bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical, radiographic and molecular characterization of two unrelated families with multicentric osteolysis, nodulosis, and arthropathy
Authors: Ishaq Tayyaba , Loid Petra , Ishaq Hafiza Abida , Seo Go Hun , Mäkitie Outi , Naz Sadaf
Published: September 2023

Background

Multicentric osteolysis nodulosis and arthropathy (MONA) is a rare autosomal recessive disorder characterized by marked progressive bone loss and joint destruction resulting in skeletal deformities. MONA is caused by MMP2 deficiency. Here we report clinical and molecular analyses of four patients in two families from Pakistan and Finland.

Methods

Clinical analyses including radiography were completed and blood samples were collected. The extracted DNA was subjected to whole-exome analysis or target gene sequencing. Segregation analyses were performed in the nuclear pedigree. Pathogenicity prediction scores for the selected variants and conservation analyses of affected amino acids were observed.

Results

The phenotype in the four affected individuals was consistent with multicentric osteolysis or MONA, as the patients had multiple affected joints, osteolysis of hands and feet, immobility of knee joint and progressive bone loss. Long-term follow up of the patients revealed the progression of the disease. We found a novelMMP2c.1336 + 2T > G homozygous splice donor variant segregating with the phenotype in the Pakistani family while aMMP2missense variant c.1188 C > A, p.(Ser396Arg) was homozygous in both Finnish patients.In-silicoanalysis predicted that the splicing variant may eventually introduce a premature stop codon inMMP2.Molecular modeling for the p.(Ser396Arg) variant suggested that the change may disturb MMP2 collagen-binding region.

Conclusion

Our findings expand the genetic spectrum of Multicentric osteolysis nodulosis and arthropathy. We also suggest that the age of onset of this disorder may vary from childhood up to late adolescence and that a significant degree of intrafamilial variability may be present.
Presentation management and outcome of phlegmonous and inflammed appendicitis in children in Ethiopia: retrospective review
Authors: Wondemagegnehu Belachew Dejene
Published: September 2023

Background

Acute appendicitis is the leading cause of emergency pediatric surgical admissions in the world. The diagnosis is may be difficult and is often dependent on clinical parameters. This study was aimed at reviewing the clinical presentations, the management and outcomes in children with inflamed and phlegmonous appendicitis with reference to the operative findings.

Methods

The records of 211 children 5 to 15 years of age who were operated for acute appendicitis with intra operative findings of inflamed or phlegmonous appendicitis who met inclusion criteria were entered and analyzed using SPSS (IBM) V.26. Descriptive and regression tests were done with p < 0.05 considered statistically significant.

Results

Of 211 children with inflamed and phlegmonous appendicitis, the M: F was 1.48:1 with a median age of 11 years. 58.3% of them presented within 24 h with the commonest symptoms being right lower abdominal pain, anorexia, and vomiting (96.2%,96.2%, 85.3%,) respectively. 96.7% of them had right lower abdominal tenderness. 73% had neutrophils ≥ 75%, and of 171 patients who had abdominal ultrasound scan, 97.7% showed appendiceal diameter ≥ 6 mm. Intraoperatively 56.4% of them were found to have phlegmonous appendicitis. In a retrospective Pediatric Appendiceal Score, only 52.6% of patients fall into the high-risk category, who could be confirmed on preoperative clinical assessment. Postoperatively 90% of them discharged improved with a mean hospital stay of 2.26(SD = 0.9) days. There was no association between the sex of the child and the intraoperative finding of inflamed or phlegmonous appendicitis (p = 0.77).

Conclusion

Pediatric appendicitis affects more male children in their second decade of life. Most had phlegmonous appendicitis and presented within 24 h. Duration of illness has little effect on the progress of appendicitis. Surgical management is safe for inflamed and phlegmonous appendicitis with a reasonable hospital stay and a low rate of complications.
A novel allogeneic acellular matrix scaffold for porcine cartilage regeneration
Authors: Jiang Huiming , Lu Jun , Li Jiawei , Liu Zizheng , Chen Fufei , Wu Rui , Xu Xingquan , Liu Yuan , Jiang Yiqiu , Shi Dongquan
Published: September 2023

Background

Cartilage defects are common sports injuries without significant treatment. Articular cartilage with inferior regenerative potential resulted in the poor formation of hyaline cartilage in defects. Acellular matrix scaffolds provide a microenvironment and biochemical properties similar to those of native tissues and are widely used for tissue regeneration. Therefore, we aimed to design a novel acellular cartilage matrix scaffold (ACS) for cartilage regeneration and hyaline-like cartilage formation.

Methods

Four types of cartilage injury models, including full-thickness cartilage defects (6.5 and 8.5 mm in diameter and 2.5 mm in depth) and osteochondral defects (6.5 and 8.5 mm in diameter and 5 mm in depth), were constructed in the trochlear groove of the right femurs of pigs (n = 32, female, 25–40 kg). The pigs were divided into 8 groups (4 in each group) based on post-surgery treatment differences. was assessed by macroscopic appearance, magnetic resonance imaging (MRI), micro–computed tomography (micro-CT), and histologic and immunohistochemistry tests.

Results

At 6 months, the ACS-implanted group exhibited better defect filling and a greater number of chondrocyte-like cells in the defect area than the blank groups. MRI and micro-CT imaging evaluations revealed that ACS implantation was an effective treatment for cartilage regeneration. The immunohistochemistry results suggested that more hyaline-like cartilage was generated in the defects of the ACS-implanted group.

