bluuebunny/crossref_metadata_2025 huggingface dataset:
Tryptophan depletion sensitizes the AHR pathway by increasing AHR expression and GCN2/LAT1-mediated kynurenine uptake, and potentiates induction of regulatory T lymphocytes
Authors: Solvay Marie , Holfelder Pauline , Klaessens Simon , Pilotte Luc , Stroobant Vincent , Lamy Juliette , Naulaerts Stefan , Spillier Quentin , Frédérick Raphaël , De Plaen Etienne , Sers Christine , Opitz Christiane A , Van den Eynde Benoit J , Zhu Jingjing
Published: June 2023

Background

Indoleamine 2,3-dioxygenase 1 (IDO1) and tryptophan-dioxygenase (TDO) are enzymes catabolizing the essential amino acid tryptophan into kynurenine. Expression of these enzymes is frequently observed in advanced-stage cancers and is associated with poor disease prognosis and immune suppression. Mechanistically, the respective roles of tryptophan shortage and kynurenine production in suppressing immunity remain unclear. Kynurenine was proposed as an endogenous ligand for the aryl hydrocarbon receptor (AHR), which can regulate inflammation and immunity. However, controversy remains regarding the role of AHR in IDO1/TDO-mediated immune suppression, as well as the involvement of kynurenine. In this study, we aimed to clarify the link between IDO1/TDO expression, AHR pathway activation and immune suppression.

Methods

AHR expression and activation was analyzed by RT-qPCR and western blot analysis in cells engineered to express IDO1/TDO, or cultured in medium mimicking tryptophan catabolism by IDO1/TDO. In vitro differentiation of naïve CD4+T cells into regulatory T cells (Tregs) was compared in T cells isolated from mice bearing differentAhralleles or a knockout ofAhr, and cultured in medium with or without tryptophan and kynurenine.

Results

We confirmed that IDO1/TDO expression activated AHR in HEK-293-E cells, as measured by the induction of AHR target genes. Unexpectedly, AHR was also overexpressed on IDO1/TDO expression. AHR overexpression did not depend on kynurenine but was triggered by tryptophan deprivation. Multiple human tumor cell lines overexpressedAHRon tryptophan deprivation.AHRoverexpression was not dependent on general control non-derepressible 2 (GCN2), and strongly sensitized the AHR pathway. As a result, kynurenine and other tryptophan catabolites, which are weak AHR agonists in normal conditions, strongly induced AHR target genes in tryptophan-depleted conditions. Tryptophan depletion also increased kynurenine uptake by increasing SLC7A5 (LAT1) expression in a GCN2-dependent manner. Tryptophan deprivation potentiated Treg differentiation from naïve CD4+T cells isolated from mice bearing an AHR allele of weak affinity similar to the human AHR.

Conclusions

Tryptophan deprivation sensitizes the AHR pathway by inducingAHRoverexpression and increasing cellular kynurenine uptake. As a result, tryptophan catabolites such as kynurenine more potently activate AHR, and Treg differentiation is promoted. Our results propose a molecular explanation for the combined roles of tryptophan deprivation and kynurenine production in mediating IDO1/TDO-induced immune suppression.
Discovery of a novel dual-targeting D-peptide to block CD24/Siglec-10 and PD-1/PD-L1 interaction and synergize with radiotherapy for cancer immunotherapy
Authors: Shen Wenhui , Shi Peishang , Dong Qingyu , Zhou Xiuman , Chen Chunxia , Sui Xinghua , Tian Wentong , Zhu Xueqin , Wang Xiaoxi , Jin Shengzhe , Wu Yahong , Chen Guanyu , Qiu Lu , Zhai Wenjie , Gao Yanfeng
Published: June 2023

Background

Aside from immune checkpoint inhibitors targeting programmed cell death protein 1 (PD-1) and programmed death ligand 1 (PD-L1), intervention of CD47/Sirpα mediated ‘don’t eat me’ signal between macrophage and tumor cell is considered as a promising therapeutic approach for cancer immunotherapy. Compared with CD47, the novel immune checkpoint CD24/Siglec-10 can also deliver ‘don’t eat me’ signal and CD24 shows much lower expression level in normal tissue which might avoid unwanted side effects.

Methods

Cell-based phage display biopanning and D-amino acid modification strategy were used to identify the CD24/Siglec-10 blocking peptide. Cell-based blocking assay and microscale thermophoresis assay were used to validate the blocking and binding activities of the peptide. Phagocytosis and co-culture assays were used to explore the in vitro function of the peptide. Flow cytometry was performed to assess the immune microenvironment after the peptide treatment in vivo.

Results

A CD24/Siglec-10 blocking peptide (CSBP) with hydrolysis-resistant property was identified. Surprisingly, we found that CSBP could not only block the interaction of CD24/Siglec-10 but also PD-1/PD-L1. CSBP could induce the phagocytosis of tumor cell by both the macrophages and monocytic myeloid-derived suppressor cells (M-MDSCs), which can further activate CD8+T cells. Besides, combination of radiotherapy and CSBP synergistically reduced tumor growth and altered the tumor microenvironment in both anti-PD-1-responsive MC38 and anti-PD-1-resistant 4T1 tumor models.

