bluuebunny/crossref_metadata_2025 huggingface dataset:
Mechanical Characteristics and Energy Dissipation Trends of Coal-Rock Combination System Samples with Different Inclination Angles under Uniaxial Compression
Authors: Wei Zhen , Yang Ke , He Xiang , Chi Xiaolou , Zhao Xinyuan , Zhang Jiqiang
Published: August 2021

Coal mines are composed of multiple complex rock strata with different mechanical characteristics and energy accumulation and release performances. This implies uneven energy distribution in the coal-rock combination system (CRCS). To explore the effect of the included angle between the loading direction and the coal-rock contact surface on the mechanical properties, crack propagation mode, and energy evolution characteristics of the CRCS, the uniaxial compression tests were carried out on the CRCS samples with zero and 30° inclination angles. The obtained mechanical properties and energy dissipation trends of the tested samples were similar to those of the pure (raw) coal and rock ones but strongly depended on the inclination angles. The impact energy index of the CRCS samples was smaller than those of the pure coal and pure rock samples, and its impact tendency was less pronounced. The deformation and failure of the CRCS samples occurred in the coal part, the rock part inhibiting the development and deformation of the coal. According to the deformation and failure characteristics of the CRCS, the coal support far away from the contact surface should be strengthened in engineering practice to avoid the rock mass failure caused by the expansion and evolution of cracks in the coal part. At a 30° inclination angle, the CRCS sample was tensioned at the coal-rock contact surface, and the original cracks and pores were gradually compacted under the stress component perpendicular to the contact surface. With an increase in the inclination angle, the difference between the total energy accumulated before the peak and the released energy after the peak was reduced, and the difference between the total energy accumulated before the peak and the dissipated energy increased gradually. CRCS samples with different inclinations exhibited three damage stages: initial damage, stable damage growth, and rapid damage growth. The results obtained are considered instrumental in rockburst preventing, monitoring, and early warning under different stress environments.
Effect of MiR‐210 on the Chemosensitivity of Breast Cancer by Regulating JAK‐STAT Signaling Pathway
Authors: Xing Zeyu , Wang Xin , Liu Jiaqi , Liu Gang , Zhang Menglu , Feng Kexin , Wang Xiang
Published: August 2021

The study is aimed at exploring the effect of microribonucleic acid‐ (miR‐) 210 on the chemosensitivity of breast cancer and its potential molecular mechanism. Cell Counting Kit‐8 (CCK‐8) was applied to detect the half maximal inhibitory concentration (IC50) of cisplatin (DDP) on cell, and quantitative polymerase chain reaction (qPCR) was carried out to measure the relative expression level of miR‐210. The IC50 value of DDP on cells was detected via CCK‐8 after downregulating the expression of miR‐210 in MCF‐7/DDP cells. Flow cytometry and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) confirmed the effect of themiR‐210 downregulation on the apoptosis of drug‐resistant MCF‐7/DDP cells. Besides, the impacts of the miR‐210 downregulation on apoptosis‐related proteins and Janus‐activated kinase‐ (JAK‐) signal transducer and activator of transcription (STAT) signaling pathway‐related proteins were examined by Western blotting. The interaction between miR‐210 and the target protein was detected through luciferase activity assay, qPCR, and Western blotting. Drug‐resistant MCF‐7/DDP cells had significantly stronger resistance to DDP and a remarkably higher expression level of miR‐210 than control parental MCF‐7 cells (p < 0.05). After the downregulation of the miR‐210 expression, MCF‐7/DDP cells had markedly reduced resistance but obviously increased sensitivity to DDP (p < 0.05). MiR‐210 downregulation increased the apoptosis of MCF‐7/DDP cells (p < 0.05). In addition, after miR‐210 was knocked down, the expression level of b‐cell lymphoma 2 (Bcl‐2) was decreased, while the expression levels of Bcl‐2‐associated X protein (Bax) and cysteinyl aspartate‐specific proteinase‐3 (caspase‐3) were increased. Besides, miR‐210 was able to suppress the expression of protein inhibitor of the activated STAT 4 (PIAS4) gene by directly targeting its 3 ′ untranslated region (3 ′UTR). The expression of miR‐210 has a correlation with chemoresistance of breast cancer MCF‐7 cells. MiR‐210 regulates the JAK‐STAT signal transduction pathway by targeting PIAS4, thus exerting an effect on breast cancer chemosensitivity.
[Retracted] Process Development for Edible Film Preparation Using Avocado Seed Starch: Response Surface Modeling and Analysis for Water‐Vapor Permeability
Authors: Ramesh R. , Palanivel Hemalatha , Venkatesa Prabhu S. , Tizazu Belachew Zegale , Woldesemayat Adugna Abdi
Published: August 2021

Starch‐based edible films are gaining huge interest in food packaging industries. In the present work, avocado seed starch (ASS) was extracted and used to develop an edible film. The influence of four important process factors, starch, agar, sorbitol, and Tween‐20, was studied on one of the important barrier properties, water‐vapor permeability (WP), of developed edible film. The three‐level RSM design with Box–Behnken approach was carried out to investigate the film property, WP. ASS‐based edible films were prepared by the casting method. The results revealed that the increment in the contents of Tween‐20 and sorbitol reduces the WP of the film. Using the response surface analysis, the effect of the aforementioned factors was analyzed; they showed significant impact on WP. To predict the influence of the selected process parameters, a second‐order polynomial equation was constructed. Additionally, Pareto analysis of variance was employed over the obtained results to investigate the significance of the developed process model.
Integrated Analysis of miRNA-mRNA Regulatory Networks Associated with Osteonecrosis of the Femoral Head
Authors: Yu Liwei , Yao Tengfei , Jiang Zhoulei , Xu Tong
Published: August 2021

