bluuebunny/crossref_metadata_2025_split huggingface dataset:
p53 partial loss-of-function mutations sensitize to chemotherapy
Authors: Klimovich Boris , Merle Nastasja , Neumann Michelle , Elmshäuser Sabrina , Nist Andrea , Mernberger Marco , Kazdal Daniel , Stenzinger Albrecht , Timofeev Oleg , Stiewe Thorsten 
Published: December 2021

AbstractThe tumor suppressive transcription factor p53 is frequently inactivated in cancer cells by missense mutations that cluster in the DNA binding domain. 30% hit mutational hotspot residues, resulting in a complete loss of transcriptional activity and mutant p53-driven chemotherapy resistance. Of the remaining 70% of non-hotspot mutants, many are partial loss-of-function (partial-LOF) mutants with residual transcriptional activity. The therapeutic consequences of a partial-LOF have remained largely elusive. Using a p53 mutation engineered to reduce DNA binding, we demonstrate that partial-LOF is sufficient to enhance oncogene-driven tumorigenesis in mouse models of lung and pancreatic ductal adenocarcinoma and acute myeloid leukemia. Interestingly, mouse and human tumors with partial-LOF mutations showed mutant p53 protein accumulation similar as known for hotspot mutants. Different from the chemotherapy resistance caused by p53-loss, the partial-LOF mutant sensitized to an apoptotic chemotherapy response and led to a survival benefit. Mechanistically, the pro-apoptotic transcriptional activity of mouse and human partial-LOF mutants was rescued at high mutant protein levels, suggesting that accumulation of partial-LOF mutants enables the observed apoptotic chemotherapy response. p53 non-hotspot mutants with partial-LOF, therefore, represent tumorigenic p53 mutations that need to be distinguished from other mutations because of their beneficial impact on survival in a therapy context.
CRISPR/Cas9 genome-wide screening identifies LUC7L2 that promotes radioresistance via autophagy in nasopharyngeal carcinoma cells
Authors: Shen Lin , Li Chao , Chen Fang , Shen Liangfang , Li Zhanzhan , Li Na 
Published: December 2021

AbstractRadioresistance emerges as the major obstacle to nasopharyngeal carcinoma (NPC) treatment, further understanding of underlying mechanisms is necessary to overcome the radioresistance and improve the therapeutic effect. In this study, we first identified a candidate radioresistant-related gene LUC7L2 via CRISPR/Cas9 high-throughput screening and quantitative proteomic approach. Overexpression of LUC7L2 in NPC cells promoted cell viability following exposure to ionizing radiation (IR), while knockdown of LUC7L2 significantly slowed down the DNA replication and impaired cell survival, sensitized NPC-radioresistant cells to IR. Using immunoprecipitation assay, we found SQSTM1, an autophagy receptor, was a potential binding partner of LUC7L2. Down-regulation of LUC7L2 in NPC-radioresistant cells led to reduction of SQSTM1 expression and enhancement of autophagy level. Furthermore, LUC7L2 knockdown in combination with autophagy inhibitor, chloroquine (CQ), resulted in more NPC-radioresistant cell death. Besides, LUC7L2 was obviously distributed in NPC tissues, and high LUC7L2 expression correlated with shorter survival in NPC patients. Our data suggest that LUC7L2 plays a huge part in regulating radioresistance of NPC cells, and serves as a promising therapeutic target in re-sensitizing NPC to radiotherapy.
TRAP1 inhibits MIC60 ubiquitination to mitigate the injury of cardiomyocytes and protect mitochondria in extracellular acidosis
Authors: Zhang Lingxiao , Su Ning , Luo Yuanyuan , Chen Siyin , Zhao Tongfeng 
Published: December 2021

AbstractExtracellular acidosis-induced mitochondrial damage of cardiomyocytes leads to cardiac dysfunction, but no detailed mechanism or efficient therapeutic target has been reported. Here we found that the protein levels of MIC60 were decreased in H9C2 cells and heart tissues in extracellular acidosis, which caused mitochondrial damage and cardiac dysfunction. Overexpression of MIC60 maintains H9C2 cells viability, increases ATP production and mitochondrial membrane potential, mitigates the disruptions of mitochondrial structure and cardiac injury. Mechanistically, extracellular acidosis excessively promoted MIC60 ubiquitin-dependent degradation. TRAP1 mitigated acidosis-induced mitochondrial impairments and cardiac injury by directly interacting with MIC60 to decrease its ubiquitin-dependent degradation in extracellular acidosis.
Comparing alternatives to the fixed degree sequence model for extracting the backbone of bipartite projections
Authors: Neal Zachary P. , Domagalski Rachel , Sagan Bruce 
Published: December 2021

