bluuebunny/crossref_metadata_2025 huggingface dataset:
Implementation of The Blue Ocean Strategy to The Financial Performance of Village Credit Institutions (LPD) In Bali
Authors: Bontot I Nyoman , Wibowo Martino
Published: November 2023

LPD as a microfinance institution belonging to a traditional village in Bali, specializes in serving village communities, including those who are unbankable. Having an unbankable market has the potential to increase NPLs and reduce financial performance. Many LPDs have small company sizes (depending on the potential of the village) and are managed by unprofessional management. But LPDs were able to grow and survive 35 years of competition. The purpose of this research is to examine LPD strategies to be able to grow and survive in the midst of increasingly fierce competition for microfinance institutions. Using qualitative research methods supported by quantitative data sourced from LPLPD Bali Province in 2022 with an ethnographic approach, and unstructured interview techniques. This study concludes that the LPD is a microfinance institution belonging to a traditional village, benefit-oriented, not profit-oriented. The financial performance of LPDs is relatively good. Only a small proportion (around 7%) experienced problems, mostly caused by factors of business size and governance, only a small portion due to NPLs. LPD's ability to grow and survive is due to implementing the Blue Ocean Strategy by creating a market for indigenous villagers, who are known and trusted, and are not affordable by competitors. This article is the result of research, has never been published by anyone
The Role of Sugar Cane Plantations to Improve the Welfare of Sugar Cane Farmers in an Islamic Perspective
Authors: Fatmawati  , Sugiarti Dian
Published: November 2023

This study aims to determine the sugarcane plantation business in the village of Kedungrejo and to determine its role in improving the welfare of the people of Kedungreejo village in an Islamic economic perspective. Viewed from an Islamic economic perspective, this sugar cane business is in accordance with Islamic economic values ​​in the form of Mudharabah cooperation between the PG Wonolangan Sugar Factory and Sugar Cane Farmers. In this case Sugarcane Farmers get facilities in the form of assistance to get capital loan assistance so that cost problems in the sugarcane farming business can be overcome PG Wonolangan partner farmers are satisfied with the pattern and implementation of the partnership at PG Wonolangan
Sharia Economics on Payment Methods Paylater (Pay Later) among Millennials
Authors: Permata Dyah Alvira Anggun , Sugiarti Dian
Published: November 2023

Referring to the problems and research questions, this research aims to analyze the sharia economic view of paylater payment methods and the attitude of the millennial generation in using paylater but in accordance with sharia economics. This research is descriptive research using a qualitative approach. In this research, data analysis was carried out by conducting in-depth data processing from various articles or journals related to the application of sharia economics in deferred payment methods (paylater) among millennials. Paylater is a delayed payment method that has developed in Indonesia. Based on Research and Market report data, the market value of paylater services in Indonesia has reached $1.5 billion in 2021, and will experience growth of up to $9.2 billion in 2028 with a CAGR of 29.2%. The advantage of using this paylater feature is buy now, pay later. These advantages are excellent for society, especially the millennial generation. The aim of this research is to analyze the sharia economic view of paylater payment methods among millennials.
Analysis of the Effect Spin-Off Increasing Shariah Compliance in Indonesian Islamic Bank
Authors: Hadziq M. Fuad , Mardoni Yosi , Solihat Iis , Rahmanto Mukhlis
Published: November 2023

Sharia banks are committed to growing with the potential and sharia market. But sharia banks also want to be pure sharia everywhere. One way is by spin off, but it turned out to be stagnant and not in accordance with the percentage of the sharia market in Indonesia. Sharia bank efficiency does not grow rapidly and profits are minimal when spin off. The aim of this research is to analyze the impact of bank spin-offs on Sharia bank compliance. This research method uses a causative qualitative method, based on qualitative data looking at the cause and effect relationship of a policy. To strengthen the results, deep structured open interviews were used from policy makers (BI), academics and Islamic bank spin-off actors. The results show that Spin off is a necessity as mandated by Law No. 21 of 2008, because on the one hand it wants to be a goal for halal Islamic banks in a big way. The impact is that banks that have been spun off will increase their sharia compliance more than UUS, even though the growth is not very significant and their business is not very efficient.
Small and Medium Enterprises (SMES) Perceptions of Drivers and Barriers to E-Commerce Adoption
Authors: Harsasi Meirani , Mulyana Andy , Mutmainah Isbandriyati , Hidayati Aprihatiningruh , Ernawati Erni
Published: November 2023

The research aims to analyze the intention of SMEs in adopting e-commerce, the driving and inhibiting factors. The study used survey data on 344 SMEs who were collected using the convenience sampling method. Furthermore, the data were analyzed using a quantitative descriptive analysis method. The study shows that SMEs are interested in adopting e-commerce. They also agree that they face strong competitive pressures in their business operations, but they have a high level of entrepreneurial mindset. Regarding the adoption of e- commerce, respondents are aware of the benefits of adopting e-commerce in their businesses and are willing to share knowledge with fellow SMEs regarding e-commerce adoption. In terms of barrier factors for e- commerce adoption, respondents agree that factors such as cultural environment, laws and regulations related to e-commerce, consumer readiness, trust, infrastructure, technology, human resources, and financial aspects are obstacles for them in adopting e-commerce, while political and organizational factors are not seen as barriers factors.The results of this study enrich empirical studies on e-commerce adoption, the driver and the barrier factors in the context of Indonesian.
Deformation of the Juan de Fuca Plate Beneath the Central Cascadia Continental Margin (44°-45°N) in Response to an Upper Plate Load
Authors: Tréhu Anne M. , Davenport Kathy , Kenyon Christopher B. , Carbotte Suzanne M. , Nabelek John L. , Toomey Douglas R. , Wilcock William S. D.
Published: November 2023

