bluuebunny/crossref_metadata_2025 huggingface dataset:
STRATEGI PERTAHANAN MARITIM INDONESIA SEBAGAI RESPON TERHADAP SENGKETA DI WILAYAH LAUT CINA SELATAN
Authors: Pasaribu Nico Daniel , Prakoso Lukman Yudho
Published: February 2024

Abstrak: Dinamika lingkungan strategis di kawasan Laut China Selatan terus mengalamiperubahan. Indonesia yang secara tegas mendeklarasikan dirinya sebagai non-claimantstatesturutdalam arena persengketaan dalam upaya claimant-states dalam merebutkan hak di Laut CinaSelatan. Sengketa tersebut melibatkan Indonesia akibat adanya klaim wilayah Laut Cina Selatanoleh Tiongkok yang beririsan dengan wilayah yurisdiksi ZEE Indonesia di laut Natuna Utara.Tujuan penelitian ini adalah untuk menjelaskan lebih lanjut mengenai stratrgi pertahanan maritimIndonesia sebagai respon terhadap konflik Laut Cina Selatan. Penelitian ini dikembangkanmenggunakan metode studi kepustakaan. Hasil penelitian menunjukkan bahwa pemerintah telahmelakukan sejumlah upaya yang diperlukan terkait dengan sengketa Laut Cina Selatan melaluiproses diplomasi dan menghadirkan kekuatan militer dan nonmiliter di Laut Natuna Utara.Kesimpulan penelitian ini adalah pemerintah Indonesia telah melakukan sejumlah cara untukmenyelesaikan sengketa di laut Natuna Utara melalui diplomasi dan menghadirkan kekuatanmiliter. Pemerintah Indonesia harus senantiasa mencermati perkembangan dinamika yang terjadidi LCS dan meningkatkan koordinasi antar institusi terkait dalam menangani sengketa di Laut CinaSelatan tsb. Koordinasi institusi yang terkait seperti TNI AL, BAKAMLA, KPLP, POLAIR, PSDKP harusterus dijaga dan ditingkatkan untuk mempertahankan kedaulatan NKRI. Pengerahan alutsistatambahan berupa kapal patroli dan khususnya pesawat dapat dilakukan sebagai salah satu carauntuk memperbesar wilayah pengawasan TNI AL dan instansi terkait lainnya untuk menjaga danmempertahankan kedaulatan wilayah Indonesia. Dengan hadirnya kekuatan militer dan non militersecara aktif di wilayah Natuna Utara akan menunjukkan bahwa Indonesia akan selalumempertahankan serta menjaga wilayah kedaulatannya dan juga hal tersebut akan mempersempitcelah bagi negara Tiongkok untuk mengklaim wilayah laut Natuna Utara.Kata Kunci: Laut Cina Selatan, Laut Natuna Utara, Strategi Pertahanan Maritim.
PENERAPAN KONSEP "BLUE ECONOMY" SEBAGAI PENGEMBANGAN KEMAMPUAN PERTAHANAN LAUT
Authors: Arum Dyah Sekar
Published: February 2024

Permasalahan perbatasan Laut Natuna Utara dinilai sebagai sebuah ancaman Kawasan bagi Indonesia. Mengingat letak geografis LNU yang berbatasan langsung dengan negara-negara ASEAN dan konflik Laut China Selatan yang sedang berlangsung. Melalui ini, maka penting bagi Indonesia untuk dapat mempersiapkan kedua kemungkinan, yang pertama perebutan Kawasan LNU, yang kedua dampak perang laut dari adanya konflik LCS. Maka konsep Ekonomi biru hadir, guna untuk dapat meningkatkan perekonomian negara dan menghidupkan Masyarakat pesisir. Sehingga dapat mengembangkan pertahanan laut secara bertahap, didaerah pesisir melalui adanya aktivitas ekonomi yang padat di perairan. Oleh karena itu, Indonesia diharuskan untuk mencoba memperkuat pertahanan laut melalui penerapan ekonomi biru. Dalam penelitian ini, maka peneliti akan difokuskan dengan studi kasus LNU dan urgensi penerapan ekonomi biru di Kawasan LNU sebagai pengembangan kemampuan pertahanan laut di Indonesia. Penelitian ini menggunakan metode penelitian kualitatif deskriptif dengan sumber data sekunder.
Phosphatase, Mg2+/Mn2+ dependent 1B regulates the hematopoietic stem cells homeostasis via the Wnt/β-catenin signaling
Authors: Lu Zhiyuan , Yu Hanzhi , Li Yanxia , Xu Guangsen , Li Xiaoxun , Liu Yongjun , Shen Yuemao , Cai Zhigang , Zhao Baobing
Published: February 2024

