bluuebunny/crossref_metadata_2025 huggingface dataset:
Genoa 1450–1700
Authors: Taviani Carlo
Published: November 2023

Compared to the history of Florence, Venice, Rome, or even Milan, the history of Genoa has been overlooked in past centuries and decades, probably because of the difficulty to reduce it to a common model, especially in the field of political and institutional history. The fortunes of a small center with several external subjected territories during the Middle Ages, and the misfortunes of a weak state with a prosperous commercial diaspora in the following centuries, have characterized the history of this city and its scholarship. The role of private institutions, trade, finance, diaspora, and factions, on one hand, and of weak but flexible political institutions, on the other, makes Genoa an interesting—because uncommon—case study. A persistent dichotomy has also characterized Genoese scholarship. Several historians have looked at the history of Genoa, while others have studied the history of the Genoese people—famous seafarers, rich traders, and many migrants—abroad. If the history of Genoa is that of a small state during the Early Modern age, that of its people is a history of a wide and persistent diasporic movement abroad. This bibliography offers an overview of the first topic, Genoa, with the explicit purpose not to mix and confuse it with the history of the Genoese abroad. A few works which refer to the Genoese abroad are however mentioned here, but only since they consistently deal with the history of Genoa. The time period analyzed by this bibliography (1450–1700) is characterized by a hiatus in the scholarship. A group of studies have focused on the period 1450–1528, while others on the period 1550–1700. Quite recently, global history is marking a shift in the trend of Genoese scholarship, but it can only be partially mentioned here, since some of the most recent studies focus on earlier or later periods, and not on the period between 1450 and 1700, and because some research works and projects are still ongoing and unpublished.
Youssef Chahine
Authors: Wharton Barrie
Published: November 2023

Youssef Chahine is widely considered as one of the foremost cinema directors in the Arab world whose work transcended the region’s borders to reach a global audience. Although most commonly celebrated internationally for his post-Nasserist semi-autobiographical Alexandria Quartet—Alexandria....Why?) (1978), An Egyptian Tale (1982), Alexandria Again and Again (1990), and Alexandria-New York (2004)—which delve into such themes as homosexuality and liberalism in Arab society, Chahine was also the cinematic poet and chronicler of marginalization and social inequity in Egypt. In fact, Chahine, through films with an overt sociocultural and political message such as Bab al-Hadid (Cairo Main Station) (1958), Al Nasser Salah ad-Din (Saladin) (1963), and Al-Ard (The Land) (1969), was the pioneer of social realism in Arab cinema and his work played a fundamental part in what was the most important project of national identity creation in modern Egyptian history during the tumultuous years of the Nasserist era. Youssef Chahine’s death in July 2008 left Egyptian cinema without its colossus but Egypt also lost its eyes, its ears, and most importantly, its conscience. Chahine will be remembered for taking on fundamentalism in the contemporary era, but he had taken on the yoke of imperialism almost fifty years before with his vision for a new Egypt which he would tragically never see. This eventual failure of Nasserism to realize the project of a new just Egyptian society, based on principles of secularism, tolerance, and equality, is a historical reality with myriad cause factors but this doesn’t denigrate or diminish in any way the fundamental role of Youssef Chahine in this social, cultural, and political project for almost twenty years. Chahine, like Nasser, knew that Egypt had to face her memory and by extension, her fears before she could embrace her hopes and her future. Yet, as Nasserist ideology fades into history in a contemporary climate of increasing religious radicalism, the “Nasserist” films of Youssef Chahine such as the aforementioned Cairo Main Station and The Land remain as powerful celluloid advertisements for and testaments to one of the potentially most powerful sociocultural ideologies of the last century. Successive Egyptian heads of state have gone to great lengths to cast off and exorcize the legacy of Nasserism as a sociocultural beacon from contemporary Egyptian society but their efforts will have been in vain as long as the cinematic legacy of Youssef Chahine survives.
Ming and Qing Drama
Authors: Fox Ariel
Published: November 2023

Drama occupied a central place in the culture of the Ming and Qing dynasties. As a performance practice that traversed social strata and a textual tradition of composition and criticism, drama was enmeshed in the spaces and activities of everyday life. A secluded garden, a bustling temple market, a small pleasure boat, a rowdy teashop, or a serene palace could all be sites of performances either carefully orchestrated or impromptu, by household actors, traveling troupes, or enthusiastic amateurs. While the long-form genre of chuanqi傳奇 (southern drama), dominated this period, the earlier form of zaju雜劇 (variety play, or northern drama) continued to compel writers, audiences, and critics alike, as an entertainment in the early Ming court, a site of late Ming scholarly interest, and a living form for playwrights throughout this period. Chuanqi, predominately written to be performed in the kunqu崑曲 (Kun opera) music system, circulated as elaborated published play texts of extraordinary length and were performed occasionally as complete works, though more frequently as excerpted scenes on mixed bills. Over the course of the Qing, mobile performance spaces gave way to more static venues such as the teashop, and kunqu declined in popularity as a number of regional opera forms proliferated in urban centers, foremost among them jingju京劇 (Peking opera). Beyond the pages and stages of the plays themselves, drama so dominated the cultural imaginary that its modes and practices—theatricality, role play, spectatorship—provided late imperial subjects with a heuristic for understanding how the self was fashioned and performed in the world.
Newly detected paediatric melioidosis cases in a single referral children's hospital in Ho Chi Minh City indicate the probable underrecognition of melioidosis in South Vietnam
Authors: Pham Thai Son , König Elisabeth , Bui The Trung , Vu Thi Ngoc Anh , Nguyen Tran Nam , Do Chau Viet , Lichtenegger Sabine , Bui Nguyen Hai Linh , Trinh Huu Tung , Steinmetz Ivo , Trinh Thanh Trung
Published: November 2023

Background

The epidemiology of melioidosis in Vietnam, a disease caused by the soil bacterium Burkholderia pseudomallei, remains unclear. This study aimed to detect paediatric melioidosis in South Vietnam and describe clinical features and the geographic distribution.

