bluuebunny/crossref_metadata_2025 huggingface dataset:
Comprehensive transcriptome and methylome analysis delineates the biological basis of hair follicle development and wool-related traits in Merino sheep
Authors: Zhao Bingru , Luo Hanpeng , He Junmin , Huang Xixia , Chen Siqian , Fu Xuefeng , Zeng Weidan , Tian Yuezhen , Liu Shuli , Li Cong-jun , Liu George E. , Fang Lingzhao , Zhang Shengli , Tian Kechuan
Published: September 2021

Background

Characterization of the molecular mechanisms underlying hair follicle development is of paramount importance in the genetic improvement of wool-related traits in sheep and skin-related traits in humans. The Merino is the most important breed of fine-wooled sheep in the world. In this study, we systematically investigated the complexity of sheep hair follicle development by integrating transcriptome and methylome datasets from Merino sheep skin.

Results

We analysed 72 sequence datasets, including DNA methylome and the whole transcriptome of four gene types, i.e. protein-coding genes (PCGs), lncRNAs, circRNAs, and miRNAs, across four embryonic days (E65, E85, E105, and E135) and two postnatal days (P7 and P30) from the skin tissue of 18 Merino sheep. We revealed distinct expression profiles of these four gene types across six hair follicle developmental stages, and demonstrated their complex interactions with DNA methylation. PCGs with stage-specific expression or regulated by stage-specific lncRNAs, circRNAs, and miRNAs were significantly enriched in epithelial differentiation and hair follicle morphogenesis. Regulatory network and gene co-expression analyses identified key transcripts controlling hair follicle development. We further predicted transcriptional factors (e.g. KLF4, LEF1, HOXC13, RBPJ, VDR, RARA, and STAT3) with stage-specific involvement in hair follicle morphogenesis. Through integrating these stage-specific genomic features with results from genome-wide association studies (GWAS) of five wool-related traits in 7135 Merino sheep, we detected developmental stages and genes that were relevant with wool-related traits in sheep. For instance, genes that were specifically upregulated at E105 were significantly associated with most of wool-related traits. A phenome-wide association study (PheWAS) demonstrated that candidate genes of wool-related traits (e.g.SPHK1,GHR,PPP1R27,CSRP2,EEF1A2, andPTPN1) in sheep were also significantly associated with dermatological, metabolic, and immune traits in humans.

Conclusions

Our study provides novel insights into the molecular basis of hair follicle morphogenesis and will serve as a foundation to improve breeding for wool traits in sheep. It also indicates the importance of studying gene expression in the normal development of organs in understanding the genetic architecture of economically important traits in livestock. The datasets generated here are useful resources for functionally annotating the sheep genome, and for elucidating early skin development in mammals, including humans.
Single-cell analysis at the protein level delineates intracellular signaling dynamic during hematopoiesis
Authors: Wang Jinheng , Tu Chenggong , Zhang Hui , Huo Yongliang , Menu Eline , Liu Jinbao
Published: September 2021

Background

Hematopoietic stem and progenitor cell (HSPC) subsets in mice have previously been studied using cell surface markers, and more recently single-cell technologies. The recent revolution of single-cell analysis is substantially transforming our understanding of hematopoiesis, confirming the substantial heterogeneity of cells composing the hematopoietic system. While dynamic molecular changes at the DNA/RNA level underlying hematopoiesis have been extensively explored, a broad understanding of single-cell heterogeneity in hematopoietic signaling programs and landscapes, studied at protein level and reflecting post-transcriptional processing, is still lacking. Here, we accurately quantified the intracellular levels of 9 phosphorylated and 2 functional proteins at the single-cell level to systemically capture the activation dynamics of 8 signaling pathways, including EGFR, Jak/Stat, NF-κB, MAPK/ERK1/2, MAPK/p38, PI3K/Akt, Wnt, and mTOR pathways, during mouse hematopoiesis using mass cytometry.

Results

With fine-grained analyses of 3.2 million of single hematopoietic stem and progenitor cells (HSPCs), and lineage cells in conjunction with multiparameter cellular phenotyping, we mapped trajectories of signaling programs during HSC differentiation and identified specific signaling biosignatures of cycling HSPC and multiple differentiation routes from stem cells to progenitor and lineage cells. We also investigated the recovery pattern of hematopoietic cell populations, as well as signaling regulation in these populations, during hematopoietic reconstruction. Overall, we found substantial heterogeneity of pathway activation within HSPC subsets, characterized by diverse patterns of signaling.

Conclusions

These comprehensive single-cell data provide a powerful insight into the intracellular signaling-regulated hematopoiesis and lay a solid foundation to dissect the nature of HSC fate decision. Future integration of transcriptomics and proteomics data, as well as functional validation, will be required to verify the heterogeneity in HSPC subsets during HSC differentiation and to identify robust markers to phenotype those HSPC subsets.
The cell adhesion molecule TMIGD1 binds to moesin and regulates tubulin acetylation and cell migration
Authors: Rahimi Nader , Ho Rachel X. Y. , Chandler Kevin Brown , De La Cena Kyle Oliver Corcino , Amraei Razie , Mitchel Ashley J. , Engblom Nels , Costello Catherine E.
Published: September 2021

Background

The cell adhesion molecule transmembrane and immunoglobulin (Ig) domain containing1 (TMIGD1) is a novel tumor suppressor that plays important roles in regulating cell–cell adhesion, cell proliferation and cell cycle. However, the mechanisms of TMIGD1 signaling are not yet fully elucidated.

