bluuebunny/crossref_metadata_2025 huggingface dataset:
Suicide ideation and the related factors among Iranian transgender people: a cross-sectional study
Authors: Arianmehr Taranom , Mohammadi Younes
Published: September 2023

Objective

Suicide is a significant public health concern worldwide, and efforts to prevent it are crucial. This study aims to assess suicide ideation among transgender individuals in Iran. A cross-sectional design was used, with 235 transgender participants recruited through snowball sampling across Iran. The data collection included a questionnaire containing demographic inquiries, while the Beck Scale for Suicide Ideation was employed to gather data. Descriptive and analytical statistics were performed using SPSS software.

Results

The findings indicate that the prevalence of suicidal ideation among the transgender individuals in the study was 83%, with a mean score of 12.8 ± 8.8 on the suicide ideation scale. Individuals with lower levels of education, younger age, unemployment, and being divorced or single demonstrated significantly higher scores compared to others (p < 0.05). This study highlights the high prevalence of suicidal ideation among Iranian transgender individuals, particularly among those with lower age and education levels, as well as those who have not undergone gender reassignment surgery.
Local transplantation of mesenchymal stem cells improves encephalo-myo-synangiosis-mediated collateral neovascularization in chronic brain ischemia
Authors: Zhang Xincheng , Huang Yimin , Liu Yuan , Liu Yanchao , He Xuejun , Ma Xiaopeng , Gan Chao , Zou Xin , Wang Sheng , Shu Kai , Lei Ting , Zhang Huaqiu
Published: September 2023

Background

To explore whether local transplantation of mesenchymal stem cells (MSCs) in temporal muscle can promote collateral angiogenesis and to analyze its main mechanisms of promoting angiogenesis.

Methods

Bilateral carotid artery stenosis (BCAS) treated mice were administrated with encephalo-myo-synangiosis (EMS), and bone marrow mesenchymal stem cells (BMSCs) were transplanted into the temporal muscle near the cerebral cortex. On the 30th day after EMS, the Morris water maze, immunofluorescence, laser speckle imaging, and light sheet microscopy were performed to evaluate angiogenesis; In addition, rats with bilateral common carotid artery occlusion were also followed by EMS surgery, and BMSCs from GFP reporter rats were transplanted into the temporal muscle to observe the survival time of BMSCs. Then, the concentrated BMSC-derived conditioned medium (BMSC-CM) was used to stimulate HUVECs and BMECs for ki-67 immunocytochemistry, CCK-8, transwell and chick chorioallantoic membrane assays. Finally, the cortical tissue near the temporal muscle was extracted after EMS, and proteome profiler (angiogenesis array) as well as RT-qPCR of mRNA or miRNA was performed.

Results

The results of the Morris water maze 30 days after BMSC transplantation in BCAS mice during the EMS operation, showed that the cognitive impairment in the BCAS + EMS + BMSC group was alleviated (P < 0.05). The results of immunofluorescence, laser speckle imaging, and light sheet microscopy showed that the number of blood vessels, blood flow and astrocytes increased in the BCAS + EMS + BMSC group (P < 0.05). The BMSCs of GFP reporter rats were applied to EMS and showed that the transplanted BMSCs could survive for up to 14 days. Then, the results of ki-67 immunocytochemistry, CCK-8 and transwell assays showed that the concentrated BMSC-CM could promote the proliferation and migration of HUVECs and BMECs (P < 0.05). Finally, the results of proteome profiler (angiogenesis array) in the cerebral cortex showed that the several pro-angiogenesis factors (such as MMP-3, MMP-9, IGFBP-2 or IGFBP-3) were notably highly expressed in MSC transplantation group compared to others.

Conclusions

Local MSCs transplantation together with EMS surgery can promote angiogenesis and cognitive behavior in chronic brain ischemia mice. Our study illustrated that MSC local transplantation can be the potential therapeutical option for improving EMS treatment efficiency which might be translated into clinical application.
Transplanted ENSCs form functional connections with intestinal smooth muscle and restore colonic motility in nNOS-deficient mice
Authors: Hotta Ryo , Rahman Ahmed , Bhave Sukhada , Stavely Rhian , Pan Weikang , Srinivasan Shriya , de Couto Geoffrey , Rodriguez-Borlado Luis , Myers Richard , Burns Alan J. , Goldstein Allan M.
Published: September 2023

Background

Enteric neuropathies, which result from abnormalities of the enteric nervous system, are associated with significant morbidity and high health-care costs, but current treatments are unsatisfactory. Cell-based therapy offers an innovative approach to replace the absent or abnormal enteric neurons and thereby restore gut function.

Methods

Enteric neuronal stem cells (ENSCs) were isolated from the gastrointestinal tract of Wnt1-Cre;R26tdTomato mice and generated neurospheres (NS). NS transplants were performed via injection into the mid-colon mesenchyme of nNOS−/− mouse, a model of colonic dysmotility, using either 1 (n = 12) or 3 (n = 12) injections (30 NS per injection) targeted longitudinally 1–2 mm apart. Functional outcomes were assessed up to 6 weeks later using electromyography (EMG), electrical field stimulation (EFS), optogenetics, and by measuring colorectal motility.

