bluuebunny/crossref_metadata_2025 huggingface dataset:
The role of intra-articular neuronal CCR2 receptors in knee joint pain associated with experimental osteoarthritis in mice
Authors: Ishihara Shingo , Obeidat Alia M. , Wokosin David L. , Ren Dongjun , Miller Richard J. , Malfait Anne-Marie , Miller Rachel E.
Published: April 2021

Background

C–C chemokine receptor 2 (CCR2) signaling plays a key role in pain associated with experimental murine osteoarthritis (OA) after destabilization of the medial meniscus (DMM). Here, we aimed to assess if CCR2 expressed by intra-articular sensory neurons contributes to knee hyperalgesia in the early stages of the model.

Methods

DMM surgery was performed in the right knee of 10-week-old male wild-type (WT), Ccr2 null, or Ccr2RFP C57BL/6 mice. Knee hyperalgesia was measured using a Pressure Application Measurement device. CCR2 receptor antagonist (CCR2RA) was injected systemically (i.p.) or intra-articularly (i.a.) at different times after DMM to test its ability to reverse knee hyperalgesia. In vivo Ca2+ imaging of the dorsal root ganglion (DRG) was performed to assess sensory neuron responses to CCL2 injected into the knee joint cavity. CCL2 protein in the knee was measured by ELISA. Ccr2RFP mice and immunohistochemical staining for the pan-neuronal marker, protein gene product 9.5 (PGP9.5), or the sensory neuron marker, calcitonin gene-related peptide (CGRP), were used to visualize the location of CCR2 on intra-articular afferents.

Results

WT, but not Ccr2 null, mice displayed knee hyperalgesia 2–16 weeks after DMM. CCR2RA administered i.p. alleviated established hyperalgesia in WT mice 4 and 8 weeks after surgery. Intra-articular injection of CCL2 excited sensory neurons in the L4-DRG, as determined by in vivo calcium imaging; responses to CCL2 increased in mice 20 weeks after DMM. CCL2, but not vehicle, injected i.a. rapidly caused transient knee hyperalgesia in naïve WT, but not Ccr2 null, mice. Intra-articular CCR2RA injection also alleviated established hyperalgesia in WT mice 4 and 7 weeks after surgery. CCL2 protein was elevated in the knees of both WT and Ccr2 null mice 4 weeks after surgery. Co-expression of CCR2 and PGP9.5 as well as CCR2 and CGRP was observed in the lateral synovium of naïve mice; co-expression was also observed in the medial compartment of knees 8 weeks after DMM.

Conclusions

The findings suggest that CCL2-CCR2 signaling locally in the joint contributes to knee hyperalgesia in experimental OA, and it is in part mediated through direct stimulation of CCR2 expressed by intra-articular sensory afferents.
Analysis of the clinical characteristics of insulin autoimmune syndrome induced by exogenous insulin in diabetic patients
Authors: Li Zuojun , Yi Dan , Zheng Lijuan , Li Shiran , Fang Weijin , Wang Chunjiang
Published: April 2021

Background

The exact incidence, clinical features and uniform diagnostic criteria of exogenous insulin autoimmune syndrome (EIAS) are still unclear. The purpose of this study is to explore the clinical characteristics of EIAS and to provide a structural approach for clinical diagnosis, treatment and prevention.

Methods

The literature on EIAS in Chinese and English from 1970 to 2020 was collected for retrospective analysis.

Results

A total of 122 patients (33 males and 73 females) were included in the study with a median age of 67 years (range 14–86) and a median HbA1c of 7.7%. EIAS mainly occurred in type 2 diabetes mellitus patients using premixed insulin. Symptoms manifested were hypoglycemia in 86.54%, recurrent episodes of symptomatic hypoglycemia in 35.58%, nocturnal hypoglycemia along with daytime hyperglycemia in 21.15% and recurrent hypoglycemia after discontinued insulin in 64.43%. The onset of symptoms occurred at night, in the early morning or during fasting, ranging from a few days to 78 months after the administration of insulin. The mean blood glucose level during the hypoglycemic phase was 2.21 mmol/L (range 1–3.4), and the serum insulin levels were mainly ≥ 100 U/mL and were associated with low C-peptide levels (≤ 10 ng/ml). Insulin autoantibodies (IAAs) were positive in all EIAS patients. The 75-g extended oral glucose tolerance test (OGTT) mainly showed a diabetic curve. Pancreatic imaging was unremarkable. Withdrawal of insulin alone or combination of oral hypoglycemic agents or replacement of insulin formulations or with corticosteroid treatment eliminated hypoglycemia in a few days to 3 months. IAA turned negative in 6 months (median, range 1–12). No hypoglycemia episodes were observed at a median follow-up of 6 months (range 0.5–60).

Conclusions

EIAS is an autoimmune disease caused by insulin-binding antibodies in susceptible subjects. Insulin antibodies change glucose dynamics and could increase the incidence of hypoglycemic episodes. Detection of insulin antibodies is the diagnostic test. Changing therapeutic modalities reduced the incidence of hypoglycemic episodes.
Athletic identity and sport commitment in athletes after anterior cruciate ligament reconstruction who have returned to sports at their pre-injury level of competition
Authors: Ohji Shunsuke , Aizawa Junya , Hirohata Kenji , Mitomo Sho , Ohmi Takehiro , Jinno Tetsuya , Koga Hideyuki , Yagishita Kazuyoshi
Published: April 2021

Background

This study aimed to determine the relationships between athletic identity and sport commitment and return to sports (RTS) status in athletes after anterior cruciate ligament reconstruction (ACLR).

