mejdi , Ammous Imen , Zhioua Raja
Published: January 2021

Purpose

To evaluate and compare the effect of silicone oil and gas tamponade on the macular area using swept source optical coherence tomography (SS‐OCT) and optical coherence tomography angiography (OCT‐A).

Methods

In this retrospective study, we included patients who underwent pars plana vitrectomy with silicone oil or gas tamponade for uncomplicated rhegmatogenous retinal detachment (RRD). The thickness of retinal layers was measured automatically with the Early Treatment Diabetic Retinopathy Study (ETDRS) grid on SS‐OCT. Foveal avascular zone (FAZ) was analyzed in the superficial capillary plexus (SCP) and in the deep capillary plexus (DCP). The retinal vessel density (VD) was automatically assessed in the SCP.

Results

Eyes in the silicone oil group (n = 23) had a statistically significant decreased parafoveal retinal thickness compared to the gas group (n = 23) with a mean of 279.61 ± 31.15 µm vs 308.42 ± 32.06 µm, respectively (p = 0.003) and compared to the fellow eyes (p = 0.03). Eyes in the silicone oil group had a larger FAZ in the SCP and the DCP compared to the gas group (p = 0.021 and p = 0.002, respectively) and a larger FAZ only in the DCP compared to the fellow eyes (p < 0.001). No significant difference in central and parafoveal VD was found between silicone oil group and gas group. Postoperatively, the best‐corrected visual acuity in the silicone oil group was significantly worse than that in the gas group (p = 0.032).

Conclusions

Silicone oil tamponade probably induces a significant reduction of retinal thickness and enlargement of the FAZ area compared to gas tamponade in the repair of uncomplicated RRD. However, macular vessel density seems not to be affected.
Secondary immune thrombocytopenia in children: Characteristics and outcome of a large cohort from two Spanish centres
Authors: Berrueco Rubén , Sebastián Elena , Solsona María , González de Pablo Jesús , Ruiz‐Llobet Anna , Mesegué Montse , Gálvez Eva , Sevilla Julián
Published: January 2021

Aim

To evaluate the incidence and outcome of secondary immune thrombocytopenia (ITP) in a large cohort of paediatric Spanish patients.

Methods

A retrospective observational study was conducted in two paediatric University hospitals in Spain between 2009 and 2019, which included children from 4 months to 18 years old diagnosed with ITP. Data were recorded from clinical charts: gender, age at diagnosis, coexisting condition and associated characteristics, outcome and treatment.

Results

Secondary ITP was diagnosed in 87 out of 442 patients (19.6%). Post‐immunisation ITP was seen in younger children. The onset of secondary ITP to autoimmune diseases (AD) and immunodeficiencies (ID) was at an older age and had more tendency to be insidious, and platelet level was higher than primary ITP. Mean time from ITP onset to AD diseases or ID diagnosis was 1.2 and 2.6 years, respectively. Whereas the cumulative incidence of remission was significantly higher in post‐immunisation and post‐viral infection (compared with primary ITP patients), it was worse in AD and ID patients.

Conclusions

Identification of secondary ITP is important as it predicts outcome. Most of them are diagnosed at ITP onset, but AD diseases and ID should be ruled out periodically as they are usually identified later.
Outcomes of upper gastrointestinal bleeding are similar between direct oral anticoagulants and vitamin K antagonists
Authors: Gouriou Claire , Bouguen Guillaume , Lahmek Pierre , Pelaquier Agnes , Arotcarena Ramuntxo , Garioud Armand , De Montigny‐Lenhardt Stephanie , Pauwels Arnaud , Zanditenas David , Charpignon Claire , Combes Remi , Nahon Stephane , Quentin Vincent
Published: January 2021

Background

The increased risk of upper gastrointestinal bleeding (UGIB) related to direct oral anticoagulants (DOACs) as compared to vitamin K antagonists (VKA) remains debated.

Aims

To describe the epidemiology and outcomes of UGIB in patients treated with oral anticoagulants.

Methods

A prospective, multicentre study in French general hospitals enrolled all consecutive patients with UGIB during one year. Patients treated with oral anticoagulants were retrieved from the cohort. Main outcomes were mortality and rebleeding during the first 6 weeks and need for non‐endoscopic treatment (surgery or interventional radiology).