Conclusions

In summary, this is the first CD24/Siglec-10 blocking peptide which blocked PD-1/PD-L1 interaction as well, functionedviaenhancing the phagocytosis of tumor cells by macrophages and M-MDSCs, and elevating the activity of CD8+T cells for cancer immunotherapy.
New hormone receptor-positive breast cancer mouse cell line mimicking the immune microenvironment of anti-PD-1 resistant mammary carcinoma
Authors: Perez-Lanzon Maria , Carbonnier Vincent , Cordier Pierre , De Palma Fatima Domenica Elisa , Petrazzuolo Adriana , Klein Christophe , Arbaretaz Floriane , Mangane Khady , Stoll Gautier , Martins Isabelle , Fohrer Ting Helene , Paillet Juliette , Mouillet-Richard Sophie , Le Corre Delphine , Xiao Wenjjin , Sroussi Marine , Desdouets Chantal , Laurent-Puig Pierre , Pol Jonathan , Lopez-Otin Carlos , Maiuri Maria Chiara , Kroemer Guido
Published: June 2023

Background

Progress in breast cancer (BC) research relies on the availability of suitable cell lines that can be implanted in immunocompetent laboratory mice. The best studied mouse strain, C57BL/6, is also the only one for which multiple genetic variants are available to facilitate the exploration of the cancer-immunity dialog. Driven by the fact that no hormone receptor-positive (HR+) C57BL/6-derived mammary carcinoma cell lines are available, we decided to establish such cell lines.

Methods

BC was induced in female C57BL/6 mice using a synthetic progesterone analog (medroxyprogesterone acetate, MPA) combined with a DNA damaging agent (7,12-dimethylbenz[a]anthracene, DMBA). Cell lines were established from these tumors and selected for dual (estrogen+progesterone) receptor positivity, as well as transplantability into C57BL/6 immunocompetent females.

Results

One cell line, which we called B6BC, fulfilled these criteria and allowed for the establishment of invasive estrogen receptor-positive (ER+) tumors with features of epithelial to mesenchymal transition that were abundantly infiltrated by myeloid immune populations but scarcely by T lymphocytes, as determined by single-nucleus RNA sequencing and high-dimensional leukocyte profiling. Such tumors failed to respond to programmed cell death-1 (PD-1) blockade, but reduced their growth on treatment with ER antagonists, as well as with anthracycline-based chemotherapy, which was not influenced by T-cell depletion. Moreover, B6BC-derived tumors reduced their growth on CD11b blockade, indicating tumor sustainment by myeloid cells. The immune environment and treatment responses recapitulated by B6BC-derived tumors diverged from those of ER+TS/A cell-derived tumors in BALB/C mice, and of ER–E0771 cell-derived and MPA/DMBA-induced tumors in C57BL/6 mice.

Conclusions

B6BC is the first transplantable HR+BC cell line derived from C57BL/6 mice and B6BC-derived tumors recapitulate the complex tumor microenvironment of locally advanced HR+BC naturally resistant to PD-1 immunotherapy.
Trajectory of a medical career: a perspective regarding a proposed model
Authors: Stoller James K
Published: June 2023

A career as a physician offers so many options—clinical care, research, education, leadership, etc. Still, a general trajectory of a medical career can be usefully modelled. Based on a USA-centric lens, this proposed model—which is based on a personal reflection and conversation with colleagues—consists of an initial two-component linear phase, followed later by a non-linear phase. The linear phase requires mastery of a large body of knowledge, acquiring cognitive and technical skills, and achieving prescribed milestones. Two components of the linear trajectory are early education through medical school, and then graduate medical education through the initial career path. A non-linear phase follows, characteristically beginning after graduate medical training and the initial ‘hitting stride’ in the first post-training position.

At this point, the physician’s choices regarding career direction are wide open. Yet, the intense focus needed to master the prolonged linear phase of the physician’s career can exert opposing effects on preparedness for the subsequent non-linear phase; years of satisfying prescribed curricula and examinations may blunt the self-directed learning and intrinsic motivation needed for the non-linear phase while also stimulating the appetite to get beyond the guardrails of the linear phase.

This model has implications for early training, namely encouraging a focus on mindfulness and introducing this model as part of professional identity formation. Given differences in medical training across the globe, generalisability of the model to settings outside the United States would require validation by others.
Five hats of effective leaders: teacher, mentor, coach, supervisor and sponsor
Authors: Winters Richard C , Chan Teresa M , Barth Bradley E
Published: June 2023

Background/aim

Teaching, mentoring, coaching, supervising and sponsoring are often conflated in the literature. In this reflection, we clarify the distinctions, the benefits and the drawbacks of each approach. We describe a conceptual model for effective leadership conversations where leaders dynamically and deliberately ‘wear the hats’ of teacher, mentor, coach, supervisor and/or sponsor during a single conversation.

Methods

As three experienced physician leaders and educators, we collaborated to write this reflection on how leaders may deliberately alter their approach during dynamic conversations with colleagues. Each of us brings our own perspective and lens.

Results

We articulate how each of the ‘five hats’ of teacher, mentor, coach, supervisor and sponsor may help or hinder effectiveness. We discuss how a leader may ‘switch’ hats to engage, support and develop colleagues across an ever-expanding range of contexts and settings. We demonstrate how a leader might ‘wear the five hats’ during conversations about career advancement and burn-out.

