bluuebunny/crossref_metadata_2025 huggingface dataset:
Modification of High-Quality Porous Concrete Asphalt with Local Materials as an Alternative to Flexible Pavement
Authors: Irawati Irawati , Dewi Ilanka Cahya
Published: June 2024

Environmental issues and a lack of attention to open space as rainwater catchment areas cause flooding problems in urban areas. Constructing environmentally friendly roads with permeable capabilities is one way to prevent waterlogging along the road in the rainy season. This study evaluated the type of porous asphalt concrete called Open Graded Friction Course specification Japanese standard. This study modified porous asphalt concrete using bamboo fiber and hydrated lime. Stability testing is conducted by the Marshall method, and the volumetric mixture is analyzed. Stability testing is carried out by the Marshall method and analysis of the volumetry of the mixture is carried out. The results showed that adding bamboo fiber and hydrated lime increased stability and maintained the porosity of the porous asphalt concrete.
Molecular targets and therapeutic potential of baicalein: a review
Authors: Munjal Kavita , Goel Yash , Gauttam Vinod Kumar , Chopra Hitesh , Singla Madhav , Smriti  , Gupta Saurabh , Sharma Rohit
Published: June 2024

Aim: Researchers using herbs and natural products to find new drugs often prefer flavonoids because of their potential as antioxidants and anti-inflammatories. The planned review addressed baicalein research findings in detail. This manuscript provides a complete review of baicalein’s potential pharmacological effects along with several molecular targets for better understanding of its therapeutic activities.
Materials and methods: We targeted the review on in vitro and in vivo studies reported on baicalein. For this, the literature is gathered from the database available on search engines like PubMed, ScienceDirect, Scopus, and Google Scholar up to 21 December 2023. The keywords “Scutellaria baicalensis”, “Oroxylum indicum”, “Neuroprotective”, “Cardioprotective”, “Toxicity studies”, and “Baicalein” were used to fetch the content.
Results: Baicalein’s molecular receptor binding approach has shown anticancer, antidiabetic, antimicrobial, antiaging, neuroprotective, cardioprotective, respiratory protective, gastroprotective, hepatic protective, and renal protective effects. The synergistic effects of this drug with other selective herbs are also contributed towards significant therapeutic potential.
Conclusion: This systematic review article from a contemporary and scientific perspective offers fresh insight into S. baicalensis, O. indicum, and its bioactive component baicalein as a potential complementary medicine. Baicalein may be transformed into more efficacious and acceptable evidence-based medicine. However, we recommend more clinical and mechanistic approaches to confirm safety and efficacy of baicalein.
Do Changes in Demographic Factors Affect Public Health Expenditures? The Case of Turkiye
Authors: Sarı Sacit
Published: June 2024

The main objective of this study is to analyze the effect of demographic factors on public health expenditures in the Turkish economy for the period between 1980 and 2021. Time series methods are employed in this analysis. The stationarity of the variables is tested with the conventional unit root test, while Zivot-Andrews unit root test is employed to identify potential structural breaks in the data. The existence of long-run relationships between non-stationary variables is investigated using the ARDL bounds test method. According to the analysis results, a persistent and statistically significant association exists between public health expenditures and GDP, contingent upon variables such as the old dependent population ratio, urbanization, and population. While increases in national product decrease public health expenditures, increases in demographic variables cause an overall rise in total public health expenditures. Increasing life expectancy, changing demographic structure, urbanization, and advances in medical technology have significantly increased health expenditures. Policymakers must establish strategies to boost the representation of the private sector in the health market if public health spending is to be sustainable and efficient.
Under the cover of ice: Trematode infections affect survival and growth of wintering mussels
Authors: Selbach C , de Framond-Benard E , Mouritsen KN
Published: June 2024

Parasites play many regulating roles that are increasingly recognized in different ecosystems. In coastal ecosystems, the trematode Himasthla elongata infects blue mussel Mytilus edulis, a foundation species that shapes the functioning of intertidal communities. Although the largest impacts of infections occur during the summer months, the parasites form long-lived cysts that can be harmful to their host mussels under winter conditions. Here, we experimentally show that even moderate levels of infection by H. elongata have a detrimental effect on the survival and growth rate of wintering blue mussels. These parasite-induced costs during winter may potentially affect populations of blue mussels in coastal habitats, with ramifications for the whole ecosystem.
Surveillance of Surgical Site Infections in Post-operative Patients and Bacterial Susceptibility in Tanzania
Authors: Karuhanga Theresia A , Madoshi Philbert B , Machang’u Robert S
Published: June 2024

Surgical site infections (SSI) are infections occurring within 30 days of the post-operative procedure. They are common post-operative morbid complications that may cause death if not treated timely. The common causes of SSI include infectious bacteria, such as Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, and some Enterobacteriaceae.

This was a cross-sectional study conducted at St. Francis Referral Hospital, Ifakatra, Tanzania over a period of 12 months to investigate the causes of SSI and antimicrobial susceptibility of the causal agents. The study included consenting patients who developed post-operative wound infections during the study period. Identification of infecting micro-organisms and their antimicrobial susceptibility was done at St Francis Referral Hospital Laboratory. Antibiotic susceptibility tests of the isolates were performed by the Kirby–Bauer (K–B 1966) disc diffusion test, and extended spectrum β-lactamase producing Gram-negative species were tested by using the modified double disc synergy test.

