bluuebunny/crossref_metadata_2025 huggingface dataset:
Prevalence and characterization of anti-VWF antibodies in a population of patients with type 3 VWD
Authors: Perry Crystal L. , Christopherson Pamela A. , Agostini Tina A. , Haberichter Sandra L. , Montgomery Robert R. , Flood Veronica H.
Published: August 2024

von Willebrand disease (VWD) is an inherited bleeding disorder caused by quantitative or qualitative defects in the von Willebrand factor (VWF) protein. Type 3 VWD has a severe bleeding phenotype caused by the absence of VWF, in which treatment usually involves replacement therapy with VWF-containing products. The immune system can react to the VWF product and form anti-VWF antibodies to neutralize or clear the VWF, which can compromise efficacy of treatment or lead to anaphylaxis. Current diagnostic testing is limited to the detection of anti-VWF antibodies that neutralize VWF binding to platelets by using a ristocetin cofactor assay. We set out to develop assays to identify both neutralizing and nonneutralizing antibodies to screen, quantify, and characterize anti-VWF antibodies in samples from the Zimmerman Program, a large multicenter study of patients with VWD. We detected anti-VWF immunoglobulin G (IgG) or IgM antibodies in 18% of 49 unrelated individuals with type 3 VWD. The antibodies ranged in concentration and consisted of 33% nonneutralizing and 67% neutralizing to factor VIII, collagen III, platelet glycoprotein Ib alpha (GPIbα), and/or collagen IV binding. Of the positive type 3 VWD samples, 8 of 9 were IgG, which were further subclassified into mostly IgG1 and IgG4 antibodies. Through a series of testing methods, we identified VWF-specific antibodies in 9 unrelated individuals with type 3 VWD with varying demographics, bleeding phenotypes, and genetic variants. This anti-VWF antibody testing strategy provides a useful tool to assess risk and better navigate treatment options for patients with type 3 VWD.
Multi-Objective Optimization of the Ultrasonic Scalpel Rod and Tip with Improved Performance: Vibration Frequency, Amplitude, and Service Life
Authors: Zhao Jiaqi , Zhai Yuhao , Jia Xuzhe , Deng Naiwen , Li Kunxu , Han Guangchao , Chen Rong , Wang Dong , Bai Wei
Published: August 2024

Ultrasonic scalpel design for minimally invasive surgical procedures is mainly focused on optimizing cutting performance. However, an important issue is the low fatigue life of traditional ultrasonic scalpels, which affects their long-term reliability and effectiveness and creates hidden dangers for surgery. In this study, a multi-objective optimal design for the cutting performance and fatigue life of ultrasonic scalpels was proposed using finite element analysis and fatigue simulation. The optimal design parameters of resonance frequency and amplitude were determined. By setting the transition fillet and keeping the gain structure away from the node position to enable the scalpel to have a high service life with excellent cutting performance. The frequency modulation method of setting the vibration node bosses at the node position and setting the vibration antinode grooves at the antinode position was compared. Then, the mechanism of the influence of various design elements, such as tip, shank, node position, and antinode position, on the resonance frequency, amplitude, and fatigue life of the ultrasonic scalpel was analyzed, and the optimal design principles of the ultrasonic scalpel were obtained. The proposed ultrasonic scalpel design was confirmed by simulations, impedance measurements, and liver tissue cutting experiments, demonstrating its feasibility and enhanced performance. This research introduces innovative design strategies to improve the fatigue life and performance of ultrasonic scalpels to address an important issue in minimally invasive surgery.
Perfusion and pulsatile pressure: their relationship with target organ damage in the African-PREDICT study
Authors: Rooi Donavan , Botha-Le Roux Shani , Breet Yolandi
Published: August 2024

Background

Hypertension is the leading risk factor for subclinical target-organ damage (TOD) and cardiovascular disease (CVD). Little is known about the relationship between different pressure measures and subclinical TOD, especially in young populations. We compared the strength of associations of subclinical TOD markers with perfusion and pulsatile pressure in young adults.

Methods

A total of 1 187 young adults from the African-PREDICT study were included. Ambulatory mean arterial pressure (MAP) and pulse pressure (PP) was obtained. Markers of subclinical TOD were measured and included left ventricular mass index (LVMi), carotid intimamedia thickness (cIMT), carotidfemoral pulse wave velocity (cfPWV), central retinal arteriolar equivalent (CRAE) and albumin to creatinine ratio (ACR).

Results

Measures of sub-clinical TOD (cIMT, cfPWV and CRAE), associated stronger with perfusion pressure (all p < 0.001) than pulsatile pressure in unadjusted models. Stronger associations were found between cfPWV (adjusted R2 = 0.26), CRAE (adjusted R2 = 0.12) and perfusion pressure (all p ≤ 0.001) than pulsatile pressure independent of several non-modifiable and modifiable risk factors.

Conclusions

In young, healthy adults, perfusion pressure is more strongly associated with subclinical TOD markers than pulsatile pressure. These findings contribute to the understanding of the development of early cardiovascular changes and may guide future intervention strategies.
Investigating the relationship between aging perception and self-efficacy in the older adults: a cross-sectional study in Eastern Iran
Authors: Arjmand-sangani Mohsen , Sharifzadeh Gholamreza , Soltani Narges , Torshizi Marzieh
Published: August 2024

Background

With the global increase in the older adults population, understanding factors that impact their quality of life is crucial. The perception of aging and self-efficacy are significant factors affecting older adults health outcomes. This descriptive cross-sectional study investigates the relationship between Aging Perception and self-efficacyamong older adults individuals in Birjand city, a demographic that is rapidly increasing but under-research.

