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DOAJ Open Access 2026
Improvement of speech perception following articulatory-target based production training for second language acquisition

Atsuo Suemitsu, Takayuki Ito, Jianwu Dang et al.

Direct training of articulatory movements can be an effective and efficient tool for second language learning. We have previously developed an articulatory target-based training method using electromagnetic articulography for second language pronunciation. In this training, an estimate of a participant's target midsagittal tongue posture is presented on a display together with the real-time position of their tongue, and used as feedback for adjusting their tongue position to the target position. We showed that Japanese participants improved their pronunciation of American English vowel /æ/, which is not in the Japanese vowel inventory, toward more native-like pronunciation following the training. The current study investigates whether this articulatory target-based training approach, which demonstrably improves production, enhances perception of the corresponding speech sounds. Seven Japanese male speakers participated, performing an ABX perceptual test before and after training, contrasting minimal pairs: /æ/-/ɑ/, /æ/-/ʌ/, and /ɑ/-/ʌ/ within consonant-vowel-consonant words. Results showed that, in spite of the large range of observed variability in individual participants' responses to the articulatory target-based training, overall, there were significant improvements in both production and perception of /æ/. Our findings suggest that motor processing related to speech production contributes to the improvement of speech perception for the second language acquisition, and shows that articulatory target-based training approaches can be useful for enhancing both production and perception in second language acquisition.

Neurosciences. Biological psychiatry. Neuropsychiatry
DOAJ Open Access 2025
PRAS40 promotes colorectal cancer stemness by enhancing glycolysis through triggering PGK1 acetylation

Chengfei Zhang, Yufei Bo, Ting Zhang et al.

Abstract Cancer stem cells (CSCs) play a pivotal role in driving colorectal cancer (CRC) progression and therapeutic resistance. However, the molecular mechanisms regulating CRC-CSC properties are not fully understood. Proline-rich Akt substrate 40 (PRAS40) is involved in various tumorigenic processes, yet little is known about its contribution to cancer stemness. In this study, we demonstrated that PRAS40 was overexpressed in CRC tissues and its elevated expression positively correlated with poor patient survival. Genetic ablation of PRAS40 suppressed tumorigenesis in CRC mouse models. Notably, PRAS40 enhanced the stemness of CRC cells, as evidenced by increased sphere formation, upregulation of stem cell markers, enrichment of the CD133+CD44+ cell population, and enhanced tumor initiation capacity in vivo. Mechanistically, PRAS40 induced a glycolytic phenotype by interacting with and activating the glycolytic enzyme phosphoglycerate kinase 1 (PGK1). Furthermore, PRAS40 enhanced the interaction between PGK1 and the acetyltransferase p300/CBP-associated factor (PCAF), thereby promoting PGK1 acetylation, which contributes to glycolysis activation and the maintenance of CRC stemness. Pharmacological inhibition of acetylation attenuated PRAS40-mediated CRC stemness and colorectal carcinogenesis. Collectively, our findings uncover a novel PRAS40/PGK1 regulatory axis that promotes CRC stemness and tumorigenesis through enhanced glycolysis, suggesting potential therapeutic strategies targeting this axis for CRC treatment.

Neoplasms. Tumors. Oncology. Including cancer and carcinogens
DOAJ Open Access 2024
Investigating TREM2-mediated vasculo-protection during chronic mild hypoxia in vivo

