bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmaceutical prospects of Silymarin for the treatment of neurological patients: an updated insight
Authors: Ranjan Shovit , Gautam Akash 
Published: May 2023

BackgroundSilymarin is a polyphenolic flavonoid complex extricated from dried fruits and seeds of the plant Silybum marianum L. Chemically, it is a mixture of flavonolignan complexes consisting of silybin, isosilybin, silychristin, silydianin, a minor quantity of taxifolin, and other polyphenolic compounds, which possess different bio medicinal values.PurposeThis review critically looks into the current status, pharmaceutical prospects and limitations of the clinical application of Silymarin for treating neurological disorders. In particular, Silymarin’s medicinal properties and molecular mechanisms are focused on providing a better-compiled understanding helpful in its neuro-pharmacological or therapeutic aspects.MethodsThis review was compiled by the literature search done using three databases, i.e., PubMed (Medline), EMBASE and Science Direct, up to January 2023, using the keywords-Silymarin, neurological disorders, cognitive disorders, Type 2 Diabetes, pharmaceutical prospects and treatment. Then, potentially relevant publications and studies (matching the eligible criteria) were retrieved and selected to explain in this review using PRISMA 2020 (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) study flow chart.ResultSince its discovery, it has been widely studied as a hepatoprotective drug for various liver disorders. However, in the last 10–15 years, several research studies have shown its putative neuroprotective nature against various brain disorders, including psychiatric, neurodegenerative, cognitive, metabolic and other neurological disorders. The main underlying neuroprotective mechanisms in preventing and curing such disorders are the antioxidant, anti-inflammatory, anti-apoptotic, pro-neurotrophic and pro-estrogenic nature of the bioactive molecules.ConclusionThis review provides a lucid summary of the well-studied neuroprotective effects of Silymarin, its underlying molecular mechanisms and current limitations for its usage during neurological disorders. Finally, we have suggested a future course of action for developing it as a novel herbal drug for the treatment of brain diseases.
FKBP5 genetic variants are associated with respiratory- and sleep-related parameters in Chinese patients with obstructive sleep apnea
Authors: Wang Anzhao , Wei Zhicheng , Yuan Haolin , Zhu Yaxin , Peng Yu , Gao Zhenfei , Liu Yuenan , Shen Jinhong , Xu Huajun , Guan Jian , Yin Shankai , Liu Feng , Li Xinyi 
Published: May 2023

IntroductionObstructive sleep apnea (OSA) has been associated with psychiatric disorders, especially depression and posttraumatic stress disorder (PTSD). FKBP5 genetic variants have been previously reported to confer the risk of depression and PTSD. This study aimed to investigate the association of single nucleotide polymorphisms (SNPs) in the FKBP5 gene with OSA and OSA-related quantitative traits.MethodsFour SNPs within the FKBP5 gene (rs1360780, rs3800373, rs9296158, rs9470080) were genotyped in 5773 participants with anthropometric and polysomnography data. Linear regression and logistic regression analyses were performed to evaluate the relationship between FKBP5 SNPs and OSA-related traits. Binary logistic regression was used to assess the effect of SNPs on OSA susceptibility. Interacting genes of SNPs were assessed based on the 3DSNP database, and expression quantitative trait loci (eQTL) analysis for SNPs was adopted to examine the correlation of SNPs with gene expression. Gene expression analyses in human brains were performed with the aid of Brain Atlas.ResultsIn moderate-to-severe OSA patients, all four SNPs were positively associated with AHIREM, and rs9296158 showed the strongest association (ß = 1.724, p = 0.001). Further stratified analyses showed that in men with moderate OSA, rs1360780, rs3800373 and rs9470080 were positively associated with wake time (p = 0.0267, p = 0.0254 and p = 0.0043, respectively). Rs1360780 and rs3800373 were 28 and 29.4%more likely to rate a higher ordered MAI category (OR (95% CI) = 1.280 (1.042 – 1.575), p = 0.019; OR (95% CI) = 1.294 (1.052 – 1.592), p = 0.015, respectively). Rs9296158 and rs9470080 increased the risk of low sleep efficiency by 25.7 and 28.1% (OR (95% CI) = 1.257 (1.003 – 1.575), p = 0.047; OR (95% CI) = 1.281 (1.026–1.6), p = 0.029, respectively). Integrated analysis of eQTL and gene expression patterns revealed that four SNPs may exert their effects by regulating FKBP5, TULP1, and ARMC12.ConclusionSingle nucleotide polymorphisms in the FKBP5 gene were associated with sleep respiratory events in moderate-to-severe OSA patients during REM sleep and associated with sleep architecture variables in men with moderate OSA. FKBP5 variants may be a potential predisposing factor for sleep disorders, especially in REM sleep.
New flavors from old wheats: exploring the aroma profiles and sensory attributes of local Mediterranean wheat landraces
Authors: Frankin Sivan , Cna'ani Alon , Bonfil David J. , Tzin Vered , Nashef Kamal , Degen Doron , Simhon Yasmin , Baizerman Marina , Ibba Maria Itria , González Santoyo Héctor Ignacio , Luna Cyntia Velazquez , Cervantes Lopez Jose Fausto , Ogen Anomarel , Goldberg B. Z. , Abbo Shahal , Ben-David Roi 
Published: May 2023

