bluuebunny/crossref_metadata_2025 huggingface dataset:
Clustering care pathways of people with alcohol dependence using a data linkage of routine data in Bremen, Germany
Authors: Möckl Justin , Manthey Jakob , Murawski Monika , Lindemann Christina , Schulte Bernd , Reimer Jens , Pogarell Oliver , Kraus Ludwig
Published: May 2024

Background

Although many individuals with alcohol dependence (AD) are recognized in the German healthcare system, only a few utilize addiction-specific treatment services. Those who enter treatment are not well characterized regarding their prospective pathways through the highly fragmented German healthcare system. This paper aims to (1) identify typical care pathways of patients with AD and their adherence to treatment guidelines and (2) explore the characteristics of these patients using routine data from different healthcare sectors.

Methods

We linked routinely collected register data of individuals with a documented alcohol-related diagnosis in the federal state of Bremen, Germany, in 2016/2017 and their addiction-specific health care: two statutory health insurance funds (outpatient pharmacotherapy for relapse prevention and inpatient episodes due to AD with and without qualified withdrawal treatment (QWT)), the German Pension Insurance (rehabilitation treatment) and a group of communal hospitals (outpatient addiction care). Individual care pathways of five different daily states of utilized addiction-specific treatment following an index inpatient admission due to AD were analyzed using state sequence analysis and cluster analysis. The follow-up time was 307 days (10 months). Individuals of the clustered pathways were compared concerning current treatment recommendations (1: QWT followed by postacute treatment; 2: time between QWT and rehabilitation). Patients’ characteristics not considered during the cluster analysis (sex, age, nationality, comorbidity, and outpatient addiction care) were then compared using a multinomial logistic regression.

Results

The analysis of 518 individual sequences resulted in the identification of four pathway clusters differing in their utilization of acute and postacute treatment. Most did not utilize subsequent addiction-specific treatment after their index inpatient episode (n = 276) or had several inpatient episodes or QWT without postacute treatment (n = 205). Two small clusters contained pathways either starting rehabilitation (n = 26) or pharmacotherapy after the index episode (n = 11). Overall, only 9.3% utilized postacute treatment as recommended.

Conclusions

A concern besides the generally low utilization of addiction-specific treatment is the implementation of postacute treatments for individuals after QWT.
Chronic endometritis and the endometrial microbiota: implications for reproductive success in patients with recurrent implantation failure
Authors: Zhang Hong , Zou Heng , Zhang Chanyu , Zhang Shen
Published: May 2024

Background

Chronic endometritis (CE) is associated with poor reproductive outcomes, yet the role of endometrial microbiota in patients with recurrent implantation failure (RIF) and CE remains unclear. This study aims to characterize endometrial microbiota in RIF patients with CE and assess its implications for reproductive outcomes.

Methods

In this prospective study, we enrolled RIF patients both with and without CE. Endometrial and cervical samples were collected for 16 S rRNA gene sequencing. Microbiota composition was compared between groups using diversity indices, phylum, and genus-level analysis. Canonical correlation analysis (CCA) and Spearman’s correlation coefficients were used to assess relationships between CE, reproductive outcomes, and microbiota. Predictive functional profiling was performed to evaluate metabolic pathways associated with CE.

Results

Endometrial microbiota in CE patients exhibited greater diversity and evenness compared to non-CE patients. Principal coordinates analysis (PCoA) revealed distinct clustering between CE and non-CE groups. Linear discriminant analysis (LDA) identified Proteobacteria, Aminicenantales, and Chloroflexaceae as characteristic of CE, while Lactobacillus, Acinetobacter, Herbaspirillum, Ralstonia, Shewanela, and Micrococcaceae were associated with non-CE. CCA demonstrated associations between CE, adverse reproductive outcomes, and specific bacterial taxa. Microbial metabolic pathways significantly differed between CE and non-CE groups, with enrichment in pathways related to cofactors, vitamins, secondary metabolites, and the immune system in CE patients.

Conclusion

RIF patients with CE exhibit distinct endometrial microbiota compositions associated with adverse reproductive outcomes. The increased microbial diversity and altered metabolic pathways in CE suggest a potential correlation with reproductive outcomes, although further studies are necessary to elucidate the causal relationship between microbiota alterations and fertility. Modulating the endometrial microbiome may represent a novel therapeutic strategy to improve IVF outcomes in patients with CE.
Molecular classification and biomarkers of outcome with immunotherapy in extensive-stage small-cell lung cancer: analyses of the CASPIAN phase 3 study
Authors: Xie Mingchao , Vuko Miljenka , Rodriguez-Canales Jaime , Zimmermann Johannes , Schick Markus , O’Brien Cathy , Paz-Ares Luis , Goldman Jonathan W. , Garassino Marina Chiara , Gay Carl M. , Heymach John V. , Jiang Haiyi , Barrett J. Carl , Stewart Ross A. , Lai Zhongwu , Byers Lauren A. , Rudin Charles M. , Shrestha Yashaswi
Published: May 2024

Background

We explored potential predictive biomarkers of immunotherapy response in patients with extensive-stage small-cell lung cancer (ES-SCLC) treated with durvalumab (D) + tremelimumab (T) + etoposide-platinum (EP), D + EP, or EP in the randomized phase 3 CASPIAN trial.

