bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prenatal diagnosis of Roberts syndrome in a Chinese family based on ultrasound findings and whole exome sequencing: a case report
Authors: Zhu LiFen , Cao DingYa , Chen Min , Zhang Huimin , Sun XiaoFang , Liu WeiQiang 
Published: January 2022

Abstract
Background
Roberts syndrome (RBS) is a rare autosomal recessive disorder caused by variations in the ESCO2 gene; however, prenatal diagnosis of RBS has never been reported in Chinese families. Additionally, fetal-specific phenotypic characteristics associated with ESCO2 variants have not been reported.

Case presentation
A fetus in a healthy, nonconsanguineous Chinese family with multiple serious congenital malformations was diagnosed prenatally. Two consecutive fetuses in this family presented with tetraphocomelia, growth restriction, cleft lip and palate bilaterally, and other abnormalities. The main phenotypic characteristics of this case were strongly suspected to be associated with RBS. Finally, whole exome sequence analysis revealed the insertion of a homozygous base pair in exon 6 of the ESCO2 gene (NM_001017420.3, c.1111insA, NP_001017420.1, p.Thr371fs). Both of the couples were heterozygous carriers for this variant.

Conclusion
We are the first to report a prenatal case of RBS diagnosed in a Chinese family. Here, we have confirmed that the rare variant is a definite pathogenic variant, and we provide detailed phenotypic characteristics for the prenatal diagnosis of RBS due to this causative variant.
Optimism is associated with respiratory symptoms and functional status in chronic obstructive pulmonary disease
Authors: Koo Hyeon-Kyoung , Hoth Karin F. , Make Barry J. , Regan Elizabeth A. , Crapo James D. , Silverman Edwin K. , DeMeo Dawn L. 
Published: January 2022

AbstractBackgroundOptimism is the general belief that good things will occur in the future; optimism is modifiable by cognitive behavioral therapy (CBT). Previous studies have associated higher optimism with improved health outcomes and lower all-cause mortality.Research questionInvestigate association between optimism and disease-related characteristics in chronic obstructive pulmonary disease (COPD).Study design and methodsCurrent and former smokers with/without COPD and Preserved Ratio Impaired Spirometry (PRISm) from the 10-year follow-up visit for the Genetic Epidemiology of COPD (COPDGene) study were included. Optimism was assessed at the 10-year visit using the Life Orientation Test-Revised. Models of optimism as a predictor of lung function, COPD-associated phenotypes including exacerbations, and functional assessments, were adjusted for demographic confounders, smoking status, and comorbidities.ResultsAmong 1967 subjects, higher optimism was significantly associated with older age, non-Hispanic white race, marital status, quitting smoking status, absence of COPD, and absence of depression. In multivariable analysis, higher optimism was independently associated with fewer prior exacerbations of COPD (coef = − 0.037, P < 0.001). Higher optimism was also related to better MMRC scores (coef = − 0.041, P < 0.001), CAT scores (coef = − 0.391, P < 0.001), SGRQ scores (coef = − 0.958, P < 0.001), BODE index (coef = − 0.059, P < 0.001), and longer 6-min walk distance (coef = 10.227, P < 0.001). After stratification by severity of COPD, these associations with optimism were still significant in all groups. No significant association was observed for cross-sectional FEV1(%) or FVC (%) with optimism score.InterpretationFewer exacerbations and less severe respiratory symptoms and higher functional capacity were associated with higher optimism, which may impact health outcomes in current and former smokers with and without COPD. Optimism is a modifiable trait and these results may further support a role for CBT to improve outcomes in COPD.
Consequences of the COVID-19 pandemic on lung cancer care and patient health in a German lung cancer center: results from a cross-sectional questionnaire
Authors: Walter Julia , Sellmer Laura , Kahnert Kathrin , Kiefl Rosemarie , Syunyaeva Zulfiya , Kauffmann-Guerrero Diego , Manapov Farkhad , Schneider Christian , Behr Juergen , Tufman Amanda 
Published: January 2022