Methods

This cross-sectional study was conducted from September 2022 to September 2023 on 400 older adults individuals in Birjand city. Participants were selected using a random sampling method from four regions, ensuring a representative sample. Data were collected through two main questionnaires: the Shortened Perceived Aging Questionnaire (SPAQ) and the General Self-Efficacy Questionnaire (GSE), both validated for the Persian-speaking population. Statistical analysis was performed using SPSS SOFTWARE. ARMONK, NY: IBM CORP. version 26, employing nonparametric tests due to the non-normal distribution of data.

Results

The study found a strong positive correlation between Aging Perception and self-efficacy (Spearman’s R = 0.79, p < 0.001), indicating that a more positive perception of aging is associated with higher self-efficacy. The analysis also revealed that men generally reported a more positive perception of aging and higher self-efficacy compared to women. However, underlying diseases and marital status did not significantly affect the Aging Perception or self-efficacy scores.

Conclusions

The findings suggest that enhancing self-efficacy among the older adults could improve their perception of aging, potentially leading to better health outcomes and quality of life. This study underscores the need for targeted interventions that consider cultural and gender-specific factors. Further research using longitudinal designs is recommended to explore the causality between Aging Perception and self-efficacy and to confirm these findings across different regions and cultural backgrounds in Iran.
Analysis of early warning indicators of death in patients with severe fever with thrombocytopenia syndrome
Authors: Yang Mianyu , Yin Ming , Hou Bingmei , Zhou Lijuan , Wang Jiling , Zhao Zonghao
Published: August 2024

Background

Since its discovery, severe fever with thrombocytopenia syndrome (SFTS) has been characterized by rapid progression and poor prognosis, and no specific treatment is available. The aim of this study was to investigate the early warning indicators of mortality in SFTS patients.

Methods

This is a retrospective cross-sectional study. The study subjects were patients who were admitted to the hospital with a confirmed diagnosis of SFTS from January 2023 to October 2023, and their clinical symptoms and signs at the time of admission, as well as the laboratory indexes of the first blood collection after admission were collected, grouped according to the prognosis, and statistically analyzed.

Results

A total of 141 patients were collected, of which 27 patients died and 114 patients were in the survival group. Through statistical analysis, patients with combined hemorrhagic manifestations, disturbance of consciousness, lymphopenia, elevated lipase, and prolonged thrombin time on admission were independent risk factors for patients’ death. By plotting the working characteristic curve of the subjects, as well as calculating the area under the curve, the results showed that the AUC of lymphopenia count was 0.670, 95% CI (0.563–0.776), P = 0.006; the AUC of elevated serum lipase index was 0.789, 95% CI (0.699–0.878), p < 0.001; the AUC of prolonged thrombin time was 0.749, 95% CI (0.645–0.854), p < 0.001.

Conclusion

Patients with hemorrhagic manifestations, disturbance of consciousness, lymphocyte reduction, elevated serum lipase, and prolonged thrombin time on admission are more worthy of the clinician’s attention, and require early and effective interventions to avoid further disease progression.
Epidemiological distribution of high-risk human papillomavirus genotypes and associated factors among patients with esophageal carcinoma at Bugando medical center in Mwanza, Tanzania
Authors: Ndemela Lilian M. , Ottoman Oscar M. , Chitemo Heaven D. , Minja Caroline Anold , Rambau Peter F. , Kidenya Benson R.
Published: August 2024

Background

Esophageal carcinoma is a growing concern in regions that have a high incidence of human papillomavirus (HPV) infection such as East Africa. HPV, particularly the high-risk genotypes, is increasingly recognized as a risk factor for esophageal carcinoma. We set out to investigate the prevalence and associated factors of high-risk HPV in formalin-fixed paraffin-embedded (FFPE) tissue blocks with esophageal carcinoma at Bugando Medical Center, a tertiary referral hospital in Mwanza, Tanzania, East Africa.

Methods

A total of 118 esophageal carcinoma FFPE tissue blocks, collected from January 2021 to December 2022, were analyzed. Genomic DNA was extracted from these tissues, and multiplex polymerase chain reaction (PCR) was performed to detect HPV using degenerate primers for the L1 region and type-specific primers for detecting HPV16, HPV18, and other high-risk HPV genotypes. Data were collected using questionnaires and factors associated with high-risk HPV genotypes were analyzed using STATA version 15 software.

Results

Of the 118 patients’ samples investigated, the mean age was 58.3 ± 13.4 years with a range of 29–88 years. The majority of the tissue blocks were from male patients 81/118 (68.7%), and most of them were from patients residing in Mwanza region 44/118 (37.3%). Esophageal Squamous Cell Carcinoma (ESCC) was the predominant histological type 107/118 (91.0%). Almost half of the tissue blocks 63/118 (53.3%) tested positive for high-risk HPV. Among these, HPV genotype 16 (HPV16) was the most common 41/63 (65.1%), followed by HPV genotype 18 (HPV18) 15/63 (23.8%), and the rest were other high-risk HPV genotypes detected by the degenerate primers 7/63 (11.1%). The factors associated with high-risk HPV genotypes were cigarette smoking (p-value < 0.001) and alcohol consumption (p-value < 0.001).