Osteonecrosis of the femoral head (ONFH) accounts for as many as 18% of total hip arthroplasties. Knowledge of genetic changes and molecular abnormalities could help identify individuals considered to be at a higher risk of developing ONFH. In this study, we sought to identify differentially expressed miRNAs (DEmiRs) and genes (DEGs) associated with ONFH by integrated bioinformatics analyses as well as to construct the miRNA-mRNA regulatory network involving in the pathogenesis of ONFH. We performed differential expression analysis using a gene expression profile GSE123568 and a miRNA expression profile GSE89587 deposited in the Gene Expression Omnibus and identified 47 DEmiRs (24 upregulated miRNAs and 23 downregulated miRNAs) and 529 DEGs (218 upregulated genes and 311 downregulated genes). Gene Ontology enrichment analyses of DEGs suggested that DEGs were significantly enriched in neutrophil activation, cytosol, and ubiquitin-protein transferase activity. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses of DEGs revealed that DEGs were significantly enriched in transcriptional misregulation in cancer. DEGs-based miRNA-mRNA regulatory networks were obtained by searching miRNA-mRNA prediction databases, TargetScan, miTarBase, miRMap, miRDB, and miRanda databases. Then, overlapped miRNAs were selected between these putative miRNAs and DEmiRs between ONFH and non-ONFH, and pairs of the DEmiR-DEG regulatory network were finally depicted. There were 12 nodes and 64 interactions for upDEmiR-downDEG regulatory networks and 6 nodes and 16 interactions for downDEmiR-upDEG regulatory networks. Using the STRING database, we established a protein-protein interaction network based on the overlapped DEGs between ONFH and non-ONFH. C5AR1, CDC27, CDC34, KAT2B, CPPED1, TFDP1, and MX2 were identified as the hub genes. The present study characterizes the miRNA profile, gene profile, and miRNA-mRNA regulatory network in ONFH, which may contribute to the interpretation of the pathogenesis of ONFH and the identification of novel biomarkers and therapeutic targets for ONFH.
Big Data Integration Method of Mathematical Modeling and Manufacturing System Based on Fog Calculation
Authors: Chen Xin
Published: August 2021

Using big data to promote economic development, improve social governance, and improve service and regulatory capabilities is becoming a trend. However, the current cloud computing for data processing has been difficult to meet the demand, and the server pressure has increased dramatically, so people pay special attention to the big data integration of fog computing. In order to make the application of big data meet people’s needs, we have established relevant mathematical models based on fog calculation, made system big data integration, collected relevant data, designed experiments, and obtained relevant research data by reviewing relevant literature and interviewing professionals. The research shows that big data integration using fog computing modeling has the characteristics of fast response and stable function. Compared with cloud computing and previous computer algorithms, big data integration has obvious advantages, and the computing speed is nearly 20% faster than cloud computing and about 35% higher than other computing methods. This shows that big data integration built by fog computing can have a huge impact on people’s lives.
MTAP Deficiency–Induced Metabolic Reprogramming Creates a Vulnerability to Cotargeting De Novo Purine Synthesis and Glycolysis in Pancreatic Cancer
Authors: Hu Qiangsheng , Qin Yi , Ji Shunrong , Shi Xiuhui , Dai Weixing , Fan Guixiong , Li Shuo , Xu Wenyan , Liu Wensheng , Liu Mengqi , Zhang Zheng , Ye Zeng , Zhou Zhijun , Yang Jingxuan , Zhuo Qifeng , Yu Xianjun , Li Min , Xu Xiaowu
Published: August 2021

Methylthioadenosine phosphorylase (MTAP) is a key enzyme associated with the salvage of methionine and adenine that is deficient in 20% to 30% of pancreatic cancer. Our previous study revealed that MTAP deficiency indicates a poor prognosis for patients with pancreatic ductal adenocarcinoma (PDAC). In this study, bioinformatics analysis of The Cancer Genome Atlas (TCGA) data indicated that PDACs with MTAP deficiency display a signature of elevated glycolysis. Metabolomics studies showed that that MTAP deletion–mediated metabolic reprogramming enhanced glycolysis and de novo purine synthesis in pancreatic cancer cells. Western blot analysis revealed that MTAP knockout stabilized hypoxia-inducible factor 1α (HIF1α) protein via posttranslational phosphorylation. RIO kinase 1 (RIOK1), a downstream kinase upregulated in MTAP-deficient cells, interacted with and phosphorylated HIF1α to regulate its stability. In vitro experiments demonstrated that the glycolysis inhibitor 2-deoxy-d-glucose (2-DG) and the de novo purine synthesis inhibitor l-alanosine synergized to kill MTAP-deficient pancreatic cancer cells. Collectively, these results reveal that MTAP deficiency drives pancreatic cancer progression by inducing metabolic reprogramming, providing a novel target and therapeutic strategy for treating MTAP-deficient disease.