Conclusions

ACS implantation promoted cartilage repair in full-thickness cartilage defects and osteochondral defects with increased hyaline-like cartilage formation at the 6-month follow-up.
The modulation of platelet function by growth hormone in growth hormone deficient Hypopituitary patients
Authors: Oglesby Irene K , Slattery David , Glynn Nigel , Gupta Saket , Duggan Karen , Cuesta Martin , Dunne Eimear , Garrahy Aoife , Toner Siobhan , Kenny Dermot , Agha Amar
Published: September 2023

Background

Growth hormone deficiency (GHD) has been implicated in increased cardiovascular and cerebrovascular disease risk seen in hypopituitarism, however the mechanism remains speculative. We hypothesise that platelet abnormalities may play a contributory role. Herein we examined platelet behaviour in GHD hypopituitary patients, pre- and post-growth hormone (GH) replacement.

Methods

This study utilizes a physiological flow-based assay to quantify platelet function in whole blood from patient cohorts under arterial shear. Thirteen GH Naïve hypopituitary adults with GHD and thirteen healthy matched controls were studied. Patients were assessed before and after GH treatment. All other pituitary replacements were optimised before the study. In addition to a full endocrine profile, whole blood was labelled and perfused over immobilised von Willibrand factor (vWF). Seven parameters of dynamic platelet-vWF interactions were recorded using digital image microscopy and analysed by customised platelet tracking software.

Results

We found a significantly altered profile of platelet-vWF interactions in GHD individuals compared to healthy controls. Specifically, we observed a marked increase in platelets shown to form associations such as tethering, rolling and adherence to immobilized vWF, which were reduced post GH treatment. Speed and distance platelets travelled across vWF was similar between controls and pre-therapy GHD patients, however, this was considerably increased post treatment. This may indicate reduced platelet signaling resulting in less stable adhesion of platelets post GH treatment.

Conclusions

Taken together observed differences in platelet behaviour may contribute to an increased risk of thrombosis in GHD which can in part be reversed by GH therapy.
Development of geographic inequality in dental caries and its association with socioeconomic factors over an 18-year period in Denmark
Authors: Sengupta Kaushik , Bihrmann Kristine , Christensen Lisa Bøge , Mortensen Laust Hvas , Andersen Ingelise , Ersbøll Annette Kjær
Published: September 2023

Background

Few studies have examined the development of geographic and socioeconomic inequalities in caries over time or have simultaneously assessed individual-level socioeconomic position (SEP) and neighborhood-level factors as a multi-layered phenomenon influencing caries inequalities. This study examined (i) the trends in geographic inequalities in caries among adolescents in Denmark and (ii) how the association between SEP and caries has progressed over time, when accounting for individual and neighborhood-level confounding factors.

Methods

This nationwide repeated cross-sectional study included 15-year-olds in Denmark from 1995, 2003, and 2013 (n = 149,808). The outcome was caries experience (measured by the decayed, missing, and filled tooth surfaces [DMFS] index). The exposure of interest was SEP, indicated by the previous year’s parental education, occupational social class, and (equivalized) disposable household income. Covariates included individual-level factors (immigration status, country of origin, number of children and persons in the family, and household type) and neighborhood (residence municipality)-level factors (Gini index; proportion of unemployed, low-educated, and unmarried/non-cohabiting individuals; proportion of single-parent households and households with overcrowding). Data sources included the Danish national dental and administrative social registers and Statistics Denmark’s statistics database (StatBank). Data were analyzed using spatial and spatiotemporal modelling utilizing zero-inflated negative binomial regressions and integrated nested Laplace approximations for Bayesian parametric inference. Observed caries experience geo-maps of the Danish municipalities for 1995, 2003, and 2013 were created.

Results

Between 1995 and 2013, caries prevalence in the 15-year-olds declined sharply (1995, 71%; 2013, 45%). Caries experience declined in nearly all socioeconomic subgroups and municipalities. However, geographic inequalities persisted with higher caries levels largely concentrated in the relatively deprived areas of Denmark. Increasing relative socioeconomic inequalities in caries over time were observed with significant graded associations between SEP and caries despite adjustment for the various individual and neighborhood-level covariates and the effect of assessment year (e.g., 15-year-olds with parents having basic education had 1.91-fold [95% CI: 1.86–1.95] higher caries experience than those having parents with high education).

Conclusions

Reducing these enduring inequalities will likely require additional resources and targeted supportive and preventive measures for adolescents from lower SEP backgrounds and those residing in municipalities with higher caries prevalence.
Dimensions of spiritual well-being in relation to physical and psychological symptoms: a cross-sectional study of advanced cancer patients admitted to a palliative care unit
Authors: Yang Yilong , Zhao Xinxin , Cui Meng , Wang Yumei
Published: September 2023

Objectives

Advanced cancer patients face various symptoms, which can cause physical and psychological distress. As a multidimensional construct, spiritual well-being (SWB) may be an inner resource for dealing with these problems. Our study explored the impact of different dimensions of SWB on physical and psychological symptoms in advanced cancer patients admitted to a palliative care unit.

Methods

This cross-sectional study was conducted among 108 advanced cancer patients in the Hospice Ward, Shengjing Hospital of China Medical University. Patients completed questionnaires on SWB and cancer-related symptoms (insomnia, fatigue, pain, depression and anxiety) at the time of admission. Linear regression analysis was applied to determine the relationship between SWB (meaning, peace and faith) and symptom distress.

