bluuebunny/crossref_metadata_2025 huggingface dataset:
QUALITY PERCEPTION ANALYSIS ON PURCHASE INTENTION (DING TEA BRAND IN BATAM)
Authors: Purba Tiurniari , Nainggolan Nora Pitri , Heryenzus Heryenzus
Published: October 2023

Perceived quality can be a company marketing strategy over a product and forming a relationship between producers and consumers. This study aims to examine and analyze the influence of factor effecting purchase intention of brand Ding Tea in Batam. By using purposive sampling obtained 195 respondents. Using multiple linear regression to data analysis and validity, reliability and classical assumption tests. this study proves perceived quality affect purchase intentions. From this study, it is expected that companies pay more attention to product quality and consumer reviews to increase purchase intention.
Pengaruh Disiplin Kerja Dan Motivasi Kerja Terhadap Kinerja Karyawan Pada PT Osi Electronics Batam
Authors: Syaifullah Syaifullah
Published: October 2023

The purpose of this research is to determine 1. Effect of Work Discipline on Employee Performance in PT Osi Electronics Batam partially; 2. Effect of Work Motivation on Employee Performance partially; and (3) Effect of Work Discipline and Motivation on Employee Performance Work simultaneously. Methods: Total population in this study was 138 employees and the amount of sample in this study was 138 employees, Data Collection Techniques by questionnaire, sampling technique research using sampling techniques saturated. Analysis method is Quantitative Analysis, Quantitative Analysis with Multiple Linear Regression, determination (R Square), to determine the factors that influence employee performance with the coefficient of determination in Partial (r2) and simultaneous (R2). To test the hypothesis with the t-Test (Partial) and F-Test (Simultaneously), with a significance level (α = 0.05). The results showed that the influence of the variable Work Discipline Employee Performance is equal to 0.537 (53.70%). Work Motivation variable amount of influence on employee performance is equal to 0.887 (88.70%). The magnitude of the effect of variable Work Discipline and Motivation on Employee Performance Working simultaneously on PT Osi Electronics Batam amounted to 4,065 (40.65%).
Pelatihan Pembuatan Laporan Keuangan Menggunakan Aplikasi Excel Pada Umkm Usaha Dagang R3 Di Kota Batam
Authors: Lubis Syarif Hidayah , Ayuningtyas Ni Putu Winda , Bahar Hardi
Published: October 2023

MSME is one type of business that really needs financial reports because it invites strategic elements in the structure of the national and regional economy but is a Trading Business Partner (UD) R3 as MSMEs do not yet have financial reports so they do not know the benefits that have the potential to not continue the business. The purpose of this service is to provide counseling about financial reports and procedures for making financial reports using the excel application. The expected output target is the ability of the R3 Trading Business (UD) to prepare financial reports that comply with standards. The output is aimed at partners being able to understand financial reports and being able to make standard and practical financial reports using the Excel application. The results of the dedication show that UD R3 has been able to make standard and practical financial reports using the excel application, has been able to understand the basics of financial reports and their benefits so that in the end partners are able to prepare their own financial reports for their business, can practice directly by inputting each transactions for sales or purchases with Directions from the service team, can recognize computer applications in the form of excel which have been formulated so that every UD R3 partner transaction only makes a journal and finally obtains the necessary financial reports, can understand financial reports produced in practice which have been directly guided by the service team.
An implementation of Hurdle models for spatial count data. Study case: civil war as a risk factor for the development of childhood leukemia in Colombia
Authors: Montilla Velásquez María del Pilar , Bohorquez Castañeda Martha Patricia , Rentería Ramos Rafael
Published: October 2023

We propose a novel, efficient, and powerful methodology to deal with overdispersion, excess zeros, heterogeneity, and spatial correlation. It is based on the combination of Hurdle models and Spatial filtering Moran eigenvectors. Hurdle models are the best option to manage the presence of overdispersion and excess of zeros, separating the model into two parts: the first part models the probability of the zero value, and the second part models the probability of the non-zero values. Finally, gathering the spatial information in new covariates through a spatial filtering Moran vector method involves spatial correlation and spatial heterogeneity to improve the model fitting and explain spatial effects of variables that were not possible to measure. Thus, our proposal adapts usual regression models for count data so that it is possible to deal with phenomena where the usual theoretical assumptions, such as constant variance, independence, and unique distribution are not fulfilled. In addition, this research shows how a prolonged armed conflict can impact the health of children. The data includes children exposed to armed conflict in Colombia, a country enduring a non-international armed conflict lasting over 60 years. The findings indicate that children exposed to high levels of violence, as measured by the armed conflict index, demonstrate a significant association with the incidence and mortality rate of LAP in children. This fact is illustrated here using one of the most catastrophic conditions in childhood, as is Pediatric Acute Leukemia (LAP). The association between armed conflict and LAP has its conceptual basis in the epidemiology literature, given that, the incidence and mortality rates of neoplastic diseases increase with exposure to toxic and chronic stress during gestation and childhood. Our methodology provides a valuable framework for complex data analysis and contributes to understanding the health implications in conflict-affected regions.
Preparation of fish collagen and vancomycin microspheres based on microfluidic technology and its application in osteomyelitis
Authors: Hu Xiaowu , Tang Jinshan , Yu Huaixi , Yang Hanshi , Lu Xiaoqing , Zheng Donghui
Published: October 2023

