bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cost-effectiveness analysis of newborn screening by tandem mass spectrometry in Shenzhen, China: value and affordability of new screening technology
Authors: Yu Mingren , Xu Juan , Song Xiaohong , Du Jiayue 
Published: August 2022

AbstractBackgroundNewborn screening (NBS) can prevent inborn errors of metabolism (IEMs), which may cause long-term disability and even death in newborns. However, in China, tandem mass spectrometry (MS/MS) screening has just started. This study aimed to assess the cost-effectiveness of NBS using MS/MS in Shenzhen under the nationally recommended program, as well as evaluate the value and affordability of introducing this new screening technology.MethodsA Markov model was built to estimate the cost and quality-adjusted life-years (QALYs) of different screening programs. We compared PKU screening using traditional immunofluorescence (IF) with the other 11 IEMs not screened and all 12 IEMs screened using MS/MS, and the programs detecting different numbers of IEMs chosen from the national recommended program were also compared. A sensitivity analysis and budget impact analysis (BIA) were performed.ResultsThe incremental cost-effectiveness ratio (ICER) of detecting all 12 IEMs in the national program is 277,823 RMB per QALY, below three times per capita GDP in Shenzhen. MS/MS screening in Shenzhen can be cost-effective only if at least three diseases (PKU, PCD and MMA) are covered and when the screening program covers five diseases (PKU, PCD, MMA, MSUD, IVA), the ICER closely approaches its critical threshold. The BIA indicated the implementation cost of the national program to be around 490 million RMB over 10 years and showed no difference in budget between programs detecting different numbers of IEMs.ConclusionsWe conclude that the newborn screening using MS/MS in Shenzhen is cost-effective, and the budget affordable for the Shenzhen government. Two concepts for selecting the IEMs to be detected are also presented. One is to choose the most cost-effective screening programs detecting highest number of IEMs to achieve a minimal ICER. The other considers the curability and affordability of the disease as the basis of healthcare decisions to screen suitable IEMs, achieving an ICER under the threshold and close to the minimum value.
Novel compound heterozygous mutations in the desert hedgehog (DHH) gene in cases of siblings with 46,XY disorders of sexual development
Authors: Wei Jia , Wu Jiaqi , Ru Wei , Chen Guangjie , Gao Lei , Tang Daxing 
Published: August 2022

Abstract
Background
Disorders of sex development (DSD) are congenital disorders in which the development of the chromosomal, gonadal, or anatomical sex is atypical. Mutations in various genes can impede gonadal development, hormone synthesis, or hormone function and cause DSD.

Methods
Exome sequencing was performed for two siblings with 46,XY DSD. All mutations identified by exome sequencing were confirmed by Sanger sequencing.

Results
The 13-month-old younger sibling had a female appearance of the external genital with a clitoris that was assessed as Prader III and scored 2 in the external masculinization score evaluative test. The 16-year-old elder sibling had severe hypospadias. Exome sequencing revealed compound heterozygous mutations in exon 3 of DHH in the siblings with 46,XY DSD. The frameshift mutation (NM_021044.3: c.602delC) was derived from the father and was predicted to be deleterious. The (c.937G > T) substitution mutation was derived from the mother.

Conclusions
Novel compound heterozygous mutations of DHH led to 46,XY DSD in two siblings. This study expands the phenotypic mutation spectra of DHH in patients with 46,XY DSD.
Potential mechanisms of quercetin in cancer prevention: focus on cellular and molecular targets
Authors: Asgharian Parina , Tazekand Abbas Pirpour , Hosseini Kamran , Forouhandeh Haleh , Ghasemnejad Tohid , Ranjbar Maryam , Hasan Muzaffar , Kumar Manoj , Beirami Sohrab Minaei , Tarhriz Vahideh , Soofiyani Saiedeh Razi , Kozhamzharova Latipa , Sharifi-Rad Javad , Calina Daniela , Cho William C. 
Published: August 2022