Methods

We introduced a simple laboratory algorithm for detecting B. pseudomallei from clinical samples at Children's Hospital 2 in Ho Chi Minh City in July 2015. A retrospective observational study of children <16 y of age with culture-confirmed melioidosis between July 2015 and August 2019 was undertaken.

Results

Thirty-five paediatric cases of melioidosis were detected, with cases originating from 13 of 32 provinces and cities in South Vietnam. The number of paediatric melioidosis cases detected from a certain region correlated with the overall number of inpatients originating from the respective geographic area. Suppurative parotitis (n=15 [42.8%]) was the most common clinical presentation, followed by lung infection (n=10 [28.6%]) and septicaemia (n=7 [20%]). Fourteen (40%) children had disseminated disease, including all cases of lung infection, four cases with central nervous system symptoms and four (11.4%) deaths.

Conclusions

The patients’ origin indicates a wide distribution of melioidosis in South Vietnam. It seems probable that cases not only in children, but also in adults, remain grossly undiagnosed. Further awareness raising and laboratory capacity strengthening are needed in this part of the country.
Association between sociodemographic and clinical features, health behaviors, and health literacy of patients with prostate cancer and prostate cancer prognostic stage
Authors: Braga Raquel , Araújo Natália , Costa Adriana , Lopes Catarina , Silva Isa , Correia Rita , Carneiro Filipa , Braga Isaac , Pacheco-Figueiredo Luis , Oliveira Jorge , Morais Samantha , Tedim Cruz Vítor , Pereira Susana , Lunet Nuno
Published: November 2023

Patient characteristics may influence access and acceptance of Prostate Specific Antigen test, and therefore, the timing of prostate cancer (PCa) diagnosis. A group of 361 patients from a cohort (n = 451) diagnosed with PCa in 2018–2020 at the Portuguese Institute of Oncology of Porto was evaluated before treatment, using a structured interview, the Medical Term Recognition Test, and the EORTC Quality of Life Questionnaire QLQ-PR25. PCa prognostic stages (I, II, III, IV) were attributed according to the American Joint Committee on Cancer eighth edition. Multinomial logistic regression was used to compute the odds ratio and 95% confidence interval (OR [95% CI]), considering PCa stage II, the most frequent, as reference. Older age (OR = 4.21 [2.24–7.93]), living outside the Porto Metropolitan Area while having low income (OR = 6.25 [1.53–25.62]), and erectile dysfunction (OR = 2.22 [0.99–4.99]) were associated with stage III, while urination during the night (OR = 3.02 [1.42–6.41]) was associated with stage IV. Urine leakage was less frequent in stage III (OR = 0.23 [0.08–0.68]), and living with a partner (OR = 0.41 [0.19–0.88]) and family history of cancer (OR = 0.25 [0.07–0.86]) in stage IV. Health literacy was not associated with PCa stage but lower education was less frequent in stage I (OR = 0.27 [0.11–0.69]). Patient sociodemographic and clinical characteristics should be considered as targets to improve PCa early detection and prognosis.
Epidemiological trend of lung cancer burden caused by residential radon exposure in China from 1990 to 2019
Authors: Wang Chengzhi , Shi Lei
Published: November 2023

Objective

This study employed time series data to assess long-term changes in the burden of lung cancer (LC) caused by residential radon exposure, an important environmental risk factor, so as to develop evidence-based strategies for future public health management.

Methods

Based on the open data from the Global Burden of Disease (GBD 2019) database, we conducted an analysis of the residential radon exposure-caused LC mortality, disability-adjusted life years (DALYs), and corresponding crude rates and age-standardized rates (ASRs) for various age groups. We employed the employed age-period-cohort (APC) model to investigate the age, period, and cohort effects of the data, allowing us to discern the trends in LC disease burden attributable to radon exposure in residential settings over time.

Results

From 1990 to 2019, age-standardized mortality rates (ASMR) and age-standardized DALYs rates of LC caused by residential radon exposure in China demonstrated an overall increasing trend, with males higher than females. The CMR and crude DALYs rate for males were higher than those for females across all age groups. The APC analysis revealed that the local drift of LC death and DALYs rates in males and females showed a decreasing trend before 60 and an increasing trend after 60.

Conclusion

The persistent presence of residential radon exposure as a crucial risk factor for LC underscores the need for public health authorities and policymakers to take more proactive measures to reduce radon exposure. Particularly, attention should be paid on the elderly population and male patients.
Meta-analysis of the prognostic value of serum carcinoembryonic antigen in patients with colorectal cancer liver metastases after hepatectomy
Authors: Yuan Chenzhao , Zeng Lumin , Duan Hongxiang , Suksatit Benjamas
Published: November 2023

Objectives

Carcinoembryonic antigen (CEA) is a broad-spectrum tumor marker for differential diagnosis, monitoring, and response assessment of a variety of malignancies. This meta-analysis was aimed at evaluating whether serum CEA could predict the prognosis in patients with colorectal cancer liver metastasis (CRCLM) before and after liver resection (LR).

