bluuebunny/crossref_metadata_2025 huggingface dataset:
IN SILICO TRIAL APPROACHES BETWEEN PHYTOCHEMICAL COMPOSITION OF VERBENA OFFICINALIS AND LIVER CANCER TARGETS
Authors: Akkaya Hatice , Özmaldar Aydın
Published: July 2024

Objective: The abundance of bioactive metabolites in Verbena officinalis explains the biological benefits and folkloric use of the plant. Liver cancer is an extremely heterogeneous malignant disease compared to other defined tumors. To explore the potential therapeutic value of bioactive metabolites in Verbena officinalis, this study aimed to filter secondary metabolites, conduct ADME-Tox assessments, perform drug similarity tests, and analyze with molecular dynamic simulations. The objective was to evaluate how potential drug candidates derived from Verbena officinalis behave in biological systems and assess their potential toxicity risks.
Material and Method: Ligands selected from the ADME assay were utilized in in silico molecular docking studies against Glucose-6-phosphate dehydrogenase enzyme in the oxidative part of the pentose phosphate pathway, which is crucial for liver diseases. These studies were conducted using Autodock Vina embedded in Chimera 1.16. Molecular dynamics simulations were performed with the AMBER16.
Result and Discussion: When the ADME test results were evaluated, 88 secondary metabolites were identified as ligands. Among all the ligands evaluated against Glucose-6-phosphate dehydrogenase enzyme, which is the key enzyme of the pentose phosphate pathway, quercetin flavonoid was determined to be the most active ligand with a docking score of -8.1 kcal/mol and binding energy of -118.51 kcal/mol. A molecular dynamics simulation performed for 300 nanoseconds confirmed that quercetin can remain stable in its microenvironment. The activity of this metabolite is worthy of further testing in vitro and in vivo as it may highlight a therapeutic modality within the pentose phosphate pathway.
FORMULASI KEBIJAKAN PENERAPAN SISTEM ELECTRONIC ROAD PRICING (ERP) PEMERINTAH PROVINSI DKI JAKARTA
Authors: Hamzah Teguh Saeful , Kurniawan Teguh
Published: July 2024

Pertumbuhan pesat dari kepemilikan dan lalu lintas kendaraan pribadi mendorong pemerintah untuk menerapkan kebijakan Electronic Road Pricing (ERP) dalam mengendalikan tingkat kemacetan di DKI Jakarta. Metode penelitian ini melibatkan tinjauan literatur dan studi kasus dengan menggunakan metode deskriptif kualitatif dan data sekunder untuk mengetahui bagaiamana formulasi kebijakan penerapan ERP di DKI Jakarta. Hasil analisis menunjukkan bahwa formulasi kebijakan yang berkelanjutan dalam siklus perencanaan ERP akan menghasilkan peraturan yang holistik dan inklusif, serta memperkuat komitmen dintara para pemangku kepentingan terkait dalam implementasi kebijakan ERP di DKI Jakarta.
STUDY OF THE POPULATION LEVEL AND MICROECOLOGICAL INDICATORS OF THE MICROBIOTA OF THE EARLY CONTENTS OF COMBAT INJURIES
Authors: Ya . F. Kutasevych ,   SE « Institute  of  Dermatology  and  Venereology  of  NAMS  of  Ukraine», S . K. Dzhoraieva , V . V. Honcharenko , E . M. Khoroshun , N . A. Lyapunov , V . V. Negoduyko , O . K. Ivantsova , I . O. Mashtakova , M . S. Biryukov , O . I. Oliinyk ,   SE « Institute  of  Dermatology  and  Venereology  of  NAMS  of  Ukraine»,   SE « Institute  of  Dermatology  and  Venereology  of  NAMS  of  Ukraine»,   Military  Medical  Clinical  Center  of  the  Northern  Region  of  the  Command  of  the  Medical  Forces  of  the  Armed  Forces  of  Ukraine,   DNU « Scientific  and  technological  complex « Institute  of  single  crystals»  of  the  National  Academy  of  Sciences  of  Ukraine,   Military  Medical  Clinical  Center  of  the  Northern  Region  of  the  Command  of  the  Medical  Forces  of  the  Armed  Forces  of  Ukraine,   SE « Institute  of  Dermatology  and  Venereology  of  NAMS  of  Ukraine»,   SE « Institute  of  Dermatology  and  Venereology  of  NAMS  of  Ukraine»,   Military  Medical  Clinical  Center  of  the  Northern  Region  of  the  Command  of  the  Medical  Forces  of  the  Armed  Forces  of  Ukraine,   SE « Institute  of  Dermatology  and  Venereology  of  NAMS  of  Ukraine»
Published: July 2024

The purpose of the work is to establish the taxonomic composition, colonization level and microecological indicators of the «macro-organism-microbiota» ecosystem of wound contents in patients with combat wounds Materials and methods.The total group of patients with combat wounds who were undergoing inpatient treatment at the Military Medical Clinical Center of the Northern Region of the Command of the Medical Forces of the Armed Forces of Ukraine consisted of 64 people. All patients were male, with a mean age of (34.3 ± 1.1) years. Microbiological studies were conducted on the basis of the laboratory of microbiology, immunology and molecular genetics of the SE «Institute of Dermatology and Venereology of the National Academy of Medical Sciences of Ukraine» using generally accepted methods. The results.It was established that the leading causative agents of combat wound infection are gram-negative microorganisms (per-manence index–59.5%, dominated by varieties of the genera Klebsiella and Pseudomonas aeruginosa), additional microbial agents were recognized as gram-positive cocci, which have a cumulative permanence index of almost 24%. Analysis of the spectrum of microbial contamination of wound contents showed the presence of multicomponent associations consisting of 2 or 3 different taxa of microorganisms–42.2% and 32.8%, respectively Conclusions.Taking into account the population level and microecological indicators of opportunistic bacteria contaminating the contents of wounds, the therapeutic tactics of their treatment should take into account the data of bacteriological studies with the determination of the level of contamination of wounds and sensitivity to antibiotics of leading infectious agents.
RETROSPECTIVE ANALYSIS OF THE PREVALENCE OF MIXED BACTERIAL-FUNGAL INFECTIONS AMONG PATIENTS WITH DERMATOVENEROLOGICAL PATHOLOGY
Authors: H . M. Bondarenko ,   SE « Institute  of  Dermatology  and  Venereology  of  NAMS  of  Ukraine», S . K. Dzhoraieva , V . V. Honcharenko ,   SE « Institute  of  Dermatology  and  Venereology  of  NAMS  of  Ukraine»,   SE « Institute  of  Dermatology  and  Venereology  of  NAMS  of  Ukraine»
Published: July 2024

