bluuebunny/crossref_metadata_2025_split huggingface dataset:
Selenomethionine supplementation and expression of selenosugars, selenocysteine, and other selenometabolites in rat liver
Authors: Bierla Katarzyna , Szpunar Joanna , Lobinski Ryszard , Sunde Roger A 
Published: October 2023

Abstract
Selenomethionine (SeMet) as a methionine analog can be incorporated into protein. In turkeys, we recently found that selenium (Se) as selenite is not metabolized to SeMet but rather to selenosugars (seleno-N-acetyl galactosamine) bound to protein as well as to selenocysteine (Sec) in selenoproteins. To characterize the metabolism of SeMet, we fed rats graded levels of SeMet from 0 to 5 µg Se/g in a Se-deficient diet for 4 wk, and investigated the fate and accumulation of liver Se using high pressure liquid chromatography (HPLC) coupled with Se-specific inductively coupled plasma mass spectrometry (ICP–MS) and molecule specific (Orbitrap MS/MS) detection. Up to 0.24 µg Se/g (Se requirement for maximal glutathione peroxidase activity), Sec accounted for ∼40% of total liver Se whereas SeMet only accounted for 3–11%. Analysis of water-soluble extracts found negligible low molecular weight (LMW) Se species in rats fed 0 and 0.08 µg Se/g, including no SeMet. At 0.24 µg Se/g and above, SeMet accounted for only 10% of LMW Se species, whereas methyl- and glutathionyl-selenosugars accounted for 70% of LMW Se species. Above the Se requirement, SeMet was ∼30% of the proteinaceous amino acids, whereas Sec levels fell to 5% in rats fed 5 µg Se/g as SeMet. Last, considerably less inorganic Se was bound to liver protein with high SeMet as compared to selenite in a parallel study. SeMet is efficiently metabolized and mixes with the common Se metabolite pool, where Se is preferentially incorporated into Sec and Sec-selenoproteins until selenoproteins plateau; with high SeMet intake, Se is increasingly accumulated as LMW selenosugars and as selenosugar-decorated proteins.
The Limited and The Limitless: Harmonic Voltas and Puns in the Third Movement of Ben Johnston’s Seventh String Quartet
Authors: Willis Laurence Sinclair 
Published: October 2023

Abstract
Extended just intonation confronts us with musical problems arising from the sheer array and variety of pitch relationships that can be written, played, and heard. Through an analysis of Ben Johnston’s Seventh String Quartet as a case study, this essay addresses the diversity of these pitch relationships by suggesting a three-way categorization of just intonation ratios: primary intervals (simple integer ratios), ectopic intervals (ratios with no primary interval analogue), and intermediary intervals (ratios with a close primary interval analogue). I suggest a listening strategy based on the categorization resulting in two analytical models. A voltaic analysis recognizes changes in the pitch domain indicated by the differences between primary and intermediary intervals. A pitch pun analysis emphasizes the small magnitude of the differences between primary and intermediary intervals and the slow drift away from a secure sense of pitch place. Finally, I combine these views to compare the two analytical strategies as applied to the last measures of Johnston’s Seventh String Quartet and speculate on the implications of these strategies for hearing and conceiving of pitch intervals.
Functionally comparable but evolutionarily distinct nucleotide-targeting effectors help identify conserved paradigms across diverse immune systems
Authors: Nicastro Gianlucca G , Burroughs A Maxwell , Iyer Lakshminarayan M , Aravind L 
Published: October 2023

Abstract
While nucleic acid-targeting effectors are known to be central to biological conflicts and anti-selfish element immunity, recent findings have revealed immune effectors that target their building blocks and the cellular energy currency—free nucleotides. Through comparative genomics and sequence-structure analysis, we identified several distinct effector domains, which we named Calcineurin-CE, HD-CE, and PRTase-CE. These domains, along with specific versions of the ParB and MazG domains, are widely present in diverse prokaryotic immune systems and are predicted to degrade nucleotides by targeting phosphate or glycosidic linkages. Our findings unveil multiple potential immune systems associated with at least 17 different functional themes featuring these effectors. Some of these systems sense modified DNA/nucleotides from phages or operate downstream of novel enzymes generating signaling nucleotides. We also uncovered a class of systems utilizing HSP90- and HSP70-related modules as analogs of STAND and GTPase domains that are coupled to these nucleotide-targeting- or proteolysis-induced complex-forming effectors. While widespread in bacteria, only a limited subset of nucleotide-targeting effectors was integrated into eukaryotic immune systems, suggesting barriers to interoperability across subcellular contexts. This work establishes nucleotide-degrading effectors as an emerging immune paradigm and traces their origins back to homologous domains in housekeeping systems.
MethMarkerDB: a comprehensive cancer DNA methylation biomarker database
Authors: Zhu Zhixian , Zhou Qiangwei , Sun Yuanhui , Lai Fuming , Wang Zhenji , Hao Zhigang , Li Guoliang 
Published: October 2023