AbstractBackgroundThe novel coronavirus SARS-CoV-2 has caused a global COVID-19 pandemic, leading to worldwide changes in public health measures. In addition to changes in the public sector (lockdowns, contact restrictions), hospitals modified care to minimize risk of infection and to mobilize resources for COVID-19 patients. Our study aimed to assess the impact of these measures on access to care and behaviour of patients with thoracic malignancies.MethodsThoracic oncology patients were surveyed in October 2020 using paper-based questionnaires to assess access to ambulatory care services and tumor-directed therapy during the COVID-19 pandemic. Additionally, behaviour regarding social distancing and wearing of face masks were assessed, as well as COVID-19 exposure, testing and vaccination. Results are presented as absolute and relative frequencies for categorical variables and means with standard deviation for numerical variables. We used t-test, and ANOVA to compare differences in metric variables and Chi2-test to compare proportions between groups.Results93 of 245 (38%) patients surveyed completed the questionnaire. Respiration therapy and physical therapy were unavailable for 57% to 70% of patients during March/April. Appointments for tumor-directed therapy, tumor imaging, and follow-up care were postponed or cancelled for 18.9%, 13.6%, and 14.8% of patients, respectively. Patients reported their general health as mostly unaffected. The majority of patients surveyed did not report reducing their contacts with family. The majority reduced contact with friends. Most patients wore community masks, although a significant proportion reported respiratory difficulties during prolonged mask-wearing. 74 patients (80%) reported willingness to be vaccinated against SARS-CoV-2.ConclusionsThis survey provides insights into the patient experience during the second wave of the COVID-19 pandemic in Munich, Germany. Most patients reported no negative changes to cancer treatments or general health; however, allied health services were greatly impacted. Patients reported gaps in social distancing, but were prepared to wear community masks. The willingness to get vaccinated against SARS-CoV-2 was high. This information is not only of high relevance to policy makers, but also to health care providers.
FOXM1-induced TYMS upregulation promotes the progression of hepatocellular carcinoma
Authors: Wang Liang , Shi Caiyan , Yu Jie , Xu Yilin 
Published: January 2022

Abstract
Background
Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer and one of the major causes of cancer-related death. Thymidylate synthase (TYMS) catalyzes the methylation of deoxy guanosine to deoxy thymidylate, which is a crucial gene for DNA repair and replication. Thus, TYMS was reported to be closely associated with developing a variety of tumors, but it has been poorly studied in HCC.

Materials and methods
We used the cell counting kit-8 (CCK-8), BrdU, and CFSE assay to measure cell proliferation. The flow cytometry assay and the TUNEL assay were used for assessing cell apoptosis. The flow cytometry assay was used to analyze the cell cycle. The Transwell invasion assay and the wound healing assay were conducted to determine the invasive ability of the cells. RT-qPCR and Western blot analyses were performed to evaluate the mRNA and protein expression levels of specific genes, respectively.

Results
TYMS was found to be upregulated in both HCC cells and patient samples. High expression of TYMS was associated with an unfavorable prognosis in HCC patients based on the TCGA-LIHC dataset. Cell proliferation, apoptosis, and invasion assays revealed that TYMS promoted the proliferation and invasion of HCC cells as well as inhibited apoptosis. In addition, TYMS is a downstream target of FOXM1. TYMS knockdown reversed the 5-FU resistance caused by FOXM1 overexpression and re-sensitized HCC cells to 5-FU treatment.

Conclusion
This study suggested that TYMS serves as an oncogene in HCC, and targeting the FOXM1-TYMS axis may help improve the survival of HCC patients as well as provide new insights for treating advanced HCC patients.
Pan-cancer analysis combined with experiments explores the oncogenic role of spindle apparatus coiled-coil protein 1 (SPDL1)
Authors: Song Peng , Wusiman Dilinaer , Li Fenglan , Wu Xiaoxuan , Guo Lei , Li Wenbin , Gao Shugeng , He Jie 
Published: January 2022

Abstract
Background
The function of spindle apparatus coiled-coil protein 1 (SPDL1) as a cancer-promoting gene has been reported in a number of studies. However, the pan-cancer analysis of SPDL1 is still lacking. Here, we performed this pan-cancer analysis to evaluate the expression and prognostic value of SPDL1 and gain insights into the association between SPDL1 and immune infiltration.

Methods
In this study, based on the datasets of The cancer genome atlas (TCGA), Gene expression omnibus (GEO), The Genotype-Tissue Expression (GTEx) and Clinical Proteomic Tumor Analysis Consortium (CPTAC), we used R4.1.0 software and the online tools, including TIMER2.0, GEPIA2, cBioPortal, Modbase, UALCAN, MEXPRESS, STRING, Ensembl, NCBI, HPA, Oncomine, PhosphoNET and the Kaplan-Meier plotter, to explore the potential oncogenic roles of SPDL1. The expression of SPDL1 was also further verified by immunohistochemistry (IHC) in lung adenocarcinoma (LUAD) tissues.

