bluuebunny/crossref_metadata_2025 huggingface dataset:
Immunological Role of TP53 Somatic Mutation Classification in Human Cancers
Authors: Fang Jianfei , Yang Ying , Xie Lina , Yin Wenjuan
Published: February 2023

Background. TP53 is a very common tumor suppressor gene and has implicated in various cancers. A systematic immunological analysis of TP53 somatic mutation classification in multiple cancers is still lacking. Methods. To assess the immunological value of TP53 somatic mutation classification in various cancers, we integrated a series of bioinformatics methods to analyze the role of TP53 gene across the public databases, such as UCSC Xena, Cancer Cell Line Encyclopedia (CCLE), Ensembl, and Genotype−Tissue Expression (GTEx). Results. The results revealed that the TP53 expression level had significant difference in tumor tissues and normal tissues, and it had a high expression level in most malignant tumors. Moreover, the missense mutation is the most common type of TP53 mutation in most cancers. In addition, the Cox proportional hazards model analysis and Kaplan−Meier (KM) survival analysis demonstrated that the TP53 expression is a high-risk factor in brain lower-grade glioma (LGG), prostate adenocarcinoma (PRAD), and uterine carcinosarcoma (UCS), which is opposite in uterine corpus endometrial carcinoma (UCEC). Besides, compared to the TP53 nontruncating mutation classification samples, we found that TP53 truncating mutation samples had lower TP53 expression levels in certain types of cancer. Notably, TP53 was associated with the mismatch repair (MMR) gene in some cancers which contained truncating or nontruncating mutation. Based on the classification of truncating or nontruncating mutation, we also discovered that TP53 expression was positively or negatively correlated with the immune score, stromal score, and the levels of immune cell infiltration in different cancers. Conclusions. Our research reveals an overarching landscape of immunological value on TP53 status in various malignant tumors. According to our results, we demonstrate that TP53 also plays an immunological role in various cancers.
Development and Validation of a Prognostic Signature Based on the Lysine Crotonylation Regulators in Head and Neck Squamous Cell Carcinoma
Authors: Jiang Linlin , Yin Xiteng , Zhang Hongbo , Zhang Xinyu , Cao Zichen , Zhou Meng , Xu Wenguang
Published: February 2023

Background. Lysine crotonylation (Kcr) is a newly identified posttranslational modification type regulated by various enzymes and coenzymes, including lysine crotonyltransferase, lysine decrotonylase, and binding proteins. However, the role of Kcr regulators in head and neck squamous cell carcinoma (HNSCC) remains unknown. The aim of this study was to establish and validate a Kcr‐related prognostic signature of HNSCC and to assess the clinical predictive value of this signature. Methods. The mRNA expression profiles and clinicopathological data from The Cancer Genome Atlas (TCGA) database were downloaded to explore the clinical significance and prognostic value of these regulators in HNSCC. The least absolute shrinkage and selection operator (LASSO) Cox regression model was used to generate the Kcr‐related prognostic signature for HNSCC. Subsequently, the GSE65858 dataset from the Gene Expression Omnibus (GEO) database was used to validate the signature. The prognostic value of the signature was evaluated using the Kaplan‐Meier survival, receiver operating characteristic (ROC) curve, and univariate and multivariate Cox regression analyses. Results. We established a nine‐gene risk signature associated with the prognosis of HNSCC based on Kcr regulators. High‐risk patients demonstrated significantly poorer overall survival (OS) than low‐risk patients in the training (TCGA) and validation (GEO) datasets. Then, the time‐dependent receiver operating characteristic (ROC) curve analysis showed that the nine‐gene risk signature was more accurate for predicting the 5‐year OS than other clinical parameters, including age, gender, T stage, N stage, and histologic grade in the TCGA and GEO datasets. Moreover, the Cox regression analysis showed that the constructed risk signature was an independent risk factor for HNSCC. Conclusion. Our study identified and validated a nine‐gene signature for HNSCC based on Kcr regulators. These results might contribute to prognosis stratification and treatment escalation for HNSCC patients.
Association of Anemia with Parathyroid Hormone Levels and Other Factors in Patients with End-Stage Renal Disease Undergoing Hemodialysis: A Cross-Sectional, Real-World Data Study in Pakistan
Authors: Bukhari Humera , Ahmad Aneeqa , Noorin Amna , Khan Aimal , Mushtaq Mehwish , Naeem Aamir , Iqbal Muhammad Rashid , Naureen Faiza , Shah Yasar , Qayyum Ahad , Munib Syed , Azhar Amer , Ullah Farman , Khan Faris Farooq Saeed
Published: February 2023