Conclusion

Effective leaders teach, mentor, coach, supervise and sponsor during conversations with colleagues. These leaders employ a deliberate, dynamic and adaptive approach to better serve the needs of their colleagues at the moment.
Towards a quantitative definition of Cyanobacteria blooms
Authors: Frau Diego
Published: June 2023

Cyanobacteria blooms represent a global problem with human health and economic and ecosystem nuisance effects. Until now, we have used arbitrary and sometimes confusing criteria to decide whether we are in the presence of a Cyanobacteria bloom. Through scientometric analysis of studies published between 1953 and 2022, I aimed to identify a threshold value that can be used to quantify Cyanobacteria blooms numerically. I considered several methodological approaches (field, field-experimental, and satellite data) and kinds of environments (coastal, marine, and continental ecosystems). The analysis revealed that 48% of the papers used “cyanobacteria bloom” or similar terms qualitatively without providing or employing a quantitative definition. These papers were focused on other topics related to the ecology of Cyanobacteria (78%), while some others (21%) defined blooms by using visual criteria (scum visualization or water discoloration). Of the other half (52%), a few were mathematical models or review papers (5%), while the rest (65%) defined blooms quantitatively. Of these, most reports (approximately 80%) were from eutrophic inland waters and reported mean values for blooms between 80 000 and 249 000 cells mL−1 or 41 and 69 µg L−1 of chlorophyll- a. Calculations were also carried out for oligotrophic to mesotrophic inland waters and marine-coastal waters, which had fewer reports available in the literature. This is a first attempt to identify a consensual definition based on values reported as blooms in nature, a threshold that can undoubtedly be useful in the future to make possible comparisons among several environments and temporal scales.
An anisotropic stellar fluid configuration with vanishing complexity
Authors: Andrade J. , Santana D.
Published: June 2023

In this work, we construct a new stellar model in the regime of anisotropic fluid pressure using the concept of vanishing complexity for spherically symmetric fluid distributions (Herrera in Phys Rev D 97:044010, 2018) and a convenient ansatz in order to close the Einstein’s field equations. The resulting model fulfills the fundamental physical acceptability stellar conditions for a specific set of compactness factor. The stability and its response against fluctuations in the matter sector is also investigated.
Pentaquark interpretation of $$\Lambda _{c}$$ states in the quark model
Authors: Yan Ye , Hu Xiaohuang , Wu Yuheng , Huang Hongxia , Ping Jialun , Yang Youchang
Published: June 2023

Motivated by the recent observation of the$$\Lambda _c(2910)^+$$Λc(2910)+state in the$$\Sigma _{c}(2455)^{0,++}\pi ^{\pm }$$Σc(2455)0,++π±spectrum by the Belle Collaboration, we investigate the explanation of$$\Lambda _{c}$$Λcstates within the pentaquark framework using the quark delocalization color screening model (QDCSM). To check for bound states and resonance states, we utilize the real-scaling method. Additionally, we calculate the root mean square of cluster spacing to study the structure of the states and further estimate whether a state is a resonance state or not. Our numerical results show that$$\Lambda _{c}(2910)$$Λc(2910)cannot be interpreted as a molecular state, and$$\Sigma _{c}(2800)$$Σc(2800)cannot be explained as theNDmolecular state with$$J^P=1/2^-$$JP=1/2-. However, we find that$$\Lambda _{c}(2595)$$Λc(2595)can be interpreted as a molecular state with$$J^P=\frac{1}{2}^-$$JP=12-, where the main component is$$\Sigma _{c}\pi $$Σcπ. Similarly, we interpret$$\Lambda _{c}(2625)$$Λc(2625)as a molecular state with$$J^P=\frac{3}{2}^-$$JP=32-, where the main component is$$\Sigma _{c}^{*}\pi $$Σc∗π. We also suggest that$$\Lambda _{c}(2940)$$Λc(2940)is likely to be interpreted as a molecular state with$$J^P=3/2^-$$JP=3/2-, where the main component is$$ND^{*}$$ND∗. In addition, we predict two new states: a$$J^P=3/2^-$$JP=3/2-$$\Sigma _{c}\rho $$Σcρresonance state with a mass of 3140–3142 MeV, and a$$J^P=\frac{5}{2}^-$$JP=52-$$\Sigma _{c}^*\rho $$Σc∗ρstate with a mass about 3187–3188 MeV.
Skeletal muscle protein turnover responses to parenteral nutrition in patients with alcoholic liver cirrhosis and sarcopenia
Authors: Iepsen Ulrik Winning , Rinnov Anders Rasmussen , Munch Gregers Winding , Rugbjerg Mette , Winding Kamilla Munch , Lauridsen Carsten , Berg Ronan M. G. , Pedersen Bente Klarlund , Gluud Lise Lotte , van Hall Gerrit
Published: June 2023

Muscle protein turnover responses to parenteral nutritional (PN) supplementation have not previously been studied in stable alcoholic liver cirrhosis (ALC). We applied stable isotope tracers of amino acids to directly quantify net muscle protein turnover responses to PN in sarcopenic males with ALC and healthy controls. We found a higher net muscle protein gain in ALC during PN, thereby providing the physiological rationale for future clinical trials of PN as a potential countermeasure to sarcopenia.
Mechanisms of SARS-CoV-2-associated anosmia
Authors: Tsukahara Tatsuya , Brann David H. , Datta Sandeep Robert
Published: June 2023