Results

Transplanted ENSCs formed nitrergic neurons in the nNOS−/− recipient colon. Multiple injections of ENSCs resulted in a significantly larger area of coverage compared to single injection alone and were associated with a marked improvement in colonic function, demonstrated by (1) increased colonic muscle activity by EMG recording, (2) faster rectal bead expulsion, and (3) increased fecal pellet output in vivo. Organ bath studies revealed direct neuromuscular communication by optogenetic stimulation of channelrhodopsin-expressing ENSCs and restoration of smooth muscle relaxation in response to EFS.

Conclusions

These results demonstrate that transplanted ENSCs can form effective neuromuscular connections and improve colonic motor function in a model of colonic dysmotility, and additionally reveal that multiple sites of cell delivery led to an improved response, paving the way for optimized clinical trial design.
Sex differences in distribution and identity of aromatase gene expressing cells in the young adult rat brain
Authors: Immenschuh Jana , Thalhammer Stefan Bernhard , Sundström-Poromaa Inger , Biegon Anat , Dumas Sylvie , Comasco Erika
Published: September 2023

Background

Aromatase catalyzes the synthesis of estrogens from androgens. Knowledge on its regional expression in the brain is of relevance to the behavioral implications of these hormones that might be linked to sex differences in mental health. The present study investigated the distribution of cells expressing the aromatase coding gene (Cyp19a1) in limbic regions of young adult rats of both sexes, and characterized the cell types expressing this gene.

Methods

Cyp19a1 mRNA was mapped using fluorescent in situ hybridization (FISH). Co-expression with specific cell markers was assessed with double FISH; glutamatergic, gamma-aminobutyric acid (GABA)-ergic, glial, monoaminergic, as well as interneuron markers were tested. Automated quantification of the cells expressing the different genes was performed using CellProfiler. Sex differences in the number of cells expressing Cyp19a1 was tested non-parametrically, with the effect size indicated by the rank-biserial correlation. FDR correction for multiple testing was applied.

Results

In the male brain, the highest percentage of Cyp19a1+ cells was found in the medial amygdaloid nucleus and the bed nucleus of stria terminalis, followed by the medial preoptic area, the CA2/3 fields of the hippocampus, the cortical amygdaloid nucleus and the amygdalo-hippocampal area. A lower percentage was detected in the caudate putamen, the nucleus accumbens, and the ventromedial hypothalamus. In females, the distribution of Cyp19a1+ cells was similar but at a lower percentage. In most regions, the majority of Cyp19a1+ cells were GABAergic, except for in the cortical-like regions of the amygdala where most were glutamatergic. A smaller fraction of cells co-expressed Slc1a3, suggesting expression of Cyp19a1 in astrocytes; monoaminergic markers were not co-expressed. Moreover, sex differences were detected regarding the identity of Cyp19a1+ cells.

Conclusions

Females show overall a lower number of cells expressing Cyp19a1 in the limbic brain. In both sexes, aromatase is expressed in a region-specific manner in GABAergic and glutamatergic neurons. These findings call for investigations of the relevance of sex-specific and region-dependent expression of Cyp19a1 in the limbic brain to sex differences in behavior and mental health.
Cost-utility analysis of valsartan, enalapril, and candesartan in patients with heart failure in Iran
Authors: Ravangard Ramin , Jalali Farideh Sadat , Hajahmadi Marjan , Jafari Abdosaleh
Published: September 2023

Background

Today, heart failure is one of the leading causes of death and disability in most developed and developing countries. By 2030, more than 23.3 million people are projected to die of cardiovascular diseases each year, and the prevalence of heart failure is expected to increase by 25%. One of the preventive interventions is pharmacological interventions which can be used to reduce the complications of cardiovascular diseases such as heart failure. One of the most important pharmacological interventions in patients with heart failure is the use of antihypertensive drugs such as candesartan, enalapril, and valsartan. This study aimed to compare the cost-utility of candesartan, enalapril, and valsartan in patients with heart failure using the Markov model in Iran in 2020.

Methods

In the present study, a four-state Markov model was designed to compare the cost-utility of candesartan, enalapril, and valsartan for a hypothetical cohort of 10,000 heart failure patients older than 24 years. The payers’ perspective was used to calculate the costs. The Markov states included outpatients with heart failure, patients with heart failure admitted to general hospital wards, patients with heart failure admitted to the intensive care units (ICUs), and death. The effectiveness measure in this study was the quality-adjusted life years (QALYs). The one-way and probabilistic sensitivity analyses were used to determine the robustness of the results. The TreeAge Pro 2011 software was used for data analysis.

Results

The results showed that the average expected costs and QALYs were 119645.45 USD and 16.15 for valsartan, 113,019.68 USD and 15.16 for enalapril, and 113,093.37 USD and 15.06 for candesartan, respectively. Candesartan was recognized as the dominated option. Because the calculated incremental cost-effectiveness ratio (ICER) value (6,692.69 USD) was less than the threshold value (7,256 USD), valsartan was cost-effective compared to enalapril. The results of the cost-effectiveness acceptability curve showed that at the threshold of 7,256 USD, valsartan had a 60% chance of being cost-effective compared to enalapril. The results of one-way and probabilistic sensitivity analyses confirmed the robustness of the results. Moreover, the results showed that ICU (1,112 USD) had the highest cost among cost items.