Results
SPDL1 was overexpressed in most tumors compared with adjacent normal tissues, and SPDL1 expression was significantly correlated with the prognosis in most tumor types. The main type of genetic mutation of SPDL1 was missense mutation and the frequency of R318Q/W mutation was highest (4/119). The expression of SPDL1 was closely associated with genomic instability. The SPDL1 phosphorylation levels in S555 was enhanced in ovarian cancer. The SPDL1 expression was positively correlated with the immune infiltration of CD8+ T-cells and cancer-associated fibroblasts (CAFs) in most of the tumor types. Nuclear division, organelle fission and chromosome segregation were involved in the functional mechanisms of SPDL1.

Conclusions
These findings suggested that SPDL1 might serve as a biomarker for poor prognosis and immune infiltration in cancers, shedding new light on therapeutics of cancers.
ERBB3 binding protein 1 promotes the progression of malignant melanoma through activation of the Wnt/ β-catenin signaling pathway
Authors: Bao Yanqiu , Cui Jingshu , Yue Yuyang , Cao Shuxia , Li Xiangdan , Liu Lan 
Published: January 2022

Abstract
Background
Malignant melanoma (MM) is highly metastatic and has the highest mortality rate in patients with skin cancer. The ERBB3 binding protein 1 (Ebp1) has been linked to the onset and progression of a number of malignancies. However, the role of Ebp1 in MM has not yet been reported.

Methods
Multiple databases were analyzed for comparing the expression of Ebp1 in normal skin and MM. Ebp1 expression was knocked down in A375 and B16 cells, and the impact of Ebp1 on the cell growth was tested by CCK-8, plate clone colony, and cell cycle assays. Scratch, transwell, and in vivo caudal vein lung metastasis tests were also used to confirm the effects of Ebp1 on melanoma cells migration, invasion, and metastasis. Furthermore, the possible molecular mechanism of Ebp1 was predicted by set enrichment analysis and verified by western blotting.

Results
Ebp1 expression was substantially higher in MM than it was in normal skin, and Ebp1 was linked to the clinical stage and lymph node metastases of patients with MM. Knockdown of Ebp1 inhibited cell proliferation, migration, and invasion. In vivo experiments further verified that the knockdown of Ebp1 had an obvious inhibitory effect on lung metastasis in nude mice. Knockdown of Ebp1 reduced vimentin, N-cadherin, slug, and snail expression while increasing E-cadherin expression. Furthermore, knockdown of Ebp1 reduced the expression of β-catenin, as well as its downstream targets CyclinD1 and p-GSK3β; however, a Wnt/β-catenin agonist could reverse this effect.

Conclusion
Ebp1 may promote the proliferation and metastasis of melanoma cells through activation of the Wnt/β-catenin pathway.

Graphical Abstract
Intermittent parathyroid hormone treatment affects the bone structural parameters and mechanical strength of the femoral neck after ovariectomy-induced osteoporosis in rats
Authors: Wang Shun-Ping , Chen Ying-Ju , Hsu Cheng-En , Chiu Yung-Cheng , Tsai Ming-Tzu , Hsu Jui-Ting 
Published: January 2022

Abstract
Background
Menopause-induced decline in estrogen levels in women is a main factor leading to osteoporosis. The objective of this study was to investigate the effect of intermittent parathyroid hormone (PTH) on bone structural parameters of the femoral neck in ovariectomized rats, in addition to correlations of maximum fracture force.

Methods
Fifteen female Wister rats were divided into three groups: (1) control group; (2) ovariectomized (OVX) group; and (3) OVX  +  PTH group. All rats were then killed and the femurs extracted for microcomputed tomography scanning to measure volumetric bone mineral density (vBMD) and bone structural parameters of the femoral neck. Furthermore, the fracture forces of femoral neck were measured using a material testing system.

Results
Compared with the control and OVX  +  PTH groups, the OVX group had significantly lower aBMD, bone parameter, and mechanical strength values. A comparison between OVX and OVX  +  PTH groups indicated that PTH treatment increased several bone parameters. However, the OVX  +  PTH groups did not significantly differ with the control group with respect to the bone structural parameters, except for trabecular bone thickness of cancellous bone, which was greater. In addition, among the bone structural parameters, the CSA and BSI of cortical bone were significantly correlated with the maximum fracture force of the femoral neck, with correlations of, respectively, 0.682 (p  = 0.005) and 0.700 (p  = 0.004).