Mila Redzic, Stefan Szymkowiak, Barry McColl

Cerebrovascular dysfunction, leading to inadequate brain perfusion and oxygenation, is a major contributor to cognitive decline and dementia. Chronic hypoxia is a putative mechanism of vascular-mediated brain damage, particularly in relation to white matter lesions, as demonstrated by human neuroimaging and histopathology studies. Moreover, increasing evidence suggests that microglia, the primary immune cells of the brain parenchyma, may play a key role in modulating cerebrovascular disease outcomes. Indeed, unpublished work from our lab using a model of chronic cerebral hypoperfusion found greater vascular and white matter abnormalities concomitant with reduced microglial-vascular interactions in mice lacking the microglial immunoreceptor triggering receptor expressed on myeloid cells 2 (TREM2). However, the underlying mechanisms remain incompletely understood. Therefore, this project aims to further investigate whether microglial TREM2 signalling contributes to cerebrovascular resilience, and specifically vasculoprotection, focusing on the context of hypoxia. To address this, we are housing mice at 8%O2 to achieve chronic mild hypoxia (CMH). As corroborated by our studies, CMH induces cerebral microbleeds associated with parenchymal fibrinogen leakage in both grey and white matter regions (Figure 1), and is thus a reductionist approach well-suited for examining microglial mechanisms conferring vasculoprotection. Ongoing studies in young (5-6 months) and aged (15-18 months) cohorts are utilising histology and immunostaining to determine the impact of TREM2 deficiency and ageing on CMH-induced phenotypes, with particular focus on profiling microbleed burden, BBB integrity and interactions between microglia and other cell types within the neurovascular unit. Given that TREM2 is a key regulator of microglial metabolism and lipid processing, future work will utilise flow cytometry and spatial lipidomics to characterise microglia and brain lipid metabolism during CMH, thus providing insight into immunometabolic changes that may underpin microglial vasculoprotection in hypoxia. Findings from these studies will increase our understanding of microglia-vascular interactions, which can ultimately be exploited to promote resilience to cerebrovascular and other hypoxia- related pathologies.

Specialties of internal medicine, Neurosciences. Biological psychiatry. Neuropsychiatry
DOAJ Open Access 2024
The development and maintenance of immunity against visceral leishmaniasis

Rahul Tiwari, Awnish Kumar, Vishal Kumar Singh et al.

Understanding the development and maintenance of immunological memory is important for efforts to eliminate parasitic diseases like leishmaniasis. Leishmaniasis encompasses a range of pathologies, resulting from infection with protozoan parasites belonging to the subgenera Leishmania and Viannia of the genus Leishmania. A striking feature of these infections is that natural or drug-mediated cure of infection generally confers life-long protection against disease. The generation of protective T cell responses are necessary to control Leishmania infections. CD4+ T helper (Th) cells orchestrate immune responses in leishmaniasis and IFNγ+ Tbet+ CD4+ T (Th1) cells are required for the activation of phagocytes to kill captured or resident parasites, while other Th cell subset, including FoxP3+ natural regulatory T cells and Th2 cells can promote disease progression by suppressing the activities of Th1 cells. Upon resolution of a primary Leishmania infection, different subsets of CD4+ T cells, including tissue-resident memory T cells, effector memory T cells, central memory T cells, and short-lived effector T cells, help to confer resistance against reinfection. To maintain long-term protective Leishmania-specific CD4+ T cells responses, it is believed that persistent parasites or re-exposure to parasites at regular intervals is required (concomitant immunity). Despite the advances in our understanding about the immune responses during leishmaniasis, the generation of long-lasting protective immunity via vaccination has yet to be achieved. In this review, we summarize our current understanding about the formation and maintenance of immunological memory and control of leishmaniasis at the individual and population level. We will focus on Indian visceral leishmaniasis and discuss T cell responses that contribute to susceptibility to leishmaniasis, parasite persistence in populations and the environment, as well as describing advances in the development of leishmaniasis vaccines aimed at inducing protective CD4+ T cell responses.

Immunologic diseases. Allergy
DOAJ Open Access 2024
Study on the impact of meteorological factors on influenza in different periods and prediction based on artificial intelligence RF-Bi-LSTM algorithm: to compare the COVID-19 period with the non-COVID-19 period

Hansong Zhu, Si Chen, Weixia Qin et al.