Methods

805 treatment-naïve patients with ES-SCLC were randomized (1:1:1) to receive D + T + EP, D + EP, or EP. The primary endpoint was overall survival (OS). Patients were required to provide an archived tumor tissue block (or ≥ 15 newly cut unstained slides) at screening, if these samples existed. After assessment for programmed cell death ligand-1 expression and tissue tumor mutational burden, residual tissue was used for additional molecular profiling including by RNA sequencing and immunohistochemistry.

Results

In 182 patients with transcriptional molecular subtyping, OS with D ± T + EP was numerically highest in the SCLC-inflamed subtype (n = 10, median 24.0 months). Patients derived benefit from immunotherapy across subtypes; thus, additional biomarkers were investigated. OS benefit with D ± T + EP versus EP was greater with high versus low CD8A expression/CD8 cell density by immunohistochemistry, but with no additional benefit with D + T + EP versus D + EP. OS benefit with D + T + EP versus D + EP was associated with high expression of CD4 (median 25.9 vs. 11.4 months) and antigen-presenting and processing machinery (25.9 vs. 14.6 months) and MHC I and II (23.6 vs. 17.3 months) gene signatures, and with higher MHC I expression by immunohistochemistry.

Conclusions

These findings demonstrate the tumor microenvironment is important in mediating better outcomes with D ± T + EP in ES-SCLC, with canonical immune markers associated with hypothesized immunotherapy mechanisms of action defining patient subsets that respond to D ± T.

Trial registration

ClinicalTrials.gov, NCT03043872.
Understanding adverse childhood experiences and the call for trauma-informed healthcare system in Turkey: a review
Authors: Yildiz Nadire Gülçin , Aydin Halide Z. , Aydin Kemal , Yildiz Hatice , Sambo Grace , Mwamulima Bwanalori , Zonda Joe Maganga , Phiri Doreen , Phiri Yohane Vincent Abero
Published: May 2024

Over the past four decades, research has underscored the significance of approaching and preventing trauma from a systemic standpoint. Trauma-informed care (TIC) methodologies offer a structure for healthcare practices, striving to convert organizations into trauma-informed systems that employ trauma-specific interventions. This review employs epidemiological and household data from Turkey to underscore the importance of integrating trauma-informed care as a means of prevention and intervention. Through a desk review, the study examines the role of adverse childhood experiences (ACEs), delving into their origin from family dynamics, migration, violence, exposure to violence, juvenile delinquency, and child maltreatment. The research highlights innovative healthcare approaches that leverage data to address complex patient health issues while considering mental health needs. In contemporary times, healthcare organizations acknowledge the value of a data-driven approach to make informed clinical decisions, enhance treatment procedures, and improve overall healthcare outcomes. The reviewed research and empirical data furnish proof of the importance of effective and efficient treatment methods that prioritize trauma prevention and treatment, integrating the role of ACEs. This paper seeks to contribute to discussions on transforming the healthcare system to meet the healthcare needs of Turkish households, all the while taking into account the evolving sociopolitical factors that shape Turkey's population characteristics.
Explore the practice and barriers of collaborative health policy and system research-priority setting exercise in Ethiopia
Authors: Tilahun Binyam , Amare Getasew , Endehabtu Berhanu Fikadie , Atnafu Asmamaw , Derseh Lemma , Gurmu Kassu Ketema , Delllie Endalkachew , Nigusie Adane
Published: May 2024

Introduction

Collaboration is gaining prominence in the priority setting of Health Policy And System Research (HPSR). However, its practice and challenges are not well explored in Ethiopia. Understanding the practice and barriers of collaborative Health Policy and System Research will help design approaches and platforms for setting inclusive and participatory policy and system-level health research topics. This paper explores the practice and barriers of collaborative HPSR-priority setting exercise in Ethiopia.

Methods

This study investigates the practice and barriers of collaborative health policy and system research priority-setting exercises in Ethiopia. Utilizing a mixed-methods approach, we conducted Key Informant Interviews (KIIs) and an online self-administered survey with open-ended questionnaires to capture diverse perspectives from stakeholders involved in the research priority-setting process. Through conventional content analysis, we identified key contents related to current practices, challenges, and opportunities for enhancing collaboration in health policy and system research prioritization.

Results

Our findings reveal a complex landscape characterized by varying levels of stakeholder engagement, institutional capacity constraints, and competing priorities within the health research ecosystem. Despite notable efforts to foster collaboration, stakeholders identified persistent challenges such as limited resources, institutional fragmentation, and inadequate coordination mechanisms as barriers to effective priority-setting processes. The implications of our research extend beyond academic discourse, with direct relevance to health policy and system research practice in Ethiopia. By shedding light on the dynamics of collaborative priority-setting exercises, our findings offer valuable insights for policymakers, researchers, and practitioners seeking to enhance the effectiveness and inclusivity of health research prioritization processes. Addressing the identified barriers and leveraging existing strengths in the research ecosystem can contribute to more evidence-informed health policies and programs, ultimately improving health outcomes for Ethiopian populations.

