bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intensity Meters: New Notes and Discoveries on the Invention of Early Modern Precision Instruments
Authors: Bigotti Fabrizio 
Published: December 2023

Abstract
The article sheds light on the invention of early modern precision instruments and their application in medicine, by analysing a neglected work by one of the Italian pupils of the physician Santorio Santori (1561–1636). This source provides vital information on Santorio’s experimental sample, and on the practical use and dimensions of instruments such as thermometers, hygrometers, pulsimeters and precision scales, showing that they also had a normative purpose: regulating the environmental factors affecting human health. The article first establishes the derivative nature of the source from Santorio’s teachings, and then contextualises the invention of precision instruments with regard to Santorio’s published and unpublished output. In the conclusions, I argue that the new instruments were meant to address the shortcomings of the traditional diagnostic rationale and are best conceptualised as ‘intensity meters’ meant to assess ‘the magnitude’ (magnitudo) of a patient’s illness in degrees.
Jerónimo Muñoz’s Reception of Proclus’ In Euclidem: Philosophy of Mathematics and an Attempt to Prove the Parallel Postulate
Authors: Campillo Bo Álvaro José 
Published: December 2023

Abstract
The goal of this paper is to show – by way of a case study – how the contents of Proclus’ Commentary on the First Book of Euclid’s Elements were incorporated into university teaching in the sixteenth century. I analyse the impact of Proclus on the works of the Spanish mathematician and university professor Jerónimo Muñoz (ca. 1520–1591). In order to do so, I examine two manuscripts: Adnotationes in commentaria Procli super Euclidem (MS Vat. Lat. 6996), and Astrologicarum et geographicarum institutionum libri sex (MS Vat. Lat. 6998). I show that the contents of Proclus’ commentary pervade Muñoz’s mathematical writings and influence his mathematical ontology, his classification of mathematical disciplines, and the history and terminology of geometry that he adopts. Moreover, I expound on how Proclus’ text inspired Muñoz to maintain that the fifth postulate was a theorem, leading him to attempt a demonstration of it which pre-dates knowledge in the Latin West of Naṣīr ad-Dīn’s (1201–1274) previous attempt.
Difficulties of Translating Al-Mušākalah (Homonymy) in the Holy Qurʾan: A Comparative Analytical Study
Authors: Al-Wadhan Trad , Al-Abbas Linda S. 
Published: December 2023

Abstract
This study aims to highlight the difficulties of translating Al-Mušākalah in the Holy Qurʾan into English by selecting six pairs that involve this phenomenon. It examines the accuracy of the English renditions of these expressions in five well-known English translations of the Holy Qurʾan, namely: Sahih International (1997), Yusuf Ali (1982), Abdel-Haleem (2005), Al-Hilali & Khan (2018), and Shakir (1987), based on a number of popular exegeses in the Islamic world. The English equivalents selected by the translators were looked up in Collins English Dictionary to check their compatibility with the interpretations given in the exegeses. The study found that the translators could not fully reflect the slight differences between the homonymous pairs in some cases. The translation of Al-Hilali and Khan was the most successful in achieving the intended meanings, followed by Yusuf Ali’s. Shakir and Abdel-Haleem had almost the same level of accuracy, and Sahih International translation was the least consistent with the Qurʾanic interpretations.
The Clinton Administration’s Policy of Democracy Promotion in Ukraine (1993–2001)
Authors: Boys James D. 
Published: December 2023

Abstract
The violence perpetrated against Ukraine has raised questions regarding the direction of U.S. grand strategy since the end of the Cold War, with the Clinton administration’s decision to pursue a policy of democratic promotion in central and eastern Europe coming under specific scrutiny. Was this, as critics suggest, a strategic blunder that prompted Moscow’s apparent attempt to re-establish control over its former satellites, or, as was believed at the time, a necessary step towards political and economic reform of the European continent following the Cold War? This paper reveals how the Democracy Promotion pillar of the Clinton administration’s policy of Engagement and Enlargement aided the development of Ukraine without antagonizing the Kremlin, and the lessons that the Biden administration could glean from this policy thirty years later.
Planning GvHD preemptive therapy: risk factors, biomarkers, and prognostic scores
Authors: Rozmus Jacob , Levine John E. , Schultz Kirk R. 
Published: December 2023