Results

Among the 2498 patients included, 475 (19%) had an oral anticoagulant, mostly with VKA (267 patients [56.2%]). Baseline characteristics were similar between the groups except for renal failure and cirrhosis that were more prevalent in the VKA group. Gastroscopy was normal in 73 patients (15.3%); peptic lesions were the main cause of UGIB (n = 233, 49%). Endoscopic treatment was performed in 128 patients (26.9%), leading to bleeding resolution in 74% (n = 95). Mortality rate at 6 weeks was 12.4% (59 patients), and was higher in the VKA group compared to DOACs (16.1% vs 7.8%, P < 0.01). By multivariate analysis, only the Charlson index ≥ 5 and UGIB occurrring in in‐patients were independently associated with mortality. Rebleeding (56 patients [11.8%]) and need for non‐endoscopic treatment (18 patients [3.8%]) were not associated with the type of anticoagulant.

Conclusion

DOACs do not alter outcomes of UGIB as compared to VKA. Comorbidities and associated treatment are the most important factors worsening the prognosis of UGIB.
Investigations of the ancient ceramic sherds excavated from Börükçü site in Muğla, south‐western Turkey, by ATR‐FTIR spectroscopy and statistical multivariate analysis
Authors: Işık İlker , Tarhan İsmail
Published: January 2021

This paper presents the mineralogical characterization of 56 sherd samples from the Börükçü site in Muğla, Turkey. Principal component analysis (PCA) employing raw attenuated total reflectance Fourier‐transform infrared (ATR‐FTIR) spectra (825–400 cm−1) with 17 smoothing points discriminated the sherd samples into five different groups (A–E). The second‐derivative ATR‐FTIR spectra (two polynomial degrees and 11 smoothing points) between 1700 and 400 cm−1were successfully used to assess the firing conditions. The obtained results showed that the firing temperatures are about 600–800°C for sherd groups A, C and D and about 800–950°C for sherd groups E and B.
Genomic imprinting variances of beef carcass traits and physiochemical characteristics in Japanese Black cattle
Authors: Inoue Keiichi , Inoue Yoshinobu , Oe Toshiaki , Nishimura Masami
Published: January 2021

The objective of this study was to estimate variance components related to imprinting for carcass traits and physiochemical characteristics in Japanese Black cattle. The carcass records obtained from 4,220 Japanese Black feedlot cattle included carcass weight (CW), rib eye area (REA), rib thickness, subcutaneous fat thickness, and beef marbling score (BMS), and the physiochemical characteristics were fat, moisture, glycogen per proportion of moisture content, oleic acid, and monounsaturated fatty acids (MUFA). To detect gametic effects, an imprinting model was fitted. High additive heritabilities were estimated for all traits (from 0.516 for glycogen to 0.853 for fat) and were reduced in Mendelian heritability. The range of the differences was from 0.002 (CW) to 0.331 (fat and moisture), and the reductions were due to their imprinting variances. The ratio of the imprinting variance to the total additive genetic variance for REA (0.374), BMS (0.291), fat (0.387), moisture (0.388), and MUFA (0.337) were large (p < 0.05). These imprinting variances were due to the maternal contribution and suggested the existence of maternally expressed genomic imprinting effects on the traits in Japanese Black cattle. Therefore, maternal gametic effects should be considered in breeding programs for Japanese Black cattle.
The Early‐life Political Event Experience of the Chair of the Board and the Firm's Innovation Decision
Authors: Zhou Donghua , Bai Min , Liang Xiaoqin , Qin Yafeng
Published: January 2021

Early life experience may influence an executive's psychology and behaviour, which affects the company's financial policy. Using a unique early life political event, this paper finds that the ‘Down to the Countryside’ experience of board chairs in China increases their risk aversion and reduces the firms’ innovation investments. Such an effect is robust to a series of alternative tests. Further analysis shows that this impact is not weakened by chairs’ higher education, and their increased risk aversion results in the chairs being more prudent and making more efficient investment decisions.
Confident championing: A grounded theory of parental adjustment following a child’s diagnosis of developmental disability
Authors: O' Connor Anne B. , Carpenter Barry , Coughlan Barry
Published: January 2021

Accessible summary

This paper is about how parents adjust to parenting their child who has a developmental disability.

