bluuebunny/crossref_metadata_2025_split huggingface dataset:
Analysis of bowel function, urogenital function, and long-term follow-up outcomes associated with robotic and laparoscopic sphincter-preserving surgical approaches to total mesorectal excision in low rectal cancer: a retrospective cohort study
Authors: Yang Bo , Zhang Shangxin , Yang Xiaodong , Wang Yigao , Li Deguan , Zhao Jian , Li Yongxiang 
Published: May 2022

Abstract
Objective
The present study comparatively analyzed short-term clinical effectiveness and long-term follow-up endpoints associated with robotic-assisted sphincter-preserving surgery (RAS) and laparoscopic-assisted sphincter-preserving surgery (LAS) when used to treat low rectal cancer.

Method
Within such a single-center retrospective cohort analysis, low rectal cancer patients that underwent RAS (n=200) or LAS (n=486) between January 2015 and beginning of July 2018 were enrolled.

Results
The mean operative durations in the RAS and LAS cohorts were 249±64 min and 203±47 min, respectively (P<0.001). Temporary ileostomy rates in the RAS and LAS cohorts were 64.5% and 51.6% (P = 0.002). In addition, major variations across such cohorts regarding catheter removal timing, time to liquid intake, time to first leaving bed, and length of hospitalization (all P<0.001). This distal resection margin distance within the RAS cohort was diminished in comparison to LAS cohort (P=0.004). For patients within the LAS cohort, the time required to recover from reduced urinary/female sexual function was > 6 months post-surgery (P<0.0001), whereas within the RAS cohort this interval was 3 months (P<0.0001). At 6 months post-surgery, male sexual function within RAS cohort was improved in comparison to LAS cohort (P<0.001). At 6 months post-surgery, Wexner scores revealed similar results (P<0.001). No major variations within overall or disease-free survival were identified across these cohorts at 3 or 5 years post-surgery.

Conclusion
Robotic sphincter-preserving surgery is a safe and effective surgical technique in low rectal patients in terms of postoperative oncological safety and long-term endpoints. And the RAS strategy provides certain additional benefits with respect to short-term urogenital/anorectal functional recovery in treated patients compared to LAS.
Verification of genetic differences and immune cell infiltration subtypes in the neuroblastoma tumour microenvironment during immunotherapy
Authors: Qian Bo , Sun Jing , Zuo Pengcheng , Da Min , Mo Xuming , Fang Yongjun 
Published: May 2022

Abstract
Background
Improved understanding of the tumour microenvironment (TME) has enabled remarkable advancements in research on cancer progression in the past few years. It is crucial to understand the nature and function of the TME because precise treatment strategies, including immunotherapy, for managing specific cancers have received widespread attention. The immune infiltrative profiles of neuroblastoma (NB) have not yet been completely illustrated. The purpose of this research was to analyse tumour immune cell infiltration (ICI) in the microenvironment of NB.

Methods
We applied the CIBERSORT and ESTIMATE algorithms to evaluate the ICI status of 438 NB samples. Three ICI models were selected, and ICI scores were acquired. Subgroups with high ICI scores determined based on the presence of immune activation signalling pathways had better overall survival.

Results
Genes involved in the immunosuppressive heparan sulphate glycosaminoglycan biosynthesis signalling pathway were markedly enriched in the low ICI score subgroup. It was inferred that patients with high ICI NB subtypes were more likely to respond to immunotherapy and have a better prognosis than those of patients with low ICI NB subtypes.

Conclusion
Notably, our ICI data not only provide a new clinical and theoretical basis for mining NB prognostic markers related to the microenvironment but also offer new ideas for the development of NB precision immunotherapy methods.
Ahi1 regulates serotonin production by the GR/ERβ/TPH2 pathway involving sexual differences in depressive behaviors
Authors: Wang Bin , Shi Haixia , Ren Liyan , Miao Zhigang , Wan Bo , Yang Hao , Fan Xiaotang , Gustafsson Jan-Ake , Sun Miao , Xu Xingshun 
Published: May 2022

Abstract
Background
Depression is one of the most common psychiatric diseases. The monoamine transmitter theory suggests that neurotransmitters are involved in the mechanism of depression; however, the regulation on serotonin production is still unclear. We previously showed that Ahi1 knockout (KO) mice exhibited depression-like behavior accompanied by a significant decrease in brain serotonin.