A 3D crustal model for the central Cascadia continental shelf and Coast Range between 44°N and 45°N shows that the crystalline crust of the forearc wedge beneath the coastline is characterized by a NW-trending, vertical slab of high-velocity rock interpreted to represent the dike complex that fed the Yachats Basalt, which was intruded into the forearc approximately 37 million years ago. A spatial correlation is observed between downward deflection of the crust of the subducting Juan de Fuca plate, inferred from inversion of PmP arrivals to image the Moho surface, and the high velocity (and consequently high density) anomaly underlying the Yachats Basalt. Apparent subsequent rebound of the subducting plate at greater depth suggests a primarily elastic response of the subducting plate to this load. Calculations for a range of plausible values for the magnitude of the load and the width and depth of the depression indicate that the effective elastic thickness of the subducted Juan de Fuca plate is < 6 km. Although our simple analytical models do not include partial support of the load of the slab by the adjacent upper plate crust or time dependence to account for the motion of the slab beneath the load, incorporation of those effects should decrease rather than increase the apparent strength of the subducted plate. We conclude that the subducted Juan de Fuca plate beneath the central Oregon margin is elastically thin and has the potential to store elastic strain energy before rupturing. Our model of a well-defined, focused and static upper plate load that locally deforms the subducted plate within the nominally seismogenic or transitional part of the Cascadia plate boundary may be unique in providing a relatively straightforward scenario for estimating the mechanical properties of the subducted Juan de Fuca plate. We extrapolate from these results to speculate that elastic deformation of the subducting plate may contribute to the low level of seismicity throughout much of the Cascadia forearc in the inter-seismic period between great earthquakes but note that our local results do not preclude faulting or elasto-plastic deformation of a thin and weak plate as it subducts. These results also suggest that the subducting plate should deform in response to larger scale variations in upper plate thickness and density.
Simulation and experimental study on the stability and comfortability of the wheelchair human system under uneven pavement
Authors: Luo Haitao , Cao Xuan , Dong Yuming , Li Yuxin
Published: November 2023

With the improvement in the level of science and technology and the improvement of people’s living standards, the functions of traditional manual wheelchairs have been unable to meet people’s living needs. Therefore, traditional wheelchairs have been gradually replaced by smart wheelchairs. Compared with traditional wheelchairs, smart wheelchairs have the characteristics of light operation and faster speed. However, when driving on some complex road surfaces, the vibration generated by the bumps of the motorcycle will cause damage to the human body, so wheelchairs with good electric power and stability can better meet the needs of people and make up for their travel needs. Based on the traditional vehicle stability analysis method, the mathematical theory of roll stability and pitch stability of the wheelchair–human system was established. We built a multi-body dynamics model with human skeleton and joint stiffness based on the multi-body dynamics method. The functioning of the wheelchair–human system was simulated and analyzed on the ditch, step, and combined road. The acceleration and Euler angle changes of the human head, chest, and wheelchair truss position were obtained, and the data results were analyzed to evaluate the stability and comfort of the system. Finally, a wheelchair test platform was built, and the road driving test was carried out according to the simulation conditions to obtain the system acceleration and angle data during the driving process. The simulation analysis was compared to verify the accuracy of the multi-body dynamics method, and the stability and comfort of the system were evaluated.
Utilization of the dimensions of learning organization for enhanced hospital performance
Authors: Alrashidi Nojoud Abdullah , Lagura Grace Ann Lim , Celdran Ma Christina Bello
Published: November 2023

Background

The healthcare system of Saudi Arabia has evolved radically into an institution that is adaptive to global change and is abreast with new advances in medical field to meet Saudi Vision 2030. The concept and practice of the dimensions of learning organization could provide a framework to significantly improve organizational performance. This study explores the practice of the seven dimensions of LO and determines their utilization toward enhanced performance at hospitals in Hail, Kingdom of Saudi Arabia (KSA). The findings of this study will help improve organizational (hospital) performance.

Method

This cross-sectional study included 117 nurse respondents from various government and private hospitals in the Hail region. Staff nurses were surveyed using the Dimensions of Learning Organization Questionnaire (DLOQ), and supervisors and managers were interviewed.

Results

Creation of continuous learning opportunities, team learning and collaboration, and strategic leadership in learning were perceived to be very satisfactorily utilized. Promotion of dialogue and inquiry, systems to capture and share learning, and empowerment and connection of the organization to the community were perceived to be satisfactorily utilized. Furthermore, the dimensions were found to be directly correlated, evidently signifying a strong relationship.