Conclusions

Most institutions do not apply health policy and system research-priority setting to conduct informed decision-making. The barriers explored were weak integration, lack of knowledge, system, and platforms for the priority setting of Health Policy and System Resreach. So, it is recommended to build skills of different actors in the Health Policy and System Research-priority setting exercise and design a system and platform to integrate different stakeholders for collaborative research topics priority setting.
CircDCAF8 promotes the progression of hepatocellular carcinoma through miR-217/NAP1L1 Axis, and induces angiogenesis and regorafenib resistance via exosome-mediated transfer
Authors: Gong Jiahao , Han Guoyong , Chen Zhiqiang , Zhang Yinqi , Xu Bin , Xu Chao , Gao Wen , Wu Jindao
Published: May 2024

Background

Circular RNAs (circRNAs), which are a new type of single-stranded circular RNA, have significant involvement in progression of many diseases, including tumors. Currently, multiple circRNAs have been identified in hepatocellular carcinoma (HCC). Our study aims to investigate the function and mechanism of circDCAF8 in HCC.

Methods

The expression of circDCAF8 (hsa_circ_0014879) in HCC and para-carcinoma tissue samples was determined using quantitative real-time polymerase chain reaction (qRT-PCR). The biological function of circDCAF8 in HCC was confirmed by experiments conducted both in vitro and in vivo. And the relationship between circDCAF8, miR-217 and NAP1L1 was predicted by database and verified using qRT-PCR, RNA-binding protein immunoprecipitation (RIP) and dual-luciferase reporter assays. Exosomes isolated from HCC cells were utilized to assess the connection of exosomal circDCAF8 with HCC angiogenesis and regorafenib resistance.

Results

CircDCAF8 is upregulated in HCC tissues and cell lines, and is linked to an unfavourable prognosis for HCC patients. Functionally, circDCAF8 was proved to facilitate proliferation, migration, invasion and Epithelial-Mesenchymal Transformation (EMT) in HCC cells. Animal examinations also validated the tumor-promoting characteristics of circDCAF8 on HCC. Besides, exosomal circDCAF8 promoted angiogenesis in HUVECs. Mechanistically, circDCAF8 interacted with miR-217 and NAP1L1 was a downstream protein of miR-217. CircDCAF8 promoted NAP1L1 expression by sponging miR-217. In addition, exosomes may transfer circDCAF8 from regorafenib-resistant HCC cells to sensitive cells, where it would confer a resistant phenotype.

Conclusion

CircDCAF8 facilitates HCC proliferation and metastasis via the miR-217/NAP1L1 axis. Meanwhile, circDCAF8 can promote angiogenesis and drive resistance to regorafenib, making it a viable therapeutic target for HCC patients.
BIBR1532 combined with radiotherapy induces ferroptosis in NSCLC cells and activates cGAS-STING pathway to promote anti-tumor immunity
Authors: Bao Yawei , Pan Zhipeng , Zhao Luqi , Qiu Jieping , Cheng Jingjing , Liu Lei , Qian Dong
Published: May 2024

Background

Telomerase, by safeguarding damaged telomeres and bolstering DNA damage repair, has the capacity to heighten the radioresistance of tumour cells. Thus, in turn, can compromise the efficacy of radiotherapy (RT) and radioimmunotherapy. Our previous studies have revealed that the highly selective telomerase inhibitor, BIBR1532, possesses the potential to enhance the radiosensitivity of Non-small cell lung cancer (NSCLC). In this study, we delve further into the impact of BIBR1532 on the immune activation induced by RT and elucidate the underlying mechanisms.

Methods

Biological information analyses, immunofluorescence assays, western blot assays, flow cytometry analysis were conducted to elucidate the functions of the combination of BIBR1532 with radiotherapy in NSCLC. Intracellular levels of lipid peroxides, glutathione, malondialdehyde, and Fe2+ were measured as indicators of ferroptosis status. Both in vitro and in vivo studies were conducted to examine the antitumor effects.

Results

Our findings indicate that the confluence of BIBR1532 with RT significantly augments the activation of the cGAS-STING pathway in both in vivo and in vitro settings, thereby fostering an effective anti-tumoral immune response. The effects can be ascribed to two key processes. Firstly, ionizing radiation, in precipitating DNA double-strand breaks (DSBs), prompts the release of tumour-derived double-stranded DNA (dsDNA) into the cytoplasm. Subsequently, BIBR1532 amplifies the activation of antigen-presenting cells by dsDNA post-RT and instigates the cGAS-STING pathway. Secondly, BIBR1532 enhances the ferroptosis response in NSCLC following RT, thereby promoting unrestrained lipid peroxidation and elevated levels of reactive oxygen species (ROS) within tumour cells. This ultimately leads to mitochondrial stress and the release of endogenous mitochondrial DNA (mtDNA) into the cytoplasm, thus facilitating the activation of the STING pathway and the induction of a type I interferon (IFN)-linked adaptive immune response.

Conclusion

This study underscores the potential of BIBR1532 as an efficacious and safe radiosensitizer and radioimmunotherapy synergist, providing robust preclinical research evidence for the treatment of NSCLC.
Neuromodulation of inhibitory control using phase-lagged transcranial alternating current stimulation
Authors: Kim Yukyung , Lee Je-Hyeop , Park Je-Choon , Kwon Jeongwook , Kim Hyoungkyu , Seo Jeehye , Min Byoung-Kyong
Published: May 2024

Background

Transcranial alternating current stimulation (tACS) is a prominent non-invasive brain stimulation method for modulating neural oscillations and enhancing human cognitive function. This study aimed to investigate the effects of individualized theta tACS delivered in-phase and out-of-phase between the dorsal anterior cingulate cortex (dACC) and left dorsolateral prefrontal cortex (lDLPFC) during inhibitory control performance.