Conclusion

According to the results, it is recommended that health policymakers consider the use of valsartan by cardiologists when designing clinical guidelines for the treatment of patients with heart failure.
Whole genome sequencing and analysis of selenite-reducing bacteria Bacillus paralicheniformis SR14 in response to different sugar supplements
Authors: Wang Fengqin , Gong Tao , Du Man , Xiao Xiao , Jiang Zipeng , Hu Weilian , Wang Yizhen , Cheng Yuanzhi
Published: September 2023

The biosynthetic process of selenium nanoparticles (SeNPs) by specific bacterial strain, whose growth directly affects the synthesis efficiency, has attracted great attentions. We previously reported that Bacillus paralicheniformis SR14, a SeNPs-producing bacteria, could improve intestinal antioxidative function in vitro. To further analyze the biological characteristics of SR14, whole genome sequencing was used to reveal the genetic characteristics in selenite reduction and sugar utilization. The results reviewed that the genome size of SR14 was 4,448,062 bp, with a GC content of 45.95%. A total of 4300 genes into 49 biological pathways was annotated to the KEGG database. EC: 1.1.1.49 (glucose-6-phosphate 1-dehydrogenase) and EC: 5.3.1.9 (glucose-6-phosphate isomerase), were found to play a potential role in glucose degradation and EC:2.7.1.4 (fructokinase) might be involved in the fructose metabolism. Growth profile and selenite-reducing ability of SR14 under different sugar supplements were determined and the results reviewed that glucose had a better promoting effect on the reduction of selenite and growth of bacteria than fructose, sucrose, and maltose. Moreover, RT-qPCR experiment proved that glucose supplement remarkably promoted the expressions of thioredoxin, fumarate reductase, and the glutathione peroxidase in SR14. Analysis of mRNA expression showed levels of glucose-6-phosphate dehydrogenase and fructokinase significantly upregulated under the supplement of glucose. Overall, our data demonstrated the genomic characteristics of SR14 and preliminarily determined that glucose supplement was most beneficial for strain growth and SeNPs synthesis.
Cardiac-to-adipose axis in metabolic homeostasis and diseases: special instructions from the heart
Authors: Tang Songling , Li Ruixin , Ma Wen , Lian Liu , Gao Jiuyu , Cao Yu , Gan Lu
Published: September 2023

Adipose tissue is essential for maintaining systemic metabolic homeostasis through traditional metabolic regulation, endocrine crosstalk, and extracellular vesicle production. Adipose dysfunction is a risk factor for cardiovascular diseases. The heart is a traditional pump organ. However, it has recently been recognized to coordinate interorgan cross-talk by providing peripheral signals known as cardiokines. These molecules include specific peptides, proteins, microRNAs and novel extracellular vesicle-carried cargoes. Current studies have shown that generalized cardiokine-mediated adipose regulation affects systemic metabolism. Cardiokines regulate lipolysis, adipogenesis, energy expenditure, thermogenesis during cold exposure and adipokine production. Moreover, cardiokines participate in pathological processes such as obesity, diabetes and ischemic heart injury. The underlying mechanisms of the cardiac-to-adipose axis mediated by cardiokines will be further discussed to provide potential therapeutic targets for metabolic diseases and support a new perspective on the need to correct adipose dysfunction after ischemic heart injury.
Addressing the second victim phenomenon in Israeli health care institutions
Authors: Cohen Rinat , Sela Yael , Nissanholtz-Gannot Rachel
Published: September 2023

Background

The ‘second victim’ phenomenon (SVP) refers to practitioners who experience a negative physical or emotional response, as well as a professional decline, after participating or witnessing an adverse event. Despite the Israeli Ministry of Health’s implementation of specific protocols regarding the overall management of adverse events in health organizations over the past decade, there is limited knowledge regarding healthcare managers’ perceptions of the ‘second victim’ occurrence.

Methods

A phenomenological qualitative approach was used to identify an accurate view of policy. Fifteen senior risk manager/and policy makers were interviewed about their knowledge and perceptions of the ‘second victim’. Topics addressed included reporting mechanisms of an adverse event, the degree of organizational awareness of ‘second victim’, and identifying components of possible intervention programs and challenges to implementing those programs.

Results

Examining current procedures reveals that there is limited knowledge about uniform guidance for health care organizations on how to identify, treat, or prevent SVP among providers. The employee support programs that were offered were sporadic in nature and depended on the initiative of a direct manager or the risk manager.

Conclusions

Currently, there is little information or organizational discussion about the possible negative effects of AE on healthcare practitioners. To provide overall medical care that is safe and effective for patients, the health system must also provide a suitable response to the needs of the medical provider. This could be achieved by establishing a national policy for all healthcare organizations to follow, raising awareness of the possible occurrence of SVP, and creating a standard for the subsequent identification, treatment and future prevention for providers who may be suffering.
Impact of COVID-19 on subnational variations in life expectancy and life disparity at birth in India: evidence from NFHS and SRS data
Authors: Yadav Pawan Kumar , Yadav Suryakant
Published: September 2023

Background

Measuring life expectancy and life disparity can assist in comprehending how the COVID-19 pandemic has affected the mortality estimates in the Indian population. The present study aims to study the life expectancy and life disparity at birth at the national and subnational levels before and during the COVID-19 pandemic using the NFHS and SRS data.

