bluuebunny/crossref_metadata_2025 huggingface dataset:
Enhanced numeracy skills following team-based learning in United States pharmacy students: a longitudinal cohort study
Authors: Carpenter Rob Edwin , Coyne Leanne , Silberman Dave , Takemoto Jody Kyoto
Published: October 2022

Purpose: The literature suggests that the ability to numerate cannot be fully understood without accounting for the social context in which mathematical activity is represented. Team-based learning (TBL) is an andragogical approach with theoretical links to sociocultural and community-of-practice learning. This study aimed to quantitatively explore the impact of TBL instruction on numeracy development in 2 cohorts of pharmacy students and identify the impact of TBL instruction on numeracy development from a social perspective for healthcare education.Methods: Two cohorts of students were administered the Health Science Reasoning Test-Numeracy (HSRT-N) before beginning pharmacy school. Two years after using TBL as the primary method of instruction, both comprehensive and domain data from the HSRT-N were analyzed.Results: In total, 163 pharmacy student scores met the inclusion criteria. The students’ numeracy skills measured by HSRT-N improved after 2 years of TBL instruction.Conclusion: Numeracy was the most significantly improved HSRT-N domain in pharmacy students following two years of TBL instruction. Although a closer examination of numeracy development in TBL is warranted, initial data suggest that TBL instruction may be an adequate proxy for advancing numeracy in a cohort of pharmacy students. TBL may encourage a social practice of mathematics to improve pharmacy students’ ability to numerate critically.
The Program on the Surgical Control of the Hyperlipidemias (POSCH) and the Lipid Regulatory Hypothesis
Authors: Feeman, Jr. William E. , Williams Stanley E. , Buchwald Henry
Published: October 2022

Background: The Lipid Regulatory Hypothesis (LRH) states that the best way to regress atherosclerotic plaque is to simultaneously decrease the cholesterol being transported into the arterial wall by low-density lipoprotein (LDL) and increase the cholesterol being removed from the arterial wall, via reverse cholesterol transport, by high-density lipoprotein (HDL). The cholesterol retention fraction (CRF) is defined as (LDL cholesterol minus HDL cholesterol) divided by LDL cholesterol. The Program on the Surgical Control of the Hyperlipidemias (POSCH), which employed partial ileal bypass as the intervention modality, was selected for verification of the LRH and the validity of the CRF.
Methods: POSCH coronary arteriographic plaque progression or non-progression (stabilisation/regression) from baseline to 3 years was stratified on a five-by-five factorial grid with 25 cohort cells combining LDL cholesterol and HDL cholesterol changes from baseline to 1 year following intervention. Predictive capacity for arteriography changes of LDL cholesterol and CRF were compared. Statistics used were logistic regressions.
Results: There were 731 paired arteriographic assessments of individual POSCH patients: 163 progression (22%) and 568 non-progression (stabilisation/regression) (78%). A reciprocal LDL cholesterol and HDL cholesterol relationship represented as a five-by-five factorial showed non-progression above and progression below the dividing diagonal. 100% (163/163) of patients with plaque progression had a rise in their CRF; and 100% (568/568) of patients with plaque non-progression had a fall in their CRF. LDL cholesterol, HDL cholesterol, and CRF were all highly significant predictors of plaque progression and non-progression (p<0.0001).
Conclusion: In POSCH, the partial ileal bypass-induced changes in the LDL cholesterol, HDL cholesterol, and the CRF are highly correlated with the sequential coronary arteriography changes of plaque progression and non-progression. This study affirms that individual patient prognosis can be predicted by the magnitude of response to lipid intervention.
Spotlight on Acne
Authors: Lloyd Jenny
Published: October 2022

Prof Fabbrocini gave an overview of the current European and American guidelines for acne treatment. She highlighted some important new recommendations from the Global Alliance consensus, including that oral isotretinoin should be continued until full acne clearance and that early, effective treatment is important to minimise scarring. She then discussed various gaps between guidelines and clinical practice, including adherence, scar prevention, physical modalities, dermocosmetics, skin of colour, diet, and truncal acne. Dr Stein Gold then spoke about the epidemiology of acne and the traditional and emerging concepts relating to its pathogenesis. She discussed the important role of inflammation, which is now known to be present throughout acne progression, and highlighted that inflammation is not just a response to Cutibacterium acnes proliferation. She then discussed the impact of the inflammatory process on the risk of acne scarring, the negative effects of scarring on patients, and the importance of early treatment to minimise or even prevent scarring; the problem of post-inflammatory hyperpigmentation (PIH) in patients with skin of colour; and adult acne, which predominantly affects women. Lastly, she highlighted the under-recognised problem of truncal acne which, despite affecting approximately 50–60% of patients with facial acne, lacks specific treatment guidelines. Prof Tan then discussed some interesting studies on the current and emerging treatments for PIH (tretinoin 0.1% cream, azelaic acid 15.0% gel, dapsone 7.5% gel), adult female acne (dapsone 5.0% gel, azelaic acid 15.0% gel, adapalene 0.1% gel, spironolactone), acne scarring (adapalene 0.3% gel, adapalene 0.1% or 0.3% plus benzoyl peroxide [BPO] 2.5% gel), and truncal acne (dapsone 7.5% gel, azelaic acid 15.0% foam, drospirenone 3 mg/ethinyl oestradiol 0.02 mg, trifarotene 50 µg/g cream). Trifarotene is one of the first treatments that has been shown to be effective and safe for the treatment of truncal acne in a robust Phase III programme.
A Smart Learner to Smart Employee: Moodle as a Smart E-learning Platform to Strengthen the Smartness of University Students in a Developing Country
Authors: Sylvestre Munyengabe , Regine Musengimana , Providence Sibomana , Karungi Cissy , Gaspard Aparayi
Published: October 2022

