bluuebunny/crossref_metadata_2025 huggingface dataset:
ANALISIS PERENCANAAN PEKERJAAN DRAINASE TIPE U-DITCH BETON BERTULANG JALAN A. YANI KOTA PAYAKUMBUH
Authors: Rahman Andika , Eka Priana Surya , Herista Febrimen
Published: June 2023

Banjir dan genangan air telah menjadi masalah yang cukup lama terjadi pada kawasan Jalan A. Yani Kota Pyakumbuh. Masalah tersebut disebabkan karena daerah tersebut  cenderung datar, sehingga aliran air hujan relatif lambat dan kecepatan aliran dapat mendekati titik nol, serta kualitas saluran yang tidak memadai untuk menampung debit yang datang dari saluran primer. Tujuan dari penelitian ini untuk merencanakan sistem drainase pada jalan A. Yani Kota Payakumbuh.  Metode pengolahan data menggunakan metode Log Normal untuk menentukan hujan rencana dan perhitungan secara manual dengan metode rasional untuk menghitung debit hujan, dan rumus Manning untuk debit saluran. Setelah dilakukan perhitungan maka didapat debit maksimal dari dimensi saluran drainase eksisting tahunan dalam 2 tahun = 1.13 m3/dtk , 5 tahun = 1.56 m3/dtk  dan 10 tahun = 2.23  m3/dtk. Maka direncanakan dimensi saluran drainase untuk saluran drainase sekunder jalan A.Yani Kota Payakumbuh dengan tipe saluran U-Ditch yaitu dengan saluran kanan U-Ditch 1.2 m  x 1.4 m dan saluran kiri U-Ditch  1,25 m  x1,45 m. Dengan kemampuan debit maksimal rencana saluran kanan sebesar  2.58 m3/dtk dan debit maksimal rencana saluran kiri sebesar  2.872 m3/dtk. Kata Kunci :  Drainase , Metode Log Normal, U-Ditch,  Debit Hujan(Q).
PERBANDINGAN PERENCANAAN TEBAL PERKERASAN LENTUR DENGAN MDPJ 2017 DAN METODE ANALISA KOMPONEN 1987 (STUDI KASUS JALAN SUBARANG TARAM KABUPATEN LIMAPULUH KOTA)
Authors: Nazar Uhlul , Yermadona Helga , Dewi Selpa
Published: June 2023

Jalan merupakan sarana transportasi darat yang digunakan pengguna jalan sebagai jalur perpindahan dari suatu tempat ke tempat tujuan dan juga memegang peranan sangat penting untuk menunjang pertumbuhan ekonomi. Untuk itu diperlukan penambahan kapasitas jalan raya yang memenuhi unsur keselamatan pengguna jalan dan tidak mengganggu ekosistem di sekitarnya. Namun pada saat ini banyak ditemui jalan yang mengalami kerusakan seperti jalan Subarang Taram, Kabupaten Limapuluh kota. Pada titik tertentu,jalan ini mengalami kondisi sangat memprihatinkan. Kondisi jalan ini yang mengalami kerusakan berupa jalan yang berlobang, retak buaya, tambalan, pelepasan butiran, retak pinggir sehingga mengganggu kenyamanan dan keamanan pengguna jalan. Pengambilan judul ini bertujuan untuk menghitung tebal perkerasan lentur (Flexible Pavement) dengan menggunakan metode Bina Marga 2017 dan metode Analisa Komponen 1987. Perhitungan untuk mengetahui ketebalan perkerasan jalan ini menggunakan dua metode, yaitu metode bina marga 2017 dan metode analisa komponen 1987. Perhitungan untuk perkerasan jalan ini diawali dengan menghitung data tanah, menghitung lalu lintas kendaraan, dan menghitung tebal perkerasan untuk masing-masing metode. Untuk metode bina marga 2017 didapat lapisan AC WC 40 mm, AC BC 60 mm, AC Base 0 mm, LPA Kelas A 400 mm. Metode analisa komponen 1987 didapat laston 75 mm, batu pecah kelas A 200 mm, dan sirtu kelas A 110 mm.Kata Kunci : Jalan, Perkerasan Lentur, Lalu Linta, Metode Bina Marga 2017, Metode Analisa Komponen 1987.
Memories of Home: The Belfast Films of Mark Cousins and Kenneth Branagh
Authors: Barton Ruth
Published: June 2023

This article discusses Mark Cousin’s I Am Belfast (2015) and Kenneth Branagh’s Belfast (2022) as autobiographical cinema. While acknowledging the multiple differences between each film, I argue that they also share many common themes and motifs. These include a determination to depict Belfast as a city shaped as much by a down-to-earth working class identified by their sense of community as by its official history of the Troubles. Both celebrate friendships across the religious divide, and both share a utopian sensibility, expressed as much through aesthetics as narrative devices. My argument centres on the imaginative construction of Belfast in both films, while also drawing attention to how devices, such as the inclusion of songs by Van Morrison, open the works up to a wider process of exilic identity construction. I also consider the issue of ‘cultural Protestantism’ as evidenced in Branagh’s film and how cinema’s own history intersects with the personal histories of both film-makers.
Out of Time: BBC Northern Ireland and the Paradoxes of Partition
Authors: Butler David , Baker Stephen
Published: June 2023

