bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy and safety outcomes of a compounded testosterone pellet versus a branded testosterone pellet in men with testosterone deficiency: a single-center, open-label, randomized trial
Authors: Kresch Eliyahu , Lima Thiago Fernandes Negris , Molina Manuel , Deebel Nicholas A , Reddy Rohit , Patel Mehul , Loloi Justin , Carto Chase , Nackeeran Sirpi , Gonzalez Daniel C , Ory Jesse , Ramasamy Ranjith 
Published: March 2023

AbstractBackgroundTestosterone deficiency (TD) is a prevalent condition, especially in men ≥45 years old, and testosterone therapy (TTh) can improve the quality of life in these patients.AimTo evaluate the safety profile of compounded subcutaneous testosterone pellets and to compare the efficacy between compounded and market brand testosterone pellets for TTh: E100 (Empower Pharmacy) and Testopel (Food and Drug Administration approved), respectively.MethodsThis was a prospective, phase 3, randomized, noninferiority clinical trial. We enrolled 75 men diagnosed with TD and randomized them 1:1 to a market brand group and a compounded pellet group. The patients were implanted with their respective testosterone pellets: Testopel (10 pellets of 75 mg) and E100 (8 pellets of 100 mg).OutcomesWe evaluated adverse events after implantation and followed men at 2, 4, and 6 months for morning laboratory levels (prior to 10 am): serum testosterone, estradiol, hematocrit, and prostate-specific antigen.ResultsAfter randomization, 33 participants were enrolled in the Testopel arm and 42 in the E100 arm. Serum testosterone levels were similar between the groups at 2, 4, and 6 months, with most men (82%) dropping to &lt;300 ng/dL by the end of the trial. Adverse events were also similar, such as elevations in prostate-specific antigen, estradiol, and hematocrit. Most dropouts were related to persistent TD symptoms and serum testosterone &lt;300 ng/dL, with similar rates between the groups in the study.Clinical ImplicationsMen treated with Testopel and E100 pellets had comparable serum testosterone levels and similar adverse event rates, providing an effective choice of long-term TTh among men with TD.Strengths and LimitationsStrengths include the prospective, randomized, single-blinded study design and adequate follow-up. Limitations include the lack of external validity and the single-institution cohort.ConclusionE100 compounded testosterone pellets are a noninferior option of TTh as compared with Testopel for men presenting with TD.
Feasibility Study of Cord Tissue Derived Mesenchymal Stromal Cells in COVID-19-Related Acute Respiratory Distress Syndrome
Authors: Shaz Beth H , Kraft Bryan D , Troy Jesse D , Poehlein Emily , Chen Lingye , Cheatham Lynn , Manyara Raha , Hanafy Khalid , Brown Linda , Scott Margaret , Palumbo Ralph , Vrionis Frank , Kurtzberg Joanne 
Published: March 2023

AbstractBackgroundTreatment options for patients with COVID-19-related acute respiratory distress syndrome (ARDS) are desperately needed. Allogeneic human umbilical cord derived mesenchymal stromal cells (hCT-MSCs) have potential therapeutic benefits in these critically ill patients, but feasibility and safety data are lacking.Materials and MethodsIn this phase I multisite study, 10 patients with COVID-19-related ARDS were treated with 3 daily intravenous infusions of hCT-MSCs (1 million cells/kg, maximum dose 100 million cells). The primary endpoint assessed safety.ResultsTen patients (7 females, 3 males; median age 62 years (range 39-79)) were enrolled at 2 sites and received a total of 30 doses of study product. The average cell dose was 0.93 cells/kg (range 0.56-1.45 cells/kg and total dose range 55-117 million cells) with 5/30 (17%) of doses lower than intended dose. Average cell viability was 85% (range 63%-99%) with all but one meeting the &gt;70% release criteria. There were no infusion-related reactions or study-related adverse events, 28 non-serious adverse events in 3 unique patients, and 2 serious adverse events in 2 unique patients, which were expected and unrelated to the study product. Five patients died: 3 by day 28 and 5 by day 90 of the study (median 27 days, range 7-76 days). All deaths were determined to be unrelated to the hCT-MSCs.ConclusionWe were able to collect relevant safety outcomes for the use of hCT-MSCs in patients with COVID-19-related ARDS. Future studies to explore their safety and efficacy are warranted.
HBx downregulated decorin and decorin‐derived peptides inhibit the proliferation and tumorigenicity of hepatocellular carcinoma cells
Authors: Li Yong , Gan Lipeng , Lu Min , Zhang Xiaodan , Tong Xiaomei , Qi Dandan , Zhao Yan , Ye Xin 
Published: March 2023