AbstractProjections of bipartite or two-mode networks capture co-occurrences, and are used in diverse fields (e.g., ecology, economics, bibliometrics, politics) to represent unipartite networks. A key challenge in analyzing such networks is determining whether an observed number of co-occurrences between two nodes is significant, and therefore whether an edge exists between them. One approach, the fixed degree sequence model (FDSM), evaluates the significance of an edge’s weight by comparison to a null model in which the degree sequences of the original bipartite network are fixed. Although the FDSM is an intuitive null model, it is computationally expensive because it requires Monte Carlo simulation to estimate each edge’s p value, and therefore is impractical for large projections. In this paper, we explore four potential alternatives to FDSM: fixed fill model, fixed row model, fixed column model, and stochastic degree sequence model (SDSM). We compare these models to FDSM in terms of accuracy, speed, statistical power, similarity, and ability to recover known communities. We find that the computationally-fast SDSM offers a statistically conservative but close approximation of the computationally-impractical FDSM under a wide range of conditions, and that it correctly recovers a known community structure even when the signal is weak. Therefore, although each backbone model may have particular applications, we recommend SDSM for extracting the backbone of bipartite projections when FDSM is impractical.
Changes in proportionate cardiovascular mortality in patients with chronic infectious and inflammatory conditions in the United States, 1999–2018
Authors: Groenendyk Jacob W. , Rivera Adovich S. , Sinha Arjun , Lloyd-Jones Donald M. , Feinstein Matthew J. 
Published: December 2021

AbstractTreatment options for several chronic infectious and inflammatory conditions have expanded in recent years. This may have implications for evolving competing risks for chronic inflammation-associated comorbidities, including cardiovascular diseases (CVDs). Yet sparse data exist on patterns over time in cardiovascular mortality for chronic infectious and inflammatory conditions. We used data from the Centers for Disease Control and Prevention 1999–2018 Multiple Causes of Death database to investigate patterns in CVD mortality from January 1, 1999 to December 31, 2018 in several infectious and inflammatory conditions. Specifically, we determined age-adjusted proportionate CVD mortality separately for patients with the following conditions (as well as the general population): hepatitis C virus (HCV), human immunodeficiency virus (HIV), inflammatory bowel diseases (IBD), psoriasis (PSO), rheumatoid arthritis (RA), and systemic lupus erythematosus (SLE). Proportionate CVD mortality differed significantly in 1999 and 2018 for each condition compared with the general population (p < 0.0001). Proportionate CVD mortality decreased steadily in the general population (40.9 to 30.6%) but increased for patients with HCV (7.0 to 10.2%) and HIV (1.9 to 6.7%). For IBD, PSO, RA, and SLE, proportionate CVD mortality initially decreased followed by plateauing or increasing rates. Underlying disease-specific pathophysiologies, changes in natural history, and competing risks of chronic end-organ diseases contributing to these differences merit further study.
Impact of the SARS-CoV-2 pandemic on the course and treatment of appendicitis in the pediatric population
Authors: Pawelczyk Alicja , Kowalska Malgorzata , Tylicka Marzena , Koper-Lenkiewicz Olga Martyna , Komarowska Marta Diana , Hermanowicz Adam , Debek Wojciech , Matuszczak Ewa 
Published: December 2021

