bluuebunny/crossref_metadata_2025_split huggingface dataset:
Swin Unet3D: a three-dimensional medical image segmentation network combining vision transformer and convolution
Authors: Cai Yimin , Long Yuqing , Han Zhenggong , Liu Mingkun , Zheng Yuchen , Yang Wei , Chen Liming 
Published: February 2023

Abstract
Background
Semantic segmentation of brain tumors plays a critical role in clinical treatment, especially for three-dimensional (3D) magnetic resonance imaging, which is often used in clinical practice. Automatic segmentation of the 3D structure of brain tumors can quickly help physicians understand the properties of tumors, such as the shape and size, thus improving the efficiency of preoperative planning and the odds of successful surgery. In past decades, 3D convolutional neural networks (CNNs) have dominated automatic segmentation methods for 3D medical images, and these network structures have achieved good results. However, to reduce the number of neural network parameters, practitioners ensure that the size of convolutional kernels in 3D convolutional operations generally does not exceed $$7 \times 7 \times 7$$

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, which also leads to CNNs showing limitations in learning long-distance dependent information. Vision Transformer (ViT) is very good at learning long-distance dependent information in images, but it suffers from the problems of many parameters. What’s worse, the ViT cannot learn local dependency information in the previous layers under the condition of insufficient data. However, in the image segmentation task, being able to learn this local dependency information in the previous layers makes a big impact on the performance of the model.

Methods
This paper proposes the Swin Unet3D model, which represents voxel segmentation on medical images as a sequence-to-sequence prediction. The feature extraction sub-module in the model is designed as a parallel structure of Convolution and ViT so that all layers of the model are able to adequately learn both global and local dependency information in the image.

Results
On the validation dataset of Brats2021, our proposed model achieves dice coefficients of 0.840, 0.874, and 0.911 on the ET channel, TC channel, and WT channel, respectively. On the validation dataset of Brats2018, our model achieves dice coefficients of 0.716, 0.761, and 0.874 on the corresponding channels, respectively.

Conclusion
We propose a new segmentation model that combines the advantages of Vision Transformer and Convolution and achieves a better balance between the number of model parameters and segmentation accuracy. The code can be found at https://github.com/1152545264/SwinUnet3D.
Current career situations of Chinese pharmacovigilance professionals working for pharmaceutical companies: an exploratory survey
Authors: Tang Yalan , Liu Yan , Liao Hongli , Yuan Yonghua , Jiang Qihua 
Published: February 2023

Abstract
Background
Pharmacovigilance in China has experienced rapid development in the past 30 years. The implementation of Good Pharmacovigilance Practice in China since the end of 2021 heralds a new era of pharmacovigilance affairs, which puts forward higher requirements for the quantity and quality of pharmacovigilance personnel. This study aimed to preliminarily explore the current career situations of pharmacovigilance professionals working in China for pharmaceutical companies.

Methods
A questionnaire was adapted from research in the USA and Europe with the help of several pharmacovigilance experts. Snowball sampling was used to conduct an exploratory survey to obtain the frequency of basic demographic information, work status, and career expectations of pharmacovigilance professionals working for pharmaceutical companies.

Results
The personnel engaged in pharmacovigilance work for pharmaceutical companies were mainly medical or pharmaceutical undergraduates within 3 years of graduation. Their work intensity and pressure were relatively high. The training provided by their universities and enterprises could not well meet their needs to improve their job competence. Although they were optimistic about pharmacovigilance and will not change their career, most of them were planning to change their employers.