End-stage renal disease (ESRD) patients are mostly managed with maintenance hemodialysis (MHD). ESRD patients on MHD also present with many complications, such as anemia, hyperparathyroidism, and hepatitis prevalence. This study depicts the real-world scenario of anemia among MHD and end-stage renal disease patients in the Pakistani population. A retrospective, multicentric, and real-world data analytical study was conducted at 4 dialysis centers in Pakistan. The study had a sample size of n = 342 patients on maintenance hemodialysis. The data were gathered from the medical records of patients. Data analysis was performed using STATA Version 16. Statistical significance was gauged at a 0.05 level of significance. According to our results, the mean age of the patients was 45 (±15) years. Most of the patients were male (n = 234, 68.4%), whereas 58.1% of the patients were maintained on twice-weekly hemodialysis. The most commonly reported comorbidities were hypertension and diabetes mellitus. The frequency of dialysis (P < 0.01) and comorbidities (P = 0.009) had a significant association with anemia in MHD patients. The majority of the patients had hyperparathyroidism (52%) with anemia. Upon performing binary logistic regression, multivariate analysis displayed a similar odds value for having anemia in patients with every additional month in the duration of hemodialysis (OR 1.01,P = 0.001), the odds of anemic patients having a positive antihepatitis-C antibody (OR 2.22,P = 0.013), and the odds of having anemia in patients in the age category below 45 years (OR 1.93,P = 0.013). In conclusion, the study results depict that every additional month in the duration of hemodialysis, age (<45 years), and positive anti-HCV antibody status, these variables were more likely to have anemia in our study MHD patients. While in our final multivariate model, no statistically significant association was observed between hyperparathyroidism and anemia.
Men’s Lived Experiences of Breast Cancer and Changes in Occupation
Authors: Potter Ann Marie , Bentz Breanne , Crue Lindsay , Leiby Stephanie , Bashi Sogand , Maguire Kaitlin , Meyers Jacob , Mieczkowski Kelsey
Published: February 2023

Introduction. Male breast cancer is rare and frequently diagnosed at later stages of disease with low survival rates. There is a lack of knowledge of how breast cancer impacts men’s occupations. Objectives. This study is aimed at understanding the lived experiences of men with breast cancer and their changes in occupation. Methodology. Twenty-four men with breast cancer participated in semistructured phone interviews. Data was open-coded and analyzed for themes. Findings. The six major themes are as follows: (1) death as a reality, (2) unique personal insights, (3) social environment, (4) interactions with the healthcare system, (5) decreased engagement in occupations, and (6) finding meaning in new occupations. Conclusion. The healthcare team can improve the patient experience by discussing and responding to the client’s experience throughout the diagnosis, intervention, and survival continuum. The scope of occupational therapy is well suited to address the needs of men with breast cancer to maintain optimal levels of functioning.
Single-Cell Discovery and Multiomic Characterization of Therapeutic Targets in Multiple Myeloma
Authors: Yao Lijun , Wang Julia T. , Jayasinghe Reyka G. , O'Neal Julie , Tsai Chia-Feng , Rettig Michael P. , Song Yizhe , Liu Ruiyang , Zhao Yanyan , Ibrahim Omar M. , Fiala Mark A. , Fortier Julie M. , Chen Siqi , Gehrs Leah , Rodrigues Fernanda Martins , Wendl Michael C. , Kohnen Daniel , Shinkle Andrew , Cao Song , Foltz Steven M. , Zhou Daniel Cui , Storrs Erik , Wyczalkowski Matthew A. , Mani Smrithi , Goldsmith Scott R. , Zhu Ying , Hamilton Mark , Liu Tao , Chen Feng , Vij Ravi , Ding Li , DiPersio John F.
Published: February 2023

Multiple myeloma (MM) is a highly refractory hematologic cancer. Targeted immunotherapy has shown promise in MM but remains hindered by the challenge of identifying specific yet broadly representative tumor markers. We analyzed 53 bone marrow (BM) aspirates from 41 MM patients using an unbiased, high-throughput pipeline for therapeutic target discovery via single-cell transcriptomic profiling, yielding 38 MM marker genes encoding cell-surface proteins and 15 encoding intracellular proteins. Of these, 20 candidate genes were highlighted that are not yet under clinical study, 11 of which were previously uncharacterized as therapeutic targets. The findings were cross-validated using bulk RNA sequencing, flow cytometry, and proteomic mass spectrometry of MM cell lines and patient BM, demonstrating high overall concordance across data types. Independent discovery using bulk RNA sequencing reiterated top candidates, further affirming the ability of single-cell transcriptomics to accurately capture marker expression despite limitations in sample size or sequencing depth. Target dynamics and heterogeneity were further examined using both transcriptomic and immuno-imaging methods. In summary, this study presents a robust and broadly applicable strategy for identifying tumor markers to better inform the development of targeted cancer therapy.

Significance:

Single-cell transcriptomic profiling and multiomic cross-validation to uncover therapeutic targets identifies 38 myeloma marker genes, including 11 transcribing surface proteins with previously uncharacterized potential for targeted antitumor therapy.
Application of Novel Breast Biospecimen Cell-Type Adjustment Identifies Shared DNA Methylation Alterations in Breast Tissue and Milk with Breast Cancer–Risk Factors
Authors: Muse Meghan E. , Carroll Connolly D. , Salas Lucas A. , Karagas Margaret R. , Christensen Brock C.
Published: February 2023

Background:

DNA methylation patterning is cell-type–specific and altered DNA methylation is well established to occur early in breast carcinogenesis, affecting non-cancerous, histopathologically normal breast tissue. Previous work assessing risk factor–associated alterations to DNA methylation in breast tissue has been limited, with even less published research in breast milk, a noninvasively obtained biospecimen containing sloughed mammary epithelial cells that may identify early alterations indicative of cancer risk.

Methods:

Here, we present a novel library for the estimation of the cellular composition of breast tissue and milk and subsequent assessment of cell-type–independent alterations to DNA methylation associated with established breast cancer–risk factors in solid breast tissue (n = 95) and breast milk (n = 48) samples using genome-scale DNA methylation measures from the Illumina HumanMethylation450 array.

Results:

We identified 772 hypermethylated CpGs (P < 0.01) associated with age consistent between breast tissue and breast milk samples. Age-associated hypermethylated CpG loci were significantly enriched for CpG island shore regions known to be important for regulating gene expression. Among the overlapping hypermethylated loci mapping to genes, a differentially methylated region was identified in the promoter region of SFRP2, a gene observed to undergo promoter hypermethylation in breast cancer.