The purpose of the work:analysis of the components of the bacterial and fungal content in multicomponent associations found in women of reproductive age with inflammatory diseases of the lower parts of the genital tract. Materials and methods:The study included 232 female patients aged 18 to 40 years who were undergoing inpatient and outpatient treatment at the clinic of the SE «Institute of Dermatology and Venereology of the NAMS of Ukraine» for inflammatory diseases of the lower parts of the genital tract. Microbiological studies were conducted on the basis of the laboratory of microbiology, immunology and molecular genetics using generally accepted methods. Results:The etiological structure of the causative agents of opportunistic infections among 232 women of reproductive age with inflammatory diseases of the genitourinary tract was analyzed. Varieties of conditionally pathogenic microflora and fungi of the Candida genus were ranked according to the frequency of isolation in multicomponent associations. It was established that about 30% of strains of staphylococci and enterobacteria are not sensitive,to cephalosporins, respectively ; about 85% of C. kruseistrains are resistant to fluconazole. Conclusion:The data of the retrospective analysis conducted on the basis of the results of bacteriological studies of the etiological structure of factors of inflammatory diseases of the genital tract and their ranking by significance showed that the detection of a sufficiently significant percentage of varieties of opportunistic bacterial and fungal microflora at high rates of colonization density , as components of multicomponent associations, so and monopathogens, proved the significant negative role of these microorganisms in the development of inflammatory processes in the female genital area.
TACTICS OF MANAGEMENT OF PATIENTS WITH PEMPHIGUS VULGARIS IN CONDITIONS of martial law
Authors: Ya.F. Kutasevych ,   SE « Institute  of  Dermatology  and  Venereology  of  NAMS  of  Ukraine», I . O. Oliinyk , I . O. Mashtakova ,   SE « Institute  of  Dermatology  and  Venereology  of  NAMS  of  Ukraine»,   SE « Institute  of  Dermatology  and  Venereology  of  NAMS  of  Ukraine»
Published: July 2024

The article provides data on the impact of chronic stress and changes in the conditions of providing medical care under martial law on the occurrence of chronic diseases, including skin, namely pemphigus. Purpose:to show the peculiarities of the course of pemphigus vulgaris and the management of a patient with this pathology in the condition of martial law. Results.A clinical case of a patient with pemphigus vulgaris is given. Requirements for conditions of maintenance therapy for patients with severe chronic dermatoses.
Transcriptomic analysis of primary nasal epithelial cells reveals altered interferon signalling in preterm birth survivors at one year of age
Authors: Evans Denby J. , Hillas Jessica K. , Iosifidis Thomas , Simpson Shannon J. , Kicic Anthony , Agudelo-Romero Patricia
Published: July 2024

Introduction: Many survivors of preterm birth (<37 weeks gestation) have lifelong respiratory deficits, the drivers of which remain unknown. Influencers of pathophysiological outcomes are often detectable at the gene level and pinpointing these differences can help guide targeted research and interventions. This study provides the first transcriptomic analysis of primary nasal airway epithelial cells in survivors of preterm birth at approximately 1 year of age.

Methods: Nasal airway epithelial brushings were collected, and primary cell cultures established from term (>37 weeks gestation) and very preterm participants (≤32 weeks gestation). Ex vivo RNA was collected from brushings with sufficient cell numbers and in vitro RNA was extracted from cultured cells, with bulk RNA sequencing performed on both the sample types. Differential gene expression was assessed using the limma-trend pipeline and pathway enrichment identified using Reactome and GO analysis. To corroborate gene expression data, cytokine concentrations were measured in cell culture supernatant.

Results: Transcriptomic analysis to compare term and preterm cells revealed 2,321 genes differentially expressed in ex vivo samples and 865 genes differentially expressed in cultured basal cell samples. Over one third of differentially expressed genes were related to host immunity, with interferon signalling pathways dominating the pathway enrichment analysis and IRF1 identified as a hub gene. Corroboration of disrupted interferon release showed that concentrations of IFN-α2 were below measurable limits in term samples but elevated in preterm samples [19.4 (76.7) pg/ml/µg protein, p = 0.03]. IFN-γ production was significantly higher in preterm samples [3.3 (1.5) vs. 9.4 (17.7) pg/ml/µg protein; p = 0.01] as was IFN-β [7.8 (2.5) vs. 13.6 (19.5) pg/ml/µg protein, p = 0.01].

Conclusion: Host immunity may be compromised in the preterm nasal airway epithelium in early life. Altered immune responses may lead to cycles of repeated infections, causing persistent inflammation and tissue damage which can have significant impacts on long-term respiratory function.
A network meta-analysis: evaluating the efficacy and safety of concurrent proton pump inhibitors and clopidogrel therapy in post-PCI patients
Authors: Ai Ming-Ying , Chen Yan-Zuo , Kuo Chien-Liang , Chang Wei-Lun
Published: July 2024

Introduction

The objective of this research was to evaluate the risk of major adverse cardiovascular events (MACEs) associated with the use of various proton pump inhibitors (PPIs) in combination with clopidogrel in patients who underwent percutaneous coronary intervention (PCI).