Methods

The participants engaged in a Stroop task with phase-lagged theta tACS over individually optimized high-density electrode montages targeting the dACC and lDLPFC. We analyzed task performance, event-related potentials, and prestimulus electroencephalographic theta and alpha power.

Results

We observed significantly reduced reaction times following out-of-phase tACS, accompanied by reduced frontocentral N1 and N2 amplitudes, enhanced parieto-occipital P1 amplitudes, and pronounced frontocentral late sustained potentials. Out-of-phase stimulation also resulted in significantly higher prestimulus frontocentral theta and alpha activity.

Conclusions

These findings suggest that out-of-phase theta tACS potently modulates top-down inhibitory control, supporting the feasibility of phase-lagged tACS to enhance inhibitory control performance.
High-throughput color determination of red raspberry puree and correlation of color parameters with total anthocyanins
Authors: Baldassi Claudia , Lee Clover , Dossett Michael , Castellarin Simone D.
Published: May 2024

Background

Red raspberry fruit color is a key driver of consumer preference and a major target of breeding programs worldwide. Screening for fruit color typically involves the determination of anthocyanin content and/or the assessment of color through a colorimeter. However, both procedures are time-consuming when the analyses involve hundreds or thousands of samples. The objectives of this study were to develop a high-throughput method for red raspberry puree color measurement and to test the correlations between color parameters and total anthocyanin content. Color coordinates were collected with a colorimeter on 126 puree samples contained in Petri dishes and with the Tomato Analyzer Color Test (TACT) module to assess the same samples prepared in Petri dishes and in 96-well plates. An additional 425 samples were analyzed using only 96-well plates. Total anthocyanins were extracted from all 551 samples.

Results

Regression models for L*, a*, b* measured with the colorimeter and TACT using Petri dishes were all significant (p < 0.001), but very consistent only for L* (R2 = 0.94). Significant (p < 0.001) and very consistent regressions (R2 = 0.94 for L* and b*, R2 = 0.93 for a*) were obtained for color parameters measured with TACT using Petri dishes and TACT using plates. Of the color parameters measured with the colorimeter, only L*, a*/b*, and hue significantly correlated with total anthocyanins (p < 0.05), but, except for L* (R = − 0.79), the correlations were weak (R = − 0.23 for a*/b* and R = 0.22 for hue). Conversely, all correlations with total anthocyanins and color parameters measured with TACT were significant (p < 0.001) and moderately strong (e.g., R = − 0.69 for L* and R = 0.55 for a*/b*). These values were indicative of darker colors as total anthocyanin content increased.

Conclusions

While the colorimeter and TACT-based methods were not fully interchangeable, TACT better captured color differences among raspberry genotypes than the colorimeter. The correlations between color parameters measured with TACT and total anthocyanins were not strong enough to develop prediction models, yet the use of TACT with 96-well plates instead of Petri dishes would enable the high-throughput measurement of red raspberry puree color.
School refusal behavior in children and adolescents: a five-year narrative review of clinical significance and psychopathological profiles
Authors: Di Vincenzo Cristina , Pontillo Maria , Bellantoni Domenica , Di Luzio Michelangelo , Lala Maria Rosaria , Villa Marianna , Demaria Francesco , Vicari Stefano
Published: May 2024

The aim of the study was to explore the clinical significance of school refusal behavior, its negative impact on psychological well-being of children and adolescents and its relationship with the most common psychopathological conditions during childhood and adolescence (e.g. neurodevelopmental disorders, psychiatric disorders). School refusal behavior refers to a distressing condition experienced by children and adolescents that compromise regular school attendance and determine negative consequences on mental health and adaptive functioning. A narrative review of the literature published between January 2019 and March 2023 was conducted. Ten studies (n = 10) were included from a literature search of the electronic databases PubMed, CINAHL, PsycInfo, MedLine, and Cochrane Library. The results indicate that school refusal is highly present in neurodevelopmental disorders such as autism and attention-deficit/hyperactivity disorder due to the presence of behavioral problems and deficits in communication skills. As for psychiatric disorders, school refusal appears to be highly common in anxiety disorders, depressive disorders, and somatic symptoms. We also found that school refusal behavior may be associated with various emotional and behavioral conditions that act as risk factors. Especially, but are not limited to, it may be associated with a diminished self-concept, exposure to cyberbullying, specific affective profiles and excessive technology usage. Our results indicate that school refusal is a condition with many clinical facets. It can be attributed to both vulnerability factors, both temperamental and relational, and to various psychopathological conditions that differ significantly from each other, such as neurodevelopmental disorders and psychiatric disorders. Recognizing these aspects can improve the implementation of patient-tailored therapeutic interventions that are consequently more likely to produce effective outcomes. The therapeutic intervention should facilitate the recognition of cognitive biases regarding school as a threatening environment, while regulating negative emotions associated with school attendance. Additionally, therapeutic intervention programs linked to social skill training and problem-solving training, conducted directly within the school setting, can enhance children’s abilities to cope with academic performance and social relationships, ultimately preventing school refusal.
EDI3 knockdown in ER-HER2+ breast cancer cells reduces tumor burden and improves survival in two mouse models of experimental metastasis
Authors: Glotzbach Annika , Rohlf Katharina , Gonscharow Anastasia , Lüke Simon , Demirci Özlem , Begher-Tibbe Brigitte , Overbeck Nina , Reinders Jörg , Cadenas Cristina , Hengstler Jan G. , Edlund Karolina , Marchan Rosemarie
Published: May 2024