Methods

PubMed, Embase, Cochrane, and Web of Science were systematically searched to retrieve literature, with a search cutoff date of 27 February 2023. Articles were strictly screened for inclusion according to pre-specified inclusion and exclusion criteria. Data were pooled and analyzed using Stata 16.0.

Results

This meta-analysis included 36 studies involving a total of 11 143 CRCLM patients. The results showed that a high pre-LR serum CEA level was correlated with poor overall survival (OS: HR = 1.61, 95% CI = 1.49–1.75, P < 0.001) and recurrence-free survival (RFS: HR = 1.27, 95% CI = 1.11–1.45, P < 0.001) in CRCLM patients. A high post-LR serum CEA level predicted poor overall survival (OS: HR = 2.66, 95% CI = 2.10–3.38, P < 0.001).

Conclusion

High preoperative and postoperative serum CEA levels in patients with CRCLM were significantly associated with poor prognosis, independent of treatment modality, mode of analysis, case origin, and cutoff value classification.
Construction and validation of a nomogram prediction model for axillary lymph node metastasis of cT1 invasive breast cancer
Authors: Wang Shuqi , Wang Dongmo , Wen Xin , Xu Xiangli , Liu Dongmei , Tian Jiawei
Published: November 2023

Objective

Based on the ultrasonic characteristics of the breast mass and axillary lymph nodes as well as the clinicopathological information, a model was developed for predicting axillary lymph node metastasis in cT1 breast cancer, and relevant features associated with axillary lymph node metastasis were identified.

Methods

Our retrospective study included 808 patients with cT1 invasive breast cancer treated at the Second Affiliated Hospital and the Cancer Hospital Affiliated with Harbin Medical University from February 2012 to August 2021 (250 cases in the positive axillary lymph node group and 558 cases in the negative axillary lymph node group). We allocated 564 cases to the training set and 244 cases to the verification set. R software was used to compare clinicopathological data and ultrasonic features between the two groups. Based on the results of multivariate logistic regression analysis, a nomogram prediction model was developed and verified for axillary lymph node metastasis of cT1 breast cancer.

Results

Univariate and multivariate logistic regression analysis indicated that palpable lymph nodes (P = 0.003), tumor location (P = 0.010), marginal contour (P < 0.001), microcalcification (P = 0.010), surrounding tissue invasion (P = 0.046), ultrasonic detection of lymph nodes (P = 0.001), cortical thickness (P < 0.001) and E-cadherin (P < 0.001) are independently associated with axillary lymph node metastasis. Using these features, a nomogram was developed for axillary lymph node metastasis. The training set had an area under the curve of 0.869, while the validation set had an area under the curve of 0.820. Based on the calibration curve, the model predicted axillary lymph node metastases were in good agreement with reality (P > 0.05). Nomogram’s net benefit was good based on decision curve analysis.

Conclusion

The nomogram developed in this study has a high negative predictive value for axillary lymph node metastasis in invasive cT1 breast c ancer. Patients with no axillary lymph node metastases can be accurately screened using this nomogram, potentially allowing this group of patients to avoid invasive surgery.
Examination of the mechanisms underlying the discriminative stimulus properties of the atypical antipsychotic amisulpride
Authors: Donahue Timothy J. , Hillhouse Todd M. , Webster Kevin A. , Young Richard , De Oliveira Eliseu O. , Porter Joseph H.
Published: November 2023

Amisulpride is an atypical benzamide antipsychotic/antidepressant, whose mechanism of action is thought to depend mainly on dopamine D2/3 receptor activity, but also with some serotonin 5-HT2B/7 effects. The present study examined the role of D2/3 receptors and 5-HT2B/7 receptors in amisulpride’s discriminative stimulus. Selective agonists and antagonists of the above receptors were tested in adult, male C57BL/6 mice trained to discriminate 10 mg/kg amisulpride from vehicle in a two-lever drug discrimination assay. After acquisition of the two-lever discrimination, the amisulpride generalization curve yielded an ED50 = 0.56 mg/kg (95% CI = 0.42–0.76 mg/kg). Substitution tests found that the D2/3 antagonist raclopride (62.7% Drug Lever Responding), D2/3 agonist quinpirole (56.6% DLR), 5-HT7 agonist LP-44 (50.1% DLR) and 5-HT7 antagonist SB-269970 (36.7% DLR) produced various degrees of partial substitution for the amisulpride stimulus, whereas the 5-HT2B agonist BW 723C86 (17.9% DLR) and 5-HT2B antagonist SB-204741 (21.1% DLR) yielded negligible amisulpride-like effects. In combination tests with amisulpride, quinpirole decreased percent responding from 98.3% to 57.0% DLR, LP-44 decreased percent responding from 97.6% to 76.7% DLR, and BW 723C86 reduced percent responding from 95.66% to 74.11% DLR. Taken together, the results from stimulus generalization and antagonism studies suggest that amisulpride has a complex discriminative cue that involves mainly mixed D2/3 receptor antagonist/agonist effects and, to a lesser degree, mixed 5-HT7 receptor agonist/antagonist and perhaps 5-HT2B receptor antagonist effects.
The role of nutrition in the prevention of cognitive decline
Authors: Charbit Judith , Vidal Jean Sébastien , Hanon Olivier
Published: November 2023

Purpose of review

Dementia is a growing concern and underscores the urgent need for effective preventive measures targeting modifiable risk factors. Nutrition is a key player in the onset and progression of inflammation and cognitive decline. This review provides a comprehensive overview of the effects of different dietary patterns, vitamins and nutrients for preventing cognitive decline, mainly among healthy individuals and those with mild cognitive impairment.

