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Huai-Feng Li,1–3,* Xu-An Wang,1–3,* Shan-Shan Xiang,1–3,* Yun-Ping Hu,1–3 Lin Jiang,1–3 Yi-Jun Shu,1–3 Mao-Lan Li,1–3 Xiang-Song Wu,1–3 Fei Zhang,1–3 Yuan-Yuan Ye,1–3 Hao Weng,1–3 Run-Fa Bao,1–3 Yang Cao,1–3 Wei Lu,1–3 Qian Dong,1–3 Ying-Bin Liu1–3 1Department of General Surgery, 2Laboratory of General Surgery, 3Institute of Biliary Tract Disease, Xinhua Hospital, Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai, People’s Republic of China *These authors contributed equally to this work Abstract: Oleanolic acid (OA), a naturally occurring triterpenoid, exhibits potential antitumor activity in many tumor cell lines. Gallbladder carcinoma is the most common malignancy of the biliary tract, and is a highly aggressive tumor with an extremely poor prognosis. Unfortunately, the effects of OA on gallbladder carcinoma are unknown. In this study, we investigated the effects of OA on gallbladder cancer cells and the underlying mechanism. The results showed that OA inhibits proliferation of gallbladder cancer cells in a dose-dependent and time-dependent manner on MTT and colony formation assay. A flow cytometry assay revealed apoptosis and G0/G1 phase arrest in GBC-SD and NOZ cells. Western blot analysis and a mitochondrial membrane potential assay demonstrated that OA functions through the mitochondrial apoptosis pathway. Moreover, this drug inhibited tumor growth in nude mice carrying subcutaneous NOZ tumor xenografts. These data suggest that OA inhibits proliferation of gallbladder cancer cells by regulating apoptosis and the cell cycle process. Thus, OA may be a promising drug for adjuvant chemotherapy in gallbladder carcinoma. Keywords: oleanolic acid, gallbladder carcinoma, apoptosis, cell cycle arrest, mitochondrial pathway

Aborda o histórico da política de informação em ciência e tecnologia na República Popular da China, nos últimos 30 anos, englobando três fases, a partir de 1956, com ênfase no atual sistema de informação científica e tecnológica. Relata a política de informação em ciência e tecnologia e enumera dados estatísticos nessa area relativos a 1985, abordando também as perspectivas e recomendações do governo chinês para esse importante setor, em consonância com a política gerai do país. Preliminary study on China national scientific and technical information policy: a personal view Abstract A fairly detailed view of the historical aspects of the policies on scientific and tecnological information over the past 30 years in the People's Republic of China. It encompasses three periods starting in 1956, but the emphasis is on the last one. It describes the present policies on science and technology, and presents statistics on the subject recommendations with regard to developments in the field, in accordance with the country's overall policies.

Introduction: Small cell transformation (SCT) is a typical mechanism of adaptive resistance to third generation epidermal growth factor receptor inhibitors (EGFRi) which have become the standard of care for EGFR-driven non-small cell lung cancer (EGFR+ NSCLC). Little is known about the optimal management of SCT patients. This study aimed to compare outcomes under platinum/etoposide chemotherapy alone (chemo) or in combination with EGFR inhibitors (EGFRi+chemo) or immune checkpoint inhibitors (ICI+chemo). In addition, DLL3 expression was explored as potential novel therapeutic target., Methods: We conducted a retrospective study on patients with EGFR+ NSCLC and SCT treated at 19 centers in Europe and the United States. A total of 47 patients were included of whom 17 received chemo, 20 ICI+chemo, and 10 EGFRi+chemo. We analyzed DLL3 expression by immunohistochemistry., Results: In the entire cohort, median overall survival (OS) from start of first SCT therapy was 11 months (95 % confidence interval [95 %CI] 9.1-12.9) and median progression-free survival (PFS) was 5 months (95 %CI 4.2-5.8). Median PFS was similar in all three groups (chemo and ICI+chemo 4 months, EGFRi+chemo 6 months), and 12-months PFS was 12 % (95 %CI 2 %-31 %), 13 % (95 %CI 0 %-43 %), and 0 % for ICI+chemo, EGFRi+chemo, and chemo, respectively. Median OS in the ICI+chemo group was 13 months (95 %CI 5.5-20.5) compared to 10 months (95 %CI 7.6-12.4) with chemo and EGFRi+chemo (95 %CI 8.1-11.9), respectively. Before and after SCT, 0 % and 93 % of tumors were DLL3-positive., Conclusions: Our results suggest that ICI+chemo and DLL3-targeting agents are worth further exploration in EGFR+ NSCLC undergoing SCT., Presented Elsewhere: Part of this work has been presented at ESMO annual meeting in Madrid, Spain in October 2023 (Poster 1336 P)., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Allgäuer, M received speaker fees from Boehringer Ingelheim. Alt, J received speaker fees and/or honoraria for advisory boards by Astra Zeneca, Pfizer, Daichii Sankyo, Roche, Amgen, MSD, Novartis, Janssen, Boehringer Ingelheim, Merck, BMS. Aust, DEA received honoraria from Roche, Astra Zeneca, MSD, Pfizer, Novartis. Christopoulos. P received research funding from Roche, Amgen, Boehringer Ingelheim, Takeda, Merck, AstraZeneca, and Novartis, honoraria from Roche, Takeda, Gilead, AstraZeneca, Merck, Thermo Fisher, Janssen, Pfizer, and Novartis, travel support from AstraZeneca, Pfizer, Janssen, Merck, Gilead, Daiichi Sankyo, Takeda, Novartis, Eli Lilly and compensation for advisory roles for Pfizer, Chugai, Boehringer Ingelheim, Takeda, Janssen, Novartis, astraZeneca, MSD, Roche. Griesinger, F received speaker fees and/or honoraria for advisory boards from AstraZeneca, Boehringer, BMS, Celgene, Lilly, MSD, Novartis, Pfizer, Roche, Takeda, Ariad, Abbvie, Tesaro/GSK, Siemens, Tesaro, Amgen, Sanofi, Daiichi-Sankyo, Beigene. Grohé, C received honoraria from AstraZeneca, Amgen, Bristol-Myers Squibb, Boehringer Ingelheim, Merck Sharp & Dohme, Pfizer, and Roche, and has had consulting or advisory roles with Boehringer Ingelheim, Merck Sharp & Dohme, Pfizer, Novartis, and Roche. Hochmair, M received honoraria from AstraZeneca, Amgen, Bristol-Myers Squibb, Boehringer Ingelheim, Merck Sharp & Dohme, Pfizer, and Roche, and has had consulting or advisory roles with Boehringer Ingelheim, Merck Sharp & Dohme, Pfizer, Novartis, and Roche. Illini, O received speaker fees and/or honoraria for advisory boards from Boehringer Ingelheim, Eli Lilly, Johnson & Johnson, Menarini, Merck Sharp & Dohme, Pfizer, and Roche and received research grants from Amgen and AstraZeneca outside of the submitted study. Jöhrens, K received compensation for advisory roles for BMS, GSK, Merck Sharp & Dohme, honoraria from AstraZeneca, Agilent, Boehringer Ingelheim, and DSO, and serves as medical advisor for QuIP. Kauffmann-Guerrero received speaker fees and/or honoraria for advisory boards from AstraZeneca, Boehringer Ingelheim, BMS, Lilly, MSD, Novartis, Pfizer, Roche, Takeda. Kirfel, J received speaker fees and/or honoraria for advisory boards, from AstraZeneca, Bristol-Myers Squibb, Novartis, Pfizer and Roche. König, D received a personal grant from Geistlich-Stucki-Stiftung, consulting fees from AstraZeneca, Merck, MSD, Novartis, PharmaMar, honoraria for presentations from Amgen, BMS, Mirati, Sanofi, Swiss Oncology in Motion, support for attending meetings from Amgen, Roche, Sanofi, honoraria for advisory boards from AstraZeneca, BMS, Merck, MSD, PharmaMar, Roche. Michels, S received research grants from Novartis and Pfizer, personal fees from Eli Lilly, Janssen, and Astra Zeneca as well as support for attending meetings and/or travel from Eli Lilly, and Janssen. Overbeck, T received speaker fees and/or honoraria for advisory boards by AstraZeneca, BMS, Boehringer-Ingelheim, Eli Lilly, Janssen-Cilag, Merck, MSD, Novartis, Roche, Takeda, Tesaro/GSK, Lilly, Roche, travel reimbursement by AstraZeneca, Boehringer-Ingelheim, Janssen-Cilag, Lilly, and Roche. Rohde, G received personal fees from Astra Zeneca, Atriva, Boehringer Ingelheim, GSK, Insmed, MSD, Sanofi, Novartis and Pfizer for consultancy during advisory board meetings and personal fees from Astra Zeneca, Berlin Chemie, BMS, Boehringer Ingelheim, Chiesi, Essex Pharma, Grifols, GSK, Insmed, MSD, Roche, Sanofi, Solvay, Takeda, Novartis, Pfizer and Vertex for lectures. Rothschild, S received honoraria (institutional) from, Roche, AstraZeneca, BMS, Boheringer Ingelheim, MSD Oncology, Novartis, Amgen, Lilly, Eisai, Merck serono, Pfizer, Takeda, Bayer, Janssen Oncology, Otsuka, PharmaMar, and Sanofi, compensation for advisory roles for AstraZeneca, Boerhinger Ingelheim, BMS, Pfizer, Eisai, Eli Lilly, Merck Serono, MSD Oncology, Novartis, Roche Pharma AG, Takeda, Amgen, Otsuka, PharmaMar, serves for the speakers bureau of Roche Pharma AG, Sanodi/Aventis, Amgen, AstraZeneca, Takeda, received research funding from Abbvie, BMS, AstraZeneca, Boerhinger Ingelheim, Merck Serono, Roche Pharma AG, and travel support, accomodation, expenses from Sanofi, Roche Pharma AG, BMS, MSD Oncology, AstraZeneca, Takeda, Boehringer Ingelheim, Amgen. He serves at the Federal Drug Comission of the Federal Office of Public Health and the Swiss Group for Clinical Cancer Research (SAKK). Saalfeld, F received research funding from Roche, consultancy fees from Boehringer Ingelheim, honoraria for lectures from AstraZeneca, Janssen, Takeda, Pfizer, Novartis, Thieme, and GWT-TUD, travel support from Janssen and Eli Lilly, and compensation for advisory meetings with BMS, Pfizer, AstraZeneca, Janssen, MSD, and Roche. Stenzinger, A received research grants from Bayer, BMS, Chugai, Incyte, and MSD, and compensation for advisory boards/speaker’s bureau: Agilent, Aignostics, Amgen, Astellas, Astra Zeneca, Bayer, BMS, Eli Lilly, Illumina, Incyte, Janssen, MSD, Novartis, Pfizer, Qlucore, QuiP, Roche, Sanofi, Seagen, Servier, Takeda, Thermo Fisher. Syrigos, K received honoraria for advisory boards from Merck Sharp & Dohme, AstraZeneca, BMS Amgen. Thomas, M received research funding (institution) from AstraZeneca, BMS, Merck, Roche, Takeda, speaker fees and/or honoraria for advisory boards by Amgen, AstraZeneca, Beigene, BMS, Boehringer Ingelheim, Daiichi Sankyo, GlaxoSmithKline, Janssen Oncology, Lilly, Merck, MSD, Novartis, Pfizer, Pierre Fabre, Roche, Sanofi, Takeda. Veluswamy, R served on advisory boards for Bristol-Myers Squibb, Astrazeneca, Merck, Boehringer Ingelheim, Merus, Novocure, Regeneron, BerGenBio, and Serna Bio, on unbranded speaker’s bureau of Astrazeneca and EMD Serono, received consulting honorarium from Beigene, received research funding from Bristol-Myers Squibb, Onconova, Astrazeneca, Boehringer Ingelheim, Lung Cancer Research Foundation, Stand Up 2 Cancer. Wenzel, C received speaker fees from Astra Zeneca. Wermke, M received honorary from Lilly, Boehringer-Ingelheim, SYNLAB, Janssen, Merck Serono, GWT, Amgen, Novartis, Pfizer, BMS and has/had paid consulting or advisory positions for BMS, Novartis, Lilly, Boehringer-Ingelheim, ISA Pharmaceuticals, Amgen, Immatics, Bayer, ImCheck, AstraZeneca, Tacalyx, Regeneron, Daiichi, Zymeworks, PharmaMar. He receive research funding (instution) from Roche and travel support from Pfizer, BMS, AstraZeneca, Amgen, Gemoab, Sanofi-Aventis, Merck Serono, Immatics, Janssen, Iovance, Daiichi-Sankyo. Wesseler, C received speaker fees and/or honoraria for advisory boards from Boehringer Ingelheim, Eli Lilly, Merck Sharp & Dohme, Pfizer, Roche, MSD, Novartis, Takeda, AstraZeneca, Chugai, BMS. Wiesweg, M received honoraria and Advisory Role: Amgen, AstraZeneca, Bristol-Myers Squibb, Daiichi Sankyo, GlaxoSmithKline, Janssen, Novartis, Pfizer, Roche, Takeda, and travel costs from Amgen, Janssen, Daiichi Sankyo, and research funding from Bristol-Myers Squibb, Takeda. Klimova, A, Kulhvay, J, Möller, J, Pelusi, N, Rasokat, A, Schubart, C, Schütz, M, Wang, A, and Vathiotis, J have nothing to disclose., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