Methods

To accomplish this, we analyzed data from randomized controlled trials and retrospective cohort studies sourced from key electronic databases. These studies specifically examined the effects of different PPIs, such as lansoprazole, esomeprazole, omeprazole, rabeprazole, and pantoprazole, when used in conjunction with clopidogrel on MACEs. The primary focus was on the differential impact of these PPIs, while the secondary focus was on the comparison of gastrointestinal (GI) bleeding events in groups receiving different PPIs with clopidogrel vs. a placebo group. This study's protocol was officially registered with INPLASY (INPLASY2024-2-0009).

Results

We conducted a network meta-analysis involving 16 studies with a total of 145,999 patients. Our findings indicated that rabeprazole when combined with clopidogrel, had the lowest increase in MACE risk (effect size, 1.05, 95% CI: 0.66–1.66), while lansoprazole was associated with the highest risk increase (effect size, 1.48, 95% CI: 1.22–1.80). Esomeprazole (effect size, 1.28, 95% CI: 1.09–1.51), omeprazole (effect size, 1.23, 95% CI: 1.07–1.43), and pantoprazole (effect size, 1.38, 95% CI: 1.18–1.60) also significantly increased MACE risk. For the secondary outcome, esomeprazole (effect size, 0.30, 95% CI: 0.09–0.94), omeprazole (effect size, 0.34, 95% CI: 0.14–0.81), and pantoprazole (effect size, 0.33, 95% CI: 0.13–0.84) demonstrated an increased potential for GI bleeding prevention.

Conclusions

In conclusion, the combination of lansoprazole and clopidogrel was found to significantly elevate the risk of MACEs without offering GI protection in post-PCI patients. This study is the first network meta-analysis to identify the most effective regimen for the concurrent use of clopidogrel with individual PPIs.

Systematic Review Registration

https://inplasy.com/inplasy-2024-2-0009/, identifier (INPLASY2024-2-0009).
Exploring geothermal resources with the CSAMT and microtremor methods: a case study in Tangquan, Jiangsu Province, China
Authors: Xu Hao , Yang Xiaodong , Cai Xiangyang , Xu Ziqiao , Liao Shengzhu , Wu Xiaoping
Published: July 2024

The development of geothermal energy has received extensive attention because of global energy scarcity and environmental pollution. The Tangquan area is in the north of the Yangtze fold belt, and the lack of magmatic rock development has resulted in a low-temperature type of geothermal reservoir. There are sporadic hot springs and cold springs exposed in the study area, but the uncertain deep geological structure, unknown geothermal reservoir formation mechanism, and lack of detailed exploration data seriously restrict the exploration and development of geothermal resources in the area. Filling underground faults with water can significantly reduce electrical resistivity, while traps filled with warm water can cause a decrease in S-wave velocity. Thus, a new integrated geophysical method, including the controlled source audio-frequency magnetotelluric (CSAMT) and microtremor methods, is applied for geothermal exploration in the region. The combination of CSAMT and microtremor methods can determine thermal-controlled and water-conducting structures more effectively and locate geothermal storage more accurately. The source, channel, storage, and cover of regional geothermal reservoir formation are analyzed using geophysical and geological data. That is, the regional NE- and NW-trending faults are explained as thermal-controlled and water-conducted structures, respectively. The deep Sinian Dengying Formation supplies a heat- and water-bearing space. The tectonic intersection area, especially the tensional fault zone, is found to be closely related to the existence of geothermal reservoirs, which is well verified by later drilling results. Finally, a geothermal reservoir model is established to comprehensively understand the distribution of geothermal energy in the region.
Case report: First Chinese patient with family partial lipodystrophy type 6 due to novel compound heterozygous mutations in the LIPE gene
Authors: Zhou Yimeng , Zhang Lin , Ding Yang , Zhai Yongzhen
Published: July 2024

Background

Family partial lipodystrophy (FPLD) is a rare autosomal dominant disease characterized by disorders of variable body fat loss associated with metabolic complications. FPLD6 has only been reported in a limited number of cases. Here, we reported a Chinese FPLD6 patient with compound heterozygous mutations in the lipase E, hormone-sensitive type (LIPE) gene.

Case presentation

A 20-year-old female patient presented with hypertriglyceridemia, diabetes mellitus, hepatomegaly, and hepatic steatosis. Subcutaneous fat was significantly diminished in her face, abdomen, and limbs. The patient was assessed by detailed clinical and biochemical examinations. A liver biopsy showed severe lipodystrophy. In addition, there were retinal changes, peripheral nerve damage, and renal tubular injury. Sequencing was performed on extracted DNA. Genetic analysis revealed that the patient had compound heterozygous mutations in the LIPE gene: c.2497_250ldel (p.Glu833LysfsTer22) and c.2705del (p.Ser902ThrfsTer27) heterozygous mutations. Verification revealed that this mutation was inherited from her father and mother, respectively, and that they formed newly discovered compound heterozygous mutations occurring in the LIPE gene, causing FPLD6.

Conclusion

We reported the first case of FPLD6 in China. Gene analysis demonstrated compound heterozygous mutations in LIPE in this patient. Our case emphasizes the importance of genetic testing in young patients with severe metabolic syndromes.
Genetically predicted allergic rhinitis causally increases the risk of erectile dysfunction
Authors: Li Peng , Meng Zhaotun , Lin Liqiang , Chen Zhipeng , Lv Huaiqing
Published: July 2024

Objective

Evidence shows that allergic rhinitis (AR) may increase the risk of erectile dysfunction (ED). This study aims to investigate whether there is a causal relationship between AAR and ED by Mendelian randomization (MR) analysis.

