bluuebunny/crossref_metadata_2025 huggingface dataset:
Gorilla habituation and the role of animal agency in conservation and tourism development at Bwindi, South Western Uganda
Authors: Ampumuza Christine , Driessen Clemens
Published: October 2020

Discussions of gorilla habituation often emphasise human control of gorillas, whereby gorillas are usually singularly defined by their species membership. This perspective leaves little room for imagining the role of gorillas in habituation, conservation and tourism development processes. In this paper, we use insights from Actor Network Theory and more-than-human geography to explore and reconstruct the practice of gorilla habituation in order to understand gorillas as actors in habituation, conservation and tourism development at Bwindi Impenetrable National Park (hereafter Bwindi), Uganda. To do so, we use the concept of relational animal agency to trace the various ways in which gorillas interact with each other, various groups of people, and their environment. Ethnographic observations, unstructured interviews and document study indicate that gorillas are ‘multiple’ and thus need to be understood beyond their species membership alone. They are involved in intricate relations with each other, with other non-human and human subjects, and their shared environment. Furthermore, gorillas are not completely and passively controlled by humans through habituation: we argue that habituation as a relational process is more complex. Gorillas also habituate other gorillas and arguably can be seen to habituate humans as well. As a result, gorillas co-produce multiple versions of the Bwindi landscape, of conservation, tourism and development practices, as well as multiple ways of being gorillas. Based on these insights, we argue that instead of focusing on control, the dynamics between gorillas and their landscapes could be harnessed to explore a dynamic range of possibilities for living together with gorillas, while continuously adapting to issues that will arise in places such as Bwindi.
Valerian Root in Treating Sleep Problems and Associated Disorders—A Systematic Review and Meta-Analysis
Authors: Shinjyo Noriko , Waddell Guy , Green Julia
Published: October 2020

Sleep problems are widely prevalent and associated with various comorbidities including anxiety. Valerian ( Valeriana officinalis L.) is a popular herbal medicine used as a sleep aid, however the outcomes of previous clinical studies are inconsistent. This study was conducted to update and re-evaluate the available data in order to understand the reason behind the inconsistent outcomes and to provide a broader view of the use of valerian for associated disorders. PubMed, ScienceDirect, and Cochrane Library were searched to retrieve publications relevant to the effectiveness of valerian as a treatment of sleep problems and associated disorders. A total of 60 studies (n=6,894) were included in this review, and meta-analyses were performed to evaluate the effectiveness to improve subjective sleep quality (10 studies, n=1,065) and to reduce anxiety (8 studies, n=535). Results suggested that inconsistent outcomes were possibly due to the variable quality of herbal extracts and that more reliable effects could be expected from the whole root/rhizome. In addition, therapeutic benefits could be optimized when it was combined with appropriate herbal partners. There were no severe adverse events associated with valerian intake in subjects aged between 7 and 80 years. In conclusion, valerian could be a safe and effective herb to promote sleep and prevent associated disorders. However, due to the presence of multiple active constituents and relatively unstable nature of some of the active constituents, it may be necessary to revise the quality control processes, including standardization methods and shelf life.
Mitochondrial antiviral signaling protein is crucial for the development of pulmonary fibrosis
Authors: Kim Sang-Hun , Lee Jung Yeon , Yoon Chang Min , Shin Hyeon Jun , Lee Sei Won , Rosas Ivan , Herzog Erica , Dela Cruz Charles S. , Kaminski Naftali , Kang Min-Jong
Published: October 2020

Danger signals, or damage-associated molecular patterns (DAMPs), instigate mitochondrial innate immune responses wherein mitochondrial antiviral signaling protein (MAVS) functions as a key platform molecule to mediate them. The role of MAVS in the pathogenesis of idiopathic pulmonary fibrosis (IPF), however, has not yet been identified. Whether MAVS signalling can be modulated by currently existing drugs has also not been explored.

We used an established model of pulmonary fibrosis to demonstrate that MAVS is a critical mediator of multiple DAMP signalling pathways and the consequent lung fibrosis after bleomycin-induced injuryin vivo.

After bleomycin injury, MAVS expression was mainly observed in macrophages. Multimeric MAVS aggregation, a key event of MAVS signalling activation, was significantly increased and persisted in bleomycin-injured lungs. A proapoptotic BH3 mimetic, ABT-263, attenuated the expression of MAVS and its signalling and, consequently, the development of experimental pulmonary fibrosis. In contrast, the therapeutic effects of nintedanib and pirfenidone, two drugs approved for IPF treatment, were not related to the modulation of MAVS or its signalling. Multimeric MAVS aggregation was significantly increased in lungs from IPF patients as well.

MAVS may play an important role in the development of pulmonary fibrosis, and targeting MAVS with BH3 mimetics may provide a novel and much needed therapeutic strategy for IPF.
Clinical phenotypes of extrapulmonary sarcoidosis: an analysis of a French, multi-ethnic, multicentre cohort
Authors: Lhote Raphael , Annesi-Maesano Isabella , Nunes Hilario , Launay David , Borie Raphael , Sacré Karim , Schleinitz Nicolas , Hamidou Mohamed , Mahevas Matthieu , Devilliers Hervé , Bonniaud Philippe , Lhote François , Haroche Julien , Rufat Pierre , Amoura Zahir , Valeyre Dominique , Cohen Aubart Fleur
Published: October 2020

Sarcoidosis is a rare disease of unknown cause with wide heterogeneity in clinical features and outcomes. We aimed to explore sarcoidosis phenotypes and their clinical relevance with particular attention to extrapulmonary subgroups.

