bluuebunny/crossref_metadata_2025_split huggingface dataset:
Metabolomic Study on the Therapeutic Effect of the Jianpi Yangzheng Xiaozheng Decoction on Gastric Cancer Treated with Chemotherapy Based on GC-TOFMS Analysis
Authors: Hou Chao , Chu Hua-Jian , Dai Xiao-Jun , Wu Yin-Qiu , He Zheng-Fei , Yu Yan-Wei , Lu Qing-Yun , Liu Yan-Qing , Zhang Xiao-Chun 
Published: March 2021

Objective. This study aimed to find new biomarkers of prognosis and metabolomic therapy for gastric carcinoma (GC) treated with chemotherapy and investigate the metabolic mechanism of the Jianpi Yangzheng Xiaozheng (JPYZXZ) decoction in the treatment of GC. Methods. First, 36 patients with GC were randomly assigned to the treatment (chemotherapy plus JPYZXZ) and control (chemotherapy alone) groups. The clinical efficacy, side effects, and quality of life of patients in the two groups were evaluated after treatment. Then, the serum samples taken from 16 randomly selected patients (eight treatment cases and eight control cases with no evident pattern characters) and eight healthy volunteers were tested to identify the differential metabolite under the gas chromatography-time-of-fight mass spectrometry platform. The relevant metabolic pathways of differential substances were analyzed using multidimensional statistical analysis. Results. JPYZXZ combined with chemotherapy resulted in a lower risk of leucopenia, thrombocytopenia, and gastrointestinal reaction (

P

< 0.05). Additionally, patients in the treatment group showed a higher Karnofsky (KPS) scale (

P

< 0.05). Compared with healthy persons, patients with GC were found to have 26 significant differential metabolites after chemotherapy; these metabolites are mainly involved in 12 metabolic pathways, such as valine, leucine, and isoleucine biosynthesis. JPYZXZ primarily influences the pentose phosphate pathway; glutathione metabolism; glyoxylate and dicarboxylate metabolism; porphyrin and chlorophyll metabolism; and glycine, serine, and threonine metabolism of patients with GC treated with chemotherapy. Conclusions. The metabolic characteristics of patients with GC after chemotherapy are mainly various amino acid metabolic defects, especially L-glutamine, L-leucine, L-alloisoleucine, and L-valine. These defects lead to a series of problems, such as decreased tolerance and effectiveness of chemotherapy, increased side effects, decreased immunity, and shortened survival time. In addition, the remarkable upregulation of the gluconolactone level in patients with GC suggests the high proliferative activity of GC cells. Thus, gluconolactone may be used as a potential prognostic and diagnostic evaluation index. Moreover, JPYZXZ can reduce the incidence of ADRs and improve the life quality of patients by the correction of L-glutamine, L-leucine, L-alloisoleucine, and L-valine metabolism deficiency. In addition, gluconolactone metabolism is inhibited by JPYZXZ. Such inhibition may be one of the antitumor mechanisms of JPYZXZ.
The Transcriptomic Landscape of Mismatch Repair-Deficient Intestinal Stem Cells
Authors: Bommi Prashant V. , Bowen Charles M. , Reyes-Uribe Laura , Wu Wenhui , Katayama Hiroyuki , Rocha Pedro , Parra Edwin R. , Francisco-Cruz Alejandro , Ozcan Zuhal , Tosti Elena , Willis Jason A. , Wu Hong , Taggart Melissa W. , Burks Jared K. , Lynch Patrick M. , Edelmann Winfried , Scheet Paul A. , Wistuba Ignacio I. , Sinha Krishna M. , Hanash Samir M. , Vilar Eduardo 
Published: March 2021

