bluuebunny/crossref_metadata_2025 huggingface dataset:
Reperfusion strategies on the clinical outcomes of ST-elevation myocardial infarction patients over 80 years old in China
Authors: Qu Xinkai , Guan Shaofeng , Cai Jiasheng , Gan Qian , Han Wenzheng , Lu Liming , Fang Weiyi , Yin Peng , Shi Hong , Wang Annai , Gao Yuanchao , Zhou Maigeng , Huo Yong
Published: February 2024

Aims

This study aims to explore the efficacy of reperfusion strategies on the clinical outcomes of ST-elevation myocardial infarction (STEMI) patients over 80 years old in China.

Methods and results

A retrospective cohort study was performed on STEMI patients over 80 years old who underwent reperfusion strategies and no reperfusion between January 2014 and December 2021, based on the Chinese Cardiovascular Association (CCA) Database-Chest Pain Center. This study included a total of 42,699 patients (mean age 84.1 ± 3.6 years, 52.2% male), among whom 19,280 (45.2%) underwent no reperfusion, 20,924 (49.0%) underwent primary percutaneous coronary intervention (PCI), and 2495 (5.8%) underwent thrombolytic therapy. After adjusting for potential confounders, multivariable logistic regression analysis revealed that patients who underwent primary PCI strategy showed a significantly lower risk of in-hospital mortality [odds ratio (OR) = 0.62, 95% confidence interval (CI): 0.57–0.67, P < 0.001] and the composite outcome (OR = 0.83, 95% CI: 0.79–0.87, P < 0.001) compared to those who received no reperfusion. In contrast, patients with thrombolytic therapy exhibited a non-significantly higher risk of in-hospital mortality (OR = 0.99, 95% CI: 0.86–1.14, P = 0.890) and a significantly elevated risk of the composite outcome (OR = 1.15, 95% CI: 1.05–1.27, P = 0.004). During a median follow-up of 6.7 months post-hospital admission, there was a percentage 31.4% of patients died, and patients in the primary PCI group consistently demonstrated a reduced incidence of all-cause mortality (hazard ratio (HR) = 0.58, 95% CI: 0.56–0.61, P < 0.001).

Conclusion

STEMI patients over 80 years old who underwent the primary PCI strategy are more likely to have favourable clinical outcomes compared to those who received no reperfusion, whereas thrombolytic therapy warrants careful assessment and monitoring.
Comparison of imaging changes in pulmonary artery diameter at the occlusion site using silk or metal clamps for pulmonary artery troubles
Authors: Chiba Yoshiki , Miyajima Masahiro , Takahashi Yuki , Shindo Yuma , Tsuruta Kodai , Maki Ryunosuke , Watanabe Atsushi
Published: February 2024

OBJECTIVES

We analysed our clinical experience using silk sutures [the double-loop technique (DLT)] or DeBakey type vascular clamp (DeBakey clamp) for pulmonary artery (PA) troubles during anatomical lung resection to validate its practicality and safety.

METHODS

We retrospectively reviewed the records of patients who underwent either of the above clamping techniques during anatomical lung resection at our hospital between April 2007 and August 2022. We measured the PA diameter at the occlusion site on computed tomography images acquired within 1 year pre- and postoperatively. The difference between pre- and postoperative diameters of the occlusion sites was calculated as the change in the PA diameter. We zoned the occlusion site of the PA to adjust for variation. PA deformation was evaluated as an adverse event caused by clamping.

RESULTS

Ultimately, 27 and 26 patients who underwent the DLT and DeBakey clamp, respectively, were included. No additional injury due to the clamp procedure was found in either group. For zone R1/L1, defined as the main PA, the median changes in the PA diameter were 0.02 (–0.7 to 0.27) mm for the DLT and 0.36 (–0.28 to 0.89) mm for the DeBakey clamp. No significant differences were observed between the 2 groups (P = 0.106). Furthermore, no aneurysms, dissections, or stenoses were found in either group.

CONCLUSIONS

The DLT and DeBakey clamp had only minimal effects on the occlusion site of the PA. The DLT is a practical thoracoscopic technique for PA bleeding when primary haemostasis has been achieved.
Response to: ‘Signals, Educational Decision-Making, and Inequality’: a comment on the formal model by Holm, Hjorth-Trolle, and Jæger
Authors: Holm Anders , Hjort-Trolle Anders , Meier Jaeger Mads
Published: February 2024

In this rejoinder, we engage in the discussion raised by Yastrebov (2023) about the assumptions in the theoretical models in Holm et al. (2019) and how the implications of the theory are handled. Our original model proposes that students use signals about academic ability to make inferences about the costs and benefits of different educational options. In particular, we propose that when low-socioeconomic status (SES) student receives a negative information shock in high school, they are more likely to drop out than their high-SES counterparts, and this difference is more pronounced for high-grade point average (GPA) students than for low-GPA students. Here we show that this holds true, despite the arguments raised by Yastrebov (2023).
Kinship, heritage, and ethnic choice: ethnolinguistic registration across four generations in contemporary Finland
Authors: Saarela Jan , Kolk Martin , Obućina Ognjen
Published: February 2024

