bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical review of substitutions or alternatives for critical chemotherapy drug shortages in hematologic malignancies
Authors: Tinajero Jose , Markary Tanya , Chen Jason , Agrawal Vaibhav , Ngo Dat
Published: August 2024

Purpose

Over the past decade, drug shortages have become increasingly more problematic for clinicians, with over 300 drug shortages reported in the first quarter of 2023. Shortages of chemotherapy drugs can have a negative impact on patient care, as omission or delay of treatment can lead to worse outcomes. Although many articles have been published on this topic, currently no review articles discuss strategies for using alternative regimens or substitutions in the event of severe chemotherapy drug shortages.

In this article, we review the literature on antineoplastic agents used to treat hematologic malignancies that experienced a drug shortage from 2010 through 2023, providing recommendations for substitutions and alternative regimens in the event of a critical shortage. In particular, we discuss how shortages of fludarabine, cytarabine, daunorubicin, methotrexate, and platinum agents may be addressed, including supporting clinical evidence.

Conclusion

Further publications assessing possible alternatives and substitutions for chemotherapy agents and examining the efficacy of previous strategies are needed to mitigate potentially devastating interruptions to care for patients with cancer during severe drug shortages.
On the dilemma for partial subjunctive supposition
Authors: Zhang Snow
Published: August 2024

In ‘The logic of partial supposition’, Eva and Hartmann present a dilemma for a normative account of partial subjunctive supposition: the natural subjunctive analogue of Jeffrey conditionalization is Jeffrey imaging, but this rule violates a natural monotonicity constraint. This paper offers a partial defence of Jeffrey imaging against Eva and Hartmann’s objection. I show that, although Jeffrey imaging is non-monotonic in Eva and Hartmann’s sense, it is what I call status quo monotonic. A status quo monotonic credal revision rule is monotonic in Eva and Hartmann’s sense if it is conservative in the sense of Meehan and Zhang (‘Jeffrey meets Kolmogorov’), but Jeffrey imaging is in general non-conservative. On the other hand, Jeffrey imaging satisfies a different constraint that I call convexity, and the only rule that is both convex and conservative is Jeffrey conditionalization. To this extent, the real dilemma for a normative account of partial subjunctive supposition is not between monotonicity (broadly construed) and Jeffrey imaging, but between convexity and conservativeness.
Soft Tissue Facial Changes Following Massive Weight Loss Secondary to Medical and Surgical Bariatric Interventions: A Systematic Review
Authors: Jafar Ali B , Jacob Jerril , Kao Wee Katherine , Ho Tang
Published: August 2024

Bariatric interventions, both surgical and medical, are increasingly employed by patients to achieve weight reduction and enhance overall health. However, there is growing concern about the associated changes in soft tissue facial aesthetics resulting from these interventions. In this systematic review, the authors aimed to analyze the existing literature regarding soft tissue facial changes after bariatric interventions, with a focus on the influence of massive weight loss on facial aging, attractiveness, and considerations for facial rejuvenation. A systematic review was conducted until February 10, 2024, using electronic databases such as PubMed, Scopus, Web of Science, Embase, and Google Scholar. This review was registered in the open science framework. The Covidence software (Melbourne, VIC, Australia) facilitates title, abstract, and full-text screening, as well as data extraction. In total, 309 papers were identified, 94 duplicates were removed, and 194 studies were excluded on the basis of inclusion criteria. Of the remaining 21 studies, 13 met the inclusion criteria with an additional single study from the conference abstract. Descriptive analysis was conducted. We observed a correlation between massive weight loss and facial aging. The most significant fat regional devolumization was observed along the mid-cheek region and with central neck skin laxity. The apparent age of patients was higher among those with massive weight loss. In our study, we demonstrated that massive weight loss causes accelerated facial aging, manifested through fat devolumization, and increased skin laxity. Further quantitative volumetric facial analyses postbariatric surgery would yield valuable results.