Methods

The measures Life expectancy at birth ($${e}_{0}$$

e
0

) and Life disparity at birth ($${e}_{0}^{\dagger}$$

e

0

†

) were computed for the non-pandemic and pandemic years from NFHS (2015–16), SRS (2015) and NFHS (2019–21), SRS (2020) respectively at the national and Subnational level in India. Using NFHS data for the 36 states and SRS data for the 22 states, the study calculates $${e}_{0}$$

e
0

and $${e}_{0}^{\dagger}$$

e

0

†

by total, male and female population.

Results

The $${e}_{0}$$

e
0

for male and female decline from 64.3 years and 69.2 years in 2015–16 to 62.9 years and 68.9 years in 2019–21. The $${e}_{0}$$

e
0

shows a drop of approximately 1.4 years for males and 0.3 years for females in the pandemic year 2019–21 when compared to the non-pandemic year 2015–16. At the subnational level $${e}_{0}$$

e
0

shows a decline for 22 states in person, 23 states in males and 21 states in females in the pandemic year 2019–21 as compared to the non-pandemic years 2015–16. The $${e}_{0}^{\dagger}$$

e

0

†

shows a increase for 21 states in person, 24 states in females and 17 states in males in the pandemic year than non-pandemic year. The findings shows a significant losses in $${e}_{0}$$

e
0

and gains in $${e}_{0}^{\dagger}$$

e

0

†

for males than females in the pandemic year as compared to the non-pandemic year at the subnational level in India.

Conclusions

COVID-19 pandemic has decreased $${e}_{0}$$

e
0

and increased $${e}_{0}^{\dagger}$$

e

0

†

in the pandemic year 2019–21 at the national and subnational level in India. COVID-19 had a significant impact on the age pattern of mortality for many states and male, female population and delayed the mortality transition in India.
The type of lipid supplement has crucial implications for forage particle size in calf starter diets
Authors: Panahiha Pedram , Mirzaei-Alamouti Hamidreza , Kazemi-Bonchenari Mehdi , Poorhamdollah Mehdi , Vazirigohar Mina , Aschenbach Jörg R.
Published: September 2023

Background

Forage inclusion in starters of young dairy calves has become an acceptable strategy in the last decade. To compensate for the lower energy provided by forage, concurrent lipid supplementation can be proposed. However, ruminal microbial activity and forage digestibility may be decreased by lipid supplementation. We hypothesized that the composite effect of forage and lipid supplements may be dependent on forage particle size and the type of lipid supplement. Therefore, we evaluated the effect of long (LP; geometric mean, 4.97 mm) vs. short alfalfa hay particle sizes (SP; geometric mean, 1.26 mm) with either soybean oil (SBO) or palm fatty acids (PLF) as lipid source in a 2 × 2 factorial design with treatments SP-SBO, SP-PLF, LP-SBO, and LP-PLF. Treatments (n = 13 with 6 males and 7 females each) were offered to Holstein calves (3 days old) with equal amounts of lipid (25 g/kg DM) throughout the experimental period. The milk offering scheme (d 1 to 53) was equal for all groups. Data collection continued until 20 d post-weaning.

Results

Interaction between forage particle size and lipid supplement was significant for the following readouts: the highest and lowest starter intakes during the pre-weaning period occurred in LP-PLF and LP-SBO, respectively. This was associated with similarly contrasting changes in average daily gain (ADG) during the post-weaning period, body weight at the end of experiment, withers height, digestibility of organic matter and neutral detergent fiber, and blood serum concentrations of glucose, beta-hydroxybutyrate, and insulin during the pre-weaning period. During both pre- and post-weaning periods, the highest and lowest urinary excretion of allantoin and total purine derivatives, representing microbial protein synthesis, were observed in LP-PLF and LP-SBO, respectively, indicating that those diets were most and least favorable for rumen development. Irrespective of forage particle size, supplemental SBO vs. PLF increased serum malondialdehyde as an oxidative stress indicator across periods, increased blood urea nitrogen and feed efficiency in the pre-weaning period, and reduced hip height during the post-weaning period.

Conclusions

It can be concluded that feeding a rumen-inert, mostly saturated fatty acid source with alfalfa hay as long particle size is recommended with view on performance, whereas a combination soybean oil rich in unsaturated fatty acids should not be provided to milk-fed Holstein calves together with long particle forage. Feeding soybean oil and alfalfa hay as long particles is not advisable mainly due to lower starter consumption and impaired development of ruminal function. If dietary supplementation of soybean oil is applied, incorporation of forage as small particles should be preferred to support rumen development.
Targeting NOTCH1 in combination with antimetabolite drugs prolongs life span in relapsed pediatric and adult T-acute lymphoblastic leukemia xenografts
Authors: Minuzzo Sonia , Agnusdei Valentina , Pinazza Marica , Amaro Adriana A. , Sacchetto Valeria , Pfeffer Ulrich , Bertorelle Roberta , Spinelli Orietta , Serafin Valentina , Indraccolo Stefano
Published: September 2023

T-cell acute lymphoblastic leukemia (T-ALL) is a hematologic tumor, characterized by several genetic alterations, that constitutes 15% of pediatric and 25% of adult ALL. While with current therapeutic protocols children and adults’ overall survival (OS) rates reach 85–90% and 40–50%, respectively, the outcome for both pediatric and adult T-ALL patients that relapse or are refractory to induction therapy, remains extremely poor, achieving around 25% OS for both patient groups. About 60% of T-ALL patients show increased NOTCH1 activity, due to activating NOTCH1 mutations or alterations in its ubiquitin ligase FBXW7. NOTCH signaling has been shown to contribute to chemotherapy resistance in some tumor models. Hence, targeting the NOTCH1 signaling pathway may be an effective option to overcome relapsed and refractory T-ALL.

