bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fixed-duration venetoclax plus obinutuzumab improves quality of life and geriatric impairments in FCR-unfit patients with CLL
Authors: van der Straten Lina , Stege Claudia A. M. , Kersting Sabina , Nasserinejad Kazem , Dubois Julie , Dobber Johan A. , Mellink Clemens H. M. , van der Kevie-Kersemaekers Anne-Marie F. , Evers Ludo M. , de Boer Fransien , Koene Harry R. , Schreurs John , van der Klift Marjolein , Velders Gerjo A. , van der Spek Ellen , van der Straaten Hanneke M. , Hoogendoorn Mels , van Gelder Michel , Posthuma Eduardus F. M. , Visser Hein P. J. , Houtenbos Ilse , Idink Cecile A. M. , Issa Djamila E. , Dompeling Ellen C. , van Zaanen Henk C. T. , Veelken J. Hendrik , Levenga Henriette , Tick Lidwine W. , Terpstra Wim E. , Tonino Sanne H. , Westerweel Peter E. , Langerak Anton W. , Kater Arnon P. , Levin Mark-David 
Published: June 2023

Abstract
Chronic lymphocytic leukemia (CLL)–related symptoms and morbidity related to the advanced age at diagnosis impairs the well-being of older adult patients. Therefore, it is essential to tailor treatment according to geriatric characteristics and aim for an improvement in health-related quality of life (HRQoL) as a primary treatment goal. In the HOVON139/GiVe trial, 12 cycles of fixed-duration venetoclax plus obinutuzumab (Ven-O) were shown to be effective and tolerable in FCR (fludarabine, cyclophosphamide, rituximab)-unfit patients with CLL (n = 67). However, prolonged venetoclax exposure as consolidation treatment led to increased toxicity with limited effect on minimal residual disease. To assess the impact of geriatric assessment on treatment outcomes and the patients’ HRQoL, patient-reported outcomes (PROs), including function, depression, cognition, nutrition, physical performance, muscle parameters, comorbidities, and the European Organization for Research and Treatment of Cancer C30 and CLL17 questionnaires were assessed. At baseline, geriatric impairments were present in &gt;90% of patients and ≥2 impairments present in 60% of patients predicted grade ≥3 nonhematological toxicity. During treatment, the number of geriatric impairments diminished significantly and clinically relevant improvements in HRQoL subscales were reached for global health status, physical functioning, role functioning, emotional functioning, fatigue, dyspnea, physical condition or fatigue, and worries or fears related to health and functioning. These improvements were comparable for patients receiving venetoclax consolidation and patients in whom treatment could mostly be discontinued. Collectively, frontline fixed-duration Ven-O improves overall PROs in older, unfit patients with CLL with and without geriatric impairments. This study was registered at EudraCT as 2015-004985-27 and the Netherlands Trial Register as NTR6043.
Comparison of four different screw configurations for the fixation of Fulkerson osteotomy: a finite element analysis
Authors: Aykanat Faruk , Kose Ozkan , Guneri Bulent , Celik H. Kursat , Cakar Albert , Tasatan Ersin , Ulmeanu Mihaela-Elena 
Published: June 2023

Abstract
Background
Conventionally, two 4.5 mm cortical screws inserted toward the posterior tibial cortex are usually advocated for the fixation of Fulkerson osteotomy. This finite element analysis aimed to compare the biomechanical behavior of four different screw configurations to fix the Fulkerson osteotomy.

Materials and methods
Fulkerson osteotomy was modeled using computerized tomography (CT) data of a patient with patellofemoral instability and fixed with four different screw configurations using two 4.5 mm cortical screws in the axial plane. The configurations were as follows: (1) two screws perpendicular to the osteotomy plane, (2) two screws perpendicular to the posterior cortex of the tibia, (3) the upper screw perpendicular to the osteotomy plane, but the lower screw is perpendicular to the posterior cortex of the tibia, and (4) the reverse position of the screw configuration in the third scenario. Gap formation, sliding, displacement, frictional stress, and deformation of the components were calculated and reported.

