bluuebunny/crossref_metadata_2025 huggingface dataset:
Hortus siccus (1595) of Johann Brehe of Überlingen from the Broumov Benedictine monastery, Czech Republic, re-discovered
Authors: Skružná Jarmila , Pokorná Adéla , Dobalová Sylva , Strnadová Lucie
Published: November 2022

A forgotten Renaissance herbarium dated to 1595 is described. It is connected to herbaria created by the naturalist Hieronymus Harder (1523–1607) of Ulm. This hortus siccus was recently found in the Muzeum Broumovska, Broumov (Braunau), Czech Republic, to which it came from the collections of the local Benedictine monastery. It is the oldest hortus siccus known in collections in the Czech Republic. It contains 358 specimens as well as annotations and drawings. Its creator was Johann Brehe from Überlingen, a sixteenth-century barber-surgeon. The paper analyzes the representation of species, the purpose of the annotations, and also the meaning of the illustrations which supplement some of the specimens. It also investigates connections between Brehe’s work and Harder’s activities linked to herbaria. Brehe’s herbarium is compared with two similar collections; Johann Jakob Han’s (?1565–1616) herbarium of 1594 and Harder’s herbarium, also of 1594, and both kept in Überlingen. It shares some features with both, while differing in other respects. In particular, we compare representations of plants from the New World and the inclusion of mosses and lichens. Finally, we address the question of how a herbarium created in a town on the shores of Lake Constance, in present-day Germany, found its way to an eastern Bohemian monastery, where its presence was first documented as recently as 1937 by Pater Vincenz Maiwald OSB (1862–1951). We also highlight the importance of Czech monasteries as sources of important, unpublished documents dealing with both the natural and social sciences.
‘Perfect in her own perfection’: Women Writers in The Bell
Authors: Boumans Phyllis , D'hoker Elke
Published: November 2022

This essay examines the role played by magazine culture in the exclusion of women writers from the traditional Irish short story canon by looking at the presence and representation of women writers in The Bell (1940–1954), Ireland’s most influential mid-twentieth century literary periodical. The magazine did much to promote aspiring short story writers, but was less willing to perform their role as cultivator of new talent typical of periodical publication when it came to women apprentices. The first part of the essay gives a general picture of women’s presence in the magazine. The second part probes the underlying assumptions with have led to the systematic curtailment of women writers, and the final section maps the wider impact of these processes on the short story canon in Ireland. Despite The Bell’s progressive and inclusive credentials, the magazine proved to be an uncongenial place for women writers: with its masculine rhetoric, its representation of authorship as a male preserve, its persistent othering of women writers, its foregrounding of male experience in its fiction, and the effects of male gatekeeping, The Bell uncritically reflected and reproduced the rigid binary divisions that separated male and female spheres in Irish society at large, and ultimately contributed to the marginalization of women writers in the short story canon in Ireland.
Female Development and Fairy Tale Transformations in Frances Browne’s Granny’s Wonderful Chair, and its Tales of Fairy Times (1856)
Authors: Jamison Anne
Published: November 2022

Focusing on the changing publishing trends in children’s Irish and British fiction in the mid-nineteenth century, this essay examines Frances Browne’s popular fairy-tale collection, Granny’s Wonderful Chair, and its Tales of Fairy Times (1856), as part of a wider turn towards fantasy and fairy tale in the period. For Browne and others, the appeal of the genre lies in its ability to both entertain children, as well as instruct them in moral and social principles. As this essay aims to demonstrate, however, Browne’s text forges a significant challenge to conventional gendered patterns of social behaviour for women and imagines alternative life pathways for its young female readership as part of its didactic function. By focusing on the girl protagonist of the collection’s frame story, and her journey of maturation and acculturation, this essay finally reads Browne’s text not only for its transgressive subtext on gender conventions, but also for its implied critique of the power hierarchies that uphold the patriarchal order at the heart of these gendered social principles.
Writing from the Margins: Re-framing Teresa Deevy’s Archive and her Correspondence with James Cheasty c.1952–1962
Authors: McCarthy Kate , Kealy Úna
Published: November 2022

This essay explores a unique set of documents, comprising letters and postcards, sent by Teresa Deevy to her friend and fellow Waterford playwright, James Cheasty. To date, Deevy’s correspondence has not been considered separately from her dramatic texts, nor has Cheasty’s work received scholarly attention. Taking a feminist theatre historiographic approach, the essay theorizes the challenges of working with women’s archives, Deevy’s in particular, and conceptualizes the Deevy-Cheasty correspondence as high status research documents that raise Deevy’s archival profile. The thematic analysis of the material focuses on Deevy‘s role as Cheasty’s mentor and illuminates her engagement with Irish theatre practice of the 1950s and 60s. The essay reveals previously unknown aspects of her personal and professional life and contributes new insights relevant to scholars, practitioners, archivists, and students that redirect prevailing narratives concerning Deevy’s ambitions as a playwright and her involvement with Irish theatre practice post 1940.
The application of inferior vena cava filters in orthopaedics and current research advances
Authors: He Jingchao , Wang Zhitao , Zhou Yue Xin , Ni Hongbo , Sun XiaoHanu , Xue Jian , Chen Shanshan , Wang Shuai , Niu Meng
Published: November 2022