We spoke to parents about their experiences and developed a theory to help explain how parents adjust when their child has a developmental challenge.

As well as describing the stress, that parents experience, this theory also captures the fulfilment and sense of purpose that parents experience as they parent their child.

This research is important because it helps explain what happens for parents after their child's diagnosis and provides suggestions on how services can improve to help families.

This paper describes a study exploring the parental response to the diagnosis of their child's developmental disability. A classic grounded theory methodology was used to analyse data comprising 19 interviews and 11 memoirs written by parents. The theory explains how parents adjust to champion their child, who has been identified as having a developmental challenge. At the heart of becoming a champion is a psychological process in which parents refine their perspectives on disability awareness, their aspirations and parenting capacity as they develop their championing skills. Refining perspectives and championing are influenced by two factors: the nature of the child's challenges and service factors. The theory of Confident Championing offers a multivariant model that explains the dynamic nature of the adjustment process, capturing both the stress and the fulfilment and sense of purpose that parents experience.
A novel palmitic acid hydroxy stearic acid (5‐PAHSA) plays a neuroprotective role by inhibiting phosphorylation of the m‐TOR‐ULK1 pathway and regulating autophagy
Authors: Wang Jian‐tao , Yu Zhong‐yu , Tao Ying‐hong , Liu Ying‐chao , Wang Yan‐mei , Guo Qi‐lin , Xue Jian‐zhong , Wen Xiao‐hong , Zhang Qian , Xu Xiao‐die , He Cheng‐feng , Xue Wen‐jiao , Guo Jing‐chun , Zhou Hou‐guang
Published: January 2021

Aims

Type 2 diabetes mellitus (T2DM) can lead to brain dysfunction and a series of neurological complications. Previous research demonstrated that a novel palmitic acid (5‐PAHSA) exerts effect on glucose tolerance and chronic inflammation. Autophagy was important in diabetic‐related neurodegeneration. The aim of the present study was to investigate whether 5‐PAHSA has specific therapeutic effects on neurological dysfunction in diabetics, particularly with regard to autophagy.

Methods

5‐PAHSA was successfully synthesized according to a previously described protocol. We then carried out a series of in vitro and in vivo experiments using PC12 cells under diabetic conditions, and DB/DB mice, respectively. PC12 cells were treated with 5‐PAHSA for 24 h, while mice were administered with 5‐PAHSA for 30 days. At the end of each experiment, we analyzed glucolipid metabolism, autophagy, apoptosis, oxidative stress, cognition, and a range of inflammatory factors.

Results

Although there was no significant improvement in glucose metabolism in mice administered with 5‐PAHSA, ox‐LDL decreased significantly following the administration of 5‐PAHSA in serum of DB/DB mice (p < 0.0001). We also found that the phosphorylation of m‐TOR and ULK‐1 was suppressed in both PC12 cells and DB/DB mice following the administration of 5‐PAHSA (p < 0.05 and p < 0.01), although increased levels of autophagy were only observed in vitro (p < 0.05). Following the administration of 5‐PAHSA, the concentration of ROS decreased in PC12 cells and the levels of CRP increased in high‐dose group of 5‐PAHSA (p < 0.01). There were no significant changes in terms of apoptosis, other inflammatory factors, or cognition in DB/DB mice following the administration of 5‐PAHSA.

Conclusion

We found that 5‐PAHSA can enhance autophagy in PC12 cells under diabetic conditions. Our data demonstrated that 5‐PAHSA inhibits phosphorylation of the m‐TOR‐ULK1 pathway and suppressed oxidative stress in PC12 cells, and exerted influence on lipid metabolism in DB/DB mice.
Regulation of temozolomide resistance in glioma cells via the RIP2/NF‐κB/MGMT pathway
Authors: Hu Yu‐Hua , Jiao Bao‐Hua , Wang Cheng‐Ye , Wu Jian‐Liang
Published: January 2021

Background

Temozolomide (TMZ) is a first‐line chemotherapy drug for the treatment of malignant glioma and resistance to it poses a major challenge. Receptor‐interacting protein 2 (RIP2) is associated with the malignant character of cancer cells. However, it remains unclear whether RIP2 is involved in TMZ resistance in glioma.