AbstractOver the past few years, the cancer-related disease has had a high mortality rate and incidence worldwide, despite clinical advances in cancer treatment. The drugs used for cancer therapy, have high side effects in addition to the high cost. Subsequently, to reduce these side effects, many studies have suggested the use of natural bioactive compounds. Among these, which have recently attracted the attention of many researchers, quercetin has such properties. Quercetin, a plant flavonoid found in fresh fruits, vegetables and citrus fruits, has anti-cancer properties by inhibiting tumor proliferation, invasion, and tumor metastasis. Several studies have demonstrated the anti-cancer mechanism of quercetin, and these mechanisms are controlled through several signalling pathways within the cancer cell. Pathways involved in this process include apoptotic, p53, NF-κB, MAPK, JAK/STAT, PI3K/AKT, and Wnt/β-catenin pathways. In addition to regulating these pathways, quercetin controls the activity of oncogenic and tumor suppressor ncRNAs. Therefore, in this comprehensive review, we summarized the regulation of these signalling pathways by quercetin. The modulatory role of quercetin in the expression of various miRNAs has also been discussed. Understanding the basic anti-cancer mechanisms of these herbal compounds can help prevent and manage many types of cancer.
Qualitative and quantitative assessment of sperm miRNAs identifies hsa-miR-9-3p, hsa-miR-30b-5p and hsa-miR-122-5p as potential biomarkers of male infertility and sperm quality
Authors: Joshi Meghali , Andrabi Syed Waseem , Yadav Ranjeet Kumar , Sankhwar Satya Narayan , Gupta Gopal , Rajender Singh 
Published: August 2022

Abstract
Background
In contrast with the preceding stages of the germ cells, spermatozoa are unusually rich in small non-coding RNAs in comparison to the coding RNAs. These small RNAs may have had an essential role in the process of spermatogenesis or may have critical roles in the post-fertilization development. Sporadic efforts have identified a few differentially expressed miRNAs in infertile individuals, which do not replicate in other studies.

Methods
In order to identify miRNAs signatures of infertility or poor sperm quality, we compared miRNA differential expression data across nine datasets, followed by their analysis by real-time PCR in a case–control study. This was followed by the validation of potential biomarkers in yet another set of cases and controls. For this, total RNA was isolated from 161 sperm samples. miRNA expression levels in infertile cases and fertile controls were measured using TaqMan real-time PCR. Meta-analyses of two miRNAs (hsa-miR-9-3p and hsa-miR-122-5p) were performed using Comprehensive Meta‐Analysis Software (version 2). All statistical analyses were performed with the help of GraphPad Prism Software (version 8).

Results
Literature search identified seven miRNAs (hsa-let-7a-5p, hsa-miR-9-3p, hsa-miR-22-5p, has-miR-30b-5p, hsa-miR-103-3p, hsa-miR-122-5p and hsa-miR-335-5p) showing consistent dysregulation in infertility across a minimum of four studies. In the discovery phase, six miRNAs showed strong association with infertility with four (hsa-miR-9-3p, hsa-miR-30b-5p, hsa-miR-103-3p and hsa-miR-122-5p) showing consistent differential regulation across all sub-groups. Receiver operating characteristic (ROC) curve analysis showed that the area under curve of > 0.75 was achieved by three (hsa-mir-9-3p, hsa-miR-30b-5p and hsa-miR-122-5p) miRNAs. In the validation phase, these three miRNAs showed consistent association with infertility (hsa-mir-9-3p, hsa-miR-30b-5p, and hsa-miR-122-5p). Meta-analysis on hsa-miR-122-5p showed its significant quantitative association with infertility [Hedge’s g = -2.428, p = 0.001 (Random effects)].

Conclusions
Three miRNAs (hsa-miR-9-3p, hsa-miR-30b-5p and hsa-miR-122-5p) have strong linkage with infertility and a high potential as sperm quality biomarkers.
Hyperphosphorylated tau mediates neuronal death by inducing necroptosis and inflammation in Alzheimer’s disease
Authors: Dong Yue , Yu Hanqiao , Li Xueqi , Bian Kelong , Zheng Yayuan , Dai Mingrui , Feng Xuejian , Sun Yao , He Yu , Yu Bin , Zhang Haihong , Wu Jiaxin , Yu Xianghui , Wu Hui , Kong Wei 
Published: August 2022

Abstract
Background
Progressive neuronal death is the key pathological feature of Alzheimer’s disease (AD). However, the molecular mechanisms underlying the neuronal death in AD patients have not been fully elucidated. Necroptosis reportedly activates and induces neuronal death in patients with Alzheimer’s disease (AD); however, the main mediators and mechanisms underlying necroptosis induction in AD remain elusive.