Conclusion

A substantial number of esophageal carcinomas from Bugando Medical Center in Tanzania tested positive for HPV, with HPV genotype 16 being the most prevalent. This study also revealed a significant association between HPV status and cigarette smoking and alcohol consumption. These findings provide important insights into the role of high-risk HPV in esophageal carcinoma in this region.
ADH4—a potential prognostic marker for hepatocellular carcinoma with possible immune-related implications
Authors: Li Ling , Huang Yong-ta , Wang Li-ting , Wang Xiao-ling , Chen Zhen-yu , Jiang Shao-lan , Zeng Qiu-ling , Huang Hui-pin , Li Xiao-long
Published: August 2024

Objective

This study aims to explore ADH4 expression in hepatocellular carcinoma (HCC), its prognostic impact, and its immune correlation to provide novel insights into HCC prognostication and treatment.

Methods

HCC prognostic marker genes were rigorously selected using GEO database, Lasso regression, GEPIA, Kaplan-Meier and pROC analyses. The expression of interested markers (ADH4, DNASE1L3, RDH16, LCAT, HGFAC) in HCC and adjacent tissues was assessed by Immunohistochemistry (IHC). We observed that ADH4 exhibited low expression levels in liver cancer tissues and high expression levels in normal liver tissues. However, the remaining four genes did not manifest any statistically significant differences between hepatocellular carcinoma (HCC) tissue and adjacent non-cancerous tissue. Consequently, ADH4 became the primary focus of our research. ADH4 expression was validated by signed-rank tests and unpaired Wilcoxon rank sum tests across pan-cancer and HCC datasets. Clinical significance and associations with clinicopathological variables were determined using Kaplan-Meier, logistic regression and Cox analyses on TCGA data. The ADH4-related immune responses were explored by Spearman correlation analysis using TIMER2 data. CD68, CD4, and CD19 protein levels were confirmed by IHC in HCC and non-cancerous tissues.

Results

ADH4 showed significant downregulation in various cancers, particularly in HCC. Moreover, low ADH4 expression was associated with clinicopathological variables and served as an independent prognostic marker for HCC patients. Additionally, ADH4 affects a variety of biochemical functions and may influence cancer development, prognosis, and treatment by binding to immune cells. Furthermore, at the immune level, the low expression pattern of ADH4 is TME-specific, indicating that ADH4 has the potential to be used as a target for cancer immunotherapy.

Conclusion

This study highlights the diagnostic, prognostic and immunomodulatory roles of ADH4 in HCC. ADH4 could serve as a valuable biomarker for HCC diagnosis and prognosis, as well as a potential target for immunotherapeutic interventions.
The effect of cycloplegia in the accuracy of autorefraction, keratometry and axial length using the Myopia Master
Authors: Peñaranda Agustin , Torrado Oscar , Márquez Ana , Baptista António M. , Serra Pedro Miguel
Published: August 2024

Background

Assessing refractive errors under cycloplegia is recommended for paediatric patients; however, this may not always be feasible. In these situations, refraction has to rely on measurements made under active accommodation which may increase measurements variability and error. Therefore, evaluating the accuracy and precision of non-cycloplegic refraction and biometric measurements is clinically relevant. The Myopia Master, a novel instrument combining autorefraction and biometry, is designed for monitoring refractive error and ocular biometry in myopia management. This study assessed its repeatability and agreement for autorefraction and biometric measurements pre- and post-cycloplegia.

Methods

A prospective cross-sectional study evaluated a cohort of 96 paediatric patients that underwent ophthalmologic examination. An optometrist performed two repeated measurements of autorefraction and biometry pre- and post-cycloplegia. Test-retest repeatability (TRT) was assessed as differences between consecutive measurements and agreement as differences between post- and pre-cycloplegia measurements, for spherical equivalent (SE), refractive and keratometric J0/J45 astigmatic components, mean keratometry (Km) and axial length (AL).

Results

Cycloplegia significantly improved the SE repeatability (TRT, pre-cyclo: 0.65 D, post-cyclo: 0.31 D). SE measurements were more repeatable in myopes and emmetropes compared to hyperopes. Keratometry (Km) repeatability did not change with cycloplegia (TRT, pre-cyclo: 0.25 D, post-cyclo:0.27 D) and AL repeatability improved marginally (TRT, pre-cyclo: 0.14 mm, post-cyclo: 0.09 mm). Regarding pre- and post-cycloplegia agreement, SE became more positive by + 0.79 D, varying with refractive error. Myopic eyes showed a mean difference of + 0.31 D, while hyperopes differed by + 1.57 D. Mean keratometry, refractive and keratometric J0/J45 and AL showed no clinically significant differences.

Conclusions

Refractive error measurements, using the Myopia Master were 2.5x less precise pre-cycloplegia than post-cycloplegia. Accuracy of pre-cycloplegic refractive error measurements was often larger than the clinically significant threshold (0.25 D) and was refractive error dependent. The higher precision compared to autorefraction measurements, pre- and post-cycloplegia agreement and refractive error independence of AL measurements emphasize the superiority of AL in refractive error monitoring.
The safety and efficacy of binimetinib for lung cancer: a systematic review
Authors: Zahmatyar Mahdi , Kharaz Ladan , Abiri Jahromi Negin , Jahanian Ali , Shokri Pourya , Nejadghaderi Seyed Aria
Published: August 2024

Background

Lung cancer, accounting for a significant proportion of global cancer cases and deaths, poses a considerable health burden. Non-small cell lung cancer (NSCLC) patients have a poor prognosis and limited treatment options due to late-stage diagnosis and drug resistance. Dysregulated of the mitogen-activated protein kinase (MAPK) pathway, which is implicated in NSCLC pathogenesis, underscores the potential of MEK inhibitors such as binimetinib. Despite promising results in other cancers, comprehensive studies evaluating the safety and efficacy of binimetinib in lung cancer are lacking. This systematic review aimed to investigate the safety and efficacy of binimetinib for lung cancer treatment.