With the rapid development of informatization, a vast amount of data is continuously generated and accumulated, leading to the emergence of cloud storage services. However, data stored in the cloud is beyond the control of users, posing various security risks. Cloud data auditing technology enables the inspection of data integrity in the cloud without the necessity of data downloading. Among these, public auditing schemes have experienced rapid development due to their ability to avoid additional user auditing expenses. However, malicious third-party auditors can compromise data privacy. This paper proposes an improved identity-based cloud auditing scheme that can resist malicious auditors. This scheme is also constructed on an identity-based public auditing scheme using blockchain to prevent malicious auditing. We found the scheme is not secure because a malicious cloud server can forge authentication tags for outsourced data blocks, while our scheme has not these security flaws. Through security proofs and performance analysis, we further demonstrate that our scheme is secure and efficient. Additionally, our scheme has typical application scenarios., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: The corresponding author Xu An Wang is an Advisory Board Member of Information Science Section at Heliyon., (© 2024 The Author(s).)

Background: Treatment for dural recurrence of olfactory neuroblastoma (ONB) is not standardized. We assess the outcomes of stereotactic body radiotherapy (SBRT) in this population., Methods: ONB patients with dural recurrences treated between 2013 and 2022 on a prospective registry were included. Tumor control, survival, and patient-reported quality of life were analyzed., Results: Fourteen patients with 32 dural lesions were evaluated. Time to dural recurrence was 58.3 months. Thirty lesions (94%) were treated with SBRT to a median dose of 27 Gy in three fractions. Two patients (3 of 32 lesions; 9%) developed in-field radiographic progression, five patients (38%) experienced progression in non-contiguous dura. Two-year local control was 85% (95% CI: 51-96%). There were no >grade 3 acute toxicities and 1 case of late grade 3 brain radionecrosis., Conclusion: In this largest study of SBRT reirradiation for ONB dural recurrence to date, high local control rates with minimal toxicity were attainable., (© 2024 Wiley Periodicals LLC.)

Purpose: In addition to epilepsy, individuals with tuberous sclerosis complex (TSC) experience a wide range of behavioral, psychiatric, intellectual, academic, and psychosocial problems. They usually exert a large psychological burden on individuals with these illnesses., Methods: This cross-sectional study used TSC-associated neuropsychiatric disorders (TAND) checklist interviews conducted at a single medical center. The enrollment of all subjects was > 6 years, and the comorbidities of neurodevelopmental disorders were assessed by clinical psychologists before enrollment. To assess the spectrum of TAND, the TAND checklist was applied as stated in the protocol, and the responses to the TAND checklist were evaluated by clinical psychologists., Results: In the behavioral concerns of patients with TSC without epilepsy, those with epilepsy had excessive shyness, language delay, lack of eye contact, rigid behavior, inattentiveness, and restlessness. In psychiatric disorders, autism spectrum disorder and attention-deficit/hyperactivity disorder are significantly correlated with epilepsy history. Diminished academic skills, including reading, writing, and mathematics skills, are significantly associated with epilepsy history. For intellectual ability, TSC patients without epilepsy is associated normal intelligence level. Among neuropsychological skills, deficits in attention, dual tasking/multi-tasking, visuospatial tasking, and executive skills are significantly associated with epilepsy history., Conclusions: Epilepsy in patients with TSC contributes to comorbid neuropsychiatric disorders. In addition to epilepsy evaluation, it is crucial to evaluate the heterogeneous spectrum of neuropsychiatric disorders using a standard checklist during the annual clinical follow-up of patients with TSC., (© 2024. The Author(s) under exclusive licence to Belgian Neurological Society.)