Anosmia, the loss of the sense of smell, is one of the main neurological manifestations of COVID-19. Although the SARS-CoV-2 virus targets the nasal olfactory epithelium, current evidence suggests that neuronal infection is extremely rare in both the olfactory periphery and the brain, prompting the need for mechanistic models that can explain the widespread anosmia in COVID-19 patients. Starting from work identifying the non-neuronal cell types that are infected by SARS-CoV-2 in the olfactory system, we review the effects of infection of these supportive cells in the olfactory epithelium and in the brain and posit the downstream mechanisms through which sense of smell is impaired in COVID-19 patients. We propose that indirect mechanisms contribute to altered olfactory system function in COVID-19-associated anosmia, as opposed to neuronal infection or neuroinvasion into the brain. Such indirect mechanisms include tissue damage, inflammatory responses through immune cell infiltration or systemic circulation of cytokines, and downregulation of odorant receptor genes in olfactory sensory neurons in response to local and systemic signals. We also highlight key unresolved questions raised by recent findings.
Inflammatory Myo-Fibroblastic Tumor of the Gallbladder with Multivisceral Involvement: Successful Treatment with Radical Surgery
Authors: Losuwarat Kwanchanok , Luvira Vor , Thanasukarn Vasin , Tipwaratorn Theerawee , Ungarreevittaya Piti
Published: June 2023

Inflammatory myo-fibroblastic tumor (IMT) of the gallbladder is an extremely rare condition. Only seven cases have been reported. All of these were presented either with polyp/mass inside the gallbladder or gallbladder wall thickening, involving just one adjacent organ. We herein present a case of IMT of gallbladder presenting with a huge mass replacing the gallbladder with multiple organ involvement, successfully treated by en bloc multivisceral resection. Moreover, we have compared it with the characteristics of all reported cases of IMT of the gallbladder.
The Development of Ambulatory Cancer Care in the UK: A Scoping Review of the Literature
Authors: Finch Alison , Cooper Silvie , Raine Rosalind , Taylor Rachel M. , Gibson Faith
Published: June 2023

Introduction. Ambulatory Care (AC), where patients receive inpatient cancer treatment on an outpatient basis, was introduced into the United Kingdom (UK) National Health Service (NHS) in 2004. Although now well established within some services, the development of AC across the NHS is yet to be described. We report findings of a scoping review that set out to understand the provenance of the clinical pathway, whilst exploring drivers for the development of AC in the UK. Methods. Using scoping review methods, database citation, and grey literature, searches were undertaken to map the storyline of AC’s development internationally. The Joanna Briggs Institute guidance was followed; this included consultation with six professionals considered critical to the development of AC. Results. From the 57 records identified between 1979 and 2022, four domains were identified through a narrative synthesis that reflected the following drivers for AC: financial; optimisation of bed capacity; advances in technology and supportive care; and professional motivation to improve patient experience. Conclusion. We report the first descriptive analysis of the international development of AC, locating the UK cancer service within its commissioning, operational, and philosophical foundations. The review additionally highlights limited research exploring the experience of the AC model from the patients’ perspective.
YAP1 as a Novel Negative Biomarker of Immune Checkpoint Inhibitors for EGFR-Mutant Non-Small-Cell Lung Cancer
Authors: Li Ling-Chen , Chen Xie-Wan , Fang Ling , Jian Chun-Li , Yu Yong-Xin , Liao Xing-Yun , Sun Jian-Guo
Published: June 2023

Background. Immune checkpoint inhibitors (ICIs) have become a standard care in non-small-cell lung cancer (NSCLC). However, its application to epidermal growth factor receptor (EGFR)-mutant NSCLC patients is confronted with drug resistance. This study aimed to clarify the potential role of Yes1-associated transcriptional regulator (YAP1) in ICIs treatment for EGFR-mutant NSCLC population. Methods. All the clinical data of NSCLC were downloaded from Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) for GSE11969 and GSE72094. Based on YAP1 expression, all the NSCLC patients including the EGFR-mutant and EGFR-wildtype (WT) patients were divided into two groups, YAP1_High and YAP1_Low. Using cBioPortal, genetic alterations were analyzed for identification of immunogenicity in EGFR-mutant NSCLC. MR analysis was used to analyze the hub gene of EGFR. The infiltration of immune cells and the expression of the identified tumor-associated antigens were identified with TIMER. By graph learning-based dimensionality reduction analysis, the immune landscape was visualized. Moreover, survival analysis was performed to verify the predictive value of YAP1 in ICIs treatment for EGFR-mutant NSCLC population using Ren’s research data (NCT03513666). Results. YAP1 was a poor prognostic factor of EGFR-mutant NSCLC population rather than lung adenocarcinoma (LUAD) patients. MR analysis revealed that the EGFR gene regulated YAP1 expression. YAP1 was identified as a hub gene closely associated with immunosuppressive microenvironment and poor prognosis in EGFR-mutant NSCLC population in TCGA LUAD. Tumors with YAP1_High showed an immune-“cold” and immunosuppressive phenotype, whereas those with YAP1_Low demonstrated an immune-“hot” and immunoactive phenotype. More importantly, it was verified that YAP1_High subpopulation had a significantly shorter progression-free survival (PFS) and overall survival (OS) after ICIs treatment in EGFR-mutant NSCLC patients in the clinical trial. Conclusions. YAP1 mediates immunosuppressive microenvironment and poor prognosis in EGFR-mutant NSCLC population. YAP1 is a novel negative biomarker of ICIs treatment in EGFR-mutant NSCLC population. Clinical Trials. This trial is registered with NCT03513666.
Antiradical Activity Studies of Ultrasound-Assisted Extraction of Total Flavonoids from Sanghuangporus vaninii Fruit Bodies
Authors: Lin Guo , Dou Xin , Gao NengBin , Hu DianJie , Zhang Lihong
Published: June 2023