Abstract Objective At different times, public health faces various challenges and the degree of intervention measures varies. The research on the impact and prediction of meteorology factors on influenza is increasing gradually, however, there is currently no evidence on whether its research results are affected by different periods. This study aims to provide limited evidence to reveal this issue. Methods Daily data on influencing factors and influenza in Xiamen were divided into three parts: overall period (phase AB), non-COVID-19 epidemic period (phase A), and COVID-19 epidemic period (phase B). The association between influencing factors and influenza was analysed using generalized additive models (GAMs). The excess risk (ER) was used to represent the percentage change in influenza as the interquartile interval (IQR) of meteorology factors increases. The 7-day average daily influenza cases were predicted using the combination of bi-directional long short memory (Bi-LSTM) and random forest (RF) through multi-step rolling input of the daily multifactor values of the previous 7-day. Results In periods A and AB, air temperature below 22 °C was a risk factor for influenza. However, in phase B, temperature showed a U-shaped effect on it. Relative humidity had a more significant cumulative effect on influenza in phase AB than in phase A (peak: accumulate 14d, AB: ER = 281.54, 95% CI = 245.47 ~ 321.37; A: ER = 120.48, 95% CI = 100.37 ~ 142.60). Compared to other age groups, children aged 4–12 were more affected by pressure, precipitation, sunshine, and day light, while those aged ≥ 13 were more affected by the accumulation of humidity over multiple days. The accuracy of predicting influenza was highest in phase A and lowest in phase B. Conclusions The varying degrees of intervention measures adopted during different phases led to significant differences in the impact of meteorology factors on influenza and in the influenza prediction. In association studies of respiratory infectious diseases, especially influenza, and environmental factors, it is advisable to exclude periods with more external interventions to reduce interference with environmental factors and influenza related research, or to refine the model to accommodate the alterations brought about by intervention measures. In addition, the RF-Bi-LSTM model has good predictive performance for influenza.

Infectious and parasitic diseases
DOAJ Open Access 2024
Asymmetric dimethylarginine serum concentration in normal weight and obese CKD patients treated with hemodialysis

Elham Alipoor, Shiva Salehi, Sahar Dehghani et al.

Abstract Introduction Asymmetric dimethylarginine (ADMA), a cardiovascular risk factor, increases in renal failure. The aim of this study was to investigate ADMA levels in normal weight and obese patients on hemodialysis. Methods In this cross-sectional study, 43 normal weight and 43 obese patients on regular hemodialysis were examined. Malnutrition-inflammation score (MIS), anthropometry, circulating ADMA, lipid profiles including triglycerides (TG), total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL) and lipid ratios, glucose homeostasis parameters, blood pressure, and high-sensitivity C-reactive protein (hs-CRP) were assessed. Results Serum levels of ADMA were significantly lower in the obese compared to the normal weight patients (10268.2 ± 10092.4 vs. 13765.2 ± 9951.3 ng/l, P = 0.03). At the same time MIS score (6.1 ± 2.4 vs. 10.7 ± 3.2, P < 0.001), systolic blood pressure (119 ± 26.8 vs. 134.2 ± 24.7 mmHg, P = 0.018) and mean arterial pressure (91.3 ± 18.6 vs. 100.9 ± 15.9 mmHg, P = 0.028) were significantly lower in the obese than the normal weight group. Fasting blood glucose (P = 0.045), TG/HDL (P = 0.03), TC/HDL (P = 0.019), and LDL/HDL (P = 0.005) ratios, and hs-CRP (P = 0.015) levels were significantly higher in the obese than in the normal weight group. Conclusion Circulating ADMA was significantly lower in obese than in normal weight patients on hemodialysis, which was concomitant with lower MIS, indicating a better nutritional inflammatory status, and lower blood pressure.

Diseases of the genitourinary system. Urology
DOAJ Open Access 2023
The Effects of Stepping Exercise on Blood Pressure, Physical Performance, and Quality of Life in Female Older Adults with Stage 1 Hypertension: a Randomized Controlled Trial

Chawin Sarinukul, Taweesak Janyacharoen, Wanida Donpunha et al.

Background Hypertension is a common disease, particularly in older adults. In a previous study, we found that an eight-week course of stepping exercise improved physical performance in healthy older adults as measured using the six-minute walk test (468 vs. 426 m in controls; p = .01). This study aims to further evaluate the effects of stepping exercise on blood pressure, physical performance, and quality of life in older adults with stage 1 hypertension. Methods This was a randomized, controlled trial comparing older adults with stage 1 hypertension who performed stepping exercise with controls. The stepping exercise (SE) was performed at moderate intensity three times/week over an eight-week period. Participants in the control group (CG) received verbal and written (pamphlet) lifestyle modification advice. Blood pressure at Week 8 was the primary outcome, while quality of life score and physical performance on the 6-minute walk test (6MWT), timed up and go test (TUGT), and five times sit to stand test (FTSST) were secondary outcomes. Results There were 17 female patients in each group (total of 34). After eight weeks of training, participants in the SE group showed significant improvements in systolic blood pressure (SBP; 132.0 vs. 145.1 mmHg; p<.01), diastolic blood pressure (DBP; 67.3 vs. 87.6 mmHg; p<.01), 6MWT (465.6 vs. 437.0; p<.01), TUGT (8.1 vs. 9.2 sec; p<.01), and FTSST (7.9 vs. 9.1 sec; p<.01) compared to controls. Regarding within-group comparison, participants in the SE also showed significant improvement in all outcomes from baseline, while any such outcomes in the CG were comparable from baseline (SBP: 144.1 to 145.1 mmHg; p = .23; DBP: 84.3 to 87.6 mmHg; p = .90). Conclusions The stepping exercise examined is an effective non-pharmacological intervention for blood pressure control in female older adults with stage 1 hypertension. This exercise also resulted in improvements in physical performance and quality of life.

