bluuebunny/crossref_metadata_2025_split huggingface dataset:
Real-world systemic sequential therapy with regorafenib for recurrent hepatocellular carcinoma: analysis of 93 cases from a single center
Authors: Zhu Qingwei , Rao Wei , Huo Junyu , Li Zixiang , Wang Song , Qiu Wensheng , Guan Ge , Xin Yang , Fan Ning , Cai Jinzhen , Wu Liqun 
Published: February 2023

Abstract
Background
Regorafenib is an oral multikinase inhibitor and became the first second-line systemic treatment for hepatocellular carcinoma (HCC) following the phase III RESORCE trial. This single-center study retrospectively analyzed the clinical data and follow-up results of patients with recurrent HCC treated with regorafenib and discussed the prognostic factors to provide guidance for clinical treatment.

Methods
Ninety-three recurrent HCC patients were enrolled in the research and follow up from December 2017 to December 2020. Clinical and pathological data were collected. SPSS software v26.0 was used (Chicago, IL, USA) for statistical analysis. A two-sided P < 0.05 was considered statistically significant.

Results
The patients included 81 males and 12 females with a median age of 57 years. Eighty-seven patients had hepatitis B virus (HBV) infection. The objective response rate (ORR) was 14.0%, and the disease control rate (DCR) was 62.4%. The median overall survival (mOS) and median time to progression (mTTP) were 15.9 and 5.0 months. Multivariate analysis showed that Child–Pugh classification, the Eastern Cooperative Oncology Group performance status (ECOG PS), the neutrophil-to-lymphocyte ratio (NLR), combined treatment, and the time from first diagnosis of HCC to second-line treatment were independent factors affecting the prognosis of recurrent HCC patients.

Conclusions
This real-world study demonstrated similar findings to those of the RESORCE trial. Regorafenib could effectively improve the prognosis of patients after first-line treatment failure. Combination therapy under multidisciplinary treatment (MDT) team guidance could be effective in impeding tumor progression and improving the prognosis of recurrent HCC patients.
Sex differences in changes of depressive symptoms among older adults before and during the COVID-19 pandemic: evidence from two longitudinal cohorts
Authors: Zheng Fanfan , Li Chenglong , Hua Rong , Liang Jie , Gao Darui , Xie Wuxiang 
Published: February 2023

AbstractBackgroundMajor concerns about the adverse mental health impact of the rapidly spread COVID-19 pandemic have been raised. Previous studies on changes of depressive symptoms during the COVID-19 pandemic have yielded inconsistent results regarding the sex differences. Since women have higher depressive symptoms even without the pandemic, it is essential to consider the pre-existing change of depressive symptoms of a similar period to discern the effect of the pandemic on depression. This study aimed to evaluate sex differences in depressive symptoms before and during the pandemic.MethodsData from the Health and Retirement Study (HRS; waves 13 to 15) and the English Longitudinal Study of Ageing (ELSA; wave 8 to COVID-19 wave 2) were analyzed. Depressive symptoms were assessed by the 8-item Center for Epidemiological Studies Depression (CES-D) scale. According to the time of COVID-19 outbreak in the US and the UK, the intervals from waves 13 to 14 surveys of the HRS and from waves 8 to 9 surveys of the ELSA were employed as pre-pandemic periods to control for the pre-existing depressive symptoms, respectively. Changes of CES-D scores during the pre-pandemic and pandemic periods were assessed by linear mixed models.ResultsNine thousand, seven hundred thirty-seven participants (mean age: 66.7 ± 10.7 years) from the HRS and 5,098 participants (mean age: 68.7 ± 10.0 years) from the ELSA were included. CES-D scores among women were significantly higher than those among men at all waves in both cohorts. During the pre-pandemic period, no significant sex difference on changes of CES-D scores was detected in either the HRS or the ELSA. During the pandemic period, CES-D scores were increased in both men and women and the sex differences in CES-D increments of the two cohorts were both significant. Enlarged sex differences were demonstrated in increments of CES-D scores during the pandemic period.ConclusionsOur results suggest women suffered from worse depressive symptoms in response to the pandemic, although the changes of depression were similar between men and women before the pandemic. These findings underscore the necessity to support the vulnerable populations, especially women, to manage the distress brought by the pandemic and maintain optimal mental health status.
Factors associated with the uptake of clinical breast examination among women of reproductive age in Lesotho: analysis of a national survey
Authors: Afaya Agani , Laari Timothy Tienbia , Seidu Abdul Aziz , Afaya Richard Adongo , Daniels-Donkor Silas Selorm , Yakong Vida Nyagre , Ahinkorah Bright Opoku 
Published: February 2023

