bluuebunny/crossref_metadata_2025_split huggingface dataset:
RNA interference therapy in acute hepatic porphyrias
Authors: Yasuda Makiko , Keel Siobán , Balwani Manisha 
Published: April 2023

Abstract
The acute hepatic porphyrias (AHPs) are inherited disorders of heme biosynthesis characterized by life-threatening acute neurovisceral attacks precipitated by factors that upregulate hepatic 5-aminolevulinic acid synthase 1 (ALAS1) activity. Induction of hepatic ALAS1 leads to the accumulation of porphyrin precursors, in particular 5-aminolevulinic acid (ALA), which is thought to be the neurotoxic mediator leading to acute attack symptoms such as severe abdominal pain and autonomic dysfunction. Patients may also develop debilitating chronic symptoms and long-term medical complications, including kidney disease and an increased risk of hepatocellular carcinoma. Exogenous heme is the historical treatment for attacks and exerts its therapeutic effect by inhibiting hepatic ALAS1 activity. The pathophysiology of acute attacks provided the rationale to develop an RNA interference therapeutic that suppresses hepatic ALAS1 expression. Givosiran is a subcutaneously administered N-acetylgalactosamine–conjugated small interfering RNA against ALAS1 that is taken up nearly exclusively by hepatocytes via the asialoglycoprotein receptor. Clinical trials established that the continuous suppression of hepatic ALAS1 mRNA via monthly givosiran administration effectively reduced urinary ALA and porphobilinogen levels and acute attack rates and improved quality of life. Common side effects include injection site reactions and increases in liver enzymes and creatinine. Givosiran was approved by the US Food and Drug Administration and European Medicines Agency in 2019 and 2020, respectively, for the treatment of patients with AHP. Although givosiran has the potential to decrease the risk of chronic complications, long-term data on the safety and effects of sustained ALAS1 suppression in patients with AHP are lacking.
A fixed-duration immunochemotherapy approach in CLL: 5.5-year results from the phase 2 ICLL-07 FILO trial
Authors: Michallet Anne-Sophie , Letestu Rémi , Le Garff-Tavernier Magali , Campos Lydia , Ticchioni Michel , Dilhuydy Marie-Sarah , Morisset Stephane , Rouille Valérie , Mahé Béatrice , Laribi Kamel , Villemagne Bruno , Ferrant Emmanuelle , Tournilhac Olivier , Delmer Alain , Molina Lysiane , Leblond Véronique , Tomowiak Cécile , de Guibert Sophie , Orsini-Piocelle Frederique , Banos Anne , Carassou Philippe , Cartron Guillaume , Fornecker Luc Mathieu , Ysebaert Loic , Dartigeas Caroline , Truchan-Graczyk Margot , Vilque Jean-Pierre , Schleinitz Thérèse Aurran , Cymbalista Florence , Leprêtre Stéphane , Lévy Vincent , Nguyen-Khac Florence , Feugier Pierre 
Published: April 2023