Methods

RIP2 expression was inhibited in TMZ‐resistant glioma cells and normal glioma cells by using small interfering RNA (siRNA) against RIP2. Plasmid transfection method was used to overexpress RIP2. Cell counting kit‐8 assays were performed to evaluate cell viability. Western blotting or immunofluorescence was performed to determine RIP2, NF‐κB, and MGMT expression in cells. Flow cytometry was used to investigate cell apoptosis. TMZ‐resistant glioma xenograft models were established to evaluate the role of the RIP2/NF‐κB/MGMT signaling pathway in drug resistance.

Results

We observed that RIP2 expression was upregulated in TMZ‐resistant glioma cells, whereas silencing of RIP2 expression enhanced cellular sensitivity to TMZ. Similarly, upon the induction of RIP2 overexpression, glioma cells developed resistance to TMZ. The molecular mechanism underlying the process indicated that RIP2 can activate the NF‐κB signaling pathway and upregulate the expression of O6‐methylguanine‐DNA methyltransferase (MGMT), following which the glioma cells develop drug resistance. In the TMZ‐resistant glioma xenograft model, treatment with JSH‐23 (an NF‐κB inhibitor) and lomeguatrib (an MGMT inhibitor) could enhance the sensitivity of the transplanted tumor to TMZ.

Conclusion

We report that the RIP2/NF‐κB/MGMT signaling pathway is involved in the regulation of TMZ resistance. Interference with NF‐κB or MGMT activity could constitute a novel strategy for the treatment of RIP2‐positive TMZ‐resistant glioma.
Circ_SMAD4 promotes gastric carcinogenesis by activating wnt/β‐catenin pathway
Authors: Wang Liyan , Li Bin , Yi Xiaoyuan , Xiao Xuhua , Zheng Qinghua , Ma Lei
Published: January 2021

Objectives

Circular RNAs (circRNAs) are essential participants in tumour progression. This study focused on investigating the mechanism of a novel functional circRNA in gastric cancer (GC).

Methods

Gene expression was detected by qRT‐PCR or Western blot. Survival curves were generated via Kaplan‐Meier method. In vitro and in vivo assays were used to investigate the impact of circ_SMAD4 on GC cell growth and tumorigenesis. Agarose gel electrophoresis assay, RNase R treatment and Sanger sequencing were utilized for confirming the circular structure of circ_SMAD4. Relationship between molecules was monitored by a series of mechanical experiments, as needed.

Results

Circ_SMAD4 expression was potentiated in GC. Circ_SMAD4 depletion impeded GC cell growth in vitro and restrained tumorigenesis in vivo. Mechanically, nuclear circ_SMAD4 recruited TCF4 to facilitate CTNNB1 transcription, while cytoplasmic circ_SMAD4 sequestered miR‐1276 to prevent the silence of CTNNB1 mRNA, leading to activation of Wnt/β‐catenin pathway. Rescue experiments validated that circ_SMAD4 depended on miR‐1276/TCF4‐regulated CTNNB1 to elicit accelerating effects on GC cell growth.

Conclusion

Circ_SMAD4 facilitated GC tumorigenesis by activating CTNNB1‐dependent Wnt/β‐catenin pathway. Hopefully, the findings could provide new clues for improving GC prognosis and treatment.
Using cultural heritage sites in Mexico to understand the poverty alleviation impacts of protected areas
Authors: Quadri‐Barba Paulo , Sims Katharine R.E. , Millard‐Ball Adam
Published: January 2021