Results

TMIGD1 binds to the ERM family proteins moesin and ezrin, and an evolutionarily conserved RRKK motif on the carboxyl terminus of TMIGD1 mediates the interaction of TMIGD1 with the N-terminal ERM domains of moesin and ezrin. TMIGD1 governs the apical localization of moesin and ezrin, as the loss of TMIGD1 in mice altered apical localization of moesin and ezrin in epithelial cells. In cell culture, TMIGD1 inhibited moesin-induced filopodia-like protrusions and cell migration. More importantly, TMIGD1 stimulated the Lysine (K40) acetylation of α-tubulin and promoted mitotic spindle organization and CRISPR/Cas9-mediated knockout of moesin impaired the TMIGD1-mediated acetylation of α-tubulin and filamentous (F)-actin organization.

Conclusions

TMIGD1 binds to moesin and ezrin, and regulates their cellular localization. Moesin plays critical roles in TMIGD1-dependent acetylation of α-tubulin, mitotic spindle organization and cell migration. Our findings offer a molecular framework for understanding the complex functional interplay between TMIGD1 and the ERM family proteins in the regulation of cell adhesion and mitotic spindle assembly, and have wide-ranging implications in physiological and pathological processes such as cancer progression.
Design, synthesis, and preliminary evaluation of a potential synthetic opioid rescue agent
Authors: Hedrick Sidnee L. , Luo Dan , Kaska Sophia , Niloy Kumar Kulldeep , Jackson Karen , Sarma Rupam , Horn Jamie , Baynard Caroline , Leggas Markos , Butelman Eduardo R. , Kreek Mary Jeanne , Prisinzano Thomas E.
Published: September 2021

Background

One of the most prominent opioid analgesics in the United States is the high potency agonist fentanyl. It is used in the treatment of acute and chronic pain and as an anesthetic adjuvant. When used inappropriately, however, ingestion of just a few milligrams of fentanyl or other synthetic opioid can cause opioid-induced respiratory depression (OIRD), often leading to death. Currently, the treatment of choice for OIRD is the opioid receptor antagonist naloxone. Recent reports, however, suggest that higher doses or repeated dosing of naloxone (due to recurrence of respiratory depression) may be required to reverse fully fentanyl-induced respiratory depression, rendering this treatment inadequate. To combat this synthetic opioid overdose crisis, this research aims at identifying a novel opioid reversal agent with enhanced efficacy towards fentanyl and other synthetic opioids.

Methods

A series of naltrexone analogues were characterized for their ability to antagonize the effects of fentanyl in vitro utilizing a modified forskolin-induced cAMP accumulation assay. Lead analogue 29 was chosen to undergo further PK studies, followed by in vivo pharmacological analysis to determine its ability to antagonize opioid-induced antinociception in the hot plate assay.

Results

A series of potent MOR antagonists were identified, including the highly potent analogue 29 (IC50 = 2.06 nM). Follow-up PK studies revealed 29 to possess near 100% bioavailability following IP administration. Brain concentrations of 29 surpassed plasma concentrations, with an apparent terminal half-life of ~ 80 min in mice. In the hot plate assay, 29 dose-dependently (0.01–0.1 mg/kg; IP) and fully antagonized the antinociception induced by oxycodone (5.6 mg/kg; IP). Furthermore, the dose of 29 that is fully effective in preventing oxycodone-induced antinociception (0.1 mg/kg) was ineffective against locomotor deficits caused by the KOR agonist U50,488.

Conclusions

Methods have been developed that have utility to identify enhanced rescue agents for the treatment of OIRD. Analogue 29, possessing potent MOR antagonist activity in vitro and in vivo, provides a promising lead in our search for an enhanced synthetic opioid rescue agent.
Positive association between the ratio of triglycerides to high-density lipoprotein cholesterol and diabetes incidence in Korean adults
Authors: Kim Joungyoun , Shin Sang-Jun , Kim Ye-Seul , Kang Hee-Taik
Published: September 2021

Background

Insulin resistance is associated with the incidence of diabetes and cardiovascular diseases such as myocardial infarction. The ratio of triglycerides (TG) to high-density lipoprotein cholesterol (HDL-C) (TG/HDL-C ratio) is positively correlated with insulin resistance. This study aimed to investigate the relationship between the TG/HDL-C ratio and the incidence of diabetes in Korean adults.

Methods

This retrospective study used data from the National Health Insurance Service-National Health Screening Cohort. The TG/HDL-C ratio was divided into three tertiles, the T1, T2, and T3 groups, based on sex. We estimated the hazard ratios (HRs) and 95% confidence intervals (CIs) for diabetes using multivariate Cox proportional hazards regression analyses.

Results

A total of 80,693 subjects aged between 40 and 79 years were enrolled. The median follow-up period was 5.9 years. The estimated cumulative incidence of diabetes in the T1, T2, and T3 groups was 5.94%, 8.23%, and 13.50%, respectively, in men and 4.12%, 4.72%, and 6.85%, respectively, in women. Compared to T1, the fully adjusted HRs (95% CIs) of the T2 and T3 groups for new-onset diabetes were 1.17 (1.06–1.30) and 1.47 (1.34–1.62), respectively, in men and 1.20 (1.02–1.42) and 1.52 (1.30–1.78), respectively, in women.