Deep vein thrombosis is a common clinical peripheral vascular disease that occurs frequently in orthopaedic patients and may lead to pulmonary embolism (PE) if the thrombus is dislodged. pulmonary embolism can be prevented by placing an inferior vena cava filter (IVCF) to intercept the dislodged thrombus. Thus, IVCFs play an important role in orthopaedics. However, the occurrence of complications after inferior vena cava filter placement, particularly recurrent thromboembolism, makes it necessary to carefully assess the risk-benefit of filter placement. There is no accepted statement as to whether IVCF should be placed in orthopaedic patients. Based on the problems currently displayed in the use of IVCFs, an ideal IVCF is proposed that does not affect the vessel wall and haemodynamics and intercepts thrombi well. The biodegradable filters that currently exist come close to the description of an ideal filter that can reduce the occurrence of various complications. Currently available biodegradable IVCFs consist of various organic polymeric materials. Biodegradable metals have shown good performance in making biodegradable IVCFs. However, among the available experimental studies on degradable filters, there are no experimental studies on filters made of degradable metals. This article reviews the use of IVCFs in orthopaedics, the current status of filters and the progress of research into biodegradable vena cava filters and suggests possible future developments based on the published literature by an electronic search of PubMed and Medline databases for articles related to IVCFs searchable by October 2022 and a manual search for citations to relevant studies.
Optimization of chondrocyte isolation from human articular cartilage to preserve the chondrocyte transcriptome
Authors: Shen Ping , Wu Peihua , Maleitzke Tazio , Reisener Marie-Jacqueline , Heinz Gitta A. , Heinrich Frederik , Durek Pawel , Gwinner Clemens , Winkler Tobias , Pumberger Matthias , Perka Carsten , Mashreghi Mir-Farzin , Löhning Max
Published: November 2022

The isolation of chondrocytes from human articular cartilage for single-cell RNA sequencing requires extensive and prolonged tissue digestion at 37 C. Modulations of the transcriptional activity likely take place during this period such that the transcriptomes of isolated human chondrocytes no longer match their original status in vivo. Here, we optimized the human chondrocyte isolation procedure to maximally preserve the in vivo transcriptome. Cartilage tissues were transferred into a hypoxia chamber (4% O2) immediately after being removed from OA patients and minced finely. Collagenase II at concentrations of 0.02%, 0.1%, 0.25%, 0.5%, 1%, and 2% was applied for 0.5, 1, 2, 4, and 18 h to digest the minced tissue. Actinomycin D (ActD) was added to test its capacity in stabilizing the transcriptome. Cell yield, viability, cell size, and transcriptome were determined using counter chamber, flow cytometry, and RNA sequencing (RNA-seq). Collagenase II at 2% concentration released small chondrocytes from cartilage matrix during the first digestion hour and started to release large cells thereafter, reaching a complete release at 4 h. During 4-h digestions, collagenase II at 2% and 1% but not at lower concentrations yielded maximal release also of the large chondrocyte population. RNA-seq analysis revealed that a 4-h digestion period with 1% or 2% collagenase II plus Actinomycin D optimally preserved the transcriptome. Thus, this study provides an isolation protocol for single chondrocytes from human articular cartilage optimized for transcriptome preservation and RNA-seq analysis.
Systematic evaluation of agarose- and agar-based bioinks for extrusion-based bioprinting of enzymatically active hydrogels
Authors: Wenger Lukas , Radtke Carsten P. , Gerisch Eva , Kollmann Max , Niemeyer Christof M. , Rabe Kersten S. , Hubbuch Jürgen
Published: November 2022

Extrusion-based 3D bioprinting enables the production of customized hydrogel structures that can be employed in flow reactors when printing with enzyme-containing inks. The present study compares inks based on either low-melt agarose or agar at different concentrations (3–6%) and loaded with the thermostable enzyme esterase 2 from the thermophilic organism Alicyclobacillus acidocaldarius (AaEst2) with regard to their suitability for the fabrication of such enzymatically active hydrogels. A customized printer setup including a heatable nozzle and a cooled substrate was established to allow for clean and reproducible prints. The inks and printed hydrogel samples were characterized using rheological measurements and compression tests. All inks were found to be sufficiently printable to create lattices without overhangs, but printing quality was strongly enhanced at 4.5% polymer or more. The produced hydrogels were characterized regarding mechanical strength and diffusibility. For both properties, a strong correlation with polymer concentration was observed with highly concentrated hydrogels being more stable and less diffusible. Agar hydrogels were found to be more stable and show higher diffusion rates than comparable agarose hydrogels. Enzyme leaching was identified as a major drawback of agar hydrogels, while hardly any leaching from agarose hydrogels was detected. The poor ability of agar hydrogels to permanently immobilize enzymes indicates their limited suitability for their employment in perfused biocatalytic reactors. Batch-based activity assays showed that the enzymatic activity of agar hydrogels was roughly twice as high as the activity of agarose hydrogels which was mostly attributed to the increased amount of enzyme leaching. Agarose bioinks with at least 4.5% polymer were identified as the most suitable of the investigated inks for the printing of biocatalytic reactors with AaEst2. Drawbacks of these inks are limited mechanical and thermal stability, not allowing the operation of a reactor at the optimum temperature of AaEst2 which is above the melting point of the employed low-melt agarose.
Reduced LYNX1 expression in transcriptome of human iPSC-derived neural progenitors modeling fragile X syndrome
Authors: Talvio Karo , Minkeviciene Rimante , Townsley Kayla G. , Achuta Venkat Swaroop , Huckins Laura M. , Corcoran Padraic , Brennand Kristen J. , Castrén Maija L.
Published: November 2022