We studied how individuals’ ethnolinguistic affiliation relates to the ethnolinguistic structure of kinship in contemporary Finland, a society in which Finnish-speaking and Swedish-speaking ethnolinguistic groups have coexisted for centuries and mixed marital unions are common. Using multigenerational data from the population register, we determined how the ethnolinguistic registration of children born in 1990–2015 relates to three generations of ancestors. We created a family tree that links children to their parents, four grandparents and eight great grandparents. Our intention was to both map the ethnolinguistic background of young people and predict a child’s affiliation based on their ancestry. The data revealed that ethnolinguistic affiliation is a more fluid and complex feature than expected when assessed only through child and parental characteristics. We found substantial diversity in ethnolinguistic background within the Swedish-speaking minority group, while most individuals in the Finnish-speaking majority group had a uniform background. We identified three types of bias in the ethnolinguistic affiliation of mixed-origin children: a matrilineal bias, a kinship majority bias and a Swedish ethnic minority bias. The analyses advanced our understanding of how the size of minority groups can shrink even when most couples in mixed unions favour minority group affiliation for their children.
Improved ERT imaging with 3-D surface-to-horizontal borehole configurations: relevance to dense non-aqueous phase liquids
Authors: Servos Maxwell , Power Christopher
Published: February 2024

Accurate characterization and monitoring strategies are essential for designing and implementing remedial programs for sites polluted with dense non-aqueous phase liquids (DNAPLs). Electrical resistivity tomography (ERT) is a widely used geophysical technique for mapping subsurface features and processes of interest, and exhibits desirable characteristics for DNAPL sites due to its ability to gather large volumes of continuous subsurface information in a non-invasive, cost-effective and time-efficient manner. However, ERT measured only from the surface suffers from poor imaging quality with depth. Enhanced ERT imaging can be obtained via electrodes deployed on the surface and within horizontal boreholes, but so far it has only been investigated for 2-D imaging. This study evaluates the potential of 3-D surface-to-horizontal borehole (S2HB) ERT configurations for imaging 3-D DNAPL source zones. Laboratory tank experiments were first conducted with a 3-D S2HB ERT configuration, which consisted of a surface grid and a single borehole line of electrodes, being used to monitor DNAPL migration within porous media. Results demonstrate that 3-D S2HB ERT with a single borehole provides improved sensitivity at depth, and therefore enhanced imaging compared to conventional 3-D surface ERT. Further tank experiments were performed to assess the performance of single borehole S2HB ERT when (i) the distance between surface and borehole is increased, and (ii) additional horizontal boreholes are included. The S2HB ERT with a single borehole significantly outperforms surface ERT at larger depths, and performs comparably to S2HB ERT using multiple boreholes. This study suggests that 3-D S2HB ERT with a single borehole can provide the enhanced imaging ability needed to map DNAPLs, while also being relatively practical for implementation at field sites.
The genetic dissection of fetal haemoglobin persistence in sickle cell disease in Nigeria
Authors: Ojewunmi Oyesola O , Adeyemo Titilope A , Oyetunji Ajoke I , Inyang Bassey , Akinrindoye Afolashade , Mkumbe Baraka S , Gardner Kate , Rooks Helen , Brewin John , Patel Hamel , Lee Sang Hyuck , Chung Raymond , Rashkin Sara , Kang Guolian , Chianumba Reuben , Sangeda Raphael , Mwita Liberata , Isa Hezekiah , Agumadu Uche-Nnebe , Ekong Rosemary , Faruk Jamilu A , Jamoh Bello Y , Adebiyi Niyi M , Umar Ismail A , Hassan Abdulaziz , Grace Christopher , Goel Anuj , Inusa Baba P D , Falchi Mario , Nkya Siana , Makani Julie , Ahmad Hafsat R , Nnodu Obiageli , Strouboulis John , Menzel Stephan
Published: February 2024

The clinical severity of sickle cell disease (SCD) is strongly influenced by the level of fetal haemoglobin (HbF) persistent in each patient. Three major HbF loci (BCL11A, HBS1L-MYB, and Xmn1-HBG2) have been reported, but a considerable hidden heritability remains. We conducted a genome-wide association study for HbF levels in 1006 Nigerian patients with SCD (HbSS/HbSβ0), followed by a replication and meta-analysis exercise in four independent SCD cohorts (3,582 patients). To dissect association signals at the major loci, we performed stepwise conditional and haplotype association analyses and included public functional annotation datasets. Association signals were detected for BCL11A (lead SNP rs6706648, β = −0.39, P = 4.96 × 10−34) and HBS1L-MYB (lead SNP rs61028892, β = 0.73, P = 1.18 × 10−9), whereas the variant allele for Xmn1-HBG2 was found to be very rare. In addition, we detected three putative new trait-associated regions. Genetically, dissecting the two major loci BCL11A and HBS1L-MYB, we defined trait-increasing haplotypes (P < 0.0001) containing so far unidentified causal variants. At BCL11A, in addition to a haplotype harbouring the putative functional variant rs1427407-‘T’, we identified a second haplotype, tagged by the rs7565301-‘A’ allele, where a yet-to-be-discovered causal DNA variant may reside. Similarly, at HBS1L-MYB, one HbF-increasing haplotype contains the likely functional small indel rs66650371, and a second tagged by rs61028892-‘C’ is likely to harbour a presently unknown functional allele. Together, variants at BCL11A and HBS1L-MYB SNPs explained 24.1% of the trait variance. Our findings provide a path for further investigation of the causes of variable fetal haemoglobin persistence in sickle cell disease.
Variants of the promoter of MYH6 gene in congenital isolated and sporadic patent ductus arteriosus: case-control study and cellular functional analyses
Authors: Zuo Ji-Yang , Chen Huan-Xin , Yang Qin , He Guo-Wei
Published: February 2024