Mitochondrial protein homeostasis is crucially regulated by protein degradation processes involving both mitochondrial proteases and cytosolic autophagy. However, it remains unclear how plant cells regulate autophagy in the scenario of lacking a major mitochondrial Lon1 protease. In this study, we observed a notable downregulation of core autophagy proteins in Arabidopsis Lon1 knockout mutant lon1-1 and lon1-2 , supporting the alterations in the relative proportions of mitochondrial and vacuolar proteins over total proteins in the plant cells. To delve deeper into understanding the roles of the mitochondrial protease Lon1 and autophagy in maintaining mitochondrial protein homeostasis and plant development, we generated the lon1-2atg5-1 double mutant by incorporating the loss-of-function mutation of the autophagy core protein ATG5, known as atg5-1 . The double mutant exhibited a blend of phenotypes, characterized by short plants and early senescence, mirroring those observed in the individual single mutants. Accordingly, distinct transcriptome alterations were evident in each of the single mutants, while the double mutant displayed a unique amalgamation of transcriptional responses. Heightened severity, particularly evident in reduced seed numbers and abnormal embryo development, was observed in the double mutant. Notably, aberrations in protein storage vacuoles (PSVs) and oil bodies were evident in the single and double mutants. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses of genes concurrently downregulated in lon1-2 , atg5-1 , and lon1-2atg5-1 unveiled a significant suppression of genes associated with brassinosteroid (BR) biosynthesis and homeostasis. This downregulation likely contributes to the observed abnormalities in seed and embryo development in the mutants.

Bud sport is a common and stable somatic variation in perennial fruit trees, and often leads to significant modification of fruit traits and affects the breeding value. To investigate the impact of bud sport on the main metabolites in the fruit of white-fleshed loquat, we conducted a multi-omics analysis of loquat fruits at different developmental stages of a white-fleshed bud sport mutant of Dongting loquat (TBW) and its wild type (TBY). The findings from the detection of main fruit quality indices and metabolites suggested that bud sport resulted in a reduction in the accumulation of carotenoids, fructose, titratable acid and terpenoids at the mature stage of TBW, while leading to the accumulation of flavonoids, phenolic acids, amino acids and lipids. The comparably low content of titratable acid further enhances the balanced and pleasent taste profile of TBW. Expression patterns of differentially expressed genes involved in fructose metabolism exhibited a significant increase in the expression level of S6PDH ( EVM0006243 , EVM0044405 ) prior to fruit maturation. The comparison of protein sequences and promoter region of S6PDH between TBY and TBW revealed no structural variations that would impact gene function or expression, indicating that transcription factors may be responsible for the rapid up-regulation of S6PDH before maturation. Furthermore, correlation analysis helped to construct a comprehensive regulatory network of fructose metabolism in loquat, including 23 transcription factors, six structural genes, and nine saccharides. Based on the regulatory network and existing studies, it could be inferred that transcription factors such as ERF, NAC, MYB, GRAS, and bZIP may promote fructose accumulation in loquat flesh by positively regulating S6PDH . These findings improve our understanding of the nutritional value and breeding potential of white-fleshed loquat bud sport mutant, as well as serve as a foundation for exploring the genes and transcription factors that regulate fructose metabolism in loquat., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Song, Zhao, Pei, Chen, Wang, Jiang, Xie, Chen and Gong.)

The early development of the gut microbiome is governed by multiple factors and has significantly long-term effects on later-in-life health. To minimize inter-individual variations in the environment, we determined developmental trajectories of the gut microbiome in 28 healthy neonates during their stay at a postpartum center. Stool samples were collected at three time points: the first-pass meconium within 24 h of life, and at 7 and 28 days of age. Illumina sequencing of the V3-V4 region of 16S rRNA was used to investigate microbiota profiles. We found that there was a distinct microbiota structure at each time point, with a significant shift during the first week. Proteobacteria was most abundant in the first-pass meconium; Firmicutes and Actinobacteria increased with age and were substituted as the major components. Except for a short-term influence of different delivery modes on the microbiota composition, early microbiome development was not remarkably affected by gravidity, maternal intrapartum antibiotic treatment, premature rupture of membranes, or postnatal phototherapy. Hence, our data showed a similar developmental trajectory of the gut microbiome during the first month in healthy neonates when limited in environmental variations. Environmental factors external to the host were crucial in the early microbiome development., (© 2024. The Author(s).)

Geological events can strongly affect the genetic structures and differentiation of fish populations. Especially, as an endemic fish of the genus Sinocyclocheilus in the Yunnan-Guizhou Plateau, the effects of key geological events on the distributions and genetic structures remain poorly understood. Examining the phylogeographic patterns of Sinocyclocheilus fishes can be useful for elucidating the spatio-temporal dynamics of their population size, dispersal history and extent of geographical isolation, thereby providing a theoretical basis for their protection. Here, we used single nucleotide polymorphisms (SNP) method to investigate the phylogeographic patterns of Sinocyclocheilus fishes. Our analysis supports the endemicity of Sinocyclocheilus , but the samples of different regions of Sinocyclocheilus contain multiple ancestral components, which displayed more admixed and diversified genetic components, this may be due to the polymorphism of the ancestors themselves, or gene infiltration caused by hybridization between adjacent species of Sinocyclocheilus . We estimate that the most recent common ancestor (MRCA) of Sinocyclocheilus fish in the Central Yunnan Basin at approximately 3.75~3.11 Ma, and infer that the evolution of Sinocyclocheilus in the central Yunnan Basin is closely related to the formation of plateau lakes (around 4.0~0.02 Ma), and identifies the formation of Dianchi Lake and Fuxian Lake as key geological events shaping Sinocyclocheilus population structure. It is also the first time to prove that the altitude change has a great influence on the genetic variation among the populations of Sinocyclocheilus., Competing Interests: None declared., (© 2024 The Authors. Ecology and Evolution published by John Wiley & Sons Ltd.)

Unconjugated bilirubin (UB) levels during the first week after birth are related to outcomes in neonatal hypoxic-ischemic encephalopathy (HIE). Clinical Sarnat staging of HIE, brain magnetic resonance imaging (MRI), hearing outcomes, and neurodevelopmental outcomes ≥ 1 year were used to correlate UB in 82 HIE patients. The initial UB level was significantly correlated with lactic acid levels. The peak UB was higher (p < 0.001) in stage I (10.13 ± 4.03 mg/dL, n = 34) than in stages II and III (6.11 ± 2.88 mg/dL, n = 48). Among the 48 patients receiving hypothermia treatment, a higher peak UB was significantly (p < 0.001) correlated with unremarkable brain MRI scans and unremarkable neurodevelopmental outcomes at age ≥ 1 year. The peak UB were higher (P = 0.015) in patients free of seizures until 1 year of age (6.63 ± 2.91 mg/dL) than in patients with seizures (4.17 ± 1.77 mg/dL). Regarding hearing outcomes, there were no significant differences between patients with and without hearing loss. The UB level in the first week after birth is an important biomarker for clinical staging, MRI findings, seizures after discharge before 1 year of age, and neurodevelopmental outcomes at ≥ 1 year of age., (© 2023. The Author(s).)

Background: We report visual outcomes and ocular complications in patients with lacrimal gland carcinoma who had eye-sparing surgery followed by radiotherapy., Methods: This review included consecutive patients with lacrimal gland carcinoma who underwent eye-sparing surgery and adjuvant radiotherapy or concurrent chemoradiation therapy between 2007 and 2018. Clinical data, including details of ophthalmological examinations and radiation treatment were reviewed., Results: The study included 23 patients, 15 males and 8 females, with median age 51 years. Twenty patients (87%) received intensity-modulated proton therapy; 3 (13%) received intensity-modulated radiotherapy. Nineteen patients (83%) received concurrent chemotherapy. After a median follow-up time of 37 months (range: 8-83), 13 patients (57%) had best-corrected visual acuity 20/40 or better, 3 (13%) had moderate vision loss (between 20/40 and 20/200) and 7 (30%) had severe vision loss (20/200 or worse). The most common ocular complications were dry eye disease (21 patients; 91%), radiation retinopathy (16; 70%) and cataract progression (11; 49%). Tumour crossing the orbital midline (p=0.014) and Hispanic ethnicity (p=0.014) were associated with increased risk of severe vision loss. The risk of radiation retinopathy was significantly different among the three racial groups; Hispanic patients (n=3) had the highest rate of retinopathy (p<0.001). Tumour size, initial T category and total prescribed radiation dose were not significantly associated with severe vision loss., Conclusion: Eye-sparing surgery followed by adjuvant radiotherapy in patients with lacrimal gland carcinoma has a reasonable overall visual prognosis. Patients with tumours crossing the orbital midline and Hispanic patients have a higher risk of severe vision loss., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To investigate the clinical value of the novel approach,radical resection of the retroperitoneal lipo-lymphatic layer (RRRLLL),in the surgical treatment of resectable pancreatic head cancer. Methods: Between June 2020 and June 2022,a total of 221 patients with pancreatic head cancer underwent surgical treatment using the RRRLLL approach(RRRLLL group),while 107 patients received traditional surgical treatment(traditional group) in five high-volume pancreatic centers in China. Data from surgical technique and clinical perioperative outcomes,including lymph node harvested,surgical time,and complications,were analyzed. The RRRLLL group consisted of 144 males and 77 females with an age of (67.5±9.0) years(range:41.3 to 81.1 years). The traditional group included 71 males and 36 females,with an age of (66.3±8.1) years(range:45.1 to 79.2 years). Statistical analysis was performed using the K-S test, Z test,or χ 2 test. Results: Pancreaticoduodenectomy was performed successfully in all patients,achieving R0 resection. RRRLLL group surgery required mobilization of retroperitoneal adipose and lymphatic tissues starting from the right edge of the inferior vena cava and extending to the left side,up to the superior mesenteric artery,down to the inferior mesenteric artery,and left to the left side of the aorta,including the perineural and lymphatic tissues around the superior mesenteric artery and the sheath of the mesenteric artery. However,the traditional group did not include the areas mentioned above in the scope of clearance. There were no statistically significant differences between the RRRLLL group and the traditional group in terms of age,sex,tumor size,T stage,and vascular invasion (all P >0.05). However,the number of lymph nodes harvested in the RRRLLL group was significantly higher at 28.7±9.0 (range: 18 to 39) compared to 18.2±8.0 (range: 12 to 21) in the traditional group ( Z =-10.691, P <0.05). There were no statistically significant differences in the number of positive lymph nodes,N staging,and postoperative complications between the two groups. Conclusion: The RRRLLL approach improved lymph node dissection compared to the traditional approach,potentially leading to reduced recurrence rates.

