bluuebunny/crossref_metadata_2025_split huggingface dataset:
Synthesis and histone deacetylases inhibitory activity of pyrimidine‐based 1,3,4‐oxadiazoles
Authors: Jakubkiene V. , Labalaukyte I. , Schweipert M. , Zubriene A. , Meyer‐Almes F.‐J. , Matulis D. , Tumkevicius S. 
Published: July 2024

AbstractThe histone deacetylases (HDACs) are being explored as a promising therapeutic target for the treatment of various diseases. Here, the synthesis of a series of pyrimidine‐based 1,3,4‐oxadiazoles, in which the oxadiazole scaffold is attached to the pyrimidine ring via a methyleneoxy spacer, is described and their HDAC inhibitory activity studied. The target compounds were synthesized by sequence of reactions involving O‐alkylation of 2‐(methylthio)pyrimidin‐4(3H)‐ones with ethyl 2‐bromoethanoate followed by oxidation of the 2‐methylthio group, displacement of the obtained 2‐methylsulfonyl group with amines, hydrazinolysis of the obtained ethyl (2‐amino‐substituted pyrimidin‐4‐yloxy)acetates to give the corresponding hydrazides and their cyclization under the treatment with ethyl O‐ethyl xanthate or carbonyldiimidazole to 1,3,4‐oxadiazole‐2(3H)‐thiones and 1,3,4‐oxadiazol‐2(3H)‐one, correspondingly. In addition, two 1,3,4‐oxadiazole‐2(3H)‐thiones were converted into (N3)‐morpholinomethyl derivatives by the Mannich reaction with formaldehyde and morpholine. The yields of intermediates and target compounds ranged from moderate to excellent. The synthesized compounds were characterized by 1H and 13C NMR spectra and HRMS data, their purity was controlled by TLC. The synthesized pyrimidine‐based 1,3,4‐oxadiazoles (18 compounds) were tested as inhibitors of the HDAC4 and HDAC8 isoforms and their inhibitory activity was compared with that of Vorinostat. Most of the oxadiazolethiones containing methyl group at the position 6 of the pyrimidine moiety were found to be more selective towards HDAC8, while oxadiazolethiones with propyl group in the pyrimidine ring were active against HDAC4. Among the tested compounds, 5‐((2‐(dibutylamino)‐6‐propylpyrimidin‐4‐yloxy)methyl)‐1,3,4‐oxadiazole‐2(3H)‐thione (48) was found to have the strongest inhibitory activity for HDAC4 isoform (IC50 = 4.2 μM vs. IC50 = 59 μM for Vorinostat) while 5‐((2‐(cyclopentylamino)‐6‐propylpyrimidin‐4‐yloxy)methyl)‐1,3,4‐oxadiazole‐2(3H)‐thione (50) was the most potent HDAC8 inhibitor (IC50 = 6.8 μM).
Structure–activity relationship investigations probing the cytotoxicity of 9‐aminoacridine derivatives with PC3 and A549
Authors: Blount Grace S. , Seymour Austin , Williams Dylan , Douglas Daylon , Miller Joshua , Sejoro Sarah , Peace Karl E. , Kocerha Jannet , Aiken Karelle S. 
Published: July 2024

Abstract9‐Aminoacridine structures hold much potential for accessing small molecule therapeutics. This core is present in a range of pharmaceuticals for the treatment of ailments such as malaria, inflammation, viral and bacterial infections, and cancer. For the latter, there remains a need to develop and/or improve chemotherapeutics to counteract issues of uptake, drug resistance, and selectivity for cancer cells over healthy cells. In the design of molecules to address these issues, identifying structural units that present as promising leads for drug development is key. In this study, four 9‐aminoacridine derivatives under consideration as precursors for a drug design project are assessed for their cytotoxicity with representative cell lines PC3 and A549 and for their leadlikeness with SwissADME. Together, the cytotoxicity and in silico investigations coalesce around the same derivative as the most promising lead.
Excessive weight in pregnant women increases the chance of diagnosing periodontitis combined with tooth loss
Authors: Batista Josicélia Estrela Tuy , Figueiredo Ana Claudia Morais Godoy , Souza Elivan Silva , Lyrio Amanda Oliveira , Passos‐Soares Johelle Santana , Trindade Soraya Castro , Alves Claudia Maria Coêlho , Vianna Maria Isabel Pereira , Coelho Julita Maria Freitas , Conceição Sarah dos Santos , Cerqueira Eneida de Moraes Marcílio , Hintz Alexandre Marcelo , Seymour Gregory John , Scannapieco Frank Andrew , Loomer Peter Michael , Gomes‐Filho Isaac Suzart , Cruz Simone Seixas da 
Published: July 2024