Significance:

This study demonstrates that MTAP status impacts glucose and purine metabolism, thus identifying multiple novel treatment options against MTAP-deficient pancreatic cancer.
Radiation-Induced Phosphorylation of a Prion-Like Domain Regulates Transformation by FUS-CHOP
Authors: Chen Mark , Foster Joseph P. , Lock Ian C. , Leisenring Nathan H. , Daniel Andrea R. , Floyd Warren , Xu Eric , Davis Ian J. , Kirsch David G.
Published: August 2021

Chromosomal translocations generate oncogenic fusion proteins in approximately one-third of sarcomas, but how these proteins promote tumorigenesis is not well understood. Interestingly, some translocation-driven cancers exhibit dramatic clinical responses to therapy, such as radiotherapy, although the precise mechanism has not been elucidated. Here we reveal a molecular mechanism by which the fusion oncoprotein FUS-CHOP promotes tumor maintenance that also explains the remarkable sensitivity of myxoid liposarcomas to radiation therapy. FUS-CHOP interacted with chromatin remodeling complexes to regulate sarcoma cell proliferation. One of these chromatin remodelers, SNF2H, colocalized with FUS-CHOP genome-wide at active enhancers. Following ionizing radiation, DNA damage response kinases phosphorylated the prion-like domain of FUS-CHOP to impede these protein–protein interactions, which are required for transformation. Therefore, the DNA damage response after irradiation disrupted oncogenic targeting of chromatin remodelers required for FUS-CHOP–driven sarcomagenesis. This mechanism of disruption links phosphorylation of the prion-like domain of an oncogenic fusion protein to DNA damage after ionizing radiation and reveals that a dependence on oncogenic chromatin remodeling underlies sensitivity to radiation therapy in myxoid liposarcoma.

Significance:

Prion-like domains, which are frequently translocated in cancers as oncogenic fusion proteins that drive global epigenetic changes, confer sensitivity to radiation via disruption of oncogenic interactions.
Stem Cell Factor SOX2 Confers Ferroptosis Resistance in Lung Cancer via Upregulation of SLC7A11
Authors: Wang Xinbo , Chen Yueqing , Wang Xudong , Tian Hongling , Wang Yanjin , Jin Jiali , Shan Zezhi , Liu Yu'e , Cai Zhenyu , Tong Xinyuan , Luan Yi , Tan Xiao , Luan Bing , Ge Xin , Ji Hongbin , Jiang Xuejun , Wang Ping
Published: August 2021

Ferroptosis is a lipid peroxidation-dependent cell death caused by metabolic dysfunction. Ferroptosis-associated enzymes are promising therapeutic targets for cancer treatment. However, such therapeutic strategies show limited efficacy due to drug resistance and other largely unknown underlying mechanisms. Here we report that cystine transporter SLC7A11 is upregulated in lung cancer stem-like cells (CSLC) and can be activated by stem cell transcriptional factor SOX2. Mutation of SOX2 binding site in SLC7A11 promoter reduced SLC7A11 expression and increased sensitivity to ferroptosis in cancer cells. Oxidation at Cys265 of SOX2 inhibited its activity and decreased the self-renewal capacity of CSLCs. Moreover, tumors with high SOX2 expression were more resistant to ferroptosis, and SLC7A11 expression was positively correlated with SOX2 in both mouse and human lung cancer tissue. Together, our study provides a mechanism by which cancer cells evade ferroptosis and suggests that oxidation of SOX2 can be a potential therapeutic target for cancer treatment.

Significance:

This study uncovers a SOX2–SLC7A11 regulatory axis that confers resistance to ferroptosis in lung cancer stem-like cells.
Testicular Cancer: Biology to Bedside
Authors: King Jennifer , Adra Nabil , Einhorn Lawrence H.
Published: August 2021

Testicular cancer is the first solid tumor with a remarkably high cure rate. This success was only made possible through collaborative efforts of basic and clinical research. Most patients with distant metastases can be cured. However, the majority of these patients are diagnosed at a young age, leaving many decades for the development of treatment-related complications. This has magnified the importance of research into survivorship issues after exposure to platinum-based chemotherapy. This research, along with research into newer biomarkers that will aid in the diagnosis and surveillance of patients and survivors of testicular cancer, will continue to advance the field and provide new opportunities for these patients. There also remains the need for further therapeutic options for patients who unfortunately do not respond to standard treatment regimens and ultimately die from this disease, including a cohort of patients with late relapses and platinum-refractory disease. Here we discuss the advancements in management that led to a highly curable malignancy, while highlighting difficult situations still left to solve as well as emerging research into novel biomarkers.
TargetingHER2Exon 20 Insertion–Mutant Lung Adenocarcinoma with a Novel Tyrosine Kinase Inhibitor Mobocertinib
Authors: Han Han , Li Shuai , Chen Ting , Fitzgerald Michael , Liu Shengwu , Peng Chengwei , Tang Kwan Ho , Cao Shougen , Chouitar Johara , Wu Jiansheng , Peng David , Deng Jiehui , Gao Zhendong , Baker Theresa E. , Li Fei , Zhang Hua , Pan Yuanwang , Ding Hailin , Hu Hai , Pyon Val , Thakurdin Cassandra , Papadopoulos Eleni , Tang Sittinon , Gonzalvez Francois , Chen Haiquan , Rivera Victor M. , Brake Rachael , Vincent Sylvie , Wong Kwok-Kin
Published: August 2021

No targeted treatments are currently approved for HER2 exon 20 insertion–mutant lung adenocarcinoma patients. Mobocertinib (TAK-788) is a potent irreversible tyrosine kinase inhibitor (TKI) designed to target human epidermal growth factor receptor 2 (HER2/ERBB2) exon 20 insertion mutations. However, the function of mobocertinib on HER2 exon 20 insertion–mutant lung cancer is still unclear. Here we conducted systematic characterization of preclinical models to understand the activity profile of mobocertinib against HER2 exon 20 insertions. In HER2 exon 20 insertion–mutant cell lines, the IC50 of mobocertinib was higher than poziotinib and comparable with or slightly lower than afatinib, neratinib, and pyrotinib. Mobocertinib had the lowest HER2 exon 20 insertion IC50/wild-type (WT) EGFR IC50 ratio, indicating that mobocertinib displayed the best selectivity profile in these models. Also, mobocertinib showed strong inhibitory activity in HER2 exon 20YVMA allograft and patient-derived xenograft models. In genetically engineered mouse models, HER2 exon 20G776>VC lung tumors exhibited a sustained complete response to mobocertinib, whereas HER2 exon 20YVMA tumors showed only partial and transient response. Combined treatment with a second antibody–drug conjugate (ADC) against HER2, ado-trastuzumab emtansine (T-DM1), synergized with mobocertinib in HER2 exon 20YVMA tumors. In addition to the tumor cell autonomous effect, sustained tumor growth control derived from M1 macrophage infiltration and CD4+ T-cell activation. These findings support the ongoing clinical development of mobocertinib (NCT02716116) and provide a rationale for future clinical evaluation of T-DM1 combinational therapy in HER2 exon 20YVMA insertion–mutant lung adenocarcinoma patients.