Results

SWB accounted for an additional variance of cancer-related symptoms (17.8% to 44.4%). Meaning was negatively associated with insomnia (β = -0.516, p < 0.001) and fatigue (β = -0.563, p < 0.001). Peace and faith were related to lower psychological symptoms, while meaning represented a positive effect on anxiety (β = 0.275, p = 0.036). Higher peace was associated with lower cancer pain (β = -0.422, p < 0.001).

Conclusions

Our findings suggested that achieving peace and faith appeared to function consistently as a positive resource for advanced cancer patients on depression, anxiety and pain, while meaning may serve to facilitate or hinder positive adjustment. Future studies should focus on the potential clinical implications by identifying the distinct dimension of SWB as symptom management targets in the palliative care practice.
The impact of clinical education on knowledge and attitudes towards brain death among Polish medical students – a cross-sectional study
Authors: Kowalski Krzysztof , Marschollek Julia , Nowakowska-Kotas Marta , Budrewicz Sławomir
Published: September 2023

Background

Understanding brain death is essential for progress in organ transplantation; however, it remains a challenging ethical matter. In 2019, Poland revised its legislation on brain death to align with international standards. This study aimed to evaluate the knowledge and worldview concerning brain death among Polish medical students, categorised according to their stage of education.

Methods

An online questionnaire was administered to 169 medical students from four Polish medical universities. The participants were divided into preclinical (n = 94) and clinical (n = 75) groups. The questionnaire consisted of two parts, with the first part comprising 13 questions focusing on knowledge about brain death and the process of its determination. The second part contained six questions related to the participants' worldview regarding brain death, particularly concerning organ transplantation.

Results

The average score obtained by the respondents was 7.53 (± 2.35; min. 1, max. 13) in knowledge checking part of the developed questionnaire (maximal score:13). Students in the clinical stage of their education achieved significantly higher scores compared to preclinical students (mean 8.84; ± 1.89 vs mean 6.49; ± 2.15; p < 0.001). Significant correlations were found between the results of the knowledge part of the questionnaire and responses to worldview questions.

Conclusions

The stage of education influenced the knowledge of brain death among medical students, although the overall test scores were unsatisfactory. Higher test scores were associated with worldview responses indicating compliance with the current legislation in Poland and evidence-based medicine.
Telemedicine-assisted structured self-monitoring of blood glucose in management of T2DM results of a randomized clinical trial
Authors: Han Chen-Yu , Zhang Jian , Ye Xiao-Mei , Lu Jia-Ping , Jin Hai-Ying , Xu Wei-Wei , Wang Ping , Zhang Min
Published: September 2023

Background

This prospective study aimed to compare telemedicine-assisted structured self-monitoring of blood glucose(SMBG) with a traditional blood glucose meter (BGM) in adults of type 2 diabetes mellitus (T2DM).

Methods

Adult participants with T2DM were assigned to an intervention group or a control group. The patients in the intervention group received a connected BGM with real-time data submission as well as individual needs-based tele-coaching to address and improve motivation and daily diabetes self-management. The patients in the control group received a traditional BGM. Changes in glycated hemoglobin(HbA1c), low blood glucose index(LBGI), and diabetes self-management behaviors were analyzed.

Results

The study demonstrated the superiority of the telemedicine-assisted structured SMBG versus the traditional BGM for improving HbA1c. Additionally, the telemedicine-assisted SMBG reduced the risk of hypoglycemia and enhanced diabetes self-management behaviors, as differences in the LBGI and the Diabetes Self-Management Questionnaire(DSMQ) results between the groups after 6 months were found to be significant.

Conclusions

Telemedicine-assisted structured SMBG helps physicians and patients to achieve a specific level of glycemic control and reduce hypoglycemia. The use of coaching applications and telemedicine-assisted SMBG indicated beneficial effects for T2DM self-management, which may help limit disease progression.

Trial registration

Chinese Clinical Trail Registry No: ChiCTR2300072356 on 12/06/2023. Retrospectively registered.
Multi-class/residue method for determination of veterinary drug residues, mycotoxins and pesticide in urine using LC-MS/MS technique
Authors: Hajrulai-Musliu Zehra , Uzunov Risto , Jovanov Stefan , Musliu Dea , Dimitrieska-Stojkovikj Elizabeta , Stojanovska-Dimzoska Biljana , Angeleska Aleksandra , Stojkovski Velimir , Sasanya James Jacob
Published: September 2023

Background

Veterinary drugs are widely used in animals to prevent diseases and are a complex set of drugs with very different chemical properties. Multiclass and multi-residue methods for simultaneous detection of residues from veterinary drugs and contaminants in urine are very rare or non-existent. Therefore, the aim of this study was to develop and validate a sensitive and reliable quantitative LC-MS/MS method for simultaneous determination of a wide range of veterinary drug and pesticide residues and mycotoxins in bovine urine. This involved 42 veterinary drug residues (4 thyreostats, 6 anabolic hormones, 2 lactones, 10 beta agonists, 15 antibiotics, 5 sulphonamides), 28 pesticides and 2 mycotoxins. Stable isotopically labelled internal standards were used to facilitate effective quantification of the analytes. Analysis was performed in both positive and negative ionization modes with multiple reaction monitoring transitions over a period of 12 min.