Flavonoids are a class of secondary metabolites present in many plant species. Flavonoids are important active components in Sanghuangporus vaninii. It has attracted widely attention because of its unique antitumor, antioxidation, immunomodulatory, bacteriostatic, and other biological activities. In this study, the Sanghuangporus vaninii fruit bodies are used as raw materials to study the optimal extraction technology of the Sanghuangporus flavonoids. In addition, the antioxidant and bacteriostatic abilities of Sanghuangporus vaninii are analyzed through antioxidant and bacteriostatic experiments. Ultrasound-assisted ethanol extraction is used to extract Sanghuangporus flavonoids. The optimum extraction process was determined by single factor test and response surface analysis, namely, ratio of material to liquid 1 : 60, ethanol concentration 80%, ultrasonic temperature 70°C, and ultrasonic time 40 min. Under these conditions, the flavonoids content is 90.24 ± 0.89 mg/g (on dry weight basis). Using VC as the reference substance, the total flavonoid concentration was tested for its ability to scavenge free radicals such as DPPH, ABTS+, OH, and O2-. The reducing power of total crude flavonoids, the scavenging ability of NO2- , and the antibacterial and anti-inflammatory abilities are also used as evaluation indicators for this experiment. The results showed that the best scavenging rates of Sanghuangporus vaninii flavonoids for DPPH, ABTS+,· OH, and O2-.were, respectively, 92.17 ± 1.33%, 92.49 ± 1.55%, 94.85 ± 1.39%, and 86.01 ± 1.21%. In terms of reducibility, the absorbance of Sanghuangporus vaninii flavonoids at 0.008 mg/ml was 2.65 ± 0.04, which was higher than that of positive control VC at 0.90 ± 0.05. Sanghuangporus vaninii flavonoids at 200 μg/mL could effectively inhibit the NO2- content in vitro to 9.38 ± 0.23 pg/ml. The inhibitory rates of Sanghuangporus vaninii flavonoids on Escherichia coli, Staphylococcus aureus, and Bacillus subtilis were 79.48 ± 1.57%, 85.64 ± 1.22%, and 80.29 ± 0.04%. When the concentration of Sanghuangporus vaninii flavonoids was 200 μg/mL, the concentration of NO was 9.38 ± 0.23 pg/ml.
Bioprospection of Selected Plant Secondary Metabolites as Modulators of the Proteolytic Activity of Plasmodium falciparum Plasmepsin V
Authors: Sulyman Abdulhakeem Olarewaju , Aje Oluwapelumi Oluwaseun , Ajani Emmanuel Oladipo , Abdulsalam Rukayat Abiola , Balogun Fatai Oladunni , Sabiu Saheed
Published: June 2023

Malaria is a devastating disease, and its management is only achieved through chemotherapy. However, resistance to available medication is still a challenge; therefore, there is an urgent need for the discovery and development of therapeutics with a novel mechanism of action to counter the resistance scourge consistent with the currently available antimalarials. Recently, plasmepsin V was validated as a therapeutic target for the treatment of malaria. The pepsin‐like aspartic protease anchored in the endoplasmic reticulum is responsible for the trafficking of parasite‐derived proteins to the erythrocytic surface of the host cells. In this study, a small library of compounds was preliminarily screened in vitro to identify novel modulators of Plasmodium falciparum plasmepsin V (PfPMV). The results obtained revealed kaempferol, quercetin, and shikonin as possible PfPMV inhibitors, and these compounds were subsequently probed for their inhibitory potentials using in vitro and in silico methods. Kaempferol and shikonin noncompetitively and competitively inhibited the specific activity of PfPMV in vitro with IC50 values of 22.4 and 43.34 μM, respectively, relative to 62.6 μM obtained for pepstatin, a known aspartic protease inhibitor. Further insight into the structure‐activity relationship of the compounds through a 100 ns molecular dynamic (MD) simulation showed that all the test compounds had a significant affinity for PfPMV, with quercetin (‐36.56 kcal/mol) being the most prominent metabolite displaying comparable activity to pepstatin (‐35.72 kcal/mol). This observation was further supported by the compactness and flexibility of the resulting complexes where the compounds do not compromise the structural integrity of PfPMV but rather stabilized and interacted with the active site amino acid residues critical to PfPMV modulation. Considering the findings in this study, quercetin, kaempferol, and shikonin could be proposed as novel aspartic protease inhibitors worthy of further investigation in the treatment of malaria.
A Wideband Highly Efficient Omnidirectional Compact Antenna for WiMAX/Lower 5G Communications
Authors: Paul Liton Chandra , Ankan Sarker Saleh Ahmed , Rani Tithi , Karaaslan Muharrem , Hossain Md. Najmul , Al-Gburi Ahmed Jamal Abdullah , Saha Himel Kumar , Alkurt Fatih Özkan
Published: June 2023

Microstrip patch antenna (MPA) is widely used for different wireless communications such as WiMAX and fifth generation (5G). In this paper, a wideband, highly efficient, omnidirectional, compact novel patch antenna has been designed and reported for WiMAX/lower 5G communications. The proposed compact MPA is made on Rogers RT 5880 (

ɛ

r

=
2.2

and

tan
 

δ

=
0.0009

). The physical volume of the MPA is compact (

32
×
32
×
0.79

 mm3). The MPA consists of seven small square-shaped elements that are diagonally connected with each other. The 7-element antenna works at 3.592 GHz with a suitable reflection coefficient of -46.78 dB and a -10 dB bandwidth (BW) of 1.40 GHz, covering 3.10-4.50 GHz. The apex gain (

