bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cardiac electrical instability in Erdheim-Chester disease: a case report
Authors: Urbani Andrea , Pensotti Filippo , Castini Diego , Magnani Silvia , Simeoli Pasquale Simone , Campochiaro Corrado , Dagna Lorenzo , Cappelletti Alberto M , Sponzilli Carlo , Guazzi Marco 
Published: July 2022

ABSTRACT
Erdheim-Chester disease (ECD) is a rare multisystemic disorder of non-Langerhans histiocytic cells with a pleomorphic clinical presentation. It affects bones, skin, central nervous system, pituitary gland, ocular tissue, kidneys and perirenal tissue and lungs. Cardiac involvement presents usually with pericardial effusion and right atrial masses, but rarely with conduction system infiltration and subsequent arrhythmic events. Following the discovery of mutations of activating signaling kinase proteins (BRAF, MEK, ALK), the therapeutic landscape has changed to a more precise targeted treatment. Currently vemurafenib is approved for patient with end-organ dysfunction and BRAF-V600E mutation and the prognosis has dramatically improved. Here we present a case of ECD with electrical instability as main clinically relevant manifestation of cardiac involvement.
Minimally invasive fenestration for congenital hepatic cyst in infant
Authors: Muta Yuki , Odaka Akio , Inoue Seiichiro , Takechi Yuta , Beck Yoshifumi 
Published: July 2022

ABSTRACT
A 19-year-old woman underwent prenatal ultrasonography, which confirmed the presence of an isolated cystic mass in the upper abdominal cavity of a fetus. A female infant weighing 3085 g was delivered at 36 weeks’ gestation. Ultrasonography and computed tomography examination revealed a clear unilocular cyst and occupying the right side of the abdomen. The infant’s respiratory status was unstable, and she fed poorly, owing to compression by the hepatic cyst. We performed ultrasound-guided aspiration of a hepatic cyst at 15 days old, but it rapidly re-grew. Therefore, we performed laparoscopic findings and fenestration of the hepatic cyst via an umbilical arc incision and the cyst wall was excised at 43 days old. The histopathological diagnosis was mesothelial cell-derived hepatic cyst. Three years after the operation, no recurrence has been observed. Hepatic cyst fenestration by umbilical incision can be performed safely in infants and it is a cosmetically superior method.
Transcript and metabolite network perturbations in lignin biosynthetic mutants of Arabidopsis
Authors: Wang Peng , Guo Longyun , Morgan John , Dudareva Natalia , Chapple Clint 
Published: July 2022

Abstract
Lignin, one of the most abundant polymers in plants, is derived from the phenylpropanoid pathway, which also gives rise to an array of metabolites that are essential for plant fitness. Genetic engineering of lignification can cause drastic changes in transcription and metabolite accumulation with or without an accompanying development phenotype. To understand the impact of lignin perturbation, we analyzed transcriptome and metabolite data from the rapidly lignifying stem tissue in 13 selected phenylpropanoid mutants and wild-type Arabidopsis (Arabidopsis thaliana). Our dataset contains 20,974 expressed genes, of which over 26% had altered transcript levels in at least one mutant, and 18 targeted metabolites, all of which displayed altered accumulation in at least one mutant. We found that lignin biosynthesis and phenylalanine supply via the shikimate pathway are tightly co-regulated at the transcriptional level. The hierarchical clustering analysis of differentially expressed genes (DEGs) grouped the 13 mutants into 5 subgroups with similar profiles of mis-regulated genes. Functional analysis of the DEGs in these mutants and correlation between gene expression and metabolite accumulation revealed system-wide effects on transcripts involved in multiple biological processes.
High temperature restricts cell division and leaf size by coordination of PIF4 and TCP4 transcription factors
Authors: Saini Kumud , Dwivedi Aditi , Ranjan Aashish 
Published: July 2022