Background

Despite progress understanding the mechanisms underlying tumor spread, metastasis remains a clinical challenge. We identified the choline-producing glycerophosphodiesterase, EDI3 and reported its association with metastasis-free survival in endometrial cancer. We also observed that silencing EDI3 slowed cell migration and other cancer-relevant phenotypes in vitro. Recent work demonstrated high EDI3 expression in ER-HER2+ breast cancer compared to the other molecular subtypes. Silencing EDI3 in ER-HER2+ cells significantly reduced cell survival in vitro and decreased tumor growth in vivo. However, a role for EDI3 in tumor metastasis in this breast cancer subtype was not explored. Therefore, in the present work we investigate whether silencing EDI3 in ER-HER2+ breast cancer cell lines alters phenotypes linked to metastasis in vitro, and metastasis formation in vivo using mouse models of experimental metastasis.

Methods

To inducibly silence EDI3, luciferase-expressing HCC1954 cells were transduced with lentiviral particles containing shRNA oligos targeting EDI3 under the control of doxycycline. The effect on cell migration, adhesion, colony formation and anoikis was determined in vitro, and significant findings were confirmed in a second ER-HER2+ cell line, SUM190PT. Doxycycline-induced HCC1954-luc shEDI3 cells were injected into the tail vein or peritoneum of immunodeficient mice to generate lung and peritoneal metastases, respectively and monitored using non-invasive bioluminescence imaging. Metabolite levels in cells and tumor tissue were analyzed using targeted mass spectrometry and MALDI mass spectrometry imaging (MALDI-MSI), respectively.

Results

Inducibly silencing EDI3 reduced cell adhesion and colony formation, as well as increased susceptibility to anoikis in HCC1954-luc cells, which was confirmed in SUM190PT cells. No influence on cell migration was observed. Reduced luminescence was seen in lungs and peritoneum of mice injected with cells expressing less EDI3 after tail vein and intraperitoneal injection, respectively, indicative of reduced metastasis. Importantly, mice injected with EDI3-silenced cells survived longer. Closer analysis of the peritoneal organs revealed that silencing EDI3 had no effect on metastatic organotropism but instead reduced metastatic burden. Finally, metabolic analyses revealed significant changes in choline and glycerophospholipid metabolites in cells and in pancreatic metastases in vivo.

Conclusions

Reduced metastasis upon silencing supports EDI3’s potential as a treatment target in metastasizing ER-HER2+ breast cancer.
Long-term prosthetic-associated subclinical thrombotic events evaluation by cardiac CTA after transcatheter aortic valve implantation: incidence and outcomes
Authors: Zhou Qijing , Wen Jiaqi , Zhu Qifeng , Fan Jiaqi , Guan Xiaojun , Chen Xinyi , He Yuxin , Guo Yuchao , Jiang Jubo , Ding Xinfa , Pu Zhaoxia , Huang Zhaoxu , Li Cheng , Zhang Minming , Liu Xianbao , Xu Xiaojun , Wang Jian’an
Published: May 2024

Objective

To observe prosthetic-associated subclinical thrombotic events (PASTE) after transcatheter aortic valve implantation (TAVI) by cardiac CTA, and assess their impact on long-term patient outcomes.

Materials

We prospectively and consecutively enrolled 188 patients with severe aortic stenosis treated with TAVI from February 2014 to April 2017. At 5 years, 61 of 141 survived patients who had completed annual follow-up CTA (≥ 5 years) were included. We analyzed PASTE by CTA, including hypoattenuated leaflet thickening (HALT), sinus filling defect (SFD), and prosthesis filling defect (PFD). The primary outcome was a major adverse cardiovascular composite outcome (MACCO) of stroke, cardiac re-hospitalization, and bioprosthetic valve dysfunction (BVD); the secondary outcomes were bioprosthetic hemodynamics deterioration (PGmean) and cardiac dysfunction (LVEF).

Results

During a median follow-up time of 5.25 years, long-term incidence of HALT, SFD, and PFD were 54.1%, 37.7%, and 73.8%, respectively. In the primary outcome, SFD and early SFD were associated with the MACCO (SFD: p = 0.005; early SFD: p = 0.018), and SFD was a predictor of MACCO (HR: 2.870; 95% CI: 1.010 to 8.154, p = 0.048). In the secondary outcomes, HALT was associated with increased PGmean (p = 0.031), while persistent HALT was correlated with ΔPGmean (β = 0.38, p = 0.035). SFD was negatively correlated with ΔLVEF (β = −0.39, p = 0.041), and early SFD was negatively correlated with LVEF and ΔLVEF (LVEF: r = −0.50, p = 0.041; ΔLVEF: r = −0.53, p = 0.030).

Conclusions

PASTE were associated with adverse long-term outcomes, bioprosthetic hemodynamics deterioration, and cardiac dysfunction. In particular, SFD was a predictor of MACCO and may be a potential target for anticoagulation after TAVI (NCT02803294).

Registration

URL: https://www.clinicaltrials.gov; Unique identifier: NCT02803294.

Critical relevance statement

PASTE, especially SFD, after TAVI based on cardiac CTA findings impacts the long-term outcomes of patients which is a predictor of long-term major adverse outcomes in patients and may be a potential target for anticoagulation after TAVI.

Key Points

Transcatheter aortic valve implantation is being used more often; associated subclinical thromboses have not been thoroughly evaluated.