Abstract

Lynch syndrome is the most common cause of hereditary colorectal cancer and is secondary to germline alterations in one of four DNA mismatch repair (MMR) genes. Here we aimed to provide novel insights into the initiation of MMR-deficient (MMRd) colorectal carcinogenesis by characterizing the expression profile of MMRd intestinal stem cells (ISC). A tissue-specific MMRd mouse model (Villin-Cre;Msh2LoxP/LoxP) was crossed with a reporter mouse (Lgr5-EGFP-IRES-creERT2) to trace and isolate ISCs (Lgr5+) using flow cytometry. Three different ISC genotypes (Msh2-KO, Msh2-HET, and Msh2-WT) were isolated and processed for mRNA-seq and mass spectrometry, followed by bioinformatic analyses to identify expression signatures of complete MMRd and haplo-insufficiency. These findings were validated using qRT-PCR, IHC, and whole transcriptomic sequencing in mouse tissues, organoids, and a cohort of human samples, including normal colorectal mucosa, premalignant lesions, and early-stage colorectal cancers from patients with Lynch syndrome and patients with familial adenomatous polyposis (FAP) as controls. Msh2-KO ISCs clustered together with differentiated intestinal epithelial cells from all genotypes. Gene-set enrichment analysis indicated inhibition of replication, cell-cycle progression, and the Wnt pathway and activation of epithelial signaling and immune reaction. An expression signature derived from MMRd ISCs successfully distinguished MMRd neoplastic lesions of patients with Lynch syndrome from FAP controls. SPP1 was specifically upregulated in MMRd ISCs and colocalized with LGR5 in Lynch syndrome colorectal premalignant lesions and tumors. These results show that expression signatures of MMRd ISC recapitulate the initial steps of Lynch syndrome carcinogenesis and have the potential to unveil novel biomarkers of early cancer initiation.

Significance:
The transcriptomic and proteomic profile of MMR-deficient intestinal stem cells displays a unique set of genes with potential roles as biomarkers of cancer initiation and early progression.
Porphyromonas gingivalis Promotes Colorectal Carcinoma by Activating the Hematopoietic NLRP3 Inflammasome
Authors: Wang Xi , Jia Yiqun , Wen Liling , Mu Wenxin , Wu Xianrui , Liu Tao , Liu Xiangqi , Fang Juan , Luan Yizhao , Chen Ping , Gao Jinlong , Nguyen Ky-Anh , Cui Jun , Zeng Gucheng , Lan Ping , Chen Qianming , Cheng Bin , Wang Zhi 
Published: March 2021

Abstract

Porphyromonas gingivalis (P. gingivalis) is a keystone periodontal pathogen associated with various digestive cancers. However, whether P. gingivalis can promote colorectal cancer and the underlying mechanism associated with such promotion remains unclear. In this study, we found that P. gingivalis was enriched in human feces and tissue samples from patients with colorectal cancer compared with those from patients with colorectal adenoma or healthy subjects. Cohort studies demonstrated that P. gingivalis infection was associated with poor prognosis in colorectal cancer. P. gingivalis increased tumor counts and tumor volume in the ApcMin/+ mouse model and increased tumor growth in orthotopic rectal and subcutaneous carcinoma models. Furthermore, orthotopic tumors from mice exposed to P. gingivalis exhibited tumor-infiltrating myeloid cell recruitment and a proinflammatory signature. P. gingivalis promoted colorectal cancer via NLRP3 inflammasome activation in vitro and in vivo. NLRP3 chimeric mice harboring orthotopic tumors showed that the effect of NLRP3 on P. gingivalis pathogenesis was mediated by hematopoietic sources. Collectively, these data suggest that P. gingivalis contributes to colorectal cancer neoplasia progression by activating the hematopoietic NLRP3 inflammasome.

Significance:
This study demonstrates that the periodontal pathogen P. gingivalis can promote colorectal tumorigenesis by recruiting myeloid cells and creating a proinflammatory tumor microenvironment.
Long-term Patterns of Excess Mortality among Endometrial Cancer Survivors
Authors: Anderson Chelsea , Bae-Jump Victoria L. , Broaddus Russell R. , Olshan Andrew F. , Nichols Hazel B. 
Published: March 2021

Abstract

Background:
We investigated excess mortality after endometrial cancer using conditional relative survival estimates and standardized mortality ratios (SMR).

Methods:
Women diagnosed with endometrial cancer during 2000–2017 (N = 183,153) were identified in the Surveillance Epidemiology and End Results database. SMRs were calculated as observed deaths among endometrial cancer survivors over expected deaths among demographically similar women in the general U.S. population. Five-year relative survival was estimated at diagnosis and each additional year survived up to 12 years post-diagnosis, conditional on survival up to that year.

Results:
For the full cohort, 5-year relative survival was 87.7%, 96.2%, and 97.1% at 1, 5, and 10 years post-diagnosis, respectively. Conditional 5-year relative survival first exceeded 95%, reflecting minimal excess mortality compared with the general population, at 4 years post-diagnosis overall. However, in subgroup analyses, conditional relative survival remained lower for Black women (vs. White) and for those with regional/distant stage disease (vs. localized) throughout the study period. The overall SMR for all-cause mortality decreased from 5.90 [95% confidence interval (CI), 5.81–5.99] in the first year after diagnosis to 1.16 (95% CI, 1.13–1.19) at 10+ years; SMRs were consistently higher for non-White women and for those with higher stage or grade disease.

