bluuebunny/crossref_metadata_2025_split huggingface dataset:
Copy number aberrations in circulating tumor DNA enables prognosis prediction and molecular characterization of breast cancer
Authors: Kim Min Hwan , Kim Gun Min , Ahn Jin Mo , Ryu Won-Ji , Kim Seul-Gi , Kim Jee Hung , Kim Tae Yeong , Han Hyun Ju , Kim Jee Ye , Park Hyung Seok , Park Seho , Park Byeong Woo , Kim Seung Il , Jeong Joon , Lee Jieun , Paik Soonmyung , Kim Sangwoo , Jung Kyung Hae , Cho Eun Hae , Sohn Joohyuk 
Published: May 2023

Abstract

Background
Low-pass whole-genome sequencing (LP-WGS)–based circulating tumor DNA (ctDNA) analysis is a versatile tool for somatic copy number aberration (CNA) detection, and this study aims to explore its clinical implication in breast cancer.

Methods
We analyzed LP-WGS ctDNA data from 207 metastatic breast cancer (MBC) patients to explore prognostic value of ctDNA CNA burden and validated it in 465 stage II-III triple-negative breast cancer (TNBC) patients who received neoadjuvant chemotherapy in phase III PEARLY trial (NCT02441933). The clinical implication of locus level LP-WGS ctDNA profiling was further evaluated.

Results
We found that a high baseline ctDNA CNA burden predicts poor overall survival and progression-free survival of MBC patients. The post hoc analysis of the PEARLY trial showed that a high baseline ctDNA CNA burden predicted poor disease-free survival independent from pathologic complete response (pCR), validating its robust prognostic significance. The 24-month disease-free survival rate was 96.9% and 55.9% in [pCR(+) and low I-score] and [non-pCR and high I-score] patients, respectively. The locus-level ctDNA CNA profile classified MBC patients into 5 molecular clusters and revealed targetable oncogenic CNAs. LP-WGS ctDNA and in vitro analysis identified the BCL6 amplification as a resistance factor for CDK4/6 inhibitors. We estimated ctDNA-based homologous recombination deficiency status of patients by shallowHRD algorithm, which was highest in the TNBC and correlated with platinum-based chemotherapy response.

Conclusions
These results demonstrate LP-WGS ctDNA CNA analysis as an essential tool for prognosis prediction and molecular profiling. Particularly, ctDNA CNA burden can serve as a useful determinant for escalating or de-escalating (neo)adjuvant strategy in TNBC patients.
Outcomes of a Comprehensive Forest Landowner Extension Program
Authors: Guynn Susan T , Hiesl Patrick , Bible Joe , Steele Janet 
Published: May 2023

AbstractForestry in South Carolina has an annual economic impact of $23 billion and provides over 100,000 jobs statewide. Approximately 87% of forest lands in South Carolina is privately owned and faces shifts in ownership and management practices that may impact forest health. We conducted a bus tour that demonstrated the entire life cycle of a loblolly pine (Pinus taeda) forest from final harvest through forest maturity. The bus tour was aimed at increasing landowner knowledge and influencing the likelihood that they will implement forest management practices. An evaluation using multiple methods was conducted to determine whether the bus tour achieved its objectives. Qualitative and quantitative data converged to show that the forest management bus tour appeared to have been effective in increasing forest landowner knowledge and intent to implement forest management practices, thus potentially increasing forest health across the state.
Fatigue, Stress Appraisal, and Emotional Functioning Among Youth With Sickle Cell Disease: A Daily Diary Study
Authors: Reinman Laura , Schatz Jeffrey , Johnston Julia , Bills Sarah 
Published: May 2023