The Epidemiology of Sarcoidosis (EpiSarc) study is a French retrospective multicentre study. Sarcoidosis patients were identified through national hospitalisation records using appropriate codes from 11 hospital centres between 2013 and 2016 according to a standardised protocol. Medical charts were reviewed. The phenotypes of sarcoidosis were defined using a hierarchical cluster analysis.

A total of 1237 patients were included (562 men and 675 women). The mean age at sarcoidosis diagnosis was 43.5±13 years. Hierarchical cluster analysis identified five distinct phenotypes according to organ involvement and disease type and symptoms: 1) erythema nodosum, joint involvement and hilar lymph nodes (n=180); 2) eye, neurological, digestive and kidney involvement (n=137); 3) pulmonary involvement with fibrosis and heart involvement (n=630); 4) lupus pernio and a high percentage of severe involvement (n=41); and 5) hepatosplenic, peripheral lymph node and bone involvement (n=249). Phenotype 1 was associated with being European/Caucasian and female and with non-manual work, phenotype 2 with being European/Caucasian, and phenotypes 3 and 5 with being non-European/Caucasian. The labour worker proportion was significantly lower in phenotype 5 than in the other phenotypes.

This multicentre study confirms the existence of distinct phenotypes of sarcoidosis, with a non-random distribution of organ involvement. These phenotypes differ according to sex, geographical origin and socioprofessional category.
Pharmacological and nonpharmacological interventions to improve symptom control, functional exercise capacity and quality of life in interstitial lung disease: an evidence synthesis
Authors: Bajwah Sabrina , Colquitt Jill , Loveman Emma , Bausewein Claudia , Almond Howard , Oluyase Adejoke , Dzingina Mendy , Maddocks Matthew , Higginson Irene J. , Wells Athol
Published: October 2020

We assessed efficacy and effectiveness of pharmacological and nonpharmacological interventions in improving symptom control, functional exercise capacity and quality of life (QoL) in people living with fibrotic interstitial lung disease (ILD).

We summarised evidence from three previous reviews (to June 2014) and conducted an updated search of nine databases and grey literature (2011–2019) (registration: CRD42017065933) for prospective studies of interventions aimed to alleviate symptoms, improve QoL or functional exercise capacity in fibrotic ILD. Data were synthesised through narrative synthesis or meta-analysed as appropriate.

Forty-seven studies with 2527 participants were included. From 22 pharmacological studies of 11 different interventions (n=1683), the most tested interventions were bosentan and sildenafil. From 25 nonpharmacological studies, the most tested intervention was for pulmonary rehabilitation/exercise training (PR) (22 studies, n=748). There was an improvement in 6-min walk distance immediately following PR (six studies; n=200, mean difference (MD) (95% CI) 39.9 m (18.2 to 61.5)), but not longer term (3 or 6 months, four studies; n=147, MD 5.3 m (−12.9 to 23.4). Multiple, varied outcome measures were used (e.g.37 studies assessing dyspnoea used 10 different scales with a lack of reporting of rate of deterioration in outcomes). Evidence gap mapping highlighted the most and least researched symptoms, as dyspnoea and cough, respectively.

This evidence synthesis highlights overwhelmingly that the most researched symptom is dyspnoea and the strongest evidence base is for short-term PR. The least researched symptom was cough. Research going forward must focus on prioritising and standardising meaningful outcomes and focussing interventions on neglected symptoms.
Adherence to disease-specific drug treatment among patients with pulmonary arterial hypertension or chronic thromboembolic pulmonary hypertension
Authors: Kjellström Barbro , Sandqvist Anna , Hjalmarsson Clara , Nisell Magnus , Näsman Per , Ivarsson Bodil
Published: October 2020

Background

Pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) require lifelong treatment. The aim of the present study was to investigate adherence to disease-specific treatment in patients with PAH or CTEPH.

Methods

The study comprised an adult population diagnosed with PAH (n=384) or CTEPH (n=187) alive in 2016–2017. The study utilised three registries: the Swedish PAH registry, the National Board of Health and Welfare, and Statistics Sweden. Withdrawals from pharmacies of disease-specific oral treatments were studied. Adherence was assessed as: 1) Number of days covered defined as the difference between the total number of daily dosages dispensed and the total number of days covered; and 2) Manual assessment by two persons that independently reviewed each patient's prescription fill history to detect anomalies or patterns of deteriorating or improving adherence over time.

Results

The mean age was 61±16 years, 61% were female and mean time since diagnosis was 4.6 years. Adherence was 62% using the Number of days covered method and 66% by the Manual assessment method. Drug-specific adherence varied from 91% for riociguat to 60% for sildenafil. Good adherence was associated with shorter time since diagnosis in patients with PAH and with lower number of concomitant other chronic treatments in patients with CTEPH. Age, sex, socioeconomic status or number of pulmonary hypertension (PH) treatments were not associated with adherence.

Conclusion

Adherence to oral disease-specific treatment was 60–66% and associated with time since diagnosis and number of concomitant chronic treatments. Sex, age or socioeconomic factors did not affect adherence.
Preclinical evaluation of the epithelial sodium channel inhibitor BI 1265162 for treatment of cystic fibrosis
Authors: Nickolaus Peter , Jung Birgit , Sabater Juan , Constant Samuel , Gupta Abhya
Published: October 2020

Background

Epithelial sodium channel (ENaC) is an important regulator of airway surface liquid volume; ENaC is hyperactivated in cystic fibrosis (CF). ENaC inhibition is a potential therapeutic target for CF. Here, we reportin vitroandin vivoresults for BI 1265162, an inhaled ENaC inhibitor currently in Phase II clinical development, administeredviathe Respimat® Soft Mist™ inhaler.