This article considers the contradictions of British broadcasting in northern Ireland. Established in 1924, following war and partition, the BBC in the sectarian state of Northern Ireland was permitted to develop at an arm’s length and out of sync with the national model of British broadcasting. Structured on the colonial presumption of neutrality on the part of British interests in Ireland, British television, during the Troubles, took for granted the legitimacy of partition and, as a result, misconstrued the causes of conflict. Throughout the period up to negotiation of the 1998 settlement – the Good Friday Agreement – and down to the present era, British perspectives on the crisis neglected the precedence of parallels in the Irish experience of partition, notably, since 2010, when confronted with the resurgent forces of ethnic nationalism (aka Brexit). In its post-public-service dotage, the BBC has responded poorly to a constitutional crisis from which the Union of Great Britain and Northern Ireland (that is, the UK) may not recover. So much so that, by now, amid a series of politically awkward centenaries, it is argued, the BBC and the partitionist project of NI, are each in their own way manifesting signs of morbidity, and both are running out of time.
Effect of Pre-treatment on The Impregnation of Osmotically Dehydrated Fruits: A Review
Authors: ASMAN SALIZA , RAJA SHALINI
Published: June 2023

Osmotic dehydration is one of the alternative methods that is most frequently employed in the food industry to prevent large accumulation of food waste and postharvest losses, although it has a devastating influence on the textural and structural properties of the fruits. Considering that, this review offers innovative ideas and views on the impact of calcium salts, specifically calcium chloride and calcium lactate, on the impregnation of osmotically dehydrated fruits, along with various pre-treatments. Calcium chloride and calcium lactate salts assist in conserving the quality of fruits in the sense of colour, sensory, textural, structural, and other characteristics since some fruits are very perishable and rapidly degrade. Additional data showed that pre-treatments like blanching, freezing, drying, and ultrasound negatively affect calcium salt impregnation on fruit samples. The focus of this review is mainly on the preservation method of impregnating osmotically dehydrated fruits with calcium chloride and calcium lactate salt treatments, as well as blanching, freezing, drying, and ultrasound pre-treatments.
Experimental investigation of the influence of film cooling hole diameter on the total cooling effectiveness for cyclone-cooled turbine blades
Authors: Bicat Dogan , Stichling Katharina , Elfner Maximilian , Bauer Hans-Jörg , Lehmann Knut
Published: June 2023

Cyclone cooling is a promising method for a more effective internal cooling of turbine rotor blades with simplified internal channels including a swirling flow to enhance internal heat transfer. Previous studies have led to the conclusion that improving the cooling performance requires an adapted film cooling design, tailored to the cyclone cooling application. In this paper, a turbine rotor blade with realistic, complex features including the cyclone cooling design is investigated experimentally using infrared thermography to capture surface temperature. The objective is to analyze the influence of increased film cooling hole diameter on a cyclone-cooled blade’s surface temperature. For this purpose, the diameter of the holes at the blade’s leading edge, which are fed by the cyclone channel, is increased. The tests are performed for different coolant mass flow rates and swirl numbers. Additionally, CFD simulations are performed to analyze the aerodynamics of the cooling air. The test results show that the surface temperature at the leading edge can be decreased by increasing the diameter of the film cooling holes, however, adversely affecting the remaining blade surface. This can be explained by a redistribution of the supplied coolant. The increase of cooling effectiveness at the leading edge is at the highest when a low swirl is generated.
Unlocking the Black Box: Explainable Artificial Intelligence (XAI) for Trust and Transparency in AI Systems
Authors: Thalpage Nipuna
Published: June 2023

Explainable Artificial Intelligence (XAI) has emerged as a critical field in AI research, addressing the lack of transparency and interpretability in complex AI models. This conceptual review explores the significance of XAI in promoting trust and transparency in AI systems. The paper analyzes existing literature on XAI, identifies patterns and gaps, and presents a coherent conceptual framework. Various XAI techniques, such as saliency maps, attention mechanisms, rule-based explanations, and model-agnostic approaches, are discussed to enhance interpretability. The paper highlights the challenges posed by black-box AI models, explores the role of XAI in enhancing trust and transparency, and examines the ethical considerations and responsible deployment of XAI. By promoting transparency and interpretability, this review aims to build trust, encourage accountable AI systems, and contribute to the ongoing discourse on XAI.
Accessibility to Join Bone Marrow Donor Registry for Volunteers
Authors: Gerova Olga , Shikina Irina
Published: June 2023

Recruitment of potential bone marrow donors is information and engagement (registration) of volunteers in the register of potential bone marrow donors. The entry of a potential donor into the registry is the organization of obtaining informed consent, collecting biological samples and delivering them to the laboratory. Accessibility to join the bone marrow donor registry for volunteers depends from way of collection biologic samples. There are four ways: Blood Service, commercial laboratories, post and at the event. We have developed a scale for assessing the criteria for the accessibility of entry into the register depending on the entry method. The high accessibility of entry into the register can be ensured by interaction with the Russian Post and a network of commercial laboratories that scored the highest score of 10 out of 12 during the accessibility assessment. It is possible to use the full potential of 54 million residents of the Russian Federation aged 18-45 years to form a register of bone marrow donors regardless of the territorial basis only through the interaction of large public and private structures.
Design and computational optimization of compliance-matching aortic grafts
Authors: Rovas Georgios , Bikia Vasiliki , Stergiopulos Nikolaos
Published: June 2023

Introduction: Synthetic vascular grafts have been widely used in clinical practice for aortic replacement surgery. Despite their high rates of surgical success, they remain significantly less compliant than the native aorta, resulting in a phenomenon called compliance mismatch. This incompatibility of elastic properties may cause serious post-operative complications, including hypertension and myocardial hypertrophy.

