bluuebunny/crossref_metadata_2025_split huggingface dataset:
NS398 as a potential drug for autosomal‐dominant polycystic kidney disease: Analysis using bioinformatics, and zebrafish and mouse models
Authors: Chen Sixiu , Huang Linxi , Zhou Shoulian , Zhang Qingzhou , Ruan Mengna , Fu Lili , Yang Bo , Xu Dechao , Mei Changlin , Mao Zhiguo 
Published: September 2021

AbstractAutosomal‐dominant polycystic kidney disease (ADPKD) is characterized by uncontrolled renal cyst formation, and few treatment options are available. There are many parallels between ADPKD and clear‐cell renal cell carcinoma (ccRCC); however, few studies have addressed the mechanisms linking them. In this study, we aimed to investigate their convergences and divergences based on bioinformatics and explore the potential of compounds commonly used in cancer research to be repurposed for ADPKD. We analysed gene expression datasets of ADPKD and ccRCC to identify the common and disease‐specific differentially expressed genes (DEGs). We then mapped them to the Connectivity Map database to identify small molecular compounds with therapeutic potential. A total of 117 significant DEGs were identified, and enrichment analyses results revealed that they are mainly enriched in arachidonic acid metabolism, p53 signalling pathway and metabolic pathways. In addition, 127 ccRCC‐specific up‐regulated genes were identified as related to the survival of patients with cancer. We focused on the compound NS398 as it targeted DEGs and found that it inhibited the proliferation of Pkd1−/− and 786‐0 cells. Furthermore, its administration curbed cystogenesis in Pkd2 zebrafish and early‐onset Pkd1‐deficient mouse models. In conclusion, NS398 is a potential therapeutic agent for ADPKD.
Circular RNA WHSC1 exerts oncogenic properties by regulating miR‐7/TAB2 in lung cancer
Authors: Guan Sisi , Li Li , Chen Wen‐Shu , Jiang Wen‐Yang , Ding Yun , Zhao Li‐Lan , Shi Yi‐Fan , Wang Jun , Gui Qi , Xu Cheng‐Cheng , Cheng Yang , Zhang Wenjuan 
Published: September 2021

AbstractCircular RNA is a newly discovered member of non‐coding RNA (ncRNA) and regulates the target gene by acting as a micro‐RNA sponge. It plays vital roles in various diseases. However, the functions of circular RNA in non‐small cell lung cancer (NSCLC) remain still unclear. Our data showed that circ‐WHSC1 was highly expressed in NSCLC cells and tissues. Both in vitro and in vivo experiments showed that circ‐WHSC1 promoted NSCLC proliferation. circ‐WHSC1 also promoted the migration and invasion of lung cancer cells. Through bioinformatic analysis and functional experiments, we showed that circ‐WHSC1 could act as a sponge for micro‐RNA‐7 (miR‐7) and regulate the expression of TAB2 (TGF‐beta activated kinase one binding protein two). Inhibition of the circ‐WHSC1/miR‐7/TAB2 pathway could effectively attenuate lung cancer progression. In summary, this study confirmed the existence and oncogenic function of circ‐WHSC1 in NSCLC. The research suggests that the circ‐WHSC1/miR‐7/TAB2 axis might be a potential target for NSCLC therapy.
Dipeptidyl peptidase‐4 inhibitor and insulin combination treatment in type 2 diabetes and chronic kidney disease: A meta‐analysis
Authors: Zhou Xianling , Shi Heng , Zhu Shiping , Wang Haixia , Sun Shengyun 
Published: September 2021