A total of 130 patients developed post-operative wound infection. Third and fourth decades were the most affected age groups; females were the dominant group with a 1:1.4 male: female ratio. Out of the 130 specimens, 121 isolates were obtained, and nine specimens were negative for culture. P. aeruginosa was the most commonly isolated agent (42.1%), followed by S. aureus (19.8%), while the least were Streptococcus spp. at 0.8%. The isolates showed the highest resistance to ampicillin (91.7%), and least to ciprofloxacin (1.7%). P. aeruginosa was highly resistant to both amoxicillin + clavulanic acid (98%), and to ampicillin (98.0%). Extended spectrum β-lactamase E. coli producers were 68.4%.

The bacteria causing SSI require continuous monitoring to obtain data that will support local and national guidelines in the battle against antimicrobial resistance, and improve therapeutic outcomes following surgical interventions.
Uncovering African Agency: The Media, Civil Society Organizations and Sino-Ghana Relations
Authors: NUNOO ISAAC
Published: June 2024

The burgeoning ‘ChinAfrica’ debates often fail to consider questions of African agency and in particular, the role played by civil society organizations (CSOs), the media and local groupings to give greater voice to African agency in Sino-African relations. Drawing on qualitative methods (interviews and content analysis), the study examines the relationship and focuses primarily on the case of Ghana to investigate how CSOs and the media engage, negotiate, influence, and resist Chinese actors' involvement in Africa. The findings posit that both Ghanaian state and non-state actors make efforts to influence and shape their engagement with the Chinese. Significantly, the media and CSOs, local community and private groupings exert greater agency and prompt state-level agency in Sino-African relations. Strikingly, it is revealed that the media, CSOs and local communities are sometimes complicit in the whole attempt at challenging and exposing Chinese activities in Ghana, especially in the mining and retail sectors.
Pendampingan Perancangan dan Pembuatan Neon Box Papan Reklame Display Produk Anyaman Bambu di Desa Duwet Kecamatan Tumpang Kabupaten Malang
Authors: Annisa Taufika Firdausi  , Putra Prima Arhandi  , Usman Nurhasan  , Ade Ismail  , Sofyan Noor Arief  , Fullchis Nurtjahjani
Published: June 2024

Kelompok pengrajin anyaman bambu menghadapi kesulitan dalam memasarkan produk kerajinan anyaman bambu. Serta bagaimana cara agar konsumen bisa mengetahui adanya produk kerajinan hasil anyaman bambu di desa Duwet kabupaten Malang dengan mudah. Untuk dapat mengatasi masalah tersebut maka diperlukan beberapa papan reklame neon box sebagai media promosi produk kerajinan anyaman bambu. Dalam rangka mengenalkan produk hasil pengrajin anyaman bambu diharapkan kelompok pengrajin anyaman dapat meningkatkan pengunjung yang datang untuk membeli produk mereka. Pengabdian ini melakukan beberapa kegiatan dengan survey lokasi untuk menentukan tempat mana yang sesuai dipasang papan reklame neon box. Selanjutnya adalah mendesain model yang menarik dan mudah dikenali dan dipahami oleh pengunjung. Setelah selesai mendesain maka dapat melakukan pemasangan komponen peralatan papan reklame neon box. Sesudah melakukan pemasangan setiap komponen papan reklame neon box selanutnya melakukan tahap finishing berupa pemasangan system kelistrikan yang desain dan kontennya sudah disetujui bersama dengan pihak mitra. Sesudah melakukan tahap instalasi kelistrikan maka di lakukan pemasangan pada titik lokasi yang sudah di tentukan. Untuk hasil akhir program adalah dapat meningkatkan pengunjung yang akan berwisata ke daerah desa Duwet Kabupaten Malang dan memperkenalkan kerajinan anyaman bambu yang telah diproduksi oleh penduduk setempat.
Peningkatan Kinerja TPST3R Tumpang Lestari
Authors: Muhammad Akhlis Rizza  , Hudriyah Mundzir
Published: June 2024

Peningkatan kinerja di TPST sangat diperlukan untuk meningkatkan kinerja penanganan sampah Peningkatan kinerja yang dilaksanakan ialah peningkatan efisiensi waktu, tempat, biaya, dan peningkatan kesehatan. Metode yang dipilih untuk peningkatan kinerja ialah mekanisasi proses dan peningkatan keselamatan kerja. Proses press sampah selama ini dilakukan manual sehingga memakan waktu lama dan hasilnya tidak maksimal. Selama ini proses sekali press sekitar 1 jam, dan ukurannya masih di atas 1 meter kubik. Oleh karena itu perlu dilakukan mekanisasi dengan membuat mesin press, sehingga proses pres sampah semakin cepat (1x press sekitar 10 menit) dan hasilnya bisa menghemat tempat hingga 50%. Selain itu dilakukan pemberian ceramah keselamatan kerja dan alat-alat keselamatan kerja untuk meninjgkatkan Kesehatan kerja para pekerja. Dengan terlaksananya pengabdian Masyarakat ini, maka kinerja TPST3R Tumpang Lestari bisa meningkat.
Pelatihan Kelistrikan Rumah Tangga Sederhana di Lembaga Bina Ummat Al-Furqon Sumbersekar, Kecamatan Dau
Authors: Nurul Achmadiah Mas , Setiawan Budhy , Muhammad Rifai  , Edi Sulistio Budi  , Gillang Al Azhar
Published: June 2024