Win—win outcomes between biodiversity conservation and local economic development are now a goal of many governments and conservation organizations but can be difficult to achieve. Where they occur, reductions in poverty from protected areas are often thought to be driven by economic gains from tourism that are sufficient to outweigh losses due to restrictions on land‐use or resource extraction. However, evidence about this channel is scarce. In this paper, we explore the potential compensatory effect of tourism by comparing poverty alleviation outcomes for cultural heritage sites in Mexico across two decades from 1990 to 2010. These sites are similar to protected areas in terms of attracting tourists, but they do not impose substantial restrictions on local land or resource use, allowing us to isolate tourism as a possible channel for economic development. Overall, we find mixed evidence that proximity to cultural heritage sites is associated with poverty reduction. During the first study period (1990–2000), localities close to cultural heritage sites saw reduced poverty of 0.034 standard deviations for each additional site. However, during the second period (2000–2010), localities close to heritage sites saw less poverty reduction than the comparison group (−0.014 standard deviations for each additional site). In both periods, poverty alleviation effects were not consistently correlated with the total number of visitors, but were larger further from cities, where baseline poverty was higher, and in the Yucatán Peninsula. This heterogeneity indicates that variability in the ability of local communities to capture benefits from tourism depends on a particular combination of institutional and geographic factors—as was the case in the Yucatan peninsula, where cultural heritage sites had consistent poverty alleviation effects over two decades.
Late occurrence of progressive multifocal leukoencephalopathy after anti‐CD19 chimeric antigen receptor T‐cell therapy
Authors: Mian Agrima , Andrapalliyal Nirmal , Weathers Allison L. , Pohlman Brad , Hill Brian T.
Published: January 2021

Progressive multifocal leukoencephalopathy (PML) is a life‐threatening infection of the central nervous system in immunocompromised patients, with an established predilection in non‐Hodgkin's lymphoma and stem cell transplant recipients. In the era of chimeric antigen receptor T‐cell therapy (CAR T‐cell), the occurrence of new‐onset neurological symptoms and encephalopathy in this patient population can be attributed to a variety of factors, including therapy‐related neurotoxicity or disease progression. PML has not been implicated as a common cause of encephalopathy in CAR T‐cell therapy recipients, and the identification of such rare infections is important to guide prognosis and treatment decisions. We hereby report the first case of late occurrence of PML, over one year after CAR T‐cell therapy, for a patient with relapsed large B‐cell lymphoma.
A plea for equitable global access to COVID‐19 diagnostics, vaccination and therapy: The NeuroCOVID‐19 Task Force of the European Academy of Neurology
Authors: Sellner Johann , Jenkins Thomas M. , von Oertzen Tim J. , Bassetti Claudio L. , Beghi Ettore , Bereczki Daniel , Bodini Benedetta , Cavallieri Francesco , Di Liberto Giovanni , Helbok Raimund , Macerollo Antonella , Maia Luis F. , Oreja‐Guevara Celia , Özturk Serefnur , Rakusa Martin , Pisani Antonio , Priori Alberto , Sauerbier Anna , Soffietti Riccardo , Taba Pille , Zedde Marialuisa , Crean Michael , Burlica Anja , Twardzik Alex , Moro Elena ,   for the EAN NeuroCOVID‐19 Task Force
Published: January 2021

Coronavirus disease 2019 (COVID‐19), a multi‐organ disease caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), continues to challenge health and care systems around the globe. The pandemic has disrupted acute neurology services and routine patient care and has impacted the clinical course in patients with chronic neurological disease. COVID‐19 appears to have exposed inequalities of societies and healthcare systems and had a disproportionate impact on already vulnerable communities. The next challenge will be to set up initiatives to stop disparities in all aspects related to COVID‐19. From the medical perspective, there is a need to consider inequalities in prevention, treatment and long‐term consequences. Some of the issues of direct relevance to neurologists are summarised. With this appraisal, the European Academy of Neurology NeuroCOVID‐19 Task Force intends to raise awareness of the potential impact of COVID‐19 on inequalities in healthcare and calls for action to prevent disparity at individual, national and supranational levels.
Parkinson's disease patients' needs during the COVID‐19 pandemic in a red zone: A framework analysis of open‐ended survey questions
Authors: Cavallieri Francesco , Sireci Francesca , Fioravanti Valentina , Toschi Giulia , Rispoli Vittorio , Antonelli Francesca , Costantini Massimo , Ghirotto Luca , Valzania Franco
Published: January 2021

Background and purpose

During the first phase of the COVID‐19 pandemic, a lockdown was imposed in Italy. The aim of this study was to investigate the perceptions, feelings and unmet needs of Parkinson's disease (PD) patients who experienced the 2‐month lockdown in a “red zone” in the northern part of Italy during the COVID‐19 outbreak.