Here, we focused on the therapeutic activity of the NOTCH1-specific monoclonal antibody OMP-52M51 in combination either with drugs used during the induction, consolidation, or maintenance phase in mice xenografts established from pediatric and adult relapsed NOTCH1 mutated T-ALL samples. Interestingly, from RNAseq data we observed that anti-NOTCH1 treatment in vivo affects the purine metabolic pathway. In agreement, both in vitro and in vivo, the greatest effect on leukemia growth reduction was achieved by anti-NOTCH1 therapy in combination with antimetabolite drugs. This result was further corroborated by the longer life span of mice treated with the anti-NOTCH1 in combination with antimetabolites, indicating a novel Notch-targeted therapeutic approach that could ameliorate pediatric and adult T-ALL patients outcome with relapse disease for whom so far, no other therapeutic options are available.
Effective investigation of murine femoral bone development utilizing correlative light and electron microscopy (CLEM)
Authors: Kwon Yong-Eun , Kim Jung-Kyun , Kim Youn-Joong , Je A. Reum , Guim Hwanuk , Kim Jin-Gyu
Published: September 2023

Background

For effective investigation of the developing structure and chemistry of bone, comprehensive studies including compositional analysis can be achieved through the gradual observation from the micro- to nanometer scale via correlative light and electron microscopy (CLEM). This technique is particularly useful considering the complex hierarchical arrangement of bioapatite and collagen fibrils which may vary according to specific bone tissue types (i.e., lamellar bone and woven bone) and different growth stages. Scanning electron microscopy (SEM) accompanied with the attachment of the scanning transmission electron microscopy (STEM) detector, referred to as the STEM-in-SEM can be utilized to produce high contrast images from materials composed of light elements, and efficiently allows the selection of suitable accelerating voltage for energy-dispersive spectroscopy (EDS). This study aims to emphasize the efficacy of CLEM techniques through applying STEM-in-SEM and EDS analyses, and its application to comparative murine bone investigation in differing ontogenetic stages.

Findings

We have designed a new grid-holder which can be used for both light and electron microscopy, and we presented an imaging technique for TEM specimens via reflective light microscopy (RLM). For performing CLEM, ultra-thin-sections (UTS) prepared from the femoral bones of 1- to 16-week old of Sprague-Dawley (SD) rats provided light and electron micrographs that can be correlated based on the regions of interest (ROIs). STEM-in-SEM micrographs revealed information not attainable by secondary electron (SE) and back-scattered electron (BSE) micrographs. In addition, for analyzing chemical variation according to growth and development of femoral bones from 1- to 16-week-old rats, comparative chemical analysis was performed through STEM-in-SEM EDS with two reference materials.

Conclusion

Herein, from femoral bones of SD rats, we have confirmed the rapid chemical and structural variations within the first 8 weeks after birth. STEM-in-SEM micrographs revealed the bone development process of the early stage porous bone matrix subsequently being filled with collagen fibrils and bioapatite. In addition, chemical analysis for carbon and oxygen showed the ratios of inorganic to organic phases according to growth and progress in bone mineralization. As a result, we were able to postulate the growth mechanism of murine femoral bone in the neonatal stages of development. We also anticipate that our CLEM techniques can be further utilized for more thorough investigation of bone structure and chemistry in diverse scales.
Amide proton transfer (APT) and magnetization transfer (MT) in predicting short-term therapeutic outcome in nasopharyngeal carcinoma after chemoradiotherapy: a feasibility study of three-dimensional chemical exchange saturation transfer (CEST) MRI
Authors: Liu Wenguang , Wang Xiao , Xie Simin , Liu Weiyin Vivian , Masokano Ismail Bilal , Bai Yu , Chen Juan , Zhong Linhui , Luo Yijing , Zhou Gaofeng , Li Wenzheng , Pei Yigang
Published: September 2023

Background

The three-dimensional chemical exchange saturation transfer (3D CEST) technique is a novel and promising magnetic resonance sequence; however, its application in nasopharyngeal carcinoma (NPC) lacks sufficient evaluation. This study aimed to assess the feasibility of the 3D CEST technique in predicting the short-term treatment outcomes for chemoradiotherapy (CRT) in NPC patients.