G

) and the directivity (

D

) of the designed prototype are 3.90 dB and 4.20 dBi, respectively. The antenna maintains a high efficiency of 94-98% over the 3.10-4.50 GHz operating range. The VSWR of the antenna is close to unity, which is 1.0092 at 3.592 GHz. Initially, CST is used to design the antenna, and then, all the properties have been buttressed by using high frequency structure simulator (HFSS). Finally, a prototype of the compact 7-element antenna has been developed and measured. Owing to getting good results for the intended applications, the presented compact antenna can be a reliable candidate for WiMAX (3.4-3.6 GHz) and lower 5G (3.3-4.2 GHz).
Design, Analysis, and Control of Biomedical Healthcare Modular Wheelchair with Posture Transformation
Authors: Rahman Muhammad Zia Ur , Ali Imran , Ishfaque Asif , Riaz Muhammad Tanveer , Ahmad Nasir , Al Mahmud M. M. Sayed , Tanveer Rimsha
Published: June 2023

The majority of people with disabilities in the world have impairments that affect their lower bodies. In most of these cases, it was found that the affected person’s upper body was in good health and capable of carrying out all activities; however, the spinal cord injury results in significant health challenges with body functions like urination, bowel movements, heart rate, and respiratory, cardiovascular, and sexual function, which require prompt medical treatment and mobility aids. This study presents the mechanical layout of a wheelchair that can switch between a sitting and a standing position. The center of gravity must be taken into account when creating an electric standing wheelchair. It is designed specifically for people with disabilities to lessen the need of outside assistance, allowing the disabled person to savour a sense of adoration. In the simulation, the electric standing wheelchair analysis is carried out by loading with a human weight of 40 and 100 kg, and the transformation angle is adjusted between 0 and 90 degrees to compare the center of gravity displacement. SolidWorks and ANSYS are used to design the prototype, assemble the product, and establish the safety factor bounds of the structure and capabilities as required. The research focuses to achieve control of speed deviation and acceleration using a fuzzy control technique. The Arduino oversees the operation of the drive system as a controller, and a linear actuator is utilized for standing and sitting positions. This method is affordable, easily constructed, and highly secure.
Study on Interfacial Interaction of Cement-Based Nanocomposite by Molecular Dynamic Analysis and an RVE Approach
Authors: Roopa A. K. , Hunashyal A. M. , Patil Arun Y. , Kamadollishettar Abhishek , Patil Bharatkumar , Soudagar Manzoore Elahi M. , Shahapurkar Kiran , Khan T. M. Yunus , Kalam M. A.
Published: June 2023

There is an increased demand for cement nanocomposites in the twenty-first century due to their composition, higher strength, high efficiency, and multiscale nature. As carbon nanotubes (CNTs) possess extremely high strength, resilience, and stiffness, inclusion of carbon nanotubes in small quantities to the concrete mix makes them a multifunctional material. A molecular level understanding is significant to capacitate the macrolevel properties of these composites. In the proposed work, molecular dynamics (MD) simulations are used to understand the behaviour of the composites at the atomic level and continuum mechanics with representative volume element (RVE) homogenization modelling is carried out for interfacial interaction study of composites. The mechanical properties such as Young’s modulus, shear modulus, and poisons are evaluated using previous methods of simulations for different compositions of nanomaterials in cement matrix. The FORCITE module of MD simulation and square RVE model is used to determine the mechanical, electrical properties, and elastic constants of the cement nanocomposite. The MD simulation describes the linking effect of CNT into cement matric, and the RVE modelling study reveals the pull-out effect of CNT from matrix. From experimental and analytical studies, it is found that increase in CNT till 0.5% weight fraction increases the mechanical properties about 12% and further increasing of CNT weight fraction causes a reduction in mechanical properties about 5% due to the agglomeration of nanotubes. The density of states method in MD simulation indicates that mobility of the electrons increases with an increase in carbon nanotube proportion in the composites. The experimental test results substantiate the analytical studies, and the error obtained from both approaches is less than 20%. From the analytical study, the average maximum Young’s modulus, shear modulus, and bulk modulus are obtained as 46 GPa, 31 GPa, and 32 GPa for 0.5% weight fraction of CNT in cement matrix. Hence, it is concluded that 0.5% weight fraction of CNT is considered as optimum dosage to obtain better electrical and mechanical properties.
Prevalence of CCR5 Delta 32 Genetic Variant in the Turkmen Population of Golestan Province, Northeast of Iran
Authors: Norasi Elmira , Rastegar Mostafa , Hosseini Seyedeh Delafruz , Aghcheli Bahman , Tahamtan Alireza
Published: June 2023

The 32 bp deletion in the chemokine receptor (C‐C motif) 5 gene (CCR5Δ32) is a natural loss of function polymorphism that prevents the protein from locating on the cell surface. This genetic variation acts as a double‐edge sword in the pathogenesis/defense mechanism of different health conditions, such as viral infections, autoimmune diseases, and cancers. Here, we evaluated the prevalence of the CCR5Δ32 polymorphism in the Turkmen population of Golestan province, northeast of Iran. Blood samples were collected from 400 randomly selected Turkmen populations (199 women and 201 men), and genomic DNA was extracted. Characterization of CCR5Δ32 genotypes was performed by PCR using primers flanking the 32‐nucleotide deletion in the CCR5 gene. The amplified DNA fragments were visualized on 2% agarose gel electrophoresis with cybergreen staining under UV light. All individuals were of Turkmen ethnicity and lived in the Golestan province, northeast of Iran. The mean age of all participants was 35.46 years, with a 20‐45 year range. All the studied subjects were healthy without any severe conditions such as autoimmune disease and viral infections. All individuals had no history of HIV infection. The PCR product visualization showed that all the samples are at the 330 bp size, which means the CCR5Δ32 allele was utterly absent from the study population. The presence of the CCR5Δ32 allele among Turkmens may be attributed to the admixture with European descent people. We conclude that the CCR5Δ32 polymorphism may be absent in the Iranian Turkmen population, and further studies with a large population are needed.
Scaled Conjugate Gradient Artificial Neural Network-Based Ripple Current Correlation MPPT Algorithms for PV System
Authors: Noman Abdullah M. , Khan Hamed , Sher Hadeed Ahmed , Almutairi Sulaiman Z. , Alqahtani Mohammed H. , Aljumah Ali S.
Published: June 2023