Patent ductus arteriosus (PDA) is a common form of congenital heart disease. The MYH6 gene has important effects on cardiovascular growth and development, but the effect of variants in the MYH6 gene promoter on ductus arteriosus is unknown. DNA was extracted from blood samples of 721 subjects (428 patients with isolated and sporadic PDA and 293 healthy controls) and analyzed by sequencing for MYH6 gene promoter region variants. Cellular function experiments with three cell lines (HEK-293, HL-1, and H9C2 cells) and bioinformatics analyses were performed to verify their effects on gene expression. In the MYH6 gene promoter, 11 variants were identified. Four variants were found only in patients with PDA and 2 of them (g.3434G>C and g.4524C>T) were novel. Electrophoretic mobility shift assay showed that the transcription factors bound by the promoter variants were significantly altered in comparison to the wild-type in all three cell lines. Dual luciferase reporter showed that all the 4 variants reduced the transcriptional activity of the MYH6 gene promoter (P < 0.05). Prediction of transcription factors bound by the variants indicated that these variants alter the transcription factor binding sites. These pathological alterations most likely affect the contraction of the smooth muscle of ductus arteriosus, leading to PDA. This study is the first to focus on variants at the promoter region of the MYH6 gene in PDA patients with cellular function tests. Therefore, this study provides new insights to understand the genetic basis and facilitates further studies on the mechanism of PDA formation.
Assessing diversification behavior of small-scale commercial fishers
Authors: White Shelby B , Scheld Andrew M
Published: February 2024

Diversification within and outside of small-scale fisheries (SSF) is a common strategy to stabilize revenues and increase resilience following disturbances. Using SSF in Virginia, USA as a case study, Herfindahl–Hirschman Indices (HHIs) were used to characterize individual and fleet levels of income diversification, while generalized linear mixed models were used to examine drivers of diversification behavior. HHI income values indicate that fishers tended to exhibit specialized behavior. More diversified fishers tended to have less interannual revenue variability and higher annual incomes. Decisions to increase or decrease diversification were associated with various factors, including total years of participation, annual income, the type of licenses held, landings levels, participation in marine-related business outside of SSF, and market prices. An understanding of diversification levels and associated drivers of behavior can help fishery managers and governing entities predict how fishers will react to perturbations. Environmental changes that alter species distributions and increase the potential for invasive species, as well as shifting sociodemographics within the fishing industry, will likely continue to influence diversification behavior in the future. Developing strategies to reduce the impact of these events on fishers and fishing communities will help to increase resilience and reduce vulnerability in SSF.
Safety risk assessment model of a subway tunnel collapse system based on improved DOW-FFTA method
Authors: Li Wen , Lu Xuesong , Wu Menglong
Published: February 2024

Green construction considers factors such as quality, safety, efficiency, environmental protection and ecology. Under the premise of balancing basic construction capacity and green construction, prioritizing construction safety requirements and exploring the risk assessment system for the green construction of subway projects is crucial. Traditional risk assessment methods in the study of local system risks have been mostly applied to simple systems; thus, risk identification and assessment methods lack universality. The questions of how to change the existing structure of the system safety risk assessment model and establish a realistic modeling approach, as well as implement dynamic risk supervision, have become urgent problems. Here, we investigated the event risk point and proposed an integrated evaluation method of inherent, initial and real risks based on system attributes. The improved DOW chemical method was used to solve the static inherent risk severity index, and fuzzy fault tree analysis (FFTA) was used to judge the probability of out-of-control local state management. Considering the abnormal situation and the emergence of new risk information, a dynamic correction model was proposed. Finally, a static risk assessment model was established in line with the actual state of the system with local management and realistic risk assessment models that could modify the initial risk over time.
Level of exposure to aflatoxins during pregnancy and its association with adverse birth outcomes in Africa: a meta-analysis
Authors: Hassen Jemal Y , Debella Adera , Eyeberu Addis , Mussa Ibsa
Published: February 2024

Background

Aflatoxins are various poisonous carcinogens and mutagens produced by Aspergillus species. Exposure to aflatoxins during pregnancy results in adverse birth outcomes. This meta-analysis was carried out to determine the estimates of how much aflatoxin is harmful to the pregnancy and its outcome, including birthweight, birth length, low birthweight (LBW), small for gestational age (SGA), stunting, poverty, food insecurity, income, pesticides and stillbirth, in an African context.

Methods

Both published and unpublished studies in Africa were searched on MEDLINE, PubMed, Embase, SCOPUS, Web of Science and Google Scholar. Stata version 18.2 software was used for cleaning and analysis. The prevalence with a 95% confidence interval (CI) was estimated using the random effects model and a forest plot was used to present the findings. In addition, the heterogeneity of the study was assessed using Cochrane I2 statistics and publication bias was assessed using Egger's intercept and funnel plot.

Results

This review included 28 studies with a total of 6283 pregnant women and newborns. The analysis showed the overall level of exposure to aflatoxins was 64% (95% CI 48 to 78, τ2=0.66, I2=99.34%, p=0.001). In the subgroup analysis by publication year, the highest level of exposure to aflatoxins (82% [95% CI 69 to 92]) was observed among studies published from 2020 to 2023. This study also found that exposure to aflatoxins during pregnancy had an association with prematurity, LBW, SGA and stillbirth.