Methods

Thirty-nine participants post-ACLR (8–24 months) were included in this cross-sectional study. Measures included the athletic identity measurement scale and sport commitment scale. In addition, we measured kinesiophobia and psychological readiness using the Tampa Scale for Kinesiophobia and ACL-Return to sport after injury scale. The subjects were categorized into Yes-RTS or No-RTS based on two questions to determine whether they were returning to sport at the same level of competition as before the injury. A Chi-squared test, Fisher’s exact test, unpaired t-test, and Mann-Whitney’s U test were used to analyze the data.

Results

The Yes-RTS group had significantly higher scores on the athletic identity measurement scale (P = 0.023, effect size [ES] = − 0.36), sport commitment scale (P = 0.027, ES = − 0.35), and ACL-Return to sport after injury scale (P = 0.002, ES = − 0.50) and significantly lower Tampa Scale for Kinesiophobia scores (P = 0.014, ES = − 0.39) compared to the No-RTS group.

Conclusion

Athletes who returned to sports at the same level of competition as before the injury had higher athletic identity and sport commitment and lower kinesiophobia compared to those who did not return to sports at the same level of competition. These self-beliefs regarding sport may play an important role in post-ACLR athletes’ RTS.
The dark side of histones: genomic organization and role of oncohistones in cancer
Authors: Amatori Stefano , Tavolaro Simona , Gambardella Stefano , Fanelli Mirco
Published: April 2021

Background

The oncogenic role of histone mutations is one of the most relevant discovery in cancer epigenetics. Recurrent mutations targeting histone genes have been described in pediatric brain tumors, chondroblastoma, giant cell tumor of bone and other tumor types. The demonstration that mutant histones can be oncogenic and drive the tumorigenesis in pediatric tumors, led to the coining of the term “oncohistones.” The first identified histone mutations were localized at or near residues normally targeted by post-translational modifications (PTMs) in the histone N-terminal tails and suggested a possible interference with histone PTMs regulation and reading.

Main body

In this review, we describe the peculiar organization of the multiple genes that encode histone proteins, and the latter advances in both the identification and the biological role of histone mutations in cancer. Recent works show that recurrent somatic mutations target both N-terminal tails and globular histone fold domain in diverse tumor types. Oncohistones are often dominant-negative and occur at higher frequencies in tumors affecting children and adolescents. Notably, in many cases the mutations target selectively only some of the genes coding the same histone protein and are frequently associated with specific tumor types or, as documented for histone variant H3.3 in pediatric glioma, with peculiar tumors arising from specific anatomic locations.

Conclusion

The overview of the most recent advances suggests that the oncogenic potential of histone mutations can be exerted, together with the alteration of histone PTMs, through the destabilization of nucleosome and DNA–nucleosome interactions, as well as through the disruption of higher-order chromatin structure. However, further studies are necessary to fully elucidate the mechanism of action of oncohistones, as well as to evaluate their possible application to cancer classification, prognosis and to the identification of new therapies.
The pharmacokinetics of [18F]UCB-H revisited in the healthy non-human primate brain
Authors: Goutal Sébastien , Guillermier Martine , Becker Guillaume , Gaudin Mylène , Bramoullé Yann , Luxen André , Lemaire Christian , Plenevaux Alain , Salmon Eric , Hantraye Philippe , Barret Olivier , Van Camp Nadja
Published: April 2021

Background

Positron Emission Tomography (PET) imaging of the Synaptic Vesicle glycoprotein (SV) 2A is a new tool to quantify synaptic density. [18F]UCB-H was one of the first promising SV2A-ligands to be labelled and used in vivo in rodent and human, while limited information on its pharmacokinetic properties is available in the non-human primate. Here, we evaluate the reliability of the three most commonly used modelling approaches for [18F]UCB-H in the non-human cynomolgus primate, adding the coupled fit of the non-displaceable distribution volume (VND) as an alternative approach to improve unstable fit. The results are discussed in the light of the current state of SV2A PET ligands.

Results

[18F]UCB-H pharmacokinetic data was optimally fitted with a two-compartment model (2TCM), although the model did not always converge (large total volume of distribution (VT) or large uncertainty of the estimate). 2TCM with coupled fit K1/k2 across brain regions stabilized the quantification, and confirmed a lower specific signal of [18F]UCB-H compared to the newest SV2A-ligands. However, the measures of VND and the influx parameter (K1) are similar to what has been reported for other SV2A ligands. These data were reinforced by displacement studies using [19F]UCB-H, demonstrating only 50% displacement of the total [18F]UCB-H signal at maximal occupancy of SV2A. As previously demonstrated in clinical studies, the graphical method of Logan provided a more robust estimate of VT with only a small bias compared to 2TCM.

Conclusions

Modeling issues with a 2TCM due to a slow component have previously been reported for other SV2A ligands with low specific binding, or after blocking of specific binding. As all SV2A ligands share chemical structural similarities, we hypothesize that this slow binding component is common for all SV2A ligands, but only hampers quantification when specific binding is low.
Straw mulching and nitrogen application altered ammonia oxidizers communities and improved soil quality in the alkaline purple soil of southwest China
Authors: Chen Songhe , Gao Rencai , Xiang Xiaoling , Yang Hongkun , Ma Hongliang , Zheng Ting , Xiao Yun , Zhang Xue , Li Han , Fan Gaoqiong , Yu Yang
Published: April 2021