Lack of FMR1 protein results in fragile X syndrome (FXS), which is the most common inherited intellectual disability syndrome and serves as an excellent model disease to study molecular mechanisms resulting in neuropsychiatric comorbidities. We compared the transcriptomes of human neural progenitors (NPCs) generated from patient-derived induced pluripotent stem cells (iPSCs) of three FXS and three control male donors. Altered expression of RAD51C, PPIL3, GUCY1A2, MYD88, TRAPPC4, LYNX1, and GTF2A1L in FXS NPCs suggested changes related to triplet repeat instability, RNA splicing, testes development, and pathways previously shown to be affected in FXS. LYNX1 is a cholinergic brake of tissue plasminogen activator (tPA)-dependent plasticity, and its reduced expression was consistent with augmented tPA-dependent radial glial process growth in NPCs derived from FXS iPSC lines. There was evidence of human iPSC line donor-dependent variation reflecting potentially phenotypic variation. NPCs derived from an FXS male with concomitant epilepsy expressed differently several epilepsy-related genes, including genes shown to cause the auditory epilepsy phenotype in the murine model of FXS. Functional enrichment analysis highlighted regulation of insulin-like growth factor pathway in NPCs modeling FXS with epilepsy. Our results demonstrated potential of human iPSCs in disease modeling for discovery and development of therapeutic interventions by showing early gene expression changes in FXS iPSC-derived NPCs consistent with the known pathophysiological changes in FXS and by revealing disturbed FXS progenitor growth linked to reduced expression of LYNX1, suggesting dysregulated cholinergic system.
3D organ-on-a-chip: The convergence of microphysiological systems and organoids
Authors: Baptista Leandra S. , Porrini Constance , Kronemberger Gabriela S. , Kelly Daniel J. , Perrault Cecile M.
Published: November 2022

Medicine today faces the combined challenge of an increasing number of untreatable diseases and fewer drugs reaching the clinic. While pharmaceutical companies have increased the number of drugs in early development and entering phase I of clinical trials, fewer actually successfully pass phase III and launch into the market. In fact, only 1 out of every 9 drugs entering phase I will launch. In vitro preclinical tests are used to predict earlier and better the potential of new drugs and thus avoid expensive clinical trial phases. The most recent developments favor 3D cell culture and human stem cell biology. These 3D humanized models known as organoids better mimic the 3D tissue architecture and physiological cell behavior of healthy and disease models, but face critical issues in production such as small-scale batches, greater costs (when compared to monolayer cultures) and reproducibility. To become the gold standard and most relevant biological model for drug discovery and development, organoid technology needs to integrate biological culture processes with advanced microtechnologies, such as microphysiological systems based on microfluidics technology. Microphysiological systems, known as organ-on-a-chip, mimic physiological conditions better than conventional cell culture models since they can emulate perfusion, mechanical and other parameters crucial for tissue and organ physiology. In addition, they reduce labor cost and human error by supporting automated operation and reduce reagent use in miniaturized culture systems. There is thus a clear advantage in combining organoid culture with microsystems for drug development. The main objective of this review is to address the recent advances in organoids and microphysiological systems highlighting crucial technologies for reaching a synergistic strategy, including bioprinting.
RNA G-quadruplex forming regions from SARS-2, SARS-1 and MERS coronoviruses
Authors: Kabbara Amani , Vialet Brune , Marquevielle Julien , Bonnafous Pierre , Mackereth Cameron D. , Amrane Samir
Published: November 2022

COVID-19 (Corona Virus Disease 2019), SARS (Severe Acute Respiratory Syndrome) and MERS (Middle East Respiratory Syndrome) are infectious diseases each caused by coronavirus outbreaks. Small molecules and other therapeutics are rapidly being developed to treat these diseases, but the threat of new variants and outbreaks argue for the identification of additional viral targets. Here we identify regions in each of the three coronavirus genomes that are able to form G-quadruplex (G4) structures. G4s are structures formed by DNA or RNA with a core of two or more stacked planes of guanosine tetrads. In recent years, numerous DNA and RNA G4s have emerged as promising pharmacological targets for the treatment of cancer and viral infection. We use a combination of bioinformatics and biophysical approaches to identify conserved RNA G4 regions from the ORF1A and S sequences of SARS-CoV, SARS-CoV-2 and MERS-CoV. Although a general depletion of G4-forming regions is observed in coronaviridae, the preservation of these selected G4 sequences support a significance in viral replication. Targeting these RNA structures may represent a new antiviral strategy against these viruses distinct from current approaches that target viral proteins.
Percutaneous stent implantation for occluded central shunts in adults: A case report and review of current evidence
Authors: Jenab Yaser , Rezaee Malihe , Hosseini Kaveh , Ghaderian Homa , Haddad Raymond N. , Zaidi Ali N.
Published: November 2022

Background

Patients with cyanotic complex congenital heart defects (CHDs) commonly undergo palliation with interposition of systemic-to-pulmonary shunts (SPSs). These palliative shunts are rarely found in adults with CHDs and can be complicated with progressive obstruction or total occlusion during follow-up. The best treatment option for shunt re-permeabilization is challenging and case-oriented because most patients are high risk candidates for redo surgeries. We aimed to review the current evidence on percutaneous stent implantation to treat failed SPSs.