Significance:

This study elucidates the potent inhibitory activity of mobocertinib against HER2 exon 20 insertion–mutant lung cancer and the synergic effect of combined mobocertinib and T-DM1, providing a strong rationale for clinical investigation.
Preclinical and Clinical Characterization of Fibroblast-derived Neuregulin-1 on Trastuzumab and Pertuzumab Activity in HER2-positive Breast Cancer
Authors: Guardia Cristina , Bianchini Giampaolo , Arpí-LLucià Oriol , Menendez Silvia , Casadevall David , Galbardi Barbara , Dugo Matteo , Servitja Sonia , Montero Juan Carlos , Soria-Jiménez Luis , Sabbaghi MohammadA , Peña Raul , Madoz-Gúrpide Juan , Lloveras Belen , Lluch Ana , Eroles Pilar , Arribas Joaquin , Pandiella Atanasio , Gianni Luca , Rojo Federico , Rovira Ana , Albanell Joan
Published: August 2021

Purpose:

To characterize expression of neuregulin-1 (NRG1), an HER3 ligand, in HER2-positive breast cancer and its relation with the efficacy of trastuzumab with or without pertuzumab.

Experimental Design:

Characterization of NRG1 expression in tumor cell lines, in tumor specimens, and in cancer-associated fibroblasts (CAFs). Patient-derived CAFs were used to investigate NRG1 impact on the activity of trastuzumab with or without pertuzumab in HER2-positive breast cancer cells. The relationship between NRG1 expression and pathologic response to anti-HER2–based neoadjuvant therapy was assessed in a retrospective patient cohort and in the NeoSphere trial.

Results:

NRG1 was expressed in HER2-positive breast cancer–derived fibroblasts at significantly higher levels than in cancer cells. NRG1 and the conditioned media (CM) from CAFs phosphorylated HER3 and AKT in cancer cells and mediated trastuzumab resistance. Stable genetic depletion of NRG1 from CAFs overcame trastuzumab resistance. Pertuzumab effectively suppressed trastuzumab resistance mediated by either NRG1 or CAF's CM. NRG1 engaged an epithelial-to-mesenchymal transition that was prevented by trastuzumab and pertuzumab. In clinical samples, stromal and/or tumor cell expression of NRG1 determined by immunohistochemistry was uncommon (13.2%) yet significantly linked with residual disease following trastuzumab-based neoadjuvant therapy. In the NeoSphere trial, the magnitude of the difference of pathologic complete response rates favoring the pertuzumab arm was higher in the NRG1-high group.

Conclusions:

CAF-derived NRG1 mediates trastuzumab resistance through HER3/AKT, which might be reverted by pertuzumab. In patients with HER2-positive breast cancer, high expression of NRG1 was associated to poor response to trastuzumab, but not in combination with pertuzumab.
Main Physical Features, Echocardiographic and Renal Ultrasonographic Findings of Turner Syndrome in 107 Pediatric Patients
Authors: Akalın Akçahan , Ertuğrul İlker , Şimşek-Kiper Pelin Özlem , Utine Gülen Eda , Boduroğlu Koray
Published: August 2021

Turner syndrome (TS) is one of the most common malformation syndromes in females. A total number of 107 TS patients, diagnosed between 2000 and 2018, were evaluated for their phenotypic features, and cardiac and renal findings. The mean age of patients at admission was 10.08 ± 4.9 years (range, newborn to 18 years). Four different karyotype groups were encountered, and the most common findings in all groups were short stature, followed by cubitus valgus. Echocardiographic findings of 85 patients were available among which 63 (n = 63/85, 74.1%) were found to be normal. The most common cardiac anomaly was left ventricular outflow tract/aortic arch pathology detected in 9 patients (n = 9/22, 40.9%). Renal malformations were detected in 15 patients (n = 15/84, 17.9%) by renal ultrasonography, and horseshoe kidney was the most common renal malformation, followed by left multicystic dysplastic kidney. There was no significant difference in the frequency of renal malformation and cardiac anomalies among the 4different karyotype groups (χ2 exact test, p > 0.05). Compared with the literature, the frequency of renal anomalies was detected at a lower rate. Karyotype analysis should be carried out in all female patients with short stature, even if there are no associated phenotypic findings suggestive of TS. Since cardiac anomalies are frequently seen in TS patients and they represent a common cause of mortality, echocardiography should be carried out as soon as the definite diagnosis is established. Renal anomalies may be less frequent than cardiac anomalies; however, evaluation of TS patients with renal ultrasonography should be done at the time of diagnosis. Although renal ultrasonography can be used as the initial renal screening in TS patients, it may underestimate the frequency of renal malformation; hence, further management may be required.
Cytoreductive Thoracic Surgery Combined with Hyperthermic Chemoperfusion for Pleural Malignancies: A Single-Center Experience
Authors: Klotz Laura V. , Gruenewald Christiane , Bulut Elena L. , Eichhorn Florian , Thomas Michael , Shah Rajiv , Kriegsmann Mark , Schmidt Werner , Kofler Othmar , Winter Hauke , Eichhorn Martin E.
Published: August 2021

