bluuebunny/crossref_metadata_2025_split huggingface dataset:
Considerations for developing a targeted amino acid supplement for people with Parkinson’s disease that promotes health while accounting for pathophysiology and medication interference
Authors: Earp Jacob E , Colon-Semenza Cristina , LoBuono Dara L 
Published: February 2023

AbstractFor individuals with Parkinson’s disease (PD), dietary habits affect disease symptoms, progression, and overall health. Protein consumption is of great interest because of the direct and indirect effects of specific amino acids (AAs) on disease progression and interference with levodopa medication. Proteins comprise 20 distinct AAs with varying effects on overall health, disease progression, and medication interference. Therefore, it is important to consider both the potential beneficial and detrimental effects of each AA when considering supplementation for an individual with PD. Such consideration is of particular importance because PD pathophysiology, altered dietary patterns associated with PD, and competitive absorption with levodopa have been shown to result in characteristically altered AA profiles (eg, some AAs are stored in excess while others are deficient). To address this problem, considerations for the development of a precision nutritional supplement that targets AAs specific to the needs of people with PD are discussed. The objective of this review is to provide a theoretical framework for such a supplement, detailing the current state of knowledge relating relevant evidence to such a supplement, and highlighting areas of future research. Specifically, the general need for such a supplement is discussed before a systematic examination is provided of the potential benefits and risks of dietary supplementation of each AA in people with PD. As a part of this discussion, evidence-based recommendations are provided regarding the inclusion or exclusion of each AA for such a supplement for people with PD, and areas are highlighted where additional research is needed.
Commentary: When applying dietary therapies for gastrointestinal conditions, family values, culture, and social challenges matter
Authors: Iacovou Marina , Lewis James D 
Published: February 2023

Abstract
Some gastrointestinal conditions now have diet as a cornerstone to therapy. Three examples include the low-fermentable, oligosaccharide, disaccharide, monosaccharide, and polyol diet for irritable bowel syndrome, a gluten-free diet for celiac disease, and a hypoallergenic diet for eosinophilic esophagitis. All have been shown to be effective in Western or highly industrialized countries. However, these gastrointestinal conditions occur worldwide. Less is known regarding the effectiveness of dietary therapies in cultures and regions of dense religious and traditional practices where food is a central focus. This includes South Asia, the Mediterranean region, Africa, the Middle East, South America, and within Indigenous communities. Hence, there is a need to reproduce dietary intervention studies within cultures of dense traditional dietary practices to understand the applicability and acceptability of dietary therapy to establish generalizability. Furthermore, there is a need for nutrition experts to have a deep understanding of various cultural cuisines, practices, values, and customs. To achieve this, increasing the diversity of students in the sciences and having a diverse workforce of nutrition experts and health professionals that reflects the patient population will allow for more personalized care. In addition, there are social challenges, including a lack of medical insurance coverage, the cost of dietary interventions, and inconsistent nutrition messaging. Although there are many cultural considerations and social challenges to implementing effective dietary interventions around the world, these barriers are addressable through research methodologies that address culture and society challenges, and enhanced training of dietitians.
Plant organellar RNA maturation
Authors: Small Ian , Melonek Joanna , Bohne Alexandra-Viola , Nickelsen Jörg , Schmitz-Linneweber Christian 
Published: February 2023

AbstractPlant organellar RNA metabolism is run by a multitude of nucleus-encoded RNA-binding proteins (RBPs) that control RNA stability, processing, and degradation. In chloroplasts and mitochondria, these post-transcriptional processes are vital for the production of a small number of essential components of the photosynthetic and respiratory machinery—and consequently for organellar biogenesis and plant survival. Many organellar RBPs have been functionally assigned to individual steps in RNA maturation, often specific to selected transcripts. While the catalog of factors identified is ever-growing, our knowledge of how they achieve their functions mechanistically is far from complete. This review summarizes the current knowledge of plant organellar RNA metabolism taking an RBP-centric approach and focusing on mechanistic aspects of RBP functions and the kinetics of the processes they are involved in.
O‐glycan structures in apo(a) subunit of human lipoprotein(a) suppresses the pro‐angiogenic activity of galectin‐1 on human umbilical vein endothelial cells
Authors: Kalaivani Vasantha , Krishna Mahesh S. , Kumar Asokan Aneesh , Satheesh Gopika , Jaleel Abdul 
Published: February 2023