Conclusions

The data analysed in this study indicated that three of every five pregnant women had exposure to aflatoxins in Africa. Moreover, pregnant women exposed to aflatoxins had a higher likelihood of having a LBW and SGA newborn. Thus governments and all stakeholders should initiate policies that mitigate the toxicity of aflatoxins in pregnant women, foetuses and newborns.
Differences in antibiotic use between COPD and non-COPD residents based on the health information system
Authors: Yin Xin , Jiang Yonggen , Wu Yiling , Su Xuyan , Hou Shanshan , Li Jing , Luo Wei , Yu Minjun , Zang Jinxin , Wang Wei , Zhao Qi , Zhu Yinfeng , Zhao Genming , Jiang Qingwu , Wang Na
Published: February 2024

Objectives

To compare the differences in antibiotic use between COPD and non-COPD residents, and to explore the effect of COPD on antibiotic use.

Methods

Participants aged 40 years old or over from the Songjiang Adult Cohort were included. Information on prescription and baseline survey was collected based on the health information system. A logit-negative binomial Hurdle model was used to explore correlations between COPD and percentage of antibiotic use and average rate of antibiotic prescribing of different types of antibiotic. Multinomial logistic regression was used to assess the association between COPD and antimicrobial combination therapy and routes of administration.

Results

A total of 34576 individuals were included and 1594 (4.6%) were COPD patients. During the 6 years’ follow-up, the percentage of antibiotic use for COPD patients was 98.4%, which was 7.88 (95%CI: 5.24–11.85) times of that for non-COPD patients after adjusting for potential confounders. The prescribing rate was 3220 prescriptions (95%CI: 3063.6–3385.2) per 1000 person-years for COPD patients, which was 1.96 (95%CI: 1.87–2.06) times of that for non-COPD patients. Other beta-lactam antibacterials, Macrolides, lincosamides and streptogramins, and quinolone antibacterials were the most commonly used types of antibiotic. Except for aminoglycoside antibacterials, both percentage of antibiotic use and rate of antibiotic prescription were increased in COPD patients. COPD patients were more likely to be prescribed a maximum of two antibiotics (OR=1.34, 95%CI: 1.20–1.50); and were more likely to use antibiotics intravenously (OR=2.77, 95%CI: 2.47–3.11).

Conclusion

COPD patients were more likely to have increased antibiotic use in a large-scale population-based adult cohort, suggesting COPD patients are a high-priority group for the management of antibiotic use in communities.
Breast Radiologists’ Perceptions on the Detection and Management of Invasive Lobular Carcinoma: Most Agree Imaging Beyond Mammography Is Warranted
Authors: Coffey Kristen , Berg Wendie A , Dodelzon Katerina , Jochelson Maxine S , Mullen Lisa A , Parikh Jay R , Hutcheson Laurie , Grimm Lars J
Published: February 2024

Objective

To determine breast radiologists’ confidence in detecting invasive lobular carcinoma (ILC) on mammography and the perceived need for additional imaging in screening and preoperative settings.

Methods

A 16-item anonymized survey was developed, and IRB exemption obtained, by the Society of Breast Imaging (SBI) Patient Care and Delivery Committee and the Lobular Breast Cancer Alliance. The survey was emailed to 2946 radiologist SBI members on February 15, 2023. The survey recorded demographics, perceived modality-specific sensitivity for ILC to the nearest decile, and opinions on diagnosing ILC in screening and staging imaging. Five-point Likert scales were used (1 = strongly disagree, 2 = disagree, 3 = neutral, 4 = agree, 5 = strongly agree).

Results

Response rate was 12.4% (366/2946). Perceived median (interquartile range) modality-specific sensitivities for ILC were MRI 90% (80–90), contrast-enhanced mammography 80% (70–90), molecular breast imaging 80% (60–90), digital breast tomosynthesis 70% (60–80), US 60% (50–80), and 2D mammography 50% (30–60). Only 25% (85/340) respondents were confident in detecting ILC on screening mammography in dense breasts, while 67% (229/343) were confident if breasts were nondense. Most agreed that supplemental screening is needed to detect ILC in women with dense breasts (272/344, 79%) or a personal history of ILC (248/341, 73%), with 34% (118/334) indicating that supplemental screening would also benefit women with nondense breasts. Most agreed that additional imaging is needed to evaluate extent of disease in women with newly diagnosed ILC, regardless of breast density (dense 320/329, 97%; nondense 263/329, 80%).

Conclusion

Most breast radiologists felt that additional imaging beyond mammography is needed to more confidently screen for and stage ILC.
Impact of CYP2C19 metabolizer status on esophageal mucosal inflammation, acid exposure, and motility among patients on chronic proton-pump inhibitor therapy with refractory symptoms of gastroesophageal reflux disease
Authors: Tai Cheng-Chun , Medwid Samantha , Mclntosh Keith , Chande Nilesh , Kim Richard B , Gregor James
Published: February 2024

Background

The extent of disease severity remains unclear among CYP2C19 rapid and ultra-rapid metabolizers with refractory symptoms of gastroesophageal reflux disease (GERD) on chronic proton-pump inhibitors (PPIs).

Aims

To determine the impact of CYP2C19 metabolizer status in relation to chronic PPI therapy with a focus on the extent of esophageal inflammation, acid exposure, and motor function.

Methods

This retrospective study included 54 patients with refractory GERD symptoms who underwent CYP2C19 genotyping for PPI metabolism, esophagogastroduodenoscopy, ambulatory pH study, and high-resolution esophageal manometry. Patients were divided into three groups: normal metabolizer (NM) group, intermediate metabolizer/poor metabolizer (IM/PM) group, and rapid metabolizer/ultra-rapid metabolizer (RM/UM) group. The Chi-square test was used to analyze categorical variables, and one-way ANOVA for comparing means.