Methods
The function of hyperphosphorylated tau (pTau) in inducing necroptosis in neuronal cell was examined using Western blotting, RT-PCR and flow cytometry. Tau-induced inflammation was identified via RNA sequencing and transwell assay. Pharmacological methods and CRISPR–Cas9 technology were used to verify the role of necrosome proteins in pTau-stimulated neuronal death and inflammation. TauP301S model mice were treated with Nec-1 s to evaluate the role of necroptosis in tau pathology.

Results
Hyperphosphorylated tau could induce necroptosis in neuronal cells by promoting the formation of the RIPK1/RIPK3/MLKL necrosome. In addition, pTau significantly stimulated cell-autonomous overexpression of cytokines and chemokines via the intracellular nuclear factor kappa B (NF-κB) signaling pathway. Importantly, the RIPK1/RIPK3/MLKL axis was essential for the pTau-mediated NF-κB activation and cytokine storm. Furthermore, necroptosis stimulation, NF-κB activation, and cytokine induction have been detected in TauP301S mice and blocking necroptosis markedly ameliorated behavioral defects and excessive neuroinflammation in AD mice.

Conclusions
Our study, for the first time, revealed that pTau contributes to neuronal death by inducing necroptosis and inflammation, mediated by activating the RIPK1/RIPK3/MLKL and NF-κB pathways, thereby delineating the hierarchical molecular network of neuronal necroptosis induction in AD.
Evaluation of anti-Müllerian hormone in pre-menopausal women stratified according to thyroid function, autoimmunity and age
Authors: Giusti Massimo , Mittica Miranda 
Published: August 2022

Abstract
Background
AMH is a reliable index of ovarian reserve. It is not clear whether, or how much, thyroid function and/or thyroid autoimmunity can impair ovarian function and AMH secretion in the long term.

Aim
This retrospective cross-sectional study compared AMH levels in pre-menopausal women with/without positive thyroid autoimmunity or hypofunction.

Methods
From January 2019 to May 2022, AMH was evaluated in 250 pre-menopausal women not undergoing assisted fertility procedures who were referred to a secondary endocrine centre. Thyroid function and autoimmunity, sonographically measured thyroid volume, FSH and E2 in the early follicular phase, and PRL and progesterone in the luteal phase were also evaluated. Exclusion criteria were: age < 18 years, genetic hypogonadism, pregnancy and previous treatments that have potentially damaging effects on gonads.

Results
We evaluated 171 women (mean age ± SD: 31.5 ± 9.0 years) off L-T4 treatment and 79 women on L-T4 treatment (39.7 ± 9.5 years; P < 0.001). AMH (median, IQR, CI) was 16.1 pmol/l (7.1 – 35.7 pmol/l, 21.4 – 29.9 pmol/l) and 7.6 pmol/l (1.4 – 17.8 pmol/l, 8.6 – 14.7 pmol/l; P < 0.001), respectively. When the women were stratified according to age (18-25, 26-30, 31-35, 36-40, 41-45, > 46 years) no significant difference emerged between those on/off L-T4 treatment in groups of the same age-range. In women on- or off-L-T4 treatment, AMH was negatively related with age on univariate and multivariate analyses (P < 0.0001). In both groups, AMH was negatively related to FSH (P < 0.0001). On multivariate analysis, AMH was positively related to the age of the mother on spontaneous menopause (P = 0.006) and negatively to thyroid volume (P = 0.02) in women on L-T4. AMH levels were significantly (P = 0.03) higher in TPOAb-negative than in TPOAb-positive women, but age was significantly (P = 0.001) lower in TPOAb-negative than in TPOAb-positive women.

Conclusions
In our cohort of women, age proved to be a better predictor of AMH levels than any of the other factors linked to thyroid function and autoimmunity. Our data do not support the hypothesis that subclinical hypothyroidism and/or autoimmunity are associated with decreased ovarian reserve. However, a larger number of cases is needed in order to obtain conclusive data.
Interviews with primary care physicians identify unmet transition needs after ICU
Authors: Hauschildt Katrina E. , Hechtman Rachel K. , Prescott Hallie C. , Cagino Leigh M. , Iwashyna Theodore J. 
Published: August 2022

Abstract
Aim
We sought to explore unmet needs in transitions of care for critical illness survivors that concern primary care physicians.

Findings
Semi-structured interviews with primary care physicians identified three categories of concerns about unmet transition needs after patients’ ICU stays: patients’ understanding of their ICU stay and potential complications, treatments or support needs not covered by insurance, and starting and maintaining needed rehabilitation and assistance across transitions of care.