IntroductionDuring the 20th century, the worldwide genetic diversity of wheat was sharply eroded by continual selection for high yields and industry demands for particular standardized qualities. A collection of Israeli and Palestinian landraces (IPLR) was established to represent genetic diversity, accumulated for ten millennia under diverse environments, which was mostly lost in this transition. As our long-term goal is to study this pre- Green Revolution genetic reservoir, herein we focus on its flour and bread quality and sensorial attributes.MethodsInitially, a database was built for the entire IPLR collection (n=901) holding both Triticum durum (durum wheat) and T. aestivum (bread wheat) which included genetic and phenotypic characterization of agronomic traits, grain and flour quality. Then, a representative subset of the IPLR was selected and compared to modern varieties for dough quality, rheology, aroma and taste using both whole and refined flours and breads. The sensory panel used 40 subjects who evaluated common protocol or sourdough breads made by four artisan bakers.ResultsResults show modern durum cultivar C-9 had superior rheological properties (gluten index, elasticity, dough development time) as compared with landraces, while bread landrace 'Diar Alla' was markedly preferable for baking in relation to the modern cultivar Gadish. Baking tests and subsequent sensory evaluation clearly demonstrated a preference toward refined breads, apart from whole breads prepared using sourdough starters. In bread wheat, loaves baked using landrace flour were scored higher in several quality parameters, whereas in durum lines, the opposite trend was evident. Loaves baked from landraces 'Diar Alla' and to a lesser extent 'Hittia Soada' presented a markedly different aroma from the control loaves prepared from modern flours, both in terms of overall compositions and individual compounds, including classes such as pyranones, pyrazines, furans and pyrroles (maltol). Modern lines, on the other hand, were consistently richer in terpenes and phenylpropanoids. Further analysis demonstrated a significant association between specific aroma classes and sensory attributes scored by panelists.DiscussionThe findings of the study may help advance new niches in the local wheat market aimed at health and nutrition including adapting durum varieties to the bread market and developing flavor-enhanced wholemeal breads.
Alternate-day modified fasting diet improves weight loss, subjective sleep quality and daytime dysfunction in women with obesity or overweight: a randomized, controlled trial
Authors: Hooshiar Saeedeh Hosseini , Yazdani Akram , Jafarnejad Sadegh 
Published: May 2023