Abstract
In previously untreated, medically fit patients with chronic lymphocytic leukemia (CLL), research is focused on developing fixed-duration strategies to improve long-term outcomes while sparing patients from serious toxicities. The ICLL-07 trial evaluated a fixed-duration (15-month) immunochemotherapy approach in which after obinutuzumab-ibrutinib induction for 9 months, patients (n = 10) in complete remission (CR) with bone marrow (BM) measurable residual disease (MRD) &lt;0.01% continued only ibrutinib 420 mg/day for 6 additional months (I arm), whereas the majority (n = 115) received up to 4 cycles of fludarabine/cyclophosphamide-obinutuzumab 1000 mg alongside the ibrutinib (I-FCG arm). Primary analysis at month 16 showed that 84 of 135 (62.2%) patients enrolled achieved CR with a BM MRD &lt;0.01%. Here, we report follow-up at median 63 months. Peripheral blood (PB) MRD was assessed 6 monthly beyond the end of treatment using a highly sensitive (10-6) flow cytometry technique. In the I-FCG arm, the PB MRD &lt;0.01% rate (low-level positive &lt;0.01% or undetectable with limit of detection ≤10-4) in evaluable patients was still 92.5% (74/80) at month 40 and 80.6% (50/62) at month 64. No differences in the PB MRD status were apparent per to the IGHV mutational status. In the overall population, 4-year progression-free and overall survival rates were 95.5% and 96.2%, respectively. Twelve deaths occurred overall. Fourteen serious adverse events occurred beyond the end of treatment. Thus, our fixed-duration immunochemotherapy approach produced deep and sustained PB MRD responses, high survival rates, and low long-term toxicity. A randomized trial is needed to compare our immunochemotherapy approach with a chemotherapy-free strategy. This trial was registered at www.clinicaltrials.gov as #NCT02666898.
Efficacy of checkpoint inhibition after CAR-T failure in aggressive B-cell lymphomas: outcomes from 15 US institutions
Authors: Major Ajay , Yu Jovian , Shukla Navika , Che Yan , Karrison Theodore G. , Treitman Rachel , Kamdar Manali K. , Haverkos Bradley M. , Godfrey James , Babcook Melissa A. , Voorhees Timothy J. , Carlson Sophie , Gaut Daria , Oliai Caspian , Romancik Jason T. , Winter Allison M. , Hill Brian T. , Bansal Radhika , Villasboas Bisneto Jose C. , Nizamuddin Imran A. , Karmali Reem , Fitzgerald Lindsey A. , Stephens Deborah M. , Pophali Priyanka A. , Trabolsi Asaad , Schatz Jonathan H. , Hu Marie , Bachanova Veronika , Slade Michael J. , Singh Nathan , Ahmed Nausheen , McGuirk Joseph P. , Bishop Michael R. , Riedell Peter A. , Kline Justin 
Published: April 2023

AbstractCheckpoint inhibitor (CPI) therapy with anti–PD-1 antibodies has been associated with mixed outcomes in small cohorts of patients with relapsed aggressive B-cell lymphomas after CAR-T failure. To define CPI therapy efficacy more definitively in this population, we retrospectively evaluated clinical outcomes in a large cohort of 96 patients with aggressive B-cell lymphomas receiving CPI therapy after CAR-T failure across 15 US academic centers. Most patients (53%) had diffuse large B-cell lymphoma, were treated with axicabtagene ciloleucel (53%), relapsed early (≤180 days) after CAR-T (83%), and received pembrolizumab (49%) or nivolumab (43%). CPI therapy was associated with an overall response rate of 19% and a complete response rate of 10%. Median duration of response was 221 days. Median progression-free survival (PFS) and overall survival (OS) were 54 and 159 days, respectively. Outcomes to CPI therapy were significantly improved in patients with primary mediastinal B-cell lymphoma. PFS (128 vs 51 days) and OS (387 vs 131 days) were significantly longer in patients with late (&gt;180 days) vs early (≤180 days) relapse after CAR-T. Grade ≥3 adverse events occurred in 19% of patients treated with CPI. Most patients (83%) died, commonly because of progressive disease. Only 5% had durable responses to CPI therapy. In the largest cohort of patients with aggressive B-cell lymphoma treated with CPI therapy after CAR-T relapse, our results reveal poor outcomes, particularly among those relapsing early after CAR-T. In conclusion, CPI therapy is not an effective salvage strategy for most patients after CAR-T, where alternative approaches are needed to improve post–CAR-T outcomes.
Dynamic susceptibility of Fe3O4 nanotubes
Authors: Pusiol Enzo Fabrizio , Saavedra Eduardo , Pereira Alejandro , Palma Juan Luis , Bajales Noelia , Escrig Juan 
Published: April 2023

AbstractIn this work we performed a detailed numerical analysis to investigate the dynamic susceptibility of 1000 nm long Fe3O4 nanotubes by varying the diameter, the tube wall thickness and the magnitude of the external magnetic field applied along the tube axis. We found two well-defined modes, one of low frequency associated with the caps of the nanotubes, and another of high frequency associated with the central area of the nanotubes, which can be controlled by varying the geometry of the tubes or the external magnetic field to which they are subjected. These results allow us to suggest the use of these nanotubes in applications that require controlling the resonant frequency in the GHz range.
Automatic block-wise genotype-phenotype association detection based on hidden Markov model
Authors: Du Jin , Wang Chaojie , Wang Lijun , Mao Shanjun , Zhu Bencong , Li Zheng , Fan Xiaodan 
Published: April 2023

