bluuebunny/crossref_metadata_2025_split huggingface dataset:
Relentless placoid chorioretinitis: A review of four cases in pediatric and young adult patients with a discussion of therapeutic strategies
Authors: Zaheer Haniah A. , Odden Jamie , Gagrani Meghal , Zaguia Fatma , Lowder Careen , Coca Andreea , Rosenkranz Margalit E. , Patil-Chhablani Preeti , Ores Raphaelle , Boussion Francois , Indermill Chad , Sahel José-Alain , Nischal Ken , Goldstein Debra A. , Errera Marie-Helene 
Published: March 2023

IntroductionRelentless placoid chorioretinitis (RPC) is a rare, bilateral disease of the retinal pigment epithelium. The clinical course is prolonged and relapsing. No standard treatment has been established to date. The purpose of this case series is to report four cases of RPC in pediatric and young adult patients in which varying treatments were used, comparing them to previously published cases.MethodsA literature review was conducted to investigate currently published presentations and treatment options for RPC. A multicenter retrospective chart review was also performed on four consecutive patients. These patients were diagnosed with RPC because of new chorioretinitis lesions continuing to appear without or despite therapy for 5–36 months (2 patients), with a clinical course prolonged and relapsing, or because of the atypical location of the multiple lesions (&gt;50) extending from the posterior pole to the equator and mid-peripheral retina (all four patients), which were not consistent with other entities like acute posterior multifocal placoid pigment epitheliopathy and serpiginous choroiditis.ResultsAll four cases of RPC received oral or IV steroids acutely, and three of these patients were transitioned to a steroid-sparing agent and biologic therapy: anti-TNF alpha or anti-IL-6. Quiescence of the chorioretinitis lesions was obtained after 7 months, 1 month, and 36 months; however, the latter had issues with treatment adherence. Mycophenolate mofetil was insufficient to control the disease in one patient, but tocilizumab and infliximab thereafter were effective after cessation of adalimumab due to side effects. Adalimumab when started the first month after the presentation was effective in controlling the disease in one patient. After the failure of interferon-alpha-2a, one patient displayed long-term control with infliximab. One patient did not require a steroid-sparing agent after oral prednisone taper as there was no evidence of progression or recurrence.ConclusionThis case series adds to the current knowledge regarding potential treatments for RPC, specifically the use of anti-TNF-alpha treatment and anti-IL-6 tocilizumab. In this case study, relapses of RPC were found among patients on mycophenolate mofetil and interferon-alpha-2a, and one case did not relapse on oral steroids without a steroid-sparing agent. Our findings suggest that adalimumab, infliximab, and tocilizumab may be useful medications to obtain quiescence of RPC.
Small molecules targeting Pin1 as potent anticancer drugs
Authors: Zhang Jing , Zhou Wenwen , Chen Yunyu , Wang Yanchang , Guo Zongru , Hu Wenhui , Li Yan , Han Xiaomin , Si Shuyi 
Published: March 2023

Background: Pin1 is a member of the evolutionarily conserved peptidyl-prolyl isomerase (PPIase) family of proteins. Following phosphorylation, Pin1-catalyzed prolyl-isomerization induces conformational changes, which serve to regulate the function of many phosphorylated proteins that play important roles during oncogenesis. Thus, the inhibition of Pin1 provides a unique means of disrupting oncogenic pathways and therefore represents an appealing target for novel anticancer therapies.Methods: As Pin1 is conserved between yeast and humans, we employed budding yeast to establish a high-throughput screening method for the primary screening of Pin1 inhibitors. This effort culminated in the identification of the compounds HWH8-33 and HWH8-36. Multifaceted approaches were taken to determine the inhibition profiles of these compounds against Pin1 activity in vitro and in vivo, including an isomerization assay, surface plasmon resonance (SPR) technology, virtual docking, MTT proliferation assay, western blotting, cell cycle analysis, apoptosis analysis, immunofluorescence analysis, wound healing, migration assay, and nude mouse assay.Results:In vitro, HWH8-33 and HWH8-36 could bind to purified Pin1 and inhibited its enzyme activity; showed inhibitory effects on cancer cell proliferation; led to G2/M phase arrest, dysregulated downstream protein expression, and apoptosis; and suppressed cancer cell migration. In vivo, HWH8-33 suppressed tumor growth in the xenograft mice after oral administration for 4 weeks, with no noticeable toxicity. Together, these results show the anticancer activity of HWH8-33 and HWH8-36 against Pin1 for the first time.Conclusion: In summary, we identified two hit compounds HWH8-33 and HWH8-36, which after further structure optimization have the potential to be developed as antitumor drugs.
Endothelial activation impairs the function of small extracellular vesicles
Authors: Herrera-Zelada Nicolas , Zúñiga-Cuevas Úrsula , Ramírez-Reyes Andrés , Norambuena-Soto Ignacio , Venegas-Zamora Leslye , Troncoso Mayarling F. , Hernández Alejandra , Sánchez Gina , Pedrozo Zully , Lavandero Sergio , Riquelme Jaime A. 
Published: March 2023