Abstract
Background
In low-resource settings with weak health systems, the WHO recommends clinical breast examination (CBE) as the most cost-effective breast screening modality for women. Evidence shows that biennial CBE leads to significant downstaging of breast cancer in all women. Breast cancer is the second most common cancer among women in Lesotho with a weaker healthcare system and a low breast cancer screening rate. This study investigated the prevalence and factors associated with the uptake of CBE among women of reproductive age in Lesotho.

Methods
This study used cross-sectional data from the 2014 Lesotho Demographic and Health Survey. A sample of 6584 reproductive-age women was included in this study. We conducted both descriptive and multivariable logistic regression analyses. The study results were presented in frequencies, percentages, and adjusted odds ratios (aOR) with their corresponding confidence intervals (CIs).

Results
The prevalence of CBE uptake was 9.73% (95% CI: 8.91, 10.61). Women who were covered by health insurance (aOR = 2.31, 95% CI [1.37, 3.88]), those who were pregnant (aOR = 2.34, 95% CI [1.64, 3.35]), those who had one to three children (aOR = 1.81, 95% CI [1.29,2.52]), and women who frequently read newspapers or magazines (aOR = 1.33, 95% CI [1.02,1.72]) were more likely to undergo CBE than their counterparts. Women who were aware of breast cancer (aOR = 2.54, 95% CI [1.63,3.97]), those who have ever had breast self-examination (BSE) within the last 12 months prior to the study (aOR = 5.30, 95% CI [4.35,6.46]), and those who visited the health facility in the last 12 months prior to the study (aOR = 1.57, 95% CI [1.27,1.95]) were also more likely to undergo CBE than their counterparts. Women residing in the Qacha’s-nek region (aOR = 0.42, 95% CI [0.26,0.67]) were less likely to undergo CBE than those in the Botha-bothe region.

Conclusion
The study found a low prevalence of CBE uptake among reproductive-age women in Lesotho. Factors associated with CBE uptake include health insurance coverage, being pregnant, those who had one to three children, exposure to media, breast cancer awareness, ever had BSE, and those who visited a health facility. To increase CBE uptake, these factors should be considered when designing cancer screening interventions and policies in order to help reduce the burden of breast cancer in Lesotho.
Prevalence and predictors of adverse events following exposure to long-lasting insecticidal nets used for malaria prevention: a community based cross-sectional study in the Democratic Republic of the Congo
Authors: Ilombe Gillon , Mpiempie Thérèse , Mesia Gauthier , Matangila Junior R. , Lulebo Aimée M. , Maketa Vivi , Mabanzila Baby , Muela Nicole M. , Muanda Flory T. , Linsuke Sylvie , van Geertruyden Jean-Pierre , Lutumba Pascal 
Published: February 2023

AbstractBackgroundMalaria morbidity and mortality increase in the Democratic Republic of the Congo (DRC) may be the consequence of the low utilization rate of long-lasting insecticidal nets (LLINs) resulting from poor compliance due to adverse events (AEs). This study aimed at determining the prevalence and predictors of AEs following the mass distribution of LLINs in the Kisantu Health Zone (KHZ), a high malaria-endemic region in the DRC.MethodsA community-based cross-sectional study embedded was conducted within a randomized controlled trial (RCT) after the mass distribution of LLINs in 30 villages located in DRC KHZ. A three-stage sampling method was used without replacement to select 1790 children. Data was collected on adverse events (AEs) using a reporting form and information on demographics, nutritional status, and house characteristics. This was done using a structured questionnaire administered to household heads. Logistic regression models were used to identify predictors of AEs following the mass distribution of LLINs.ResultIn a total of 1790 children enrolled, 17.8% (95% CI 16.1–19.7) experienced AEs. The most common AEs were respiratory-related (61%). Around 60% of AEs occurred within 24 h of use, and 51% were resolved without treatment. Sleeping under deltamethrin LLINs (Adjusted OR, 95% CI 5.5 [3.8–8.0]) and zinc roofing (Adjusted OR, 95% CI 1.98 [1.1–3.57]) were associated with the risk of reporting an AE following the mass distribution of LLINs.ConclusionApproximately 1 out of 5 children had an AE within 24 h following LLIN use. These adverse events were often respiratory-related. LLINs and roofing types were associated with a higher risk of reporting AEs. However, further research using a robust study design is needed to confirm these findings. Future studies should design and implement interventions aiming to reduce AEs and improve compliance with LLINs.
The correlation between blood-lipid ratio in the first trimester and large-for-gestational-age infants
Authors: Wang Zixuan , Peng Yaru , Mao Shufang , Zhang Liqian , Guo Yanwei 
Published: February 2023

