bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of prior inotuzumab ozogamicin treatment on brexucabtagene autoleucel outcomes in adults with B-cell ALL
Authors: Aldoss Ibrahim , Roloff Gregory W. , Faramand Rawan , Kopmar Noam E. , Lin Chenyu , Advani Anjali S. , Dekker Simone E. , Gupta Vishal K. , O'Connor Timothy E. , Jeyakumar Nikeshan , Muhsen Ibrahim N. , Valtis Yannis , Zhang Amy , Miller Katharine , Sutherland Katherine , Dykes Kaitlyn C. , Ahmed Mohamed , Chen Evan , Zambrano Hector , Bradshaw Danielle , Mercadal Santiago , Schwartz Marc , Tracy Sean , Dholaria Bhagirathbhai , Kubiak Michal , Mukherjee Akash , Majhail Navneet , Battiwalla Minoo , Mountjoy Luke , Malik Shahbaz A. , Mathews John , Shaughnessy Paul , Logan Aaron C. , Ladha Abdullah , Stefan Maryann , Guzowski Caitlin , Hoeg Rasmus T. , Hilal Talal , Moore Jozal , Connor Matthew , O'Dwyer Kristen M. , Hill LaQuisa C. , Tsai Stephanie B. , Sasine Joshua , Solh Melhem M. , Lee Catherine J. , Kota Vamsi K. , Koura Divya , Veeraputhiran Muthu , Blunk Betsy , Oliai Caspian , Leonard Jessica T. , Frey Noelle V. , Park Jae H. , Luskin Marlise R. , Bachanova Veronika , Galal Ahmed , Bishop Michael R. , Stock Wendy , Cassaday Ryan D. , Pullarkat Vinod , Shah Bijal D. , Muffly Lori S. 
Published: August 2024

Abstract
The effect of prior inotuzumab ozogamicin (InO) treatment on brexucabtagene autoleucel (brexu-cel) outcomes remains unclear in adults with acute lymphoblastic leukemia (ALL). We conducted a retrospective multicenter analysis of 189 patients with relapsed/refractory ALL treated with brexu-cel. Over half of the patients received InO before brexu-cel (InO exposed). InO-exposed patients were more heavily pretreated (P = .02) and frequently had active marrow disease before apheresis (P = .03). Response rate and toxicity profile after brexu-cel were comparable for InO-exposed and InO-naïve patients; however, consolidation therapy after brexu-cel response was used at a higher rate in InO-naïve patients (P = .005). With a median follow-up of 11.4 months, InO-exposed patients had inferior progression-free survival (PFS; P = .013) and overall survival (OS; P = .006) in univariate analyses; however, prior InO exposure did not influence PFS (hazard ratio, 1.20; 95% confidence interval, 0.71-2.03) in multivariate models. Within InO-exposed patients, InO responders had superior PFS (P = .002) and OS (P &lt; .0001) relative to InO-refractory patients. The timing of administering InO did not affect brexu-cel outcomes, with comparable PFS (P = .51) and OS (P = .86) for patients receiving InO as bridging therapy or before apheresis. In conclusion, although InO exposure was associated with inferior survival outcomes after brexu-cel in unadjusted analyses, these associations were no longer significant in multivariate analyses, suggesting it is unlikely that InO negatively affects brexu-cel efficacy. Our data instead imply that InO-exposed recipients of brexu-cel tend to be higher-risk patients with intrinsic adverse leukemia biology.
DSN-BR-Based Online Inspection Method and Application for Surface Defects of Pharmaceutical Products in Aluminum-Plastic Blister Packages
Authors: Liu Mingzhou , Gong Yu , Wang Xiaoqiao , Liu Conghu , Hu Jing 
Published: August 2024

AbstractEnsuring high product quality is of paramount importance in pharmaceutical drug manufacturing, as it is subject to rigorous regulatory practices. This study presents a research focused on the development of an on-line detection method and system for identifying surface defects in pharmaceutical products packaged in aluminum-plastic blisters. Firstly, the aluminum-plastic blister packages exhibit multi-scale features and inter-class indistinction. To address this, the deep semantic network with boundary refinement (DSN-BR) model is proposed, which leverages semantic segmentation domain knowledge, to accurately segment the defects in pixel level. Additionally, a specialized image acquisition module that minimizes the impact of ambient light is established, ensuring high-quality image capture. Finally, the image acquisition module, image detection module, and data management module are designed to construct a comprehensive online surface defect detection system. To validate the effectiveness of our approach, we employ a real dataset for instance verification on the implemented system. The experimental results substantiate the outstanding performance of the DSN-BR, achieving the mean intersection over union (MIoU) of 90.5%. Furthermore, the proposed system achieves an inference speed of up to 14.12 f/s, while attaining an F1-Score of 98.25%. These results demonstrate that the system meets the actual needs of the enterprise and provides theoretical and methodological support for intelligent inspection of product surface quality. By standardizing the control process of pharmaceutical manufacturing and improving the management capability of the manufacturing process, our approach holds significant market application prospects.
A rare case of concomitant endometrioid adenocarcinoma arising from uterine adenomyosis and clear cell carcinoma arising from parametrial deep endometriosis
Authors: Zhou Cailu , Luo Xiaojing , Tang Mengjie , Luo Fangyuan , Liao Zhi 
Published: August 2024