ABSTRACTAims/IntroductionThe union of dipeptidyl peptidase‐4 inhibitors and insulin in patients with type 2 diabetes and chronic kidney disease provides satisfactory glucose management without increasing adverse events (AEs). This research appraised the therapeutic effect and safety of combination therapy in patients with type 2 diabetes and chronic kidney disease.Materials and MethodsWe carried out a meta‐analysis of randomized controlled trials to analyze AEs, hypoglycemia, serious AEs, severe hypoglycemia, estimated glomerular filtration rate, fasting plasma glucose, glycated hemoglobin, insulin dose, low‐density lipoprotein cholesterol, uric acid and weight between combination treatment groups and control groups by searching the Cochrane Library, Excerpta Medica Database (Embase), PubMed and Web of Science databanks until October 2020.ResultsFive studies (6 trials, 1,278 participants) met the inclusion criteria. The evidence quality ranged from moderate to high. Glycated hemoglobin (standardized mean difference −0.29, 95% confidence interval −0.44 to −0.14) and insulin dose (standardized mean difference −0.16, 95% confidence interval −0.29 to −0.02) were obviously smaller in the combination cure patients than in the control patients. Compared with the control groups, combination treatment did not increase AEs, hypoglycemia, serious AEs or severe hypoglycemia.ConclusionsThis study showed the effectiveness and safety of dipeptidyl peptidase‐4 inhibitors bonded with insulin in patients with type 2 diabetes and chronic kidney disease, but the protective actions of this cure on kidney and cardiovascular outcomes, as well as the functions of other dipeptidyl peptidase‐4 inhibitors, need to be affirmed by more good‐quality randomized controlled trials.
Epistatic interactions between sex chromosomes and autosomes can affect the stability of sex determination systems
Authors: Schenkel Martijn A. , Beukeboom Leo W. , Pen Ido 
Published: September 2021

AbstractSex determination (SD) is an essential and ancient developmental process, but the genetic systems that regulate this process are surprisingly variable. Why SD mechanisms vary so much is a longstanding question in evolutionary biology. SD genes are generally located on sex chromosomes which also carry genes that interact epistatically with autosomes to affect fitness. How this affects the evolutionary stability of SD mechanisms is still unknown. Here, we explore how epistatic interactions between a sexually antagonistic (SA) non‐SD gene, located on either an ancestral or novel sex chromosome, and an autosomal gene affect the conditions under which an evolutionary transition to a new SD system occurs. We find that when the SD gene is linked to an ancestral sex‐chromosomal gene which engages in epistatic interactions, epistasis enhances the stability of the sex chromosomes so that they are retained under conditions where transitions would otherwise occur. This occurs both when weaker fitness effects are associated with the ancestral sex chromosome pair or stronger fitness effects associated with a newly evolved SD gene. However, the probability that novel SD genes spread is unaffected if they arise near genes involved in epistasis. This discrepancy occurs because, on autosomes, SA allele frequencies are typically lower than on sex chromosomes. In our model, increased frequencies of these alleles contribute to a higher frequency of epistasis which may therefore more readily occur on sex chromosomes. Because sex chromosome–autosome interactions are abundant and can take several forms, they may play a large role in maintaining sex chromosomes.
Beyond Hermetia illucens: An investigation of the garden soldier fly Exaireta spinigera as a potential bioconverter of food waste
Authors: Mackillop Stephanie , Keitel Claudia , Latty Tanya 
Published: September 2021

AbstractUsing insects to convert food waste into useable products, such as livestock feed, is an elegant solution to the twin crises of waste disposal and food production. To date, the black soldier fly (Hermetia illucens) has garnered intense research interest as an excellent bioconverter that consumes wastes and converts them into high protein larval biomass that can be fed to livestock or used to make biodiesel. However, other members of the soldier fly family (Stratiomyidae) have received far less attention despite similar life‐history traits. Here, we examine the seasonality and performance (protein content and protein conversion efficiency) of larval Australian garden soldier flies, Exaireta spinigera. We first examined the state of knowledge about E. spinigera's biology and life history via a literature search. Next, we used a global biodiversity database to infer the seasonality of E. spinigera in Australia. Finally, we conducted outdoor feeding experiments to investigate protein content and protein conversion efficiency of larvae fed wastes ranging from 100% fruit and vegetable waste (low protein) to 100% poultry feed (higher protein). E. spinigera appears to be a autumn/spring active species, with reported sightings peaking during cooler months of the year. E. spinigera larvae also dominated outdoor bucket traps during the winter, when H. illucens was otherwise inactive. E. spinigera larvae had decreased protein content and decreased protein conversion efficiency when fed foods that contained a high proportion of low‐protein food waste. However, even in the 100% food waste treatment, the protein content of E. spinigera was relatively high at 38.6% crude protein. We suggest that E. spinigera is an excellent candidate for further research as it can convert low‐quality food waste into high protein larvae at colder temperatures than H. illucens. Our results highlight the benefits of investigating a wider range of dipteran species for their bioconversion abilities.
The Critical Role of Midwives in Safe Self‐Managed Abortion
Authors: Eagen‐Torkko Meghan , Yanow Susan 
Published: September 2021

