bluuebunny/crossref_metadata_2025 huggingface dataset:
Sevoflurane Inhibits Metastasis in Hepatocellular Carcinoma by Inhibiting MiR-665-Induced Activation of the ERK/MMP Pathway
Authors: Zhu Xiaoyan , Peng Chuchu , Peng Zhiyong , Chang Ruimin , Guo Qulian
Published: June 2022

Recent evidence has indicated that inhalational anesthetics may affect the growth and malignant potential of tumor cells and ultimately influence tumor recurrence after surgery. Sevoflurane, a volatile anesthetic, is used extensively in hepatectomy. However, the effect of sevoflurane on the growth of hepatocellular carcinoma (HCC) cells remains unknown. The aim of this study was to explore the effects of sevoflurane on HCC metastasis and its potential mechanisms in the human HCC cell lines, HepG2 and SMMC7721. HepG2 and SMMC7721 cells were treated with 1.7%, 3.4%, and 5.1 % sevoflurane for 6 h. Cell migration was analyzed using invasion, migration, and scratch assays. Based on previous literature, several microRNAs (miRNAs) were screened to determine regulatory miRNA targets of sevoflurane in HepG2 and SMMC7721 cells; miR-665 was detected as a potential target and overexpressed or inhibited in HepG2 and SMMC7721 cells by a lentiviral system. The p-ERK/MMP pathway was also measured by western blotting. Sevoflurane inhibited the migration and invasion of HCC cells in a dose-dependent manner. It also inhibited miR-665 expression in HCC cells. We further observed that sevoflurane inhibited HCC metastasis via miR-665. Sevoﬂurane-induced downregulation of miRNA-665 led to phosphorylation of ERK and matrix metalloproteinase (MMP-9) via suppression of SPRED1. These results demonstrated that sevoflurane may inhibit invasion and migration via the p-ERK/MMP-9 signaling pathway in HCC cells.
Covid-19 Vaccine Acceptance and Determinant Factors among General Public in East Africa: A Systematic Review and Meta-Analysis
Authors: Alemayehu Astawus , Demissie Abebaw , Yusuf Mohammed , Gemechu Lencha Abebe , Oljira Lemessa
Published: June 2022

Background

Vaccines are an effective and ideal solution that can reduce the burden of disease worldwide. Although vaccines are the most effective way to prevent infectious diseases. Anti-vaccine conspiracy theories impair vaccination acceptance intentions. Several studies were conducted in East Africa. However, these studies had reported inconsistent findings. Therefore, this systematic review aimed to pool the prevalence of COVID-19 vaccine acceptance and identify its determinants.

Methods

PubMed, Google Scholar, and GLOBAL HEALTH databases were used to retrieve previously published studies. All papers published in the English language up to February 28, 2022 were included. The result was written and reported according to the PRISMA updated guideline. A random-effect model was used to estimate the pooled prevalence and effect sizes. Heterogeneity was assessed using I2 test statistics. Publication bias was assessed using funnel plot and egger’s test statistics. Statistical tests result at P-value<0.05 were declared as having significance. Result: A total of 25 Cross-sectional studies with a total sample size of 33,044 were included in this study. The pooled prevalence of Covid-19 vaccine acceptance was 60.2%, (95%CI: 52.8- 67.3). Egger’s test statistics (P = 0.003) showed there is a significant publication bias. Attending above secondary school (AOR: 2.1, 95%CI: 1.37, 2.96), having good knowledge about the vaccine (AOR: 2.1, 95%CI: 1.6, 2.8), having a positive attitude towards vaccine (AOR: 3.8, 95%CI: 2.3, 6.2), history of COVID-19 infection (AOR: 2.7, 95%CI: 1.6, 4.7) and being male (AOR: 1.8, 95%CI: 1.2, 2.7) were found to have a significant association with COVID-19 vaccine acceptance.

Conclusion

The COVID-19 vaccination acceptance rate was good, but it could be improved. The findings could help governments to figure out the best way to carry out COVID-19 mass vaccination campaigns. There is a lack of data in most countries. Therefore, we suggest more studies be conducted in the future.
Combined transcriptome and metabolome analysis of Nerium indicum L. elaborates the key pathways that are activated in response to witches’ broom disease
Authors: Wang Shengjie , Wang Shengkun , Li Ming , Su Yuhang , Sun Zhan , Ma Haibin
Published: June 2022

Background

Nerium indicumMill. is an ornamental plant that is found in parks, riversides, lakesides, and scenic areas in China and other parts of the world. Our recent survey indicated the prevalence of witches’ broom disease (WBD) in Guangdong, China. To find out the possible defense strategies against WBD, we performed a MiSeq based ITS sequencing to identify the possible casual organism, then did a de novo transcriptome sequencing and metabolome profiling in the phloem and stem tip ofN. indicumplants suffering from WBD compared to healthy ones.