DOAJ Open Access 2023
SLEEP DISTURBANCES AMONG UNIVERSITY STUDENTS : A TUNISIAN STUDY

M. Turki, J. Firas, H. E. Mhiri et al.

Introduction Poor sleep quality is a major health problem worldwide. University students tend to suffer from problems of sleep regularity, quantity and quality, which can affect their academic performance, and have a serious impact on their psychological and physical well-being. Objectives The aim of this study was to assess the prevalence of insomnia among Tunisian university students, and to identify its associated factors. Methods We conducted a cross-sectional web-based study among university students from several Tunisian faculties. Data were collected using a questionnaire spread throughout social media (Facebook), using the Google Forms® platform, during September and October 2022. We used the “Insomnia Severity Index” (ISI) to assess the severity of insomnia. Results A total of 144 students completed the questionnaire. Their mean age was 23.38±3.27 years, with a sex-ration (F/M) of 2.8. Among them, 70.1% were single and 68.8% lived with family. Among our participants, 10.4% were followed for chronic somatic disease, 11.1% for chronic mental disease, while 29.2% have already been diagnosed and treated for sleep disturbances. ISI showed that 72.2% of students suffered from insomnia: 45.1% Subthreshold insomnia, 19.4% moderate clinical insomnia and 7.6% severe clinical insomnia. Insomnia was significantly more frequent among psychoactive substances users (75.7% vs 57.6%; p=0.043). ISI scores were significantly higher among cannabis users (17.4 vs 11.06; p=0.025). Conclusions Our study highlighted that insomnia is prevalent within the university student population, and psychoactive substances consumption seems to worsen it. Thus, when designing interventions to improve sleep quality among students, the main determinants need to be taken into consideration. Disclosure of Interest None Declared

DOAJ Open Access 2023
In vitro adhesion, pilus expression, and in vivo amelioration of antibiotic-induced microbiota disturbance by Bifidobacterium spp. strains from fecal donors

Aki Ronkainen, Imran Khan, Eva Krzyżewska-Dudek et al.

ABSTRACTFecal microbiota transplantation (FMT) is used routinely to treat recurrent Clostridioides difficile infection (rCDI) and investigated as a treatment for numerous conditions associated with gut microbiota alterations. Metagenomic analyses have indicated that recipient colonization by donor bacteria may be associated with favorable clinical outcomes. Bifidobacteria are abundant gut commensals associated with health. We have previously demonstrated that Bifidobacterium strains transferred in FMT can colonize recipients in long term, at least for a year, and recovered such strains by cultivation. This study addressed in vitro adhesion and pilus gene expression of long-term colonizing Bifidobacterium strains from FMT donors as well as in vivo colonization and capability to ameliorate antibiotic-induced microbiota disturbance. RNA-Seq differential gene expression analysis showed that the strongly adherent B. longum strains DY_pv11 and DX_pv23 expressed tight adherence and sortase-dependent pilus genes, respectively. Two B. longum strains, adherent DX_pv23 and poorly adhering DX_pv18, were selected to address in vivo colonization and efficacy to restore antibiotic-disturbed microbiota in C57BL/6 murine model. DX_pv23 colonized mice transiently with a rate comparable to that of the B. animalis BB-12 used as a reference. Although long-term colonization was not observed with any of the three strains, 16S rRNA gene profiling revealed that oral administration of DX_pv23 enhanced the recovery of antibiotic-disturbed microbiota to the original configuration significantly better than the other strains. The findings suggest that selected strains from FMT donors, such as DX_pv23 in this study, may have therapeutic potential by in vitro expression of colonization factors and boosting endogenous gut microbiota.