Conclusions:

Our findings suggest the potential to identify epigenetic biomarkers of breast cancer risk in noninvasively obtained, tissue-specific breast milk specimens.

Impact:

This work demonstrates the potential of using breast milk as a noninvasive biomarker of breast cancer risk, improving our ability to detect early-stage disease and lowering the overall disease burden.
Cell-Free Urine and Plasma DNA Mutational Analysis Predicts Neoadjuvant Chemotherapy Response and Outcome in Patients with Muscle-Invasive Bladder Cancer
Authors: Christensen Emil , Nordentoft Iver , Birkenkamp-Demtröder Karin , Elbæk Sara K. , Lindskrog Sia V. , Taber Ann , Andreasen Tine G. , Strandgaard Trine , Knudsen Michael , Lamy Philippe , Agerbæk Mads , Jensen Jørgen B. , Dyrskjøt Lars
Published: February 2023

Purpose:

To investigate the use of plasma and urine DNA mutation analysis for predicting neoadjuvant chemotherapy (NAC) response and oncological outcome in patients with muscle-invasive bladder cancer.

Experimental Design:

Whole-exome sequencing of tumor and germline DNA was performed for 92 patients treated with NAC followed by radical cystectomy (RC). A custom NGS-panel capturing approximately 50 mutations per patient was designed and used to track mutated tumor DNA in plasma and urine. A total of 447 plasma samples, 281 urine supernatants, and 123 urine pellets collected before, during, and after treatment were analyzed. Patients were enrolled from 2013 to 2019, with a median follow-up time of 41.3 months after RC.

Results:

We identified tumor DNA before NAC in 89% of urine supernatants, 85% of urine pellets, and 43% of plasma samples. Tumor DNA levels were higher in urine supernatants and urine pellets compared with plasma samples (P < 0.001). In plasma, detection of circulating tumor DNA (ctDNA) before NAC was associated with a lower NAC response rate (P < 0.001). Detection of tumor DNA after NAC was associated with lower response rates in plasma, urine supernatant, and urine pellet (P < 0.001, P = 0.03, P = 0.002). Tumor DNA dynamics during NAC was predictive of NAC response and outcome in urine supernatant and plasma (P = 0.006 and P = 0.002). A combined measure from plasma and urine supernatant tumor DNA dynamics stratified patients by outcome (P = 0.003).

Conclusions:

Analysis of tumor DNA in plasma and urine samples both separately and combined has a potential to predict treatment response and outcome.
Identification ofIGF2as Genomic Driver and Actionable Therapeutic Target in Hepatoblastoma
Authors: Abril-Fornaguera Jordi , Torrens Laura , Andreu-Oller Carmen , Carrillo-Reixach Juan , Rialdi Alex , Balaseviciute Ugne , Pinyol Roser , Montironi Carla , Haber Philipp K. , Del Río-Álvarez Álvaro , Domingo-Sàbat Montserrat , Royo Laura , Akers Nicholas K. , Willoughby Catherine E. , Peix Judit , Torres-Martin Miguel , Puigvehi Marc , Cairo Stefano , Childs Margaret , Maibach Rudolf , Alaggio Rita , Czauderna Piotr , Morland Bruce , Losic Bojan , Mazzaferro Vincenzo , Guccione Ernesto , Sia Daniela , Armengol Carolina , Llovet Josep M.
Published: February 2023

Management of hepatoblastoma (HB), the most frequent pediatric liver cancer, is based on surgical resection and perioperative chemotherapy regimens. In this study, we aimed to identify actionable targets in HB and assess the efficacy of molecular therapies in preclinical models of HB. Paired tumor and adjacent tissues from 31 HBs and a validation set of 50 HBs were analyzed using RNA-seq, SNP, and methylation arrays. IGF2 overexpression was identified as the top targetable HB driver, present in 71% of HBs (22/31). IGF2high tumors displayed progenitor cell features and shorter recurrence-free survival. IGF2 overexpression was associated in 91% of cases with fetal promoter hypomethylation, ICR1 deregulation, 11p15.5 loss of heterozygosity or miR483-5p overexpression. The antitumor effect of xentuzumab (a monoclonal antibody targeting IGF1/2) alone or in combination with the conventional therapeutic agent cisplatin was assessed in HB cell lines, in PDX-derived HB organoids and in a xenograft HB murine model. The combination of xentuzumab with cisplatin showed strong synergistic antitumor effects in organoids and in IGF2high cell lines. In mice (n = 55), the combination induced a significant decrease in tumor volume and improved survival compared with cisplatin alone. These results suggest that IGF2 is an HB actionable driver and that, in preclinical models of HB, the combination of IGF1/2 inhibition with cisplatin induces superior antitumor effects than cisplatin monotherapy. Overall, our study provides a rationale for testing IGF2 inhibitors in combination with cisplatin in HB patients with IGF2 overexpression.
Inhibition of LILRB2 by a Novel Blocking Antibody Designed to Reprogram Immunosuppressive Macrophages to Drive T-Cell Activation in Tumors
Authors: Umiker Ben , Hashambhoy-Ramsay Yasmin , Smith Jeff , Rahman Tanzila , Mueller Amy , Davidson Rachel , Meyer Christina , Patankar Gayatri , Alam Mohammad Murshid , Jaffe Sarah , Krukenberg Kristin , Goodman Allison , Spaulding Vikki , Priess Michelle , Dhaneshwar Abha , Wong Masie , Diiorio Alexa , O'Malley Kristin , McGrath Lara , Willer Margaret , Pepper Lauren , Gostissa Monica , Kis-Toth Katalin , Wiederschain Dmitri , Cohen Heather , Shaffer Donald R.
Published: February 2023