At present, the clinical treatment of osteomyelitis and osteomyelitis-induced bone defects is challenging, easy to recur, drug toxic side effects, secondary or multiple surgeries, etc. The design of biodegradable composite biomaterials to improve antibiotics in the local precise anti-infection at the same time to complete the repair of bone defects is the current research hot spot. Herein, a composite hydrogel with a double bond at the end (FA-MA) was prepared by affinity addition reaction between fish collagen (FA) and methacrylic anhydride (MA) under photoinitiator initiation conditions, then, FA-MA was amino-activated by EDC/NHC, and vancomycin was attached to FA-MA via amide bonding to prepare FA-MA-Van hydrogels, and finally, the composite hydrogel microspheres were prepared by microfluidic technology. The structure of the hydrogel was confirmed by SEM (elemental analysis), optical microscopy, FTIR, and XPS to confirm the successful preparation. The composite hydrogel microspheres showed the better antimicrobial effect of hydrogel microspheres by bacterial coated plate experiments and SEM morphology results, with the antimicrobial class reaching 99.8%. The results of immunofluorescence staining and X-ray experiments showed that the hydrogel microspheres had a better effect on promoting bone repair. This engineered design of hydrogel microspheres provides clinical significance for treating osteomyelitis at a later stage.
Unravelling hierarchical patterning of biomaterial inks with 3D microfluidic-assisted spinning: a paradigm shift in bioprinting technologies
Authors: Mohammadi Sajad , Cidonio Gianluca
Published: October 2023

For decades, 3D bioprinting has offered a revolutionising approach to combine living cells and biomaterials to engineer complex, yet functional constructs. However, traditional 3D bioprinting platforms fall short of the ability to pattern complex gradients of biomaterials, cells, and ultimately bio-physical properties to drive tissue formation and regeneration. Recently, 3D microfluidic-assisted bioprinting (3DMB) has risen as a new hybrid approach for the fabrication of physiologically relevant tissues, adopting a microfluidic chip as functional printhead to achieve hierarchical patterning of bioinks and precise control over the microscale architecture of printed constructs, enabling the creation of multi-layered tissues. This review explores recent advancements in graded biomaterial patterning using microfluidic-assisted spinning and novel 3D bioprinting technologies. The physiological hierarchical arrangement of human tissues and the crucial role of biomaterials in achieving ordered assembly is hereby discussed. Lastly, the integration of microfluidic-assisted techniques with new bioprinting platforms is highlighted, examining the latest advancements in tissue regeneration and disease modelling.
In vivo validation of a mechanically adaptive microfluidic intracortical device as a platform for sustained local drug delivery
Authors: Kim Youjoung , Druschel Lindsey N. , Mueller Natalie , Sarno Danielle , Gisser Kaela , Hess-Dunning Allison , Capadona Jeffrey R.
Published: October 2023

Introduction: Intracortical microelectrodes (IME) are vital to properly functioning brain-computer interfacing (BCI). However, the recording electrodes have shown a steady decline in performance after implantation, mainly due to chronic inflammation. Compliant materials have been explored to decrease differential strain resulting in lower neural inflammation. We have previously developed a fabrication method for creating mechanically adaptive microfluidic probes made of a cellulose nanocrystal (CNC) polymer nanocomposite material that can become compliant after implantation. Here, we hypothesized that our device, would have a similar tissue response to the industry standard, allowing drug delivery therapeutics to improve neural inflammation in the future.

Methods: RNA expression analysis was performed to determine the extent of neural inflammation and oxidative stress in response to the device compared to controls and to naïve shame tissue.

Results: Results presented for both four- and eight-weeks post-implantations suggest that our device offers a promising platform technology that can be used to deliver therapeutic strategies to improve IME performance.
Potential chemoprotective effects of active ingredients in Salvia miltiorrhiza on doxorubicin-induced cardiotoxicity: a systematic review of in vitro and in vivo studies
Authors: Wang Qingqing , Li Jiaxian , Chu Xuelei , Jiang Xiaochen , Zhang Chuanlong , Liu Fudong , Zhang Xiyuan , Li Yi , Shen Qian , Pang Bo
Published: October 2023

Background

Recently, attention has been paid to the protective properties of active ingredients in Salvia miltiorrhiza (AISM) against organ toxicity induced by chemotherapy drugs. Purpose of the present systematic review is to evaluate the chemoprotective effects and mechanisms of AISM on in vitro and in vivo models of doxorubicin-induced cardiotoxicity (DIC).

Methods

According to the PRISMA guideline, the current systematic review was conducted in the Web of Science, PubMed, Embase, and the Cochrane Library to collect all relevant in vitro and in vivo studies on “the role of AISM on DIC” published up until May 2023. The SYRCLE's tool was used to identify potential risk of bias.

Results

Twenty-two eligible articles were included in this systematic review. Eleven types of active ingredients in Salvia miltiorrhiza were used for DIC, which have the following effects: improvement of physical signs and biochemical indicators, reduction of cardiac function damage caused by DIC, protection of heart tissue structure, enhancement of myocardial cell viability, prevention of cardiomyocyte apoptosis, increase of the chemosensitivity of cancer cells to Doxorubicin, etc. The cardioprotective mechanism of AISM involves inhibiting apoptosis, attenuating oxidative stress, suppressing endoplasmic reticulum (ER) stress, decreasing inflammation, improving mitochondrial structure and function, affecting cellular autophagy and calcium homeostasis. The quality scores of included studies ranged from 4 to 7 points (a total of 10 points), according to SYRCLE's risk of bias tool.