Methods

We performed a comprehensive literature review on percutaneous stent implantation to treat failed and occluded SPSs. We also reported the case of a 33-year-old man with cyanotic CHD and an occluded central aorto-pulmonary shunt, who was successfully treated with percutaneous balloon dilatation and subsequently stent implantation at our institution.

Result

We identified and included 31 articles reporting on 150 patients and 165 stent implantations in failed SPSs. The age of patients at the time of stent implantation ranged from 6 days to 47 years. The time between the surgical shunt creation and transcatheter intervention ranged from 1 day to 17 years. Overall, 161/165 (97.5%) stent implantations were successful. The most common clinical presentation was cyanosis and decreased atrial oxygen saturations and the indication for stent implantation was shunt obstruction and stenosis.

Conclusion

This review highlights the benefits of endovascular stenting to permeabilize failed SPSs in children and adults with complex CHD who are classified as poor candidates for re-surgical repair.
Association of malleable factors with adoption of research-based instructional strategies in introductory chemistry, mathematics, and physics
Authors: Yik Brandon J. , Raker Jeffrey R. , Apkarian Naneh , Stains Marilyne , Henderson Charles , Dancy Melissa H. , Johnson Estrella
Published: November 2022

Active learning pedagogies are shown to enhance the outcomes of students, particularly in disciplines known for high attrition rates. Despite the demonstrated benefits of active learning, didactic lecture continues to predominate in science, technology, engineering, and mathematics (STEM) courses. Change agents and professional development programs have historically placed emphasis on develop–disseminate efforts for the adoption of research-based instructional strategies (RBIS). With numerous reported barriers and motivators for trying out and adopting active learning, it is unclear to what extent these factors are associated with adoption of RBIS and the effectiveness of change strategies. We present the results of a large-scale, survey-based study of introductory chemistry, mathematics, and physics instructors and their courses in the United States. Herein, we evaluate the association of 17 malleable factors with the tryout and adoption of RBIS. Multilevel logistic regression analyses suggest that several contextual, personal, and teacher thinking factors are associated with different stages of RBIS adoption. These results are also compared with analogous results evaluating the association of these factors with instructors’ time spent lecturing. We offer actionable implications for change agents to provide targeted professional development programming and for institutional leaders to influence the adoption of active learning pedagogies in introductory STEM courses.
Potential role of microRNAs in selective hepatic insulin resistance: From paradox to the paradigm
Authors: Palihaderu Palihaderu Arachchige Dineth Supasan , Mendis Balapuwaduge Isuru Layan Madusanka , Premarathne Jayasekara Mudiyanselage Krishanthi Jayarukshi Kumari , Dias Wajjakkara Kankanamlage Ruwin Rangeeth , Yeap Swee Keong , Ho Wan Yong , Dissanayake Arosha Sampath , Rajapakse Iyanthimala Harshini , Karunanayake Panduka , Senarath Upul , Satharasinghe Dilan Amila
Published: November 2022

The paradoxical action of insulin on hepatic glucose metabolism and lipid metabolism in the insulin-resistant state has been of much research interest in recent years. Generally, insulin resistance would promote hepatic gluconeogenesis and demote hepatic de novo lipogenesis. The underlying major drivers of these mechanisms were insulin-dependent, via FOXO-1-mediated gluconeogenesis and SREBP1c-mediated lipogenesis. However, insulin-resistant mouse models have shown high glucose levels as well as excess lipid accumulation. As suggested, the inert insulin resistance causes the activation of the FOXO-1 pathway promoting gluconeogenesis. However, it does not affect the SREBP1c pathway; therefore, cells continue de novo lipogenesis. Many hypotheses were suggested for this paradoxical action occurring in insulin-resistant rodent models. A “downstream branch point” in the insulin-mediated pathway was suggested to act differentially on the FOXO-1 and SREBP1c pathways. MicroRNAs have been widely studied for their action of pathway mediation via suppressing the intermediate protein expressions. Many in vitro studies have postulated the roles of hepato-specific expressions of miRNAs on insulin cascade. Thus, miRNA would play a pivotal role in selective hepatic insulin resistance. As observed, there were confirmations and contradictions between the outcomes of gene knockout studies conducted on selective hepatic insulin resistance and hepato-specific miRNA expression studies. Furthermore, these studies had evaluated only the effect of miRNAs on glucose metabolism and few on hepatic de novo lipogenesis, limiting the ability to conclude their role in selective hepatic insulin resistance. Future studies conducted on the role of miRNAs on selective hepatic insulin resistance warrant the understanding of this paradoxical action of insulin.
Development and validation of a predictive risk model based on retinal geometry for an early assessment of diabetic retinopathy
Authors: Wang Minglan , Zhou Xiyuan , Liu Dan Ning , Chen Jieru , Zheng Zheng , Ling Saiguang
Published: November 2022

Aims

This study aimed to develop and validate a risk nomogram prediction model based on the retinal geometry of diabetic retinopathy (DR) in patients with type 2 diabetes mellitus (T2DM) and to investigate its clinical application value.