AbstractObjectiveThe aim of this study was to assess how fatigue is related to mood among youth with sickle cell disease (SCD) by evaluating if the cognitive appraisal of stress moderates the impact of fatigue on emotional functioning consistent with the Risk-and-Resistance Model of Chronic Illness.MethodsDaily diaries assessing fatigue (Numerical Rating Scale), pain intensity (Numerical Rating Scale), mood (Positive and Negative Affect Schedule for Children), and cognitive appraisal of stress (Stress Appraisal Measure for Adolescents) were collected from 25 youth with SCD (ages 11–18 years) for 8 consecutive weeks resulting in 644 daily diaries for analyses.ResultsWhen measured concurrently, higher fatigue was associated with higher negative mood controlling for pain and prior-night sleep quality. Fatigue predicted next-day negative mood through its interaction with primary and secondary appraisal of stress, consistent with stress appraisal as a protective factor. A similar pattern was observed for pain, which, like fatigue, is a common SCD-related stressor.ConclusionFatigue and negative mood are inter-related when concurrently assessed, but their temporal association in SCD suggests that mood changes are not an inevitable sequalae of increased fatigue; fatigue influenced subsequent levels of negative mood, but only in the presence of less adaptive cognitions about stress; specifically, a higher perceived threat from stress and a lower belief in the ability to manage stress. The results suggest specific cognitive targets for reducing the negative impact of fatigue on mood in SCD.
Combination of metabolomics and network pharmacology analysis to decipher the mechanisms of total flavonoids of Litchi seed against prostate cancer
Authors: Cui Dianxin , Luo Zhuo , Liu Xi , Chen Xin , Zhang Qiuping , Yang Xin , Lu Qinpei , Su Zhiheng , Guo Hongwei 
Published: May 2023

Abstract

Objectives
To explore the underlying mechanism of total flavonoids of Litchi seed (TFLS) in treating prostate cancer (PCa).

Methods
Cell Counting Kit-8 (CCK-8), EdU incorporation assay, trypan blue dye assay and colony formation assay were employed to evaluate the effect of TFLS on PCa in vitro. The xenograft mouse model was established to explore the anti-tumour effect of TFLS in vivo. Alterations in the metabolic profiles of the PC3 cells and mouse serum were obtained by untargeted metabolomics. Combination with metabolomics analysis and network pharmacology strategies, the potential targets were predicted and further validated by RT-qPCR.

Key findings
TFLS attenuated PCa progression both in vitro and in vivo. Metabolomics results yielded from cells and serum indicated that the anti-cancer effect of TFLS was correlated with synergistic modulation of five common metabolic pathways including glycerophospholipid metabolism, arginine and proline metabolism, glycine, serine and threonine metabolism, tryptophan metabolism and steroid biosynthesis. Using in silico prediction and RT-qPCR analysis, we further revealed that TFLS exerted anti-PCa activities via regulating the expressions of nine genes, including MAOA, ACHE, ALDH2, AMD1, ARG1, PLA2G10, PLA2G1B, FDFT1 and SQLE.

Conclusions
TFLS suppressed tumour proliferation in PCa, which may be associated with regulating lipid and amino acid metabolisms.
Euterpe oleracea Mart. (Açai) seed extract improves physical performance in old rats by restoring vascular function and oxidative status and activating mitochondrial muscle biogenesis
Authors: de Andrade Soares Ricardo , Cardoso de Oliveira Beatriz , dos Santos Ferreira Flávia , Pontes de Menezes Matheus , Henrique Romão Matheus , Freitas de Bem Graziele , Nascimento Ana Lúcia Rosa , José de Carvalho Jorge , Aguiar da Costa Cristiane , Teixeira Ognibene Dayane , Soares de Moura Roberto , Castro Resende Angela 
Published: May 2023

Abstract

Objectives
Alterations in cardiovascular and skeletal muscle function are hallmarks of ageing that lead to exercise intolerance. We aimed to examine whether the treatment with Euterpe oleracea Mart. seed extract (ASE) associated with exercise training improves aerobic exercise performance by promoting healthy ageing in the elderly.

Methods
Male Wistar rats were divided into five groups: Young (3 months), Old (18 months), Old+ASE (ASE 200 mg/kg/day), Old+Training (exercise training 30 min/day; 5 days/week) and Old+Training+ASE, for 4 weeks.

Key findings
ASE treatment increased the exercise time and the running distance concerning the initial maximal treadmill stress test (MTST) in the Old+Training+ASE group. Exercise training or ASE treatment restored the aorta oxidative damage and antioxidant defence. It reduced the acetylcholine (ACh)-induced vasodilation in the aorta of old animals to the same values as the young and improved hypertension. Only the association of both strategies restored the ACh-induced vasodilation in mesentery arteries. Remarkably, exercise training associated with ASE increased the antioxidant defence, nitrite levels and expression of the mitochondrial SIRT-1, PGC1α in soleus muscle homogenates.