Conclusion

This systematic review demonstrated that AISM have chemoprotective effects on DIC in vivo and in vitro models through several main mechanisms such as anti-apoptosis, antioxidant effects, anti-ER stress, and anti-inflammatory.
Relationship between plasma leucine-rich α-2-glycoprotein 1 and urinary albumin excretion in patients with type 2 diabetes
Authors: Chung Jin Ook , Park Seon-Young , Cho Dong Hyeok , Chung Dong Jin , Chung Min Young
Published: October 2023

Aims

To explore the relationship between plasma leucine-rich α-2-glycoprotein 1 (LRG1) level and the degree of urinary albumin excretion in patients with type 2 diabetes.

Methods

We evaluated 332 patients with type 2 diabetes in a cross-sectional study.

Result

The plasma LRG1 level differed significantly according to the quartiles of urinary albumin excretion (Q1 [<7.7 mg/g], 17.1 μg/mL; Q2 [7.7–15.0 mg/g], 17.5 μg/mL; Q3 [15.1–61.4 mg/g], 18.6 μg/mL; Q4 [≥61.5 mg/g], 22.3 μg/mL; p for trend = 0.003) under adjustment with other covariates. A positive correlation was found between plasma LRG1 level and urinary albumin excretion (ρ = 0.256, p <0.001). According to a multivariate model, the association between LRG1 and urinary albumin excretion remained significant, under adjustment for confounding factors (β = 0.285, p <0.001).

Conclusion

Plasma LRG1 level was independently associated with urinary albumin excretion in patients with type 2 diabetes. This study suggests that LRG1 may be associated with increased excretion of urinary albumin in the early stages of diabetic nephropathy.
Associations between genetically predicted sex and growth hormones and facial aging in the UK Biobank: a two−sample Mendelian randomization study
Authors: Zhao Mingjian , Lv Huiyun , Zhang Yunshu , Zhao Hongliang , Qin Hongzhi
Published: October 2023

Background

Aging is an inescapable process, but it can be slowed down, particularly facial aging. Sex and growth hormones have been shown to play an important role in the process of facial aging. We investigated this association further, using a two-sample Mendelian randomization study.

Methods

We analyzed genome-wide association study (GWAS) data from the UK Biobank database comprising facial aging data from 432,999 samples, using two-sample Mendelian randomization. In addition, single-nucleotide polymorphism (SNP) data on sex hormone-binding globulin (SHBG) and sex steroid hormones were obtained from a GWAS in the UK Biobank [SHBG, N = 189,473; total testosterone (TT), N = 230,454; bioavailable testosterone (BT), N = 188,507; and estradiol (E2), N = 2,607)]. The inverse-variance weighted (IVW) method was the major algorithm used in this study, and random-effects models were used in cases of heterogeneity. To avoid errors caused by a single algorithm, we selected MR-Egger, weighted median, and weighted mode as supplementary algorithms. Horizontal pleiotropy was detected based on the intercept in the MR-Egger regression. The leave-one-out method was used for sensitivity analysis.

Results

SHBG plays a promoting role, whereas sex steroid hormones (TT, BT, and E2) play an inhibitory role in facial aging. Growth hormone (GH) and insulin-like growth factor-1 (IGF-1) levels had no significant effect on facial aging, which is inconsistent with previous findings in vitro.

Conclusion

Regulating the levels of SHBG, BT, TT, and E2 may be an important means to delay facial aging.
Factors associated with weight loss and health gains in a structured lifestyle modification programme for adults with severe obesity: a prospective cohort study
Authors: Finucane Francis M. , Gibson Irene , Hughes Robert , Murphy Enda , Hynes Lisa , Harris Aisling , McGuire Brian E. , Hynes Mary , Collins Chris , Cradock Kevin , Seery Suzanne , Jones Jennifer , O’Brien Tim , O’Donnell Martin J.
Published: October 2023

Background

Individual responses to behavioural weight loss interventions can vary significantly, and a better understanding of the factors associated with successful treatment might help to target interventions for those who will benefit the most. We sought to identify demographic and clinical characteristics that predicted intervention “success” (defined as ≥5% weight loss) and other health gains in patients with severe obesity attending a ten-week structured lifestyle modification programme.

Methods

We conducted a prospective cohort study of all 1122 patients (751 (66.9%) female, mean age 47.3 ± 11.9 years, mean body mass index (BMI) 46.7 ± 7.8 kgm-2) referred from our hospital-based obesity clinic, who started the structured lifestyle programme between 2012-2019. We compared routine clinical measures such as weight, fitness, blood pressure, lipids and HbA1c at baseline and follow-up. We also used validated questionnaires to quantify anxiety, depression and health-related quality of life.

Results

Of 1122 patients who started, 877 (78.2%) completed the programme and attended for follow up. Of these, 12.8% lost ≥5% body weight. The amount of weight lost was a strong and consistent predictor of improvements in metabolic, cardiovascular, and mental health, even after adjusting for age, sex, programme attendance and baseline fitness. Older age, male sex, being physically active and having lower anxiety and depression scores at baseline predicted greater weight loss. Younger age, depression and longer wait time to start the intervention were associated with drop-out.