Methods

In vitroinhibition of sodium ion (Na+) transport by BI 1265162 was tested in mouse renal collecting duct cells (M1) and human bronchial epithelial cells (NCI-H441); inhibition of water transport was measured using M1 cells.In vivoinhibition of liquid absorption from rat airway epithelium and acceleration of mucociliary clearance (MCC) in sheep lungs were assessed. Fully differentiated normal and CF human epithelium was used to measure the effect of BI 1265162 with or without ivacaftor and lumacaftor on water transport and MCC.

Results

BI 1265162 dose-dependently inhibited Na+transport and decreased water resorption in cell line models. BI 1265162 reduced liquid absorption in rat lungs and increased MCC in sheep. No effects on renal function were seen in the animal models. BI 1265162 alone and in combination with CF transmembrane conductance regulator (CFTR) modulators decreased water transport and increased MCC in both normal and CF airway human epithelial models and also increased the effects of CFTR modulators in CF epithelium to reach the effect size seen in healthy epithelium with ivacaftor/lumacaftor alone.

Conclusion

These results demonstrate the potential of BI 1265162 as a mutation agnostic, ENaC-inhibitor-based therapy for CF.
Microarray analysis identifies defects in regenerative and immune response pathways in COPD airway basal cells
Authors: Pineau Fanny , Shumyatsky Gabriella , Owuor Nicole , Nalamala Nisha , Kotnala Sudhir , Bolla Sudhir , Marchetti Nathaniel , Kelsen Steven , Criner Gerard J. , Sajjan Uma S.
Published: October 2020

Background

Airway basal cells are specialised stem cells and regenerate airway epithelium. Airway basal cells isolated from patients with COPD regenerate airway epithelium with an abnormal phenotype. We performed gene expression analysis to gain insights into the defective regenerative programme in COPD basal cells.

Methods

We conducted microarray analysis and compared COPDversusnormal basal cells to identify differentially regulated genes (DEGs) and the enriched biological pathways. We determined the correlation of DEGs with cell polarisation and markers of ciliated and goblet cells.HOXB2was knocked down in 16HBE14o− cells and monitored for polarisation of cells.HOXB2expression in the lung sections was determined by immunofluorescence.

Results

Comparison of normal and COPD basal cell transcriptomic profiles highlighted downregulation of genes associated with tissue development, epithelial cell differentiation and antimicrobial humoral response. Expression of one of the tissue development genes,HOXB2showed strong correlation with transepithelial resistance and this gene was downregulated in COPD basal cells. Knockdown ofHOXB2, abrogated polarisation of epithelial cells in normal cells. Finally,HOXB2expression was substantially reduced in the bronchial epithelium of COPD patients.

Conclusions

Defect in gene signatures involved in tissue development and epithelial differentiation were implicated in COPD basal cells. One of the tissue developmental genes, HOXB2, is substantially reduced in bronchial epithelium of COPD patients. Since HOXB2 contributes to airway epithelial cell polarisation, we speculate that reduced expression of HOXB2 in COPD may contribute to abnormal airway epithelial regeneration in COPD.
Combined Transcriptome and Metabolome analysis of Pitaya fruit unveiled the mechanisms underlying Peel and pulp color formation
Authors: Zhou Zhaoxi , Gao Hongmao , Ming Jianhong , Ding Zheli , Lin Xing’e , Zhan Rulin
Published: October 2020

Background

Elucidating the candidate genes and key metabolites responsible for pulp and peel coloration is essential for breeding pitaya fruit with new and improved appeal and high nutritional value. Here, we used transcriptome (RNA-Seq) and metabolome analysis (UPLC-MS/MS) to identify structural and regulatory genes and key metabolites associated with peel and pulp colors in three pitaya fruit types belonging to two different Hylocereus species.

Result

Our combined transcriptome and metabolome analyses suggest that the main strategy for obtaining red color is to increase tyrosine content for downstream steps in the betalain pathway. The upregulation of CYP76ADs is proposed as the color-breaking step leading to red or colorless pulp under the regulation by WRKY44 transcription factor. Supported by the differential accumulation of anthocyanin metabolites in red pulped pitaya fruit, our results showed the regulation of anthocyanin biosynthesis pathway in addition to betalain biosynthesis. However, no color-breaking step for the development of anthocyanins in red pulp was observed and no biosynthesis of anthocyanins in white pulp was found. Together, we propose that red pitaya pulp color is under the strict regulation of CYP76ADs by WRKYs and the anthocyanin coexistence with betalains is unneglectable. We ruled out the possibility of yellow peel color formation due to anthocyanins because of no differential regulation of chalcone synthase genes between yellow and green and no detection of naringenin chalcone in the metabolome. Similarly, the no differential regulation of key genes in the carotenoid pathway controlling yellow pigments proposed that the carotenoid pathway is not involved in yellow peel color formation.

Conclusions

Together, our results propose several candidate genes and metabolites controlling a single horticultural attribute i.e. color formation for further functional characterization. This study presents useful genomic resources and information for breeding pitaya fruit with commercially attractive peel and pulp colors. These findings will greatly complement the existing knowledge on the biosynthesis of natural pigments for their applications in food and health industry.
A qualitative study of facilitators and barriers to participate in a needle exchange program for women who inject drugs
Authors: Värmå Falk Malin , Strömdahl Susanne , Ekström Anna Mia , Kåberg Martin , Karlsson Niklas , Dahlborn Helena , Hammarberg Anders
Published: October 2020

Background

Women who inject drugs (WWID) show higher levels of injecting risk behaviour compared to men, putting them at risk of contracting HIV and hepatitis C (HCV). Compared to men, WWID are also less present in harm reduction programs such as needle exchange programs (NEP). The aim of this study is to investigate reasons for, and barriers to, participation in NEP among WWID in Sweden, and to identify measures that could be taken to strengthen the program and increase participation among WWID.