Results

Rapid metabolizer/ultra-rapid metabolizer (RM/UM) group more frequently had either Los Angeles grade C or D GERD (7/19, 36.8% vs 1/21, 4.8%, P = 0.011) and metaplasia of the esophagus (9/19, 47.4% vs 2/21, 9.5%, P = 0.007) when compared to the NM group. RM/UM group were more frequently offered dilatation for nonobstructive dysphagia (8/19, 42.1% vs 3/21, 14.3%, P = 0.049) and more exhibited a hypotensive lower esophageal sphincter (LES) resting pressure compared to the NM group (10/19, 52.6% vs 4/21, 19%, P = 0.026). All three groups exhibited comparable DeMeester scores when PPIs were discontinued 72 hours before the ambulatory pH study.

Conclusion

CYP2C19 RMs and UMs on chronic PPI with refractory GERD symptoms exhibited greater esophageal mucosal inflammation, as observed both endoscopically and histologically, and more were found to have hypotensive LES resting pressures and more were offered esophageal dilatation.
Using electric fields to control insects: current applications and future directions
Authors: Jobe Ndey Bassin , Chourasia Astha , Smith Brian H , Molins Elies , Rose Andreas , Pavlic Theodore P , Paaijmans Krijn P
Published: February 2024

Chemical-based interventions are mostly used to control insects that are harmful to human health and agriculture or that simply cause a nuisance. An overreliance on these insecticides however raises concerns for the environment, human health, and the development of resistance, not only in the target species. As such, there is a critical need for the development of novel nonchemical technologies to control insects. Electrocution traps using UV light as an attractant are one classical nonchemical approach to insect control but lack the specificity necessary to target only pest insects and to avoid harmless or beneficial species. Here we review the fundamental physics behind electric fields (EFs) and place them in context with electromagnetic fields more broadly. We then focus on how novel uses of strong EFs, some of which are being piloted in the field and laboratory, have the potential to repel, capture, or kill (electrocute) insects without the negative side effects of other classical approaches. As EF–insect science remains in its infancy, we provide recommendations for future areas of research in EF–insect science.
The trajectory of prognostic cognition in patients with advanced cancer: is the traditional advance care planning approach desirable for patients?
Authors: Hasegawa Takaaki , Okuyama Toru , Akechi Tatsuo
Published: February 2024

Most patients with advanced cancer initially express a desire to be informed of their prognosis, and prognostic discussions between patients and their oncologists can trigger the subsequent trajectory of prognostic cognitions. On the continuum of prognostic cognition, including inaccurate/accurate prognostic awareness (awareness of incurability of cancer, terminal nature of illness or life expectancy) and prognostic acceptance (accepting one's prognosis), patients’ perceptions of being informed of their prognosis by oncologists and patients’ coping strategy for serious medical conditions regulate prognostic cognitions. However, nearly half of the patients with advanced cancer have poor prognostic awareness, and few patients achieve prognostic acceptance. These phenomena partly act as barriers to participation in advance care planning. When oncologists engage in advance care planning conversations, they must assess the patient’s prognostic cognition and readiness for advance care planning. Considering the inaccurate prognostic awareness in a non-negligible proportion of patients and that astatic patients’ preferences for future treatment and care are influenced by prognostic cognition, more research on decision-making support processes for high-quality and goal-concordant end-of-life care is needed along with research of advance care planning. In addition to making decisions regarding future medical treatment and care, oncologists must engage in continuous and dynamic goal-of-care conversations with empathic communication skills and compassion from diagnosis to end-of-life care.
Trends in endometrial carcinoma: experience of a single institute for four decades
Authors: Yamaguchi Masayuki , Kushiya Naohisa , Tamura Ryo , Nishikawa Nobumichi , Kikuchi Akira
Published: February 2024

Objective

To determine the current prognosis of endometrial carcinoma in Japan by analyzing long-term trends in endometrial carcinoma at our hospital.

Methods

We divided 1463 patients with endometrial carcinoma who visited our hospital between 1984 and 2022 into group 1984–1991, group 1992–1999, group 2000–2006, group 2007–2014 and group 2015–2022. Trends were determined using the Jonckheere–Terpstra and Cochran–Armitage tests. Data were analyzed using Cox regression analysis.

Results

When group 2015–2022 was used as a reference in the univariate analysis, the hazard ratios for the other groups were <1. In particular, the hazard ratio for group 2007–2014 was 0.65 (95% confidence interval, 0.47–0.90, P = 0.009), suggesting that the prognosis of group 2015–2022 was worse than that of group 2007–2014 and seemed to be the worst among all prognoses. In multivariate analysis, the hazard ratios for each group were 1.38, 1.42, 1.88, 1.16 and 1, respectively; the group with the worst prognosis changed from group 2015–2022 to group 2000–2006 (hazard ratio, 1.88; 95% confidence interval, 1.27–2.78, P = 0.001). Age and the rate of non-endometrioid carcinoma exhibited significantly increasing trends (P < 0.001 and P < 0.001, respectively), as did the rates of serous and mixed carcinomas (P = 0.001 and 0.024, respectively). The rates of non-endometrioid carcinoma, serous carcinoma and mixed carcinoma were 19.0%, 5.5% and 3.1% in group 2007–2014 and 28.2%, 10.8% and 4.6% in group 2015–2022, respectively.