Small extracellular vesicles are nanosized vesicles (30–200 nm) that can ferry proteins, nucleic acids, and lipids between cells and therefore, have significant potential as biomarkers, drug delivery tools or therapeutic agents. SEVs of endothelial origin have been shown to -among other functions-reduce in vitro ischemia/reperfusion (I/R) injury in cardiomyocytes, but whether a pro-inflammatory state of the endothelium impairs the functionality of these SEVs remains to be elucidated. To test this, human umbilical vein endothelial cells cells were treated with TNF-α 10 ng/mL and the expression of the pro-inflammatory parameters VCAM-1, ICAM-1 and eNOS were determined by Western blot. SEVs were isolated from endothelial cells treated with or without TNF-α 10 ng/mL using size exclusion chromatography. The size and concentration of SEVs was measured by Nanoparticle Tracking Analysis. The expression of the surface marker CD81 was determined by immunoassay, whereas their morphology was assessed by electron microscopy. The function of endothelial SEVs was assessed by evaluating their cardioprotective effect in an ex vivo model of global I/R using isolated hearts from adult C57BL/6 mice. Treatment of HUVECs with TNF-α induced the expression of VCAM-1 and ICAM-1, whereas eNOS levels were decreased. TNF-α did not affect the production, size, morphology, or expression of CD81. SEVs significantly reduced the infarct size as compared with untreated mice hearts, but SEVs isolated from TNF-α treated cells were unable to achieve this effect. Therefore, a pro-inflammatory state induced by TNF-α does not alter the production of endothelial SEVs but impairs their function in the setting of I/R injury.
Differential effects of ELX/TEZ/IVA on organ-specific CFTR function in two patients with the rare CFTR splice mutations c.273+1G>A and c.165-2A>G
Authors: Pallenberg Sophia T. , Held Inka , Dopfer Christian , Minso Rebecca , Nietert Manuel M. , Hansen Gesine , Tümmler Burkhard , Dittrich Anna-Maria 
Published: March 2023

Introduction: Evidence for the efficiency of highly-effective triple-CFTR-modulatory therapy with elexacaftor/tezacaftor/ivacaftor (ETI), either demonstrated in clinical trials or by in vitro testing, is lacking for about 10% of people with cystic fibrosis (pwCF) with rare mutations. Comprehensive assessment of CFTR function can provide critical information on the impact of ETI on CFTR function gains for such rare mutations, lending argument of the prescription of ETI. The mutation c.165-2A&gt;G is a rare acceptor splice mutation that has not yet been functionally characterized. We here describe the functional changes induced by ETI in two brothers who are compound heterozygous for the splice mutations c.273+1G&gt;C and c.165-2A&gt;G.Methods: We assessed the effects of ETI on CFTR function by quantitative pilocarpine iontophoresis (QPIT), nasal potential difference measurements (nPD), intestinal current measurements (ICM), β-adrenergic sweat secretion tests (SST) and multiple breath washout (MBW) prior to and 4 months after the initiation of ETI.Results: Functional CFTR analysis prior to ETI showed no CFTR function in the respiratory and intestinal epithelia and in the sweat gland reabsorptive duct in either brother. In contrast, β-adrenergic stimulated, CFTR-mediated sweat secretion was detectable in the CF range. Under ETI, both brothers continued to exhibit high sweat chloride concentration in QPIT, evidence of low residual CFTR function in the respiratory epithelia, but normalized β-adrenergically stimulated production of primary sweat.Discussion: Our results are the first to demonstrate that the c.165-2A&gt;G/c.273+1G&gt;C mutation genotype permits mutant CFTR protein expression. We showed organ-specific differences in the expression of CFTR and consecutive responses to ETI of the c.165-2A&gt;G/c.273+1G&gt;C CFTR mutants that are probably accomplished by non-canonical CFTR mRNA isoforms. This showcase tells us that the individual response of rare CFTR mutations to highly-effective CFTR modulation cannot be predicted from assays in standard cell cultures, but requires the personalized multi-organ assessment by CFTR biomarkers.
Meta-analysis and trial sequential analysis of ezetimibe for coronary atherosclerotic plaque compositions
Authors: Chai Bofeng , Shen Youlu , Li Yuhong , Wang Xiaoyu 
Published: March 2023