AbstractAs access to legal abortion in the United States becomes more complex, there is increasing interest in self‐managed abortion. Choosing to seek abortion care outside the clinical setting can also help people marginalized or harmed by existing health care systems to access needed care in a way that feels safe and empowering. However, patients and midwives alike often have a lack of information about expected outcomes and potential complications that may arise, as well as how to manage these in a health care system that may make appropriate follow‐up difficult to access if needed. This article discusses patient education as a harm‐reduction approach, and reviews ways that midwives may strategically and ethically participate in this patient education need. As trusted health care providers who are expert in pregnancy and reproductive health, midwives are ideally positioned to meet patient knowledge needs around self‐managed abortion.
A feature‐based statistical shape model for geometric analysis of the human talus and development of universal talar prostheses
Authors: Vafaeian Behzad , Riahi Hossein Tajmir , Amoushahi Hossein , Jomha Nadr M. , Adeeb Samer 
Published: September 2021

AbstractStatistical data pertaining to anatomic variations of the human talus contain valuable information for advances in biological anthropology, diagnosis of the talar pathologies, and designing talar prostheses. A statistical shape model (SSM) can be a powerful data analysis tool for the anatomic variations of the talus. The main concern in constructing an SSM for the talus is establishing the true geometric correspondence between the talar geometries. The true correspondence complies with biological and/or mathematical homologies on the talar surfaces. In this study, we proposed a semi‐automatic approach to establish a dense correspondence between talar surfaces discretized by triangular meshes. Through our approach, homologous salient surface features in the form of crest lines were detected on 49 talar surfaces. Then, the point‐wise correspondence information of the crest lines was recruited to create posterior Gaussian process morphable models that non‐rigidly registered the talar meshes and consequently established inter‐mesh dense correspondence. The resultant correspondence perceptually represented the true correspondence as per our visual assessments. Having established the correspondence, we computed the mean shape using full generalized Procrustes analysis and constructed an SSM by means of principal component analysis. Anatomical variations and the mean shape of the talus were predicted by the SSM. As a clinically related application, we considered the mean shape and investigated the feasibility of designing universal talar prostheses. Our results suggest that the mean shape of (the shapes of) tali can be used as a scalable shape template for designing universal talar prostheses.
Melatonin enhances cisplatin‐induced cell death through inhibition of DERL1 in mesenchymal‐like CD44high OSCC cells
Authors: Shigeishi Hideo , Yokoyama Sho , Murodumi Hiroshi , Sakuma Miyuki , Fukada Shohei , Okuda Satoshi , Yamakado Nao , Ono Shigehiro , Takechi Masaaki , Ohta Kouji 
Published: September 2021

AbstractBackgroundMelatonin is a hormone that is primarily produced in the pineal gland and is involved in wide range of biological functions. However, the impact of melatonin on chemotherapy‐induced cell death remains to be elucidated in oral squamous cell carcinoma (OSCC) cells. The objective of this study was to clarify the role of melatonin in cisplatin‐induced cytotoxicity in CD44high OSCC cells.MethodsCD44high OSCC cells were cultured on fibronectin‐coated hydrogel. A lactate dehydrogenase cytotoxicity assay was performed to evaluate cisplatin‐induced cell death. The effect of melatonin on cisplatin‐induced cell death and Derlin‐1 (DERL1) endoplasmic reticulum membrane protein expression was investigated.ResultsCD44high OSCC cells exhibited mesenchymal‐like features when cultured on fibronectin‐coated hydrogel. Mesenchymal‐like CD44high OSCC cells demonstrated strong resistance to cisplatin‐induced cell death compared with epithelial‐like CD44high OSCC cells. DERL1 mRNA and DERL1 protein expression levels were significantly higher in mesenchymal‐like CD44high cells compared with epithelial‐like CD44high cells. Cisplatin‐induced cell death was significantly enhanced after DERL1 siRNA knockdown, suggesting that DERL1 is involved in resistance to cisplatin‐induced cell death. Melatonin significantly inhibited DERL1 expression and enhanced cisplatin‐induced cell death in mesenchymal‐like CD44high cells. miR‐181c‐5p expression was significantly upregulated in the presence of melatonin. Furthermore, melatonin‐inhibited DERL1 expression was significantly recovered by miR‐181c‐5p inhibitor. In addition, melatoninenhanced cisplatin‐induced cell death was attenuated by miR‐181c‐5p inhibitor. These results suggest that melatonin‐induced miR‐181c‐5p enhances cisplatin‐induced cell death through inhibition of DERL1 in mesenchymal‐like CD44high cells.ConclusionsMelatonin plays a vital role in promoting cisplatin‐induced cytotoxicity in mesenchymal‐like CD44high OSCC cells.
What Promotes Transfer of Staff Training Related to Challenging Behavior Displayed by Adults With Intellectual Disabilities?
Authors: Martin Aisling , Tyrrell Sophie , Honey Emma , Rodgers Jacqui , Ingham Barry 
Published: September 2021