Methods

We searched PubMed, Scopus, Web of Science, and Google Scholar until September 2023. Clinical trials evaluating the efficacy or safety of binimetinib for lung cancer treatment were included. Studies were excluded if they included individuals with conditions unrelated to lung cancer, investigated other treatments, or had different types of designs. The quality assessment was conducted utilizing the National Institutes of Health tool.

Results

Seven studies with 228 participants overall were included. Four had good quality judgments, and three had fair quality judgments. The majority of patients experienced all-cause adverse events, with diarrhea, fatigue, and nausea being the most commonly reported adverse events of any grade. The objective response rate (ORR) was up to 75%, and the median progression-free survival (PFS) was up to 9.3 months. The disease control rate after 24 weeks varied from 41% to 64%. Overall survival (OS) ranged between 3.0 and 18.8 months. Notably, treatment-related adverse events were observed in more than 50% of patients, including serious adverse events such as colitis, febrile neutropenia, and pulmonary infection. Some adverse events led to dose limitation and drug discontinuation in five studies. Additionally, five studies reported cases of death, mostly due to disease progression. The median duration of treatment ranged from 14.8 weeks to 8.4 months. The most common dosage of binimetinib was 30 mg or 45 mg twice daily, sometimes used in combination with other agents like encorafenib or hydroxychloroquine.

Conclusions

Only a few studies have shown binimetinib to be effective, in terms of improving OS, PFS, and ORR, while most of the studies found nonsignificant efficacy with increased toxicity for binimetinib compared with traditional chemotherapy in patients with lung cancer. Further large-scale randomized controlled trials are recommended.
Clinical outcome after open-wedge high tibial osteotomy: comparison of double-triangle locking compression plate (DT-LCP) and T-shaped locking compression plate (T-LCP)
Authors: Chen Pengzhao , Yu Jiahao , Guo Haichuan , Yuwen Peizhi , Zhu Yanbin , Zhang Yingze
Published: August 2024

Background

The objective of this study was to compare the clinical outcomes of two internal fixation methods for high tibial osteotomy (HTO): double-triangle locking compression plate (DT-LCP) and T-shaped locking compression plate (T-LCP).

Methods

202 adult patients in our hospital between January 2018 and December 2021 were included and followed up for at least one year: group 1(DT-LCP, 98 patients) and group 2 (T-LCP, 104 patients). Detailed information on demographics, preoperative and postoperative follow-up, surgical procedures, and complications were collected. The information of the International Knee Documentation Committee Knee Evaluation Form (IKDC), Knee Injury and Osteoarthritis Outcome Score (KOOS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) were collected before surgery and at the last follow-up.

Results

A total of 202 patients were included in the per-protocol analysis. No significant difference was found in terms of demographic data between groups, except for age and BMI. Clinically relevant improvements in knee pain were reached up to last follow-up after the operation in both groups. The mean pain scores (KOOS, WOMAC) at the final follow-up were significantly higher among group 1 compared to group 2 (P = 0.040 and P = 0.023). Furthermore, the DT-LCP internal fixation exerted more excellent effects on other symptoms, function and quality of life than T-LCP internal fixation.

Conclusions

Our study demonstrated that DT-LCP provided better clinical performance due to its implant irritant pain, compared with T-LCP. Thus, DT-LCP is a feasible alternative for the fixation of OW-HTO.
Exploring the deep learning of artificial intelligence in nursing: a concept analysis with Walker and Avant’s approach
Authors: Wangpitipanit Supichaya , Lininger Jiraporn , Anderson Nick
Published: August 2024

Background

In recent years, increased attention has been given to using deep learning (DL) of artificial intelligence (AI) in healthcare to address nursing challenges. The adoption of new technologies in nursing needs to be improved, and AI in nursing is still in its early stages. However, the current literature needs more clarity, which affects clinical practice, research, and theory development. This study aimed to clarify the meaning of deep learning and identify the defining attributes of artificial intelligence within nursing.

Methods

We conducted a concept analysis of the deep learning of AI in nursing care using Walker and Avant’s 8-step approach. Our search strategy employed Boolean techniques and MeSH terms across databases, including BMC, CINAHL, ClinicalKey for Nursing, Embase, Ovid, Scopus, SpringerLink and Spinger Nature, ProQuest, PubMed, and Web of Science. By focusing on relevant keywords in titles and abstracts from articles published between 2018 and 2024, we initially found 571 sources.

Results

Thirty-seven articles that met the inclusion criteria were analyzed in this study. The attributes of evidence included four themes: focus and immersion, coding and understanding, arranging layers and algorithms, and implementing within the process of use cases to modify recommendations. Antecedents, unclear systems and communication, insufficient data management knowledge and support, and compound challenges can lead to suffering and risky caregiving tasks. Applying deep learning techniques enables nurses to simulate scenarios, predict outcomes, and plan care more precisely. Embracing deep learning equipment allows nurses to make better decisions. It empowers them with enhanced knowledge while ensuring adequate support and resources essential for caregiver and patient well-being. Access to necessary equipment is vital for high-quality home healthcare.