Conclusions

In adults with severe obesity completing a structured lifestyle modification programme, older age and good mental health were associated with programme completion and attaining ≥5% weight loss. The magnitude of weight lost was a strong predictor of improvements in cardiovascular, metabolic and mental health associated with programme completion.
Stem cells and exosomes: as biological agents in the diagnosis and treatment of polycystic ovary syndrome (PCOS)
Authors: Hadidi Mahta , Karimabadi Keyvan , Ghanbari Elham , Rezakhani Leila , Khazaei Mozafar
Published: October 2023

A typical condition of the female reproductive system is polycystic ovary syndrome (PCOS). Hyperinsulinemia, insulin resistance, obesity, and hyperandrogenism are just a few of the metabolic abnormalities linked to this disease. Type 2 diabetes, hypertension, and cardiovascular disease are further issues related to PCOS. One consequence of this syndrome for which numerous treatment procedures have been developed is infertility. Metformin and clomiphene, two common allopathic medications used to treat PCOS, both have drawbacks and are ineffective. It is vital to seek novel therapeutic modalities to address these constraints. Exosomes (EXOs) are a particular class of extracellular vesicles that cells release, and they are known to play a significant role in mediating intercellular communication. A wide range of cargo, including lipids, proteins, mRNA, miRNAs, and numerous other noncoding RNAs, are contained in the nanoscale lipid bilayer exosomes. The cytokine effects of stem cells and EXOs derived from them enable the defense against metabolic diseases like PCOS. Moreover, EXO microRNAs can potentially be employed as biomarkers in the detection and management of PCOS. In this study, the potential of stem cells and exosomes are specifically investigated in the diagnosis and treatment of PCOS as one of the diseases of the female reproductive system.
Machine learning algorithms for lithological mapping using Sentinel-2 and SRTM DEM in highly vegetated areas
Authors: Chen Yansi , Dong Yulong , Wang Yunchen , Zhang Feng , Liu Genyuan , Sun Peiheng
Published: October 2023

Lithological mapping in highly vegetated areas using remote sensing techniques poses a significant challenge. Inspired by the concept of “geobotany”, we attempted to distinguish lithologies indirectly using machine learning algorithms (MLAs) based on Sentinel-2 and SRTM DEM in Zhangzhou City, Fujian Province. The study area has high vegetation cover, with lithologies that are largely obscured. After preprocessing such as cloud masking, resampling, and median image synthesis, 17 spectral bands and features from Sentinel-2 and 9 terrain features from DEM were extracted. Five widely used MLAs, MD, CART, SVM, RF, and GBDT, were trained and validated for lithological mapping. The results indicate that advanced MLAs, such as GBDT and RF, are highly effective for nonlinear modeling and learning with relative increases reaching 8.18%∼11.82% for GBDT and 6.36%∼10% for RF. Compared with optical imagery or terrain data alone, combining Sentinel-2 and DEM significantly improves the accuracy of lithological mapping, as it provides more comprehensive and precise spectral characteristics and spatial information. GBDT_Sen+DEM utilizing integrated data achieved the highest classification accuracy, with an overall accuracy of 63.18%. This study provides a case study for lithological mapping of areas with high vegetation cover at the local level. This also reinforces the idea that merging remote sensing and terrain data significantly enhances the precision and reliability of the lithological mapping methods.
Satralizumab as an add-on treatment in refractory pediatric AQP4-antibody-positive neuromyelitis optica spectrum disorder: a case report
Authors: Li Xiaojing , Wu Wenlin , Zeng Yiru , Wu Wenxiao , Hou Chi , Zhu Haixia , Liao Yinting , Tian Yang , Chen Zongzong , Peng Bingwei , Chen Wen-Xiong
Published: October 2023

Neuromyelitis optica spectrum disorder (NMOSD) is a rare autoimmune disease of the central nervous system. Relapse and incomplete recovery from relapse are common in NMOSD. Most patients with NMOSD have IgG to aquaporin-4 (AQP4-IgG). New biological agents for AQP4-IgG-seropositive NMOSD, such as satralizumab, have become available for maintenance therapy. Satralizumab is an anti-interleukin-6 receptor monoclonal antibody. To date, few studies have evaluated satralizumab as an add-on treatment in pediatric NMOSD patients. Here, we report an 11-year-old girl with NMOSD who frequently relapsed under long-term treatment, including oral prednisone, rituximab, mycophenolate mofetil (MMF), and maintenance intravenous immunoglobulin treatment even with B-cell depletion. For the poor treatment response and to improve the efficacy of relapse prevention further, the patient received satralizumab treatment as an add-on therapy to MMF plus oral prednisone, with a dose of 120 mg administered subcutaneously at weeks 0, 2, and 4 and every 4 weeks after that. After initiating satralizumab, the patient remained relapse-free for 14 months at the last follow-up. Satralizumab might be effective and safe as an add-on treatment in refractory pediatric AQP4-IgG-seropositive NMOSD under B-cell depletion.
Case Report: Successful immune checkpoint inhibitor-based rechallenge in a patient with advanced renal clear cell cancer
Authors: He Shengxiu , Wang Liang , Sun Yan , Du Huakun , Yu Xiaomin
Published: October 2023

