bluuebunny/crossref_metadata_2025 huggingface dataset:
Draft genome of six Cuban Anolis lizards and insights into genetic changes during their diversification
Authors: Kanamori Shunsuke , Díaz Luis M. , Cádiz Antonio , Yamaguchi Katsushi , Shigenobu Shuji , Kawata Masakado
Published: November 2022

Background

Detecting genomic variants and their accumulation processes during species diversification and adaptive radiation is important for understanding the molecular and genetic basis of evolution. Anolis lizards in the West Indies are good models for studying evolutionary mechanisms because of the repeated evolution of their morphology and the ecology. We performed de novo genome assembly of six Cuban Anolis lizards with different ecomorphs and thermal habitats (Anolis isolepis, Anolis allisoni, Anolis porcatus, Anolis allogus, Anolis homolechis, and Anolis sagrei). We carried out a comparative analysis of these genome assemblies to investigate the genetic changes that occurred during their diversification.

Results

We reconstructed novel draft genomes with relatively long scaffolds and high gene completeness, with the scaffold N50 ranging from 5.56 to 39.79 Mb and vertebrate Benchmarking Universal Single-Copy Orthologs completeness ranging from 77.5% to 86.9%. Comparing the repeat element compositions and landscapes revealed differences in the accumulation process between Cuban trunk-crown and trunk-ground species and separate expansions of several families of LINE in each Cuban trunk-ground species. Duplicated gene analysis suggested that the proportional differences in duplicated gene numbers among Cuban Anolis lizards may be associated with differences in their habitat ranges. Additionally, Pairwise Sequentially Markovian Coalescent analysis suggested that the effective population sizes of each species may have been affected by Cuba’s geohistory.

Conclusions

We provide draft genomes of six Cuban Anolis lizards and detected species and lineage-specific transposon accumulation and gene copy number changes that may be involved in adaptive evolution. The change processes in the past effective population size was also estimated, and the factors involved were inferred. These results provide new insights into the genetic basis of Anolis lizard diversification and are expected to serve as a stepping stone for the further elucidation of their diversification mechanisms.
Serum angiopoietin-1 concentration does not distinguish patients with ischaemic stroke from those presenting to hospital with ischaemic stroke mimics
Authors: Moxon Joseph V. , Kraeuter Ann-Katrin , Phie James , Juliano Sheryl , Anderson Georgina , Standley Glenys , Sealey Cindy , White Richard P. , Golledge Jonathan
Published: November 2022

Background

A previous study found that circulating angiopoietin-1 (angpt-1) concentrations were significantly lower in patients who had a recent ischaemic stroke compared to healthy controls. The primary aim of this study was to assess whether serum angpt-1 could be used as a diagnostic test of ischemic stroke in patients presenting to hospital as an emergency. Exploratory analyses investigated the association of proteins functionally related to angpt-1 (angpt-2, Tie-2, matrix metalloproteinase-9 and vascular endothelial growth factors A, C and D) with ischaemic stroke diagnosis.

Methods

Patients presenting to Townsville University Hospital for emergency assessment of stroke-like symptoms were consecutively recruited and provided a blood sample. After assessment by a consultant neurologist, patients were grouped into those who did, or did not have ischaemic stroke. The potential for serum angpt-1 to diagnose ischaemic stroke was assessed using receiver operator characteristic (ROC) curves. Cross-sectional analyses appraised inter-group differences in the serum concentration of other proteins.

Results

One-hundred and twenty-six patients presenting to Townsville University Hospital for emergency assessment of stroke-like symptoms were recruited (median time from symptom onset to hospital presentation: 2.6 (inter-quartile range: 1.2–4.6) hours). Serum angpt-1 had poor ability to diagnose ischaemic stroke in analyses using the whole cohort, or in sensitivity analyses (area under the ROC curve 0.51 (95% CI: 0.41–0.62) and 0.52 (95% CI: 0.39–0.64), respectively). No associations of serum angpt-1 concentration with ischaemic stroke severity, symptom duration or aetiology were observed. Serum concentrations of the other assessed proteins did not differ between patient groups.

Conclusions

Serum angpt-1 concentration is unlikely to be useful for emergency diagnosis of ischaemic stroke.
Utility of diffusion weighted imaging-based radiomics nomogram to predict pelvic lymph nodes metastasis in prostate cancer
Authors: Liu Xiang , Tian Jingyi , Wu Jingyun , Zhang Yaofeng , Wang Xiangpeng , Zhang Xiaodong , Wang Xiaoying
Published: November 2022

Background

Preoperative pelvic lymph node metastasis (PLNM) prediction can help clinicians determine whether to perform pelvic lymph node dissection (PLND). The purpose of this research is to explore the feasibility of diffusion-weighted imaging (DWI)-based radiomics for preoperative PLNM prediction in PCa patients at the nodal level.

Methods

The preoperative MR images of 1116 pathologically confirmed lymph nodes (LNs) from 84 PCa patients were enrolled. The subjects were divided into a primary cohort (67 patients with 192 positive and 716 negative LNs) and a held-out cohort (17 patients with 43 positive and 165 negative LNs) at a 4:1 ratio. Two preoperative pelvic lymph node metastasis (PLNM) prediction models were constructed based on automatic LN segmentation with quantitative radiological LN features alone (Model 1) and combining radiological and radiomics features (Model 2) via multiple logistic regression. The visual assessments of junior (Model 3) and senior (Model 4) radiologists were compared.