Methods

Forty NPC patients and fourteen healthy volunteers were enrolled and underwent the pre-treatment 3D CEST magnetic resonance imaging and diffusion-weighted imaging (DWI). The reliability of 3D CEST was assessed in healthy volunteers by calculating the intra- and inter-observer correlation coefficient (ICC) for amide proton transfer weighted-signal intensity (APTw-SI) and magnetization transfer ratio (MTR) values. NPC patients were divided into residual and non-residual groups based on short-term treatment outcomes after CRT. Whole-tumor regions of interest (ROIs) were manually drawn to measure APTw-SI, MTR and apparent diffusion coefficient (ADC) values. Multivariate analysis and the receiver operating characteristic curve (ROC) were used to evaluate the prediction performance of clinical characteristics, APTw-SI, MTR, ADC values, and combined models in predicting short-term treatment outcomes in NPC patients.

Results

For the healthy volunteer group, all APTw-SI and MTR values exhibited good to excellent intra- and inter-observer agreements (0.736–0.910, 0.895–0.981, all P > 0.05). For NPC patients, MTR values showed a significant difference between the non-residual and residual groups (31.24 ± 5.21% vs. 34.74 ± 1.54%, P = 0.003) while no significant differences were observed for APTw-SI and ADC values (P > 0.05). Moreover, the diagnostic power of MTR value was superior to APTw-SI (AUC: 0.818 vs. 0.521, P = 0.017) and comparable to ADC values (AUC: 0.818 vs. 0.649, P > 0.05) in predicting short-term treatment outcomes for NPC patients. The prediction performance did not improve even when combining MTR values with APTw-SI and/or ADC values (P > 0.05).

Conclusions

The pre-treatment MTR value acquired through 3D CEST demonstrated superior predictive performance for short-term treatment outcomes compared to APTw-SI and ADC values in NPC patients after CRT.
Assessing the impact of climate change on sediment discharge using a large ensemble rainfall dataset in Pekerebetsu River basin, Hokkaido
Authors: Kido Riho , Inoue Takuya , Hatono Misako , Yamanoi Kazuki
Published: September 2023

Increased rainfall associated with climate change can increase sediment discharge. The supply of fine sediment from slope failures inhibits bed armoring of mountain rivers and increases sediment discharge to the downstream reaches. Floods without slope failures lead to bed erosion and armoring and may ultimately decrease sediment discharge. Thus, it is important to consider sediment discharge from slope failure and bed erosion as factors affecting sediment production. Climate change affects not only the rainfall amount, but also the temporal rainfall pattern; consequently, the pattern affects the sediment production factors and the amount of sediment discharge. However, changes in sediment discharge due to climate change based on sediment production sources have not yet been clarified. In this study, we statistically analyzed 1200 results simulated using a physics-based sediment runoff model to assess the impact of changes in temporal rainfall patterns on sediment discharge and sediment production sources in the Pekerebetsu River Basin. In the simulations, we used the rainfall predicted in d4PDF (Database for policy decision-making for future climate change), a large ensemble climate simulation database at 5 km and 20 km resolutions. Our results showed that the climate-driven increase in sediment discharge was considerably larger than that of rainfall. An increase in short-term heavy rainfall increased the supply of fine sediments from slope failure. This resulted in the suppression of bed armoring and a large increase in sediment discharge. Thus, the increase in sediment discharge is not only caused by an increase in rainfall but also by changes in temporal rainfall patterns and sediment production factors. The sediment discharge calculated for the 20 km resolution climate projection was nearly one order of magnitude smaller than that for the 5 km resolution. This suggests that the 20 km resolution climate projections do not adequately represent orographic rainfall in the mountains and thus, do not adequately reproduce extreme sediment discharge events. An increased sediment supply causes bed aggradation and decreases the river conveyance capacity of the downstream channel. The model developed in this study will contribute to flood risk analysis and flood control planning for increased rainfall due to climate change.
Multidimensional analysis for fabric drapability
Authors: Shin Bona , Yun Changsang
Published: September 2023

This study analyzed fabric drapability in one, two, and three dimensions to provide an assessment method reflecting real conditions. One-dimensional analysis of drapability involved observing the fabric movement by reciprocating motion. The movement appeared differently depending on the fabric characteristics, and the shape and location of the node showed differently, which were considered to be influenced by the weight of the sample along with the drape coefficient. Two-dimensional analysis identified the significant factors for the drape information. This examination confirmed that, even if drape factors were similar, differences in draped shape were observed based on the factors related to node shapes. Three-dimensional analysis, using a 3D scanner, involved the use of the mean distances between draped samples and the standard truncated cone, their standard deviation, and the coefficient of variation. The coefficient of variation was high in the groups wherein the shape of the drape was irregular. In the 3D analysis, the distances between samples and the standard truncated cone were expressed in colors to intuitively deliver the drape information. To determine a factor that could indicate drapability among the factors derived from each dimension, the existing drape coefficient was employed for correlation analysis. Three pairs of samples with similar drape coefficients but different drape shapes were selected to verify the above results. In conclusion, one-dimensional node location, two-dimensional standard deviation of node severity, and three-dimensional coefficient of variation were shown to effectively demonstrate the drape characteristic that the drape coefficient could not indicate.
Significance of pharmacist intervention to oral antithrombotic therapy in the pharmaceutical outpatient clinic of cardiovascular internal medicine: a retrospective cohort study
Authors: Kurimura Tomoko , Yamamoto Kazuhiro , Tanaka Hidekazu , Toba Takayoshi , Kimura Takeshi , Habu Yasushi , Itohara Kotaro , Kitahiro Yumi , Omura Tomohiro , Yano Ikuko
Published: September 2023

Background

Optimised antithrombotic therapy requires clinical experience and an understanding of the current guidelines. This retrospective study aimed to evaluate whether pharmacist interviews and interventions with patients taking oral antithrombotic drugs in the pharmaceutical outpatient cardiology clinic had favourable clinical outcomes including decreased bleeding.

