bluuebunny/crossref_metadata_2025_split huggingface dataset:
Duhuo Jisheng Decoction suppresses apoptosis and mitochondrial dysfunction in human nucleus pulposus cells by miR-494/SIRT3/mitophagy signal axis
Authors: Liu Wei , Zhao Xiaolong , Wu Xuejian 
Published: March 2023

Abstract
Background
Increasing evidence suggests that mitophagy is responsible for the pathogenesis of intervertebral disk (IVD) degeneration. Previous studies have shown that Duhuo Jisheng Decoction (DHJSD), a classic Fangji of traditional Chinese medicine, can delay IVD degeneration; however, its specific mechanism of action is unknown. In this study, we investigated the mechanism by which DHJSD treatment prevented IVD degeneration in IL-1β-treated human nucleus pulposus (NP) cells in vitro.

Methods
Cell Counting Kit-8 was performed to explore the effects of DHJSD on the viability of NP cells exposed to IL-1β. The mechanism by which DHJSD delays IVD degeneration was explored using luciferase reporter assay, RT-qPCR, western blotting, TUNEL assay, mitophagy detection assay, Mito-SOX, Mitotracker and in situ hybridization.

Results
We observed that DHJSD enhanced the viability of NP cells treated with IL-1β in a concentration-time dependent approach. Moreover, DHJSD lessened IL-1β-induced NP apoptosis and mitochondrial dysfunction and activated mitophagy in NP cells treated with IL-1β. Mitophagy suppressor cyclosporin A reversed the beneficial impacts of DHJSD in NP cells. In addition, the differential expression of miR-494 regulated IL-1β-induced NP apoptosis and mitochondrial dysfunction, and the protective impact of miR-494 on NP cells treated with IL-1β was achieved by mitophagy activation, which was regulated by its target gene, sirtuin 3 (SIRT3). Finally, we observed that DHJSD treatment could effectively delay IL-1β-induced NP apoptosis by affecting the miR-494/SIRT3/mitophagy signal axis.

Conclusions
These results show that the miR-494/SIRT3/mitophagy signaling pathway is responsible for the apoptosis and mitochondrial dysfunction of NP cells and that DHJSD may exert protective effects against IVD degeneration by regulating the miR-494/SIRT3/mitophagy signal axis.
Brazilian registry of patients with porphyria: REBRAPPO study
Authors: Souza Paulo Victor Sgobbi , Afonso Gliciane , de Rezende Pinto Wladimir Bocca Vieira , de Lima Serrano Paulo , de Mattos Lombardi Badia Bruno , Farias Igor Braga , dos Santos Jorge Ana Carolina , Machado Roberta Ismael Lacerda , Pinto Icaro França Navarro , Barros Glenda Barbosa , de Oliveira Helvia Bertoldo , Calil Samia Rogatis , Franz Cibele , Oliveira Acary Souza Bulle 
Published: March 2023

Abstract
Background
Porphyrias are a rare group of disease due to inherited defects of heme synthesis with important systemic manifestations and great burden of disease for patients and families due to the exceptional course of disease with disabling chronic symptoms interposed by life-threatening acute attacks. Unfortunately, the porphyrias are usually underrecognized reflecting a lack of medical and disease awareness as well as few studies about natural history in large cohorts of patients. The main aim of this article is present consistent data about natural history and burden of disease in a large Brazilian cohort.

Methods
We conducted a national cross-sectional registry with retrospective clinical data of Brazilian patients with porphyria collected with Brazilian patients Association with Porphyria in collaboration with a tertiary care center for rare diseases.

Results
A cohort of 172 patients was analyzed in which 148 (86%) patients had the diagnosis of acute hepatic porphyria [AHP] that needed a mean of 62.04 medical visits and 9.6 years to achieve a definitive diagnosis. About AHP cohort, the most common first clinical manifestation were abdominal pain in 77 (52%) patients and acute muscle weakness in 23 (15.5%) with 73 (49.3%) patients presenting only one attack during disease course and 37 (25%) exhibiting 4 or more attacks in the last year. Of note, 105 patients with AHP reported chronic manifestations and the scores for quality of life are lower when compared with general healthy population.

