bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 15: Invasive Aspergillus Niger Infection Cured after V Hematopoietic Stem Cell Transplantation in a Pediatric Patient with Severe Congenital Neutropenia
Authors: Marinelli Giulia , Caddeo Giulia , Chinello Matteo , Bonetti Elisa , Pezzella Vincenza , Zaccaron Ada , Esposto Maria , Balter Rita , Cesaro Simone 
Published: August 2024

Abstract

Introduction
Severe congenital neutropenia (SCN) is a non-malignant haematological disorder characterized by a quantitative deficit of neutrophils (N&lt;500/mmc), recurrent severe infections and need for prolonged granulocyte growth factor (G- CSF) therapy.

Objectives
This clinical case describes a life-saving unrelated cord blood transplant in a patient with previous multiple graft failures while ha had a severe active maxillary aspergillosis.

Methods
R.A. is a child suffering from SCN type I (mutation of the ELANE gene) who required the administration of granulocyte growth factor (G-CSF) from birth, at progressively increasing doses. The patient was a haploidentical allogeneic HSCT given the lack of HLA matched/minor mismatched donors from the international registries. The patients received sequentially 4 haplo HSCTs (2 from father with αβ+/CD19+ depletion of the graft, 2 from mother without in vitro graft manipulation and using post-transplant cyclophosphamide) without obtaining myeloid engraftment. and remaining aplastic. DSAs (patient-specific antibodies against the donor's HLA antigens) were found after the third transplant but the desensitization procedures did not prevent the rejection of the 4th transplant. Being aplastic for 4 months, he developed a progressively worsening Aspergillus niger infection of the oral cavity, maxillary bone and right maxillary sinus, with intermediate sensitivity to amphotericin B (Image 1). After identification of a DSA-negative unrelated cord blood unit (HLA match 6/8) a 5th HSCT was performed.

Results
The 5th transplant successfully engrafted for neutrophils and platelets and the aspergillosis infection gradually solved. Currently, three years after the transplant, the patient is in good conditions with a complete donor chimerism and without significant immunological consequences post-HSCT

Discussion
in this patient, the use of an unrelated cord blood allowed to bypass the lack of donors in the international registries and the graft failure/rejection of the haploidentical donors due to DSAs. Moreover, Aspergillosis refractory to antifungal medical therapy is not a contraindication to HSCT because myeloid recovery and immune reconstitution after HSCT are able to achieve a control of the infection together with antifungal therapy.
Abstract 18: A Case of Successful Poor Graft Function Treatment with Wharton Jelly Mesenchymal Stem Cells
Authors: Romiszewski Michał , Nasadiuk Khrystyna , Malinowska Iwona , Olearczyk Aleksandra , Snarski Emilian , Ołdak Tomasz , Łaguna Paweł 
Published: August 2024

Abstract

Introduction
Poor graft function (PGF) is a life-threatening complication that occurs after hematopoietic stem cell transplantation (HSCT). This is persistent neutropenia/thrombocytopenia, with complete donor chimerism, lack of severe GVHD or relapse, during the first 12 months after HSCT.

Objectives
To present a case study of PGF treatment with Wharton jelly (WJ) mesenchymal stem cells (MSC).

Methods
A 16-year-old boy was performed allogeneic bone marrow HSCT from a fully matched family donor due to secondary myelodysplastic syndrome, diagnosed 4 years after treatment of pineablastoma. Engraftment was documented on day +28 (95%) and 99% on day +42. The patient was discharged home in good general condition on day +37 post-transplant. From day +54, a deterioration of blood count parameters was observed. Partial secondary graft failure was diagnosed and no hematological response was achieved with 4 planned doses of Rituximab. Secondary causes of bone marrow failure and cytopenias were excluded. A bone marrow biopsy showed absence of the primary disease but significantly reduced bone marrow cellularity. Finally PGF was diagnosed and the patient was re-transplanted HSC from the same donor, without conditioning with prior administration of WJ MSCs (obtained from FamiCord Group) in the number of 120 x 106. No post-transplantation immunosuppression was used.

Results
As a result of the procedure, the blood count parameters increased and stabilized at a level that no longer required additional transfusions support. No adverse effects and no early and late post-tranplant complications were observed. Currently, the patient remains in good general condition. Due to hemochromatosis previously caused by numerous red blood cells transfusions, he requires chelation therapy. Administration of MSCs is a safe method and might by an effective therapy for patients with PGF.