Methods: To mitigate the risk for these complications, we designed a multi-layer compliance-matching stent-graft, that we optimized computationally using finite element analysis, and subsequently evaluated in vitro.

Results: We found that our compliance-matching grafts attained the distensibility of healthy human aortas, including those of young adults, thereby significantly exceeding the distensibility of gold-standard grafts. The compliant grafts maintained their properties in a wide range of conditions that are expected after the implantation. Furthermore, the computational model predicted the graft radius with enough accuracy to allow computational optimization to be performed effectively.

Conclusion: Compliance-matching grafts may offer a valuable improvement over existing prostheses and they could potentially mitigate the risk for post-operative complications attributed to excessive graft stiffness.
Role of insulin-like growth factor 1 (IGF1) in the regulation of mitochondrial bioenergetics in zebrafish oocytes: lessons from in vivo and in vitro investigations
Authors: Biswas Subhasri , Ghosh Soumyajyoti , Maitra Sudipta
Published: June 2023

Optimal mitochondrial functioning is indispensable for acquiring oocyte competence and meiotic maturation, whilst mitochondrial dysfunction may lead to diminished reproductive potential and impaired fertility. The role of the intra-ovarian IGF system in ovarian follicular dynamics has been implicated earlier. Although several studies have demonstrated the role of the IGF axis in facilitating mitochondrial function over a multitude of cell lines, its role in oocyte energy metabolism remains largely unexplored. Here using zebrafish, the relative importance of IGF1 in modulating oocyte mitochondrial bioenergetics has been investigated. A dramatic increase in ovarianlhcgrandigf1expression accompanied heightened ATP levels and mitochondrial polarization in full-grown (FG) oocytes resuming meiotic maturation and ovulationin vivo. Concomitant with elevatedigf1expression and IGF1R phosphorylation, hCG (LH analog) stimulation of FG folliclesin vitroprompted a sharp increase in NRF-1 and ATP levels, suggesting a positive influence of gonadotropin action onigf1expression vis-à-vis oocyte bioenergetics. While recombinant IGF1 administration enhanced mitochondrial function, IGF1R immunodepletion or priming with PI3K inhibitor wortmannin could abrogate NRF-1 immunoreactivity, expression of respiratory chain subunits, ΔΨM,and ATP content. Mechanistically, activation of PI3K/Akt signaling in IGF1-treated follicles corroborated well with the rapid phosphorylation of GSK3β at Ser9 (inactive) followed by PGC-1β accumulation. While selective inhibition of GSK3β promoted PGC-1β, Akt inhibition could abrogate IGF1-induced p-GSK3β (Ser9) and PGC-1β immunoreactive protein indicating Akt-mediated GSK3β inactivation and PGC-1β stabilization. The IGF1-depleted follicles showed elevated superoxide anions, subdued steroidogenic potential, and attenuated G2-M1 transition. In summary, this study highlights the importance of IGF1 signaling in oocyte bioenergetics prior to resumption of meiosis.
Microbiology and prognostic prediction model of bloodstream infection in patients with hematological malignancies
Authors: Wang Jinjin , Wang Mengyao , Zhao Ailin , Zhou Hui , Mu Mingchun , Liu Xueting , Niu Ting
Published: June 2023

Background

In recent years, with the continuous development of treatments for hematological malignancies (HMs), the remission and survival rates of patients with HMs have been significantly improved. However, because of severe immunosuppression and long-term recurrent neutropenia during treatment, the incidence and mortality of bloodstream infection (BSI) were all high in patients with HMs. Therefore, we analyzed pathogens’ distribution and drug-resistance patterns and developed a nomogram for predicting 30-day mortality in patients with BSIs among HMs.

Methods

In this retrospective study, 362 patients with positive blood cultures in HMs were included from June 2015 to June 2020 at West China Hospital of Sichuan University. They were randomly divided into the training cohort (n = 253) and the validation cohort (n = 109) by 7:3. A nomogram for predicting 30-day mortality after BSIs in patients with HMs was established based on the results of univariate and multivariate logistic regression. C-index, calibration plots, and decision curve analysis were used to evaluate the nomogram.

Results

Among 362 patients with BSIs in HMs, the most common HM was acute myeloid leukemia (48.1%), and the most common pathogen of BSI was gram-negative bacteria (70.4%). The final nomogram included the septic shock, relapsed/refractory HM, albumin <30g/l, platelets <30×109/l before BSI, and inappropriate empiric antibiotic treatment. In the training and validation cohorts, the C-indexes (0.870 and 0.825) and the calibration plots indicated that the nomogram had a good performance. The decision curves in both cohorts showed that the nomogram model for predicting 30-day mortality after BSI was more beneficial than all patients with BSIs or none with BSIs.

Conclusion

In our study, gram-negative bacterial BSIs were predominant in patients with HMs. We developed and validated a nomogram with good predictive ability to help clinicians evaluate the prognosis of patients.
The imPAct of Trimetazidine on MicrOcirculation after Stenting for stable coronary artery disease (PATMOS study)
Authors: Ilic Ivan , Timcic Stefan , Milosevic Maja , Boskovic Srdjan , Odanovic Natalija , Furtula Matija , Dobric Milan , Aleksandric Srdjan , Otasevic Petar
Published: June 2023

Background

Myocardial ischemia is caused by epicardial coronary artery stenosis or atherosclerotic disease affecting microcirculation. Trimetazidine (TMZ), promotes glucose oxidation which optimizes cellular energy processes in ischemic conditions. Small studies demonstrated protective effects of TMZ in terms of reducing myocardial injury after percutaneous coronary intervention (PCI), its effect on microcirculation using contemporary investigative methods has not been studied. The aim of the study was to examine effects of trimetazidine, given before elective PCI, on microcirculation using invasively measured index of microcirculatory resistance (IMR).