Hematopoietic stem cells (HSCs) are primarily dormant in a cell-cycle quiescence state to preserve their self-renewal capacity and long-term maintenance. How HSCs maintain the balance between activation and quiescence remains largely unknown. Herein, we found that Phosphatase, Mg2+/Mn2+ Dependent 1B (Ppm1b) is required for the expansion of phenotypic HSCs in vitro. By using a conditional knockout mouse model in which Ppm1b was specifically depleted in hematopoietic cells, we demonstrated that loss of Ppm1b impaired the HSC homeostasis and hematopoietic reconstitution. Ppm1b deficiency mice also exhibited B-cell leukocytopenia, which is due to the compromised commitment and proliferation of B-biased lymphoid progenitor cells from CLPs. With the aid of a small molecular inhibitor, we confirmed the roles of Ppm1b in adult hematopoiesis that phenocopied the effects with loss of Ppm1b. Furthermore, transcriptome profiling of Ppm1b-deficient HSCs revealed the disruptive quiescence of HSC. Mechanistically, Ppm1b interacted with β-catenin and mediated its dephosphorylation. Loss of Ppm1b led to the decrease of the active β- catenin (non-phosphorylated) that interrupted the Wnt/β-catenin signaling in HSC, which consequently suppressed HSC expansion. Together, our study identified an indispensable role of Ppm1b in regulating HSC homeostasis via Wnt/β-catenin pathway.
Targeting CCR4 with mogamulizumab in refractory CD3-CD4+ lymphocytic-variant hypereosinophilic syndrome
Authors: Ledoult Emmanuel , Groh Matthieu , Meresse Bertrand , Dubois Romain , Trauet Jacques , Toussaint Elise , Delbeke Marie , Hachulla Eric , Terriou Louis , De Masson Adèle , Vasseur Michele , Labalette Myriam , Launay David , Kahn Jean-Emmanuel , Lefevre Guillaume
Published: February 2024

Not available.
A phase II randomized, placebo-controlled, multicenter trial to evaluate the efficacy of cytomegalovirus PepVax vaccine in preventing cytomegalovirus reactivation and disease after allogeneic hematopoietic stem cell transplant
Authors: Nakamura Ryotaro , La Rosa Corinna , Yang Dongyun , Hill Joshua A. , Rashidi Armin , Choe Hannah , Zhou Qiao , Lingaraju Chetan Raj , Kaltcheva Teodora , Longmate Jeffrey , Drake Jennifer , Slape Cynthia , Duarte Lupe , Al Malki Monzr M. , Pullarkat Vinod A. , Aribi Ahmed , Devine Steven , Verneris Michael R. , Miller Jeffrey S. , Forman Stephen J. , Aldoss Ibrahim , Diamond Don J.
Published: February 2024

Not available.
Be aware of the X: BCOR mutations in myeloid neoplasms
Authors: Ramil Guillermo , Pratcorona Marta , Nomdedéu Josep F.
Published: February 2024

Not available.
Peningkatan Pengetahuan Masyarakat untuk Pengelolaan Air Secara Berkelanjutan di Desa Pucangan Kabupaten Sukoharjo
Authors: Anna Alif Noor , Sari Dewi Novita , Cholil Munawar , Priyana Yuli , Fikriyah Vidya Nahdhiyatul , Rudiyanto Rudiyanto
Published: February 2024

This community service aims to increase community knowledge in sustainable water management in Pucangan Village, Kartasura District, Sukoharjo Regency. The service activities are carried out through workshops and Focus Group Discussion (FGD) methods targeting PKK mothers (family welfare development). Pre-tests and post-tests with questionnaires were carried out to measure the level of understanding of PKK mothers in managing water. The results of this community service show that there has been an increase in community knowledge about sustainable shallow groundwater management by an average of 8.8%, which consists of measuring water quality, management, and processing of groundwater.
Pemberdayaan Perempuan Melalui Penyuluhan Pencegahan Stunting di Kampung Mukim Singkir Yan Kedah Malaysia (Kolaborasi Pengabdian Internasional)
Authors: Juliana Septa , Munir Fitrisa , Ahmad Zalinah
Published: February 2024

This community service activity aims to increase women's knowledge and awareness in preventing stunting in Kampung Mukim Singkir Yan, Kedah, Malaysia. The method for implementing this service uses counseling, which includes planning, implementing and monitoring with Universiti Utara Malaysia partners. The instrument for evaluating this activity is a questionnaire, and is then analyzed descriptively. The results of this service show that women's knowledge and awareness regarding stunting prevention in Kampung Mukim Singkir Yan, Kedah, Malaysia has increased regarding understanding of stunting problems, the worse impacts of stunting, and stunting prevention.
Assisting School Teachers in Developing and Implementing Learning Modules Infused with Computational Thinking Principles
Authors: Harjanto Ignatius , Teopilus Susana , Anggraini Kristin
Published: February 2024

This community service activity program aims to guide school teachers to infuse CT principles into the learning modules and to implement their CT-infused modules in their classes. The methods for implementing community service activities were workshops and mentoring activities. The target of the activity was pre-school, elementary, and junior-high school teachers at School Foundation of Yohanes Gabriel sub-District Tuban. The instruments used to collect data were a survey, observation sheets, and learning-module documents. The data were analyzed to describe the teachers’ abilities to create CT-infused modules and their skills to carry out these modules in their instructional practices. The results of this program showed that the teachers understood CT principles and taxonomy and could create appropriate teaching modules infused with CT principles. It implies that this community service program could improve teachers’ teaching skills through their efforts to integrate computational thinking into their instructional practices.
Species range shifts, biological invasions and ocean warming
Authors: Wesselmann M , Apostolaki ET , Anton A
Published: February 2024