Abstract

Background
Carcinomatous changes from the ectopic endometrial glands in endometriosis have been reported in many studies, but malignant transformation from uterine adenomyosis/adenomyoma is rare. And clear cell-like adenocarcinoma represents a seldom-encountered malignant pathological variant of ectopic endometrium.

Case presentation
This case report presents a case of a 44-year-old nulliparous woman begun with abdominal pain and intestinal obstruction. Past medical history showed laparoscopic ovarian endometriotic cyst excision. Ultrasound indicated adenomyoma and a parametrial hypoechoic nodule with abundant blood flow signals and unclear boundaries. Deep invasive endometriosis was considered preoperatively. The patient underwent laparoscopic subtotal hysterectomy and bilateral adnexa resection. Chocolate cyst-like lesion was observed in the parametral lesion. Postoperative pathological examinations suggested endometrioid adenocarcinoma arising from eutopic endometrium and adenomyoma. Ectopic endometrium in the myometrium combined with atypical hyperplasia and formation of endometrioid adenocarcinoma. Left parametrial lesions suggested poorly differentiated endometrioid adenocarcinoma combined with clear cell carcinoma. CD10 + endometrial stromal cells were observed surrounding tumor cell masses. Combined with surgical founding and pathological characters of the left parametrial adenocarcinoma, the parametrial lesions were more likely to be carcinomatous changes of the original deep endometriosis.The patient underwent subsequent transabdominal tumor cell reduction surgery and chemotherapy.

Conclusion
We herein present a rare case of combined endometrioid adenocarcinoma arising from uterine adenomyosis and clear cell carcinoma arising from parametrial deep endometriosis that may help inspire additional studies in the future. The patient underwent robot-assisted laparoscopic subtotal hysterectomy, bilateral adnexa resection, deep endometriosis lesion resection and bilateral ureteral stent placement. Following surgery, a chemotherapy regimen of Taxol and Carboplatin was administered.
Highly regenerative species-specific genes improve age-associated features in the adult Drosophila midgut
Authors: Nagai Hiroki , Adachi Yuya , Nakasugi Tenki , Takigawa Ema , Ui Junichiro , Makino Takashi , Miura Masayuki , Nakajima Yu-ichiro 
Published: August 2024

Abstract
Background
The remarkable regenerative abilities observed in planarians and cnidarians are closely linked to the active proliferation of adult stem cells and the precise differentiation of their progeny, both of which typically deteriorate during aging in low regenerative animals. While regeneration-specific genes conserved in highly regenerative organisms may confer regenerative abilities and long-term maintenance of tissue homeostasis, it remains unclear whether introducing these regenerative genes into low regenerative animals can improve their regeneration and aging processes.

Results
Here, we ectopically express highly regenerative species-specific JmjC domain-encoding genes (HRJDs) in Drosophila, a widely used low regenerative model organism. Surprisingly, HRJD expression impedes tissue regeneration in the developing wing disc but extends organismal lifespan when expressed in the intestinal stem cell lineages of the adult midgut under non-regenerative conditions. Notably, HRJDs enhance the proliferative activity of intestinal stem cells while maintaining their differentiation fidelity, ameliorating age-related decline in gut barrier functions.

Conclusions
These findings together suggest that the introduction of highly regenerative species-specific genes can improve stem cell functions and promote a healthy lifespan when expressed in aging animals.
Semi-field evaluation of aquatic predators for the control of Anopheles funestus in rural south-eastern Tanzania
Authors: Mahenge Herieth H. , Muyaga Letus L. , Nkya Joel D. , Kafwenji Andrew D. , Mwalugelo Yohana A. , Kahamba Najat F. , Ngowo Halfan S. , Kaindoa Emmanuel W. 
Published: August 2024

Abstract
Background
Biological control is a promising alternative or complementary approach for controlling vector populations in response to the spread of insecticide resistance in malaria vectors. This study evaluated the efficacy of three selected potential predators on the density and fitness parameters of Anopheles funestus larvae in rural Tanzania.

