bluuebunny/crossref_metadata_2025 huggingface dataset:
STRATEGI KOMUNIKASI PEMASARAN DIGITAL ONLINE SHOP “ BUKA LAPAK” DALAM MENINGKATKAN PENJUALAN SAAT PANDEMI COVID-19
Authors: Novianita Riastri rias , Cindrakasih RR.Rosita Rosita , Yunita pratiwi Cindya Cindy , Anisti Anisti Anisti
Published: May 2024

Salah satu dari dampak dari pendemi COVID-19 adalah kemrosotan dalam dunia bisnis dan ekonomi. Dengan demikian pemasar maupun pengusaha harus menemukan alternatif solusi untuk bisa memasarkan produk atau jasa mereka ke konsumen. Para pelaku bisnis mengoptimalkan pemasaran online dan digital branding sebagai sarana komunikasi dengan target konsumennya. Belanja saat pandemi melalui online (online shop) merupakan cara lain belanja yang ditawarkan oleh teknologi internet saat ini dengan berbagai kemudahan yang diberikan, seperti kemudahan waktu dalam melakukan pekerjaan tanpa harus bertatap muka terlebih dahulu. Bukalapak adalah salah satu situs belanja online pendatang baru, jika dibandingkan dengan situs belanja online lainnya. Strategi komunikasi bisnis Bukalapak melalui marketplace. Dengan memudahkan para penjual serta pembeli dalam berinteraksi melalui fitur live chatnya, Bukalapak juga menyediakan banyak produk mulai dari gadget, fashion, kosmetik, elektronik, otomotif dan lain sebagainya. Tujuan dari penelitian pada artikel ini ada dua. 1) Menganalisis strategi Komunikasi Pemasaran online Buka Lapak. 2) Mendeskripsikan pemasaran online dan digital branding Buka Lapak ditengah pandemi COVID 19. Jenis penelitian ini adalah penelitian referensi yang pengambilan datanya berorientasi pada beberapa referensi yang sesuai. Dengan menggunakan metode penelitian kualitatif,  dan paradigma yang digunakan dalam penelitian ini adalah paradigma interpretif , didapatkan bahwa strategi pemasaran situs online shop Bukalapak yang dilakukan ditengah pandemi COVID 19 dinilai cukup efektif dilaksanakan pada saat pandemic.
Advances in ex vivo expansion of hematopoietic stem and progenitor cells for clinical applications
Authors: Branco André , Rayabaram Janakiram , Miranda Cláudia C. , Fernandes-Platzgummer Ana , Fernandes Tiago G. , Sajja Suchitra , da Silva Cláudia L. , Vemuri Mohan C.
Published: May 2024

As caretakers of the hematopoietic system, hematopoietic stem cells assure a lifelong supply of differentiated populations that are responsible for critical bodily functions, including oxygen transport, immunological protection and coagulation. Due to the far-reaching influence of the hematopoietic system, hematological disorders typically have a significant impact on the lives of individuals, even becoming fatal. Hematopoietic cell transplantation was the first effective therapeutic avenue to treat such hematological diseases. Since then, key use and manipulation of hematopoietic stem cells for treatments has been aspired to fully take advantage of such an important cell population. Limited knowledge on hematopoietic stem cell behavior has motivated in-depth research into their biology. Efforts were able to uncover their native environment and characteristics during development and adult stages. Several signaling pathways at a cellular level have been mapped, providing insight into their machinery. Important dynamics of hematopoietic stem cell maintenance were begun to be understood with improved comprehension of their metabolism and progressive aging. These advances have provided a solid platform for the development of innovative strategies for the manipulation of hematopoietic stem cells. Specifically, expansion of the hematopoietic stem cell pool has triggered immense interest, gaining momentum. A wide range of approaches have sprouted, leading to a variety of expansion systems, from simpler small molecule-based strategies to complex biomimetic scaffolds. The recent approval of Omisirge, the first expanded hematopoietic stem and progenitor cell product, whose expansion platform is one of the earliest, is predictive of further successes that might arise soon. In order to guarantee the quality of these ex vivo manipulated cells, robust assays that measure cell function or potency need to be developed. Whether targeting hematopoietic engraftment, immunological differentiation potential or malignancy clearance, hematopoietic stem cells and their derivatives need efficient scaling of their therapeutic potency. In this review, we comprehensively view hematopoietic stem cells as therapeutic assets, going from fundamental to translational.
Effects of rock types and crushing mechanism on the 3D morphological parameters of manufactured sands: a combination study of 3D scanning and spherical harmonic analysis
Authors: Qiu Peiyun , Wang Huaizhi , Wang Peng , Xiao Min , Wei Jiangxiong
Published: May 2024

This study aims to investigate the effect of rock types, i.e., granite, conglomerate rock, limestone, and crushing mechanism, i.e., Vertical Shaft Impact (VSI) crusher, Horizontal Shaft Impact (HSI) crusher, on the morphology of manufactured sands. By combining the 3D scanning and spherical harmonic analysis, the morphological parameters of manufactured sands such as elongation ratio (EL), flatness ratio (Fl), aspect ratio (AR), edge angle (EA), sphericity (SH), and fractal dimension were quantified. The results indicate limestone is more readily broken into blade-shaped particles without being able to blunt sharp edges through constant abrasion. The proportion of bladed particles in manufactured sand prepared from limestone is 1.91 times higher than the proportion of bladed particles in conglomerates. Additionally, the HSI crusher has a more significant effect on rocks with smaller strength. For the same parent rock, manufactured sand from a VSI crusher contains 30% more spherical and oblate particles than from an HSI crusher.
Metabolic syndrome and pharmacotherapy outcomes in patients with type 2 diabetes mellitus
Authors: Alawdi Shawqi H. , Al-Dholae Mohammed , Al-Shawky Salah
Published: May 2024

Background

Metabolic syndrome is a group of metabolic abnormalities that increase predisposition to several diseases including ischemic heart disease and diabetes mellitus. The study aimed to investigate metabolic syndrome among patients with type-2 diabetes mellitus (DM), and its impact on pharmacotherapy outcomes.