Abstract
Prevention of acute and chronic graft-versus-host disease (aGvHD and cGvHD) is an important objective of allogeneic hematopoietic cell transplantation (HCT). While there is has been significant progress in preventative approaches in the peritransplant period to minimize development of GvHD, no preventative approach has completely eliminated development of either aGvHD or cGvHD. Recently, posttransplant immune biomarker profiling early post-HCT by the Mount Sinai Acute GvHD International Consortium group has resulted in a validated risk assignment algorithm and development of preemptive approaches to decrease aGvHD and mortality in high-risk patients. cGvHD risk assignment algorithms have been developed based on measurements at day 100 and may be used for future preemptive intervention trials to minimize cGvHD. This article discusses the current state of the art in aGvHD and cGvHD preemptive algorithms and therapeutic interventions and what is needed to move these into validated approaches.
A rational approach to functional high-risk myeloma
Authors: Gay Francesca , Bertuglia Giuseppe , Mina Roberto 
Published: December 2023

Abstract
Multiple myeloma is a clinically and biologically highly heterogeneous disease, as the overall survival can vary from more than a decade in patients with standard risk disease treated with intensive chemotherapy to 2−3 years in patients with high-risk features. The current staging systems, which rely on baseline biological risk factors to stratify patients into groups with differing risks of progression or death, are sometimes suboptimal tools for identifying high-risk patients. This is particularly evident when considering the so-called functional high-risk patients—patients who do not necessarily display baseline high-risk features but typically show a suboptimal response to induction therapy or relapse early after treatment initiation: the survival of these patients is particularly poor even in the context of newer therapies. The prompt identification, as well as a consistent definition, of this subset of patients, as well as their management, currently represents an unmet medical need. In this review we explore the main characteristics of functional high-risk patients, the available known risk factors and scoring systems, and the possible management.
The sum of the parts: what we can and cannot learn from comorbidity scores in allogeneic transplantation
Authors: Shouval Roni , Fein Joshua A. 
Published: December 2023

Abstract
Allogeneic hematopoietic cell transplantation (alloHCT) requires the comprehensive evaluation of patients across multiple dimensions. Among the factors considered, comorbidities hold great significance in the pretransplant assessment. As many as 40% of alloHCT recipients will have a high burden of comorbidities in contemporary cohorts. To ensure a standardized evaluation, several comorbidity scores have been developed; however, they exhibit variations in properties and performance. This review examines the strengths and weaknesses associated with these comorbidity scores, critically appraising these models and proposing a framework for their application in considering the alloHCT candidate. Furthermore, we introduce the concept that comorbidities may have specific effects depending on the chosen transplantation approach and outline the findings of key studies that consider the impact of individual comorbidities on alloHCT outcomes. We suggest that a personalized transplantation approach should not rely solely on the overall burden of comorbidities but should also take into account the individual comorbidities themselves, along with other patient, disease, and transplantation-related factors.
Pyruvate kinase activators: targeting red cell metabolism in sickle cell disease
Authors: Xu Julia Z. , Vercellotti Gregory M. 
Published: December 2023

Abstract
Hemoglobin S (HbS) polymerization, red blood cell (RBC) sickling, chronic anemia, and vaso-occlusion are core to sickle cell disease (SCD) pathophysiology. Pyruvate kinase (PK) activators are a novel class of drugs that target RBC metabolism by reducing the buildup of the glycolytic intermediate 2,3-diphosphoglycerate (2,3-DPG) and increasing production of adenosine triphosphate (ATP). Lower 2,3-DPG level is associated with an increase in oxygen affinity and reduction in HbS polymerization, while increased RBC ATP may improve RBC membrane integrity and survival. There are currently 3 PK activators in clinical development for SCD: mitapivat (AG-348), etavopivat (FT-4202), and the second-generation molecule AG-946. Preclinical and clinical data from these 3 molecules demonstrate the ability of PK activators to lower 2,3-DPG levels and increase ATP levels in animal models and patients with SCD, as well as influence a number of potential pathways in SCD, including hemoglobin oxygen affinity, RBC sickling, RBC deformability, RBC hydration, inflammation, oxidative stress, hypercoagulability, and adhesion. Furthermore, early-phase clinical trials of mitapivat and etavopivat have demonstrated the safety and tolerability of PK activators in patients with SCD, and phase 2/3 trials for both drugs are ongoing. Additional considerations for this novel therapeutic approach include the balance between increasing hemoglobin oxygen affinity and tissue oxygen delivery, the cost and accessibility of these drugs, and the potential of multimodal therapy with existing and novel therapies targeting different disease mechanisms in SCD.
How to manage hemostasis in patients with liver disease during interventions
Authors: Roberts Lara N. 
Published: December 2023