Methods

We performed a two-sample MR analysis using genome-wide association studies (GWAS) summary data. Single nucleotide polymorphisms (SNPs) associated with AR and ED were obtained from the GWAS database. The MR analysis primarily employed the inverse variance weighted (IVW), MR Egger, and weighted median (WM) methods. We assessed pleiotropy using the MR-PRESSO global test and MR-Egger regression. Cochran’s Q test was used to evaluate heterogeneity, and a leave-one-out analysis was performed to verify the robustness and reliability of the results.

Results

The IVW analysis demonstrated a positive association between genetic susceptibility to AR and an elevated relative risk of ED (IVW OR = 1.40, p = 0.01, 95% CI 1.08–1.80). The results obtained from MR-Egger regression and WM methods exhibited a consistent trend with the results of the IVW method. Sensitivity analyses showed no evidence of heterogeneity nor horizontal pleiotropy. The leave-one-out analysis showed that the findings remained robust and were unaffected by any instrumental variables.

Conclusion

This study presents genetic evidence that indicates a causal association between AR and ED.
Avatrombopag as alternative therapy for severe aplastic anemia patients who are intolerant or unresponsive to eltrombopag
Authors: Zhang Ting , Yu Qingling , Chen Xiaoyu , Yang Hui , Gong Yuemin , Zhang Yawen , Liu Xiaoqing , Yang Zhinan , Fang Yu , Yan Xue , Zhou Xuan , Shi Jinning , He Guangsheng
Published: July 2024

Introduction

Eltrombopag (EPAG), a thrombopoietin receptor agonist, was approved for the treatment of severe aplastic anemia (SAA) combined with immunosuppressive therapy (IST). However, EPAG contains a typical biphenyl structure, which causes liver function damage.

Methods

Twenty patients with SAA who were intolerant or refractory to EPAG were enrolled in a multicenter prospective registry of the Chinese Eastern Collaboration Group of Anemia (ChiCTR2100045895) from October 2020 to June 2023.

Results

Eight patients who were ineffective to EPAG, six with kidney impairment, and nine with abnormal liver function (two with concomitant liver and kidney impairment) were converted to avatrombopag (AVA) therapy with the median duration of AVA treatment was 6 (3-24) months. 17 cases (85%) achieved trilineage hematological response (HR): complete remission (CR) in 3 cases (15%), good partial remission (GPR) in 4 cases (20%), partial remission (PR) in 10 cases (50%), and no response (NR) in 3 cases (15%). The median time to response was 1.7 (0.5-6.9) months, with 16 cases (94%) achieving response within six months and 17 cases (100%) within 12 months. 9 cases (50%) achieved transfusion independence. AVA converted treatment was associated with higher neutrophil counts (0.8×109/L vs 2.2×109/L, p=0.0003), platelet counts (11×109/L vs 39×109/L, p=0.0008), hemoglobin count (59g/L vs 98g/L, p=0.0002), red cell count (1.06×1012/L vs 2.97×1012/L, p=0.001), and absolute reticulocyte count (31.99 ×109/L vs 67.05×109/L p=0.0004) were all significantly elevated compared with the pre-treatment level. After the conversion to AVA therapy, liver and kidney function indexes were maintained within the normal range, no AVA related grade 2 or higher adverse events occurred, and no thrombotic events occurred.

Conclusion

The conversion to AVA was an optimal choice for patients with SAA who were EPAG intolerant or refractory.

Clinical trial registration

http://www.chictr.org.cn/showproj.html?proj=125480, identifier ChiCTR2100045895.
The optimal dose of dexmedetomidine as a 0.59% ropivacaine adjuvant for epidural anesthesia in great saphenous varicose vein surgery, based on hemodynamics and anesthesia efficacy: a randomized, controlled, double-blind clinical trial
Authors: Zeng Sisi , Li Xuechao , Xu Hongchun , Ye Qin , Li Zhaogang , Wang Fangjun
Published: July 2024

Objective

This study aimed to explore the optimal dose of dexmedetomidine as a 0.59% ropivacaine adjuvant for epidural anesthesia on perioperative hemodynamics and anesthesia efficacy in patients undergoing great saphenous varicose vein surgery.

Methods

A total of 90 patients were randomly divided into three groups: 0.25 μg/kg dexmedetomidine combined with 0.59% ropivacaine epidural infusion group (ED1 group), 0.5 μg/kg dexmedetomidine combined with 0.59% ropivacaine epidural infusion group (ED2 group), and 0.75 μg/kg dexmedetomidine combined with 0.59% ropivacaine epidural infusion group (ED3 group). Hemodynamics, anesthesia efficiency, and adverse reactions were recorded.