Conclusions

Increased TG/HDL-C ratio was significantly associated with a higher risk of new-onset diabetes in both sexes.
TRIB3 regulates FSHR expression in human granulosa cells under high levels of free fatty acids
Authors: Wang Nan , Si Chenchen , Xia Lan , Wu Xian , Zhao Sheng , Xu Huihui , Ding Zhide , Niu Zhihong
Published: September 2021

Background

Granulosa cells (GCs) in cumulus oophorus highly express follicle stimulating hormone receptor (FSHR), which is the most important mediator of both estradiol synthesis and oocyte maturation. Obese women have elevated free fatty acids (FFAs) levels in their follicular fluids and decreased FSHR expression in GCs, which is related to an altered protein kinase B/glycogen synthase kinase 3β (Akt/GSK3β) signaling pathway. Such FFA increases accompany 3-fold rises in pseudokinase 3 (TRIB3) expression and reduce the Akt phosphorylation status in both the human liver and in insulinoma cell lines. Therefore, in a high FFA environment, we determined if TRIB3 mediates regulation of FSHR via the Akt/GSK3β signaling pathway in human GCs.

Methods

GCs from women undergoing in vitro fertilization were collected and designated as high and low FFAs cohorts based on their follicular fluid FFA content. GCs with low FFA levels and a human granulosa-like tumor (KGN) cell line were exposed to palmitic acid (PA), which is a dominate FFA follicular fluid constituent. The effects were assessed of this substitution on the Akt/GSK3β signaling pathway activity as well as the expressions of TRIB3 and FSHR at both the gene and protein levels by qPCR, Western blot and immunofluorescence staining analyses. Meanwhile, the individual effects of TRIB3 knockdown in KGN cells and p-AKT inhibitors were compared to determine the mechanisms of FFA-induced FSHR downregulation.

Results

The average FSH dose consuming per oocyte (FSH dose/oocyte) was elevated and Top embryo quality ratio was decreased in women with high levels of FFAs in their follicular fluid. In these women, the GC TRIB3 and ATF4 protein expression levels were upregulated which was accompanied by FSHR downregulation. Such upregulation was confirmed based on corresponding increases in their gene expression levels. On the other hand, the levels of p-Akt decreased while p-GSK3β increased in the GCs. Moreover, TRIB3 knockdown reversed declines in FSHR expression and estradiol (E2) production in KGN cells treated with PA, which also resulted in increased p-Akt levels and declines in the p-GSK3β level. In contrast, treatment of TRIB3-knockdown cells with an inhibitor of p-Akt (Ser473) resulted in rises in the levels of both p-GSK3β as well as FSHR expression whereas E2 synthesis fell.

Conclusions

During exposure to a high FFA content, TRIB3 can reduce FSHR expression through stimulation of the Akt/GSK3β pathway in human GCs. This response may contribute to inducing oocyte maturation.
Inclusive planning: African policy inventory and South African mobility case study on the exclusion of persons with disabilities
Authors: Vanderschuren Marianne J. W. A. , Nnene Obiora A.
Published: September 2021

Background

The Sustainable Development Goals (SDGs) and universal design (UD) principles call for inclusive planning. Within the transportation field, this includes the development or improvement of facilities that accommodate people with disabilities. Between 10% and 20% of the African population is affected by disabilities. A lack of understanding of the needs of people with disabilities leads to isolation. Within the transportation field, isolation manifests itself as a reduction in trip-making.

Methods

This paper investigates the availability of transport policies and guidelines in 29 different African countries, focusing on the inclusion of persons with disabilities. A desktop study was conducted creating heat maps for 29 African countries, followed by the analysis of secondary data in the case study area, South Africa, demonstrating that the lack of adequate policies, guidelines, and appropriate implementation leads to a lack of accessibility, opportunities, and social isolation, measured through trip frequencies.

Results

The data analysed revealed that many African countries omit, or only superficially include, people with disabilities in their transport policy framework. Ghana has the most inclusive People with Disabilities Act, while South Africa is most inclusive regarding their planning and design of transport facilities and services. In South Africa, 4.5% of the population did not travel at all in the 7 days before the interview, as disability or age prevented them from doing so, or due to a lack of appropriate travel services. When comparing the trip rates per week, people with disabilities travel significantly less, between 27.2% and 65.8%, than their abled counterparts.

Conclusions

The study reveals that people with disability live less integrated, more isolated lives due to the lack of acknowledgement in the transport policy framework and accommodation in infrastructure and services. The results underpin the need for disability-inclusive planning in the African context and provide recommendations for actions that mitigate the isolation challenges faced by people with disabilities. Municipalities play a crucial role in improving the quality of life for people with disabilities.
A direct negative feedback loop of miR-4721/FOXA1/Nanog promotes nasopharyngeal cell stem cell enrichment and metastasis
Authors: Zhao Mengyang , Tang Zibo , Wang Yijun , Ding Jiaojiao , Guo Ying , Gao Tianhui
Published: September 2021

Objective

The recurrence and metastasis of nasopharyngeal cancer (NPC) may be mainly attributed to the persistence of cancer stem cells (CSCs); however, the linkage mechanism has yet to be fully elucidated.

