bluuebunny/crossref_metadata_2025_split huggingface dataset:
Traumatic stifle injury in 72 cats: a multicentre retrospective study
Authors: Coppola Mario , Das Smita , Matthews George , Cantatore Matteo , Silva Luis , Lafuente Pilar , Kulendra Elvin , Clarke Hannah , McCarthy Jessica , Fernandez-Salesa Nuria , Langley-Hobbs Sorrel , Aisa Josep , Parkin Timothy , Addison Elena S 
Published: July 2021

Objectives The aim of the study was to describe traumatic stifle injury in cats and report complications and long-term outcome. Methods The medical records from seven veterinary hospitals of cats treated for traumatic stifle injury were reviewed. Long-term follow-up data were collected from referring veterinarians and using the Feline Musculoskeletal Pain Index, collected from owners. Results Seventy-two cats were included in the study. The most common combination of ligament injury involved both cruciate ligaments and the lateral collateral ligament (25.4%). Medial meniscal injury was more common (66.2%) than lateral meniscal injury (59.4%). A temporary transarticular pin was used intraoperatively to aid reduction in 23/73 (31.5%) surgeries. Postoperative immobilisation was applied in 41/72 (56.9%) cats with a mean duration of 4.8 weeks. Short-term complications occurred in 40/64 (62.5%) cats. Long-term complications occurred in seven (17.5%) cats. Overall outcome was excellent in 25/61 (41%) cats, good in 13/61 (21.3%) cats, fair in 11/61 (18%) cats and poor in 12/61 (19.7%) cats. Mean length of follow-up was 29.6 months (range 0.5–204). A significantly poorer outcome was observed in cats with medial meniscal injury and those undergoing revision surgery. Use of a transarticular pin when left in situ for postoperative immobilisation was associated with a poorer outcome (P = 0.043) and a higher risk of complications (P = 0.018). Postoperative immobilisation was not related to outcome. Conclusions and relevance Traumatic stifle injury in cats can lead to rupture of multiple ligaments causing significant instability of the joint. Surgical treatment is associated with a high rate of short-term complications, although long-term outcome may still be good to excellent in the majority of cats (62.3%). In cats where follow-up was available, postoperative immobilisation had no positive effect on outcome and may not be required. Leaving a transarticular pin for postoperative immobilisation is not recommended as it was significantly associated with a poorer outcome and a higher complication rate.
Changes in maximum parental leave payment in Iceland and total fertility rates
Authors: Einarsdóttir Kristjana 
Published: July 2021

Background: Following the 2008 financial crisis, the Icelandic Government reduced the maximum parental payment until 2016, when it was increased again. The aim of this study was to investigate the effect of the changes in the maximum parental leave payment in Iceland during 2009 and 2016 on total fertility rates and birth rates during 2002–2019. Methods: Publicly available aggregated data on yearly total fertility rates, birth rates, unemployment rates, gross domestic product (GDP) and maximum parental leave payments were obtained for 2002–2019. Segmented regression analyses were used to measure the impact of changes in parental leave payment on term births for the two periods in which changes were implemented (2008–2010 and 2016–2017). Results: The decrease in maximum parental leave payment during 2008–2010 was associated with a 15% decrease in the estimated total fertility rate compared with the expected rate (−15.7%; 95% CI −22.7 to −8.7), whereas the increased payments during 2016–2017 indicated a possible 3% increase in the estimated total fertility rate (3.2%; 95% CI −29.1 to 35.5). Neither adjustment for the unemployment rate nor the GDP appeared to affect these results. The overall birth rate followed a similar trend and was most pronounced for women aged 25–34 years. Conclusions: These results suggest that total fertility rates in Iceland may have been affected by changes in the maximum parental leave payment that occurred in 2009 and 2016, although the effect of the 2008 financial crisis cannot be excluded despite adjustment for the unemployment rate and GDP.
Heterogeneity of Access to Diabetes Technology Depending on Area Deprivation and Demographics Between 2016 and 2019 in Germany
Authors: Auzanneau Marie , Rosenbauer Joachim , Maier Werner , von Sengbusch Simone , Hamann Johannes , Kapellen Thomas , Freckmann Guido , Schmidt Silke , Lilienthal Eggert , Holl Reinhard W. 
Published: July 2021