Microbe-mediated ammonia oxidation is a key process in soil nitrogen cycle. However, the effect of maize straw mulching on the ammonia oxidizers in the alkaline purple soil remains largely unknown. A three-year positioning experiment was designed as follows: straw mulching measures as the main-plot treatment and three kinds of nitrogen application as the sub-plot treatment. We found the contents of soil organic carbon (SOC), total nitrogen (TN), available potassium (AK), available nitrogen (AN), available phosphorus (AP), and NH4+-N were increased after straw mulching and nitrogen application in alkaline purple soil, so did theamoAgenes abundance of ammonia-oxidizing archaeal (AOA) and bacterial (AOB). Terminal restriction fragment length polymorphism (T-RFLP) analysis revealed thatThaumarchaeote(448-bp T-RF) was dominated the AOA communities, whereasNitrosospirasp (111-bp T-RF) dominated the AOB communities. The community compositions of both AOA and AOB were altered by straw mulching and nitrogen application in alkaline purple soil, however, the AOB communities was more responsive than AOA communities to the straw mulching and nitrogen application. Further analysis indicated that SOC and AP were the main factors affecting the abundance and community compositions of AOA and AOB in alkaline purple soil. The present study reported that straw mulching and nitrogen strategies differently shape the soil ammonia oxidizers community structure and abundance, which should be considered when evaluating agricultural management strategies regarding their sustainability and soil quality.
EIF5A2 controls ovarian tumor growth and metastasis by promoting epithelial to mesenchymal transition via the TGFβ pathway
Authors: Zhao Guannan , Zhang Wenjing , Dong Peixin , Watari Hidemichi , Guo Yuqi , Pfeffer Lawrence M. , Tigyi Gabor , Yue Junming
Published: April 2021

Background

Epithelial to mesenchymal transition (EMT) contributes to tumor metastasis and chemoresistance. Eukaryotic initiation factor 5A2 (EIF5A2) is highly expressed in a variety of human cancers but rarely expressed in normal tissues. While EIF5A2 has oncogenic activity in several cancers and contributes to tumor metastasis, its role in ovarian cancer is unknown. In this study, we investigate whether EIF5A2 contributes to ovarian tumor metastasis by promoting EMT.

Methods

To investigate the role of EIF5A2, we knocked out (KO) EIF5A2 using lentiviral CRISPR/Cas9 nickase in high invasive SKOV3 and OVCAR8 cells and overexpressed EIF5A2 in low invasive OVCAR3 cells using lentiviral vector. Cell proliferation, migration and invasion was examined in vitro ovarian cancer cells and tumor metastasis was evaluated in vivo using orthotopic ovarian cancer mouse models.

Results

Here we report that EIF5A2 is highly expressed in ovarian cancers and associated with patient poor survival. Lentiviral CRISPR/Cas9 nickase vector mediated knockout (KO) of EIF5A2 inhibits epithelial to mesenchymal transition (EMT) in SKOV3 and OVCAR8 ovarian cancer cells that express high levels of EIF5A2. In contrast, overexpression of EIF5A2 promotes EMT in OVCAR3 epithelial adenocarcinoma cells that express relatively low EIF5A2 levels. KO of EIF5A2 in SKOV3 and OVCAR8 cells inhibits ovarian cancer cell migration and invasion, while its overexpression promotes cell migration and invasion in OVCAR3 adenocarcinoma cells. We further demonstrate that EIF5A2 promotes EMT by activating the TGFβ pathway and KO of EIF5A2 inhibits ovarian tumor growth and metastasis in orthotopic ovarian cancer mouse models.

Conclusion

Our results indicate that EIF5A2 is an important controller of ovarian tumor growth and metastasis by promoting EMT and activating the TGFβ pathway.
A survey: applications of blockchain in the Internet of Vehicles
Authors: Wang Chao , Cheng Xiaoman , Li Jitong , He Yunhua , Xiao Ke
Published: April 2021

Blockchain technology has completely changed the area of cryptocurrency with a Peer-to-Peer system named Bitcoin. It can provide a distributed, transparent and highly confidential database by recording immutable transactions. Currently, the technique has obtained great research interest on other areas, including the Internet of vehicles (IoVs). In order to solve some centralized problems and improve the architecture of the IoVs, the blockchain technology is utilized to build a decentralized and secure vehicular environment. In this survey, we aim to construct a comprehensive analysis on the applications of blockchain in the IoV. This paper starts with the introduction of the IoVs and the blockchain. Additionally, some existing surveys on the blockchain enabled IoVs are reviewed. Besides, the combination of the blockchain technology and the IoVs is analyzed from seven aspects to describe how the blockchain is implemented in the IoVs. Finally, the future research directions related to the integration are highlighted.
An oscillation theorem for the nonlinear degenerate elliptic equation in the Heisenberg group
Authors: Wu Duan , Niu Pengcheng
Published: April 2021

The aim of this paper is to study the oscillation of solutions of the nonlinear degenerate elliptic equation in the Heisenberg group$H^{n}$Hn. We first derive a critical inequality in$H^{n}$Hn. Based on it, we establish a Picone-type differential inequality and a Sturm-type comparison principle. Then we obtain an oscillation theorem. Our result generalizes the related conclusions for the nonlinear elliptic equations in$R^{n}$Rn.
Translation and validation of the STOP-Bang questionnaire into Slovene
Authors: Pangerc Andrej , Petek Šter Marija , Dolenc Grošelj Leja
Published: April 2021

Purpose

To translate, culturally adapt and evaluate the Slovene version of the STOP-Bang questionnaire (SBQ) for use in the sleep clinic.

Methods

Standard forward–backward translation and harmonisation of the Slovene translation of the SBQ were performed. Test–retest reliability was performed on a sample of healthy subjects. A cross-sectional study was performed with patients referred for a sleep study. Patients filled out the Slovene translation of the SBQ before undergoing sleep study.