Background: Lipid aggregation, inflammatory cell infiltration, fibrous cap formation, and disruption are the major causes of atherosclerotic cardiovascular disease (ASCVD) and the pathologic features of atherosclerotic plaques. Although ezetimibe’s role in decreasing blood lipids is widely known, there are insufficient data to determine which part of the drug has an effect on atherosclerotic plaque compositions.Objective: The study aimed to systematically evaluate the efficacy of ezetimibe for coronary atherosclerotic plaque compositions.Methods: Two researchers independently searched the PubMed, Embase, Cochrane Library, and Web of Science databases for randomized controlled trials (RCTs) on the efficacy of ezetimibe for coronary atherosclerotic plaques from inception until 22 January 2023. The meta-analysis and trial sequential analysis (TSA) were performed using Stata 14.0 and TSA 0.9.5.10 Beta software, respectively.Results: Four RCTs were finally included this study, which comprised 349 coronary artery disease patients. Meta-analysis findings showed that, compared with the control group, intervention measures could effectively reduce the fibro-fatty plaque (FFP) volume [WMD = −2.90, 95% CI (−4.79 and −1.00), and p = 0.003 &lt; 0.05]; there were no significant difference in the reduction of fibrous plaque (FP) volume [WMD = −4.92, 95% CI (−11.57 and 1.74), and p = 0.15 &gt; 0.05], necrotic core (NC) volume [WMD = −2.26, 95% CI (−6.99 and 2.46), and p = 0.35 &gt; 0.05], and change dense calcification (change DC) volume [WMD = −0.07, 95% CI (−0.34 and 0.20), and p = 0.62 &gt; 0.05] between the treatment group and the control group. TSA findings showed more studies are still required to confirm the efficacy of ezetimibe for FP and NC in the future.Conclusion: Compared to the control group, ezetimibe significantly decreased FFP, but it had no statistically significant difference on FP, NC, or change DC. According to TSA, further research will be required to confirm the efficacy of ezetimibe for FP and NC in the future.
A multi-wavelength mid-IR laser based on BaGa4Se7 optical parametric oscillators
Authors: Deng Ying , Kang Minqiang , Wang Zhenguo , Li Jianbin , Jiang Xinying , Xiao Kaibo , Zhou Song , Zhang Fan , Xiang Xiangjun , Peng Zhitao , Yao Jiyong , Zhu Qihua , Feng Guoying 
Published: March 2023

A multi-wavelength mid-IR laser consisting of 3.05 μm, 4.25 μm, and 5.47 μm BaGa4Se7(BGSe)optical parametric oscillators (OPOs) switched by DKDP electro-optic switches with one 10 Hz/7.6 ns pumping wave is demonstrated. Maximum energies at 3.05 μm, 4.25 μm, and 5.47 μm are 1.35 mJ, 1.03 mJ, and 0.56 mJ, respectively, corresponding to optical-to-optical conversion efficiencies of 9.4%, 7.6%, and 4.2%. To the best of our knowledge, this study is the first of generation of three mid-IR wavelength lasers using electro-optic switches. Furthermore, this study provides a viable solution for a high-energy or high-power, compact, or even portable multi-wavelength mid-IR laser device that employs a single pumping wave.
Single-cell genetic models to evaluate orphan gene function: The case of QQS regulating carbon and nitrogen allocation
Authors: Wang Lei , Tonsager Andrew J. , Zheng Wenguang , Wang Yingjun , Stessman Dan , Fang Wei , Stenback Kenna E. , Campbell Alexis , Tanvir Rezwan , Zhang Jinjiang , Cothron Samuel , Wan Dongli , Meng Yan , Spalding Martin H. , Nikolau Basil J. , Li Ling 
Published: March 2023