Background: Despite increasing use of technology in type 1 diabetes, persistent ethnic and socio-economic disparities have been reported. We analyzed how the use of insulin pump therapy and continuous glucose monitoring (CGM) evolved over the years in Germany depending on demographics and area deprivation. Method: We investigated the use of insulin pump and CGM between 2016 and 2019 in 37,798 patients with type 1 diabetes aged < 26 years from the German Prospective Follow-up Registry (DPV). Associations with federal state, area-deprivation quintile (German Index of Multiple Deprivation 2010 on district level), gender, and migration background were investigated over time using multiple logistic regression. Results: Between 2016 and 2019, the regional distribution of insulin pump use did not change substantially and the association with area deprivation remained non-linear and statistically non-significant. The effect of area deprivation on CGM use decreased continuously and disappeared in 2019 (OR [95%-CI] Q1 vs Q5: 1.85 [1.63-2.10] in 2016; 0.97 [0.88-1.08] in 2019). The effect of migration background on the use of either technology decreased over the years but remained significant in 2019. Girls had constantly higher odds of using an insulin pump than boys (OR: 1.25 [1.18-1.31] in 2019), whereas no gender difference was identified for CGM use. Conclusions: Although disparities decreased in Germany, access to diabetes technology still depends on migration background in 2019, and gender differences in pump use persist. As technological advances are made, further research is needed to understand the reasons for these persistent disparities.
DYRK1a mediates BAFF-induced noncanonical NF-κB activation to promote autoimmunity and B-cell leukemogenesis
Authors: Li Yanchuan , Xie Xiaoping , Jie Zuliang , Zhu Lele , Yang Jin-Young , Ko Chun-Jung , Gao Tianxiao , Jain Antrix , Jung Sung Yun , Baran Natalia , Konopleva Marina Y. , Cheng Xuhong , Sun Shao-Cong 
Published: July 2021

Abstract
B-cell–activating factor (BAFF) mediates B-cell survival and, when deregulated, contributes to autoimmune diseases and B-cell malignancies. The mechanism connecting BAFF receptor (BAFFR) signal to downstream pathways and pathophysiological functions is not well understood. Here we identified DYRK1a as a kinase that responds to BAFF stimulation and mediates BAFF-induced B-cell survival. B-cell–specific DYRK1a deficiency causes peripheral B-cell reduction and ameliorates autoimmunity in a mouse model of lupus. An unbiased screen identified DYRK1a as a protein that interacts with TRAF3, a ubiquitin ligase component mediating degradation of the noncanonical nuclear factor (NF)-κB–inducing kinase (NIK). DYRK1a phosphorylates TRAF3 at serine-29 to interfere with its function in mediating NIK degradation, thereby facilitating BAFF-induced NIK accumulation and noncanonical NF-κB activation. Interestingly, B-cell acute lymphoblastic leukemia (B-ALL) cells express high levels of BAFFR and respond to BAFF for noncanonical NF-κB activation and survival in a DYRK1a-dependent manner. Furthermore, DYRK1a promotes a mouse model of B-ALL through activation of the noncanonical NF-κB pathway. These results establish DYRK1a as a critical BAFFR signaling mediator and provide novel insight into B-ALL pathogenesis.
A critical role of nuclear m6A reader YTHDC1 in leukemogenesis by regulating MCM complex–mediated DNA replication
Authors: Sheng Yue , Wei Jiangbo , Yu Fang , Xu Huanzhou , Yu Chunjie , Wu Qiong , Liu Yin , Li Lei , Cui Xiao-long , Gu Xueying , Shen Bin , Li Wei , Huang Yong , Bhaduri-McIntosh Sumita , He Chuan , Qian Zhijian 
Published: July 2021

Abstract
YTHDC1 has distinct functions as a nuclear N6-methyladenosine (m6A) reader in regulating RNA metabolism. Here we show that YTHDC1 is overexpressed in acute myeloid leukemia (AML) and that it is required for the proliferation and survival of human AML cells. Genetic deletion of Ythdc1 markedly blocks AML development and maintenance as well as self-renewal of leukemia stem cells (LSCs) in vivo in mice. We found that Ythdc1 is also required for normal hematopoiesis and hematopoietic stem and progenitor cell (HSPC) maintenance in vivo. Notably, Ythdc1 haploinsufficiency reduces self-renewal of LSCs but not HSPCs in vivo. YTHDC1 knockdown has a strong inhibitory effect on proliferation of primary AML cells. Mechanistically, YTHDC1 regulates leukemogenesis through MCM4, which is a critical regulator of DNA replication. Our study provides compelling evidence that shows an oncogenic role and a distinct mechanism of YTHDC1 in AML.
Place of study, field of study and labour-market region: What matters for wage differences among higher-education graduates?
Authors: Kopecny Silvia , Hillmert Steffen 
Published: July 2021