AbstractApolipoprotein(a) [apo(a)] is a highly polymorphic O‐glycoprotein circulating in human plasma as lipoprotein(a) [Lp(a)]. The O‐glycan structures of apo(a) subunit of Lp(a) serve as strong ligands of galectin‐1, an O‐glycan binding pro‐angiogenic lectin abundantly expressed in placental vascular tissues. But the pathophysiological significance of apo(a)‐galectin‐1 binding is not yet been revealed. Carbohydrate‐dependent binding of galectin‐1 to another O‐glycoprotein, neuropilin‐1 (NRP‐1) on endothelial cells activates vascular endothelial growth factor receptor 2 (VEGFR2) and mitogen‐activated protein kinase (MAPK) signaling. Using apo(a), isolated from human plasma, we demonstrated the potential of the O‐glycan structures of apo(a) in Lp(a) to inhibit angiogenic properties such as proliferation, migration, and tube‐formation in human umbilical vein endothelial cells (HUVECs) as well as neovascularization in chick chorioallantoic membrane. Further, in vitro protein‐protein interaction studies have confirmed apo(a) as a superior ligand to NRP‐1 for galectin‐1 binding. We also demonstrated that the protein levels of galectin‐1, NRP‐1, VEGFR2, and downstream proteins in MAPK signaling were reduced in HUVECs in the presence of apo(a) with intact O‐glycan structures compared to that of de‐O‐glycosylated apo(a). In conclusion, our study shows that apo(a)‐linked O‐glycans prevent the binding of galectin‐1 to NRP‐1 leading to the inhibition of galectin‐1/neuropilin‐1/VEGFR2/MAPK‐mediated angiogenic signaling pathway in endothelial cells. As higher plasma Lp(a) level in women is an independent risk factor for pre‐eclamsia, a pregnancy‐associated vascular complication, we propose that apo(a) O‐glycans‐mediated inhibition of the pro‐angiogenic activity of galectin‐1 may be one of the underlying molecular mechanism of pathogenesis of Lp(a) in pre‐eclampsia.
X‐ray structure and function of fibronectin domains two and three of the neural cell adhesion molecule L1
Authors: Guédez Gabriela , Loers Gabriele , Jeffries Cy M. , Kozak Sandra , Meijers Rob , Svergun Dmitri I. , Schachner Melitta , Löw Christian 
Published: February 2023

AbstractThe cell adhesion molecule L1 (L1CAM, L1 in short) plays crucial roles during neural development, regeneration after injury, synapse formation, synaptic plasticity and tumor cell migration. L1 belongs to the immunoglobulin superfamily and comprises in its extracellular part six immunoglobulin (Ig)‐like domains and five fibronectin type III homologous repeats (FNs). The second Ig‐like domain has been validated for self‐ (so‐called homophilic) binding between cells. Antibodies against this domain inhibit neuronal migration in vitro and in vivo. The fibronectin type III homologous repeats FN2 and FN3 bind small molecule agonistic L1 mimetics and contribute to signal transduction. FN3 has a stretch of 25 amino acids that can be triggered with a monoclonal antibody, or the L1 mimetics, to enhance neurite outgrowth and neuronal cell migration in vitro and in vivo. To correlate the structural features of these FNs with function, we determined a high‐resolution crystal structure of a FN2FN3 fragment, which is functionally active in cerebellar granule cells and binds several mimetics. The structure illustrates that both domains are connected by a short linker sequence allowing a flexible and largely independent organization of both domains. This becomes further evident by comparing the X‐ray crystal structure with models derived from Small‐Angle X‐ray Scattering (SAXS) data for FN2FN3 in solution. Based on the X‐ray crystal structure, we identified five glycosylation sites which we believe are crucial for folding and stability of these domains. Our study signifies an advance in the understanding of structure–functional relationships of L1.
Involvement of eNAMPT/TLR4 inflammatory signaling in progression of non‐alcoholic fatty liver disease, steatohepatitis, and fibrosis
Authors: Sun Belinda L. , Sun Xiaoguang , Kempf Carrie L. , Song Jin H. , Casanova Nancy G. , Camp Sara M. , Reyes Hernon Vivian , Fallon Michael , Bime Christian , Martin Diego R. , Travelli Cristina , Zhang Donna D. , Garcia Joe G. N. 
Published: February 2023