Lembaga Bina Ummat (LBU) Al-Furqon berkantor di Kelurahan sumbersekar, Kecamatan Dau. Lembaga yang memiliki komitmen untuk menjadi yang terdepan dalam memberikan pelayanan kepada ummat. Salah satunya yaitu mengasuh para santri duafa dan yatim yang bertempat tinggal di pondok tahfidz Al-Qur’an. Dengan perkembangan zaman yang pesat saat ini, para santri perlu dibekali banyak keahlian tepat guna. Salah satu potensi keahlian yang dapat diberikan di LBU Al-Furqon adalah kelistrikan rumah tangga, karena hampir semua alat rumah tangga menggunakan elektronik, serta banyak masyarakat yang membutuhkan kemampuan tersebut. Kendala utama yang dihadapi adalah kurangnya tenaga ahli dibidangnya dan alat peraga untuk mempermudah proses pelatihan tersebut. Berdasarkan permasalahan tersebut, rencana tim pengusul PPM berupa: (1) Pengenalan tentang alat ukur listrik rumah tangga sederhana dan (2) Pelatihan instalasi listrik rumah tangga sederhana. Setelah terselenggaranya pelatihan ini, maka santri dari Lembaga Bina Ummat Al-Furqon Sumbersekar, Kecamatan Dau memiliki pengetahuan terkait kelistrikan sederhana yang bermanfaat baik diri sendiri maupun bagi pondok pesantrennya.
An Analysis of Explicatures in English -Arabic Subtitles: The Case of Friends on Netflix.
Authors: Ali Sukayna , Eliza Abdul Rahman Wan Rose , Chow Yean Fun
Published: June 2024

Abstract
This study examines the presence of explicatures in subtitling, with a specific focus on the prioritization of different areas of explicatures in English-Arabic subtitles of the American sitcom Friends on Netflix. Sperber and Wilson (1986) introduced the concept of explicatures, which pertains to developments made by communicators to the explicit content of their utterances. This study utilizes Relevance Theory (1986) and Huang's (2014) explicature classifications. The study's findings suggest that the investigated subtitles contain all five areas of explicatures. Additionally, the study indicates that the subtitler did not consistently observe all areas of explicatures. Disambiguation was the most commonly observed, whereas saturation was the least frequently observed area.
The Flexibility of Placing the Subject in Arabic Sentences: A Study of Syntactic Word Order Restrictions and their Application to Arabic Grammar
Authors: Al-Qayyam Ismael Mahmoud ,  Rabab’ah Yousuf Abdulraheem
Published: June 2024

This research addresses the possibility of placing the subject in a pre-verb position in verbal sentences in Arabic, without necessarily stipulating that if the subject is preposed before the verb, it becomes a topic. In this way, the subject is a non-overt pronoun positioned within or after the verb, because the subject is conventionally acknowledged by grammarians to move freely to various post-verbal positions, but never pre-verbally. The research considers the views and opinions of linguists and grammarians who have dealt with this issue in detail, presenting a discussion of these views to reveal the strict restrictions imposed on the movement of the subject. It is hoped that this will contribute to the facilitation of teaching and learning Arabic grammar. It will also revitalize the discussion of views in Arabic grammatical traditions to try to establish new grammatical principles that contemporary linguists may adopt when reformulating the rules of Arabic grammar. This endeavor may simplify the task of learning rules and contribute to presenting them more flexibly and plausibly.
A Panel Data Analysis on the Relationship between Financial Development and Economic Growth: The Case of Asian Countries
Authors: Sugözü İbrahim Halil , Ünver Eriş
Published: June 2024

The causal relationship between economic growth and financial development is crucial for the dynamics of economic growth and the financial background it generates. However, doubts about the shape of the relationship may lead to indecision in the economic policies to be implemented. The aim of this study is to analyze and provide evidence on the relationship between the two variables in order to overcome this ambivalence. In this panel data analysis of 24 Asian countries covering the 2000-2020 period, firstly Cross-sectionally Augmented Dickey-Fuller (CADF) Unit Root Test, one of the second-generation unit root tests, and then Dumitrescu & Hurlin (2012) Panel Z_NT causality tests were applied. According to the causality test results, there is a bidirectional relationship between GDP and financial development. In addition, gross fixed capital formation (GFCF), which is included in the model as a control variable, is also found to have a bidirectional relationship with both variables. Thus, the evidence supporting the interaction view that combines supply and demand side theories reveals the importance of taking both variables into account in economic policy decisions.
Advancements in osteosarcoma management: integrating immune microenvironment insights with immunotherapeutic strategies
Authors: Liang Hang , Cui Min , Tu Jingyao , Chen Xinyi
Published: June 2024

