bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Linear Relationship between the Number of Cancers among First-Degree Relatives and the Risk of Multiple Primary Cancers
Authors: He Shisi , Barry Kathryn H. , Mitchell Braxton D. , Chen Shuo , Zhang Yuji , Beane Freeman Laura E. , Berndt Sonja I. 
Published: June 2024

Abstract
With advances in the early detection and treatment of cancer, the incidence of multiple primary cancers (MPC) or second primary cancers has increased over time. Characterization of etiologic risk factors, including family history of cancer, within the general population is critical for assessing MPC risk in patients. We examined the association between family history of cancer among first-degree relatives and MPC risk in a prospective study of 139,958 participants from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Cox proportional hazard models were used to calculate HRs and 95% confidence intervals (95% CI), adjusting for potential confounders. Over a median follow-up of 16 years (IQR: 11–19 years), 6,170 participants were diagnosed with MPC. Having a family history of cancer increased the risk of MPC by 18% (HR, 1.18; 95% CI, 1.12–1.24). A positive linear trend was observed between the reported number of cancers in the family history and MPC risk with HRs (95% CI) of 1.13 (1.07–1.20), 1.23 (1.14–1.33), 1.29 (1.15–1.45), and 1.42 (1.20–1.70) for one, two, three, and four or more cancers among first-degree relatives, respectively (Ptrend = 2.36 × 10−13). No significant differences were observed by cancer histology or specific cancer types reported in the family history. Our study demonstrates that the family history of cancer is an important risk factor for the development of MPCs and that a comprehensive assessment of the number of cancers reported among first-degree relatives may identify those at higher risk who may benefit from targeted cancer prevention and screening strategies.
Prevention Relevance: Our study makes a substantial contribution to the understanding of risk factors for MPCs in the general population. It demonstrates that individuals with a strong family history of cancer are at higher risk for MPCs and may benefit from more targeted cancer prevention and screening interventions.
Tumor Promoters and Opportunities for Molecular Cancer Prevention
Authors: Hill William , Weeden Clare E. , Swanton Charles 
Published: June 2024

Abstract
Environmental carcinogens increase cancer incidence via both mutagenic and non-mutagenic mechanisms. There are over 500 known or suspected carcinogens classified by the International Agency for Research on Cancer. Sequencing of both cancerous and histologically non-cancerous tissue has been instrumental in improving our understanding of how environmental carcinogens cause cancer. Understanding how and defining which environmental or lifestyle exposures drive cancer will support cancer prevention. Recent research is revisiting the mechanisms of early tumorigenesis, paving the way for an era of molecular cancer prevention.
Significance: Recent data have improved our understanding of how carcinogens cause cancer, which may reveal novel opportunities for molecular cancer prevention.
Cancer Core Europe: Leveraging Institutional Synergies to Advance Oncology Research and Care Globally
Authors: Carmona Javier , Chavarria Elena , Donoghue Kate , von Gertten Christina , Oberrauch Petra , Pailler Emma , Scoazec Giovanni , Weijer Ruud , Balmaña Judith , Brana Irene , Brunelli Cinzia , Delaloge Suzette , Deloger Marc , Delpy Pierre , Ernberg Ingemar , Fitzgerald Rebecca C. , Garralda Elena , Lablans Martin , Lëhtio Janne , Lopez Carlos , Fernández Maialen , Miceli Rosalba , Nuciforo Paolo , Perez-Lopez Raquel , Provenzano Elena , Schmidt Marjanka K. , Serrano Cesar , Steeghs Neeltje , Tamborero David , Wirta Valtteri , Baird Richard D. , Barker Karen , Barlesi Fabrice , Baumann Michael , Bergh Jonas , de Braud Filippo , Fizazi Karim , Fröhling Stefan , Piris-Giménez Alejandro , Seamon Kenneth , Van der Heijden Michiel S. , Zwart Wilbert , Tabernero Josep 
Published: June 2024