Methods
In the present study, western blot, gene knockdown, immunofluorescence, dual-luciferase reporter assay, and rescue assay were used to detect changes in the Ahi1/GR/ERβ/TPH2 pathway in the brains of male stressed mice and male Ahi1 KO mice to explain the pathogenesis of depression-like behaviors. In addition, E2 levels in the blood and brain of male and female mice were measured to investigate the effect on the ERβ/TPH2 pathway and to reveal the mechanisms for the phenomenon of gender differences in depression-like behaviors.

Results
We found that the serotonin-producing pathway-the ERβ/TPH2 pathway was inhibited in male stressed mice and male Ahi1 KO mice. We further demonstrated that glucocorticoid receptor (GR) as a transcription factor bound to the promoter of ERβ that contains glucocorticoid response elements and inhibited the transcription of ERβ. Our recent study had indicated that Ahi1 regulates the nuclear translocation of GR upon stress, thus proposing the Ahi1/GR/ERβ/TPH2 pathway for serotonin production. Interestingly, female Ahi1 KO mice did not exhibit depressive behaviors, indicating sexual differences in depressive behaviors compared with male mice. Furthermore, we found that serum 17β-estradiol (E2) level was not changed in male and female mice; however, brain E2 level significantly decreased in male but not female Ahi1 KO mice. Further, ERβ agonist LY-500307 increased TPH2 expression and 5-HT production. Therefore, both Ahi1 and E2 regulate the ERβ/TPH2 pathway and involve sexual differences in brain serotonin production and depressive behaviors.

Conclusions
In conclusion, although it is unclear how Ahi1 controls E2 secretion in the brain, our findings demonstrate that Ahi1 regulates serotonin production by the GR/ERβ/TPH2 pathway in the brain and possibly involves the regulation on sex differences in depressive behaviors.
Identification of the key exosomal lncRNAs/mRNAs in the serum during distraction osteogenesis
Authors: Zhang Tao , Jiang Weidong , Liao Fengchun , Zhu Peiqi , Guo Lina , Zhao Zhenchen , Liu Yan , Huang Xuanping , Zhou Nuo 
Published: May 2022

AbstractBackgroundDistraction osteogenesis (DO), a kind of bone regenerative process, is not only extremely effective, but the osteogenesis rate is far beyond ordinary bone fracture (BF) healing. Exosomes (Exo) are thought to play a part in bone regeneration and healing as key players in cell-to-cell contact. The object of this work was to determine whether exosomes derived from DO and BF serum could stimulate the Osteogenic Differentiation in these two processes, and if so, which genes could be involved.MethodsThe osteogenesis in DO-gap or BF-gap was evaluated using radiographic analysis and histological analysis. On the 14th postoperative day, DO-Exos and BF-Exos were isolated and cocultured with the jaw of bone marrow mesenchymal stem cells (JBMMSCs). Proliferation, migration and osteogenic differentiation of JBMMSCs were ascertained, after which exosomes RNA-seq was performed to identify the relevant gene.ResultsRadiographic and histological analyses manifested that osteogenesis was remarkably accelerated in DO-gap in comparison with BF-gap. Both of the two types of Exos were taken up by JBMMSCs, and their migration and osteogenic differentiation were also seen to improve. However, the proliferation showed no significant difference. Finally, exosome RNA-seq revealed that the lncRNA MSTRG.532277.1 and the mRNA F-box and leucine-rich repeat protein 14(FBXL14) may play a key role in DO.ConclusionsOur findings suggest that exosomes from serum exert a critical effect on the rapid osteogenesis in DO. This promoting effect might have relevance with the co-expression of MSTRG.532277.1 and FBXL14. On the whole, these findings provide new insights into bone regeneration, thereby outlining possible therapeutic targets for clinical intervention.
SOCS7/HuR/FOXM1 signaling axis inhibited high-grade serous ovarian carcinoma progression
Authors: Du Yanhua , Xu Xiang , Lv Siang , Liu Han , Sun Hong , Wu Jun 
Published: May 2022