Results

The parameters validated included linearity, limit of detection (LOD), limit of quantification (LOQ), detection capability (CCβ), decision limit (CCα), stability, accuracy and precision. The process followed guidelines of the regulation 2021/808/EC. The calibration curves were linear with coefficient of correlation (R2) from 0.991 to 0.999. The LODs were from 0.01 to 2.71 µg/L, while the LOQs were from 0.05 to 7.52 µg/L. The CCα and CCβ were in range 0.05–12.11 µg/L and 0.08–15.16 µg/L. In addition, the average recoveries of the spiked urine samples were from 71.0 to 117.0% and coefficient of variation (CV) < 21.38% (intraday and interday).

Conclusion

A new isotopic LC-MS/MS method has been developed, validated and applied for identification and quantification of 72 residues of veterinary drugs and pesticides and other contaminants such as mycotoxins in bovine urine. The most appropriated sample preparation procedures involved sodium acetate buffer, enzymatic hydrolysis using β-glucuronidase and cleanup solid phase extraction with OASIS SPE cartridges. The parameters were satisfactorily validated fulfilling requirements under Regulation 2021/808/EC. Consequently, the method could be used in routine analysis of bovine urine samples for simultaneous detection of veterinary drug and pesticide residues as well as contaminants such as mycotoxins.
High-throughput sequencing reveals Jatrorrhizine inhibits colorectal cancer growth by ferroptosis-related genes
Authors: Huang Lingyu , Sha Yu , Liang Wenken , Mo Chune , Li Chunhong , Deng Yecheng , Gong Weiwei , Hou Xianliang , Ou Minglin
Published: September 2023

Background

Colorectal cancer is a malignant tumor that poses a serious threat to human health. The main objective of this study is to investigate the mechanism by which Jatrorrhizine (JAT), a root extract from Stephania Epigaea Lo, exerts its anticancer effects in colorectal cancer.

Methods

We initially assessed the inhibitory properties of JAT on SW480 cells using MTT and cell scratch assays. Flow cytometry was employed to detect cell apoptosis. Differentially expressed genes were identified through high-throughput sequencing, and they were subjected to functional enrichment and signaling pathway analysis and PPI network construction. RT-qPCR was used to evaluate gene expression and identify critical differentially expressed genes. Finally, the function and role of differentially expressed genes produced by JAT-treated SW480 cells in colorectal cancer will be further analyzed using the TCGA database.

Results

Our study demonstrated that JAT exhibits inhibitory effects on SW480 cells at concentrations of 12.5µM, 25µM, 50µM, and 75µM without inducing cell apoptosis. Through high-throughput sequencing, we identified 244 differentially expressed genes. KEGG and GO analysis of high-throughput sequencing results showed that differentially expressed genes were significantly enriched in MAPK, Wnt, and P53 signaling pathways. Notably, JAT significantly altered the expression of genes associated with ferroptosis. Subsequent RT-qPCR showed that the expression of ferroptosis genes SLC2A3 and ASNS was significantly lower in JAT-treated SW480 cells than in the control group. Analysis by TCGA data also showed that ferroptosis genes SLC2A3 and ASNS were significantly highly expressed in COAD. The prognosis of SLC2A3 was significantly worse in COAD compared to the normal group. SLC2A3 may be a core target of JAT for the treatment of COAD.

Conclusions

JAT can inhibit COAD growth by ferroptosis-related genes. And it is a potential natural substance for the treatment of COAD.
Uncovering the ceRNA network and DNA methylation associated with gene expression in nasopharyngeal carcinoma
Authors: Zhang Ting , Pei Lu , Qiu Wen-Li , Wei Yu-xia , Liao Bi-yun , Yang Feng-lian
Published: September 2023

Objective

This study aimed to uncover abnormally expressed genes regulated by competitive endogenous RNA (ceRNA) and DNA methylation nasopharyngeal carcinoma and to validate the role of lncRNAs in the ceRNA network on nasopharyngeal carcinoma progression.

Methods

Based on the GSE64634 (mRNA), GSE32960 (miRNA), GSE95166 (lncRNA), and GSE126683 (lncRNA) datasets, we screened differentially expressed mRNAs, miRNAs and lncRNAs in nasopharyngeal carcinoma. A ceRNA network was subsequently constructed. Differentially methylated genes were screened using the GSE62336 dataset. The abnormally expressed genes regulated by both the ceRNA network and DNA methylation were identified. In the ceRNA network, the expression of RP11-545G3.1 lncRNA was validated in nasopharyngeal carcinoma tissues and cells by RT-qPCR. After a knockdown of RP11-545G3.1, the viability, migration, and invasion of CNE-2 and NP69 cells was assessed by CCK-8, wound healing and Transwell assays.

Results

This study identified abnormally expressed mRNAs, miRNAs and lncRNAs in nasopharyngeal carcinoma tissues. A ceRNA network was constructed, which contained three lncRNAs, 15 miRNAs and 129 mRNAs. Among the nodes in the PPI network based on the mRNAs in the ceRNA network, HMGA1 was assessed in relation to the overall and disease-free survival of nasopharyngeal carcinoma. We screened two up-regulated genes regulated by the ceRNA network and hypomethylation and 26 down-regulated genes regulated by the ceRNA network and hypermethylation. RP11-545G3.1 was highly expressed in the nasopharyngeal carcinoma tissues and cells. Moreover, the knockdown of RP11-545G3.1 reduced the viability, migration, and invasion of CNE-2 and NP69 cells.