It is said that there is no country which is better than its education system. Education systems define in general the overall targets of countries. In the current study, researchers intended to investigate students and lecturers’ perceptions about the attainment of the smartness required at work by the mean of using Learning Management System (Moodle) as well as integrating technology into teaching and learning activities. The study was qualitative, the thematic approach was used to analyze qualitative views collected from a sample of university’s lecturers and students. The results revealed that Moodle can strengthen lecturers and students’ attitudes to cope with technological use. It was also found that university teaching staff and students have to spend much efforts to acquire new technological skills to serve education systems in developing countries. Students and lecturers’ perceptions positively supported that Moodle as well as other Learning Management System when used properly may influence learning and teaching conditions for better attaining the required skills to become smart employees. The study recommended the use of Moodle and the continuation of researching on what could motivate both students and lecturers in their everyday lives.
The representation of gendered social actors across five manosphere communities on Reddit
Authors: Krendel Alexandra , McGlashan Mark , Koller Veronika
Published: October 2022

This paper investigates the representation of gendered social actors in a specialised corpus of 10.9 million words, collected from five Reddit communities associated with the so-called ‘manosphere’: incels (involuntary celibates), Men Going Their Own Way (male separatists), pick-up artists, men’s rights activists, and a group dedicated to wider discussions of ‘red pill’ philosophy. Thirty-four gendered social actor terms were identified as key-key-words across the manosphere corpora. Both male and female social actors are referenced using relational terms, while the latter are also referenced using derogatory terms and the former are referenced using terms for kinship and in-group identification. We then analysed the consistent collocates ( Baker et al., 2008 ) of the four most frequent gendered social actor terms ( women, girls, men and guys), to establish the topics, descriptions and actions associated with the social actors across the five groups. Gendered social actors were constructed in essentialist dichotomies, with women and girls, although objectified and passivated in dating/sexual contexts, being represented as violent towards male social actors and as holding a privileged position over men in wider society. The anti-feminist ideology reflected in manosphere discourse can be seen as a more extreme version of mainstream discourse. To the extent that manosphere discourse spreads beyond dedicated forums and websites, its views will be re-imported into the mainstream, leading to a wider radicalisation.
A rare cause of hematuria, intravesical ectopic pregnancy; case report
Authors: Tunçekin Adem , İncebıyık Adnan , Demir Mehmet , Yağmur İsmail , Pelit Eyyup Sabri , Katı Bülent , Çiftçi Halil
Published: October 2022

Intravesical ectopic pregnancy is a very rare condition. Unlike traditional ectopic pregnancies, patients generally present with hematuria. Our case presented with abdominal pain and urinary bleeding. Abdominal tenderness was observed on physical examination. The ß-HCG was measured as 10033 IU / ml. In ultrasonography, an appearance compatible with a vesicouterine fistula tract and an ectopic gestational sac in the bladder were observed. In cystoscopy, a mass compatible with a fistula tract ostium and ectopic gestational sac was observed at the junction of the right side of the bladder and the posterior wall. The observed structure was resected and cauterized to achieve hemostasis. No complications were observed during the follow-up, and the patient was discharged. Ectopic pregnancy should be one of the differential diagnoses of patients with a history of pelvic surgery who present with complaints of menstrual delay and hematuria. Keywords: vesical pregnancy, vesicouterine fistula, hematuria
A survey on the knowledge, opinions, and approaches in clinical practice of urology physicians about hyperbaric oxygen therapy application in Fournier gangrene
Authors: Özgök Kangal Kübra , Demir Kübra Canarslan
Published: October 2022

Objective: Fournier gangrene is a form of necrotizing fasciitis with high mortality. Hyperbaric oxygen therapy (HBOT) is a successful and supportive treatment option for Fournier’s gangrene (FG). This study aimed to analyze urologists’ knowledge, opinions, and preferences about HBOT application in FG. Material and Methods: An online or face-to-face questionnaire was applied to physicians who are experts in the field of Urology or who have been continuing Urology residency training for at least one year. Results: Ninety urology physicians filled out the questionnaire. Most of them (56.4%) never refer FG cases to HBOT. Physicians (55.3%) mostly preferred HBOT only in patients unresponsive to surgical debridement and antibiotherapy. Besides, 27.3% of them stated they had no information when asked to self-assess their knowledge. Only 12 physicians (13.3%) had previously been in an HBOT center, and 15 (16.7%) physicians had participated in a scientific study on HBOT. Only three physicians (3.4%) stated HBOT was not beneficial to FG patients. Urologists’ opinions about HBOT efficiency in FG were examined (3-point-Likert type questions) in 5 questions; the median score was 2 points (minimum-maximum: 1-3 points). On the other hand, physicians who did not know HBOT had more negative opinions about HBOT efficiency in FG (p = 0.002). Conclusion: Urology physicians’ knowledge of HBOT, their doubts about HBOT in FG, and their relatively low experience with HBOT are clearly shown in this study. Therefore, urology physicians should be encouraged to increase their HBOT experience in FG and participate in scientific studies. Also, Urology Associations should discuss HBOT efficiency more effectively in guidelines and meetings. Keywords: Fournier’s gangrene, hyperbaric oxygenation, questionnaire, urologists
The impact of COVID-19 pandemic on urology residency in Turkey: a nationwide survey
Authors: Kalkanlı Arif , Çilesiz Nusret Can , Gezmiş Cem Tuğrul , Kaya Coşkun , Fikri Onur , Kadıoğlu Ateş
Published: October 2022