Conclusion

This study provides a clearer understanding of the use of deep learning in nursing and its implications for nursing practice. Future research should focus on exploring the impact of deep learning on healthcare operations management through quantitative and qualitative studies. Additionally, developing a framework to guide the integration of deep learning into nursing practice is recommended to facilitate its adoption and implementation.
Literature review of complementary and alternative therapies: using text mining and analysis of trends in nursing research
Authors: Nam Jihye , Lee Hyejin , Lee Seunghyeon , Park Hyojung
Published: August 2024

Purpose

This study aimed to review the literature on complementary and alternative therapies, utilizing text mining and trend analysis in nursing research. As CAM becomes increasingly prevalent in healthcare settings, a comprehensive understanding of the current research landscape is essential to guide evidence-based practice, inform clinical decision-making, and ultimately enhance patient outcomes.

Method

This study aimed to identify CAM-related literature published from 2018 to 2023. Using the search terms 'complementary therap*', 'complementary medicine', 'alternative therap*', and 'alternative medicine', we performed a comprehensive search in eight databases, including EMBASE, Cochrane Central, PubMed Central, Korea Education and Research Information Service (RISS), Web of Science, KMbase, KISS, and CINAHL. From the text network and topic modeling analysis of 66,490 documents, 15 topics were identified. These topics were classified into two nursing-related topics through an academic classification process involving three doctors with doctoral degrees, three nurses, and three pharmacists. Based on the classified topics, research trends were comparatively analyzed by re-searching the database for 12 nursing and 22 non-nursing literature.

Result

This study found that in nursing literature, yoga is used to improve mental symptoms such as stress and anxiety. In non-nursing literature, most of the experimental studies on complementary and alternative therapies were conducted in a randomized manner, confirming that a variety of physiological and objective indicators were used. Additionally, it was discovered that there were differences in the diversity of research subjects and research design methods for the same intervention method. Therefore, future research should focus on broadening the scope of subjects and measurement tools in nursing studies. Additionally, such studies should be conducted with randomization and generalizability in the experimental design in mind.

Conclusion

This study employed text network analysis and text mining to identify domestic and international CAM research trends. Our novel approach combined big data-derived keywords with a systematic classification method, proposing a new methodological strategy for trend analysis. Future nursing research should focus on broadening the scope of subjects, diversifying measurement tools, and emphasizing randomization and generalizability in experimental designs.
Exploring the causal effect between lipid-modifying drugs and idiopathic pulmonary fibrosis: a drug-target Mendelian randomization study
Authors: Cai Gexiang , Liu Jingjing , Cai Mengsi , Shao Lianyou
Published: August 2024

Background

Idiopathic pulmonary fibrosis (IPF) is a respiratory disorder of obscure etiology and limited treatment options, possibly linked to dysregulation in lipid metabolism. While several observational studies suggest that lipid-lowering agents may decrease the risk of IPF, the evidence is inconsistent. The present Mendelian randomization (MR) study aims to determine the association between circulating lipid traits and IPF and to assess the potential influence of lipid-modifying medications for IPF.

Methods

Summary statistics of 5 lipid traits (high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglyceride, apolipoprotein A, and apolipoprotein B) and IPF were sourced from the UK Biobank and FinnGen Project Round 10. The study’s focus on lipid-regulatory genes encompassed PCSK9, NPC1L1, ABCG5, ABCG8, HMGCR, APOB, LDLR, CETP, ANGPTL3, APOC3, LPL, and PPARA. The primary effect estimates were determined using the inverse-variance-weighted method, with additional analyses employing the contamination mixture method, robust adjusted profile score, the weighted median, weighted mode methods, and MR-Egger. Summary-data-based Mendelian randomization (SMR) was used to confirm significant lipid-modifying drug targets, leveraging data on expressed quantitative trait loci in relevant tissues. Sensitivity analyses included assessments of heterogeneity, horizontal pleiotropy, and leave-one-out methods.

Results

There was no significant effect of blood lipid traits on IPF risk (all P＞0.05). Drug-target MR analysis indicated that genetic mimicry for inhibitor of NPC1L1, PCSK9, ABCG5, ABCG8, and APOC3 were associated with increased IPF risks, with odds ratios (ORs) and 95% confidence intervals (CIs) as follows: 2.74 (1.05–7.12, P = 0.039), 1.36 (1.02–1.82, P = 0.037), 1.66 (1.12–2.45, P = 0.011), 1.68 (1.14–2.48, P = 0.009), and 1.42 (1.20–1.67, P = 3.17×10-5), respectively. The SMR method identified a significant association between PCSK9 gene expression in whole blood and reduced IPF risk (OR = 0.71, 95% CI: 0.50–0.99, P = 0.043). Sensitivity analyses showed no evidence of bias.

Conclusions

Serum lipid traits did not significantly affect the risk of idiopathic pulmonary fibrosis. Drug targets MR studies examining 12 lipid-modifying drugs indicated that PCSK9 inhibitors could dramatically increase IPF risk, a mechanism that may differ from their lipid-lowering actions and thus warrants further investigation.
A nomogram predicting distant metastasis risk for gastric cancer patients with preoperative anemia: a multicenter retrospective study
Authors: Deng Guofei , Bi Bo , Deng Huachu , Fan Jingyuan , Huang Zhijian , Zhang Changhua , He Yulong
Published: August 2024

Background

Anemia represents a well-established risk factor for patients diagnosed with gastric cancer, and is often associated with an unfavorable prognosis. In this context, the timely prediction of distant metastasis risk in patients with anemic gastric cancer assumes paramount importance.