Osteosarcoma, a malignant bone tumor predominantly affecting children and adolescents, presents significant therapeutic challenges, particularly in metastatic or recurrent cases. Conventional surgical and chemotherapeutic approaches have achieved partial therapeutic efficacy; however, the prognosis for long-term survival remains bleak. Recent studies have highlighted the imperative for a comprehensive exploration of the osteosarcoma immune microenvironment, focusing on the integration of diverse immunotherapeutic strategies—including immune checkpoint inhibitors, tumor microenvironment modulators, cytokine therapies, tumor antigen-specific interventions, cancer vaccines, cellular therapies, and antibody-based treatments—that are directly pertinent to modulating this intricate microenvironment. By targeting tumor cells, modulating the tumor microenvironment, and activating host immune responses, these innovative approaches have demonstrated substantial potential in enhancing the effectiveness of osteosarcoma treatments. Although most of these novel strategies are still in research or clinical trial phases, they have already demonstrated significant potential for individuals with osteosarcoma, suggesting the possibility of developing new, more personalized and effective treatment options. This review aims to provide a comprehensive overview of the current advancements in osteosarcoma immunotherapy, emphasizing the significance of integrating various immunotherapeutic methods to optimize therapeutic outcomes. Additionally, it underscores the imperative for subsequent research to further investigate the intricate interactions between the tumor microenvironment and the immune system, aiming to devise more effective treatment strategies. The present review comprehensively addresses the landscape of osteosarcoma immunotherapy, delineating crucial scientific concerns and clinical challenges, thereby outlining potential research directions.
Fuzzy Markov model for the reliability analysis of hybrid microgrids
Authors: Swain Kunjabihari , Cherukuri Murthy , Samanta Indu Sekhar , Pati Abhilash , Giri Jayant , Panigrahi Amrutanshu , Qin Hong , Mallik Saurav
Published: June 2024

This research presents a process for analyzing a hybrid microgrid's dependability using a fuzzy Markov model. The research initiated an analysis of the various microgrid components, such as wind power systems, solar photovoltaic (PV) systems, and battery storage systems. The states that are induced by component failures are represented using a state-space model. The research continues by suggesting a hybrid microgrid reliability model that analyzes data using a Markov process. Problems arise when trying to estimate reliability metrics for the microgrid using data that is both restricted and imprecise. This is why the study takes uncertainties into account to make microgrid reliability estimations more realistic. The importance of microgrid components concerning their overall availability is evaluated using fuzzy sets and reliability assessments. The study uses numerical analysis and then carefully considers the outcomes. The overall availability of hybrid microgrids is 0.99999.
Biomechanical dysregulation of SGK-1 dependent aortic pathologic markers in hypertension
Authors: Gedney J. Ryan , Mattia Victoria , Figueroa Mario , Barksdale Christian , Fannin Ethan , Silverman Jonah , Xiong Ying , Mukherjee Rupak , Jones Jeffrey A. , Ruddy Jean Marie
Published: June 2024

Introduction

In hypertension (HTN), biomechanical stress may drive matrix remodeling through dysfunctional VSMC activity. Prior evidence has indicated VSMC tension-induced signaling through the serum and glucocorticoid inducible kinase-1 (SGK-1) can impact cytokine abundance. Here, we hypothesize that SGK-1 impacts production of additional aortic pathologic markers (APMs) representing VSMC dysfunction in HTN.

Methods

Aortic VSMC expression of APMs was quantified by QPCR in cyclic biaxial stretch (Stretch) +/− AngiotensinII (AngII). APMs were selected to represent VSMC dedifferentiated transcriptional activity, specifically Interleukin-6 (IL-6), Cathepsin S (CtsS), Cystatin C (CysC), Osteoprotegerin (OPG), and Tenascin C (TNC). To further assess the effect of tension alone, abdominal aortic rings from C57Bl/6 WT mice were held in a myograph at experimentally derived optimal tension (OT) or OT + 30% +/−AngII. Dependence on SGK-1 was assessed by treating with EMD638683 (SGK-1 inhibitor) and APMs were measured by QPCR. Then, WT and smooth muscle cell specific SGK-1 heterozygous knockout (SMC-SGK-1KO+/−) mice had AngII-induced HTN. Systolic blood pressure and mechanical stress parameters were assessed on Day 0 and Day 21. Plasma was analyzed by ELISA to quantify APMs. Statistical analysis was performed by ANOVA.

Results

In cultured aortic VSMCs, expression of all APMs was increased in response to biomechanical stimuli (Stretch +/−AngII,). Integrating the matrix contribution to signal transduction in the aortic rings led to IL-6 and CysC demonstrating SGK-1 dependence in response to elevated tension and interactive effect with concurrent AngII stimulation. CtsS and TNC, on the other hand, primarily responded to AngII, and OPG expression was unaffected in aortic ring experimentation. Both mouse strains had >30% increase in blood pressure with AngII infusion, reduced aortic distensibility and increased PPV, indicating increased aortic stiffness. In WT + AngII mice, IL-6, CtsS, CysC, and TNC plasma levels were significantly elevated, but these APMs were unaffected by HTN in the SMC-SGK-1KO+/− +AngII mice, suggesting SGK-1 plays a major role in VSMC biomechanical signaling to promote dysfunctional production of selected APMs.

Conclusion

In HTN, changes in the plasma levels of markers associated with aortic matrix homeostasis can reflect remodeling driven by mechanobiologic signaling in dysfunctional VSMCs, potentially through the activity of SGK-1. Further defining these pathways may identify therapeutic targets to reduce cardiovascular morbidity and mortality.
Non-invasive assessment of proarrhythmic risks associated with isoprenaline and the dietary supplement ingredient synephrine using human induced pluripotent stem cell-derived cardiomyocytes
Authors: Yuan Xin , Yu Tingting , Zhang Zhang , Li Sen
Published: June 2024

Background

There have been conflicting reports about the proarrhythmic risk of p-synephrine (SYN). To address this, human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) combined with the microelectrode array (MEA) system have been utilized to assess arrhythmia risks, particularly in the context of adrenomimetic drugs.