Main results

Compared with the ED1 group, the ED2 group had lower systolic blood pressure at T1-3 (T1, 95%CIs, 6.52–21.93, p < 0.001; T2, 95%CIs, 2.88–18.21, p = 0.004; T3, 95%CIs, 0.49–18.17, p = 0.035), and the diastolic blood pressure at T1-2 was decreased (T1, 95%CIs, 4.55–14.36, p < 0.001; T2, 95%CIs, 0.37–12.17, p = 0.033). Compared with the ED2 group, the ED3 group had higher systolic blood pressure at T1-2 (T1, 95%CIs, 5.90–21.46, p < 0.001; T2, 95%CIs, 2.07–17.55, p = 0.008) and higher diastolic blood pressure at T1-3 (T1, 95%CIs, 2.91–12.81, p = 0.001; T2, 95%CIs, 1.32–13.23, p = 0.011; T3, 95%CIs, 0.14–11.52, p = 0.043). Compared with the ED2 group, the heart rate was significantly decreased at T1-4 in the ED3 group (T1, 95%CIs, 2.25–15.72, p = 0.005; T2, 95%CIs, 2.35–13.82, p = 0.003; T3, 95%CIs, 0.50–9.79, p = 0.025; T4, 95%CIs, 1.46–10.36, p = 0.005). The myocardial oxygen consumption in all three groups was significantly decreased at each time point compared to T0 (p < 0.05 or < 0.001), and no significant between-group differences were detected (P>0.05). Compared with the ED1 group, the anesthesia efficiency of ED2 and ED3 groups was markedly enhanced, but the risk of bradycardia in ED2 and ED3 groups was dramatically increased (6 of 28 [21.4%] vs. 14 of 30 [46.7%] and 14 of 27 [51.9%], p = 0.023), one patient in the ED3 group experienced difficulty urinating, and remaining adverse reactions were mild in all three groups.

Conclusion

A measure of 0.5 μg/kg dexmedetomidine is the optimal dose as a 0.59% ropivacaine adjuvant for epidural anesthesia in patients undergoing great saphenous varicose vein surgery.

Clinical trial registration

http://www.chictr.org.cn/, registration number: ChiCTR2200060619.
Modeling riboflavin transporter deficiency type 2: from iPSC-derived motoneurons to iPSC-derived astrocytes
Authors: Magliocca Valentina , Lanciotti Angela , Ambrosini Elena , Travaglini Lorena , D’Ezio Veronica , D’Oria Valentina , Petrini Stefania , Catteruccia Michela , Massey Keith , Tartaglia Marco , Bertini Enrico , Persichini Tiziana , Compagnucci Claudia
Published: July 2024

Introduction

Riboflavin transporter deficiency type 2 (RTD2) is a rare neurodegenerative autosomal recessive disease caused by mutations in the SLC52A2 gene encoding the riboflavin transporters, RFVT2. Riboflavin (Rf) is the precursor of FAD (flavin adenine dinucleotide) and FMN (flavin mononucleotide), which are involved in different redox reactions, including the energetic metabolism processes occurring in mitochondria. To date, human induced pluripotent stem cells (iPSCs) have given the opportunity to characterize RTD2 motoneurons, which reflect the most affected cell type. Previous works have demonstrated mitochondrial and peroxisomal altered energy metabolism as well as cytoskeletal derangement in RTD2 iPSCs and iPSC-derived motoneurons. So far, no attention has been dedicated to astrocytes.

Results and discussion

Here, we demonstrate that in vitro differentiation of astrocytes, which guarantee trophic and metabolic support to neurons, from RTD2 iPSCs is not compromised. These cells do not exhibit evident morphological differences nor significant changes in the survival rate when compared to astrocytes derived from iPSCs of healthy individuals. These findings indicate that differently from what had previously been documented for neurons, RTD2 does not compromise the morpho-functional features of astrocytes.
The network is more important than the node: stereo-EEG evidence of neurocognitive networks in epilepsy
Authors: Murray Nicholas W. G. , Kneebone Anthony C. , Graham Petra L. , Wong Chong H. , Savage Greg , Gillinder Lisa , Fong Michael W. K.
Published: July 2024

Introduction

Neuropsychological assessment forms an integral part of the presurgical evaluation for patients with medically refractory focal epilepsy. Our understanding of cognitive impairment in epilepsy is based on seminal lesional studies that have demonstrated important structure-function relationships within the brain. However, a growing body of literature demonstrating heterogeneity in the cognitive profiles of patients with focal epilepsy (e.g., temporal lobe epilepsy; TLE) has led researchers to speculate that cognition may be impacted by regions outside the seizure onset zone, such as those involved in the interictal or “irritative” network.

Methods

Neuropsychological data from 48 patients who underwent stereoelectroencephalography (SEEG) monitoring between 2012 and 2023 were reviewed. Patients were categorized based on the site of seizure onset, as well as their irritative network, to determine the impact of wider network activity on cognition. Neuropsychological data were compared with normative standards (i.e., z = 0), and between groups.

Results

There were very few distinguishing cognitive features between patients when categorized based purely on the seizure onset zone (i.e., frontal lobe vs. temporal lobe epilepsy). In contrast, patients with localized irritative networks (i.e., frontal or temporal interictal epileptiform discharges [IEDs]) demonstrated more circumscribed profiles of impairment compared with those demonstrating wider irritative networks (i.e., frontotemporal IEDs). Furthermore, the directionality of propagation within the irritative network was found to influence the manifestations of cognitive impairment.

Discussion

The findings suggest that neuropsychological assessment is sensitive to network activity beyond the site of seizure onset. As such, an overly focal interpretation may not accurately reflect the distribution of the underlying pathology. This has important implications for presurgical work-up in epilepsy, as well as subsequent surgical outcomes.
Clot patterns determined by DSA and CTA can help predict intracranial atherosclerotic stenosis in acute ischemic stroke patients
Authors: Li Jichuan , Yang Jianhong , Gao Xiang , Han Qing , Wu Yuefei , Shang Qing , Huang Yueshi , Xu Yao , Huang Yi , Lin Longting
Published: July 2024

Background

This study examines whether clot patterns at large artery occlusion sites, as observed using digital subtraction angiography (DSA) and computed tomography angiography (CTA), can reliably indicate intracranial atherosclerotic stenosis (ICAS) in acute ischemic stroke (AIS) patients.