AbstractHepatitis B virus (HBV) is one of the important risk factors in inducing the occurrence and development of liver cancer, while the mechanism has not been fully clarified. In this study, we found decorin (DCN) was significantly reduced in HBV transgenic cell line HepG2‐4D14 compared to HepG2. The data from hepatocellular carcinoma (HCC) patients indicated that the level of DCN mRNA was significantly lower in tumor tissues than healthy control and positively correlated with the survival of HCC patients. We revealed that HBV HBx can inhibit the transcription of DCN by blocking p53 activity. Functional analysis demonstrated that overexpression of DCN substantially inhibits the proliferation of HCC cells, while knockdown of DCN enhances the proliferation of HCC cells. It is known that DCN could competitively bind to c‐Met to inhibit HGF/c‐Met signaling pathway to inhibit the development of HCC. Therefore, we screened the novel antitumor peptides derived from DCN based on the sequence of DCN and the complex structure of HGF/c‐Met with virtual screening and identified a set of DCN‐derived peptides (DCN‐Ps) which may competitively bind to c‐Met. We found that 5 of peptides can reduce the proliferation and migration of HepG2 cells significantly. Among them, DCN‐P#3 can inhibit the growth of HCC cells both in vitro and in vivo. In conclusion, we discovered that HBV HBx downregulates the expression of DCN, which in turn promotes the proliferation of hepatocytes and the development of HCC. We identified DCN‐derived antitumor peptides which provides the candidates for developing novel drugs against HCC.
Hematopoietic/erythroid enhancers activate nearby target genes by extending histone H3K27ac and transcribing intergenic RNA
Authors: Kim Yea Woon , Kang Jin , Kim AeRi 
Published: March 2023

AbstractEnhancers activate gene transcription remotely, which requires tissue specific transcription factors binding to them. GATA1 and TAL1 are hematopoietic/erythroid‐specific factors and often bind together to enhancers, activating target genes. Interestingly, we found that some hematopoietic/erythroid genes are transcribed in a GATA1‐dependent but TAL1‐independnet manner. They appear to have enhancers within a relatively short distance. In this study, we paired highly transcribed hematopoietic/erythroid genes with the nearest GATA1/TAL1‐binding enhancers and analyzed these putative enhancer‐gene pairs depending on distance between them. Enhancers located at various distances from genes in the pairs, which was not related to transcription level of the genes. However, genes with enhancers at short distances away tended to be transcriptionally unaffected by TAL1 depletion. Histone H3K27ac extended from the enhancers to target genes. The H3K27ac extension was maintained without TAL1, even though it disappeared owing to the loss of GATA1. Intergenic RNA was highly transcribed from the enhancers to nearby target genes, independent of TAL1. Taken together, TAL1‐independent transcription of hematopoietic/erythroid genes appears to be promoted by enhancers present in a short distance. These enhancers are likely to activate nearby target genes by tracking the intervening regions.
Deficiency of G protein‐coupled receptor Gpr111/Adgrf2 causes enamel hypomineralization in mice by alteration of the expression of kallikrein‐related peptidase 4 (Klk4) during pH cycling process
Authors: Chiba Yuta , Yoshizaki Keigo , Sato Hiroshi , Ikeuchi Tomoko , Rhodes Craig , Chiba Mitsuki , Saito Kan , Nakamura Takashi , Iwamoto Tsutomu , Yamada Aya , Yamada Yoshihiko , Fukumoto Satoshi 
Published: March 2023