Conclusion

Our findings uncovered the epigenetic regulation in nasopharyngeal carcinoma and identified the implications of RP11-545G3.1 on the progression of nasopharyngeal carcinoma.
Association of FTO gene variant rs9939609 with polycystic ovary syndrome from Gujarat, India
Authors: Chaudhary Hiral , Patel Jalpa , Jain Nayan K. , Panchal Sonal , Laddha Naresh , Joshi Rushikesh
Published: September 2023

Background

Polycystic ovary syndrome is a multifactorial endocrine disorder impacting women of reproductive age. Variations within the FTO gene have been linked to both obesity and type 2 diabetes mellitus. Given that PCOS is frequently associated with obesity and compromised glucose tolerance, we investigated the prevalence of the rs9939609 variant within the FTO gene among women diagnosed with PCOS and a control group. Our aim is to uncover potential correlations between this genetic variant, metabolic attributes, and endocrine markers within the Gujarat province of India.

Method

We enrolled a total of 114 participants, (62 individuals diagnosed with PCOS and 52 healthy controls). DNA extraction from venous blood was conducted for all participants. The rs9939609 polymorphism was investigated through tetra-primer amplification refractory mutation system-polymerase chain reaction. Furthermore, we performed biochemical assessments to quantify levels of estradiol, luteinizing hormone (LH), follicle-stimulating hormone (FSH), thyroid-stimulating hormone (TSH), total testosterone, prolactin (PRL), and Dehydroepiandrosterone sulfate (DHEAS). Statistical analyses were carried out utilizing SPSS version 21 (IBM, USA).

Results

The present study did not reveal any noteworthy association between cases and controls. The frequencies of genotypes and alleles within the cohorts displayed no statistically significant differences (p = 0.25, p = 0.68, and p = 0.78, respectively). The dominant model indicated a modest risk (OR:1.13, 95%CI: 0.55 to 2.38) toward PCOS development. There was a noticeable statistical difference observed in the levels of total testosterone, DHEAS, and BMI between the case and control groups (p < 0.002, p < 0.0002, p < 0.0008). However, no variations in clinical variables were observed among genotypes within the PCOS group.

Conclusion

This is the first study to investigate the association of FTO gene polymorphism and PCOS in Gujarati population. Our study findings indicate that the FTO gene variant is not directly linked to the onset of PCOS. However, it appears to exert an influence on metabolic factors such as obesity and insulin resistance. Notably, our results suggest that insulin resistance is more frequently observed among PCOS patients who are obese, as compared to those with non-obese PCOS patients.
Expanding applications of allogeneic platelets, platelet lysates, and platelet extracellular vesicles in cell therapy, regenerative medicine, and targeted drug delivery
Authors: Burnouf Thierry , Chou Ming-Li , Lundy David J. , Chuang Er-Yuan , Tseng Ching-Li , Goubran Hadi
Published: September 2023

Platelets are small anucleated blood cells primarily known for their vital hemostatic role. Allogeneic platelet concentrates (PCs) collected from healthy donors are an essential cellular product transfused by hospitals to control or prevent bleeding in patients affected by thrombocytopenia or platelet dysfunctions. Platelets fulfill additional essential functions in innate and adaptive immunity and inflammation, as well as in wound-healing and tissue-repair mechanisms. Platelets contain mitochondria, lysosomes, dense granules, and alpha-granules, which collectively are a remarkable reservoir of multiple trophic factors, enzymes, and signaling molecules. In addition, platelets are prone to release in the blood circulation a unique set of extracellular vesicles (p-EVs), which carry a rich biomolecular cargo influential in cell–cell communications. The exceptional functional roles played by platelets and p-EVs explain the recent interest in exploring the use of allogeneic PCs as source material to develop new biotherapies that could address needs in cell therapy, regenerative medicine, and targeted drug delivery. Pooled human platelet lysates (HPLs) can be produced from allogeneic PCs that have reached their expiration date and are no longer suitable for transfusion but remain valuable source materials for other applications. These HPLs can substitute for fetal bovine serum as a clinical grade xeno-free supplement of growth media used in the in vitro expansion of human cells for transplantation purposes. The use of expired allogeneic platelet concentrates has opened the way for small-pool or large-pool allogeneic HPLs and HPL-derived p-EVs as biotherapy for ocular surface disorders, wound care and, potentially, neurodegenerative diseases, osteoarthritis, and others. Additionally, allogeneic platelets are now seen as a readily available source of cells and EVs that can be exploited for targeted drug delivery vehicles. This article aims to offer an in-depth update on emerging translational applications of allogeneic platelet biotherapies while also highlighting their advantages and limitations as a clinical modality in regenerative medicine and cell therapies.
Inflammation and oxidative stress markers in type 2 diabetes patients with Advanced Carotid atherosclerosis
Authors: Ménégaut Louise , Laubriet Aline , Crespy Valentin , Leleu Damien , Pilot Thomas , Van Dongen Kevin , de Barros Jean-Paul Pais , Gautier Thomas , Petit Jean-Michel , Thomas Charles , Nguyen Maxime , Steinmetz Eric , Masson David
Published: September 2023

Background

Type 2 diabetes mellitus (T2DM) is a major global health issue and a significant risk factor for atherosclerosis. Atherosclerosis in T2DM patients has been associated with inflammation, insulin resistance, hyperglycemia, dyslipidemia, and oxidative stress. Identifying molecular features of atherosclerotic plaques in T2DM patients could provide valuable insights into the pathogenesis of the disease.