Conclusion
Given current constraints of access to coordinated post-ICU care, efforts to identify and address the post-hospitalization needs of critical illness survivors may be improved through coordinated work across the health system.
Face Your Fears: Virtual reality-based cognitive behavioral therapy (VR-CBT) versus standard CBT for paranoid ideations in patients with schizophrenia spectrum disorders: a randomized clinical trial
Authors: Jeppesen U. N. , Due A. S. , Mariegaard L. , Pinkham A. , Vos M. , Veling W. , Nordentoft M. , Glenthøj L. B. 
Published: August 2022

Abstract
Background
Schizophrenia spectrum disorders cause suffering for patients, relatives, and the surrounding society. Paranoid ideations, encompassing ideas of social reference and manifest persecutory delusions, are among the most frequent symptoms in this population and a cause of significant distress. Recent meta-analyses of cognitive behavioral therapy (CBT) for psychosis show small to moderate effect sizes in reducing paranoid ideations. Virtual reality-based CBT (VR-CBT) could improve therapy efficacy as exposure and behavioral experiments in VR can be optimized, individualized, and carried out in a safe environment. Few VR-CBT studies exist for paranoid ideations and there is a need for large-scale, methodologically rigorous trials.

Methods
This study is a randomized, assessor-blinded parallel-groups multi-center superiority clinical trial, fulfilling the CONSORT criteria for non-pharmacological treatment. A total of 256 patients diagnosed with schizophrenia spectrum disorder, including schizotypal disorder (ICD-10 F20-29), will be allocated to either 10 sessions of symptom-specific CBT-VR plus treatment as usual—versus 10 sessions of standard symptom-specific CBT for paranoid ideations (CBT) plus treatment as usual. All participants will be assessed at baseline, treatment end (3 months post baseline), and then 9 months post baseline. A stratified block-randomization with concealed randomization sequence will be conducted. Independent assessors blinded to the treatment will evaluate the outcome. Analysis of outcome will be carried out with the intention to treat principles.
The primary outcome is ideas of social reference measured with Green Paranoid Thought Scale Part A (GPTS-A) at the cessation of treatment at 3 months post baseline. Secondary outcomes are ideas of persecution (GPTS-B), Social Interaction Anxiety Scale (SIAS), Personal and Social Performance scale (PSP), Safety Behavior Questionnaire (SBQ), and CANTAB Emotion Recognition Task.

Discussion
The trial will elucidate whether VR-CBT can enhance therapy efficacy for paranoid ideations. Additionally, Trial findings will provide evidence on the effectiveness and cost-effectiveness of VR-CBT for paranoid ideations that can guide the possible dissemination and implementation into clinical practice.

Trial registration
ClinicalTrials.govNCT04902066. Initial release April 9th, 2021.
Study protocol for a pragmatic cluster RCT on the effect and cost-effectiveness of Everyday Life Rehabilitation versus treatment as usual for persons with severe psychiatric disability living in sheltered or supported housing facilities
Authors: Lindström Maria , Lindholm Lars , Liv Per 
Published: August 2022

AbstractBackgroundPeople with severe psychiatric disabilities and impaired autonomy, living in sheltered or supported housing facilities, often lead sedentary, solitary lives indoors and have significantly poorer health than others in the population. Meaningful everyday activities are important for the recovery towards an enrichening, agentic, social, and hopeful everyday life. The Everyday Life Rehabilitation (ELR) model—a person-centred activity- and recovery-oriented intervention—has shown positive outcomes in feasibility studies, and thus a randomised controlled trial (RCT) is required to establish the effectiveness of ELR, along with calculations of cost-effectiveness.MethodsThe ELR-RCT is a pragmatic, two-parallel-armed cluster RCT evaluating the effect and cost-effectiveness of using ELR from two measurement points over 6 months (pre-post intervention) and in three waves over 3 years. The primary outcome is recovering quality of life (ReQoL) at 6 months, and the secondary outcome is self-perceived recovery and daily functioning (RAS-DS) at 6 months. Additionally, Goal Attainment Scaling (GAS) will be used for the intervention group. Power analysis has been conducted for primary outcome measure. The first wave will include an internal pilot, to be evaluated after 6 months, used as basis for decisions on updating the required sample size and any other need for adaptations before continuing with the full-scale RCT in the second and third wave. All municipalities within a geographic area in northern Sweden, with a minimum of one sheltered or supported housing facility for people with severe psychiatric or neuropsychiatric disability, including access to occupational therapy, will be enrolled. Participants will be block-randomised to receive ELR plus treatment as usual (TAU) or TAU alone for a control period. The control group will thereafter receive delayed ELR. Occupational therapists and housing staff will receive an educational package, manuals, and tools, as well as reflections with colleagues during the intervention period. Housing managers will receive questions for monthly follow-up and coaching with staff.DiscussionThis is a protocol for both an internal pilot and full trial of the first RCT study using the ELR intervention model in sheltered or supported housing facilities, evaluating the effects together with cost-effectiveness.Trial registrationClinicalTrials.gov NCT05056415. Registered on 24 September 2021.
Prolonged FOS activity disrupts a global myogenic transcriptional program by altering 3D chromatin architecture in primary muscle progenitor cells
Authors: Barutcu A. Rasim , Elizalde Gabriel , Gonzalez Alfredo E. , Soni Kartik , Rinn John L. , Wagers Amy J. , Almada Albert E. 
Published: August 2022