Conclusions
Brazilian patients with AHP had a higher prevalence of chronic disabling manifestations and a poor quality of life like other cohorts and a higher proportion of patients with recurrent attacks than previously reported.
Clinical, biochemical, and genetic analysis of 28 Chinese patients with holocarboxylase synthetase deficiency
Authors: Ling Shiying , Qiu Wenjuan , Zhang Huiwen , Liang Lili , Lu Deyun , Chen Ting , Zhan Xia , Wang Yu , Gu Xuefan , Han Lianshu 
Published: March 2023

Abstract
Background
This study aimed to describe the clinical, biochemical, and molecular characteristics of Chinese patients with holocarboxylase synthetase (HLCS) deficiency, and to investigate the mutation spectrum of HCLS deficiency as well as their potential correlation with phenotype.

Methods
A total of 28 patients with HLCS deficiency were enrolled between 2006 and 2021. Clinical and laboratory data were reviewed retrospectively from medical records.

Results
Among the 28 patients, six patients underwent newborn screening, of which only one was missed. Therefore, 23 patients were diagnosed because of disease onset. Among all the patients, 24 showed varying degrees of symptoms such as rash, vomiting, seizures, and drowsiness, while only four cases remained asymptomatic nowadays. The concentration of 3-hydroxyisovalerylcarnitine (C5-OH) in blood and pyruvate, 3-hydroxypropionate, methylcitric acid, 3-hydroxyvaleric acid, 3-methylcrotonylglycine in urine were increased greatly among affected individuals. After prompt supplement of biotin, both the clinical and biochemical symptoms were dramatically resolved and nearly all patients developed normal intelligence and physique on follow-up. DNA sequencing revealed 12 known and 6 novel variants in the HLCS gene of patients. Among them, the variant of c.1522C > T was the most common.

Conclusions
Our findings expanded the spectrum of phenotypes and genotypes for HLCS deficiency in Chinese populations and suggested that with timely biotin therapy, patients with HLCS deficiency showed low mortality and optimistic prognosis. Newborn screening is crucial for early diagnosis, treatment, and long-term outcomes.
Thrombocytopenia and PT-INR in patients with anorexia nervosa and severe liver dysfunction
Authors: Kurisu Ken , Sato Kaoruko , Matsuoka Mikiko , Otani Makoto , Yoshiuchi Kazuhiro 
Published: March 2023

Abstract
Background
We previously reported a case that led us to hypothesize that decreased production of thrombopoietin (TPO) leads to thrombocytopenia in patients with anorexia nervosa (AN) with severe liver dysfunction and that prolonged prothrombin time-international normalized ratio (PT-INR) predicts thrombocytopenia in such cases. To validate this hypothesis, we report another case in which TPO levels were measured. In addition, we examined the association between prolonged PT-INR and thrombocytopenia in such patients.

Main body
Similar to the previously reported patient, a patient with AN with severe liver dysfunction showed that TPO levels increased after improvements in liver enzyme levels and PT-INR, followed by recovery of platelet count. In addition, a retrospective study was also conducted to review patients with AN whose liver enzyme levels were > 3 × the upper limit of normal (aspartate aminotransferase > 120 U/L or alanine aminotransferase > 135 U/L). The study included 58 patients and showed a correlation coefficient of -0.486 (95% confidence interval [CI], -0.661 to -0.260; P < 0.001) between maximum PT-INR and minimum platelet count. These patients showed higher PT-INR (β, 0.07; 95% CI, 0.02 to 0.13; P = 0.005) and lower platelet count (β, -5.49; 95% CI, -7.47 to -3.52; P < 0.001) than the 58 matched control patients without severe liver dysfunction, even after adjusting for body mass index.

Conclusions
In patients with AN with severe liver dysfunction, prolongation of PT-INR could predict thrombocytopenia, which may be mediated by decreased TPO production due to decreased hepatic synthetic function.
Are population level familial risks and germline genetics meeting each other?
Authors: Hemminki Kari , Li Xinjun , Försti Asta , Eng Charis 
Published: March 2023