Method

In-depth interviews (IDIs) were conducted with 20 WWID who had participated in the Stockholm NEP for at least six months and was over 18 years old. IDIs were audio recorded and transcribedet verbatim. Qualitative content analysis was used to identify themes.

Results

The need for sterile injection equipment was identified as the main driver to join and remain in the NEP program. Continuous participation in the NEP was further driven by easy access to a multitude of health-related services. The most valued service was the sexual and reproductive health services (SRHR), allowing participants to access contraceptives, cervical cancer screening and sexually transmitted infections testing (STI-testing). NEP staffs’ respectful treatment of participants further contributed to program participation. However, participants also expressed a number of concerns around NEP participation, which created barriers to joining. These included losing custody or visitation rights to children, male partner jealousy and violence, unwillingness to spend time in the waiting area and fear of receiving positive HIV/HCV test results. Practical barriers included limited opening hours and travel distance to the NEP. To strengthen the program, most participants requested additional SRHR services. Most participants also proposed some form of “women only” access to the NEP, to strengthen the feeling of the NEP as a safe space.

Conclusion

This study identified factors that may increase uptake of NEP among WWID. Additional SRHR services and “women only” access are recommended to be implemented and evaluated as part of NEP. These findings may inform and improve the current scale-up of NEPs in Sweden to ensure equal access to services.
Reported 1-year prevalence of occupational musculoskeletal disorders in Ontario chiropractors
Authors: Howarth Samuel J. , Abbas Anser , Hogg-Johnson Sheilah , Mior Silvano
Published: October 2020

Background

Chiropractors are a particular subset of health care professionals that reportedly suffer occupational musculoskeletal disorders (MSDs), yet they have received minimal attention to date regarding mitigating risks of occupational injury. Our study determined the prevalence of occupationally-related MSDs in the preceding year, their bodily distribution, severity, and practice-related changes in practicing chiropractors in the province of Ontario.

Methods

We conducted a cross-sectional survey of chiropractors who were members of the Ontario Chiropractic Association (OCA) from January to March 2019. A three-part online survey was developed to ask chiropractors about specific details of MSDs they experienced in the past year and any practice-related changes they made as a result. Responses from participants provided both quantitative and qualitative data. Prevalence estimates were derived for quantitative data. Qualitative data were stratified by themes that were further divided into categories and subcategories. Demographic variables of the respondents and OCA membership were compared to determine representativeness.

Results

From the 432 responses (11.8% response rate), 59.1% reported experiencing an occupationally-related MSD in the past year. Survey respondents were demographically representative of the OCA membership. MSDs were most commonly reported for the lower back (38.3%), wrists/hands (38.1%) and neck (37.4%). Positioning/performing manipulation was the most common occupational activity for MSD of the upper extremity (53.1%) and lower back (34.8%). Chiropractors largely reported their MSDs did not prevent them from doing their normal work (77.4%), despite the fact that 43.2% reported experiencing their MSDs for more than 30 days in the previous year. Common reported work modifications were grouped under themes of practice and physical changes. Practice changes included reducing patient volume, hiring personnel and scheduling. Physical changes included using different office equipment, selecting different techniques requiring lower force and altering their hand contacts or body position when treating patients.

Conclusions

One-year prevalence of occupational MSDs from this study are comparable to previously reported estimates in chiropractors. These data suggest that chiropractors continue with their regular workload despite their MSDs, thereby increasing their chances of presenteeism. Chiropractors changing technique or technique parameters due to their MSDs provides direction for future research to reduce exposure to occupational MSD risk factors.
Skin stretch suturing with Nice knots in the treatment of small- or medium-sized wounds
Authors: Xu Jianmin , Chang Rui , Zhang Wei , Zhang Chengcheng , Zhu Dezhi , Liu Fanxiao , Yang Yongliang
Published: October 2020

Background

To investigate the clinical efficacy and outcomes of skin stretch suturing with self-locking sliding Nice knots in the treatment of small- or medium-sized wounds.

Methods

From June 2015 to May 2018, 26 patients with small- or medium-sized wounds were included in the present study. Skin stretch suturing with self-locking slide Nice knots was performed to gradually close the soft-tissue defects in these patients. The time of wound closure and healing was recorded. The color and blood supply of the skin, cutaneous sensation, the stretch of skin, and the hair growth situation of the skin wound were observed and recorded.

Results

There were 17 males and 9 females with an average age of 30.65 years (range, 15–48 years). The areas of the soft-tissue defects were between 3.2 × 7.1 cm and 8.0 × 15.2 cm. All patients underwent stretch suturing with self-locking slide Nice knots to close the soft-tissue defects. All wounds were successfully closed and healed. The mean time of wound closure was 10.69 days (range, 5–20 days), and the mean time of wound healing was 16.85 days (range, 10–24 days). The cutaneous sensation of skin wound recovered normally, and the color of the skin wounds was the same as that of normal skin at the last follow-up. The hair growth situation of the skin wounds also returned to normal.