Results

The validation group consisted of 256 patients, of which 237 (92.6%) were included. Mean age was 52.5 ± 14.6, 63.3% of patients were male. Obstructive sleep apnoea (OSA) (apnoea–hypopnea index (AHI) ≥ 5) was present in 69.6% of patients, of whom 22.4% had mild (AHI ≥ 5 and < 15), 21.9% moderate (AHI ≥ 15 and < 30), and 25.3% severe (AHI ≥ 30) OSA. A SBQ score of 3 had a sensitivity of 92.1 (86.9–95.7), specificity of 44.4 (32.7–56.6), PPV of 79.2 (75.5–82.4) and AUC of 0.757 (95% CI 0.692–0.823; p < 0.001) for all OSA (AHI ≥ 5). Each increase in the SBQ score was associated with an increase in the probability of OSA.

Conclusion

This study shows that the Slovene version of the SBQ is a valid tool for evaluating the risk of OSA in a sleep clinic.
Impact of micro-environmental factors on survival, reproduction and distribution of Oncomelania hupensis snails
Authors: Liu Mao-Mao , Feng Yun , Yang Kun
Published: April 2021

Background

Schistosomiasis japonica is a chronic parasitic disease that seriously harms people's health. Oncomelania hupensis is the only intermediate host of Schistosoma japonicum. The micro-environmental factors surrounding the snail have a great impact on the survival, growth and reproduction of O. hupensis, but there are few relevant systematic analyses until the present. This scoping review aims to identify and summarize the micro-environmental factors that greatly affect O. hupensis, and to find gaps in research thus to provide directions for future in-depth studies.

Main body

This scoping review searched databases with search terms of the combinations of “Micro(-)environment”, “Oncomelania” and their expanded aspects. A total of 133 original articles were recruited. Predefined data fields were extracted including research methods, influencing factors, and their effects on O. hupensis. Most studies focused on vegetation factors (54.1%), and other factors noted were soil composition (27.8%), water environmental factors (24.1%), and predator (3.0%), respectively. The factors with positive impacts included water level, pH value, soil temperature, soil humidity, the coverage and height of vegetation at suitable levels. This could provide more detailed information for O. hupensis habitat identification and prediction. The factors with negative impacts included plant extracts, snail control and disease prevention forests, and microorganisms with molluscicidal activities. It revealed a potential application as ecological molluscicides in the future. Factors such as physico-chemical properties of water, soil chemistry showed a gap in scientific studies, thus required further extensive research.

Conclusions

Micro-environmental factors including water quality, soil composition as well as the technology and application of biomolluscicides (plant extracts and microorganisms) deserve more attention. Relative study findings on micro-environment have good potentials in snail control applications. Further studies should be implemented to investigate the impact of micro-environmental factors on snails and close the research gaps.
The perception of COVID-19 among Italian dental patients: an orthodontic point of view
Authors: Martina Stefano , Amato Alessandra , Faccioni Paolo , Iandolo Alfredo , Amato Massimo , Rongo Roberto
Published: April 2021

Background

The present study aimed to investigate the patients’ perception of the dental practice during the COVID-19 outbreak, and whether the pandemic will affect the attendance of orthodontic patients at the dental practice. An online questionnaire, including the Patient Health Questionnaire-4 (PHQ-4), was submitted to Italian dental patients with items about their perceived risks when going to the dentist, concerns about continuing orthodontic treatment, and the onset of temporomandibular disorders (TMD). Data were analyzed with a chi-square test and logistic regression analysis. The level of significance was set atP< 0.05.

Results

A total of 1566 subjects completed the survey, including 486 who were under orthodontic treatment or who had a child in orthodontic treatment. A total of 866 participants (55.3%) thought the risk of contracting the COVID-19 infection was higher in a dental practice; this perception was associated with gender (women more than man), age (over 60 years old) and high levels of distress (P<0.001). However, 894 patients (57.1%) felt comfortable going back to the dentist. Most of the orthodontic patients (84%) would continue their treatment. After the lockdown, there was a slight increase in the frequency of TMD pain (356 versus 334).

Conclusions

Most of the participants believed that the dental practice is a place at greater risk of contracting COVID-19, even if they continue to go to the dentist. Gender, age, and the level of distress were associated with the increase in the fear of going to the dentist due to COVID-19. Because of the pandemic, 16% of patients undergoing orthodontic treatment would not return to the dental practice to continue their orthodontic treatment after the lockdown. The prevalence of TMD pain in the population increased due to the pandemic.
Internet use at and outside of school in relation to low- and high-stakes mathematics test scores across 3 years
Authors: Rozgonjuk Dmitri , Täht Karin , Vassil Kristjan
Published: April 2021

Background

The excessive use of Internet-based technologies has received a considerable attention over the past years. Despite this, there is relatively little research on how general Internet usage patterns at and outside of school as well as on weekends may be associated with mathematics achievement. Moreover, only a handful of studies have implemented a longitudinal or repeated-measures approach on this research question. The aim of the current study was to fill that gap. Specifically, we investigated the potential associations of Internet use at and outside of school as well as on weekends with mathematics test performance in both high- and low-stakes testing conditions over a period of 3 years in a representative sample of Estonian teenagers.