Methods

This was prospective, single blinded, randomized study performed in a single university hospital. It included consecutive patients with an indication for PCI of a single, de novo, native coronary artery lesion. Patients were randomly assigned to receive either TMZ plus standard therapy (TMZ group) or just standard therapy. Coronary physiology indices fractional flow reserve (FFR), coronary flow reserve (CFR) and index of microcirculatory resistance (IMR) were measured before and after PCI using coronary pressure wire.

Results

We randomized 71 patients with similar clinical characteristics and risk profile, previous medications and coronary angiograms. Patientshad similar values of Pd/Pa, FFR and CFR prior to PCI procedure. After PCI, FFR values were higher in TMZ group, while IMR values were lower in this group respectively (FFR TMZ + 0.89 ± 0.05 vs. TMZ – 0.85 ± 0.06, p = 0.007; CFR TMZ + 2.1 ± 0.8 vs. TMZ- 2.3 ± 1.3, p = 0.469; IMR TMZ + 18 ± 9 vs. TMZ- 24 ± 12, p = 0.028). In two-way repeated measures ANOVA PCI was associated with change in FFR values (TMZ p = 0.050; PCI p < 0.001; p for interaction 0.577) and TMZ with change in IMR values (TMZ p = 0.034, PCI p = 0.129, p for interaction 0.344).

Conclusion

Adding trimetazidine on top of medical treatment prior to elective PCI reduces microvascular dysfunction by lowering postprocedural IMR values when compared to standard therapy alone.
Economics in primary schools: an empirical experiment from Hungary
Authors: Nagy Judit
Published: June 2023

The paper highlights the importance and relevance of introducing economic studies to primary schools. The research aimed to investigate the appropriate age, environment, type, and composition of presentation for introducing combined economic knowledge. The 190 students participating in the research were students from three primary schools in Hungary from 10 classes. Given the fact that in the case of all of the significant results, a sufficient effect size could be measured, and furthermore, the relevant test value was very high, it is unambiguously proven that the size of the sample (n= 190) that was used for the examination was sufficient. The results suggest that teaching economic and financial knowledge through accounting and making lectures interactive using special tools of positive education is critical to stimulating children’s interest. Eighty percent of the students in the study liked the combined and interactive lecture. Another goal was to investigate whether those that liked the presentation would perform better on the related knowledge test, which proved to be the case. In the two target groups, students in grade 6 outperformed students in grade 3 on the test. An investigation of gender performance is also included in the research. Findings suggest that the respective education may appropriately be developed based on the close relationship between mathematics and accounting. The lectures can be adapted according to any national or international accounting standards (IFRS, etc.) and can be taught in an online classroom as well. The lectures aim to develop children’s independent problem-solving skills so they can adapt the information to their own lives and financial situations. The paper fills a gap in the research by describing a successful attempt to complex economic literacy.

JEL Classification code

A29, M21, M41
Digitalization as a way to promote the holistic approach to faculty development: a developmental evaluation
Authors: Silva Roberta
Published: June 2023

Faculty Development, in the last decades, has undergone many transformations and many scholars are now wondering what will be the main feature that will characterize the next age, an age distinguished, in the academic world, by the changes that the just experienced pandemic brought with it. One of the main changes that this pandemic has brought with itself is the increase in digitalization within academic institutions and, consequently, the increase in the number of faculty development proposals that are conveyed through online initiatives. However, this is a consideration that can be read not only as a stand-alone element but also, if properly contextualized, it could be used as a way to promote Faculty Development programs that exploit the potential offered by digitalization in order to create initiatives which are linked in a mutually reinforcing bond. This choice is consistent with the adherence to a holistic approach to Faculty Development that promotes a systemic and multifocal logic. This paper presents a study conducted at the University of Verona in order to discover if the Faculty Development programs here implemented applying this approach were been able to promote a reciprocal mirroring between them. In order to answer this question, it was considered useful to investigate the results of a survey carried out on the “Competenze Trasversali” program, in its first edition, and thus still in an “experimental” phase. In order to collect the data has been used a simplified version of SWOT Analysis was used and the answers to the open questions were analyzed using the content analysis.
Continuous vs. discontinuous purification of isolated human islets: functional and morphological comparison
Authors: Buemi Antoine , Mouard Nizar I. , Darius Tom , Devresse Arnaud , Kanaan Nada , Gianello Pierre , Mourad Michel
Published: June 2023

Background

The COBE 2991 cell processor, commonly used for pancreatic islet isolation, is no longer distributed in Europe, leading to a search for alternative purification procedures with equivalent efficacy. The aim of this study was to evaluate the efficacy of an alternative method based on the discontinuous purification of islets.

Methods

The conventional isolation procedure using a standard continuous islet purification with COBE 2991 of n = 4 human pancreas was compared to n = 8 procedures using a discontinuous purification with a “bottle” method from donors of similar characteristics. Islet equivalents, purity, and dynamic glucose-stimulated insulin secretion were evaluated.