Abstract
High ambient temperature suppresses Arabidopsis (Arabidopsis thaliana) rosette leaf area and elongates the stem and petiole. While the mechanism underlying the temperature-induced elongation response has been extensively studied, the genetic basis of temperature regulation of leaf size is largely unknown. Here, we show that warm temperature inhibits cell proliferation in Arabidopsis leaves, resulting in fewer cells compared to the control condition. Cellular phenotyping and genetic and biochemical analyses established the key roles of PHYTOCHROME-INTERACTING FACTOR4 (PIF4) and TEOSINTE BRANCHED1/CYCLOIDEA/PCF4 (TCP4) transcription factors in the suppression of Arabidopsis leaf area under high temperature by a reduction in cell number. We show that temperature-mediated suppression of cell proliferation requires PIF4, which interacts with TCP4 and regulates the expression of the cell cycle inhibitor KIP-RELATED PROTEIN1 (KRP1) to control leaf size under high temperature. Warm temperature induces binding of both PIF4 and TCP4 to the KRP1 promoter. PIF4 binding to KRP1 under high temperature is TCP4 dependent as TCP4 regulates PIF4 transcript levels under high temperature. We propose a model where a warm temperature-mediated accumulation of PIF4 in leaf cells promotes its binding to the KRP1 promoter in a TCP4-dependent way to regulate cell production and leaf size. Our finding of high temperature-mediated transcriptional upregulation of KRP1 integrates a developmental signal with an environmental signal that converges on a basal cell regulatory process.
Effective Dose to Adult Patients Undergoing Renal Scans With 99MTC (DMSA, DTPA, EC and MAG3)
Authors: Sadre Momtaz Alireza , Safarnejad Farzin 
Published: July 2022

Abstract
Renal scintigraphy plays an important role in the diagnosis of various kidney disorders. This procedure can be performed with different radiopharmaceuticals. The patients undergoing renal scintigraphy receive a radiation dose that should be assessed. In this study, the effective dose of patients due to renal scintigraphy with 99mTc (DMSA, DTPA, EC and MAG3) was calculated for the International Commission on Radiological Protection (ICRP) 110 adult reference phantoms using the Medical Internal Radiation Dose method and the ICRP 60 and 103 tissue weighting factors. The results show that the highest effective dose per unit activity administered is due to 99mTc DMSA. On average, the effective dose per unit activity administered of 99mTc DMSA is almost twice the effective dose per unit activity administered of other radiopharmaceuticals. The effective doses per unit activity administered calculated using the ICRP 103 tissue weighting factors are always lower than that calculated using the ICRP 60 tissue weighting factors and the ICRP 128 data.
Augmented Production of Platelets From Cord Blood With Euchromatic Histone Lysine Methyltransferase Inhibition
Authors: Liu Yiying , Zhao Jingjing , Wang Yan , Su Pei , Wang Hongtao , Liu Cuicui , Zhou Jiaxi 
Published: July 2022

Abstract
Cord blood hematopoietic stem/progenitor cells (CB-HSPCs) have emerged as a promising supply for functional platelets to potentially alleviate the increasing demand for platelet transfusions, but the clinical application has been limited by the undefined molecular mechanism and insufficient platelet production. Here, we performed single-cell profiling of more than 16 160 cells to construct a dynamic molecular landscape of human megakaryopoiesis from CB-HSPCs, enabling us to uncover, for the first time, cellular heterogeneity and unique features of neonatal megakaryocytes (MKs) and to also offer unique resources for the scientific community. By using this model, we defined the genetic programs underlying the differentiation process from megakaryocyte-erythroid progenitors (MEPs) to MKs via megakaryocyte progenitors (MKPs) and identified inhibitors of euchromatic histone lysine methyltransferase (EHMT), which, when applied at the early stage of differentiation, significantly increase the final platelet production. At the mechanistic level, we found that EHMT inhibitors act to selectively induce the expansion of MEPs and MKPs. Together, we uncover new mechanistic insights into human megakaryopoiesis and provide a novel chemical strategy for future large-scale generation and clinical applications of platelets.
Chemokine Assay Matrix Defines the Potency of Human Bone Marrow Mesenchymal Stromal Cells
Authors: Lipat Ariel Joy , Cottle Chasen , Pirlot Bonnie M , Mitchell James , Pando Brian , Helmly Brian , Kosko Joanna , Rajan Devi , Hematti Peiman , Chinnadurai Raghavan 
Published: July 2022