Abstract
DNA methylation plays a crucial role in tumorigenesis and tumor progression, sparking substantial interest in the clinical applications of cancer DNA methylation biomarkers. Cancer-related whole-genome bisulfite sequencing (WGBS) data offers a promising approach to precisely identify these biomarkers with differentially methylated regions (DMRs). However, currently there is no dedicated resource for cancer DNA methylation biomarkers with WGBS data. Here, we developed a comprehensive cancer DNA methylation biomarker database (MethMarkerDB, https://methmarkerdb.hzau.edu.cn/), which integrated 658 WGBS datasets, incorporating 724 curated DNA methylation biomarker genes from 1425 PubMed published articles. Based on WGBS data, we documented 5.4 million DMRs from 13 common types of cancer as candidate DNA methylation biomarkers. We provided search and annotation functions for these DMRs with different resources, such as enhancers and SNPs, and developed diagnostic and prognostic models for further biomarker evaluation. With the database, we not only identified known DNA methylation biomarkers, but also identified 781 hypermethylated and 5245 hypomethylated pan-cancer DMRs, corresponding to 693 and 2172 genes, respectively. These novel potential pan-cancer DNA methylation biomarkers hold significant clinical translational value. We hope that MethMarkerDB will help identify novel cancer DNA methylation biomarkers and propel the clinical application of these biomarkers.
Does MDMA have treatment potential in sexual dysfunction? A systematic review of outcomes across the female and male sexual response cycles
Authors: Wexler Ava , Dubinskaya Alexandra , Suyama Julie , Komisaruk Barry R , Anger Jennifer , Eilber Karyn 
Published: October 2023

Abstract

Introduction
Sexual health, an integral component of overall well-being, is frequently compromised by common yet underdiagnosed sexual dysfunctions. Traditional interventions encompass pharmaceutical and psychological treatments. Unconventional therapies, like MDMA, offer hope for sexual dysfunction. This review delves into MDMA’s effects on sexual responsiveness and its potential role in treating sexual dysfunction.

Objectives
The purpose of this review is to elucidate effects of MDMA on different domains of the female and male sexual response cycles.

Methods
We conducted a systematic review on the effects of MDMA on each domain of the female and male sexual response cycles. PubMed, MEDLINE, and EMBASE were queried, and results were screened using PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Search terms utilized were “MDMA” or “ecstasy” in combination with “desire,” “arousal,” “lubrication,” “orgasm,” “pleasure,” “libido,” “erection,” and “ejaculation.” Inclusion criteria for this review were MDMA use by study subjects and sexual outcomes in at least 1 domain of the female and/or male sexual response cycles were described and measured. Randomized controlled trials, cohort studies (both prospective and retrospective), surveys, and literature reviews published between January 2000 and June 2022 were included. Case reports and studies that did not address conditions of interest were excluded from analysis. Duplicated search results were screened out. The remaining studies were then read in full text to ensure they met inclusion and exclusion criteria for analysis.

Results
We identified 181 studies, of which 6 met criteria for assessment of the female sexual response cycle and 8 met criteria for assessment of the male sexual response cycle. Four of 6 studies reported increased sexual desire with MDMA use among women. Arousal and lubrication were improved with MDMA use in 3 of 4 studies, but they were not affected in 1 randomized control study. In men, 7 studies evaluated the effects of MDMA on desire and/or arousal, 5 studies measured impact on erection, 3 on orgasm, and 2 on ejaculation. Sixty percent of interview-based studies reported increased sexual desire in men, while 40% reported mixed or no effect. Two studies reported impairment of erection, 2 reported mixed effects, and 1 reported fear of erection impairment. In both men and women, all studies evaluating orgasm reported delay in achieving orgasm but increased intensity and pleasure if achieved. Primary outcome measures were variable and largely qualitative.