Results

A similar islet yield was obtained using continuous vs. discontinuous purification methods (76,292.5 ± 40,550.44 vs. 79,625 ± 41,484.46 islet equivalents, p = 0.89). Islets from both groups had similar purity (78.75% ± 19.73% vs. 55% ± 18.16%, p = 0.08) and functionality both in terms of stimulation index (3.31 ± 0.83 vs. 5.58 ± 3.38, p = 0.22) and insulin secretion (1.26 ± 0.83 vs. 1.53 ± 1.40 mean AUC, p = 0.73). Moreover, the size of the islets was significantly larger in the discontinuous vs. continuous purification group (19.2% ± 10.3% vs. 45.4% ± 18.8% of islets less than 100 µm, p = 0.0097 and 23.7% ± 5.3% vs. 15.6% ± 5.8% of 200–250 µm islet size, p = 0.03).

Conclusion

Compared to the conventional purification procedure, discontinuous purification with a bottle method shows similar results with regard to isolation yield and islet secretory function. Furthermore, this alternative technique allows for obtaining larger islets.
Atrial natriuretic peptide and leptin interactions in healthy men
Authors: Daniels Martin A. , Fischer-Posovszky Pamela , Boschmann Michael , Jumpertz-von Schwartzenberg Reiner , Müller Timo D. , Sandforth Leontine , Frank-Podlech Sabine , Hülskämper Sonja , Peter Andreas , Wabitsch Martin , Jordan Jens , Birkenfeld Andreas L.
Published: June 2023

Introduction

Atrial natriuretic peptide (ANP), a hormone secreted from the heart, controls cardiovascular and renal functions including arterial blood pressure and natriuresis. ANP also exerts metabolic effects in adipose tissue, liver and skeletal muscle, and interacts with the secretion of adipokines. We tested the hypothesis that ANP lowers concentrations of the anorexigenic adipokine leptin in healthy humans in vivo.

Methods

Human ANP or matching placebo was infused intravenously (iv) into healthy men in a controlled clinical trial.

Results

Within 135 minutes of iv ANP infusion, we observed an acute decrease in plasma leptin levels compared to controls. Free fatty acids markedly increased with ANP infusion in vivo, indicating activated lipolysis. In human SGBS adipocytes, ANP suppressed leptin release.

Discussion

The study shows that the cardiac hormone ANP reduces the levels of the anorexigenic adipokine leptin in healthy humans, providing further support for ANP as a cardiomyokine in a heart - adipose tissue axis. (registered in the German Clinical Trials Register and the WHO International Clinical Trials Registry Platform was granted under DRKS00024559)
A review on biochar’s effect on soil properties and crop growth
Authors: Premalatha R. P. , Poorna Bindu J. , Nivetha E. , Malarvizhi P. , Manorama K. , Parameswari E. , Davamani V.
Published: June 2023

Intensive cultivation of agricultural soils causes soil degradation which emphasizes the need for sustainable soil management. Biochar, a pyrolysed carbon rich material has gained great interests among the researchers because of its eco-friendly benefits in addition to soil quality enhancement. Reviews on biochar, mainly confined to its environmental benefits like carbon sequestration and climate change. In this review, we summarize i) the effect of biochar application on soil properties (physical, chemical, biological), ii) remediation potential of biochar in heavy metal contaminated soils and iii) its impact on crop productivity. The properties of biochar like pH, greater surface area, cation exchange capacity, and nutrient content positively influences the soil properties and ultimately improves the soil fertility. Their effectiveness depends on biochar type, its dosage, soil type, etc. General trends from this review indicated that biochar as an effective amendment in acid soils than the alkaline or calcareous soils. Furthermore, the biochar effects are studied mostly under controlled conditions in laboratory, which needs to be validated under field conditions having varied soil types and agro-climatic zones.
Long non-coding RNAs in non-small cell lung cancer: implications for EGFR-TKI resistance
Authors: Liu Detian , Lu Xiaolin , Huang Wentao , Zhuang Wei
Published: June 2023

Non-small cell lung cancer (NSCLC) is one of the most common types of malignant tumors as well as the leading cause of cancer-related deaths in the world. The application of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) has dramatically improved the prognosis of NSCLC patients who harbor EGFR mutations. However, despite an excellent initial response, NSCLC inevitably becomes resistant to EGFR-TKIs, leading to irreversible disease progression. Hence, it is of great significance to shed light on the molecular mechanisms underlying the EGFR-TKI resistance in NSCLC. Long non-coding RNAs (lncRNAs) are critical gene modulators that are able to act as oncogenes or tumor suppressors that modulate tumorigenesis, invasion, and metastasis. Recently, extensive evidence demonstrates that lncRNAs also have a significant function in modulating EGFR-TKI resistance in NSCLC. In this review, we present a comprehensive summary of the lncRNAs involved in EGFR-TKI resistance in NSCLC and focus on their detailed mechanisms of action, including activation of alternative bypass signaling pathways, phenotypic transformation, intercellular communication in the tumor microenvironment, competing endogenous RNAs (ceRNAs) networks, and epigenetic modifications. In addition, we briefly discuss the limitations and the clinical implications of current lncRNAs research in this field.
Two-Sample Mendelian Randomization detects bidirectional causality between gut microbiota and celiac disease in individuals with high genetic risk
Authors: González-García Bárbara P. , Marí Sergi , Cilleros-Portet Ariadna , Hernangomez-Laderas Alba , Fernandez-Jimenez Nora , García-Santisteban Iraia , Bilbao Jose Ramon
Published: June 2023

Background

Celiac Disease (CeD) is an autoimmune disorder triggered by gluten intake in genetically susceptible individuals. Highest risk individuals are homozygous for the Human Leucocyte Antigen (HLA) DQ2.5 haplotype or DQ2.5/DQ2.2 heterozygous. Both the HLA-DQ2-positive high genetic risk individuals and those that have developed the disease have altered intestinal microbiota, but it remains unclear whether these alterations are a cause or a consequence of CeD.