Abstract
Potency analysis of mesenchymal stromal cells (MSCs) is required for their use in advanced clinical trials. Assay matrix strategy evaluating more than a single property of MSCs is an emerging strategy in potency analysis. Here we developed an assay matrix approach focusing on the secretory chemokine responses of MSCs using multiplex analytical method. MSCs’ innate fitness in secreting matrix of chemokines is correlated with their metabolic fitness in differential degrees. In addition, innately secreting chemokines are correlated among themselves in a unique pattern. MSC’s matrix chemokine responses to exogenous stimulation of IFNγ and/or TNFα are distinct. However, the combination of IFNγ and TNFα is superior than individual stimulations in eliciting robust and broad matrix chemokine responses of MSCs. Correlation matrix analysis has identified that chemokine responses to IFNγ and/or TNFα display unique correlative secretion patterns. MSC and peripheral blood mononuclear cells coculture analysis has identified the correlation matrix responses of chemokines that predicted immune suppression. In addition, MSC-mediated blocking of T-cell proliferation predominantly correlates with chemokines in an inverse manner. Knockdown of chemokines has demonstrated that MSC-sourced inherent chemokines do not actively play a role in T-cell suppression and thus are the bystander predictors of T-cell suppression. The present analysis of MSC’s matrix chemokine responses can be deployed in the advanced potency analysis of MSCs.
Feasibility and Safety of Low-Dose Mesenchymal Stem Cell Infusion in Lung Transplant Recipients
Authors: Erasmus David Brett , Durand Nisha , Alvarez Francisco A , Narula Tathagat , Hodge David O , Zubair Abba C 
Published: July 2022

Abstract

Background
We have previously shown bone marrow-derived mesenchymal stem cells (MSCs) may shift immune responses toward anti-inflammatory pathways and stabilize the course of obstructive chronic lung allograft syndrome (o-CLAD) after lung transplantation. In this study, we measured the response of lower dose infusions.

Methods
We infused low-dose MSCs intravenously in 13 patients who had developed moderate-to-severe o-CLAD. Three had previously received an infusion of MSCs from a different donor and were re-dosed at 1 × 106 MSC/kg, while 5 received a first dose at 1 × 106 MSC/kg and five received an even lower dose at 0.5 × 106 MSC/kg. We recorded pulmonary function tests before and after infusion, and patients were followed clinically for 12 months.

Results
Infusions were well tolerated, and no significant adverse events were recorded in the first 30 days. There was significant decline (mean ± SD) in forced vital capacity (FVC) (3.49 ± 1.03 vs 3.18 ± 0.94 L, P = .03) and forced expiratory volume in 1 second (FEV1) (2.28 ± 0.86 vs 1.77 ± 0.49 L, P = .04) over the year preceding infusion. FVC (3.18 ± 0.94 vs 3.46 ± 0.99 L, P = .53) and FEV1 was not significantly changed (1.77 ± 0.49 vs 1.88 ± 0.75, P = .72) when comparing values immediately prior to infusion to those obtained 1 year after infusion, indicating a possible stabilizing effect on lung function decline due to o-CLAD.

Conclusion
Intravenous infusions of bone marrow-derived MSCs are well tolerated in lung transplant recipients with moderate-to-severe CLAD. Low-dose MSCs appear to slow progression of CLAD in some patients.
Incorporating telemedicine into an ambulatory orthopedic practice
Authors: Pelkowski Jessica N. , Gajarawala Shilpa N. , Spelsberg Sarah C. , Ledford Cameron K. 
Published: July 2022

ABSTRACT
The COVID-19 pandemic resulted in many challenges for the healthcare system. This article describes how an ambulatory orthopedic practice transitioned to telemedicine in order to continue to provide effective, efficient, and safe care for patients. Although this discipline relies heavily on physical assessment and examination, telemedicine can be successfully implemented in this area.
Selinexor therapy for multiple myeloma and non-Hodgkin lymphomas
Authors: Goldsmith Scott R. , Liu Lawrence , Shiah Kevin 
Published: July 2022

Purpose of review
In this review we highlight the most recent studies furthering the clinical development of selinexor, a novel exportin-1 inhibitor, for the treatment of multiple myeloma and non-Hodgkin lymphomas.

Recent findings
Three pivotal trials, the SADAL trial for diffuse large B-cell lymphoma, and the BOSTON and selinexor treatment of refractory myeloma trials for multiple myeloma, have recently led to the regulatory approval of selinexor monotherapy or combination regimens. They are complemented by several earlier phase clinical trials with iterative combinations, adding selinexor to novel therapies and cytotoxic chemotherapy regimens at various stages in the disease courses. In some, selinexor appears synergistic, occasionally overcoming treatment refractoriness, whereas in other situations appears additive. Consistent issues with tolerability are seen across trials, although consensus guidelines on their preemption and management have recently been adopted which may improve treatment success. While comparative data are lacking, the efficacy of selinexor-based regimens does not approach that of contemporaneous cellular and immunotherapies.