Conclusions:
Overall, endometrial cancer survivors had only a small survival deficit beyond 4 years post-diagnosis. However, excess mortality was greater in magnitude and persisted longer into survivorship for Black women and for those with more advanced disease.

Impact:
Strategies to mitigate disparities in mortality after endometrial cancer will be needed as the number of survivors continues to increase.
Weight Regain and Breast Cancer–Related Biomarkers Following an Exercise Intervention in Postmenopausal Women
Authors: Gonzalo-Encabo Paola , McNeil Jessica , Pérez-López Alberto , Valades David , Courneya Kerry S. , Friedenreich Christine M. 
Published: March 2021

Abstract

Background:
Epidemiologic studies have reported associations between weight fluctuations and postmenopausal breast cancer risk; however, the biological markers involved in this association are unknown. This study aimed to explore the associations between breast cancer–related biomarkers and weight regain following exercise-induced weight loss.

Methods:
From the 400 participants included in the Breast Cancer and Exercise Trial in Alberta, a total of 214 lost weight during the intervention and had follow-up blood samples, body composition, and covariate measurements. Outcomes were measured at baseline, 12 months (end of the study), and 24 months (follow-up).

Results:
During follow-up, weight regain was 1.80 kg [95% confidence interval (CI): –0.40–3.90], and was significantly associated with increases in estradiol [treatment effect ratio (TER) = 1.03; 95% CI, 1.01–1.04], estrone (TER = 1.02; 95% CI, 1.01–1.03), free estradiol (TER = 1.04; 95% CI, 1.02–1.05), the homeostatic model assessment for insulin resistance (TER = 1.03; 95% CI, 1.02–1.05), and insulin (TER = 1.03; 95% CI, 1.01–1.04), and decreases in sex hormone–binding globulin (SHBG; TER = 0.98; 95% CI, 0.97–0.99) levels. Nonstatistically significant associations were found for glucose and C-reactive protein. Furthermore, a statistically significant linear trend of increasing levels for all biomarkers, and decreasing SHBG, across weight regain categories was found.

Conclusions:
These results suggest that weight regain following exercise-induced weight loss is associated with breast cancer–related biomarker changes in postmenopausal women.

Impact:
These findings provide evidence to support the importance of developing effective strategies to prevent weight regain and, consequently, decrease postmenopausal breast cancer risk via changes in adiposity-related biomarkers.
Genetically Inferred Telomere Length and Testicular Germ Cell Tumor Risk
Authors: Brown Derek W. , Lan Qing , Rothman Nathaniel , Pluta John , Almstrup Kristian , Dalgaard Marlene D. , Greene Mark H. , Grotmol Tom , Loveday Chey , Schwartz Stephen M. , Turnbull Clare , Wiklund Fredrik , Kanetsky Peter A. , Nathanson Katherine L. , McGlynn Katherine A. , Machiela Mitchell J. 
Published: March 2021

Abstract

Background:
Studies evaluating the association between peripheral blood leukocyte telomere length (LTL) and testicular germ cell tumor (TGCT) risk have produced conflicting results.

Methods:
Using available genotype data from the Testicular Cancer Consortium (TECAC), polygenic risk score and Mendelian randomization analyses of genetic variants previously associated with LTL were used to assess potential etiologic associations between telomere length and TGCT risk.

Results:
Genetically inferred telomere length was not associated with TGCT risk among 2,049 cases and 6,921 controls with individual-level genotype data (OR, 1.02; 95% confidence interval, 0.97–1.07). Mendelian randomization analyses using summary statistic data further indicated no evidence for an association between telomere length and TGCT risk among all available TECAC participants (3,558 cases and 13,971 controls).

Conclusions:
Our analyses in the largest molecular genetic testicular cancer study to date provide no evidence for an association between genetically inferred peripheral blood LTL and TGCT risk.

Impact:
The lack of evidence for an overall association indicates that peripheral blood LTL is likely not a strong biomarker for TGCT risk.
Genome-Wide Association Study and Identification of a Protective Missense Variant on Lipoprotein(a) Concentration
Authors: Said M. Abdullah , Yeung Ming Wai , van de Vegte Yordi J. , Benjamins Jan Walter , Dullaart Robin P.F. , Ruotsalainen Sanni , Ripatti Samuli , Natarajan Pradeep , Juarez-Orozco Luis Eduardo , Verweij Niek , van der Harst P. 
Published: March 2021

Objective:
Lipoprotein(a) (Lp[a]) is associated with coronary artery disease (CAD) but also to LDL (low-density lipoprotein) cholesterol. The genetic architecture of Lp(a) remains incompletely understood, as well as its independence of LDL cholesterol in its association to CAD. We investigated the genetic determinants of Lp(a) concentrations in a large prospective multiethnic cohort. We tested the association for potential causality between genetically determined higher Lp(a) concentrations and CAD using a multivariable Mendelian randomization strategy.