Methods

We conducted a retrospective analysis of patients treated with stent retriever thrombectomy for intracranial occlusions at our institute since 2017, with follow-up assessments conducted at 3 months. The patients were grouped based on the initial angiography clot topographies (i.e., cut-off or tapered signs). We assessed the potential of these topographies in predicting ICAS, including a clinical outcome analysis based on clot pattern, age, Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification, and onset-to-door time.

Results

Among 131 patients (with a mean age of 66.6 years), the clot pattern emerged as a significant predictor of ICAS. The DSA-based model had a predictive area under the curve (AUC) of 0.745, with 55.1% sensitivity and 94.0% specificity. A multivariate model including age, onset-to-door time, TOAST classification as large artery atherosclerosis (LAA), and the presence of the tapered sign in clot patterns had an AUC of 0.916. In patients over 65 years of age with an onset-to-door time of >5 h and exhibiting a tapered sign in the clot pattern, the AUC reached 0.897. The predictive ability of the tapered sign was similar in DSA and CTA, showing 73.4% agreement between modalities.

Conclusion

The clot pattern with the tapered sign as observed using DSA is significantly associated with ICAS. Incorporating this clot pattern with age, TOAST classification as LAA, and onset-to-door time enhances the prediction of ICAS. The clot pattern identified by CTA is also a reliable predictor, highlighting the importance of assessing clot patterns in ICAS identification.
Acute sleep deprivation in mice generates protein pathology consistent with neurodegenerative diseases
Authors: Rowe Rachel K. , Schulz Philip , He Ping , Mannino Grant S. , Opp Mark R. , Sierks Michael R.
Published: July 2024

Introduction

Insufficient or disturbed sleep is strongly associated with adverse health conditions, including various neurodegenerative disorders. While the relationship between sleep and neurodegenerative disease is likely bidirectional, sleep disturbances often predate the onset of other hallmark clinical symptoms. Neuronal waste clearance is significantly more efficient during sleep; thus, disturbed sleep may lead to the accumulation of neuronal proteins that underlie neurodegenerative diseases. Key pathological features of neurodegenerative diseases include an accumulation of misfolded or misprocessed variants of amyloid beta (Aβ), tau, alpha synuclein (α-syn), and TarDNA binding protein 43 (TDP-43). While the presence of fibrillar protein aggregates of these neuronal proteins are characteristic of neurodegenerative diseases, the presence of small soluble toxic oligomeric variants of these different proteins likely precedes the formation of the hallmark aggregates.

Methods

We hypothesized that sleep deprivation would lead to accumulation of toxic oligomeric variants of Aβ, tau, α-syn, and TDP-43 in brain tissue of wild-type mice. Adult mice were subjected to 6 h of sleep deprivation (zeitgeber 0–6) for 5 consecutive days or were left undisturbed as controls. Following sleep deprivation, brains were collected, and protein pathology was assessed in multiple brain regions using an immunostain panel of reagents selectively targeting neurodegenerative disease-related variants of Aβ, tau, α-syn, and TDP-43.

Results

Overall, sleep deprivation elevated levels of all protein variants in at least one of the brain regions of interest. The reagent PDTDP, targeting a TDP-43 variant present in Parkinson’s disease, was elevated throughout the brain. The cortex, caudoputamen, and corpus callosum brain regions showed the highest accumulation of pathology following sleep deprivation.

Discussion

These data provide a direct mechanistic link between sleep deprivation, and the hallmark protein pathologies of neurodegenerative diseases, such as Alzheimer’s and Parkinson’s diseases.
Is freeze-dried superfood kale supplementation healthier than common green peas? Outcomes of a cross-over trial
Authors: Aldisi Dara , Sabico Shaun , Almiman Abeer , Al-Farraj Amani , Basaeed Taghreed A. , Wani Kaiser , Hussain Syed D. , Ansari Mohammed G. A. , McTernan Philip G. , Al-Daghri Nasser M.
Published: July 2024

Kale (Brassica oleracea species) is considered a functional food whose macronutrient and phytochemical contents are considered beneficial and widely considered as a superfood. In the present 6-week cross-over trial with a 2-week washout period, we compared the beneficial effects of freeze-dried kale over peas among Arab women with obesity. A total of 124 Saudi women with obesity were allocated to receive either freeze-dried kale (n = 62) or freeze-dried peas (n = 62) given in the form of 3-gram sachets thrice daily for 2 weeks, followed by a 2-week washout period and a cross-over of 4 weeks. Anthropometric measurements, glucose, lipids and markers of gut barrier function were assessed at baseline and post-intervention. Participants who took kale supplementation first resulted in significant weight reduction (p = 0.02) which was not observed among those who took peas first. Participants receiving pea supplementation first experienced a significant decline in Hba1c (p = 0.005) and CD14 (p = 0.03), but C-peptide increased (p = 0.05). Crossover analysis revealed significant carryover effects in most variables with non-significant combined treatment effects. Among the variables with no carryover effect with significant combined treatment effect include HbA1c which was in favor of the pea group (p = 0.005) and C-peptide which was modestly in favor of the kale group (p = 0.05). While both freeze dried kale and pea supplementation appear beneficial, supplementation of freeze-dried pea appears to be more effective in terms of acute glycemic control than kale. The study suggests that common but less-hyped vegetables such as pea maybe equally, if not more beneficial than the more expensive promoted superfoods such as kale. Longer clinical trials using a parallel design instead of cross-over are recommended to strengthen present findings.
Prospective study of protein intake and mortality among US adults with chronic obstructive pulmonary disease
Authors: Lu HuiLun , Zhang Qi , Long Jiao
Published: July 2024

Background

Protein is crucial for the rehabilitation of patients with chronic obstructive pulmonary disease (COPD), and appropriate daily protein intake is essential for COPD patients. However, the specific role of protein intake in COPD and its impact on mortality remain uncertain. This study aims to ascertain the relationship between protein intake and mortality in COPD patients.