Marine species are moving beyond their native geographical ranges in response to climate change and shifts in other abiotic conditions, establishing populations at higher latitudes. At the same time, species are introduced into new marine regions as a consequence of an increasingly connected world. The success of such range expansions, whether from shifts associated with climate change or human-mediated introductions, depends on the biotic interactions and environmental conditions at the recipient site and/or the capacity of species to adapt to these new conditions. Originating from a special session held at the Association for the Sciences of Limnology and Oceanography (ASLO) Aquatic Sciences Meeting 2021, the present Theme Section (TS) brings together the current research on 2 interrelated marine ecological topics: (1) invasive species in a warming ocean, and (2) climate-mediated species range shifts. Our investigation of the temporal trends in publications highlights that only one-tenth of studies on marine invasive species examine the species’ interaction with ocean warming. The topic of range shifting species receives slightly more attention than climate driven invasions, but both exhibited a comparable, similarly fast-growing publication rate. Overall, the papers in this TS provide evidence that global warming, and occasionally environmental degradation, are crucial factors altering the distribution of both marine invasive species and range-shifting species. Even though the published literature and even the contributions to this TS only infrequently focus on the interaction between these 2 topics, we propose that future collaboration between scientists from both fields would advance our understanding of the impact of global warming on the shifting distributions of native and invasive species and would allow the development of conservation and management plans in a warming ocean.
Caregiver-infant interactions and child vocabulary
Authors:   , van der Klis Anika
Published: February 2024

The goal of this dissertation is to predict variation in Dutch children’s vocabulary size using data from the large-scale, longitudinal YOUth cohort study. We take a dyadic approach to study the effects of verbal and multimodal behaviours during caregiver-infant interactions on children’s vocabulary size. This dissertation consists of four empirical articles. Three key findings emerged:

First, while there is a large interest in the annotation of infant-directed speech, the accuracy of automatic speech recognition tools has remained largely unexplored. We show researchers can use automated tools to facilitate the labour-intensive manual annotation process. Second, we show that key demographic factors explaining variation in children’s vocabulary, such as maternal education, are age-specific and task-specific. This highlights the importance of including multiple vocabulary outcomes across children’s development. Third, while there is robust evidence that infants’ gestures and vocalisations on the one hand, and caregivers’ contingent responses on the other hand, influence children’s vocabulary outcomes, we show that dyadic and multimodal combinations of these behaviours are better predictors. Infants’ pointing gestures relate to children’s later receptive vocabulary, while infants’ showing and giving gestures relate to children’s later productive vocabulary – but only when they elicited multimodal responses from caregivers during free play.

In research on children’s vocabulary development, we aim to describe how infants gather sufficient information from the language input that allows them to learn words. Studying the dyadic and multimodal nature of early caregiver-infant interactions creates a more complete picture of children’s learning environments which brings us closer to solving this puzzle.
Clinical introduction of MR-guided radiotherapy for esophageal cancer
Authors:   , Boekhoff Mick Remo
Published: February 2024

Radiotherapy for esophageal cancer requires the use of imaging to localize and visualize the tumor. This thesis describes the use of magnetic resonance imaging in the radiotherapy treatment of patients with esophageal cancer. The first part of this thesis showed that esophageal cancer tumors are subject to position and shape changes throughout the treatment period. We have calculated that a treatment margin of 8-10mm would have been sufficient to provide sufficient target coverage for most patients. However, some patients showed extreme interfraction motion, which indicates the need for adaptive treatment strategies. The second part of this thesis reported on our experiences with an online adaptive, MR-guided radiotherapy treatment workflow. This adaptive strategy used day-to-day plan adaptation with smaller treatment margins of 6 mm. We have shown that this workflow is moderately feasible, mainly caused by the long treatment time of up to one hour per treatment session. We concluded that optimization of the presented clinical workflow is required. Nevertheless, the adaptive treatment strategy resulted in a dose reduction to the organs-at-risk compared to conventional treatment. This might allow for employment of improved treatment strategies, such as boosting strategies, to use this dose reduction to potentially improve the result of radiotherapy treatments of esophageal cancer tumors.
Translating across Lines of Identity and Domination: The Case of M. NourbeSe Philip's Zong!
Authors: Bazzoni Alberica
Published: February 2024

This article examines the case of the recent ‘unauthorised’ translation of Caribbean-Canadian poet M. NourbeSe Philip's Zong! (2008) into Italian, which was at the centre of a heated debate on authorship and coloniality. The author unravels the rhetoric used in clashing arguments and identifies underlying values and assumptions to expose the system of power and the historical context in which this confrontation took place. Through an investigation of questions of authorship, authority and ethical posture, the author draws a distinction between a legalistic and a relational paradigm of translation. The article foregrounds the critical role of identity in the translation process and uncovers the enduring of colonial, racist and sexist structures embedded in the international publishing world, exposing both the limits and the creative potential of translation as a cultural practice that is deeply political.
Ethics of ‘Translational’ Acts in Islamic Feminist Writings: An Analysis of Selected Academic Contributions
Authors: Embabi Doaa
Published: February 2024

This article explores translation as a process and an act in the field of Islamic Feminism. It focuses on the interplay between translator's visibility and ethics in translational activities by Islamic Feminist writers, who mainly produce their work in English, when they cite the Qur’an and prophetic traditions and build their arguments upon this activity. Drawing on a select corpus of influential texts in the field, the article argues that translation in this faith-based approach to feminism is inevitable, and examines the ways in which this non-Arabic transnational feminist narrative contributes to changing, or at least opening spaces for, the discussion on Muslim women's issues and conditions.
The Dialectics of Essayism
Authors: Lijster Thijs
Published: February 2024