AbstractLarge amounts of germline sequencing data have recently become available and we sought to compare these results with population-based family history data. Family studies are able to describe aggregation of any defined cancers in families. The Swedish Family-Cancer Database is the largest of its kind in the world, covering the Swedish families through nearly a century with all cancers in family members since the start of national cancer registration in 1958. The database allows estimation of familial risks, ages of cancer onset and the proportion of familial cancer in different family constellations. Here, we review the proportion of familial cancer for all common cancers and specify them based on the number of affected individuals. With the exception of a few cancers, age of onset of familial cancer is not different from all cancers combined. The highest proportions of familial cancer were found for prostate (26.4%), breast (17.5%) and colorectal (15.7%) cancers, but the proportions of high-risk families with multiple affected individuals were only 2.8%, 1% and 0.9%, respectively. A large sequencing study on female breast cancer found that BRCA1 and BRCA2 mutations could account for 2% of the cases (subtracting the proportions in healthy individuals) and that all germline mutations accounted for 5.6% of the cases. Early age of onset was a distinct feature of only BRCA mutations. In heritable colorectal cancer, Lynch syndrome genes dominate. Large studies on penetrance in Lynch syndrome have shown an approximately linear increase in risk from 40–50 years up to age 80 years. Interesting novel data revealed a strong modification of familial risk by unknown factors. High-risk germline genetics of prostate cancer is characterized by BRCA and other DNA repair genes. HOXB13 encodes a transcription factor which contributes to germline risk of prostate cancer. A strong interaction was shown with a polymorphism in the CIP2A gene. The emerging germline landscape of common cancers can be reasonably accommodated by family data on these cancers as to high-risk proportions and age of onset.
Implementation of offering choice of pulmonary rehabilitation location to people with COPD: a protocol for the process evaluation of a cluster randomised controlled trial
Authors: Cox Narelle S , Holland Anne E , Jones Arwel W , McDonald Christine F , O’Halloran Paul , Mahal Ajay , Hepworth Graham , Lannin Natasha A 
Published: March 2023

Abstract
Background
Pulmonary rehabilitation (PR) is a core component of management people with chronic obstructive pulmonary disease (COPD); yet, people with COPD face significant barriers to attending centre-based PR programs. The emergence of new models of PR, remotely delivered directly into people’s homes, has the potential to improve rehabilitation access and completion by providing patients with a choice of rehabilitation location (centre or home). However, offering patients a choice of rehabilitation model is not usual practice. We are undertaking a 14-site cluster randomised controlled trial to determine whether offering choice of PR location improves rehabilitation completion rates resulting in reduced all-cause unplanned hospitalisation over 12 months. The aim of this paper is to describe the protocol for the process evaluation of the HomeBase2 trial.

Methods
A mixed methods process evaluation, to be undertaken in real time, has been developed in accordance with UK Medical Research Council (MRC) recommendations on process evaluation of complex interventions. This protocol describes the intended use of two theoretical frameworks (RE-AIM framework (Reach; Effectiveness; Adoption; Implementation; Maintenance) and Theoretical Domains Framework (TDF)) to synthesise findings and interpret data from a combination of qualitative (semi-structured interviews) and quantitative (questionnaires, clinical outcome data, intervention fidelity) methodologies. Data will be collected at an intervention, patient and clinician level. Qualitative and quantitative data will be used to derive context-specific potential and actual barriers and facilitators to offering patients choice of rehabilitation location. Acceptability and sustainability of the intervention will be evaluated for future scale-up.

Discussion
The process evaluation described here will appraise the clinical implementation of offering a choice of rehabilitation program location for people with COPD. It will identify and evaluate key factors for future scale-up and sustainability and scale-up of offering choice of pulmonary rehabilitation program model for people.

Trial registration
ClinicalTrials.gov NCT04217330 Registration date: January 3 2020.
Internet-based stress recovery intervention for adolescents: study protocol for a randomized controlled trial
Authors: Zelviene Paulina , Kairyte Agniete , Dumarkaite Austeja , Nomeikaite Augustė , Kazlauskas Evaldas 
Published: March 2023

Abstract
Background
Research reveals a high prevalence of stressors in adolescence. Mental health in adolescence is highly related to life-stressors exposure and difficulties in adjusting to stressors. Therefore, interventions for recovery from stress are in high demand. The study aims to evaluate the efficacy of the Internet-based stress recovery intervention for adolescents.

Methods
A two-arm randomized controlled trial (RCT) on the efficacy of the FOREST-A—an Internet-based stress recovery intervention for adolescents—will be conducted. The FOREST-A is an adapted version of stress recovery intervention initially developed for healthcare workers. FOREST-A is a third-wave cognitive behavioral therapy and mindfulness-based Internet-delivered 4-week psychosocial intervention, which comprises six modules: Introduction, Relaxation, Psychological detachment, Mastery, Control, and Summary. The intervention will be evaluated using the two-arm RCT with intervention and care as usual (CAU) condition at pre-test, post-test, and 3-month follow-up. The measured outcomes will be stress recovery, adjustment disorder, generalized anxiety and depression symptoms, psychological well-being, and perceived positive social support.

Discussion
The study will contribute to the development of Internet interventions—easily and broadly accessible tools—for the enhancement of adolescents’ stress recovery skills. Based on the study’s findings, further development of the FOREST-A, including upscaling and implementation, is foreseen.