Background: Lung-sparing cytoreductive surgery by extended pleurectomy and decortication (EPD) in combination with hyperthermic intrathoracic chemoperfusion (HITOC) forms a promising treatment strategy for malignant pleural mesothelioma and recurrent pleural thymic malignancies. Objectives: The objective of this study was to scrutinize the surgical procedure and perioperative patient management with emphasis on perioperative morbidity and local tumor control. Methods: In 2014, a standardized EPD and HITOC procedure was implemented at the Thoraxklinik Heidelberg. This retrospective analysis included clinical data of consecutive patients with pleural mesothelioma and pleural metastasized malignancies treated by EPD and HITOC. The surgical procedure, perioperative management, lung function data, and progression-free survival (PFS) were analyzed. Results: In the time range between April 2, 2014 and July 2018, 76 patients with pleural malignancies have been treated with EPD and HITOC, and were analyzed retrospectively. It included 61 patients with pleural mesothelioma and 15 patients with pleural metastases of thymic malignancies (12), non-small cell lung cancer (1), colorectal carcinoma (1), and sarcoma (1). Perioperative morbidity following EPD and HITOC treatments represented 23.7% of overall malignancies, while 30- and 90-day mortality were 0 and 1.3%, respectively. Median PFS lasted 18.4 months for mesothelioma and 72.2 months for thymic malignancies. Conclusion: Combining EPD with HITOC can be performed in patients with either pleural mesothelioma or pleural metastases resulting in low perioperative morbidity and mortality as well as remarkable local tumor control.
Efficiency of Noninvasive Prenatal Testing for Sex Chromosome Aneuploidies
Authors: Shi Yunfang , Li Xiaozhou , Ju Duan , Li Yan , Zhang Xiuling , Zhang Ying
Published: August 2021

Objective: This study was designed to investigate the efficiency of noninvasive prenatal testing (NIPT) for screening fetal sex chromosome aneuploidies (SCAs) through sequencing of cell-free DNA in maternal plasma. Methods: This is a retrospective study on the positive NIPT results for SCAs collected from our hospital between January 2012 and December 2018. Samples with positive NIPT results for SCAs were then confirmed by prenatal or postnatal karyotyping analysis. Results: After cytogenetic analysis, abnormal karyotypes were confirmed in 104 cases and the overall positive predictive value (PPV) of NIPT for SCAs was 43.40% (102/235). The most frequently detected karyotypes included 47,XXY (n = 42), 47,XXX (n = 20), 47,XYY (n = 16), and 45,X (n = 2). Meanwhile, 10 cases were confirmed with mosaic karyotype 45,X/46,XX and 14 cases with numerical or structural chromosome abnormalities, including a double trisomy 48,XXX,+18. Cytogenetic results from the other 131 cases showed normal XX or XY, which were discordant with NIPT results. Upon analysis of parental karyotypes, 29 (12.34%) showed false positivity in NIPT results that were caused by maternal sex chromosome abnormalities. Conclusion: NIPT is an effective screening tool for SCA with a PPV of 43.40%. Maternal karyotype abnormalities occurred in 12.34% of the cases with abnormal NIPT. Diagnostic testing of the fetus and the mother are recommended.
Neoadjuvant Therapy of Cyclin-Dependent Kinase 4/6 Inhibitors Combined with Endocrine Therapy in HR+/HER2− Breast Cancer: A Systematic Review and Meta-Analysis
Authors: Hong Kai , Yao Lingli , Sheng Xianneng , Ye Dan , Guo Yu
Published: August 2021

Background: Cyclin-dependent kinase (CDK) 4/6 inhibitors have been advocated for adjuvant therapy of metastatic hormone receptor (HR)+/human epidermal growth factor receptor 2 (HER2)− breast cancer (BC). However, the efficiency of adding CDK 4/6 inhibitors to neoadjuvant therapy was not unequivocal. Objective: The aim of the study was to evaluate the efficiency and toxicity of neoadjuvant CDK 4/6 inhibitors + endocrine therapy (ET) versus neoadjuvant endocrine monotherapy or standard neoadjuvant chemotherapy in HR+/HER2− BC. Method: We searched PubMed, the Cochrane Library, Web of Science, and Embase online databases for randomized controlled trials and single-arm studies written in English until April 2021. Results: Five studies comparing CDK 4/6 inhibitors + ET as neoadjuvant treatments to ET alone and 2 studies comparing neoadjuvant CDK 4/6 inhibitors + ET to neoadjuvant chemotherapy were analysed. Neoadjuvant CDK 4/6 inhibitors + ET improved the rate of complete cell cycle arrest (CCCA: central Ki67 < 2.7%, odds ratio [OR] = 7.91, 95% confidence interval [CI] = 4.81–13.03, p < 0.001), increased the risk of adverse events (AEs; especially ≥3 AEs; AEs of all grades: OR = 9.10, 95% CI = 2.39–34.58, p = 0.001; AEs ≥3: OR = 12.24, 95% CI = 4.17–35.88, p < 0.001), led to no significant differences in pathological complete response (pCR) in patients with BC (OR = 0.34, 95% CI = 0.04–2.85, p = 0.318) compared to endocrine monotherapy. Moreover, subgroup analysis showed that the 3 types of CDK 4/6 inhibitors all improved the rate of CCCA (ribociclib: OR = 10.31, 95% CI = 3.59–29.61, p < 0.001; palbociclib: OR = 7.39, 95% CI = 1.26–43.40, p = 0.027, and abemaciclib: OR = 8.28, 95% CI = 3.41–20.11, p < 0.001). Compared to neoadjuvant chemotherapy, neoadjuvant CDK 4/6 inhibitors plus ET decreased the risk of AEs ≥3 (OR = 0.50, 95% CI = 0.29–0.87, p = 0.015) and showed similar ability to reach pCR (OR = 0.50, 95% CI = 0.12–2.07, p = 0.342) and reduce the residual cancer burden (RCB, RCB 0–1: OR = 0.47, 95% CI = 0.18–1.22, p = 0.121; RCB 2–3: OR = 2.30, 95% CI = 0.89–5.91, p = 0.084). Conclusions: The results suggested that combination therapy had increased efficacy and toxicity compared to endocrine monotherapy and showed similar efficacy to and better safety than neoadjuvant chemotherapy.
Impact of nonpharmaceutical strategies on trends of COVID-19 in São Paulo State
Authors: Fortaleza Cristiane Ravagnani , Vilches Thomas Nogueira , Almeida Gabriel Berg de , Ferreira Claudia Pio , Souza Lenice do Rosário de , Fortaleza Carlos Magno Castelo Branco
Published: August 2021