This article argues that our current situation is one that both prevents us from telling ‘grand narratives’ and necessitates us to ‘think big’. This makes the task of the essay today a dialectical one. Following Adorno, the essay is not merely seen as a literary genre but also as a mode of thought that reflects and criticises a particular socio-historical condition. The essayistic mode of thought attempts to reinstate or revive particularity as well as our experience of it, in a world wherein all things appear as a function or exemplar of something else. At the same time, however, and exactly through this intense focus on the particular object or experience, the essay brings to light something universal. This makes the essay the philosophical and aesthetic form par excellence of our current time.
Intermittent Pre-Syncope after Surgical Correction of Aortic Stenosis Caused by Left Ventricular Outflow Obstruction by Elongated Mitral Leaflets
Authors: Davies Alys , Henein Michael Y.
Published: February 2024

Left ventricular outflow obstruction (LVOTO) is a potential complication following surgical replacement of the aortic valve. We present an 88-year-old man who experienced periodic episodes of pre-syncope following aortic valve replacement. The underlying cause was identified as LVOTO resulting from elongated mitral valve leaflets. The diagnosis was established using stress echocardiography, which detected transient LVOTO with moderate rise in heart rate. The medical approach involved administering beta-blockers and optimising hydration consumption. The patient's symptoms and quality of life showed considerable improvement during the six-month follow-up period. Timely identification and intervention are essential in managing left ventricular outflow tract obstruction (LVOTO) after aortic valve replacement, to mitigate the risk of potential adverse cardiac events.
Aldosterone Synthase Inhibitors for Treatment of Hypertension and Chronic Kidney Disease
Authors: Mikhail Nasser
Published: February 2024

Aldosterone excess is known to worsen hypertension and kidney function. Three selective aldosterone synthase inhibitors (ASIs) were evaluated in 3 phase 2 trials. In the first study, the ASI baxdrostat 2 mg orally once daily decreased systolic blood pressure (SBP) by 11.0 mmHg compared with placebo after 12 weeks in patients with treatment-resistant hypertension. In the second study including patients with uncontrolled hypertension, placebo-corrected reduction in SBP with lorundrostat 50 mg once daily was 9.6 mmHg after 8 weeks. Patients receiving thiazides and those with body mass index (BMI) > 30 kg/m2 had the optimum blood pressure (BP) response to lorundrostat, whereas plasma renin activity (PRA) did not affect its antihypertensive potency. In the third trial including patients with chronic kidney disease (CKD), the ASI BI 690517 (10 mg once daily) decreased urinary albumin creatinine ratio (UACR) by 39% after 14 weeks compared with 3% reduction with placebo. Reduction in UACR was generally similar in presence or absence of concomitant treatment with empagliflozin. The 3 ASIs mildly decreased (by <15%) estimated glomerular filtration rate (eGFR) compared with placebo. The most common adverse effects of ASIs were hyperkalemia occurring in 2.9% and 7.9% among patients randomized to baxdrostat and lorundrostat, respectively versus none in the placebo groups. In patients with CKD, frequency of hyperkalemia was higher: 14.2% and 6.0% with BI 690517 and placebo, respectively. Adrenal insufficiency was reported in 1.3% of patients randomized to BI 690517 versus 1.0% with placebo. Preliminary data suggest that selective ASIs are effective in lowering BP in patients with resistant and uncontrolled hypertension and decreasing albuminuria in CKD. Phase 3 clinical trials should be conducted to assess long-term efficacy and safety of ASIs in a wide spectrum of patients with uncontrolled BP and CKD.
Solar System Wave Packet
Authors: Soltani Abolfazl
Published: February 2024

The emptiness of the interplanetary space in the solar system from large objects is very thought-provoking. For example, Consider the distance between Earth and Venus. This distance is about 25 thousand times the total diameter of Earth and Venus. It's like placing two small gravels on either side of a football pitch. Now, it would be self-deception to imagine that the protoplanetary disk didn't have enough material to form dozens of other planets in the wide space between Earth and Venus, and only these two tiny gravels formed in this huge pitch. An event must have cleaned the objects between Earth and Venus from the protoplanetary disk. Here we show that this event is the oscillation of a huge standing wave packet, with the wavelength λ = 0.6 AU, in the protoplanetary disk of early solar system. In addition, the Solar System Wave Packet (SSWP) theory explains the reason why the Giant (Jovian) planets are heavier than the terrestrial planets, the reason for the existence of Titius-Bode law and some other phenomena. The SSWP theory can easily overcome the problems of fragmentation barrier, bouncing barrier and meter-size barrier, and unlike current theories, we provide an identical and coherent explanation for the formation of giant and terrestrials planets of solar system, super-Earths and hot Jupiters. The spherical shape of Chondrules tells us that the passage of a wave front was effective in the formation of Chondrules. Here we show that that wave front can be SSWP.
The James Webb (JWST) Anomalies Resolved
Authors: Arnold James R.
Published: February 2024

A model of the universe is offered that can derive the Hubble Constant independent of empirical measurement, using just an estimate of the age of the universe and some simple arithmetic calculations. The JWST discoveries of apparent anomalous early galaxy formations are explained without need of substantial revisions to established astrophysical theories, as the new findings from JWST have seemed to require. Concepts of “Dark energy”, cosmic flatness, and the accelerating expansion of the universe are rendered unnecessary or mistaken.
Impacts of sulfamethoxazole stress on vegetable growth and rhizosphere bacteria and the corresponding mitigation mechanism
Authors: Ren Jiawei , Lu Hongbin , Lu Shaoyong , Huang Zhanggen
Published: February 2024