AbstractEvidence is limited on the positive impact of staff training in challenging behavior of service users with ID; and the link between staff training and service user outcomes remains unclear. This review identified studies that investigate challenging behavior training for staff working with adults with ID within residential care settings to explore factors promoting transfer of training into practice. A mixed‐method review was adopted, and a systematic search identified 19 papers meeting the criteria for inclusion. The implicit themes involved in the transfer of training into practice were extracted from the literature and discussed in relation to: setting conditions; cognitive and emotional aspects; and organizational systems. As a first step toward moving forward with research in this relatively neglected area, key constructs were identified and a preliminary model of the transfer process proposed. Limitations of the review model were considered, and recommendations for future research discussed.
Shuffling between Cladocopium and Durusdinium extensively modifies the physiology of each symbiont without stressing the coral host
Authors: Abbott Evelyn , Dixon Groves , Matz Mikhail 
Published: September 2021

AbstractAs sea surface temperatures increase, many coral species that used to harbour symbionts of the genus Cladocopium have become colonized with the thermally tolerant genus, Durusdinium. Here, we asked how gene expression in the symbionts of one genus changes depending on the abundance of another symbiont genus within the same coral host, and what effect this interaction has on the host. Symbiont gene expression was overwhelmingly driven by whether the genus was the minority or the majority within the host, which affected 79% (Durusdinium) and 96% (Cladocopium) of all genes. Particularly strong effects in both genera were observed for photosynthesis components (upregulated in the minority state) and proteins putatively associated with cell motility (upregulated in the majority state). Importantly, there was no distinct gene expression signature associated with the mixed symbiosis state when both genera were represented in comparable proportions within the host, which could lead to more intense competition. The mixed symbiosis was also not associated with elevated host stress: in fact, after heat treatment, stress signatures were the lowest in mixed‐symbiosis corals compared to both Cladocopium‐ and Durusdinium‐dominated corals. In conclusion, during shuffling between Cladocopium and Durusdinium both symbiont genera go through extensive and largely reciprocal physiological transitions, but there is no evidence of intensifying antagonistic interactions that are detrimental to the host. Unless the mixed‐symbiosis corals in this study are not representative of the typical transition between Cladocopium and Durusdinium, the process of shuffling from one symbiont genus to another appears to be cost‐free for the coral host, and even appears to be associated with lower stress susceptibility. This raises optimism for the future corals, which will probably have to rely on symbiont shuffling more and more to withstand environmental challenges.
Strategic Depth Through Enclaves: Iran, Syria, and Hezbollah
Authors: Mason Robert 
Published: September 2021

AbstractThis article interrogates and extrapolates Iran's bilateral relationship with the Assad government and Hezbollah in the context of the so‐called Resistance Axis, including the Islamic Revolutionary Guard Corps's objective of enhancing its strategic depth in Syria after the onset of conflict in 2011. Utilizing a complex realist conceptual framework, and with reference to constructivism, it argues that Iran's strategic depth in Syria could have been addressed as part of a dialogue on regional security after the Joint Comprehensive Plan of Action (the Iran nuclear deal) in 2015. However, it has been reinforced by the legacy of past warfare, the Trump administration's “maximum pressure” policy, and a regional trend toward the creation of enclaves in conflict zones. This trend, including Turkey's forward‐defense strategy in Syria, could create further instabilities as state and nonstate actors vie for security and political influence and as long as enclaves remain untethered to broader interests and alliances. The case of Pakistan highlights enduring themes such as how shifting US diplomatic and military strategy and dependency could impact strategic depth.
Characterisation of the nail microbiome in psoriatic and nonpsoriatic patients with onychomycosis
Authors: Wang Shiqi , Song Yinggai , Wan Zhe , Chen Wei , Wang Ruojun , Li Ruoyu 
Published: September 2021