AbstractBackgroundExcess weight (EW), especially in women of childbearing age, those who are pregnant, as well as postpartum, is a problem worldwide. Fat accumulation deregulates the inflammatory response, contributing to the development of health problems, such as periodontitis. This study investigated the association between EW and periodontitis during pregnancy.MethodsA cross‐sectional, multicenter study involved 1745 postpartum women in Brazil. Socioeconomic‐demographic data, gestational history, lifestyle behavior, and general and oral health conditions were obtained. Pre‐pregnancy body mass index (BMI) was collected from medical records with EW being the exposure. Both tooth loss and clinical attachment level (CAL) were evaluated, and the presence of periodontitis was the outcome. Logistic regression, odds ratio (OR) and 95% confidence interval (95% CI), and quantile regression, beta coefficient and 95% CI, estimated the association between EW (BMI) and periodontitis and its combined effect with tooth loss ≥3, as dichotomous and continuous variables (CAL and tooth loss), with 5% significance level.ResultsThe EW was 27.7% prevalent and periodontitis was 11.7%. There was a positive association between EW and periodontitis: ORadjusted:1.39; 95% CI:1.01;1.92 and between EW and periodontitis combined with tooth loss ≥3: ORadjusted:1.73; 95% CI:1.36;2.20. The adjusted association between EW and periodontitis as continuous variables was also positive, showing that for each unit of increased BMI, there was an elevation in the mean CAL (p = 0.04) and tooth loss (p < 0.01), with statistical significance.ConclusionsThere was a moderate association between EW and periodontitis during pregnancy, with an even greater association of pregnant women with EW presenting periodontitis combined with tooth loss.
Anterior abdominal wall defects and their management outcomes in Tikur Anbessa Specialized Hospital, neonatal intensive care unit
Authors: Habtamu Abebe , Million Tenagne 
Published: July 2024

AbstractIntroductionGastroschisis and omphalocele are common malformations of the anterior abdominal wall and can lead to significant morbidity and mortality in neonates. Despite advances in surgical care, these conditions remain challenging to manage effectively.ObjectiveThis retrospective institutional study aimed to assess the management outcomes of neonates with anterior abdominal wall defects, specifically gastroschisis and omphalocele, in the Neonatal Intensive Care Unit (NICU) of Tikur Anbessa Specialized Hospital (TASH) (Tertiary Hospital).MethodA retrospective review was conducted on cases of gastroschisis and omphalocele managed in the NICU of TASH from August 2018 to August 2022. Patient charts of neonates with omphalocele and gastroschisis were identified and retrieved from the NICU records. The collected data were analyzed using statistical software such as SPSS.ResultsThe study included a total of 50 neonates with abdominal wall defects, consisting of 39 cases of omphalocele and 11 cases of gastroschisis. Maternal age ranged from 18 to 40 years, with a mean age of 27.6 ± 4.5 years. Associated malformations were documented in 33.3% of omphalocele cases and 18.2% of gastroschisis cases. Cardiac anomalies were the most frequently associated malformation with omphalocele. Surgical intervention was performed in 27.3% of gastroschisis cases (3 out of 11) and 41% of omphalocele cases (16 out of 39). The postsurgery mortality rate was 12.5% for both major and minor omphaloceles, with 11 deaths occurring in gastroschisis cases. Sepsis was identified as the cause of death in all neonates who did not survive.ConclusionsThe study revealed a significantly higher mortality rate in gastroschisis cases compared to omphalocele cases. Sepsis was identified as the primary cause of death in the neonates. These findings underscore the importance of effective management strategies to prevent and manage sepsis in neonates with abdominal wall defects.
Improving blueberry cold storage quality: the effect of preharvest hexanal application on chilling injuries and antioxidant defense mechanisms
Authors: Sönmez Duygu Ayvaz , Öz Ayşe Tülin , Ali Md. Arfan , Kafkas Ebru , Bilgin Ömer Faruk 
Published: July 2024