Objective: The Covid-19 pandemic, which affects all areas of life, has also deeply affected academic and health services. There has previously been no assessment of the effects of the pandemic on the academic and health services of urology residents in Turkey, for this purpose, a survey was conducted. Material and Methods: The survey consisted of a total of 31 questions under four main topics (education and research activities, working conditions in health services, social-psychological effects, and personal health) and was carried out between July-August 2020. The survey was 89 urology training centers in Turkey; among them, 76 (85.4%; 38 universities and 38 state hospitals) completed and returned the questionnaire. Results: The average weekly education hours decreased (2.43±2.46 hours to 1.3±1.8 hours; p=.00) and 67 centers (88.15%) used new technologies such as webinars and videoconferencing. The time devoted to weekly research activities also decreased during the pandemic (2.15±2.54 hours to 1.8±1.93 hours; p<0.001). However, university hospitals increased their research activities (9.9%), while state hospitals decreased (44%). The average weekly outpatient clinic hours decreased from 86.23±86.54 to 37.22±19.88 (p<0.001) and the regression was higher in state hospitals (63.61%) compared to university hospitals (42.41%) (p <0.05). A significant decrease was observed in the number of operations per week compared to the pre-pandemic period (from 40.7±24.25 to 14.3±16.44; p<0.001). In addition, 74 centers (97.36%) reported that they continued to perform emergency urological cases and 41 centers (53.9%) reported that the total working hours decreased, but 72 centers (94.7%) reported that they were employed in non-urology areas such as Covid outpatient clinics or services. For the residents, 10 centers (13.15%) provided childcare, 55 centers (72.36%) provided accommodation, and 18 centers (23.68%) provided transportation, but 33 centers (43.42%) lacked protective personal equipment and 26 centers (34.21%) gave leave to employees with comorbidity. Residents were concerned about not having enough surgical cases in 57 centers (75%), the transmission of Covid-19 to their family in 73 centers (96.05%), and in 34 centers (44.73%), they had moved away from their homes to protect their families. Furthermore, residents were isolated in 25 centers (32.89%) and swabs were taken in 54 centers (71.85%) due to the query (doubt, suspicion) of illness. Residents were diagnosed with Covid-19 in 14 centers (18.42%). Conclusion: This survey has shown that as the Covid-19 pandemic affects all areas of life, it also causes serious negatives in the academic (educational and research), social, and psychological lives of urology residents. Keywords: COVID-19, residency, pandemic, urology training, surgical training
Systematic versus cognitive targeted biopsy: evaluation of parameters related to clinically significant prostate cancer and comparison of detection rates
Authors: Ersöz Cevper , İlktaç Abdullah , Kalkan Senad , Kayalı Yunus , Akbulut Habib , Toprak Hüseyin , Doğan Bayram
Published: October 2022

Objective: This study aims to compare the clinically significant prostate cancer (csPCa) detection rates of cognitive targeted biopsy (CTB) and systematic biopsy (SB) and to reveal the factors affecting csPCa detection rates. Material and Methods: Patients diagnosed with localized prostate cancer between 2016-2019 were evaluated retrospectively. Patients who underwent SB and concomitant CTB were recorded. The number of cores taken from the index lesion in CTB, age, prostate-specific antigen (PSA) level, Gleason score, International Society of Urological Pathology (ISUP) grade, Prostate Imaging and Data Reporting System (PIRADS) score, the diameter of index lesion, and digital rectal examination (DRE) findings was recorded. We also studied whether there was a concordance between the localization of the lesion on MRI (magnetic resonance imaging) and the localization of the nodule detected on DRE. Results: Eighty patients were included in the study. csPCa was detected in 55 (68.7%) patients with SB, whereas CTB alone detected csPCa in 35 (43.7%) patients (p<0,01). SB missed 2 patients with csPCa, but 35% of the men with csPCa would be missed by CTB. Detection rates of csPCa in SB and CTB were significantly higher in patients with a concordance between DRE and mpMRI (p= 0.012 and p<0.01, respectively). In patients who had csPCa in CTB, significant differences were detected in the mean age, prostate volume, PSA, lesion diameter, number of cores, and PIRADS score (p=0.005, p=0.02, p=0.005, p=0.003, p=0.017, and p=0.002, respectively) Conclusion: SB maintains its importance in the diagnosis of csPCa. CTB can be preferred in patients with larger lesions. Keywords: Prostate cancer, prostate biopsy, magnetic resonance imaging, targeted biopsy
Does YouTube videos have reliable information on Penile Doppler Ultrasonography?
Authors: Sökmen Doğukan , Sökmen Bedriye Koyuncu , Sertkaya Zülfü , Keskin Emin Taha
Published: October 2022