Methods

In this study, we collected the clinical data of 410 patients with T2DM in the Second Affiliated Hospital of Chongqing Medical University between October 2020 and March 2022. Firstly, the patients were randomly divided into a development cohort and a validation cohort in a ratio of 7:3. Then, the modeling factors were selected using the least absolute shrinkage and selection operator (LASSO). Subsequently, a nomogram prediction model was built with these identified risk factors. Two other models were constructed with only retinal vascular traits or only clinical traits to confirm the performance advantage of this nomogram model. Finally, the model performances were assessed using the area under the receiver operating characteristic curve (AUC), calibration plot, and decision curve analysis (DCA).

Results

Five predictive variables for DR among patients with T2DM were selected by LASSO regression from 33 variables, including fractal dimension, arterial tortuosity, venular caliber, duration of diabetes mellitus (DM), and insulin dosage (P< 0.05). A predictive nomogram model based on these selected clinical and retinal vascular factors presented good discrimination with an AUC of 0.909 in the training cohort and 0.876 in the validation cohort. By comparing the models, the retinal vascular parameters were proven to have a predictive value and could improve diagnostic sensitivity and specificity when combined with clinical characteristics. The calibration curve displayed high consistency between predicted and actual probability in both training and validation cohorts. The DCA demonstrated that this nomogram model led to net benefits in a wide range of threshold probability and could be adapted for clinical decision-making.

Conclusion

This study presented a predictive nomogram that might facilitate the risk stratification and early detection of DR among patients with T2DM.
Diethylstilbestrol and autism
Authors: Soyer-Gobillard Marie-Odile , Gaspari Laura , Courtet Philippe , Sultan Charles
Published: November 2022

It is acknowledged that diethylstilbestrol (DES), a synthetic diphenol with powerful estrogenic properties, causes structural anomalies of the reproductive tract and increases the risk of cancer and genital malformations in children and grandchildren of mothers treated during pregnancy. Conversely, data on DES effects on neurodevelopment and psychiatric disorders in in-utero exposed children and their descendants are rare, especially concerning Autism Spectrum Disorders (ASD). Recent studies presented in this review strengthen the hypothesis that in-utero exposure to DES and also other synthetic estrogens and progestogens, which all are endocrine disruptors, contributes to the pathogenesis of psychiatric disorders, especially ASD. A large epidemiological study in the USA in 2010 reported severe depression in in-utero exposed children (n=1,612), and a French cohort study (n=1,002 in-utero DES exposed children) in 2016 found mainly bipolar disorders, schizophrenia, major depression, suicide attempts, and suicide. Few publications described ASD in in-utero exposed children, mainly a Danish cohort study and a large Chinese epidemiological study. Molecular studies on endocrine disruptors demonstrated the transgenerational induction of diseases and DES epigenetic impact (DNA methylation changes) at two genes implicated in neurodevelopment (ZFP57 and ADAM TS9). We recently described in an informative family, somatic and psychiatric disorders in four generations, particularly ASD in boys of the third and fourth generation. These data show that the principle of precaution must be retained for the protection of future generations: women (pregnant or not) should be extremely vigilant about synthetic hormones.
Effects of empagliflozin on the expression of kisspeptin gene and reproductive system function in streptozotocin-induced diabetic male rats
Authors: Dana Parisa , Hayati Roodbari Nasim , Yaghmaei Parichehreh , Hajebrahimi Zahra
Published: November 2022

One of the main health concerns of diabetes is testicular dysfunction and impairment of reproductive function and sperm quality which can cause male infertility. kisspeptin is a hypothalamic neuropeptide hormone that is involved in the regulation of energy metabolism, gonadotrophin-releasing hormone (GnRH), and reproductive function. In the present study, the therapeutic effects of empagliflozin (sodium-glucose co-transporter 2 inhibitors) on kisspeptin expression along with reproductive function were investigated in diabetic male Wistar rats. Diabetes was induced by a single dose injection of 60 mg/kg streptozotocin. Empagliflozin in doses of 10 and 25 mg/kg body weight was used for 8 weeks. Serum samples, testis, epididymis, and pancreas tissues were collected at the end of the experiments. Lipid profiles, oxidative stress markers, blood hormones, expression of kisspeptin along with pathological alterations of the testis were assayed using real-time PCR, biochemical, and histological technics. Data have shown that empagliflozin improved hyperglycemia, reproductive impairment, oxidative stress condition, and histopathological alterations of pancreatic and testis tissues in diabetic animals. It improved the serum levels of sex hormones, insulin, leptin, and the expression of kisspeptin in the testes tissues. Spermatogenesis is also improved in treated animals. Data indicated that the administration of empagliflozin can ameliorate symptoms of diabetes. It probably has promising antidiabetic potential and may improve the male infertility of diabetic subjects. To our knowledge, this is the first experimental evidence for the potential impact of empagliflozin on kisspeptin expression in diabetic male rats.
Kisspeptin-neuron control of LH pulsatility and ovulation
Authors: Stevenson Harvey , Bartram Samuel , Charalambides Mikaela Maria , Murthy Sruthi , Petitt Theo , Pradeep Anjali , Vineall Owen , Abaraonye Ikenna , Lancaster Amelia , Koysombat Kanyada , Patel Bijal , Abbara Ali
Published: November 2022