Methods

The MASCADI (Arachidonic Acid Metabolism in Carotid Stenosis Plaque in Diabetic Patients) study aimed to investigate the increase of 2-arachidonoyl-lysophatidylcholine (2-AA-LPC) in carotid plaques from T2DM and control patients and to explore its association with plaque vulnerability as well as with blood and intra-plaque biomarkers altered during diabetes.

Results

In a population of elderly, polymedicated patients with advanced stage of atherosclerosis, we found that T2DM patients had higher systemic inflammation markers, such as high-sensitivity C-reactive protein (hsCRP) and IL-1β, higher levels of oxysterols, increased triglyceride levels, and decreased HDL levels as compared to control patients. Furthermore, 2-AA-LPC was significantly enriched in plaques from diabetic patients, suggesting its potential role in diabetic atherosclerosis. Interestingly, 2-AA-LPC was not associated with systemic markers related to diabetes, such as hsCRP, triglycerides, or HDL cholesterol. However, it was significantly correlated with the levels of inflammatory markers within the plaques such as lysophospholipids and 25-hydroxycholesterol, strengthening the link between local inflammation, arachidonic acid metabolism and diabetes.

Conclusion

Our study is in line with a key role for inflammation in the pathogenesis of diabetic atherosclerosis and highlights the involvement of 2-AA-LPC. Further research is needed to better understand the local processes involved in the alteration of plaque composition in T2DM and to identify potential therapeutic targets.

Trial registration

The MASCADI was registered on ClinicalTrials.gov (clinical registration number: NCT03202823).
The temporal dynamics of Plasmodium species infection after artemisinin-based combination therapy (ACT) among asymptomatic children in the Hohoe municipality, Ghana
Authors: Ansah Felix , Nyame Kwamina , Laryea Rukaya , Owusu Richard , Amon Denick , Boyetey Mark-Jefferson Buer , Ayeke Dzidzor , Razak Nasibatu , Kornu Victor E. , Ashitei Sarah , Owusu-Appiah Caleb , Chirawurah Jersley D. , Abugri James , Aniweh Yaw , Opoku Nicholas , Sutherland Colin J. , Binka Fred N. , Kweku Margaret , Awandare Gordon A. , Dinko Bismarck
Published: September 2023

Background

The routine surveillance of asymptomatic malaria using nucleic acid-based amplification tests is essential in obtaining reliable data that would inform malaria policy formulation and the implementation of appropriate control measures.

Methods

In this study, the prevalence rate and the dynamics of Plasmodium species among asymptomatic children (n = 1697) under 5 years from 30 communities within the Hohoe municipality in Ghana were determined.

Results and discussion

The observed prevalence of Plasmodium parasite infection by polymerase chain reaction (PCR) was 33.6% (571/1697), which was significantly higher compared to that obtained by microscopy [26.6% (451/1697)] (P < 0.0001). Based on species-specific analysis by nested PCR, Plasmodium falciparum infection [33.6% (570/1697)] was dominant, with Plasmodium malariae, Plasmodium ovale and Plasmodium vivax infections accounting for 0.1% (1/1697), 0.0% (0/1697), and 0.0% (0/1697), respectively. The prevalence of P. falciparum infection among the 30 communities ranged from 0.0 to 82.5%. Following artesunate-amodiaquine (AS + AQ, 25 mg/kg) treatment of a sub-population of the participants (n = 184), there was a substantial reduction in Plasmodium parasite prevalence by 100% and 79.2% on day 7 based on microscopy and nested PCR analysis, respectively. However, there was an increase in parasite prevalence from day 14 to day 42, with a subsequent decline on day 70 by both microscopy and nested PCR. For parasite clearance rate analysis, we found a significant proportion of the participants harbouring residual Plasmodium parasites or parasite genomic DNA on day 1 [65.0% (13/20)], day 2 [65.0% (13/20)] and day 3 [60.0% (12/20)] after initiating treatment. Of note, gametocyte carriage among participants was low before and after treatment.

Conclusion

Taken together, the results indicate that a significant number of individuals could harbour residual Plasmodium parasites or parasite genomic DNA after treatment. The study demonstrates the importance of routine surveillance of asymptomatic malaria using sensitive nucleic acid-based amplification techniques.
Association between dietary folate intake and bone mineral density in a diverse population: a cross-sectional study
Authors: Zheng Zitian , Luo Huanhuan , Xu Wennan , Xue Qingyun
Published: September 2023

Background

Osteoporosis is a major public health problem, yet the association between dietary folate intake and bone health has been rarely studied. This study aimed to investigate the relationship between dietary folate intake and bone mineral density (BMD) in the general population of the USA.

Methods

Utilizing data from the National Health and Nutrition Examination Survey, dietary folate intake was gauged through 24-h dietary recall and BMD was determined via dual-energy X-ray absorptiometry. Multivariate linear regression models and generalized additive models were employed for correlation analysis.