Methods

PISA 2015 survey data in conjunction with national educational registry data were used for the current study. Specifically, Internet use at and outside of school as well as on weekends were queried during the PISA 2015 survey. In addition, the data set included PISA mathematics test results from 4113 Estonian 9th-grade students. Furthermore, 3758 of these students also had a 9th-grade national mathematics exam score from a couple of months after the PISA survey. Finally, of these students, the results of 12th-grade mathematics national exam scores were available for 1612 and 1174 students for “wide” (comprehensive) and “narrow” (less comprehensive) mathematics exams, respectively.

Results

The results showed that the rather low-stakes PISA mathematics test scores correlated well with the high-stakes national mathematics exam scores obtained from the 9th (completed a couple of months after the PISA survey) and 12th grade (completed approximately 3 years after the PISA survey), with correlation values ranging from r = .438 to .557. Furthermore, socioeconomic status index was positively correlated with all mathematics scores (ranging from r = .162 to .305). Controlled for age and gender, the results also showed that students who reported using Internet the longest tended to have, on average, the lowest mathematics scores in all tests across 3 years. Although effect sizes were generally small, they seemed to be more pronounced in Internet use at school.

Conclusions

Based on these results, one may notice that significantly longer time spent on Internet use at and outside of school as well as on weekends may be associated with poorer mathematics performance. These results are somewhat in line with research outlining the potentially negative associations between longer time spent on digital technology use and daily life outcomes.
l-Lactic acid production from fructose by chitosan film-coated sodium alginate-polyvinyl alcohol immobilized Lactobacillus pentosus cells and its kinetic analysis
Authors: Wang Jianfei , Guo Huanyu , Huang Jiaqi , Jiang Shaoming , Hou Shibo , Chen Xingyu , Lv Hujie , Bi Xudong , Hou Maolin , Lin Hebei , Lu Yuming , Qiao Jinyue , Yang Ruiyi , Liu Shijie
Published: April 2021

Under the optimal conditions of immobilization and fermentation, the highest LA yield of 0.966 ± 0.006 g/g fructose and production rate of 2.426 ± 0.018 g/(L × h) with an error of -0.5% and -0.2% to the predicted results were obtained from batch fermentation by the CS film-coated SA-PVA immobilized L. pentosus cells. The LA yield and production rate of these immobilized cells were 2.7% and 10.1% higher than that of normal SA-PVA immobilized cells respectively, and they were 5.7% and 48.4% higher than that of free cells, respectively. The effect of temperature on different types of immobilized cells and free cells was significantly different, but the effect of pH on different types of cells was not much different. The kinetic models could effectively describe the different fermentation performances of three types of cells. The immobilized cells have excellent reusability to conduct 9 runs of repeated batch fermentation.
Ultrasound-guided non-invasive retraction for strangulated obturator hernia allows elective radical surgery: analysis of 12 cases
Authors: Maeda Yuto , Nakahara Osamu , Saito Seiya , Nasu Jiro , Baba Hideo
Published: April 2021

Background

Obturator hernia is a life-threatening condition, requiring emergency intervention due to strangulation, if non-invasive repair for strangulation cannot be complete. Change from emergency surgery to elective surgery using minimal non-invasive options can greatly contribute to perioperative safety and curability of the underlying disease.

Case presentation

12 cases of strangulated obturator hernia from April 2013 to February 2020 with male:female patient ratio of 0:12. Reduction under ultrasound guidance was possible amongst 10 out of 12 cases. The average age was 85.3 years (74–97) and average BMI was 17.4 (15.0–20.1). Based on physical findings and CT examination, diagnosis of obturator hernia was made using echo guided non-invasive reduction. Prevention in the intestinal ischemia and perforation was observed in the treated cases. Upon request, elective radical surgery was performed in 7 of these patients after their condition improved and monitored other organs for any signs.

Conclusion

Attempt to improve the strangulation of obturator hernia under an echo-guided approach could enable elective and safe surgery and is believed to be a diagnostic treatment worth attempting.
Correction to: A comparative study of parental knowledge and adaptation of immigrant youth
Authors: Turjanmaa Elina , Jasinskaja-Lahti Inga
Published: April 2021

An amendment to this paper has been published and can be accessed via the original article.
Investigation of the effectiveness of a new portable ‘cryopen’ probe for cryotherapy (CryoTreq®)
Authors: Stalmans Peter , Vander Mijnsbrugge Joris , D’Hollander Filip , Van Ginderdeuren Rita
Published: April 2021

Background

To test the effectiveness of a new, innovative, single-use handheld ‘cryopen’ (CryoTreq®), which has been developed and marketed by Vitreq.

Methods

Animal testing of cryopexy using the Cryotreq ® in two pig eyes was performed.

Results

The biological effects of cryopexy were observed.

Conclusions

During the surgery, the handheld device was comfortable to use and offers the surgeon more freedom to move. The cryotherapy caused severe atrophy and thinning of retinal layers, pigment epithelium and choroidea in a relatively uniform thickness. The cryopen is effective and offers advantages over non-handheld cryotherapy devices.
Can we use non-invasive parameters to predict the development of gastroesophageal varices in cirrhotic patients with and without portal vein thrombosis? An observational study from the western region of Saudi Arabia
Authors: Khayyat Yasir M
Published: April 2021

Background

The prevention of portal hypertensive complications, including upper gastrointestinal bleeding, is critically important and achieved only through the use of upper endoscopy for the management of oesophageal gastric varices (EGVs). There is a paucity of data and limited utilization of non-invasive predictive parameters to guide the selection of patients who may benefit from endoscopic surveillance, especially in cirrhotic patients with coexistent portal vein thrombosis.