Conclusions

This study revealed that Nice knots yielded an accepted clinical result as a new method to close small- or medium-sized wounds that was simple and less minimally invasive, resulted in progressive tension, did not return to previous results, and partially replace flaps or free skin grafts.
Autophagy in spinal ligament fibroblasts: evidence and possible implications for ossification of the posterior longitudinal ligament
Authors: Yang Yuehua , Lin Zunwen , Chen Jiangwei , Ding Sheng , Mao Weiwei , Shi Sheng , Liang Biru
Published: October 2020

Background

The molecular mechanisms of ossification of the posterior longitudinal ligament (OPLL) remain to be elucidated. The aim of the present study was to investigate the autophagy of spinal ligament fibroblasts derived from patients with OPLL and to examine whether autophagy-associated gene expression was correlated with the expression of osteogenic differentiation genes.

Methods

Expression of autophagy-associated genes was detected in 37 samples from 21 OPLL patients and 16 non-OPLL patients. The correlation of autophagy-associated gene expression and the expression of osteogenic differentiation genes was analyzed by Pearson’s correlation. The expression of autophagy-associated genes of ligament fibroblasts was assessed by reverse transcription-quantitative polymerase chain reaction (RT-qPCR), western blotting, and immunofluorescence. The incidence of autophagy was assessed by flow cytometry. After knockdown using small interfering RNA targeting Beclin1, the expression of osteogenic differentiation genes were compared in spinal ligament fibroblasts.

Results

In clinical specimens, mRNA expression levels of microtubule-associated protein 1 light chain 3 and Beclin1 were higher in the OPLL group compared with the non-OPLL group. Pearson correlation analysis demonstrated that Beclin1 expression was positively correlated with expression of osteocalcin (OCN) (r = 0.8233, P < 0.001), alkaline phosphatase, biomineralization associated (ALP) (r = 0.7821, P < 0.001), and collagen type 1 (COL 1) (r = 0.6078, P = 0.001). Consistently, the upregulation of autophagy-associated genes in ligament fibroblasts from patients with OPLL were further confirmed by western blotting and immunofluorescence. The incidence of autophagy was also increased in ligament fibroblasts from patients with OPLL. Furthermore, knockdown of Beclin1 led to a decrease in the expression of OCN, ALP, and COL 1 by 63.2% (P < 0.01), 52% (P < 0.01), and 53.2% (P < 0.01) in ligament fibroblasts from patients with OPLL, respectively.

Conclusions

Beclin1-mediated autophagy was involved in the osteogenic differentiation of ligament fibroblasts and promoted the development of OPLL.
IPSE, an abundant egg-secreted protein of the carcinogenic helminth Schistosoma haematobium, promotes proliferation of bladder cancer cells and angiogenesis
Authors: Mbanefo Evaristus C. , Agbo Chinwike Terry , Zhao Yuanlong , Lamanna Olivia K. , Thai Kim H. , Karinshak Shannon E. , Khan Mohammad Afzal , Fu Chi-Ling , Odegaard Justin I. , Saltikova Irina V. , Smout Michael J. , Pennington Luke F. , Nicolls Mark R. , Jardetzky Theodore S. , Loukas Alex , Brindley Paul J. , Falcone Franco H. , Hsieh Michael H.
Published: October 2020

Background

Schistosoma haematobium, the helminth causing urogenital schistosomiasis, is a known bladder carcinogen. Despite the causal link between S. haematobium and bladder cancer, the underlying mechanisms are poorly understood. S. haematobium oviposition in the bladder is associated with angiogenesis and urothelial hyperplasia. These changes may be pre-carcinogenic events in the bladder. We hypothesized that the Interleukin-4-inducing principle of Schistosoma mansoni eggs (IPSE), an S. haematobium egg-secreted “infiltrin” protein that enters host cell nuclei to alter cellular activity, is sufficient to induce angiogenesis and urothelial hyperplasia. Methods: Mouse bladders injected with S. haematobium eggs were analyzed via microscopy for angiogenesis and urothelial hyperplasia. Endothelial and urothelial cell lines were incubated with recombinant IPSE protein or an IPSE mutant protein that lacks the native nuclear localization sequence (NLS-) and proliferation measured using CFSE staining and real-time monitoring of cell growth. IPSE’s effects on urothelial cell cycle status was assayed through propidium iodide staining. Endothelial and urothelial cell uptake of fluorophore-labeled IPSE was measured. Findings: Injection of S. haematobium eggs into the bladder triggers angiogenesis, enhances leakiness of bladder blood vessels, and drives urothelial hyperplasia. Wild type IPSE, but not NLS-, increases proliferation of endothelial and urothelial cells and skews urothelial cells towards S phase. Finally, IPSE is internalized by both endothelial and urothelial cells. Interpretation: IPSE drives endothelial and urothelial proliferation, which may depend on internalization of the molecule. The urothelial effects of IPSE depend upon its NLS. Thus, IPSE is a candidate pro-carcinogenic molecule of S. haematobium.

Schistosoma haematobium acts as a bladder carcinogen through unclear mechanisms. The S. haematobium homolog of IPSE, a secreted schistosome egg immunomodulatory molecule, enhances angiogenesis and urothelial proliferation, hallmarks of pre-carcinogenesis, suggesting IPSE is a key pro-oncogenic molecule of S. haematobium.
Biological and clinical impact of central nervous system hemangioblastomas in Chinese patients with von Hippel-Lindau disease: implications for treatment
Authors: Liu Zhen , Li Liang , Yi Zhiqiang , Duan Hongzhou , Lu Runchun , Li Chunwei , Li Lei , Gong Kan
Published: October 2020

Objective

Central nervous system (CNS) hemangioblastomas (HGBs) are the most frequent cause of mortality in patients with von Hippel-Lindau (VHL) genetic syndrome. However, there is a lack of large studies on the clinical features and optimal management of HGBs in Chinese patients.