Results

The survey showed that Wengyuen county and Zengcheng district had the highest disease incidence rates. The most prevalent microbial species in the diseased tissues wasCophinforma mamane. The transcriptome sequencing resulted in the identification of 191,224 unigenes of which 142,396 could be annotated. There were 19,031 and 13,284 differentially expressed genes (DEGs) between diseased phloem (NOWP) and healthy phloem (NOHP), and diseased stem (NOWS) and healthy stem (NOHS), respectively. The DEGs were enriched in MAPK-signaling (plant), plant-pathogen interaction, plant-hormone signal transduction, phenylpropanoid and flavonoid biosynthesis, linoleic acid and α-linoleic acid metabolism pathways. Particularly, we found thatN. indicumplants activated the phytohormone signaling, MAPK-signaling cascade, defense related proteins, and the biosynthesis of phenylpropanoids and flavonoids as defense responses to the pathogenic infection. The metabolome profiling identified 586 metabolites of which 386 and 324 metabolites were differentially accumulated in NOHP vs NOWP and NOHS and NOWS, respectively. The differential accumulation of metabolites related to phytohormone signaling, linoleic acid metabolism, phenylpropanoid and flavonoid biosynthesis, nicotinate and nicotinamide metabolism, and citrate cycle was observed, indicating the role of these pathways in defense responses against the pathogenic infection.

Conclusion

Our results showed that Guangdong province has a high incidence of WBD in most of the surveyed areas.C. mamaneis suspected to be the causing pathogen of WBD inN. indicum. N. indicuminitiated the MAPK-signaling cascade and phytohormone signaling, leading to the activation of pathogen-associated molecular patterns and hypersensitive response. Furthermore,N. indicumaccumulated high concentrations of phenolic acids, coumarins and lignans, and flavonoids under WBD. These results provide scientific tools for the formulation of control strategies of WBD inN. indicum.
Genome-wide investigation of histone acetyltransferase gene family and its responses to biotic and abiotic stress in foxtail millet (Setaria italica [L.] P. Beauv)
Authors: Xing Guofang , Jin Minshan , Qu Ruifang , Zhang Jiewei , Han Yuanhuai , Han Yanqing , Wang Xingchun , Li Xukai , Ma Fangfang , Zhao Xiongwei
Published: June 2022

Background

Modification of histone acetylation is a ubiquitous and reversible process in eukaryotes and prokaryotes and plays crucial roles in the regulation of gene expression during plant development and stress responses. Histone acetylation is co-regulated by histone acetyltransferase (HAT) and histone deacetylase (HDAC). HAT plays an essential regulatory role in various growth and development processes by modifying the chromatin structure through interactions with other histone modifications and transcription factors in eukaryotic cells, affecting the transcription of genes. Comprehensive analyses ofHATgenes have been performed inArabidopsis thalianaandOryza sativa. However, little information is available on theHATgenes in foxtail millet (Setaria italica[L.] P.Beauv).

Results

In this study, 24HATgenes (SiHATs) were identified and divided into four groups with conserved gene structures via motif composition analysis. Phylogenetic analysis of the genes was performed to predict functional similarities betweenArabidopsis thaliana,Oryza sativa, and foxtail millet; 19 and 2 orthologous gene pairs were individually identified. Moreover, all identifiedHATgene pairs likely underwent purified selection based on their non-synonymous/synonymous nucleotide substitutions. Using published transcriptome data, we found thatSiHATgenes were preferentially expressed in some tissues and organs. Stress responses were also examined, and data showed thatSiHATgene transcription was influenced by drought, salt, low nitrogen, and low phosphorus stress, and that the expression of fourSiHATs was altered as a result of infection bySclerospora graminicola.

Conclusions

Results indicated that histone acetylation may play an important role in plant growth and development and stress adaptations. These findings suggest thatSiHATsplay specific roles in the response to abiotic stress and viral infection. This study lays a foundation for further analysis of the biological functions ofSiHATsin foxtail millet.
Capability to make well-founded decisions: an interview study of people with experience of sickness absence who have common mental disorders
Authors: Andersson Christina , Jakobsson Annika , Priebe Gunilla , Elf Mikael , Fornazar Robin , Hensing Gunnel
Published: June 2022

Background

Sickness absence and rehabilitation processes can be challenging for an individual. At a time of generally reduced capacity, the individual must comprehend and navigate through several options. The aim of this study was to investigate the prerequisites for support, knowledge and information related to decision making experienced by people on sickness absence due to common mental disorders.

Methods

A qualitative explorative approach was used. Face-to-face interviews took place with 11 sick-listed individuals with common mental disorders. Patients were recruited from different sources in the western part of Sweden, such as primary health care centres, patient organizations and via social media. Data analysis was performed using manifest content analysis, meaning that the analysis was kept close to the original text, and on a low level of interpretation and abstraction.

Results

The analysis revealed three themes that described experiences of decision making during the sick leave and rehabilitation process: Ambiguous roles challenge possibilities for moving on; Uncertain knowledge base weakens self-management; and Perceived barriers and enablers for ending sick leave.

Conclusions

Our findings suggest that alternatives need to be found that address sickness absence and rehabilitation processes from a complex perspective. Collaboration between stakeholders as well as shared decision making should be considered when the time for return to work is discussed with sick-listed individuals. Other factors in the context of the individual must also be considered. Current knowledge on strategies to improve health/well-being while being in the sick leave process need to be elaborated, communicated and adapted to each individuals’ unique situation, including clarifying rights, obligations and opportunities during the sick-leave process.
Mental health of Covid-19 risk groups during the first Covid-19 lockdown in Germany: a cross-sectional study
Authors: Deimel Daniel , Köhler Thorsten , Dyba Janina , Graf Niels , Firk Christine
Published: June 2022

Background

The ongoing Covid-19 pandemic not only threatens physical health, but also affects the mental health of people. Yet, health consequences of the pandemic do not affect all members of society equally. We therefore assessed the mental health burden of individuals who are at increased risk of severe illness from Covid-19 compared to individuals who are at low risk of severe illness during the first lockdown (March, 2020) in Germany. Furthermore, we investigated variables mediating the effect of being an individual at increased risk of serve illness on depression.