With the rapidly evolving of immune checkpoint inhibitors (ICIs), it has shown remarkable clinical benefits in treating various cancers. However, immune-related adverse events (irAEs) remain a significant challenge in the management of patients undergoing immunotherapy. There are limited data about immunotherapy re-challenge in patients with renal clear cell cancer who had irAE in the initial ICI therapy. In this study, we reported the case of a patient with advanced renal clear cell cancer who developed serious irAEs but also achieved a partial remission of tumor after ICI combined with pazopanib in the first-line treatment. After intravenous methylprednisolone therapy for two weeks, the patient fully recovered from treatment-related toxicities. After a multidisciplinary treatment (MDT) discussion and a communication with the patient, the decision was made to undergo a new fully humanized programmed death 1 (PD-1) agent, zimberelimab, combined with pazopanib for immune restart therapy. After two cycles of treatment, the patient demonstrated a partial response (PR), and the disease remained in continuous remission without any irAE at our last follow-up after 14 months’ treatment. Re-challenging with immunotherapy after irAEs is an emerging strategy that offers the potential for additional clinical benefits to previously responding patients. However, careful patient selection and monitoring are essential to maximize the safety and efficacy of this approach.
Causal association of circulating cytokines with sepsis: a Mendelian randomization study
Authors: Lin Shan , Mao Xueyan , He Wanmei
Published: October 2023

Background

Observational studies have reported an association between circulating cytokines and sepsis. However, the precise causal relationship between these factors remains unclear. The objective of this study was to explore the causal link between circulating cytokines and sepsis using genetic data within the framework of Mendelian Randomization (MR).

Methods

We performed a two-sample MR analysis to investigate this causality relationship in individuals of European ancestry. The publicly available genome-wide association studies (GWAS) statistics were used. We selected eligible instrumental single nucleotide polymorphisms (SNPs) that were significantly related to the circulating cytokines. Multiple MR analysis approaches were carried out, which included inverse variance weighted (IVW), Weighted Median, MR-Egger, Weighted Mode, Simple Mode, and MR pleiotropy residual sum and outlier (MR-PRESSO) methods.

Results

We found evidence to support the causal role of genetically predicted circulating levels on decreased risk of sepsis, including RANTES (OR = 0.920, 95% CI: 0.849-0.997, P = 0.041) and basic fibroblast growth factor (basic-FGF) (OR = 0.869, 95% CI: 0.766-0.986, P = 0.029). Additionally, MR analysis positive causal association of between beta-nerve growth factor (β-NGF) and sepsis (OR = 1.120, 95% CI: 1.037-1.211, P = 0.004). The results of MR-Egger, Weighted Median, Weighted Mode, and Simple Mode methods were consistent with the IVW estimates. Sensitivity analysis showed no horizontal pleiotropy to bias the causal estimates.

Conclusion

This MR study provides first novel evidence that genetically predicted causal association of circulating levels of RANTES, basic-FGF, and β-NGF with altered sepsis risk. The findings shed light on the potential involvement of these cytokines in sepsis pathogenesis. Although requiring additional confirmation, the results contribute new insights into cytokine mediators in sepsis and suggest promising future research directions.
Scurvy in a young man: a rare case report
Authors: Lu Rui-Ling , Guo Jie-Wen , Sun Bao-dong , Chen Yu-Lan , Liu Dong-Zhou
Published: October 2023

Scurvy, resulting from vitamin C deficiency, has nonspecific constitutional symptoms, including weakness, malaise, and fatigue. It is frequently misdiagnosed due to the lack of specific clinical manifestations. Although there are sporadic cases of scurvy currently reported in children, scurvy in young people is seldom encountered. Here, we report on a 25-year-old male patient without any underlying conditions who presented with severe pain and ecchymoses of both lower extremities. He was diagnosed with scurvy due to a long history of staying indoors and inadequate intake of fruits or vegetables.
Immune-related adverse events of anti-PD-1 immune checkpoint inhibitors: a single center experience
Authors: Sebestyén Enikő , Major Nóra , Bodoki Levente , Makai Attila , Balogh Ingrid , Tóth Gábor , Orosz Zsuzsanna , Árkosy Péter , Vaskó Attila , Hodosi Katalin , Szekanecz Zoltán , Szekanecz Éva
Published: October 2023

Objectives

Immune checkpoint inhibitors (ICIs) stimulate antitumor immune responses and, in parallel, they might trigger autoimmune and other immunopathological mechanisms eventually leading to immune-related adverse events (irAE). In our study, we assessed patients with malignancies who underwent anti-PD-1 treatment at the University of Debrecen, Clinical Center.

Patients and methods

Between June 2017 and May 2021, 207 patients started ICI treatment at our university. A total of 157 patients received nivolumab and 50 were treated with pembrolizumab. We looked for factors associated with the development of irAEs. In addition to correlation studies, we performed binary logistic regression analysis to determine, which factors were associated with irAEs. We also performed Forward Likelihood Ratio (LR) analysis to determine independent prognostic factors.