Methods

VHL-related HGB cases treated surgically at our hospital from 2012 to 2019 were evaluated. Patients and family members meeting the clinical diagnostic criteria underwent genetic testing. Clinical, genetic and relevant imaging data were analyzed.

Results

Eighty-five VHL patients from 34 pedigrees in 16 Chinese provinces who underwent 121 operations for CNS HGBs were enrolled. Multiple operations were associated with a younger age at first operation (OR = 0.926, 95% CI = 0.871–0.985, P = 0.014, threshold: 27.5, sensitivity: 72.2%, specificity: 71.2%) and a longer postoperative period (OR = 1.096, 95% CI = 1.015–1.184, P = 0.019, threshold: 10.5, sensitivity: 66.7%, specificity: 76.3%). The age at first operation was younger in children than in their parents (23 pairs, P < 0.001). The age at first operation was younger in siblings born later than in those born earlier (10 pairs, P = 0.01). Most untreated tumors (98.2%) remained relatively stable during follow-up (range, 0.5–7; median, 2). However, new tumors continued to emerge (0.14 tumor/year).

Conclusion

VHL-associated CNS HGB is a long-term chronic disease with repeated attacks, likely with genetic anticipation in Chinese pedigrees. When the age at first operation is under 27.5 years, or the postoperative period is longer than 10.5 years, the risk of multiple operations is increased. While most unresected HGBs remain stable after surgery, new tumors may still slowly emerge; hence, scheduled follow-ups are necessary.
Pharmaceuticals and personal care products in water and wastewater: a review of treatment processes and use of photocatalyst immobilized on functionalized carbon in AOP degradation
Authors: Oluwole Adewumi Olufemi , Omotola Elizabeth Oyinkansola , Olatunji Olatunde Stephen
Published: October 2020

The presence of emerging contaminants such as pharmaceutical and personal care products in many aqueous matrices have been reported. One of such matrix is streams of wastewater, including wastewater treatment plants inflows and outflows and wastewater flow by-passing wastewater treatment plants. Their persistence arises from their resistant to breakdown, hence they may remain in the environment over long time, with a potential to cause adverse effects including endocrine disruption, gene toxicity, the imposition of sex organs, antibiotic resistance and many others in some aquatic organisms exposed to arrays of residues of pharmaceutical and personal care products. Among the treatment techniques, advanced oxidation processes have been reported to be a better technique through which these PPCPs can be degraded in the WWTPs. Heterogeneous photocatalysis using various photocatalyst immobilized on solid support such as activated carbon, graphene and carbon nanotubes in AOPs have been shown to be a viable and efficient method of PPCPs degradation. This is because, the performance of most WWTPs is limited since they were not designed to degrade toxic and recalcitrant PPCPs. This review highlight the occurrence, concentration of PPCPs in wastewater and the removal efficiency of heterogeneous photocatalysis of TiO2 immobilized on solid supports.
Detecting antibodies to Leishmania infantum in horses from areas with different epizooticity levels of canine leishmaniosis and a retrospective revision of Italian data
Authors: Gazzonis Alessia Libera , Bertero Filippo , Moretta Iolanda , Morganti Giulia , Mortarino Michele , Villa Luca , Zanzani Sergio Aurelio , Morandi Benedetto , Rinnovati Riccardo , Vitale Fabrizio , Manfredi Maria Teresa , Cardoso Luis , Veronesi Fabrizia
Published: October 2020

Background

Leishmania infantumis a vector-borne pathogen endemic in countries in the Mediterranean basin, including Italy. Dogs act as the primary reservoir for this parasite, but other animal species may also be infected. Low-to-moderate seroprevalence levels of infection have been reported in apparent healthy equine populations in southern Europe, reinforcing the importance of exploring those species, including horses, that act as a food source for vectors and may thus participate in the epizoological scenario of canine leishmaniosis (CanL) and zoonotic visceral leishmaniosis (ZVL). Since little is known regarding the exposure toL. infantumin horses in Italy, we assessed the seroprevalence in healthy equine populations from different CanL endemic areas.

Methods

The survey was conducted on 660 apparently healthy horses distributed throughout central and northern regions of Italy between 2016 and 2019. Blood samples were collected and the presence of anti-Leishmaniaantibodies (IgG) was investigated by the immunofluorescence antibody test. Information on the location and altitude of the stables, along with the horses’ breed, age, sex, and reproductive status was obtained by filling in a questionnaire. This was then used for statistical analysis by generalized linear models to explore risk factors associated with seroreactivity toL. infantum.

Results

An average seroprevalence of 13.9% was detected forL. infantumin the equine populations investigated, with statistically significant associations between seroprevalence, geographical variables (northernvscentral Italy, origin and altitude) and individual factors (i.e. age and breed morphotype).