Methods

Adult German residents (n = 2.369) provided responses to a cross-sectional online survey about risk factors for of severe illness from Covid-19 and various aspects of mental health during the first lockdown in Germany. For data collection, standardized and validated self-report measures were used and for data analysis Mann-Whitney U-tests as well as regression and mediation analyses were performed.

Results

The results clearly show that the mental health burden is higher among individuals at increased risk of severe illness from Covid-19 compared to individuals at low risk of severe illness from Covid-19. Moreover, our findings indicate that the association between Covid-19 risk status and depressive symptoms is mediated by concerns about mental health, anxiety and loneliness in a causal effect chain.

Conclusions

Individuals at increased risk of severe illness from Covid-19 have an increased need for psychosocial support during times of lockdown. Future public health policies should pay special attention to these individuals and support them by targeted offers. More research, however, is needed on possible long-term consequences of social distancing on mental health.
Probability for surgical treatment in patients with lumbar spinal stenosis according to the stenotic lesion severity: a 5–10-year follow-up study
Authors: Kang Dong-Ho , Lee Sanghoon , Kim Ho-Joong , Park Sang-Min , Yeom Jin S.
Published: June 2022

Background

We aimed (1) to clarify difference in the natural history of lumbar spinal stenosis (LSS) with respect to surgical treatment according to severity of stenosis on magnetic resonance imaging (MRI) using qualitative grading system and (2) to estimate surgical probabilities depending on radiological severity.

Methods

With the design of retrospective observational study, a total of 1,248 patients diagnosed with LSS between 2011 and 2014 at our hospital were followed up for the mean duration of 7.7 years (5.17–9.8 years). We investigated severity of central and foraminal stenoses on initial MRI using qualitative grading system and whether surgical treatment was performed. Logistic regression models were used to identify risk factors for surgery.

Results

During the mean follow-up period of 7.7 years, grade 3 maximal central stenosis showed the highest percentage of surgical treatment (57.9%–62.3%) with no significant difference in surgical probabilities according to concomitant foraminal stenosis. Surgical probabilities in grade 2 and 3 maximal foraminal stenosis, were 22.2%–62.3% and 33.3%–57.9%, respectively, depending on concomitant central stenosis. Maximal central stenosis of grades 1, 2, and 3 (odds ratio [OR]: 1.79, 2.21, and 6.26, respectively), and maximal foraminal stenosis of grades 2 and 3 (OR: 2.22 and 2.12, respectively) were significant risk factors for surgical treatment.

Conclusions

The high grades of maximal central and foraminal stenoses were risk factors for surgical treatment. Surgical probabilities were 57.9%–62.3% in grade 3 maximal central stenosis, 22.2%–62.3% and 33.3%–57.9%, respectively, in grade 2 and 3 maximal foraminal stenosis during the mean follow-up period of 7.7 years. These results indicate that the natural history of LSS differs according to grade of maximal central and foraminal stenoses.
Knowledge and practice of nursing students regarding bioterrorism and emergency preparedness: comparison of the effects of simulations and workshop
Authors: Ghahremani Mahsa , Rooddehghan Zahra , Varaei Shokouh , Haghani Shima
Published: June 2022

Background and purpose

Bioterrorism is a global threat. Nurses are one of the first groups that should be ready for it. College years are the best time to educate these issues. This study aimed to compare the effectiveness of simulation and workshop on knowledge and practice of nursing students regarding bioterrorism.

Materials and methods

This was an experimental study. The study sample consisted of 40 last-year nursing students who were randomly assigned to two groups by using random numbers table. Data was collected using a demographic questionnaire, bioterrorism knowledge scale, and an OSCE checklist. Before the intervention, the students completed the study questionnaires and a six-station OSCE test. The workshop group (20 students) learned how to deal with bioterrorism through lectures. The simulation group (20 students) participated in a simulation learning program. After one month, the students completed the study tools again. Finally, collected data were analyzed using descriptive and inferential statistics in SPSS V.16.

Results

The difference between the knowledge and performance scores of both groups (workshop and simulation), before and after the intervention, was statistically significant (P < 0.001). Students in both groups had higher knowledge and performance scores after the intervention. The simulation group scores were higher than the workshop group scores in the knowledge and the most of performance domains.

Conclusion

The simulation group had better results in terms of enhancing knowledge, preparedness, disaster triage, reporting, incident management, communication, mental disorders, and isolation domains compared to the workshop group.
Knowledge and decisions about maternal immunisation by pregnant women in Aotearoa New Zealand
Authors: Young Amber , Charania Nadia A. , Gauld Natalie , Norris Pauline , Turner Nikki , Willing Esther
Published: June 2022

Background

Maternal vaccinations for influenza and pertussis are recommended in New Zealand to protect mothers and their infant from infection. However, maternal immunisation coverage in New Zealand is suboptimal. Furthermore, there is unacceptable inequitable maternal immunisation rates across the country with Māori and Pacific women having significantly lower maternal immunisation rates than those of other New Zealanders.