Summary
Selinexor is a novel and potentially synergistic therapy for lymphoid malignancies, although requires refined supportive measures and strategies to improve its efficacy. Likely, for continued success, it will need to identify niches that complement recent advances, such as bridging to cellular therapies or maintenance thereafter.
Thermoneutrality induces vascular dysfunction and impaired metabolic function in male Wistar rats: a new model of vascular disease
Authors: Keller Amy C. , Chun Ji H. , Knaub L.A. , Henckel M.M. , Hull S.E. , Scalzo R.L. , Pott G.B. , Walker L.A. , Reusch J.E.B. 
Published: July 2022

Objective:
Cardiovascular disease is of paramount importance, yet there are few relevant rat models to investigate its pathology and explore potential therapeutics. Housing at thermoneutral temperature (30 °C) is being employed to humanize metabolic derangements in rodents. We hypothesized that housing rats in thermoneutral conditions would potentiate a high-fat diet, resulting in diabetes and dysmetabolism, and deleteriously impact vascular function, in comparison to traditional room temperature housing (22 °C).

Methods:
Male Wistar rats were housed at either room temperature or thermoneutral temperatures for 16 weeks on either a low or high-fat diet. Glucose and insulin tolerance tests were conducted at the beginning and end of the study. At the study's conclusion, vasoreactivity and mitochondrial respiration of aorta and carotid were conducted.

Results:
We observed diminished vasodilation in vessels from thermoneutral rats (P < 0.05), whereas high-fat diet had no effect. This effect was also observed in endothelium-denuded aorta in thermoneutral rats (P < 0.05). Vasoconstriction was significantly elevated in aorta of thermoneutral rats (P < 0.05). Diminished nitric oxide synthase activity and nitrotyrosine, and elevated glutathione activity were observed in aorta from rats housed under thermoneutral conditions, indicating a climate of lower nitric oxide and excess reactive oxygen species in aorta. Thermoneutral rat aorta also demonstrated less mitochondrial respiration with lipid substrates compared with the controls (P < 0.05).

Conclusion:
Our data support that thermoneutrality causes dysfunctional vasoreactivity, decreased lipid mitochondrial metabolism, and modified cellular signaling. These are critical observations as thermoneutrality is becoming prevalent for translational research models. This new model of vascular dysfunction may be useful for dissection of targetable aspects of cardiovascular disease and is a novel and necessary model of disease.
Nitroxoline Drug Combinations Are More Active Than Lyme Antibiotic Combination and Can Eradicate Stationary-Phase Borrelia burgdorferi
Authors: Alvarez-Manzo Hector S. , Zhang Yumin , Zhang Ying 
Published: July 2022

Abstract
Lyme disease (LD), caused by Borrelia burgdorferi, is the most common vector-borne disease in the United States and Europe. Despite the standard 2–4 weeks' antibiotic treatment, approximately 10%–20% of patients will develop posttreatment LD syndrome, a condition that is poorly understood. One of the probable causes is thought to be the presence of B. burgdorferi persister forms that are not effectively killed by the current LD antibiotics. In this study, we evaluated nitroxoline, an antibiotic used to treat urinary tract infections, for its activity against a stationary-phase culture enriched with persister forms of B. burgdorferi. Nitroxoline was found to be more active than doxycycline and equally active as cefuroxime (standard LD antibiotics) against B. burgdorferi. Importantly, the nitroxoline two-drug combinations nitroxoline + cefuroxime and nitroxoline + clarithromycin, as well as the nitroxoline three-drug combination nitroxoline + cefuroxime + clarithromycin, were as effective as the persister drug daptomycin-based positive control three-drug combination cefuroxime + doxycycline + daptomycin, completely eradicating stationary-phase B. burgdorferi in the drug-exposure experiments and preventing regrowth in the subculture study. Future studies should evaluate these promising drug combinations in a persistent LD mouse model.
Prospects for the Implementation of HIV Molecular Transmission Network–Informed AIDS Prevention and Control in China
Authors: Feng Yi , Xing Hui , Ruan Yuhua , Liao Lingjie , Shao Yiming 
Published: July 2022