Objective: Our objective was to evaluate the accuracy and reliability of YouTube videos about penile doppler ultrasonography (PDU), a diagnostic tool for erectile dysfunction. Material and Methods: Videos on YouTube were searched using the term “Penile Doppler Ultrasonography”. The most related 48 videos were included in to study. For each video, uploader type (physician, patient, or YouTuber), target group (physicians or non-physicians), video duration, upload date, daily view count, the total number of views, and the number of likes and comments were recorded. The reliability and quality of the content of these videos included in the study were evaluated using JAMA, DISCERN, and GQS scores. Results: The physicians uploaded all of the videos used in the study. It was shown that 27 (56%) of the videos were prepared for physicians, and the remaining videos were prepared for non-physicians. All the videos had general information about the PDU, 32 (67%) videos gave theoretical information, and 23 (48%) videos gave information about the application of the PDU. When the videos were examined according to the target group, it was shown that the videos prepared for physicians had a longer duration (p=,001) but had a lower number of comments and views (p=,012 and p=.046, respectively). In addition, when the video content quality and reliability were examined, the average JAMA score was 2.5, the GQS score was 3.44, and the DISCERN score was 52.2. It was found that the quality and reliability scores were statistically higher in the videos prepared for physicians (p<0.05). Conclusion: As a source of knowledge about health care, YouTube is frequently used by doctors and other people (including patients). High-quality information is very important for both physicians and individual patients. In this study, we showed that videos uploaded by physicians had reliable content, but these high-quality videos had longer duration and lower view count. In order to improve the quality of PDU-related videos, physicians should upload high-quality videos, and YouTube algorithms should direct patients to high-quality videos. Keywords: penile, doppler, ultrasonography, YouTube
ON AUTOMORPHISMS OF LIE ALGEBRA OF SYMMETRIC POLYNOMIALS
Authors: FINDIK Şehmus , ÖĞÜŞLÜ Nazar Şahin
Published: October 2022

Let $L_{n}$ be the free Lie algebra of rank $n$ over a field $K$ of characteristic zero, $L_{n,c}=L_{n}/(L_{n}''+\gamma_{c+1}(L_{n}))$ be the free metabelian nilpotent of class $c$ Lie algebra, and $F_{n}=L_{n}/L_{n}''$ be the free metabelian Lie algebra generated by $x_1,\ldots,x_n$ over a field $K$ of characteristic zero.
We call a polynomial $p(X_n)$ in these Lie algebras {\it symmetric} if $p(x_1,\ldots,x_n)=p(x_{\pi(1)},\ldots,x_{\pi(n)})$ for each element of the symmetric group $S_n$. The sets $L_n^{S_n}$, $F_n^{S_n}$, and $L_{n,c}^{S_n}$ of symmetric polynomials coincides with the algebras of invariants of the group $S_n$ in $L_{n}$, $F_{n}$, and $L_{n,c}$, respectively. We determine the groups $\text{\rm Inn}(L_{n,c}^{S_n})\cap \text{\rm Inn}(L_{n,c})$ and $\text{\rm Inn}(F_{n}^{S_n})\cap \text{\rm Inn}(F_{n})$ of inner automorphisms of the algebras $L_{n,c}^{S_n}$ and $F_{n}^{S_n}$ in the groups $\text{\rm Inn}(L_{n,c})$ and $\text{\rm Inn}(F_{n})$, respectively. In particular, we obtain the descriptions of the groups $\text{\rm Aut}(L_{2}^{S_2})\cap \text{\rm Aut}(L_{2})$ and $\text{\rm Aut}(F_{2}^{S_2})\cap \text{\rm Aut}(F_{2})$ of automorphisms of the algebras $L_{2}^{S_2}$ and $F_{2}^{S_2}$ in the groups $\text{\rm Aut}(L_{2})$ and $\text{\rm Aut}(F_{2})$, respectively.
Letters to leaders: Political participation and punctuated equilibrium theory
Authors: Casey Daniel
Published: October 2022

Is there a steady, consistent flow of public opinion to political leaders? Or are the public usually fairly quiet, with occasional periods of shouting from rooftops? Research has shown that policy agendas are punctuated, with long periods of stasis and short periods of major change, there is a paucity of research on punctuation of public opinion and political participation. This paper advances punctuated equilibrium theory by applying this approach to political participation. I use new datasets of the volume and topic of letters to the Australian Prime Minister and American President. I find clear evidence that that individuals’ decision to participate is punctuated. I also find that topics with a high volume of letters have a higher level of punctuation, supporting the theory that punctuations can occur when the conflict is expanded, and public is drawn into the conflict. These results extend punctuated equilibrium further up the policy process chain.
Arbuscular mycorrhizal species vary in their impact on nutrient uptake in sweet corn (Zea mays) and butternut squash (Cucurbita moschata)
Authors: Carrara Joseph E. , Heller Wade P.
Published: October 2022

An increasing demand for organic produce, coupled with the need to reduce reliance on the diminishing resource of rock phosphate, has bolstered interest in the use of arbuscular mycorrhizae (AMF) as a biofertilizer. AMF are symbiotic fungi that colonize the roots of most crops and transfer nutrients from the soil to their hosts in exchange for carbon. While past studies have shown that mixed AMF communities grown from field soil can increase the yield of many crops, the targeted use of individual AMF species on host plants is a promising avenue to enhance nutrient uptake. We inoculated sweet corn (Zea mays) and butternut squash (Cucurbita moschata) seedlings with nine individual species of AMF and one mixed indigenous population to determine the most beneficial symbionts for enhancing mineral nutrient concentration and yield. Overall, level of root colonization was correlated with phosphorus (P) concentration of aboveground biomass. Corn and squash grown in association with AMF species in the Rhizophagus genus had the highest level of root colonization and tissue P concentration. Claroideoglumus etunicatum and Gigaspora margarita increased calcium (Ca) and magnesium (Mg) concentration in corn and Gigaspora rosea increased calcium in squash. S. constrictum and G. rosea positively impacted sweet corn seedling biomass. Based on this evidence, AMF species vary in their benefit to plant nutrient uptake and the most beneficial species depend on host. Further research on the effectiveness of inoculating individual AMF species across a range of hosts and ecosystems will prove useful in the development of host-targeted AMF biofertilizers.
A biomimetic synthetic nanofiber-based model for anterior cruciate ligament regeneration
Authors: Adeoye Abass Ojo , Mukasheva Fariza , Smatov Smail , Khumyrzakh Bakhytbol , Kadyr Sanazar , Shulgau Zarina , Erisken Cevat
Published: October 2022