Methods

The levels of miR-4721, FOXA1, and Nanog expression in NPC were detected by in situ hybridization and immunohistochemistry. In vivo and in vitro metastasis assays confirmed miR-4721 promotes cell migration and invasion. Tumor spheroid formation assay, side population (SP) assay, and ALDEFLUOR assay verified miR-4721 regulates cancer stem cell-like properties. Luciferase reporter assay showed that miR-4721 directly regulates FOXA1 and FOXA1 effects the promoter activity of miR-4721 and Nanog. Chromatin immunoprecipitation (ChIP) analysis and electrophoresis mobility shift assay (EMSA) revealed that FOXA1 combined the promoter region of human miR-4721 and Nanog and the possible mechanism was also analyzed.

Results

In this study, a new mechanism of NPC tumorigenesis related to miR-4721 was verified. We found that miR-4721, FOXA1 and Nanog control their expressions through a negative feedback loop and then activate the downstream regulator of stem cell signaling to promote the enrichment and metastasis of NPC stem cells.

Conclusion

These findings elucidate that the feedback loop of miR-4721/FOXA1/Nanog can regulate stemness and metastasis in NPC and may provide an experimental theoretical basis for metastasis and treatment resistance in NPC.
Evaluating the performance of ACR, SLICC and EULAR/ACR classification criteria in childhood onset systemic lupus erythematosus
Authors: Abdwani Reem , Al Masroori Eman , Abdullah Eiman , Al Abrawi Safiya , Al-Zakwani Ibrahim
Published: September 2021

Background

The ACR 1997, SLICC 2012 and EULAR/ACR 2019 classification criteria were validated based on adult patients. To date, there are no classification criteria specific for children with SLE. The aim of the study is to compare the performance characteristics among the three SLE classification criteria (ACR-1997, SLICC-2012 and EULAR/ACR-2019) in childhood onset SLE (cSLE) cohort of Arab ethnicity from Oman.

Methods

We conducted a retrospective multicenter study in Oman of cSLE patients as cases and patients with other rheumatic disease with a positive ANA titer as controls. The cSLE cases recruited were children diagnosed with SLE before 13 years of age. Data was retrospectively collected to establish the ACR-1997, SLICC-2012 and EULAR/ACR-2019 criteria fulfilled at first visit, first year follow up and last follow up.

Results

Study population included 113 cSLE cases (mean age at diagnosis of 7.3 ± 3.4 years with disease duration of 6.1 ± 4.6 years) and 51 controls (mean age at diagnosis 5.0 ± 3.4 with disease duration 5.7 ± 3.9). The cSLE cases had higher frequency of familial SLE than controls (38% vs 7.8%; p < 0.001). The performance measures demonstrated that EULAR/ACR-2019 criteria had the highest sensitivity (81, 88, 89%) compared to ACR 1997 (49, 57, 66%) and SLICC 2012 (76, 84,86%); while the ACR 1997 had the highest specificity (96%) compared to SLICC 2012 (94%) and EULAR/ACR 2019 (90%) at first visit, first year and last assessment. When we increased the threshold score to ≥13 rather than the traditional score ≥ 10 for ACR/EULAR 2019, there was increased specificity (96%) at the expense of lower sensitivity (76, 83, and 84%) at first visit, first year and last assessment.

Conclusion

In this cSLE population, EULAR/ACR 2019 scored better at initial presentation, first year and last assessment follow up. Further multinational studies are needed to validate the appropriate cut off score for the newly proposed ACR/EULAR 2019 classification criteria in cSLE to increase early sensitivity and specificity for cSLE classification.
Associations between antiretroviral therapy-related experiences and mental health status among people living with HIV in China: a prospective observational cohort study
Authors: Xie Jinzhao , Wang Zixin , Li Quanmin , He Qiangsheng , Xu Guohong , Li Yonghong , Zhou Kai , Li Linghua , Gu Jing
Published: September 2021

Background

Mental health problems (e.g., depression and anxiety) are among the most commonly reported comorbidities of HIV. Antiretroviral therapy (ART) coverage has increased sharply. The purposes of this prospective cohort study were to investigate the ART-related experiences and whether they were associated with mental health problems among a sample of people living with HIV undergoing ART in China.

Methods

The participants were 400 people living with HIV who had started ART for the first time in Guangzhou city. They were followed-up 1-year after ART initiation. Probable depression and moderate/severe anxiety were measured at baseline and Month 12, while experiences related to ART (e.g., side effects and regained self-confidence) were measured at Month 6. Univariate and multivariate logistic regressions were used to explore the associations between baseline characteristics, ART-related experiences and mental health status.

Results

Among the 300 participants (75.0%) who completed all three surveys, a significant decline in prevalence of probable depression (23.0% at baseline vs. 14.0% at Month 12, P = 0.002) and moderate/severe anxiety (14.7% at baseline vs. 8.7% at Month 12, P = 0.023) was observed during the follow-up period. After adjustment for mental health status and potential confounders at baseline, a number of ART-related experiences at Month 6 were associated with probable depression and/or moderate/severe anxiety measured at Month 12. Improved physical health, relationships with sexual partners, and self-confidence were associated with decreased mental health issues, while the side effects of ART, AIDS-related symptoms, and inconvenience in daily life due to ART use were associated with increased mental health issues.

