bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of Hydrogel-Based Autologous Chondrocyte Implantation Versus Microfracture: A Propensity Score Matched-Pair Analysis
Authors: Niemeyer Philipp , Angele Peter , Spiro Robert C. , Kirner Alexandra , Gaissmaier Christoph 
Published: August 2023

Background: Few studies exist for large defects comparing matrix-associated autologous chondrocyte implantation (M-ACI) with other cartilage repair methods due to the limited availability of suitable comparator treatments. Purpose: To compare the clinical efficacy of a novel hydrogel-based M-ACI method (NOVOCART Inject plus) versus microfracture (MFx) in patients with knee cartilage defects. Study Design: Cohort study; Level of evidence, 3. Methods: Propensity score matched-pair analysis was used to compare the 24-month outcomes between the M-ACI treatment group from a previous single-arm phase 3 study and the MFx control group from another phase 3 study. Patients were matched based on preoperative Knee injury and Osteoarthritis Outcomes Score (KOOS), symptom duration, previous knee surgeries, age, and sex, resulting in 144 patients in the matched-pair set (72 patients per group). The primary endpoint was the change in least-squares means (ΔLSmeans) for the KOOS from baseline to the 24-month assessment. Results: Defect sizes in the M-ACI group were significantly larger than in the MFx group (6.4 versus 3.7 cm2). Other differences included defect location (no patellar or tibial defects in the MFx group), number of defects (33.3% with 2 defects in the M-ACI group versus 9.7% in the MFx group), and defect cause (more patients with degenerative lesions in the M-ACI group). The M-ACI group had higher posttreatment KOOS (M-ACI versus MFX: 81.8 ± 16.8 versus 73.0 ± 20.6 points) and KOOS ΔLSmeans from baseline to 24 months posttreatment (M-ACI versus MFX: 36.9 versus 26.9 points). Treatment contrasts in KOOS ΔLSmeans from baseline indicated statistical significance in favor of M-ACI from 3 to 24 months posttreatment ( P = .0026). Significant and clinically meaningful differences in favor of M-ACI at 24 months were also found regarding International Knee Documentation Committee (IKDC) score ΔLSmeans from baseline (37.8 versus 30.4 points; P = .0334), KOOS responder rates at 24 months (≥10-point improvement from baseline; 94.4% versus 65.3%; P < .0001), IKDC responder rates at 24 months (>20.5-point improvement from baseline; 83.3% versus 61.1%, P = .0126) and MOCART (Magnetic Resonance Observation of Cartilage Repair Tissue) score in a subgroup of patients (LS means, 86.9 versus 69.1; P = .0096). Conclusion: In this exploratory analysis, M-ACI using an in situ crosslinked hydrogel demonstrated superior clinical and structural (MOCART) 24-month outcomes compared with MFx in patients with knee cartilage defects.
Targeting cancer hallmark vulnerabilities in hematologic malignancies by interfering with Hedgehog/GLI signaling
Authors: Krenn Peter W. , Aberger Fritz 
Published: August 2023

Abstract
Understanding the genetic alterations, disrupted signaling pathways, and hijacked mechanisms in oncogene-transformed hematologic cells is critical for the development of effective and durable treatment strategies against liquid tumors. In this review, we focus on the specific involvement of the Hedgehog (HH)/GLI pathway in the manifestation and initiation of various cancer features in hematologic malignancies, including multiple myeloma, T- and B-cell lymphomas, and lymphoid and myeloid leukemias. By reviewing canonical and noncanonical, Smoothened-independent HH/GLI signaling and summarizing preclinical in vitro and in vivo studies in hematologic malignancies, we elucidate common molecular mechanisms by which HH/GLI signaling controls key oncogenic processes and cancer hallmarks such as cell proliferation, cancer stem cell fate, genomic instability, microenvironment remodeling, and cell survival. We also summarize current clinical trials with HH inhibitors and discuss successes and challenges, as well as opportunities for future combined therapeutic approaches. By providing a bird's eye view of the role of HH/GLI signaling in liquid tumors, we suggest that a comprehensive understanding of the general oncogenic effects of HH/GLI signaling on the formation of cancer hallmarks is essential to identify critical vulnerabilities within tumor cells and their supporting remodeled microenvironment, paving the way for the development of novel and efficient personalized combination therapies for hematologic malignancies.
Fractionated vs single-dose gemtuzumab ozogamicin with determinants of benefit in older patients with AML: the UK NCRI AML18 trial
Authors: Freeman Sylvie D. , Thomas Abin , Thomas Ian , Hills Robert K. , Vyas Paresh , Gilkes Amanda , Metzner Marlen , Jakobsen Niels Asger , Kennedy Alison , Moore Rachel , Almuina Nuria Marquez , Burns Sarah , King Sophie , Andrew Georgia , Gallagher Kathleen M. E. , Sellar Rob S. , Cahalin Paul , Weber Duruta , Dennis Mike , Mehta Priyanka , Knapper Steven , Russell Nigel H. 
Published: August 2023