Methods

Information of gastric cancer patients complicated with preoperative anemia in the First Affiliated Hospital of Sun Yat-sen University was collected. The cohort from the First Affiliated Hospital of Guangxi Medical University was used as an external validation set. A Nomogram was established based on the risk factors screened by univariate and multivariate logistic regression analyses.

Results

A total of 848 gastric cancer patients with preoperative anemia were enrolled. Pyloric obstruction, carcinoma antigen 125, T stage, N stage, tumor size, and preoperative weight loss were independent predictors of distant metastasis in gastric cancer patients with anemia (p < 0.05), based on which a nomogram was constructed. The accuracy, reliability and clinical value of the nomogram were evaluated by concordance index, receiver operating characteristic curve, decision curve analysis, calibration curve and showed good stability and clinical predictive value.

Conclusions

Preoperative anemic gastric cancer patients, complicated with pyloric obstruction, elevated CA125, advanced T and N stage, larger tumor size, and preoperative weight loss, should be paid more attention to distant metastasis.
The oncogenic kinase TOPK upregulates in psoriatic keratinocytes and contributes to psoriasis progression by regulating neutrophils infiltration
Authors: Zeng Fanfan , Du Shuaixian , Wu Mengjun , Dai Chan , Li Jianyu , Wang Jinbiao , Hu Guoyun , Cai Pengcheng , Wang Lin
Published: August 2024

Background

T-LAK cell-oriented protein kinase (TOPK) strongly promotes the malignant proliferation of cancer cells and is recognized as a promising biomarker of tumor progression. Psoriasis is a common inflammatory skin disease featured by excessive proliferation of keratinocytes. Although we have previously reported that topically inhibiting TOPK suppressed psoriatic manifestations in psoriasis-like model mice, the exact role of TOPK in psoriatic inflammation and the underlying mechanism remains elusive.

Methods

GEO datasets were analyzed to investigate the association of TOPK with psoriasis. Skin immunohistochemical (IHC) staining was performed to clarify the major cells expressing TOPK. TOPK conditional knockout (cko) mice were used to investigate the role of TOPK-specific deletion in IMQ-induced psoriasis-like dermatitis in mice. Flow cytometry was used to analyze the alteration of psoriasis-related immune cells in the lesional skin. Next, the M5-induced psoriasis cell model was used to identify the potential mechanism by RNA-seq, RT-RCR, and western blotting. Finally, the neutrophil-neutralizing antibody was used to confirm the relationship between TOPK and neutrophils in psoriasis-like dermatitis in mice.

Results

We found that TOPK levels were strongly associated with the progression of psoriasis. TOPK was predominantly increased in the epidermal keratinocytes of psoriatic lesions, and conditional knockout of TOPK in keratinocytes suppressed neutrophils infiltration and attenuated psoriatic inflammation. Neutrophils deletion by neutralizing antibody greatly diminished the suppressive effect of TOPK cko in psoriasis-like dermatitis in mice. In addition, topical application of TOPK inhibitor OTS514 effectively attenuated already-established psoriasis-like dermatitis in mice. Mechanismly, RNA-seq revealed that TOPK regulated the expression of some genes in the IL-17 signaling pathway, such as neutrophils chemokines CXCL1, CXCL2, and CXCL8. TOPK modulated the expression of neutrophils chemokines via activating transcription factors STAT3 and NF-κB p65 in keratinocytes, thereby promoting neutrophils infiltration and psoriasis progression.

Conclusions

This study identified a crucial role of TOPK in psoriasis by regulating neutrophils infiltration, providing new insights into the pathogenesis of psoriasis.
Prevalence and factors associated with opioid use disorder among adolescents with sickle cell disease in Mulago hospital, Uganda
Authors: Kwagala Claire , Munube Deogratias , Abbo Catherine , Muhwezi Wilson Winstons , Mwesiga Emmanuel Kiiza
Published: August 2024

Background

Opioid use disorder (OUD) among adolescents with sickle cell disease (SCD) patients increases their risk of complications from sickle cell disease, such as infections, stroke, acute chest syndrome, sudden death, and organ failure. This negatively impacts families, communities, the national health system, and the economy. This study aimed to determine the prevalence and factors associated with opioid use disorder among adolescents with SCD at Mulago Hospital Uganda.

Methods

This study was carried out at the Sickle Cell Clinic of Mulago Hospital, the national referral hospital in Uganda. The study participants were adolescents aged 10 to 19 years. Following informed consent/ assent, a sociodemographic questionnaire, the WHO Alcohol, Smoking and Substance Involvement Screening Test - Young (ASSIST-Y), the Beck Depression Inventory-II (BDI II), and Generalized Anxiety Disorder − 7 (GAD-7) questionnaires were used to collect data. Data was entered in EpiInfo and analyzed in STATA 15.

Results

The prevalence of opioid use disorder was 5.3%. The significant risk factor was increasing depressive score AOR: 1.11(95% CI: 1.01–1.22, p = 0.035), while living with a family was protective against opioid use disorders AOR: 0.01; (95% CI: 0.0004, 0.27, p = 0.007).