Conclusion
Intermittent PTH helped treat ovariectomy-induced osteoporosis of cancellous bone and cortical bone in the femoral necks of rats. The ability of the femoral neck to resist fracture was highly correlated with the two parameters, namely cross-sectional area (CSA) and bone strength index (=  vBMD  ×  CSA), of cortical bone in the femoral neck and was less correlated with aBMD or other bone structural parameters.
Risk and asset-based strategies in health: priorities in biomedical, life and environmental science literature since the early twentieth century. A rapid review
Authors: Migeot Virginie , Guihenneuc Jérémy , Ouazzani Houria El , Albouy Marion , Dupuis Antoine , Rabouan Sylvie 
Published: January 2022

Abstract
Background
In biomedical, life or environmental science research, two different strategies exist depending on the starting point of the researchers: “what makes us ill? “ or “what makes us healthy?”. Indeed, a risk-based strategy (RBS) attempts to minimize risk factors increasing the likelihood of developing a disease, while an asset-based strategy (ABS) attempts to promote and strengthen the factors that support good health and wellbeing. We provided an up-to-date overview of both research strategies in peer-reviewed scientific literature, in the fields of human health, animal and plant health and ecosystem health, to fit with the One Health framework. More particularly, we focused on human health by studying publications related to the COVID-19 at the beginning of the pandemic.

Design
A rapid review of research science literature was carried out to identify in the PubMed/MEDLINE database the proportion of peer-reviewed articles adopting either a RBS or an ABS, in the main global environment fields from January 01, 1900 to December 31, 2019 and, related to COVID-19, from December 1, 2019 to May 31, 2020.

Results
The number of published articles resulting from our search was 1,957,905, including 91.3% with an RBS and 8.7% with an ABS. When examining each field, we found that only 10.5% of human health articles deal with ABS, 5.5% for animal health, 2.2% for ecosystem health, 1.0% for plant health and 2.7% for environmental media. We noted that articles adopting both strategies were published in all health fields. Among the articles concerning COVID-19, 5,854 (55.9%), 542 articles (5.2%) adopted RBS and ABS, respectively, while 4069 (38.9%) simultaneously presenting both strategies.

Conclusion
Our results have allowed us to take stock of the biomedical research strategies prioritized during the twentieth century. It seems highly likely that the two strategies we have analyzed can now be chosen in such a way as to promote a balance in public health measures, at every level to guide One Health interventions aimed at helping people, animals, and plants to lead healthier lives.
Exosomes derived from platelet-rich plasma administration in site mediate cartilage protection in subtalar osteoarthritis
Authors: Zhang Yu , Wang Xiaowei , Chen Jian , Qian Dingfei , Gao Peng , Qin Tao , Jiang Tao , Yi Jiang , Xu Tao , Huang Yifan , Wang Qian , Zhou Zheng , Bao Tianyi , Zhao Xuan , Liu Hao , Zheng Ziyang , Fan Jin , Zhao Shujie , Li Qingqing , Yin Guoyong 
Published: January 2022

AbstractSubtalar osteoarthritis (STOA) is often secondary to chronic ankle sprains, which seriously affects the quality of life of patients. Due to its etiology and pathogenesis was not studied equivocally yet, there is currently a lack of effective conservative treatments. Although they have been used for tissue repair, platelet-rich plasma-derived exosomes (PRP-Exo) have the disadvantage of low retention and short-lived therapeutic effects. This study aimed to determine whether incorporation of PRP-Exo in thermosensitive hydrogel (Gel) increased their retention in the joint and thereby playing a therapeutic role on STOA due to chronic mechanical instability established by transecting lateral ligaments (anterior talofibular ligament (ATFL)/calcaneal fibular ligament (CFL)). PRP-Exo incorporated Gel (Exo-Gel) system, composed of Poloxamer-407 and 188 mixture-based thermoresponsive hydrogel matrix in an optimal ratio, was determined by its release ability of Exo and rheology of Gel response to different temperature. The biological activity of Exo-Gel was evaluated in vitro, and the therapeutic effect of Exo-Gel on STOA was evaluated in vivo. Exo released from Exo-Gel continuously for 28 days could promote the proliferation and migration of mouse bone mesenchymal stem cells (mBMSCs) and chondrocytes, at the same time enhance the chondrogenic differentiation of mBMSCs, and inhibit inflammation-induced chondrocyte degeneration. In vivo experiments confirmed that Exo-Gel increased the local retention of Exo, inhibited the apoptosis and hypertrophy of chondrocytes, enhanced their proliferation, and potentially played the role in stem cell recruitment to delay the development of STOA. Thus, Delivery of PRP-Exo incorporated in thermosensitive Gel provides a novel approach of cell-free therapy and has therapeutic effect on STOA.
Graphical Abstract
pH-responsive hierarchical H2S-releasing nano-disinfectant with deep-penetrating and anti-inflammatory properties for synergistically enhanced eradication of bacterial biofilms and wound infection
Authors: Zhang Yue , Yue Tianxiang , Gu Wenting , Liu Aidi , Cheng Mengying , Zheng Hongyue , Bao Dandan , Li Fanzhu , Piao Ji-Gang 
Published: January 2022