Abstract
Addition of gemtuzumab ozogamicin (GO) to induction chemotherapy improves outcomes in older patients with acute myeloid leukemia (AML), but it is uncertain whether a fractionated schedule provides additional benefit to a single dose. We randomized 852 older adults (median age, 68-years) with AML/high-risk myelodysplasia to GO on day 1 (GO1) or on days 1 and 4 (GO2) of course 1 induction. The median follow-up period was 50.2 months. Although complete remission (CR) rates after course 1 did not significantly differ between arms (GO2, 63%; GO1, 57%; odds ratio [OR], 0.78; P = .08), there were significantly more patients who achieved CR with a measurable residual disease (MRD)&lt;0.1% (50% vs 41%; OR, 0.72; P = .027). This differential MRD reduction with GO2 varied across molecular subtypes, being greatest for IDH mutations. The 5-year overall survival (OS) was 29% for patients in the GO2 arm and 24% for those in the GO1 arm (hazard ratio [HR], 0.89; P = .14). In a sensitivity analysis excluding patients found to have adverse cytogenetics or TP53 mutations, the 5-year OS was 33% for GO2 and 26% for GO1 (HR, 0.83; P = .045). In total, 228 (27%) patients received an allogeneic transplantation in first remission. Posttransplant OS was superior in the GO2 arm (HR, 0.67; P = .033); furthermore, the survival advantage from GO2 in the sensitivity analysis was lost when data of patients were censored at transplantation. In conclusion, GO2 was associated with a greater reduction in MRD and improved survival in older adults with nonadverse risk genetics. This benefit from GO2 was dependent on allogeneic transplantation to translate the better leukemia clearance into improved survival. This trial was registered at www.isrctn.com as #ISRCTN 31682779.
Malignancy-associated hemophagocytic lymphohistiocytosis in Sweden: incidence, clinical characteristics, and survival
Authors: Löfstedt Alexandra , Jädersten Martin , Meeths Marie , Henter Jan-Inge 
Published: August 2023

Abstract
We evaluated malignancy-associated hemophagocytic lymphohistiocytosis (mal-HLH) in Sweden regarding population-based incidence, clinical features, and survival. From 1997 to 2018, we identified 307 adults (≥18 years old) and 9 children (209 males, 107 females; P &lt; .001) with both an HLH-related diagnosis and malignant disease, corresponding to 0.19 per 100 000 adults annually (0.15/100 000 for the entire population), increasing from 0.026 (1997-2007) to 0.34 (2008-2018) (P &lt; .001). In the latest 7-year period (2012-2018), the annual incidence was 0.45 per 100 000 adults (n = 246). This incidence varied between the 6 health care regions in Sweden, from 0.18 to 0.71 (Region Stockholm) per 100 000 adults annually (P &lt; .001), likely due to variable awareness. Mal-HLH was reported in 0.6% of all hematological malignancies, with the highest proportion (2.5%) in young males. Among the 316 patients, the 1-month probability of survival, likely representing the HLH episode, increased significantly from 52% (95% confidence interval [CI], 40-63) (1997-2007) to 71% (95% CI, 65-76) (2008-2018), whereas 2-year survival remained poor (25%; 95% CI, 20-30). Altogether, 52% were lymphomas, 29% leukemias, 8% other hematological malignancies, and 11% solid tumors. Males were more affected than females by mal-HLH, also taking the over-representation of males with hematological malignancies into account (P = .0012). Validation by medical-file reviews revealed 13% over-reporting of HLH. We conclude that the annual mal-HLH incidence has increased 10-fold and was at least 0.71 per 100 000 adults from 2012 to 2018, that is, 0.62 per 100 000 adults considering 13% estimated HLH over-reporting, and that early survival improved significantly, likely due to increased awareness and more HLH-directed therapy.
Genetic alterations and MRD refine risk assessment for KMT2A-rearranged B-cell precursor ALL in adults: a GRAALL study
Authors: Kim Rathana , Bergugnat Hugo , Pastoret Cédric , Pasquier Florence , Raffoux Emmanuel , Larcher Lise , Passet Marie , Grardel Nathalie , Delabesse Eric , Kubetzko Susanne , Caye-Eude Aurélie , Meyer Claus , Marschalek Rolf , Lafage-Pochitaloff Marine , Thiebaut-Bertrand Anne , Balsat Marie , Escoffre-Barbe Martine , Blum Sabine , Baumann Michael , Banos Anne , Straetmans Nicole , Gallego-Hernanz Maria-Pilar , Chalandon Yves , Graux Carlos , Soulier Jean , Leguay Thibaut , Hunault Mathilde , Huguet Françoise , Lhéritier Véronique , Dombret Hervé , Boissel Nicolas , Clappier Emmanuelle 
Published: August 2023