Aim

This study aims to determine whether MEA recordings from hiPSC-CMs could predict the proarrhythmic risk of adrenomimetic drugs and to investigate the cardiovascular effects and mechanisms of SYN.

Materials and methods

We employed MEA recordings to assess the electrophysiological properties of hiPSC-CMs and conducted concentration-response analyses to evaluate the effects of SYN and Isoprenaline (ISO) on beating rate and contractility. A risk scoring system for proarrhythmic risks was established based on hiPSC-CMs in this study. ISO, a classic beta-adrenergic drug, was also evaluated. Furthermore, the study evaluated the risk of SYN and recorded the concentration-response of beating rate, contractility and the change in the presence or absence of selective β1, β2 and β3 adrenergic blockers.

Results

Our results suggested that ISO carries a high risk of inducing arrhythmias, aligning with existing literature. SYN caused a 30% prolongation of the field potential duration (FPD) at a concentration of 206.326 μM, a change significantly different from baseline measurements and control treatments. The half maximal effective concentration (EC50) of SYN (3.31 μM) to affect hiPSC-CM beating rate is much higher than that of ISO (18.00 nM). The effect of SYN at an EC50 of 3.31 μM is about ten times more potent in hiPSC-CMs compared to neonatal rat cardiomyocytes (34.12 μM). SYN increased the contractility of cardiomyocytes by 29.97 ± 11.65%, compared to ISO's increase of 50.56 ± 24.15%. β1 receptor blockers almost eliminated the beating rate increase induced by both ISO and SYN, while neither β2 nor β3 blockers had a complete inhibitory effect.

Conclusion

The MEA and hiPSC-CM system could effectively predict the risk of adrenomimetic drugs. The study concludes that the proarrhythmia risk of SYN at conventional doses is low. SYN is more sensitive in increasing beating rate and contractility in human cardiomyocytes compared to rats, primarily activating β1 receptor.
Effect of blood flow-restrictive resistance training on metabolic disorder and body composition in older adults with type 2 diabetes: a randomized controlled study
Authors: Ma Xiaojun , Ai Yuxin , Lei Fulian , Tang Xuan , Li Qingmei , Huang Yixin , Zhan Yating , Mao Quan , Wang Liduo , Lei Fenfang , Yi Qinyu , Yang Fan , Yin Xiaogang , He Binghua , Zhou Lei , Ruan Sijie
Published: June 2024

Introduction

To explore whether blood flow-restrictive resistance exercise (BFRE) can be used as an alternative strategy to moderate-intensity resistance training (RT) to improve metabolic disorder and body composition in older adults with type 2 diabetes (T2DM).

Methods

This is a single-blind, randomized, controlled trial. Ninety-eight older adults with T2DM were randomly divided into three groups: BFRE group (n = 34), RT group (n = 31) and control group (n = 33). Two exercise groups received supervised collective training for a period of six months, each lasting 50 min, three times a week. The primary outcomes included fasting plasma glucose (FPG), Glycosylated hemoglobin (HbA1c), blood lipids, blood pressure, and body composition. The secondary outcome was muscle performance.

Results

After six months of intervention, the FPG, HbA1c, blood lipids, diastolic blood pressure, body composition, and muscle performance of the two exercise groups were significantly improved relative to the control group and baseline measurements (P < 0.05). There was no significant increase in lean mass between the two exercise groups compared to the control group and baseline (p > 0.05). There was no significant decrease in systolic blood pressure between the two exercise groups compared to the control group (p > 0.05), but it was significantly lower than their baseline (P < 0.05). There was no significant difference in all indicators between the two exercise groups at the baseline, third and sixth months of intervention (p > 0.05).

Discussion

BFRE can safely and effectively improve the metabolic disorder and body composition of older adults with T2DM. For elderly exercise beginners, BFRE can be used as an alternative strategy to moderate-intensity resistance training.

Clinical trial registration

https://www.chictr.org.cn/showproj.html?proj=178886, identifier ChiCTR2300074357.
High coverage of targeted lipidomics revealed lipid changes in the follicular fluid of patients with insulin-resistant polycystic ovary syndrome and a positive correlation between plasmalogens and oocyte quality
Authors: Zhang Meizi , Wang Yuanyuan , Di Jianyong , Zhang Xuanlin , Liu Ye , Zhang Yixin , Li Bowen , Qi Simeng , Cao Xiaomin , Liu Li , Liu Shouzeng , Xu Fengqin
Published: June 2024

Background

Polycystic ovary syndrome with insulin resistance (PCOS-IR) is the most common endocrine and metabolic disease in women of reproductive age, and low fertility in PCOS patients may be associated with oocyte quality; however, the molecular mechanism through which PCOS-IR affects oocyte quality remains unknown.

Methods

A total of 22 women with PCOS-IR and 23 women without polycystic ovary syndrome (control) who underwent in vitro fertilization and embryo transfer were recruited, and clinical information pertaining to oocyte quality was analyzed. Lipid components of follicular fluid (FF) were detected using high-coverage targeted lipidomics, which identified 344 lipid species belonging to 19 lipid classes. The exact lipid species associated with oocyte quality were identified.

Results

The number (rate) of two pronuclear (2PN) zygotes, the number (rate) of 2PN cleaved embryos, and the number of high-quality embryos were significantly lower in the PCOS-IR group. A total of 19 individual lipid classes and 344 lipid species were identified and quantified. The concentrations of the 19 lipid species in the normal follicular fluid (control) ranged between 10-3 mol/L and 10-9 mol/L. In addition, 39 lipid species were significantly reduced in the PCOS-IR group, among which plasmalogens were positively correlated with oocyte quality.