AbstractThis paper focuses on the structure and extent of wage differences among graduates of different higher-education institutions in Germany. We ask how large these differences are and how they relate to fields of study and regional labour markets. The results from our application of cross-classified random-effects models to a cohort of the DZHW Graduate Panel show that there is a considerable amount of wage variation depending on the graduates’ alma mater. However, this variation can be fully explained by structural characteristics: Selection based on individual characteristics is of only minor importance, while regional labour markets do matter. Most of all, however, the differences relate to fields of study.
Selection for environmental variance of litter size in rabbits involves genes in pathways controlling animal resilience
Authors: Casto-Rebollo Cristina , Argente María José , García María Luz , Blasco Agustín , Ibáñez-Escriche Noelia 
Published: July 2021

Abstract
Background
Environmental variance (VE) is partially under genetic control, which means that the VE of individuals that share the same environment can differ because they have different genotypes. Previously, a divergent selection experiment for VE of litter size (LS) during 13 generations in rabbit yielded a successful response and revealed differences in resilience between the divergent lines. The aim of the current study was to identify signatures of selection in these divergent lines to better understand the molecular mechanisms and pathways that control VE of LS and animal resilience. Three methods (FST, ROH and varLD) were used to identify signatures of selection in a set of 473 genotypes from these rabbit lines (377) and a base population (96). A whole-genome sequencing (WGS) analysis was performed on 54 animals to detect genes with functional mutations.

Results
By combining signatures of selection and WGS data, we detected 373 genes with functional mutations in their transcription units, among which 111 had functions related to the immune system, stress response, reproduction and embryo development, and/or carbohydrate and lipid metabolism. The genes TTC23L, FBXL20, GHDC, ENSOCUG00000031631, SLC18A1, CD300LG, MC2R, and ENSOCUG00000006264 were particularly relevant, since each one carried a functional mutation that was fixed in one of the rabbit lines and absent in the other line. In the 3ʹUTR region of the MC2R and ENSOCUG00000006264 genes, we detected a novel insertion/deletion (INDEL) variant.

Conclusions
Our findings provide further evidence in favour of VE as a measure of animal resilience. Signatures of selection were identified for VE of LS in genes that have a functional mutation in their transcription units and are mostly implicated in the immune response and stress response pathways. However, the real implications of these genes for VE and animal resilience will need to be assessed through functional analyses.
Disruption of Drosophila larval muscle structure and function by UNC45 knockdown
Authors: Karunendiran Abiramy , Nguyen Christine T. , Barzda Virginijus , Stewart Bryan A. 
Published: July 2021

Abstract
Background
Proper muscle function is heavily dependent on highly ordered protein complexes. UNC45 is a USC (named since this region is shared by three proteins UNC45/CRO1/She4P) chaperone that is necessary for myosin incorporation into the thick filaments. UNC45 is expressed throughout the entire Drosophila life cycle and it has been shown to be important during late embryogenesis when initial muscle development occurs. However, the effects of UNC45 manipulation at later developmental times, after muscle development, have not yet been studied.

Main results
UNC45 was knocked down with RNAi in a manner that permitted survival to the pupal stage, allowing for characterization of sarcomere organization in the well-studied third instar larvae. Second harmonic generation (SHG) microscopy revealed changes in the striated pattern of body wall muscles as well as a reduction of signal intensity. This observation was confirmed with immunofluorescence and electron microscopy imaging, showing diminished UNC45 signal and disorganization of myosin and z-disk proteins. Concomitant alterations in both synaptic physiology and locomotor function were also found. Both nerve-stimulated response and spontaneous vesicle release were negatively affected, while larval movement was impaired.