Reconstructed ACL cannot completely restore its functions due to absence of physiologically viable environment for optimal biomaterial-cell interaction. Currently available procedures only mechanically attach grafts to bone without any biological integration. How the ACL cells perform this biological attachment is not fully understood partly due to the absence of appropriate environment to test cell behavior both in vitro and in vivo. Availability of biomimetic models would enable the scientists to better explore the behavior of cells at health and during tissue healing. In this study, it is hypothesized that the collagen fibril diameter distribution in rat ACL changes from a bimodal distribution in the healthy ACL to a unimodal distribution after injury, and that this change can be mimicked in synthetic nanofiber-based constructs. This hypothesis was tested by first creating an injured rat ACL model by applying a mechanical tensile force to the healthy ACL tissue until rupture. Secondly, the collagen fibril diameter distributions of healthy and injured ACL tissue were determined, and polycaprolactone (PCL) constructs were created to mimic the distributions of collagen fibrils in healthy and injured tissues. Findings reveal that the fiber diameter distribution of aligned bimodal PCL constructs were similar to that of the collagen fibrils in native ACL tissue. This study is significant because suggested bimodal and unimodal fibrous model constructs, respectively, represent a healthy and injured tissue environment and the behavior of ACL cells cultured on these constructs may provide significant input on ACL regeneration mechanism.
BIM leadership theory for organisational BIM transformation
Authors: Olugboyega Oluseye
Published: October 2022

Construction firms are struggling to stay in business as a result of BIM’s new and compelling business model and potential. As a result, businesses must adapt their current operations to the BIM paradigm by developing new organisational leadership capabilities. While such BIM leadership capacity is critical in designing, advancing, and driving a competitive and successful BIM transformation, BIM researchers have largely ignored it. Thus, this research explores the leadership capacities to drive BIM transformation in construction organisations in order to determine whether it will provide a leadership model as a solution to the leadership demands of organisations undergoing BIM transformation. The study design was a confirmatory sequential mixed methods research strategy that included a theoretical framework established through literature synthesis, qualitative grounded theory, and artificial intelligence (AI)-based modelling. Following the GT analysis, leadership capacity to drive organisational BIM transformation equates to the capability to develop a BIM-friendly leadership orientation, build a BIM-focused leadership procedure, perform BIM-related leadership responsibilities, generate a BIM-enabled leadership environment, and reach maturity within the realms of these strengths. The overall results of the AI-based modelling demonstrated that the acceptable capacity needed by the leadership that is pivoting organisational BIM transformation is the capability to coordinate functions, individuals, and transition alignment; produce BIM-related policies and a positive atmosphere for BIM implementation; and impartiality in recruiting individuals for BIM leadership roles. The study’s findings have implications for targeting key initiatives that might aid leaders in constructing adaptation strategies for organisational BIM transformation.
Potential Mechanisms of the Impact of Hepatocyte Growth Factor Gene-Modified Tendon Stem Cells on Tendon Healing
Authors: Zhang Mingzhao , Liu Hengchen , Shi Manyu , Zhang Tingting , Lu Wenjun , Yang Shulong , Cui Qingbo , Li Zhaozhu
Published: October 2022

The therapeutic impact of stem cells is potentially largely attributable to secretion of exosomes and soluble factors. The present study evaluates the impact of hepatocyte growth factor (HGF)–expressing tendon stem cells (TSCs) on tendon healing in a rat model. Patellar tendon TSCs were isolated and underwent transfection with lentiviral vectors containing HGF or green fluorescent protein (GFP) genes. In vivo, immunohistochemistry of tendons sampled 1 week postsurgery demonstrated that all stem cell–treated groups exhibited higher numbers of CD163+ M2 monocytes and IL-10+ cells (anti-inflammatory), and lower numbers of CCR7+ M1 monocytes and IL-6+ as well as COX-2+ cells (pro-inflammatory). Effects were most pronounced in the HGF-expressing TSCs (TSCs + HGF) treated group. Histology ± immunohistochemistry of tendons sampled 4 and 8 weeks postsurgery demonstrated that all stem cell–treated groups exhibited more ordered collagen fiber arrangement and lower levels of COLIII, α-SMA, TGF-β1, and fibronectin (proteins relevant to fibroscarring). Effects were most pronounced in the TSCs + HGF–treated group. For the in vitro study, isolated tendon fibroblasts pretreated with TGF-β1 to mimic the in vivo microenvironment of tendon injury were indirectly cocultured with TSCs, TSCs + GFP, or TSCs + HGF using a transwell system. Western blotting demonstrated that all stem cell types decreased TGF-β1-induced increases in fibroblast levels of COX-2, COLIII, and α-SMA, concomitant with decreased activation of major TGF-β1 signaling pathways (p38 MAPK, ERK1/2, but not Smad2/3). This effect was most pronounced for TSCs + HGF, which also decreased the TGF-β1-induced increase in activation of the Smad2/3 signaling pathway. The presence of specific inhibitors of these pathways during fibroblast TGF-β1 stimulation also attenuated increases in levels of COX-2, COLIII, and α-SMA. In conclusion, TSCs + HGF, which exhibit HGF overexpression, may promoting tendon healing via decreasing inflammation and fibrosis, perhaps partly via inhibiting TGF-β1-induced signaling. These findings identify a novel potential therapeutic strategy for tendon injuries, warranting additional research.
Heterogeneity and regulation of oligodendrocyte morphology
Authors: Osanai Yasuyuki , Yamazaki Reiji , Shinohara Yoshiaki , Ohno Nobuhiko
Published: October 2022