Conclusion
There was a gap between the demand and supply of pharmacovigilance personnel. Relevant regulatory authorities and industry associations should guide higher education institutions to collaborate with pharmacovigilance specialists to strengthen pharmacovigilance education for medical or pharmaceutical students, on the basis of which pharmacovigilance certification courses and continuing education courses can be developed. Meanwhile, pharmaceutical enterprises should consider reasonably adjusting work intensity and income to avoid a high turnover rate.
Approaches to optimising access to NICE-approved biologic anti-TNFs for patients with rheumatoid arthritis with moderately active disease
Authors: Taylor Peter C. , Askari Ayman , Choy Ernest , Ehrenstein Michael R. , Else Sara , Nisar Muhammad K. 
Published: February 2023

Abstract
Background
Rheumatoid arthritis (RA) is a chronic inflammatory disease that is associated with joint pain and stiffness. Biologics represent some of the most effective treatments for RA, but previous guidance from the National Institute for Health and Care Excellence (NICE) has limited their use to patients with severely active disease. This has meant patients with moderately active RA have been treated as if they have an acceptable disease state, despite many cases where the inflammation has a major impact on joint damage, mobility, pain and quality of life. However, recent guideline changes (NICE TA715) have approved the use of three biologics — adalimumab, etanercept and infliximab — for the treatment of moderately active RA.

Main body
In response to these changes, we have held discussions with medical teams from across the UK to consider the main implications for implementation of these new recommendations, as well as any differences in approach that may exist at a local level. Several key challenges were identified. These included establishing methods of educating both physicians and patients concerning the new availability of the biologic treatments, with suggestions of various organisations that could be approached to circulate informative material. Identifying which patients with moderately active RA stand to benefit was another discussion topic. Relying solely on scoring systems like Disease Activity Score in 28 Joints (DAS28) was acknowledged to have limitations, and alternative complementary approaches such as ultrasound, as well as assessing a patient’s co-morbidities, could also be useful tools in determining those who could benefit from biologics. An additional challenge for the process of patient identification has been the increase in the use of telemedicine consultations in response to the coronavirus disease 2019 (COVID-19) pandemic. More use of patient-reported outcomes was raised as one possible solution, and the importance of maintaining up-to-date databases on patient disease scores and treatment history was also stressed.

Conclusion
While challenges exist in education and identifying patients who may benefit from the use of biologics, the NICE TA715 recommendations hold great potential in addressing an unmet need for the treatment of moderate RA.
Leveraging massively parallel reporter assays for evolutionary questions
Authors: Gallego Romero Irene , Lea Amanda J. 
Published: February 2023

AbstractA long-standing goal of evolutionary biology is to decode how gene regulation contributes to organismal diversity. Doing so is challenging because it is hard to predict function from non-coding sequence and to perform molecular research with non-model taxa. Massively parallel reporter assays (MPRAs) enable the testing of thousands to millions of sequences for regulatory activity simultaneously. Here, we discuss the execution, advantages, and limitations of MPRAs, with a focus on evolutionary questions. We propose solutions for extending MPRAs to rare taxa and those with limited genomic resources, and we underscore MPRA’s broad potential for driving genome-scale, functional studies across organisms.
Early diagnosis of ovarian cancer based on methylation profiles in peripheral blood cell-free DNA: a systematic review
Authors: Terp Simone Karlsson , Stoico Malene Pontoppidan , Dybkær Karen , Pedersen Inge Søkilde 
Published: February 2023

AbstractPatients diagnosed with epithelial ovarian cancer (OC) have a 5-year survival rate of 49%. For early-stage disease, the 5-year survival rate is above 90%. However, advanced-stage disease accounts for most cases as patients with early stages often are asymptomatic or present with unspecific symptoms, highlighting the need for diagnostic tools for early diagnosis. Liquid biopsy is a minimal invasive blood-based approach that utilizes circulating tumor DNA (ctDNA) shed from tumor cells for real-time detection of tumor genetics and epigenetics. Increased DNA methylation of promoter regions is an early event during tumorigenesis, and the methylation can be detected in ctDNA, accentuating the promise of methylated ctDNA as a biomarker for OC diagnosis. Many studies have investigated multiple methylation biomarkers in ctDNA from plasma or serum for discriminating OC patients from patients with benign diseases of the ovaries and/or healthy females. This systematic review summarizes and evaluates the performance of the currently investigated DNA methylation biomarkers in blood-derived ctDNA for early diagnosis of OC. PubMed’s MEDLINE and Elsevier’s Embase were systematically searched, and essential results such as methylation frequency of OC cases and controls, performance measures, as well as preanalytical factors were extracted. Overall, 29 studies met the inclusion criteria for this systematic review. The most common method used for methylation analysis was methylation-specific PCR, with half of the studies using plasma and the other half using serum. RASSF1A, BRCA1, and OPCML were the most investigated gene-specific methylation biomarkers, with OPCML having the best performance measures. Generally, methylation panels performed better than single gene-specific methylation biomarkers, with one methylation panel of 103,456 distinct regions and 1,116,720 CpGs having better performance in both training and validation cohorts. However, the evidence is still limited, and the promising methylation panels, as well as gene-specific methylation biomarkers highlighted in this review, need validation in large, prospective cohorts with early-stage asymptomatic OC patients to assess the true diagnostic value in a clinical setting.
Targeting ovarian cancer stem cells: a new way out
Authors: Ma Huiying , Tian Tian , Cui Zhumei 
Published: February 2023