Methods

An observational cross-sectional study was performed on 910 patients with type-2 DM between June and December 2023. Fasting blood sugar, triglycerides, high-density lipoproteins (HDL), blood pressure, and abdominal obesity were measured. Metabolic syndrome was identified according to the National Cholesterol Education Program Adult Treatment Panel III criteria. Pharmacotherapy outcomes were assessed according to American Association of Clinical Endocrinologists and American Diabetes Association guidelines using the ability to achieve adequate glycemic control and normal levels of blood pressure and fasting plasma lipoproteins.

Results

In total, 87.5% of type-2 DM patients had metabolic syndrome; the prevalence increased with age and was higher among females. Metabolic syndrome showed the following distribution of risk factors: insulin resistance (100%), low HDL (95.3%), elevated blood pressure (83%), triglycerides dyslipidemia (80.1%), and abdominal obesity (62.5%). Majority of the patients had either 5 or 4 risk factors of metabolic syndrome. The most common comorbidities were dyslipidemia (97.7%) and hypertension (83%). Treatment outcomes were insufficient where adequate glycemic control was only achieved in 12% of type-2 DM patients, and proper management of comorbid dyslipidemia and hypertension was achieved in 29% and 40.9% of patients, respectively. Adequate blood pressure control was less achieved in patients with metabolic syndrome (34.4%) than those without metabolic syndrome (77.2%). Similarly, dyslipidemia was less controlled in patients with metabolic syndrome (26.9%) than in those without metabolic syndrome (47.3%).

Conclusion

Pharmacotherapy outcomes were inadequate for most patients with type-2 diabetes mellitus. Adopting early preventive and therapeutic interventions for metabolic syndrome is advised to improve treatment outcomes of the comorbid dyslipidemia and hypertension.
German demonstrative pronouns differ in their sensitivity to discourse and sentence topics
Authors: Buchholz Timo , von Heusinger Klaus
Published: May 2024

German has two demonstrative pronoun series: the short form der, die, das, and the long form dieser, diese, dieses. Both forms can be used anaphorically, and they contrast with the personal pronouns er, sie, es in that they refer to an antecedent that is less prominent at that point in the discourse when the discourse provides different potential antecedents. Demonstrative pronouns are typically used in the preverbal position in a German sentence, i.e., the topic position. Thus, they are assumed to be topic shifters (from a non-topical antecedent to the topical argument in the current sentence). However, der can be repeated, yielding topic chains, thus referring back to a topical antecedent, while this is not the case for dieser. In this article, we argue that der and dieser both contribute to topic management, but they do this in different ways: der is a marker of a sentence topic, while dieser is a marker of discourse topic shift. We present the results of two experiments that compare the use of personal pronouns with either demonstrative pronoun manipulating sentence topic or discourse topic. First, both experiments show that the personal pronoun is not sensitive to either type of topichood of its antecedent. Second, Experiment 1 shows that both demonstrative pronouns prefer a context where discourse topic and sentence topic are shifted. Third, Experiment 2 shows that only dieser prefers a context with a shifted discourse topic, but der is not sensitive to discourse topichood alone. We take the results as supporting our claim that the two demonstratives have different discourse functions: der marks a sentence topic, while dieser is a shifter (and marker) of the discourse topic.
Looking Back to Look Ahead: COVID-19, domestic violence, and digital activism in India
Authors: Mukherjee Ishani , Williams Maggie G. , Sen Soham
Published: May 2024

We look back to explore the impact of COVID-19 lockdowns on domestic violence amplification in India and the digital activisms that spotlighted this social and health injustice. This analysis focuses on two case studies – the #LockDownMeinLockUp [#LDMLU] campaign mobilized on Instagram, and articles drawn from the digital feminist publication, Feminism in India [FII]. We share our perspectives on how the #LDMLU campaign visually politicized the public nature of a silenced and normalized injustice against at-risk women during a pan-national health crisis. We turn to FII’s reporting on DV exacerbation during India’s pandemic that vocalized this issue from three critical perspectives: structural problems that contribute to gender injustices; financial violence; and mental, emotional, and physical health impacts on abused and at-risk women. In addition to this ‘look back,’ we look ahead to consider calls-to-action and opportunities, digital and/or on-ground, that remain imperative after the urgency of the viral lockdown. We are still at the threshold of activisms waiting, and needing, to happen. We conclude with questions for ourselves and our readers about what happens to advocacy when urgency ends. This growing body of feminist work demonstrates that advocacy will persist across physical and virtual landscapes. It is our responsibility and hope, as gender and communication scholars, to rally challenges against oppression based on gender or sex. Domestic violence against Indian women is continually overlooked. Our collective perspective intends to consolidate visibility toward such acts of abuse at the center of this scholarly piece.
Assessing the effect of Augmented Reality on English language learning and student motivation in secondary education
Authors: Marrahi-Gomez Victor , Belda-Medina Jose
Published: May 2024