Results

No significant difference was found between the area under the curve (AUCs) of Models 1 and 2 (0.89 vs. 0.90; P = 0.573) in the held-out cohort. Model 2 showed the highest AUC (0.83, 95% CI 0.76, 0.89) for PLNM prediction in the LN subgroup with a short diameter ≤ 10 mm compared with Model 1 (0.78, 95% CI 0.70, 0.84), Model 3 (0.66, 95% CI 0.52, 0.77), and Model 4 (0.74, 95% CI 0.66, 0.88). The nomograms of Models 1 and 2 yielded C-index values of 0.804 and 0.910, respectively, in the held-out cohort. The C-index of the nomogram analysis (0.91) and decision curve analysis (DCA) curves confirmed the clinical usefulness and benefit of Model 2.

Conclusions

A DWI-based radiomics nomogram incorporating the LN radiomics signature with quantitative radiological features is promising for PLNM prediction in PCa patients, particularly for normal-sized LNM.
Barriers to physical activity in pregnant women living in Iran and its predictors: a cross sectional study
Authors: Dolatabadi Zari , Amiri-Farahani Leila , Ahmadi Katayon , Pezaro Sally
Published: November 2022

Background and aims

Despite the benefits of physical activity (PA) on maternal and fetal health, the level of PA is low among pregnant women globally. The aim of this study was to determine the barriers to PA and its predictors in Iranian pregnant women specifically.

Methods

This cross-sectional study included 300 pregnant women referred to the Ilam health centers of Iran. The sampling strategy used stratified random proportional allocation sampling from both comprehensive health centers and health bases. Data were collected from September to December 2018 in relation to individual characteristics. Data collection tools used included the Pregnancy Physical Activity Questionnaire and the Barriers to Physical Activity during Pregnancy Scale. To analyze the data, descriptive statistics and statistical tests of analysis including variance, independent t-test and multiple linear regression were used.

Results

The mean and SD of the total score of PA barriers was 88.55 and 19.28, respectively. The highest and lowest mean scores of the subscale of PA barriers were related to interpersonal and environmental barriers, respectively. Among the intrapersonal barriers related to pregnancy; fear of pregnancy complications, drowsiness, and nausea and vomiting, heaviness or swelling barriers scored higher than other barriers. Lack of regular schedule, insufficient time, and lack of motivation received the highest score in terms of intrapersonal barriers non-related to pregnancy. In the interpersonal subscale; lack of knowledge about how to be physically active during pregnancy, forbiddance of PA by friends and family, as well as lack of advice from physicians and midwives scored higher than other barriers. Lack of adequate facilities and air pollution were identified as barriers to PA in the environmental subscale. PA barriers were significantly associated with pre-pregnancy or early pregnancy body mass index (B = − 14.643), level of education (B = 17.215), and habitual exercise pre-pregnancy (B = − 7.15).

Conclusion

Interpersonal barriers were reported to be the most common barriers to PA during pregnancy. Perinatal care providers should encourage, educate and reassure pregnant women, their spouses and their families about the benefits, type and frequency of safe PA in pregnancy. PA interventions focused on women with lower levels of education and income in particular are required.
Frozen-thawed embryo transfer in modified natural cycles: a retrospective analysis of pregnancy outcomes in ovulatory women with vs. without spontaneous luteinizing hormone surge
Authors: Ye Hongjuan , Shi Liya , Quan Xinxin , Xue Xue , Qian Ying , Tian Hui , Xue Songguo , Sun Lihua
Published: November 2022

Background

Timing of frozen embryo transfer (FET) in natural endometrial preparation cycles is often based on luteinizing hormone (LH) surge. However, some patients do not show spontaneous LH surge despite follicular maturation. The objective of this study was to evaluate the impact of spontaneous LH surge on pregnancy outcomes in modified natural cycles (mNC).

Methods

This retrospective analysis included 1897 FET cycles with modified natural endometrial preparation in normo-ovulatory women between January 1, 2015, to December 31, 2019, at our center: 920 cycles with spontaneous LH surge (≥ 20 IU/L) and 977 without. For cleavage embryos, FET was conducted 4 and 5 days after hCG injection in women with and without LH surge, respectively. For blastocysts, FET was conducted 6 and 7 days after hCG injection in women with and without LH surge, respectively. Multivariate regression was conducted to examine the factors associated with live birth.

Results

Live birth rate was 43.7% in patients with spontaneous LH surge vs. 43.8% in women without LH surge (P = 0.961). The two groups also had similar implantation rate (36.2% vs. 36.7%, P = 0.772), biochemical pregnancy rate (54.8% vs. 55.4%, P = 0.796) and clinical pregnancy rate (50.9% vs. 51.7%, P = 0.721). In multivariate regression, live birth was not associated with LH surge (aOR, 0.947, 95% CI, 0.769, 1.166).

Conclusion

Pregnancy outcomes were similar in mNC-FET in cycles with vs. without spontaneous LH surge if FET timing is adjusted.
Eyelid and scleral thermal injury following phacoemulsification in silicone oil: a case report
Authors: Lee Yu-Kuei , Chen Szu-Han , Hung Jia-Horung
Published: November 2022

Background

Phacoemulsification has been the mainstay method for extracapsular cataract extraction surgery in the anterior segment; for cases of posterior drop of lens fragments into the vitreous, a posterior segment phacoemulsification instrument (fragmatome; Alcon, Inc., Fort Worth, TX) can be employed to remove the dislocated lens materials. Studies have reported on thermal injury to the cornea during phacmoemulsification of the anterior segment. However, few studies have investigated thermal burn in the simultaneous sclera and eyelid induced by the fragmatome. Currently, there is no reports and lack of optimal strategy for the management of nucleus drop in a vitreous cavity filled with silicon oil.