AbstractAlthough the progression of non‐alcoholic fatty liver disease (NAFLD) from steatosis to steatohepatitis (NASH) and cirrhosis remains poorly understood, a critical role for dysregulated innate immunity has emerged. We examined the utility of ALT‐100, a monoclonal antibody (mAb), in reducing NAFLD severity and progression to NASH/hepatic fibrosis. ALT‐100 neutralizes eNAMPT (extracellular nicotinamide phosphoribosyltransferase), a novel damage‐associated molecular pattern protein (DAMP) and Toll‐like receptor 4 (TLR4) ligand. Histologic and biochemical markers were measured in liver tissues and plasma from human NAFLD subjects and NAFLD mice (streptozotocin/high‐fat diet—STZ/HFD, 12 weeks). Human NAFLD subjects (n = 5) exhibited significantly increased NAMPT hepatic expression and significantly elevated plasma levels of eNAMPT, IL‐6, Ang‐2, and IL‐1RA compared to healthy controls, with IL‐6 and Ang‐2 levels significantly increased in NASH non‐survivors. Untreated STZ/HFD‐exposed mice displayed significant increases in NAFLD activity scores, liver triglycerides, NAMPT hepatic expression, plasma cytokine levels (eNAMPT, IL‐6, and TNFα), and histologic evidence of hepatocyte ballooning and hepatic fibrosis. Mice receiving the eNAMPT‐neutralizing ALT‐100 mAb (0.4 mg/kg/week, IP, weeks 9 to 12) exhibited marked attenuation of each index of NASH progression/severity. Thus, activation of the eNAMPT/TLR4 inflammatory pathway contributes to NAFLD severity and NASH/hepatic fibrosis. ALT‐100 is potentially an effective therapeutic approach to address this unmet NAFLD need.
Independent Associations of Neighborhood Deprivation and Patient-Level Social Determinants of Health With Textbook Outcomes After Inpatient Surgery
Authors: Schmidt Susanne , Kim Jeongsoo , Jacobs Michael A. , Hall Daniel E. , Stitzenberg Karyn B. , Kao Lillian S. , Brimhall Bradley B. , Wang Chen-Pin , Manuel Laura S. , Su Hoah-Der , Silverstein Jonathan C. , Shireman Paula K. 
Published: February 2023

Objective:
Assess associations of social determinants of health (SDoH) using area deprivation index (ADI), race/ethnicity and insurance type with textbook outcomes (TO).

Background:
Individual- and contextual-level SDoH affect health outcomes, but only one SDoH level is usually included.

Methods:
Three healthcare system cohort study using National Surgical Quality Improvement Program (2013–2019) linked with ADI risk-adjusted for frailty, case status, and operative stress examining TO/TO components (unplanned reoperations, complications, mortality, emergency department/observation stays, and readmissions).

Results:
Cohort (34,251 cases) mean age 58.3 [SD = 16.0], 54.8% females, 14.1% Hispanics, 11.6% Non-Hispanic Blacks, 21.6% with ADI >85, and 81.8% TO. Racial and ethnic minorities, non-private insurance, and ADI >85 patients had increased odds of urgent/emergent surgeries (adjusted odds ratios [aORs] range: 1.17–2.83, all P < 0.001). Non-Hispanic Black patients, ADI >85 and non-Private insurances had lower TO odds (aORs range: 0.55–0.93, all P < 0.04), but ADI >85 lost significance after including case status. Urgent/emergent versus elective had lower TO odds (aOR = 0.51, P < 0.001). ADI >85 patients had higher complication and mortality odds. Estimated reduction in TO probability was 9.9% (95% confidence interval [CI] = 7.2%–12.6%) for urgent/emergent cases, 7.0% (95% CI = 4.6%–9.3%) for Medicaid, and 1.6% (95% CI = 0.2%–3.0%) for non-Hispanic Black patients. TO probability difference for lowest-risk (White-Private-ADI <85-elective) to highest-risk (Black-Medicaid-ADI >85-urgent/emergent) was 29.8% for very frail patients.