AbstractBackgroundHigh-grade serous ovarian carcinoma (HGSOC) is clinically dominant and accounts for ~ 80% deaths in all types of ovarian cancer. The delayed diagnosis, rapid development, and wide dissemination of HGSOC collectively contribute to its high mortality rate and poor prognosis in the patients. Suppressors of cytokine signaling 7 (SOCS7) can regulate cytokine signaling and participate in cell cycle arrest and regulation of cell proliferation, which might also be involved in carcinogenesis. Here, we designated to investigate the functions and mechanisms of SOCS7 in HGSOC.MethodsThe clinical correlation between SOCS7 and HGSOC was examined by both bioinformatics and analysis of tissue samples in patients. Gain/Loss-of-function examinations were carried out to assess the effectiveness of SOCS7 in cell viability, cell cycle, and tumor growth of HGSOC. Furthermore, the underlying mechanisms were explored by identifying the downstream proteins and their interactions via proteomics analysis and immunoprecipitation.ResultsThe expression of SOCS7, which was decreased in HGSOC tissues, was correlated with the clinical pathologic characteristics and overall survival of HGSOC patients. SOCS7 acted as a HGSOC suppressor by inhibiting cancer cell viability and tumor growth in vivo. The anti-HGSOC mechanism involves SOCS7’s regulatory effect on HuR by mediating its ubiquitination, the regulation of FOXM1 mRNA by HuR, as well as the interplays among these three clinically relevant factors.ConclusionsThe SOCS7 correlates with HGSOC and suppresses its tumorigenesis through regulating HuR and FOXM1, which also suggests that SOCS7 is a prospective biomarker for the clinical management of ovarian cancer, especially HGSOC.
Motivations, sources of influence and barriers to being a podiatrist: a national questionnaire of student views
Authors: Wallis Lucy , Faulkner James , Locke Rachel , Harden Beverley , Cowley Emma E. 
Published: May 2022

AbstractBackgroundPodiatry is an allied health profession which has seen a substantial decline in numbers in recent years. Every effort is required to recruit more students to reverse this diminishing supply and meet national foot health needs. To increase the number of applications to podiatry courses and encourage individuals to choose podiatry careers, the aim of this study was to understand the key motivations, sources of influence and barriers to choosing a podiatry career among current podiatry students, and consider the influence of choosing podiatry before or after a first career.MethodsAn online questionnaire, comprising mainly Likert‐scale questions, was disseminated to podiatry students in England between February and March 2021. Respondents to the questionnaire were categorised as individuals who had either decided to engage in the profession ‘before’ or ‘after’ a first career. Mann‐Whitney U non‐parametric difference tests were performed to compare outcome questions relating to motivations, sources of influence and barriers between groups.ResultsOne hundred and fifteen students completed the questionnaire. Overall, the study demonstrated many similarities between the groups (before and after a first career). However, there were distinct differences when considering some of the motivations (i.e., intellectually stimulating, student bursaries), sources of influence (i.e., own patient experience) and barriers (i.e., financial, job availability) associated with engaging in the podiatry profession. Overall, altruistic reasons were the key motivations for choosing podiatry. Personal sources of influence such as conducting own research, was the most important source of influence. Similar to other studies, a lack of awareness of the podiatry profession and what it entails remains problematic.ConclusionsThis is the first national questionnaire investigating career choice decision‐making for podiatry students in England or in any other country. The similarities suggest that marketing is applicable to both groups. However, an absolute must is a future national strategy that makes educational sources more impactful. Additionally, following the Covid‐19 pandemic, the increased interest in health and care professions suggests now is the right time to market podiatry to individuals looking for a career change. Finally, the influence of personal encounters with podiatrists shows the transformational role podiatrists can have in recruiting to the profession.
Are prime numbers special? Insights from the life sciences
Authors: Loconsole Maria , Regolin Lucia 
Published: May 2022