AbstractBackgroundFor detecting genotype-phenotype association from case–control single nucleotide polymorphism (SNP) data, one class of methods relies on testing each genomic variant site individually. However, this approach ignores the tendency for associated variant sites to be spatially clustered instead of uniformly distributed along the genome. Therefore, a more recent class of methods looks for blocks of influential variant sites. Unfortunately, existing such methods either assume prior knowledge of the blocks, or rely on ad hoc moving windows. A principled method is needed to automatically detect genomic variant blocks which are associated with the phenotype.ResultsIn this paper, we introduce an automatic block-wise Genome-Wide Association Study (GWAS) method based on Hidden Markov model. Using case–control SNP data as input, our method detects the number of blocks associated with the phenotype and the locations of the blocks. Correspondingly, the minor allele of each variate site will be classified as having negative influence, no influence or positive influence on the phenotype. We evaluated our method using both datasets simulated from our model and datasets from a block model different from ours, and compared the performance with other methods. These included both simple methods based on the Fisher’s exact test, applied site-by-site, as well as more complex methods built into the recent Zoom-Focus Algorithm. Across all simulations, our method consistently outperformed the comparisons.ConclusionsWith its demonstrated better performance, we expect our algorithm for detecting influential variant sites may help find more accurate signals across a wide range of case–control GWAS.
Risk factors associated with home care safety for older people with dementia: family caregivers’ perspectives
Authors: Yin Guo , Lin Siting , Chen Linghui 
Published: April 2023

AbstractBackgroundMany older people with dementia currently prefer home care; however, homes are neither professionally designed nor regulated like health care facilities, and home care is more prone to safety incidents. Many studies have examined home care safety for older people with dementia. However, factors contributing to safety incidents in home care have not been adequately considered. This study explored the risk factors for home care safety for older people with dementia based on the perspective of family caregivers.MethodsThis study used a qualitative research approach; a total of 24 family caregivers were interviewed face-to-face and semi-structured from February 2022 to May 2022, and the Colaizzi seven-step phenomenological research method was used to analyze the data and refine the themes.ResultsSafety risks in home care for older people with dementia stem from five areas: poor health of older people with dementia, dementia symptoms, unsafe home environment, the insufficient caring ability of family caregivers, and lack of safety awareness of family caregivers.ConclusionThe risk factors for home care safety for older people with dementia are complex. And as the primary caregivers of older people with dementia, the caregiving ability and safety awareness of family caregivers primarily determine the safety of home care for older people with dementia. Therefore, when addressing home care safety for older people with dementia, the focus should be on providing targeted education programs and support services for family caregivers of older people with dementia.
Healthcare expenditure and technology use in pediatric diabetes care
Authors: de Vries Silvia A. G. , Bak Jessica C. G. , Verheugt Carianne L. , Stangenberger Vincent A. , Mul Dick , Wouters Michel W. J. M. , Nieuwdorp Max , Sas Theo C. J. 
Published: April 2023

Abstract
Background
Diabetes mellitus is one of the most common chronic diseases in childhood. With more advanced care options including ever-evolving technology, allocation of resources becomes increasingly important to guarantee equal care for all. Therefore, we investigated healthcare resource utilization, hospital costs, and its determinants in Dutch children with diabetes.

Methods
We conducted a retrospective, observational analysis with hospital claims data of 5,474 children with diabetes mellitus treated in 64 hospitals across the Netherlands between 2019–2020.