Conclusion:
Multilevel SDoH had independent effects on TO, predominately affecting outcomes through increased rates/odds of urgent/emergent surgeries driving complications and worse outcomes. Lowest-risk versus highest-risk scenarios demonstrated the magnitude of intersecting SDoH variables. Combination of insurance type and ADI should be used to identify high-risk patients to redesign care pathways to improve outcomes. Risk adjustment including contextual neighborhood deprivation and patient-level SDoH could reduce unintended consequences of value-based programs.
Honokiol attenuates mitochondrial fission and cell apoptosis by activating Sirt3 in intracerebral hemorrhage
Authors: Zheng Xue cheng , Gao Jun ling , Zhao Man man , Han Ling ling , Zhang De xin , Wang Kai jie , Cui Jian zhong 
Published: February 2023

Abstract

Background:
Sirtuin-3 (Sirt3) has been documented to protect against mitochondrial dysfunction and apoptosis. Honokiol (HKL) is a Sirt3 pharmacological activator with reported neuroprotective effects in multiple neurological disorders. The present study aimed to explore the neuroprotective effects of HKL and the role of Sirt3 following intracerebral hemorrhage (ICH).

Methods:
An in vivo ICH model in rats was established by injecting autologous blood into the right basal ganglia. PC12 cells were stimulated with hemin. For the in vivo investigation, the modified Neurological Severity Scores and the Morris water maze test were performed to assess neurological deficits. Hematoxylin–Eosin and Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling staining were employed to evaluate the histopathology and apoptosis. Immunohistochemical staining was used to investigate the expression of Sirt3. Adenosine triphosphate (ATP) levels were quantified to assess mitochondrial dysfunction. Cell counting kit-8, lactate dehydrogenase assay, and flow cytometry were used to analyze cell vitality and apoptosis in vitro. Immunofluorescence staining was performed to observe mitochondrial morphology and dynamin-related protein 1 (Drp1) localization to mitochondria. Western blot was applied to quantify the expression of Sirt3, Bax, Bcl-2, cleaved-caspase-3, Drp1, phosphorylation of Drp1 at serine-616, and phosphorylation of Drp1 at serine-637 in vivo and in vitro.

Results:
HKL treatment alleviated neurological deficits, attenuated the histopathological damage and cell apoptosis, and restored the decreased ATP levels in ICH rats. HKL improved cell survival rate, reduced cell apoptosis, and inhibited mitochondrial fission in PC12 cells. Moreover, both in vivo and in vitro models showed increased phosphorylation of Drp1 at Ser616, and reduced phosphorylation of Drp1 at Ser637. Meanwhile, immunofluorescence co-localization analysis revealed that hemin increased the overlap of Drp1 and mitochondria in PC12 cells. The phosphorylation and mitochondrial translocation of Drp1 were effectively reversed by HKL treatment. Importantly, the selective Sirt3 inhibitor 3-(1H-1,2,3-triazol-4-yl) pyridine suppressed these effects.

Conclusion:
Our findings demonstrated that HKL ameliorated ICH-induced apoptosis and mitochondrial fission by Sirt3, suggesting that HKL has immense prospects for the treatment of ICH.
Impact of vaccination against COVID-19 on the outcomes of in vitro fertilization–embryo transfer: a retrospective cohort study
Authors: Yin Jingwen , Wang Yang , Tao Liyuan , Chen Lixue , Liu Ping , Li Rong 
Published: February 2023

Abstract

Background:
Vaccination against coronavirus disease 2019 (COVID-19) has become the primary approach in the fight against the spread of COVID-19. Studies have shown that vaccination against COVID-19 has adverse effects, particularly on human reproductive health, despite the fact that vaccination rates are still on the rise. However, few studies have reported whether vaccination affects the outcome of in vitro fertilization–embryo transfer (IVF–ET) or not. In this study, we compared the outcome of IVF–ET and the development of follicles and embryos between vaccinated and unvaccinated groups.

Methods:
A single-center retrospective cohort study of 10,541 in vitro fertilization (IVF) cycles was conducted from June 2020 to August 2021. 835 IVF cycles with a history of vaccination against COVID-19 and 1670 IVF cycles that served as negative controls were selected and analyzed utilizing the Matchlt package of R software (http://www.R-project.org/) and the nearest neighbor matching algorithm for propensity-matched analysis at a 1:2 ratio.