AbstractEnamel is formed by the repetitive secretion of a tooth‐specific extracellular matrix and its decomposition. Calcification of the enamel matrix via hydroxyapatite (HAP) maturation requires pH cycling to be tightly regulated through the neutralization of protons released during HAP synthesis. We found that Gpr115, which responds to changes in extracellular pH, plays an important role in enamel formation. Gpr115‐deficient mice show partial enamel hypomineralization, suggesting that other pH‐responsive molecules may be involved. In this study, we focused on the role of Gpr111/Adgrf2, a duplicate gene of Gpr115, in tooth development. Gpr111 was highly expressed in mature ameloblasts. Gpr111‐KO mice showed enamel hypomineralization. Dysplasia of enamel rods and high carbon content seen in Gpr111‐deficient mice suggested the presence of residual enamel matrices in enamel. Depletion of Gpr111 in dental epithelial cells induced the expression of ameloblast‐specific protease, kallikrein‐related peptidase 4 (Klk4), suggesting that Gpr111 may act as a suppressor of Klk4 expression. Moreover, reduction of extracellular pH to 6.8 suppressed the expression of Gpr111, while the converse increased Klk4 expression. Such induction of Klk4 was synergistically enhanced by Gpr111 knockdown, suggesting that proper enamel mineralization may be linked to the modulation of Klk4 expression by Gpr111. Furthermore, our in vitro suppression of Gpr111 and Gpr115 expression indicated that their suppressive effect on calcification was additive. These results suggest that both Gpr111 and Gpr115 respond to extracellular pH, contribute to the expression of proteolytic enzymes, and regulate the pH cycle, thereby playing important roles in enamel formation.
Immediate treatment for recent hepatitis C infection in people with high-risk behaviors: a systematic review and meta-analysis
Authors: Manoharan Lakshmi , Latham Ned H. , Munari Stephanie C. , Traeger Michael W. , Menon Vinay , Luhmann Niklas , Baggaley Rachel , Macdonald Virginia , Verster Annette , Siegfried Nandi , Matthews Gail V. , Stoové Mark , Hellard Margaret E. , Doyle Joseph S. 
Published: March 2023

Background and Aims:
Direct-acting antivirals (DAAs) are almost exclusively approved for the treatment of chronic HCV. This poses a significant barrier to the treatment of recently acquired HCV because of the limited access to DAAs. This review seeks to address this issue by synthesizing evidence of the benefits and harms of immediate treatment after the detection of recently acquired HCV in people at higher risk of infection.

Approach and Results:
A systematic review and meta-analysis were conducted reporting on populations with recently acquired HCV at higher risk of infection. Studies were included if they assessed standard duration DAA treatment regimens and reported on the benefits and harms of immediate treatment (within one year of diagnosis). Outcomes included sustained virological response at 12 weeks post-treatment (SVR12), incidence, treatment initiation and adherence, overtreatment, engagement in care, and adverse events. Eight cohort studies, 3 open-label trials, and 1 case series study were included, reporting on 2085 participants with recently acquired HCV infection. No studies included a comparison group. Eight studies assessed DAA treatment in either men who have sex with men or men who have sex with men with HIV, 2 studies assessed treatment in people who inject drugs, and 2 among people living with HIV. Immediate treatment of HCV was associated with a pooled SVR12 of 95.9% (95% CI, 92.6%–99.3%). Three studies reported on hepatitis C incidence, where most participants were treated in the chronic phase of infection. A treatment completion rate of 100% was reported in 2 studies, and only 1 serious adverse event was described.

Conclusions:
High rates of cure were achieved with the treatment of recently acquired hepatitis C in people at higher risk of infection. Serious adverse events were rare, highlighting individual benefits consistent with the treatment of chronic hepatitis C. The impact of immediate treatment on HCV incidence requires further evaluation.
Humoral and T-cell–mediated immunity to SARS-CoV-2 vaccination in patients with liver disease and transplant recipients
Authors: Willauer Alexandra N. , Rouster Susan D. , Meeds Heidi L. , Jennings Carrie L. , Abdel-Hameed Enass A. , Daria Diane E. , Stambrook Elizabeth P. , Shata Mohamed Tarek M. , Sherman Kenneth E. 
Published: March 2023

Background:
SARS-CoV-2 vaccination induces a varied immune response among persons with chronic liver disease (CLD) and solid organ transplant recipients (SOTRs). We aimed to evaluate the humoral and T-cell–mediated immune responses to SARS-CoV-2 vaccination in these groups.

Methods:
Blood samples were collected following the completion of a standard SARS-CoV-2 vaccination (2 doses of either BNT162b2 or mRNA-12732), and a subset of patients had a blood sample collected after a single mRNA booster vaccine. Three separate methods were utilized to determine immune responses, including an anti-spike protein antibody titer, neutralizing antibody capacity, and T-cell–mediated immunity.

Results:
The cohort included 24 patients with chronic liver disease, 27 SOTRs, and 9 controls. Patients with chronic liver disease had similar immune responses to the wild-type SARS-CoV-2 compared with controls following a standard vaccine regimen and single booster vaccine. SOTRs had significantly lower anti-S1 protein antibodies (p < 0.001), neutralizing capacity (p < 0.001), and T-cell–mediated immunity response (p = 0.021) to the wild-type SARS-CoV-2 compared with controls following a standard vaccine regimen. Following a single booster vaccine, immune responses across groups were not significantly different but numerically lower in SOTRs. The neutralization capacity of the B.1.1.529 Omicron variant was not significantly different between groups after a standard vaccine regimen (p = 0.87) and was significantly lower in the SOTR group when compared with controls after a single booster vaccine (p = 0.048).