AbstractOvarian cancer (OC) is the most lethal gynecological malignancy due to tumor heterogeneity, the lack of reliable early diagnosis methods and the high incidence of chemoresistant recurrent disease. Although there are developments in chemotherapies and surgical techniques to improve the overall survival of OC patients, the 5-year survival of advanced OC patients is still low. To improve the prognosis of OC patients, it is important to search for novel therapeutic approaches. Cancer stem cells (CSCs) are a subpopulation of tumor cells that participate in tumor growth, metastasis and chemoresistance. It is important to study the role of CSCs in a highly heterogeneous disease such as OC, which may be significant to a better understanding of the oncogenetic and metastatic pathways of the disease and to develop novel strategies against its progression and platinum resistance. Here, we summarized the current findings about targeting methods against ovarian cancer stem cells, including related signaling pathways, markers and drugs, to better manage OC patients using CSC-based therapeutic strategies.
Role of functional fatty acids in modulation of reproductive potential in livestock
Authors: Zeng Xiangzhou , Li Siyu , Liu Lu , Cai Shuang , Ye Qianhong , Xue Bangxin , Wang Xinyu , Zhang Shihai , Chen Fang , Cai Chuanjiang , Wang Fenglai , Zeng Xiangfang 
Published: February 2023

AbstractFatty acids are not only widely known as energy sources, but also play important roles in many metabolic pathways. The significance of fatty acids in modulating the reproductive potential of livestock has received greater recognition in recent years. Functional fatty acids and their metabolites improve follicular development, oocyte maturation and embryo development, as well as endometrial receptivity and placental vascular development, through enhancing energy supply and precursors for the synthesis of their productive hormones, such as steroid hormones and prostaglandins. However, many studies are focused on the impacts of individual functional fatty acids in the reproductive cycle, lacking studies involved in deeper mechanisms and optimal fatty acid requirements for specific physiological stages. Therefore, an overall consideration of the combination and synergy of functional fatty acids and the establishment of optimal fatty acid requirement for specific stages is needed to improve reproductive potential in livestock.
Native knee kinematics is not reproduced after sensor guided cruciates substituting total knee arthroplasty
Authors: Indelli Pier Francesco , Giuntoli Michele , Zepeda Karlos , Ghirardelli Stefano , Valtanen Rosa Susanna , Iannotti Ferdinando 
Published: February 2023