Abstract
Background
To investigate the correlation between maternal glucose and lipid metabolism indexes and blood-lipid ratio in the first trimester and large-for- gestational-age (LGA) infants.

Methods
Women in the first trimester of pregnancy who underwent regular obstetric examination in the obstetric outpatient department of the Affiliated Hospital of Chengde Medical College from June 2018 to March 2019 were included according to the standard. Basic information were collected based on questionnaires at the first visit of pregnant women, including early fasting blood glucose (FBG), fasting insulin (FINS), glycated hemoglobin (HbA1c), high-density lipoprotein (HDL), low-density lipoprotein (LDL), triglyceride (TG), total cholesterol (TC), apolipoprotein A1 (APO-A1), apolipoprotein B (APO-B), lipoprotein a (LP(a)), LDL/HDL, TG/HDL, TC/HDL, APO-B/APO-A1 ratio, birth weight of newborns, gestational age at delivery etc.

Results
A total of 418 cases were included for analysis. The incidence rate of LGA infants was 13.88%, and that of small-for-gestational-age (SGA) infants was 4.78%. Univariate analysis revealed that the age, pre-pregnancy body mass index (BMI), weight gain during pregnancy, APO-B/APO-A1 between LGA group and appropriate-for-gestational-age (AGA) group were significantly different (P < 0.05); multivariate stepwise logistic regression analysis indicated that the correlation between maternal age, pre-pregnancy BMI, weight gain during pregnancy, APO-B/APO-A1 level and LGA were statistically significant (P < 0.05); compared with the reference range of APO-B/APO-A1 of 0.46–0.65, values < 0.46 and > 0.65 were protective factor of LGA (P < 0.05). The receiver operating curve(ROC) indicated that the area under the curve (AUC)s for predicting LGA using maternal age, pre-pregnancy BMI, weight gain during pregnancy, and early pregnancy APO-B/APO-A1 were 0.585, 0.606, 0.637, 0.531, respectively. The AUC for a combined prediction model was 0.742, showing greater predictive value than any other factors individually.

Conclusion
Maternal age, pre-pregnancy BMI, weight gain during pregnancy, and APO-B/APO-A1 levels in first trimester are significant factors influencing the occurrence of LGA infants, and the combination of the four factors would have certain predictive value for LGA.
Influence of femoral bowing on stress distribution of the proximal femur: a three-dimensional finite element analysis
Authors: Kaku Nobuhiro , Hosoyama Tsuguaki , Shibuta Yutaro , Kimura Makoto , Tsumura Hiroshi 
Published: February 2023

Abstract
Background
Whether femoral bowing or its direction has a mechanical effect on the proximal femur is unclear. This study aimed to define the changes in stress distribution in the proximal femur associated with femoral bowing using finite element analysis.

Methods
We created four femoral models: original, entire lateral bowing, entire anterior bowing, and the middle of both (50% anterolateral bowing) from computed tomography data of women with standard bowing. Each model’s stress distribution was compared by two-layering the stress distribution under loading conditions during walking. We also evaluated displacement vectors.

Results
In all directions of femoral bowing, the stress increased in the femoral neck and the femoral trochanter in the 50% anterolateral bowing. The direction of deformation of the vector for the femoral head increased anteroinferiorly in the 50% anterolateral bowing.

Conclusions
This study showed that the stress distribution at the proximal femur shifted laterally. The high-stress area increased at the femoral neck or trochanter due to increasing femoral bowing. Femoral bowing also increases the anteroinferior vector in the femoral head. This study provides valuable insights into the mechanism of proximal femoral fractures in older adults.
Clinicopathologic characteristics of thymic clear cell carcinoma: a case report with literature review
Authors: Zhao Zuxuan , Zeng Qingpeng , Li Jiangtao , Zheng Shan 
Published: February 2023

Abstract
Background
Thymic clear cell carcinoma is a rare mediastinal neoplasm, with only 25 reported cases to date. We report a case of a 45-year-old man with thymic clear cell carcinoma. We think imaging and laboratory tests may be helpful for differential diagnosis.