Methods

The participants included patients visiting the outpatient clinic of cardiovascular internal medicine at the Kobe University Hospital from January–December 2017, and were taking oral antithrombotic medication. The observation period was from the first visit to the outpatient clinic to October 2021 or death. Patients who received pharmacist intervention more than twice were defined as the pharmacist intervention group. Two control patients per one pharmacist intervention group individual were selected from the non-intervention pool matched for age, gender and antithrombotic medication type.

Results

Of the 895 eligible patients, 132 were in the pharmacist intervention group and 264 were selected for the matched non-intervention group. Bleeding events according to the Bleeding Academic Research Consortium criteria over type 2 were significantly lower in the pharmacist intervention group compared with the non-intervention group (17.4% versus 28.4%, P = 0.019). There were no significant differences in mortality and heart failure hospitalisation frequency, stroke, or cardiovascular events between the groups. Multivariate analysis identified age (≥ 65 years) and pharmacist intervention as factors associated with bleeding (odds ratio = 2.29 and 0.51, respectively).

Conclusion

Pharmacist intervention in the outpatient clinic of cardiovascular internal medicine was effective in reducing the risk of bleeding in patients undergoing antithrombotic therapy.
Study protocol for a feasibility study of an online educational programme for people working and living with persistent low back pain
Authors: Marley Joanne , Larsson Caroline , Piccinini Flavia , Howes Sarah , Casoni Elisa , Hansson Eva Ekvall , McDonough Suzanne
Published: September 2023

Background

Low back pain (LBP) is the main cause of activity limitation and work absence across the world, leading to a high social and economic burden for individuals, families, the labour market and society. The overall aim of this multicentre study is to test the usability, acceptability and feasibility of an evidence-based, digital education programme for people living and working with persistent LBP who are in sedentary or physically demanding jobs and need advice on ergonomics, self-management of pain and healthy behavioural strategies.

Methods

This is the protocol of a multinational, multicentre, prospective uncontrolled feasibility study targeting people with persistent LBP in Lithuania, Northern Ireland, Italy, Sweden and Portugal. Eligible participants will be offered the opportunity to use the MyRelief educational platform as part of their care and will undergo evaluations at baseline (enrollment) and 1-month follow-up. Feasibility will be assessed using measures of recruitment and retention, intervention engagement, outcome measure completion rates and within-group effect sizes in response to the digital education programme.

Discussion

This study will identify the challenges and implications of delivering a digital training programme in advance of potentially delivering the programme via an online educational platform available on mobile devices. The findings will inform the design of a future randomised controlled trial if it proves feasible.

Trial registration

ClinicalTrials.gov, NCT04673773. Registered 17 December 2020.
Reducing kidney uptake of radiolabelled exendin-4 using variants of the renally cleavable linker MVK
Authors: Trachsel Belinda , Valpreda Giulia , Lutz Alexandra , Schibli Roger , Mu Linjing , Béhé Martin
Published: September 2023

Background

Peptidic radiotracers are preferentially excreted through the kidneys, which often results in high persistent renal retention of radioactivity, limiting or even preventing therapeutic clinical translation of these radiotracers. Exendin-4, which targets the glucagon-like-peptide 1 receptor (GLP-1R) overexpressed in insulinomas and in congenital hyperinsulinism, is an example thereof. The use of the tripeptide MVK, which is readily cleaved between methionine and valine by neprilysin at the renal brush border membrane, already showed promising results in reducing kidney uptake as reported in the literature. Based on our previous findings we were interested how linker variants with multiple copies of the MV-motive influence renal washout of radiolabelled exendin-4.

Results

Three exendin-4 derivatives, carrying either one MVK, a MV-MVK or a MVK-MVK linker were synthesized and compared to a reference compound lacking a cleavable linker. In vivo results of a biodistribution in GLP-1R overexpressing tumour bearing mice at 24 h post-injection demonstrated a significant reduction (at least 57%) of renal retention of all 111In-labeled exendin-4 compounds equipped with a cleavable linker compared to the reference compound. While the insertion of the single linker MVK led to a reduction in kidney uptake of 70%, the dual approach with the linker MV-MVK slightly, but not significantly enhanced this effect, with 77% reduction in kidney uptake compared to the reference. In vitro IC50 and cell uptake studies were conducted and demonstrated that though the cleavable linkers negatively influenced the affinity towards the GLP-1R, cell uptake remained largely unaffected, except for the MV-MVK cleavable linker conjugate, which displayed lower cell uptake than the other compounds. Importantly, the tumour uptake in the biodistribution study was not significantly affected with 2.9, 2.5, 3.2 and 1.5% iA/g for radiolabelled Ex4, MVK-Ex4, MV-MVK-Ex4 and MVK-MVK-Ex4, respectively.