Abstract
KMT2A-rearranged (KMT2A-r) B-cell precursor acute lymphoblastic leukemia (BCP-ALL) is widely recognized as a high-risk leukemia in both children and adults. However, there is a paucity of data on adults treated in recent protocols, and the optimal treatment strategy for these patients is still a matter of debate. In this study, we set out to refine the prognosis of adult KMT2A-r BCP-ALL treated with modern chemotherapy regimen and investigate the prognostic impact of comutations and minimal residual disease (MRD). Of 1091 adult patients with Philadelphia-negative BCP-ALL enrolled in 3 consecutive trials from the Group for Research on Adult Acute Lymphoblastic Leukemia (GRAALL), 141 (12.9%) had KMT2A-r, with 5-year cumulative incidence of relapse (CIR) and overall survival (OS) rates of 40.7% and 53.3%, respectively. Molecular profiling highlighted a low mutational burden in this subtype, reminiscent of infant BCP-ALL. However, the presence of TP53 and/or IKZF1 alterations defined a subset of patients with significantly poorer CIR (69.3% vs 36.2%; P = .001) and OS (28.1% vs 60.7%; P = .006) rates. Next, we analyzed the prognostic implication of MRD measured after induction and first consolidation, using both immunoglobulin (IG) or T-cell receptor (TR) gene rearrangements and KMT2A genomic fusion as markers. In approximately one-third of patients, IG/TR rearrangements were absent or displayed clonal evolution during the disease course, compromising MRD monitoring. In contrast, KMT2A-based MRD was highly reliable and strongly associated with outcome, with early good responders having an excellent outcome (3-year CIR, 7.1%; OS, 92.9%). Altogether, our study reveals striking heterogeneity in outcomes within adults with KMT2A-r BCP-ALL and provides new biomarkers to guide risk-based therapeutic stratification.
A novel GATA2 distal enhancer mutation results in MonoMAC syndrome in 2 second cousins
Authors: West Robert R. , Bauer Thomas R. , Tuschong Laura M. , Embree Lisa J. , Calvo Katherine R. , Tillo Desiree , Davis Joie , Holland Steven M. , Hickstein Dennis D. 
Published: August 2023

Abstract
Mutations in the transcription factor GATA2 can cause MonoMAC syndrome, a GATA2 deficiency disease characterized by several findings, including disseminated nontuberculous mycobacterial infections, severe deficiencies of monocytes, natural killer cells, and B lymphocytes, and myelodysplastic syndrome. GATA2 mutations are found in ∼90% of patients with a GATA2 deficiency phenotype and are largely missense mutations in the conserved second zinc-finger domain. Mutations in an intron 5 regulatory enhancer element are also well described in GATA2 deficiency. Here, we present a multigeneration kindred with the clinical features of GATA2 deficiency but lacking an apparent GATA2 mutation. Whole genome sequencing revealed a unique adenine-to-thymine variant in the GATA2 –110 enhancer 116,855 bp upstream of the GATA2 ATG start site. The mutation creates a new E-box consensus in position with an existing GATA-box to generate a new hematopoietic regulatory composite element. The mutation segregates with the disease in several generations of the family. Cell type–specific allelic imbalance of GATA2 expression was observed in the bone marrow of a patient with higher expression from the mutant-linked allele. Allele-specific overexpression of GATA2 was observed in CRISPR/Cas9-modified HL-60 cells and in luciferase assays with the enhancer mutation. This study demonstrates overexpression of GATA2 resulting from a single nucleotide change in an upstream enhancer element in patients with MonoMAC syndrome. Patients in this study were enrolled in the National Institute of Allergy and Infectious Diseases clinical trial and the National Cancer Institute clinical trial (both trials were registered at www.clinicaltrials.gov as #NCT01905826 and #NCT01861106, respectively).
Understanding the process of improving accessibility and affordability of inter-municipal bus transport system
Authors: Mutiganda Jean C. , Skoog Matti , Igudia Eghosa 
Published: August 2023