Conclusion
Our findings suggest that MDMA generally increases sexual desire and intensifies orgasm when achieved. While producing conflicting evidence on sexual arousal in both sexes, MDMA may impair erectile and ejaculatory function in men.
Characterization of Soybean Events with Enhanced Expression of the Microtubule-Associated Protein 65-1 (MAP65-1)
Authors: Kim Panya , Mahboob Samira , Nguyen Hanh T. , Eastman Samuel , Fiala Olivia , Sousek Matthew , Gaussoin Roch E. , Brungardt Jae L. , Jackson-Ziems Tamra A. , Roston Rebecca , Alfano James R. , Clemente Tom Elmo , Guo Ming 
Published: October 2023

Microtubule-associated protein 65-1 (MAP65-1) protein plays an essential role in plant cellular dynamics through impacting stabilization of the cytoskeleton by serving as a crosslinker of microtubules. The role of MAP65-1 in plants has been associated with phenotypic outcomes in response to various environmental stresses. The Arabidopsis MAP65-1 ( AtMAP65-1) is a known virulence target of plant bacterial pathogens and is thus a component of plant immunity. Soybean events were generated that carry transgenic alleles for both AtMAP65-1 and GmMAP65-1, the soybean AtMAP65-1 homolog, under control of cauliflower mosaic virus 35S promoter. Both AtMAP65-1 and GmMAP65-1 transgenic soybeans are more resistant to challenges by the soybean bacterial pathogen Pseudomonas syringae pv. glycinea and the oomycete pathogen Phytophthora sojae, but not the soybean cyst nematode, Heterodera glycines. Soybean plants expressing AtMAP65-1 and GmMAP65-1 also display a tolerance to the herbicide oryzalin, which has a mode of action to destabilize microtubules. In addition, GmMAP65-1-expressing soybean plants show reduced cytosol ion leakage under freezing conditions, hinting that ectopic expression of GmMAP65-1 may enhance cold tolerance in soybean. Taken together, overexpression of AtMAP65-1 and GmMAP65-1 confers tolerance of soybean plants to various biotic and abiotic stresses. [Formula: see text] Copyright © 2024 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
Retracted: Methionine‐CBS axis promotes intracellular ROS levels by reprogramming serine metabolism
Authors: Chen Jingyun , Cui Xiangyan , Fang Ning , Wu Yu , Yu Shujian , Xiao Dong 
Published: October 2023

AbstractAs a non‐essential amino acid, cysteine could be obtained through both exogenous uptake and endogenous de novo synthesis pathways. Research has demonstrated that restricting the uptake of cystine could result in a depletion of intracellular cysteine and glutathione, ultimately leading to an increase in intracellular reactive oxygen species (ROS) levels. However, the role of methionine in regulating intracellular ROS levels is currently unclear. Here, we want to explore the role of methionine in regulating intracellular ROS levels. We found that methionine restriction could lead to a decrease in intracellular ROS levels, while supplementation with SAM can restore these levels through flow cytometry. Mechanically, we found that the methionine‐SAM axis relies on CBS when regulating intracellular ROS levels. Furthermore, we speculate and prove that the methionine‐SAM‐CBS axis alters the metabolism of serine, thereby reducing intracellular reductive power, therefore promoting intracellular ROS levels through changing metabolite levels and genetic methods. Finally, our study revealed that high expression of CBS in tumor cells could lead to increased intracellular ROS levels, ultimately resulting in faster proliferation rates. Together, our study confirmed that methionine plays a promoting role in the regulation of intracellular ROS levels.
Fragility of Statistically Significant Outcomes in Colonic Diverticular Disease Randomized Trials: A Systematic Review
Authors: McKechnie Tyler , Yang Shuling , Wu Kathy , Sharma Sahil , Lee Yung , Park Lily , Passos Edward , Doumouras Aristithes , Hong Dennis , Parpia Sameer , Bhandari Mohit , Eskicioglu Cagla 
Published: October 2023

BACKGROUND:
The p value has been criticized for an oversimplified determination of whether a treatment effect exists. One alternative is the fragility index. It is a representation of the minimum number of non-events that would need to be converted to events to increase the p value above 0.05.