BackgroundBoth sleep time and quality can be associated with overweight or obesity. In obese people, visceral fat tissue develops, which results in an increment in the production of cytokines. The increased production of inflammatory cytokines can disturb the sleep/wake cycle. Therefore, weight loss by reducing fat tissue can improve sleep disorders. Intermittent fasting diets are popular and effective diets that can decrease body weight and improve anthropometric data and body composition. The present study aimed to evaluate the effect of Alternate-day Modified Fasting (ADMF) on sleep quality, body weight, and daytime sleepiness.MethodsClassification of 56 obese or overweight women, based on age and body mass index (BMI), was done using stratified randomization. Then individuals were assigned to the ADMF group (intervention) or Daily Calorie Restriction (CR) group (control) using the random numbers table for 8 weeks. We measured the Pittsburgh sleep quality Index (PSQI), weight, BMI, and the Epworth sleepiness scale (ESS) as primary outcomes and assessed subjective sleep quality (SSQ), sleep latency, sleep disturbances, habitual sleep efficiency, daytime dysfunction, and sleep duration as secondary outcomes at baseline and after the study.ResultsFollowing an ADMF diet resulted in a greater decrease in weight (kg) [−5.23 (1.73) vs. −3.15 (0.88); P &lt; 0.001] and BMI (kg/m2) [−2.05 (0.66) vs. −1.17 (0.34); P &lt; 0.001] compared to CR. No significant differences were found in the changes of PSQI [−0.39 (1.43) vs. −0.45 (1.88); P = 0.73] and ESS [−0.22 (1.24) vs. −0.54 (1.67); P = 0.43] between two groups. Also, following the ADMF diet led to significant changes in SSQ [−0.69 (0.47) vs. −0.08 (0.40); P = &lt;0.001], and daytime dysfunction [−0.65 (0.57) vs. 0.04 (0.75); P: 0.001] in compare with CR diet.ConclusionThese results suggested that an ADMF could be a beneficial diet for controlling body weight and BMI. The ADMF diet didn’t affect PSQI and ESS in women with overweight or obesity but significantly improved SSQ and daytime dysfunction.Clinical Trial RegistrationThe Iranian Registry of Clinical Trials (IRCT20220522054958N3), https://www.irct.ir/trial/64510.
Evaluating the baseline hemoglobin, albumin, lymphocyte, and platelet (HALP) score in the United States adult population and comorbidities: an analysis of the NHANES
Authors: Antar Ryan , Farag Christian , Xu Vincent , Drouaud Arthur , Gordon Olivia , Whalen Michael J. 
Published: May 2023

IntroductionAs a composite immunonutritional biomarker, the Hemoglobin, Albumin, Lymphocyte, Platelet (HALP) score has shown promise in assessing a patient's overall health status by integrating several routinely collected laboratory indicators. This biomarker has been examined in many different populations of patients and disease states (i.e., cancer), but an integrated, universal rubric using standardized thresholds has not thus far been developed. Pre-existing large population-based databases represent an ideal source to examine the distribution of HALP and the influence of diverse health statuses on this score.MethodsWe conducted a cross-sectional study using data from the National Health and Nutrition Examination Survey (NHANES) between 2017–2020, evaluating 8,245 participants across numerous demographic, socioeconomic, and health-related variables. Univariate and multivariate linear regression analyses assessed the associations between HALP scores and these factors.ResultsOur findings revealed significant associations between HALP scores and various demographic, socioeconomic, and health conditions. The median HALP score among the representative population was 49.0, with varying median scores across different groups and normal reference ranges for males and females. Multivariate regression analysis showed that anemia treatment, age over 65 years, weak/failing kidneys, and cancer were independent risk factors associated with lower HALP scores. Male participants demonstrated higher HALP scores than female participants, and age was inversely related to HALP. Moreover, HALP scores were negatively associated with the number of comorbidities.Conclusion/discussionThis study set out to explore the HALP score from a population-based perspective, uncovering notable associations that offer vital insights into the score's clinical relevance and future applications. By determining a median HALP score of 49.0 and normal reference ranges within our diverse, representative sample, we establish a robust foundation for researchers to refine optimal HALP applications and thresholds. Considering the growing focus on personalized medicine, HALP holds promise as a prognostic tool, enabling clinicians to comprehend their patients' immunonutritional status better and deliver customized care.
The association between CTSZ methylation in peripheral blood and breast cancer in Chinese women
Authors: Li Jinyu , Zhou Xiajie , Li Lixi , Ji Longtao , Li Jiaqi , Qu Yunhui , Wang Zhi , Zhao Yutong , Zhang Jie , Liang Feifei , Liu Jingjing , Gu Wanjian , Yang Rongxi , Ma Fei , Dai Liping 
Published: May 2023