Level of Evidence: 3 (Therapeutic)
Inhibitory effects of extracts from Eucalyptus gunnii on α-synuclein amyloid fibrils
Authors: So Masatomo , Ono Misaki , Oogai Shigeki , Kondo Minako , Yamazaki Kaede , Nachtegael Charlotte , Hamajima Hiroshi , Mutoh Risa , Kato Masaki , Kawate Hisaya , Oki Tomoyuki , Kawata Yasushi , Kumamoto Shiho , Tokui Noritaka , Takei Toshiki , Shimizu Kuniyoshi , Inoue Akio , Yamamoto Naoki , Unoki Motoko , Tanabe Kenichi , Nakashima Kinichi , Sasaki Hiroyuki , Hojo Hironobu , Nagata Yasuo , Suetake Isao
Published: August 2024

Amyloid fibril formation is associated with various amyloidoses, including neurodegenerative diseases such as Alzheimer's and Parkinson's diseases. Despite the numerous studies on the inhibition of amyloid formation, the prevention and treatment of a majority of amyloid-related disorders are still challenging. In this study, we investigated the effects of various plant extracts on amyloid formation of α-synuclein. We found that the extracts from Eucalyptus gunnii are able to inhibit amyloid formation, and to disaggregate preformed fibrils, in vitro. The extract itself did not lead to cell damage. In the extract, miquelianin, which is a glycosylated form of quercetin and has been detected in the plasma and the brain, was identified and assessed to have a moderate inhibitory activity, compared to the effects of ellagic acid and quercetin, which are strong inhibitors for amyloid formation. The properties of miquelianin provide insights into the mechanisms controlling the assembly of α-synuclein in the brain.
GR-pKa: a message-passing neural network with retention mechanism for pKa prediction
Authors: Miao Runyu , Liu Danlin , Mao Liyun , Chen Xingyu , Zhang Leihao , Yuan Zhen , Shi Shanshan , Li Honglin , Li Shiliang
Published: August 2024

During the drug discovery and design process, the acid–base dissociation constant (pKa) of a molecule is critically emphasized due to its crucial role in influencing the ADMET (absorption, distribution, metabolism, excretion, and toxicity) properties and biological activity. However, the experimental determination of pKa values is often laborious and complex. Moreover, existing prediction methods exhibit limitations in both the quantity and quality of the training data, as well as in their capacity to handle the complex structural and physicochemical properties of compounds, consequently impeding accuracy and generalization. Therefore, developing a method that can quickly and accurately predict molecular pKa values will to some extent help the structural modification of molecules, and thus assist the development process of new drugs. In this study, we developed a cutting-edge pKa prediction model named GR-pKa (Graph Retention pKa), leveraging a message-passing neural network and employing a multi-fidelity learning strategy to accurately predict molecular pKa values. The GR-pKa model incorporates five quantum mechanical properties related to molecular thermodynamics and dynamics as key features to characterize molecules. Notably, we originally introduced the novel retention mechanism into the message-passing phase, which significantly improves the model’s ability to capture and update molecular information. Our GR-pKa model outperforms several state-of-the-art models in predicting macro-pKa values, achieving impressive results with a low mean absolute error of 0.490 and root mean square error of 0.588, and a high R2 of 0.937 on the SAMPL7 dataset.
Disease gene prioritization with quantum walks
Authors: Saarinen Harto , Goldsmith Mark , Wang Rui-Sheng , Loscalzo Joseph , Maniscalco Sabrina
Published: August 2024

Motivation

Disease gene prioritization methods assign scores to genes or proteins according to their likely relevance for a given disease based on a provided set of seed genes. This scoring can be used to find new biologically relevant genes or proteins for many diseases. Although methods based on classical random walks have proven to yield competitive results, quantum walk methods have not been explored to this end.

Results

We propose a new algorithm for disease gene prioritization based on continuous-time quantum walks using the adjacency matrix of a protein–protein interaction (PPI) network. We demonstrate the success of our proposed quantum walk method by comparing it to several well-known gene prioritization methods on three disease sets, across seven different PPI networks. In order to compare these methods, we use cross-validation and examine the mean reciprocal ranks of recall and average precision values. We further validate our method by performing an enrichment analysis of the predicted genes for coronary artery disease.

Availability and implementation

The data and code for the methods can be accessed at https://github.com/markgolds/qdgp.
GTAM: A Molecular Pretraining Model with Geometric Triangle Awareness
Authors: Hou Xiaoyang , Zhu Tian , Ren Milong , Duan Bo , Zhang Chunming , Bu Dongbo , Sun Shiwei
Published: August 2024

Motivation

Molecular representation learning is pivotal for advancing deep learning applications in quantum chemistry and drug discovery. Existing methods for molecular representation learning often fall short of fully capturing the intricate interactions within chemical bonds of 2D topological graphs and the multifaceted effects of 3D geometric conformations.