Summary:
Cancer Core Europe brings together the expertise, resources, and interests of seven leading cancer institutes committed to leveraging collective innovation and collaboration in precision oncology. Through targeted efforts addressing key medical challenges in cancer and partnerships with multiple stakeholders, the consortium seeks to advance cancer research and enhance equitable patient care.
Identification of Core Techniques That Enhance Genome Editing of Human T Cells Expressing Synthetic Antigen Receptors
Authors: Chang Ju-Fang , Wellhausen Nils , Engel Nils W. , Landmann Jack H. , Hopkins Caitlin R. , Salas-McKee January , Bear Adham S. , Selli Mehmet E. , Agarwal Sangya , Jadlowsky Julie K. , Linette Gerald P. , Gill Saar , June Carl H. , Fraietta Joseph A. , Singh Nathan 
Published: June 2024

Abstract
Genome editing technologies have seen remarkable progress in recent years, enabling precise regulation of exogenous and endogenous genes. These advances have been extensively applied to the engineering of human T lymphocytes, leading to the development of practice changing therapies for patients with cancer and the promise of synthetic immune cell therapies for a variety of nonmalignant diseases. Many distinct conceptual and technical approaches have been used to edit T-cell genomes, however targeted assessments of which techniques are most effective for manufacturing, gene editing, and transgene expression are rarely reported. Through extensive comparative evaluation, we identified methods that most effectively enhance engineering of research-scale and preclinical T-cell products at critical stages of manufacturing.
PAI-1 Regulates the Cytoskeleton and Intrinsic Stiffness of Vascular Smooth Muscle Cells
Authors: Khoukaz Hekmat B. , Vadali Manisha , Schoenherr Alex , Ramirez-Perez Francisco I. , Morales-Quinones Mariana , Sun Zhe , Fujie Shumpei , Foote Christopher A. , Lyu Zhen , Zeng Shuai , Augenreich Marc A. , Cai Dunpeng , Chen Shi-You , Joshi Trupti , Ji Yan , Hill Michael A. , Martinez-Lemus Luis A. , Fay William P. 
Published: June 2024

BACKGROUND:
Plasma concentration of PAI-1 (plasminogen activator inhibitor-1) correlates with arterial stiffness. Vascular smooth muscle cells (SMCs) express PAI-1, and the intrinsic stiffness of SMCs is a major determinant of total arterial stiffness. We hypothesized that PAI-1 promotes SMC stiffness by regulating the cytoskeleton and that pharmacological inhibition of PAI-1 decreases SMC and aortic stiffness.

METHODS:
PAI-039, a specific inhibitor of PAI-1, and small interfering RNA were used to inhibit PAI-1 expression in cultured human SMCs. Effects of PAI-1 inhibition on SMC stiffness, F-actin (filamentous actin) content, and cytoskeleton-modulating enzymes were assessed. WT (wild-type) and PAI-1–deficient murine SMCs were used to determine PAI-039 specificity. RNA sequencing was performed to determine the effects of PAI-039 on SMC gene expression. In vivo effects of PAI-039 were assessed by aortic pulse wave velocity.

RESULTS:
PAI-039 significantly reduced intrinsic stiffness of human SMCs, which was accompanied by a significant decrease in cytoplasmic F-actin content. PAI-1 gene knockdown also decreased cytoplasmic F-actin. PAI-1 inhibition significantly increased the activity of cofilin, an F-actin depolymerase, in WT murine SMCs, but not in PAI-1–deficient SMCs. RNA-sequencing analysis suggested that PAI-039 upregulates AMPK (AMP-activated protein kinase) signaling in SMCs, which was confirmed by Western blotting. Inhibition of AMPK prevented activation of cofilin by PAI-039. In mice, PAI-039 significantly decreased aortic stiffness and tunica media F-actin content without altering the elastin or collagen content.

CONCLUSIONS:
PAI-039 decreases intrinsic SMC stiffness and cytoplasmic stress fiber content. These effects are mediated by AMPK-dependent activation of cofilin. PAI-039 also decreases aortic stiffness in vivo. These findings suggest that PAI-1 is an important regulator of the SMC cytoskeleton and that pharmacological inhibition of PAI-1 has the potential to prevent and treat cardiovascular diseases involving arterial stiffening.
Study on different isolation technology on the performance of blue micro-LEDs array applications
Authors: Lin Shao-Hua , Lo Yu-Yun , Hsu Yu-Hsuan , Lin Chien-Chung , Zan Hsiao-Wen , Lin Yi-Hsin , Wuu Dong-Sing , Hsiao Ching-Lien , Horng Ray-Hua 
Published: June 2024