Oligodendrocytes form multiple myelin sheaths in the central nervous system (CNS), which increase nerve conduction velocity and are necessary for basic and higher brain functions such as sensory function, motor control, and learning. Structures of the myelin sheath such as myelin internodal length and myelin thickness regulate nerve conduction. Various parts of the central nervous system exhibit different myelin structures and oligodendrocyte morphologies. Recent studies supported that oligodendrocytes are a heterogenous population of cells and myelin sheaths formed by some oligodendrocytes can be biased to particular groups of axons, and myelin structures are dynamically modulated in certain classes of neurons by specific experiences. Structures of oligodendrocyte/myelin are also affected in pathological conditions such as demyelinating and neuropsychiatric disorders. This review summarizes our understanding of heterogeneity and regulation of oligodendrocyte morphology concerning central nervous system regions, neuronal classes, experiences, diseases, and how oligodendrocytes are optimized to execute central nervous system functions.
The modulation of potassium channels by estrogens facilitates neuroprotection
Authors: Li Xian-Tao
Published: October 2022

Estrogens, the sex hormones, have the potential to govern multiple cellular functions, such as proliferation, apoptosis, differentiation, and homeostasis, and to exert numerous beneficial influences for the cardiovascular system, nervous system, and bones in genomic and/or non-genomic ways. Converging evidence indicates that estrogens serve a crucial role in counteracting neurodegeneration and ischemic injury; they are thereby being considered as a potent neuroprotectant for preventing neurological diseases such as Alzheimer’s disease and stroke. The underlying mechanism of neuroprotective effects conferred by estrogens is thought to be complex and multifactorial, and it remains obscure. It is well established that the K+ channels broadly expressed in a variety of neural subtypes determine the essential physiological features of neuronal excitability, and dysfunction of these channels is closely associated with diverse brain deficits, such as ataxia and epilepsy. A growing body of evidence supports a neuroprotective role of K+ channels in malfunctions of nervous tissues, with the channels even being a therapeutic target in clinical trials. As multitarget steroid hormones, estrogens also regulate the activity of distinct K+ channels to generate varying biological actions, and accumulated data delineate that some aspects of estrogen-mediated neuroprotection may arise from the impact on multiple K+ channels, including Kv, BK, KATP, and K2P channels. The response of these K+ channels after acute or chronic exposure to estrogens may oppose pathological abnormality in nervous cells, which serves to extend our understanding of these phenomena.
Synthesis and evaluation of 3-alkynyl-5-aryl-7-aza-indoles as broad-spectrum antiviral agents
Authors: Martinez-Gualda Belén , Graus Mirthe , Camps Anita , Vanhulle Emiel , Saul Sirle , Azari Siavash , Nhu Tran Do Hoang , Vangeel Laura , Chiu Winston , Neyts Johan , Schols Dominique , Einav Shirit , Vermeire Kurt , De Jonghe Steven
Published: October 2022

RNA viral infections, including those caused by respiratory syncytial virus (RSV), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and Venezuelan Equine encephalitis virus (VEEV), pose a major global health challenge. Here, we report the synthesis and screening of a series of pyrrolo[2,3-b]pyridines targeting RSV, SARS-CoV-2 and/or VEEV. From this campaign, a series of lead compounds was generated that demonstrated antiviral activity in the low single-digit micromolar range against the various viruses and did not show cytotoxicity. These findings highlight the potential of 3-alkynyl-5-aryl-7-aza-indoles as a promising chemotype for the development of broad-spectrum antiviral agents.
Identification of in vivo induced antigens of the malacosporean parasite Tetracapsuloides bryosalmonae (Cnidaria) using in vivo induced antigen technology
Authors: Kumar Gokhlesh , Sudhagar Arun , Shivam Saloni , Nilsen Frank , Bartholomew Jerri L. , El-Matbouli Mansour
Published: October 2022