Antibiotics are an important pharmaceutical class excessively used by humans. Its presence in the soil can impact plant growth and induce antibiotic resistance. This research studies the effect of sulfamethoxazole (SMX) on plant growth, rhizosphere bacteria composition, and resistance genes. Two sets of vegetables (basil, cilantro, and spinach) were treated separately with water and SMX solution. The plant growth data and soil samples were collected and analyzed. The results revealed that SMX increased spinach leaf length (34.0%) while having no significant impacts on basil and cilantro. On the other hand, SMX improved the bacterial diversity in all samples. The shifts in the abundance of plant growth-promoting bacteria could indirectly affect vegetable stem and leaf length. SMX also significantly increased the abundance of resistance genes Sul1 and Sul2. A further study into the correlation between bacteria highlights the importance of Shingomonas and Alfipia for inhibiting the spread of key resistance gene hosts, namely, Pseudomonas, Stenotrophomonas, and Agrobacterium. This research provides insight into SMX’s impact on vegetable growth and microbial diversity. It also points out important microbial interactions that could potentially be utilized to mitigate ARG proliferation.
Effects of different contact angles during forefoot running on the stresses of the foot bones: a finite element simulation study
Authors: Zhou Huiyu , Xu Datao , Quan Wenjing , Ugbolue Ukadike Chris , Gu Yaodong
Published: February 2024

Introduction: The purpose of this study was to compare the changes in foot at different sole-ground contact angles during forefoot running. This study tried to help forefoot runners better control and improve their technical movements by comparing different sole-ground contact angles.

Methods: A male participant of Chinese ethnicity was enlisted for the present study, with a recorded age of 25 years, a height of 183 cm, and a body weight of 80 kg. This study focused on forefoot strike patterns through FE analysis.

Results: It can be seen that the peak von Mises stress of M1-5 (Metatarsal) of a (Contact angle: 9.54) is greater than that of b (Contact angle: 7.58) and c (Contact angle: 5.62) in the three cases. On the contrary, the peak von Mises stress of MC (Medial Cuneiform), IC (Intermediate Cuneiform), LC (Lateral Cuneiform), C (Cuboid), N (Navicular), T (Tarsal) in three different cases is opposite, and the peak von Mises stress of c is greater than that of a and b. The peak von Mises stress of b is between a and c.

Conclusion: This study found that a reduced sole-ground contact angle may reduce metatarsal stress fractures. Further, a small sole-ground contact angle may not increase ankle joint injury risk during forefoot running. Hence, given the specialized nature of the running shoes designed for forefoot runners, it is plausible that this study may offer novel insights to guide their athletic pursuits.
iPSC-derived cells for whole liver bioengineering
Authors: Telles-Silva Kayque Alves , Pacheco Lara , Chianca Fernanda , Komatsu Sabrina , Chiovatto Caroline , Zatz Mayana , Goulart Ernesto
Published: February 2024

Liver bioengineering stands as a prominent alternative to conventional hepatic transplantation. Through liver decellularization and/or bioprinting, researchers can generate acellular scaffolds to overcome immune rejection, genetic manipulation, and ethical concerns that often accompany traditional transplantation methods, in vivo regeneration, and xenotransplantation. Hepatic cell lines derived from induced pluripotent stem cells (iPSCs) can repopulate decellularized and bioprinted scaffolds, producing an increasingly functional organ potentially suitable for autologous use. In this mini-review, we overview recent advancements in vitro hepatocyte differentiation protocols, shedding light on their pivotal role in liver recellularization and bioprinting, thereby offering a novel source for hepatic transplantation. Finally, we identify future directions for liver bioengineering research that may allow the implementation of these systems for diverse applications, including drug screening and liver disease modeling.
In vitro characterization of 3D culture-based differentiation of human liver stem cells
Authors: Tapparo Marta , Saccu Gabriele , Pasquino Chiara , Fonsato Valentina , Medana Claudio , Schiavo Valentina , Mecarelli Enrica , Maccagno Monica , Silengo Lorenzo , Bruno Stefania , Camussi Giovanni , Herrera Sanchez Maria Beatriz
Published: February 2024

Introduction: The lack of functional hepatocytes poses a significant challenge for drug safety testing and therapeutic applications due to the inability of mature hepatocytes to expand and their tendency to lose functionality in vitro. Previous studies have demonstrated the potential of Human Liver Stem Cells (HLSCs) to differentiate into hepatocyte-like cells within an in vitro rotary cell culture system, guided by a combination of growth factors and molecules known to regulate hepatocyte maturation. In this study, we employed a matrix multi-assay approach to comprehensively characterize HLSC differentiation.

Methods: We evaluated the expression of hepatic markers using qRT-PCR, immunofluorescence, and Western blot analysis. Additionally, we measured urea and FVIII secretion into the supernatant and developed an updated indocyanine green in vitro assay to assess hepatocyte functionality.

Results: Molecular analyses of differentiated HLSC aggregates revealed significant upregulation of hepatic genes, including CYP450, urea cycle enzymes, and uptake transporters exclusively expressed on the sinusoidal side of mature hepatocytes, evident as early as 1 day post-differentiation. Interestingly, HLSCs transiently upregulated stem cell markers during differentiation, followed by downregulation after 7 days. Furthermore, differentiated aggregates demonstrated the ability to release urea and FVIII into the supernatant as early as the first 24 h, with accumulation over time.