Conclusions

The increasing rates of non-endometrioid carcinoma—especially serous and mixed carcinoma—may be associated with the worsening prognosis of endometrial carcinoma at our institution. Careful monitoring is needed to confirm whether this phenomenon is observed throughout Japan.
Impact of frailty on cancer-related fatigue and quality of life in outpatients with prostate cancer: a cross-sectional study of patient-reported outcomes
Authors: Tohi Yoichiro , Kato Takuma , Honda Tomoko , Osaki Yu , Abe Yohei , Naito Hirohito , Matsuoka Yuki , Okazoe Homare , Taoka Rikiya , Ueda Nobufumi , Sugimoto Mikio
Published: February 2024

Objective

To investigate the prevalence of frailty and its effects on cancer-related fatigue and quality of life among patients with prostate cancer.

Methods

In this cross-sectional study, questionnaires were administered to 254 outpatients who visited the Department of Urology at Kagawa University Hospital for prostate cancer; finally, 108 outpatients were analyzed. Frailty, cancer-related fatigue and quality of life were assessed using the G8 screening tool, Japanese version of the Brief Fatigue Inventory and Japanese version of the Short Form 8 Health Survey, respectively. We defined frailty based on a score ≤14 points and divided the patients into frailty and no-frailty groups. We also compared the severity of cancer-related fatigue and quality of life between groups.

Results

The prevalence of frailty among 108 outpatients was 63%. Older age correlated with frailty severity (P = 0.0007) but not cancer-related fatigue severity (P = 0.2391). The proportion of patients on treatment or with metastasis was not significantly different between groups. The frailty group had higher cancer-related fatigue severity (P = 0.004) and decreased levels of general activity, mood, walking ability, normal work and enjoyment of life, especially on the Brief Fatigue Inventory subscale. The frailty group had lower physical and mental quality of life than the no-frailty group or general population.

Conclusions

The frailty rate for these patients increased with age, exceeding 60% regardless of the treatment status, and was associated with worsened cancer-related fatigue severity and reduced quality of life. Our study highlights the importance of assessing frailty when selecting treatment, especially in older patients.
Current methods for monitoring Pseudomonas syringae biofilm development
Authors: Budil Jakub , Lišková Petra
Published: February 2024

This work reviews biofilm investigation techniques and highlights the benefits and drawbacks of each approach focusing especially on Pseudomonas syringae and may serve as a comprehensive guide for any early-career researchers starting with the topic of biofilm. Each approach with applications of individual microscopy and spectroscopy techniques is summarized together with characterization of Pseudomonas syringae and its role in pathogenesis.
Probing the origin of the two-component structure of broad-line region by reverberation mapping of an extremely variable quasar
Authors: Nagoshi Shumpei , Iwamuro Fumihide , Yamada Satoshi , Ueda Yoshihiro , Oikawa Yuto , Otsuka Masaaki , Isogai Keisuke , Mineshige Shin
Published: February 2024

The physical origins of quasar components, such as the broad-line region (BLR) and dust torus, remain under debate. To gain insights into them, we focused on changing-state quasars (CSQs) which provide a unique perspective through structural changes associated with accretion disc state transitions. We targeted SDSS J125809.31+351943.0, an extremely variable CSQ, to study its central core structure and kinematics. We conducted reverberation mapping with optical spectroscopy to explore the structure of the BLR and estimate the black hole mass. The results from Hβ reverberation mapping indicated a black hole mass of $10^{9.64^{+0.11}_{-0.20}}\rm {M_\odot }$. Additionally, we analysed variations in the optical to X-ray spectral indices, αox, before and after the state transition, to investigate the accretion disc. These variations in αox and the Eddington ratio (from 0.4  per cent to 2.4  per cent) exhibitied behaviour similar to state transitions observed in X-ray binary systems. Spectral analysis of Hβ revealed a predominantly double-peaked profile during dim periods, transitioning to include a single-peaked component as the quasar brightened, suggesting that Hβ contains a mixture of two components. Each of these components has its distinct characteristics: the first is a double-peaked profile that remains stable despite changes in the accretion rate, while the second is a variable single-peaked profile. Using time-lags from reverberation mapping, we estimated the spatial relationships between these BLR components, the accretion disc, and the dust torus. Our results suggest that the BLR consists of two distinct components, each differing in location and origin.
The frequency and mass-ratio distribution of binaries in clusters II: radial segregation in the nearby dissolving open clusters Hyades and Praesepe
Authors: Albrow Michael D
Published: February 2024

We have determined the mass functions, mass-ratio distribution functions, and fractions of binary stars with mass ratios above particular thresholds for radially separated populations of stars in the nearby open clusters Hyades and Praesepe. Radial mass segregation is detected, with the populations of stars within the tidal radii having much flatter mass functions than those outside the tidal radii. Within the tidal radii, the frequency of binary stars with mass ratio q > 0.5 is 50–75 per cent higher for Hyades and 5–30 per cent higher for Praesepe. We also, for the first time, detect mass-ratio radial segregation. Of the binaries for which q > 0.5, ∼80 per cent of the inner Hyades population also have q > 0.75, while for the extra-tidal population, the ratio is ∼50 per cent. For Praesepe, ∼67 per cent of the inner sample have q > 0.75, and 35–45 per cent of the outer sample.
A candidate for central tidal disruption event in the broad line AGN SDSS J1605 with double-peaked broad H β
Authors: Zhang Xue-Guang
Published: February 2024