Conclusions

ART-related experiences were associated with mental health problems, tailored mental health promotion interventions targeting these experiences are needed.
Walking with robot-generated haptic forces in a virtual environment: a new approach to analyze lower limb coordination
Authors: Sorrento Gianluca U. , Archambault Philippe S. , Fung Joyce
Published: September 2021

Background

Walking with a haptic tensile force applied to the hand in a virtual environment (VE) can induce adaptation effects in both chronic stroke and non-stroke individuals. These effects are reflected in spatiotemporal outcomes such as gait speed. However, the concurrent kinematic changes occurring in bilateral lower limb coordination have yet to be explored.

Methods

Chronic stroke participants were stratified based on overground gait speed into lower functioning (LF < 0.8 m/s, N = 7) and higher functioning (HF ≥ 0.8 m/s, N = 7) subgroups. These subgroups and an age-matched control group (N = 14, CG) walked on a self-paced treadmill in a VE with either robot-generated haptic leash forces delivered to the hand and then released or with an instrumented cane. Walking in both leash (10 and 15 N) and cane conditions were compared to pre-force baseline values to evaluate changes in lower limb coordination outcomes.

Results

All groups showed some kinematic changes in thigh, leg and foot segments when gait speed increased during force and post-force leash as well as cane walking. These changes were also reflected in intersegmental coordination and 3D phase diagrams, which illustrated increased intersegmental trajectory areas (p < 0.05) and angular velocity. These increases could also be observed when the paretic leg transitions from stance to swing phases while walking with the haptic leash. The Sobolev norm values accounted for both angular position and angular velocity, providing a single value for potentially quantifying bilateral (i.e. non-paretic vs paretic) coordination during walking. These values tended to increase (p < 0.05) proportionally for both limbs during force and post-force epochs as gait speed tended to increase.

Conclusions

Individuals with chronic stroke who increased their gait speed when walking with tensile haptic forces and immediately after force removal, also displayed moderate concurrent changes in lower limb intersegmental coordination patterns in terms of angular displacement and velocity. Similar results were also seen with cane walking. Although symmetry was less affected, these findings appear favourable to the functional recovery of gait. Both the use of 3D phase diagrams and assigning Sobolev norm values are potentially effective for detecting and quantifying these coordination changes.
PAL1 gene of the phenylpropanoid pathway increases resistance to the Cassava brown streak virus in cassava
Authors: Kavil Siji , Otti Gerald , Bouvaine Sophie , Armitage Andrew , Maruthi Midatharahally N.
Published: September 2021

Background

The phenylalanine ammonia lyase genes play crucial role in plant response to biotic and abiotic stresses. In this study, we characterized the role of PAL genes in increasing resistance to the Cassava brown streak virus that causes the economically important cassava brown streak disease (CBSD) on cassava in Africa.

Methods

The whole transcriptomes of eight cassava varieties differing in resistance to CBSD were obtained at 1, 5 and 8 weeks after CBSV infection.

Results

Analysis of RNA-Seq data identified the overexpression of PAL1, PAL2, cinnamic acid and two chalcone synthase genes in CBSD-resistant cassava varieties, which was subsequently confirmed by RT-qPCR. The exogenous application of Acibenzolar-S-Methyl induced PAL1 gene expression to enhance resistance in the susceptible var. Kalawe. In contrast, the silencing of PAL1 by RNA interference led to increased susceptibility of the resistant var. Kaleso to CBSD.

Conclusions

PAL1 gene of the phenylpropanoid pathway has a major role in inducing resistance to CBSD in cassava plants and its early induction is key for CBSD resistance.
Evaluation of auto-segmentation accuracy of cloud-based artificial intelligence and atlas-based models
Authors: Urago Yuka , Okamoto Hiroyuki , Kaneda Tomoya , Murakami Naoya , Kashihara Tairo , Takemori Mihiro , Nakayama Hiroki , Iijima Kotaro , Chiba Takahito , Kuwahara Junichi , Katsuta Shouichi , Nakamura Satoshi , Chang Weishan , Saitoh Hidetoshi , Igaki Hiroshi
Published: September 2021

Background

Contour delineation, a crucial process in radiation oncology, is time-consuming and inaccurate due to inter-observer variation has been a critical issue in this process. An atlas-based automatic segmentation was developed to improve the delineation efficiency and reduce inter-observer variation. Additionally, automated segmentation using artificial intelligence (AI) has recently become available. In this study, auto-segmentations by atlas- and AI-based models for Organs at Risk (OAR) in patients with prostate and head and neck cancer were performed and delineation accuracies were evaluated.

Methods

Twenty-one patients with prostate cancer and 30 patients with head and neck cancer were evaluated. MIM Maestro was used to apply the atlas-based segmentation. MIM Contour ProtégéAI was used to apply the AI-based segmentation. Three similarity indices, the Dice similarity coefficient (DSC), Hausdorff distance (HD), and mean distance to agreement (MDA), were evaluated and compared with manual delineations. In addition, radiation oncologists visually evaluated the delineation accuracies.

Results

Among patients with prostate cancer, the AI-based model demonstrated higher accuracy than the atlas-based on DSC, HD, and MDA for the bladder and rectum. Upon visual evaluation, some errors were observed in the atlas-based delineations when the boundary between the small bowel or the seminal vesicle and the bladder was unclear. For patients with head and neck cancer, no significant differences were observed between the two models for almost all OARs, except small delineations such as the optic chiasm and optic nerve. The DSC tended to be lower when the HD and the MDA were smaller in small volume delineations.