Results

The study incorporated 9839 participants (48.88% males, aged 20–85 years, mean age: 47.62 ± 16.22). The average dietary folate intake stood at 401.1 ± 207.9 μg/day. And the average total femur, femoral neck, trochanter, intertrochanter, and lumbar BMD were 0.98 ± 0.16 g/cm2, 0.84 ± 0.15 g/cm2, 0.73 ± 0.13 g/cm2, 1.16 ± 0.19 g/cm2, and 1.03 ± 0.15 g/cm2, respectively. The higher quartiles of dietary folate intake directly correlated with increased total femoral, femoral neck, intertrochanteric, and lumbar BMD (P for trend = 0.003, 0.016, < 0.001, and 0.033, respectively). A consistent positive association between folate intake and BMD across age groups was observed, with significant findings for individuals over 80 years and non-Hispanic whites. Physical activity level and serum 25-hydroxyvitamin D levels influenced the association, with an optimal daily folate intake of 528–569 µg recommended for postmenopausal women.

Conclusion

In summary, our study reveals a significant positive association between dietary folate intake and BMD, across different age groups and particularly among individuals over 80 years old. Non-Hispanic whites benefit the most from increased folate intake. Physical activity level and serum 25-hydroxyvitamin D levels interact with this association. Screening and early intervention for osteoporosis may be essential for individuals with low dietary folate intake.
Genomic profiling of post-transplant lymphoproliferative disorders using cell-free DNA
Authors: Veltmaat Nick , Zhong Yujie , de Jesus Filipe Montes , Tan Geok Wee , Bult Johanna A. A. , Terpstra Martijn M. , Mutsaers Pim G. N. J. , Stevens Wendy B. C. , Mous Rogier , Vermaat Joost S. P. , Chamuleau Martine E. D. , Noordzij Walter , Verschuuren Erik A. M. , Kok Klaas , Kluiver Joost L. , Diepstra Arjan , Plattel Wouter J. , van den Berg Anke , Nijland Marcel
Published: September 2023

Diagnosing post-transplant lymphoproliferative disorder (PTLD) is challenging and often requires invasive procedures. Analyses of cell-free DNA (cfDNA) isolated from plasma is minimally invasive and highly effective for genomic profiling of tumors. We studied the feasibility of using cfDNA to profile PTLD and explore its potential to serve as a screening tool. We included seventeen patients with monomorphic PTLD after solid organ transplantation in this multi-center observational cohort study. We used low-coverage whole genome sequencing (lcWGS) to detect copy number variations (CNVs) and targeted next-generation sequencing (NGS) to identify Epstein-Barr virus (EBV) DNA load and somatic single nucleotide variants (SNVs) in cfDNA from plasma. Seven out of seventeen (41%) patients had EBV-positive tumors, and 13/17 (76%) had stage IV disease. Nine out of seventeen (56%) patients showed CNVs in cfDNA, with more CNVs in EBV-negative cases. Recurrent gains were detected for 3q, 11q, and 18q. Recurrent losses were observed at 6q. The fraction of EBV reads in cfDNA from EBV-positive patients was 3-log higher compared to controls and EBV-negative patients. 289 SNVs were identified, with a median of 19 per sample. SNV burden correlated significantly with lactate dehydrogenase levels. Similar SNV burdens were observed in EBV-negative and EBV-positive PTLD. The most commonly mutated genes were TP53 and KMT2D (41%), followed by SPEN, TET2 (35%), and ARID1A, IGLL5, and PIM1 (29%), indicating DNA damage response, epigenetic regulation, and B-cell signaling/NFkB pathways as drivers of PTLD. Overall, CNVs were more prevalent in EBV-negative lymphoma, while no difference was observed in the number of SNVs. Our data indicated the potential of analyzing cfDNA as a tool for PTLD screening and response monitoring.
Biological roles of RNA m7G modification and its implications in cancer
Authors: Zhang Xin , Zhu Wen-Yan , Shen Shu-Yi , Shen Jia-Hao , Chen Xiao-Dong
Published: September 2023

M7G modification, known as one of the common post-transcriptional modifications of RNA, is present in many different types of RNAs. With the accurate identification of m7G modifications within RNAs, their functional roles in the regulation of gene expression and different physiological functions have been revealed. In addition, there is growing evidence that m7G modifications are crucial in the emergence of cancer. Here, we review the most recent findings regarding the detection techniques, distribution, biological functions and Regulators of m7G. We also summarize the connections between m7G modifications and cancer development, drug resistance, and tumor microenvironment as well as we discuss the research’s future directions and trends.
Comparative HPTLC study for simultaneous determination of ivabradine and metoprolol using UV and fluorescence detectors
Authors: Rizk M. , Mowaka Shereen , Mohamed Mariam , Abou El-Alamin Maha M.
Published: September 2023