Results

The study was conducted in eight hospitals in the western region of Saudi Arabia over the period of 2015–2017. Among 1349 chronic liver disease patients, eighty-five patients with complete endoscopic findings were included in the study. Twenty-eight patients were diagnosed with non-malignant PVT. Twenty-five patients (89%) developed oesophageal varices, compared with 57 patients with cirrhosis without PVT. A predictive factor for the development of oesophageal varices of statistical significance was hypoalbuminemia in PVT patients (p=0.04). No statistically significant differences were found in other biochemical markers (p<0.05) between the PVT and non-PVT groups.

Conclusions

The prevalence of oesophageal varices is increased in PVT patients. Serum albumin can be utilized as a predictor of varices development in cirrhosis patients.
Successful Delivery in 17,20-Lyase Deficiency
Authors: Blumenfeld Zeev , Koren Ilana
Published: April 2021

Context

Pregnancy achievement in an infertile patient with 17,20-lyase deficiency.

Objective

To study and describe the achievement of successful pregnancy and delivery in a patient with 17,20-lyase deficiency.

Method

Controlled ovarian stimulation (COS) and in vitro fertilization (IVF), cryopreservation of embryos and frozen-thawed embryo transfer (ET). Controlled ovarian stimulation, follicular aspiration egg retrieval, IVF, embryo cryopreservation, thawed ET. A 24-year-old, infertile patient with 17,20-lase deficiency.

Results

Isolated 17,20-lyase deficiency is caused by mutations in the CYP17A1 gene (coding for cytochrome P450c17), POR (coding for cytochrome P450 oxidoreductase), and CYB5A (coding for microsomal cytochrome b5) genes. A 24-year-old patient with 17,20-lyase deficiency had undergone IVF with gonadotropin releasing hormone agonist (GnRHa) protocol, prednisone, and gonadotropins. After the human chorionic gonadotropin (hCG) trigger, 37 oocytes were retrieved, 25 ova fertilized, and 17 embryos cryopreserved. After menstrual bleeding, the endometrium was stimulated with oral estradiol, under progesterone suppression with long acting GnRHa and prednisone. When endometrial width of 8.5 mm was reached, vaginal progesterone was added, while gradually decreasing prednisone. On the fourth day of progesterone supplement, 2 thawed embryos were transferred. After 11 days of human menopausal gonadotropin (hMG), estradiol concentration moderately increased, but progesterone levels remained high; therefore, no fresh ET was performed. Twelve days after thawed ET, hCG was positive, and 7 days later, an intrauterine gestational sac was detected, but the pregnancy ended in missed abortion. After 2 months, another frozen-thawed embryo transfer (FET) was performed, generating a normal gestation, which ended in successful delivery.

Conclusion

Pregnancy can be achieved in patients with 17,20-lyase deficiency, by IVF, freezing all embryos, and ET in a subsequent cycle, while suppressing endogenous ovarian progesterone with a GnRHa and adrenal suppression with high-dose glucocorticoids.
Maternal Adiposity and Energy Balance After Normotensive and Preeclamptic Pregnancies
Authors: McLennan Sarah L , Henry Amanda , Roberts Lynne M , Siritharan Sai S , Ojurovic Melissa , Yao Amanda , Davis Gregory K , Mangos George , Pettit Franziska , Brown Mark A , O’Sullivan Anthony J
Published: April 2021

Background

Preeclampsia is a major pregnancy complication associated with long-term maternal cardiometabolic disease. Research generally is focused on metabolic and pathophysiological changes during pregnancy; however, there is much less focus on the early postpartum period in subjects who suffered preeclampsia. The aim of this study was to (1) characterize energy intake and expenditure 6 months following normotensive and preeclamptic pregnancies and (2) examine associations between energy balance, body composition, insulin resistance measures (HOMA-IR), and clinical characteristics.

Design

A cross-sectional study 6 months following normotensive (n = 75) and preeclamptic (n = 22) pregnancies was performed. Metabolic measurements included anthropometrics measures, body composition via bioelectrical impedance analysis, 24-h energy expenditure via SenseWear Armbands, energy intake via a 3-day food diary, and serum metabolic parameters.

Results

Six months following preeclampsia, women had a significantly higher weight (77.3 ± 20.9 kg vs 64.5 ± 11.4 kg, P = 0.01), fat mass percentage (FM%; 40.7 ± 7.4% vs 34.9 ± 8.1%, P = 0.004), and insulin resistance (HOMA-IR 2.2 ± 1.5 vs 1.0 ± 0.7, P = 0.003), as well as reduced HDL levels (1.5 ± 0.4 mmol/L vs 1.8 ± 0.4 mmol/L, P = 0.01) compared to normotensive women. Women post-preeclampsia had lower activity-related energy expenditure (P = 0.02) but a decreased total energy intake (P = 0.02), leading to a more negative energy balance compared to their normotensive counterparts (−1942 kJ/24 h vs −480 kJ/24 h, P = 0.02).