Prosthetic-associated subclinical thrombotic events were associated with adverse outcomes, bioprosthetic hemodynamics deterioration, and cardiac dysfunction.

Studies should be directed at these topics to determine if they should be intervened upon.

Graphical Abstract
MolScore: a scoring, evaluation and benchmarking framework for generative models in de novo drug design
Authors: Thomas Morgan , O’Boyle Noel M. , Bender Andreas , De Graaf Chris
Published: May 2024

Generative models are undergoing rapid research and application to de novo drug design. To facilitate their application and evaluation, we present MolScore. MolScore already contains many drug-design-relevant scoring functions commonly used in benchmarks such as, molecular similarity, molecular docking, predictive models, synthesizability, and more. In addition, providing performance metrics to evaluate generative model performance based on the chemistry generated. With this unification of functionality, MolScore re-implements commonly used benchmarks in the field (such as GuacaMol, MOSES, and MolOpt). Moreover, new benchmarks can be created trivially. We demonstrate this by testing a chemical language model with reinforcement learning on three new tasks of increasing complexity related to the design of 5-HT2a ligands that utilise either molecular descriptors, 266 pre-trained QSAR models, or dual molecular docking. Lastly, MolScore can be integrated into an existing Python script with just three lines of code. This framework is a step towards unifying generative model application and evaluation as applied to drug design for both practitioners and researchers. The framework can be found on GitHub and downloaded directly from the Python Package Index.

Scientific Contribution

MolScore is an open-source platform to facilitate generative molecular design and evaluation thereof for application in drug design. This platform takes important steps towards unifying existing benchmarks, providing a platform to share new benchmarks, and improves customisation, flexibility and usability for practitioners over existing solutions.

Graphical Abstract
Anatomy and size of Megateuthis, the largest belemnite
Authors: Klug Christian , Schweigert Günter , Hoffmann René , Fuchs Dirk , Pohle Alexander , Weis Robert , De Baets Kenneth
Published: May 2024

Belemnite rostra are very abundant in Mesozoic marine deposits in many regions. Despite this abundance, soft-tissue specimens of belemnites informing about anatomy and proportions of these coleoid cephalopods are extremely rare and limited to a few moderately large genera like Passaloteuthis and Hibolithes. For all other genera, we can make inferences on their body proportions and body as well as mantle length by extrapolating from complete material. We collected data of the proportions of the hard parts of some Jurassic belemnites in order to learn about shared characteristics in their gross anatomy. This knowledge is then applied to the Bajocian genus Megateuthis, which is the largest known belemnite genus worldwide. Our results provide simple ratios that can be used to estimate belemnite body size, where only the rostrum is known.
The effectiveness of e-mental health interventions on stress, anxiety, and depression among healthcare professionals: a systematic review and meta-analysis
Authors: Zhang Zemiao , Hu Yinhuan , Liu Sha , Feng Xiandong , Yang Jinhong , Cheng Ling Jie , Ramazanu Sheena , Wu Xi Vivien
Published: May 2024

Background

Many healthcare professionals are experiencing psychological distress. Electronic mental health (e-mental health) interventions are convenient and multifunctional. This review aimed to examine the effectiveness of e-mental health interventions in enhancing the well-being of healthcare professionals and to identify moderating factors.

Methods

A comprehensive and systematic retrieval of randomized controlled trial (RCT) studies was conducted across eight databases. Population, intervention, comparison, and outcome (PICO) were used to define eligibility criteria. Stress, anxiety, and depression were included as the main outcomes. The overall effect was calculated based on the random effect model, and the effect size was presented using the standardized mean difference. The characteristics of the research design, intervention object, and intervention design were further selected as potential moderating factors for subgroup analysis. Meta-regression analyses were finally performed, incorporating intervention duration and sample size as independent variables.

Results

A total of 20 studies were included in the systematic review, and 17 were included in the meta-analysis. A large effect on relieving stress and anxiety and a small-to-medium effect on reducing depression were observed. Subgroup analyses showed that features including mindfulness approaches, online courses, computer use, group interventions, and professional guidance were more favorable in the design of services. Meta-regression revealed that intervention duration only affected anxiety symptoms. Caution should be exercised, as some subgroups had fewer studies and higher heterogeneity. For the secondary outcomes, a large effect on emotional exhaustion and a small-to-medium effect on well-being were observed.

Conclusion

In general, e-mental health interventions significantly improve the psychological health of healthcare staff. Future high-quality, large-scale studies targeting healthcare professionals and specific intervention scenarios are warranted.
How much online pornography is too much? A comparison of two theoretically distinct assessment scales
Authors: Vera Cruz Germano , Aboujaoude Elias , Liberacka-Dwojak Magdalena , Wiłkość-Dębczyńska Monika , Rochat Lucien , Khan Riaz , Khazaal Yasser
Published: May 2024

Background

Online pornography use, an ever more common activity, has raised myriad psychosocial and clinical concerns. While there is a need to screen for and measure its problematic dimension, there is a debate about the adequacy of existing assessment tools.

Objective

The study compares two instruments for measuring pathological online pornography use (POPU) that are based on different theoretical frameworks—one in line with DSM-5 criteria and the six-component addiction model and one in line with ICD-11 criteria.

Methods

An international sample of 1,823 adults (Mean age = 31.66, SD = 6.74) answered an online questionnaire that included the Short Version of the Problematic Pornography Consumption Scale (PPCS-6) and the Assessment of Criteria for Specific Internet-Use Disorders (ACSID-11). Factorial, correlational, and network analyses were conducted on the data.