Conclusions
This study highlights the dependency of normal sarcomere structure on UNC45 expression. We confirm the known role of UNC45 for myosin localization and further show the I-Z-I complex is also disrupted. This suggests a broad need for UNC45 to maintain sarcomere integrity. Newly discovered changes in synaptic physiology reveal the likely presence of a homeostatic response to partially maintain synaptic strength and muscle function.
Genome sequence of Apostasia ramifera provides insights into the adaptive evolution in orchids
Authors: Zhang Weixiong , Zhang Guoqiang , Zeng Peng , Zhang Yongqiang , Hu Hao , Liu Zhongjian , Cai Jing 
Published: July 2021

AbstractBackgroundThe Orchidaceae family is one of the most diverse among flowering plants and serves as an important research model for plant evolution, especially “evo-devo” study on floral organs. Recently, sequencing of several orchid genomes has greatly improved our understanding of the genetic basis of orchid biology. To date, however, most sequenced genomes are from the Epidendroideae subfamily. To better elucidate orchid evolution, greater attention should be paid to other orchid lineages, especially basal lineages such as Apostasioideae.ResultsHere, we present a genome sequence ofApostasia ramifera, a terrestrial orchid species from the Apostasioideae subfamily. The genomes ofA. ramiferaand other orchids were compared to explore the genetic basis underlying orchid species richness. Genome-based population dynamics revealed a continuous decrease in population size over the last 100 000 years in all studied orchids, although the epiphytic orchids generally showed larger effective population size than the terrestrial orchids over most of that period. We also found more genes of the terpene synthase gene family, resistant gene family, andLOX1/LOX5homologs in the epiphytic orchids.ConclusionsThis study provides new insights into the adaptive evolution of orchids. TheA. ramiferagenome sequence reported here should be a helpful resource for future research on orchid biology.
Transcriptome analysis uncovers the key pathways and candidate genes related to the treatment of Echinococcus granulosus protoscoleces with the repurposed drug pyronaridine
Authors: Yu Yingfang , Li Jun , Wang Weisi , Wang Tian , Qi Wenjing , Zheng Xueting , Duan Lei , Chen Jiaxu , Li Shizhu , Han Xiumin , Zhang Wenbao , Duan Liping 
Published: July 2021

Abstract
Background
Cystic echinococcosis (CE) is a life-threatening zoonosis caused by the larval form of Echinococcus granulosus tapeworm. Our previous study showed that an approved drug pyronaridine (PND) is highly effective against CE, both in vitro and in an animal model. To identify possible target genes, transcriptome analysis was performed with E. granulosus sensu stricto protoscoleces treated with PND.

Results
A total of 1,321 genes were differentially expressed in protoscoleces treated with PND, including 541 upregulated and 780 downregulated genes. Gene ontology and KEGG analyses revealed that the spliceosome, mitogen-activated protein kinase (MAPK) pathway and ATP-binding cassette (ABC) transporters were the top three enriched pathways. Western blot analysis showed that PND treatment resulted in a dose-dependent increase in protein expression levels of EgMKK1 (MKK3/6-like) and EgMKK2 (MEK1/2-like), two members of MAPK cascades. Interestingly, several heat shock protein (HSP) genes were greatly downregulated including stress-inducible HSPs and their constitutive cognates, and some of them belong to Echinococcus-specific expansion of HSP70.

Conclusions
PND has a great impact on the spliceosome, MAPK pathway and ABC transporters, which may underline the mechanisms by which PND kills E. granulosus protoscoleces. In addition, PND downregulates HSPs expression, suggesting a close relationship between the drug and HSPs.
Genome-wide identification and expression analysis of aquaporin family in Canavalia rosea and their roles in the adaptation to saline-alkaline soils and drought stress
Authors: Lin Ruoyi , Zheng Jiexuan , Pu Lin , Wang Zhengfeng , Mei Qiming , Zhang Mei , Jian Shuguang 
Published: July 2021

AbstractBackgroundCanavalia rosea(Sw.) DC. (bay bean) is an extremophile halophyte that is widely distributed in coastal areas of the tropics and subtropics. Seawater and drought tolerance in this species may be facilitated by aquaporins (AQPs), channel proteins that transport water and small molecules across cell membranes and thereby maintain cellular water homeostasis in the face of abiotic stress. InC. rosea, AQP diversity, protein features, and their biological functions are still largely unknown.ResultsWe describe the action of AQPs inC. roseausing evolutionary analyses coupled with promoter and expression analyses. A total of 37 AQPs were identified in theC. roseagenome and classified into five subgroups: 11 plasma membrane intrinsic proteins, 10 tonoplast intrinsic proteins, 11 Nod26-like intrinsic proteins, 4 small and basic intrinsic proteins, and 1 X-intrinsic protein. Analysis of RNA-Seq data and targeted qPCR revealed organ-specific expression of aquaporin genes and the involvement of some AQP members in adaptation ofC. roseato extreme coral reef environments. We also analyzedC. roseasequences for phylogeny reconstruction, protein modeling, cellular localizations, and promoter analysis. Furthermore, one of PIP1 gene,CrPIP1;5, was identified as functional using a yeast expression system and transgenic overexpression inArabidopsis.ConclusionsOur results indicate that AQPs play an important role inC. rosearesponses to saline-alkaline soils and drought stress. These findings not only increase our understanding of the role AQPs play in mediatingC. roseaadaptation to extreme environments, but also improve our knowledge of plant aquaporin evolution more generally.
Current status and etiology of valvular heart disease in China: a population-based survey
Authors: Yang Ying , Wang Zengwu , Chen Zuo , Wang Xin , Zhang Linfeng , Li Suning , Zheng Congyi , Kang Yuting , Jiang Linlin , Zhu Zhenhui , Gao Runlin 
Published: July 2021