The integration of Augmented Reality (AR) in language learning has garnered attention in the field of education, yet its effectiveness in enhancing grammar proficiency among secondary school students remains relatively unexplored, especially given that previous research has predominantly focused on vocabulary acquisition at the primary and college levels. This study, based on a mixed-methods approach and convenience sampling, is aimed at assessing students’ attitudes toward the integration of technology (H1) in language learning and examining the impact of using AR on grammar learning (H2) and motivation (H3) among secondary education students. Employing a mixed-method approach and convenience sampling, the research involved 130 students aged 14 to 15 from two secondary schools, divided into an experimental group (n = 64) and a control group (n = 66). Both groups received instruction on English comparative and superlative forms and completed a variety of exercises. The control group followed a traditional approach using a printed handbook, while the experimental group engaged with an AR-based lesson containing equivalent grammar activities and vocabulary in a multimedia format. Pre and post-tests were administered to evaluate grammar proficiency, accompanied by pre and post-surveys. Semi-structured discussion was used for the qualitative data. The findings revealed a strong interest in integrating AR technology into grammar learning, underscored by a positive attitude toward its implementation in secondary education. However, no statistically significant differences were detected in grammar learning performance between the two student groups. These findings emphasize the importance of providing proper teacher training in secondary education to effectively utilize AR technology and highlight the need for further research to explore its effectiveness and long-term impact.
Association between heme oxygenase-1 and hyperlipidemia in pre-diabetic patients: a cross-sectional study
Authors: Fan Shujin , Yang Yulin , Li Xiaoyu , Liu Jing , Qiu Yue , Yan Li , Ren Meng
Published: May 2024

Background

Although the importance and benefit of heme oxygenase-1 (HO-1) in diabetes rodent models has been known, the contribution of HO-1 in the pre-diabetic patients with hyperlipidemia risk still remains unclear. This cross-sectional study aims to evaluate whether HO-1 is associated with hyperlipidemia in pre-diabetes.

Methods

Serum level of HO-1 was detected using commercially available ELISA kit among 1,425 participants aged 49.3–63.9 with pre-diabetes in a multicenter Risk Evaluation of cAncers in Chinese diabeTic Individuals: A lONgitudinal (REACTION) prospective observational study. Levels of total cholesterol (TC) and triglyceride (TG) were measured and used to defined hyperlipidemia. The association between HO-1 and hyperlipidemia was explored in different subgroups.

Result

The level of HO-1 in pre-diabetic patients with hyperlipidemia (181.72 ± 309.57 pg/ml) was obviously lower than that in pre-diabetic patients without hyperlipidemia (322.95 ± 456.37 pg/ml). High level of HO-1 [(210.18,1,746.18) pg/ml] was negatively associated with hyperlipidemia (OR, 0.60; 95% CI, 0.37–0.97; p = 0.0367) after we adjusted potential confounding factors. In subgroup analysis, high level of HO-1 was negatively associated with hyperlipidemia in overweight pre-diabetic patients (OR, 0.50; 95% CI, 0.3–0.9; p = 0.034), especially in overweight women (OR, 0.42; 95% CI, 0.21–0.84; p = 0.014).

Conclusions

In conclusion, elevated HO-1 level was negatively associated with risk of hyperlipidemia in overweight pre-diabetic patients, especially in female ones. Our findings provide information on the exploratory study of the mechanism of HO-1 in hyperlipidemia, while also suggesting that its mechanism may be influenced by body weight and gender.
Research progress on the fanconi anemia signaling pathway in non-obstructive azoospermia
Authors: Xu Haohui , Zhang Yixin , Wang Caiqin , Fu Zhuoyan , Lv Jing , Yang Yufang , Zhang Zihan , Qi Yuanmin , Meng Kai , Yuan Jinxiang , Wang Xiaomei
Published: May 2024

Non-obstructive azoospermia (NOA) is a disease characterized by spermatogenesis failure and comprises phenotypes such as hypospermatogenesis, mature arrest, and Sertoli cell-only syndrome. Studies have shown that FA cross-linked anemia (FA) pathway is closely related to the occurrence of NOA. There are FA gene mutations in male NOA patients, which cause significant damage to male germ cells. The FA pathway is activated in the presence of DNA interstrand cross-links; the key step in activating this pathway is the mono-ubiquitination of the FANCD2-FANCI complex, and the activation of the FA pathway can repair DNA damage such as DNA double-strand breaks. Therefore, we believe that the FA pathway affects germ cells during DNA damage repair, resulting in minimal or even disappearance of mature sperm in males. This review summarizes the regulatory mechanisms of FA-related genes in male azoospermia, with the aim of providing a theoretical reference for clinical research and exploration of related genes.
A corrosion model for CZ cladding based on in-pile irradiation data
Authors: Duoting Xu , Xiaoyan Wei , Xiaohan Liu , Xin Jin , Tao Wang
Published: May 2024