Background: Three-dimensional visualization preoperative evaluation (3D-VPE) and enhanced recovery after surgery (ERAS) have been suggested to improve outcomes of cancer surgery in patients, yet little is known regarding their clinical benefit in patients with gallbladder cancer (GBC). We hypothesized that the combination of 3D-VPE and ERAS would improve the outcome of patients undergoing surgery for GBC., Objective: This study aimed to determine if 3D-VPE and ERAS can improve the outcomes and overall survival in patients with GBC, establishing a novel patient management strategy for GBC., Methods: A total of 227 patients with GBC were recruited and divided into two groups: those who received traditional treatment between January 2000 and December 2010 (n = 86; the control group) and those who underwent 3D-VPE and ERAS between January 2011 and December 2017 (n = 141). Univariate and multivariate analyses were employed to assess the relationship among disease stages, lymph node invasion, and cell differentiation between the two groups. Cox regression analysis was used to investigate patient survival in these groups., Results: Patients who underwent 3D-VPE and ERAS showed a significantly higher R0 resection rate (67.4% vs. 20.9%, p < 0.001) and dissected lymph node number (26.6 ± 12.6 vs. 16.3 ± 7.6 p < 0.001) compared to the control group. The median survival was 27.4 months, and the 1- and 3-year survival rates were 84.4% and 29.8%, respectively, in patients who received combined management; in the control cohort, the median survival was 12.7 months, and the 1- and 3-year survival rates were 53.5% and 15.1%, respectively. In addition, some postoperative complications and risk factors were diminished relative to the traditionally treated patients., Conclusion: The implementation of 3D-VPE and ERAS can significantly improve the prognosis and outcomes of patients with GBC and should be considered for wide use in clinical practice., (© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

The autofluorescence phenomenon is an inherent characteristic of lignified cells. However, in the case of Lophira alata ( L. alata ), the autofluorescence is nearly imperceptible during occasional fluorescence observations. The aim of this study is to investigate the mechanism behind the quenching of lignin's autofluorescence in L. alata by conducting associated experiments. Notably, the autofluorescence image of L. alata observed using optical microscopy appears to be quite indistinct. Abundant extractives are found in the longitudinal parenchyma, fibers, and vessels of L. alata . Remarkably, when subjected to a benzene-alcohol extraction treatment, the autofluorescence of L. alata becomes progressively enhanced under a fluorescence microscope. Additionally, UV-Vis absorption spectra demonstrate that the extractives derived from L. alata exhibit strong light absorption within the wavelength range of 200-500 nm. This suggests that the abundant extractives in L. alata are probably responsible for the autofluorescence quenching observed in the cell walls. Moreover, the presence and quantity of these extractives have a significant impact on the fluorescence intensity of lignin in wood, resulting in a significant decrease therein. In future studies, it would be interesting to explore the role of complex compounds such as polyphenols or terpenoids, which are present in the abundant extractives, in interfering with the fluorescence quenching of lignin in L. alata .

The foliar disease, which is the primary complex disease of Pseudostellaria heterophylla, can be caused by multiple co-infecting pathogens, resulting in a significant reduction in yield. However, there is a lack of research on the relationship between co-infection of various pathogens and the response of resistance-related genes in P. heterophylla. Through the use of 18S rDNA sequencing and pathogenicity testing, it has been determined that Fusarium oxysporum, Alternaria alternata, Arcopilus aureus, Botrytis cinerea, Nemania diffusa, Whalleya microplaca, and Cladosporium cladosporioides are co-infecting pathogens responsible for foliar diseases in P. heterophylla. Furthermore, the qRT-PCR analysis revealed that F. oxysporum, A. alternata, B. cinerea, A. aureus, N. diffusa, Schizophyllum commune, C. cladosporioides, and Coprinellus xanthothrix upregulated ten, two, three, four, seven, thirteen, five, one, and six resistance-related genes, respectively. These findings suggest that a total of 22 resistance-related genes were implicated in the response to diverse fungi, and the magnitude and frequency of induction of resistance-related genes varied considerably among the different fungi. The aforementioned gene associated with resistance was found to be implicated in the response to multiple fungi, including PhPRP1, PhBDRN15, PhBDRN11, and PhBDRN3, which were found to be involved in the resistance response to nine, five, four, and four fungi, respectively. The findings indicate that the PhPRP1, PhBDRN15, PhBDRN11, and PhBDRN3 genes exhibit a broad-spectrum resistance to various fungi. Furthermore, the avirulence fungi C. xanthothrix, which is known to affect P. heterophylla, was found to prime a wide range of resistance responses in P. heterophylla, thereby enhancing its disease resistance. This study provided insight into the management strategies for foliar diseases of P. heterophylla and new genetic materials for disease-resistant breeding., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Gut microbiome development during early life has significant long-term effects on health later in life. The first-pass meconium is not sterile, and it is important to know the initial founder of the subsequent gut microbiome. However, there is limited data on the microbiota profile of the first-pass meconium in healthy neonates. To determine the early gut microbiota profile, we analyzed 39 samples of the first-pass meconium from healthy neonates using 16S rRNA sequencing. Our results showed a similar profile of the microbiota composition in the first-pass meconium samples. Pseudomonas was the most abundant genus in most samples. The evenness of the microbial communities in the first-pass meconium was extremely poor, and the average Shannon diversity index was 1.31. An analysis of the relationship between perinatal characteristics and the meconium microbiome revealed that primigravidae babies had a significantly higher Shannon diversity index ( p = 0.041), and the Bacteroidales order was a biomarker for the first-pass meconium of these neonates. The Shannon diversity index was not affected by the mode of delivery, maternal intrapartum antibiotic treatment, prolonged rupture of membranes, or birth weight. Our study extends previous research with further characterization of the gut microbiome in very early life.

Understanding of a variety of membranous structures throughout the body,such as the fascia,the serous membrane,is of great importance to surgeons. This is especially valuable in abdominal surgery. With the rise of membrane theory in recent years,membrane anatomy has been widely recognized in the treatment of abdominal tumors,especially of gastrointestinal tumors. In clinical practice. The appropriate choice of intramembranous or extramembranous anatomy is appropriate to achieve precision surgery. Based on the current research results,this article described the application of membrane anatomy in the field of hepatobiliary surgery,pancreatic surgery,and splenic surgery,with the aim of blazed the path from modest beginnings.

Exploration of highly efficient and robust catalyst is pivotal for electrocatalytic degradation of dye wastewater, but it still is a challenge. Here, we develop a three-dimensional self-supported SnO 2 -Mn 2 O 3 hybrid nanosheets grown on carbon cloth (noted by SnO 2 -Mn 2 O 3 @CC) electrode via a simple hydrothermal method and annealing treatment. Benefitting from the interlaced nanosheets architecture that enlarges the surface area and the synergetic component effect that accelerates the interfacial electronic transfer, SnO 2 -Mn 2 O 3 @CC electrode exhibits a superior electrocatalytic degradation efficiency for cationic blue X-GRRL dye in comparison with the single metal oxide electrode containing SnO 2 @CC and Mn 2 O 3 @CC. The degradation efficiency of cationic blue X-GRRL on SnO 2 -Mn 2 O 3 @CC electrode can reach up to 97.55% within 50 min. Furthermore, self-supported architecture of nanosheets on carbon cloth framework contributes to a robust stability compared with the traditional electrode via the multiple dip/brush coating accompanied by the thermal decomposition method. SnO 2 -Mn 2 O 3 @CC electrode exhibits excellent recyclability, which can still retain a degradation efficiency of 94.12% after six cycles. This work may provide a new pathway for the design and exploration of highly efficient and robust electrooxidation catalysts for dye degradation.