Results
Total hospital costs were €33,002,652 per year, and most of these costs were diabetes-associated (€28,151,381; 85.3%). Mean annual diabetes costs were €5,143 per child, and treatment-related costs determined 61.8%. Diabetes technology significantly increased yearly diabetes costs compared to no technology: insulin pumps € 4,759 (28.7% of children), Real-Time Continuous Glucose Monitoring € 7,259 (2.1% of children), and the combination of these treatment modalities € 9,579 (27.3% of children). Technology use increased treatment costs significantly (5.9 – 15.3 times), but lower all-cause hospitalisation rates were observed. In all age groups, diabetes technology use influenced healthcare consumption, yet in adolescence usage decreased and consumption patterns changed.

Conclusions
These findings suggest that contemporary hospital costs of children with diabetes of all ages are driven primarily by the treatment of diabetes, with technology use as an important additive factor. The expected rise in technology use in the near future underlines the importance of insight into resource use and cost-effectiveness studies to evaluate if improved outcomes balance out these short-term costs of modern technology.
Circulating levels of adropin and diabetes: a systematic review and meta-analysis of observational studies
Authors: Soltani Sepideh , Beigrezaei Sara , Malekahmadi Mahsa , Clark Cain C. T. , Abdollahi Shima 
Published: April 2023

Abstract
Objective
Adropin, a newly identified regulatory protein has garnered attention given its potential role in metabolism regulation, especially glucose metabolism and insulin resistance. However, studies on the association between adropin and type 2 diabetes mellitus (T2DM) are equivocal. The aim of this study is to assess the association between serum adropin levels and T2DM using a systematic review and meta-analysis of observational studies.

Methods
PubMed, Scopus, ISI Web of science, and Google Scholar were searched, up to August 2022, for studies that reported the association between serum levels of adropin in adults with T2DM compared to a control group without diabetes. A random-effect model was used to compute the pooled weighted mean difference (WMD) with 95% confidence intervals (CI).

Results
Meta-analysis of 15 studies (n = 2813 participants) revealed that the serum adropin concentrations were significantly lower in patients with T2DM compared with the control group (WMD= -0.60 ng/mL, 95% CI: -0.70 to -0.49; I2 = 99.5%). Subgroup analysis also found lower concentration of adropin in patients with T2DM who were otherwise healthy compared to a control group (n = 9; WMD=-0.04 ng/ml, 95% CI= -0.06 to -0.01, p = 0.002; I2 = 96.4).

Conclusions
Our study showed adropin levels are lower in patients with diabetes compared to a control group without diabetes. However, the limitations of observational studies challenge the validity of the results, and further investigations are needed to confirm the veracity of these findings and additionally explore possible mechanisms.
Learning needs of nursing postgraduates in Southwest China based on Hutchinson’s learning needs theory: a qualitative research
Authors: Zhang Suofei , Ma Huijuan , Zhu Xiaoli , Niu Aifang , Luo Yu 
Published: April 2023

Abstract
Background
The process of education is mutual. The learning needs of students need to be paid attention to and can affect the learning outcome. In order to make nursing postgraduates’ curriculum better, meet the learning needs of students, and help to achieve the learning objectives of students, this study based on Hutchinson’s learning needs theory, aims to collect the learning experience of nursing graduates, as well as the gap between learning needs and target needs, and explore the benefits and barriers of nursing graduates in the curriculum learning. It may provide beneficial reference for further optimizing teaching content and improving teaching methods.

Methods
This study was designed as a qualitative research. Purposive sampling was used to recruit 17 nursing postgraduates in the only two universities in Chongqing, Southwest China, 2021. Semi-structured, in-depth individual interviews were conducted to explore how they subjectively experience the benefits and demands of the professional curriculum. Data was analyzed using Colaizzi’s seven-step analysis.

Results
Three main themes “clear learning cognition and goals,” “positive learning attitude,” and “the gap between learning goals and actual needs” were identified from the original data. Respectively, Subthemes concerning the first theme included “improve scientific research capabilities, enlighten thinking and broaden your horizons, and learn new knowledge and new skills.” Subthemes of the second theme were “improve abilities in practice and actively seek diversification of course content and format.” Subthemes of the third theme included “the course has a certain depth and breadth, but the course study does not meet the needs of scientific research, the course contents are theoretical, not knowing how to use the research method in certain conditions.”