Corrosion resistance is the critical in-pile property for developing new Zircaloy cladding. As a new Zircaloy developed by China General Nuclear Power Corporation, CZ will be used as fuel rod cladding. This study is devoted to investigating the corrosion behavior of CZ. A two-stage Arrhenius equation is proposed to model the corrosion rate. A total of 1,510 measurement data points taken from 151 fuel rods irradiated for 1–4 cycles were used to develop the corrosion model. The burnup of these fuel rods ranges from 13.7 MWd/kgU to 55.9 MWd/kgU. The mean value and standard deviation of P−M (predicted value minus measured value) are 0.54 and 3.65 microns, respectively, and the mean value and standard deviation of P/M (predicted value divided by measured value) are 1.09 and 0.34 microns, respectively. P−M and P/M increase with the local burnup. When the burnup is greater than 40 MWd/kgU, the mean values of P−M and P/M are 6.2 and 1.20 microns, respectively; on the other hand, the prediction of the proposed model is more conservative in high burnup. In the typical case in which the average burnup reaches 57 MWd/kgU, the oxide thickness of CZ cladding is much less than 30 microns, whereas the oxide thickness of Zr-4 cladding is approximately 80 microns, and this manifests that CZ cladding possesses excellent performance in corrosion resistance.
Low-carbon economic scheduling of virtual power plant considering carbon emission flow and demand response
Authors: Wang Yongchao , Xu Jiantie , Pei Wenhui , Wang Hanyang , Zhang Zhuang
Published: May 2024

To fully explore the potential low-carbon and economic advantages of a virtual power plant (VPP) that aggregates multiple distributed resources, the paper proposes a VPP scheduling model that considers the carbon emission flow (CEF) and demand response (DR), which is characterized by electro-carbon coupling and source-load interaction. First, the electric-carbon characteristics of each distributed resource under VPP are modeled, and the source-load electric-carbon coupling characteristic model is modeled through the CEF theory. On this basis, a load-side multi-type DR model is established to achieve the purpose of source-load synergy to reduce carbon emissions from VPP. To this end, a two-stage scheduling model of VPP considering the source-load electro-carbon coupling relationship is established, and the implementation of the model can reduce power generation costs, carbon emissions and promote clean energy, and the simulation results of the improved IEEE-14 node system verify the effectiveness of the proposed model.
Applying colloidal silica suspensions injection and sequential gelation to block vertical water flow in well annulus: laboratory testing on rheology, gelation, and injection
Authors: Zhong Lirong , Mackley Rob , Li Lan , Thomle Jon , Day-Lewis Fred , Saslow Sarah
Published: May 2024

We evaluated the application of silica suspension injection and sequential gelation to block vertical water flow in the annuli of long-screened wells. First, we studied the viscosity, rheological behavior, and gelation performance of colloidal silica suspensions in batch tests. Then, we tested the injection of silica suspensions and the water flow blocking efficiency of the later formed silica gel in column and bench-scale sandbox experiments. Micron-sized fumed powder silica suspensions and nanosized silica suspensions recovered from geothermal fluids were tested in this work. Fumed silica suspensions showed shear thinning, while nanosized silica suspensions exhibited Newtonian flow behavior. During the gelation process, the nanosized silica suspension changed from a Newtonian fluid to a shear thinning fluid while increasing its overall viscosity. At comparable concentrations, the nanosized silica suspensions have much lower viscosity than that of the fumed silica suspensions. Increases in the Na+ concentration and silica particle concentration in these suspensions shortened the gelation time. Silica suspension gelation in sand columns completely blocked the water flow and sustained the injection pressure up to 50 psig (344.7 kPa). A silica suspension was successfully injected into the target zone in the annulus of a bench-scale sandbox mimicking long-screened wells in the field. The silica gel formed in the annulus effectively blocked chemical transport through the gelled zone. Our research reveals that a process using silica suspension injection and sequential gelation technology is promising for blocking the vertical water flow and chemical transport through the filter pack in targeted zones within the annulus of long-screened well systems.
Case report: Early use of whole exome sequencing unveils HNRNPU-related neurodevelopmental disorder and answers additional clinical questions through reanalysis
Authors: Dreikorn Erika Nicole , Munro Christine , Robin Berman Natasha , Kunovac Amina , Bellissimo Daniel , Massart Mylynda B.
Published: May 2024

This case report chronicles the diagnostic odyssey and resolution of a 27-year-old female with a complex neurodevelopmental disorder (NDD) using Whole Exome Sequencing (WES). The patient presented to a precision medicine clinic with multiple diagnoses including intellectual disability, autism spectrum disorder (ASD), obsessive-compulsive disorder (OCD), tics, seizures, and pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS). Although this patient previously had chromosomal microarray and several single-gene tests, the underlying cause of this patient’s symptoms remained elusive. WES revealed a pathogenic missense mutation in the HNRNPU gene, associated with HNRNPU-related neurodevelopmental disorder (HNRNPU-NDD) and developmental and epileptic encephalopathy-54 (DEE54, OMIM: # 617391). Following this diagnoses, other treating clinicians identified additional indications for genetic testing, however, as the WES data was readily available, the clinical team was able to re-analyze the WES data to address their inquiries without requiring additional tests. This emphasizes the pivotal role of WES in expediting diagnoses, reducing costs, and providing ongoing clinical utility throughout a patient’s life. Accessible WES data in primary care settings can enhance patient care by informing future genetic inquiries, enhancing coordination of care, and facilitating precision medicine interventions, thereby mitigating the burden on families and the healthcare system.
Second trimester vaginal Candida colonization among pregnant women attending antenatal care in Bukavu, Democratic Republic of the Congo: prevalence, clinical correlates, risk factors and pregnancy outcomes
Authors: Mulinganya Mulumeoderhwa Guy , De Keyser Karen , Mongane Irenge Jules , Kampara Mirindi Freddy , De Vulder Annelies , Boelens Jerina , Duyvejonck Hans , Hendwa Erick , Kujirakwinja Bisimwa Yvette , Bisimwa Balaluka Ghislain , Rodriguez Antonio , Vaneechoutte Mario , Callens Steven , Cools Piet
Published: May 2024

Introduction

Vaginal Candida colonization (CC) can lead to vulvovaginal candidiasis, the second most prevalent vaginal condition worldwide, and has been associated with adverse birth outcomes. However, no data on CC in the Democratic Republic of the Congo are available. We investigated the prevalence, Candida species, clinical correlates, risk factors and pregnancy outcomes in women with CC in the second trimester of pregnancy.