Case Presentation

We present the case of a 53-year-old male patient with a thermal burn wound on the upper eyelid and sclera following phacoemulsification for a dropped lens in a silicone oil-filled vitreous. We further designed an experiment to verify our hypothesis that thermal injury could be induced by the high temperature of the metal tip during phacoemulsification in silicone oil. In our experiment, during 420 s of continuous ultrasonic wave, the temperature of the fragmatome tip in the balanced salt solution (BSS) increased from 22.0 to 24.0 ºC, while the temperature of the fragmatome tip in the silicone oil group increased from 22.0 to 43.0 ºC.

Conclusions

The temperature of the fragmatome tip increased significantly in silicone oil compared to BSS in the experiment. Thus, physicians should be aware of possible thermal complications when using fragmatome in eyes filled with silicone oil.
Exploring knowledge of parents and caregivers on cancer symptoms in children: an observational study regarding the need for educational tools and health promotion in low- and middle-income countries
Authors: Uribe-Ortiz Leslie V. , Garza-Ornelas Bárbara M. , Vázquez-Fernández Ana C. , Castorena-Torres Fabiola , Rodríguez-De-Ita Julieta
Published: November 2022

Background

Although most cases of childhood cancer are unlikely to be prevented, by today’s standards, most children with cancer can now be cured. However, disparities about survival exist among countries; in Mexico, the overall survival is 49.6%, with 70% of childhood cancers diagnosed at advanced stages. Therefore, parents and caregivers must have optimal knowledge of the early signs and symptoms of childhood malignancies as they are largely non-specific. This study was designed to explore the current knowledge of childhood cancer among parents and caregivers in Mexico and identify the need for education and health promotion in low- and middle-income countries.

Methods

An online survey of 112 parents and caregivers was performed to assess their knowledge of childhood cancer, focusing on the signs and symptoms and early diagnostic strategies.

Results

Sixty-nine (61.6%) mothers, 23 (20.5%) fathers, 17 (15.2%) familiar caregivers, and 3 (2.7%) non-familiar caregivers responded. Forty-six (41.1%) respondents said that they knew a child diagnosed with cancer, 92.9% mentioned leukemia as the most common type of cancer among children, the most highly ranked option when asked which sign/symptom they considered as a warning for suspicion was growth/lump in any part of the body, 97.3% considered that an early diagnosis is related to a higher cure rate, and 92.9% expressed the desire to receive reliable information about childhood cancer.

Conclusions

Although parents and caregivers have some knowledge of childhood cancer, there are concepts that should be reinforced to improve their understanding of this group of diseases, as they are the frontline for children to seek medical attention. In the future, the use of tools that help educate more caregivers will strengthen knowledge and contribution regarding this issue and promote the generation of public policies that support the early diagnosis of childhood cancer.
Relationship of serum homocysteine and vitamin D with positive, negative, and extrapyramidal symptoms in schizophrenia: a case–control study in Iran
Authors: Shahini Najmeh , Jazayeri Seyed Mohammad Mousavi Zade , Jahanshahi Reza , Charkazi Abdurrahman
Published: November 2022

Background

Schizophrenia is a devastating condition characterized by frequent recurrences, cognitive decline, and emotional and functional disabilities. This condition includes positive and negative symptoms and cognitive impairments resistant to drug treatment. According to studies, many biomarkers can affect this disorder. However, there is little information about vitamin D and homocysteine levels in patients with disease complications. We aimed to investigate this relationship in schizophrenia.

Method

In this case–control study, 33 patients with schizophrenia and 33 healthy individuals were enrolled from Golestan, the north of Iran, in 2021. Blood samples were taken from all participants to assess vitamin D and homocysteine serum levels. In addition, schizophrenic patients completed the Positive And Negative Syndrome Scale (PANSS) and Simpson-Angus Extrapyramidal Side Effects Scale (SAS). Data analysis was performed at a significance level of 0.05 using SPSS 16 software.

Results

Of the 66 participants, 66.7% had vitamin D deficiency, and 71.2% had normal homocysteine levels. However, the serum level of vitamin D was lower in schizophrenic patients than in controls (p = 0.035), and serum homocysteine levels were higher in the schizophrenic group than in controls (p < 0.001). Vitamin D levels in patients with schizophrenia were significantly correlated with the overall assessment of extrapyramidal symptoms (r = 0.35, p = 0.04). However, no significant relationship existed between vitamin D and homocysteine levels and PANSS results (p > 0.05).

Conclusion

Serum levels of vitamin D and homocysteine were significantly lower and higher in schizophrenic patients than in the control group. Improvement of extrapyramidal symptoms in schizophrenic patients had a direct and significant relationship with serum vitamin D.
COVID-19 impact on the psychological health of Latinx transgender and non-binary individuals in mainland United States and Puerto Rico: a mixed-methods study
Authors: Ramos-Pibernus Alíxida , Rodríguez-Madera Sheilla , Rosario-Hernández Ernesto , Moreta-Ávila Fabián , Silva-Reteguis Julián , Rivera-Segarra Eliut
Published: November 2022

Background

The COVID-19 pandemic continues to generate an unprecedented impact on all aspects of everyday life across the world. However, those with historically and currently marginalized identities (i.e., gender or ethnicity) who already experience a wide range of structural inequities have been disproportionally impacted. LTNB are a particularly at-risk population as they lie at the intersection of race/ethnicity, gender identity, language, migration status, geographical location, among others, which could further increase their COVID-19 and other health-related risks and disparities. The objective of this study was to examine the impact of key social determinants of health (i.e., gender identity, country, health insurance, employment) among a sample of LTNB individuals.