Results

Both tools adequately screened for online “addictive” behavior, but the ACSID-11 was superior in assessing the degree of clinical risk.

Conclusion

Depending on the specific aim of the assessment (screening vs. clinical diagnostics), both online pornography measurement tools may be useful.
Thyroid Malignancy in Patients Who Underwent Thyroidectomy for Multinodular Goiter and Solitary Thyroid Nodule
Authors: Gedamu Desalew , Shimels Tariku , Kassie Daniel , Chanyalew Zewditu , Eyasu Mebrahtu
Published: May 2024

PURPOSE

Worldwide, incidence of thyroid malignancy is increasing. The purpose of this study was to evaluate the pattern and magnitude of nodule types.

METHODS

A cross-sectional retrospective study was performed at Saint Paul's Hospital Millennium Medical College, Addis Ababa, Ethiopia, among patients who underwent thyroidectomy from May 2018 to June 2022. Data were extracted using a structured format. Descriptive statistics were performed using SPSS version 26 software. Results were presented in terms of percentages and frequencies.

RESULTS

During a 4-year period, 1,476 patients had thyroidectomies and histopathologic information of 212 malignant cases was studied. Within multinodular goiter (MNG), thyroid cancer accounted for 69.8% (n = 148) of patients, whereas in solitary nodules, it accounted for 30.2%. From the total, 160 participants (75.5%) were female, and the female:male ratio was 3.1 (mean, 41.72; ± standard deviation [SD], 16.44) years, and age range of 12-88 years versus men, who have a mean of 44.71 (±SD, 14.91) years and an age range of 21-78 years. The mean age of male cases with solitary nodule and MNG was 40.6 and 46.5 years, respectively. The most frequent cancer in both types of nodules, accounting for 59% of patients, was papillary carcinoma, which was found in 64% of solitary nodules and 57.4% of multinodular nodules. Overall, 14.1% of tumors had multiple centers (17.4% in multinodular nodules and 6.9% in solitary nodules). In 7.1% of patients, microcarcinoma (<1 cm) was found, with papillary carcinoma accounting for 91.7% of the total.

CONCLUSION

Compared with men, women with cancer typically manifested at a younger age. Males with malignancy in solitary nodules had a lower mean age than those with MNGs. The most frequent and significant cause of multicentric presentation is papillary carcinoma.
Therapy for Stage IV Non–Small Cell Lung Cancer With Driver Alterations: ASCO Living Guideline, Version 2024.1
Authors: Owen Dwight H. , Ismaila Nofisat , Freeman-Daily Janet , Roof Logan , Singh Navneet , Velazquez Ana I. , Leighl Natasha B.
Published: May 2024

Living guidelines are developed for selected topic areas with rapidly evolving evidence that drives frequent change in recommended clinical practice. Living guidelines are updated on a regular schedule by a standing expert panel that systematically reviews the health literature on a continuous basis, as described in the ASCO Guidelines Methodology Manual . ASCO Living Guidelines follow the ASCO Conflict of Interest Policy Implementation for Clinical Practice Guidelines . Living Guidelines and updates are not intended to substitute for independent professional judgment of the treating provider and do not account for individual variation among patients. See appendix for disclaimers and other important information ( Appendix 1 and Appendix 2 ). Updates are published regularly and can be found at https://ascopubs.org/nsclc-da-living-guideline .
Categorical Displacement
Authors: Moffett-Bateau Courtney
Published: May 2024

This article offers a history of Black thought as it has been represented or underrepresented in the university by tracing the phenomenon of the US American cultural wars to the Civil War. The article discusses the displacement of Black knowledges from predominantly white institutional structures as a categorical problem that spreads across all disciplines by identifying four formative aspects of the university: understanding the university as an institution, its relationship with society and literature, and the canon-building discourses that fuel a market demand for certain Black knowledges. Finding that the displacement of Black knowledges is facilitated by a logic of institutional discrimination, which cannot be reduced to only a problem of the university, this article argues that the displacement of Black knowledges is a central problem of American education and foundational to American society and history.
Sibling Availability, Sibling Sorting, and Subjective Health Among Chinese Adults
Authors: Wang Haowei , Verdery Ashton M. , Margolis Rachel
Published: May 2024

Despite rising numbers of only children in China, little is known about their family dynamics and well-being in adulthood—for example, how often they marry other only children and whether those in siblingless families have worse or better health than others. Theoretical expectations produce opposing predictions: siblings might provide social and emotional support and reduce parental caregiving pressures, but only children might receive more support from parents and grandparents. Using the 2010 China Family Panel Study, we examine marital sorting on Chinese adults’ number of siblings and test whether sibling availability and sibling sorting are associated with subjective physical and mental health. Despite general perceptions that China has an exceedingly high prevalence of adults with no siblings that might produce very small families, results demonstrate a low prevalence of siblingless couples (i.e., both spouses are only children). Married adults with no siblings or siblings-in-law have better subjective physical health but similar levels of subjective mental health relative to their counterparts with siblings. The health advantages of siblingless marital unions are greater for rural and female adults. Declining sibling prevalence in China will shape future family demographic dynamics but appears less detrimental to population health than sometimes assumed.
On Archipelagic Memory: A Conversation with Michael Rothberg and Vijaya Teelock
Authors: Raimondi Luca , Kabir Ananya Jahanara
Published: May 2024