Conclusions
ASE treatment associated with exercise training contributes to better exercise performance and tolerance in ageing by improving vascular function, oxidative stress and activating the muscle SIRT-1/PGC-1α pathway.
Chrysin prevents inflammation-coinciding liver steatosis via AMPK signalling
Authors: Gao Chuanyue , Zhang Huan , Nie Lulin , He Kaiwu , Li Peimao , Wang Xingxing , Zhang Zaijun , Xie Yongmei , Li Shupeng , Liu Gongping , Huang Xinfeng , Deng Huiping , Liu Jianjun , Yang Xifei 
Published: May 2023

Abstract

Objectives
We aimed to elucidate the therapeutic potential of Chrysin (CN) against the high-fat diet (HFD) induced non-alcoholic fatty liver disease (NAFLD) and its mechanism.

Methods
To assess the hypothesis, NAFLD was induced in C57BL/6 mice by feeding a high-fat diet for up to two months, followed by CN administration (for three months). Liver injury/toxicity, lipid deposition, inflammation and fibrosis were detected via molecular and biochemical analysis, including blood chemistry, immunoimaging and immunoblotting. Moreover, we performed proteomic analysis to illuminate Chrysin’s therapeutic effects further.

Key findings
CN treatment significantly reduced liver-fat accumulation and inflammation, ultimately improving obesity and liver injury in NAFLD mice. Proteomic analysis showed that CN modified the protein expression profiles in the liver, particularly improving the expression of proteins related to energy, metabolism and inflammation. Mechanistically, CN treatment increased AMP-activated protein and phosphorylated CoA (P-ACC). Concurrently, it reduced inflammation and inflammation activation by inhibiting NLRP3 expression.

Conclusions
In summary, CN treatment reduced lipid metabolism by AMPK and inflammasome activation by NLRP3 inhibition, ultimately improving NAFLD progression. These findings suggest that CN could be a potential treatment candidate for the NFLAD condition.
Nobiletin attenuates monocrotaline-induced pulmonary arterial hypertension through PI3K/Akt/STAT3 pathway
Authors: Yin Qin , Wang Sen , Yang Jie , Fan Cunyu , Yu Yihan , Li Juan , Mei Feng , Zhang Shiwei , Xi Rengang , Zhang Xiuyun 
Published: May 2023

Abstract

Objectives
Nobiletin is a flavonoid found in the peel of Citrus sinensis (oranges). The purpose of this study is to investigate whether Nobiletin can alleviate the monocrotaline (MCT)-induced pulmonary arterial hypertension (PAH) and explore the underlying mechanisms.

Methods
The PAH rat model was replicated by subcutaneous injection of MCT. Nobiletin (1, 5 and 10 mg/kg) was administered by gavage from day 1 to day 21. After 21 days of MCT injection, the mean pulmonary artery pressure, pulmonary vascular resistance, Fulton Index, pulmonary artery remodelling, blood routine parameters, liver and kidney functions was measured. The level of inflammatory cytokines and PI3K/Akt/STAT3 were detected by qPCR, ELISA and western blot, the proliferation of pulmonary artery smooth muscle cells (PASMCs) was evaluated by CCK-8.

Key findings
Nobiletin (10 mg/kg) inhibited the MCT-induced increase in mean pulmonary artery pressure and pulmonary vascular resistance, right ventricular hypertrophy and pulmonary artery remodelling in rats. Nobiletin decreased the levels of inflammatory cytokines and phosphorylation level of PI3K/Akt/STAT3 in lungs of MCT-treated rats. Nobiletin inhibited the proliferation and lowered the inflammatory cytokines level induced by PDGF-BB in PASMCs.

Conclusion
Nobiletin attenuates MCT-induced PAH, and the potential mechanism is to inhibit inflammation through PI3K/Akt/STAT3 pathway.
Diagnosed Behavioral Health Disorders, Related Duty Limitations, and Return to Duty Time in the U.S. Army: Population-based Data, from 2017 to 2019
Authors: Carreno-Davidson Jamie T , Faller Theresa N , Richardson Melissa , Roy Tanja C 
Published: May 2023