Methods

This investigation included 522 adult COPD patients from the National Health and Nutrition Examination Survey (NHANES) between 2013 and 2018, with a focus on evaluating protein intake. Multivariate Cox proportional hazard models were constructed to analyze the correlation between protein intake and the prognosis of COPD patients. Additionally, the restricted cubic spline (RCS) was employed to investigate the potential non-linear association between protein intake and mortality.

Results

A total of 522 patients with COPD were categorized into 4 groups based on the quartiles of protein intake: Q1 (< 25th percentile, 11.7–48.5 gm), Q2 (25–50th percentile, 48.5–67.7 gm), Q3 (50–75th percentile, 67.7–94.3 gm), and Q4 (≥ 75th percentile, 94.3–266.6 gm). Cox regression analysis revealed a significant trend in the p value of the Q3 group compared to the Q1 group when adjusting for other variables. The RCS-fitted Cox regression model indicated no non-linear relationship between protein intake levels and COPD mortality.

Conclusion

There is no evidence of a non-linear relationship between protein intake and all-cause mortality in COPD patients. Further investigation is warranted to comprehend the intricate relationship between protein intake and COPD outcomes.
Synergistic impact of plasma albumin and cognitive function on all-cause mortality in Chinese older adults: a prospective cohort study
Authors: Li Zhi-qiang , Liu Xin-xin , Wang Xue-feng , Shen Chen , Cao Feng , Guan Xin-miao , Zhang Ying , Liu Jian-ping
Published: July 2024

Background

Hypoalbuminemia and cognitive impairment (CI) each independently increase the mortality risk in older adults. However, these two geriatric syndromes can occur simultaneously. In community-dwelling older adults, is the combination of hypoalbuminemia and CI linked to a higher mortality risk than either condition alone?

Objective

We aimed to investigate the association between plasma albumin, cognitive function, and their synergistic effect on mortality in Chinese community-dwelling older adults.

Methods

Data from the Chinese Longitudinal Healthy Longevity Survey (2012) included 1,858 participants aged ≥65. Baseline assessments comprised albumin levels and cognitive status. All-cause mortality was confirmed through 2014–2018 surveys. Cox proportional hazards models assessed associations, and restricted cubic splines explored albumin-mortality relationship.

Results

During a median follow-up of 48.85 months, 921 deaths. Albumin≥35 g/L vs < 35g/L [HR: 1.33 (95%CI, 1.10, 1.62)] and CI vs normal cognition [HR: 1.69 (95%CI, 1.43, 1.99)] independently predicted mortality. A dose–response relationship with mortality was observed for albumin quartiles (p < 0.001). Each SD increase in MMSE or albumin correlated with 22% and 15% lower mortality risk, respectively. Combined hypoproteinemia and CI increased the mortality risk by 155%, with a notably higher risk in males, those aged <85 years, and individuals living in rural areas. Interaction effects of albumin and CI on mortality were observed (p < 0.001). In the single CI group, older adults had a 61% increased risk of mortality in the hypoproteinaemia group compared with the albumin-normal group. Restricted cubic spline revealed a reverse J-shaped association, particularly for participants without CI. For individuals with CI, albumin levels were inversely associated with mortality risk.

Conclusion

Hypoproteinemia and CI, individually and combined, increased all-cause mortality risk in Chinese older adults, with stronger effects observed in males, younger older adults, and those living in rural areas. These findings emphasize the importance of targeted adjustments and early nutrition programs in health prevention and clinical care for older adults.
Dietary protein, amino acids and type 2 diabetes mellitus: a short review
Authors: Mensink Marco
Published: July 2024

Diabetes is a widespread metabolic disorder and results from insulin resistance and impaired insulin secretion. Modifiable factors like diet, physical activity, and body weight play crucial roles in diabetes prevention, with targeted interventions reducing diabetes risk by about 60%. High-protein consumption, above the recommended intake of 0.8 g/kg body weight per day, have often explored in relation to diabetes risk. However, the relationship between dietary protein and diabetes is multifaceted. Observational studies have linked high total and animal protein intake to an increased risk of type 2 diabetes, particularly in obese women. Elevated levels of branched-chain amino acids (BCAA), which can result from dietary intake, protein breakdown, as well as an impaired catabolism, are strong predictors of cardiometabolic risk and insulin resistance. With several mechanism linking BCAA to insulin resistance. On the other hand, intervention studies suggest that high-protein diets can support weight loss and improve cardiometabolic risk factors. However, the impact on insulin sensitivity and glucose homeostasis is not straightforward. Proteins and amino acids stimulate both insulin and glucagon secretion, influencing glucose levels, but chronic effects remain uncertain. This short narrative review aims to provide an update on the relationship between increased dietary protein intake, amino acids, insulin resistance and type 2 diabetes, and to describe protein recommendations for type 2 diabetes.
Efficacy of novel allogeneic cancer cells vaccine to treat colorectal cancer
Authors: Alzeeb George , Tortorelli Corinne , Taleb Jaqueline , De Luca Fanny , Berge Benoit , Bardet Chloé , Limagne Emeric , Brun Marion , Chalus Lionel , Pinteur Benoit , Bravetti Paul , Gongora Céline , Apetoh Lionel , Ghiringhelli Francois
Published: July 2024