Methods

This research set out to explore what pregnant/recently pregnant Māori and Pacific women knew about immunisation during pregnancy and what factors influenced their decision to be vaccinated. A semi-structured interview guide was developed with questions focusing on knowledge of pertussis and influenza vaccination during pregnancy and decision-making. Māori and Pacific women aged over 16 years were purposively sampled and interviewed in Dunedin and Gisborne, New Zealand between May and August 2021. Interviews were analysed following a directed qualitative content approach. Data were arranged into coding nodes based on the study aims (deductive analysis) informed by previous literature and within these participant experiences were inductively coded into themes and subthemes.

Results

Not all women were aware of maternal vaccine recommendations or they diseases they protected against. Many underestimated how dangerous influenza and pertussis could be and some were more concerned about potential harms of the vaccine. Furthermore, understanding potential harms of infection and protection provided by vaccination did not necessarily mean women would choose to be vaccinated. Those who decided to vaccinate felt well-informed, had vaccination recommended by their healthcare provider, and did so to protect their and their infant’s health. Those who decided against vaccination were concerned about safety of the vaccines, lacked the information they needed, were not offered the vaccine, or did not consider vaccination a priority.

Conclusions

There is a lack of understanding about vaccine benefits and risks of vaccine-preventable diseases which can result in the reinforcement of negative influences such as the fear of side effects. Furthermore, if vaccine benefits are not understood, inaccessibility of vaccines and the precedence of other life priorities may prevent uptake. Being well-informed and supported to make positive decisions to vaccinate in pregnancy is likely to improve vaccine coverage in Māori and Pacific Island New Zealanders.
The Every Woman Every Child initiative: supporting countries in Latin America and the Caribbean to reduce social inequalities in health
Authors: Sanhueza Antonio , Carvajal Liliana , Cueva Daniel A. , Caffe Sonja , Camacho Alma Virginia , Berroterán María Alejandra , Horowitz Deborah , Gordillo-Tobar Amparo , Mujica Oscar J. ,   Every Woman Every Child Latin America and the Caribbean
Published: June 2022

The Every Woman Every Child Latin America and the Caribbean (EWEC-LAC) initiative was established in 2017 as a regional inter-agency mechanism. EWEC-LAC coordinates the regional implementation of the Global Strategy for Women’s, Children’s and Adolescents’ Health in Latin America and the Caribbean (LAC), including adaptation to region specific needs, to end preventable deaths, ensure health and well-being and expand enabling environments for the health and well-being of women, children and adolescents. To advance the equitable achievement of these objectives, EWEC-LAC’s three working groups collectively support LAC countries in measuring and monitoring social inequalities in health, advocating for their reduction, and designing and implementing equity-oriented strategies, policies and interventions. This support for data-driven advocacy, capacity building, and policy and program solutions toward closing current gaps ensures that no one is left behind. Members of EWEC-LAC include PAHO, UNAIDS, UNFPA, UNICEF, UN WOMEN, the World Bank, the Inter-American Development Bank, USAID, LAC Regional Neonatal Alliance, and the LAC Regional Task Force for the Reduction of Maternal Mortality. To date, EWEC-LAC has developed and collected innovative tools and resources and begun to engage with countries to utilize them to reduce equity gaps. These resources include a framework for the measurement of social inequalities in health, data use and advocacy tools including a data dashboard to visualize trends in social inequalities in health in LAC countries, a methodology for setting targets for the reduction of inequalities, and a compendium of tools, instruments and methods to identify and address social inequalities in health. EWEC-LAC has also engaged regionally to emphasize the importance of recognizing these inequalities at social and political levels, and advocated for the reduction of these gaps. Attention to closing health equity gaps is ever more critical in the face of the COVID-19 pandemic which has exploited existing vulnerabilities. More equitable health systems will be better prepared to confront future health shocks.
Recent advances in exosome-mediated nucleic acid delivery for cancer therapy
Authors: Zhang Ying , Liu Qiqi , Zhang Xinmeng , Huang Haoqiang , Tang Shiqi , Chai Yujuan , Xu Zhourui , Li Meirong , Chen Xin , Liu Jia , Yang Chengbin
Published: June 2022

Cancer is a leading public health problem worldwide. Its treatment remains a daunting challenge, although significant progress has been made in existing treatments in recent years. A large concern is the poor therapeutic effect due to lack of specificity and low bioavailability. Gene therapy has recently emerged as a powerful tool for cancer therapy. However, delivery methods limit its therapeutic effects. Exosomes, a subset of extracellular vesicles secreted by most cells, have the characteristics of good biocompatibility, low toxicity and immunogenicity, and great designability. In the past decades, as therapeutic carriers and diagnostic markers, they have caught extensive attention. This review introduced the characteristics of exosomes, and focused on their applications as delivery carriers in DNA, messenger RNA (mRNA), microRNA (miRNA), small interfering RNA (siRNA), circular RNA (circRNA) and other nucleic acids. Meanwhile, their application in cancer therapy and exosome-based clinical trials were presented and discussed. Through systematic summarization and analysis, the recent advances and current challenges of exosome-mediated nucleic acid delivery for cancer therapy are introduced, which will provide a theoretical basis for the development of nucleic acid drugs.

Graphical Abstract
Primary tumor volume and prognosis for patients with p16-positive and p16-negative oropharyngeal squamous cell carcinoma treated with radiation therapy
Authors: Adrian Gabriel , Carlsson Henrik , Kjellén Elisabeth , Sjövall Johanna , Zackrisson Björn , Nilsson Per , Gebre-Medhin Maria
Published: June 2022

Background

The prescribed radiation dose to patients with oropharyngeal squamous cell carcinoma (OPSCC) is standardized, even if the prognosis for individual patients may differ. Easy-at-hand pre-treatment risk stratification methods are valuable to individualize therapy. In the current study we assessed the prognostic impact of primary tumor volume for p16-positive and p16-negative tumors and in relationship to other prognostic factors for outcome in patients with OPSCC treated with primary radiation therapy (RT).