Results
The osteotomy fragment moved superiorly after loading the models with 1654 N patellar tendon traction force. Since the proximal cut is sloped (bevel-cut osteotomy), the osteotomy fragment slid and rested on the upper tibial surface. Afterward, the upper surface of the osteotomy fragment acted as a fulcrum, and the distal part of the fragment began to separate from the tibia while the screws resisted the displacement. The resultant total displacement was 0.319 mm, 0.307 mm, 0.333 mm, and 0.245 mm from the first scenario to the fourth scenario, respectively. The minimum displacement was detected in the fourth scenario (upper screw perpendicular to the osteotomy plane and lower screw perpendicular to the posterior tibial cortex). Maximum frictional stress and maximum pressure between components on both surfaces were highest in the first scenario (both screws perpendicular to the osteotomy plane).

Conclusions
A divergent screw configuration in which the upper screw is inserted perpendicular to the osteotomy plane and the lower screw is inserted perpendicular to the posterior tibial cortex might be a better option for the fixation of Fulkerson osteotomy.
Level of evidence Level V, mechanism-based reasoning.
Factors associated with mortality after proximal femoral fracture
Authors: Walter Nike , Szymski Dominik , Kurtz Steve , Alt Volker , Lowenberg David W. , Lau Edmund , Rupp Markus 
Published: June 2023

AbstractProximal femoral fractures are a serious complication, especially for elderly patients. Therefore, we have aimed to answer the following research question: What is the postfracture mortality rate in the elderly population and what are associated risk factors? For this, proximal femoral fractures that occurred between 1 January 2009 and 31 December 2019 were identified from the Medicare Physician Service Records database. The Kaplan–Meier (KM) method with the Fine and Gray subdistribution adaptation was used to determine rates of mortality. A semiparametric Cox regression model was applied, incorporating 23 measures as covariates to identify risk factors. The estimated 1 year mortality rate was 26.8% after head/neck fracture, 28.2% after intertrochanteric fracture, and 24.2% after subtrochanteric fracture. Male sex, age over 70 years, chronic obstructive pulmonary disease (COPD), cerebrovascular disease, chronic kidney disease, a concomitant fracture, congestive heart failure, diabetes mellitus, hypertension, insulin use, ischemic heart disease, morbid obesity, osteoporosis, tobacco dependence, and median household income were determined as risk factors for increased mortality. An early assessment of individual risk factors accessible for therapeutic treatment is crucial in the management of proximal femur fractures to aid in attempts at reducing the high mortality apparent in the elderly US population.
The DNA methylation status of the serotonin metabolic pathway associated with reproductive inactivation induced by long-light exposure in Magang geese
Authors: Liu Jiaxin , Xu Yanglong , Wang Yushuai , Zhang Jinning , Fu Yuting , Liufu Sui , Jiang Danli , Pan Jianqiu , Ouyang Hongjia , Huang Yunmao , Tian Yunbo , Shen Xu 
Published: June 2023

AbstractBackgroundDomestic geese are seasonal breeders and have the lowest reproductive capacity among all poultry species. Magang geese is a topical short-day breeder, short photoperiod exposure stimulates its reproductive activity while long photoperiod inhibits. To explore epigenetic change that could influence reproductive activity, we performed whole genome bisulfite sequencing and transcriptome sequencing in the hypothalamus at three reproductive stages during long-light exposure in male Magang geese.ResultsA total number of 10,602 differentially methylated regions (DMRs) were identified among three comparison groups. We observed that the vast majority of DMRs were enriched in intron regions. By integrating the BS-sequencing and RNA-seq data, the correlation between methylation changes of CG DMRs and expression changes of their associated genes was significant only for genes containing CG DMRs in their intron. A total of 278 DMR-associated DEGs were obtained among the three stages. KEGG analysis revealed that the DMR-associated DEGs were mainly involved in 11 pathways. Among them, the neuroactive ligand-receptor interaction pathway was significantly enriched in both two comparisons (RA vs.RD and RD vs.RI); the Wnt signaling pathway, apelin signaling pathway, melanogenesis, calcium signaling pathway, focal adhesion, and adherens junction were significantly enriched in the RA vs. RI comparison. In addition, the expression level of two serotonin-metabolic genes was significantly altered during reproductive axis inactivation by the methylation status of their promoter region (TPH2) and intron region (SLC18A2), respectively. These results were confirmed by Bisulfite sequencing PCR (BSP), pyrosequencing, and real-time qPCR, indicating that serotonin metabolic signaling may play a key role in decreasing the reproductive activity of Magang geese induced by long-light exposure. Furthermore, we performed a metabolomics approach to investigate the concentration of neurotransmitters among the three stages, and found that 5-HIAA, the last product of the serotonin metabolic pathway, was significantly decreased in the hypothalamus during RI.ConclusionsOur study reveals that the methylation status of the serotonin metabolic pathway in the hypothalamus is associated with reproductive inactivation, and provided new insight into the effect of DNA methylation on the reproductive regulation of the hypothalamus in Magang geese.
Homoeologous evolution of the allotetraploid genome of Poa annua L.
Authors: Benson Christopher W. , Sheltra Matthew R. , Maughan Peter J. , Jellen Eric N. , Robbins Matthew D. , Bushman B. Shaun , Patterson Eric L. , Hall Nathan D. , Huff David R. 
Published: June 2023