Conclusion

Overall, hospitals in the Hail region were found to be learning organizations. The dimensions of learning organization were utilized very satisfactorily, and the culture of learning was strongly embedded in the hospitals' systems and practices.
Comparison of surgical and endovascular left subclavian artery revascularization during thoracic aortic endovascular repair: a systematic review and meta-analysis
Authors: Lin Feng , He Zhipeng , Gao Junpeng , Huang Xiaoci , Wang Haoran , Han Long , Zhu Xingyang , Zhan Yanqing , Wang Wenbin
Published: November 2023

Objective

The purpose of this systematic review and meta-analysis was to incorporate data from the latest clinical studies and compare the safety and efficacy of surgical left subclavian artery (LSA) revascularization and endovascular LSA revascularization during thoracic endovascular aortic repair (TEVAR).

Methods

This study was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and was registered with the PROSPERO database on 16 April 2023 (CRD42023414579). The Embase, MEDLINE (PubMed), and the Cochrane Library databases were searched from January 2000 to May 2023.

Results

A total of 14 retrospective cohort studies with a total of 1,695 patients, were included for review. The peri-operative stroke rates of the surgical and endovascular LSA revascularization groups were 3.8% and 2.6%, respectively (P = 0.97). The peri-operative technical success rates for the surgical and endovascular LSA revascularization groups were 95.6% and 93.0%, respectively (P = 0.24). The peri-operative spinal cord ischemia rates were 1.6% (n = 18) and 1.9% (n = 7) in the surgical and endovascular LSA revascularization groups, respectively (P = 0.90). The peri-operative type Ⅰ endoleak rates for the surgical and endovascular LSA revascularization groups were 6.6% and 23.2%, respectively (P = 0.25). The subgroup analysis showed that the incidence of peri-operative type I endoleak in the parallel stent group was significantly higher than that in the surgical LSA revascularization group (P < 0.0001). The peri-operative left upper limb ischemia rates for the surgical and endovascular LSA revascularization groups were 1.2% and 0.6%, respectively (P = 0.96). The peri-operative mortality rates of the surgical and endovascular LSA revascularization groups were 2.0% and 2.0%, respectively (P = 0.88).

Conclusion

There was no significant difference in the terms of short-term outcomes when comparing the two revascularization techniques. The quality of evidence assessed by GRADE scale was low to very-low. Surgical and endovascular LSA revascularization during TEVAR were both safe and effective. Compared with surgical LSA revascularization techniques, parallel stent revascularization of LSA significantly increased the rate of type I endoleak.
No longer hype, not yet mainstream? Recalibrating city digital twins' expectations and reality: a case study perspective
Authors: Calzati Stefano
Published: November 2023

While the concept of digital twin has already consolidated in industry, its spinoff in the urban environment—in the form of a City Digital Twin (CDT)—is more recent. A CDT is a dynamic digital model of the physical city whereby the physical and the digital are integrated in both directions, thus mutually affecting each other in real time. Replicating the path of smart cities, literature remarks that agendas and discourses around CDTs remain (1) tech-centered, that is, focused on overcoming technical limitations and lacking a proper sociotechnical contextualization of digital twin technologies; (2) practice-first, entailing hands-on applications without a long-term strategic governance for the management of these same technologies. Building on that, the goal of this article is to move beyond high-level conceptualizations of CDT to (a) get a cognizant understanding of what a CDT can do, how, and for whom; (b) map the current state of development and implementation of CDTs in Europe. This will be done by looking at three case studies—Dublin, Helsinki, and Rotterdam—often considered as successful examples of CDTs in Europe. Through exiting literature and official documents, as well as by relying on primary interviews with tech experts and local officials, the article explores the maturity of these CDTs, along the Gartner's hype-mainstream curve of technological innovations. Findings show that, while all three municipalities have long-term plans to deliver an integrated, cyber-physical real-time modeling of the city, currently their CDTs are still at an early stage of development. The focus remains on technical barriers—e.g., integration of different data sources—overlooking the societal dimension, such as the systematic involvement of citizens. As for the governance, all cases embrace a multistakeholder approach; yet CDTs are still not used for policymaking and it remains to see how the power across stakeholders will be distributed in terms of access to, control of, and decisions about CDTs.
Examination of the mechanism of Piezo ion channel in 5-HT synthesis in the enterochromaffin cell and its association with gut motility
Authors: Zhu Zhenya , Chen Xiaolong , Chen Shuang , Hu Chenmin , Guo Rui , Wu Yuhao , Liu Ziyu , Shu Xiaoli , Jiang Mizu
Published: November 2023

In the gastrointestinal tract, serotonin (5-hydroxytryptamine, 5-HT) is an important monoamine that regulates intestinal dynamics. QGP-1 cells are human-derived enterochromaffin cells that secrete 5-HT and functionally express Piezo ion channels associated with cellular mechanosensation. Piezo ion channels can be blocked by Grammostola spatulata mechanotoxin 4 (GsMTx4), a spider venom peptide that inhibits cationic mechanosensitive channels. The primary aim of this study was to explore the effects of GsMTx4 on 5-HT secretion in QGP-1 cells in vitro. We investigated the transcript and protein levels of the Piezo1/2 ion channel, tryptophan hydroxylase 1 (TPH1), and mitogen-activated protein kinase signaling pathways. In addition, we observed that GsMTx4 affected mouse intestinal motility in vivo. Furthermore, GsMTx4 blocked the response of QGP-1 cells to ultrasound, a mechanical stimulus.The prolonged presence of GsMTx4 increased the 5-HT levels in the QGP-1 cell culture system, whereas Piezo1/2 expression decreased, and TPH1 expression increased. This effect was accompanied by the increased phosphorylation of the p38 protein. GsMTx4 increased the entire intestinal passage time of carmine without altering intestinal inflammation. Taken together, inhibition of Piezo1/2 can mediate an increase in 5-HT, which is associated with TPH1, a key enzyme for 5-HT synthesis. It is also accompanied by the activation of the p38 signaling pathway. Inhibitors of Piezo1/2 can modulate 5-HT secretion and influence intestinal motility.
What motivates firms to adopt a green supply chain and how much does it matter?
Authors: Wang Mengmeng , Zhang Guocheng
Published: November 2023