Approach and Results:

We studied 371 212 participants of the UK Biobank with available Lp(a) and genome-wide genetic data. Genome-wide association analyses confirmed 2 known and identified 37 novel loci (
P
<5×10
−8
) associated with Lp(a). Testing these loci as instrumental variables in an independent cohort with 60 801 cases and 123 504 controls, each SD genetically elevated Lp(a) conferred a 1.30 ([95% CI, 1.20–1.41]
P
=5.53×10
−
11
) higher odds of CAD. Importantly, this association was independent of LDL cholesterol. Genetic fine-mapping in the
LPA
gene region identified 15 potential causal variants. This included a rare missense variant (rs41267813[A]) associated with lower Lp(a) concentration. We observed a strong interaction between rs41267813 and rs10455872 on Lp(a) concentrations, indicating a protective effect of rs41267813(A).

Conclusions:

This study supports an LDL cholesterol–independent causal link between Lp(a) and CAD. A rare missense variant in the
LPA
gene locus appears to be protective in people with the Lp(a) increasing variant of rs10455872. In the search for therapeutic targets of Lp(a), future work should focus on understanding the functional consequences of this missense variant.
Neural Repetition Suppression Modulates Time Perception: Evidence From Electrophysiology and Pupillometry
Authors: Kruijne Wouter , Olivers Christian N. L. , van Rijn Hedderik 
Published: March 2021

Abstract
Human time perception is malleable and subject to many biases. For example, it has repeatedly been shown that stimuli that are physically intense or that are unexpected seem to last longer. Two competing hypotheses have been proposed to account for such biases: One states that these temporal illusions are the result of increased levels of arousal that speeds up neural clock dynamics, whereas the alternative “magnitude coding” account states that the magnitude of sensory responses causally modulates perceived durations. Common experimental paradigms used to study temporal biases cannot dissociate between these accounts, as arousal and sensory magnitude covary and modulate each other. Here, we present two temporal discrimination experiments where two flashing stimuli demarcated the start and end of a to-be-timed interval. These stimuli could be either in the same or a different location, which led to different sensory responses because of neural repetition suppression. Crucially, changes and repetitions were fully predictable, which allowed us to explore effects of sensory response magnitude without changes in arousal or surprise. Intervals with changing markers were perceived as lasting longer than those with repeating markers. We measured EEG (Experiment 1) and pupil size (Experiment 2) and found that temporal perception was related to changes in ERPs (P2) and pupil constriction, both of which have been related to responses in the sensory cortex. Conversely, correlates of surprise and arousal (P3 amplitude and pupil dilation) were unaffected by stimulus repetitions and changes. These results demonstrate, for the first time, that sensory magnitude affects time perception even under constant levels of arousal.
Relating the Past with the Present: Information Integration and Segregation during Ongoing Narrative Processing
Authors: Chang Claire H. C. , Lazaridi Christina , Yeshurun Yaara , Norman Kenneth A. , Hasson Uri 
Published: March 2021

AbstractThis study examined how the brain dynamically updates event representations by integrating new information over multiple minutes while segregating irrelevant input. A professional writer custom-designed a narrative with two independent storylines, interleaving across minute-long segments (ABAB). In the last (C) part, characters from the two storylines meet and their shared history is revealed. Part C is designed to induce the spontaneous recall of past events, upon the recurrence of narrative motifs from A/B, and to shed new light on them. Our fMRI results showed storyline-specific neural patterns, which were reinstated (i.e., became more active) during storyline transitions. This effect increased along the processing timescale hierarchy, peaking in the default mode network. Similarly, the neural reinstatement of motifs was found during Part C. Furthermore, participants showing stronger motif reinstatement performed better in integrating A/B and C events, demonstrating the role of memory reactivation in information integration over intervening irrelevant events.
Educating dog owners: how owner–dog interactions can benefit from addressing the human caregiving system and dog-directed parenting styles
Authors: van Herwijnen I.R. 
Published: March 2021