With the rapid development of cloud storage and cloud computing technology, users tend to store data in the cloud for more convenient services. In order to ensure the integrity of cloud data, scholars have proposed cloud data integrity verification schemes to protect users' data security. The storage environment of the Internet of Things, in terms of big data and medical big data, demonstrates a stronger demand for data integrity verification schemes, but at the same time, the comprehensive function of data integrity verification schemes is required to be higher. Existing data integrity verification schemes are mostly applied in the cloud storage environment but cannot successfully be applied to the environment of the Internet of Things in the context of big data storage and medical big data storage. To solve this problem when combined with the characteristics and requirements of Internet of Things data storage and medical data storage, we designed an SM2-based offline/online efficient data integrity verification scheme. The resulting scheme uses the SM4 block cryptography algorithm to protect the privacy of the data content and uses a dynamic hash table to realize the dynamic updating of data. Based on the SM2 signature algorithm, the scheme can also realize offline tag generation and batch audits, reducing the computational burden of users. In security proof and efficiency analysis, the scheme has proven to be safe and efficient and can be used in a variety of application scenarios.

To exploit high-performance and stable sensing materials with a room working temperature is pivotal for portable and mobile sensor devices. However, the common sensors based on metal oxide semiconductors usually need a higher working temperature (usually above 300 °C) to achieve a good response toward gas detection. Currently, metal halide perovskites have begun to rise as a promising candidate for gas monitoring at room temperature but suffer phase instability. Herein, we construct 1D/3D PyPbI 3 /FA 0.83 Cs 0.17 PbI 3 (denoted by PyPbI 3 /FACs) bilayer perovskite by post-processing spin-coating Pyrrolidinium hydroiodide (PyI) salt on top of 3D FACs film. Benefitting from the 1D PyPbI 3 coating layer, the phase stability of 1D/3D PyPbI 3 /FACs significantly improves. Simultaneously, the gas sensor based on the 1D/3D PyPbI 3 /FACs bilayer perovskite presents a superior selectivity and sensitivity toward NO 2 detection at room temperature, with a low detection limit of 220 ppb. Exposed to a 50 ± 3% relative humidity (RH) level environment for a consecutive six days, the 1D/3D PyPbI 3 /FACs perovskite-based sensor toward 10 ppm NO 2 can still maintain a rapid response with a slight attenuation. Gas sensors based on hybrid 1D/3D-structured perovskite in this work may provide a new pathway for highly sensitive and stable gas sensors in room working temperature, accelerating its practical application and portable device.

Introduction: Gallbladder cancer (GBC) is an aggressive type of digestive system cancer with a dismal outcome. Given the lack of effective treatment options, the disease rapidly reoccurs and 5-year survival rate is <5%. Our team previously found that a significant percentage of GBC tissues harboured mutations of the ErbB-related pathway. Afatinib is a chemically synthesised drug specifically targeting the ErbB pathway mutations. However, its efficacy in the treatment of patients with GBC remains unknown. Circulating tumour DNA (ctDNA) refers to a proportion of cell-free DNA in the blood which is released by apoptotic and necrotic cells from tumours in situ, metastatic foci or circulating tumour cells. ctDNA-based liquid biopsy is a non-invasive pathological detection method that offers additional value to evaluate the therapeutic efficacy of antitumour drugs., Methods and Analysis: We conduct a multicentre and randomised study on afatinib combined with gemcitabine and oxaliplatin (GEMOX) in patients with ErbB pathway mutated GBC. Clinical and biological evaluation involving ErbB pathway ctDNA detection will be made during the 3-year follow-up after participation. The primary objective of this clinical trial is to evaluate the clinical efficacy of afatinib. Disease-free survival is the primary end point and will be correlated with plasma ctDNA of patients in the treatment with afatinib. In addition, we will evaluate the sensitivity and specificity of plasma ctDNA for monitoring tumour recurrence and progression. Finally, we will assess the safety of afatinib by keeping an eye on the safety indicators., Ethics and Dissemination: The study was approved by the medical-ethical review committee of Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine and Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine. The clinical trials results, even inconclusive, will be published in peer-reviewed journals., Trial Registration Number: NCT04183712., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Aplastic anemia (AA), a rare but potentially life-threatening disease, is a paradigm of bone marrow failure syndromes characterized by pancytopenia in the peripheral blood and hypocellularity in the bone marrow. The pathophysiology of acquired idiopathic AA is quite complex. Mesenchymal stem cells (MSCs), an important component of the bone marrow, are crucial in providing the specialized microenvironment for hematopoiesis. MSC dysfunction may result in an insufficient bone marrow and may be associated with the development of AA. In this comprehensive review, we summarized the current understanding about the involvement of MSCs in the pathogenesis of acquired idiopathic AA, along with the clinical application of MSCs for patients with the disease. The pathophysiology of AA, the major properties of MSCs, and results of MSC therapy in preclinical animal models of AA are also described. Several important issues regarding the clinical use of MSCs are discussed finally. With evolving knowledge from basic studies and clinical applications, we anticipate that more patients with the disease can benefit from the therapeutic effects of MSCs in the near future.

The most common complications after pancreaticoduodenectomy include pancreatic fistula, biliary fistula, delayed gastric emptying, bleeding, and abdominal infection. Although advances in surgery have led to a significant decrease in perioperative mortality in recent years, the risk of complications after pancreaticoduodenectomy remains. Thus, prevention and treatment of various complications are important to improve the prognosis of patients.

Fibrinogen plays an important role in tumor progression. Here, we explored the role of fibrinogen in gallbladder cancer (GBC) metastasis. The plasma fibrinogen level in M1 GBC patients was higher than in M0 GBC patients, indicating that fibrinogen may participate in GBC metastasis. Treatment of GBC cell lines with fibrinogen promoted metastasis and induced the expression of intercellular adhesion molecule 1 (ICAM1). ICAM1 overexpression promoted metastasis and knockdown inhibited it. The cell adhesion and transendothelial migration of GBC cells were enhanced by fibrinogen treatment and ICAM1 overexpression. In addition, the medium of fibrinogen-treated and overexpression-ICAM1 NOZ cells exhibited enhanced macrophages recruitment. This may work in concert to promote angiogenesis. Immunohistochemistry results on clinical specimens showed that higher fibrinogen levels, higher ICAM1 expression, higher blood vessel density, and higher macrophage levels were present simultaneously. Collectively, this study indicates fibrinogen promotes metastasis and extravasation by inducing ICAM1 expression to enhance tumor cell migration, cell adhesion, transendothelial migration and promote angiogenesis and increase vascular endothelial permeability., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

IoT-based crowd-sensing network, which aims to achieve data collection and task allocation to mobile users, become more and more popular in recent years. This data collected by IoT devices may be private and directly transmission of these data maybe incur privacy leakage. With the help of homomorphic encryption (HE), which supports the additive and/or multiplicative operations over the encrypted data, privacy preserving crowd-sensing network is now possible. Until now several such secure data aggregation schemes based on HE have been proposed. In many cases, ciphertext comparison is an important step for further secure data processing. However efficient ciphertext comparison is not supported by most such schemes. In this paper, aiming at enabling ciphertext comparison among multiple users in crowd-sensing network, with Lagrange's interpolation technique we propose comparable homomorphic encryption (CompHE) schemes. We also prove our schemes' security, and the performance analysis show our schemes are practical. We also discuss the applications of our IoT based crowd-sensing network with comparable homomorphic encryption for combatting COVID19, including the first example of privacy preserving close contact determination based on the spatial distance, and the second example of privacy preserving social distance controlling based on the spatial difference of lockdown zones, controlled zones and precautionary zones. From the analysis we see our IoT based crowd-sensing network can be used for contact tracing without worrying about the privacy leakage. Compared with the existing CompHE schemes, our proposals can be collusion resistance or secure in the semi-honest model while the previous schemes cannot achieve this easily. Our schemes only need 4 or 5 modular exponentiation when implementing the most important comparison algorithm, which are better than the existing closely related scheme with advantage of 50% or 37.5%., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 Elsevier B.V. All rights reserved.)