Conclusions

In terms of efficiency, the processing time for head and neck cancers was much shorter than manual delineation. While quantitative evaluation with AI-based segmentation was significantly more accurate than atlas-based for prostate cancer, there was no significant difference for head and neck cancer. According to the results of visual evaluation, less necessity of manual correction in AI-based segmentation indicates that the segmentation efficiency of AI-based model is higher than that of atlas-based model. The effectiveness of the AI-based model can be expected to improve the segmentation efficiency and to significantly shorten the delineation time.
Functional results after carpal tunnel release in mucopolysaccharidosis
Authors: Giostri Giana Silveira , Souza Camila Deneka Arantes , Nagai Alencar Kenji , Santos Mara Lucia Schmitz Ferreira , Sampaio José Silvany Pacheco , de Masi Nassif Flavia David João
Published: September 2021

Background

Mucopolysaccharidosis consists of a group of diseases caused by the deficiency of lysosomal enzymes, which may lead to the compression of the median nerve in the carpal tunnel due to the accumulation of glycosaminoglycan, resulting in the hand disability. The study purpose is to present functional results of carpal tunnel release in mucopolysaccharidosis patients. Patients were selected from an enzyme replacement group in the Department of Pediatric Neurology. The legal guardians of the patients were informed about the likely functional change of the hands induced by compression of the median nerve. Clinical evaluation was performed in those patients who received their legal guardians’ consent to participate and was included inspection, assessment of functional level, wrinkle test and the digital pinch function to manipulate small and large objects. Ultrasound and electromyography were performed to confirm the clinical median nerve compression. Bilateral extended opening technique was performed to access the carpal tunnel and analyze the anatomic findings of the median nerve and the flexed tendons of the fingers. After the surgical release of the carpal tunnel, the clinical evaluation was repeated. Subjective observations of the legal guardians were also considered.

Results

Seven patients underwent bilateral surgical opening of the carpal tunnel; six boys, mean age of 9.5 (5 to 13), five of them presenting Type II mucopolysaccharidosis, 1 Type I and 1 Type VI. The average follow-up was 12 months (10–13 months). The functional results observed included the improvement in the handling of small and large objects in all children who underwent decompression of the median nerve. The comparison between the pre-operative and post-operative functional levels revealed that 2 patients evolved from Level II to IV, 3 from Level III to IV, 1 from Level IV to V and 1 patient remained in Level III. Tenosynovitis around the flexor tendons and severe compression of the median nerve in the fourteen carpal tunnels were observed during the surgical procedure. In 6 wrists, partial tenosynovitis was performed.

Conclusions

Despite the improvement in the overall function of the children' hands, we cannot conclude that only surgery was responsible for the benefit. Better designed studies are required
Monogenic mutations in four cases of neonatal-onset watery diarrhea and a mutation review in East Asia
Authors: Yan Weihui , Xiao Yongtao , Zhang Yunyi , Tao Yijing , Cao Yi , Liu Kunhui , Cai Wei , Wang Ying
Published: September 2021

Background

Infants with neonatal-onset diarrhea present with intractable diarrhea in the first few weeks of life. A monogenic mutation is one of the disease etiologies and the use of next-generation sequencing (NGS) has made it possible to screen patients for their mutations.

Main body

We retrospectively reviewed the clinical data of four children from unrelated families, who presented with neonatal-onset, chronic, watery, non-bloody diarrhea. After genetic whole-exome sequencing, novel mutations were identified in the EPCAM gene of two children. Congenital chloride diarrhea was diagnosed in one case, which was associated with an SLC26A3 mutation, in which the patient presented with watery diarrhea, malnutrition, and hypochloremic alkalosis. Patient 4 was diagnosed with microvillus inclusion disease and possessed novel compound heterozygous mutations in the MYO5B gene. A review of the genetic variants of SLC26A3 reported in East Asia revealed that c.269_270 dupAA (p.G91Kfs*3) is the most frequent SLC26A3 mutation in China, compared with c.2063-1 G > T in Japan and Korea. EPCAM and MYO5B genetic variants were only sporadically reported in East Asia.

Conclusion

This study expands our knowledge of the clinical manifestations and molecular genetics of neonatal-onset watery diarrhea. Early diagnosis could be achieved by genomic analysis in those infants whose histology features are not typical. The discovery of four novel mutations in the EPCAM gene and two novel mutations in the MYO5B gene provides further etiological evidence for the association of genetic mutations with neonatal-onset diarrhea. To date, c.269_270 dupAA is the most frequent SLC26A3 mutation in China.
Perceived mental health in parents of children with rare congenital surgical diseases: a double ABCX model considering gender
Authors: Boettcher Johannes , Zapf Holger , Fuerboeter Mareike , Nazarian Rojin , Reinshagen Konrad , Wiegand-Grefe Silke , Boettcher Michael
Published: September 2021

Background

Previous research has supported the utility of the Double ABCX model of family adaptation for parents in various diseases. Nonetheless, it remains unclear how raising a child with rare congenital surgical diseases impacts the mental health of both mothers and fathers.

Methods

The potential predictors of maternal and paternal mental health in a German sample of 210 parents of children with rare congenital surgical diseases were investigated. Parents were investigated cross-sectionally utilizing standardized psychometric questionnaires that assessed factors attributed to parental adaptation within the Double ABCX model.