Conclusions

Our results highlight that horses are frequently exposed toL. infantum. Further prevalence surveys in horses, also using direct methods (e.g. PCR), are warranted to clarify the role of these hosts in the epidemiology ofLeishmaniain Italy.
Real-time PCR on skin biopsies for super-spreaders’ detection in bovine besnoitiosis
Authors: Grisez Christelle , Bottari Leslie , Prévot Françoise , Alzieu Jean-Pierre , Liénard Emmanuel , Corbière Fabien , Rameil Marie , Desclaux Xavier , Lacz Christophe , Boulon Christian , Petermann Julie , Le Mével Jeanne , Vilardell Carine , Jacquiet Philippe
Published: October 2020

Background

Bovine besnoitiosis, an emerging disease in Europe that can be transmitted by vectors, is caused by the apicomplexan Besnoitia besnoiti. Bovine besnoitiosis is difficult to control due to the complexity of its diagnosis in the acute stage of the disease, poor treatment success and chronically asymptomatic cattle acting as parasite reservoirs. When serological prevalence is low, detection and specific culling of seropositive cattle is feasible; however, economic considerations preclude this approach when serological prevalence is high. The aims of this study were to evaluate the accuracy of detection of super-spreaders in highly infected herds and to test their selective elimination as a new control strategy for bovine besnoitiosis.

Methods

Previous real-time PCR analyses performed on skin tissues from 160 asymptomatic animals sampled at slaughterhouses showed that the tail base was the best location to evaluate the dermal parasite DNA load. All seropositive animals (n = 518) from eight dairy or beef cattle farms facing a high serological prevalence of besnoitiosis were sampled at the tail base and their skin sample analysed by real-time PCR. A recommendation of rapid and selective culling of super-spreaders was formulated and provided to the cattle breeders. Subsequent serological monitoring of naïve animals was used to evaluate the interest of this control strategy over time.

Results

Among the 518 seropositive animals, a low proportion of individuals (14.5%) showed Cq values below 36, 17.8% had doubtful results (36 < Cq ≤ 40) and 67.8% had negative PCR results. These proportions were grossly similar on the eight farms, regardless of their production type (beef or dairy cattle), size, geographical location or history of besnoitiosis. Within two weeks of the biopsy, the rapid culling of super-spreaders was implemented on only three farms. The numbers of newly infected animals were lower on these farms compared to those where super-spreaders were maintained in the herd.

Conclusions

Real-time PCR analyses performed on skin biopsies of seropositive cattle showed huge individual variabilities in parasite DNA load. The rapid culling of individuals considered as super-spreaders seems to be a new and encouraging strategy for bovine besnoitiosis control.
Wnt-regulated lncRNA discovery enhanced by in vivo identification and CRISPRi functional validation
Authors: Liu Shiyang , Harmston Nathan , Glaser Trudy Lee , Wong Yunka , Zhong Zheng , Madan Babita , Virshup David M. , Petretto Enrico
Published: October 2020

Background

Wnt signaling is an evolutionarily conserved developmental pathway that is frequently hyperactivated in cancer. While multiple protein-coding genes regulated by Wnt signaling are known, the functional lncRNAs regulated by Wnt signaling have not been systematically characterized.

Methods

We comprehensively mapped Wnt-regulated lncRNAs from an orthotopic Wnt-addicted pancreatic cancer model and examined the response of lncRNAs to Wnt inhibition between in vivo and in vitro cancer models. We further annotated and characterized these Wnt-regulated lncRNAs using existing genomic classifications (using data from FANTOM5) in the context of Wnt signaling and inferred their role in cancer pathogenesis (using GWAS and expression data from the TCGA). To functionally validate Wnt-regulated lncRNAs, we performed CRISPRi screens to assess their role in cancer cell proliferation both in vivo and in vitro.

Results

We identified 3633 lncRNAs, of which 1503 were regulated by Wnt signaling in an orthotopic Wnt-addicted pancreatic cancer model. These lncRNAs were much more sensitive to changes in Wnt signaling in xenografts than in cultured cells. Our analysis suggested that Wnt signaling inhibition could influence the co-expression relationship of Wnt-regulated lncRNAs and their eQTL-linked protein-coding genes. Wnt-regulated lncRNAs were also implicated in specific gene networks involved in distinct biological processes that contribute to the pathogenesis of cancers. Consistent with previous genome-wide lncRNA CRISPRi screens, around 1% (13/1503) of the Wnt-regulated lncRNAs were found to modify cancer cell growth in vitro. This included CCAT1 and LINC00263, previously reported to regulate cancer growth. Using an in vivo CRISPRi screen, we doubled the discovery rate, identifying twice as many Wnt-regulated lncRNAs (25/1503) that had a functional effect on cancer cell growth.

Conclusions

Our study demonstrates the value of studying lncRNA functions in vivo, provides a valuable resource of lncRNAs regulated by Wnt signaling, and establishes a framework for systematic discovery of functional lncRNAs.
The presence of membrane bound CD99 ligands on leukocyte surface
Authors: Takheaw Nuchjira , Pata Supansa , Laopajon Witida , Roytrakul Sittiruk , Kasinrerk Watchara
Published: October 2020

Objective

CD99, a leukocyte surface molecule, reportedly plays an important role in several cellular processes. However, the role of CD99 in T cell regulation remains unclear, as the CD99 ligand associated with T-cell regulation has not yet been identified. Our previous study showed that recombinant CD99 bound to CD99 ligands was expressed on monocytes, NK cells and dendritic cells. This interaction regulates the expression of IL-6 and TNF-α in CD3 + T cells following T cell activation. In the present study, we confirmed the presence of CD99 ligands in immune cells.