Conclusions

This study measured the levels of various lipids in follicular fluid, identified a significantly altered lipid profile in the FF of PCOS-IR patients, and established a correlation between poor oocyte quality and plasmalogens in PCOS-IR patients. These findings have contributed to the development of plasmalogen replacement therapy to enhance oocyte quality and have improved culture medium formulations for oocyte in vitro maturation (IVM).
Beta cell dedifferentiation in type 1 diabetes: sacrificing function for survival?
Authors: Webster Kierstin L. , Mirmira Raghavendra G.
Published: June 2024

The pathogeneses of type 1 and type 2 diabetes involve the progressive loss of functional beta cell mass, primarily attributed to cellular demise and/or dedifferentiation. While the scientific community has devoted significant attention to unraveling beta cell dedifferentiation in type 2 diabetes, its significance in type 1 diabetes remains relatively unexplored. This perspective article critically analyzes the existing evidence for beta cell dedifferentiation in type 1 diabetes, emphasizing its potential to reduce beta cell autoimmunity. Drawing from recent advancements in both human studies and animal models, we present beta cell identity as a promising target for managing type 1 diabetes. We posit that a better understanding of the mechanisms of beta cell dedifferentiation in type 1 diabetes is key to pioneering interventions that balance beta cell function and immunogenicity.
Conceptualising energy nationalism in the context of climate change: framework and review
Authors: Żuk Piotr , Conversi Daniele , Żuk Paweł
Published: June 2024

This article argues that the more energy policies are circumscribed within the borders of individual nation states, the more difficult it will be to implement the climate action on a global scale. The authors shed light on the relationship between nationalism and the simultaneous challenges of environmental protection, energy transition and climate change mitigation. Based on the review of various publications referring to nationalism in the context of energy policy and energy transition, the authors conceptualise this notion. Energy nationalism is defined here as any political decision, economic action and ideological justifications used to circumscribe energy policy within the nation state and subordinate it to “national interests,” “national security” and the “protection of national sovereignty.” Energy nationalism should be distinguished from both economic nationalism and resource nationalism, yet they are part of a continuum, in which economic considerations are upheld in the pursuit of strict national “interests” and, therefore, of the ruling elites in each nation state. The article explores the differences and mutual interconnections between the three. It finally explains why the notion of energy nationalism may better render the ongoing conflict between resource-focused elites and the international community–particularly in the context of the current climate emergency.
An efficient multi-timescale regulation strategy for distribution networks based on active and passive resources combined
Authors: Li Kewen , Lin Xinhao , Zhang Wei , Yu Lei , Chen Qianyi , Liu Yinliang , Ou Shifeng , Xu Min , Li Junhao
Published: June 2024

Introducing solar and wind power into distribution networks (DNs) is an important initiative to promote the cleanliness and low-carbonization operation of DNs. However, the source and load outputs are uncertain in DNs, which will lead to problems of inaccurate regulation and insufficient renewable energy utilization. Therefore, this study provides an efficient multi-timescale regulation strategy for DNs based on active and passive resources combined. First, the day-ahead regulation model is constructed to minimize the total operating cost in a day for DNs. It aims to determine the on-load tap changer (OLTC) and capacitor bank (CB) switching schemes and consider them as the constraints for intraday regulation by power flow unification. Then, an intraday source and load uncertainty model is considered, which aims to cope with the problems of inaccuracies in the day-ahead source and load prediction. Based on this, the objective function of the intraday regulation model is set. It aims to minimize the deviation from the total day-ahead cost and then ensure the optimal system economy and determine the intraday new energy and energy storage system (ESS) short-time action scheme. Finally, the example results show that the proposed scheme can achieve the maximum utilization of renewable energy and improve the low-carbon economic operation of the whole system.
Micro-electric tractors for deep bed farming and sustainable micro-grid electricity
Authors: Williams Toby , Wilson Jonathan , Partington Lee , Andrews Cameron , Chavula Isaac , Gondwe France , Betts Tom , Strickland Dani
Published: June 2024

This paper describes an innovative method to provide a micro-electric tractor which has been developed as part of an initiative that aims to provide socially inclusive and affordable green energy solutions to smallholders in sub-Saharan Africa. It utilizes a 15.0-kW solar array and battery system to power micro-electric tractors for an agricultural practice called deep bed farming in Malawi. Deep bed farming increases smallholder crop yield by about two and half times, which increases revenue by up to 12 times. The extra revenue can then be used to perpetually purchase domestic energy from the solar array, creating a self-sustaining model for decentralized energy access. However, the requirement for land preparation is onerous, and mechanization is needed to help overcome barriers to entry. This paper describes the technical requirements of a solar base station and micro-tractor for use with the deep bed farming technique. The paper covers the 5.9 kWp modular solar design and a 10.0-kWh rated micro-tractor. Testing was undertaken at an isolated grid in Loughborough as a precursor for large-scale testing in Malawi.
Worldwide cohort study of 46, XY differences/disorders of sex development genetic diagnoses: geographic and ethnic differences in variants
Authors: Jiali Chen , Huifang Peng , Yuqing Jiang , Xiantao Zeng , Hongwei Jiang
Published: June 2024