This study integrates the elaboration likelihood model, institutional theory, and the image management perspective to identify the internal and external forces that can effectively drive firms to adopt a green supply chain. Using survey data from a sample of 246 firms in the Chinese manufacturing sector, we empirically examine how the internal green process and green product innovation of firms and different types of external institutional pressures contribute to their adoption of a green supply chain, which in turn can explain the variation in their environmental and new-product development performance. Results of our structural equation modeling analysis reveal that the internal green process and green product innovation of firms and three types of external institutional pressures (i.e., coercive, normative, and mimetic pressures) play an important role in driving green supply chain adoption. Moreover, firms can improve their environmental and new-product development performance by adopting a green supply chain. In addition, though the image management motivation of firms tends to play a negative moderating role in the relationship between their green process innovation and green supply chain adoption, such motivation positively moderates the contribution of coercive pressure to their green supply chain adoption. Our findings can help explain why emerging-market firms tend to adopt a green supply chain and do not follow the pattern predicted by classical strategic management theories. The results of our study clearly demonstrate the determinants and consequences of the adoption of a green supply chain of firms and confirm that their green supply chain adoption can exert a positive effect on their environmental and new-product development performance. Overall, our research highlights the importance of recognizing internal innovation and external institutional forces in driving the green supply chain adoption of firms, which in turn will contribute to their environmental and new-product development performance. In this regard, our study extends the stream of research on green supply chains and sheds new light on the importance of abandoning the conventional supply chain and adopting a green one. Our study also provides important implications for research, practice, and policymaking.
Modeling the crosstalk between malignant B cells and their microenvironment in B-cell lymphomas: challenges and opportunities
Authors: Brauge Baptiste , Dessauge Elise , Creusat Florent , Tarte Karin
Published: November 2023

B-cell lymphomas are a group of heterogeneous neoplasms resulting from the clonal expansion of mature B cells arrested at various stages of differentiation. Specifically, two lymphoma subtypes arise from germinal centers (GCs), namely follicular lymphoma (FL) and GC B-cell diffuse large B-cell lymphoma (GCB-DLBCL). In addition to recent advances in describing the genetic landscape of FL and GCB-DLBCL, tumor microenvironment (TME) has progressively emerged as a central determinant of early lymphomagenesis, subclonal evolution, and late progression/transformation. The lymphoma-supportive niche integrates a dynamic and coordinated network of immune and stromal cells defining microarchitecture and mechanical constraints and regulating tumor cell migration, survival, proliferation, and immune escape. Several questions are still unsolved regarding the interplay between lymphoma B cells and their TME, including the mechanisms supporting these bidirectional interactions, the impact of the kinetic and spatial heterogeneity of the tumor niche on B-cell heterogeneity, and how individual genetic alterations can trigger both B-cell intrinsic and B-cell extrinsic signals driving the reprogramming of non-malignant cells. Finally, it is not clear whether these interactions might promote resistance to treatment or, conversely, offer valuable therapeutic opportunities. A major challenge in addressing these questions is the lack of relevant models integrating tumor cells with specific genetic hits, non-malignant cells with adequate functional properties and organization, extracellular matrix, and biomechanical forces. We propose here an overview of the 3D in vitro models, xenograft approaches, and genetically-engineered mouse models recently developed to study GC B-cell lymphomas with a specific focus on the pros and cons of each strategy in understanding B-cell lymphomagenesis and evaluating new therapeutic strategies.
Development of a novel in vitro strategy to understand the impact of shaving on skin health: combining tape strip exfoliation and human skin equivalent technology
Authors: Costello Lydia , Goncalves Kirsty , Maltman Victoria , Barrett Nicole , Shah Kous , Stephens Alison , Dicolandrea Tereasa , Ambrogio Ilaria , Hodgson Erica , Przyborski Stefan
Published: November 2023

Introduction

The removal of unwanted hair is a widespread grooming practice adopted by both males and females. Although many depilatory techniques are now available, shaving remains the most common, despite its propensity to irritate skin. Current techniques to investigate the impact of shaving regimes on skin health rely on costly and lengthy clinical trials, which hinge on recruitment of human volunteers and can require invasive biopsies to elucidate cellular and molecular-level changes.

Methods

Well-characterised human skin equivalent technology was combined with a commonplace dermatological technique of tape stripping, to remove cellular material from the uppermost layer of the skin (stratum corneum). This method of exfoliation recapitulated aspects of razor-based shaving in vitro, offering a robust and standardised in vitro method to study inflammatory processes such as those invoked by grooming practices.