Recent findings

The Mediterranean diet, omega-3 long-chain polyunsaturated fatty acids and B vitamins are the most investigated, with evidence supporting protection against cognitive decline among older adults varying across studies. More recent interventions examined in this review, such as MIND Diet, are promising with positive results, but further research is needed to conclusively establish their efficacy. It is also crucial to consider complete lifestyle as physical activity for preventing cognitive decline.

Definitive conclusions are difficult to draw. Future studies should adopt a comprehensive approach and focus on multinutrient strategies and whole diets.
New primary immunodeficiencies 2023 update
Authors: Yu Joyce E.
Published: November 2023

Purpose of review

Primary immunodeficiency diseases (PIDs), also called inborn errors of immunity (IEI), are genetic disorders characterized by increased susceptibility to infection and/or aberrant regulation of immunological pathways. This review summarizes and highlights the new IEI disorders in the International Union of Immunological Societies (IUIS) 2022 report and current trends among new PIDs.

Recent findings

Since the 2019 IUIS report and the 2021 IUIS interim update, the IUIS IEI classification now includes 485 validated IEIs. Increasing utilization of genetic testing and advances in the strategic evaluation of genetic variants has continued to drive the identification of, not only novel IEI disorders, but additional genetic etiologies for known IEI disorders and phenotypes.

The recognition of new IEIs continues to advance at a rapid pace, which is due in part to increased performance and application of genetic modalities as well as expansion of the underlying science that is applied to convincingly establish causality. These disorders, as a whole, continue to emphasize the specificity of immunity, complexity of immune mechanisms, and the fine balance that defines immune homeostasis.
Where a child lives matters: neighborhood deprivation and pediatric obesity
Authors: Ikomi Chijioke , Baker-Smith Carissa M.
Published: November 2023

Purpose of review

This article outlines what is currently known regarding the relationship between neighborhood deprivation and pediatric obesity. It discusses the intersectionality between neighborhood deprivation, race, ethnicity, and pediatric obesity. We conclude by proposing several potential solutions to disparities in pediatric obesity related to neighborhood deprivation.

Recent findings

Neighborhood deprivation, independent of individual socioeconomic status, is a risk factor for pediatric obesity. The obesogenic characteristics of high deprivation neighborhoods (e.g., lack of safe spaces to be active, easy access to fast food) and the psychological aspects of residing within high deprivation neighborhoods may also contribute to this risk. Intervention strategies and policies designed to address neighborhood related risk for pediatric obesity are needed.

Pediatric obesity is a growing problem of complex etiology. Neighborhood risk factors should be considered when assessing risk burden and when designing intervention strategies.
A Cellular atlas of the human fallopian tube reveals the metamorphosis of secretory epithelial cells during the menstrual cycle and menopause
Authors: Weigert M , Li Y , Zhu L , Eckart H , Bajwa P , Krishnan R , Ackroyd S , Lastra RR , Bilecz A , Basu A , Lengyel E , Chen M
Published: November 2023

The fallopian tube, connecting the uterus with the ovary, is a dynamic organ that undergoes cyclical changes and is the site of several diseases, including serous cancer. Here, we use single-cell technologies to construct a comprehensive cell map of healthy pre-menopausal fallopian tubes, capturing the impact of the menstrual cycle and menopause on different fallopian tube cells at the molecular level. The comparative analysis between pre- and post-menopausal fallopian tubes reveals substantial shifts in cellular abundance and gene expression patterns, highlighting the physiological changes associated with menopause. Further investigations into menstrual cycle phases illuminate distinct molecular states in secretory epithelial cells caused by hormonal fluctuations. The markers we identified characterizing secretory epithelial cells provide a valuable tool for classifying ovarian cancer subtypes.

Graphical summary

Graphical summary of results. During the proliferative phase (estrogenhigh) of the menstrual cycle, SE2 cells (OVGP1+) dominate the fallopian tube (FT) epithelium, while SE1 cells (OVGP1-) dominate the epithelium during the secretory phase. Though estrogen levels decrease during menopause, SE post-cells (OVGP1+, CXCL2+) make up most of the FT epithelium.
Prioritization of therapeutic targets for amyotrophic lateral sclerosis using protein-wide Mendelian randomization analysis
Authors: Geng Jiawei , Chen Lu-Xi , Yang Chao-Sen , Ruan Xixian , Hu Shixian , Chen Jie , Wu Zhi-Ying
Published: November 2023

Background and Objectives

Amyotrophic lateral sclerosis (ALS) is a rapidly progressing neurodegenerative disease with an increasing global burden. Available treatments for ALS present marginal efficacy. To identify novel candidate therapeutic targets for ALS, we conducted a proteome-wide Mendelian randomization (MR) study.

Methods

We leveraged data from the largest summary statistics for ALS to date (27,205 patients with ALS and 110,881 controls). Genetic instruments of more than 4,000 proteins defined bycis-protein quantitative loci (pQTL) genetic instruments on plasma and cerebrospinal fluid (CSF) were obtained from Fenland (discovery, n=10,709), deCODE (replication, n=35,559), and a recently published dataset (replication, n=971). To investigate the causal ALS-associated proteins, proteome-wide Mendelian randomization based on summary-data-based MR (SMR and multi-SNP-based SMR) were performed. Then, two-sample MR analyses using five additional methods were conducted as sensitivity analyses. To further address the linkage disequilibrium bias, heterogeneity in dependent instruments test and colocalization analyses were performed. Steiger filtering and bi-directional MR analyses were conducted to address the potential reverse causality. Four drug target datasets were searched to extract druggability profiles for candidate target proteins. In addition, we carried out a case-control study involving up to 21 patients with ALS and 21 matched controls to assess the protein levels difference in CSF for evidence triangulation.