Case presentation
A 45-year-old male was admitted to a local hospital for chest distress with cardiopalmus. CT showed a mediastinal mass. Laboratory examination results were all in the normal range. Histologically, the tumor cells had a clear cytoplasm, and immunohistochemically, the tumor cells were positive for epithelial markers. We performed abdominal and pelvic CT and further examined serum levels of thyroxine, parathyroid hormone and AFP postoperatively, which were normal. The patient received postoperative radiotherapy, and CT showed left adrenal metastasis at 20 months after surgery.

Conclusion
Thymic clear cell carcinoma is a rare malignant neoplasm. Adrenal metastasis can occur. Patients undergo thymectomy with chemotherapy or with radiotherapy have better outcoming. Metastasis, direct invasion of parathyroid carcinoma and other primary tumors in the mediastinum should be excluded. Immunohistochemical markers, imaging and laboratory examination can help to exclude metastasis.
The collateral activity of RfxCas13d can induce lethality in a RfxCas13d knock-in mouse model
Authors: Li Yunfei , Xu Junjie , Guo Xuefei , Li Zhiwei , Cao Lili , Liu Shengde , Guo Ying , Wang Guodong , Luo Yujie , Zhang Zeming , Wei Xuemei , Zhao Yingchi , Liu Tongtong , Wang Xiao , Xia Huawei , Kuang Ming , Guo Qirui , Li Junhong , Chen Luoying , Wang Yibing , Li Qi , Wang Fengchao , Liu Qinghua , You Fuping 
Published: February 2023

Abstract
Background
The CRISPR-Cas13 system is an RNA-guided RNA-targeting system and has been widely used in transcriptome engineering with potentially important clinical applications. However, it is still controversial whether Cas13 exhibits collateral activity in mammalian cells.

Results
Here, we find that knocking down gene expression using RfxCas13d in the adult brain neurons caused death of mice, which may result from the collateral activity of RfxCas13d rather than the loss of target gene function or off-target effects. Mechanistically, we show that RfxCas13d exhibits collateral activity in mammalian cells, which is positively correlated with the abundance of target RNA. The collateral activity of RfxCas13d could cleave 28s rRNA into two fragments, leading to translation attenuation and activation of the ZAKα-JNK/p38-immediate early gene pathway.

Conclusions
These findings provide new mechanistic insights into the collateral activity of RfxCas13d in mammalian cells and warn that the biosafety of the CRISPR-Cas13 system needs further evaluation before application to clinical treatments.
Hetrombopag plus porcine ATG and cyclosporine for the treatment of aplastic anaemia: early outcomes of a prospective pilot study
Authors: Yang Wenrui , Zhao Xin , Liu Xu , Xiong Youzhen , Fan Huihui , Zhang Li , Li Jianping , Ye Lei , Zhou Kang , Li Yuan , Yang Yang , Peng Guangxin , Jing Liping , Zhang Fengkui 
Published: February 2023

AbstractHetrombopag, a small molecular thrombopoietin-receptor agonist, has shown encouraging efficiency in immunosuppressive therapy refractory or relapsed severe aplastic anaemia. To investigate the response rate of hetrombopag combined with IST as first-line treatment, we designed a prospective pilot study including 32 patients with SAA treated with anti-human T lymphocyte porcine immunoglobulin (p-ATG), cyclosporine, and hetrombopag. In addition, 96 patients with SAA treated with p-ATG and cyclosporine alone were matched as controls. In total, 21.9% of patients treated with hetrombopag achieved complete response (CR) at 3 months, while 5.2% of patients achieved CR in the control group (P = 0.005). At 6 months, the CR rates were 34.4% in the hetrombopag group and 14.6% in the control group (P = 0.015). The overall response rates at 6 months were 68.7% and 50.0% in the hetrombopag and control groups, respectively. The median time to haematologic response was 56 days and 77 days, and to CR was 96 days and 214 days in the hetrombopag and control groups, respectively. In conclusion, adding hetrombopag to IST as first-line treatment resulted in faster and better haematologic response in SAA.
Rhizosphere phage communities drive soil suppressiveness to bacterial wilt disease
Authors: Yang Keming , Wang Xiaofang , Hou Rujiao , Lu Chunxia , Fan Zhe , Li Jingxuan , Wang Shuo , Xu Yangchun , Shen Qirong , Friman Ville-Petri , Wei Zhong 
Published: February 2023