Methods

The team implemented a cross-sectional exploratory design with an online survey technique using the secure web platforms REDcap and SurveyMonkey. A total of 133 participants completed the online survey. Most of the sample self-identified as transwomen (38.8%), transmen (26.3%), and non-binary (21.8%) between the ages of 21 to 72. All participants were Latinx living in either Puerto Rico (47.7%) or mainland United States (52.3%). Descriptive statistics, reliability tests, Mann-Whitney and rapid thematic analysis test were conducted.

Results

Findings show that most participants were always (38.1%) or almost always (33.3%) worried about contracting COVID-19. Individuals living in Puerto Rico reported more difficulties than those residing in the mainland US regarding COVID-19 impact on psychosocial, emotional, and COVID-related thinking. Most participants’ answers for the COVID-19 open-ended questions focused on three main domains: income, access to trans-affirmative health care, and coping strategies.

Discussion

Findings evidence that although most of LTNB participants were negatively impacted by the COVID-19 pandemic in multiple aspects of their lives, those living in Puerto Rico experienced these differently when compared to those in mainland US. More research is needed to understand better the mechanisms and pathways through which this context specifically impacts LTNB health and wellbeing, particularly in Puerto Rico. This study could help shape the public health response taking into account the geographical location and other intersectional identities that play critical roles in the production and reproduction of inequities.
Long-term evaluation of safety and biological effects of Korean Red Ginseng (Panax Ginseng): a long-term in vivo study
Authors: Park Soo Kyung , Kim Sung-Won , Seo Hwi Won , Hyun Sun Hee , Kyung Jong-Su , Youn Soo-Hyun , So Seung Ho , In Gyo , Park Chae-Kyu , Yi Eugene C. , Han Chang-Kyun , Lee Yong Yook
Published: November 2022

Background

Although Korean Red Ginseng (KRG) is safe, this finding was only evaluated in 3-mo-long studies. Its safety was verified through a 6-mo KRG administration clinical study, but long-term studies beyond 6 mo are insufficient. This study investigated the safety and efficacy of 12-mo KRG administration.

Methods

In this study, 300 mg/kg of KRG was administered to male and female Sprague Dawley rats for 4, 8, and 12 mo to evaluate its efficacy and safety. Clinical signs, including pathological examination and haematological analyses, were observed. Flow cytometric analyses were utilised to analyse spleen and thymus immune cell counts after 12 mo. Proteomic analysis of the sera was performed using a nanospray-interfaced mass spectrometer with an 11-plex Tandem Mass Tag (TMT) labelling system. Bioinformatic analysis was then performed using Ingenuity Pathway Analysis and PANTHER. Data are available via ProteomeXchange with identifier PXD032036.

Results

No significant body and organ weight changes were observed, and haematological and serum biochemical analyses did not show clinical significance. The effectiveness of long-term KRG administration was confirmed through increased immune cell distribution and activity. Changes in proteins correlated with viral infection reduction were confirmed through proteomic analysis.

Conclusion

The results suggested that 12-mo KRG intake is safe, improves immune system activity, and reduces viral infections with no significant changes in toxicological aspects.
Lack of causal association between heart failure and osteoporosis: a Mendelian randomization study
Authors: Chen Heng , Ye Runze , Guo Xiaogang
Published: November 2022

Objectives

Heart failure (HF) has been implicated in osteoporosis. However, causality remains unestablished. Here, we sought to assess causal associations of genetic liability to HF with osteoporosis using Mendelian randomization (MR) analyses.

Methods

Independent single nucleotide polymorphisms associated with HF at genome-wide significance were derived from a large genome-wide association study (GWAS) (including up to 977,323 individuals). We obtained summary statistics for forearm (FA) bone mineral density (BMD) (n = 8,143), femoral neck (FN) BMD (n = 32,735), lumbar spine (LS) BMD (n = 28,498), heel (HE) BMD (n = 426,824), and fracture (n = 1,214,434) from other GWAS meta-analyses. Inverse variance weighted (IVW) and several supplementary methods were performed to calculate the MR estimates.

Results

Genetically determined HF has no causal effect on FA-BMD (odds ratio (OR) 1.17; 95% confidence interval (CI) 0.82, 1.66; P = 0.389), FN-BMD (OR 1.01; 95% CI 0.85, 1.19; P = 0.936), LS-BMD (OR 0.96; 95% CI 0.80, 1.17; P = 0.705), HE-BMD (OR 1.01; 95% CI 0.90, 1.13; P = 0.884), and fracture risk (OR 1.00; 95% CI 0.92, 1.10; P = 0.927). Complementary analyses returned broadly consistent results.