We demonstrate two synthetic single-cell systems that can be used to better understand how the acquisition of an orphan gene can affect complex phenotypes. The Arabidopsis orphan gene, Qua-Quine Starch (QQS) has been identified as a regulator of carbon (C) and nitrogen (N) partitioning across multiple plant species. QQS modulates this important biotechnological trait by replacing NF-YB (Nuclear Factor Y, subunit B) in its interaction with NF-YC. In this study, we expand on these prior findings by developing Chlamydomonas reinhardtii and Saccharomyces cerevisiae strains, to refactor the functional interactions between QQS and NF-Y subunits to affect modulations in C and N allocation. Expression of QQS in C. reinhardtii modulates C (i.e., starch) and N (i.e., protein) allocation by affecting interactions between NF-YC and NF-YB subunits. Studies in S. cerevisiae revealed similar functional interactions between QQS and the NF-YC homolog (HAP5), modulating C (i.e., glycogen) and N (i.e., protein) allocation. However, in S. cerevisiae both the NF-YA (HAP2) and NF-YB (HAP3) homologs appear to have redundant functions to enable QQS and HAP5 to affect C and N allocation. The genetically tractable systems that developed herein exhibit the plasticity to modulate highly complex phenotypes.
An encounter with the self: A thematic and content analysis of the DMT experience from a naturalistic field study
Authors: Michael Pascal , Luke David , Robinson Oliver 
Published: March 2023

IntroductionN,N-Dimethyltryptamine (DMT) is an endogenous serotonergic psychedelic capable of producing radical shifts in an experience that have significant implications for consciousness and its neural correlates, especially given the “disconnected consciousness” suggested by the “breakthrough” DMT state. Its increasing usage and clinical trial indicate the growing importance of a thorough elucidation of the experience's qualitative content, over and above the phenomenological structure. This is particularly in light of the intensely pervasive effects of DMT occasions in all dimensions of the self, which are often ontologically challenging yet potentially transformative.MethodsThis is the second report on the first naturalistic field study of DMT use exploring its qualitative analysis. Screened, healthy, anonymized, and experienced DMT users were observed during their non-clinical use of the drug at home (40–75-mg inhaled). In-depth semi-structured interviews, inspired by the micro-phenomenological technique, were employed immediately after their experience. This study reports on the thematic and content analysis of one major domain of the breakthrough experiences elicited, the “self”; where analyses of the “other” were previously reported. A total of 36 post-DMT experience interviews with mostly Caucasian (83%) men (eight women) of a mean of 37 years were predominantly inductively coded.ResultsInvariably, profound and highly intense experiences occurred. The first overarching category comprised the onset of effects, encompassing super-ordinate themes including sensory, emotion and body, and space-time shifts; the second category comprised bodily effects, encompassing themes including pleasurable, neutral/both, and uncomfortable; the third category comprised the sensorial effects, encompassing open-eye, visual, and cross-modal and other; the fourth comprised the psychological effects, encompassing memory and language, awareness and sense of self, and time distortions; and the fifth comprised the emotional effects, encompassing positive, neither/both, and challenging experiences. Many further subthemes also illuminate the rich content of the DMT experience.DiscussionThe present study provides a systematic and nuanced analysis of the content of the breakthrough DMT state pertaining to one's personal and self-referential experiences of the body, senses, psychology, and emotions. The resonances both with previous DMT studies and other types of extraordinary experiences, such as the alien abduction, shamanic and near-death experiences, are also elaborated upon. Putative neural mechanisms and their promise as a psychotherapeutic agent, especially owing to deep emotional impact, are discussed.
Carer involvement in the assessment of personal recovery: A naturalistic study of assertive community treatment in Norway
Authors: Israel Pravin , Ruud Torleif , Weimand Bente 
Published: March 2023