Trial registration
ClinicalTrials.gov NCT05688254. Registered on January 6, 2023.
Caffeine ameliorates the metabolic syndrome in diet-induced obese mice through regulating the gut microbiota and serum metabolism
Authors: Chen Li , Wang Xian-jun , Chen Jie-xin , Yang Jing-cheng , Ling Lin  , Cai Xian-Bin , Chen Yong-song 
Published: March 2023

Abstract
Objective
Obesity is associated with gut microbiota disorders, which has been related to developing metabolic syndromes. The research aims to investigate the effects of caffeine treatment on insulin resistance, intestinal microbiota composition and serum metabolomic changes in high-fat diet (HFD)-induced obesity mice.

Methods
Eight-week-old male C57BL/6 J mice were fed a normal chow diet (NCD) or HFD with or without different concentrations of caffeine. After 12 weeks of treatment, body weight, insulin resistance, serum lipid profiles, gut microbiota and serum metabolomic profiles were assessed.

Results
Caffeine intervention improved the metabolic syndrome in HFD-fed mice, such as serum lipid disorders and insulin resistance. 16S rRNA Sequencing analysis revealed that caffeine increased the relative abundance of Dubosiella, Bifidobacterium and Desulfovibrio and decreased that of Bacteroides, Lactobacillus and Lactococcus to reverse HFD-fed obesity in mice. Additionally, Caffeine Supplementation also altered serum metabolomics, mainly focusing on lipid metabolism, bile acid metabolism and energy metabolism. Caffeine increased its metabolite 1,7-Dimethylxanthine, which was positively correlated with Dubosiella.

Conclusions
Caffeine exerts a beneficial effect on insulin resistance in HFD-mice, and the underlying mechanism may be partly related to altered gut microbiota and bile acid metabolism.
Liquid biopsy by analysis of circulating myeloma cells and cell-free nucleic acids: a novel noninvasive approach of disease evaluation in multiple myeloma
Authors: Li Shuchan , Zhang Enfan , Cai Zhen 
Published: March 2023

AbstractMultiple myeloma (MM) is an incurable hematological cancer with high spatial- and temporal-heterogeneity. Invasive single-point bone marrow sampling cannot capture the tumor heterogeneity and is difficult to repeat for serial assessments. Liquid biopsy is a technique for identifying and analyzing circulating MM cells and cell products produced by tumors and released into the circulation, allowing for the minimally invasive and comprehensive detection of disease burden and molecular alterations in MM and monitoring treatment response and disease progression. Furthermore, liquid biopsy can provide complementary information to conventional detection approaches and improve their prognostic values. This article reviewed the technologies and applications of liquid biopsy in MM.
Free sugar intake from snacks and beverages in Canadian preschool- and toddler-aged children: a cross-sectional study
Authors: Yu Jessica , Mahajan Anisha , Darlington Gerarda , Buchholz Andrea C. , Duncan Alison M. , Haines Jess , Ma David W. L. ,   Guelph Family Health Study
Published: March 2023

Abstract
Background
Excess consumption of free sugar (FS) increases the risk of dental caries and unhealthy weight gain. However, the contribution of snacks and beverages to young children’s FS intake is not well understood. The purpose of this study was to determine FS intake from snacks and beverages among preschool-aged Canadian children.

Methods
This cross-sectional study examined baseline data from 267 children 1.5 to 5 y enrolled in the Guelph Family Health Study. Dietary assessment was completed over a 24-h period using ASA24-Canada-2016 to, 1) estimate the proportion of children whose FS intake from snacks and beverages consumed exceeded 5% total energy intake (TE) and 10% TE, and 2) identify the top snack and beverage sources of FS.

Results
FS contributed 10.6 ± 6.9% TE (mean ± SD). 30 and 8% of children consumed ≥ 5% TE and ≥ 10% TE from snack FS, respectively. Furthermore, 17 and 7% of children consumed ≥ 5% TE and ≥ 10% TE from beverages FS, respectively. Snacks and beverages accounted for 49 ± 30.9% of FS energy. Top snack sources of FS (% children, children’s %TE from FS) were bakery products (55%, 2.4%), candy and sweet condiments (21%, 3.0%), and sugar-containing beverages (20%, 4.1%). Top sugar-containing beverage sources of FS (48%, 5.3%) were 100% fruit juice (22%, 4.6%) and flavored milk (11%, 3.1%).