Feedback from oestradiol (E2) plays a critical role in the regulation of major events in the physiological menstrual cycle including the release of gonadotrophins to stimulate follicular growth, and the mid-cycle luteinising hormone (LH) surge that leads to ovulation. E2 predominantly exerts its action via oestrogen receptor-alpha (ERα), however, as gonadotrophin releasing hormone (GnRH) neurons lack ERα, E2-feedback is posited to be indirectly mediated via upstream neurons. Kisspeptin (KP) is a neuropeptide expressed in hypothalamic KP-neurons that control GnRH secretion and plays a key role in the central mechanism regulating the hypothalamic-pituitary-gonadal (HPG) axis. In the rodent arcuate (ARC) nucleus, KP is co-expressed with Neurokinin B and Dynorphin; and thus, these neurons are termed ‘Kisspeptin-Neurokinin B-Dynorphin’ (KNDy) neurons. ARC KP-neurons function as the ‘GnRH pulse generator’ to regulate GnRH pulsatility, as well as mediating negative feedback from E2. A second KP neuronal population is present in the rostral periventricular area of the third ventricle (RP3V), which includes anteroventral periventricular (AVPV) nucleus and preoptic area neurons. These RP3V KP-neurons mediate positive feedback to induce the mid-cycle luteinising hormone (LH) surge and subsequent ovulation. Here, we describe the role of KP-neurons in these two regions in mediating this differential feedback from oestrogens. We conclude by considering reproductive diseases for which exploitation of these mechanisms could yield future therapies.
Equilibrium analysis of carbon decision behavior for the evolutionary game between the government and enterprises
Authors: Ding Youqiang , Hu Yufeng , Liu Jun
Published: November 2022

With the implementation of the carbon-neutral goal, an evolutionary game of carbon decision behavior was derived from the difference between government carbon mitigation and enterprises’ performance growth. This paper constructed a double-performance (DP) objective function of environmental performance and corporate performance. Four carbon decision factors, namely, carbon emission rights, carbon tax, green innovation, and green subsidy, were added separately into the DP model to search for the equilibrium point using the Stackelberg game. The research shows the following: (ⅰ) the price effect of carbon emission rights can restrain excess carbon emission of enterprises to a certain extent; (ⅱ) the reverse effect of a carbon tax can force enterprises to achieve the carbon mitigation goal through green innovation; (ⅲ) the reinforcement effect of green innovation can strengthen the promotion of environmental performance but accelerate the decline of corporate performance; and (ⅳ) the incentive effect of green subsidy can make corporate performance reach the inflection point ahead of time and realize DP synergistic growth. The evolutionary game between the government and enterprises results in the fluctuation change that causes DP to rise first, then decrease, and finally increase. Also, DP can be developed in a synergistic way under collaborative governance for its consistency of carbon decision behavior.
Role of constructed wetlands in mitigating the challenges of industrial growth and climate change impacts in the context of developing countries
Authors: Islam Md. Al Sadikul , Saeed Tanveer , Majed Nehreen
Published: November 2022

One of the most persistent issues affecting individuals in developing countries is the lack of access to safe drinking water and sanitary facilities. The adoption of centralized water, energy, and cost-intensive technology has proven ineffective in addressing the complex water-related challenges that have arisen as a consequence of growing urbanization in developing nations. Constructed wetlands have emerged as an effective wastewater treatment solution with natural applications. The fundamental goal of this study is to offer a complete overview of the wide variety of practices, uses, and investigations of constructed wetlands systems for eliminating different pollutants from wastewater in developing countries leading to placing them in the context of climate change, environmental resource planning, and sustainable wastewater treatment systems. CWs offer significant levels of treatment performances with hybrid systems achieving contaminant removal efficiencies up to 93.82% for total suspended solids, 85.65% for chemical oxygen demand, and 80.11% for ammonia nitrogen which is adequate with respect to other viable alternatives. In terms of Biological Oxygen Demand (BOD5), the highest elimination (84.06%) was achieved in hybrid systems when compared to Free water surface CWs (65.34%), Horizontal sub-surface CWs (75.1%), and Floating treatment wetland (55.29%). The maximum power density generation through the microbial fuel cell-based constructed wetlands ranges between 50 and 86 mW/m2in Bangladesh (integrated tidal flow) and 852 mW/m3in China (vertical flow), and the production of bioenergy has been evidenced up to 1,836.5 GJ/hector/year. Annually, wastewater treatment plant systems (WTPs) generate around a hundred times more Methane (CH4), Nitrous oxide (N2O), and carbon dioxide (CO2) than CWs. In metropolitan cities, WTPs may lead to a considerable increase in upstream land use, which could be minimized by promoting CWs in these areas. The potential utility of different CWs in protecting and preserving estuarine quality within the present regulatory framework is finally addressed in the study, emphasizing that it can balance the impacts of industrial expansions in developing countries for subsequent mitigation and adaptation to climate change.
Body temperature and activity patterns modulate glucocorticoid levels across lizard species: A macrophysiological approach
Authors: Rubalcaba Juan G. , Jimeno Blanca
Published: November 2022