Tumor-associated macrophages (TAM) play an important role in maintaining the immunosuppressive state of the tumor microenvironment (TME). High levels of CD163+ TAMs specifically are associated with poor prognosis in many solid tumor types. Targeting TAMs may represent a key approach in development of the next generation of cancer immune therapeutics. Members of the leukocyte immunoglobulin-like receptor B (LILRB) family, including LILRB2 (ILT4), are known to transmit inhibitory signals in macrophages and other myeloid cells. Leveraging bulk and single cell RNA-sequencing datasets, as well as extensive immunophenotyping of human tumors, we found that LILRB2 is highly expressed on CD163+ CD11b+ cells in the TME and that LILRB2 expression correlates with CD163 expression across many tumor types. To target LILRB2, we have developed JTX-8064, a highly potent and selective antagonistic mAb. JTX-8064 blocks LILRB2 binding to its cognate ligands, including classical and nonclassical MHC molecules. In vitro, JTX-8064 drives the polarization of human macrophages and dendritic cells toward an immunostimulatory phenotype. As a result, human macrophages treated with a LILRB2 blocker are reprogrammed to increase the activation of autologous T cells in co-culture systems. Furthermore, JTX-8064 significantly potentiates the activity of anti-PD-1 in allogeneic mixed lymphocyte reaction. In a human tumor explant culture, pharmacodynamic activity of JTX-8064 was observed in monotherapy and in combination with anti-PD-1. Collectively, our work provides strong translational and preclinical rationale to target LILRB2 in cancer.
Point of Care Ultrasound Training in Nephrology: Twitter Poll as a Modern Tool for Development of an Effective Curriculum
Authors: Vasudev Krish , Kazory Amir , Ronco Claudio , Bhattacharya Deepti , Koratala Abhilash
Published: February 2023

Introduction: Point of care ultrasonography (POCUS) is being increasingly recognized as an adjunct to physical examination in the field of nephrology. However, paucity of trained faculty and standardized curricula remain key barriers to widespread adoption of this skill as well as development of reliable quality assessment programs at the institutional level. Herein, we sought to explore the utility of Twitter polls to gain insights into knowledge deficits of the learners for making curricular improvements while simultaneously disseminating POCUS pearls and pitfalls. Methods: A series of 57 single-question polls were tweeted over a 12-month period, each containing an ultrasound image or a video asking for correct interpretation. These were sent out from the Twitter handle of NephroPOCUS.com (@NephroP), an online POCUS education tool. The answer and a brief explanation were shared in a subsequent tweet at the end of the voting period. Information on the percentage of correct answers, Tweet impressions, and engagements was collected and analyzed by the pre-determined difficulty level (I-III) and the organ/learning objective being tested. Results: The number of responses per poll was 228 ± 94.6 (mean ± SD), and the percentage of correct responses was 57.9 ± 17.5 (mean ± SD). 16 (of 57) polls received less than 50% correct responses, of which 8 belonged to level III difficulty. The learning objectives that received the least number of correct responses in the kidney, cardiac, lung, vascular, and other categories were identification of end-stage kidney (16.2% correct answers), right pleural effusion on the parasternal short axis view of the heart (29%), right pleural effusion from the subxiphoid window (39%), grading of systemic venous congestion (27.3%), and identification of ascites on the right lateral chest window (15%), respectively. The overall engagement rate was 6.96%, which was above the median for health and higher education-related tweets on Twitter. Targeted didactic material was developed based on these results, published on various open-access nephrology education platforms. Conclusions: Twitter polls aid in identifying the knowledge gaps among POCUS learners. Information obtained from the polls can be used to improve POCUS-related curricula and develop targeted educational material to facilitate remote learning.
Análise de projetos e engajamento de partes interessadas em obras de saneamento: estudo de caso
Authors: Wyse Mariana , Nascimento Guilherme Caetano do , Blanco Fernando , Borges Fernanda Varella , Pedrotti Flavia Sartorato
Published: February 2023

Obras de infraestrutura têm características de complexidade, multidisciplinaridade de projetos e grande quantidade de partes interessadas, aumentando sua sofisticação, necessidade de integração, variáveis e incertezas. Diversos referenciais apontam como causa de falhas em obras a qualidade deficitária do projeto-design, gerando atrasos e retrabalhos e falha no engajamento das partes interessadas. A legislação vigente não contempla com clareza requisitos mínimos para licitações públicas de projetos específicos de saneamento e se observa a falta de equipe preparada para análises técnicas específicas. Ao mesmo tempo, a influência de diversas partes interessadas é fundamental neste contexto frente à análise e detalhamento de soluções. Buscando avaliar a suficiência de informações em projetos praticada atualmente no setor face àquilo considerado necessário e o engajamento das partes interessadas no processo, o presente trabalho realizou estudo de caso em 21 empreendimentos de saneamento em 18 cidades e 3 distritos do interior do Estado de São Paulo, e analisou-os conforme metodologia qualiquantitativa. Os resultados apontam insuficiência de informações sugerindo qualidade deficitária dos projetos, destacando as disciplinas de Serviços de Campo, Projeto Executivo e Concepção como mais críticas. Foram mapeadas as partes interessadas recorrentes e foi verificado como ocorre e como deveria ocorrer seu engajamento, com o objetivo de mitigar o risco identificado da ausência de informações em projetos. A partir do conjunto de análises realizadas, foram propostas recomendações de melhoria para a gestão de projetos de saneamento, para a minimização dos problemas encontrados e considerações acerca do engajamento das partes interessadas mais impactantes.
Avaliação pós-ocupação em centros de atenção psicossocial: identificando as demandas e especificidades desta tipologia arquitetônica
Authors: Goulart Fernanda de Moraes , Ono Rosaria
Published: February 2023