Results

Tape strip insult induced inflammatory changes in the skin equivalent such as: increased epidermal proliferation, epidermal thickening, increased cytokine production and impaired barrier function. These changes paralleled effects seen with a single dry razor pass, correlated with the number of tape strips removed, and were attenuated by pre-application of shaving foam, or post-application of moisturisation.

Discussion

Tape strip removal is a common dermatological technique, in this study we demonstrate a novel application of tape stripping, to mimic barrier damage and inflammation associated with a dry shave. We validate this method, comparing it to razor-based shaving in vitro and demonstrate the propensity of suitable shave- and skin-care formulations to mitigate damage. This provides a novel methodology to examine grooming associated damage and a platform for screening potential skin care formulations.
The effects of perioperative dexmedetomidine infusion on hemodynamic stability during laparoscopic adrenalectomy for pheochromocytoma: a randomized study
Authors: Kim Youngwon , Yoo Young Chul , Kim Na Young , Shin Hye Jung , Kweon Ki Hong , Moon Jiae , Kang Sang-Wook
Published: November 2023

Introduction

Pheochromocytoma is a rare catecholamine-producing neuroendocrine tumor originating from the adrenal medulla chromaffin cells. Hemodynamic instability can occur during the induction of anesthesia and surgical manipulation of the tumor. This study investigated the effects of intraoperative dexmedetomidine administration on hemodynamic stability in patients undergoing laparoscopic adrenalectomy for pheochromocytoma.

Methods

Forty patients who underwent laparoscopic adrenalectomy for pheochromocytoma were randomly assigned to the dexmedetomidine (n = 20) or control (n = 20) group. The primary outcome of this study was intraoperative hemodynamic stability, and the secondary endpoint was the plasma catecholamine concentrations, specifically of epinephrine and norepinephrine.

Results

The intraoperative maximum blood pressures were significantly lower in the dexmedetomidine group (control vs. dexmedetomidine group: 182 ± 31 vs. 161 ± 20, 102 ± 17 vs. 90 ± 10, and 128 ± 22 vs. 116 ± 12 [mean ± SD] mmHg and p = 0.020, 0.015, and 0.040 for systolic, diastolic, and mean blood pressure, respectively). The maximum heart rate during surgery was 108 ± 15 bpm in the control group and 95 ± 12 bpm in the dexmedetomidine group (p = 0.010). Other parameters of hemodynamic instability were comparable between both groups. Plasma catecholamine concentrations did not differ between the groups.

Conclusion

Dexmedetomidine infusion following the induction of anesthesia at a rate of 0.5 μg/kg/h significantly attenuated the maximum intraoperative SBP, DBP, MBP, and HR, contributing to improved hemodynamic stability.
Natural biomass-derived carbon dots as a potent solubilizer with high biocompatibility and enhanced antioxidant activity
Authors: Wu Tong , Li Menghan , Li Tingjie , Zhao Yafang , Yuan Jinye , Zhao Yusheng , Tian Xingrong , Kong Ruolan , Zhao Yan , Kong Hui , Zhang Yue , Qu Huihua
Published: November 2023

Numerous natural compounds exhibit low bioavailability due to suboptimal water solubility. The solubilization methods of the modern pharmaceutical industry in contemporary pharmaceutical research are restricted by low efficiency, sophisticated technological requirements, and latent adverse effects. There is a pressing need to elucidate and implement a novel solubilizer to ameliorate these challenges. This study identified natural biomass-derived carbon dots as a promising candidate. We report on natural fluorescent carbon dots derived from Aurantia Fructus Immatures (AFI-CDs), which have exhibited a remarkable solubilization effect, augmenting naringin (NA) solubility by a factor of 216.72. Subsequent analyses suggest that the solubilization mechanism is potentially contingent upon the oration of a nanostructured complex (NA-AFI-CDs) between AFI-CDs and NA, mediated by intermolecular non-covalent bonds. Concomitantly, the synthesized NA-AFI-CDs demonstrated high biocompatibility, exceptional stability, and dispersion. In addition, NA-AFI-CDs manifested superior free radical scavenging capacity. This research contributes foundational insights into the solubilization mechanism of naringin-utilizing AFI-CDs and proffers a novel strategy that circumvents the challenges associated with the low aqueous solubility of water-insoluble drugs in the field of modern pharmaceutical science.
Structural understanding of SARS-CoV-2 virus entry to host cells
Authors: Le Kim , Kannappan Shrute , Kim Truc , Lee Jung Heon , Lee Hye-Ra , Kim Kyeong Kyu
Published: November 2023

Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a major global health concern associated with millions of fatalities worldwide. Mutant variants of the virus have further exacerbated COVID-19 mortality and infection rates, emphasizing the urgent need for effective preventive strategies. Understanding the viral infection mechanism is crucial for developing therapeutics and vaccines. The entry of SARS-CoV-2 into host cells is a key step in the infection pathway and has been targeted for drug development. Despite numerous reviews of COVID-19 and the virus, there is a lack of comprehensive reviews focusing on the structural aspects of viral entry. In this review, we analyze structural changes in Spike proteins during the entry process, dividing the entry process into prebinding, receptor binding, proteolytic cleavage, and membrane fusion steps. By understanding the atomic-scale details of viral entry, we can better target the entry step for intervention strategies. We also examine the impacts of mutations in Spike proteins, including the Omicron variant, on viral entry. Structural information provides insights into the effects of mutations and can guide the development of therapeutics and vaccines. Finally, we discuss available structure-based approaches for the development of therapeutics and vaccines. Overall, this review provides a detailed analysis of the structural aspects of SARS-CoV-2 viral entry, highlighting its significance in the development of therapeutics and vaccines against COVID-19. Therefore, our review emphasizes the importance of structural information in combating SARS-CoV-2 infection.
Effectiveness of acupuncture treatment for stroke and stroke complications: a protocol for meta-analysis and systematic review based on randomized, single-blind, controlled trials
Authors: Wang Xiao-Yu , Liu Wei , Li Huan , Rong Meng-Ying , Li Jing-Yu , Wang Shao-Kang , Du Yu-Zheng , Zhao Qi
Published: November 2023