Objective

To investigate a potential bidirectional causality between gut microbiota (GM) and CeD in HLA-DQ2 high genetic risk individuals.

Materials and Methods

We performed a bidirectional Two-Sample Mendelian Randomization (2SMR) test using summary statistics from the largest publicly available Genome-Wide Association Study (GWAS) of GM and the summary statistics of the Immunochip CeD study of those individuals with the HLA-DQ2 high-risk haplotype. To test whether changes in GM composition were causally linked to CeD, GM data were used as exposure and CeD data as outcome; to test for reverse causation, the exposure and outcome datasets were inverted.

Results

We identified several bacteria from Ruminococcaceae and Lachnospiraceae families of the Firmicutes phylum as potentially causal in both directions. In addition, our results suggest that changes in the abundance of Veillonellaceae family might be causal in the development of CeD, while alterations in Pasteurellaceae family might be a consequence of the disease itself.

Conclusion

Our results suggest that the relationship between GM and HLA-DQ2 high risk individuals is highly complex and bidirectional.
Age-related changes of the innate immune system of the palatine tonsil in a healthy cohort
Authors: Andreas Nico , Geißler Katharina , Priese Juliane , Guntinas-Lichius Orlando , Kamradt Thomas
Published: June 2023

Although tonsillectomy is performed frequently, the role of palatine tonsils in life long immune protection or tolerance is still debated and the consequences of their removal for the immune system are of general interest. We analysed the tonsillar myeloid compartment in healthy subjects across a wide range of age (64% male; age range: 3 - 85 years) and compared its composition to the peripheral blood. We could observe a strong accumulation of all granulocyte subsets in the aging tonsil, which was most pronounced for basophils and mast cells. On functional level, an increase of CD163 and CD206 expression among monocytes and an increase of neutrophils expressing the inhibitory FcγRIIb correlated with increasing age. While the age-related shift of the leukocyte composition towards monocytes in blood is not reflected in tonsils, the increasing immunoregulatory phenotype of tonsilar monocytes is potentially counteracting the phenomenon of inflammaging at higher age.
Expression of HMGCS2 in intestinal epithelial cells is downregulated in inflammatory bowel disease associated with endoplasmic reticulum stress
Authors: Martín-Adrados Beatriz , Wculek Stefanie K. , Fernández-Bravo Sergio , Torres-Ruiz Raúl , Valle-Noguera Ana , Gomez-Sánchez Maria José , Hernández-Walias José Carlos , Ferreira Frederico Moraes , Corraliza Ana María , Sancho David , Esteban Vanesa , Rodriguez-Perales Sandra , Cruz-Adalia Aránzazu , Nakaya Helder I. , Salas Azucena , Bernardo David , Campos-Martín Yolanda , Martínez-Zamorano Elena , Muñoz-López Diego , Gómez del Moral Manuel , Cubero Francisco Javier , Blumberg Richard S. , Martínez-Naves Eduardo
Published: June 2023

Introduction

The Unfolded Protein Response, a mechanism triggered by the cell in response to Endoplasmic reticulum stress, is linked to inflammatory responses. Our aim was to identify novel Unfolded Protein Response-mechanisms that might be involved in triggering or perpetuating the inflammatory response carried out by the Intestinal Epithelial Cells in the context of Inflammatory Bowel Disease.

Methods

We analyzed the transcriptional profile of human Intestinal Epithelial Cell lines treated with an Endoplasmic Reticulum stress inducer (thapsigargin) and/or proinflammatory stimuli. Several genes were further analyzed in colonic biopsies from Ulcerative Colitis patients and healthy controls. Lastly, we generated Caco-2 cells lacking HMGCS2 by CRISPR Cas-9 and analyzed the functional implications of its absence in Intestinal Epithelial Cells.

Results

Exposure to a TLR ligand after thapsigargin treatment resulted in a powerful synergistic modulation of gene expression, which led us to identify new genes and pathways that could be involved in inflammatory responses linked to the Unfolded Protein Response. Key differentially expressed genes in the array also exhibited transcriptional alterations in colonic biopsies from active Ulcerative Colitis patients, including NKG2D ligands and the enzyme HMGCS2. Moreover, functional studies showed altered metabolic responses and epithelial barrier integrity in HMGCS2 deficient cell lines.

Conclusion

We have identified new genes and pathways that are regulated by the Unfolded Protein Response in the context of Inflammatory Bowel Disease including HMGCS2, a gene involved in the metabolism of Short Chain Fatty Acids that may have an important role in intestinal inflammation linked to Endoplasmic Reticulum stress and the resolution of the epithelial damage.
Global trends in surface eddy mixing from satellite altimetry
Authors: Zhang Guangchuang , Chen Ru , Li Laifang , Wei Hao , Sun Shantong
Published: June 2023