AbstractPurposeGait analysis was used to evaluate knee kinematics in patients who underwent successful primary total knee arthroplasty (TKA) using two modern bi‐cruciate substituting designs. The knee joint was balanced intraoperatively using real‐time sensor technology, developed to provide dynamic feedback regarding stability and tibiofemoral load. The authors hypothesized that major differences exist in gait parameters between healthy controls and post‐TKA patients.MethodsTen patients who underwent successful TKA using bi‐cruciate substituting designs were evaluated at a minimum of 9 months postoperatively using three‐dimensional knee kinematic analysis; a multi‐camera optoelectronic system and a force platform were used. Sensor‐extracted kinematic data included knee flexion angle at heel‐strike (KFH), peak midstance knee flexion angle (MSKFA), maximum and minimum knee adduction angle (KAA) and knee rotational angle at heel‐strike. Multiple gait analysis data from the study group were compared to a group of ten healthy controls who were matched by age, sex and BMI. Clinical outcome in the TKA group was also measured using the Knee injury and Osteoarthritis Outcome Score (KOOS).ResultsClinically, at final follow‐up, a statistically significant difference in pain, general symptoms, and activities of daily living was seen between the groups. From a gait analysis standpoint, TKA patients had significantly less rotation at heel strike (p = 0.04), lower late stance peak extension moments (p = 0.02), and less Knee Adduction Angle excursion during swing phase (p = 0.04) compared to the control group. No statistically significant difference was observed for knee flexion angle at heel strike, knee adduction moment, or peak knee flexion moment between the groups.ConclusionsModern bi‐cruciate substituting TKA designs failed to reproduce normal knee kinematics. The lack of full knee extension during the stance phase, absence of the “screw‐home mechanism” typical of an ACL functioning knee, and the reduced fluctuation in knee adduction angle during the swing phase still represent major proprioceptive and muscular recruitment differences between normal and replaced knees.
Degenerative tendon matrix induces tenogenic differentiation of mesenchymal stem cells
Authors: Hwang Joongwon , Lee Seung Yeon , Jo Chris Hyunchul 
Published: February 2023

AbstractPurposeMesenchymal stem cells (MSCs) react dynamically with the surrounding microenvironment to promote tissue‐specific differentiation and hence increase targeted regenerative capacity. Extracellular matrix (ECM) would be the first microenvironment to interact with MSCs injected into the tissue lesion. However, degenerative tissues would have different characteristics of ECM in comparison with healthy tissues. Therefore, the influence of degenerative ECM on tissue‐specific differentiation of MSCs and the formation of matrix composition need to be considered for the sophisticated therapeutic application of stem cells for tissue regeneration.MethodsHuman degenerative tendon tissues were obtained from patients undergoing rotator cuff repair and finely minced into 2 ~ 3 mm fragments. Different amounts of tendon matrix (0.005 g, 0.01 g, 0.025 g, 0.05 g, 0.1 g, 0.25 g, 0.5 g, 1 g, and 2 g) were co‐cultured with bone marrow MSCs (BM MSCs) for 7 days. Six tendon‐related markers, scleraxis, tenomodulin, collagen type I and III, decorin, and tenascin‐C, osteogenic marker, alkaline phosphatase (ALP), and chondrogenic marker, aggrecan (ACAN), were analyzed by qRT‐PCR. Cell viability and senescence‐associated beta‐galactosidase assays were performed. The connective tissue growth factor was used as a positive control.ResultsThe expressions of six tendon‐related markers were significantly upregulated until the amount of tendon matrix exceeded 0.5 g, the point where the mRNA expressions of all six genes analyzed started to decrease. The tendon matrix exerted an inhibitory effect on ACAN expression but had a negligible effect on ALP expression. Cell viability did not change significantly over the culture period. The amount of tendon matrix exceeding 0.01 g significantly increased the SA‐βgal activity of BM MSCs.ConclusionThis study successfully demonstrated tendon ECM‐stimulated tenogenesis of BM MSCs through an indirect co‐culture system without the use of exogenous growth factors and the alteration of cellular viability. In contrast to the initial hypothesis, the tenogenesis of BM MSCs induced with the degenerative tendon matrix accompanied cellular senescence.
Cultivating interlanguage pragmatic comprehension through concurrent and cumulative group dynamic assessment: a mixed-methods study
Authors: Rezai Afsheen 
Published: February 2023