Abstract
Background
The epidemiology of valvular heart disease (VHD) has changed markedly over the last 50 years worldwide, and the prevalence and features of VHD in China are unknown. The objective of this study was to investigate the current status and etiology of VHD in China.

Methods
We used a cross-sectional national survey with stratified multistage random sampling from the general Chinese population to estimate the VHD burden. Data on demographic characteristics, medical history, physical examination, blood tests, and potential etiology were collected. Echocardiography was used to detect VHD.

Results
The national survey enrolled 34,994 people aged 35 years or older across China. Overall, 31,499 people were included in the final analysis, and 1309 participants were diagnosed with VHD. The weighted prevalence was 3.8%, with an estimated 25 million patients in China. The prevalence of VHD increased with age and was higher in participants with hypertension or chronic kidney disease than in their counterparts. Among participants with VHD, 55.1% were rheumatic and 21.3% were degenerative. The proportion of rheumatic decreased with age, and the proportion of degenerative rose with age. However, the prevalence of rheumatic disease was still higher in the elderly population than in the younger population. Logistic regression revealed that age and hypertension were correlated with VHD.

Conclusions
In China, rheumatic heart disease was still the major cause of the VHD, with a significant increase in degenerative heart disease. Age and hypertension are important and easily identifiable markers of VHD.
Clinical characteristics and disease outcomes in ER+ breast cancer: a comparison between HER2+ patients treated with trastuzumab and HER2- patients
Authors: Li Shuai , Wu Jiayi , Huang Ou , He Jianrong , Zhu Li , Chen Weiguo , Li Yafen , Chen Xiaosong , Shen Kunwei 
Published: July 2021

Abstract
Background
Trastuzumab has changed the prognosis of HER2+ breast cancer. We aimed to investigate the prognosis of ER+/HER2+ patients treated with trastuzumab, thus to guide escalation endocrine treatment in ER+ breast cancer.

Methods
ER-positive early breast cancer patients operated at Ruijin Hospital between Jan. 2009 and Dec. 2017 were retrospectively included. Eligible patients were grouped as HER2-negative (HER2-neg) or HER2-positive with trastuzumab treatment (HER2-pos-T). Kaplan-Meier analysis and Cox proportional hazards model were used to compare the disease-free survival (DFS) and overall survival (OS) between these two groups.

Results
A total of 3761 patients were enrolled: 3313 in the HER2-neg group and 448 in the HER2-pos-T group. Patients in the HER2-pos-T group were associated with pre/peri-menopause, higher histological grade, LVI, higher Ki-67 level, lower ER and PR levels (all P <  0.05). At a median follow-up of 62 months, 443 DFS events and 191 deaths were observed. The estimated 5-year DFS rate was 89.7% in the HER2-neg group and 90.2% in the HER2-pos-T group (P = 0.185), respectively. Multivariable analysis demonstrated that patients in the HER2-pos-T group had a better DFS than patients in the HER2-neg group (HR 0.52, 95% CI: 0.37–0.73, P <  0.001). The estimated 5-year OS rates were 96.0% and 96.3% in the two groups, respectively (P = 0.133). Multivariate analysis found that HER2-pos-T group was still associated with significantly better OS compared with the HER2-neg group (HR 0.38, 95% CI: 0.22–0.67, P = 0.037).

Conclusion
ER+/HER2+ breast cancer patients treated with trastuzumab were associated with superior outcome compared with ER+/HER2- patients, indicating HER2-positivity itself may not be an adverse factor for ER+ patients in the era of trastuzumab.