Methods
Common predator families Aeshnidae (dragonflies), Coenagrionidae (damselflies), and Notonectidae (backswimmers) and An. funestus group larvae were collected from natural aquatic habitats in rural south-eastern Tanzania. Predators were starved for 12-h while An. funestus larvae were given fish food before starting the experiment. Anopheles funestus larvae were placed into artificial habitats containing predators, exposing them to potential predation. The number of surviving An. funestus larvae were counted every 24-h. An emergence traps were placed at the top of artificial habitats to capture emerging mosquitoes. Emerged mosquitoes were monitored until they died. Female wings were measured and used as a proxy for body size. Generalized linear mixed models (GLMM) with binomial variates at 95% CI and Cox proportional hazard models were used to assess the proportion of dead mosquitoes and the daily survival determined.

Results
There were significant differences in the number of emerged mosquitoes between the treatment and control groups (P < 0.001). Thus, all predator species played a significant role in reducing the density of An. funestus mosquitoes (P < 0.001). Furthermore, these predators had notable effects on the fitness parameters and survival of emerged mosquitoes (P < 0.001). Among the three predators studied, Coenagrionidae (damselflies) were most efficient followed by Notonectidae (backswimmers), with Aeshnidae (dragonflies) being the least efficient.

Conclusion
Selected aquatic predators have the potential to reduce the survival and density of An. funestus larvae. They might eventually be included within an integrated malaria vector control strategy, ultimately leading to a reduction in malaria transmission.
Cancer, metastasis, and the epigenome
Authors: Kiri Saurav , Ryba Tyrone 
Published: August 2024

AbstractCancer is the second leading cause of death worldwide and disease burden is expected to increase globally throughout the next several decades, with the majority of cancer-related deaths occurring in metastatic disease. Cancers exhibit known hallmarks that endow them with increased survival and proliferative capacities, frequently as a result of de-stabilizing mutations. However, the genomic features that resolve metastatic clones from primary tumors are not yet well-characterized, as no mutational landscape has been identified as predictive of metastasis. Further, many cancers exhibit no known mutation signature. This suggests a larger role for non-mutational genome re-organization in promoting cancer evolution and dissemination. In this review, we highlight current critical needs for understanding cell state transitions and clonal selection advantages for metastatic cancer cells. We examine links between epigenetic states, genome structure, and misregulation of tumor suppressors and oncogenes, and discuss how recent technologies for understanding domain-scale regulation have been leveraged for a more complete picture of oncogenic and metastatic potential.
Genetic insights into the complexity of premature ovarian insufficiency
Authors: Nie Linhang , Wang Xiaojie , Wang Songyuan , Hong Zhidan , Wang Mei 
Published: August 2024

AbstractPremature Ovarian Insufficiency (POI) is a highly heterogeneous condition characterized by ovarian dysfunction in women occurring before the age of 40, representing a significant cause of female infertility. It manifests through primary or secondary amenorrhea. While more than half of POI cases are idiopathic, genetic factors play a pivotal role in all instances with known causes, contributing to approximately 20–25% of cases. This article comprehensively reviews the genetic factors associated with POI, delineating the primary candidate genes. The discussion delves into the intricate relationship between these genes and ovarian development, elucidating the functional consequences of diverse mutations to underscore the fundamental impact of genetic effects on POI. The identified genetic factors, encompassing gene mutations and chromosomal abnormalities, are systematically classified based on whether the resulting POI is syndromic or non-syndromic. Furthermore, this paper explores the genetic interplay between mitochondrial genes, such as Required for Meiotic Nuclear Division 1 homolog Gene (RMND1), Mitochondrial Ribosomal Protein S22 Gene (MRPS22), Leucine-rich Pentapeptide Repeat Gene (LRPPRC), and non-coding RNAs, including both microRNAs and Long non-coding RNAs, with POI. The insights provided serve to consolidate and enhance our understanding of the etiology of POI, contributing to establishing a theoretical foundation for diagnosing and treating POI patients, as well as for exploring the mechanisms underlying the disease.
Are physical activity referral scheme components associated with increased physical activity, scheme uptake, and adherence rate? A meta-analysis and meta-regression
Authors: Mino Eriselda , Pfeifer Klaus , Hanson Coral L. , Schuler Michael , Brandmeier Anna , Klamroth Sarah , Naber Inga , Weissenfels Anja , McHale Sheona , Abu-Omar Karim , Gelius Peter , Whiting Stephen , Wickramasinghe Kremlin , Galea Gauden , Geidl Wolfgang 
Published: August 2024

Abstract
Background
Physical activity referral schemes (PARS) are composed of various components, such as a written prescription or a person-centered approach. The role of these components in their effectiveness is yet to be understood. Therefore, we aimed to explore the relationships between PARS components and physical activity, scheme uptake, and adherence rate; and to estimate the effect of PARS.