Abstract
Dogs need to adapt to a human environment to enhance their welfare and to avoid risks of undesired dog behaviour and relinquishment. Crucial to this adaptation may be how an owner interacts with the dog. Owner–dog interactions may be influenced by the human caregiving system with regard to how care, protection and resources are provided. This narrative review discusses how a consideration of the human caregiving system can benefit owner–dog interactions. Literature suggests that the human caregiving system and parenting styles could influence owner–dog interactions. Owner–dog education may improve these interactions. However, studies on owner–dog education present mixed outcomes for the dog. Also, only a few studies address owner outcomes, indicating a gap that needs filling. It is concluded that, when intervening in owner–dog interactions, more attention should be directed to aspects of human psychology. Dog-directed parenting styles can form one strategy as to improve owner–dog interactions and dog welfare.
A review on the therapeutic role of Piper betle, Syzygium aromaticum and their bioactive component eugenol in cancer research
Authors: Azhagumeena Chandrasekaran , Padma Palghat Ragunathan 
Published: March 2021

Abstract
Nature has provided man with a bountiful supply of components that have the potential to improve the life of man on earth. Among the foremost widely recognized in this category are medicinal plants. Medicinal plants have been a rich source of therapeutic compounds used in various traditional medicines worldwide for thousands of years, due to the presence of active phytocomponents, which help in preventing various diseases. The betel (Piper betle L.) is that the leaf of a vine belonging to the Piperaceae family, which is taken into account a medicinal plant in Southeast Asia. Piper betle leaves have a number of bioactivities and are utilized in traditional medicinal systems. Cloves (Syzygium aromaticum L.) is a tree belonging to the family Myrtaceae. Unopened flowering buds are used as a spice in food preparations all over the world. Eugenol is present abundantly in both Piper betle leaves and Syzygium aromaticum flowers. In the splendid of the above, we thought it significant to aggregate the exceptional review of writing on Piper betle, Syzygium aromaticum and their bioactive component eugenol, covering its, chemical constituents, therapeutic role and medicinal uses.
Influence: On Rhetoric and Biblical Interpretation
Authors: Dinkler Michal Beth 
Published: March 2021

Abstract
The influence of the Bible in human history is staggering. Biblical texts have inspired grand social advancements, intellectual inquiries, and aesthetic achievements. Yet, the Bible has also given rise to hatred, violence, and oppression—often with deadly consequences. How does the Bible exert such extraordinary influence? The short answer is rhetoric. In Influence: On Rhetoric and Biblical Interpretation, Michal Beth Dinkler demonstrates that, contrary to popular opinion, rhetoric is not inherently “empty” or disingenuous. Rhetoric refers to the art of persuasion. Dinkler argues that the Bible is by nature rhetorical, and that understanding the art of persuasion is therefore vital for navigating biblical literature and its interpretation. Influence invites readers to think critically about biblical rhetoric and the rhetoric of biblical interpretation, and offers a clear and compelling guide for how to do so.
Was Democritus a Pythagorean? The Case of psychē
Authors: Cornelli Gabriele , Gomes Gustavo Laet 
Published: March 2021

Abstract
According to Glaucus of Rhegium Democritus was “a disciple of a Pythagorean” (dk 68 A1, 38). The tetralogical catalog of his works prepared by Thrasylus begins its section on ethics with the three following works: Pythagoras; On the Disposition of the Wise Man; On the Things in Hades (dk 68 B0a–c). The very order of the first three ethical works of Democritus could point to some sort of dependence on Pythagoreanism. This was suggested earlier by Frank (1923: 67), who believes that this is due to the fact that Democritus saw Pythagoras as basically the founder of an ethic-religious sect. Without being forced to agree with Frank, it is undeniable that there are many similarities between Pythagorean and Democritean ethics. The Democritean sentences that speak about the sense of shame before oneself as a way of preventing evil deeds (dk 68 B84, 244, and 264) recalls the practice of anamnesis, the examination of conscience in the Pythagorean tradition. Even more important are the parallel uses of measure as a basis for ethical reasoning. This paper aims to review this connection between Pythagorean traditions and Democritus, examining what emerges as the most probable core issue to determine how close this relation between atomists and Pythagoreans could have been: the Aristotelian testimony (de An. 1.2 404a16-20 [dk 58 B40]) on the material conception of the Pythagorean soul. In fact, a corpuscular conception of the soul (“dust in the air”), foreshadowing the psychology of Democritus, is attributed to the Pythagoreans. Is the argument of de An. 1.2 404a16-20 a misunderstanding by Aristotle? Or does this testimony represent an actual dialogue that Pythagoreans were having with atomists in the fifth century bce?