Methods

The study had a descriptive design that used a cross‐sectional online survey which included open‐ended questions to elicit responses on the participant's feelings concerning their risk of contracting coronavirus, how their physical activity had changed, and their personal needs, dictated by their condition, which were not met in this pandemic period as compared to previous periods. Demographic data were analysed using descriptive frequencies, while the open‐ended questions were analysed using thematic framework analysis.

Results

The study included 103 participants (63 men/40 women [61.17 vs. 38.83%]). Framework analysis led to the identification of four main themes: (i) fearing the risk of contracting coronavirus; (ii) reduction of physical activity; (iii) perception of the risk of not being able to access outpatient clinics or support services; and (iv) negative experiences of the important reduction in socialization. The perceptions of unmet needs appeared to be greater than the actual experience, particularly for the reduction in physical activity and the interruption of contacts with the neurologist and other specialists.

Conclusions

This study highlights how perceptions and actual experience shape the meaning of living with PD during the pandemic. Worth noting is the divergence between perceptions and real impact in some aspects of the COVID‐19 outbreak.
Consumption of the ectomycorrhizal fungi Rhizopogon roseolus and R. luteolus by Chamaesyrphus japonicus (Diptera: Syrphidae)
Authors: Okada Hidehito , Sueyoshi Masahiro , Suetsugu Kenji
Published: January 2021

In spite of the uniform flower feeding habitat of adult hoverflies, their larval feeding ecology is diverse. The genus Chamaesyrphus Mik, 1895, is rare and its larval feeding ecology is entirely unknown. Here we reported larval feeding ecology of Chamaesyrphus japonicus Shiraki, 1956. We found that nine larvae of Cha. japonicus fed on five fruitbodies of ectomycorrhizal hypogeous basidiomycete fungi Rhizopogon roseolus (Corda) Th. Fr., Svensk, 1909, while two larvae of Cha. japonicus fed on two fruitbodies of Rhizopogon luteolus Fr. & Nordholm, 1817. This is the first documentation of the mycophagy in the genus Chamaesyrphus. Gut contents of the dissected larvae contained a lot of undamaged spores, suggesting that Cha. japonicus larvae may be spore transporter of them.
Post‐exercise endoscopic and cytologic diagnosis of equine asthma syndrome in asymptomatic Brazilian pacers
Authors: Beling J. C. F. , Santos D. M. S. A. , Ferreira M. P. , Silva P. C. A. R. , Costa M. F. M. , Lessa D. A. B.
Published: January 2021

The objectives were: 1. to investigate the occurrence of equine asthma syndrome (EAS) in a group of Campolina and Mangalarga Marchador horses through post‐exercise respiratory endoscopy and cytology; 2. compare the efficiency of different diagnostic criteria; and 3. compare the incidence of EAS by breed, age group and sex. A standardised exercise test was conducted in the field, followed by respiratory endoscopy and bronchoalveolar lavage and fluid collection 30 min post‐exercise. Clinical evaluation pre‐ and post‐exercise, respiratory endoscopy post‐exercise and bronchoalveolar lavage, also post‐exercise, were conducted in 30 horses (15 Campolina and 15 Mangalarga Marchador) aged 3–18 years, without a history of respiratory illness and without clinical evidence of active respiratory disease. All horses were in active training and were considered fit to participate in equestrian competition characteristic of these breeds. Post‐collection, the horses were subdivided into healthy or EAS‐positive, depending on several diagnostic criteria. Statistical comparisons between breeds, age brackets (up to 7 years of age and above 7 years of age) and sex were conducted using appropriate statistical tests. According to bronchoalveolar lavage fluid (BALF) cytology, 56.7% of the horses showed at least one inclusion criteria that contributed to classification as EAS‐positive. Of those, only one was classified as moderate EAS, while the others were classified as mild. Total cell count in the BALF above 530 cells/µL was the single most common diagnostic criteria (100%), followed by increased tracheal mucus (53%) at endoscopy, eosinophilia (47%) and neutrophilia (35%) in BALF. Significant differences were found between macrophage and lymphocyte numbers according to breed, but no other differences between breeds, age brackets, sex or status (healthy vs. EAS‐positive). A high occurrence of EAS was found in competition‐ready Mangalarga and Campolina pacer horses in this study.
Teriflunomide‐associated urolithiasis: a new adverse reaction explained by its uricosuric effect
Authors: Largeau Bérenger , Béra Frédéric , Vannier Jacques , Jonville‐Béra Annie‐Pierre
Published: January 2021