Methods
We searched Scopus, PubMed, Web of Science, CINAHL, ScienceDirect, SpringerLink, HTA, Wiley Online Library, SAGE Journals, Taylor & Francis, Google Scholar, OpenGrey, and CORE. Eligible studies were published between 1990 and November 2023 in English or German, investigated PARS with participants aged ≥ 16 years, and reported physical activity, scheme uptake, or scheme adherence. Separate random-effects meta-analysis by comparison group were conducted for physical activity. Scheme uptake and adherence rates were pooled using proportional meta-analysis. The components were analyzed via univariate meta-regression. We rated the risk of bias using RoB2 and ROBINS-I, and the certainty of evidence using GRADE.

Results
Fifty-two studies were included. PARS were more effective in increasing physical activity than usual care (k = 11, n = 5046, Hedges’ g = 0.18, 95%CI 0.12 to 0.25; high certainty of evidence). When PARS were compared with physical activity advice or enhanced scheme versions, the pooled Hedges’ g values for physical activity were -0.06 (k = 5, n = 1082, 95%CI -0.21 to 0.10; low certainty of evidence), and 0.07 (k = 9, n = 2647, 95%CI -0.03 to 0.18; low certainty of evidence) respectively. Scheme uptake was 87% (95%CI 77% to 94%, k = 14, n = 5000) across experimental studies and 68% (95%CI 51% to 83%, k = 14, n = 25,048) across non-experimental studies. Pooled scheme adherence was 68% (95%CI 55% to 80%, k = 16, n = 3939) and 53% (95%CI 42% to 63%, k = 18, n = 14,605). The meta-regression did not detect any significant relationships between components and physical activity or scheme uptake. A person-centered approach, screening, and brief advice were positively associated with scheme adherence, while physical activity sessions were negatively associated.

Conclusion
PARS are more effective in increasing physical activity than usual care only. We did not identify any components as significant predictors of physical activity and scheme uptake. Four components predicted scheme adherence, indicating that the component-effectiveness relationship warrants further research.
FGF4 ameliorates the liver inflammation by reducing M1 macrophage polarization in experimental autoimmune hepatitis
Authors: Lin Jing , Lin Hong-wei , Wang Yu-xing , Fang Yan , Jiang Hui-mian , Li Ting , Huang Jia , Zhang Hua-dong , Chen Da-zhi , Chen Yong-ping 
Published: August 2024

Abstract
Background
The global prevalence of autoimmune hepatitis (AIH) is increasing due in part to the lack of effective pharmacotherapies. Growing evidence suggests that fibroblast growth factor 4 (FGF4) is crucial for diverse aspects of liver pathophysiology. However, its role in AIH remains unknown. Therefore, we investigated whether FGF4 can regulate M1 macrophage and thereby help treat liver inflammation in AIH.

Methods
We obtained transcriptome-sequencing and clinical data for patients with AIH. Mice were injected with concanavalin A to induce experimental autoimmune hepatitis (EAH). The mechanism of action of FGF4 was examined using macrophage cell lines and bone marrow-derived macrophages.

Results
We observed higher expression of markers associated with M1 and M2 macrophages in patients with AIH than that in individuals without AIH. EAH mice showed greater M1-macrophage polarization than control mice. The expression of M1-macrophage markers correlated positively with FGF4 expression. The loss of hepatic Fgf4 aggravated hepatic inflammation by increasing the abundance of M1 macrophages. In contrast, the pharmacological administration of FGF4 mitigated hepatic inflammation by reducing M1-macrophage levels. The efficacy of FGF4 treatment was compromised following the in vivo clearance of macrophage populations. Mechanistically, FGF4 treatment activated the phosphatidylinositol 3-kinase (PI3K)–protein kinase B (AKT)-signal pathway in macrophages, which led to reduced M1 macrophages and hepatic inflammation.