Discussion
Our clinical case is consistent with several literary reports showing efficacy of third parties MSCs in the treatment of PGF. The mechanism of therapeutic effect of MSCs in PGF is poorly known, it may be hypothesized that MSCs modulate bone marrow microenvironment and exert pracrine regenerative effect.
Abstract 27: Physiologic Oxygen Expansion Enhances Lymphocyte and Neutrophil Recovery Following Transplantation
Authors: Gutch Sarah , Ropa Jim , Beasley Lindsay , Whitacre Grace , Hof Wouter Van't , Capitano Maegan 
Published: August 2024

Abstract

Introduction
Expeditious recovery of lymphocytes after hematopoietic cell transplantation is a major determinant of patient outcome. There are few efficient clinical therapies to enhance lymphocyte recovery, indicating a clear unmet need. Ex vivo expansion of cord blood (CB) units is an approved therapy to increase numbers of hematopoietic stem and progenitor cells, but impact on lymphocyte recovery remains uncertain. Moreover, culture in physioxic (physiological oxygen) conditions results in increased lymphoid-biased RNA levels.

Objectives
We hypothesize that ex vivo expansion in physioxic conditions will increase lymphoid-biased cells and increase lymphocyte counts post-transplantation (PT). The objective of this study is to increase lymphocyte numbers following transplantation without sacrificing reconstitution of potent hematopoietic cells.

Methods
Three independent transplants were conducted. 1) Murine lineage- bone marrow (BM) was expanded for 7 days then transplanted into lethally irradiated mice with/without additional common lymphoid progenitors (CLPs). 2) Murine lineage- BM was expanded in 1%, 3%, 5%, 14%, and 21% O2 for 7 days and transplanted into lethally irradiated mice. 3) Human CD34+ CB cells were expanded for 7 days in 1%, 3%, 5%, 14%, and 21% O2 and transplanted into NSG mice. Unexpanded BM or CB cells were used as controls.

Results
Additional CLPs did not contribute to lymphocyte recovery. Mice transplanted with expanded BM had increased lymphocyte counts compared to transplantations with unexpanded BM at weeks 2 and 5 PT via complete blood count (CBC) and increased B-cell reconstitution in the spleen, BM, and peripheral blood (PB) at weeks 2, 5, and 8 PT. LSK (Lin- SCA1+ cKIT+) and neutrophil frequencies were increased at 3% O2 in the BM and 5% O2 in the PB, respectively. Compared to 21% O2, CB cells expanded at 1%, 3%, 5%, 14% O2 had increased neutrophil and lymphocyte frequencies in the PB at weeks 2 and 10, respectively, and demonstrated greater recovery than unexpanded at week 2.

Discussion
Expansion increases lymphocyte counts via CBC and immunophenotyping. Physioxic expansion increases numbers of potent hematopoietic cell subpopulations and frequencies of specific lymphocyte compartments in multiple organs. Thus, expansion under physioxia is a viable strategy to enhance recovery of lymphocytes PT.
Abstract 28: Cord Blood Derived Macrophages Promote the Differentiation of Oligodendrocyte Precursor Cells
Authors: Xu Li , O'Neil Shane , Min Hyunjung , Ozamiz April , Kurtzberg Joanne , Filiano Anthony 
Published: August 2024

Abstract

Introduction
Krabbe Disease (KD) is a rare neurodegenerative disorder caused by a mutation in the gene encoding galactocerebrosidase (GALC). GALC deficiency leads to accumulation of the toxic metabolite psychosine in myelin-forming oligodendrocytes causing severe demyelination. Presymptomatic hematopoietic stem cell transplants can slow the progression of disease, but ultimately there is no cure. We previously demonstrated that DUOC-01, a first-generation macrophage cell-therapy manufactured from banked human umbilical cord blood cells, which when injected into the corpus callosum, enhanced remyelination in immunocompromised mice treated with the demyelinating agent, cuprizone. Further, DUOC-01 could promote the maturation of oligodendrocyte precursor cells (OPCs) into mature oligodendrocytes via remyelinating factors (Remy-Macs).

Objectives
In this study, we set out to test if DUOC-01 and their secreted Remy-Macs could rescue oligodendrocyte deficits and improve survival in GALC deficient mice.