AbstractPrime numbers have been attracting the interest of scientists since the first formulation of Euclid’s theorem in 300 B.C. Nowadays, physicists and mathematicians continue to formulate new theorems about prime numbers, trying to comprehensively explain their articulated properties. However, evidence from biology and experimental psychology suggest that prime numbers possess distinctive natural properties that pre-exist human grasping. The present work aims at reviewing the existing literature on prime numbers in the life sciences, including some recent experimental contributions employing newly hatched domestic chicks as animal model to test for spontaneous mechanisms allowing discrimination of primes from non-primes. Our overarching goal is that of discussing some instances of prime numbers in nature, with particular reference to their peculiar, non-mathematical, perceptual properties.
A refined and updated health impact assessment of the Global Programme to Eliminate Lymphatic Filariasis (2000–2020)
Authors: Turner Hugo C. , Ottesen Eric A. , Bradley Mark H. 
Published: May 2022

Abstract
Background
Lymphatic filariasis (LF) is a neglected tropical disease (NTD). In 2000 the World Health Organization (WHO) established the Global Programme to Eliminate Lymphatic Filariasis (GPELF). A key component of this programme is mass drug administration (MDA). Between 2000 and 2020, the GPELF has delivered over 8.6 billion treatments to at-risk populations. The last impact assessment of the programme evaluated the treatments provided between 2000–2014. The goal of this analysis is to provide an updated health impact assessment of the programme, based on the numbers treated between 2000–2020.

Methods
We updated and refined a previously established model that estimates the number of clinical manifestations and disability-adjusted life years (DALYs) averted by the treatments provided by the GPELF. The model comprises three different population cohorts that can benefit from MDA provided (those protected from acquiring infection, those with subclinical morbidity prevented from progressing and those with clinical disease alleviated). The treatment numbers were updated for all participating countries using data from the WHO. In addition, data relating to the estimated number of individuals initially at risk of LF infection were updated where possible. Finally, the DALY calculations were refined to use updated disability weights.

Results
Using the updated model and corresponding treatment data, we projected that the total benefit cohort of the GPELF (2000–2020) would consist of approximately 58.5 million individuals and the programme would avert 44.3 million chronic LF cases. Over the lifetime of the benefit cohorts, this corresponded to 244 million DALYs being averted.

Conclusion
This study indicates that substantial health benefits have resulted from the first 20 years of the GPELF. It is important to note that the GPELF would have both additional benefits not quantified by the DALY burden metric as well as benefits on other co-endemic diseases (such as soil-transmitted helminths, onchocerciasis and scabies)—making the total health benefit underestimated. As with the past impact assessments, these results further justify the value and importance of continued investment in the GPELF.

Graphical Abstract
Defining the mechanisms of action and mosquito larva midgut response to a yeast-encapsulated orange oil larvicide
Authors: Kelly Patrick H. , Yingling Alexandra V. , Ahmed Anwar , Hurwitz Ivy , Ramalho-Ortigao Marcelo 
Published: May 2022

Abstract
Background
Yeast-encapsulated orange oil (YEOO) is a novel, ingestible larvicide that combines the benefits of a low-cost essential oil with yeast, an attractive food source for mosquito larvae. In this work, we investigated the underlying mechanisms of action associated with YEOO ingestion by Aedes aegypti larvae.

Methods
Aedes aegypti third-stage larvae (L3) were treated with sublethal or lethal concentrations of YEOO. Genes associated with apoptosis, autophagy and innate immune responses were investigated by RT-qPCR in guts and carcasses dissected from treated and control larvae. Differential expression of cytochrome P450 genes in the CYP6 and CYP9 families were also investigated. Confocal and transmission electron microscopy were used to assess damage caused by YEOO throughout the larval alimentary canal. TUNEL was used to assess apoptosis via DNA fragmentation.

Results
The apoptosis genes IAP1 and IAP2 in larvae displayed opposing effects following exposure to lethal doses of YEOO, with a 26-fold induction of IAP1 at 8 h post YEOO ingestion. The effector caspase CASPS8 displayed a 6.7-fold induction in the gut and concomitant 70-fold induction in the carcass at 8 h post YEOO ingestion. The midgut epithelia regenerator, Vein, had an 11-fold induction in the gut after 4 h and was repressed 7.6-fold in the carcass at 24 h. Sublethal concentrations (< LC50) led to significant differential expression of CYP6 and CYP9 genes. Midgut epithelial damage was highlighted by the destruction of microvilli, vacuolization of midgut cells and damage to cell junctions and basal lamina as early as 30 min. Larval type 2 peritrophic matrix structural integrity and porosity remain unchanged.