Results

Genetically predicted levels of six circulating proteins were associated with incident ALS in primary SMR analysis. After removing proteins with any linkage disequilibrium bias, SHBG,SIGLEC7, and SIGLEC9presented consistent associations with ALS risk, supported by medium-to-high colocalization across both plasma pQTL datasets. In CSF, higher level ofSHBGwas also causally associated with the risk of ALS. There was no reverse causality detected. The case-control study using CSF proteomics conducted in our center observed consistent alteration in the levels ofSHBGandSIGLEC7with MR prediction, further suggesting their functionally relevant to ALS as potential druggable targets.

Discussion

Combined with the findings from MR and our observational study, we prioritizeSHBG,SIGLEC7,andSIGLEC9as drug candidate proteins for ALS, and further studies are needed to verify our findings and elucidate the underlying mechanism.
Characterizing US spatial connectivity: implications for geographical disease dynamics and metapopulation modeling
Authors: Pullano Giulia , Alvarez-Zuzek Lucila G. , Colizza Vittoria , Bansal Shweta
Published: November 2023

Background

Human mobility is expected to be a critical factor in the geographic diffusion of infectious diseases, and this assumption led to the implementation of social distancing policies during the early fight against the COVID-19 emergency in the United States. Yet, because of substantial data gaps in the past, what still eludes our understanding are the following questions: 1) How does mobility contribute to the spread of infection within the United States at local, regional, and national scales? 2) How do seasonality and shifts in behavior affect mobility over time? 3) At what geographic level is mobility homogeneous across the United States? Addressing these questions is critical to developing accurate transmission models, predicting the spatial propagation of disease across scales, and understanding the optimal geographical and temporal scale for the implementation of control policies.

Methods

We address this problem using high-resolution human mobility data measured via mobile app usage. We compute the daily connectivity network between US counties to understand the spatial clustering and temporal stability of mobility patterns. We then integrate our mobility data into a spatially explicit transmission model to reproduce the national invasion of the first wave of SARS-CoV-2 in the US, and characterize the impact of the spatio-temporal scale of mobility data on disease predictions.

Findings

Temporally, we observe that intercounty connectivity is annually stable, and was unperturbed by mobility restrictions during the early phase of the COVID-19 pandemic, despite significant changes in overall activity. Spatially, we identify 104 geographic clusters of US counties that are highly connected by mobility within the cluster and more sparsely connected to counties outside the cluster. Together, these results suggest that intercounty connectivity in the US is relatively static across time and is highly connected at the sub-state level. We find that the stability in temporal patterns allows static mobility data to effectively capture infection dynamics. On the other hand, spatial uniformity at the sub-state (cluster)-scale does not capture spatial dynamics; instead, mobility data at the county-scale is necessary to better predict spatial disease diffusion.

Interpretation

Our work demonstrates that intercounty mobility was negligibly affected out-side the lockdown period of Spring 2020, explaining the broad spatial distribution of COVID-19 outbreaks in the US during the early phase of the pandemic. Such geographically dispersed outbreaks place a significant strain on national public health resources and necessitate complex metapopulation modeling approaches for predicting disease dynamics and control design. We thus inform the design of such metapopulation models to balance high disease predictability with low data requirements.
Differential Prognostic Value of Angiography-Derived Microcirculatory Resistance for Coronary Artery Bypass Grafting of Intermediate Coronary Stenosis
Authors: Yan Wenlong , Wang Yangyang , Hu Haoyu , Wang Wei , Li Zhenfu , Zheng Xin , Yang Sumin
Published: November 2023

BACKGROUND

For patients with intermediate coronary stenoses, the prognostic value of coronary artery bypass grafting (CABG) remains controversial. The prognostic impact of CABG may be different according to Murray law-based quantitative flow ratio (μQFR) and angiography-derived microcirculatory resistance (AMR) in patients with intermediate coronary stenoses.

METHODS AND RESULTS

Clinical data of 1411 cases who were diagnosed with multivessel coronary artery disease and had coronary artery intermediate stenoses (50% to 70% by visual assessment) between January 2013 and January 2020 were collected. Patients were categorized into CABG and defer groups based on the decision to bypass intermediate stenoses. These patients were further divided into different subgroups based on μQFR and AMR. The primary outcome was the major adverse cardiac and cerebrovascular events (MACCE), defined as a composite of cardiac death, target vessel myocardial infarction, target vessel revascularization and stroke. Multivariable analysis showed AMR (HR = 1.68, 95% CI 1.18-4.14, P = 0.008) was independent factor associated with MACCE in all patients. On receiver-operating characteristic (ROC) curve analysis, the estimated area under the curve was 0.75 (95% CI: 0.72-0.79) for MACCE. Using the maximum Youden’s index, the optimal cutoff value for AMR to predict MACCE was 2.50 mmHg*s/cm. In defer group, MACCE was significantly lower in patients with both μQFR > 0.80 and AMR < 2.50 mmHg*s/cm as compared with patients with μQFR > 0.80 (13.2% vs 22.0%, P = 0.031) or AMR < 2.50 mmHg*s/cm (13.2% vs 23.6%, P = 0.012) alone. Compared with patients with both normal μQFR and AMR, patients with both abnormal μQFR and AMR carried the highest risk for MACCE (HR = 3.46, 95% CI 2.10-5.71, P < 0.001). CABG was associated with a lower risk of MACCE compared with the deferral strategy when both μQFR and AMR were abnormal. In contrast, at normal μQFR and AMR, patients in both CABG and defer groups had similar MACCE outcomes.