Objective: High-grade serous ovarian cancer, the most frequent type of ovarian cancer, has a poor prognosis and novel treatments are needed for patients with platinum resistant/refractory disease. New therapeutic strategies targeting cell cycle checkpoints, including CHK1 inhibition with prexasertib, may help improve clinical response and overcome resistance., Methods: Patients with ovarian cancer (N = 169) were assigned to 4 cohorts as part of the Phase 2 multicenter trial (NCT03414047): Cohort 1: platinum resistant, BRCA-wildtype with ≥3 lines prior therapy; Cohort 2: platinum resistant BRCA-wildtype with <3 lines prior therapy; Cohort 3: platinum resistant, BRCA-mutated with prior PARP inhibitor therapy; Cohort 4: platinum refractory, BRCA-mutated, or BRCA-wildtype with any number of prior therapy lines. The primary endpoint was objective response rate (ORR) and secondary endpoints included disease control rate (DCR), and safety. DNA from tumor biopsies was sequenced to identify biomarkers., Results: The ORR in platinum resistant patients (Cohorts 1--3) was 12.1%, and 6.9% in platinum refractory patients. In platinum resistant patients, DCR was 37.1%, and consistent across cohorts. In platinum refractory patients, DCR was 31.0%. Consistent with the prexasertib mechanism of action, the most common treatment related adverse events of all grades included thrombocytopenia, neutropenia, fatigue, nausea, and anemia., Conclusions: Prexasertib demonstrated durable single agent activity in a subset of patients with recurrent ovarian cancer regardless of clinical characteristics, BRCA status, or prior therapies, including PARPi. There was no obvious correlation with genomic alterations in responders vs non-responders, emphasizing the need for alternative biomarker approaches for responder identification., Competing Interests: Declaration of Competing Interest Nicoletta Colombo: Consultant/advisor: Roche, PharmaMar, AstraZeneca, Clovis Oncology, MSD, GlaxoSmithKline, Tesaro, Pfizer, BIOCAD, Immunogen, Mersana, Eisai, Oncxerna. Promotional ppeaker: AstraZeneca, Tesaro, Novartis, Clovis, MSD, GlaxoSmithKline, Eisai. Investigator/researcher: AstraZeneca, PharmaMar, Roche. Nonfinancial interests: Steering Committee member for ESMO Clinical Guidelines, Chair Scientific Committee ACTO onlus., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Pulmonary arterial hypertension (PAH) is a progressive disease. Although great progress has been made in its diagnosis and treatment in recent years, its mortality rate is still very significant. The pathophysiology and pathogenesis of PAH are complex and involve endothelial dysfunction, chronic inflammation, smooth muscle cell proliferation, pulmonary arteriole occlusion, antiapoptosis and pulmonary vascular remodeling. These factors will accelerate the progression of the disease, leading to poor prognosis. Therefore, accurate etiological diagnosis, treatment and prognosis judgment are particularly important. Here, we systematically review the pathophysiology, diagnosis, genetics, prognosis and treatment of PAH., (© 2022. The Author(s).)

Background: At present, COVID-19 is a global pandemic and is seriously harmful to humans. In this retrospective study, the aim was to investigate the interaction between CVD and COVID-19., Methods: A total of 180 patients diagnosed with COVID-19 in Yichang Central People's Hospital from 29 January to 17 March 2020 were initially included. The medical history, clinical manifestations at the time of admission, laboratory test results, hospitalization time and complications were recorded. According to the medical history, the patients were assigned to the nonsevere group with non-CVD (n=90), the nonsevere group with CVD (n=22), the severe group with non-CVD (n=40) and the severe group with CVD (n=28)., Results: In the severe group, compared with non-CVD patients, CVD patients had a significantly higher incidence of fever (P<0.05). However, compared with the nonsevere group, the severe group had significantly higher proportions of patients with hypertension, type 2 diabetes mellitus, CHD and HF (all P<0.05). Among the patients with nonsevere COVID-19, the WBC count and the levels of IL-6, CRP, D-dimer, NT-proBNP, and FBG were significantly higher and the Hb level was significantly lower in the CVD patients than in the non-CVD patients (all P<0.05). However, among the patients with severe COVID-19, only the level of NT-proBNP was significantly higher in CVD patients than in non-CVD patients (P<0.05). In addition, the WBC count and the levels of IL-6, CRP, D-dimer, CKMB, ALT, AST, SCR, NT-proBNP, and FBG were significantly higher and the Hb level was significantly lower in the severe group than in the nonsevere group (all P<0.05). However, among the patients with severe COVID-19, the incidences of acute myocardial injury, acute kidney injury, arrhythmia, and sudden death were significantly higher in the CVD group than in the non-CVD group (all P<0.05). The same results were found in the comparison of the nonsevere group with the severe group. Among the patients with nonsevere COVID-19, those without CVD had a mean hospitalization duration of 25.25 (SD 7.61) days, while those with CVD had a mean hospitalization duration of 28.77 (SD 6.11) days; the difference was significant (P<0.05). The same results were found in the comparison of the severe group., Conclusions: CVD affects the severity of COVID-19. COVID-19 also increases the risk of severe CVD., (Copyright © 2021 Elsevier España, S.L.U. All rights reserved.)

Objective: In a cohort assembled during the height of mortality-associated coronavirus disease 2019 (COVID-19) in New York City, the objectives of this qualitative-quantitative mixed-methods study were to assess COVID-related stress at enrollment with subsequent stress and clinical and behavioral characteristics associated with successful coping during longitudinal follow-up., Methods: Patients with rheumatologist-diagnosed rheumatic disease taking immunosuppressive medications were interviewed in April 2020 and were asked open-ended questions about the impact of COVID-19 on psychological well-being. Stress-related responses were grouped into categories. Patients were interviewed again in January-March 2021 and asked about interval and current disease status and how well they believed they coped. Patients also completed the 29-item Patient-Reported Outcomes Measurement Information System (PROMIS-29) measuring physical and emotional health during both interviews., Results: Ninety-six patients had follow-ups; 83% were women, and mean age was 50 years. Patients who reported stress at enrollment had improved PROMIS-29 scores, particularly for the anxiety subscale. At the follow-up, patients reported persistent and new stresses as well as numerous self-identified coping strategies. Overall coping was rated as very well (30%), well (48%), and neutral-fair-poor (22%). Based on ordinal logistic regression, variables associated with worse overall coping were worse enrollment-to-follow-up PROMIS-29 anxiety (odds ratio [OR], 4.4; confidence interval [CI], 1.1-17.3; p = 0.03), not reporting excellent/very good disease status at follow-up (OR, 2.7; CI, 1.1-6.5; p = 0.03), pandemic-related persistent stress (OR, 5.7; CI, 1.6-20.1; p = 0.007), and pandemic-related adverse long-lasting effects on employment (OR, 6.1; CI, 1.9-20.0; p = 0.003) and health (OR, 3.0; CI, 1.0-9.0; p = 0.05)., Conclusions: Our study reflects the evolving nature of COVID-related psychological stress and coping, with most patients reporting they coped well. For those not coping well, multidisciplinary health care providers are needed to address long-lasting pandemic-associated adverse consequences., Competing Interests: The authors declare no conflict of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) in mammals is a multifunctional protein. In this study, PCSK9 of marine fish Epinephelus coioides was characterized. The full-length cDNA of E. coioides PCSK9 was 2458 bp in length containing 185 bp 5' UTR, 263 bp 3' UTR and 2010 bp open reading frame (ORF) encoding 669 amino acids with the predicted molecular weight of 71 kDa and the theoretical PI of 6.6. Similar to other members of PCSK9 family, E. coioides PCSK9 has three conserved domains: Inhibitor&#95; I9 super family, Peptidases&#95; S8&#95; PCSK9&#95; Proteinase K&#95; like, and PCSK9&#95; C-CRD super family. E. coioides PCSK9 mRNA could be detected in all the tissues examined by real-time quantitative PCR, with the highest expression in the brain, followed by skin, trunk kidney, head kidney, intestine, blood, liver, spleen, gill, muscle and heart. E. coioides PCSK9 was distributed in both the cytoplasm and nucleus. The expression of E. coioides PCSK9 was significantly upregulated during Singapore grouper iridovirus (SGIV) infection. Upregulated PCSK9 could significantly affect the activities of nuclear factor kappaB (NF-κB) promoter, SGIV-induced apoptosis, and the expressions of the key SGIV genes (ICP18, LITAT, MCP, and VP19) and the E. coioides proinflammatory factors (IL-6, IL-1β, IL-8, and TNF-α). The results illustrated that E. coioides PCSK9 might be involved in the pathogen infection by regulating the innate immune response., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Introduction: The hepatocyte growth factor receptor MET represents a resistance mechanism to epidermal growth factor receptor (EGFR) inhibition in EGFR mutant (mt) non-small cell lung cancer (NSCLC). This Phase 2 study tested whether acquired resistance to erlotinib in MET protein positive NSCLC patients enriched for EGFRmt can be overcome by emibetuzumab plus erlotinib., Patient and Methods: Patients with Stage IV NSCLC with acquired resistance to erlotinib and MET diagnostic (+) (≥ 10% of cells expressing MET at ≥ 2+ IHC staining intensity at any time) were randomized (3:1) to receive emibetuzumab 750 mg every 2 weeks with or without erlotinib 150 mg once daily. The primary objective was to evaluate the overall response rate (ORR) relative to historic control, with a co-primary objective of ORR in patients with MET expression in ≥ 60% of cells ≥ 2+ (MET ≥ 60%)., Results: One hundred and eleven MET+ patients received emibetuzumab plus erlotinib (N = 83) or emibetuzumab monotherapy (N = 28). 89 of 111 MET+ samples were post-erlotinib. ORR was 3.0% for emibetuzumab plus erlotinib (95% CI: 0.4, 10.5) and 4.3% for emibetuzumab (95% CI: 0.1, 21.9), in patients with post-erlotinib progression biopsies available (n = 89). Similar results were observed in patients with MET ≥ 60% expression (n = 74). Disease control rate and progression-free survival were higher for emibetuzumab plus erlotinib (50%/3.3 months) than for emibetuzumab (26%/1.6 months). No unexpected safety signals emerged. Partial responses were observed in patients with and without EGFRmt or MET amplification. EGFR sensitizing mutations were identified retrospectively in 84.2% of those with available tissue (85/101)., Conclusion: Acquired resistance to erlotinib in MET diagnostic (+) patients was not reversed by emibetuzumab plus erlotinib or emibetuzumab monotherapy, although a subset of patients obtained clinical benefit., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Introduction: Even though adrenocorticotropic hormone (ACTH) demonstrated powerful efficacy in the initially successful treatment of infantile spasms (IS), nearly one-half of patients whose spasms were once suppressed experienced relapse. There is currently no validated method for the prediction of the risk of relapse. The Burden of Amplitudes and Epileptiform Discharges (BASED) score is an electroencephalogram (EEG) grading scale for children with infantile spasms. We sought to determine whether an association exists between the BASED score after ACTH treatment and relapse after initial response with ACTH., Methods: Children with IS who achieved initial response after ACTH treatment were selected as the study subjects. Those who experienced relapse within 12 months after ACTH treatment were categorized as the relapse group, and those who did not were categorized as the non-relapse group. Their general clinical data and EEG data (using BASED scoring) after ACTH treatment were collected, and compared between groups. Cox proportional hazards models were fit to determine factors associated with relapse., Results: A total of 64 children with IS were enrolled in the study, of which 37 (57.8%) experienced a relapse, and the median duration after ACTH treatment was 3 (1.5, 6) months. The BASED score was significantly higher in the relapse group than in the non-relapse group. Cox modeling demonstrated that BASED score was independently associated with relapse. The patients with a score greater than or equal to 3 showed a high rate (89.3%) of relapse. The relapse group had stronger, more stable EEG functional networks than the non-relapse group, and there were obvious correlations between BASED score and functional connectivity., Conclusion: This study suggests the BASED score after ACTH treatment has potential value as a predictor for relapse after initial response. Children with IS who have a BASED score greater than or equal to 3 after the initial response of ACTH carry a high risk of relapse within 1 year., (© 2022. The Author(s).)