In this letter, motivated by double-peaked broad Balmer emission lines probably related to tidal disruption events (TDEs), a potential TDE candidate is reported in Sloan Digital Sky Survey (SDSS) J160536+134838 (=SDSS J1605) at z ∼ 0.44 having quasar-like spectrum but with double-peaked broad H β. The long-term Catalina Sky Survey (CSS) light curve can be naturally described by a main-sequence star of $2.82_{-0.19}^{+0.20}{\rm M_\odot }$ disrupted by the central black hole (BH) of $144_{-21}^{+26} \times 10^6{\rm M_\odot }$ in SDSS J1605. Meanwhile, the All-Sky Automated Survey for SuperNovae light curves afterwards show none apparent trend variability, indicating the bright CSS flare in SDSS J1605 unique and different enough from variability of normal active galactic nuclei (AGN). Furthermore, there is a consistency between the TDE model determined sizes of debris with the sizes of emission regions for the double-peaked broad H β described by the accretion disc model, supporting the disc-like broad emission line regions (BLRs) probably related to a central TDE in SDSS J1605. And the virial BH mass ∼7 times higher than the TDE model determined value can be naturally explained by R–L relation determined BLRs sizes very larger than the actual distance of emission regions related to TDEs debris in SDSS J1605. Although no clear conclusion on double-peaked broad lines absolutely related to TDEs, the results here provide clues to detect potential TDEs in AGN with double-peaked broad lines.
G-quadruplexes on chromosomal DNA negatively regulates topoisomerase 1 activity
Authors: Liang Hui-ting , Yan Jiang-yu , Yao Hao-jun , Zhang Xue-nan , Xing Zhi-ming , Liu Lin , Chen Yao-qing , Li Guo-rui , Huang Jing , He Yi-de , Zheng Ke-wei
Published: February 2024

Human DNA topoisomerase 1 (Top1) is a crucial enzyme responsible for alleviating torsional stress on DNA during transcription and replication, thereby maintaining genome stability. Previous researches had found that non-working Top1 interacted extensively with chromosomal DNA in human cells. However, the reason for its retention on chromosomal DNA remained unclear. In this study, we discovered a close association between Top1 and chromosomal DNA, specifically linked to the presence of G-quadruplex (G4) structures. G4 structures, formed during transcription, trap Top1 and hinder its ability to relax neighboring DNAs. Disruption of the Top1–G4 interaction using G4 ligand relieved the inhibitory effect of G4 on Top1 activity, resulting in a further reduction of R-loop levels in cells. Additionally, the activation of Top1 through the use of a G4 ligand enhanced the toxicity of Top1 inhibitors towards cancer cells. Our study uncovers a negative regulation mechanism of human Top1 and highlights a novel pathway for activating Top1.
Molecular and thermodynamic determinants of self-assembly and hetero-oligomerization in the enterobacterial thermo-osmo-regulatory protein H-NS
Authors: Lukose Bincy , Maruno Takahiro , Faidh Mohammed A , Uchiyama Susumu , Naganathan Athi N
Published: February 2024

Environmentally regulated gene expression is critical for bacterial survival under stress conditions, including extremes in temperature, osmolarity and nutrient availability. Here, we dissect the thermo- and osmo-responsory behavior of the transcriptional repressor H-NS, an archetypal nucleoid-condensing sensory protein, ubiquitous in enterobacteria that infect the mammalian gut. Through experiments and thermodynamic modeling, we show that H-NS exhibits osmolarity, temperature and concentration dependent self-association, with a highly polydisperse native ensemble dominated by monomers, dimers, tetramers and octamers. The relative population of these oligomeric states is determined by an interplay between dimerization and higher-order oligomerization, which in turn drives a competition between weak homo- versus hetero-oligomerization of protein-protein and protein-DNA complexes. A phosphomimetic mutation, Y61E, fully eliminates higher-order self-assembly and preserves only dimerization while weakening DNA binding, highlighting that oligomerization is a prerequisite for strong DNA binding. We further demonstrate the presence of long-distance thermodynamic connectivity between dimerization and oligomerization sites on H-NS which influences the binding of the co-repressor Cnu, and switches the DNA binding mode of the hetero-oligomeric H-NS:Cnu complex. Our work thus uncovers important organizational principles in H-NS including a multi-layered thermodynamic control, and provides a molecular framework broadly applicable to other thermo-osmo sensory proteins that employ similar mechanisms to regulate gene expression.
Extending DeepTrio for sensitive detection of complex de novo mutation patterns
Authors: Brand Fabian , Guski Jannis , Krawitz Peter
Published: February 2024

De novo mutations (DNMs), and among them clustered DNMs within 20 bp of each other (cDNMs) are known to be a potential cause of genetic disorders. However, identifying DNM in whole genome sequencing (WGS) data is a process that often suffers from low specificity. We propose a deep learning framework for DNM and cDNM detection in WGS data based on Google's DeepTrio software for variant calling, which considers regions of 110 bp up- and downstream from possible variants to take information from the surrounding region into account. We trained a model each for the DNM and cDNM detection tasks and tested it on data generated on the HiSeq and NovaSeq platforms. In total, the model was trained on 82 WGS trios generated on the NovaSeq and 16 on the HiSeq. For the DNM detection task, our model achieves a sensitivity of 95.7% and a precision of 89.6%. The extended model adds confidence information for cDNMs, in addition to standard variant classes and DNMs. While this causes a slight drop in DNM sensitivity (91.96%) and precision (90.5%), on HG002 cDNMs can be isolated from other variant classes in all cases (5 out of 5) with a precision of 76.9%. Since the model emits confidence probabilities for each variant class, it is possible to fine-tune cutoff thresholds to allow users to select a desired trade-off between sensitivity and specificity. These results show that DeepTrio can be retrained to identify complex mutational signatures with only little modification effort.
Genome-wide transcriptome analysis reveals the diversity and function of long non-coding RNAs in dinoflagellates
Authors: Chen Yibi , Dougan Katherine E , Nguyen Quan , Bhattacharya Debashish , Chan Cheong Xin
Published: February 2024