Material and methods

In Bukavu, the Democratic Republic of the Congo, pregnant women were recruited during antenatal care between 16 and 20 weeks of gestation from January 2017 to October 2017 and followed until delivery. Sociodemographics, sexual behavioral, hygienic and clinical characteristics, microbiological data and pregnancy outcomes were collected. Candida detection and speciation was performed with microscopy (Gram-stained smears and wet-mount) and/or quantitative PCR. Multivariate regression models were used to estimate the different associations with CC.

Results

The prevalence of CC by wet mount, microscopy of Gram-stain smears and qPCR was 27.9%, 28.1% and 38.2%, respectively. C. albicans was the most prevalent Candida species (91.0%). Previous genital infections, an intermediate vaginal microbiota, bacterial vaginosis, and the use of pit toilets were risk factors for CC. Clinically, CC was associated with itching only. Women with CC had twice the odds for preterm birth, if Candida concentration was high, the odds were four times higher.

Conclusions

In Bukavu, the Democratic Republic of the Congo, the prevalence of CC was high and associated with microbiological and modifiable risk factors. Screening and treatment for CC during antenatal care should be investigated as a possible strategy to reduce preterm birth.
Macrophage-derived macrophage migration inhibitory factor mediates renal injury in anti-glomerular basement membrane glomerulonephritis
Authors: Yang Hui , Li Jinhong , Huang Xiao-ru , Bucala Richard , Xu Anping , Lan Hui-Yao
Published: May 2024

Macrophages are a rich source of macrophage migration inhibitory factor (MIF). It is well established that macrophages and MIF play a pathogenic role in anti-glomerular basement membrane crescentic glomerulonephritis (anti-GBM CGN). However, whether macrophages mediate anti-GBM CGN via MIF-dependent mechanism remains unexplored, which was investigated in this study by specifically deleting MIF from macrophages in MIFf/f−lysM−cre mice. We found that compared to anti-GBM CGN induced in MIFf/f control mice, conditional ablation of MIF in macrophages significantly suppressed anti-GBM CGN by inhibiting glomerular crescent formation and reducing serum creatinine and proteinuria while improving creatine clearance. Mechanistically, selective MIF depletion in macrophages largely inhibited renal macrophage and T cell recruitment, promoted the polarization of macrophage from M1 towards M2 via the CD74/NF-κB/p38MAPK-dependent mechanism. Unexpectedly, selective depletion of macrophage MIF also significantly promoted Treg while inhibiting Th1 and Th17 immune responses. In summary, MIF produced by macrophages plays a pathogenic role in anti-GBM CGN. Targeting macrophage-derived MIF may represent a novel and promising therapeutic approach for the treatment of immune-mediated kidney diseases.
CLEC7A regulates M2 macrophages to suppress the immune microenvironment and implies poorer prognosis of glioma
Authors: Wang Jinchao , Li Xiaoru , Wang Kai , Li Kaiji , Gao Yalong , Xu Jianye , Peng Ruilong , Zhang Xu , Zhang Shu , Zhou Yuan , Xu Shangchen , Zhang Jianning
Published: May 2024

Background

Gliomas constitute a category of malignant tumors originating from brain tissue, representing the majority of intracranial malignancies. Previous research has demonstrated the pivotal role of CLEC7A in the progression of various cancers, yet its specific implications within gliomas remain elusive. The primary objective of this study was to investigate the prognostic significance and immune therapeutic potential of CLEC7A in gliomas through the integration of bioinformatics and clinical pathological analyses.

Methods

This investigation involved examining and validating the relationship between CLEC7A and glioma using samples from Hospital, along with data from TCGA, GEO, GTEx, and CGGA datasets. Subsequently, we explored its prognostic value, biological functions, expression location, and impact on immune cells within gliomas. Finally, we investigated its potential impact on the chemotaxis and polarization of macrophages.

Results

The expression of CLEC7A is upregulated in gliomas, and its levels escalate with the malignancy of tumors, establishing it as an independent prognostic factor. Functional enrichment analysis revealed a significant correlation between CLEC7A and immune function. Subsequent examination of immune cell differential expression demonstrated a robust association between CLEC7A and M2 macrophages. This conclusion was further substantiated through single-cell analysis, immunofluorescence, and correlation studies. Finally, the knockout of CLEC7A in M2 macrophages resulted in a noteworthy reduction in macrophage chemotaxis and polarization factors.