CONCLUSIONS

In patients with intermediate coronary stenoses, the prognostic value of treatment strategy differed according to μQFR and AMR, with a significant interaction. The combination of μQFR and AMR can help stratify risk and guide treatment strategies for patients with intermediate coronary stenoses.
Perceptual salience is insufficient for auditory streaming in eastern gray treefrogs (Hyla versicolor)
Authors: Kalra Lata , Altman Shoshana , Bee Mark A.
Published: November 2023

Auditory streaming underlies a receiver’s ability to organize complex mixtures of auditory input into distinct perceptual “streams” that represent different sound sources in the environment. During auditory streaming, sounds produced by the same source are integrated through time into a single, coherent auditory stream that is perceptually segregated from other concurrent sounds. Based on human psychoacoustic studies, a prominent hypothesis regarding auditory streaming is thatanyperceptually salient acoustic difference between sounds can promote their segregation into distinct auditory streams. Here, we used the eastern gray treefrog,Hyla versicolor, to test this hypothesis in the context of vocal communication in a non-human animal. In this system, females choose their mate based on perceiving features of a male’s pulsatile advertisement calls in social environments (choruses) characterized by mixtures of overlapping vocalizations. We employed an experimental paradigm from human psychoacoustics to design interleaved pulsatile sequences (ABAB…) that mimicked key features of the species’ advertisement call, and in which alternating pulses differed in pulse rise time, which is a robust species recognition cue in eastern gray treefrogs. Using phonotaxis assays, we found no evidence that perceptually salient differences in pulse rise time promoted the segregation of interleaved pulse sequences into distinct auditory streams. These results suggest the hypothesis that any perceptually salient acoustic difference can be exploited as a cue for stream segregation is not supported in all species. We discuss these findings in the context of cues used for species recognition and auditory streaming.
Upstream open reading frames dynamically modulate CLOCK protein translation to regulate circadian rhythm and sleep
Authors: Sun Yuanqiang , Shui Ke , Li Qinyu , Liu Chenlu , Jin Wanting , Ni Jian-Quan , Lu Jian , Zhang Luoying
Published: November 2023

The circadian rhythm is an evolutionarily conserved mechanism with translational regulation increasingly recognized as pivotal in its modulation. In this study, we found that upstream open reading frames (uORFs) are enriched in circadian rhythm genes, with particularly conserved uORFs present in core circadian clock genes. We demonstrate evidence that the uORFs of the core clock gene,Clock(Clk), rhythmically and substantially attenuate CLK protein translation inDrosophila, with pronounced suppression occurring during daylight hours. EliminatingClkuORFs results in elevated CLK protein levels during the day and a compressed circadian cycle, along with a broad shift in clock gene expression rhythms. Interestingly,ClkuORF deletion also augments morning sleep by reducing dopaminergic activity. Beyond daily circadian adjustments,ClkuORFs play a role in modulating sleep patterns in response to the varying day lengths of different seasons, inhibiting translation in a day-length contingent manner. Furthermore, theClkuORFs act as a master regulator to shape the rhythmic expression of a vast array of genes and influence multifaceted physiological outcomes. Collectively, our research sheds light on the intricate ways uORFs dynamically adjust downstream coding sequences to acclimate to environmental shifts.
Multiparametric MRI detects multi-organ impairment in patients with chronic myeloid neoplasms with normal serum biomarkers
Authors: Reed Sophie , Diamond Charlie , Mahmood Samiya , Rymell Soubera , Smith Michael , Pansini Michele , Psaila Bethan , Mead Adam J. , Thomaides-Brears Helena , Chowdhury Onima
Published: November 2023

Assessment of organ impairment in patients with chronic myeloid neoplasms is pivotal in selecting treatments and for accurate prognostication of patient outcomes. In order to determine the multi-organ health of patients with chronic myeloid neoplasms, we conducted a prospective, observational study utilising a novel MRI technology which quantitatively assesses the health of multiple organs in one scan. Organ impairment was significantly higher in the patient cohort compared to healthy controls, most notably with increased rates of kidney fibroinflammation 28% vs 0% (p-value = 0.002). MRI-defined kidney impairment was prevalent in patients with normal serum biomarkers of kidney disease, demonstrating the added value of MRI as a tool to identify occult organ impairment. This has wider implications for enhancing the assessment of organ health in patients with a variety of blood cancers at diagnosis and throughout treatment, guiding more personalised strategies and improving patient outcomes.
Fine-Tuning the Llama2 Large Language Model Using Books on the Diagnosis and Treatment of Musculoskeletal System in Physical Therapy
Authors: Kim Jun-hee
Published: November 2023

Backgroud

Generative language models (GLM) utilize machine learning algorithms to perform various tasks such as text generation, question response, and sentence completion by imitating the language that humans understand and use.

Purpose

This study was to fine-tune the Llama2 language model using text data from books on the diagnosis and treatment of musculoskeletal system in physical therapy and compare it to the base model to determine its usability in medical fields.

Results

Compared to the base model, the fine-tuned model consistently generated answers specific to the musculoskeletal system diagnosis and treatment, demonstrating improved understanding of the specialized domain.