AbstractBlueberries are vulnerable to chilling injury (CI). This can lead to limited longevity when they are subjected to cold storage conditions. This study investigated the effectiveness of a preharvest spray containing 0.02% hexanal in reducing CI and improving the postharvest storage quality of ‘Star’ and ‘Biloxi’ blueberries. The blueberries were stored for a period of 5 weeks at 2 °C and in 90% relative humidity (RH). The findings revealed that the preharvest hexanal spraying of both cultivars delayed senescence by mitigating CI, as evidenced by the bolstering of the antioxidant defense system through increased superoxide dismutase (SOD), ascorbate peroxidase (APX), peroxidase (POD), catalase (CAT), and phenylalanine ammonia lyase (PAL) enzyme activity. The treated fruit also maintained elevated levels of total phenol content (TPC), total flavonoids (TFC), and vitamin C, demonstrating enhanced free radical scavenging capacity (FRSC), while exhibiting reduced polyphenoloxidase (PPO) activity, and reduced malondialdehyde (MDA), and H2O2 content in comparison with the control group. The preharvest hexanal treatment also suppressed fruit softening by maintaining greater firmness and higher membrane stability index (MSI) scores, inhibiting the activity of polygalacturonase (PG), pectinmethylesterase (PME), xylanase, and α‐amylase, and reducing microbial counts (MC) and incidence of decay (DI) in comparison with the control. Preharvest hexanal treatment also improved the overall storage quality by reducing weight loss, total soluble solids (TSS), pH, and the TSS/acid ratio, while increasing titratable acidity (TA) in comparison with the control during cold storage. The findings suggest that hexanal, as a preharvest application, delays senescence effectively and preserves overall quality by enhancing cold tolerance through antioxidant defense mechanisms in blueberry storage under cold conditions. © 2024 The Author(s). Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.
The effect of Lactobacillus reuteri on pulmonary function test and growth of cystic fibrosis patients
Authors: Tabatabaii Seyed Ahmad , Khanbabaee Ghamartaj , Sadr Saeed , Farahbakhsh Nazanin , Modarresi Seyedeh Zalfa , Pourghasem Matin , Hajipour Mahmoud 
Published: July 2024

AbstractINTRODUCTIONCystic fibrosis (CF) patients frequently experience gut microbiota dysbiosis. Probiotic supplementation is a potential therapeutic approach to modify gut microbiota and improve CF management through the gut–lung axis. The aim of this study was to investigate the effect of Lactobacillus reuteri supplementation on pulmonary function test, respiratory symptoms and growth in CF patients.METHODSA randomized, placebo‐controlled clinical trial was carried out on 40 children with CF aged from 6 to 20 years. Participants were designated to receive either L. reuteri or placebo daily for 4 months. Pulmonary function tests, weight, height and body mass index (BMI) z‐scores were measured pre and post treatment.RESULTSThe median baseline BMI of the patients was 16.28 kg m−2. A significant change in the probiotic group's BMI z‐score after the study period was observed (P = 0.034) but not for weight and height z‐scores (P > 0.05). After treatment, Pseudomonas aeruginosa grew in sputum cultures of seven in the placebo and one patient in the intervention group (P = 0.03) while at baseline it grew in the sputum of four patients in each group. There was no significant difference in forced expiratory volume in the first second, forced expiratory flow at 25–75% or forced vital capacity change between the two groups after the treatment period (P > 0.05). Additionally, no significant differences were found in pulmonary exacerbations, hospitalization frequencies or COVID‐19 infection between the two groups during the study (P > 0.05).CONCLUSIONThe results suggest that L. reuteri supplementation may impact the growth of severely malnourished CF patients. Furthermore, it may be concluded that this strain might reduce P. aeruginosa in the sputum culture of CF patients. © 2024 Society of Chemical Industry.
Mechanically aligned total knee arthroplasty does not yield uniform outcomes across all coronal plane alignment of the knee (CPAK) phenotypes
Authors: Franceschetti Edoardo , Campi Stefano , Giurazza Giancarlo , Tanzilli Andrea , Gregori Pietro , Laudisio Alice , Hirschmann Michael T. , Samuelsson Kristian , Papalia Rocco 
Published: July 2024