Results

A recombinant CD99-human IgG fusion protein, CD99HIgG, was produced and used to search for CD99 ligand expression in various hematopoietic cell lines. Among several cell lines, THP-1 monocytic cell line showed strong positive reaction for CD99HIgG, and CD99 and CD99 ligand complexes were pulled-down using a DTSSP cross-linker. The study demonstrated the presence of the membrane bound CD99 ligand, and CD99 ligand candidates were identified via LC–MS/MS. These results may be useful to further identify the CD99 ligands, and to fully comprehend the role of CD99 in immunoregulation.
Genome-wide methylation analysis in Silver–Russell syndrome, Temple syndrome, and Prader–Willi syndrome
Authors: Hara-Isono Kaori , Matsubara Keiko , Fuke Tomoko , Yamazawa Kazuki , Satou Kazuhito , Murakami Nobuyuki , Saitoh Shinji , Nakabayashi Kazuhiko , Hata Kenichiro , Ogata Tsutomu , Fukami Maki , Kagami Masayo
Published: October 2020

Background

Imprinting disorders (IDs) show overlapping phenotypes, particularly in Silver–Russell syndrome (SRS), Temple syndrome (TS14), and Prader–Willi syndrome (PWS). These three IDs include fetal and postnatal growth failure, feeding difficulty, and muscular hypotonia as major clinical features. However, the mechanism that causes overlapping phenotypes has not been clarified. To investigate the presence or absence of methylation signatures associated with overlapping phenotypes, we performed genome-wide methylation analysis (GWMA).

Results

GWMA was carried out on 36 patients with three IDs (SRS [n = 16], TS14 [n = 7], PWS [n = 13]) and 11 child controls using HumanMethylation450 BeadChip including 475,000 CpG sites across the human genome. To reveal an aberrantly methylated region shared by SRS, TS14, and PWS groups, we compared genome-wide methylation data of the three groups with those of control subjects. All the identified regions were known as SRS-, TS14-, and PWS-related imprinting-associated differentially methylated regions (iDMRs), and there was no hypermethylated or hypomethylated region shared by different ID groups. To examine the methylation pattern shared by SRS, TS14, and PWS groups, we performed clustering analysis based on GWMA data. The result focusing on 620 probes at the 62 known iDMRs (except for SRS-, TS14-, and PWS-related iDMRs) classified patients into two categories: (1) category A, grossly normal methylation patterns mainly consisting of SRS group patients; and (2) category B, broad and mild hypermethylation patterns mainly consisting of TS14 and PWS group patients. However, we found no obvious relationship between these methylation patterns and phenotypes of patients.

Conclusions

GWMA in three IDs found no methylation signatures shared by SRS, TS14, and PWS groups. Although clustering analysis showed similar mild hypermethylation patterns in TS14 and PWS groups, further study is needed to clarify the effect of methylation patterns on the overlapping phenotypes.
Novel presentation of intraocular metastases in a patient with penile squamous cell carcinoma: a case report
Authors: Li Shanshan , Zhao Haifeng , Qiu Cui , Wu Changfan
Published: October 2020

Background

The choroid is the most common site for intraocular tumor metastasis because of its abundant vascular supply. However, choroidal metastasis in penile cancer is highly unusual. Here, we report the first case of diagnosis of choroidal metastasis at presentation in a patient with penile squamous cell carcinoma.

Case presentation

A 43-year-old Asian man with a 3-year history of penile cancer presented with metastasis in the right intraocular sites. Magnetic resonance imaging showed hyperintensity in the T1-weighted images and hypointensity in the T2-weighted images of the right eye. After enucleation of his right eye, histopathological analysis led to a diagnosis of metastatic, moderately differentiated penile squamous cell carcinoma.

Conclusions

Penile cancer typically occurs as penile squamous cell carcinoma, and its most common metastatic sites are the inguinal lymph nodes. Hemorrhagic transfer of tumor cells is extremely rare, especially to intraocular sites. Intraocular metastatic tumors have a unique presentation on imaging, as observed on magnetic resonance imaging and histopathological analysis. This novel finding of intraocular metastasis in penile squamous cell carcinoma is of great significance to optic surgeons and oncologists as it has new implications in the diagnosis of and timely intervention for penile cancer metastasis.
Interactive effects of asparagine and aspartate homeostasis with sex and age for the risk of type 2 diabetes risk
Authors: Luo Hui-Huan , Feng Xiao-Fei , Yang Xi-Lin , Hou Rui-Qin , Fang Zhong-Ze
Published: October 2020

Background

Asparagine and aspartate homeostasis are linked with type 2 diabetes (T2D). This study aimed to explore whether asparagine and aspartate metabolism interacted with sex and age to increase the risk of T2D.

Methods

From 27 May 2015 to 3 August 2016, we consecutively retrieved 1032 T2D patients and 1522 subjects without T2D from a tertiary care hospital in Liaoning, China. Restricted cubic spline nested in the logistic regression was used to draw odds ratio curves of plasma asparagine to aspartate ratio for T2D by sex and age. Cut-off point was selected where curves went apart, indicating possible interaction. Addictive interactions of asparagine to aspartate ratio with sex or age and secondary interaction with copresence of unfavorable sex and age were further estimated using relative excess risk due to interaction (RERI), attributable proportion due to interaction (AP), and synergy index (S).

Results

Ratio of asparagine to aspartate > 1.5 was associated with elevated risk of T2D (OR 7.99, 95%CI 5.50 to 11.6), which was enhanced by female gender to 13.6, (95%CI 8.10–22.9) and by > 50 years of age to 28.7 (14.6–56.3), with significant additive interactions. There was a significant secondary-interaction of copresence of female sex and > 50 years of age with high asparagine to aspartate ratio for increased T2D risk with the OR being further increased to 34.4 (20.5–57.5).

Conclusions

High asparagine to aspartate ratio was associated with markedly increased risk of T2D, which was further amplified by either female gender or > 50 years of age, and especially both.