ABSTRACTIntroductionLess than half of service members with a behavioral health (BH) problem seek care. Soldiers may avoid seeking needed care because of concerns related to being placed on a duty-limiting profile and the related medical disclosures that follow.Materials and MethodsThis study used a retrospective population-based design to identify all new BH diagnoses across the U.S. Army. The relationship between diagnostic category, risk of being issued a duty limitation (profile), and time until return to full duty was also examined. Data were collected from a comprehensive data repository that includes medical and administrative records. Soldiers with a new BH diagnosis were identified from 2017 to 2018. All duty limitation profiles within 12 months of initial diagnosis were identified.ResultsRecords for 614,107 unique service members were reviewed. This cohort was mostly male, enlisted, unmarried, and White. The mean age was 27.13 years (SD = 8.05). Soldiers with a new BH diagnosis accounted for 16.7% (n = 102,440) of the population. The most common diagnostic category was adjustment disorder (55.7%). About a quarter (23.6%) of soldiers with a new diagnosis were issued a related profile. The mean length of these profiles was 98.55 days (SD = 56.91). Of those with a new diagnosis, sex and race failed to have an effect on the odds of being placed on a profile. Overall, enlisted, unmarried, or younger soldiers had greater odds of being placed on a profile.ConclusionThese data provide relevant information for both the service member who seeks care and command teams seeking readiness projections.
Historical Routes for Diversification of Domesticated Chickpea Inferred from Landrace Genomics
Authors: Igolkina Anna A , Noujdina Nina V , Vishnyakova Margarita , Longcore Travis , von Wettberg Eric , Nuzhdin Sergey V , Samsonova Maria G 
Published: May 2023

Abstract
According to archaeological records, chickpea (Cicer arietinum) was first domesticated in the Fertile Crescent about 10,000 years BP. Its subsequent diversification in Middle East, South Asia, Ethiopia, and the Western Mediterranean, however, remains obscure and cannot be resolved using only archeological and historical evidence. Moreover, chickpea has two market types: “desi” and “kabuli,” for which the geographic origin is a matter of debate.
To decipher chickpea history, we took the genetic data from 421 chickpea landraces unaffected by the green revolution and tested complex historical hypotheses of chickpea migration and admixture on two hierarchical spatial levels: within and between major regions of cultivation.
For chickpea migration within regions, we developed popdisp, a Bayesian model of population dispersal from a regional representative center toward the sampling sites that considers geographical proximities between sites. This method confirmed that chickpea spreads within each geographical region along optimal geographical routes rather than by simple diffusion and estimated representative allele frequencies for each region. For chickpea migration between regions, we developed another model, migadmi, that takes allele frequencies of populations and evaluates multiple and nested admixture events. Applying this model to desi populations, we found both Indian and Middle Eastern traces in Ethiopian chickpea, suggesting the presence of a seaway from South Asia to Ethiopia. As for the origin of kabuli chickpeas, we found significant evidence for its origin from Turkey rather than Central Asia.
GeneRanger and TargetRanger: processed gene and protein expression levels across cells and tissues for target discovery
Authors: Marino Giacomo B , Ngai Michael , Clarke Daniel J B , Fleishman Reid H , Deng Eden Z , Xie Zhuorui , Ahmed Nasheath , Ma’ayan Avi 
Published: May 2023

Abstract
Several atlasing efforts aim to profile human gene and protein expression across tissues, cell types and cell lines in normal physiology, development and disease. One utility of these resources is to examine the expression of a single gene across all cell types, tissues and cell lines in each atlas. However, there is currently no centralized place that integrates data from several atlases to provide this type of data in a uniform format for visualization, analysis and download, and via an application programming interface. To address this need, GeneRanger is a web server that provides access to processed data about gene and protein expression across normal human cell types, tissues and cell lines from several atlases. At the same time, TargetRanger is a related web server that takes as input RNA-seq data from profiled human cells and tissues, and then compares the uploaded input data to expression levels across the atlases to identify genes that are highly expressed in the input and lowly expressed across normal human cell types and tissues. Identified targets can be filtered by transmembrane or secreted proteins. The results from GeneRanger and TargetRanger are visualized as box and scatter plots, and as interactive tables. GeneRanger and TargetRanger are available from https://generanger.maayanlab.cloud and https://targetranger.maayanlab.cloud, respectively.
Role of diet quality in bone health in children and adolescents: a systematic review
Authors: Suhett Lara Gomes , Filgueiras Mariana De Santis , de Novaes Juliana Farias , Sukumar Deeptha 
Published: May 2023

Abstract

Context
Poor diet quality and unhealthy dietary patterns have been linked to poor bone health, yet few studies have investigated the role of diet quality in bone health in pediatric populations.

Objective
This systematic review aims to assess the available evidence on the association between diet quality and bone health markers in children and adolescents.

Data Sources
The PubMed, Scopus, and Virtual Health Library databases were searched electronically from October to November 2022, without any restrictions on date or language. The STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) checklist was used to assess the quality of the studies.