Conclusion

Increases in insulin resistance and FM%, reduced high-density lipoprotein, and more sedentary lifestyles characterize the postpartum period following preeclamptic compared with normotensive pregnancies. Early post-preeclampsia interventions, such as lifestyle behavior change, should be implemented and assessed to determine whether they reduce long-term cardiometabolic risk in women who experienced preeclampsia during pregnancy.
Distal Enhancer Potentiates Activin- and GnRH-Induced Transcription of FSHB
Authors: Bohaczuk Stephanie C , Cassin Jessica , Slaiwa Theresa I , Thackray Varykina G , Mellon Pamela L
Published: April 2021

FSH is critical for fertility. Transcription of FSHB, the gene encoding the beta subunit, is rate-limiting in FSH production and is regulated by both GnRH and activin. Activin signals through SMAD transcription factors. Although the mechanisms and importance of activin signaling in mouse Fshb transcription are well-established, activin regulation of human FSHB is less well understood. We previously reported a novel enhancer of FSHB that contains a fertility-associated single nucleotide polymorphism (rs10031006) and requires a region resembling a full (8 base-pair) SMAD binding element (SBE). Here, we investigated the role of the putative SBE within the enhancer in activin and GnRH regulation of FSHB. In mouse gonadotrope-derived LβT2 cells, the upstream enhancer potentiated activin induction of both the human and mouse FSHB proximal promoters and conferred activin responsiveness to a minimal promoter. Activin induction of the enhancer required the SBE and was blocked by the inhibitory SMAD7, confirming involvement of the classical SMAD signaling pathway. GnRH induction of FSHB was also potentiated by the enhancer and dependent on the SBE, consistent with known activin/GnRH synergy regulating FSHB transcription. In DNA pull-down, the enhancer SBE bound SMAD4, and chromatin immunoprecipitation demonstrated SMAD4 enrichment at the enhancer in native chromatin. Combined activin/GnRH treatment elevated levels of the active transcriptional histone marker, histone 3 lysine 27 acetylation, at the enhancer. Overall, this study indicates that the enhancer is directly targeted by activin signaling and identifies a novel, evolutionarily conserved mechanism by which activin and GnRH can regulate FSHB transcription.
Regulation of Pancreatic β-Cell Function by the NPY System
Authors: Yang Chieh-Hsin , Onda Danise-Ann , Oakhill Jonathan S , Scott John W , Galic Sandra , Loh Kim
Published: April 2021

The neuropeptide Y (NPY) system has been recognized as one of the most critical molecules in the regulation of energy homeostasis and glucose metabolism. Abnormal levels of NPY have been shown to contribute to the development of metabolic disorders including obesity, cardiovascular diseases, and diabetes. NPY centrally promotes feeding and reduces energy expenditure, while the other family members, peptide YY (PYY) and pancreatic polypeptide (PP), mediate satiety. New evidence has uncovered additional functions for these peptides that go beyond energy expenditure and appetite regulation, indicating a more extensive function in controlling other physiological functions. In this review, we will discuss the role of the NPY system in the regulation of pancreatic β-cell function and its therapeutic implications for diabetes.
On Playwright Canonization
Authors: Zarhy-Levo Yael
Published: April 2021

This article engages with the issue of the factors determining theatrical prominence, endorsing the “institutional approach.” In discussing the major mediating role played by theater reviewers in the canonization of individual playwrights, the article focuses particularly on two essential factors that contribute to and affect the processes of their canonization: a convergence of the mediating agents concerning the prominent theatrical contribution of the playwright in question; and the formulation of the playwright’s critical construct (an aggregation of traits recurring in the works seen as typifying the playwright in terms of influences and innovations). The careers of four British playwrights, Harold Pinter, John Arden, Sarah Kane, and Martin McDonagh, serve as the case studies. Three of these — Pinter, Arden, and Kane — demonstrate three differing trajectories that represent two distinctive possibilities, whereby either both factors are at play and canonization follows, or neither is at play and canonization fails. McDonagh represents an intriguing, different possibility in which one factor is at play while the other is absent. Thus, while the careers of three of the playwrights demonstrate the effectivity and consequent implications of the two factors, McDonagh’s trajectory illustrates the consequent effectivity of each factor separately and the relevant implications of such effectivity.
Defamiliarization of Spatial Metaphors for Voice in the Work of Herta Müller
Authors: Shopin Pavlo
Published: April 2021

In this article, the author analyzes spatial metaphors for voice in the work of Herta Müller. His analysis shows how she evokes spatial experience to convey her vision of voice. Drawing on conceptual metaphor theory and Viktor Shklovsky’s concept of defamiliarization, the author argues that Müller defamiliarizes conventional spatial language used to make sense of voice. She encourages her readers to recognize the figurative meaning of such language and invites them to build new and original associations between space and voice. The analysis focuses on verticality, figure-ground organization, motion, and container image schema as source domains for voice. The author’s research demonstrates that voice is associated with different sensory experiences and does not exist as a purely acoustic image. He claims that metaphorical conceptualization helps understand voice because the latter has different meanings depending on the context and is a complex physical, linguistic, and cultural phenomenon. The article concludes that Müller both relies on and defamiliarizes the tentative yet motivated association between space and voice.
Violência física contra mulheres: estudo em três bases de dados nacionais (SINAN, SIH e SIM) e no contexto da COVID-19
Authors: Bordoni Polyanna Helena Coelho , De Assis Fernando Henrique , De Oliveira Naiana Andrade , Aguiar Raiza de Almeida , Da Silva Valéria Corrêa , Bordoni Leonardo Santos
Published: April 2021

Objetivo: avaliar agressões físicas contra mulheres, ocorridas em Minas Gerais em 2018 e no contexto da pandemia de COVID-19 (internações entre março a agosto de 2019/2020). Métodos: foi realizado estudo transversal com dados do Sistema de Informação de Agravo de Notificação (SINAN), Sistema de Informações Hospitalares (SIH) e o Sistema de Informação sobre Mortalidade (SIM). Resultados: a faixa etária mais prevalente abrangeu 15 a 49 anos. A raça/cor parda foi a mais comum, bem como o ensino fundamental incompleto. A residência foi o local onde ocorreram mais agressões, sendo os parceiros íntimos e os familiares os principais agressores. A razão de prevalência de internação para 2020/2019 foi de 0,84 (IC 0,73-0,96). Houve perda de informações em todas as bases de dados, mas, principalmente, nos dados do SIH. Conclusões: as mulheres com maior vulnerabilidade social foram as mais afetadas, e a violência doméstica a mais comum. Restrição de acesso aos serviços de saúde pode ter influenciado na redução da prevalência de internações no contexto da pandemia. Esses dados podem contribuir para o entendimento e melhor dimensionamento do problema, podendo direcionar a formulação de melhores políticas públicas, sendo importante o investimento em melhorias no registro dos casos.
Αφηγηματικά και λειτουργικά μοτίβα και συμμετοχικός σχεδιασμός ψηφιακών παιχνιδιών για την αειφορική διαχείριση δημόσιου χώρου
Authors: Τραγαζίκης Παναγιώτης
Published: April 2021