Methods
First, we generated primary OPC cultures from GALC deficient mice and measured OPC maturation by immunohistochemistry and qRT-PCR of myelin basic protein (MBP). To test if DUOC-01 impacted OPCs via secreted factors, we incorporated the use of transwell assays. To test if DUOC-01 or Remy-Macs could promote remyelination in vivo, we injected DUOC-01 or used Alzet osmotic pumps to deliver therapies into the cerebrospinal fluid (CSF).

Results
We first tested the effects of DUOC-01 and Remy-Macs on primary OPC cultures isolated from neonatal control of GALC deficient mice. We observed comparable oligosphere growth in cultures derived from GALC deficient mice and their wild-type litter mates, indicating a normal function for twitcher OPC proliferation. However, OPC differentiation was compromised in GALC deficient mice, demonstrated by decreased MBP expression. DUOC-01 and Remy-Macs increased the production of MBP at both mRNA and protein levels. Additionally, infusion of Remy-Macs into the CSF of GALC deficient mice improved survival.

Discussion
Our data demonstrated that DUOC-01 or Remy-Macs promoted the differentiation of OPCs isolated from GALC deficient mice. Further, infusing Remy-Macs into the CSF of GALC deficient mice extended life span. Our data suggest DUOC-01 or Remy-Macs have the potential to be further developed into a novel cell-therapy to treat Krabbe and other demyelinating diseases.
Abstract 33: Transcriptomic Identification of Functionally Potent Umbilical Cord Blood Units
Authors: Ropa James , Gutch Sarah , Beasley Lindsay , Hof Wouter Van't , Sun Jessica , Capitano Maegan , Kaplan Mark 
Published: August 2024

Abstract

Introduction
Umbilical cord blood (UCB) is an important donor source for standard of care cellular therapies as well as innovative new treatments. Universal potency criteria for cord blood unit (CBU) selection for different cellular therapy applications are still desired and efficient methods to elucidate these criteria remain elusive.

Objectives
Our goal is to find molecular markers that identify potent CBUs for use in cellular therapies. Here, we utilized transcriptomics to reveal genes associated with hematopoietic stem and progenitor cell (HSC/HPC) potency in hematopoietic cell transplantation.

Methods
We performed three separate transcriptomic analyses of human UCB used in mouse models of transplantation. This included bulk RNA-sequencing of HSCs/HPCs from CBUs with known engraftment capacities (n=9 CBUs), bulk RNA-sequencing of homed/early engrafted CD34+ cells (n=3 CBUs), and single cell RNA-sequencing of CD34+ cells expanded in varying oxygen tensions, which affects their transplantation potency (n=4 CBUs).

Results
HSCs/HPCs enriched for dehydrogenase and cell cycle associated genes yield better repopulating cell frequency. Early homed CD34+ cells have enriched expression of immune activation and cell cycle genes compared to input transplanted cells. Distinct clusters of UCB cells marked by genes such as PRSS2 and AVP are enriched in oxygenation conditions that drive increased potency. Dehydrogenase and stress response genes are enriched in populations predicted to be more functional regardless of HSC/HPC subpopulation. Integration of all three studies reveals genes that may define highly potent CBUs, including DDIT4, a stress response gene. Indeed, DDIT4 independently predicts engraftment outcomes in mouse models of transplantation. Future work will examine a qPCR based gene panel potency assay to predict outcomes in patient transplantations.

Discussion
We have identified genes associated with HSC/HPC potency using transcriptomic approaches. These findings have immediate translational implications for CBU selection for transplantation, but also provides a blueprint for finding CBUs best suited for use in developing off-the-shelf immune effector therapies or those that are best for treating non-hematologic central nervous system disorders such as cerebral palsy, among other applications. Importantly, this study highlights the importance for omics technology as a valuable tool to define potency criteria for UCB as a donor source for cellular therapies.
Unveiling the science behind erectile dysfunction topical therapy: investigating transdermal papaverine as a novel treatment approach
Authors: Rezaiezadeh Hojjat , Ranjbar Tavakoli Marziyeh , Langarizadeh Mohammad Amin , Saeedi Garaghani Zahra , Karami-Mohajeri Somayyeh 
Published: August 2024

Abstract

Introduction
Erectile dysfunction is among the most prevalent urologic issues affecting men globally and is characterized by a high incidence rate. This condition significantly affects the quality of life of patients and their sexual partners.