Conclusion

This MR study provides genetic evidence that HF may not lead to an increased risk of reduced BMDs or fracture.
Combinatorial targeting of menin and the histone methyltransferase DOT1L as a novel therapeutic strategy for treatment of chemotherapy-resistant ovarian cancer
Authors: Alexandrova Elena , Lamberti Jessica , Memoli Domenico , Quercia Claudia , Melone Viola , Rizzo Francesca , Tarallo Roberta , Giurato Giorgio , Nassa Giovanni , Weisz Alessandro
Published: November 2022

Background

Ovarian cancer (OC) is characterized by a low response rate and high frequency of resistance development to currently available treatments. The therapeutic potential of histone methyltransferase DOT1L inhibitor in OC cells has been demonstrated, but optimal efficacy and safety of this targeted therapy approach still require improvement. We set forth to evaluate if this problem can be overcome by combinatorial targeting of this epigenetic modifier and menin, one of its functional partners in chromatin.

Methods

siRNA-mediated gene knock-down and pharmacological inhibition of menin, a key component of the MLL/SET1 complex and a fitness gene in OC cells, coupled to cell proliferation assays on a panel of high grade serous OC cell lines, including chemotherapy-sensitive and -resistant clones, were applied in order to evaluate how depletion or blockade of this enzyme influences growth and viability of OC cells. RNA sequencing was applied to identify menin target genes and pathways, and the effects of combined inhibition of menin and DOT1L on growth and transcriptome of these OC models were evaluated.

Results

Silencing and pharmacological inhibition of menin exert antiproliferative effects in all OC cells tested and, in PEO1 and PEO4 cells, a profound impact on transcriptome via down-regulation of cell cycle regulatory pathways, aryl hydrocarbon receptor, MYC and KRAS signalling. We demonstrated association of menin and DOT1L in OC cells and identified a subset of genes co-regulated by the two factors. Interestingly, co-treatment with DOT1L and menin pharmacological inhibitors exerts an additive effect on growth inhibition on chemotherapy-sensitive and -refractory OC cells mediated by transcriptome changes controlled by menin and DOT1L activities.

Conclusion

These results indicate that menin functionally cooperates with DOT1L in OC cells modulating transcription of genes involved in key cellular functions including, among others, cell proliferation and survival, that are strongly affected by combined inhibition of these two epigenetic regulators, suggesting that this may represent a novel therapeutic strategy for chemotherapy-resistant OCs.

Trial registration

NA; The manuscript does not contain clinical trials.
Identification of the intersegmental plane by arterial ligation method during thoracoscopic segmentectomy
Authors: He Haiqi , Zhao Heng , Ma Lei , Fan Kun , Feng Jinteng , Zhao Rui , Wen Xiaopeng , Zhang Jia , Wu Qifei , Fu Junke , Zhang Guangjian
Published: November 2022

Background

Thoracoscopic segmentectomy is a common surgical procedure in thoracic surgery today. However, identifying the intersegmental plane is difficult in the surgical process. Therefore, we evaluated the feasibility of the arterial ligation method for determining the intersegmental plane and compared the demarcation status with the intravenous indocyanine green (ICG).

Methods

We retrospectively reviewed the records of 35 patients with peripheral small lung nodules who underwent thoracoscopic segmentectomy between May and December 2020. First, the preoperative three-dimensional reconstruction was performed to distinguish the location of lung nodules and the anatomical structures of targeted segmental arteries, veins, and bronchi. Second, the targeted segmental arteries were ligated, and the intersegmental plane was determined by the inflation-deflation technique. The waiting time for the appearance of the inflation-deflation line was recorded. Thirdly, the intersegmental plane was identified again using the ICG fluorescence method. Finally, the consistency of the two intersegmental planes was evaluated.

Results

The intersegmental planes were successfully observed in all patients using the arterial ligation method. Thirty-four patients underwent segmentectomy as planned, and one patient finally underwent lobectomy due to insufficient surgical margin. The waiting time for the appearance of the intersegmental plane by arterial ligation method was 13.7 ± 3.2 min (6–19 min). The intersegmental planes determined by the arterial ligation method and the ICG fluorescence method were comparable, with a maximum distance of no more than 5 mm between the two planes. The mean operative duration was 119.1 ± 34.9 min, and the mean blood loss was 76.9 ± 70.3 ml. No evident air leakage was found during the operation. Only one patient experienced a prolonged air leak (≥ 5 days) during the postoperative recovery. No atelectasis occurred in all cases. The chest tube duration was 3.1 ± 0.9 days.

Conclusion

The arterial ligation method can efficiently and accurately identify the intersegmental plane, comparable to the ICG fluorescence method.
Carbohydrates and ginsenosides in shenmai injection jointly improve hematopoietic function during chemotherapy-induced myelosuppression in mice
Authors: Zhang Shiyu , Mi Yinxiao , Ye Tingting , Lu Xiaoyan , Liu Li , Qian Jing , Fan Xiaohui
Published: November 2022

Background

Shenmai injection (SMI), a traditional Chinese medicine (TCM) injection prepared from Red ginseng and Ophiopogon japonicus, is widely used in clinics to treat chemotherapy-induced myelosuppression. Similar to other TCM injections, SMI contains a high amount of carbohydrates (fructose, sucrose, and maltose) in addition to the bioactive substances, specifically ginsenosides (Rg1, Re, and Rb1). To date, the role of these carbohydrates in the hematopoietic function of SMI remains unclear.

Purpose

We aimed to investigate the hematopoietic effects and potential mechanisms of SMI and its components, focusing on the carbohydrates present in SMI.

Experimental design/methods

First, we evaluated the hematopoietic effect of SMI on 5-fluorouracil (5-FU)-induced myelotoxicity in a tumor-bearing mouse model. Then we prepared mixtures of ginsenosides and carbohydrates according to their proportions in SMI and evaluated their hematopoietic function in mice with 5-FU-induced myelosuppression. Finally, hematopoiesis-related molecular networks were built based on RNA sequencing (RNA-seq) of the bone marrow stromal cells (BMSCs), and the potential mechanisms of carbohydrates and ginsenosides were evaluated.