Results:
The number of oocytes collected in the vaccinated group and the unvaccinated group were 8.00 (0, 40.00) and 9.00 (0, 77.00) (P = 0.073) and the good-quality embryo rates of the two groups were 0.56±0.32 and 0.56±0.31 averagely (P = 0.964). Clinical pregnancy rates for the vaccinated group and unvaccinated group were 42.4% (155/366) and 40.2% (328/816) (P = 0.486) and biochemical pregnancy rates were 7.1% (26/366) and 8.7% (71/816) (P = 0.355). Two other factors were analyzed in this study; vaccination among different genders and different types (inactivated vaccine or recombinant adenovirus vaccine) showed no statistically significant effect on the above outcomes.

Conclusions:
In our findings, vaccination against COVID-19 showed no statistically significant effect on the outcomes of IVF-ET and the development of follicles and embryos, nor did the gender of the vaccinated person or the formulation of vaccines showed significant effects.
Pseudolymphoma to Lymphoma: A Case of Chronic Reactive Lymphoid Hyperplasia Transforming to Primary Cutaneous Marginal Zone Lymphoma
Authors: Singh Neha , Fagan Kiley K. , Patel Riya T. , Grider Douglas J. 
Published: February 2023

Abstract:
Primary cutaneous marginal zone lymphoma (PCMZL) is a low-grade malignant B-cell lymphoma that originates from the skin. It often presents as erythematous solitary or multiple papules, nodules, and/or plaques. It is one of the 3 main subtypes of primary cutaneous B-cell lymphomas. PCMZLs are believed to develop from chronic antigenic stimulation such as from tick-borne bacteria, vaccines, tattoo pigment, or other foreign body. In addition, cutaneous lymphoid hyperplasia, a documented precursor to malignant PCMZL, often presents in response to areas of chronic inflammation. Cutaneous lymphoid hyperplasia and PCMZL share several clinical and histological similarities that require clinicopathologic suspicion, immunohistochemical ancillary studies, and histopathologic analysis to accurately differentiate the 2 entities. Although gene rearrangement studies have historically been of limited value in the diagnosis of PCMZL, recent studies investigating molecular markers have identified the presence of multiple genetic abnormalities that have helped to better characterize the disease and aid in diagnosis. In addition, newer studies have found associations between PCMZL and gastrointestinal disorders, including Helicobacter pylori and inflammatory bowel disorders. In this article, we describe a case of a 56-year-old patient with a history of ulcerative colitis presenting with chronic reactive lymphoid hyperplasia that transformed to primary cutaneous marginal zone lymphoma.
Impact of setanaxib on quality of life outcomes in primary biliary cholangitis in a phase 2 randomized controlled trial
Authors: Jones David , Carbone Marco , Invernizzi Pietro , Little Nicola , Nevens Frederik , Swain Mark G. , Wiesel Philippe , Levy Cynthia 
Published: February 2023

Background:
There is a real unmet need for primary biliary cholangitis (PBC) treatments that can improve quality of life impacting symptoms. In this post hoc analysis, we evaluated potential effects of the NADP oxidase 1/4 inhibitor, setanaxib, on patient-reported quality of life from a phase 2 trial in PBC.

Patients and Methods:
The underpinning double-blind, randomized, placebo-controlled trial (NCT03226067) recruited 111 patients with PBC and inadequate response/intolerance to ursodeoxycholic acid. Patients self-administered oral placebo (n=37), setanaxib 400 mg once daily (OD; n=38), or setanaxib 400 mg twice daily (BID; n=36), in addition to ursodeoxycholic acid for 24 weeks. Quality of life outcomes were assessed using the validated PBC-40 questionnaire. Patients were stratified post hoc by baseline fatigue severity.

Results:
At week 24, patients treated with setanaxib 400 mg BID reported greater mean (SE) absolute reductions from baseline in PBC-40 fatigue domain score [–3.6 (1.3)] versus those receiving setanaxib 400 mg OD [–0.8 (1.0)]) or placebo [0.6 (0.9)]. Similar observations were made across all PBC-40 domains except itch. In the setanaxib 400 mg BID arm, patients with moderate-to-severe fatigue at baseline had a greater reduction in mean fatigue score at week 24 [–5.8 (2.1)] versus those with mild fatigue [–0.6 (0.9)]; results were similar across all domains. Reduced fatigue was correlated with emotional, social, symptom, and cognitive improvements.

Conclusions:
These results support further investigation of setanaxib as a treatment for patients with PBC, particularly for those with clinically significant fatigue.