Data Extraction
Published observational studies in children and adolescents (ages 2 to 19 years) that investigated the association between diet quality and bone health were eligible for inclusion. Two researchers independently analyzed and selected all articles using the Rayyan app. Initially, 965 papers were identified. A total of 12 observational studies qualified, including 8 cross-sectional and 4 longitudinal studies. The sample comprised 7130 individuals aged 3 to 17.9 years, representing both sexes. Bone health was evaluated by measures of bone mineral density and bone mineral content.

Data Analysis
Seven studies (58.3%) showed significant associations between diet quality and bone health markers, all of which evaluated diet quality by identifying dietary patterns. Diet quality as evaluated by all dietary indexes was not associated with bone health markers.

Conclusions
Adherence to a healthy diet may benefit bone health in children and adolescents. These findings emphasize the importance of developing effective public health policies that encourage healthy eating habits from childhood to preserve bone health. Longitudinal research using a specific tool to assess diet quality in relation to bone health is warranted. Future studies should also measure bone-regulating hormones and markers of bone turnover.

Systematic Review Registration
PROSPERO registration no. CRD42022368610.
Impact of metformin treatment on cobalamin status in persons with type 2 diabetes
Authors: Fituri Sundus , Akbar Zoha , Ganji Vijay 
Published: May 2023

Abstract
Over the last decades, low vitamin B12 status has been reported in individuals with type 2 diabetes mellitus (T2DM). Metformin, the first-line therapy for lowering blood glucose, is the main driving factor behind this association. Although the relationship between vitamin B12 deficiency and metformin is well established, results of studies on the exact effect of the dose and duration of the therapy remain inconsistent. Additionally, a lack of consensus on the definition of vitamin B12 deficiency adds to the conflicting literature. The objectives of this review were to analyze and synthesize the findings on the effects of metformin dose and duration on vitamin B12 status in patients with T2DM and to outline the potential mechanisms underlying metformin’s effect on vitamin B12. Metformin therapy has adversely affected serum vitamin B12 concentrations, a marker of vitamin B12 status. The metformin usage index (a composite score of metformin dose and duration) might serve as a potential risk assessment tool for vitamin B12 screening in patients with T2DM. Considering the health implications of suboptimal vitamin B12 status, vitamin B12 concentrations should be monitored periodically in high-risk patients, such as vegans who are receiving metformin therapy for T2DM. Additionally, it is prudent to implement lifestyle strategies concurrent with metformin therapy in individuals with T2DM, promoting an overall synergistic effect on their glycemic control.
Blueberry, cranberry, raspberry, and strawberry as modulators of the gut microbiota: target for treatment of gut dysbiosis in chronic kidney disease? From current evidence to future possibilities
Authors: Coutinho-Wolino Karen S , Melo Manuela F S , Mota Jessica C , Mafra Denise , Guimarães Jonas T , Stockler-Pinto Milena B 
Published: May 2023

Abstract
Gut dysbiosis is common in patients with chronic kidney disease (CKD) and is associated with uremic toxin production, inflammation, oxidative stress, and cardiovascular disease development. Therefore, healthy dietary patterns are essential modulators of gut microbiota. In this context, studies suggest that consuming berry fruits, rich in polyphenols and nutrients, may positively affect the gut microbiota, promoting the selective growth of beneficial bacteria and improving clinical status. However, studies on the effects of berry fruits on gut microbiota in CKD are scarce, and a better understanding of the possible mechanisms of action of berry fruits on gut microbiota is needed to guide future clinical studies and clinical practice in CKD. The objective was to discuss how berry fruits (blueberry, cranberry, raspberry, and strawberry) could be a therapeutic strategy to modulate the gut microbiota and possibly reverse the dysbiosis in CKD. Overall, available evidence shows that berry fruits can promote an increase in diversity by affecting the abundance of mucus-producing bacteria and short-chain fatty acids. Moreover, these fruits can increase the expression of mRNA involved in tight junctions in the gut such as occludin, tight junction protein 1 (TJP1), and mucin. Studies on the exact amount of berries leading to these effects show heterogeneous findings. However, it is known that, with 5 mg/day, it is already possible to observe some effects in animal models. Wild berries could possibly improve the uremic condition by reducing the levels of uremic toxins via modulation of the gut microbiota. In the long term, this could be an excellent strategy for patients with CKD. Therefore, clinical studies are encouraged to evaluate better these effects on CKD as well as the safe amount of these fruits in order to promote a better quality of life or even the survival of these patients.