Dinoflagellates are a diverse group of phytoplankton, ranging from harmful bloom-forming microalgae to photosymbionts of coral reefs. Genome-scale data from dinoflagellates reveal atypical genomic features, extensive genomic divergence, and lineage-specific innovation of gene functions. Long non-coding RNAs (lncRNAs), known to regulate gene expression in eukaryotes, are largely unexplored in dinoflagellates. Here, using high-quality genome and transcriptome data, we identified 48039 polyadenylated lncRNAs in three dinoflagellate species: the coral symbionts Cladocopium proliferum and Durusdinium trenchii, and the bloom-forming species, Prorocentrum cordatum. These lncRNAs have fewer introns and lower G+C content than protein-coding sequences; 37 768 (78.6%) are unique with respect to sequence similarity. We classified all lncRNAs based on conserved motifs (k-mers) into distinct clusters, following properties of protein-binding and/or subcellular localisation. Interestingly, 3708 (7.7%) lncRNAs are differentially expressed under heat stress, algal lifestyle, and/or growth phase, and share co-expression patterns with protein-coding genes. Based on inferred triplex interactions between lncRNA and putative promoter regions, we identified 19 460 putative gene targets for 3721 lncRNAs; 907 genes exhibit differential expression under heat stress. These results reveal, for the first time, the diversity of lncRNAs in dinoflagellates and how lncRNAs may regulate gene expression as a heat-stress response in these ecologically important microbes.
Proton Pump Inhibitors and Cyclin-Dependent Kinase 4/6 Inhibitors in Patients With Breast Cancer
Authors: Takahashi Kaori , Uozumi Ryuji , Mukohara Toru , Hayashida Tetsu , Iwabe Midori , Iihara Hirotoshi , Kusuhara-Mamishin Kanako , Kitagawa Yuko , Tsuchiya Masami , Kitahora Mika , Nagayama Aiko , Kosaka Shinkichi , Asano-Niwa Yoshimi , Seki Tomoko , Ohnuki Koji , Suzuki Akio , Ono Fumiko , Futamura Manabu , Kawazoe Hitoshi , Nakamura Tomonori
Published: February 2024

Background

Proton pump inhibitors (PPIs) reduce the bioavailability of several anticancer drugs. The impact of PPIs co-administered with cyclin-dependent kinase 4 and 6 inhibitors is controversial. We aimed to clarify whether the concomitant use of PPIs impacts palbociclib and abemaciclib effectiveness in breast cancer treatment.

Patients and Methods

This multicenter, retrospective, observational study, conducted across 4 medical institutions in Japan, consecutively included patients with endocrine-resistant metastatic breast cancer, receiving palbociclib or abemaciclib between December 2017 and August 2022. Propensity score-matched analyses were performed. Treatment efficacy and safety with and without PPIs were compared. Progression-free survival and overall survival were estimated using the Kaplan-Meier method and compared using a log-rank test. A Cox proportional hazards model was used to estimate the hazard ratio.

Results

The study included 240 patients. After 1:1 matching, 112 patients were treated with and without PPIs. The median progression-free survival period was 1.2 years in the PPI group and 1.3 years in the non-PPI group (hazard ratio, 1.19; 95% CI, 0.70-2.02). The median overall survival period was 3.6 years in the PPI group, whereas it was not reached in the non-PPI group (hazard ratio, 1.23; 95% CI, 0.61-2.47). Consistent results were obtained for subgroups receiving palbociclib (n = 177) and abemaciclib (n = 63) without propensity score matching. Adverse event incidence and severity were similar in both groups.

Conclusion

The effectiveness of cyclin-dependent kinase 4/6 inhibitors is unlikely to be affected by concomitant PPI use. Future prospective pharmacokinetic studies are warranted.
AI-related data ethics oversight in UK policing
Authors: Sorell Tom
Published: February 2024

This paper considers the question of how police-related AI projects and data projects in general are normatively assessed in the UK. After locating data ethics in relation to policing ethics, I shall consider the workings of perhaps the leading regional data ethics committee in the UK. I go on to consider the approach of another committee that might in the future provide national data ethics advice for the police. Finally, I summarize the normative ethics frameworks in use in the two committees and their heavy reliance on the concepts of necessity and proportionality. I suggest that these concepts may have to be supplemented by systematic thinking about varieties of harm and the way in which severe harm may generate obligations to prevent it, where prevention may be assisted by AI models.
Enhanced Classical Radiation Damping of Electronic Cyclotron Motion in the Vicinity of the Van Hove Singularity in a Waveguide
Authors: Goto Yuki , Garmon Savannah , Petrosky Tomio
Published: February 2024

We study the damping process of electron cyclotron motion and the resulting emission in a waveguide using the classical Friedrichs model without relying on perturbation analysis such as Fermi’s golden rule. A Van Hove singularity appears at the lower bound (or cutoff frequency) of the dispersion associated with each of the electromagnetic field modes in the waveguide. In the vicinity of the Van Hove singularity, we found that not only is the decay process associated with the resonance pole enhanced (amplification factor ∼104) but the branch-point effect is also comparably enhanced. As a result, the timescale on which most of the decay occurs is dramatically shortened. Further, this suggests that the non-Markovian branch-point effect should be experimentally observable in the vicinity of the Van Hove singularity. Our treatment yields a physically acceptable solution without the problematic runaway solution that is well known to appear in the traditional treatment of classical radiation damping based on the Abraham–Lorentz equation.