Os Centros de Atenção Psicossocial (CAPS) fornecem o atendimento integral à saúde mental, com equipe multidisciplinar em um equipamento público próprio. Atualmente, a maior parte das unidades está instalada em construções pré-existentes adaptadas, por vezes sem a participação dos trabalhadores no desenvolvimento das adequações arquitetônicas. Soma-se a isso o fato das principais referências para o projeto destes espaços carecerem de definições quanto a aspectos da humanização, do conforto e da otimização do trabalho. Este estudo visa verificar o quão adequadas estão as instalações para o desempenho das atividades que compõem o tratamento da saúde mental. Para tal, foram realizadas Avaliações Pós-Ocupação em três unidades da cidade de São Paulo, cujas edificações foram reformadas para servirem como CAPS AD III. Um levantamento técnico coletou dados acerca da arquitetura dos edifícios e trabalhadores responderam a um questionário acerca de sua percepção da qualidade ambiental. 100 pessoas participaram do estudo. Os resultados indicam que as exigências do Manual de Estrutura Física dos CAPS, bem como os requisitos dispostos nas normativas correspondentes aos CAPS, não contemplam todo o programa de necessidades. Na discussão, são tratadas demandas e especificidades identificadas para esta tipologia, como: o seu estilo residencial, a oportunidade de personalização do espaço, a promoção do acolhimento e da autonomia, o conforto ambiental e os espaços exclusivos para a equipe. Como contribuição principal, este estudo mostra o quanto a inclusão do usuário no processo de projeto é essencial para uma melhor adequação do programa às necessidades de um estabelecimento assistencial à saúde mental.
Editorial V17 N4: Qualidade do Projeto
Authors: Imai Cesar , Ono Rosaria
Published: February 2023

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Anesthetic Care of the Pregnant Patient With Cardiovascular Disease: A Scientific Statement From the American Heart Association
Authors: Meng Marie-Louise , Arendt Katherine W. , Banayan Jennifer M. , Bradley Elisa A. , Vaught Arthur J. , Hameed Afshan B. , Harris Jade , Bryner Benjamin , Mehta Laxmi S. ,   on behalf of the American Heart Association Council on Cardiovascular Surgery and Anesthesia; Council on Cardiopulmonary, Critical Care, Perioperative and Resuscitation; and Council on Peripheral Vascular Disease
Published: February 2023

The pregnancy-related mortality rate in the United States is excessively high. The American Heart Association is dedicated to fighting heart disease and recognizes that cardiovascular disease, preexisting or acquired during pregnancy, is the leading cause of maternal mortality in the United States. Comprehensive scientific statements from cardiology and obstetrics experts guide the treatment of cardio-obstetric patients before, during, and after pregnancy. This scientific statement aims to highlight the role of specialized cardio-obstetric anesthesiology care, presenting a systematic approach to the care of these patients from the anesthesiology perspective. The anesthesiologist is a critical part of the pregnancy heart team as the perioperative physician who is trained to prevent or promptly recognize and treat patients with peripartum cardiovascular decompensation. Maternal morbidity is attenuated with expert anesthesiology peripartum care, which includes the management of neuraxial anesthesia, inotrope and vasopressor support, transthoracic echocardiography, optimization of delivery location, and consideration of advanced critical care and mechanical support when needed. Standardizing the anesthesiology approach to patients with high peripartum cardiovascular risk and ensuring that cardio-obstetrics patients have access to the appropriate care team, facilities, and advanced cardiovascular therapies will contribute to improving peripartum morbidity and mortality.
Maternal Exposure to PM
2.5
and the Risk of Congenital Heart Defects in 1.4 Million Births: A Nationwide Surveillance-Based Study
Authors: Yuan Xuelian , Liang Fengchao , Zhu Jun , Huang Keyong , Dai Li , Li Xiaohong , Wang Yanping , Li Qi , Lu Xiangfeng , Huang Jianfeng , Liao Lihui , Liu Yang , Gu Dongfeng , Liu Hanmin , Liu Fangchao
Published: February 2023

Background:

Evidence remains limited about the association of maternal exposure to ambient fine particulate matter (airborne particles with an aerodynamic diameter ≤2.5 µm [PM
2.5
]) with fetal congenital heart defects (CHDs) in highly polluted regions, and few studies have focused on preconception exposure.

Methods:

Using a nationwide surveillance-based case-control design in China, we examined the association between maternal exposure to PM
2.5
during periconception (defined as 3 months before conception until 3 months into pregnancy) and risk of CHD in offspring. The study included 1 434 998 births involving 7335 CHDs from 2014 through 2017 on the basis of the National Population-Based Birth Defects Surveillance System, covering 30 provinces, municipalities, or municipal districts in China. We assigned maternal PM
2.5
exposure during the periconception period to each participant using satellite-based PM
2.5
concentrations at 1-km spatial resolution. Multilevel logistic regression models were used to calculate the multivariable-adjusted odds ratio and 95% CI for CHDs in offspring associated with maternal PM
2.5
exposure, and the exposure–response association was investigated using restricted cubic spline analysis. Subgroup or sensitivity analyses were conducted to identify factors that may modify the association.