AbstractBackgroundOnychomycosis (OM) is the most common infectious nail disease, and it occurs frequently in patients with psoriasis. Microbial community shifts have been suggested to play a role in psoriasis and fungal infection occurrence.ObjectivesTo investigate and compare nail microbial community compositions in psoriatic and nonpsoriatic patients with OM.MethodsToenail samples were collected from nonpsoriatic patients with OM, psoriatic patients with nail psoriasis (NP) and OM, patients with only NP and healthy controls. Bacterial and fungal community compositions were analysed by amplicon sequencing of the V3‐V4 regions of the 16S rDNA gene and the ITS1 region, respectively.ResultsPsoriatic OM patients had higher bacterial and fungal alpha diversities. Taxonomic analysis revealed a significantly lower relative abundance of Trichophyton rubrum (32.88% vs 82.18%, p < .001) and an increased trend of the abundance of Candida in psoriatic patients with OM than in nonpsoriatic patients. Nonpsoriatic patients with OM had a higher abundance of Staphylococcus than healthy controls (59.66% vs 45.76%, p < .05). Trichophyton, Alternaria and Malassezia could accurately differentiate psoriatic and nonpsoriatic patients with OM, with an area under the curve (AUC) of 0.86. The severity of OM was positively correlated with the relative abundance of Trichophyton rubrum. Further, Trichophyton was positively correlated with Staphylococcus and negatively correlated with Corynebacterium, Anaerococcus, Malassezia and Alternaria.ConclusionsThe nail microbiome in psoriatic patients with OM has distinct bacterial and fungal signatures, suggesting that different dysbiosis is associated with the pathogenesis of OM in psoriatic and nonpsoriatic patients.
Do rectus muscle parameters vary between emmetropes and myopes?
Authors: Vasudeva Ashish , Dhakal Rohit , Vupparaboina Kiran Kumar , Verkicharla Pavan K 
Published: September 2021

AbstractPurposeThis study investigated the thickness, area, and insertion site of the medial (MR) and lateral (LR) rectus muscles in individuals with emmetropia and different degrees of myopia.MethodsSwept‐source optical coherence tomography images of the MR and LR muscles in 80 participants including emmetropes (spherical equivalent refractive error [SER] ±0.50 D, N = 14) and myopes (≤ −0.75 D, N = 66), were analysed. Custom‐designed, semi‐automated software was used to measure parameters such as insertion distance from limbus, muscle thickness at every 1 mm interval to 3 mm periphery and muscle area from insertion site to 3 mm.ResultsThe median (Q1, Q3) SER error and axial length were −6.00 D (−13.25, −2.12) and 25.78 mm (23.78, 28.61), respectively. The MR was significantly thinner (mean ± SE: 137.7 ± 8.9 vs. 159.7 ± 8.9 µm, p < 0.01) and occupied less area than the LR (0.35 ± 0.01 vs. 0.42 ± 0.01 mm2, respectively, p < 0.01). The thickness of the MR gradually increased from the insertion site to a 3 mm peripheral eccentric location (106.5 3.8 µm at 1 mm, 135.5 ± 4.5 µm at 2 mm and 156.1 ± 5.9 µm at 3 mm, p < 0.01). The overall median thickness of the MR was significantly less in myopes (129 µm [111.5, 152.2]) than emmetropes (158.1 [134.3, 167.7] µm, p = 0.03). However, no such trend was seen in the LR muscle. Muscle area and insertion distance were not different between emmetropes and myopes in both horizontal rectus muscles.ConclusionUnlike the LR, the parameters of the MR (thin and occupying less area) show significant association with myopia. While the key finding of this study indicates the possible association of MR parameters with myopia, the clinical relevance of this finding and its role in myopiogenesis/progression needs to be investigated further.