Η διατριβή στοχεύει να εξετάσει τις παραμέτρους ανάπτυξης και χρήσης ψηφιακών παιχνιδιών, τα οποία παίζονται με φορητές συσκευές και διαπραγματεύονται ζητήματα αειφορίας, ακολουθώντας μια διαδικασία βασισμένη στην αφήγηση, ενταγμένη στην κανονική ροή του σχολικού προγράμματος, με μαθητές της έκτης τάξης του δημοτικού, οι οποίοι συμμετέχουν στο σχεδιασμό των παιχνιδιών. Ειδικότερα, προκειμένου να πετύχει την κατανόηση διαδικασιών επίλυσης προβλημάτων, τα οποία αφορούν το δημόσιο χώρο και την αειφορική του διαχείριση, ώστε να ενισχύσει την πιθανότητα ανάληψης δράσης, χρησιμοποιεί τον σχεδιασμό ψηφιακών παιχνιδιών, ενσωματώνοντας τη γνώμη των μαθητών σε σχέση με τα σχεδιαστικά μοτίβα των ψηφιακών παιχνιδιών. Για το λόγο αυτό ασχολήθηκε, με την καταγραφή των σχεδιαστικών μοτίβων ψηφιακών παιχνιδιών μαθησιακού σκοπού τα οποία αρέσουν στους μαθητές, χρησιμοποίησε τα μοτίβα αυτά για τη δημιουργία των παιχνιδιών βασισμένων στην έννοια του λειτουργικού μοτίβου και έλαβε υπόψη τις προτάσεις σχεδιασμού των μαθητών. Επιπλέον χρησιμοποίησε ως σχεδιαστική βάση την αφήγηση, με τη δημιουργία μιας ιστορίας, η οποία αναπτύχθηκε βασισμένη στο αφηγηματικό μοντέλο του Προπ και η οποία δημιουργήθηκε συνεργατικά από την ομάδα των μαθητών. Η αξιολόγηση του τελικού αποτελέσματος η οποία έγινε από μια άλλη ομάδα μαθητών της ίδιας τάξης, διαπίστωσε, ότι τόσο η διαδικασία όσο και το περιεχόμενο των παιχνιδιών, δύναται να αποτελέσουν μια ικανοποιητική αφετηρία για την ανάληψη αειφορικών δράσεων, σε ένα σύστημα που αφορά το δημόσιο χώρο.
A Hydrostratigraphic Framework for the Paleozoic Bedrock of Southern Ontario
Authors: Carter Terry R. , Fortner Lee D. , Russell Hazen A.J. , Skuce Mitchell E. , Longstaffe Fred J. , Sun Shuo
Published: April 2021

Groundwater systems in the intermediate to deep subsurface of southern Ontario are poorly understood, despite their value for a number of societal uses. A regional hydrostratigraphic framework is a necessary precursor for improving our understanding of groundwater systems and enabling development of a 3-D hydrostratigraphic model to visualize these groundwater systems. This study is a compilation and integration of published and unpublished geological, hydrogeological, hydrochemical and isotopic data collected over the past 10 years to develop that framework.Bedrock is covered by a thin veneer of surficial sediments that comprise an aquifer/aquitard system of considerable local variability and complexity. Aquifers in the bedrock are thin and regionally extensive, separated by thick aquitards, within a well-defined lithostratigraphic framework and a well-developed hydrochemical depth zonation comprising a shallow fresh water regime, an intermediate brackish to saline sulphur water regime, and a deep brine regime of ancient, evaporated seawater. Occurrence and movement of groundwater in shallow bedrock is principally controlled by modern (Quaternary) karstic dissolution of subcropping carbonate and evaporite rocks, and in the intermediate to deep subsurface by paleokarst horizons developed during the Paleozoic. Flow directions in the surficial sediments of the shallow groundwater regime are down-gradient from topographic highs and down the regional dip of bedrock formations in the intermediate regime. Shallow karst is the entry point for groundwater penetration into the intermediate regime, with paleo-recharge by glacial meltwater and limited recent recharge by meteoric water at subcrop edges, and down-dip hydraulic gradients in confined aquifers. Hydraulic gradient is up-dip in the deep brine regime, at least for the Guelph Aquifer and the Cambrian Aquifer, with no isotopic or hydrochemical evidence of infiltration of meteoric water and no discharge to the surface.Fourteen bedrock hydrostratigraphic units are proposed, and one unit comprising all the surficial sediments. Assignment of lithostratigraphic units as hydrostratigraphic units is based principally on hydrogeological characteristics of Paleozoic bedrock formations in the intermediate to deep groundwater regimes, below the influence of modern meteoric water. Carbonate and evaporite rocks which form aquitards in the subsurface may form aquifers at or near the surface, due to karstic dissolution by acidic meteoric water, necessitating compromises in assignment of hydrostratigraphic units.