AbstractThis study explored the effects of concurrent group dynamic assessment (G-DA) and cumulative G-DA on Iranian pre-intermediate English as a foreign language (EFL) learners’ interlanguage pragmatic comprehension (ILPC). To this end, a total of 97 pre-intermediate learners took the key English test (KET) test and 45 learners whose scores fell between − 1 and + 1 SD were selected and randomly assigned to experimental groups, namely concurrent G-DA (n = 15), cumulative G-DA (n = 15), and a control group, namely immediate feedback (IF) group (n = 15). Then, they went through pre-test, interventions (lasting fifteen 1-h sessions held three times a week), and post-test procedures, as well as the interactions among the teachers and learners were recorded. The data were analyzed through a one-way analysis of covariance (ANCOVA) and a microgenetic development approach. Results revealed that the concurrent G-DA and cumulative G-DA outperformed the IP group concerning the gains in the ILPC on the post-test. Additionally, the complementary microgenetic findings demonstrated the ways through which the concurrent G-DA and cumulative G-DA could lead to improving the learners’ ILPC.
The association between metamemory, subjective memory complaints, mood, and well-being: the Hungarian validation of Multifactorial Memory Questionnaire
Authors: Csábi Eszter , Hallgató Emese , Volosin Márta 
Published: February 2023

AbstractThe current study addressed the relationship between subjective memory complaints and negative affect, well-being, and demographic variables by investigating the Hungarian version of Multifactorial Memory Questionnaire. The original factor structure showed a poor fit on our data; therefore, principal component analysis was conducted on data from 577 participants, ranging in age from 18 to 92 years. Our analysis provided a six-component solution:Satisfaction,Retrospective memory mistakes,Prospective memory mistakes,External Strategies,Internal Strategies,andFrustration. To improve the reliability and internal consistency indicators we created four subscales by combiningFrustrationwithSatisfaction,andRetrospectiveandProspective memory mistakes subscales. Thus, we were able to preserve the factor structure similar to the original. Subjective memory complaints were correlated positively with anxiety and depression and were associated negatively with well-being. We found a slight positive correlation between age and memory ability, and age was associated negatively with the frequency of external strategy use. Individuals with higher education were satisfied with their memory, used more frequent external strategies. Furthermore, men were more satisfied with their memory and reported better memory ability, while women tended to use more external and internal strategies. Women also showed a higher level of anxiety and depression than men. In conclusion, self-reported memory changes are of particular importance because of their association with perceived mental health status and implications for later disease development.
Host metabolome and faecal microbiome shows potential interactions impacted by age and weaning times in calves
Authors: Amin Nida , Schwarzkopf Sarah , Tröscher-Mußotter Johanna , Camarinha-Silva Amélia , Dänicke Sven , Huber Korinna , Frahm Jana , Seifert Jana 
Published: February 2023

Abstract
Background
Calves undergo nutritional, metabolic, and behavioural changes from birth to the entire weaning period. An appropriate selection of weaning age is essential to reduce the negative effects caused by weaning-related dietary transitions. This study monitored the faecal microbiome and plasma metabolome of 59 female Holstein calves during different developmental stages and weaning times (early vs. late) and identified the potential associations of the measured parameters over an experimental period of 140 days.

Results
A progressive development of the microbiome and metabolome was observed with significant differences according to the weaning groups (weaned at 7 or 17 weeks of age). Faecal samples of young calves were dominated by bifidobacterial and lactobacilli species, while their respective plasma samples showed high concentrations of amino acids (AAs) and biogenic amines (BAs). However, as the calves matured, the abundances of potential fiber-degrading bacteria and the plasma concentrations of sphingomyelins (SMs), few BAs and acylcarnitines (ACs) were increased. Early-weaning at 7 weeks significantly restructured the microbiome towards potential fiber-degrading bacteria and decreased plasma concentrations of most of the AAs and SMs, few BAs and ACs compared to the late-weaning event. Strong associations between faecal microbes, plasma metabolites and calf growth parameters were observed during days 42–98, where the abundances of Bacteroides, Parabacteroides, and Blautia were positively correlated with the plasma concentrations of AAs, BAs and SMs as well as the live weight gain or average daily gain in calves.

Conclusion
The present study reported that weaning at 17 weeks of age was beneficial due to higher growth rate of late-weaned calves during days 42–98 and a quick adaptability of microbiota to weaning-related dietary changes during day 112, suggesting an age-dependent maturation of the gastrointestinal tract. However, the respective plasma samples of late-weaned calves contained several metabolites with differential concentrations to the early-weaned group, suggesting a less abrupt but more-persistent effect of dietary changes on host metabolome compared to the microbiome.