AbstractIn this study, a 3 × 3 blue micro-LED array with a pixel size of 10 × 10 μm2 and a pitch of 15 μm was fabricated on an epilayer grown on a sapphire substrate using metalorganic chemical vapor deposition technology. The fabrication process involved photolithography, wet and dry etching, E-beam evaporation, and ion implantation technology. Arsenic multi-energy implantation was utilized to replace the mesa etching for electrical isolation, where the implantation depth increased with the average energy. Different ion depth profiles had varying effects on electrical properties, such as forward current and leakage currents, potentially causing damage to the n-GaN layer and increasing the series resistance of the LEDs. As the implantation depth increased, the light output power and peak external quantum efficiency of the LEDs also increased, improving from 5.33 to 9.82%. However, the efficiency droop also increased from 46.3 to 48.6%.
High heteroplasmy is associated with low mitochondrial copy number and selection against non-synonymous mutations in the snail Cepaea nemoralis
Authors: Davison Angus , Chowdhury Mehrab , Johansen Margrethe ,   Wellcome Sanger Institute Tree of Life programme, Uliano-Silva Marcela , Blaxter Mark 
Published: June 2024

AbstractMolluscan mitochondrial genomes are unusual because they show wide variation in size, radical genome rearrangements and frequently show high variation (> 10%) within species. As progress in understanding this variation has been limited, we used whole genome sequencing of a six-generation matriline of the terrestrial snail Cepaea nemoralis, as well as whole genome sequences from wild-collected C. nemoralis, the sister species C. hortensis, and multiple other snail species to explore the origins of mitochondrial DNA (mtDNA) variation. The main finding is that a high rate of SNP heteroplasmy in somatic tissue was negatively correlated with mtDNA copy number in both Cepaea species. In individuals with under ten mtDNA copies per nuclear genome, more than 10% of all positions were heteroplasmic, with evidence for transmission of this heteroplasmy through the germline. Further analyses showed evidence for purifying selection acting on non-synonymous mutations, even at low frequency of the rare allele, especially in cytochrome oxidase subunit 1 and cytochrome b. The mtDNA of some individuals of Cepaea nemoralis contained a length heteroplasmy, including up to 12 direct repeat copies of tRNA-Val, with 24 copies in another snail, Candidula rugosiuscula, and repeats of tRNA-Thr in C. hortensis. These repeats likely arise due to error prone replication but are not correlated with mitochondrial copy number in C. nemoralis. Overall, the findings provide key insights into mechanisms of replication, mutation and evolution in molluscan mtDNA, and so will inform wider studies on the biology and evolution of mtDNA across animal phyla.
Identification of genetic variants controlling diosgenin content in Dioscorea zingiberensis tuber by genome-wide association study
Authors: Sun Shi xian , Li Yanmei , Jia Lu , Ye Shili , Luan Yunpeng 
Published: June 2024

Abstract
Background
Diosgenin is an important steroidal precursor renowned for its diverse medicinal uses. It is predominantly sourced from Dioscorea species, particularly Dioscorea zingiberensis. Dioscorea zingiberensis has an ability to accumulate 2–16% diosgenin in its rhizomes. In this study, a diverse population of 180 D. zingiberensis accessions was used to evaluate the genomic regions associated with diosgenin biosynthesis by the genome wide association study approach (GWAS).

Results
The whole population was characterized for diosgenin contents from tubers by gas chromatography mass spectrometry. The individuals were genotyped by the genotyping-by-sequencing approach and 10,000 high-quality SNP markers were extracted for the GWAS. The highest significant marker-trait-association was observed as an SNP transversion (G to T) on chromosome 10, with 64% phenotypic variance explained. The SNP was located in the promoter region of CYP94D144 which is a member of P450 gene family involved in the independent biosynthesis of diosgenin from cholesterol. The transcription factor (TF) binding site enrichment analysis of the promoter region of CYP94D144 revealed NAC TF as a potential regulator. The results were further validated through expression profiling by qRT-PCR, and the comparison of high and low diosgenin producing hybrids obtained from a bi-parental population.