Introduction

The treatment and rehabilitation of stroke and its complications have become major global health issues. Acupuncture is widely used as a complementary and alternative treatment for stroke. Many clinical studies have evaluated the efficacy and safety of acupuncture, but the research results need to be more consistent. The quality of research based on previously published meta-analyzes is uneven, leading to unstable conclusions. This study aims to provide a comprehensive and systematic analysis of the efficacy of high-quality, randomized controlled trials (RCTs) based on blinded designs for treating stroke and its complications. It also aims to review the characteristics of blinded designs and the current use of sham/placebo acupuncture controls in treating stroke.

Methods and analysis

This study will be conducted under the reporting guidelines for systematic reviews and meta-analyzes. Randomized controlled trials using acupuncture as the primary measure for stroke will be searched in databases such as China National Knowledge Infrastructure (CNKI), Chongqing VIP (CQVIP), Wan-fang, PubMed, Embase, Cochrane Library, and Web of Science. To evaluate high-quality research based on a blind design, if the trial evaluates the efficacy of any acupuncture intervention by including a sham/placebo acupuncture control, it will be included. The primary outcome indicator will be the ability to perform daily activities. Secondary outcome indicators include evaluating quality of life and related functions in stroke-related sequelae. We will assess the quality of evidence, reporting quality, and risk of bias for the acupuncture intervention in the literature included in this study using the GRADE system, the STRICTA 2010 checklist, and ROB2.0, respectively. RevMan 5.4 software will be used to conduct the meta-analysis, and Stata 15.0 software will be used for sensitivity analysis and publication bias testing.

Discussion

By analyzing high-quality, well-designed, randomized controlled trials of acupuncture, the results of this study may contribute to a more objective and standardized evaluation of acupuncture efficacy in treating stroke and its complications.

Systematic review registration: PROSPERO, Identifier (CRD42023378930).
Mechanisms associated with post-stroke depression and pharmacologic therapy
Authors: Zhan Qingyang , Kong Fanyi
Published: November 2023

Stroke is one of the most common cerebrovascular diseases, which is the cause of long-term mental illness and physical disability, Post-stroke depression (PSD) is the most common neuropsychiatric complication after stroke, and its mechanisms are characterized by complexity, plurality, and diversity, which seriously affects the quality of survival and prognosis of patients. Studies have focused on and recognized neurotransmitter-based mechanisms and selective serotonin-reuptake inhibitors (SSRIs) can be used to treat PSD. Neuroinflammation, neuroendocrinology, neurotrophic factors, and the site of the stroke lesion may affect neurotransmitters. Thus the mechanisms of PSD have been increasingly studied. Pharmacological treatment mainly includes SSRIs, noradrenergic and specific serotonergic antidepressant (NaSSA), anti-inflammatory drugs, vitamin D, ect, which have been confirmed to have better efficacy by clinical studies. Currently, there is an increasing number of studies related to the mechanisms of PSD. However, the mechanisms and pharmacologic treatment of PSD is still unclear. In the future, in-depth research on the mechanisms and treatment of PSD is needed to provide a reference for the prevention and treatment of clinical PSD.
Immune signatures of the POLE mutation in endometrial carcinomas: a systematic study based on TCGA data and clinical cohort validation
Authors: Wang Tieyan , Yu Dan , Wang Juanjuan , Zhu Ningning , Tang Xian-bin , Chen Xiuwen , Su Xiao-min , Huang Yu-gang
Published: November 2023

Background

POLE is a critical biomarker for endometrial cancer (ECs) prognosis and therapeutic decision. However, the immune infiltration and immunotherapy-related gene expression in the tumor microenvironment (TME) of POLE-mutated ECs remain unresolved.

Methods

The TCGA database was used to characterize the TME of POLE mutants, which primarily included immune cells and co-expression genes. We used immunohistochemistry (IHC) to determine immune cell abundance and PD-L1 expression in 104 EC tissues, including 11 POLE mutants and 93 wild-type.

Results

The bioinformatic study found significant differences in gene expression of the chemokine family, immune-cell markers, and lysozyme in POLE mutants, along with immune response activation. In POLE-mutated ECs, the abundance of CD4+T, CD8+T, M1 macrophages, and dendritic cells increased considerably. Furthermore, POLE mutations may enhance immune cell recruitment or activation and lymphocyte homing in ECs. POLE mutants also had increased expression of immune-checkpoint suppressor genes such as PD-L1, CTLA-4, TIM-3, and others. The tumor mutation burden (TMB) was higher in ECs with POLE mutation. In the validation cohort, we discovered that POLE mutations were related to the immune infiltration abundance of CD8+, CD4+, and Foxp3+ cells and PD-L1 expression by IHC. The prognosis of TCGA-ECs showed that the survival time of the CD8, CD4, PD-L1, or Foxp3 over-expression subgroup of the POLE mutants was significantly prolonged compared to the down-regulation subgroup or the POLE wild-type.