Discussion: These findings suggest that a 3D rotation culture system may facilitate rapid hepatic differentiation of HLSCs. Despite the limitations of this rotary culture system, its unique advantages hold promise for characterizing HLSC GMP batches for clinical applications.
Anti-oxidant and neuro-modulatory effects of bioactive Byttneria pilosa leaf extract in swiss albino mice using behavioral models
Authors: Jyoti Mifta Ahmed , Shah Md. Shahin , Uddin Mohammad Najim , Hossain Mohammed Kamrul , Han Aixia , Geng Peiwu , Islam Mohammad Nazmul , Mamun Abdullah Al
Published: February 2024

Byttneria pilosa, a flowering plant from the Malvaceae family traditionally used to treat ailments such as boils and scabies, is here investigated for its potential health benefits. The study focused on evaluating its antioxidant and antidiabetic properties in vitro, as well as the in vivo anxiolytic and antidepressant activities of the methanol extract of B. pilosa leaf (MEBP). The study employed various assays to evaluate antioxidant activity, including 2, 2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging, reducing power capacity, and quantification of the total phenolic and flavonoid contents of MEBP. Additionally, anxiolytic and antidepressant activities were evaluated through four tests: elevated plus-maze test (EPMT), light–dark box test (LDBT), forced swimming test (FST), and tail suspension test (TST). Antidiabetic effect was determined using α-amylase inhibition assay. Docking analysis was performed using BIOVIA and Schrödinger Maestro (v11.1), and the absorption, distribution, metabolism, and excretion/toxicity (ADME/T) properties of bioactive substances were investigated using a web-based technique. MEBP exhibited moderate antioxidant activity in DPPH radical scavenging and reducing power capacity assays, with a dose-dependent response. The total phenolic and flavonoid contents measured were 70 ± 1.53 mg and 22.33 ± 1.20 mg, respectively. MEBP demonstrated significant effects in α-amylase inhibition comparable to acarbose. In behavioral tests, MEBP dose-dependently altered time spent in open arms/light box and closed arms/dark box, indicating anxiolytic effects. Moreover, MEBP significantly reduced immobility duration in FST and TST, suggesting antidepressant properties. Molecular docking analysis revealed favorable interactions between beta-sitosterol and specific targets, suggesting the potential mediation of anxiolytic and antidiabetic effects. Overall, MEBP exhibits notable anxiolytic and antidepressant properties, along with moderate antioxidant and antidiabetic activities.
Exemplification in news narratives: stigmatizing and securitizing effects
Authors: Sellnow-Richmond Deborah D. , Lukacovic Marta N. , Sellnow-Richmond Scott A.
Published: February 2024

Exemplification, the use of emotionally evocative messages to elicit a response based on impression formation, are frequently present in news messages. The present study examined the use of positive vs. negative exemplars in news stories to determine the role of stigmatization and securitization in these messages and whether this impacts perceptions of the importance and quality of news. This study tested exemplification's effects using three conditions: positive, negative, and non-exemplar news stories—two valences of exemplification and a control condition. Results indicate that as stigmatized impressions increase, securitization decreases, valence of exemplification predicts perceptions on the quality of news, and valence of exemplification predicts perceptions on the general interest of the issues. Implications suggest news message creators should consider positive exemplars in place of negative exemplars to minimize unintended negative effects.
Parallel paired electrolysis of green oxidizing agents by the combination of a gas diffusion cathode and boron-doped diamond anode
Authors: Hamm Christin M. , Schneider Selina , Hild Stefanie , Neuber Rieke , Matthée Thorsten , Krümberg Jens , Stöckl Markus , Mangold Klaus-Michael , Kintrup Jürgen
Published: February 2024

The generation of “green” oxidizing agents by electrochemical synthesis opens the field for sustainable, on-demand, and on-site production, which is often based on non-critical starting materials. In this study, electrosyntheses were carried out on different cathode and anode materials. In half-cell experiments, the cathodic synthesis of peracetic acid (PAA) was investigated on gas diffusion electrodes (GDEs), reaching 22.6 mmol L−1 of PAA with a current efficiency (CE) of 7.4%. Moreover, peroxodicarbonate (PODIC®) was produced anodically on boron-doped diamond (BDD) electrodes with concentrations as high as 42.7 mmol L−1 PODIC® and a CE of 30.3%. Both cathodic and anodic processes were individually examined and improved. Finally, the half-cell reactions were combined as a proof of concept in a parallel paired electrolysis cell for the first time to achieve an increased overall CE.
Projected heatwaves in Xinjiang Uygur autonomous region, China
Authors: Dong Diwen , Tao Hui , Zhang Zengxin , Mondal Sanjit Kumar
Published: February 2024

Introduction: Heatwaves (HWs) are the serious natural disaster that exert great impacts on human health and social economy. Projecting future changes in HWs is crucial for the development of effective adaptation strategies.

Method: This study investigates the variations of HWs in Xinjiang for three time periods (near-term, mid-term, and long-term) under four Shared Socioeconomic Pathways (SSP1-2.6, SSP2-4.5, SSP3-7.0, and SSP5-8.5) using multi-model ensemble (MME). To enhance confidence in HWs projection, we evaluate the performance of 17 climate models in simulating HWs in terms of interannual variability and spatial patterns using interannual variability skill score (IVS) and distance between indices of simulation and observation (DISO), respectively, and generate MME using the overall performance.