Abstract
Background
Poa annua (annual bluegrass) is an allotetraploid turfgrass, an agronomically significant weed, and one of the most widely dispersed plant species on earth. Here, we report the chromosome-scale genome assemblies of P. annua’s diploid progenitors, P. infirma and P. supina, and use multi-omic analyses spanning all three species to better understand P. annua’s evolutionary novelty.

Results
We find that the diploids diverged from their common ancestor 5.5 – 6.3 million years ago and hybridized to form P. annua ≤ 50,000 years ago. The diploid genomes are similar in chromosome structure and most notably distinguished by the divergent evolutionary histories of their transposable elements, leading to a 1.7 × difference in genome size. In allotetraploid P. annua, we find biased movement of retrotransposons from the larger (A) subgenome to the smaller (B) subgenome. We show that P. annua’s B subgenome is preferentially accumulating genes and that its genes are more highly expressed. Whole-genome resequencing of several additional P. annua accessions revealed large-scale chromosomal rearrangements characterized by extensive TE-downsizing and evidence to support the Genome Balance Hypothesis.

Conclusions
The divergent evolutions of the diploid progenitors played a central role in conferring onto P. annua its remarkable phenotypic plasticity. We find that plant genes (guided by selection and drift) and transposable elements (mostly guided by host immunity) each respond to polyploidy in unique ways and that P. annua uses whole-genome duplication to purge highly parasitized heterochromatic sequences. The findings and genomic resources presented here will enable the development of homoeolog-specific markers for accelerated weed science and turfgrass breeding.
Long-wave opsin involved in body color plastic development in Nilaparvata lugens
Authors: Lu Jia-Bao , Li Ze-Dong , Ye Zhuang-Xin , Huang Hai-Jian , Chen Jian-Ping , Li Jun-Min , Zhang Chuan-Xi 
Published: June 2023

Abstract
Background
As one of the components of visual photopigments in photoreceptor cells, opsin exhibits different spectral peaks and plays crucial roles in visual function. Besides, it is discovered to evolve other functions despite color vision. However, research on its unconventional function is limited nowadays. With the increase in genome database numbers, various numbers and types of opsins have been identified in insects due to gene duplications or losses. The Nilaparvata lugens (Hemiptera) is a rice pest known for its long-distance migration capability. In this study, opsins were identified in N. lugens and characterized by genome and transcriptome analyses. Meanwhile, RNA interference (RNAi) was carried out to investigate the functions of opsins, and then the Illumina Novaseq 6000 platform-based transcriptome sequencing was performed to reveal gene expression patterns.

Results
Four opsins belonging to G protein-coupled receptors were identified in the N. lugens genome, including one long-sensitive opsin (Nllw) together with two ultraviolet-sensitive opsins (NlUV1/2) and an additional new opsin with hypothesized UV peak sensitivity (NlUV3-like). A tandem array of NlUV1/2 on the chromosome suggested the presence of a gene duplication event, with similar exons distribution. Moreover, as revealed by spatiotemporal expression, the four opsins were highly expressed in eyes with age-different expression levels. Besides, RNAi targeting each of the four opsins did not significantly affect the survival of N. lugens in phytotron, but the silencing of Nllw resulted in the melanization of body color. Further transcriptome analysis revealed that silencing of Nllw resulted in up-regulation of a tyrosine hydroxylase gene (NlTH) and down-regulation of an arylalkylamine-N-acetyltransferases gene (NlaaNAT) in N. lugens, demonstrating that Nllw is involved in body color plastic development via the tyrosine-mediated melanism pathway.