Results

At the time of data analysis, the mean duration of treatment was 2.03 ± 0.69 years. ROC analysis determined that 9 or more treatment cycles were associated with a significantly higher risk of irAEs. A total of 125 patients received ≥9 treatment cycles. Three times more patients were treated with nivolumab than pembrolizumab. Of the 207 patients, 66 (32%) developed irAEs. Among the 66 patients who developed irAEs, 36 patients (55%) developed one, 23 (35%) developed two, while 7 (10%) developed three irAEs in the same patient. The most common irAEs were thyroid (33 cases), dermatological (25 cases), pneumonia (14 cases) and gastrointestinal complications (13 cases). Patients who developed irAEs received significantly more treatment cycles (21.8 ± 18.7 versus 15.8 ± 17.4; p=0.002) and were younger at the start of treatment (60.7 ± 10.8 versus 63.4 ± 10.1 years; p=0.042) compared to patients without irAEs. Pembrolizumab-treated patients developed more but less severe irAEs compared to those receiving nivolumab.

Conclusion

ICI treatment is very effective, however, irAEs may develop. These irAEs might be related to the number of treatment cycles and the type of treated malignancy.
Enhancing glioblastoma treatment through the integration of tumor-treating fields
Authors: Szklener Katarzyna , Bilski Mateusz , Nieoczym Karolina , Mańdziuk Dominika , Mańdziuk Sławomir
Published: October 2023

Glioblastoma (GBM) represents a significant therapeutic challenge due to its aggressive nature. Tumor Treating Fields (TTFields) present a promising approach to GBM therapy. The primary mechanism of TTFields, an antimitotic effect, alongside numerous indirect effects including increased cell membrane permeability, signifies their potential in combination with other treatment modalities. Current combinations often include chemotherapy, particularly with temozolomide (TMZ), however, emerging data suggests potential synergy with targeted therapies, radiotherapy, and immunotherapy as well. TTFields display minimal side effects, predominantly skin-related, posing no significant barrier to combined therapies. The effectiveness of TTFields in GBM treatment has been demonstrated through several post-registration studies, advocating for continued research to optimize overall survival (OS) and progression-free survival (PFS) in patients, as opposed to focusing solely on quality of life.
Checkpoint inhibition in hematologic malignancies
Authors: Tsumura Aaron , Levis Daniel , Tuscano Joseph M.
Published: October 2023

Checkpoint inhibitor therapy has emerged as an effective therapeutic strategy for many types of malignancies, especially in solid tumors. Within the last two decades, numerous monoclonal antibody drugs targeting the CTLA-4 and PD-1/PD-L1 checkpoint pathways have seen FDA approval. Within hematologic malignancies, Hodgkin Lymphoma has seen the greatest clinical benefits thus far with more recent data showing efficacy in the front-line setting. As our understanding of checkpoint inhibition expands, using these pathways as a therapeutic target has shown some utility in the treatment of other hematologic malignancies as well, primarily in the relapsed/refractory settings. Checkpoint inhibition also appears to have a role as a synergistic agent to augment clinical responses to other forms of therapy such as hematopoietic stem cell transplant. Moreover, alternative checkpoint molecules that bypass the well-studied CTLA-4 and PD-1/PD-L1 pathways have emerged as exciting new therapeutic targets. Most excitingly is the use of anti-CD47 blockade in the treatment of high risk MDS and TP-53 mutated AML. Overall, there has been tremendous progress in understanding the benefits of checkpoint inhibition in hematologic malignancies, but further studies are needed in all areas to best utilize these agents. This is a review of the most recent developments and progress in Immune Checkpoint Inhibition in Hematologic Malignancies in the last decade.
Early biochemical outcomes following neoadjuvant/adjuvant relugolix with stereotactic body radiation therapy for intermediate to high risk prostate cancer
Authors: Gallagher Lindsey , Xiao Jerry , Hsueh Jessica , Shah Sarthak , Danner Malika , Zwart Alan , Ayoob Marilyn , Yung Thomas , Simpson Tiffany , Fallick Mark , Kumar Deepak , Leger Paul , Dawson Nancy A. , Suy Simeng , Collins Sean P.
Published: October 2023

Introduction

Injectable GnRH receptor agonists have been shown to improve cancer control when combined with radiotherapy. Prostate SBRT offers an abbreviated treatment course with comparable efficacy to conventionally fractionated radiotherapy. Relugolix is a new oral GnRH receptor antagonist which achieves rapid, sustained testosterone suppression. This prospective study sought to evaluate early testosterone suppression and PSA response following relugolix and SBRT for intermediate to high prostate cancer.

Methods

Relugolix was initiated at least 2 months prior to SBRT. Interventions to improve adherence were not utilized. PSA and total testosterone levels were obtained prior to and 1-4 months post SBRT. Profound castration was defined as serum testosterone ≤ 20 ng/dL. Early PSA nadir was defined as the lowest PSA value within 4 months of completion of SBRT. Per prior trials, we examined the percentage of patients who achieved PSA level of ≤ 0.5 ng/mL and ≤ 0.2 ng/mL during the first 4 months post SBRT.

Results

Between July 2021 and January 2023, 52 men were treated at Georgetown with relugolix (4-6 months) and SBRT (36.25-40 Gy in 5 fractions) per an institutional protocol (IRB 12-1775). Median age was 71 years. 26.9% of patients were African American and 28.8% were obese (BMI ≥30 kg/m2). The median pretreatment PSA was 9.1 ng/ml. 67% of patients were ≥ Grade Group 3. 44 patients were intermediate- and 8 were high-risk. Patients initiated relugolix at a median of 3.6 months prior to SBRT with a median duration of 6.2 total months. 92.3% of patients achieved profound castration during relugolix treatment. Poor drug adherence was observed in 2 patients. A third patient chose to discontinue relugolix due to side effects. By post-SBRT month 4, 87.2% and 74.4% of patients achieved PSA levels ≤ 0.5 ng/ml and ≤ 0.2 ng/ml, respectively.