Conclusion

CLEC7A expression is intricately linked to the pathology and molecular characteristics of gliomas, establishing its role as an independent prognostic factor for gliomas and influencing macrophage function. It could be a promising target for immunotherapy in gliomas.
Predicting chemotherapy toxicity in multiple myeloma: the prognostic value of pre-treatment serum cytokine levels of interleukin-6, interleukin-8, monocyte chemoattractant protein-1, and vascular endothelial growth factor
Authors: Mielnik Michał , Podgajna-Mielnik Martyna , Szudy-Szczyrek Aneta , Homa-Mlak Iwona , Mlak Radosław , Gorący Aneta , Hus Marek
Published: May 2024

Introduction

Multiple Myeloma (MM), a prevalent hematological malignancy, poses significant treatment challenges due to varied patient responses and toxicities to chemotherapy. This study investigates the predictive value of pretreatment serum levels of interleukin-6 (IL-6), interleukin-8 (IL-8), monocyte chemoattractant protein-1 (MCP-1), and vascular endothelial growth factor (VEGF) for chemotherapy-induced toxicities in newly diagnosed MM patients. We hypothesized that these cytokines, pivotal in the tumor microenvironment, might correlate with the incidence and severity of treatment-related adverse events.

Methods

We conducted a prospective observational study with 81 newly diagnosed MM patients, analyzing serum cytokine levels using the multiplex cytometric bead assay (CBA) flow cytometry method. The study used non-parametric and multivariate analysis to compare cytokine levels with treatment-induced toxicities, including lymphopenia, infections, polyneuropathy, and neutropenia.

Results

Our findings revealed significant associations between cytokine levels and specific toxicities. IL-8 levels were lower in patients with lymphopenia (p=0.0454) and higher in patients with infections (p=0.0009) or polyneuropathy (p=0.0333). VEGF concentrations were notably lower in patients with neutropenia (p=0.0343). IL-8 demonstrated an 81% sensitivity (AUC=0.69; p=0.0015) in identifying infection risk. IL-8 was an independent predictor of lymphopenia (Odds Ratio [OR]=0.26; 95% Confidence Interval [CI]=0.07-0.78; p=0.0167) and infection (OR=4.76; 95% CI=0.07-0.62; p=0.0049). High VEGF levels correlated with a 4-fold increased risk of anemia (OR=4.13; p=0.0414).

Conclusions

Pre-treatment concentrations of IL-8 and VEGF in serum can predict hematological complications, infections, and polyneuropathy in patients with newly diagnosed MM undergoing chemotherapy. They may serve as simple yet effective biomarkers for detecting infections, lymphopenia, neutropenia, and treatment-related polyneuropathy, aiding in the personalization of chemotherapy regimens and the mitigation of treatment-related risks.
Palmitate and group B Streptococcus synergistically and differentially induce IL-1β from human gestational membranes
Authors: Gaddy Jennifer A. , Moore Rebecca E. , Lochner Jonathan S. , Rogers Lisa M. , Noble Kristen N. , Giri Ayush , Aronoff David M. , Cliffel David , Eastman Alison J.
Published: May 2024

Introduction

Rupture of the gestational membranes often precedes major pregnancy complications, including preterm labor and preterm birth. One major cause of inflammation in the gestational membranes, chorioamnionitis (CAM) is often a result of bacterial infection. The commensal bacterium Streptococcus agalactiae, or Group B Streptococcus (GBS) is a leading infectious cause of CAM. Obesity is on the rise worldwide and roughly 1 in 4 pregnancy complications is related to obesity, and individuals with obesity are also more likely to be colonized by GBS. The gestational membranes are comprised of several distinct cell layers which are, from outermost to innermost: maternally-derived decidual stromal cells (DSCs), fetal cytotrophoblasts (CTBs), fetal mesenchymal cells, and fetal amnion epithelial cells (AECs). In addition, the gestational membranes have several immune cell populations; macrophages are the most common phagocyte. Here we characterize the effects of palmitate, the most common long-chain saturated fatty acid, on the inflammatory response of each layer of the gestational membranes when infected with GBS, using human cell lines and primary human tissue.

Results

Palmitate itself slightly but significantly augments GBS proliferation. Palmitate and GBS co-stimulation synergized to induce many inflammatory proteins and cytokines, particularly IL-1β and matrix metalloproteinase 9 from DSCs, CTBs, and macrophages, but not from AECs. Many of these findings are recapitulated when treating cells with palmitate and a TLR2 or TLR4 agonist, suggesting broad applicability of palmitate-pathogen synergy. Co-culture of macrophages with DSCs or CTBs, upon co-stimulation with GBS and palmitate, resulted in increased inflammatory responses, contrary to previous work in the absence of palmitate. In whole gestational membrane biopsies, the amnion layer appeared to dampen immune responses from the DSC and CTB layers (the choriodecidua) to GBS and palmitate co-stimulation. Addition of the monounsaturated fatty acid oleate, the most abundant monounsaturated fatty acid in circulation, dampened the proinflammatory effect of palmitate.

Discussion

These studies reveal a complex interplay between the immunological response of the distinct layers of the gestational membrane to GBS infection and that such responses can be altered by exposure to long-chain saturated fatty acids. These data provide insight into how metabolic syndromes such as obesity might contribute to an increased risk for GBS disease during pregnancy.
Effect of pharmaceutical promotion and incentives offered by pharmaceutical companies on the prescribing pattern of medical students: a cross-sectional study from a developing nation Pakistan
Authors: Gillani Ali Hassan , Arshad Hafsa , Umer Muhammad Farooq , Arshed Muhammad , Khan Farman Ullah , Bashir Kamran , Xu Sen , Mujtaba Hasan , Mohamed Ibrahim Mohamed Izham , Fang Yu
Published: May 2024

Background

Pharmaceutical companies continuously pursue healthcare professionals, starting from the medical college level, which can ultimately lead to irrational prescribing of drugs and antibiotics. Therefore, our main aim was to evaluate the opinions and attitudes of medical students toward pharmaceutical promotion.