Environmental and intrinsic factors interact to determine energy requirements in vertebrates. Glucocorticoid hormones (GCs) are key mediators of this interaction, as they fluctuate with energetic demands and regulate physiological and behavioral responses to environmental challenges. While a great body of research has focused on GC variation among individuals, the mechanisms driving GC variation across species and at broad spatial scales remain largely unexplored. Here, we adopted a macrophysiological approach to investigate the environmental factors and life-history traits driving variation in baseline GCs across lizard species. We tested three hypotheses: (1) If GCs increase with body temperature to meet higher metabolic demand, we expect an association between average baseline GCs and the mean species’ body temperature in the field (GC-temperature dependence hypothesis); (2) If GCs mediate behavioral responses to avoid thermal extremes, we expect that individuals frequently exposed to extreme conditions exhibit higher baseline GC levels (Behavioral thermoregulation hypothesis); (3) If GCs increase to support higher energy demands in active foragers during their period of activity, we expect that active foraging species have higher baseline GCs than sit-and-wait foragers, and that GC levels increase in relation to the duration of daily activity windows (Activity hypothesis). We used biophysical models to calculate operative temperatures and the activity patterns of lizards in sun-exposed and shaded microenvironments. Then, we tested the association between baseline GCs, body temperature, operative temperatures, foraging mode, and activity windows across 37 lizard species, using data from HormoneBase. Our comparative analyses showed that variation in baseline GCs was primarily related to the mean field body temperature and foraging mode, with higher baseline GCs in active foragers with higher body temperatures. Our results suggest that body temperature and foraging mode drive GC variation through their effects on energy requirements across lizard species.
Single-step genomic BLUP with many metafounders
Authors: Kudinov Andrei A. , Koivula Minna , Aamand Gert P. , Strandén Ismo , Mäntysaari Esa A.
Published: November 2022

Single-step genomic BLUP (ssGBLUP) model for routine genomic prediction of breeding values is developed intensively for many dairy cattle populations. Compatibility between the genomic (G) and the pedigree (A) relationship matrices remains an important challenge required in ssGBLUP. The compatibility relates to the amount of missing pedigree information. There are two prevailing approaches to account for the incomplete pedigree information: unknown parent groups (UPG) and metafounders (MF). unknown parent groups have been used routinely in pedigree-based evaluations to account for the differences in genetic level between groups of animals with missing parents. The MF approach is an extension of the UPG approach. The MF approach defines MF which are related pseudo-individuals. The MF approach needs a Γ matrix of the size number of MF to describe relationships between MF. The UPG and MF can be the same. However, the challenge in the MF approach is the estimation of Γ having many MF, typically needed in dairy cattle. In our study, we present an approach to fit the same amount of MF as UPG in ssGBLUP with Woodbury matrix identity (ssGTBLUP). We used 305-day milk, protein, and fat yield data from the DFS (Denmark, Finland, Sweden) Red Dairy cattle population. The pedigree had more than 6 million animals of which 207,475 were genotyped. We constructed the preliminary gamma matrix (Γpre) with 29 MF which was expanded to 148 MF by a covariance function (Γ148). The quality of the extrapolation of the Γpre matrix was studied by comparing average off-diagonal elements between breed groups. On average relationships among MF in Γ148 were 1.8% higher than in Γpre. The use of Γ148 increased the correlation between the G and A matrices by 0.13 and 0.11 for the diagonal and off-diagonal elements, respectively. [G]EBV were predicted using the ssGTBLUP and Pedigree-BLUP models with the MF and UPG. The prediction reliabilities were slightly higher for the ssGTBLUP model using MF than UPG. The ssGBLUP MF model showed less overprediction compared to other models.
A comprehensive prognostic and immune infiltration analysis of EXOC3L1 in pan-cancer
Authors: Zhang Zhan-Fei
Published: November 2022

Exocyst complex component 3 like 1 (EXOC3L1) is widely present in various human tissues, which mainly regulates insulin secretion. However, its roles in tumors remain unclear. In the present study, we aimed to investigate the roles of EXOC3L1 in pan-cancer, and the data was downloaded from of the University of California Santa Cruz (UCSC) Xena and the Cancer Genome Atlas (TCGA). The expression status of EXOC3L1 was studied in the TCGA_GTEx samples, TCGA samples and paired samples in TCGA, respectively. Subsequently, Kaplan-Meier analysis was applied to 33 kinds of tumors in TCGA, among the cancers that EXOC3L1 can affect prognosis, clinical correlation analysis and univariate Cox regression analysis were performed. Furthermore, representative cancers kidney renal clear cell carcinoma (KIRC) and lung squamous cell carcinoma (LUSC) with a sample size larger than 500 were selected to construct nomogram models to confirm the prognostic value of EXOC3L1 in cancers. Additionally, the associations of EXOC3L1 with immune cell infiltrations were performed as well. Mechanistically, functional enrichment analysis was performed to explore potential signaling pathways that EXOC3L1 may involve in. Our study found that EXOC3L1 was differentially expressed in a variety of tumors and was associated with the clinical outcomes and immune microenvironment of several tumors, it may affect the occurrence and development of tumors through NOTCH signaling pathway, PI3K-AKT signaling pathway and immune-related pathways. In conclusion, we propose that EXOC3L1 may serve as a potential prognostic biomarker and a promising target for cancer immunotherapy in a variety of cancers.
Heterochromatin in the fungal plant pathogen, Zymoseptoria tritici: Control of transposable elements, genome plasticity and virulence
Authors: Fraser Callum J. , Whitehall Simon K.
Published: November 2022