Results

SMI attenuated 5-FU-induced myelotoxicity in tumor-bearing mice. Both ginsenosides and carbohydrates increased the bone marrow nucleated cell (BMNC) count and improved the bone marrow morphology in myelosuppressive mice; they promoted the proliferation of BMSCs derived from those myelosuppressive mice. Bioinformatics analyses revealed ECM-receptor interaction, Hippo signaling, and Wnt signaling are common pathways regulated by both ginsenosides and carbohydrates; Gstt1, Gstp2, Gsta4 and Oplah in Glutathione metabolism pathway and Cd19, Cd79a, and Cd79b in B cell receptor pathway are uniquely regulated genes related to carbohydrates but not ginsenosides.

Conclusions

Carbohydrates may collaborate with ginsenosides and contribute to the hematopoietic function of SMI. Carbohydrates could be considered as a bioactive component in this TCM injection.

Graphical Abstract
Olfactory marker protein contains a leucine-rich domain in the Ω-loop important for nuclear export
Authors: Nakashima Noriyuki , Nakashima Akiko , Nakashima Kie , Takano Makoto
Published: November 2022

Olfactory marker protein (OMP) is a cytosolic protein expressed in mature olfactory receptor neurons (ORNs). OMP modulates cAMP signalling and regulates olfactory sensation and axonal targeting. OMP is a small soluble protein, and passive diffusion between nucleus and cytoplasm is expected. However, OMP is mostly situated in the cytosol and is only sparsely detected in the nuclei of a subset of ORNs, hypothalamic neurons and heterologously OMP-expressing cultured cells. OMP can enter the nucleus in association with transcription factors. However, how OMP is retained in the cytosol at rest is unclear. Because OMP is proposed to affect cell differentiation, it is important to understand how OMP is distributed between cytoplasm and nucleus. To elucidate the structural profile of OMP, we applied several bioinformatics methods to a multiple sequence alignment (MSA) of OMP protein sequences and ranked the evolutionarily conserved residues. In addition to the previously reported cAMP-binding domain, we identified a leucine-rich domain in the Ω-loop of OMP. We introduced mutations into the leucine-rich region and heterologously expressed the mutant OMP in HEK293T cells. Mutations into alanine increased the nuclear distribution of OMP quantified by immunocytochemistry and western blotting. Therefore, we concluded that OMP contains a leucine-rich domain important for nuclear transport.
Effect of early stellate ganglion block in cerebral vasospasm after aneurysmal subarachnoid hemorrhage (BLOCK-CVS): study protocol for a randomized controlled trial
Authors: Jing Longnian , Wu Youxuan , Liang Fa , Jian Minyu , Bai Yang , Wang Yunzhen , Liu Haiyang , Wang Anxin , Chen Xiaolin , Han Ruquan
Published: November 2022

Introduction

Stellate ganglion block has been reported to expand cerebral vessels and alleviate vasospasm after aneurysmal subarachnoid hemorrhage. However, the causal relationship between early stellate ganglion block and cerebral vasospasm prevention has not yet been established. The purpose of this study was to explore the effectiveness and safety of early stellate ganglion block as a preventive treatment for cerebral vasospasm and delayed cerebral ischemia.

Methods/design

This is a single-center, prospective, randomized, controlled, blinded endpoint assessment superiority trial. A total of 228 patients will be randomized within 48 h of aneurysmal subarachnoid hemorrhage onset in a 1:1 ratio into two groups, one group receiving an additional e-SGB and the other group receiving only a camouflaging action before anesthesia induction in the operating room. The primary outcome is the incidence of symptomatic vasospasm within 14 days after aSAH. Further safety and efficacy parameters include the incidence of radiographic vasospasm, new cerebral infarction, postoperative delirium, and complications up to 90 days after surgery; postoperative cerebral hemodynamics; Mini-Mental State Examination score; modified Rankin scale score; and all-cause mortality up to 90 days after surgery.

Discussion

This is a randomized controlled trial to explore the effectiveness and safety of early stellate ganglion block as a preventive treatment to reduce cerebral vasospasm in patients with aneurysmal subarachnoid hemorrhage. If the results are positive, it may provide a new direction for the prevention and treatment of cerebral vasospasm and delayed cerebral ischemia.

Trial registration

The study was registered on Clincaltrials.gov on December 13, 2020 (NCT04691271).
Association between water, sanitation, and hygiene access and the prevalence of soil-transmitted helminth and schistosome infections in Wolayita, Ethiopia
Authors: Phillips Anna E. , Ower Alison K. , Mekete Kalkidan , Liyew Ewnetu Firdawek , Maddren Rosie , Belay Habtamu , Chernet Melkie , Anjulo Ufaysa , Mengistu Birhan , Salasibew Mihretab , Tasew Geremew , Anderson Roy
Published: November 2022

Background

The Geshiyaro project is a 5-year intervention to assess the impact of community- and school-based water, sanitation, and hygiene (WaSH) interventions on reducing infection with soil-transmitted helminths (STH) and schistosome parasites in combination with deworming in Wolayita zone, Ethiopia.

Methods

A population-based, cross-sectional census and parasitological mapping activity was conducted between 2018 and 2019. Individuals in the census were identified using either a registered study ID card or biometric fingerprint to enable linkage of their household WaSH data with baseline STH and schistosome prevalence for risk analysis.