Results:

The average maternal exposure to PM
2.5
levels across all participants was 56.51 μg/m
3
(range, 10.95 to 182.13 μg/m
3
). For each 10 μg/m³ increase in maternal PM
2.5
exposure, the risk of CHDs in offspring was increased by 2% (odds ratio, 1.02 [95% CI, 1.00 to 1.05]), and septal defect was the most influenced subtype (odds ratio, 1.04 [95% CI, 1.01 to 1.08]). The effect of PM
2.5
on CHD risk was more pronounced during the preconception period. Mothers <35 years of age, those living in northern China, and those living in low-income areas were more susceptible to PM
2.5
exposure than their counterparts (all
P
<0.05). PM
2.5
exposure showed a linear association with total CHDs or specific CHD types.

Conclusions:

High maternal PM
2.5
exposure, especially during the preconception period, increases risk of certain types of CHD in offspring. These findings are useful for CHD prevention and highlight the public health benefits of improving air quality in China and other highly polluted regions.
Homogenization of Observed Surface Wind Speed Based on Geostrophic Wind Theory over China from 1970 to 2017
Authors: Zhang Zhengtai , Wang Kaicun
Published: February 2023

The observed surface wind speed (SWS) over China has declined in the past four decades, and recently, the trend has reversed, which is known as SWS stilling and recovery. The observed SWS is vulnerable to changes in nonclimatic factors, i.e., inhomogeneity. Unfortunately, most of the existing studies on the long-term trend of SWS were based on raw datasets without homogenization. In this study, by means of geostrophic wind speed and penalized maximal t test, we conduct a systematic homogeneity test and exploration of the homogenization impact for SWS at over 2000 stations in China from 1970 to 2017. The results show that the inhomogeneity in the observed SWS over China is detectable at 59% of national weather stations. The breakpoint years are mainly concentrated in the late 1970s, mid-1990s, and early 2000s. Overall, 18% of breakpoints are caused by station relocations, and the remaining breakpoints are likely related to anemometer replacement and measurement environment changes that occurred during the mid-1990s and early 2000s. After homogenization, the decreasing trend in SWS during 1970–2017 decreased from −0.15 to −0.05 m s−1 decade−1. The homogenized SWS recovery period advanced from the early twenty-first century to the early 1990s, which is consistent with the SWS variations, excluding the impact of urbanization around weather stations. The phase change in the Western Hemisphere warm pool (WHWP) might be one of the causes of homogenized SWS recovery.
Destinations and Pathways of the Indonesian Throughflow Water in the Indian Ocean
Authors: Guo Yaru , Li Yuanlong , Wang Fan
Published: February 2023

Passage of the Indonesian Throughflow (ITF) water through the Indian Ocean constitutes an essential section of the upper limb of the global ocean conveyor belt. Although existing studies have identified a major exit of the ITF water to the Atlantic Ocean through the Agulhas Current system, our knowledge regarding other possible destinations and primary pathways remains limited. This study applies the Connectivity Modeling System (CMS) particle tracking algorithm to seven model-based ocean current datasets. The results reveal a robust return path of the ITF water to the Pacific Ocean. The partition ratio between the Atlantic and Pacific routes is 1.60 ± 0.54 to 1, with the uncertainty representing interdataset spread. The average transit time across the Indian Ocean is 10–20 years to the Atlantic and 15–30 years to the Pacific. The “transit velocity” is devised to describe the three-dimensional pathways in a quantitative sense. Its distribution demonstrates that the recirculation structures in the southwestern subtropical Indian Ocean favor the exit to the Atlantic, while the Antarctic Circumpolar Current in the Southern Ocean serves as the primary corridor to the Pacific. Our analysis also suggests the vital impact of vertical motions. In idealized tracing experiments inhibiting vertical currents and turbulent mixing, more water tends to linger over the Indian Ocean or return to the Pacific. Turbulence mixing also contributes to vertical motions but only slightly affects the destinations and pathways of ITF water.
Intriguing Capital– Identity Relationship Dalits and Caste in India
Authors: Trivedi Prashant K.
Published: February 2023

The article interrogates the claim that capitalism would replace caste and liberate Dalits. People at the bottom rung of the caste hierarchy are exhorted to support neoliberal capitalism, a crusader against caste. This claim is based on the premise that capitalism abolishes all pre-existing social relations. Dealing with this argument at both empirical and theoretical levels, the article argues that this unilinear understanding of capital’s negotiation with other relationships is ahistorical. Capital does not necessarily abolish non-capitalist social relations but modifies and appropriates them for expansion. Relying on several studies from India, the article points out that interactions between capital and caste have been intriguing, with both entities being altered in the process.
Updating the probability of study success for combination therapies using related combination study data
Authors: Graham Emily , Harbron Chris , Jaki Thomas
Published: February 2023

Combination therapies are becoming increasingly used in a range of therapeutic areas such as oncology and infectious diseases, providing potential benefits such as minimising drug resistance and toxicity. Sets of combination studies may be related, for example, if they have at least one treatment in common and are used in the same indication. In this setting, value can be gained by sharing information between related combination studies. We present a framework that allows the study success probabilities of a set of related combination therapies to be updated based on the outcome of a single combination study. This allows us to incorporate both direct and indirect data on a combination therapy in the decision-making process for future studies. We also provide a robustification that accounts for the fact that the prior assumptions on the correlation structure of the set of combination therapies may be incorrect. We show how this framework can be used in practice and highlight the use of the study success probabilities in the planning of clinical studies.
Does Science Shape Sentiment? Scientific Inputs and the Deliberations in the Convention on Biological Diversity
Authors: Stevens Casey
Published: February 2023