Interrupted time series analyses were conducted to measure the impact of social distancing policies (instituted on March 22, 2020) and of subsequent mandatory masking in the community (instituted on May 4, 2020) on the incidence and effective reproductive number of COVID-19 in São Paulo State, Brazil. Overall, the impact of social distancing both on incidence and Rt was greater than the incremental effect of mandatory masking. Those findings may reflect either a small impact of face masking or the loosening of social distancing after mandatory use of masks.
Vesseg
Authors: Murray Jacob M. , Pfeffer Phillip , Seifert Robert , Hermann Alexander , Handke Jessica , Kummer Laura , Janssen Henrike , Weigand Markus A. , Schlemmer Heinz-Peter , Larmann Jan , Kleesiek Jens
Published: August 2021

Objective:

Manual plaque segmentation in microscopy images is a time-consuming process in atherosclerosis research and potentially subject to unacceptable user-to-user variability and observer bias. We address this by releasing Vesseg a tool that includes state-of-the-art deep learning models for atherosclerotic plaque segmentation.

Approach and Results:

Vesseg is a containerized, extensible, open-source, and user-oriented tool. It includes 2 models, trained and tested on 1089 hematoxylin-eosin stained mouse model atherosclerotic brachiocephalic artery sections. The models were compared to 3 human raters. Vesseg can be accessed at
https://vesseg
.online or downloaded. The models show mean Soerensen-Dice scores of 0.91±0.15 for plaque and 0.97±0.08 for lumen pixels. The mean accuracy is 0.98±0.05. Vesseg is already in active use, generating time savings of >10 minutes per slide.

Conclusions:

Vesseg brings state-of-the-art deep learning methods to atherosclerosis research, providing drastic time savings, while allowing for continuous improvement of models and the underlying pipeline.
Innovative Managed Care May Be Related to Improved Prognosis for Acute Myocardial Infarction Survivors
Authors: Jankowski Piotr , Topór-Mądry Roman , Gąsior Mariusz , Cegłowska Urszula , Eysymontt Zbigniew , Gierlotka Marek , Wita Krystian , Legutko Jacek , Dudek Dariusz , Sierpiński Radosław , Pinkas Jarosław , Kaźmierczak Jarosław , Witkowski Adam , Szumowski Łukasz
Published: August 2021

Background:

Mortality following discharge in myocardial infarction survivors remains high. Therefore, we compared outcomes in myocardial infarction survivors participating and not participating in a novel, nationwide managed care program for myocardial infarction survivors in Poland.

Methods:

We used public databases. We included all patients hospitalized due to acute myocardial infarction in Poland between October 1, 2017 and December 31, 2018. We excluded from the analysis all patients aged <18 years as well as those who died during hospitalization or within 10 days following discharge from hospital. All patients were prospectively followed. The primary end point was defined as death from any cause.

Results:

The mean follow-up was 324.8±140.5 days (78 034.1 patient-years; 340.0±131.7 days in those who did not die during the observation). Participation in the managed care program was related to higher odds ratio of participating in cardiac rehabilitation (4.67 [95% CI, 4.44–4.88]), consultation with a cardiologist (7.32 [6.83–7.84]), implantable cardioverter-defibrillator (1.40 [1.22–1.61]), and cardiac resynchronization therapy with cardioverter-defibrillator implantation (1.57 [1.22–2.03]) but lower odds of emergency (0.88 [0.79–0.98]) and nonemergency percutaneous coronary intervention (0.88 [0.83–0.93]) and coronary artery bypass grafting (0.82 [0.71–0.94]) during the follow-up. One-year all-cause mortality was 4.4% among the program participants and 6.0% in matched nonparticipants. The end point consisting of all-cause death, myocardial infarction, or stroke occurred in 10.6% and 12.0% (
P
<0.01) of participants and nonparticipants respectively, whereas all-cause death or hospitalization for cardiovascular reasons in 42.2% and 47.9% (
P
<0.001) among participants and nonparticipants, respectively. The difference in outcomes between patients participating and not participating in the managed care program could be explained by improved access to cardiac rehabilitation, cardiac care, and cardiac procedures.