Objectives
Due to the interactions, contraindications, and side effects associated with systemic drugs, recent research has increasingly focused on topical and transdermal medications for the treatment of erectile dysfunction.

Methods
Based on previous studies, this article examines papaverine in terms of local effectiveness, methods of increasing therapeutic efficiency, possible local side effects, and evaluation of its various formulations.

Results
Among these approaches, notable strategies include using novel formulations and nanoformulations as compared with classic ones, employing permeation enhancers, and combining treatments with other oral and topical drugs with synergistic mechanisms. These methods aim to improve transdermal papaverine’s bioavailability and therapeutic efficacy while minimizing side effects and enhancing patient compliance.

Conclusion
Transdermal papaverine may not be as effective as its injectable form, but the treatment path is more pleasant, with less pain and fewer side effects for patients. For this reason, using solutions that remove the penile skin and fascial absorption barrier can be very effective.
Taxation of Czech trust funds and foundations in the international context
Authors: Bartíková Andrea 
Published: August 2024

Abstract
The foundation’s purpose is traditionally public benefit activities in the Czech environment. In addition to a foundation, a trust fund, primarily used for the management of family assets but often for public benefit purposes, can be used for philanthropic purposes. Foundations and trust funds are subject to different tax regimes depending on the purpose for which they were established. The aim of this article is to use the analytical-descriptive and comparative method to explain, also in the international context, the tax aspects of foundations and trust funds, their different purposes and potential problems, as in the Czech environment we can still encounter the belief that foundations and trust funds serve to circumvent the tax system.
Mental health disparities in people living with human immunodeficiency virus: A cross-sectional study on physician-patient concordance and treatment regimens
Authors: Shi Jinchuan , Zhang Zhongdong , Zhang Junyan , Zhang Yishu , Qiu Jiating , Liu Fang , Song Daoyuan , Ma Yanfang , Zhong Lianmei , Wang Hongxing , Liu Xiaolei 
Published: August 2024

Abstract

Background:
Human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) can profoundly affect the mental health of the people living with HIV (PLWH), with higher rates of anxiety, depression, and sleep disturbances. The disparities in neuropsychological problems evaluated by physicians and self-assessed by patients are still unknown.

Methods:
A total of 5000 PLWH and 500 physicians from 167 hospitals were enrolled in this cross-sectional study from September 2022 to February 2023. 4-Item Patient Health Questionnaire (PHQ-4) was used for the evaluation of depressive issues and anxiety issues by PLWH. Each physician assessed 10 PLWH under their care for the presence of depressive or anxiety issues. The primary outcomes of this study are the concordance rates on the depressive issues and anxiety issues evaluation between physicians and PLWH. The Cohen’s kappa test was used to assess the agreement between physicians and PLWH.

Results:
The concordance rate for the evaluation of depressive issues is 73.84% (95% confidence interval [CI]: 72.60–75.04%), and it is significantly different from the expected rate of 80% (P <0.001). Similarly, the concordance rate for the evaluation of anxiety issues is 71.74% (95% CI: 70.47–72.97%), which is significantly different from the expected rate of 80% as per the null hypothesis (P <0.001). The overestimation rate by physicians on depressive issues is 12.20% (95% CI: 11.32–13.14%), and for anxiety issues is 12.76% (95% CI: 11.86–13.71%). The mismatch rate for depressive issues is 26.16% (95% CI: 24.96–27.40%), and for anxiety issues is 28.26% (95% CI: 27.02–29.53%). The underestimation rate by physicians on depressive issues is 13.96% (95% CI: 13.03–14.95%), and for anxiety issues is 15.50% (95% CI: 14.52–16.53%). For the treatment regiments, PLWH sustained on innovative treatment regimen (IR) related to a lower prevalence of depressive issues (odds ratio [OR] = 0.71, 95% CI: 0.59–0.87, P = 0.003) and a lower prevalence of anxiety issues (OR = 0.63, 95% CI: 0.52–0.76, P <0.001). PLWH switch from conventional treatment regimen (CR) to IR also related to a lower prevalence of depressive issues (OR = 0.79, 95% CI: 0.64–0.98) and a lower prevalence of anxiety issues (OR = 0.81, 95% CI: 0.67–0.99).