Abstract
Background
The AP-1 transcription factor, FBJ osteosarcoma oncogene (FOS), is induced in adult muscle satellite cells (SCs) within hours following muscle damage and is required for effective stem cell activation and muscle repair. However, why FOS is rapidly downregulated before SCs enter cell cycle as progenitor cells (i.e., transiently expressed) remains unclear. Further, whether boosting FOS levels in the proliferating progeny of SCs can enhance their myogenic properties needs further evaluation.

Methods
We established an inducible, FOS expression system to evaluate the impact of persistent FOS activity in muscle progenitor cells ex vivo. We performed various assays to measure cellular proliferation and differentiation, as well as uncover changes in RNA levels and three-dimensional (3D) chromatin interactions.

Results
Persistent FOS activity in primary muscle progenitor cells severely antagonizes their ability to differentiate and form myotubes within the first 2 weeks in culture. RNA-seq analysis revealed that ectopic FOS activity in muscle progenitor cells suppressed a global pro-myogenic transcriptional program, while activating a stress-induced, mitogen-activated protein kinase (MAPK) transcriptional signature. Additionally, we observed various FOS-dependent, chromosomal re-organization events in A/B compartments, topologically associated domains (TADs), and genomic loops near FOS-regulated genes.

Conclusions
Our results suggest that elevated FOS activity in recently activated muscle progenitor cells perturbs cellular differentiation by altering the 3D chromosome organization near critical pro-myogenic genes. This work highlights the crucial importance of tightly controlling FOS expression in the muscle lineage and suggests that in states of chronic stress or disease, persistent FOS activity in muscle precursor cells may disrupt the muscle-forming process.
Possible limits of calibrating reading charts with the Landolt ring: a microscopic study
Authors: Radner Wolfgang , Radner Michael , Daxer Barbara , Ettl Armin 
Published: August 2022

Abstract
Purpose
To evaluate microscopically whether the print quality and accuracy of sizing of Landolt ring near vision charts are adequate for the calibration of reading charts.

Methods
Near vision charts with Landolt rings from Oculus GmbH (C-Test; Wetzlar, Germany), Precision Vision (Woodstock, IL) and the RADNER Charts were examined, as well as custom-made Landolt rings optimized for print quality. Microscopic investigations and measurements were performed by using a Huvitz HSZ 600 stereomicroscope (Nikon NIS Elements software) to evaluate the height of the Landolt rings, the thickness of the lines, and the width of the openings. The deviations from the mathematically correct values, which were calculated as given in the EN/ISO 8596 and by the International Council of Ophthalmology (ICO), were analyzed (calculated for a test distance of 40 cm).

Results
All the near vision charts showed notable deficiencies in print quality and aberrations from the nominal values in the height, thickness of the lines, and width of the openings. The openings were too narrow, whereas the height and thickness of the lines were larger than the nominal values. Even the openings of Landolt rings optimized for print quality were not always within an acceptable 5% tolerance and need further improvement.

Conclusion
This study reports inaccuracies in the heights, thicknesses of the lines, and widths of the openings of Landolt rings in all the near vision charts investigated. The extent of these inaccuracies excludes such near vision charts as reference tests for the calibration of reading charts. The x-height in relation to the visual angle still seems to be the most reliable method for standardizing the print sizes for reading charts.