Conclusion

The infiltration abundance of CD8+ T, CD4+ T, Foxp3+ T cells, and the expression of PD-L1 harbor crucial value for the prognosis or individualized therapy of POLE-mutated ECs.
Dramatic response and acquired resistance to savolitinib in advanced intrahepatic cholangiocarcinoma with MET amplification: a case report and literature review
Authors: Zhou Kexun , Liu Yingping , Zhu Hong
Published: November 2023

Background

Cholangiocarcinoma (CCA) is an aggressive disease with limited treatment options. Despite substantial efforts to explore better regimens, gemcitabine-based chemotherapy has been the standard first-line treatment for decades. With the growing field of precision medicine, biomarker-guided treatments are gaining popularity. MET alteration is a frequent occurrence in various cancer types, making it a promising target.

Case presentation

A 53-year-old man visited our hospital with a complaint of upper abdominal pain. Advanced CCA was diagnosed based on the biopsy of the metastatic lymph nodes and immunohistochemistry. Next-generation sequencing revealed MET amplification. As the patient was intolerant to traditional chemotherapy, savolitinib (a c-MET inhibitor) was administered. Partial response was achieved, and the treatment was well tolerated. After 1 year, the patient developed progressive disease, to which the emergence of epidermal growth factor receptor amplification may have contributed.

Conclusion

Our study verified the therapeutic value of a c-MET inhibitor in advanced CCA-harboring MET amplification and provides an alternative strategy for patients who are intolerant to chemotherapy.
Antiparasitic activity of FLLL-32 against four Babesia species, B. bovis, B. bigemina, B. divergens and B. caballi, and one Theileria species, Theileria equi in vitro, and Babesia microti in mice
Authors: El-Sayed Shimaa Abd El-Salam , El-Alfy El-Sayed , Baghdadi Hanadi B. , Sayed-Ahmed Mohamed Z. , Alqahtani Saad S. , Alam Nawazish , Ahmad Sarfaraz , Ali Md. Sajid , Igarashi Ikuo , Rizk Mohamed Abdo
Published: November 2023

Introduction: FLLL-32, a synthetic analog of curcumin, is a potent inhibitor of STAT3’s constitutive activation in a variety of cancer cells, and its anticancer properties have been demonstrated both in vitro and in vivo. It is also suggested that it might have other pharmacological activities including activity against different parasites.

Aim: This study therefore investigated the in vitro antiparasitic activity of FLLL-32 against four pathogenic Babesia species, B. bovis, B. bigemina, B. divergens, and B. caballi, and one Theileria species, Theileria equi. In vivo anti-Babesia microti activity of FLLL-32 was also evaluated in mice.

Methods: The FLLL-32, in the growth inhibition assay with a concentration range (0.005–50 μM), was tested for it’s activity against these pathogens. The reverse transcription PCR (RT-PCR) assay was used to evaluate the possible effects of FLLL-32 treatment on the mRNA transcription of the target B. bovis genes including S-adenosylhomocysteine hydrolase and histone deacetylase.

Results: The in vitro growth of B. bovis, B. bigemina, B. divergens, B. caballi, and T. equi was significantly inhibited in a dose-dependent manner (in all cases, p < 0.05). FLLL-32 exhibits the highest inhibitory effects on B. bovis growth in vitro, and it’s IC50 value against this species was 9.57 μM. The RT-PCR results showed that FLLL-32 inhibited the transcription of the B. bovis S-adenosylhomocysteine hydrolase gene. In vivo, the FLLL-32 showed significant inhibition (p < 0.05) of B. microti parasitemia in infected mice with results comparable to that of diminazene aceturate. Parasitemia level in B. microti-infected mice treated with FLLL-32 from day 12 post infection (pi) was reduced to reach zero level at day 16 pi when compared to the infected non-treated mice.

Conclusion: The present study demonstrated the antibabesial properties of FLLL-32 and suggested it’s usage in the treatment of babesiosis especially when utilized in combination therapy with other antibabesial drugs.
Apoptosis mechanisms induced by 15d-PMJ2 in HCT116 colon cancer cells: insights into CHOP10/TRB3/Akt signaling
Authors: Albassam Hussam , Ladin Daniel A. , Elhassanny Ahmed , Burns Colin , Van Dross-Anderson Rukiyah
Published: November 2023