Methods

This study utilized a cross-sectional online survey that applied the snowball sampling technique. Data were collected from three public and three private sector medical colleges in Punjab, Pakistan using snowball sampling. A modified version of a pre-structured questionnaire was used to collect data between October 2020 and January 2021. Medical students from the third year onward were captivated. The tool was made available on Google Forms and students could access it by clicking the link shared. The effect of promotion on prescribing pattern and future prescribing of antibiotics were measured. Descriptive statistics, chi-square, and t-test were used to analyze the data.

Results

A total of 1,301 students filled out the survey, but only 1,227 responses were acceptable. The average age was found to be 23.4 ± 1.59 years. Slightly more than half of the respondents were male participants (57.7%), and a significant proportion (84.1%) reported being aware of pharmaceutical promotion. A smaller number (27.7%) felt that physicians who meet medical representatives more frequently tend to prescribe more antibiotics and 46.3% indicated they would be willing to prescribe antibiotics under the promotional influence. Medical students who were male, in senior college years, attended government institutions, and had lower parental income showed significantly higher perception and attitude scores (p < 0.05) which, in turn, may show their inclination to promotional activities. Many students agreed with the view that pharmaceutical promotion (PP) activities may alter prescribing practices and also believed that they contribute to the increased irrational prescribing of drugs and antibiotics.

Conclusion

The study revealed that only a small number of students are willing to engage in promotional activities and accept rewards, which influences their choice toward selection of drugs and antibiotics. This study highlighted the necessity of giving proper educational instructions regarding the promotion of drugs to medical students. This study also focused on the educational prerequisites of the students.
Characteristics of “do not resuscitate” orders among elderly patients receiving mechanical ventilation in the intensive care unit in Taiwan
Authors: Chen Pei-Jun , Ho Chung-Han , Lin Ying-Jia , Chang Ming-Hung , Liao Kuang-Ming
Published: May 2024

Objective

As patient life expectancy has increased and people are living longer than before, the rate of mechanical ventilation among elderly patients in the intensive care unit has increased. Older patients who receive mechanical ventilation and have multiple comorbidities are more likely to have a do not resuscitate order than are younger patients with fewer comorbidities. The aim of our study was to describe the patient characteristics and predictive factors of do not resuscitate orders during hospitalization among elderly patients who received ventilation in the intensive care unit.

Methods

This was a retrospective review of the electronic medical records of patients in the intensive care unit of a teaching hospital in southern Taiwan. We enrolled patients admitted to the general intensive care unit from January 1, 2018, to September 31, 2020, and patients older than 80 years who experienced respiratory failure, were intubated and received mechanical ventilation. We analyzed patient demographics, disease severity during hospitalization and comorbidities. If a patient had multiple admissions to the intensive care unit, only the first admission was recorded.

Results

Of the 305 patients over 80 years of age with respiratory failure who were intubated and placed on a ventilator, 66 were excluded because of incomplete data, and 13 were excluded because they had already signed a do not resuscitate order prior to admission to the hospital. Ultimately, 226 patients were included in this study. A higher acute physiology and chronic health evaluation II score (>30) was also associated with an increased likelihood of a do not resuscitate order (odds ratio (OR) = 3.85, 95% CI = 1.09–13.62, p = 0.0362). Patients who had acute kidney injury or cerebrovascular accident were more likely to have a do not resuscitate order (OR = 2.74, 95% CI = 1.03–7.28, p = 0.0428 and OR = 7.32, 95% CI = 2.02–26.49, p = 0.0024, respectively).

Conclusion

Our study showed that older age, greater disease severity, and certain critical interventions were associated with a greater propensity for do not resuscitate orders, which is crucial for understanding patient preferences and guiding end-of-life care discussions. These findings highlight the importance of clinical severity and specific health events in predicting end-of-life care preferences in older patient groups.
Exploring the genetic makeup of Xanthomonas species causing bacterial spot in Taiwan: evidence of population shift and local adaptation
Authors: Chen Jaw-Rong , Aguirre-Carvajal Kevin , Xue Dao-Yuan , Chang Hung-Chia , Arone-Maxwell Lourena , Lin Ya-Ping , Armijos-Jaramillo Vinicio , Oliva Ricardo
Published: May 2024

The introduction of plant pathogens can quickly reshape disease dynamics in island agro-ecologies, representing a continuous challenge for local crop management strategies. Xanthomonas pathogens causing tomato bacterial spot were probably introduced in Taiwan several decades ago, creating a unique opportunity to study the genetic makeup and adaptive response of this alien population. We examined the phenotypic and genotypic identity of 669 pathogen entries collected across different regions of Taiwan in the last three decades. The analysis detected a major population shift, where X. euvesicatoria and X. vesicatoria races T1 and T2 were replaced by new races of X. perforans. After its introduction, race T4 quickly became dominant in all tomato-growing areas of the island. The genomic analysis of 317 global genomes indicates that the Xanthomonas population in Taiwan has a narrow genetic background, most likely resulting from a small number of colonization events. However, despite the apparent genetic uniformity, X. perforans race T4 shows multiple phenotypic responses in tomato lines. Additionally, an in-depth analysis of effector composition suggests diversification in response to local adaptation. These include unique mutations on avrXv3 which might allow the pathogen to overcome Xv3/Rx4 resistance gene. The findings underscore the dynamic evolution of a pathogen when introduced in a semi-isolated environment and provide insights into the potential management strategies for this important disease of tomato.
Improving associative memory in younger and older adults with unitization: evidence from meta-analysis and behavioral studies
Authors: Liu Zejun , Wang Yujuan , Zhu Yajun , Yuan Jing , Liu Wei
Published: May 2024

Introduction

The finding that familiarity can support associative memory by unitizing the to -be-learned items into a novel representation has been widely accepted, but its effects on overall performance of associative memory and recollection are still controversial.