Conclusion

There was a significant problem of OUD among adolescents with SCD. There is, therefore, needed to integrate screening of OUD and mental illnesses like depression among adolescents with SCD and to emphasize the importance of family support in their care.
Intersocietal survey on real-world asthma management in Italian children
Authors: Tosca Maria Angela , D’Avino Antonio , Di Mauro Giuseppe , Marseglia Gian Luigi , Miraglia del Giudice Michele , Ciprandi Giorgio ,   SIAIP Delegates, Leone Maddalena , Licari Amelia , Naso Sara Manti. Matteo , Trincianti Chiara ,   FIMP Delegates, Bellodi Simona , Ottonello Giancarlo , Fiore Michele , Terracciano Luigi , Zecca Silvia
Published: August 2024

Pediatric asthma management is a compelling challenge for every pediatrician. Different aspects require attention and definition. The present Intersocietal Survey aimed to collect real-world experiences from a sample of Italian pediatricians. A web platform was used to collect anonymous answers to the survey questions.

Four hundred four pediatricians participated in this initiative promoted by the Italian Society of Pediatric Allergy and Immunology (SIAIP), the Society of Preventive and Social Pediatrics (SIPPS), and the Federation of Italian Pediatricians (FIMP).

The results showed an extensive participation of primary care pediatricians (72%). There was a large consensus about diagnostic criteria and medication choice. However, treatment duration and device choice were various. Adherence to guidelines on general aspects of practical clinical management was high.

In conclusion, the present Intersocietal Survey confirmed that pediatric asthma management is rather satisfactory, even if further improvement should concern a more widespread use of ICS for acute asthma/wheezing attacks, a better definition of the duration of ICS and bronchodilator use, and hospital-primary care integration.
Efficacy of acoustic stimulation techniques on cognitive functions in individuals with Alzheimer’s disease—a scoping review
Authors: Thamizhmani Leelavathi , Ganapathy Kanaka , Palaniswamy Hari Prakash , Patil Divya Sussana , Purdy Suzanne Carolyn
Published: August 2024

Background

Alzheimer's disease (AD) is a progressive neurodegenerative disorder that severely affects cognitive functions and social behaviors, leading to a significant decline in an individual’s quality of life. Auditory processing deficits often precede the clinical symptoms of AD, prompting interest in auditory-based interventions as potential treatments. This scoping review aimed to compile the existing evidence on active and passive auditory-based interventions for individuals with AD and its prodromal stages.

Method and results

This scoping review followed Arksey and O’Malley's five-step framework to identify the existing evidence on auditory-based interventions for AD. Four databases (PubMed, Web of Science, CINAHL, and Embase) were used to search for studies on auditory stimulation techniques to treat cognitive decline in AD patients. In total, 14 studies were included in the analysis. Seven studies explored active auditory stimulation techniques, such as the Brain Fitness Program (BrainHQ), aiming to improve cognitive function in individuals with Mild Cognitive Impairment (MCI). The other seven studies focused on passive auditory stimulation, often combined with other sensory stimuli such as light or tactile inputs. Passive stimulation studies have focused mainly on Gamma Entrainment Using Sensory Stimulation (GENUS). The intervention frequency and duration varied across studies, ranging from one session lasting 8 h to a year. Both active and passive auditory stimulation showed potential for enhancing cognitive function in individuals with AD.

Conclusion

The literature suggests that auditory stimulation may positively influence cortical wiring and enhance cognitive abilities. Multimodal interventions that combine auditory stimulation with other sensory or behavioural approaches could yield more substantial effects on global cognition. However, the study design, intervention characteristics and outcome measures varied across studies, underscoring the necessity for standardised reporting. Well-designed studies using standard cognitive assessment protocols are recommended.
Severe hypoglycemia in a diabetic patient with pituitary apoplexy: a case report
Authors: Getahun Binyam Melese , Gebeyehu Medhanet Azene , Getahun Amsalu Molla , Kassie Yoseph Gebremedhin
Published: August 2024

Introduction

Hypoglycemia is a common occurrence in diabetic patients. But unlike non diabetic patients, its causes are frequently related to drugs they are receiving to control blood glucose. But this may not always be the case. Here we report a type 2 diabetic patient with severe hypoglycemia owing to acute hypopituitarism secondary to pituitary apoplexy.

Case presentation

A 45 year old male diabetic patient from Ethiopia taking 2 mg of oral glimepiride daily who presented with change in mentation of 30 minutes and blood glucose recording of 38 mg/dl upon arrival to the emergency room. Brain magnetic resonance imaging showed pituitary macroadenoma with hemorrhage suggestive of pituitary apoplexy. Blood work up showed low adrenocorticotropic hormone, cortisol, and serum sodium levels. Subsequently transsphenoidal hypophysectomy was done.

Conclusion

The occurrence of hypoglycemia in a diabetic patient taking sulphonylurea monotherapy is common. But when it is severe enough to cause altered mentation, patients should be approached differently. In the presence of clinical clues suggesting cortisol deficiency, hypopituitarism can be a possible cause.
Postbiotics from Saccharomyces cerevisiae fermentation stabilize microbiota in rumen liquid digesta during grain-based subacute ruminal acidosis (SARA) in lactating dairy cows
Authors: Guo Junfei , Zhang Zhengxiao , Guan Le Luo , Yoon Ilkyu , Plaizier Jan C. , Khafipour Ehsan
Published: August 2024