PurposePrevious studies have shown that DNA methylation in peripheral blood may be associated with breast cancer (BC). To explore the association between the methylation level of the Cathepsin Z (CTSZ) gene in peripheral blood and BC, we conducted a case–control study in the Chinese population.MethodsPeripheral blood samples were collected from 567 BC cases, 635 healthy controls, and 303 benign breast disease (BBD) cases. DNA extraction and bisulfite-specific PCR amplification were performed for all samples. The methylation levels of seven sites of the CTSZ gene were quantitatively determined by Mass spectrometry. The odds ratios (ORs) of CpG sites were evaluated for BC risk using per 10% reduction and quartiles analyses by logistic regression.ResultsOur analysis showed that five out of the seven CpG sites exhibited significant associations with hypomethylation of CTSZ and BC, compared to healthy controls. The highest OR was for Q2 of CTSZ_CpG_1 (OR: 1.62, P=0.006), particularly for early-stage breast cancer in the case of per 10% reduction of CTSZ_CpG_1 (OR: 1.20, P=0.003). We also found that per 10% reduction of CTSZ_CpG_5 (OR: 1.39, P=0.004) and CTSZ_CpG_7,8 (OR: 1.35, P=0.005) were associated with increased BC risk. Our study also revealed that four out of seven CpG sites were linked to increased BC risk in women under 50 years of age, compared to healthy controls. The highest OR was for per 10% reduction of CTSZ_CpG_1 (OR: 1.47, P&lt;0.001). Additionally, we found that BC exhibited lower methylation levels than BBD at CTSZ_CpG_4 (OR for Q1: 2.18, P&lt;0.001) and CTSZ_CpG_7,8 (OR for Q1: 2.01, P=0.001). Furthermore, we observed a correlation between methylation levels and tumor stage, ER, and HER2 status in BC patients.ConclusionOverall, our findings suggest that altered CTSZ methylation levels in peripheral blood may be associated with breast cancer, particularly in young women, and may serve as a potential biomarker for early-stage BC.
Efficacy and survival of anti-PD-1 antibody in combination with trastuzumab and chemotherapy versus trastuzumab and chemotherapy as first-line treatment of HER2-positive metastasis gastric adenocarcinoma: a retrospective study
Authors: Deng Ting , Li Danyang , Yang Yuchong , Wang Feixue , Bai Ming , Liu Rui , Li Hongli , Ba Yi 
Published: May 2023

BackgroundThe KEYNOTE-811 study exhibited promising preliminary results for HER2-positive metastasis gastric adenocarcinoma; however, long-term survival benefit remains to be determined.MethodsIn this single-center, controlled, retrospective study, patients with histologically confirmed HER2-positive unresectable or metastatic gastric/gastroesophageal adenocarcinoma received either anti-PD-1 antibody combined with trastuzumab and chemotherapy (cohort A) or trastuzumab and chemotherapy treatment (cohort B). The primary end points were progression-free survival (PFS) and overall survival (OS). The secondary end points were objective response rate (ORR), disease control rate (DCR), and duration of response (DoR).ResultsA total of 56 patients were eligible to join the study, with 30 patients in cohort A and 26 patients in cohort B. The median PFS (mPFS) was 16.2 months (95% CI, 15.093–17.307) in cohort A versus 14.5 months (95% CI, 9.491–19.509) in cohort B (p = 0.58). The median OS in cohort A was 28.1 months (95% CI, 17.625–38.575) versus 31.6 months (95% CI, 13.757–49.443) in cohort B (p = 0.534). ORRs were 66.7% and 50% in the two groups, respectively. DCRs were 90% and 84.6% in the two groups. Median DoR was not reached in cohort A and it was 16.3 (95% CI, 8.453–24.207) months in cohort B (p = 0.141). The most common irAEs were grade 1 hypothyroidism (33.3%) in cohort A. No treatment-related deaths occurred in this study.ConclusionsThis retrospective cohort study provided a preliminary picture on the long-term follow-up of combining anti-PD-1 antibody with trastuzumab and chemotherapy in HER2-positive GC, and a trend with longer DoR and ORR was identified. Further studies with larger sample sizes and more in-depth molecular investigation are needed.
Efficacy and safety of ripretinib in Chinese patients with advanced gastrointestinal stromal tumors: a real-world, multicenter, observational study
Authors: Yang Weili , Qian Haoran , Yang Litao , Wang Pengfei , Qian Hailong , Chu Binbin , Liu Zhuo , Sun Jingyu , Wu Dan , Sun Lifeng , Zhou Wenqiang , Hu Jingwei , Chen Xiaolei , Shou Chunhui , Ruan Lingxiang , Zhang Yunyun , Yu Jiren 
Published: May 2023