Mixing induced by oceanic mesoscale eddies can affect tracer distributions in the ocean and thus modulate the evolution of the physical and biochemical marine system. In the context of global warming, regionally different trends in eddy mixing could exist. Motivated by this hypothesis, we quantified the trend in surface eddy diffusivity, a metric widely used to quantify the eddy mixing rate, in the global ocean using satellite altimetry data. The global average of the particle-based eddy diffusivity increases by 284.1 m2s−1 per decade during the period of 1994-2017, or 3.7% per decade relative to its climatological mean value. In 54% of the global ocean, eddy diffusivity shows an increasing trend. The diffusivity trend can be decomposed into two components: one related to changes in eddy mixing length and the other related to eddy velocity magnitude. In 73% of the global ocean, changes in eddy mixing length account for more than 50% of the diffusivity trend. The suppressed mixing length theory (SMLT) is employed to interpret the trend in eddy mixing length. SMLT well captures the sign of the trend in two of the representative regions. Among all the parameters (e.g., eddy size, phase speed) inherent in SMLT, the eddy velocity magnitude plays a dominant role in determining the trend in the SMLT-based eddy mixing length. Diagnosing the geostrophic eddy kinetic energy budget reveals that the dominant mechanism for the trend in eddy velocity magnitude is the pressure work induced by ageostrophic flows. Our results suggest that a time-dependent eddy parameterization scheme should be employed in non-eddy-resolving models to account for the trend in eddy mixing.
Fatal fulminant hepatitis in a patient taking abiraterone acetate: a case report
Authors: Akpokavie Dela , Gubert Capucine , Abdelli Imene , Stern Alix O'Meara , Zender Hervé
Published: June 2023

Abiraterone acetate is a steroidal inhibitor of cytochrome P450 17A1 indicated in the treatment of metastatic prostate cancer. This report examines the case of a 66-year-old patient diagnosed with prostate adenocarcinoma that had metastasized to the bones and lymph nodes. Treatment with abiraterone acetate and corticosteroid co-administration as well as LH-RH analog hormone therapy was initiated. Four and a half months later, the patient consulted for deterioration of general condition. Biologically, he developed a fulminant hepatitis of which he eventually died. An infectious or metabolic origin was ruled out. Oncological cause by either disease progression or second neoplastic process was eliminated by means of imaging. Hepatic toxicity was imputed to the treatment with abiraterone acetate. This case suggests that fulminant hepatitis on abiraterone acetate may be underestimated, and underscores the importance of regular monitoring of liver tests on this therapy.
Neutrophil-to-lymphocyte ratio predicts 30-, 90-, and 180-day readmissions of patients with hepatic encephalopathy
Authors: Zhang Lin , Zhang Wei , Wang Jian , Jin Qian , Ma Danli , Huang Rui
Published: June 2023

Introduction

Hepatic encephalopathy (HE) is a significant complication of cirrhosis, known to be associated with hospital readmission. However, few new serological indicators associated with readmission in HE patients have been identified and reported. The objective of our study was to identify simple and effective predictors reated to readmission in HE patients.

Materials and methods

We conducted a retrospective study at a single center on adult patients admitted with HE from January 2018 to December 2022. The primary endpoint was the first liver-related readmission within 30, 90, and 180 days, and we collected electronic medical records from our hospital for sociodemographic, clinical, and hospitalization characteristics. We utilized logistic regression analysis and multiple linear regression analysis to determine the predictors that were associated with the readmission rate and the length of the first hospitalization.

Results

A total of 424 patients were included in the study, among whom 24 (5.7%), 63 (14.8%), and 92 (21.7%) were readmitted within 30, 90, and 180 days, respectively. Logistic regression analysis showed that insurance status, alcoholic liver disease (ALD), ascites, the model for end-stage liver disease (MELD) score, and neutrophil-to-lymphocyte ratio (NLR) were significantly associated with 30-, 90-, and 180-day readmissions. Age and hepatocellular carcinoma (HCC) were predictors of 90- and 180-day readmissions. ALD was identified as a unique predictor of readmission in men, while hypertension was a predictor of 180-day readmission in women. Variceal bleeding, chronic kidney disease, and MELD score were associated with the length of the first hospitalization.

Conclusions

NLR at discharge was identified as a significant predictor of 30-, 90- and 180-day readmissions in patients with HE. Our findings suggest that incorporating NLR into routine clinical assessments could improve the evaluation of the prognosis of liver cirrhosis.
The triangle relationship between human genome, gut microbiome, and COVID-19: opening of a Pandora’s box
Authors: Tong Jie , Chen Yuran , He Mei , Wang Wenjing , Wang Yiyang , Li Na , Xia Qianfeng
Published: June 2023

Since the pandemic started, the coronavirus disease 2019 (COVID-19) has spread worldwide. In patients with COVID-19, the gut microbiome (GM) has been supposed to be closely related to the progress of the disease. The gut microbiota composition and human genetic variation are also connected in COVID-19 patients, assuming a triangular relationship between the genome, GM, and COVID-19. Here, we reviewed the recent developments in the study of the relationship between gut microbiota and COVID-19. The keywords “COVID-19,” “microbiome,” and “genome” were used to search the literature in the PubMed database. We first found that the composition of the GM in COVID-19 patients varies according to the severity of the illness. Most obviously, Candida albicans abnormally increased while the probiotic Bifidobacterium decreased in severe cases of COVID-19. Interestingly, clinical studies have consistently emphasized that the family Lachnospiraceae plays a critical role in patients with COVID-19. Additionally, we have demonstrated the impact of microbiome-related genes on COVID-19. Specially, we focused on angiotensin-converting enzyme 2’s dual functions in SARS-CoV-2 infection and gut microbiota alternation. In summary, these studies showed that the diversity of GMs is closely connected to COVID-19. A triangular relationship exists between COVID-19, the human genome, and the gut flora, suggesting that human genetic variations may offer a chance for a precise diagnosis of COVID-19, and the important relationships between genetic makeup and microbiome regulation may affect the therapy of COVID-19.
Identification of microbial metabolic functional guilds from large genomic datasets
Authors: Reynolds Ryan , Hyun Sangwon , Tully Benjamin , Bien Jacob , Levine Naomi M.
Published: June 2023