Abstract
Patients with advanced chronic liver disease (CLD) often need procedures to both treat and prevent complications of portal hypertension such as ascites or gastrointestinal bleeding. Abnormal results for hemostatic tests, such as prolonged prothrombin time, international normalized ratio, and/or thrombocytopenia, are commonly encountered, raising concerns about increased bleeding risk and leading to transfusion to attempt to correct prior to interventions. However hemostatic markers are poor predictors of bleeding risk in CLD, and routine correction, particularly with fresh frozen plasma and routine platelet transfusions, should be avoided. This narrative review discusses the hemostatic management of patients with CLD using 2 case descriptions.
The range of haploidentical transplant protocols in sickle cell disease: all haplos are not created equally
Authors: Kassim Adetola A. , DeBaun Michael R. 
Published: December 2023

Abstract
The ideal curative therapy for sickle cell disease (SCD) must be applicable across all ages and include individuals with strokes and preexisting heart, lung, and kidney disease. Myeloablative, matched sibling donor hematopoietic stem cell transplant (HCT) for children with SCD has shown excellent outcomes over the past 3 decades but has been restricted due to the limited availability of a human leukocyte antigen–matched sibling donor (10%-15%) and increased treatment-related death in adults with myeloablative conditioning. To overcome these 2 significant barriers to curative therapy in SCD, related haploidentical HCT has become an active area of research. The use of related haploidentical donors (first- and second-degree relatives) increases the donor pool to at least 90% of those eligible across the life span. Importantly, most adults, even with strokes or significant comorbidities, can tolerate the nonmyeloablative conditioning regimen without treatment-related death. Since 2013, at least 3 related haploidentical HCT strategies have emerged as potential curative therapies for SCD: (1) a nonmyeloablative, T-cell replete, bone marrow transplant with thiotepa and posttransplant cyclophosphamide with a goal of complete donor chimerism; (2) a nonmyeloablative, in vivo T-cell depletion, using peripheral blood stem cells (PBSCs) with a goal of stable mixed donor-recipient chimerism; and (3) a myeloablative, ex vivo T-cell depletion using PBSCs and advanced-technology graft manipulation, with a goal of complete donor chimerism. We review the similarities, differences, outcomes, and gaps in knowledge with these 3 haploidentical HCT approaches for SCD.
Management of Fanconi anemia beyond childhood
Authors: Olson Timothy S. 
Published: December 2023

Abstract
Fanconi anemia (FA) has long been considered a severe inherited bone marrow failure (BMF) disorder of early childhood. Thus, management of this multisystem disorder has previously been unfamiliar to many hematologists specializing in the care of adolescents and young adults (AYA). The increased diagnosis of FA in AYA patients, facilitated by widely available germline genomic testing, improved long-term survival of children with FA following matched sibling and alternative donor hematopoietic stem cell transplantation (HSCT) performed for BMF, and expanding need in the near future for long-term monitoring in patients achieving hematologic stabilization following ex vivo gene therapy are all reasons why management of FA in AYA populations deserves specific consideration. In this review, we address the unique challenges and evidence-based practice recommendations for the management of AYA patients with FA. Specific topics addressed include hematologic monitoring in AYA patients yet to undergo HSCT, management of myeloid malignancies occurring in FA, diagnosis and management of nonhematologic malignances and organ dysfunction in AYA patients with FA, and evolving considerations for the long-term monitoring of patients with FA undergoing gene therapy.
Inpatient recognition and management of HLH
Authors: Zoref-Lorenz Adi , Ellis Martin , Jordan Michael B. 
Published: December 2023