IntroductionMutations in KIT proto-oncogene, receptor tyrosine kinase (KIT) and platelet-derived growth factor receptor-α (PDGFRA) render the available tyrosine kinase inhibitors (TKI) ineffective in treating advanced gastrointestinal stromal tumors (GIST). Ripretinib, a broad-spectrum switch-control kinase inhibitor, has shown increased efficacy and manageable safety, but real-world evidence remains scarce. This study evaluates the efficacy and safety of ripretinib among Chinese patients in a real-world setting.MethodsAdvanced GIST patients (N=23) receiving ripretinib following progression on previous lines of TKI treatment were enrolled to determine the efficacy [progression-free survival (PFS) and overall survival (OS)]. Safety was assessed by the incidence and severity of adverse events (AEs). All statistical analyses were performed using SPSS version 20.0 and a p-value of &lt;0.05 was considered significant.ResultsThe median PFS (mPFS) of efficacy analysis set (EAS) (N=21) was 7.1 months. mPFS of patients receiving ripretinib following ≤2 lines of previous TKI treatment and ≥3 prior lines of therapy were 7.1 and 9.2 months, respectively. The median OS (mOS) was 12.0 months and shorter interval between the end of the latest TKI and ripretinib therapy was correlated with longer median PFS and OS (p=0.054 and p=0.046), respectively. Alopecia and asthenia were the most common AEs observed.ConclusionCompared to previous lines of TKI in advanced GIST patients, ripretinib showed superior efficacy with clinically manageable AEs. Real-world results are comparable to that of phase III INVICTUS study and its Chinese bridging study. Hence, ripretinib can be used for the clinical management of advanced GIST patients.
Levels of oxidative stress in patients with neoadjuvant chemotherapy for gastric cancer: correlation with treatment response
Authors: Lu Jiatong , Guan Shaoyu , Luo Jiajun , Yuan Jingwen , Yan Junfeng , Yang Chen , Tong Qiang 
Published: May 2023

ObjectiveThe intent of this study was to investigate the relationship between oxidative stress and treatment response in gastric cancer patients undergoing neoadjuvant chemotherapy.MethodsBlood samples from 108 patients and 108 healthy subjects were collected, and all patients were enrolled in SOX chemotherapy. The patients received four cycles of neoadjuvant chemotherapy. Blood samples were collected to determine oxidative stress levels at baseline prior to beginning chemotherapy, and at the end of cycles 2 and 4. The patients receiving neoadjuvant chemotherapy were followed up for several months to years. A survival curve was created according to the follow-up information from the patients. In addition, the correlation between oxidative stress level and treatment effect was evaluated and ROC curves were plotted according to the final collected data.ResultsCompared with the normal group, the levels of the antioxidant index decreased while the peroxide index increased in the patients. Conversely, when patients were compared before and after chemotherapy, the antioxidant index increased but the peroxide index decreased. Furthermore, the antioxidant index increased in the response group while the peroxide index decreased in the non-response group.ConclusionPatients with an increased antioxidant index after chemotherapy have good treatment responsiveness. These indicators can also be used as predictors to judge the patients’ response to chemotherapy.
Impact of IPSS-M implementation in real-life clinical practice
Authors: Zamanillo Irene , Poza Maria , Ayala Rosa , Rapado Inmaculada , Martinez-Lopez Joaquín , Cedena Maria Teresa 
Published: May 2023

ObjectivesThe IPSS-M is a recently published score for risk stratification in myelodysplastic syndromes (MDS), based on clinical and molecular data. We aimed to evaluate its relevance on treatment choice in a real-life setting.MethodsWe retrospectively collected clinical, cytogenetic and molecular data from 166 MDS patients. We calculated IPSS-R and IPSS-M scores and compared Overall Survival (OS) and Leukemia Free Survival (LFS). We also analyzed which patients would have been affected by the re-stratification in terms of clinical management.ResultsWe found that 86.1% of the patients had at least one genetic alteration. The most frequent mutated genes were SF3B1 (25.9%), DNMT3A (16.8%) and ASXL1 (14.4%). IPSS-M re-stratified 48.2% of the patients, of which 16.9% were downgraded and 31.3% were upgraded. IPSS-M improved outcome prediction, with a Harrell’s c-index of 0.680 vs 0.626 for OS and 0.801 vs 0.757 for LFS. In 22.2% of the cohort, the reclassification of the IPSS-M could potentially affect clinical management; 17.4% of the patients would be eligible for treatment intensification and 4.8% for treatment reduction.ConclusionsIPSS-M implementation in clinical practice could imply different treatment approaches in a significant number of patients. Our work validates IPSS-M in an external cohort and confirms its applicability in a real-life setting.