Discussion

Relugolix combined with SBRT allows for high rates of profound castration with low early PSA nadirs. We observed a 96% testosterone suppresion rate without the utilization of scheduled cues/reminders. This finding supports the notion that patients with localized prostate cancer can consistently and successfully follow an oral ADT protocol without daily reminders. Given relugolix’s potential benefits over injectable GnRH receptor agonists, its usage may be preferred in specific patient populations (fear of needles, prior cardiovascular events). Future studies should focus on boundaries to adherence in specific underserved populations.
Cytokine responses to SARS-COV2 infection in mother-infant dyads: a systematic review and meta-analysis
Authors: Jain Samhita , Allen Isabel Elaine , Song Dongli , Piao Xianhua
Published: October 2023

Background

The COVID-19 pandemic has affected a significant number of pregnant women worldwide, but studies on immune responses have presented conflicting results. This study aims to systematically review cytokine profiles in pregnant women with SARS-CoV-2 infection and their infants to evaluate immune responses and potential transplacental transfer of cytokines.

Materials and methods

A comprehensive search of 4 databases was conducted to identify relevant studies. Inclusion criteria included studies measuring individual cytokines in pregnant women and/or their neonates. Studies were evaluated for quality, and data were extracted for analysis. Meta-analyses were performed using the random-effects model.

Results

Seventeen studies met the inclusion criteria, including data from 748 pregnant women and 287 infants. More than three of these studies evaluated data of 20 cytokines in maternal serum, and data of 10 cytokines was available from cord blood samples. Only the serum level of CXCL10 was significantly up-regulated in SARS-CoV-2 positive pregnant women (n = 339) compared to SARS-CoV-2 negative pregnant women (n = 409). Subset analysis of maternal samples (n = 183) collected during the acute phase of COVID-19 infection showed elevated CXCL10 and IFN-γ. No significant differences in cytokine levels were found between cord blood samples collected from infants born to mothers with (n = 97) and without (n = 190) COVID-19 during gestation. Subset analysis of cord blood samples collected during the acute phase of maternal infection was limited by insufficient data. The heterogeneity among the studies was substantial.

Conclusion

The findings suggest that maternal cytokines responses to SARS-CoV-2 infection during pregnancy are not significantly dysregulated, except for CXCL10 and IFN-γ during the acute phase of illness. No evidence of increased cytokine levels in cord blood samples was observed, although this could be impacted by the time period between initial maternal infection and cord blood collection. These results provide some reassurance to parents and healthcare providers but should be interpreted cautiously due to study variations and limitations.
Case report: Uniportal video-assisted thoracoscopic sleeve lobectomy in a 6-year-old patient with inflammatory myofibroblastic tumor (IMT)
Authors: Geng Zhen-Yang , Li Zi-Hao , Li Shi-Hao , Wu Bin , Sheng Yin-Liang , Yuan Ping , Li Feng , Qi Yu
Published: October 2023

Inflammatory myofibroblastic tumor (IMT) is a rare neoplasm that can occur in various organs, including the lung. Surgical resection is usually the preferred treatment for localized IMT.A 6-year-old female was admitted to our hospital with complaints of “coughing and vomiting for 6 days”. A chest CT scan revealed occlusion of the left main bronchus, segmental atelectasis of the left lower lung, and cystic low-density shadows along the bronchial pathway. Subsequent fiberoptic bronchoscopy confirmed the diagnosis of IMT through pathological biopsy. After excluding surgical contraindications, the patient underwent uniportal video-assisted thoracoscopic sleeve lobectomy for treatment. The patient had an uneventful postoperative course and was discharged four days after surgery. After one month, the patient received a follow-up examination and reported no significant discomfort. A chest CT scan revealed no postoperative complications.Our experience suggests that uniportal video-assisted thoracoscopic surgery may be a safe and effective approach for the treatment of pediatric patients with IMT requiring complex surgical procedures such as sleeve lobectomy and tracheoplasty.
NFIA haploinsufficiency: case series and literature review
Authors: Dini Gianluca , Verrotti Alberto , Gorello Paolo , Soliani Luca , Cordelli Duccio Maria , Antona Vincenzo , Mencarelli Amedea , Colavito Davide , Prontera Paolo
Published: October 2023

Background

NFIA-related disorder (OMIM #613735) is an autosomal dominant neurodevelopmental disorder characterized by a variable degree of cognitive impairment and non-specific dysmorphic features. To date, fewer than thirty patients affected by this disorder have been described.

Methods

Our study included three children with NFIA haploinsufficiency recruited from three medical genetics centers. Clinical presentations were recorded on a standardized case report form.

Results

All patients presented a variable degree of intellectual disability. None of the individuals in our cohort had urinary tract malformations. Three novel mutations, c.344G>A, c.261T>G, and c.887_888del are reported here.