Differences/disorders of sex development (DSDs) in individuals with a 46, XY karyotype are a group of congenital disorders that manifest as male gonadal hypoplasia or abnormalities of the external genitalia. Approximately 50% of patients with 46, XY DSDs cannot obtain a molecular diagnosis. The aims of this paper were to review the most common causative genes and rare genes in patients with 46, XY DSDs, analyze global molecular diagnostic cohorts for the prevalence and geographic distribution of causative genes, and identify the factors affecting cohort detection results. Although the spectrum of genetic variants varies across regions and the severity of the clinical phenotype varies across patients, next-generation sequencing (NGS), the most commonly used detection method, can still reveal genetic variants and aid in diagnosis. A comparison of the detection rates of various sequencing modalities revealed that whole-exome sequencing (WES) facilitates a greater rate of molecular diagnosis of the disease than panel sequencing. Whole-genome sequencing (WGS), third-generation sequencing, and algorithm advancements will contribute to the improvement of detection efficiency. The most commonly mutated genes associated with androgen synthesis and action are AR, SR5A2, and HSD17B3, and the most commonly mutated genes involved in gonadal formation are NR5A1 and MAP3K1. Detection results are affected by differences in enrollment criteria and sequencing technologies.
Garlic bioactive substances and their therapeutic applications for improving human health: a comprehensive review
Authors: El-Saadony Mohamed T. , Saad Ahmed M. , Korma Sameh A. , Salem Heba M. , Abd El-Mageed Taia A. , Alkafaas Samar Sami , Elsalahaty Mohamed I. , Elkafas Sara Samy , Mosa Walid F. A. , Ahmed Ahmed Ezzat , Mathew Betty T. , Albastaki Noor A. , Alkuwaiti Aysha A. , El-Tarabily Marawan K. , AbuQamar Synan F. , El-Tarabily Khaled A. , Ibrahim Salam A.
Published: June 2024

Garlic (Allium sativum L.) is a widely abundant spice, known for its aroma and pungent flavor. It contains several bioactive compounds and offers a wide range of health benefits to humans, including those pertaining to nutrition, physiology, and medicine. Therefore, garlic is considered as one of the most effective disease-preventive diets. Many in vitro and in vivo studies have reported the sulfur-containing compounds, allicin and ajoene, for their effective anticancer, anti-diabetic, anti-inflammatory, antioxidant, antimicrobial, immune-boosting, and cardioprotective properties. As a rich natural source of bioactive compounds, including polysaccharides, saponins, tannins, linalool, geraniol, phellandrene, β-phellandrene, ajoene, alliin, S-allyl-mercapto cysteine, and β-phellandrene, garlic has many therapeutic applications and may play a role in drug development against various human diseases. In the current review, garlic and its major bioactive components along with their biological function and mechanisms of action for their role in disease prevention and therapy are discussed.
Investigating cellular similarities and differences between upper tract urothelial carcinoma and bladder urothelial carcinoma using single-cell sequencing
Authors: Zhang Qingyun , Wang Chengbang , Qin Min , Ye Yu , Mo Yingxi , Meng Qinggui , Yang Guanglin , Feng Guanzheng , Lin Rui , Xian Shinan , Wei Jueling , Chen Shaohua , Wang Shan , Mo Zengnan
Published: June 2024

Background

Upper tract urothelial carcinoma (UTUC) and bladder urothelial carcinoma (BLCA) both originate from uroepithelial tissue, sharing remarkably similar clinical manifestations and therapeutic modalities. However, emerging evidence suggests that identical treatment regimens may lead to less favorable outcomes in UTUC compared to BLCA. Therefore, it is imperative to explore molecular processes of UTUC and identify biological differences between UTUC and BLCA.

Methods

In this study, we performed a comprehensive analysis using single-cell RNA sequencing (scRNA-seq) on three UTUC cases and four normal ureteral tissues. These data were combined with publicly available datasets from previous BLCA studies and RNA sequencing (RNA-seq) data for both cancer types. This pooled analysis allowed us to delineate the transcriptional differences among distinct cell subsets within the microenvironment, thus identifying critical factors contributing to UTUC progression and phenotypic differences between UTUC and BLCA.

Results

scRNA-seq analysis revealed seemingly similar but transcriptionally distinct cellular identities within the UTUC and BLCA ecosystems. Notably, we observed striking differences in acquired immunological landscapes and varied cellular functional phenotypes between these two cancers. In addition, we uncovered the immunomodulatory functions of vein endothelial cells (ECs) in UTUC, and intercellular network analysis demonstrated that fibroblasts play important roles in the microenvironment. Further intersection analysis showed that MARCKS promote UTUC progression, and immunohistochemistry (IHC) staining revealed that the diverse expression patterns of MARCKS in UTUC, BLCA and normal ureter tissues.

Conclusion

This study expands our multidimensional understanding of the similarities and distinctions between UTUC and BLCA. Our findings lay the foundation for further investigations to develop diagnostic and therapeutic targets for UTUC.
Genetic association of the gut microbiota with epigenetic clocks mediated by inflammatory cytokines: a Mendelian randomization analysis
Authors: Tian Siyu , Liao Xingyu , Chen Siqi , Wu Yu , Chen Min
Published: June 2024

Background

A new aging biomarker epigenetic clock has been developed. There exists a close link between aging and gut microbiota, which may be mediated by inflammatory cytokines. However, the relationship between the epigenetic clock, gut microbiota, and the mediating substances is unclear.