Agents that stimulate the endoplasmic reticulum (ER) stress pathway are being exploited pharmacologically to induce cancer cell death. Cytotoxic ER stress is typically regulated by the transcription factor, C/EBP homologous protein 10 (CHOP10). Products of CHOP10 transcription include the pro-apoptotic proteins: ER oxidoreductase 1α (ERO1α), death receptor-5 (DR5), and tribbles-related protein 3 (TRB3). Our previous findings showed cell death induced by 15-deoxy- Δ12,14 prostamide J2 (15d-PMJ2) occurred in an ER stress-dependent manner. However, the pathway by which 15d-PMJ2 regulates ER stress-mediated death downstream of CHOP10 has not been identified. Our results demonstrate 5 µM 15d-PMJ2 increased CHOP10 expression and apoptosis in HCT116 colon cancer cells. In cells treated with pharmacological inhibitors of ER stress, 15d-PMJ2-induced apoptosis was reliant upon the ER stress pathway. To investigate the role of CHOP10 and its transcriptional products in apoptosis, genetic deletion of CHOP10 (CHOP10-KO) was performed using the CRISPR/Cas9 system. The apoptotic action of 15d-PMJ2 was blunted in cells lacking CHOP10 expression. The deletion of CHOP10 reduced the expression of DR5, ERO1α, and TRB3 although only the expression of TRB3 was significantly reduced. Therefore, we overexpressed TRB3 in CHOP10-KO cells and observed that the activation of Akt was inhibited and 15d-PMJ2-induced apoptosis was restored. Thus, a mechanism of apoptosis elicited by 15d-PMJ2 includes the stimulation of CHOP10/TRB3/Akt inhibition. Given the important role these signaling molecules play in cancer cell fate, 15d-PMJ2 may be an effective inducer of apoptosis in cancer cells.
Research on vertical GaN devices based on gradient Al components
Authors: Chen Yonghe , Yang Ye , Zhai Jianghui , Sun Yuanyuan
Published: November 2023

A groove-gate power device with a linearly gradient Al composition P-type AlGaN superjunction (abbreviated as LG-SJCAVET) is proposed, which uses polarized P-type AlGaN material instead of the traditional P-type GaN buried layer, avoiding the technical bottleneck of achieving high-aspect-ratio P-type doping in GaN materials. Simulation results show that, under the same structural parameters, the breakdown voltage of LG-SJCAVET reaches 2954V, and the on-resistance is 1.669 mΩ⋅cm2, which is due to no current flowing through the P-pillar, resulting in an increase in on-resistance, while affecting the DC characteristics of the device. The power figure of merit of the device is 5.27 GW/cm2, which is 67.11% and 27.38% higher than that of the traditional device and P-type GaN buried layer device, respectively. Therefore, the LG-SJCAVET device solves the problems of the high technical difficulty of the traditional P-type GaN buried layer process, difficulty in activating acceptor impurities, and poor thermal stability of the device, exhibiting superior breakdown voltage characteristics.
Low-field MRI at high magnetic field instability and inhomogeneity conditions
Authors: Rodriguez Gonzalo G. , Schürrer Clemar A. , Anoardo Esteban
Published: November 2023

Understanding the effects of the magnetic field time instabilities in magnetic resonance imaging (MRI) is fundamental for the success of portable and low-cost MRI hardware based on electromagnets. In this work we propose a magnetic field model that considers the field instability in addition to the inhomogeneity. We have successfully validated the model on signals acquired with a commercial NMR instrument. It was used to simulate the image defects due to different types of instability for both the spin-echo and the gradient-echo sequences. We have considered both random field fluctuations, and an instability having a dominant harmonic component. Strategies are suggested to minimize the artifacts generated by these instabilities. Images were acquired using a home-made MRI relaxometer to show the consistency of the analysis.
Prediction of additive, epistatic, and dominance effects using models accounting for incomplete inbreeding in parental lines of hybrid rye and sugar beet
Authors: Kristensen Peter Skov , Sarup Pernille , Fé Dario , Orabi Jihad , Snell Per , Ripa Linda , Mohlfeld Marius , Chu Thinh Tuan , Herrström Joakim , Jahoor Ahmed , Jensen Just
Published: November 2023

Genomic models for prediction of additive and non-additive effects within and across different heterotic groups are lacking for breeding of hybrid crops. In this study, genomic prediction models accounting for incomplete inbreeding in parental lines from two different heterotic groups were developed and evaluated. The models can be used for prediction of general combining ability (GCA) of parental lines from each heterotic group as well as specific combining ability (SCA) of all realized and potential crosses. Here, GCA was estimated as the sum of additive genetic effects and within-group epistasis due to high degree of inbreeding in parental lines. SCA was estimated as the sum of across-group epistasis and dominance effects. Three models were compared. In model 1, it was assumed that each hybrid was produced from two completely inbred parental lines. Model 1 was extended to include three-way hybrids from parental lines with arbitrary levels of inbreeding: In model 2, parents of the three-way hybrids could have any levels of inbreeding, while the grandparents of the maternal parent were assumed completely inbred. In model 3, all parental components could have any levels of inbreeding. Data from commercial breeding programs for hybrid rye and sugar beet was used to evaluate the models. The traits grain yield and root yield were analyzed for rye and sugar beet, respectively. Additive genetic variances were larger than epistatic and dominance variances. The models’ predictive abilities for total genetic value, for GCA of each parental line and for SCA were evaluated based on different cross-validation strategies. Predictive abilities were highest for total genetic values and lowest for SCA. Predictive abilities for SCA and for GCA of maternal lines were higher for model 2 and model 3 than for model 1. The implementation of the genomic prediction models in hybrid breeding programs can potentially lead to increased genetic gain in two different ways: I) by facilitating the selection of crossing parents with high GCA within heterotic groups and II) by prediction of SCA of all realized and potential combinations of parental lines to produce hybrids with high total genetic values.