Conclusions
This study not only enhanced the understanding of the genetic basis of diosgenin biosynthesis but also serves as a valuable reference for future genomic investigations on CYP94D144, with the aim of augmenting diosgenin production in yam tubers.
Compounding stress: A mixed-methods study on the psychological experience of miscarriage amid the COVID-19 pandemic
Authors: Fernandez-Pineda Madeline , Swift Alison , Dolbier Christyn , Banasiewicz Kaitlin Guard 
Published: June 2024

AbstractBackgroundExperiencing a miscarriage can have profound psychological implications, and the added strain of the COVID-19 pandemic may have compounded these effects. This study aimed to explore the psychological experiences, assess the levels of psychological distress (depression, anxiety, and post-traumatic stress disorder), and examine the relationships of personal significance of miscarriage and perceived stress with psychological distress of women in North Carolina who suffered a miscarriage of a desired pregnancy between March 30, 2020, and February 24, 2021, of the COVID-19 pandemic, at 14 to 31 months after the loss.MethodsWe conducted a cross-sectional mixed-methods study using a convergent parallel design. A total of 71 participants from North Carolina completed the online survey and 18 completed in-depth interviews. The survey assessed demographics, mental health and reproductive history, personal significance of miscarriage, perceived stress, anxiety, depression, and PTSD. Interview questions asked about the psychological experience of the miscarriage and how the COVID-19 pandemic affected them and their experience.ResultsFindings indicated moderate to severe levels of depression, anxiety, and PTSD, which persisted 14 to 31 months post-miscarriage. After conducting hierarchical binary logistic regressions, we found that perceived stress and prior trauma increased the odds of depression, perceived stress increased the odds of anxiety, and personal significance and prior trauma increased the odds of PTSD symptoms 14–31 months post-miscarriage. Notably, a subsequent successful childbirth emerged as a protective factor against depression, anxiety, and PTSD. Qualitative findings depicted emotions such as profound isolation, guilt, and grief. Women noted that additional pandemic-specific stressors exacerbated their distress. The categories identified via conventional content analysis fell under five broader thematic groups: mental health disorders, negative emotions/feelings, positive emotions/feelings, thoughts, and other experiences.ConclusionsMiscarriage during the COVID-19 pandemic intensified and added complexity to the psychological distress experienced by affected women. The study underscores the need for comprehensive mental health screenings, specialized support for vulnerable groups, and the necessity of trauma-informed care. Providers are strongly encouraged to adopt a multifaceted, individualized approach to patient care that is cognizant of the unique stressors introduced by the pandemic.
Genetic and clinical landscape of Chinese frontotemporal dementia: dominance of TBK1 and OPTN mutations
Authors: Nan Haitian , Kim Yeon-Jeong , Chu Min , Li Dan , Li Jieying , Jiang Deming , Wu Yiming , Ohtsuka Toshihisa , Wu Liyong 
Published: June 2024

Abstract
Background
Our study aims to evaluate the genetic and phenotypic spectrum of Frontotemporal dementia (FTD) gene variant carriers in Chinese populations, investigate mutation frequencies, and assess the functional properties of TBK1 and OPTN variants.

Methods
Clinically diagnosed FTD patients underwent genetic analysis through exome sequencing, repeat-primed polymerase chain reaction, and Sanger sequencing. TBK1 and OPTN variants were biologically characterized in vitro using immunofluorescence, immunoprecipitation, and immunoblotting analysis. The frequencies of genes implicated in FTD in China were analyzed through a literature review and meta-analysis.

Results
Of the 261 Chinese FTD patients, 61 (23.4%) carried potential causative variants in FTD-related genes, including MAPT (n = 17), TBK1 (n = 7), OPTN (n = 6), GRN (n = 6), ANXA11 (n = 4), CHMP2B (n = 3), C9orf72 GGGGCC repeats (n = 2), CYLD (n = 2), PRNP (n = 2), SQSTM1 (n = 2), TARDBP (n = 2), VCP (n = 1), CCNF (n = 1), CHCHD10 (n = 1), SIGMAR1 (n = 1), CHCHD2 (n = 1), FUS (n = 1), TMEM106B (n = 1), and UBQLN2 (n = 1). 29 variants can be considered novel, including the MAPT p.D54N, p.E342K, p.R221P, p.T263I, TBK1 p.E696G, p.I37T, p.E232Q, p.S398F, p.T78A, p.Q150P, p.W259fs, OPTN p.R144G, p.F475V, GRN p.V473fs, p.C307fs, p.R101fs, CHMP2B p.K6N, p.R186Q, ANXA11 p.Q155*, CYLD p.T157I, SQSTM1 p.S403A, UBQLN2 p.P509H, CCNF p.S160N, CHCHD10 p.A8T, SIGMAR1 p.S117L, CHCHD2 p.P53fs, FUS p.S235G & p.S236G, and TMEM106B p.L144V variants. Patients with TBK1 and OPTN variants presented with heterogeneous clinical phenotypes. Functional analysis demonstrated that TBK1 I37T and E232Q mutants showed decreased autophosphorylation, and the OPTN phosphorylation was reduced by the TBK1 I37T mutant. The OPTN-TBK1 complex formation was enhanced by the TBK1 E696G mutant, while OPTN R144G and F475V mutants exhibited reduced recruitment to autophagosomes compared to the wild-type. The overall frequency of TBK1 and OPTN in Chinese FTD patients was 2.0% and 0.3%, respectively.