AbstractPurposePatient dissatisfaction rates following total knee arthroplasty (TKA) reported in the literature reach 20%. The optimal coronal alignment is still under debate. The aim of this retrospective study was to compare clinical outcomes in different coronal plane alignment of the knee (CPAK) phenotypes undergoing mechanically aligned (MA) TKA. The hypothesis was that knees with preoperative varus arithmetic hip‐knee‐ankle angle (aHKA) would achieve inferior clinical outcomes after surgery compared to other aHKA categories. Additionally, another objective was to assess CPAK phenotypes distribution in the study population.MethodsA retrospective selection was made of 180 patients who underwent MA TKA from April 2021 to December 2022, with a 1‐year follow‐up. Coronal knee alignment was classified according to the CPAK classification. Clinical outcome evaluations were measured using the Knee Society Score (KSS), Oxford Knee Score (OKS), Short Form Survey 12 and Forgotten Joint Score (FJS). Differences in clinical outcomes were considered statistically significant with a p value <0 .05.ResultsPatients with varus aHKA achieved significantly inferior outcomes at final follow‐up compared to other aHKA categories in KSS pt. 1 (79.7 ± 17.2 vs. 85.6 ± 14.7; p = 0.028), OKS (39.2 ± 9.2 vs. 42.2 ± 7.2; p = 0.019) and FJS (75.4 ± 31.0 vs. 87.4 ± 22.9; p =0 .003). The most common aHKA category was the varus category (39%). The most common CPAK phenotypes were apex distal Types I (23.9%), II (22.8%) and III (13.3%).ConclusionMA TKA does not yield uniform outcomes across all CPAK phenotypes. Varus aHKA category shows significantly inferior results at final follow‐up. The most prevalent CPAK categories are varus aHKA and apex distal JLO, with phenotypes I, II and III being the most common. However, their gender distribution varies significantly.Level of EvidenceLevel IV.
The ischemia‐enhanced myocardial infarction protection‐related lncRNA protects against acute myocardial infarction
Authors: Wu Rongzhou , Wu Tingting , Wang Qiaoyu , Shi Youyang , Dong Qianqian , Rong Xing , Chen Meiting , He Zhiyu , Fu Yu , Liu Lei , Shao Shuai , Guan Xueqiang , Zhang Chunxiang 
Published: July 2024

AbstractLong non‐coding RNA RP11‐64B16.4 (myocardialinfarctionprotection‐relatedlncRNA [MIPRL]) is among the most abundant and the most upregulated lncRNAs in ischemic human hearts. However, its role in ischemic heart disease is unknown. We found MIPRL was conserved between human and mouse and its expression was increased in mouse hearts after acute myocardial infarction (AMI) and in cultured human and mouse cardiomyocytes after hypoxia. The infarcted size, cardiac cell apoptosis, cardiac dysfunction, and cardiac fibrosis were aggravated in MIPRL knockout mice after AMI. The above adverse results could be reversed by re‐expression of MIPRL via adenovirus expressing MIPRL. Both in vitro and in vivo, we identified that heat shock protein beta‐8 (HSPB8) was a target gene of MIPRL, which was involved in MIPRL‐mediated anti‐apoptotic effects on cardiomyocytes. We further discovered that MIPRL could combine with the messenger RNA (mRNA) of HSPB8 and increase its expression in cardiomyocytes by enhancing the stability of HSPB8 mRNA. In summary, we have found for the first time that the ischemia‐enhanced lncRNA MIPRL protects against AMI via its target gene HSPB8. MIPRL might be a novel promising therapeutic target for ischemic heart diseases such as AMI.
Unraveling dynamic immunological landscapes in intracerebral hemorrhage: insights from single‐cell and spatial transcriptomic profiling
Authors: Gu Lingui , Chen Hualin , Sun Mingjiang , Chen Yihao , Shi Qinglei , Chang Jianbo , Wei Junji , Ma Wenbin , Bao Xinjie , Wang Renzhi 
Published: July 2024

AbstractIntracerebral hemorrhage (ICH) poses a formidable challenge in stroke management, with limited therapeutic options, particularly in the realm of immune‐targeted interventions. Clinical trials targeting immune responses post‐ICH have encountered setbacks, potentially attributable to the substantial cellular heterogeneity and intricate intercellular networks within the brain. Here, we present a pioneering investigation utilizing single‐cell RNA sequencing and spatial transcriptome profiling at hyperacute (1 h), acute (24 h), and subacute (7 days) intervals post‐ICH, aimed at unraveling the dynamic immunological landscape and spatial distributions within the cerebral tissue. Our comprehensive analysis revealed distinct cell differentiation patterns among myeloid and lymphocyte populations, along with delineated spatial distributions across various brain regions. Notably, we identified a subset of lymphocytes characterized by the expression of Spp1 and Lyz2, termed macrophage‐associated lymphocytes, which exhibited close interactions with myeloid cells. Specifically, we observed prominent interactions between Lgmn+Macro‐T cells and microglia through the spp1–cd44 pathway during the acute phase post‐ICH in the choroid plexus. These findings represent a significant advancement in our understanding of immune cell dynamics at single‐cell resolution across distinct post‐ICH time points, thereby laying the groundwork for exploring critical temporal windows and informing the development of targeted therapeutic strategies.
Identification of an alternative ligand‐binding pocket in peroxisome proliferator‐activated receptor gamma and its correlated selective agonist for promoting beige adipocyte differentiation
Authors: Tian Qiang , Wang Miaohua , Wang Xueting , Lei Zhenli , Ahmad Owais , Chen Dianhua , Zheng Wei , Shen Pingping , Yang Nanfei 
Published: July 2024