DNA mechanical properties play a critical role in every aspect of DNA-dependent biological processes. Recently a high throughput assay named loop-seq has been developed to quantify the intrinsic bendability of a massive number of DNA fragments simultaneously. Using the loop-seq data, we develop a software tool, DNAcycP, based on a deep-learning approach for intrinsic DNA cyclizability prediction. We demonstrate DNAcycP predicts intrinsic DNA cyclizability with high fidelity compared to the experimental data. Using an independent dataset from in vitro selection for enrichment of loopable sequences, we further verified the predicted cyclizability score, termed C-score, can well distinguish DNA fragments with different loopability. We applied DNAcycP to multiple species and compared the C-scores with available high-resolution chemical nucleosome maps. Our analyses showed that both yeast and mouse genomes share a conserved feature of high DNA bendability spanning nucleosome dyads. Additionally, we extended our analysis to transcription factor binding sites and surprisingly found that the cyclizability is substantially elevated at CTCF binding sites in the mouse genome. We further demonstrate this distinct mechanical property is conserved across mammalian species and is inherent to CTCF binding DNA motif., (© The Author(s) 2022. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Background and Objective: Ferroptosis is a recently discovered form of cell death which differs from other forms of cell death in terms of morphology, biochemistry, and regulatory mechanisms. Ferroptosis is regulated by a complex system and the precise molecular mechanisms are still being elucidated. Over the past few years, extensive research has revealed that the essence of ferroptosis is iron-dependent accumulation of lipid hydroperoxides induced by oxidative stress, and the System Xc-glutathione (GSH)-glutathione peroxidase 4 (GPX4) pathway is the main ferroptosis prevention system. Meanwhile, other antioxidant systems have also been implicated in regulating ferroptosis, including the transsulfuration pathway, mevalonate pathway, ferroptosis inhibitory protein 1 (FSP1)-Coenzyme Q10 (CoQ10) pathway, dihydroorotate dehydrogenase (DHODH)-dihydroubiquione (CoQH2) pathway, and GTP cyclohydrolase-1 (GCH1)-tetrahydrobiopterin (BH4) pathway. This article reviews the molecular mechanisms of ferroptosis and its critical role in antioxidant systems, aiming to reveal that antioxidation is an important method of inhibiting ferroptosis and to provide a new direction for the treatment of ferroptosis-related diseases., Methods: We searched all original papers and reviews about the molecular mechanisms of ferroptosis in antioxidant systems using PubMed to November 2021. The search terms used included: 'ferroptosis', 'ferroptosis inducers', 'ferroptosis inhibitors', 'ferroptosis and GSH', 'ferroptosis and GPX4', 'ferroptosis and System Xc-', 'SLC7A11', 'P53', 'NRF2 and ferroptosis', 'iron metabolism', 'lipid peroxidation', 'antioxidant systems', 'transsulfuration pathway', 'mevalonate pathway', 'FSP1-CoQ10', 'DHODH-CoQH2', and 'GCH1-BH4'., Key Content and Findings: We first introduced the origin of ferroptosis and its common inhibitors and inducers. Next, we discussed the molecular mechanisms of ferroptosis and its role in antioxidant systems in existing studies. Finally, we briefly summarized the relationship between ferroptosis and diseases. It reveals that antioxidation is an important method of inhibiting ferroptosis., Conclusions: This review discusses the recent rapid progress in the understanding of the molecular mechanisms of ferroptosis and its role in several antioxidant systems., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://atm.amegroups.com/article/view/10.21037/atm-21-6942/coif). The authors have no conflicts of interest to declare., (2022 Annals of Translational Medicine. All rights reserved.)

Background: Coping with stress is part of self-managing systemic rheumatic diseases. Our objective was to assess stress and coping during the coronavirus disease 2019 (COVID-19) pandemic., Methods: During the pandemic in New York City, patients taking disease-modifying antirheumatic drugs answered open-ended questions about the pandemic's effects on daily life and their rheumatic condition. Themes of stress and coping were discerned from volunteered responses. Patients also completed the standard Generalized Anxiety Disorder (GAD-7) scale/PROMIS Anxiety surveys. Anxiety scores were independent variables in multivariable analyses with stress and coping themes as combined dependent variables., Results: Of the 112 patients interviewed (86% women; mean age, 50 years), 72 volunteered COVID-19-related stress on their rheumatic condition, home, work, and finances. Patients volunteering stress were younger, had disease longer, were taking more than 1 medication, had worse GAD-7 scores and a positive anxiety screen, and had worse PROMIS scores that were significantly worse than population norms (all comparisons, p ≤ 0.01; all variables remained associated in multivariable analyses). Fourty-one patients volunteered coping mechanisms including support from others, engaging in activities, and resilience already establish in dealing with rheumatic diseases. Of these, 18 volunteered both coping and stress and 23 volunteered coping and no stress. Patients in the latter (coping-only) group were more likely to be older, taking only 1 medication, and had better GAD-7 and PROMIS scores (all comparisons, p ≤ 0.02). In multivariable analysis, older age (p = 0.02) and lower GAD-7 (p = 0.03) or PROMIS scores (p = 0.03) remained associated., Conclusions: Patients reported stress and coping due to the COVID-19 pandemic. Analyses with standard anxiety measures demonstrated lower anxiety in patients who volunteered coping mechanisms., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