Conclusions
This study provides the first evidence in a Hemipteran insect that an opsin (Nllw) takes part in the regulation of cuticle melanization, confirming a cross-talk between the gene pathways underlying the visual system and the morphological differentiation in insects.
Inter-provincial variation in older home care clients and their pathways: a population-based retrospective cohort study in Canada
Authors: Mitchell Lori , Poss Jeffrey , MacDonald Martha , Burke Rosanne , Keefe Janice M. 
Published: June 2023

Abstract
Background
In Canada, publicly-funded home care programs enable older adults to remain and be cared for in their home for as long as possible but they often differ in types of services offered, and the way services are delivered. This paper examines whether these differing approaches to care shape the pathway that home care clients will take. Older adult client pathways refer to trajectories within, and out of, the home care system (e.g., improvement, long term care (LTC) placement, death).

Methods
A retrospective analysis of home care assessment data (RAI-HC was linked with health administrative data, long-term care admissions and vital statistics in Nova Scotia Health (NSH) and Winnipeg Regional Health Authority (WRHA). The study cohort consists of clients age 60 + years, admitted to home care between January 1, 2011 to December 31, 2013 and up to four years from baseline. Differences in home care service use, client characteristics and their pathways were tested across the two jurisdictions overall, and among the four discharge streams within jurisdictions using t-tests and chi-square tests of significance.

Results
NS and WHRA clients were similar in age, sex, and marital status. NS clients had higher levels of need (ADL, cognitive impairment, CHESS) at base line and were more likely discharged to LTC (43% compared to 38% in WRHA). Caregiver distress was a factor correlated with being discharged to LTC. While a third remained as home care clients after 4 years; more than half were no longer in the community – either discharged to LTC placement or death. Such discharges occurred on average at around two years, a relatively short time period.

Conclusions
By following older clients over 4 years, we provide enhanced evidence of client pathways, the characteristics that influence these paths, as well as the length of time to the outcomes. This evidence is central to identification of clients at risk in the community and aids in planning for future home care servicing needs that will allow more older adults to remain living in the community.
Role of previous infection with SARS-CoV-2 in protecting against omicron reinfections and severe complications of COVID-19 compared to pre-omicron variants: a systematic review
Authors: Arabi Maryam , Al-Najjar Yousef , Sharma Omna , Kamal Ibtihal , Javed Aimen , Gohil Harsh S. , Paul Pradipta , Al-Khalifa Aljazi M. , Laws Sa’ad , Zakaria Dalia 
Published: June 2023

Abstract
Background
The SARS-CoV-2 virus elicited a major public concern worldwide since December 2019 due to the high number of infections and deaths caused by COVID-19. The Omicron variant was detected in October 2021 which evolved from the wild-type SARS-CoV-2 and was found to possess many mutations. Omicron exhibited high transmissibility and immune evasion as well as reduced severity when compared to the earlier variants. Although vaccinated individuals were largely protected against infections in previous waves, the high prevalence of both reinfections and breakthrough infections with Omicron was observed. The aim of this review is to understand the effectiveness of previous infection on subsequent reinfection, given its significance in driving public health policy, including vaccination prioritization and lockdown requirements.

Methods
A comprehensive literature search was conducted using several databases to target studies reporting data related to the effectiveness of the previous infection with SARS-CoV-2 in protecting against the Omicron variant. Screening of the studies, quality assessment and data extraction were conducted by two reviewers for each study.

Results
Only 27 studies met our inclusion criteria. It was observed that previous infection was less effective in preventing reinfections with the Omicron variant compared to the Delta variant irrespective of vaccination status. Furthermore, being fully vaccinated with a booster dose provided additional protection from the Omicron variant. Additionally, most infections caused by Omicron were asymptomatic or mild and rarely resulted in hospitalizations or death in comparison to the Delta wave.