Conclusion:
Nearly one in three PLWH had their condition misjudged by their physicians. The findings underscore the need for improved communication and standardized assessment protocols in the care of PLWH, especially during the acute phase of HIV infection.
Reconstruction of Nasal Deformity Resulting from Mucormycosis Using a Chin Silicone Implant
Authors: Ahmad Ahmad Fayez 
Published: August 2024

Summary:
The clinical manifestations of mucormycosis vary depending on the location of the infection. In general, sepsis begins within the oral cavity or nose and then spreads to the central nervous system through the eyes. It is typically seen in immunocompromised patients, including those who have been exposed to high doses of cortisone, such as corona virus disease 2019 patients. The infection can lead to severe destruction of the bones of the palate, nose, and maxillary and sinusoid areas. Treatment may require both medical and surgical intervention. In the secondary stage of recovery from mucormycosis, various methods of reconstructive surgery for the external nasal structure can be used. To my knowledge, this is the first case that compares to secondary nasal restoration. A former patient with mucormycosis was treated using an autologous bone graft from the ilium, and after 2 years, the restoration was done using a silicone implant due to the absorption of the bone graft. The restoration using the silicone implant led to satisfactory results for the patient and the surgeon from an aesthetic standpoint, and we did not notice any inflammatory or infectious symptoms during the 11-month follow-up period.
Reproductive and pregnancy control in Wilson disease patients in Spain
Authors: Romero-Gutiérrez Marta , Alonso Pablo , Berenguer Marina , Olveira Antonio , González-Diéguez María Luisa , Iruzubieta Paula , Masnou Helena , Delgado Manuel , Hernández-Guerra Manuel , Lorente Sara , Lázaro María , Moreno-Planas José María , González Concepción , Fernández-Álvarez Paula , Cuenca Francisca , Gómez Judith , García-Villareal Luis , Rodríguez Olga , Mariño Zoe ,   on behalf of the AEEH Wilson Registry (Registro Wilson AEEH)
Published: August 2024

Background and aim
Recommendations on pregnancy, lactation, and contraception in women with Wilson disease are briefly stated in international guidelines but are not entirely homogeneous. Data regarding the management of these special events among patients with Wilson disease in Spain are lacking. We used the Wilson Registry platform of the Spanish Association for the Study of the Liver to question patients on their reproductive and gestational lives.

Methods
This was a multicentre ambispective study including adult women with Wilson disease in the Spanish Wilson Registry interviewed about their contraception, childbearing, pregnancy, and lactation experiences. Clinical and analytical data were extracted from the registry.

Results
The study included 92 women from 17 centres in Spain. Most (63%) reported having a previous pregnancy history. The rate of spontaneous miscarriages was 21.6%, mainly occurring in the first trimester and up to one third among undiagnosed patients. Most pregnant women received chelator therapy during pregnancy, but dose reduction was recommended in less than 10%. After delivery, artificial lactation predominated (60.3%) and its use was mainly based on physician’s recommendations (68%). Up to 40% of the women included reported some concerns about their reproductive lives, mainly related to the potential drug toxicity to their children. Most of the patients considered the information given by specialists to be sufficient.

Conclusion
Gestational management among women with Wilson disease in Spain was found to be highly heterogeneous and frequently different from what is described in international guidelines. Education on rare liver diseases should be a priority for scientific societies in order to homogenize patient follow-up and recommendations.
Glycemic Outcomes and Nurse Perceptions of Continuous Glucose Monitoring for Hospitalized Patients
Authors: Thullen Alexandra , Gerber Rebecca , Keen Alyson 
Published: August 2024

Background:
Continuous glucose monitoring (CGM) can decrease hypoglycemic events and health care costs; however, barriers and facilitators that influence CGM use are unknown.

Purpose:
The purpose of this study was to evaluate hypoglycemic events and cost outcomes after CGM implementation and describe associated barriers and facilitators.

Methods:
A mixed-methods study design was used to evaluate CGM implementation on 2 pulmonary units within an academic health center. Hypoglycemic events were evaluated before and after CGM implementation, and nurses were interviewed about facilitators and barriers that influence CGM use.

Results:
Hypoglycemic events decreased from a rate of 0.0906 per 1000 patient days to 0.0503 postimplementation, P < .0001. A $105 766 cost avoidance was recognized. Barriers and facilitators to CGM use are described.

Conclusions:
Findings support CGM implementation, while uniquely contributing financial impact and device use barriers and facilitators. Hospitals may consider CGM use to improve timely identification and treatment of hypoglycemia.