Abstract
Background
Bacterial viruses, phages, play a key role in nutrient turnover and lysis of bacteria in terrestrial ecosystems. While phages are abundant in soils, their effects on plant pathogens and rhizosphere bacterial communities are poorly understood. Here, we used metagenomics and direct experiments to causally test if differences in rhizosphere phage communities could explain variation in soil suppressiveness and bacterial wilt plant disease outcomes by plant-pathogenic Ralstonia solanacearum bacterium. Specifically, we tested two hypotheses: (1) that healthy plants are associated with stronger top-down pathogen control by R. solanacearum-specific phages (i.e. ‘primary phages’) and (2) that ‘secondary phages’ that target pathogen-inhibiting bacteria play a stronger role in diseased plant rhizosphere microbiomes by indirectly ‘helping’ the pathogen.

Results
Using a repeated sampling of tomato rhizosphere soil in the field, we show that healthy plants are associated with distinct phage communities that contain relatively higher abundances of R. solanacearum-specific phages that exert strong top-down pathogen density control. Moreover, ‘secondary phages’ that targeted pathogen-inhibiting bacteria were more abundant in the diseased plant microbiomes. The roles of R. solanacearum-specific and ‘secondary phages’ were directly validated in separate greenhouse experiments where we causally show that phages can reduce soil suppressiveness, both directly and indirectly, via top-down control of pathogen densities and by alleviating interference competition between pathogen-inhibiting bacteria and the pathogen.

Conclusions
Together, our findings demonstrate that soil suppressiveness, which is most often attributed to bacteria, could be driven by rhizosphere phage communities that regulate R. solanacearum densities and strength of interference competition with pathogen-suppressing bacteria. Rhizosphere phage communities are hence likely to be important in determining bacterial wilt disease outcomes and soil suppressiveness in agricultural fields.
Prey ingestion rates revealed by back-mounted accelerometers in Eurasian spoonbills
Authors: Lok Tamar , van der Geest Matthijs , Bom Roeland A. , de Goeij Petra , Piersma Theunis , Bouten Willem 
Published: February 2023

Abstract
Background
Quantifying foraging success in space and time and among individuals is essential for answering many ecological questions and may guide conservation efforts. However, collecting this information is challenging for species that forage on mobile prey and are difficult to observe visually, for example, because they forage in inaccessible areas or at night. In such cases, the use of tracking devices that simultaneously collect location and acceleration data may provide a solution if foraging success can be extracted successfully. The aim of this study was to assess how well searching for and ingesting prey, among other behaviours, could be distinguished from 20 Hz acceleration data collected by GPS/ACC-trackers mounted on the back of Eurasian spoonbills Platalea leucorodia. Upon capturing a prey, spoonbills make a distinct movement with their head and back to throw the prey from the tip of the bill into the throat.

Methods
We compared the behavioural classification performance of random forest models that were trained and tested on video-annotated acceleration data segments of different (fixed or flexible) lengths. The best-performing model was then applied to 4 years of data of spoonbills foraging in the Wadden Sea during the breeding season, to explore seasonal and annual variation in prey ingestion rates.

Results
Highest classification accuracies (as indicated by the F-measure, a balanced measure of precision and sensitivity) of foraging behaviours were achieved by analysing short fixed-length segments (0.4–0.8 s) or “flexibly-cut” segments. The F-measure was very high (> 0.90) for searching, standing, sitting and flying (distinguishing active and passive flight), 0.73 for ingesting prey and 0.65 for walking. False positive and negative prey ingestions were equally likely and most often confused with searching, resulting in a close match between the predicted and observed prey ingestion rates. Application of the best-performing model revealed strong seasonal patterns in prey ingestion rates in the Wadden Sea that varied between years.

Conclusions
We show that prey ingestion rates of spoonbills can be fairly accurately estimated from acceleration data. These results are promising for the use of spoonbills equipped with GPS/ACC-trackers as monitors of spatial and temporal variation in the availability of small fish and shrimp, which is key to understand the foraging and migratory movements of spoonbills and provides information on the quality of (coastal) wetlands.