Conclusions
The learning needs of nursing postgraduates in Southwest China could be divided into two parts: benefits and barriers, among which the benefits were participants had clear learning goals and positive learning attitudes. When curriculum could not meet their needs, they actively sought methods (e.g., networks or off-campus resources) to close the gap between those needs and their goals. Follow-up educators should focus on learning needs and build curricula by optimizing the contents and methods of existing teaching resources.
Newly qualified registered nurses’ and midwives’ experiences from rural health district placement in Namibia
Authors: Katuta Martha N , Nuuyoma Vistolina 
Published: April 2023

Abstract
Background
The transition period for newly qualified registered nurses/midwives (NQRN/Ms) is a fundamental phase in their career. Yet, transition experiences have been studied mostly within urban and/or specialised healthcare settings in high-resource countries. This study aimed to explore and describe the experiences of NQRN/Ms in a rural health district in Namibia.

Methods
A qualitative, descriptive, explorative, and contextual design was followed. The sample consisted of eight participants who were purposively selected. Data were collected via in-depth individual interviews and analysed following a reflexive thematic analysis. The researchers were guided by Lincoln and Guba’s strategies for establishing trustworthiness.

Findings
Themes conceptualised from the analysis include encounters with rural community members; encounters with colleagues; staffing, management, and supervision; shortage of resources; poor infrastructure; unreliable communication networks; and the lack of social life.

Conclusion
The NQRN/Ms had mixed experiences related to a variety of aspects such as social life, resources, colleagues and community members. These findings can be used to improve undergraduate nursing curricula, as well as to create graduate job preparation workshops and support networks.
Back to the roots, desiccation and radiation resistances are ancestral characters in bdelloid rotifers
Authors: Hespeels Boris , Fontaneto Diego , Cornet Valérie , Penninckx Sébastien , Berthe Jérémy , Bruneau Lucie , Larrick James W. , Rapport Eloïse , Bailly Jérémie , Debortoli Nicolas , Iakovenko Nataliia , Janko Karel , Heuskin Anne-Catherine , Lucas Stéphane , Hallet Bernard , Van Doninck Karine 
Published: April 2023

AbstractBackgroundBdelloid rotifers are micro-invertebrates distributed worldwide, from temperate latitudes to the most extreme areas of the planet like Antarctica or the Atacama Desert. They have colonized any habitat where liquid water is temporarily available, including terrestrial environments such as soils, mosses, and lichens, tolerating desiccation and other types of stress such as high doses of ionizing radiation (IR). It was hypothesized that bdelloid desiccation and radiation resistance may be attributed to their potential ability to repair DNA double-strand breaks (DSBs). Here, these properties are investigated and compared among nine bdelloid species collected from both mild and harsh habitats, addressing the correlation between the ability of bdelloid rotifers to survive desiccation and their capacity to repair massive DNA breakage in a phylogenetically explicit context. Our research includes both specimens isolated from habitats that experience frequent desiccation (at least 1 time per generation), and individuals sampled from habitats that rarely or never experienced desiccation.ResultsOur analysis reveals that DNA repair prevails in somatic cells of both desiccation-tolerant and desiccation-sensitive bdelloid species after exposure to X-ray radiation. Species belonging to both categories are able to withstand high doses of ionizing radiation, up to 1000 Gy, without experiencing any negative effects on their survival. However, the fertility of two desiccation-sensitive species,Rotaria macruraandRotaria rotatoria, was more severely impacted by low doses of radiation than that of desiccation-resistant species. Surprisingly, the radioresistance of desiccation-resistant species is not related to features of their original habitat. Indeed, bdelloids isolated from Atacama Desert or Antarctica were not characterized by a higher radioresistance than species found in more temperate environments.ConclusionsTolerance to desiccation and radiation are supported as ancestral features of bdelloid rotifers, with a group of species of the genus Rotaria having lost this trait after colonizing permanent water habitats. Together, our results provide a comprehensive overview of the evolution of desiccation and radiation resistance among bdelloid rotifers.