AbstractSARS-CoV-2 is a highly contagious virus causing mainly respiratory track disease called COVID-19, which dissemination in the whole world in the 2020 has resulted in World Health Organisation (WHO) announcing the pandemic. As a consequence Polish Government made a decision to go into a lockdown in order to secure the population against SARS-CoV-2 outbreak what had its major influence on the Polish Health Care System. All of the social and medical factors caused by the pandemic might influence children’s health care, including urgent cases. The aim of this survey was the analysis of medical charts with focus on the course and results of surgical treatment of children who underwent appendectomy before and during the COVID-19 pandemic. Material and methods: We performed analysis of charts of 365 subjects hospitalized in the Pediatric Surgery Department from 1st January 2019 to 31st December 2020 because of acute appendicitis. Patients were divided into two groups—those treated in 2019—before pandemic outbreak, and those treated in 2020 in the course of pandemic. Results: the most common type of appendicitis was phlegmonous (61% of cases in 2019 and 51% of cases in 2020). Followed by diffuse purulent peritonitis (18% of cases in 2019 vs 31% of cases in 2020), gangrenous (19% of cases in 2019 vs 15% of cases in 2020) and simple superficial appendicitis (1% of cases in 2019 vs 3% of cases in 2020). There was statistically significant difference in the length of hospitalization: in 2019 the mean length of hospi-talization was 4.761 vs 5.634 in 2020. Laparoscopic appendectomy was performed more frequently before the COVID period (63% of cases treated in 2019 vs 61% of cases treated in 2020). In the pandemic year 2020, there was double increase in the number of conversion from the laparoscopic approach to the classic open surgery. In the year 2019 drainage of abdominal cavity was necessary in 22% of patients treated with appendectomy, in 2020 the amount of cases threated with appendectomy and drainage increased to 32%. Conclusions: fear of being infected, the limited availability of appointments at General Practitioners and the new organisation of the medical health care system during pandemic, delay proper diagnosis of appendicitis. Forementioned delay leads to higher number of complicated cases treated with open appendectomy and drainage of abdominal cavity, higher number of conversions from the laparoscopic to classic open technique, and longer hospitalization of children treated with appendectomy in the year of pandemic.
Uncovering drug repurposing candidates for head and neck cancers: insights from systematic pharmacogenomics data analysis
Authors: Chai Annie Wai Yeeng , Tan Aik Choon , Cheong Sok Ching 
Published: December 2021

AbstractEffective treatment options for head and neck squamous cell carcinoma (HNSCC) are currently lacking. We exploited the drug response and genomic data of the 28 HNSCC cell lines, screened with 4,518 compounds, from the PRISM repurposing dataset to uncover repurposing drug candidates for HNSCC. A total of 886 active compounds, comprising of 418 targeted cancer, 404 non-oncology, and 64 chemotherapy compounds were identified for HNSCC. Top classes of mechanism of action amongst targeted cancer compounds included PI3K/AKT/MTOR, EGFR, and HDAC inhibitors. We have shortlisted 36 compounds with enriched killing activities for repurposing in HNSCC. The integrative analysis confirmed that the average expression of EGFR ligands (AREG, EREG, HBEGF, TGFA, and EPGN) is associated with osimertinib sensitivity. Novel putative biomarkers of response including those involved in immune signalling and cell cycle were found to be associated with sensitivity and resistance to MEK inhibitors respectively. We have also developed an RShiny webpage facilitating interactive visualization to fuel further hypothesis generation for drug repurposing in HNSCC. Our study provides a rich reference database of HNSCC drug sensitivity profiles, affording an opportunity to explore potential biomarkers of response in prioritized drug candidates. Our approach could also reveal insights for drug repurposing in other cancers.
Optimization of critical parameters for coating of polymeric nanoparticles with plasma membrane vesicles by sonication
Authors: Yang Feipeng , Cabe Maleen H. , Ogle Sean D. , Sanchez Veronica , Langert Kelly A. 
Published: December 2021

AbstractTop-down functionalization of nanoparticles with cellular membranes imparts nanoparticles with enhanced bio-interfacing capabilities. Initial methods for membrane coating involved physical co-extrusion of nanoparticles and membrane vesicles through a porous membrane; however, recent works employ sonication as the disruptive force to reform membranes around the surface of nanoparticles. Although sonication is widely used, there remains a paucity of information on the effects of sonication variables on coating efficiency, leading to inconsistent membrane coating across studies. In this work, we present a systematic analysis of the sonication parameters that influence the membrane coating. The results showed that sonication amplitude, time, temperature, membrane ratio, sample volume, and density need to be considered in order to optimize membrane coating of polymeric nanoparticles.
Relativistic Coulomb screening in pulsational pair instability supernovae
Authors: Famiano M. A. , Mori K. , Balantekin A. B. , Kajino T. , Kusakabe M. , Mathews G. 
Published: December 2021

Context.Pulsational pair-instability supernovae (PPISNe) and pair instability supernovae (PISNe) are the result of a thermonuclear runaway in the presence of a background electron-positron pair plasma. As such, their evolution and resultant black hole masses could possibly be affected by screening corrections due to the electron pair plasma.Aims.The sensitivity of PISNe and PPISNe to relativistic weak screening has been explored.Methods.In this paper a weak screening model that includes effects from relativistic pair production has been developed and applied at temperatures approaching and exceeding the threshold for pair production. This screening model replaces “classical” screening commonly used in astrophysics. Modifications to the weak screening electron Debye length were incorporated in a computationally tractable analytic form.Results.In PPISNe the BH masses were found to increase somewhat at high temperatures, though this increase is small. The BH collapse is also found to occur at earlier times, and the pulsational morphology also changes. In addition to the resultant BH mass, the sensitivity to the screening model of the pulsational period, the pulse structure, the PPISN-to-PISN transition, and the shift in the BH mass gap has been analyzed. The dependence of the composition of the ejected mass was also examined.
Ability of ergonomic timeout to reduce musculoskeletal discomfort related to fluoroscopic endoscopy
Authors: Hori Yasuki , Nagai Taisei , Hayashi Kazuki , Izumi Hiroyuki , Yokoyama Kiyoko , Ebara Takeshi 
Published: December 2021