BackgroundThe user and carer movements have come a long way in becoming embedded in mainstream mental health services for individuals with serious mental illness. However, implementing recovery-oriented practice continues to be plagued by an individualistic clinical focus. The carers do not feel integrated despite policies and best intentions. The implementation of Assertive Community Treatment (ACT) provided an opportunity to involve the carers and compare their assessment of personal recovery with the users.AimsThe aims of this study were to examine (i) how family carers and users differed in their assessment of personal recovery, (ii) whether familial and personal relationships influenced how carers assess personal recovery of users, and (iii) if the experience of family carers with the ACT team was associated with personal recovery.MethodsThe naturalistic, explorative study recruited 69 users and 36 family carers from 12 Norwegian ACT teams. The users and carers assessed the user's personal recovery. Family carers also reported their experience and satisfaction with the ACT teams. Analyses included independent and paired sample T-tests and correlation analysis.ResultsFamily carers were significantly more conservative than the users' assessment of the intrapsychic and interpersonal subscales of personal recovery. The pattern held true whether the family carers were matched to the users or part of the total sample. Lastly, there was a significant negative correlation between the family carer's experience of cooperation with the ACT team and their assessment of the user's intrapersonal process of recovery.ConclusionsThe results of our study were consistent with previous research on carer involvement in MHS. However, it is the first study that engaged carers and assessed personal recovery of the users of ACT services. Discrepancy between carers and users is the rule. Clinicians are encouraged to embrace the discrepancy and diversity carers bring and learn the methodology of multi-informant assessments. There also is a need to address, update, and integrate the personal, familial, and relational aspects of recovery. Modification of recovery measures such as QPR and their creative use with carers has the potential to generate valuable third-party information and to involve them meaningfully in mental health services.
Exploring the relationship between air quality and health shocks to the elderly: A retrospective cross-sectional study in China
Authors: Li Xinyu , Lyu Yanxia , Dong Wanyue , Xu Aijun 
Published: March 2023

MethodsWe selected 5,172 microdata on individuals from the China Health and Retirement Longitudinal Study (CHARLS) 2018. The binary logit model, the ordered logit model, and the stepwise regression were employed to compare the effects of air pollution on self-rated health (SRH) and activities of daily living (ADL) in an elderly population. The effects on health shocks were explored in different age groups, different gender groups, different regions and different sources of pollutants, respectively.ResultsWe found that air pollution significantly increased the risk of health shocks in the elderly population, especially in the 60–69 year age group, and the eastern/central region, where NO2 and O3 were important pollutant sources.ConclusionTargeted management of the environment is necessary to improve the health status of China's elderly population. In addition, paying attention to the health status of vulnerable populations is needed to achieve social equity.
A Keynesian perspective on the health economics of kidney transplantation would strengthen the value of the whole organ donation and transplantation service
Authors: Leonardis Francesca , Gitto Lara , Favi Evaldo , Oliva Angelo , Angelico Roberta , Mitterhofer Annapaola , Cacciola Irene , Santoro Domenico , Manzia Tommaso Maria , Tisone Giuseppe , Cacciola Roberto 
Published: March 2023

BackgroundIn this study, the Keynesian principle “savings may be used as investments in resources” is applied to Kidney Transplantation (KT), contextualizing the whole Organs Donation and Transplantation (ODT) service as a unique healthcare entity. Our aim was to define the financial resources that may be acquired in the form of savings from the KT activity.MethodsWe analyzed registry and funding data for ODT in our region, between 2015 and 2019. Our hypotheses aimed to evaluate whether the savings would offset the Organ Donation (OD) costs, define the scope for growth, and estimate what savings could be generated by higher KT activity. To facilitate the evaluation of the resources produced by KT, we defined a coefficient generated from the combination of clinical outcomes, activity, and costs.ResultsThe ODT activity reached a peak in 2017, declining through 2018–2019. The savings matured in 2019 from the KT activity exceeded €15 million while the OD costs were less than €9 million. The regional KT activity was superior to the national average but inferior to international benchmarks. The estimated higher KT activity would produce savings between €16 and 20 million.ConclusionThe financial resources produced by KT contribute to defining a comprehensive perspective of ODT finance. The optimization of the funding process may lead to the financial self-sufficiency of the ODT service. The reproducible coefficient allows a reliable estimate of savings, subsequently enabling adequate investments and budgeting. Applying such a perspective jointly with reliable estimates would establish the basis for an in-hospital fee-for-value funding methodology for ODT.