Results: Compared to the observed data, the overall performance of MME outperforms most of individual models, although many models effectively capture the characteristics of HWs. Projections indicate that HWs in Xinjiang will become more longer lasting and severe. Specifically, heatwave frequency (HWF) and heatwave duration (HWD) are projected to reach 7.5 times and 61 days, respectively, in the long-term under the SSP5-8.5 scenario. The spatial distribution of HWs exhibits significant heterogeneity, with high value regions primarily distributed in eastern Xinjiang and the eastern part of southern Xinjiang. Although the HWs area is projected to expand under all scenarios, the spatial pattern is anticipated to remain largely unchanged.

Conclusion: These findings provide a comprehensive assessment of future variations in HWs, which are necessary for improving regional adaptive capacity to extreme heat risk.
Numerical simulation of water-bearing coal goaf using ground-borehole TEM—a case study of Tongxin Coal Mine, Shanxi Provice, China
Authors: Yang Yang , Peng Sanxi , Shan Huimei , Peng Qinghua
Published: February 2024

Transient electromagnetic method (TEM) is widely used in coalfield hydrogeological exploration and goaf investigation. However, given the limitations of the method, the vertical resolution of ground TEM is somewhat low for effectively detecting water-bearing coal goaf. Compared with ground TEM, ground-borehole TEM is characterized by a relatively better ability for detecting low-resistivity target bodies. In this study, a low-resistivity thin plate model was established, and the ground-borehole TEM electromagnetic responses of different points (within and without of the plate) were numerically simulated. We considered an exploration project in Datong City (Shanxi Province, China) as a study case, to conduct the field investigation, examine the characteristics of ground-borehole TEM electromagnetic responses under different situations, and validate the numerical model as well, including (a) water-bearing coal goaf and (b) solid coal. The result showed that, (a) the longer the sampling time is, the weaker the electromagnetic response of ground-borehole TEM will be; (2) ground-borehole TEM stands out with a high vertical resolution for water-bearing coal goaf; (c) the extreme points of the Z component and the polarity changing points of the X and Y components can indicate the interface where the physical properties alternated.
Identification of important modules and biomarkers in diabetic cardiomyopathy based on WGCNA and LASSO analysis
Authors: Cui Min , Wu Hao , An Yajuan , Liu Yue , Wei Liping , Qi Xin
Published: February 2024

Background

Diabetic cardiomyopathy (DCM) lacks specific and sensitive biomarkers, and its diagnosis remains a challenge. Therefore, there is an urgent need to develop useful biomarkers to help diagnose and evaluate the prognosis of DCM. This study aims to find specific diagnostic markers for diabetic cardiomyopathy.

Methods

Two datasets (GSE106180 and GSE161827) from the GEO database were integrated to identify differentially expressed genes (DEGs) between control and type 2 diabetic cardiomyopathy. We assessed the infiltration of immune cells and used weighted coexpression network analysis (WGCNA) to construct the gene coexpression network. Then we performed a clustering analysis. Finally, a diagnostic model was built by the least absolute shrinkage and selection operator (LASSO).

Results

A total of 3066 DEGs in the GSE106180 and GSE161827 datasets. There were differences in immune cell infiltration. According to gene significance (GS) > 0.2 and module membership (MM) > 0.8, 41 yellow Module genes and 1474 turquoise Module genes were selected. Hub genes were mainly related to the “proteasomal protein catabolic process”, “mitochondrial matrix” and “protein processing in endoplasmic reticulum” pathways. LASSO was used to construct a diagnostic model composed of OXCT1, CACNA2D2, BCL7B, EGLN3, GABARAP, and ACADSB and verified it in the GSE163060 and GSE175988 datasets with AUCs of 0.9333 (95% CI: 0.7801-1) and 0.96 (95% CI: 0.8861-1), respectively. H9C2 cells were verified, and the results were similar to the bioinformatics analysis.

Conclusion

We constructed a diagnostic model of DCM, and OXCT1, CACNA2D2, BCL7B, EGLN3, GABARAP, and ACADSB were potential biomarkers, which may provide new insights for improving the ability of early diagnosis and treatment of diabetic cardiomyopathy.
Exploring the molecular mechanism of Xuebifang in the treatment of diabetic peripheral neuropathy based on bioinformatics and network pharmacology
Authors: Hu Faquan , Lin Jiaran , Xiong Liyuan , Li Zhengpin , Liu Wen-ke , Zheng Yu-jiao
Published: February 2024

Background

Xuebifang (XBF), a potent Chinese herbal formula, has been employed in managing diabetic peripheral neuropathy (DPN). Nevertheless, the precise mechanism of its action remains enigmatic.

Purpose

The primary objective of this investigation is to employ a bioinformatics-driven approach combined with network pharmacology to comprehensively explore the therapeutic mechanism of XBF in the context of DPN.

Study design and Methods

The active chemicals and their respective targets of XBF were sourced from the TCMSP and BATMAN databases. Differentially expressed genes (DEGs) related to DPN were obtained from the GEO database. The targets associated with DPN were compiled from the OMIM, GeneCards, and DrugBank databases. The analysis of GO, KEGG pathway enrichment, as well as immuno-infiltration analysis, was conducted using the R language. The investigation focused on the distribution of therapeutic targets of XBF within human organs or cells. Subsequently, molecular docking was employed to evaluate the interactions between potential targets and active compounds of XBF concerning the treatment of DPN.