Diseases of the digestive system. Gastroenterology
S2 Open Access 2022
Changing the Assessment Paradigm: Promoting a Growth Mindset Across the Medical Education Continuum.

MD Aditi Puri, MD Milad Memari, MD Elisa M. Sottile et al.

AAIM is the largest academically focused specialty organization representing departments of internal medicine at medical schools and teaching hospitals in the United States and Canada. As a consortium of five organizations, AAIM represents department chairs and chiefs; clerkship, residency, and fellowship program directors; division chiefs; and academic and business administrators as well as other faculty and staff in departments of internal medicine and their divisions. s Changing the Assessment Paradigm: Promoting a Growth Mindset Across the Medical Education Continuum Aditi Puri, MD, Milad Memari, MD, Elisa M. Sottile, MD, Laura K. Snydman, MD, Wei Wei Lee, MD, MPH, Rachel A. Bonnema, MD, Danielle Jones, MD, D. Rani Nandiwada, MD Department of Internal Medicine, MacNeal Hospital, Loyola University Health System, North Riverside, Ill; Division of General Internal Medicine University of Pittsburgh Medical Center, Pa; Division of General Internal Medicine, University of Florida College of Medicine − Jacksonville; Division of General Internal Medicine, Tufts Medical Center, Boston, Mass; Section of General Internal Medicine, University of Chicago Pritzker School of Medicine, Ill; Division of General Internal Medicine, University of Texas Southwestern School of Medicine, Dallas; Division of General Internal Medicine, Emory University of Medicine, Atlanta, Ga; Division of General Internal Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pa.

21 sitasi en Medicine
DOAJ Open Access 2022
Supported employment for people with severe mental illness: a pilot study of an Italian social enterprise with a special ingredient

Alessandra Martinelli, Chiara Bonetto, Federica Bonora et al.

Abstract Background People with mental disorders are far more likely to be unemployed than the general population. Two internationally recognized, evidence-based models of interventions for employment for people with severe mental health problems are Individual Placement Support and the Clubhouse. In Italy, a common model is the ‘social enterprise’ (SE), which is a programme run by non-profit organisations that help individuals with disabilities to be employed. Despite SEs spread and relevance in Italy, there are no studies about Italian samples. This paper reports on a pilot evaluation of psychosocial and work outcomes of a SE based in Verona, Italy. The study aims to investigate if people with SMI involved in SE job placements may achieve personal recovery and better outcomes over time, and in comparison with a comparable group of users. Methods This is a pilot descriptive study with three components. A longitudinal design that comprised a functioning description of 33 SE members with a psychiatric disability in two time-points (when they joined the SE—on average 5 years before the study recruitment, and at the study recruitment—year 2018); and a repeated collection of job details of the 33 members in three time points: 2 years before the recruitment,—year 2016; 1 year before the recruitment – year 2017; and at the recruitment—year 2018. An assessment at the recruitment time—year 2018, of SE users’ satisfaction with the job placement, symptoms, functioning, and quality of life (QoL). A cross-sectional study that compared the 33 SE members at the recruitment time—year 2018, with a matched group of people with the following criteria: living in local supported accommodations, being unemployed and not SE members. The two groups were compared on ratings of psychopathology, functioning, and QoL. Descriptive analyses were done. Results At the recruitment time – year 2018, all SE participants showed a significant better functioning (p < 0.001) than when they joined the SE—when they had been employed for an average of 5 years. In comparison to the matched group, SE members had significantly better functioning (p = 0.001), psychopathology (p = 0.007), and QoL (p = 0.034). According to their SE membership status, participants comprised trainees (21.2%) and employee members (78.8%). Trainees compared to employees had lower autonomies, functioning, QoL and more severe psychopathology. Over the two years prior to study recruitment, trainees showed stable poor autonomies, while employee members showed a variation from average autonomies in the 2 years before the recruitment time – year 2016, to good ones at the recruitment time – year 2018. Over the two years, all SE members set increasing numbers of objectives in all three domains. All SE participants reported high levels of satisfaction with all aspects of the job placement. Conclusions SE that provides tailored support to assist people to gain employment skills may be an effective component in helping recovery from SMI.