OBJECTIVE:
To determine the fragility index of randomized controlled trials assessing the efficacy of interventions for patients with diverticular disease since 2010 to assess the robustness of current evidence.

DATA SOURCES:
MEDLINE, Embase, and CENTRAL were searched from inception to August 2022.

STUDY SELECTION:
Articles were eligible for inclusion if they were randomized trials conducted between 2010 and 2022 with parallel, superiority designs evaluating interventions in patients with diverticular disease. Only randomized trials with dichotomous primary outcomes with an associated p-value of less than 0.05 were considered for inclusion.

INTERVENTION(S):
Any surgical or medical intervention for patients with diverticular disease.

MAIN OUTCOME MEASURES:
The fragility index was determined by adding events and subtracting non-events from the groups with the smaller number of events. Events were added until the p-value exceeded 0.05. The smallest number of events required was considered the fragility index.

RESULTS:
After screening 1,271 citations, 15 randomized trials met inclusion criteria. Nine of the studies evaluated surgical interventions and six evaluated medical interventions. The mean number of patients randomized and lost to follow-up per RCT was 92 (SD 35.3) and 9 (SD 11.4), respectively. The median fragility index was 1 (range: 0-5). The fragility indices for the included studies did not correlate significantly with any study characteristics.

LIMITATIONS:
Small sample, heterogeneity, and lack of inclusion of studies with continuous outcomes.

CONCLUSIONS:
The randomized trials evaluating surgical and medical interventions for diverticular disease are not robust. Changing a single outcome event in most studies was sufficient to make a statistically significant study finding non-significant.
Ferroptosis Involved in Cardiovascular Diseases: Mechanism Exploration of Ferroptosis' Role in Common Pathological Changes
Authors: Gao Dongjie , Hu Leilei , Lv Hao , Lian Lu , Wang Mingyang , Fan Xinbiao , Xie Yingyu , Zhang Junping 
Published: October 2023

Abstract:
Regulated cell death is a controlled form of cell death that protects cells by adaptive responses in pathophysiological states. Ferroptosis has been identified as a novel method of controlling cell death in recent years. Several cardiovascular diseases (CVDs) are shown to be profoundly influenced by ferroptosis, and ferroptosis is directly linked to the majority of cardiovascular pathological alterations. Despite this, it is still unclear how ferroptosis affects the pathogenic alterations that take place in CVDs. Based on a review of the mechanisms that regulate ferroptosis, this review explores the most recent research on the role of ferroptosis in the major pathological changes associated with CVDs, to provide new perspectives and strategies for cardiovascular research and clinical treatment.
SARS-CoV-2 viral liver aggregates and scarce parenchymal infection implicate systemic disease as a driver of abnormal liver function
Authors: Pepe-Mooney Brian J. , Smith Colton J. , Sherman Marc S. , North Trista E. , Padera Robert F. , Goessling Wolfram 
Published: October 2023

Background:
Liver function tests (LFTs) are elevated in >50% of hospitalized individuals infected with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), with increased enzyme levels correlating with a more severe COVID-19 course. Despite these observations, evaluations of viral presence within liver parenchyma and viral impact on liver function remain controversial.

Methods and Results:
Our work is a comprehensive immunopathological evaluation of liver tissue from 33 patients with severe, and ultimately fatal, cases of SARS-CoV-2 infection. Coupled with clinical data, we reveal the absence of SARS-CoV-2 infection in cholangiocytes and hepatocytes despite dramatic systemic viral presence. Critically, we identify significant focal viral sinusoidal aggregates in 2/33 patients and single viral RNA molecules circulating in the hepatic sinusoids of 15/33 patients. Utilizing co-immunofluorescence, focal viral liver aggregates in patients with COVID-19 were colocalized to platelet and fibrin clots, indicating the presence of virus-containing sinusoidal microthrombi. Furthermore, this patient cohort, from the initial months of the COVID-19 pandemic, demonstrates a general downtrend of LFTs over the course of the study timeline and serves as a remarkable historical time point of unattenuated viral replication within patients.