Heterochromatin is a repressive chromatin state that plays key roles in the functional organisation of eukaryotic genomes. In fungal plant pathogens, effector genes that are required for host colonization tend to be associated with heterochromatic regions of the genome that are enriched with transposable elements. It has been proposed that the heterochromatin environment silences effector genes in the absence of host and dynamic chromatin remodelling facilitates their expression during infection. Here we discuss this model in the context of the key wheat pathogen, Zymoseptoria tritici. We cover progress in understanding the deposition and recognition of heterochromatic histone post translational modifications in Z. tritici and the role that heterochromatin plays in control of genome plasticity and virulence.
Genomic profiling and network-level understanding uncover the potential genes and the pathways in hepatocellular carcinoma
Authors: El-Kafrawy Sherif A. , El-Daly Mai M. , Bajrai Leena H. , Alandijany Thamir A. , Faizo Arwa A. , Mobashir Mohammad , Ahmed Sunbul S. , Ahmed Sarfraz , Alam Shoaib , Jeet Raja , Kamal Mohammad Amjad , Anwer Syed Tauqeer , Khan Bushra , Tashkandi Manal , Rizvi Moshahid A. , Azhar Esam Ibraheem
Published: November 2022

Data integration with phenotypes such as gene expression, pathways or function, and protein-protein interactions data has proven to be a highly promising technique for improving human complex diseases, particularly cancer patient outcome prediction. Hepatocellular carcinoma is one of the most prevalent cancers, and the most common cause is chronic HBV and HCV infection, which is linked to the majority of cases, and HBV and HCV play a role in multistep carcinogenesis progression. We examined the list of known hepatocellular carcinoma biomarkers with the publicly available expression profile dataset of hepatocellular carcinoma infected with HCV from day 1 to day 10 in this study. The study covers an overexpression pattern for the selected biomarkers in clinical hepatocellular carcinoma patients, a combined investigation of these biomarkers with the gathered temporal dataset, temporal expression profiling changes, and temporal pathway enrichment following HCV infection. Following a temporal analysis, it was discovered that the early stages of HCV infection tend to be more harmful in terms of expression shifting patterns, and that there is no significant change after that, followed by a set of genes that are consistently altered. PI3K, cAMP, TGF, TNF, Rap1, NF-kB, Apoptosis, Longevity regulating pathway, signaling pathways regulating pluripotency of stem cells, Cytokine-cytokine receptor interaction, p53 signaling, Wnt signaling, Toll-like receptor signaling, and Hippo signaling pathways are just a few of the most commonly enriched pathways. The majority of these pathways are well-known for their roles in the immune system, infection and inflammation, and human illnesses like cancer. We also find that ADCY8, MYC, PTK2, CTNNB1, TP53, RB1, PRKCA, TCF7L2, PAK1, ITPR2, CYP3A4, UGT1A6, GCK, and FGFR2/3 appear to be among the prominent genes based on the networks of genes and pathways based on the copy number alterations, mutations, and structural variants study.
Distinct clinical pattern of colorectal cancer patients with POLE mutations: A retrospective study on real-world data
Authors: Jiang Miao , Jia Yongliang , Han Jinming , Shi Jianxiang , Su Chang , Zhang Rui , Xing Menglu , Jin Shuiling , Zong Hong
Published: November 2022

Objective: Studies have demonstrated an association between somatic POLE exonuclease domain mutations (EDMs) and the prognosis of colorectal cancer (CRC). However, the prognostic value of POLE non-EDMs remains unclear. This retrospective study aimed to explore the possible relationships between POLE mutation subtypes and CRC prognosis.

Methods: The 272 CRC patients from the First Affiliated Hospital of Zhengzhou University (ZZ cohort) and 499 CRC patients from The Cancer Genome Atlas database (TCGA cohort) were retrospectively collected. The cases were divided into subgroups based on POLE mutation sites and microsatellite instability (MSI) status. The continuous variables were compared among three subgroups with Kruskal-Wallis tests. Pairwise comparisons between three groups were performed by Bonferroni correction method, and adjusted p < 0.05 was considered statistically significant. The categorical variables were compared with Chi-square test and Fisher’s exact test. The Kaplan—Meier curves and Cox regression models were conducted to evaluate prognostic values of POLE mutations.

Results: In the ZZ cohort, POLE EDMs (2.6%) were significantly associated with younger age (p = 0.018) and localized in the left colon (p = 0.001). POLE non-EDMs were significantly associated with MSI-high status (p < 0.001) and localization in the right colon (p = 0.001). In the TCGA cohort, the tumor mutation burden (TMB) of both POLE EDM tumors (p < 0.001) and POLE non-EDM tumors (p < 0.001) was significantly higher than that of POLE wild-type (WT) tumors. A similar trend was observed in the ZZ cohort, although there were no significant differences. In the ZZ cohort, the POLE EDM group had higher progression-free survival (PFS) (p = 0.002) and overall survival (OS) (p = 0.042) than the POLE non-EDM group and POLE WT group. We also report one CRC patient harboring a germline POLE mutation who received camrelizumab and exhibited long-term stable disease.

Conclusion: Both POLE-EDMs and POLE non-EDMs were associated with significantly increased TMB in CRC and may be biomarkers for CRC treatment and prognosis. Current evidence does not support an effect of POLE non-EDMs on PFS and OS. A significant association between POLE EDMs and improved PFS and OS may exist, but future studies with larger sample sizes are needed. Entire coding region of the POLE gene should be screened.