Methods

Two large genome-wide association meta-analyses were analyzed by two-sample Mendelian randomization. The results between gut microbiota and epigenetic clock were investigated using the four methods (Inverse variance weighted, MR-Egger, weighted median, MR-PRESSO). Genetic correlation was measured by Linked disequilibrium score regression (LDSC). The correctness of the study direction was checked by the Steiger test. Cochran’s Q statistic and MR-Egger intercept were used as sensitivity analyses of the study. The two-step method was used to examine the mediating role of inflammatory cytokines. We use the Benjamini-Hochberg correction method to correct the P value.

Results

After FDR correction, multiple bacterial genera were significantly or suggestively associated with four epigenetic clocks (GrimAge, HannumAge, IEAA, PhenoAge). And we detected several inflammatory factors acting as mediators of gut microbiota and epigenetic clocks.

Conclusion

This study provides genetic evidence for a positive and negative link between gut microbiota and aging risk. We hope that by elucidating the genetic relationship and potential mechanisms between aging and gut microbiota, we will provide new avenues for continuing aging-related research and treatment.
A pan-cancer single-cell transcriptional analysis of antigen-presenting cancer-associated fibroblasts in the tumor microenvironment
Authors: Chen Juntao , Chen Renhui , Huang Jingang
Published: June 2024

Background

Cancer-associated fibroblasts (CAFs) are the primary stromal cells found in tumor microenvironment, and display high plasticity and heterogeneity. By using single-cell RNA-seq technology, researchers have identified various subpopulations of CAFs, particularly highlighting a recently identified subpopulation termed antigen-presenting CAFs (apCAFs), which are largely unknown.

Methods

We collected datasets from public databases for 9 different solid tumor types to analyze the role of apCAFs in the tumor microenvironment.

Results

Our data revealed that apCAFs, likely originating mainly from normal fibroblast, are commonly found in different solid tumor types and generally are associated with anti-tumor effects. apCAFs may be associated with the activation of CD4+ effector T cells and potentially promote the survival of CD4+ effector T cells through the expression of C1Q molecules. Moreover, apCAFs exhibited highly enrichment of transcription factors RUNX3 and IKZF1, along with increased glycolytic metabolism.

Conclusions

Taken together, these findings offer novel insights into a deeper understanding of apCAFs and the potential therapeutic implications for apCAFs targeted immunotherapy in cancer.
Healthcare resource utilization patterns in psoriasis patients using biologic and conventional treatments in Finland
Authors: Vesikansa Aino , Mehtälä Juha , Aaltonen Jaakko , Konttinen Riikka , Tasanen Kaisa , Huilaja Laura
Published: June 2024

Introduction and aim

Psoriasis vulgaris is associated with a significant healthcare burden, which increases over time as the disease progresses. The aim of this retrospective, population-based registry study was to characterize healthcare resource utilization (HCRU) in patients with psoriasis using biologics and oral immunosuppressants (conventionals) in Finland.

Materials and methods

The study cohort included all patients with a diagnosis of psoriasis vulgaris in the secondary healthcare setting between 2012–2018, who initiated a biologic (n=1,297) or conventional (n=4,753) treatment between 2013–2017. Data on primary and secondary HCRU were collected from nationwide healthcare registries.

Results

The results indicated a remarkable decrease in contacts with a dermatologist after the treatment initiation among patients starting biologic (mean annual number of contacts 5.4 per person before and 2.3 after the initiation), but not conventional (3.3 and 3.2) treatment. For conventional starters there was a high level of contacts with a dermatologist surrounding times of treatment switching, which was not observed for biologic starters.

Conclusion

Overall, primary and other secondary care contacts did not decrease after the initiation or switch of treatment. The results highlight the importance of thorough consideration of the most optimal treatment alternatives, considering the overall disease burden to patients and healthcare systems.
Human milk oligosaccharides regulate human macrophage polarization and activation in response to Staphylococcus aureus
Authors: Jepsen Stine Dam , Lund Astrid , Matwiejuk Martin , Andresen Lars , Christensen Kristine Rothaus , Skov Søren
Published: June 2024

Human milk oligosaccharides (HMOs) are present in high numbers in milk of lactating women. They are beneficial to gut health and the habitant microbiota, but less is known about their effect on cells from the immune system. In this study, we investigated the direct effect of three structurally different HMOs on human derived macrophages before challenge with Staphylococcus aureus (S. aureus). The study demonstrates that individual HMO structures potently affect the activation, differentiation and development of monocyte-derived macrophages in response to S. aureus. 6´-Sialyllactose (6’SL) had the most pronounced effect on the immune response against S. aureus, as illustrated by altered expression of macrophage surface markers, pointing towards an activated M1-like macrophage-phenotype. Similarly, 6’SL increased production of the pro-inflammatory cytokines TNF-α, IL-6, IL-8, IFN-γ and IL-1β, when exposing cells to 6’SL in combination with S. aureus compared with S. aureus alone. Interestingly, macrophages treated with 6’SL exhibited an altered proliferation profile and increased the production of the classic M1 transcription factor NF-κB. The HMOs also enhanced macrophage phagocytosis and uptake of S. aureus. Importantly, the different HMOs did not notably affect macrophage activation and differentiation without S. aureus exposure. Together, these findings show that HMOs can potently augment the immune response against S. aureus, without causing inflammatory activation in the absence of S. aureus, suggesting that HMOs assist the immune system in targeting important pathogens during early infancy.