This article proposes a hybrid scheme of maximum power point tracking (MPPT) based on artificial neural network (ANN) and ripple current correlation (RCC). ANN model is established using the data generated through RCC MPPT. Scaled conjugate gradient ANN is applied to gauge the performance improvement. The proposed scheme is validated through simulations. For this, the proposed system is applied to three different environmental scenarios which are standard testing condition of a PV module, under variable irradiance condition, and variable temperature condition. It is established that the proposed system is well capable of tracking the maximum power point under various test conditions.
Recurrent Hyponatremia in the Setting of Autoimmune Disease with Sicca Syndrome: A Case Report
Authors: El-Moussa Ahmad , Mohsin Syed Umer , Alrawi Omer , Yaseen Obead , Osman Malik Yahya
Published: June 2023

Sjogren’s syndrome is an autoimmune disease associated with xerostomia and xerophthalmia. The association of Sjogren’s with hyponatremia has rarely been reported and has been attributed to syndrome of inappropriate antidiuretic hormone secretion. Here, we report a case of polydipsia secondary to xerostomia as a cause of chronic hyponatremia in the setting of Sjogren’s syndrome. Analysis of the patient’s medical record, including medication reconciliation and dietary habits, revealed several underlying causes of her recurrent hyponatremia. A thorough review of the patient’s clinical history and good bedside examination may reduce prolonged hospitalizations and improve the quality of life of a hyponatremic population of patients who are predominantly elderly.
The Influence of Brand Ambassador, Digital Marketing and Merchandise on Consumer Purchase Decisions on Blackpink Oreo Products
Authors: Noor Fadlian , Nasution Dito Aditia Darma
Published: June 2023

The spread of Hallyu or the Korean Wave (Korean wave) over the past few years has continued to increase. Korean wave or Hallyu has a variety of products ranging from K-dramas, films, music (K-pop), fashion and also food from South Korea which is now common among Indonesians. Currently, what is very popular among Indonesian people, from teenagers to adults, both women and men, from their teens to their tens, is K-Pop. K-pop has an important role in popularizing the Korean wave in Indonesia. This study uses a quantitative method using a questionnaire in the form of google form as the instrument. The population in this study are BLINKs who have purchased Oreo x Blackpink products. The sample in this study used non-probability sampling with purposive sampling of 96 respondents. The data analysis technique in this study is Instrument Test, classical assumption test, multiple linear regression, determination test and hypothesis testing. The results of this research show that together the independent variables have an influence on purchasing decisions.
The Influence of Human Resources Level, Internal Control, Information Technology on The Quality of Financial Reports (Study Case UD Central Buana Motor)
Authors: Ahliawan Angelica Stefanny , Widagdo Suwignyo , Ningsih Wiwik Fitria
Published: June 2023

The phenomenon of very tight competition in business requires companies to be able to apply the right strategy in accordance with the market conditions they face and have quality reports so that research is conducted which aims to analyze the Effect of Competency Levels of Human Resources, Internal Control Systems, Utilization of Information Technology on the Quality of Financial Reports At UD Central Buana Motor Bondowoso. This type of research used is quantitative research. The data used are primary data and secondary data with data collection techniques namely observation, interviews, document recording, questionnaires/questions. Data collection techniques using a questionnaire a number of 30 respondents or people. The sampling technique used a saturated sample, namely all populations were sampled in this study, namely all employees of UD Central Buana Motor Bondowoso. The population in this study is UD Central Buana Motor. The data analysis method used is the data instrument test, classical assumption test, multiple regression analysis, hypothesis testing and the coefficient of determination. Testing data using the SPSS application version 22. After conducting research at UD Central Buana Motor Bondowoso, the results obtained showed that the level of competence of human resources, internal control systems, and utilization of information technology had a partial effect on the quality of financial reports. Simultaneously the level of competence of human resources, internal control systems, use of information technology affect the quality of financial reports.
GCG Effect and CSR of Sharia Banking in Indonesia
Authors: Wulandari Soliyah , Suganda Asep Dadan
Published: June 2023

This study aims to prove empirically the effect of good corporate governance on corporate social responsibility, in which good corporate governance refers to the audit committee, board independence, government ownership, and institutional ownership. The object of this research was Islamic Commercial Banks, mostly owned by State-Owned Enterprises (BUMN) or Regional-Owned Enterprises (BUMD). The sample selection was carried out using the purposive sampling method. Based upon the sample criteria applied in this study, there were six Islamic banks with 30 observations. The secondary data was collected from the annual report of the six Islamic banks. The data was processed using a statistical test of multiple regression models. The results of this study indicate that board independence and government ownership affect the corporate social responsibility of Islamic banking in Indonesia. Meanwhile, the audit committee and institutional ownership did not affect the corporate social responsibility of Islamic banking in Indonesia
The Effect of Implementation and Socialization of E-Invoice 3.0 on Compliance of Taxable Entrepreneurs For Reporting Value Added Tax Annual Notice
Authors: Aprilina Vita , Bariyanto Muhammad Sugeng
Published: June 2023