Methods

Five hundred twenty-three OPSCC patients with p16-status treated with primary RT (68.0 Gy to 73.1 Gy in 7 weeks, or 68.0 Gy in 4.5 weeks), with or without concurrent chemotherapy, within three prospective trials were included in the study. Local failure (LF), progression free survival (PFS) and overall survival (OS) in relationship to the size of the primary gross tumor volume (GTV-T) and other prognostic factors were investigated. Efficiency of intensified RT (RT with total dose 73.1 Gy or given within 4.5 weeks) was analyzed in relationship to tumor volume.

Results

The volume of GTV-T and p16-status were found to be the strongest prognostic markers for LF, PFS and OS. For p16-positive tumors, an increase in tumor volume had a significantly higher negative prognostic impact compared with p16-negative tumors. Within a T-classification, patients with a smaller tumor, compared with a larger tumor, had a better prognosis. The importance of tumor volume remained after adjusting for nodal status, age, performance status, smoking status, sex, and hemoglobin-level. The adjusted hazard ratio for OS per cm3 increase in tumor volume was 2.3% (95% CI 0–4.9) for p16-positive and 1.3% (95% 0.3–2.2) for p16-negative. Exploratory analyses suggested that intensified RT could mitigate the negative impact of a large tumor volume.

Conclusions

Outcome for patients with OPSCC treated with RT is largely determined by tumor volume, even when adjusting for other established prognostic factors. Tumor volume is significantly more influential for patients with p16-positive tumors. Patients with large tumor volumes might benefit by intensified RT to improve survival.
Mechanisms of structural chromosomal rearrangement formation
Authors: Burssed Bruna , Zamariolli Malú , Bellucco Fernanda Teixeira , Melaragno Maria Isabel
Published: June 2022

Structural chromosomal rearrangements result from different mechanisms of formation, usually related to certain genomic architectural features that may lead to genetic instability. Most of these rearrangements arise from recombination, repair, or replication mechanisms that occur after a double-strand break or the stalling/breakage of a replication fork. Here, we review the mechanisms of formation of structural rearrangements, highlighting their main features and differences. The most important mechanisms of constitutional chromosomal alterations are discussed, including Non-Allelic Homologous Recombination (NAHR), Non-Homologous End-Joining (NHEJ), Fork Stalling and Template Switching (FoSTeS), and Microhomology-Mediated Break-Induced Replication (MMBIR). Their involvement in chromoanagenesis and in the formation of complex chromosomal rearrangements, inverted duplications associated with terminal deletions, and ring chromosomes is also outlined. We reinforce the importance of high-resolution analysis to determine the DNA sequence at, and near, their breakpoints in order to infer the mechanisms of formation of structural rearrangements and to reveal how cells respond to DNA damage and repair broken ends.
Impaired mitochondrial accumulation and Lewy pathology in neuron-specific FBXO7-deficient mice
Authors: Noda Sachiko , Sato Shigeto , Fukuda Takahiro , Ueno Shinichi , Tada Norihiro , Hattori Nobutaka
Published: June 2022

Parkinson’s disease, the second most common neurodegenerative disorder, is characterized by the loss of nigrostriatal dopamine neurons. FBXO7 (F-box protein only 7) (PARK15) mutations cause early-onset Parkinson’s disease. FBXO7 is a subunit of the SCF (SKP1/cullin-1/F-box protein) E3 ubiquitin ligase complex, but its neuronal relevance and function have not been elucidated. To determine its function in neurons, we generated neuronal cell-specific FBXO7 conditional knockout mice (FBXO7flox/flox: Nestin-Cre) by crossing previously characterized FBXO7 floxed mice (FBXO7flox/flox) with Nestin-Cre mice (Nestin-Cre). The resultant Fbxo7flox/flox: Nestin-Cre mice showed juvenile motor dysfunction, including hindlimb defects and decreased numbers of dopaminergic neurons. Fragmented mitochondria were observed in dopaminergic and cortical neurons. Furthermore, p62- and synuclein-positive Lewy body-like aggregates were identified in neurons. Our findings highlight the unexpected role of the homeostatic level of p62, which is regulated by a non-autophagic system that includes the ubiquitin–proteasome system, in controlling intracellular inclusion body formation. These data indicate that the pathologic processes associated with the proteolytic and mitochondrial degradation systems play a crucial role in the pathogenesis of PD.
The interplay between noncoding RNA and YAP/TAZ signaling in cancers: molecular functions and mechanisms
Authors: Zhang Yirao , Wang Yang , Ji Hao , Ding Jie , Wang Keming
Published: June 2022