Heterotrophic microbes play an important role in the Earth System as key drivers of major biogeochemical cycles. Specifically, the consumption rate of organic matter is set by the interaction between diverse microbial communities and the chemical and physical environment in which they reside. Modeling these dynamics requires reducing the complexity of microbial communities and linking directly with biogeochemical functions. Microbial metabolic functional guilds provide one approach for reducing microbial complexity and incorporating microbial biogeochemical functions into models. However, we lack a way to identify these guilds. In this study, we present a method for defining metabolic functional guilds from annotated genomes, which are derived from both uncultured and cultured organisms. This method utilizes an Aspect Bernoulli (AB) model and was tested on three large genomic datasets with 1,733–3,840 genomes each. Ecologically relevant microbial metabolic functional guilds were identified including guilds related to DMSP degradation, dissimilatory nitrate reduction to ammonia, and motile copiotrophy. This method presents a way to generate hypotheses about functions co-occurring within individual microbes without relying on cultured representatives. Applying the concept of metabolic functional guilds to environmental samples will provide new insight into the role that heterotrophic microbial communities play in setting rates of carbon cycling.
The platelet transcriptome and proteome in Alzheimer’s disease and aging: an exploratory cross-sectional study
Authors: de Sousa Diana M. Bessa , Poupardin Rodolphe , Villeda Saul A. , Schroer Adam B. , Fröhlich Thomas , Frey Vanessa , Staffen Wolfgang , Mrowetz Heike , Altendorfer Barbara , Unger Michael S. , Iglseder Bernhard , Paulweber Bernhard , Trinka Eugen , Cadamuro Janne , Drerup Martin , Schallmoser Katharina , Aigner Ludwig , Kniewallner Kathrin M.
Published: June 2023

Introduction: Alzheimer’s disease (AD) and aging are associated with platelet hyperactivity. However, the mechanisms underlying abnormal platelet function in AD and aging are yet poorly understood.

Methods: To explore the molecular profile of AD and aged platelets, we investigated platelet activation (i.e., CD62P expression), proteome and transcriptome in AD patients, non-demented elderly, and young individuals as controls.

Results: AD, aged and young individuals showed similar levels of platelet activation based on CD62P expression. However, AD and aged individuals had a proteomic signature suggestive of increased platelet activation compared with young controls. Transcriptomic profiling suggested the dysregulation of proteolytic machinery involved in regulating platelet function, particularly the ubiquitin-proteasome system in AD and autophagy in aging. The functional implication of these transcriptomic alterations remains unclear and requires further investigation.

Discussion: Our data strengthen the evidence of enhanced platelet activation in aging and provide a first glimpse of the platelet transcriptomic changes occurring in AD.
Task-specific training versus usual care to improve upper limb function after stroke: the “Task-AT Home” randomised controlled trial protocol
Authors: van Vliet Paulette , Carey Leeanne Mary , Turton Ailie , Kwakkel Gert , Palazzi Kerrin , Oldmeadow Christopher , Searles Andrew , Lavis Heidi , Middleton Sandy , Galloway Margaret , Dimech-Betancourt Bleydy , O'Keefe Sophie , Tavener Meredith
Published: June 2023

Background

Sixty percent of people have non-functional arms 6 months after stroke. More effective treatments are needed. Cochrane Reviews show low-quality evidence that task-specific training improves upper limb function. Our feasibility trial showed 56 h of task-specific training over 6 weeks resulted in an increase of a median 6 points on the Action Research Arm test (ARAT), demonstrating the need for more definitive evidence from a larger randomised controlled trial. Task-AT Home is a two-arm, assessor-blinded, multicentre randomised, controlled study, conducted in the home setting.

Aim

The objective is to determine whether task-specific training is a more effective treatment than usual care, for improving upper limb function, amount of upper limb use, and health related quality of life at 6 weeks and 6 months after intervention commencement. Our primary hypothesis is that upper limb function will achieve a ≥ 5 point improvement on the ARAT in the task-specific training group compared to the usual care group, after 6 weeks of intervention.

Methods

Participants living at home, with remaining upper limb deficit, are recruited at 3 months after stroke from sites in NSW and Victoria, Australia. Following baseline assessment, participants are randomised to 6 weeks of either task-specific or usual care intervention, stratified for upper limb function based on the ARAT score. The task-specific group receive 14 h of therapist-led task-specific training plus 42 h of guided self-practice. The primary outcome measure is the ARAT at 6 weeks. Secondary measures include the Motor Activity Log (MAL) at 6 weeks and the ARAT, MAL and EQ5D-5 L at 6 months. Assessments occur at baseline, after 6 weeks of intervention, and at 6 months after intervention commencement. Analysis will be intention to treat using a generalised linear mixed model to report estimated mean differences in scores between the two groups at each timepoint with 95% confidence interval and value of p.

Discussion

If the task-specific home-based training programme is more effective than usual care in improving arm function, implementation of the programme into clinical practice would potentially lead to improvements in upper limb function and quality of life for people with stroke.

Clinical Trial Registration

ANZCTR.org.au/ACTRN12617001631392p.aspx