AbstractEndoscopists performing fluoroscopy procedures often suffer from musculoskeletal disorders (MSDs) due to persistent static muscle contraction and the load imposed by radiation personal protective equipment. We devised the “practical load-on-the-shoulders releasing technique” (PoRT), integrated it within the work-rest schedule, and investigated its ability to reduce muscular discomfort. The results showed that PoRT lowered discomfort, including by maintaining the head angle closer to the neutral position and keeping the trunk in a stable state, which together resulted in an ideal posture. As a simple, no-cost intervention based on an ergonomic approach, PoRT may contribute to reducing MSDs.
Complicações funcionais do tratamento da instabilidade patelar com reconstrução do ligamento femoropatelar medial com terço medial do tendão patelar com acompanhamento mínimo de 5 anos
Authors: Camanho Gilberto Luis , Gobbi Riccardo Gomes , Andrade Marta Halasz de 
Published: December 2021

Resumo
Objetivo Avaliar complicações maiores após um mínimo de 5 anos de acompanhamento após luxação aguda ou recidivante da patela tratada com reconstrução do ligamento femoropatelar medial (LFPM) com terço medial do tendão patelar, com ou sem medialização da tuberosidade anterior da tíbia (TAT) associada.
Métodos Um total de 50 pacientes foram incluídos, com acompanhamento mínimo de 5 anos. Os pacientes foram avaliados em relação à ocorrência de complicações como rigidez articular, recidiva de luxação patelar ou instabilidade subjetiva relatada pelos pacientes, e incapacidade de retorno ao nível prévio de atividades físicas.
Resultados O acompanhamento médio foi de 8,9 ± 2,6 anos, com mínimo de 6 e máximo de 15 anos; 64% dos pacientes eram mulheres, com média de idade de 27 ± 11,2 anos; 24% dos pacientes foram submetidos a osteotomia da TAT para medialização concomitantemente; e 46% eram casos agudos. Foram constatados apenas 9 maus resultados (18%), todos decorrentes de recidiva da luxação (12%) e de queixa de instabilidade subjetiva (6%), ocorridos entre 36 e 60 meses de acompanhamento. Não ocorreram outras complicações. Dentre os maus resultados, cinco ocorreram em casos de luxação aguda, e quatro em casos recidivantes, e apenas um havia sido submetido a osteotomia da TAT.
Conclusão A reconstrução do LFPM com terço medial do tendão patelar, associada ou não à osteotomia de medialização da TAT, é uma alternativa no tratamento da instabilidade patelar aguda ou crônica, com falha de apenas 18% em acompanhamento mínimo de 5 anos. Além disso, é um tratamento seguro, sem apresentar outras complicações.
Avaliação da confiabilidade e reprodutibilidade da classificação de Roussouly para os tipos de lordose lombar
Authors: Yamazato Camila Oda , Ribeiro Gustavo , Paula Fabio Chaud de , Soares Ramon Oliveira , Cruz Paulo Santa , Kanas Michel 
Published: December 2021

Resumo
Objetivo Determinar a confiabilidade e reprodutibilidade intra- e interavaliadores da classificação dos tipos de lordose lombar de Roussouly.
Métodos Foram utilizadas 104 radiografias panorâmicas da coluna vertebral em incidência de perfil, de banco de dados, de indivíduos do sexo masculino com idade entre 18 e 40 anos. Utilizando o software Surgimap (Nemaris Inc., Nova York, NY, EUA), seis examinadores com diferentes níveis de experiência aferiram os ângulos espinopélvicos e classificaram o tipo de lordose de acordo com a classificação de Roussouly. Após um intervalo de 1 mês, as mensurações foram realizadas novamente, sendo calculadas as concordâncias intra- e interavaliadores através do teste Kappa de Fleiss.
Resultados O estudo demonstrou evidências positivas em relação à reprodutibilidade da classificação de Roussouly, com teste Kappa de Fleiss para concordância intra-avaliador entre razoável à quase perfeita (0,307–0,827), e interavaliador entre moderada (0,43) e razoável (0,369). Os examinadores mais experientes apresentaram maior concordância interavaliador, variando entre substancial (0,619) e moderada (0,439).
Conclusão A classificação de Roussouly, demonstrou boa confiabilidade e reprodutibilidade, tendo em vista que a concordância intra- e interavaliadores foi considerada no mínimo razoável, podendo atingir os níveis de substanciais à quase perfeitos em algumas situações. Os avaliadores com maior nível de experiência apresentaram maior concordância intra- e interavaliadores.
Mining the Twittersphere: Insights about Public Interest in Facial Reanimation Surgery from a Decade of Twitter Data
Authors: Rudy Hayeem L. , Ricci Joseph A. 
Published: December 2021