Results

Stressor pile-up, family functioning, perceived stress, and mental health were positively associated with mothers and fathers. However, further analyses revealed that family functioning, social support, and perceived stress fully mediated the positive association between stressor pile-up and mental health in mothers, but not fathers.

Conclusion

Our findings suggest that parental adaptation to a rare congenital surgical disease in their children may be improved by increased intra- and extrafamilial resources and decreased perceived family-related stress in mothers, but not fathers. Our results may help to identify gender-specific factors that may guide clinicians and future interventions.
Pediatric health care professionals’ vaccine knowledge, awareness and attitude: a survey within the Italian Society of Pediatric Allergy and Immunology
Authors: Del Duca Elisabetta , Chini Loredana , Graziani Simona , Sgrulletti Mayla , Moschese Viviana ,   with the Italian Pediatric Immunology and Allergology Society (SIAIP) Vaccine Committee, Moschese V. , Chini L. , Sgrulletti M. , Dellepiane R. M. , Martire B. , Sangerardi M. , Montin D. , Ottaviano G. , Rizzo C. , Duse M. , Marseglia G.
Published: September 2021

Background

Physicians play a key role in driving vaccine acceptance and their recommendations are crucial to address vaccine hesitancy. The aim of the study was to assess knowledge, awareness and attitude of Italian Pediatric Health Care Professionals (pHCPs) on vaccinations.

Methods

An anonymous on-line questionnaire was developed within the Vaccine Committee of Italian Society of Pediatric Allergy and Immunology (SIAIP) and spontaneously completed by 231 Pediatricians and Pediatric Nurses (PN).

Results

An accurate vaccine education was reported by 70% of pediatricians and 13% of PN but 11% of pediatricians versus 26% of PN consult social media instead of scientific sources for their vaccine update. The investigation on the pHCPs attitudes to vaccination in a personal and family setting highlights poor adherence to vaccinations. Only 63% of pediatricians versus 16% of PN (p < 0.0001) annually received the Flu vaccine. In their family setting 93% of pediatricians versus 51% of PN recommended all vaccinations (p < 0.0001). Anti-flu, anti-rotavirus, anti-zoster and anti-pneumococcal vaccines were not regularly recommended by all pHCPs due to doubts of uselessness (55% of pediatricians versus 40% of PN) and preference for “natural immunity” (44% of pediatricians versus 40% of PN).

Conclusions

Our results indicate that pHCPs’ attitude and confidence in regards to vaccines remain suboptimal. Current COVID-19 pandemic and the rapid development of vaccines could increase vaccine hesitancy. Due to the documented pHCPs’ influence in the parental decision, educational interventions are needed to improve their level of knowledge and counselling skills in order to address parental vaccine hesitancy and to maintain continuity of immunization services.
Evaluation of some aspects in supervised cell type identification for single-cell RNA-seq: classifier, feature selection, and reference construction
Authors: Ma Wenjing , Su Kenong , Wu Hao
Published: September 2021

Background

Cell type identification is one of the most important questions in single-cell RNA sequencing (scRNA-seq) data analysis. With the accumulation of public scRNA-seq data, supervised cell type identification methods have gained increasing popularity due to better accuracy, robustness, and computational performance. Despite all the advantages, the performance of the supervised methods relies heavily on several key factors: feature selection, prediction method, and, most importantly, choice of the reference dataset.

Results

In this work, we perform extensive real data analyses to systematically evaluate these strategies in supervised cell identification. We first benchmark nine classifiers along with six feature selection strategies and investigate the impact of reference data size and number of cell types in cell type prediction. Next, we focus on how discrepancies between reference and target datasets and how data preprocessing such as imputation and batch effect correction affect prediction performance. We also investigate the strategies of pooling and purifying reference data.

Conclusions

Based on our analysis results, we provide guidelines for using supervised cell typing methods. We suggest combining all individuals from available datasets to construct the reference dataset and use multi-layer perceptron (MLP) as the classifier, along with F-test as the feature selection method. All the code used for our analysis is available on GitHub (https://github.com/marvinquiet/RefConstruction_supervisedCelltyping).
Electroacupuncture for postoperative ileus after laparoscopic surgery on colorectal cancer: study protocol for a randomized controlled trial
Authors: Shao Jia-Kai , Liu Qian , Pei Wei , Wang Yu , Yang Na-Na , Qi Ling-Yu , Huang Jin , Yang Jing-Wen , Liu Cun-zhi
Published: September 2021

Background

Postoperative ileus (POI) occurs in almost all patients after abdominal laparoscopic surgery, resulting in complications and increasing the length of hospitalization. Electroacupuncture has been used as an alternative therapy for gastrointestinal dysfunction, but its efficacy for POI is inconclusive. The study is designed to determine whether electroacupuncture can accelerate recovery from POI.

Methods/design

This study is a three-arm, randomized controlled trial. A total of 105 patients will be randomized into a group receiving electroacupuncture at Tianshu (ST25), a group receiving electroacupuncture at Zusanli (ST36), or a control group in a 1:1:1 ratio. Patients in the electroacupuncture groups will receive electroacupuncture treatment for 4 days from the first day after surgery. The primary outcome consists of the time to first flatus and the time to first defecation. Secondary outcomes include the time to first tolerance of liquid and semiliquid food; the length of the hospital stay; postoperative pain, nausea, and vomiting; abdominal distension; the time to first get out of bed; and postoperative complications. The outcomes will be assessed by the patients themselves every day during hospitalization. Surgeons, nurses, assessors, and statisticians will be blinded to the group assignments. Patients in the two electroacupuncture groups, but not in the control group, will be blinded to the group assignments. The acupuncturists will not be blinded.