ABSTRACTThe pharmacological activation of peroxisome proliferator‐activated receptor gamma (PPARγ) is a convenient and promising strategy for promoting beige adipocyte biogenesis to combat obesity‐related metabolic disorders. However, thiazolidinediones (TZDs), the full agonists of PPARγ exhibit severe side effects in animal models and in clinical settings. Therefore, the development of efficient and safe PPARγ modulators for the treatment of metabolic diseases is emerging. In this study, using comprehensive methods, we report a previously unidentified ligand‐binding pocket (LBP) in PPARγ and link it to beige adipocyte differentiation. Further virtual screening of 4097 natural compounds based on this novel LBP revealed that saikosaponin A (NJT‐2), a terpenoid compound, can bind to PPARγ to induce coactivator recruitment and effectively activate PPARγ‐mediated transcription of the beige adipocyte program. In a mouse model, NJT‐2 administration efficiently promoted beige adipocyte biogenesis and improved obesity‐associated metabolic dysfunction, with significantly fewer adverse effects than those observed with TZD. Our results not only provide an advanced molecular insight into the structural ligand‐binding details in PPARγ, but also develop a linked selective and safe agonist for obesity treatment.
Investigating the Brain Mechanisms of Externally Cued Sit‐to‐Stand Movement in Parkinson's Disease
Authors: Mustile Magda , Kourtis Dimitrios , Ladouce Simon , Edwards Martin G. , Volpe Daniele , Pilleri Manuela , Pelosin Elisa , Donaldson David I. , Ietswaart Magdalena 
Published: July 2024

AbstractBackgroundOne of the more challenging daily‐life actions for Parkinson's disease patients is starting to stand from a sitting position. Parkinson's disease patients are known to have difficulty with self‐initiated movements and benefit from external cues. However, the brain processes underlying external cueing as an aid remain unknown. The advent of mobile electroencephalography (EEG) now enables the investigation of these processes in dynamic sit‐to‐stand movements.ObjectiveTo identify cortical correlates of the mechanisms underlying auditory cued sit‐to‐stand movement in Parkinson's disease.MethodsTwenty‐two Parkinson's disease patients and 24 healthy age‐matched participants performed self‐initiated and externally cued sit‐to‐stand movements while cortical activity was recorded through 32‐channel mobile EEG.ResultsOverall impaired integration of sensory and motor information can be seen in the Parkinson's disease patients exhibiting less modulation in the θ band during movement compared to healthy age‐matched controls. How Parkinson's disease patients use external cueing of sit‐to‐stand movements can be seen in larger high β power over sensorimotor brain areas compared to healthy controls, signaling sensory integration supporting the maintenance of motor output. This appears to require changes in cognitive processing to update the motor plan, reflected in frontal θ power increases in Parkinson's disease patients when cued.ConclusionThese findings provide the first neural evidence for why and how cueing improves motor function in sit‐to‐stand movement in Parkinson's disease. The Parkinson's disease patients' neural correlates indicate that cueing induces greater activation of motor cortical areas supporting the maintenance of a more stable motor output, but involves the use of cognitive resources to update the motor plan. © 2024 International Parkinson and Movement Disorder Society.
Universal mental health curricula in public schools: Integrating mental health into physical education
Authors: Oh Hans , Formigoni Marco 
Published: July 2024

AbstractMental health problems are ubiquitous, yet public schooling lacks comprehensive mental health curricula. The purpose of public education, in part, is to prepare people to face life and contribute to society. In the same vein as physical education (PE), we argue that a universal mental health curriculum could benefit the entire population. Schools across the globe, including in the United States, are beginning to explore universal mental health curricula, which could yield benefits that reach beyond mental health and wellness, to improve physical health, reduce behavioral problems, and increase academic performance. But the road ahead is marked with considerable economic and political barriers. We argue for incorporating mental health into the PE curriculum to gain traction toward a more comprehensive mental health curriculum.