Conclusions:

Managed care following myocardial infarction may be related to improved prognosis as it may facilitate access to cardiac rehabilitation and may provide a higher standard of outpatient cardiac care.
New Characteristics and Hedonic Price Index Numbers
Authors: Crawford Ian , Neary J. Peter
Published: August 2021

Changes in product characteristics on the extensive margin (the addition of new features and the removal of old ones) are an important and hitherto neglected dimension of quality change. Standard techniques for adjusting price indices for new goods cannot handle such changes satisfactorily, and this leads to an economically and statistically significant bias in the measurement of prices and real output. We combine insights from the theories of exact index numbers and demand for characteristics to develop a new method for incorporating changes on the extensive characteristic margin. Applied to U.K. data on new car sales, our method leads to revisions in estimated inflation rates for this commodity group that are both plausible and quantitatively important.
On the Estimation of Cross-Firm Productivity Spillovers with an Application to FDI
Authors: Malikov Emir , Zhao Shunan
Published: August 2021

We develop a novel methodology for the proxy variable identification of firm productivity in the presence of productivity-modifying learning and spillovers, which facilitates a unified internally consistent analysis of the spillover effects among firms. Contrary to the popular two-step empirical approach, ours does not postulate contradictory assumptions about firm productivity across the estimation steps. Instead, we explicitly accommodate cross-sectional dependence in productivity induced by spillovers, which facilitates identification of both the productivity and spillover effects simultaneously. We apply our model to study cross-firm spillovers in China's electric machinery manufacturing, with a particular focus on productivity effects of inbound FDI.
Benign Effects of Automation: New Evidence from Patent Texts
Authors: Mann Katja , Püttmann Lukas
Published: August 2021

We provide a new measure of automation based on patents and study its employment effects. Classifying all U.S. patents granted between 1976 and 2014 as automation or nonautomation patents, we document a strong rise in the number and share of automation patents. We link patents to their industries of use and to commuting zones. To estimate the effect of automation, we use an instrumental variables strategy that relies on innovations developed independently from U.S. labor market trends. We find that automation technology has a positive effect on employment in local labor markets, driven by job growth in the service sector.
Discrimination, Narratives, and Family History: An Experiment with Jordanian Host and Syrian Refugee Children
Authors: Barron Kai , Harmgart Heike , Huck Steffen , Schneider Sebastian O. , Sutter Matthias
Published: August 2021

We measure the prevalence of discrimination between Jordanian host and Syrian refugee children attending school in Jordan. Using a simple sharing experiment, we find only a small degree of out-group discrimination. However, Jordanian children with Palestinian roots do not discriminate at all, suggesting that a family history of refugee status can generate solidarity with new refugees. We also find that parents’ narratives about the refugee crisis are correlated with their children's degree of out-group discrimination, particularly among Syrian refugee children, suggesting that discriminatory preferences are being transmitted through parental attitudes.
Crisis and the Trajectory of Science: Evidence from the 2014 Ebola Outbreak
Authors: Fry Caroline Viola
Published: August 2021

When crises such as disease outbreaks occur in low-income countries, the global response can influence the output of researchers in the most affected locations. This paper investigates the impact of the 2014 West African Ebola epidemic on publication outcomes of endemic country scientists. Driven by collaborations with high-income country scientists in Ebola publications, endemic country scientists with relevant experience increase their publication output. However, the productivity of scientists without relevant experience falls, driving a reduction in non-Ebola publications. Any benefits arising from increased visibility during the epidemic does not appear to spill over to non-Ebola or Africa-led research in the long run.
The Speed of Justice
Authors: Kondylis Florence , Stein Mattea
Published: August 2021

Can procedural reforms improve judicial efficiency? And do improvements in judicial efficiency benefit firms? We combine the staggered rollout of a reform that required judges in Senegal to complete pretrials within four months with high-frequency caseload data and firm tax filings. The reform improved judicial efficiency, with no effect on quality. Firm monthly revenues drop by 8–11% upon entering pretrial and decline by on average 3.2–5.0% for every hundred days a case spends in pretrial. Survey results show firms are willing to pay higher legal fees to achieve postreform speed, suggesting positive benefits of the reform on firms.
Do We or Don’t We? Muslim Women Wearing the Hijab in the South African Work Environment
Authors: Carrim Nasima MH , Paruk Zeenat
Published: August 2021

This article examines the experiences of Muslim women who wear hijab in corporate South Africa. Muslim women from diverse organisations wearing hijab were interviewed. The study produced mixed results. While women who don the hijab were discriminated against in some organisations, in the majority of organisations religious pluralism is embraced. The results further indicate that although South Africa is a secular country, there are various pieces of legislation that protect employees from religious discrimination in the workplace. Employees who don the hijab at lower levels experienced more discrimination compared to those at higher levels. The study further revealed that donning the hijab for Muslim women is viewed from a holistic perspective which includes behaving appropriately and not attending social functions where their religious convictions are jeopardized. The results indicate that wearing the hijab does not impede their career advancement although it does have a negative impact when they attend job interviews in organisations other than their own.
Questioning Growth: Christianity, Development, and the Perils of Wealth in Southern Ethiopia
Authors: Sommerschuh Julian
Published: August 2021

Research on the economic effects of African Christianity has mainly focused on Pentecostalism. The dominant opinion of this literature is that Pentecostalism stimulates economic activity and supports economic development. This article looks beyond Pentecostalism by discussing the case of an Evangelical church in southern Ethiopia. Covering a period of two decades, I trace a shift in the relation between Evangelicalism and local aspirations for economic development. Initially seen as a means to achieve religious ends, the pursuit of development has recently been problematized as a source of social and spiritual ills. The church now discourages excessive participation in the commercial economy, and dedicated Evangelicals relinquish economic opportunities that they fear could lead them into sin. This shows that while Christianity can stimulate processes of economic development it can also constrain these, motivating people to renounce the quest for wealth in favour of other values.
The Vetting Impasse: The ‘Churches Law’ and Kenya’s Religious Regulation Debate
Authors: Gez Yonatan N.
Published: August 2021