Conclusion

Cleavable linkers are highly efficient in reducing the radioactivity burden in the kidney. Though the dual linker approach using the instillation of MV-MVK or MVK-MVK between exendin-4 and the radiometal chelator did not significantly outperform the single cleavable linker MVK, further structural optimization or the combination of different cleavable linkers could be a stepping stone in reducing radiation-induced nephrotoxicity.
Prognosis and prediction of antibiotic benefit in adults with clinically diagnosed acute rhinosinusitis: an individual participant data meta-analysis
Authors: Hoogland Jeroen , Takada Toshihiko , van Smeden Maarten , Rovers Maroeska M. , de Sutter An I. , Merenstein Daniel , Kaiser Laurent , Liira Helena , Little Paul , Bucher Heiner C. , Moons Karel G. M. , Reitsma Johannes B. , Venekamp Roderick P.
Published: September 2023

Background

A previous individual participant data meta-analysis (IPD-MA) of antibiotics for adults with clinically diagnosed acute rhinosinusitis (ARS) showed a marginal overall effect of antibiotics, but was unable to identify patients that are most likely to benefit from antibiotics when applying conventional (i.e. univariable or one-variable-at-a-time) subgroup analysis. We updated the systematic review and investigated whether multivariable prediction of patient-level prognosis and antibiotic treatment effect may lead to more tailored treatment assignment in adults presenting to primary care with ARS.

Methods

An IPD-MA of nine double-blind placebo-controlled trials of antibiotic treatment (n=2539) was conducted, with the probability of being cured at 8–15 days as the primary outcome. A logistic mixed effects model was developed to predict the probability of being cured based on demographic characteristics, signs and symptoms, and antibiotic treatment assignment. Predictive performance was quantified based on internal-external cross-validation in terms of calibration and discrimination performance, overall model fit, and the accuracy of individual predictions.

Results

Results indicate that the prognosis with respect to risk of cure could not be reliably predicted (c-statistic 0.58 and Brier score 0.24). Similarly, patient-level treatment effect predictions did not reliably distinguish between those that did and did not benefit from antibiotics (c-for-benefit 0.50).

Conclusions

In conclusion, multivariable prediction based on patient demographics and common signs and symptoms did not reliably predict the patient-level probability of cure and antibiotic effect in this IPD-MA. Therefore, these characteristics cannot be expected to reliably distinguish those that do and do not benefit from antibiotics in adults presenting to primary care with ARS.
Detecting compromised email accounts via login behavior characterization
Authors: Zhao Jianjun , Yang Can , Wu Di , Cao Yaqin , Liu Yuling , Cui Xiang , Liu Qixu
Published: September 2023

The illegal use of compromised email accounts by adversaries can have severe consequences for enterprises and society. Detecting compromised email accounts is more challenging than in the social network field, where email accounts have only a few interaction events (sending and receiving). To address the issue of insufficient features, we propose a novel approach to detecting compromised accounts by combining time zone differences and alternate logins to identify abnormal behavior. Based on this approach, we propose a compromised email account detection framework that relies on widely available and less sensitive login logs and does not require labels. Our framework characterizes login behaviors to identify logins that do not belong to the account owner and outputs a list of account-subnet pairs ranked by their likelihood of having abnormal login relationships. This approach reduces the number of account-subnet pairs that need to be investigated and provides a reference for investigation priority. Our evaluation demonstrates that our method can detect most email accounts that have been accessed by disclosed malicious IP addresses and outperforms similar research. Additionally, our framework has the capability to uncover undisclosed malicious IP addresses.
TRPC expression in human periodontal ligament cells and the periodontal tissue of periodontitis mice: a preliminary study
Authors: Kim Aeryun , Kim Ae Ri , Jeon Yeong-Eui , Yoo Yun‑Jung , Yang Yu-Mi , Bak Eun‑Jung
Published: September 2023

Background

Transient receptor potential canonical (TRPC) channels are non-selective cationic channels with permeability to Ca2+ and Na+. Despite their importance, there are currently few studies on TRPC in the periodontal ligament (PDL) and bone cells in the dental field. To provide biological information regarding TRPC in PDL cells and periodontal tissue, we evaluated TRPC channels expression in the osteoblast differentiation of PDL cells and periodontitis-induced tissue. Human PDL cells were cultured in osteogenic differentiation media for 28 days, and the expression of Runx2, osteocalcin (OCN), and TRPC1, 3, 4, and 6 was evaluated by real-time PCR. In ligature-induced periodontitis mice, the alveolar bone and osteoid areas, the osteoclast number, and the expression of Runx2, OCN, TRPC3, and TRPC6 was evaluated by H&E staining, TRAP staining, and immunohistochemistry, respectively.

Results

In the PDL cell differentiation group, TRPC6 expression peaked on day 7 and TRPC3 expression generally increased during differentiation. During the 28 days of periodontitis progression, alveolar bone loss and osteoclast numbers increased compared to the control group during the experimental period and the osteoid area increased from day 14. TRPC6 expression in the periodontitis group increased in the PDL area and in the osteoblasts compared to the control group, whereas TRPC3 expression increased only in the PDL area on days 7 and 28.

Conclusions

These results indicate changes of TRPC3 and TRPC6 expression in PDL cells that were differentiating into osteoblasts and in periodontitis-induced tissue, suggesting the need for research on the role of TRPC in osteoblast differentiation or periodontitis progression.