Results

The study successfully identified a total of 122 active compounds and 272 targets associated with XBF. 5 core targets of XBF for DPN were discovered by building PPI network. According to GO and KEGG pathway enrichment analysis, the mechanisms of XBF for DPN could be related to inflammation, immune regulation, and pivotal signalling pathways such as the TNF, TLR, CLR, and NOD-like receptor signalling pathways. These findings were further supported by immune infiltration analysis and localization of immune organs and cells. Moreover, the molecular docking simulations demonstrated a strong binding affinity between the active chemicals and the carefully selected targets.

Conclusion

In summary, this study proposes a novel treatment model for XBF in DPN, and it also offers a new perspective for exploring the principles of traditional Chinese medicine (TCM) in the clinical management of DPN.
Oral Chinese Herbal Medicine plus usual care for diabetic kidney disease: study protocol for a randomized, double-blind, placebo-controlled pilot trial
Authors: Liu Meifang , Di Yuan Ming , Zhang Lei , Yang Lihong , Zhang La , Chen Junhui , Wang Ruobing , Xie Xiaoning , Lan Fang , Xie Liping , Huang Juan , Zhang Anthony Lin , Xue Charlie Changli , Liu Xusheng
Published: February 2024

Background

Diabetic kidney disease (DKD) has become the leading cause of kidney failure, causing a significant socioeconomic burden worldwide. The usual care for DKD fails to achieve satisfactory effects in delaying the persistent loss of renal function. A Chinese herbal medicine, Tangshen Qushi Formula (TQF), showed preliminary clinical benefits with a sound safety profile for people with stage 2-4 DKD. We present the protocol of an ongoing clinical trial investigating the feasibility, efficacy, and safety of TQF compared to placebo in delaying the progressive decline of renal function for people with stage 2-4 DKD.

Methods

A mixed methods research design will be used in this study. A randomized, double-blind, placebo-controlled pilot trial will evaluate the feasibility, efficacy, and safety of TQF compared to placebo on kidney function for people with stage 2-4 DKD. An embedded semi-structured interview will explore the acceptability of TQF granules and trial procedures from the participant’s perspective. Sixty eligible participants with stage 2-4 DKD will be randomly allocated to the treatment group (TQF plus usual care) or the control group (TQF placebo plus usual care) at a 1:1 ratio for 48-week treatment and 12-week follow-up. Participants will be assessed every 12 weeks. The feasibility will be assessed as the primary outcome. The changes in the estimated glomerular filtration rate, urinary protein/albumin, renal function, glycemic and lipid markers, renal composite endpoint events, and dampness syndrome of Chinese medicine will be assessed as the efficacy outcomes. Safety outcomes such as liver function, serum potassium, and adverse events will also be evaluated. The data and safety monitoring board will be responsible for the participants’ benefits, the data’s credibility, and the results’ validity. The intent-to-treat and per-protocol analysis will be performed as the primary statistical strategy.

Discussion

Conducting a rigorously designed pilot trial will be a significant step toward establishing the feasibility and acceptability of TQF and trial design. The study will also provide critical information for future full-scale trial design to further generate new evidence supporting clinical practice for people with stage 2-4 DKD.

Trial registration number

https://www.chictr.org.cn/, identifier ChiCTR2200062786.
Peripheral blood mononuclear cell low molecular mass protein 7 in acute ischemic stroke: vertical change from admission to discharge and correlation with disability, stroke recurrence, and death
Authors: Hou Lujia , Zhang Yanlei
Published: February 2024

Objective

Low molecular mass protein 7 (LMP7) aggravates abnormal T cell differentiation and atherosclerosis, but its clinical role in acute ischemic stroke (AIS) is still unclear. This study aimed to investigate the correlation of peripheral blood mononuclear cell (PBMC) LMP7 with T cell subsets, disease severity, and prognosis in AIS patients.

Methods

A total of 162 AIS patients were enrolled for detecting PBMC LMP7 and T helper (Th) 1, Th2, and Th17 cells via reverse transcriptase-polymerase chain reaction and flow cytometry, respectively. In addition, PBMC LMP7 at discharge was also quantified.

Results

Increased LMP7 at admission was associated with decreased Th2 cells (P=0.014), elevated Th17 cells (P<0.001), C-reactive protein (P=0.005), National Institutes of Health Stroke Scale (NIHSS) score (P=0.007), and disease severity (defined by NIHSS score) (P=0.010). LMP7 at admission reflected a high risk of stroke recurrence (area under curve (AUC): 0.748, 95% confidence interval (CI): 0.564-0.932), but not mRS score at month 3 (M3) >2 (AUC: 0.585, 95%CI: 0.479-0.691), or death (AUC: 0.723, 95%CI: 0.338-1.000). LMP7 at discharge was reduced compared to that at admission (P<0.001). LMP7 at discharge was positively correlated with the risk of stroke recurrence (AUC: 0.849, 95%CI: 0.735-0.963) and death (AUC: 0.919, 95%CI: 0.836-1.000), but had a weak capacity to reflect mRS score at M3 >2 (AUC: 0.671, 95%CI: 0.578-0.765).

Conclusion

PBMC LMP7 positively correlates with Th17 cells, inflammation, and disease severity in AIS patients, meanwhile, its level at discharge shows a good ability to reflect the risks of stroke recurrence and death.