Conclusion
A majority of the studies reached a consensus that although previous infection provides some degree of immunity against Omicron reinfection, it is much lower in comparison to Delta. Full vaccination with two doses was more protective against Delta than Omicron. Receiving a booster dose provided additional protection against Omicron. It is therefore clear that neither vaccination nor previous infection alone provide optimal protection; hybrid immunity has shown the best results in terms of protecting against either Omicron or Delta variants. However, additional research is needed to quantify how long immunity from vaccination versus previous infection lasts and whether individuals will benefit from variant-specific vaccinations to enhance protection from infection.
Decision-analytic evaluation of the comparative effectiveness and cost-effectiveness of strategies to prevent breast and ovarian cancer in German women with BRCA-1/2 mutations
Authors: Hallsson Lára R. , Sroczynski Gaby , Engel Jutta , Siebert Uwe 
Published: June 2023

Abstract
Background
Women with inherited mutations in the BRCA1 or BRCA2 genes have increased lifetime risks for developing breast and/or ovarian cancer and may develop these cancers around the age of 30 years. Therefore, prevention of breast and ovarian cancer in these women may need to start relatively early in life. In this study we systematically evaluate the long-term effectiveness and cost effectiveness of different prevention strategies for breast and ovarian cancer in women with BRCA-1/2 mutation in Germany.

Methods
A decision-analytic Markov model simulating lifetime breast and ovarian cancer development in BRCA-1/2 carriers was developed. Different strategies including intensified surveillance (IS), prophylactic bilateral mastectomy (PBM), and prophylactic bilateral salpingo-oophorectomy (PBSO) alone or in combination at different ages were evaluated. German clinical, epidemiological, and economic (in 2022 Euro) data were used. Outcomes included cancer incidences, mortality, life years (LYs), quality-adjusted life years (QALYs), and discounted incremental cost-effectiveness ratios (ICER). We adopted the German health-care system perspective and discounted costs and health effects with 3% annually.

Results
All intervention strategies are more effective and less costly than IS alone. Prevention with PBM plus PBSO at age 30 maximizes life expectancy with 6.3 LYs gained, whereas PBM at age 30 with delayed PBSO at age 35 improves quality of life with 11.1 QALYs gained, when compared to IS alone. A further delay of PBSO was associated with lower effectiveness. Both strategies are cost effective with ICERs significantly below 10,000 EUR/LYG or QALY.

Conclusion
Based on our results, PBM at age 30 plus PBSO between age 30 and 40 prolongs life and is cost effective in women with BRCA-1/2 mutations in Germany. Serial preventive surgeries with delayed PBSO potentially improve quality of life for women. However, delaying PBM and/or PBSO further may lead to increased mortality and reduced QALYs.
Time to recovery from severe acute malnutrition and its predictors among under five children admitted to therapeutic feeding units of general and referral hospitals in Tigray, Ethiopia, 2020: a prospective cohort study
Authors: Kidane Gebretsadkan Fisseha , Zereabruk Kidane , Aberhe Woldu , Hailay Abrha , Mebrahtom Guesh , Gebremeskel Gebreamlak Gebremedhn , Haile Teklehaimanot Gereziher , Teklemichael Desalegn Massa 
Published: June 2023

Abstract
Background
Across the globe, an estimated 16 million children under the age of 5 are affected by severe acute malnutrition. Children with severe acute malnutrition are nine times more likely to die than well-nourished children. In Ethiopia, 7% of children under five are wasted, and 1% of these are severely wasted. A prolonged hospital stay increases the incidence of hospital-acquired infections. The aim of this study was to assess the time to recovery and its predictors among children 6–59 months old with severe acute malnutrition admitted to therapeutic feeding units of selected general and referral hospitals in Tigray, Ethiopia.

Methods
A prospective cohort study design was conducted among children aged 6–59 months admitted with severe acute malnutrition in selected hospitals in Tigray that have therapeutic feeding units. The data were cleaned, coded, entered into Epi-data Manager, and exported to STATA 14 for analysis.

Result
Among 232 children followed in the study, 176 have recovered from severe acute malnutrition with a recovery rate of 54 per 1000 person-days observation and the median time to recovery was 16 days with an inter-quartile range of 8. In a multivariable Cox Regression, feeding plumpy nut [AHR 0.49 (95% CI 0.2717216-0.8893736)] and failing to gain 5 gr/kg/day for three successive days after feeding freely on F-100 [AHR 3.58 (95% CI 1.78837–7.160047)] were found to have an association with time to recovery.

Conclusion
Despite the median time to recovery is shorter than what has been reported in a few studies, we can conclude that this could not let children avoid any possible hospital-acquired infections. The impact of staying in a hospital may also extend to the mother/caregiver in terms of the infection that they may acquire or the costs imposed on them.