Abstract
The human immunodeficiency virus (HIV)–infected population with a transmission link has a strong genetic similarity in viral gene sequences that tend to cluster. In recent years, a strategy for guiding HIV/acquired immunodeficiency syndrome (AIDS) prevention using sequence-based transmission networks has been proposed. The execution of this strategy provides an opportunity to effectively control the spread of the AIDS epidemic in China. HIV molecular transmission network research has been actively pursued by a number of Chinese research groups. Medium- and long-term strategies were created with the goal of using HIV molecular transmission networks to guide targeted prevention and control in China. Technical guidelines for HIV transmission network monitoring and intervention have been written and released. Pilot studies are continuing in the meantime. Despite the fact that this strategy has a bright future, there are still many challenges to overcome to achieve the intended AIDS prevention and control goals.
Virginity Testing
Authors:   International Association of Forensic Nurses
Published: July 2022

ABSTRACT
Virginity testing is a human rights violation involving an examination of the female genitalia, often by a healthcare professional, intended to correlate the appearance of the hymen in women or girls with previous sexual intercourse. Virginity testing examinations are conducted under a variety of circumstances and settings: before marriage to establish virginity, to disprove or prove an allegation of sexual violence, to legally assess the allegation of a woman or girl not being a virgin in the absence of bleeding on her wedding night, and to intimidate political activists and detainees. Despite the United Nations Human Rights Office, United Nations Women, and World Health Organization calling for a ban on this practice, it remains common practice in various regions around the world. It is the position of the International Association of Forensic Nurses that virginity testing cannot accurately determine if consensual sexual activity or sexual abuse has occurred and can result in significant physical, psychological, and social consequences.
The role of PET in the management of sarcoidosis
Authors: Vender Robert J. , Aldahham Hamad , Gupta Rohit 
Published: July 2022

Purpose of review
PET has emerged as method to determine the location and extent of disease activity in sarcoidosis. As most clinicians do not routinely utilize PET in the management of sarcoidosis, an understanding of the imaging technique is needed to comprehend the impact that PET abnormalities have on diagnosis, prognosis, and treatment.

Recent findings
Although PET can detect inflammation because of sarcoidosis throughout the body, it is most often utilized for the diagnosis of cardiac sarcoidosis for which it may provide information about prognosis and adverse events. Whenever PET is combined with cardiac magnetic resonance (CMR), clinicians may be able to increase the diagnostic yield of imaging. Furthermore, PET abnormalities have the potential to be utilized in the reduction or augmentation of therapy based on an individual's response to treatment. Although various biomarkers are used to monitor disease activity in sarcoidosis, an established and reproducible relationship between PET and biomarkers does not exist.

Summary
PET has the potential to improve the diagnosis of sarcoidosis and alter treatment decisions but prospective trials are needed to define the role of PET while also standardizing the performance and interpretation of the imaging modality.
Hit-hard and early versus step-up treatment in severe sarcoidosis
Authors: Vorselaars Adriane D.M. , Culver Daniel A. 
Published: July 2022

Purpose of review
The treatment of sarcoidosis remains uncertain, despite 70 years of study. The conventional approach is to initiate corticosteroids in individuals who require treatment. The position of more aggressive regimes is unknown.

Recent findings
Recent recognition that many patients will require prolonged therapy, and the observation that corticosteroids lead to overt and insidious toxicities, have led to suggestions that steroid-sparing medications be used earlier in the management of sarcoidosis. Individuals with poor prognostic features, designated as ‘high-risk’ sarcoidosis may, especially benefit from a broader palette of therapeutic options in the initial treatment regimen. An even more aggressive approach, known as ‘top-down’ or ‘hit-hard and early’ therapy has emerged in the fields of gastroenterology and rheumatology in the past 15 years, on the premise that highly effective early control of inflammation leads to better outcomes. These regimens typically involve early initiation of biologic therapies.

Summary
For certain subpopulations of sarcoidosis patients, ‘top-down’ therapy could be helpful. Severe pulmonary sarcoidosis, neurosarcoidosis, cardiac sarcoidosis and multiorgan sarcoidosis are phenotypes that may be most relevant for revised therapeutic algorithms. Precision medicine approaches and randomized trials will be necessary to confirm a role for top-down therapy in the routine management of sarcoidosis.