Tetracapsuloides bryosalmonae is a malacosporean endoparasite that causes proliferative kidney disease (PKD) in wild and farmed salmonids in Europe and North America. The life cycle of T. bryosalmonae completes between invertebrate bryozoan and vertebrate fish hosts. Inside the fish, virulence factors of T. bryosalmonae are induced during infection or interactions with host cells. T. bryosalmonae genes expressed in vivo are likely to be important in fish pathogenesis. Herein, we identify in vivo induced antigens of T. bryosalmonae during infection in brown trout (Salmo trutta) using in vivo induced antigen technology (IVIAT). Brown trout were exposed to the spores of T. bryosalmonae and were sampled at different time points. The pooled sera were first pre-adsorbed with antigens to remove false positive results. Subsequently, adsorbed sera were used to screen a T. bryosalmonae cDNA phage expression library. Immunoscreening analysis revealed 136 immunogenic T. bryosalmonae proteins induced in brown trout during parasite development. They are involved in signal transduction, transport, metabolism, ion-protein binding, protein folding, and also include hypothetical proteins, of so far unknown functions. The identified in vivo induced antigens will be useful in the understanding of T. bryosalmonae pathogenesis during infection in susceptible hosts. Some of the antigens found may have significant implications for the discovery of candidate molecules for the development of potential therapies and preventive measures against T. bryosalmonae in salmonids.
Infections of Cryptococcus species induce degeneration of dopaminergic neurons and accumulation of α-Synuclein in Caenorhabditis elegans
Authors: Kitisin Thitinan , Muangkaew Watcharamat , Sukphopetch Passanesh
Published: October 2022

Cryptococcosis in the central nervous system (CNS) can present with motor declines described as Parkinsonism. Although several lines of evidence indicate that dopaminergic (DA) neuron degeneration and α-synuclein accumulation contribute to the hallmark of Parkinsonism and Parkinson’s disease (PD), little is known about cryptococcal infections associated with neuronal degeneration. In this study, the effects of Cryptococcus neoformans and C. gattii infections on dopaminergic neuron degeneration, α-synuclein accumulation, and lifespan in Caenorhabditis elegans were investigated. The results showed that cryptococcal infections significantly (P<0.05) induced DA neuron degeneration similar to a selective cathecholamine neurotoxin 6-hydroxydopamine (6-OHDA) in C. elegans (BZ555 strain) when compared to mock infected controls. Cryptococcal infections also significantly (P< 0.05) induced α-synuclein aggregation in C. elegans (NL5901 strain). Moreover, lifespan of the infected worms was significantly decreased (P<0.0001). In conclusion, DA neurodegeneration and α-synuclein accumulation are associated with lifespan reduction during cryptococcal infection in C elegans.
mRNA, lncRNA, and circRNA expression profiles in a new aortic dissection murine model induced by hypoxia and Ang II
Authors: Li Yuanyuan , Ma Xiaozhu , Mei Shuai , Ji Yueping , Wang Dong , He Liqun , Sun Dating , Yan Jiangtao
Published: October 2022

Background and aims

Aortic dissection (AD) is a cardiovascular emergency with degeneration of the aortic media. Mounting evidence indicates obstructive sleep apnea (OSA) as an independent risk factor for AD development with unknown mechanisms. This study aims to establish a stable murine model of OSA-related AD (OSA-AD) and uncover the potential changes in gene transcripts in OSA-AD.

Materials and methods

ApoE–/–mice were exposed to the chronic intermittent hypoxia (CIH) system combined with Ang II administration to establish the OSA-AD model. Pathological staining was performed to exhibit the physiological structure of the mouse aorta. The SBC mouse ceRNA microarray was used to identify significantly differentially expressed (DE) mRNAs, DE long-non-coding RNAs (DElncRNAs), and DE circular RNAs (DEcircRNAs) in OSA-AD tissues. Subsequently, bioinformatics analysis, including Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genome (KEGG), and protein–protein interaction (PPI) analyses, were performed to evaluate the function of the significantly differentially expressed transcripts (DETs). The hub genes were confirmed using quantitative real-time polymerase chain reaction (qRT-PCR).

Results

ApoE–/–mice exposed to CIH and Ang II showed a high ratio of aortic accident (73.33%) and significant aortic diameter dilatation (1.96 ± 0.175 mm). A total of 1,742 mRNAs, 2,625 lncRNAs, and 537 circRNAs were identified as DETs (LogFC ≥ 1.5 or ≤ –1.5,P< 0.05). GO and KEGG analyses demonstrated that the differentially expressed mRNAs (DEmRNAs) were most enriched in cell proliferation, migration, apoptosis, inflammation, and hypoxia-related terms, which are closely related to aortic structural homeostasis. The PPI network contained 609 nodes and 934 connections, the hub genes were highlighted with the CytoHubba plugin and confirmed by qRT-PCR in AD tissues. KEGG pathway analysis revealed that thecis-regulated genes of DElncRNAs and circRNAs-host genes were enriched in aortic structural homeostasis-related pathways.

Conclusion

Our findings help establish ade novoOSA-AD animal model using ApoE–/–mice. Many DEmRNAs, DElncRNAs, and DEcircRNAs were screened for the first time in OSA-AD tissues. Our findings provide useful bioinformatics data for understanding the molecular mechanism of OSA-AD and developing potential therapeutic strategies for OSA-AD.
Burden of atrial fibrillation and its attributable risk factors from 1990 to 2019: An analysis of the Global Burden of Disease study 2019
Authors: Xu Shangbo , Chen Yangbo , Lin Rui , Huang Weipeng , Zhou Haoyue , Lin Yongjian , Xu Mingwei
Published: October 2022

Background

Understanding the pattern and trend of the atrial fibrillation (AF) burden are essential for developing effective preventive strategies. The purpose of this study was to estimate AF burdens and risk factors in 204 countries and territories between 1990 and 2019.

Materials and methods

Data were extracted from the Global Burden of Disease 2019, including incidence, death, disability-adjusted life-years (DALYs), and the attributable risk factors. In order to quantify changes in the age-standardized incidence rate (ASIR), age-standardized death rate (ASDR), and age-standardized DALY rate between 1990 and 2019, the estimated annual percentage change (EAPC) was used. Also, AF burden was assessed in relation to the Socio-demographic Index (SDI).