The Hippo signaling pathway was found coordinately modulates cell regeneration and organ size. Its dysregulation contributes to uncontrolled cell proliferation and malignant transformation. YAP/TAZ are two critical effectors of the Hippo pathway and have been demonstrated essential for the initiation or growth of most tumors. Noncoding RNAs (ncRNAs), including miRNAs, lncRNAs, and circRNAs, have been shown to play critical roles in the development of many cancers. In the past few decades, a growing number of studies have revealed that ncRNAs can directly or indirectly regulate YAP/TAZ signaling. YAP/TAZ also regulate ncRNAs expression in return. This review summarizes the interactions between YAP/TAZ signaling and noncoding RNAs together with their biological functions on cancer progression. We also try to describe the complex feedback loop existing between these components.
E-cigarettes and youth: an unresolved Public Health concern
Authors: Virgili Fabrizio , Nenna Raffaella , Ben David Shira , Mancino Enrica , Di Mattia Greta , Matera Luigi , Petrarca Laura , Midulla Fabio
Published: June 2022

The use of electronic cigarettes (e-cigarette) and vaping devices started as a potential aid for cessation and reducing the harmful consequences of cigarette smoking, mainly in the adult population. Today e-cigarette use is highly increasing in vulnerable populations, especially young and pregnant women, due to the misconception of its harmless use.

Despite the growing acknowledgment in e-cigarette as a potential harmful device, and due to mixed information found concerning its beneficial aid for smokers, along with an insufficient clinical study done in human models, it is important to further evaluate the possible benefits and risks of non-combusting, vaping nicotine or non-nicotine delivery devices.

In this review we tried to summarize the latest updated information found in the literature, concentrating mainly in the variety of adverse effects of e-cigarette use and its contribution for recent and future health concerns.
Urothelial carcinoma of the prostate with raised β-hCG levels: a case report
Authors: Sołek Julia , Kalwas Marta , Sobczak Magdalena , Dębska-Szmich Sylwia , Kupnicki Piotr , Jesionek-Kupnicka Dorota
Published: June 2022

Background

Trophoblastic differentiation in primary urothelial carcinoma of the prostate is extremely rare. An increased level of β-subunit human chorionic gonadotropin in serum in urothelial carcinoma is detected in approximately 30% of cases. To our knowledge, increased concentration of β-subunit human chorionic gonadotropin in serum in prostatic urothelial carcinoma has never been reported and its clinical significance is not evaluated yet.

Case report

Here we present the case of a 67-year-old European patient who was admitted to the hospital with hematuria, dysuria, and enlarged painful testis. Ultrasonographic examination of the testis did not reveal any focal lesion. Magnetic resonance imaging of the pelvis showed a tumor of 62 mm diameter mainly located in the posterior part of the prostatic gland. A pathological examination from cystoscopy biopsy allowed us to set the diagnosis of high-grade invasive urothelial carcinoma with trophoblastic differentiation. The patient received neoadjuvant treatment. Nonetheless, after a short period of disease stabilization, he developed progression and brain metastasis. He died 9 months after diagnosis. During the disease course, his β-human chorionic gonadotropin level was measured repeatedly and analyzed in relation to disease progression. The level of serum β-human chorionic gonadotropin corresponded with the therapy response; it was at its lowest during stabilization and the highest in the metastatic stage.

Conclusion

Our case study provides the first report of urothelial cancer of the prostate, with a concomitant increase of β-subunit human chorionic gonadotropin level with testis enlargement. Besides its rarity, it constitutes an interesting observation of increasing β-subunit human chorionic gonadotropin concentration with concomitant disease progression.
A qualitative study of barriers to antimicrobial stewardship in Indonesian hospitals: governance, competing interests, cost, and structural vulnerability
Authors: Limato Ralalicia , Broom Alex , Nelwan Erni J. , Hamers Raph L.
Published: June 2022

Background

Antimicrobial resistance (AMR) is one of the leading global public health threats of the 21st Century. Antimicrobial stewardship (AMS) programmes have been shown to improve antibiotic use and clinical outcomes in high-income settings, but context-specific evidence is lacking on the value and effectiveness of current AMS programmes in low-resource settings. This study sought to explore context-specific underlying barriers to AMS implementation in Indonesian hospitals with a focus on governance practices and structural vulnerabilities.

Methods

We conducted semi-structured interviews with physicians, surgeons, clinical microbiologists, pharmacists, AMS team leaders, hospital managers, medical students, and national AMR stakeholders, and performed a thematic analysis.

Results

Based on 51 interviews conducted between January and October 2020, four main barriers to AMS implementation were evident in the participants' experiences: (1) Ineffective resourcing and institutional buy-in regarding mandatory AMS under hospital accreditation; (2) Entangled priorities to generate profits and interprofessional relationships between doctors and hospital managers or AMS leaders; (3) Cost-prohibitive bacterial culture testing and thresholds of national health insurance coverage; (4) Unreliable infrastructures, including microbiology laboratory and surgical facilities, ensuring high antibiotic usage to cover structural vulnerabilities.

Conclusions

Limited progress will be made with implementing AMS in Indonesian hospitals, and in settings with similar structural features, without addressing concerns around governance, competing interests, cost and structural vulnerabilities.
Associations between therapy experiences and perceived helpfulness of treatment for people with eating disorders
Authors: Mital Rahul , Hay Phillipa , Conti Janet E. , Mannan Haider
Published: June 2022

Background

Although eating disorders cause significant impairment to an individual’s function, many people disengage from treatment. There is a paucity of literature that focuses on both positive and negative aspects of eating disorder treatment experiences as perceived by the experiencing person. This study aimed to identify the associations between features of therapy with perceived treatment helpfulness across individuals’ most and least helpful treatment experiences.

Methods

An online cross-sectional survey was developed and disseminated, with the data of participants (n = 235) being utilised for statistical analyses, including multiple linear regressions.