Conclusion

The model fine-tuned for musculoskeletal diagnosis and treatment books provided more detailed information related to musculoskeletal topics, and the use of this fine-tuned model could be helpful in medical education and the acquisition of specialized knowledge.
Medial temporal lobe hyperconnectivity is key to Alzheimer’s disease: Insight from physiological aging to dementia
Authors: Chauveau Léa , Landeau Brigitte , Dautricourt Sophie , Turpin Anne-Laure , Delarue Marion , Hébert Oriane , de La Sayette Vincent , Chételat Gaël , de Flores Robin
Published: November 2023

Curing Alzheimer’s disease (AD) remains hampered by an incomplete understanding of its pathophysiology and progression. Dysfunction within medial temporal lobe networks may provide key insights, as AD proteins seem to propagate specifically through the anterior-temporal (AT) and posterior-medial (PM) systems. Using monocentric longitudinal data from 267 participants spanning physiological aging to the full AD continuum, we found that advancing age was associated with decreased PM connectivity and increased AT connectivity over adult life. When specifically assessing AD-relevant connectivity changes, all AD-associated clinicopathological features, including elevated amyloid burden, AD-typical glucose hypometabolism, hippocampal atrophy, greater cognitive impairment and faster progression from MCI to AD-dementia, were consistently linked to AT hyperconnectivity in healthy to AD-demented older adults. Our comprehensive approach allowed us to reveal that excessive connectivity within the AT network is a pivotal mechanism catalysing pathological process and progression of AD. Such findings hold promise for early diagnosis and therapeutic strategies targeting these specific network alterations.
Hydroxyurea maintains working memory function in pediatric sickle cell disease
Authors: Lai Jesyin , Zou Ping , Dalboni da Rocha Josue L. , Heitzer Andrew M. , Patni Tushar , Li Yimei , Scoggins Matthew A. , Sharma Akshay , Wang Winfred C. , Helton Kathleen J. , Sitaram Ranganatha
Published: November 2023

Pediatric patients with sickle cell disease (SCD) have decreased oxygen-carrying capacity in the blood and reduced or restricted cerebral blood flow resulting in neurocognitive deficits and cerebral infarcts. The standard treatment for children with SCD is hydroxyurea; however, the treatment-related neurocognitive effects are unclear. A key area of impairment in SCD is working memory, which is implicated in other cognitive and academic skills. N-back tasks are commonly used to investigate neural correlates of working memory. We analyzed functional magnetic resonance imaging (fMRI) of patients with SCD while they performed n-back tasks by assessing the blood-oxygenation level-dependent (BOLD) signals during working memory processing. Twenty hydroxyurea-treated and 11 control pediatric patients with SCD (7–18 years old) performed 0-, 1-, and 2-back tasks at 2 time points, once before hydroxyurea treatment (baseline) and ∼1 year after treatment (follow-up). Neurocognitive measures (e.g., verbal comprehension, processing speed, full-scale intelligence quotient, etc.) were assessed at both time points. Although no significant changes in behavior performance of n-back tasks and neurocognitive measures were observed in the treated group, we observed a treatment-by-time interaction in the right cuneus and angular gyrus for the 2-> 0-back contrast. Through searchlight-pattern classifications in the treated and control groups to identify changes in brain activation between time points during the 2-back task, we found more brain areas, especially the posterior region, with changes in the pattern and magnitude of BOLD signals in the control group compared to the treated group. In the control group, increases in 2-back BOLD signals were observed in the right crus I cerebellum, right inferior parietal lobe, right inferior temporal lobe, right angular gyrus, left cuneus and left middle frontal gyrus at 1-year follow-up. Moreover, BOLD signals elevated as the working memory load increased from 0- to 1-back but did not increase further from 1- to 2-back in the right inferior temporal lobe, right angular gyrus, and right superior frontal gyrus. These observations may result from increased cognitive effort during working memory processing with no hydroxyurea treatment. In contrast, we found fewer changes in the pattern and magnitude of BOLD signals across time points in the treated group. Furthermore, BOLD signals in the left crus I cerebellum, right angular gyrus, left cuneus and right superior frontal gyrus of the treated group increased continuously with increasing working memory load from 0- to 2-back, potentially related to a broader dynamic range in response to task difficulty and cognitive effort. Collectively, these findings suggest that hydroxyurea treatment helped maintain working memory function in SCD.
Avian influenza viruses in wild birds in Canada following incursions of highly pathogenic H5N1 virus from Eurasia in 2021/2022
Authors: Giacinti Jolene A. , Signore Anthony V. , Jones Megan E. B. , Bourque Laura , Lair Stéphane , Jardine Claire , Stevens Brian , Bollinger Trent , Goldsmith Dayna ,   British Columbia Wildlife AIV Surveillance Program (BC WASPs), Pybus Margo , Stasiak Iga , Davis Richard , Pople Neil , Nituch Larissa , Brook Rodney W. , Ojkic Davor , Massé Ariane , Dimitri-Masson Gabrielle , Parsons Glen J. , Baker Meghan , Yason Carmencita , Harms Jane , Jutha Naima , Neely Jon , Berhane Yohannes , Lung Oliver , French Shannon K. , Myers Lawrna , Provencher Jennifer F. , Avery-Gomm Stephanie , Robertson Gregory J. , Barychka Tatsiana , Gurney Kirsty E. B. , Wight Jordan , Rahman Ishraq , Hargan Kathryn , Lang Andrew S. , Brown Michael G. C. , Pekarik Cynthia , Thompson Trevor , McLaughlin Angela , Willie Megan , Wilson Laurie , Flemming Scott A. , Ross Megan V. , Leafloor Jim , Baldwin Frank , Sharp Chris , Lewis Hannah , Beaumont Matthieu , Hanson Al , Ronconi Robert A. , Reed Eric , Campbell Margaret , Saunders Michelle , Soos Catherine
Published: November 2023