Conclusions:
Together, our findings indicate that elevated LFTs found in our patient cohort are not due to direct viral parenchymal infection with SARS-CoV-2 but rather likely a consequence of systemic complications of COVID-19. This work aids in the clinical treatment considerations of patients with SARS-CoV-2 as therapies for these patients may be considered in terms of their direct drug hepatotoxity rather than worsening hepatic function due to direct infection.
Predictors of treatment intensification in uncontrolled hypertension
Authors: Kasanagottu Koushik , Mukamal Kenneth J. , Landon Bruce E. 
Published: October 2023

Purpose:
Prior studies have shown that treatment intensification for patients presenting with uncontrolled hypertension (HTN) rarely occurs, even during visits to the patient's own primary care physicians (PCPs). In this article, we identified predictors of treatment intensification for uncontrolled HTN.

Methods:
We conducted a cross-sectional study using nationally representative survey data on visits by patients aged 18 or above with uncontrolled HTN, defined as a recorded SBP at least 140 and/or a DBP at least 90 using data from the National Ambulatory Medical Care Survey (NAMCS) 2008–2018. Our outcome is treatment intensification defined as the addition of a new blood pressure medication.

Results:
We analyzed 22 559 visits to PCPs where uncontrolled HTN was noted, representing 801 023 786 visits nationally. Among these encounters, 2138 (10.3%) of the visits resulted in treatment intensification. Visits with the patient's own PCP had higher rates of treatment intensification than visits to another PCP (10.8 vs. 5.9%, P < 0.0001). Visits for patients previously on antihypertensive medications had lower rates of treatment intensification (11% for no medications, 10.4% for one medication, 6.6% for ≥2 medications, P < 0.0001), but there were no statistically significant differences in rates of intensification for those with relevant comorbidities (9.4% for no chronic conditions, 10.8% for one to two chronic conditions, 8.9% for at least three chronic conditions, P = 0.12). Multivariable adjusted results were similar to the unadjusted findings.

Conclusion:
Visits for patients with uncontrolled HTN rarely result in treatment intensification. Substantial opportunity exists to improve management of HTN, particularly for patients on fewer medications or seen by a covering provider.
Persistently elevated sFlt-1 and recovery of reduced ADAMTS13 activity in malignant hypertension
Authors: Ma Hongkun , Wang Chongjian , Jiang Mengdi , Jin Kexin , Xu Tingting , Wang Zhiyu , Xu Jing , Ni Liyan , Shi Hao , Shen Pingyan , Chen Yongxi , Feng Xiaobei , Zhang Wen 
Published: October 2023

Background and objectives:
Malignant hypertension (MHT) characterized by acute hypertension with retinopathy or multiorgan damage, is a severe form of hypertensive emergency and associated with target organ involvement and poor kidney outcome. However, the underlying mechanisms are unclear.

Methods:
Eighty-four patients with acute severe hypertension from the Nephrology Department and Emergency Department in a single center during January 2016 and December 2017 were prospectively enrolled and divided into MHT (n = 48) and non-MHT (n = 36) subgroups according to target organ evaluation. Forty healthy controls were recruited. Serum soluble Fms-like tyrosine kinase-1 (sFlt-1) levels and plasma ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type 1 motif, member 13) activity were examined at baseline and 12-month follow-up. Renal endpoints were defined as a significant decrease in the estimated glomerular filtration rate (eGFR) of more than 40% or the occurrence of end-stage renal disease.

Results:
Serum sFlt-1 levels were persistently elevated in MHT. Baseline serum sFLT-1 levels were correlated with plasma ADAMTS13 activity and markers of target organ damage. Plasma ADAMTS13 activity was reduced in both MHT and non-MHT patients and recovered to the normal range at 12-month follow-up. During an average follow-up time of 53 ± 13 months, the restoration of reduced ADAMTS13 activity was correlated with the improvement of kidney function and independently reduced the risk of renal endpoints.

Conclusions:
Abnormal angiogenesis and endothelial damage are involved in the pathophysiology of hypertensive emergency. Evaluation of ADAMTS13 and sFlt-1 may help in the diagnosis and assessment of MHT. Recovery of ADAMTS13 predicts better renal outcome in patients with hypertensive emergencies.