Over the last decade Kenya has been seeing a lively debate over the regulation of its ever-expanding religious market and demands for a new ‘Churches Law’. Tales of hypocritical abuse of power and of emerging cults coalesced with security concerns regarding religious extremism, leading to the proposal to tighten regulatory control over the religious market, which expanded rapidly since the 1990s. Despite widespread recognition of the problem, new legislative steps have failed so far, notably even leading to a controversial 2014 moratorium on the registration of new religious denominations. This article analyzes this legislative impasse and offers an explanation in terms of the ambivalent yet symbiotic relations between religion and state in Kenya.
Hornera currieae n. sp. (Cyclostomatida: Horneridae): a new bathyal cyclostome bryozoan with reproductively induced skeletal plasticity
Authors: BATSON PETER B. , TAMBERG YUTA , GORDON DENNIS P. , NEGRINI MARIANNE , SMITH ABIGAIL M.
Published: August 2021

Here we describe a new hornerid, Hornera currieae n. sp. (Bryozoa: Cyclostomatida) from bathyal depths across the New Zealand region. Colonies are irregular, finely branched fans attaining ~40 mm or more in height. Key characters include: (1) thick, semi-hyaline porcellanous skeleton; (2) loss or reduction of nervi (longitudinal striae) away from growing tips; (3) sparse, threadlike cancelli; and (4) small (61–87 µm), widely spaced autozooidal apertures. Diagnostic hornerid traits possessed by H. currieae n. sp. include vertical ancestrular tube, periancestrular budding of daughter zooids, and skeletal ultrastructure dominated by hexagonal semi-nacre grading to pseudofoliated fabric. The abfrontal incubation chamber develops from a cryptic tube arising from the frontally positioned aperture of the fertile zooid. We used SEM, micro-CT and electron backscatter diffractometry (EBSD) to investigate the ultrastructure and internal architecture of H. currieae n. sp. EBSD reveals that crystalline c-axes of laminated crystallites are perpendicular to skeletal walls. Threadlike cancelli, which traverse secondary calcification, connect autozooidal chambers to the colony-wide hypostegal cavity. Micro-CT reveals that abfrontal cancelli usually bend proximally towards the base, but turn distally towards reproductively active regions of the colony in synchrony with gonozooid development. The zone of affected cancelli extends for 4–7 branch internodes below the gonozooid. We assessed whether skeletal ultrastructure was similarly affected, but neither cancellus direction, nor gonozooid proximity, were predictive of the crystallite imbrication direction. We hypothesise that (1) hornerid cancelli are active conduits for colonial metabolite transport and (2) that changes in gradients of metabolites and/or reproductive morphogens within the hypostegal cavity affect cancellus morphogenesis. Potentially, H. currieae n. sp. skeletons may preserve a record of intra-colony metabolite translocation dynamics over time.
A new species of Lonchodryinus (Hymenoptera, Dryinidae) from Upper Eocene Baltic amber
Authors: OLMI MASSIMO , VASILENKO DMITRY V. , CAPRADOSSI LEONARDO , PERKOVSKY EVGENY E. , GUGLIELMINO ADALGISA
Published: August 2021

Lonchodryinus groehni sp. nov. (Hymenoptera: Chrysidoidea: Dryinidae) is described from Baltic amber. The new species is close to L. balticus Olmi & Guglielmino, 2012, but it can be distinguished for the different OPL/POL ratio and 2r-rs&Rs vein of the fore wing. A key to the fossil species of Lonchodryinus and a comparison with the extant species L. ruficornis (Dalman, 1818) are presented.
A cryptic new species of rupicolous Hemidactylus Goldfuss, 1820 (Squamata: Gekkonidae) allied to H. aaronbaueri Giri, 2008 from the northern Western Ghats of Maharashtra, India
Authors: KHANDEKAR AKSHAY , THACKERAY TEJAS , AGARWAL ISHAN
Published: August 2021

We describe a cryptic new species of large-bodied rupicolous Hemidactylus allied to H. aaronbaueri from Tamhini Ghat, in Raigad and Pune districts of Maharashtra state, India. Hemidactylus tamhiniensis sp. nov. falls within the prashadi group of Indian Hemidactylus and can be diagnosed from all other members of the group by combination of several morphological characters such as its large-body size (maximum SVL 126 mm), the number of femoral pores and poreless scales between the left and right series of femoral pores in males, and the number of transverse ventral scales across the belly at mid-body. The new species differs from H. aaronbaueri based on dorsal pholidosis at mid-body, the number of undivided lamellae beneath the first finger, the number of internasal scales, and subtle colour pattern differences, besides 10.6% uncorrected ND2 sequence divergence.
A revision of Sphaeridops (Hemiptera: Heteroptera: Reduviidae)
Authors: GIL-SANTANA HÉLCIO R.
Published: August 2021

Based on a re-examination of the type materials of all described species and additional non-type specimens, the genus Sphaeridops Amyot & Serville, 1843 (Hemiptera: Heteroptera: Reduviidae: Sphaeridopinae) is revised. Sphaeridops eulus Maldonado & Santiago-Blay, 1992 is downgraded to a new synonym of S. amoenus (Lepeletier & Serville, 1825); S. pallescens (Walker, 1873), erroneously treated as a junior synonym of S. amoenus by previous authors, is revalidated. A revised diagnosis and a redescription of the genus and its included species are given, all species are illustrated, and an updated key to the species of Sphaeridops is presented.