On February 1, 2022, the online seminar “Conceptualising Archipelagic Memory” was organized as the curtain-raiser event for the Archipelagic Memory project and the international conference that took place in August of the same year. The seminar brought together Professors Michael Rothberg and Vijaya Teelock, in conversation with Ananya Kabir, to initiate a discussion on practices of memory-making in archipelagic spaces and through archipelagic structures, and on the meanings and possibilities embedded in the notion of “archipelagic memory.” In this annotated transcript of the conversation, Rothberg and Teelock reflect with Kabir on their research trajectories and expertise, provoking new models of analysis constitutive of an archipelagic approach to Indian Ocean cultural history.
Establishment and maintenance of random monoallelic expression
Authors: Kanata Eleni , Duffié Rachel , Schulz Edda G.
Published: May 2024

This Review elucidates the regulatory principles of random monoallelic expression by focusing on two well-studied examples: the X-chromosome inactivation regulator Xist and the olfactory receptor gene family. Although the choice of a single X chromosome or olfactory receptor occurs in different developmental contexts, common gene regulatory principles guide monoallelic expression in both systems. In both cases, an event breaks the symmetry between genetically and epigenetically identical copies of the gene, leading to the expression of one single random allele, stabilized through negative feedback control. Although many regulatory steps that govern the establishment and maintenance of monoallelic expression have been identified, key pieces of the puzzle are still missing. We provide an overview of the current knowledge and models for the monoallelic expression of Xist and olfactory receptors. We discuss their similarities and differences, and highlight open questions and approaches that could guide the study of other monoallelically expressed genes.
An updated model of shoot apical meristem regulation by ERECTA family and CLAVATA3 signaling pathways in Arabidopsis
Authors: Uzair Muhammad , Urquidi Camacho Ricardo Andres , Liu Ziyi , Overholt Alex M. , DeGennaro Daniel , Zhang Liang , Herron Brittani S. , Hong Tian , Shpak Elena D.
Published: May 2024

The shoot apical meristem (SAM) gives rise to the aboveground organs of plants. The size of the SAM is relatively constant due to the balance between stem cell replenishment and cell recruitment into new organs. In angiosperms, the transcription factor WUSCHEL (WUS) promotes stem cell proliferation in the central zone of the SAM. WUS forms a negative feedback loop with a signaling pathway activated by CLAVATA3 (CLV3). In the periphery of the SAM, the ERECTA family receptors (ERfs) constrain WUS and CLV3 expression. Here, we show that four ligands of ERfs redundantly inhibit the expression of these two genes. Transcriptome analysis confirmed that WUS and CLV3 are the main targets of ERf signaling and uncovered new ones. Analysis of promoter reporters indicated that the WUS expression domain mostly overlaps with the CLV3 domain and does not shift along the apical-basal axis in clv3 mutants. Our three-dimensional mathematical model captured gene expression distributions at the single-cell level under various perturbed conditions. Based on our findings, CLV3 regulates cellular levels of WUS mostly through autocrine signaling, and ERfs regulate the spatial expression of WUS, preventing its encroachment into the peripheral zone.
Investigating pulmonary neuroendocrine cells in human respiratory diseases with airway models
Authors: Candeli Noah , Dayton Talya
Published: May 2024

Despite accounting for only ∼0.5% of the lung epithelium, pulmonary neuroendocrine cells (PNECs) appear to play an outsized role in respiratory health and disease. Increased PNEC numbers have been reported in a variety of respiratory diseases, including chronic obstructive pulmonary disease and asthma. Moreover, PNECs are the primary cell of origin for lung neuroendocrine cancers, which account for 25% of aggressive lung cancers. Recent research has highlighted the crucial roles of PNECs in lung physiology, including in chemosensing, regeneration and immune regulation. Yet, little is known about the direct impact of PNECs on respiratory diseases. In this Review, we summarise the current associations of PNECs with lung pathologies, focusing on how new experimental disease models, such as organoids derived from human pluripotent stem cells or tissue stem cells, can help us to better understand the contribution of PNECs to respiratory diseases.
Task-Based Discrimination
Authors: Hurst Erik , Rubinstein Yona , Shimizu Kazuatsu
Published: May 2024

We develop a task-based model of occupational sorting to identify and quantify the effect of discrimination, racial skill gaps, and aggregate task prices on Black-White differences in labor market outcomes over time. At the heart of our framework is the idea that the size and nature of racial barriers faced by Black workers vary by the task requirements of each job. We define a new task that measures the extent to which individuals interact with others as part of their job. We show that this measure is a good proxy for the extent of discrimination in the economy. (JEL J15, J23, J31, J71, M51)
Long-Run Effects of Incentivizing Work after Childbirth
Authors: Kuka Elira , Shenhav Na’ama
Published: May 2024

This paper identifies the impact of increasing post-childbirth work incentives on mothers’ long-run careers. We exploit variation in work incentives across mothers based on the timing of a first birth and eligibility for the 1993 expansion of the Earned Income Tax Credit. Ten to nineteen years after a first birth, single mothers who were exposed to the expansion immediately after birth (“early”), rather than 3–6 years later (“late”), have 0.62 more years of work experience and 4.2 percent higher earnings conditional on working. We show that higher earnings are primarily explained by improved wages due to greater work experience. (JEL H24, H31, J16, J22, J31)