Can the tone of scientific reports shape the ensuing political debates? This question is of utmost importance as global science bodies like the IPCC and IPBES release increasingly fervent calls to action. This article seeks an initial study about whether global science bodies can influence the negotiations by state parties by performing a multifaceted sentiment analysis of scientific inputs into the debates of the Convention on Biological Diversity (CBD). The article articulates two social learning pathways in which science can influence the tone of debates: pushing and participation. It then finds these pathways lacking in the incorporation of science into the CBD negotiations, and empirical work demonstrates limited effect on the sentiment or tone of debates as a result of scientific inputs. The conclusion reflects on the role that multifaceted sentiment analysis can play in understanding the increasingly complex politics of science on global governance institutions and particularly in the case of biodiversity governance.
Action Video Gaming and Attention in Young Adults: A Systematic Review
Authors: Sampalo Mar , Lázaro Esther , Luna Paula-María
Published: February 2023

Objective:

Existing research in action video games has increased in recent years due to the expansion of their use all over the world. Specifically, there is growing evidence about the positive development of the cognitive functions associated with the use of this kind of video game. Therefore, this work aims to explore the relationship between playing action video games and the development of attention span as well as the impact at the brain level from a functional perspective.

Methods:

Articles were searched in Scopus, Pubmed, and Web of Science. A total of 196 studies were retrieved, among which 13 studies were systematically reviewed.

Results:

The review has shown that playing action video games can improve cognitive functions, including attention, with reaction time and processing speed being the aspects that would most benefit from such practice, as well as the development of focused, sustained, and divided attention. Also, there are functional brain changes.

Conclusion:

It is necessary to deepen the understanding of the association between playing action video games and the development of attention.
Apolipoprotein A-IV of diabetic-foot patients upregulates tumor necrosis factor α expression in microfluidic arterial models
Authors: Ji Jun , Zhao Xiaoyu , Huang Jiajun , Wu Xuanqin , Xie Fang , Li Liang , Wang Tao , Mi Shengli
Published: February 2023

Diabetic peripheral arterial atherosclerosis is one of the important characteristics of diabetic foot syndrome. Apolipoprotein (Apo A-IV) participates in various physiological processes, and animal studies have shown that it has roles of anti-atherosclerosis, prevention of platelet aggregation and thrombosis. Apo A-IV glycosylation is closely related to the occurrence and development of diabetic peripheral atherosclerosis. This study aimed to explore the mechanism of diabetic peripheral arterial lesions caused by glycosylated Apo A-IV. Type 2 diabetes mellitus (T2DM) and T2DM with diabetic foot patients (T2DM-F; n = 45, 30) were enrolled in this study, and individuals without diabetes ( n = 35) served as normal controls (NC). In T2DM group, serum Apo A-IV content was higher than those in NC and T2DM-F group, as carboxymethyl lysine (CML) glycosylation of Apo A-IV in mixed serum from T2DM-F group was identified to be more significant than those in two other groups. Within a microfluidic arterial chip model, Apo A-IV from T2DM and T2DM-F group significantly increased transcription and protein levels of tumor necrosis factor alpha (TNF-α) in chip arteries, and CML expression was observed in T2DM-F group, which were associated with increased nuclear receptor subfamily 4 group A member 3 (NR4A3) expression. Recombinant human Apo A-IV could reverse the stimulating effect of serum Apo A-IV from T2DM-F group on TNF-α expression, and NR4A3 blocking peptide downregulated TNF-α expression by inhibiting NR4A3 expression. In the chip arteries, Apo A-IV from T2DM and T2DM-F increased TNF-α expression and turn them into a pre-atherosclerotic state, which might be one of the important mechanisms of glycosylated Apo A-IV to induce diabetic peripheral arterial lesions and eventually lead to diabetic foot.
Impaired factor V–related anticoagulant mechanisms and deep vein thrombosis associated with A2086D and W1920R mutations
Authors: Shimonishi Naruto , Ogiwara Kenichi , Yoshida Junko , Horie Kyoji , Nakajima Yuto , Furukawa Shoko , Takeyama Masahiro , Nogami Keiji
Published: February 2023