Conclusions
Our study demonstrates the extensive genetic and phenotypic heterogeneity of Chinese FTD patients. TBK1 mutations are the second most frequent cause of clinical FTD after MAPT in the Chinese.
Giant complete hydatidiform mole: a case report and review of the literature
Authors: Bonomo Iris , Fopa Suzy , Van Vinckenroy Grégory , Maillard Charlotte 
Published: June 2024

Abstract
Background
This case describes the youngest patient documented in the literature who presented with a giant hydatidiform mole, effectively addressed through conservative treatment.

Case presentation
Our department received a 20-year-old Caucasian patient who was admitted due to significant metrorrhagia in an undisclosed pregnancy. During examination, we identified a massive, highly vascularized hydatidiform mole measuring 22 cm (cm). We performed a surgical dilatation and curettage. The anatomopathological findings confirmed the presence of a complete hydatidiform mole (CHM). Following the established guidelines, we conducted weekly monitoring of human chorionic gonadotropin (hCG). Unfortunately, the patient discontinued the follow-up and became pregnant again before achieving hCG negativation.

Conclusion
This case suggests that conservative treatment is a viable option regardless of the size of gestational trophoblastic disease (GTD), especially when the preservation of fertility is a crucial consideration, as effectively demonstrated in our case.
Utilization of maternal health facilities and rural women’s well-being: towards the attainment of sustainable development goals
Authors: Adejoorin Mobolaji Victoria , Salman Kabir Kayode , Adenegan Kemisola Omorinre , Obi-Egbedi Ogheneruemu , Dairo Magbagbeola David , Omotayo Abiodun Olusola 
Published: June 2024

Abstract
Background
The sustenance of any household is tied to the well-being of the mother's health before, during, and after pregnancy. Maternal health care has continued a downward slope, increasing maternal mortality in rural communities in Nigeria. Presently, few empirical findings connect maternal healthcare facilities' use to mothers' well-being in Nigeria. Using maternal health facilities and the well-being of rural women is crucial in achieving the United Nations’ Sustainable Development Goals 1, 2, and 3 (No poverty, zero hunger, good health, and well-being).

Objective
The objective of the study was to examine the level of maternal healthcare utilization and its effect on mothers’ well-being status among mothers in rural Nigeria.

Methods
In this study, secondary data extracted from the Nigeria’s 2018 National Demographic Health Survey was used. Data was analyzed with Multiple correspondence analysis, Fuzzy set analysis, and Extended ordered logit model.

Results
Women in rural Nigeria were moderate users of maternal health care services and had moderate well-being indices (0.54 ± 0.2, 0.424 ± 0.2, respectively). Mothers' moderate well-being status was increased by using maternal health care facilities, having a larger household, and having mothers who worked exclusively in agriculture.

Conclusion
We concluded that mothers in rural Nigeria use maternal healthcare facilities moderately, and their well-being level was improved using maternal healthcare facilities. Therefore, Nigeria’s Ministry of Health should raise awareness about the vitality of mothers using health care services before, during, and after pregnancy. In order to promote greater female participation in full-scale agricultural production, it is imperative for the Nigerian government to allocate substantial resources in the form of subsidies and incentives. The Nigerian government should source these resources from various channels, including expanded development cooperation. Additionally, policymakers should focus on designing developmental programmes specifically tailored for rural households and the health sector.