Results

As predicted, factors in the therapeutic relationship such as the therapist’s ability to instil a sense of hope, provide freedom of choice, understand the person, and address participant concerns had significant explanatory value in perceived treatment helpfulness. Contrary to our hypothesis, change being retrospectively identified as important or possible by the participant did not have a high degree of relation. These outcomes highlighted the significance of the therapeutic relationship in governing positive treatment experiences and responses. The results also suggested motivation to change when commencing treatment may not be strongly related to perceived treatment helpfulness and support further exploration.
Improving treatment outcomes for adolescents with borderline personality disorder through a socioecological approach
Authors: Bo Sune , Sharp Carla , Kongerslev Mickey T. , Luyten Patrick , Fonagy Peter
Published: June 2022

Background

There is a dearth of studies evaluating treatment efficacy for adolescents diagnosed with borderline personality disorder. The few available randomized controlled trials that have been conducted show modest results and treatments appear to have equivalent effects. The current paper draws on (a) the lessons learnt from the last 50 years of psychotherapy research in general and (b) recent advances in mentalization-based understanding of why treatment works, which together point to the importance of following a socioecological approach in the treatment of personality problems in adolescence – a developmental period that insists on a treatment approach that goes beyond the therapist-client dyad.

Case presentation

Here, we describe such an approach, and offer a clinical case example with a young 16-year old girl diagnosed with borderline personality disorder, to illustrate what a shift toward a more socioecological approach would entail.

Conclusions

The clinical impact of the socioecological approach and the potential benefits as illustrated in the current case illustration, offers a framework that justifies and allows for the expansion of service delivery for youth with borderline personality disorder beyond dyadic therapist-client work.
Utilization of an Outpatient Integrated Infusion Suite to Decrease Length of Stay, Increase Revenue, and Improve Patient Experience for Elective Chemotherapy Admissions
Authors: Karkowski Katie A. , Ibrahim Samer , Thorley Katherine , Rodriguez Catherine J. , Kong Lixi , Crosby David L. , Lansigan Frederick
Published: June 2022

PURPOSE:

Reduction of chemotherapy start times (CST) and length of stay (LOS) for elective chemotherapy admissions is a priority. The aim of this project was to improve efficiency of patient care while simultaneously increasing revenue by reducing LOS and transitioning high-cost chemotherapy to the outpatient setting.

METHODS:

A multidisciplinary quality improvement team proposed building a new outpatient infusion suite in close proximity to the inpatient unit. This suite was then integrated into the flow of elective inpatient chemotherapy admissions and discharges for etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (EPOCH-R). Quality measures such as CST, LOS, and revenue were used to evaluate the new infusion suite.

RESULTS:

In the pilot phase of the study, the average CST improved by approximately 1 hour 45 minutes ( P = .0218). The mean LOS was reduced from 4.3 to 4.1 midnights ( P = .0214). In terms of hours, LOS was reduced from 105.8 to 95.5 hours ( P < .0001). A mean quarterly revenue of $309,410 US dollars was noted during the pilot that had not been previously billed. These improvements were sustained throughout the control phase.

CONCLUSION:

Delays in CST and prolonged LOS lead to patient dissatisfaction and increased cost to the health care system. Focus groups and patient feedback are important when designing and implementing new workflows. The creation of an outpatient integrated infusion suite allows medical centers to meet patients' expectations of reducing number of visits while also reducing LOS and capturing new revenue. Adherence to scheduling guidelines further reduces the CST for elective chemotherapy administration.
Daubing Titipu: Transnational Material Contexts of Nineteenth-Century Hand-Colored Photography in Japan
Authors: Sharma Rahul
Published: June 2022

This article examines the photographic paper and the colorant in an album of hand-colored photographs made in Japan and explores the interconnectedness between industry and the arts. To do so, it looks at the historical discourse over hand-coloring materials and follows the chain of manufacture for albumen paper in Europe, comparing both to the material evidence in the album. By doing so, this article shows that the networks of information transfer, labor, and capital worked in tandem to create the conditions of production for the photographs.
Casein kinase 1α regulates murine spermatogenesis via p53-Sox3 signaling
Authors: Lu Chenyang , Zhang Di , Zhang Jinglin , Li Liuhui , Qiu Jingtao , Gou Kemian , Cui Sheng
Published: June 2022

Casein kinase 1α (CK1α), acting as one member of the β-catenin degradation complex, negatively regulates the Wnt/β-catenin signaling pathway. CK1α knockout usually causes both Wnt/β-catenin and p53 activation. Our results demonstrated that conditional disruption of CK1α in spermatogonia impaired spermatogenesis and resulted in male mouse infertility. The progenitor cell population was dramatically decreased in CK1α conditional knockout (cKO) mice, while the proliferation of spermatogonial stem cells (SSCs) was not affected. Furthermore, our molecular analyses identified that CK1α loss was accompanied by nuclear stability of p53 protein in mouse spermatogonia, and dual-luciferase reporter and chromatin immunoprecipitation assays revealed that p53 directly targeted the Sox3 gene. In addition, the p53 inhibitor pifithrin α (PFTα) partially rescued the phenotype observed in cKO mice. Collectively, our data suggest that CK1α regulates spermatogenesis and male fertility through p53-Sox3 signaling, and they deepen our understanding of the regulatory mechanism underlying the male reproductive system.
Comparison of Tibial Geometry, Density, and Strength in College-Aged Female Eumenorrheic Dancers, Gymnasts, and Runners: A Peripheral Quantitative Computed Tomography Study
Authors: Freire Ribeiro Ana B. , Bruininks Brett D. , Street Glenn M. , Smock Amanda J. , Scibora Lesley M.
Published: June 2022