DOAJ Open Access 2022
An unusual ‘bow tie’ image in pacemaker implantation

Oguzhan Ekrem Turan, Resit Yigit Yilancioglu, Ahmet Anil Baskurt et al.

Upper venous system anatomic variations may cause difficulties during cardiac pacemaker implantation. Persistent left superior vena cava (PLSVC) and absent right superior vena cava could be an arrhythmogenic source of atrial arrhythmias and cardiac conduction disease. We represent dual-chamber pacemaker implantation in a patient with a very rare upper venous system anomaly, paroxysmal atrial fibrillation, sick sinus syndrome, that cause unusual fluoroscopic image.

Diseases of the circulatory (Cardiovascular) system
S2 Open Access 2020
Health Disparities and the Coronavirus Disease 2019 (COVID-19) Pandemic in the USA

S. Khatana, P. Groeneveld

(COVID-19) Pandemic in the USA Sameed Ahmed M. Khatana, MD, MPH and Peter W. Groeneveld, MD, MS Division ofCardiovascularMedicine, Perelman School ofMedicine, University of Pennsylvania Philadelphia, PA, USA; The LeonardDavis Instituteof Health Economics, University of PennsylvaniaPhiladelphia, PA, USA; Division of General Internal Medicine, Perelman School of Medicine, University of PennsylvaniaPhiladelphia, PA, USA.

60 sitasi en Medicine
DOAJ Open Access 2020
The Effects of Anesthesia on Adult Hippocampal Neurogenesis

Jenny L. Kim, Nicholas E. Bulthuis, Heather A. Cameron

In animal studies, prolonged sedation with general anesthetics has resulted in cognitive impairments that can last for days to weeks after exposure. One mechanism by which anesthesia may impair cognition is by decreasing adult hippocampal neurogenesis. Several studies have seen a reduction in cell survival after anesthesia in rodents with most studies focusing on two particularly vulnerable age windows: the neonatal period and old age. However, the extent to which sedation affects neurogenesis in young adults remains unclear. Adult neurogenesis in the dentate gyrus (DG) was analyzed in male and female rats 24 h after a 4-h period of sedation with isoflurane, propofol, midazolam, or dexmedetomidine. Three different cell populations were quantified: cells that were 1 week or 1 month old, labeled with the permanent birthdate markers EdU or BrdU, respectively, and precursor cells, identified by their expression of the endogenous dividing cell marker proliferating cell nuclear antigen (PCNA) at the time of sacrifice. Midazolam and dexmedetomidine reduced cell proliferation in the adult DG in both sexes but had no effect on postmitotic cells. Propofol reduced the number of relatively mature, 28-day old, neurons specifically in female rats and had no effects on younger cells. Isoflurane had no detectable effects on any of the cell populations examined. These findings show no general effect of sedation on adult-born neurons but demonstrate that certain sedatives do have drug-specific and sex-specific effects. The impacts observed on different cell populations predict that any cognitive effects of these sedatives would likely occur at different times, with propofol producing a rapid but short-lived impairment and midazolam and dexmedetomidine altering cognition after a several week delay. Taken together, these studies lend support to the hypothesis that decreased neurogenesis in the young adult DG may mediate the effects of sedation on cognitive function.

Neurosciences. Biological psychiatry. Neuropsychiatry
S2 Open Access 2015
Cupping therapy: A prudent remedy for a plethora of medical ailments

P. Mehta, V. Dhapte

Since ancient times, complementary and alternative medicine (CAM; 補充與替代醫學 bǔ chōng yǔ tì dài yī xué) have played an important role in human health and welfare. Many therapeutic approaches in healthcare outside the realm of conventional medicine persist in various parts of the world. There is considerable scientific and commercial potential in CAM, which needs to be explored precisely. Cupping therapy (拔罐療法 bá guàn liáo fǎ), one of the CAM, is practiced across the world. This therapy is believed to act by correcting imbalances in the internal bio field, such as by restoring the flow of “Qi (氣qì)”. Cupping involves applying a heated cup to generate a partial vacuum that mobilizes the blood flow and promotes effective healing. This review outlines various tools and techniques of cupping therapy.

163 sitasi en Medicine

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