Results

Prevalence of STH was 15.5% for any STH species, 9.47% forAscaris lumbricoides, 1.78% forTrichuris trichiura, and 7.24% for hookworm. Intestinal schistosomiasis (Schistosoma mansoni) infection prevalence was 0.85% by Kato Katz, 21.6% by POC-CCA trace positive (Tr +), and 13.3% trace negative (Tr-). Microhaematuria was 2.77%, with 0.13% of people examined withS. haematobiumeggs detected by urine filtration. At the household level, increased (> 30 min) time taken to collect drinking water, sharing a latrine, and lack of handwashing facilities were all associated with a greater risk ofA. lumbricoides, hookworm, andS. mansoniinfection. Not disposing of infant stool at the household and clothes washing/recreational freshwater contact were significantly associated with higher risk of schistosomiasis infection. Aggregating WaSH data at the community level showed odds ofA. lumbricoides,hookworm, andT. trichiurainfection were significantly lower as both community sanitation coverage and access to improved drinking water improved.

Conclusions

The principal finding of this study is that lack of access to WaSH, such as improved drinking water and shared toilet and hand-washing facilities, were linked to an increased risk of infection with STH and schistosome parasites. These associations are difficult to establish at an individual household level because of wide variability in access between houses but are detectable when coverage is aggregated at the community level. Maintenance of WaSH facilities as well as increased access within the whole community is important in influencing the community-wide prevalence of infection with STH and schistosome parasites.

Graphical Abstract
Macrophage polarization toward M1 phenotype through NF-κB signaling in patients with Behçet’s disease
Authors: Wu Xiuhua , Wang Zhimian , Shi Jing , Yu Xin , Li Chaoran , Liu Jinjing , Zhang Fengchun , Chen Hua , Zheng Wenjie
Published: November 2022

Background

Macrophages are key innate immune cells implicated in the pathogenesis of Behçet’s disease (BD), and macrophage polarization plays a pivotal role in inflammatory response. This study aimed to investigate the role of BD serum on the phenotypes and functions of macrophage polarization.

Methods

BD or HC serum-treated human monocyte-derived macrophages (HMDMs) were examined M1/M2 phenotypes using flow cytometry and ELISA. The phagocytic capacity of HMDMs and CD4+T cell differentiation facilitated by HMDMs were measured by flow cytometry. Transcriptome analysis of BD and HC serum-stimulated HMDMs was conducted to identify differentially expressed genes. NF-κB signaling was examined using western blot to explore the mechanism of macrophage polarization induced by BD serum.

Results

BD serum-treated macrophages expressed a higher level of CD86, IL-12, and TNF-α and a lower level of CD163, which were compatible with the M1-like phenotype. Furthermore, BD serum-treated macrophages showed enhanced phagocytic capacity and promoted more Th1 cell differentiation. Sixty-one differentially expressed genes were identified between BD and HC serum-treated macrophages and were enriched in NF-κB signaling. BD serum-treated macrophages showed upregulated p-p65 and downregulated IκBα, and NF-κB inhibitor attenuated BD serum-stimulated M1-like phenotype.

Conclusions

BD serum promoted macrophage polarization toward a proinflammatory M1-like phenotype through NF-κB signaling and potentially facilitated inflammation in BD. M1 polarized macrophages may be a potential therapeutic target for BD.
Effective treatment of intractable diseases using nanoparticles to interfere with vascular supply and angiogenic process
Authors: Hoseinzadeh Ahmad , Ghoddusi Johari Hamed , Anbardar Mohammad Hossein , Tayebi Lobat , Vafa Ehsan , Abbasi Milad , Vaez Ahmad , Golchin Ali , Amani Ali Mohammad , Jangjou Ali
Published: November 2022

Angiogenesis is a vital biological process involving blood vessels forming from pre-existing vascular systems. This process contributes to various physiological activities, including embryonic development, hair growth, ovulation, menstruation, and the repair and regeneration of damaged tissue. On the other hand, it is essential in treating a wide range of pathological diseases, such as cardiovascular and ischemic diseases, rheumatoid arthritis, malignancies, ophthalmic and retinal diseases, and other chronic conditions. These diseases and disorders are frequently treated by regulating angiogenesis by utilizing a variety of pro-angiogenic or anti-angiogenic agents or molecules by stimulating or suppressing this complicated process, respectively. Nevertheless, many traditional angiogenic therapy techniques suffer from a lack of ability to achieve the intended therapeutic impact because of various constraints. These disadvantages include limited bioavailability, drug resistance, fast elimination, increased price, nonspecificity, and adverse effects. As a result, it is an excellent time for developing various pro- and anti-angiogenic substances that might circumvent the abovementioned restrictions, followed by their efficient use in treating disorders associated with angiogenesis. In recent years, significant progress has been made in different fields of medicine and biology, including therapeutic angiogenesis. Around the world, a multitude of research groups investigated several inorganic or organic nanoparticles (NPs) that had the potential to effectively modify the angiogenesis processes by either enhancing or suppressing the process. Many studies into the processes behind NP-mediated angiogenesis are well described. In this article, we also cover the application of NPs to encourage tissue vascularization as well as their angiogenic and anti-angiogenic effects in the treatment of several disorders, including bone regeneration, peripheral vascular disease, diabetic retinopathy, ischemic stroke, rheumatoid arthritis, post-ischemic cardiovascular injury, age-related macular degeneration, diabetic retinopathy, gene delivery-based angiogenic therapy, protein delivery-based angiogenic therapy, stem cell angiogenic therapy, and diabetic retinopathy, cancer that may benefit from the behavior of the nanostructures in the vascular system throughout the body. In addition, the accompanying difficulties and potential future applications of NPs in treating angiogenesis-related diseases and antiangiogenic therapies are discussed.
Deficiency of exchange protein directly activated by cAMP (EPAC)-1 in mice augments glucose intolerance, inflammation, and gut dysbiosis associated with Western diet
Authors: Virwani Preeti Dinesh , Cai Lin , Yeung Patrick Ka Kit , Qian Gordon , Chen Yingxian , Zhou Lei , Wong Jason Wing Hon , Wang Yu , Ho Joshua Wing Kei , Lau Kui Kai , Qian Pei-Yuan , Chung Sookja Kim
Published: November 2022