Background

Subacute ruminal acidosis (SARA) is a common metabolic disorder of high yielding dairy cows, and it is associated with dysbiosis of the rumen and gut microbiome and host inflammation. This study evaluated the impact of two postbiotics from Saccharomyces cerevisiae fermentation products (SCFP) on rumen liquid associated microbiota of lactating dairy cows subjected to repeated grain-based SARA challenges. A total of 32 rumen cannulated cows were randomly assigned to 4 treatments from 4 weeks before until 12 weeks after parturition. Treatment groups included a Control diet or diets supplemented with postbiotics (SCFPa, 14 g/d Original XPC; SCFPb-1X, 19 g/d NutriTek; SCFPb-2X, 38 g/d NutriTek, Diamond V, Cedar Rapids, IA, USA). Grain-based SARA challenges were conducted during week 5 (SARA1) and week 8 (SARA2) after parturition by replacing 20% DM of the base total mixed ration (TMR) with pellets containing 50% ground barley and 50% ground wheat. Total DNA from rumen liquid samples was subjected to V3–V4 16S rRNA gene amplicon sequencing. Characteristics of rumen microbiota were compared among treatments and SARA stages.

Results

Both SARA challenges reduced the diversity and richness of rumen liquid microbiota, altered the overall composition (β-diversity), and its predicted functionality including carbohydrates and amino acids metabolic pathways. The SARA challenges also reduced the number of significant associations among different taxa, number of hub taxa and their composition in the microbial co-occurrence networks. Supplementation with SCFP postbiotics, in particular SCFPb-2X, enhanced the robustness of the rumen microbiota. The SCFP supplemented cows had less fluctuation in relative abundances of community members when exposed to SARA challenges. The SCFP supplementation promoted the populations of lactate utilizing and fibrolytic bacteria, including members of Ruminococcaceae and Lachnospiraceae, and also increased the numbers of hub taxa during non-SARA and SARA stages. Supplementation with SCFPb-2X prevented the fluctuations in the abundances of hub taxa that were positively correlated with the acetate concentration, and α- and β-diversity metrics in rumen liquid digesta.

Conclusions

Induction of SARA challenges reduced microbiota richness and diversity and caused fluctuations in major bacterial phyla in rumen liquid microbiota in lactating dairy cows. Supplementation of SCFP postbiotics could attenuate adverse effects of SARA on rumen liquid microbiota.
1q jumping translocation as a biomarker in myeloid malignancy: frequently mutated genes associated with bad prognosis and low survival
Authors: Halper-Stromberg Eitan , Stinnett Victoria , Morsberger Laura , Pallavajjala Aparna , Levis Mark J. , DeZern Amy E. , Lei Michelle , Phan Brian , Xian Rena R. , Gocke Christopher D. , Tang Guilin , Zou Ying S.
Published: August 2024

1q jumping translocation (JT) is rare and its molecular profiles in myeloid malignancies are not well-known. This study evaluated gene mutations in 1q-JT cohorts (0.38%) from hematological malignant specimens that underwent genetic analysis at the Johns Hopkins Hospital (n = 11,908) and the MD Anderson Cancer Center. 1q-JT had frequent mutations in eleven genes, most of which are associated with worse prognosis. BCOR mutations significantly co-occurred with others. Patients tended to have mutations in DNA-repair, spliceosome, and epigenetic modification pathways, though genes utilized within each of these pathways were not randomly distributed. Multi-, albeit overlapping, pathway interruptions tended to manifest in mutations of two gene sets. One gene set consisted of SF3B1 (spliceosome) and TET2 (epigenetic modification), while the other consisted of STAG2 (DNA repair), SRSF2, U2AF (spliceosome), ASXL1, KMT2D (epigenetic modification), BCOR, and GATA2 (transcription factors). An “intermediate” JT-like rearrangement may represent an early sign of occurring 1q-JT. Treatments (hypomethylating agents) and unique structures of the short arms of acrocentric chromosomes may contribute to 1q-JT formation in myeloid malignancies. The median overall survival after identification of a JT was 10 months (95% confidence interval, 5–15 months). Our cohort represents the largest number of myeloid malignancies from multi-centers with before and after the 1q-JT event analyzed to date. Overall, this study identified specific molecular profiles that are associated with 1q-JT in myeloid malignancies. 1q-JT could serve as a poor prognosis biomarker in myeloid malignancies, which could be important in making well-informed clinical decisions and treatment strategies.
Research on the historical spatial characteristics and conservation strategies of colonial cities in Asia and Africa: a case study of 21 typical cities
Authors: Wei Wei , Liu Liyang , Niu Zhaosong , Qiao Sufang
Published: August 2024

Colonial cities in Asia and Africa, developed under the dual influence of native and sovereign cultures during the colonial era, exhibit unique urban morphological characteristics and reflect the planning ideologies of diverse cultures. Thus, the morphological study of colonial cities in Asia and Africa is crucial for understanding and identifying the historical and cultural value of these cities, which in turn enables the formulation of precise conservation strategies. In light of this, the study develops an urban morphological analysis methodology comprising "Colonial Background Analysis—Morphological Characteristics Analysis—Driving Factor Extraction" based on the Conzenian Approach, which is used to examine the morphology of 21 typical colonial cities in Asia and Africa across various colonial periods. As a result, "Dual-City" emerges as the core spatial characteristic of colonial cities in Asia and Africa, reflecting the morphological differences in road layouts, urban fabric, and urban cores between native and European zones. Additionally, as native settlement sizes, social structures, and cultural identities differ between cities, three major spatial patterns of the "Dual-City" model can be identified: separated, mediated, and integrated spatial patterns, resulting from the varied planning approaches applied by colonizers. Furthermore, suggestions for the conservation of colonial heritage are proposed based on the driving factors analysis from the morphological study.