Factor V (FV) plays pivotal roles in both procoagulant and anticoagulant mechanisms. Genetic mutations, FV-W1920R (FVNara) and FV-A2086D (FVBesançon), in the C1 and C2 domains of FV light chain, respectively, seem to be associated with deep vein thrombosis. However, the detailed mechanism(s) through which these mutations are linked to thrombophilia remains to be fully explored. The aim of this study was to clarify thrombotic mechanism(s) in the presence of these FV abnormalities. Full-length wild-type (WT) and mutated FV were prepared using stable, human cell lines (HEK293T) and the piggyBac transposon system. Susceptibility of FVa-A2086D to activated protein C (APC) was reduced, resulting in significant inhibition of APC-catalyzed inactivation with limited cleavage at Arg306 and delayed cleavage at Arg506. Furthermore, APC cofactor activity of FV-A2086D in APC-catalyzed inactivation of FVIIIa through cleavage at Arg336 was impaired. Surface plasmon resonance–based assays demonstrated that FV-A2086D bound to Glu-Gly-Arg-chloromethylketone active site–blocked APC and protein S (P) with similar affinities to that of FV-WT. However, weakened interaction between FVa-A2086D and phospholipid membranes was evident through the prothrombinase assay. Moreover, addition of FVa-A2086D to plasma failed to inhibit tissue factor (TF)-induced thrombin generation and reduce prothrombin times. This inhibitory effect was independent of PC, PS, and antithrombin. The coagulant and anticoagulant characteristics of FV(a)-W1920R were similar to those of FV(a)-A2086D. FV-A2086D presented defects in the APC mechanisms associated with FVa inactivation and FV cofactor activity, similar to FV-W1920R. Moreover, both FV proteins that were mutated in the light chain impaired inhibition of TF-induced coagulation reactions. These defects were consistent with congenital thrombophilia.
Optimized synthesis characterization and protective activity of quercetin and quercetin–chitosan nanoformula against cardiotoxicity that was induced in male Wister rats via anticancer agent: doxorubicin
Authors: Soliman Asmaa. G. , Mahmoud Basant , Eldin Zienab E. , El-Shahawy Ahmed A. G. , Abdel-Gabbar Mohammed
Published: February 2023

The study’s goal was to look into the protective properties of quercetin (QU) in natural form and QU nanoparticles-loaded chitosan nanoparticles (QU-CHSNPs) against cardiotoxicity. The ionotropic gelation approach was adopted to form QU-CHSNPs. The characterizations were performed using advanced techniques. In vitro, the release profile of QU was studied. Cardiotoxicity was induced by doxorubicin (DOX) and protected via concurrent administration of QU and QU-CHSNPs. The heart's preventive effects of QU and QU-CHSNPs were manifested by a decrease in elevated serum activities of cardiac enzymes, as well as an improvement in the heart's antioxidant defence system and histological changes. The findings substantiated QU-CHSNPs' structure with an entrapment efficiency of 92.56%. The mean of the zeta size distribution was 150 nm, the real average particle size was 50 nm, and the zeta potential value was − 27.9 mV, exhibiting low physical stability. The percent of the free QU-cumulative release was about 70% after 12 h, and QU-CHSNPs showed a 49% continued release with a pattern of sustained release, reaching 98% after 48 h. And as such, QU and QU-CHSNPs restrained the induced cardiotoxicity of DOX in male Wistar rats, with the QU-CHSNPs being more efficient.
On the measurement of tasks: does expert data get it right?
Authors: Storm Eduard
Published: February 2023

Using German survey and expert data on job tasks, this paper explores the presence of omitted-variable bias suspected in conventional task data derived from expert assessment. I show expert task data, which is expressed at the occupation-level, introduces omitted-variable bias in task returns on the order of 26–34%. Motivated by a theoretical framework, I argue this bias results from expert data ignoring individual heterogeneity rather than fundamental differences on the assessment of tasks between experts and workers. My findings have important implications for the interpretation of conventional task models as occupational task returns are overestimated. Moreover, a rigorous comparison of the statistical performance of various models offers guidance for future research regarding choice of task data and construction of task measures.
A guide to preparing the sample of integrated labour market biographies (SIAB, version 7519 v1) for scientific analysis
Authors: Stüber Heiko , Dauth Wolfgang , Eppelsheimer Johann
Published: February 2023

The Sample of Integrated Labour Market Biographies (SIAB) is the most frequently requested data set provided by the Research Data Centre (FDZ) of the Federal Employment Agency (BA) at the Institute for Employment Research (IAB). However, preparing the SIAB for scientific analysis is a complicated and error-prone task. This article explains steps necessary to prepare the latest version of the SIAB (7519 v1) and gives examples of how the preparation can be done. Among other things, it shows how to impute right-censored wages, deal with parallel employment episodes, and clean up the data set. The supplementary material to this article contains extensively annotated Stata do-files to replicate our data preparation.
Metabolome of flue-cured tobacco is significantly affected by the presence of leaf stem
Authors: Li Yingxue , Liu Fengfeng , Sun Shubin , Xiang Yu , Jiang Xuebin , He Jiewang
Published: February 2023

Background

Leaves of tobacco (Nicotiana tabacum L.) are flue-cured to use as a key industrial supply in various parts of the world. The quality of tobacco leaves is dependent on chemical components and their proportions. Generally, the stem attached to tobacco leaf is detached before curing. However, the leaf stem remains green for an extended period of time (as compared to leaf) during flue-curing. Hence, it is expected to affect the quality of tobacco's final product.

Results

To understand the impact of the green stem of leaf on the metabolome of flue-cured tobacco, we employed a broad targeted metabolomics approach. We selected two tobacco cultivars (Yun87 and K326) and cultivated them in five geographic locations in China. For flue-curing, leaves were harvested without a stem (L) or with an attached stem (SPL). After metabolome analysis, a total of 1027 metabolites were annotated in these samples. A variable number of metabolites were differentially accumulated between both types of leaves (depending on geographic location or cultivar) representing an influence of environment or genotype. Interestingly, only 68 metabolites were differentially accumulated between L and SPL samples irrespective of the cultivar or geographic location. These differentially accumulated metabolites belonged to major groups of primary and secondary metabolites. We have discussed the importance of identified metabolites in terms of carbon, nitrogen, and polyphenolic metabolism.

Conclusion

The present research is the first comprehensive description of several metabolites in tobacco leaves related to the contribution of leaf stem. The current study opens novel prospects for investigating the potential of such metabolites in improving the quality of flue-cured tobacco.