Abstract
Hemophagocytic lymphohistiocytosis (HLH) is one of the life-threatening emergencies that a hematologist may be called upon to diagnose and manage. It is a hyperinflammatory process that develops in patients with genetic abnormalities, hematologic malignancies, chronic inflammatory states, or infections. The main clinical challenges are recognizing HLH, determining whether the immune response is aberrant or appropriate, and deciding upon therapy. Patients may present with fever, central nervous system symptoms, cytopenias, or elevated liver enzymes.
Recognizing HLH is challenging because its features overlap with numerous systemic disorders, thus requiring a high level of suspicion and timely investigations to confirm the diagnosis and detect the underlying trigger. Once HLH is diagnosed, careful consideration of immunosuppressive therapy's potential benefit versus harm is necessary. Such therapy can sometimes be tailored to the underlying trigger. In the acute setting, the competing pressures of completing a thorough diagnostic process (including evaluation for the presence of lymphoma and infection) and the need for expedited treatment must be balanced. During the management of an HLH patient, continuous vigilance for the presence of as-yet unrecognized disease triggers, monitoring response, and identifying emerging complications is critical. This review will discuss the recognition and management of HLH in the inpatient setting.
What makes a pediatric or young adult patient an appropriate transplant candidate?
Authors: Thakar Monica S. , Sorror Mohamed L. 
Published: December 2023

Abstract
A 3-year-old child with chronic granulomatous disease was brought to the transplant clinic by his parents. The patient has a history of Aspergillus fumigatus pneumonia, which required mechanical ventilation, and sepsis, resulting in several intensive care stays. He has failure to thrive and developmental delay. His parents are seeking guidance whether allogeneic hematopoietic cell transplantation (HCT) is a reasonable treatment option given concerns about his upfront major health limitations. Based on the original HCT-Comorbidity Index (CI), this child's risk for nonrelapse mortality (NRM) would be negligible with a score of 0. With use of the validated youth-nonmalignant HCT-CI, the score increases to 5, due to prior mechanical ventilation (+3), history of fungal infection (+1), and being underweight (+1), with at least 2-fold increase in risk of NRM. The role of developmental delay is unclear and not currently validated to prognosticate survival. While HCT was ultimately recommended in this case, the family was counseled to have a more realistic sense of NRM risk.
Next-generation therapy for lower-risk MDS
Authors: Sébert Marie 
Published: December 2023

Abstract
Myelodysplastic syndromes (MDS) are malignant myeloid neoplasms characterized by ineffective clonal hematopoiesis leading to peripheral blood cytopenia and a variable risk of transformation to acute myeloid leukemia. In lower-risk (LR) MDS, as defined by prognostic scoring systems recently updated with the addition of a mutation profile, therapeutic options aim to reduce cytopenia, mainly anemia. Although options for reducing the transfusion burden have recently been improved, erythropoiesis-stimulating agents (ESAs), lenalidomide, hypomethylating agents, and, more recently, luspatercept have shown efficacy in rarely more than 50% of patients with a duration of response often far inferior to the patient's life expectancy. Nevertheless, several new therapies are currently under investigation aiming at improving cytopenia in patients with LR-MDS, mostly by targeting different biological pathways. Targeting ligands of the transforming growth factor β pathway has led to the approval of luspatercept in LR-MDS with ring sideroblasts or SF3B1 mutation, potentially replacing first-line ESAs in this population. Here, we also discuss the evolving standard of care for the treatment of LR-MDS and explore some of the most promising next-generation agents under investigation.
Glabridin improves autoimmune disease in Trex1-deficient mice by reducing type I interferon production
Authors: Wen Jincai , Mu Wenqing , Li Hui , Yan Yulu , Zhan Xiaoyan , Luo Wei , Wang Zhongxia , Kan Wen , Zhao Jia , Hui Siwen , He Ping , Qin Shuanglin , Xu Yingjie , Zhang Ping , Xiao Xiaohe , Xu Guang , Bai Zhaofang 
Published: December 2023

Abstract
Background
The cGAS-STING signaling pathway is an essential section of the natural immune system. In recent years, an increasing number of studies have shown a strong link between abnormal activation of the cGAS-STING signaling pathway, a natural immune pathway mediated by the nucleic acid receptor cGAS, and the development and progression of autoimmune diseases. Therefore, it is important to identify an effective compound to specifically downregulate this pathway for disease.