Conclusion:
The immunogenicity of the SARS-CoV-2 vaccine is complex and multifactorial. Ongoing and longitudinal evaluation of SARS-CoV-2 humoral and cellular responses is valuable and necessary to allow frequent re-evaluation of these patient populations.
Long noncoding RNAs in cardiovascular disease
Authors: Kohlmaier Alexander , Holdt Lesca M. , Teupser Daniel 
Published: March 2023

Purpose of review
Here, we review recent findings on the role of long noncoding RNAs (lncRNAs) in cardiovascular disease (CVD). In addition, we highlight some of the latest findings in lncRNA biology, providing an outlook for future avenues of lncRNA research in CVD.

Recent findings
Recent publications provide translational evidence from patient studies and animal models for the role of specific lncRNAs in CVD. The molecular effector mechanisms of these lncRNAs are diverse. Overall, cell-type selective modulation of gene expression is the largest common denominator. New methods, such as single-cell profiling and CRISPR/Cas9-screening, reveal additional novel mechanistic principles: For example, many lncRNAs establish RNA-based spatial compartments that concentrate effector proteins. Also, RNA modifications and splicing features can be determinants of lncRNA function.

Summary
lncRNA research is passing the stage of enumerating lncRNAs or recording simplified on-off expression switches. Mechanistic analyses are starting to reveal overarching principles of how lncRNAs can function. Exploring these principles with decisive genetic testing in vivo remains the ultimate test to discern how lncRNA loci, by RNA motifs or DNA elements, affect CVD pathophysiology.
MACULAR ATROPHY AND PHENOTYPIC VARIABILITY IN AUTOSOMAL DOMINANT STARGARDT-LIKE MACULAR DYSTROPHY DUE TO PROM1 MUTATION
Authors: Ricca Aaron M. , Han Ian C. , HOFFMANN JEREMY , Stone Edwin M. , Sohn Elliott H. 
Published: March 2023

Purpose:
To describe the phenotypic variability and rates of progression of atrophy in patients with PROM1-associated macular dystrophy.

Methods:
Patients in this retrospective, longitudinal case series from a tertiary center had clinical examination and multimodal imaging performed. Areas of retinal pigment epithelium and ellipsoid zone loss over time by optical coherence tomography were calculated by two independent graders.

Results:
Fifteen patients from five kindreds with an Arg373Cys mutation in PROM1 were studied. The average age was 39 years, and 80% were women. The visual acuity was 20/40 at presentation and 20/57 at last follow-up (average 4.8 years). Three distinct macular phenotypes were observed: 1) central geographic atrophy (13%), 2) multifocal geographic atrophy (20%), and 3) bull's eye maculopathy (67%). The overall rate of atrophy progression was 0.36 mm2/year, but the average rate of atrophy progression varied by macular phenotype: 1.08 mm2/year for central geographic atrophy, 0.53 mm2/year for multifocal geographic atrophy, and 0.23 mm2/year for bull's eye maculopathy.

Conclusion:
Patients with PROM1-associated macular dystrophy demonstrate distinct phenotypes, with bull's eye maculopathy being the most common. The average rate of atrophy progression may be similar to reported rates for ABCA4-related Stargardt disease and less than age-related macular degeneration. These results provide important measures for following treatment response in future gene and stem cell–based therapies.
Case Study
Authors: Jellerichs Bradley , Rajendran Arun 
Published: March 2023

ABSTRACT
This is a case study of a 55-year-old woman presenting with dystrophic nails that arose during her teenage years and has worsened over the last few years. The patient reported frequent wet work, exposure to irritants, and cuticle manipulation. The physical examination showed proximal nail fold bolstering, loss of cuticle, and a wavy dorsal nail plate resembling a “washboard.” She was diagnosed with chronic paronychia and onychotillomania. She was prescribed clobetasol ointment and sulfacetamide in ethanol and was counseled on hygiene and at-home care. One month after the regimen was started, there was noticeable reduction of inflammation to the cuticle.
Nevus Simplex
Authors: Gomez Jason , Admani Shehla 
Published: March 2023