AbstractBackgroundMethicillin-resistantStaphylococcus aureus(MRSA) biofilm-associated bacterial infection is the primary cause of nosocomial infection and has long been an ongoing threat to public health. MRSA biofilms are often resistant to multiple antimicrobial strategies, mainly due to the existence of a compact protective barrier; thus, protecting themselves from the innate immune system and antibiotic treatment via limited drug penetration.ResultsA hierarchically structured hydrogen sulfide (H2S)-releasing nano-disinfectant was presented, which was composed of a zinc sulfide (ZnS) core as a H2S generator and indocyanine green (ICG) as a photosensitizer. This nano-disinfectant (ICG-ZnS NPs) sensitively responded to the biofilm microenvironment and demonstrated efficient eradication of MRSA biofilms via a synergistic effect of Zn2+, gas molecule-mediated therapy, and hyperthermia. Physically boosted by released H2S and a near-infrared spectroscopy-induced hyperthermia effect, ICG-ZnS NPs destroyed the compactness of MRSA biofilms showing remarkable deep-penetration capability. Moreover, on-site generation of H2S gas adequately ameliorated excessive inflammation, suppressed secretion of inflammatory cytokines, and expedited angiogenesis, therefore markedly accelerating the in vivo healing process of cutaneous wounds infected with MRSA biofilms.ConclusionICG-ZnS NPs combined with NIR laser irradiation exhibited significant anti-biofilm activity in MRSA biofilms, can accelerate the healing process through deep-penetration and anti-inflammatory effectuation. The proposed strategy has great potential as an alternative to antibiotic treatment when combating multidrug-resistant bacterial biofilms.Graphical Abstract
Exploring the influencing factors of the pathologic complete response in estrogen receptor-positive, HER2-negative breast cancer after neoadjuvant chemotherapy: a retrospective study
Authors: Tang Lingfeng , Shu Xiujie , Tu Gang 
Published: January 2022

Abstract
Background
Pathological complete response (pCR) is the goal of neoadjuvant chemotherapy (NACT). We aimed to develop a nomogram to predict the probability of achieving pCR in estrogen receptor-positive (ER+), HER2-negative (HER2−) breast cancer patients.

Methods
A total of 273 ER+, HER2− breast cancer patients who received 4 cycles of thrice-weekly standard NACT in the First Affiliated Hospital of Chongqing Medical University were retrospectively enrolled. Univariate and multivariate logistic regression analyses were used to screen the predictive factors to develop the nomograms. The discrimination and calibration abilities were assessed by the C-index, receiver operating characteristic curve (AUC), and calibration plot.

Results
There were 28 patients (10.3%) with overall pCR, 38 patients (13.9%) with breast pCR after NACT. ER expression, PgR expression, the neutrophil-to-lymphocyte ratio (NLR) and the Ki-67 index were independent predictive factors for achieving overall pCR. These indicators had good discrimination and calibration ability (AUC 0.843). The nomogram for breast pCR was established based on ER expression, PgR expression, the NLR, and the Ki-67 index and showed great discriminatory ability, with an AUC of 0.810. The calibration curve showed that the predictive ability of the nomogram was a good fit to actual observations.

Conclusion
The nomograms exhibited a sufficient discriminatory ability for predicting pCR after NACT in ER+, HER2− breast cancer patients. Utilizing these nomograms will enable us to identify patients at high probability for pCR after NACT and provide a reference for preoperative adjuvant therapy.