Conclusion

NFIA haploinsufficiency can be suspected through careful observation of specific dysmorphisms, including macrocephaly and craniofacial abnormalities. Instrumental tests such as MRI and renal ultrasound provide further diagnostic clues, while genetic testing can confirm the diagnosis.
Herbal medicine for the treatment of chronic cough: a systematic review and meta-analysis
Authors: Lee Boram , Kwon Chan-Young , Suh Hyo-Weon , Kim Ye Ji , Kim Kwan-Il , Lee Beom-Joon , Lee Jun-Hwan
Published: October 2023

Objectives: Chronic cough is a frequent condition worldwide that significantly impairs quality of life. Herbal medicine (HM) has been used to treat chronic cough due to the limited effectiveness of conventional medications. This study aimed to summarize and determine the effects of HM on patients with chronic cough.

Methods: A comprehensive search of 11 databases was conducted to find randomized controlled clinical trials (RCTs) that reported the effects of HM for patients with chronic cough on 16 March 2023. The primary outcome was cough severity, and the secondary outcomes included cough-related quality of life, cough frequency, total effective rate (TER), and cough recurrence rate. The methodological quality of the included studies was assessed using the Cochrane risk of bias tool, and the certainty of the evidence for effect estimates was assessed using the Grading of Recommendations, Assessment, Development, and Evaluations tool.

Results: A total of 80 RCTs comprising 7,573 patients were included. When HM was used as an alternative therapy to conventional medication, there were inconsistent results in improving cough severity. However, HM significantly improved cough-related quality of life and TER and significantly lowered the cough recurrence rate compared with conventional medication. When used as an add-on therapy to conventional medication, HM significantly improved cough severity, cough-related quality of life, and TER and significantly lowered the recurrence rate. In addition, HM had a significantly lower incidence of adverse events when used as an add-on or alternative therapy to conventional medication. The subgroup analysis according to age and cause of cough also showed a statistically consistent correlation with the overall results. The certainty of the evidence for the effect of HM was generally moderate to low due to the risk of bias in the included studies.

Conclusion: HM may improve cough severity and cough-related quality of life, and lower the cough recurrence rate and incidence of adverse events in patients with chronic cough. However, due to the high risk of bias and clinical heterogeneity of the included studies, further high-quality placebo-controlled clinical trials should be conducted using a validated and objective assessment tool.

Systematic Review Registration:https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023418736, CRD42023418736.
Effectiveness of an educational intervention about inhalation technique in healthcare professionals in primary care: a cluster randomized trial
Authors: Vázquez-González Noemí , Leiva-Fernández José , Cotta-Luque Víctor M. , Leiva-Fernández Francisca , Rius-Díaz Francisca , Martos-Crespo Francisco , Martín-Montañez Elisa , Barnestein-Fonseca Pilar
Published: October 2023

Background: Incorrect inhalation technique (IT) is an important issue for chronic obstructive pulmonary disease (COPD) patients and healthcare professionals. Studies in which counseling is carried out with healthcare professionals beforehand so that they can properly educate their patients are required. The objective of the present trial is to assess the improvement in the performance of the IT in subjects with COPD and prescribed inhaled therapy after the implementation of an educational intervention conducted by their general practitioners.

Methods: A cluster randomized clinical trial was conducted. A total of 286 COPD patients received scheduled inhalation therapy from 27 general practices in seven primary care centers. A teach-back educational intervention was implemented for both healthcare professionals and patients. The primary outcome of this study was the performance of the correct inhalation technique. It is considered a good technique if all steps in the inhalation data sheet are correctly performed. The secondary outcomes were assessed using forced spirometry, the basal dyspnea index, the Medical Research Council dyspnea scale, St George’s Respiratory Questionnaire (SGRQ), and EuroQoL5D-5L for health-related quality of life. A one-year follow-up was conducted using an intention-to-treat analysis.

Results: After the intervention, incorrect IT was observed in 92% of professionals and patients, with rates reaching 50% and 69.2%, respectively. The effectiveness in patients was significant, with a number needed to treat of 2.14 (95% CI 1.79–2.66). Factors related to correct IT in patients included the type of intervention, length of intervention (>25 min), good pulmonary function, age (youngest <=65, oldest >83), and less limitation of activity due to dyspnea. There was no relation with the cluster.

Conclusion: This study shows the effectiveness of direct inhaler technique training provided by a trained professional on an appropriate timescale (for example, a specific consultation for medication reviews), aiming to help subjects improve their performance using the teach-back method. This could be an encouraging intervention to improve medication adherence and health promotion in people with COPD.

Clinical Trial Registration:clinicaltrials.gov, identifier ISRCTN93725230.
Natural compounds as lactate dehydrogenase inhibitors: potential therapeutics for lactate dehydrogenase inhibitors-related diseases
Authors: Han Jung Ho , Lee Eun-Ji , Park Wonyoung , Ha Ki-Tae , Chung Hwan-Suck
Published: October 2023

Lactate dehydrogenase (LDH) is a crucial enzyme involved in energy metabolism and present in various cells throughout the body. Its diverse physiological functions encompass glycolysis, and its abnormal activity is associated with numerous diseases. Targeting LDH has emerged as a vital approach in drug discovery, leading to the identification of LDH inhibitors among natural compounds, such as polyphenols, alkaloids, and terpenoids. These compounds demonstrate therapeutic potential against LDH-related diseases, including anti-cancer effects. However, challenges concerning limited bioavailability, poor solubility, and potential toxicity must be addressed. Combining natural compounds with LDH inhibitors has led to promising outcomes in preclinical studies. This review highlights the promise of natural compounds as LDH inhibitors for treating cancer, cardiovascular, and neurodegenerative diseases.