ABSTRACTNevus simplex, or salmon patch, is a benign vascular malformation seen in 30%–40% of infants. Most lesions are self-limiting, resolving spontaneously between the ages of 1 and 2 years. The most affected areas of the skin are the occiput and posterior neck; however, facial, scalp, and sacral involvement can also be seen. A nevus simplex must be differentiated from a port wine stain, as port wine stains are persistent and can be associated with genetic syndromes. Although sacral lesions can be common in nevus simplex complex, when associated with a second lumbosacral anomaly, further evaluation for underlying spinal dysraphism should be considered.
Efficacy and safety of Shugan Jieyu Decoction in the treatment of coronary heart disease complicated with depression
Authors: Li Zhenzhen , Zhang Jianying , Qiao Mingqi , Wang Xiaojin , Guo Yinghui , Wang Haijun 
Published: March 2023

Background:
Coronary heart disease combined with depression is 1 of the 2 major diseases affecting physical and mental health. It has become a hot spot at the intersection of psychiatry and internal medicine. Most doctors call double heart medicine, which has a high incidence rate and a low diagnostic rate. Clinical research shows that Shugan Jieyu Decoction (SJD) has a better curative effect, increased safety, and fewer adverse reactions, but it lacks systematic evaluation. This study aims to integrate clinical data through network meta-analysis and provide more evidence-based medical evidence for clinical medication.

Methods:
We searched 8 electronic databases: China knowledge network database, Wanfang, VIP, SinoMed, PubMed, Embase, WebofScience, Cochrane Library, and selected 22 randomized controlled trials from January 2012 to January 2022. The common primary endpoint was the relief of angina pectoris and the improvement of depression. Two researchers used Endnote9.1 software to conduct literature screening and information extraction according to the developed nano-passage standard, used Cochrane collaborative tool to evaluate the bias risk in the experiment, and then used RevMan5.3 software to assess the literature and data analysis synthesis.

Results:
In 1908 patients with coronary heart disease and depression, the total effective rate of SJD in the treatment of angina pectoris was 3.49 (95% confidence interval, 1.93–6.29), as well as the network meta-analysis of improving depressive symptoms, anxiety, depression scores (SAS, SDS) and quality of life scores (HAMD), and reducing the indicators related to CPR and homocysteine.

Conclusion:
The analysis of this study shows that SJD can reduce the frequency of angina pectoris in patients with coronary heart disease and depression, alleviate anxiety and depression, provide a reference basis for clinical treatment, and select more effective intervention therapy.
Impending central retinal vein occlusion and granulomatous uveitis in a patient with Satoyoshi syndrome
Authors: Saima Yoshinari , Tanaka Yoshiaki , Kakehashi Akihiro , Kaburaki Toshikatsu 
Published: March 2023

Rationale:
Satoyoshi syndrome is a rare systemic autoimmune disease that presents with painful muscle spasms. We report a case of impending central retinal vein occlusion (CRVO) secondary to granulomatous pan-uveitis in a 32-year-old woman with Satoyoshi syndrome.

Patient concerns:
At the age of 7 years, she developed generalized hair loss and painful spasms and was diagnosed with Satoyoshi syndrome. Her current symptoms included sudden metamorphopsia and decreased visual acuity in the left eye. She visited our hospital with extensive intraretinal hemorrhage (including the macula), meandering of the retinal veins, and swelling of the optic disc. Fluorescence fundus angiography demonstrated hyper fluorescence of the optic disc and leakage from the retinal veins, suggesting CRVO associated with optic papillitis and segmental periphlebitis.

Diagnoses:
In the left eye, there were 2 + cells in the anterior chamber and 1 + in the anterior vitreous.

Interventions:
We increased the existing dose of prednisolone for the treatment of uveitis and started her on oral aspirin and kallidinogenase for CRVO.

Outcomes:
The impending CRVO gradually subsided, and her visual acuity improved. However, during the subsequent treatment course, angle nodules were observed in the left eye, and the intraocular pressure (IOP) gradually increased. Although the angled nodules disappeared with topical corticosteroid treatment, the IOP did not reduce and became uncontrolled. Therefore, we performed trabeculotomy first, followed by trabeculectomy, after which the IOP decreased to approximately 10 mm Hg.

Lessons:
Unilateral granulomatous pan-uveitis and impending CRVO were observed in this patient. Several cases of Satoyoshi syndrome complicated by various autoimmune or immunological disorders have been reported. However, to the best of our knowledge, no reports of Satoyoshi syndrome presenting with uveitis or CRVO have been published. Physicians should consider uveitis as a complication of Satoyoshi syndrome.