Abstract
Background With 500 million tweets posted daily, Twitter can provide valuable insights about public discourse surrounding niche topics, such as facial paralysis surgery. This study aims to describe public interest on Twitter relating to facial paralysis and facial reanimation surgery over the last decade.
Methods Tweets containing the keywords “facial paralysis” and “Bell's palsy” posted between January 1, 2009, and January 1, 2019, were collected using Twitter Scraper. Tweets were screened by keywords relating to facial paralysis, and usage of these terms trended over time. Logistic regression was used to identify correlations between the quantity of publications per year and these terms posted on Twitter.
Results 32,880 tweets were made during the study period, with no significant difference in the number of tweets per year. A very strong (r = 0.8–1.0) positive correlation was found between time and frequency of the term “plastic surgery” and “transfer” (p < 0.05). A strong (r = 0.60–0.79) correlation was found between time and frequency for the following terms: “facial reanimation,” “gracilis,” “masseter,” “plastics,” “transplant” (p < 0.05). A total of 619 studies with the keyword “facial reanimation” were published in PubMed within the study period. A very strong, positive correlation between publications per year and frequency was found for the terms “plastic surgery,” “function” and “esthetic,” and a strong, positive correlation was found for the “plastics,” “transplant,” “Botox,” “surgery,” “cosmetic,” “aesthetic” and “injection” (p < 0.05).
Conclusions An increasing number of discussion about facial paralysis on Twitter correlates with increased publications and likely surgeon discourse on facial reanimation surgery, driving public interest.
Elevated Levels of Urinary Biomarkers TIMP-2 and IGFBP-7 Predict Acute Kidney Injury in Neonates after Congenital Heart Surgery
Authors: Ramírez Michelle , Chakravarti Sujata , Busovsky-McNeal Melissa , McKinstry Jaclyn , Al-qaqaa Yasir , Sahulee Raj , Kumar T.K. Susheel , Li Xiaochun , Goldberg Judith D. , Gefen Ashley M. , Malaga-Dieguez Laura 
Published: December 2021

Abstract
Objectives This article investigated the utility of urine biomarkers tissue inhibitor of metalloproteinase-2 (TIMP-2) and insulin-like growth factor binding protein-7 (IGFBP-7) in identifying acute kidney injury (AKI) in neonates after congenital heart surgery (CHS). TIMP-2 and IGFBP-7 are cell cycle arrest proteins detected in urine during periods of kidney stress/injury.
Methods We conducted a single-center, prospective study between September 2017 and May 2019 with neonates undergoing CHS requiring cardiopulmonary bypass (CPB). Urine samples were analyzed using NephroCheck prior to surgery and 6, 12, 24, and 96 hours post-CPB. All patients were evaluated using the Acute Kidney Injury Network (AKIN) criteria. Wilcoxon rank sum tests were used to compare the medians of the [TIMP-2*IGFBP-7] values in the AKIN negative and positive groups at each time point. Receiver operating characteristic curves were used to measure how well the [TIMP-2*IGFBP-7] values predict AKIN status.
Results Thirty-six patients were included. No patients met the AKIN criteria for AKI preoperatively. Postoperatively, 19 patients (53%) met the AKIN criteria for AKI diagnosis: 13 (36%) stage 1, 5 (14%) stage 2, and 1 (3%) stage 3. None required renal replacement therapy. At the 24-hour time points, patients who met the AKIN criteria for AKI had a statistically significantly higher [TIMP-2*IGFBP7] values than the patients without AKI (1.1 vs. 0.27 [ng/mL]2/1,000) at 24 hours (adj-p = 0.0019).
Conclusion AKI is a serious complication associated with adverse outcomes in patients undergoing cardiac surgery. [TIMP-2*IGFBP-7] urinary level 24 hours after CPB is a good predictor of AKI in this population.