Conclusion
Our results strongly suggest that the robust larvicidal activity of YEOO is due to a generalized broad-acting mechanism combining epithelial damage and apoptosis, with concomitant expression of multiple innate response genes involved in epithelial regeneration and detoxification. YEOO’s amenability for use as part of an integrated vector management program makes this novel larvicide a practical approach for mosquito larval control in the future.

Graphical Abstract
The effectiveness of the use of telehealth programs in the care of individuals with hypertension and, or diabetes mellitus: systematic review and meta-analysis
Authors: Santos Daniel Souza , Batistelli Clara Regina Santos , Lara Marina Marilac dos Santos , Ferreira Emily de Souza , Moreira Tiago Ricardo , Cotta Rosângela Minardi Mitre 
Published: May 2022

Abstract
Introduction
Diabetes Mellitus and Hypertension are some of the main Chronic Noncommunicable Diseases, representing a big challenge for global health. In this context, Telehealth programs are presented as a tool with exciting potential to complement and support health care. This paper aimed to analyze the effectiveness of the use of Telehealth programs in the care of individuals with Hypertension and/or Diabetes Mellitus.

Methods
A systematic review with meta-analysis was carried out according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocol methodology. The following databases were used: PubMed, EMBASE, SciELO, ScienceDirect and Cochrane Library. Papers were included if they addressed the use of technologies that allow two-way communication at a distance between health professionals and patients affected by Hypertension and/or Diabetes Mellitus, type 1 or type 2. Experimental, cross-sectional, case–control, cohort, and clinical trials were included in the review.

Results
We included 164 papers in the review and 45 in the meta-analysis final synthesis. The systematic review results showed a prevalence of telemonitoring as the main form of Telehealth. The study showed a reduction in expenses with the use of Telehealth, both for the users and for the health systems providers, followed by greater satisfaction. Our meta-analysis showed that Telehealth is an effective tool in the care of diabetic patients, providing a 0.353% reduction in HbA1c compared to traditional care. No studies on Hypertension that met our eligibility criteria for inclusion in the meta-analysis were found.

Conclusions
Telehealth is an effective tool for the care of people with Diabetes Mellitus and/or Hypertension.
Designing a novel multi-epitope vaccine to evoke a robust immune response against pathogenic multidrug-resistant Enterococcus faecium bacterium
Authors: Dey Jyotirmayee , Mahapatra Soumya Ranjan , Raj T. Kiran , Kaur Taranjeet , Jain Parul , Tiwari Arushi , Patro Shubhransu , Misra Namrata , Suar Mrutyunjay 
Published: May 2022

AbstractEnterococcus faecium is an emerging ESKAPE bacterium that is capable of causing severe public health complications in humans. There are currently no licensed treatments or vaccinations to combat the deadly pathogen. We aimed to design a potent and novel prophylactic chimeric vaccine against E. faecium through an immunoinformatics approach The antigenic Penicillin-binding protein 5 (PBP 5) protein was selected to identify B and T cell epitopes, followed by conservancy analysis, population coverage, physiochemical assessment, secondary and tertiary structural analysis. Using various immunoinformatics methods and tools, two linear B-cell epitopes, five CTL epitopes, and two HTL epitopes were finally selected for vaccine development. The constructed vaccine was determined to be highly immunogenic, cytokine-producing, antigenic, non-toxic, non-allergenic, and stable, as well as potentially effective against E. faecium. In addition, disulfide engineering, codon adaptation, and in silico cloning, were used to improve stability and expression efficiency in the host E. coli. Molecular docking and molecular dynamics simulations indicated that the structure of the vaccine is stable and has a high affinity for the TLR4 receptor. The immune simulation results revealed that both B and T cells had an increased response to the vaccination component. Conclusively, the in-depth in silico analysis suggests, the proposed vaccine to elicit a robust immune response against E. faecium infection and hence a promising target for further experimental trials.