Following detection of novel highly pathogenic avian influenza virus (HPAIV) H5N1 clade 2.3.4.4b in Newfoundland, Canada in late 2021, avian influenza surveillance in wild birds was scaled-up across Canada. Herein, we present results of Canada’s Interagency Surveillance Program for Avian Influenza in wild birds during the first year (November 2021 – November 2022) following the incursions of HPAIV from Eurasia. Key objectives of the surveillance program were to (i) detect the presence, distribution and spread of HPAIV and other avian influenza viruses (AIVs), (ii) detect wild bird morbidity and mortality associated with HPAIV, (iii) identify the range of wild bird species infected by HPAIV, and (iv) characterize detected AIV. A total of 6,246 sick and dead wild birds were tested, of which 27.4% were HPAIV positive across 12 taxonomic orders and 80 species. Geographically, HPAIV detections occurred in all Canadian provinces and territories, with the highest numbers in the Atlantic and Central flyways. Temporally, peak detections differed across flyways, though the national peak occurred in April 2022. In an additional 11,295 asymptomatic harvested or live captured wild birds, 5.2% were HPAIV positive across 3 taxonomic orders and 19 species. Whole genome sequencing identified HPAIV of Eurasian origin as most prevalent in the Atlantic flyway, along with multiple reassortants of mixed Eurasian and North American origins distributed across Canada, with moderate structuring at the flyway scale. Wild birds were victims and reservoirs of HPAIV H5N1 2.3.4.4b, underscoring the importance of surveillance encompassing samples from sick and dead, as well as live and harvested birds to provide insights into the dynamics and potential impacts of the HPAIV H5N1 outbreak. This dramatic shift in presence and distribution of HPAIV in wild birds in Canada highlights a need for sustained investment in wild bird surveillance and collaboration across One Health partners.
E3 ligases RNF43 and ZNRF3 display differential specificity for endocytosis of Frizzled family members
Authors: Bugter Jeroen M. , van Kerkhof Peter , Janssen Eline , Tran Ngoc Minh Thi , Iglesias van Montfort Daniel , Jamieson Cara , Jordens Ingrid , Maurice Madelon M.
Published: November 2023

The transmembrane E3 ligases RNF43 and ZNRF3 perform key tumour suppressor roles by inducing endocytosis of members of the Frizzled (FZD) family, the primary receptors for WNT. Loss-of-function mutations inRNF43andZNRF3mediate FZD stabilisation and a WNT-hypersensitive growth state in various cancer types. Strikingly,RNF43andZNRF3mutations are differentially distributed across cancer types, raising questions about their functional redundance. Here, we compare the efficacy of RNF43 and ZNRF3 of targeting different FZDs for endocytosis. We find that RNF43 preferentially downregulates FZD1/FZD5/FZD7, while ZNRF3 displays preference towards FZD6/FZD10. We show that the RNF43 transmembrane domain (TMD) is a key molecular determinant for inducing FZD5 endocytosis. Furthermore, a TMD swap between RNF43 and ZNRF3 re-directs their preference for FZD member downregulation. We conclude that RNF43 and ZNRF3 preferentially downregulate specific FZDs by a TMD-dependent mechanism. In accordance, tissue-specific expression patterns of FZD homologues correlate with the incidence ofRNF43orZNRF3cancer mutations in those tissues. Consequently, our data point to druggable vulnerabilities of specific FZD receptors inRNF43-orZNRF3-mutant human cancers.
Pharmacological modulation of the cytosolic oscillator affects glioblastoma cell biology
Authors: Wagner Paula M , Guido Mario E
Published: November 2023

The circadian system is a conserved time-keeping machinery that regulates a wide range of processes such as sleep/wake, feeding/fasting, and activity/rest cycles to coordinate behavior and physiology. Circadian disruption can be a contributing factor in the development of metabolic diseases, inflammatory disorders, and higher risk of cancer. Glioblastoma (GBM) is a highly aggressive grade 4 brain tumor that is resistant to conventional therapies and has a poor prognosis after diagnosis, with a median survival of only 12-15 months. GBM cells kept in culture were shown to contain a functional circadian oscillator. In seeking more efficient therapies with lower side effects, we evaluated the pharmacological modulation of the circadian clock by targeting the cytosolic kinases glycogen synthase kinase-3 (GSK-3) and casein kinase ε/δ (CK1ε/δ) with specific inhibitors (CHIR99022 and PF670462, respectively), the cryptochrome protein stabilizer (KL001), or circadian disruption afterPer2 knockdown expression in GBM-derived cells. CHIR99022-treated cells had a significant effect on cell viability, clock protein expression, migration, and cell cycle distribution. Moreover, cultures exhibited higher levels of reactive oxygen species and alterations in lipid droplet content after GSK-3 inhibition as compared with control cells. The combined treatment of CHIR99022 with temozolomide was found to improve the effect on cell viability compared to temozolomide therapy alone.Per2 disruption affected both GBM migration and cell cycle progression. Overall, our results suggest that pharmacological modulation or molecular clock disruption severely affects glioblastoma cell biology.