AbstractThis paper examines the ways an inter-municipality bus system for passengers improved its accessibility and affordability for end-users at regional level. Using archetype theory, we conducted a case-study in FÖLI, a not-for-profit organization tasked with collective transport of passengers by bus in Southwest Finland. We find that FÖLI implemented a radical revolutionary change by introducing a new framework for the carriage of passengers by bus at a regional level, in which a zone free and flat fare policy applies. The sequence of change became central; with a continuous reorientation linearity aiming to improve the accessibility and affordability of collective transport by bus for commuters. The paper contributes to archetype theory by examining the relevance of accessibility and affordability in the configuration process of designing and implementing change, and extending knowledge in this area. Specifically, for the first time, our research shows the way in which FÖLI used the accessibility and affordability policy as an interpretative scheme to design and implement the change process successfully. The practical implication is that municipalities understood the relevance of improving collective transport infrastructures (roads, systems and technologies) to attract commuters as a way of saving total costs to fund underperforming buslines.
A systematic analysis of the phloem protein 2 (PP2) proteins in Gossypium hirsutum reveals that GhPP2-33 regulates salt tolerance
Authors: Wei Fei , Chen Pengyun , Jian Hongliang , Guo Xiaohao , Lv Xiaoyan , Lian Boying , Sun Mengxi , An Li , Dang Xinyu , Yang Miaoqian , Wu Hongmei , Zhang Nan , Wu Aimin , Wang Hantao , Ma Liang , Fu Xiaokang , Lu Jianhua , Yu Shuxun , Wei Hengling 
Published: August 2023

Abstract
Background
Phloem protein 2 (PP2) proteins play a vital role in the Phloem-based defense (PBD) and participate in many abiotic and biotic stress. However, research on PP2 proteins in cotton is still lacking.

Results
A total of 25, 23, 43, and 47 PP2 genes were comprehensively identified and characterized in G.arboretum, G.raimondii, G.barbadense, and G.hirsutum. The whole genome duplication (WGD) and allopolyploidization events play essential roles in the expansion of PP2 genes. The promoter regions of GhPP2 genes contain many cis-acting elements related to abiotic stress and the weighted gene co-expression network analysis (WGCNA) analysis displayed that GhPP2s could be related to salt stress. The qRT-PCR assays further confirmed that GhPP2-33 could be dramatically upregulated during the salt treatment. And the virus-induced gene silencing (VIGS) experiment proved that the silencing of GhPP2-33 could decrease salt tolerance.

Conclusions
The results in this study not only offer new perspectives for understanding the evolution of PP2 genes in cotton but also further explore their function under salt stress.
Oral microbiome homogeneity across diverse human groups from southern Africa: first results from southwestern Angola and Zimbabwe
Authors: Araújo Vítor , Fehn Anne-Maria , Phiri Admire , Wills Jeffrey , Rocha Jorge , Gayà-Vidal Magdalena 
Published: August 2023

AbstractBackgroundWhile the human oral microbiome is known to play an important role in systemic health, its average composition and diversity patterns are still poorly understood. To gain better insights into the general composition of the microbiome on a global scale, the characterization of microbiomes from a broad range of populations, including non-industrialized societies, is needed. Here, we used the portion of non-human reads obtained through an expanded exome capture sequencing approach to characterize the saliva microbiomes of 52 individuals from eight ethnolinguistically diverse southern African populations from Angola (Kuvale, Kwepe, Himba, Tjimba, Kwisi, Twa, !Xun) and Zimbabwe (Tshwa), including foragers, food-producers, and peripatetic groups (low-status communities who provide services to their dominant neighbors).ResultsOur results indicate that neither host genetics nor livelihood seem to influence the oral microbiome profile, withNeisseria,Streptococcus,Prevotella,Rothia, andPorphyromonasbeing the five most frequent genera in southern African groups, in line with what has been shown for other human populations. However, we found that some Tshwa and Twa individuals display an enrichment of pathogenic genera from theEnterobacteriaceaefamily (i.e.Enterobacter,Citrobacter,Salmonella) of theProteobacteriaphylum, probably reflecting deficient sanitation and poor health conditions associated with social marginalization.ConclusionsTaken together, our results suggest that socio-economic status, rather than ethnolinguistic affiliation or subsistence mode, is a key factor in shaping the salivary microbial profiles of human populations in southern Africa.
Self-reported musculoskeletal disorders and associated factors among HIV/AIDS patients following ART at University of Gondar Comprehensive Specialized Hospital, Gondar, Ethiopia, 2021: Aa cross-sectional study design
Authors: Kibret Alemu Kassaw , Mekie Yitayal Melisew , Eriku Getachew Azeze , Gashaw Moges , Yalew Ermias Solomon , Weldetsadik Fkrte Kebede 
Published: August 2023