Introduction: Weightbearing activities such as gymnastics, soccer, weightlifting, and running have often been used as benchmarks in skeletal research since they have been shown to promote densitometric and geometric benefits. In comparison with other sports, there is a paucity of information in relation to dance and its osteogenic potential. Objective: This study aimed to compare tibial geometry, density, and strength in college-aged dancers versus gymnasts and runners.
 Methods: A total of 60 trained eumenorrheic collegiate-aged female dancers (n = 11), gymnasts (n = 11), runners (n = 19), and sedentary controls (n = 19) were included in the study. Bone measure- ments, including total area (ToA), volumetric (total vBMD) and cortical density (CoD), compressive bone strength (BSI), and polar strength stress index (SSIp) of the dominant limb, were assessed using peripheral quantitative computed tomography (pQCT) at the distal and proximal tibia (4% and 66% of limb length).
 Results: No significant differences in ToA, CoD, CoA, and total vBMD were found between dancers and the comparison athletes at the measured sites. In addition, strength indices (BSI and SSIp) at the distal and proximal sites were similar between the dancing and both athlete groups.
 Conclusion: Results suggest dance elicits similar structural adaptations at the tibia compared to benchmark high-impact and repetitive impact sports; thus, indicating dance, in its various forms, can have a positive effect on important bone variables that influence density and strength. These adaptations may potentially delay or prevent bone fragility later in life. Future studies should compare individual styles of dance separately, longitudinally, and include other important lower (e.g., hip) and upper body (e.g., radius) sites to further identify which forms provide the greatest osteogenic benefits.
Αναστοχαστικότητα και Προσανατολισμοί Εργασίας:
Authors: Αργυροπούλου Κατερίνα , Μουράτογλου Νικόλαος
Published: June 2022

Τα τελευταία χρόνια, οι έννοιες της αναστοχαστικότητας και της απόδοσης προσωπικού νοήματος και σκοπού υπεισέρχονται ολοένα και περισσότερο στις θεωρητικές και μεθοδολογικές προσεγγίσεις της συμβουλευτικής και του επαγγελματικού προσανατολισμού, κυρίως μέσα από το αφηγηματικό παράδειγμα. Παράλληλα, αναγνωρίζοντας ότι η εργασία επιτελεί διάφορους σκοπούς στη ζωή ενός ατόμου επηρεάζοντας το νόημα ζωής του, οι προσανατολισμοί εργασίας δύνανται να διαμορφώσουν ένα λειτουργικό πλαίσιο διερεύνησης και συζήτησης των διαφορετικών πτυχών της εργασίας. Έτσι, η παρούσα έρευνα επιχειρεί να παρουσιάσει τα αποτελέσματα παρέμβασης, που υλοποιήθηκε στο πλαίσιο της κατάρτισης συμβούλων σταδιοδρομίας και που αφορούσε στις αφηγηματικές και αναστοχαστικές τεχνικές, με σκοπό τη διερεύνηση της σχέσης που μπορεί να φέρει η αναστοχαστικότητα στους προσανατολισμούς εργασίας των υποκειμένων. Οι σύμβουλοι σταδιοδρομίας που συμμετείχαν (Ν=77) συμπλήρωσαν την Κλίμακα Αναστοχαστικότητας Σχεδίων Ζωής και το Ερωτηματολόγιο Προσανατολισμού Εργασίας πριν και μετά την παρέμβαση. Τα αποτελέσματα καταδεικνύουν ότι η παρέμβαση βελτίωσε την αναστοχαστικότητα των υποκειμένων και ειδικότερα την αυθεντικότητα και τη σαφήνεια των μελλοντικών τους στόχων ζωής και σταδιοδρομίας. Επιπλέον, διαπιστώθηκε πως η αυθεντικότητα συσχετίζεται με τους προσανατολισμούς εργασίας της «κοινωνικής ενσωμάτωσης» και της «σταδιοδρομίας», ενώ η σαφήνεια με το «επάγγελμα». Συνεπώς, η βελτίωση της αναστοχαστικότητας δύναται να υποστηρίξει το άτομο στο να νοηματοδοτήσει την εργασία του (υπάρχουσα ή μελλοντική) κατά μία βιώσιμη διάσταση που υποδηλώνει ότι βασίζεται στο προσωπικό νόημα και σκοπό, αλλά και στις προσωπικές και αυθεντικές αξίες του ατόμου, απομονώνοντας τις τυχόν πιέσεις που διαμορφώνεται από τις προσδοκίες των Άλλων και την κοινωνική συναίνεση με τις αξίες και νόρμες της ευρύτερης κοινωνίας.
Formation of Students' Logical Universal Educational Actions in the Process of Teaching Chemistry As a Planned Result of the Federal State Educational Standard of General Education
Authors: Zakabluk O. , Volkova S.
Published: June 2022

Within the framework of the article, methodological features of the formation of logical universal educational actions based on the logic of selection and structuring of the content of the section "Organic Chemistry" are considered. Particular attention is paid to the procedure for entering topics. The dynamics of the level of formation of logical universal educational actions among students is demonstrated. Conclusions are drawn about the peculiarities of the formation of logical universal educational actions, taking into account the age of students and the type of educational institution.