Discussion

The aim of this trial is to provide a nonpharmacological therapy for POI and may provide evidence of the effect of electroacupuncture at ST25 or ST36 on POI.

Trial registration

Chinese Clinical Trial RegistryChiCTR1900027466. Registered on 14 November 2019.
Standardised Outcomes in Nephrology – Chronic Kidney Disease (SONG-CKD): a protocol for establishing a core outcome set for adults with chronic kidney disease who do not require kidney replacement therapy
Authors: Evangelidis Nicole , Sautenet Benedicte , Madero Magdalena , Tong Allison , Ashuntantang Gloria , Sanabria Laura Cortes , de Boer Ian H. , Fung Samuel , Gallego Daniel , Levey Andrew S. , Levin Adeera , Lorca Eduardo , Okpechi Ikechi G. , Rossignol Patrick , Sola Laura , Usherwood Tim , Wheeler David C. , Cho Yeoungjee , Howell Martin , Guha Chandana , Scholes-Robertson Nicole , Widders Katherine , Gonzalez Andrea Matus , Teixeira-Pinto Armando , Viecelli Andrea K. , Bernier-Jean Amelie , Anumudu Samaya , Dunn Louese , Wilkie Martin , Craig Jonathan C. ,   on behalf of the SONG-CKD Investigators
Published: September 2021

Background

Globally, over 1.2 million people die from chronic kidney disease (CKD) every year. Patients with CKD are up to 10 times more likely to die prematurely than progress to kidney failure requiring kidney replacement therapy. The burden of symptoms and impaired quality of life in CKD may be compounded by comorbidities and treatment side effects. However, patient-important outcomes remain inconsistently and infrequently reported in trials in patients with CKD, which can limit evidence-informed decision-making. The Standardised Outcomes in Nephrology – Chronic Kidney Disease (SONG-CKD) aims to establish a consensus-based core outcome set for trials in patients with CKD not yet requiring kidney replacement therapy to ensure outcomes of relevance to patients, caregivers and health professionals are consistently reported in trials.

Methods

SONG-CKD involves four phases: a systematic review to identify outcomes (domains and measures) that have been reported in randomised controlled trials involving adults with CKD who do not require kidney replacement therapy; stakeholder key informant interviews with health professionals involved in the care of adults with CKD to ascertain their views on establishing core outcomes in CKD; an international two-round online Delphi survey with patients, caregivers, clinicians, researchers, policy makers and industry representatives to obtain consensus on critically important outcome domains; and stakeholder consensus workshops to review and finalise the set of core outcome domains for trials in CKD.

Discussion

Establishing a core outcome set to be reported in trials in patients with CKD will enhance the relevance, transparency and impact of research to improve the lives of people with CKD.

Trial registration

Not applicable. This study is registered with the Core Outcome Measures in Effectiveness Trials (COMET) database: http://www.comet-initiative.org/Studies/Details/1653.
Evaluation of molecular assays to detect Leishmania donovani in Phlebotomus argentipes fed on post-kala-azar dermal leishmaniasis patients
Authors: Khan Md Anik Ashfaq , Faisal Khaledul , Chowdhury Rajashree , Nath Rupen , Ghosh Prakash , Ghosh Debashis , Hossain Faria , Abd El Wahed Ahmed , Mondal Dinesh
Published: September 2021

Background

Post-kala-azar dermal leishmaniasis (PKDL) caused by Leishmania donovani (LD) is a skin disorder that often appears after treatment of visceral leishmaniasis (VL) patients. PKDL patients are potential reservoirs of LD parasites, which can initiate a new epidemic of anthroponotic VL. Therefore, host infectiousness to its sand fly vector is a critical factor for transmission, and its accurate estimation can facilitate control strategies. At present, conventional microscopy serves as the reference method to detect parasites in its vector. However, low sensitivity of microscopy can be a limiting factor.

Methods

In this study, real-time quantitative PCR (LD-qPCR) and recombinase polymerase amplification (LD-RPA) assays were evaluated against microscopy for the detection of LD DNA extracted from live sand flies five days after controlled feeding on PKDL cases.

Results

The sensitivity of LD-qPCR and LD-RPA assays were found to be 96.43 and 100%, respectively, against microscopy for the selected fed sand flies (n = 28), and an absolute specificity of both molecular tools for apparently unfed sand flies (n = 30). While the proportion of infectious cases among 47 PKDL patients was estimated as 46.81% as defined by microscopic detection of LD in at least one fed sand fly per case, LD-RPA assay evaluation of only the microscopy negative sand flies fed to those 47 PKDL cases estimated an even greater proportion of infectious cases (51.06%). In overall estimation of the infectious cases in retrospective manner, discordance in positivity rate was observed (p < 0.05) between LD-RPA (59.57%) assay and microscopy (46.81%), while LD-RPA had slightly better positivity rate than LD-qPCR (55.32%) as well.

Conclusions

Considering the sensitivity, cost, detection time, and field applicability, RPA assay can be considered as a promising single molecular detection tool for investigations pertaining to LD infections in sand flies and/or host infectiousness in PKDL, while it can also be useful in confirmation of microscopy negative sand fly samples.

Graphical abstract