Colorectal cancer (CRC) remains a significant global health burden, emphasizing the need for innovative treatment strategies. 95% of the CRC population are microsatellite stable (MSS), insensitive to classical immunotherapies such as anti-PD-1; on the other hand, responders can become resistant and relapse. Recently, the use of cancer vaccines enhanced the immune response against tumor cells. In this context, we developed a therapeutic vaccine based on Stimulated Tumor Cells (STC) platform technology. This vaccine is composed of selected tumor cell lines stressed and haptenated in vitro to generate a factory of immunogenic cancer-related antigens validated by a proteomic cross analysis with patient’s biopsies. This technology allows a multi-specific education of the immune system to target tumor cells harboring resistant clones. Here, we report safety and antitumor efficacy of the murine version of the STC vaccine on CT26 BALB/c CRC syngeneic murine models. We showed that one cell line (1CL)-based STC vaccine suppressed tumor growth and extended survival. In addition, three cell lines (3CL)-based STC vaccine significantly improves these parameters by presenting additional tumor-related antigens inducing a multi-specific anti-tumor immune response. Furthermore, proteomic analyses validated that the 3CL-based STC vaccine represents a wider quality range of tumor-related proteins than the 1CL-based STC vaccine covering key categories of tumor antigens related to tumor plasticity and treatment resistance. We also evaluated the efficacy of STC vaccine in an MC38 anti-PD-1 resistant syngeneic murine model. Vaccination with the 3CL-based STC vaccine significantly improved survival and showed a confirmed complete response with an antitumor activity carried by the increase of CD8+ lymphocyte T cells and M1 macrophage infiltration. These results demonstrate the potential of this technology to produce human vaccines for the treatment of patients with CRC.
Assessing disparities through missing race and ethnicity data: results from a juvenile arthritis registry
Authors: Banschbach Katelyn M. , Singleton Jade , Wang Xing , Vora Sheetal S. , Harris Julia G. , Lytch Ashley , Pan Nancy , Klauss Julia , Fair Danielle , Hammelev Erin , Gilbert Mileka , Kreese Connor , Machado Ashley , Tarczy-Hornoch Peter , Morgan Esi M.
Published: July 2024

Introduction

Ensuring high-quality race and ethnicity data within the electronic health record (EHR) and across linked systems, such as patient registries, is necessary to achieving the goal of inclusion of racial and ethnic minorities in scientific research and detecting disparities associated with race and ethnicity. The project goal was to improve race and ethnicity data completion within the Pediatric Rheumatology Care Outcomes Improvement Network and assess impact of improved data completion on conclusions drawn from the registry.

Methods

This is a mixed-methods quality improvement study that consisted of five parts, as follows: (1) Identifying baseline missing race and ethnicity data, (2) Surveying current collection and entry, (3) Completing data through audit and feedback cycles, (4) Assessing the impact on outcome measures, and (5) Conducting participant interviews and thematic analysis.

Results

Across six participating centers, 29% of the patients were missing data on race and 31% were missing data on ethnicity. Of patients missing data, most patients were missing both race and ethnicity. Rates of missingness varied by data entry method (electronic vs. manual). Recovered data had a higher percentage of patients with Other race or Hispanic/Latino ethnicity compared with patients with non-missing race and ethnicity data at baseline. Black patients had a significantly higher odds ratio of having a clinical juvenile arthritis disease activity score (cJADAS10) of ≥5 at first follow-up compared with White patients. There was no significant change in odds ratio of cJADAS10 ≥5 for race and ethnicity after data completion. Patients missing race and ethnicity were more likely to be missing cJADAS values, which may affect the ability to detect changes in odds ratio of cJADAS ≥5 after completion.

Conclusions

About one-third of the patients in a pediatric rheumatology registry were missing race and ethnicity data. After three audit and feedback cycles, centers decreased missing data by 94%, primarily via data recovery from the EHR. In this sample, completion of missing data did not change the findings related to differential outcomes by race. Recovered data were not uniformly distributed compared with those with non-missing race and ethnicity data at baseline, suggesting that differences in outcomes after completing race and ethnicity data may be seen with larger sample sizes.
Strategies for the prevention of bronchopulmonary dysplasia
Authors: Dini Gianluca , Ceccarelli Sara , Celi Federica
Published: July 2024

Bronchopulmonary dysplasia (BPD) is a common morbidity affecting preterm infants and is associated with substantial long-term disabilities. The pathogenesis of BPD is multifactorial, and the clinical phenotype is variable. Extensive research has improved the current understanding of the factors contributing to BPD pathogenesis. However, effectively preventing and managing BPD remains a challenge. This review aims to provide an overview of the current evidence regarding the prevention of BPD in preterm infants, offering practical insights for clinicians.
Role of ursolic acid in preventing gastrointestinal cancer: recent trends and future perspectives
Authors: Chauhan Abhishek , Pathak Vinay Mohan , Yadav Monika , Chauhan Ritu , Babu Neelesh , Chowdhary Manish , Ranjan Anuj , Mathkor Darin Mansor , Haque Shafiul , Tuli Hardeep Singh , Ramniwas Seema , Yadav Vikas
Published: July 2024

Gastrointestinal malignancies are one of the major worldwide health concerns. In the present review, we have assessed the plausible therapeutic implication of Ursolic Acid (UA) against gastrointestinal cancer. By modulating several signaling pathways critical in cancer development, UA could offer anti-inflammatory, anti-proliferative, and anti-metastatic properties. However, being of low oral bioavailability and poor permeability, its clinical value is restricted. To deliver and protect the drug, liposomes and polymer micelles are two UA nanoformulations that can effectively increase medicine stability. The use of UA for treating cancers is safe and appropriate with low toxicity characteristics and a predictable pharmacokinetic profile. Although the bioavailability of UA is limited, its nanoformulations could emerge as an alternative to enhance its efficacy in treating GI cancers. Further optimization and validation in the clinical trials are necessary. The combination of molecular profiling with nanoparticle-based drug delivery technologies holds the potential for bringing UA to maximum efficacy, looking for good prospects with GI cancer treatment.