Methods

The current study aims to elucidate these discrepancies by identifying potential moderating factors through a combined approach of meta-analysis and behavioral experiment.

Results

Results consistently showed that changes in the level of unitization and age groups were two important moderators. Specifically, unitization enhanced younger and older adults’ associative memory and its supporting processes (i.e., familiarity and recollection) when the level of unitization between studied and rearranged pairs was changed. However, when this level remained constant, unitization exhibited no impact on associative memory and familiarity in younger adults, but showed an enhanced effect in older adults. Furthermore, results revealed a marked group difference between younger and older adults in associative memory when the unitization level of noncompound words remained unaltered. Upon breaking this condition, the group difference was reduced by enhancing familiarity or recollection.

Discussion

These findings not only clarify some of the inconsistencies in the literature concerning the impact of unitization on associative memory, but also suggest that unitization is a beneficial strategy for reducing group difference in associative memory, with its effectiveness varying according to the level of unitization changes.
PathFinder: a novel graph transformer model to infer multi-cell intra- and inter-cellular signaling pathways and communications
Authors: Feng Jiarui , Song Haoran , Province Michael , Li Guangfu , Payne Philip R. O. , Chen Yixin , Li Fuhai
Published: May 2024

Recently, large-scale scRNA-seq datasets have been generated to understand the complex signaling mechanisms within the microenvironment of Alzheimer’s Disease (AD), which are critical for identifying novel therapeutic targets and precision medicine. However, the background signaling networks are highly complex and interactive. It remains challenging to infer the core intra- and inter-multi-cell signaling communication networks using scRNA-seq data. In this study, we introduced a novel graph transformer model, PathFinder, to infer multi-cell intra- and inter-cellular signaling pathways and communications among multi-cell types. Compared with existing models, the novel and unique design of PathFinder is based on the divide-and-conquer strategy. This model divides complex signaling networks into signaling paths, which are then scored and ranked using a novel graph transformer architecture to infer intra- and inter-cell signaling communications. We evaluated the performance of PathFinder using two scRNA-seq data cohorts. The first cohort is an APOE4 genotype-specific AD, and the second is a human cirrhosis cohort. The evaluation confirms the promising potential of using PathFinder as a general signaling network inference model.
The safety and clinical outcomes of endovascular treatment versus microsurgical clipping of ruptured anterior communicating artery aneurysms: a 2-year follow-up, multicenter, observational study
Authors: Yang Minghao , Li Yang , Li Jia , An Xiuhu , Li Hongwen , Wang Bangyue , Zhao Yan , Zhu Xiaowei , Hou Changkai , Huan Linchun , Yang Xinyu , Yu Jianjun
Published: May 2024

Background and objective

Current data on the optimal treatment modality for ruptured anterior communicating artery (AComA) aneurysms are limited. We conducted this multicenter retrospective study to evaluate the safety and clinical outcomes of endovascular treatment (EVT) and microsurgical clipping (MC) for the treatment of ruptured AComA patients.

Methods

Patients with ruptured AComA aneurysms were screened from the Chinese Multicenter Cerebral Aneurysm Database. Propensity score matching (PSM) was used to adjust for baseline characteristic imbalances between the EVT and MC groups. The safety outcomes included total procedural complications, procedure-related morbidity/death and remedial procedure for complication. The primary clinical outcome was 2-year functional independence measured by the modified Rankin scale (mRS) score.

Results

The analysis included 893 patients with ruptured AComA aneurysms (EVT: 549; MC: 346). PSM yielded 275 pairs of patients in the EVT and MC cohorts for comparison. Decompressive craniectomy being more prevalent in the MC group (19.3% vs. 1.5%, p < 0.001). Safety data revealed a lower rate of total procedural complications (odds ratio [OR] = 0.62, 95% CI 0.39–0.99; p = 0.044) in the EVT group and similar rates of procedure-related morbidity/death (OR = 0.91, 95% CI 0.48–1.73; p = 0.880) and remedial procedure for complication (OR = 1.35, 95% CI 0.51–3.69, p = 0.657) between the groups. Compared with that of MC patients, EVT patients had a greater likelihood of functional independence (mRS score 0–2) at discharge (OR = 1.68, 95% CI 1.14–2.50; p = 0.008) and at 2 years (OR = 1.89, 95% CI 1.20–3.00; p = 0.005), a lower incidence of 2-year all-cause mortality (OR = 0.54, 95% CI 0.31–0.93; p = 0.023) and a similar rate of retreatment (OR = 1.00, 95% CI 0.23–4.40; p = 1.000).

Conclusion

Clinical outcomes after treatment for ruptured AComA aneurysms appear to be superior to those after treatment with MC, with fewer overall procedure-related complications and no increase in the retreatment rate. Additional studies in other countries are needed to verify these findings.