Abstract
Background
Musculoskeletal disorders is an inflammatory, degenerative diseases and disorders that cause pain and functional impairments. Musculoskeletal disorders are common and the major global health concern among people with human immunodeficiency virus/acquired immunodeficiency syndrome which causes physical disability. Despite, it is a recognized health problem among human immunodeficiency virus-positive patients, there is a lack of data on musculoskeletal disorders among patients following anti-retroviral therapy in sub-Saharan Africa, particularly Ethiopia. Therefore, the main aim of the study was to assess the prevalence and associated factors of musculoskeletal disorders among adult human immunodeficiency virus-positive patients following anti-retroviral therapy.

Method
An institutional-based cross-sectional study was conducted from September 1st to October 1st, 2021 at University of Gondar Comprehensive Specialized Hospital, Gondar, Ethiopia. The data was collected through an interview-administered questionnaire and patient medical record review of 324 participants. Binary logistic regression was used to identify associated risk factors of musculoskeletal disorders. The strength of the association was detected by the adjusted odds ratio and P-value.

Result
The annual prevalence of musculoskeletal disorders among participants was 158 (48.5%) with [95% CI: 43%, 54%], opportunistic infection [AOR, 10.43; 95% CI = 2.76–42.25], type of ART medication used, CD4-count [AOR, 0.13; 95% CI 0.03–0.85], and change in anti-retroviral therapy regimen change [AOR, 8.14; 95%CI 2.06–32.09] were significantly associated with musculoskeletal disorders.

Conclusion
The prevalence of musculoskeletal disorders was moderate. Recent CD4 count, opportunistic infection, antiretroviral therapy regime at initiation, and anti-retroviral therapy regime change were significantly associated with musculoskeletal disorder. A multidisciplinary approach is required for preventing and treating musculoskeletal disorders among human immunodeficiency virus-positive patients following anti-retroviral therapy.
Dose finding study for unilobar radioembolization using holmium-166 microspheres to improve resectability in patients with HCC: the RALLY protocol
Authors: Andel Daan , Lam Marnix G. E. H. , de Bruijne Joep , Smits Maarten L. J. , Braat Arthur J. A. T. , Moelker Adriaan , Vegt Erik , Ruiter Simeon J. S. , Noordzij Walter , Grazi Gianluca , Vallati Giulio E. , Bennink Roel J. , van Delden Otto M. , Kranenburg Onno W. , Ijzermans Jan N. M. , Nijkamp Maarten W. , Erdmann Joris I. , Sciuto Rosa , Hagendoorn Jeroen , Borel Rinkes Inne H. M. 
Published: August 2023

Abstract
Background
High dose unilobar radioembolization (also termed ‘radiation lobectomy’)—the transarterial unilobar infusion of radioactive microspheres as a means of controlling tumour growth while concomitantly inducing future liver remnant hypertrophy—has recently gained interest as induction strategy for surgical resection. Prospective studies on the safety and efficacy of the unilobar radioembolization-surgery treatment algorithm are lacking. The RALLY study aims to assess the safety and toxicity profile of holmium-166 unilobar radioembolization in patients with hepatocellular carcinoma ineligible for surgery due to insufficiency of the future liver remnant.

Methods
The RALLY study is a multicenter, interventional, non-randomized, open-label, non-comparative safety study. Patients with hepatocellular carcinoma who are considered ineligible for surgery due to insufficiency of the future liver remnant (< 2.7%/min/m2 on hepatobiliary iminodiacetic acid scan will be included. A classical 3 + 3 dose escalation model will be used, enrolling three to six patients in each cohort. The primary objective is to determine the maximum tolerated treated non-tumourous liver-absorbed dose (cohorts of 50, 60, 70 and 80 Gy). Secondary objectives are to evaluate dose–response relationships, to establish the safety and feasibility of surgical resection following unilobar radioembolization, to assess quality of life, and to generate a biobank.

Discussion
This will be the first clinical study to assess the unilobar radioembolization-surgery treatment algorithm and may serve as a stepping stone towards its implementation in routine clinical practice.

Trial registration
Netherlands Trial Register NL8902, registered on 2020–09-15.