Methods
The effect of Glabridin (Glab) was investigated in BMDMs and Peripheral blood mononuclear cell (PBMC) by establishing an in vitro model of cGAS-STING signaling pathway activation. An activation model stimulated by DMXAA was also established in mice to study the effect of Glab. On the other hand, we investigated the possible mechanism of action of Glab and the effect of Glab on Trex1-deficient mice.

Results
In this research, we report that Glab, a major component of licorice, specifically inhibits the cGAS-STING signaling pathway by inhibiting the level of type I interferon and inflammatory cytokines (IL-6 and TNF-α). In addition, Glab has a therapeutic effect on innate immune diseases caused by abnormal cytoplasmic DNA in Trex1-deficient mice. Mechanistically, Glab can specifically inhibit the interaction of STING with IRF3.

Conclusion
Glab is a specific inhibitor of the cGAS-STING signaling pathway and may be used in the clinical therapy of cGAS-STING pathway-mediated autoimmune diseases.
The role of N-methyladenosine modification in acute and chronic kidney diseases
Authors: Qi Saiqi , Song Jie , Chen Linjun , Weng Huachun 
Published: December 2023

AbstractN6-methyladenosine (m6A) modification is a kind of RNA modification in which methylation occurs at the sixth N position in adenosine in RNA, which can occur in various RNAs such as mRNAs, lncRNAs and miRNAs. This is one of the most prominent and frequent posttranscriptional modifications within organisms and has been shown to function dynamically and reversibly in a variety of ways, including splicing, export, attenuation and translation initiation efficiency to regulate RNA expression. There are three main enzymes associated with m6A modification: writers, readers and erasers. Increasing evidence has shown that m6A modification is associated with the onset and development of kidney disease. In this article, we address the important physiological and pathological roles of m6A modification in kidney diseases (uremia, ischemia–reperfusion kidney injury, drug-induced kidney injury, and diabetic nephropathy) and its molecular mechanisms to provide reference for the diagnosis and clinical management of kidney diseases.
Genome- and Transcriptome-wide Association Studies to Discover Candidate Genes for Diverse Root Phenotypes in Cultivated Rice
Authors: Wei Shujun , Tanaka Ryokei , Kawakatsu Taiji , Teramoto Shota , Tanaka Nobuhiro , Shenton Matthew , Uga Yusaku , Yabe Shiori 
Published: December 2023

AbstractRoot system architecture plays a crucial role in nutrient and water absorption during rice production. Genetic improvement of the rice root system requires elucidating its genetic control. Genome-wide association studies (GWASs) have identified genomic regions responsible for rice root phenotypes. However, candidate gene prioritization around the peak region often suffers from low statistical power and resolution. Transcriptomics enables other statistical mappings, such as transcriptome-wide association study (TWAS) and expression GWAS (eGWAS), which improve candidate gene identification by leveraging the natural variation of the expression profiles. To explore the genes responsible for root phenotypes, we conducted GWAS, TWAS, and eGWAS for 12 root phenotypes in 57 rice accessions using 427,751 single nucleotide polymorphisms (SNPs) and the expression profiles of 16,901 genes expressed in the roots. The GWAS identified three significant peaks, of which the most significant peak responsible for seven root phenotypes (crown root length, crown root surface area, number of crown root tips, lateral root length, lateral root surface area, lateral root volume, and number of lateral root tips) was detected at 6,199,732 bp on chromosome 8. In the most significant GWAS peak region, OsENT1 was prioritized as the most plausible candidate gene because its expression profile was strongly negatively correlated with the seven root phenotypes. In addition to OsENT1, OsEXPA31, OsSPL14, OsDEP1, and OsDEC1 were identified as candidate genes responsible for root phenotypes using TWAS. Furthermore, a cis-eGWAS peak SNP was detected for OsDjA6, which showed the eighth strongest association with lateral root volume in the TWAS. The cis-eGWAS peak SNP for OsDjA6 was in strong linkage disequilibrium (LD) with a GWAS peak SNP on the same chromosome for lateral root volume and in perfect LD with another SNP variant in a putative cis-element at the 518 bp upstream of the gene. These candidate genes provide new insights into the molecular breeding of root system architecture.