Conclusion
We identified FGF4 as a novel M1/M2 macrophage-phenotype regulator that acts through the PI3K–AKT-signaling pathway, suggesting that FGF4 may represent a novel target for treating inflammation in patients with AIH.
Experience of the first adult-focussed undiagnosed disease program in Australia (AHA-UDP): solving rare and puzzling genetic disorders is ageless
Authors: Wallis Mathew , Bodek Simon D. , Munro Jacob , Rafehi Haloom , Bennett Mark F. , Ye Zimeng , Schneider Amy , Gardiner Fiona , Valente Giulia , Murdoch Emma , Uebergang Eloise , Hunter Jacquie , Stutterd Chloe , Huq Aamira , Salmon Lucinda , Scheffer Ingrid , Eratne Dhamidhu , Meyn Stephen , Fong Chun Y. , John Tom , Mullen Saul , White Susan M. , Brown Natasha J. , McGillivray George , Chen Jesse , Richmond Chris , Hughes Andrew , Krzesinski Emma , Fennell Andrew , Chambers Brian , Santoreneos Renee , Le Fevre Anna , Hildebrand Michael S. , Bahlo Melanie , Christodoulou John , Delatycki Martin , Berkovic Samuel F. 
Published: August 2024

Abstract
Background
Significant recent efforts have facilitated increased access to clinical genetics assessment and genomic sequencing for children with rare diseases in many centres, but there remains a service gap for adults. The Austin Health Adult Undiagnosed Disease Program (AHA-UDP) was designed to complement existing UDP programs that focus on paediatric rare diseases and address an area of unmet diagnostic need for adults with undiagnosed rare conditions in Victoria, Australia. It was conducted at a large Victorian hospital to demonstrate the benefits of bringing genomic techniques currently used predominantly in a research setting into hospital clinical practice, and identify the benefits of enrolling adults with undiagnosed rare diseases into a UDP program. The main objectives were to identify the causal mutation for a variety of diseases of individuals and families enrolled, and to discover novel disease genes.

Methods
Unsolved patients in whom standard genomic diagnostic techniques such as targeted gene panel, exome-wide next generation sequencing, and/or chromosomal microarray, had already been performed were recruited. Genome sequencing and enhanced genomic analysis from the research setting were applied to aid novel gene discovery.

Results
In total, 16/50 (32%) families/cases were solved. One or more candidate variants of uncertain significance were detected in 18/50 (36%) families. No candidate variants were identified in 16/50 (32%) families. Two novel disease genes (TOP3B, PRKACB) and two novel genotype–phenotype correlations (NARS, and KMT2C genes) were identified. Three out of eight patients with suspected mosaic tuberous sclerosis complex had their diagnosis confirmed which provided reproductive options for two patients. The utility of confirming diagnoses for patients with mosaic conditions (using high read depth sequencing and ddPCR) was not specifically envisaged at the onset of the project, but the flexibility to offer recruitment and analyses on an as-needed basis proved to be a strength of the AHA-UDP.

Conclusion
AHA-UDP demonstrates the utility of a UDP approach applying genome sequencing approaches in diagnosing adults with rare diseases who have had uninformative conventional genetic analysis, informing clinical management, recurrence risk, and recommendations for relatives.
The 26 S proteasome in Entamoeba histolytica: divergence of the substrate binding pockets from host proteasomes
Authors: Joshi Nidhi , Hosen SK Yasir , Fahad Mohd. , Narooka Anil Raj , Gourinath S. , Tiwari Swati 
Published: August 2024

Abstract
Objective
Proteasomes are conserved proteases crucial for proteostasis in eukaryotes and are promising drug targets for protozoan parasites. Yet, the proteasomes of Entamoeba histolytica remain understudied. The study’s objective was to analyse the differences in the substrate binding pockets of amoeba proteasomes from those of host, and computational modelling of β5 catalytic subunit, with the goal of finding selective inhibitors.

Results
Comparative sequence analysis revealed differences in substrate binding sites of E. histolytica proteasomes, especially in the S1 and S3 pockets of the catalytic beta subunits, implying differences in substrate preference and susceptibility to inhibitors from host proteasomes. This was strongly supported by significantly lower sensitivity to MG132 mediated inhibition of amoebic proteasome β5 subunit’s chymotryptic activity compared to human proteasomes, also reflected in lower sensitivity of E. histolytica to MG132 for inhibition of proliferation. Computational models of β4 and β5 subunits, and a docked β4-β5 model revealed a binding pocket between β4-β5, similar to that of Leishmania tarentolae. Selective inhibitors for visceral leishmaniasis, LXE408 and compound 8, docked well to this pocket. This functional and sequence-based analysis predicts differences between amoebic and host proteasomes that can be utilized to develop rationally designed, selective inhibitors against E. histolytica.