The purpose of this study is to analyze the effect of the implementation of e-invoice 3.0 and the socialization of e-invoice 3.0 on the compliance of taxable entrepreneurs for reporting Value Added Tax annual report in the Bekasi Region, especially in KPP Pratama Cibitung. This study uses a quantitative method and the type of data used by the researcher is primary data collected by data collection techniques through questionnaires distribution also through Google Form.the data collected was 121 respondents and processed into 97 respondents according to predetermined criteria. The data analysis method used is multiple regression analysis. Based on the results of respondents' answers through a questionnaire and processed using the SPSS 25 application, it can be concluded that the application of e-inovice 3.0 has a positive effect on compliance with taxable entrepreneurs, and the socialization of e-invoice 3.0 has a positive effect on compliance with taxable entrepreneurs.
Indonesia's Abundant Wealth from The Baduy Culture
Authors: Saragih Febrianta Lidia , Turnip Putri Kumala , Simbolon Basbon
Published: June 2023

The Baduy community is a tribe originating from the interior of Banten and living in Kenakes Village, Leuwidar, Lebak, Banten. The Baduy community is a tribe that has not been affected by modern culture and still obeys the rules that apply in their place of residence. The Baduy people do not want to accept a new culture and deliberately alienate themselves from outside life to avoid modernization as a way for them to respect their ancestors so that the balance and harmony of the universe can be maintained. The Baduy tribe is divided into two parts, namely the Inner Baduy and Outer Baduy who live in crowded settlements. The striking difference between the two tribes is that the Inner Baduy people have not been touched by technology and modernization at all, while the Outer Baduy people.
The Hagiographic Dossier of Ss Cyrus and John and Its Latin Translations
Authors: Ronconi Filippo
Published: June 2023

This article focuses on the western cult of two saints, Cyrus and John, which was founded in Egypt – where Sophronios of Jerusalem composed the anargyroi’s hagiographic dossier in the seventh century – and quickly spread to Italy. The analysis of the manuscripts containing the Latin translations of Sophronios’s texts allows us to trace the diffusion of this hagiographic corpus in Rome, and to link its transfer and first reception in Italy to a broad Mediterranean migration.
The Awkwardness of American Exceptionalism
Authors: Furey Constance M.
Published: June 2023

American exceptionalism poses particular methodological challenges for the historian of religion. This essay acknowledges the importance of privileging historical specificity, as modeled by Dana Logan’s study of America’s formative forms of governance in her recent book, Awkward Rituals, but then argues history should be put in service to theory. It does so by arguing that Logan’s own ritual theory undermines rather than reinforces American exceptionalism – an argument reinforced with comparative examples from other eras of Christian history.
Early Safavid Campaigns in the Caucasus
Authors: Anooshahr Ali
Published: June 2023

The chronicle of Qasim Beg Hayati of Tabriz, written during the reign of Shah Tahmasp (d. 1576), provides new information on early Safavid history that is absent from the other Persian historical literature of the sixteenth and seventeenth centuries. In particular, Hayati shows how important the Caucasus was for the rise of Shaykh Junayd (d. 1460) and Shaykh Haydar Safavi (d. 1488). Using plunder and slaves gained from raids on the Circassians and the Georgians, Junayd and Haydar maneuvered themselves into a position of leadership of their familial order to which they were not entitled by birth. The disastrous ends of both men meant that there could be little continuity in the movement, but they still placed their line at the head of the shrine of Ardabil, and bequeathed to the young Shah Isma’il (d. 1524) a few surviving veterans with valuable experience about campaigning.
Ubykh Personal Names
Authors: Chirikba Viacheslav A.
Published: June 2023

The paper presents a survey of the system of Ubykh personal names. The traditional structure of Ubykh names was binary, consisting of a surname and a postposed personal name. Alternative structures included a preposed family name plus two or more personal names, or a surname, plus a patronymic, plus a personal name. Besides a few native Ubykh names, the majority of names are “Oriental” (Turkish/Turkic, Arabic, Jewish, Persian, etc.), Circassian or Abkhazian, or of unclear origin. There are also hybrid names combining names or formants of different languages.
A Quest for Meaning: Interpretation of Article 73(3) of the Law of the Sea Convention by Indonesian Supreme Court
Authors: Liliansa Dita
Published: June 2023

In the spirit of conserving the balance between the interests of the coastal State and other States in the exclusive economic zone (eez), Article 73(3) of the United Nations Convention for the Law of the Sea (unclos) establishes that coastal State penalties for violations of fisheries laws and regulations may not include imprisonment or corporal punishment unless otherwise agreed by the States concerned. As one of the countries suffering from illegal fishing, Indonesia has seen a number of domestic cases challenging the practical application of Article 73(3) due to the failure of several offenders to pay monetary penalties for violating fisheries laws and regulations in Indonesia’s eez. Article 73(3) appears to be the only unclos provision that Indonesian courts have directly applied and interpreted into domestic cases. The debate revolves around whether courts can impose default confinement for fisheries offences in the eez. This article examines how Indonesian courts interpret the meaning and scope of the term ‘imprisonment’ within the ambit of Article 73(3) of unclos, particularly in the context of confinement for fine defaults, and whether international courts or tribunals provide any guidance in this interpretation.