New, simple, accurate, sensitive and validated high performance thin layer chromatographic (HPTLC) method coupled with UV absorbance mode and fluorescence (FL) detectors which were used for simultaneous determination of ivabradine (IVA) and metoprolol (MET) in their bulk and pharmaceutical dosage form using TLC silica 60 F254 plates and non-fluorescent TLC silica gel 60 plates. The developing system was chloroform: methanol: formic acid: ammonia (8.5:1.5:0.2:0.1, v/v). Desnitometric analysis in UV absorbance mode was set at λ = 275 nm. While, fluorescence mode was performed with excitation at 260 nm for quantitative simultaneous determination of IVA and MET using optical filter K320. The retention factors values were 0.45 ± 0.05 and 0.89 ± 0.01 of IVA and MET, respectively. UV absorbance mode, linearity was 50.0–600.0 ng/band for IVA and 50.0–900.0 ng/band for MET. For fluorescence mode, the linearity ranges were 18.0–400.0 ng/band and 50.0–550.0 ng/band for IVA and MET; respectively. ICH guidelines were followed in respect to linearity and range, accuracy, precision and selectivity, limit of detection (LOD), limit of quantitation (LOQ) and robustness. The analytical eco-scale, green analytical procedure index (GAPI) and analytical greenness metric tools were used to assess the suggested method. The quantitative proposed method results showed there was no statistically significant difference at 95% confidence when compared to the reported method of high performance liquid chromatography (HPLC).
New types of general single/multiple integral inequalities
Authors: Zhang Liansheng , Meng Haosheng
Published: September 2023

By introducing some concepts such as multiple integral inner product (MIIP) and multiple integral inner product space (MIIPS), new series of single/multiple integral inequalities are developed in a systematic way, which produce more accurate bounds on the cross terms from the direct Lyapunov method than those in the literature. Some previous integral inequalities including both single and multiple integral inequalities can be regarded as special cases of the proposed inequalities. Accordingly, such integral inequalities are less conservative in comparison with the existing integral inequalities.
Are greener start-ups of superior quality? The impact of environmental orientation on innovativeness, growth orientation, and international orientation
Authors: Neumann Thomas
Published: September 2023

This paper merges the literature on green and high-quality entrepreneurship by introducing environmental orientation as an unrecognised characteristic of start-up quality and the three quality dimensions innovativeness, growth orientation, and international orientation. Entrepreneurship literature argues that only high-quality start-ups contribute to sustainable development and that a better understanding of what determines the quality of start-ups is required. Empirical research has recently shown that the environmental orientation of start-ups is one such determinant, as it significantly predicts their innovativeness. This paper pursues this novel research avenue on the importance of environmental orientation for start-up quality in two ways. First, this paper evaluates and extends this initial evidence on environmental orientation and innovativeness by examining a three times larger sample, covering additional countries and entrepreneurial stages. Second, this paper also analyses the impact of environmental orientation on the quality dimensions of growth orientation and international orientation. Investigation using Global Entrepreneurship Monitor data on 9650 entrepreneurs from 51 countries revealed that start-ups with a higher environmental orientation are of superior quality regarding their innovativeness, growth expectations, and exports. These results remain robust for start-ups at different entrepreneurial stages, and tests employing different methodological approaches and variable definitions. However, the categorisation into factor-driven, efficiency-driven, and innovation-driven countries showed that greener start-ups are more innovative in countries at all three levels of development, while the relationships with growth orientation and international orientation remained significant for only two of the three categories. The findings of this paper provide a new approach for practitioners to identify the small number of high-quality start-ups and an economic reason warranting intensified efforts to support green start-ups.
Repurposing approved non-oncology drugs for cancer therapy: a comprehensive review of mechanisms, efficacy, and clinical prospects
Authors: Mohi-ud-din Roohi , Chawla Apporva , Sharma Pooja , Mir Prince Ahad , Potoo Faheem Hyder , Reiner Željko , Reiner Ivan , Ateşşahin Dilek Arslan , Sharifi-Rad Javad , Mir Reyaz Hassan , Calina Daniela
Published: September 2023

Cancer poses a significant global health challenge, with predictions of increasing prevalence in the coming years due to limited prevention, late diagnosis, and inadequate success with current therapies. In addition, the high cost of new anti-cancer drugs creates barriers in meeting the medical needs of cancer patients, especially in developing countries. The lengthy and costly process of developing novel drugs further hinders drug discovery and clinical implementation. Therefore, there has been a growing interest in repurposing approved drugs for other diseases to address the urgent need for effective cancer treatments. The aim of this comprehensive review is to provide an overview of the potential of approved non-oncology drugs as therapeutic options for cancer treatment. These drugs come from various chemotherapeutic classes, including antimalarials, antibiotics, antivirals, anti-inflammatory drugs, and antifungals, and have demonstrated significant antiproliferative, pro-apoptotic, immunomodulatory, and antimetastatic properties. A systematic review of the literature was conducted to identify relevant studies on the repurposing of approved non-oncology drugs for cancer therapy. Various electronic databases, such as PubMed, Scopus, and Google Scholar, were searched using appropriate keywords. Studies focusing on the therapeutic potential, mechanisms of action, efficacy, and clinical prospects of repurposed drugs in cancer treatment were included in the analysis. The review highlights the promising outcomes of repurposing approved non-oncology drugs for cancer therapy. Drugs belonging to different therapeutic classes have demonstrated notable antitumor effects, including inhibiting cell proliferation, promoting apoptosis, modulating the immune response, and suppressing metastasis. These findings suggest the potential of these repurposed drugs as effective therapeutic approaches in cancer treatment. Repurposing approved non-oncology drugs provides a promising strategy for addressing the urgent need for effective and accessible cancer treatments. The diverse classes of repurposed drugs, with their demonstrated antiproliferative, pro-apoptotic, immunomodulatory, and antimetastatic properties, offer new avenues for cancer therapy. Further research and clinical trials are warranted to explore the full potential of these repurposed drugs and optimize their use in treating various cancer types. Repurposing approved drugs can significantly expedite the process of identifying effective treatments and improve patient outcomes in a cost-effective manner.