In clinical trials, few investigations have been conducted to determine the mechanism involved in teriflunomide‐associated kidney stone formation. We report the first case of recurrent teriflunomide‐induced uric acid urolithiasis. A 55‐year‐old man with relapsing‐remitting multiple sclerosis experienced three occurrences of urolithiasis several months after the initiation of teriflunomide. While serum uric acid remained stable at 280 mmol/L, 24‐h urine uric acid was increased to 2195 mmol/24 h. For the third episode, computed tomography showed three bladder stones and one stone in the right calyceal group. Endovesical lithotripsy was used to extract four orange‐colored stones of more than 20 mm. Stone analysis exhibited morphology subtype IIIb with 100% of anhydrous uric acid. Given the disease control, teriflunomide was continued. After urinary alkalinization by potassium citrate, the patient remained asymptomatic at 18 months follow‐up. An inhibitory effect of dihydroorotate and/or teriflunomide on urate tubular reabsorption could explain teriflunomide‐associated uric acid urolithiasis. This case in a patient without risk factors suggests that multiple sclerosis patients may be at greater risk of forming uric acid urinary stones when taking teriflunomide. Alkalinization of the urine may reduce the risk of recurrence, allowing further treatment with teriflunomide.
Heterotypic interactions in amyloid function and disease
Authors: Konstantoulea Katerina , Louros Nikolaos , Rousseau Frederic , Schymkowitz Joost
Published: January 2021

Amyloid aggregation results from the self‐assembly of identical aggregation‐prone sequences into cross‐beta‐sheet structures. The process is best known for its association with a wide range of human pathologies but also as a functional mechanism in all kingdoms of life. Less well elucidated is the role of heterotypic interactions between amyloids and other proteins and macromolecules and how this contributes to disease. We here review current data with a focus on neurodegenerative amyloid‐associated diseases. Evidence indicates that heterotypic interactions occur in a wide range of amyloid processes and that these interactions modify fundamental aspects of amyloid aggregation including seeding, aggregation rates and toxicity. More work is required to understand the mechanistic origin of these interactions, but current understanding suggests that both supersaturation and sequence‐specific binding can contribute to heterotypic amyloid interactions. Further unravelling these mechanisms may help to answer outstanding questions in the field including the selective vulnerability of cells types and tissues and the stereotypical spreading patterns of amyloids in disease.
Local and continental‐scale controls of the onset of spring phytoplankton blooms: Conclusions from a proxy‐based model
Authors: Gronchi Enzo , Jöhnk Klaus D. , Straile Dietmar , Diehl Sebastian , Peeters Frank
Published: January 2021

A key phenological event in the annual cycle of many pelagic ecosystems is the onset of the spring algal bloom (OAB). Descriptions of the factors controlling the OAB in temperate to polar lakes have been limited to isolated studies of single systems and conceptual models. Here we present a validated modelling approach that, for the first time, enables a quantitative prediction of the OAB and a systematic assessment of the processes controlling its timing on a continental scale. We used a weather‐driven, one‐dimensional lake model to simulate the seasonal dynamics of the underwater light climate in 16 lake types characterized by the factorial combination of four lake depths with four levels of water transparency. We did so at 1962 locations across Western Europe and over 31 years (1979–2009). Assuming that phytoplankton production is light‐limited in winter, we identified four patterns of OAB control across lake types and climate zones. OAB timing is controlled by (i) the timing of ice‐off in ice‐covered clear or shallow lakes, (ii) the onset of thermal stratification in sufficiently deep and turbid lakes and (iii) the seasonal increase in incident radiation in all other lakes, except for (iv) ice‐free, shallow and clear lakes in the south, where phytoplankton is not light‐limited. The model predicts that OAB timing should respond to two pervasive environmental changes, global warming and browning, in opposite ways. OAB timing should be highly sensitive to warming in lakes where it is controlled by either ice‐off or the onset of stratification, but resilient to warming in lakes where it is controlled by incident radiation. Conversely, OAB timing should be most sensitive to browning where it is controlled by incident radiation, but resilient to browning where it is controlled by ice‐off or the onset of stratification. Available lake data are consistent with our findings.