Conclusions
Snacks and beverages contributed nearly half of FS intake among a sample of young children in Canada. Thus, long-term monitoring of snacking behavior and consumption of FS is warranted. These findings may help inform nutritional strategies and public policies to improve diet quality and FS intake in preschool-aged children.

Trial registration
The Clinical Trial Registry number is NCT02939261 from clinicaltrials.gov. Date of Registration: October 20, 2016.
Cancer Treatment-Related Ovarian Dysfunction in Women of Childbearing Potential: Management and Fertility Preservation Options
Authors: Reynolds Anna C. , McKenzie Laurie J. 
Published: March 2023

PURPOSE To review the complex concerns of oncofertility created through increased cancer survivorship and the long-term effects of cancer treatment in young adults. DESIGN Review chemotherapy-induced ovarian dysfunction, outline how fertility may be addressed before treatment initiation, and discuss barriers to oncofertility treatment and guidelines for oncologists to provide this care to their patients. CONCLUSION In women of childbearing potential, ovarian dysfunction resulting from cancer therapy has profound short- and long-term implications. Ovarian dysfunction can manifest as menstrual abnormalities, hot flashes, night sweats, impaired fertility, and in the long term, increased cardiovascular risk, bone mineral density loss, and cognitive deficits. The risk of ovarian dysfunction varies between drug classes, number of received lines of therapy, chemotherapy dosage, patient age, and baseline fertility status. Currently, there is no standard clinical practice to evaluate patients for their risk of developing ovarian dysfunction with systemic therapy or means to address hormonal fluctuations during treatment. This review provides a clinical guide to obtain a baseline fertility assessment and facilitate fertility preservation discussions.
Coverage and Cost-of-Care Links: Addressing Financial Toxicity Among Patients With Hematologic Cancer and Their Caregivers
Authors: Edward Jean S. , McLouth Laurie E. , Rayens Mary Kay , Eisele Lori P. , Davis Tani S. , Hildebrandt Gerhard 
Published: March 2023

PURPOSE This study examined the feasibility, acceptability, and preliminary effectiveness of an oncology financial navigation (OFN) intervention, Coverage and Cost-of-Care Links ( CC Links), among patients with hematologic cancer and their caregivers who are at increased risk of experiencing financial toxicity (FT). METHODS All patients who presented to the Division of Hematology and Bone and Marrow Transplant (BMT) at an National Cancer Institute–designated cancer center between April 2021 and January 2022 were screened for FT during inpatient and outpatient visits. Patients who screened positive for FT and met the inclusion criteria were recruited to participate in CC Links that provided financial navigation and assistance via a financial navigator. Caregivers of patients undergoing BMTs were also recruited to participate. Primary outcomes were defined as improvements in FT, distress, and physical and mental quality of life. RESULTS Fifty-four patients and 32 caregivers completed the intervention and pre-/postintervention surveys. CC Links resulted in statistically significant decreases in the Comprehensive Score for FT for both patients (| t| = 2.42, P = .019) and caregivers (| t| = 2.43, P = .021) and total FT (| t| = 2.13, P = .041) and material conditions scores (| t| = 2.25, P = .031) for caregivers only. Only 27% of eligible patients participated in the study, whereas 100% of eligible caregivers participated. The majority of participants rated the intervention highly for acceptability (89%) and appropriateness (88%). An average of $2,500 (USD) in financial benefits was secured per participant via CC Links. CONCLUSION CC Links was effective in decreasing FT among patients with hematologic cancer and their caregivers while demonstrating high acceptability and appropriateness ratings.
Geometric phase acquired by the two-level atom with different trajectories in cosmic string scalar field
Authors: Yang Ying , Zhang Yao , Fu Xiangyun , Jing Jiliang 
Published: March 2023

Abstract
We consider the geometric phase induced by the two-level atom with inertial and uniformly accelerated motion, which is coupled to massless scalar field in cosmic string spacetime. Our result shows that when the atom is very close to the string, the geometric phase of cosmic string spacetime is ν times that of Minkowski spacetime. By comparing phase difference induced by the inertial and accelerated motion, we find the sensitive dependence of the phase difference on deficit angle parameter, transition frequencies of the atom, atomic acceleration and the initial state parameter. We also obtain phase difference increases with deficit angle parameter and the atomic acceleration. Although reaching the measurable magnitude of geometric phase requires extremely high acceleration, the detection experiment may be implemented in the future. Our work may suggest a possible way to detect cosmic string scalar field by using geometric phase.