The cutting power consumption of milling has direct influence on the economic benefits of manufacturing particle boards. The influence of the milling parameters on the cutting power were investigated in this study. Experiments and data analyses were conducted based on the response surface methodology. The results show that the input parameters had significant effects on the cutting power. The high rake angle reduced the cutting force. Thus, the cutting power decreased with the increase in the rake angle and the cutting energy consumption was also reduced. The cutting power increased with the rotation speed of the main shaft and the depth of milling induced the impact resistance between the milling tool and particle board and the material removal rate. The p -values of the created models and input parameters were less than 0.05, which meant they were significant for cutting power and power efficiency. The depth of milling was the most important factor, followed by the rotation speed of the main shaft and then the rake angle. Due to the high values of R 2 of 0.9926 and 0.9946, the quadratic models were chosen for creating the relationship between the input parameters and response parameters. The predicted values of cutting power and power efficiency were close to the actual values, which meant the models could perform good predictions. To minimize the cutting power and maximize the power efficiency for the particle board, the optimized parameters obtained via the response surface methodology were 2°, 6991.7 rpm, 1.36 mm for rake angle, rotation speed of the main shaft and depth of milling, respectively. The model further predicted that the optimized parameters combination would achieve cutting power and power efficiency values of 52.4 W and 11.9%, respectively, with the desirability of 0.732. In this study, the influence of the input parameters on the cutting power and power efficiency are revealed and the created models were useful for selecting the milling parameters for particle boards, to reduce the cutting power.

Unsaturated polyester resin (UPR) with good chemical resistance, excellent mechanical properties, and formaldehyde-free shows great potentials in the wood industry. In this study, the mechanical strength, thermostability, dynamic thermomechanical property, and interfacial bonding of bamboo particle boards (BPBs) made from UPR adhesives with toluene diisocyanate (TDI) as the coupling agent were explored. The results showed that covalent bonds were formed among TDI, bamboo particles, and UPR, which could significantly enhance the mechanical strength. The internal bonding strength, modulus of elasticity, and modulus of rupture of treated BPBs were 1.36, 3010, and 19.6 MPa with the increment of 1250, 514, and 833%, respectively, compared to the control samples. Also, the thickness swelling rate of the BPB was 4.6%, much lower than that of the control, with a decrease of 92%. The thermostability of the treated BPB was also improved. As a result, the BPB using UPR as the adhesive and TDI as the coupling agent shows better usability, higher efficiency, and excellent mechanical strength., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

Temperature tolerance is an important trait from both an economic and evolutionary perspective in fish. Because of difficulties with measurements, genome-wide selection using quantitative trait loci (QTLs) affecting Upper temperature tolerance may be an alternative for genetic improvement. Turbot Scophthalmus maximus (L.) is a cold-water marine fish with high economic value in Europe and Asia. The genetic bases of upper temperature tolerance (UTTs) traits have been rarely studied. In this study, we constructed a genetic linkage map of turbot using simple sequence repeats (SSRs) and single nucleotide polymorphism (SNP) markers. A total of 190 SSR and 8,123 SNP were assigned to 22 linkage groups (LGs) of a consensus map, which spanned 3,648.29 cM of the turbot genome, with an average interval of 0.44 cM. Moreover, we re-anchored genome sequences, allowing 93.8% physical sequences to be clustered into 22 turbot pseudo-chromosomes. A high synteny was observed between two assemblies from the literature. QTL mapping and validation analysis identified thirteen QLTs which are major effect QTLs, of these, 206 linked SNP loci, and two linked SSR loci were considered to have significant QTL effects. Association analysis for UTTs with 129 QTL markers was performed for different families, results showed that eight SNP loci were significantly correlated with UTT, which markers could be helpful in selecting thermal tolerant breeds of turbot. 1,363 gene sequences were genomically annotated, and 26 QTL markers were annotated. We believe these genes could be valuable candidates affecting high temperatures, providing valuable genomic resources for the study of genetic mechanisms regulating thermal stress. Similarly, they may be used in marker-assisted selection (MAS) programs to improve turbot performance., (© 2021. The Author(s).)

Identifying biomarkers for hearing impairments (HIs) in patients with neonatal hypoxic-ischemic encephalopathy (HIE), to initialize early hearing habilitation, is crucial. Seventy-eight neonates with HIE were divided into the following two groups: those with HIs and those without HIs. We compared those patients with 11,837 newborns without HIE, and analyzed the risk factors of HIs among neonatal HIE. Of the 78 patients, 11 were confirmed to have an HI, which is a substantially higher percentage than in the 11,837 newborns without HIE (14.1% vs. 0.87%; p < 0.001). More patients with moderate-to-severe HIE had confirmed HIs ( p = 0.020; odds ratio, 8.61) than those with mild HIE. Clinical staging, and blood lactate and glucose levels could be predictive factors for HIs among patients with HIE. The patients who exhibited HIs had significantly higher lactate (104.8 ± 51.0 vs. 71.4 ± 48.4; U = 181, p = 0.032) and serum glucose (159.5 ± 86.1 vs. 112.1 ± 62.3; U = 166, p = 0.036) levels than those without HIs. A higher prevalence of HIs was noted in the patients with stage III HIE than those with stage II HIE (43.8% vs. 10%; p = 0.008). The degree of HI correlated with brain anomalies and neurodevelopmental outcomes at 1 year of age. Clinical staging, and blood lactate and glucose levels could be predictive factors for HIs among patients with HIE.

Background: Recurrent head and neck cancer has poor prognosis. Stereotactic body radiotherapy (SBRT) may improve outcomes by delivering ablative radiation doses., Methods: We reviewed patients who received definitive-intent SBRT reirradiation at our institution from 2013 to 2020. Patterns of failure, overall survival (OS), and toxicities were analyzed., Results: One hundred and thirty-seven patients were evaluated. The median OS was 44.3 months. The median SBRT dose was 45 Gy and median target volume 16.9 cc. The 1-year local, regional, and distant control was 78%, 66%, and 83%, respectively. Systemic therapy improved regional (p = 0.004) and distant control (p = 0.04) in nonmetastatic patients. Grade 3+ toxicities were more common at mucosal sites (p = 0.001) and with concurrent systemic therapy (p = 0.02)., Conclusions: In a large cohort of SBRT reirradiation for recurrent, small volume head and neck cancers, a median OS of 44.3 months was observed. Systemic therapy improved regional and distant control. Toxicities were modulated by anatomic site and systemic therapy., (© 2021 Wiley Periodicals LLC.)

Initial studies that described the novel coronavirus (COVID-19) reported increased morbidity and mortality in patients with cancer. Of this group, patients with hematologic malignancies (HM) had the highest disease severity and death rates. Subsequent studies have attempted to better describe how COVID-19 affects patients with HM. However, these studies have yielded variable and often contradictory results. We present our single-institution experience with patients with HM who were diagnosed with COVID-19 from March 2020 to March 2021. We report 62 total cases with 10 patients who died during this time. The overall mortality was 16.1%. Mortality during the first two waves of COVID was 27.8% and 25%. Mortality during the third wave of COVID was 10%. The median age of patients was 67 years (range 20-89 years). 55% of patients had lymphoid malignancies and the majority had active disease at the time of diagnosis with COVID-19. 87% of patients had more than one co-morbidity. Important co-morbidities included cardiovascular disease and smoking history. 38.7% of patients had asymptomatic or mild disease, 54.8% required hospitalization, and 17.5% required ICU level care. In patients who required ICU level care, the mortality was 60%., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Wang, Binder, Gergis and Wilde.)

Aluminum phosphate (AP) shows great potential to replace formaldehyde-based adhesives in the wood industry, except for its weak hygroscopic resistance and low wet bonding strength. This study chose PVA as an AP modifier to prepare a PVA-AP organic-inorganic hybrid adhesive (PAP). The preparation, bonding mechanism and heat resistant property of PAP were studied by using X-ray photoelectron spectroscopy (XPS), Fourier transforms infrared spectroscopy (FTIR), X-ray diffraction (XRD), thermogravimetry-differential scanning calorimetry (TG-DSC), nuclear magnetic resonance (NMR) and scanning electron microscopy (SEM). The result showed that covalent bonds between PVA and AP were built. The mechanical properties of PAP improved remarkably; the dry and wet bonding strength are 2.28 and 0.79 MPa with 15.2% and 690% increment, respectively, compared to the control samples. The thermostabilities of PAP and plywood samples were improved. In conclusion, PVA could effectively improve the hygroscopic resistance and low wet bonding strength of AP adhesives., Competing Interests: The authors declare no competing financial interest., (This journal is © The Royal Society of Chemistry.)