Background

Gut microbiota (GM) dysregulation, known as dysbiosis, has been proposed as a crucial driver of obesity associated with “Western” diet (WD) consumption. Gut dysbiosis is associated with increased gut permeability, inflammation, and insulin resistance. However, host metabolic pathways implicated in the pathophysiology of gut dysbiosis are still elusive. Exchange protein directly activated by cAMP (Epac) plays a critical role in cell-cell junction formation and insulin secretion. Here, we used homozygous Epac1-knockout (Epac1–/–), Epac2-knockout (Epac2–/–), and wild-type (WT) mice to investigate the role of Epac proteins in mediating gut dysbiosis, gut permeability, and inflammation after WD feeding.

Results

The 16S rRNA gene sequencing of fecal DNA showed that the baseline GM of Epac2–/–, but not Epac1–/–, mice was represented by a significantly higher Firmicutes to Bacteroidetes ratio and significant alterations in several taxa compared to WT mice, suggesting that Epac2–/– mice had gut dysbiosis under physiological conditions. However, an 8-week WD led to a similar gut microbiome imbalance in mice regardless of genotype. While Epac1 deficiency modestly exacerbated the WD-induced GM dysbiosis, the WD-fed Epac2–/– mice had a more significant increase in gut permeability than corresponding WT mice. After WD feeding, Epac1–/–, but not Epac2–/–, mice had significantly higher mRNA levels of tumor necrosis factor-alpha (TNF-α) and F4/80 in the epididymal white adipose tissue (EWAT), increased circulating lipocalin-2 protein and more severe glucose intolerance, suggesting greater inflammation and insulin resistance in WD-fed Epac1–/– mice than corresponding WT mice. Consistently, Epac1 protein expression was significantly reduced in the EWAT of WD-fed WT and Epac2–/– mice.

Conclusion

Despite significantly dysregulated baseline GM and a more pronounced increase in gut permeability upon WD feeding, WD-fed Epac2–/– mice did not exhibit more severe inflammation and glucose intolerance than corresponding WT mice. These findings suggest that the role of gut dysbiosis in mediating WD-associated obesity may be context-dependent. On the contrary, we demonstrate that deficiency of host signaling protein, Epac1, drives inflammation and glucose intolerance which are the hallmarks of WD-induced obesity.
Bifidobacterial carbohydrate/nucleoside metabolism enhances oxidative phosphorylation in white adipose tissue to protect against diet-induced obesity
Authors: Kim Gihyeon , Yoon Youngmin , Park Jin Ho , Park Jae Won , Noh Myung-guin , Kim Hyun , Park Changho , Kwon Hyuktae , Park Jeong-hyeon , Kim Yena , Sohn Jinyoung , Park Shinyoung , Kim Hyeonhui , Im Sun-Kyoung , Kim Yeongmin , Chung Ha Yung , Nam Myung Hee , Kwon Jee Young , Kim Il Yong , Kim Yong Jae , Baek Ji Hyeon , Kim Hak Su , Weinstock George M. , Cho Belong , Lee Charles , Fang Sungsoon , Park Hansoo , Seong Je Kyung
Published: November 2022

Background

Comparisons of the gut microbiome of lean and obese humans have revealed that obesity is associated with the gut microbiome plus changes in numerous environmental factors, including high-fat diet (HFD). Here, we report that two species of Bifidobacterium are crucial to controlling metabolic parameters in the Korean population.

Results

Based on gut microbial analysis from 99 Korean individuals, we observed the abundance of Bifidobacterium longum and Bifidobacterium bifidum was markedly reduced in individuals with increased visceral adipose tissue (VAT), body mass index (BMI), blood triglyceride (TG), and fatty liver. Bacterial transcriptomic analysis revealed that carbohydrate/nucleoside metabolic processes of Bifidobacterium longum and Bifidobacterium bifidum were associated with protecting against diet-induced obesity. Oral treatment of specific commercial Bifidobacterium longum and Bifidobacterium bifidum enhanced bile acid signaling contributing to potentiate oxidative phosphorylation (OXPHOS) in adipose tissues, leading to reduction of body weight gain and improvement in hepatic steatosis and glucose homeostasis. Bifidobacterium longum or Bifidobacterium bifidum manipulated intestinal sterol biosynthetic processes to protect against diet-induced obesity in germ-free mice.

Conclusions

Our findings support the notion that treatment of carbohydrate/nucleoside metabolic processes-enriched Bifidobacterium longum and Bifidobacterium bifidum would be a novel therapeutic strategy for reprograming the host metabolic homeostasis to protect against metabolic syndromes, including diet-induced obesity.