Results

Globally, there were 4,720,324 incident cases, 117,038 deaths and 8,393,635 DALYs in 2019. There were no significant changes in ASIR, ASDR, or age-standardized DALY rates from 1990 to 2019. Although the burden and trend of AF varied in different regions and countries, the ASIR, ASDR and age-standardized DALY rate were positively correlated with SDI. Furthermore, the burden of AF was higher in males and elderly. The age-standardized DALY rate worldwide was primarily attributable to high systolic blood pressure, followed by high body-mass index, alcohol use, smoking, diet high in sodium and lead exposure.

Conclusion

AF remained a major public health challenge worldwide, with substantial variation at regional and national levels. There is an urgent need to increase public awareness about AF risk factors and to bring about cost-effective interventions for AF in order to reduce its future burden.
Subduction-zone parameters that control slab behavior at the 660-km discontinuity revealed by logistic regression analysis and model selection
Authors: Nakao Atsushi , Kuwatani Tatsu , Ueki Kenta , Yoshida Kenta , Yutani Taku , Hino Hideitsu , Akaho Shotaro
Published: October 2022

The potential mechanisms that drive the behavior of subducted oceanic plates at the 660-km discontinuity are subject to debate. Here we conduct logistic regression analysis and model selection to determine the key subduction-zone parameters in natural subduction zones that discriminate the plate behavior along the discontinuity. We select the key variables based on three information criteria: leave-one-out cross-validation score (LOO), Akaike Information Criterion (AIC), and Bayesian Information Criterion (BIC). Among the 17 subduction-zone parameters analyzed, only the trench velocity, convergence rate, and trench width are selected in the simplest model that minimizes BIC. The thermal parameter and several other variables are also selected to minimize AIC and LOO. Our results suggest that a stagnant slab occurs along the 660-km discontinuity when there is a narrow oceanic plate and a retreating trench in natural subduction zones, which has also been modeled in previous numerical simulations. Neither the stress nor the deformation rate of the upper-plate margin is selected in the three optimal models, which suggests that back-arc spreading in natural subduction zones does not globally characterize plate behavior at the 660-km discontinuity, although back-arc spreading and a stagnant slab coincide in some numerical simulations. The combination of subduction-zone data analysis and numerical simulations will therefore provide deep insights into the dynamics of Earth’s deep interior.
Education for sustainable development in physical education: Program development by use of intervention mapping
Authors: Bucht Charlotta , Mess Filip , Bachner Joachim , Spengler Sarah
Published: October 2022

There is little information on the development of school-based programs to change students’ sustainability behavior. The goal of this article is to describe the systematic development and the content of a program that includes education for sustainable development in regular physical education. The Intervention Mapping approach was used as a methodological framework for program design. Participatory workshops with relevant stakeholders and experts were part of the process. Considering the physical education curriculum with its multiple objectives, four main behavioral outcomes were derived: Reduction in clothes consumption, change in diet, change in dealing with trash and increased usage of bike/public transportation. Behavior change methods were specifically selected to be suitable for physical education. The developed practical applications are in line with the physical education curriculum. It is reflected on the use of intervention mapping as a methodological framework for program design in the specific field of sustainability behavior and the equally specific setting of physical education. Benefits and limitations of the developed program are discussed.
Pancreatic β-cell hyper-O-GlcNAcylation leads to impaired glucose homeostasis in vivo
Authors: Jo Seokwon , Pritchard Samantha , Wong Alicia , Avula Nandini , Essawy Ahmad , Hanover John , Alejandro Emilyn U.
Published: October 2022

Protein O-GlcNAcylation is a nutrient and stress-sensitive protein post-translational modification (PTM). The addition of an O-GlcNAc molecule to proteins is catalyzed by O-GlcNAc transferase (OGT), whereas O-GlcNAcase (OGA) enzyme is responsible for removal of this PTM. Previous work showed that OGT is highly expressed in the pancreas, and we demonstrated that hypo-O-GlcNAcylation in β-cells cause severe diabetes in mice. These studies show a direct link between nutrient-sensitive OGT and β-cell health and function. In the current study, we hypothesized that hyper-O-GlcNAcylation may confer protection from β-cell failure in high-fat diet (HFD)-induced obesity. To test this hypothesis, we generated a mouse model with constitutive β-cell OGA ablation (βOGAKO) to specifically increase O-GlcNAcylation in β-cells. Under normal chow diet, young male and female βOGAKO mice exhibited normal glucose tolerance but developed glucose intolerance with aging, relative to littermate controls. No alteration in β-cell mass was observed between βOGAKO and littermate controls. Total insulin content was reduced despite an increase in pro-insulin to insulin ratio in βOGAKO islets. βOGAKO mice showed deficit in insulin secretion in vivo and in vitro. When young animals were subjected to HFD, both male and female βOGAKO mice displayed normal body weight gain and insulin tolerance but developed glucose intolerance that worsened with longer exposure to HFD. Comparable β-cell mass was found between βOGAKO and littermate controls. Taken together, these data demonstrate that the loss of OGA in β-cells reduces β-cell function, thereby perturbing glucose homeostasis. The findings reinforce the rheostat model of intracellular O-GlcNAcylation where too much (OGA loss) or too little (OGT loss) O-GlcNAcylation are both detrimental to the β-cell.