Results

To overcome these challenges, we present a novel contrastive learning strategy for molecular representation learning, named Geometric Triangle Awareness Model (GTAM). This method integrates innovative molecular encoders for both 2D graphs and 3D conformations, enabling the accurate capture of geometric dependencies among edges in graph-based molecular structures. Furthermore, GTAM is bolstered by the development of two contrastive training objectives designed to facilitate the direct transfer of edge information between 2D topological graphs and 3D geometric conformations, enhancing the functionality of the molecular encoders. Through extensive evaluations on a range of 2D and 3D downstream tasks, our model has demonstrated superior performance over existing approaches.

Availability

The test code and data of GTAM are available online at https://github.com/StellaHxy/GTAM.

Supplementary information

Comprehensive implementation details, datasets, and additional experiments can be found in Supplementary Materials A-C.
Interspecific variation in paper wasp body size supports the converse Bergmann’s rule
Authors: de Souza André R , Lopez Vinicius M , Somavilla Alexandre , Nascimento Fábio S , Guillermo Ferreira Rhainer , Yotoko Karla
Published: August 2024

Variation in body size is a conspicuous phenomenon and much scientific interest has been devoted to study the processes affecting this trait. Clines of body size across geographical areas have been detected, supporting ecogeographical rules that describe spatial patterns of phenotypic differences driven by environmental variation. In social insects, the causes of body size variation have been best studied at the within-species level, even though interspecific variation is far more striking. This is the case of Polistes paper wasps, a model genus for sociobiological and ecological studies. Here, we examined whether environmental variation predicts interspecific differences in the body size of New World Polistes, a monophyletic clade widespread through the Americas. Dried museum specimens comprising females from 37 species and males from 28 species were measured. In a phylogenetically controlled analysis, body size was associated with latitude, environmental temperature, and environmental seasonality. Larger species were more likely at low latitudes, in warmer climates, or in environments with mild seasonality. There was no evidence for a phylogenetic signal in body size. These findings support a pattern consistent with the converse Bergmann’s rule, thus suggesting that the limited time for foraging and growth in environments with strong seasonality (or higher latitudes) selects for faster development and maturation at smaller sizes. If so, the evolutionary lability of body size reported here might have contributed to the geographical spread and species diversification in this genus.
Methods in cancer research: Assessing therapy response of spheroid cultures by life cell imaging using a cost-effective live-dead staining protocol
Authors: Phour Jaison , Vassella Erik
Published: August 2024

Spheroid cultures of cancer cell lines or primary cells represent a more clinically relevant model for predicting therapy response compared to two-dimensional cell culture. However, current live-dead staining protocols used for treatment response in spheroid cultures are often expensive, toxic to the cells, or limited in their ability to monitor therapy response over an extended period due to reduced stability. In our study, we have developed a cost-effective method utilizing calcein-AM and Helix NP™ Blue for live-dead staining, enabling the monitoring of therapy response of spheroid cultures for up to 10 days. Additionally, we used ICY BioImage Analysis and Z-stacks projection to calculate viability, which is a more accurate method for assessing treatment response compared to traditional methods on spheroid size. Using the example of glioblastoma cell lines and primary glioblastoma cells, we show that spheroid cultures typically exhibit a green outer layer of viable cells, a turquoise mantle of hypoxic quiescent cells, and a blue core of necrotic cells when visualized using confocal microscopy. Upon treatment of spheroids with the alkylating agent temozolomide, we observed a reduction in the viability of glioblastoma cells after an incubation period of 7 days. This method can also be adapted for monitoring therapy response in different cancer systems, offering a versatile and cost-effective approach for assessing therapy efficacy in three-dimensional culture models.
Association of genetic alterations with prognosis in extramammary Paget disease: insights into the involvement of somatic CDKN2A variants in patients with a poor prognosis
Authors: Iwasawa Okuto , Ikegami Masachika , Miyagawa Takuya , Morita Hiromichi , Saito Hinako , Omori Issei , Awaji Kentaro , Omatsu Jun , Yamada Daisuke , Kage Hidenori , Oda Katsutoshi , Sato Shinichi , Sumida Hayakazu
Published: August 2024

Background

Previous studies have reported the mutational landscape in extramammary Paget disease (EMPD); however, the prognostic implications of genetic alterations remain unexplored. While CDKN2A loss is known to be associated with tumour progression or poor prognosis in some types of cancer, its significance in EMPD has not been investigated.

Objectives

To examine the association between common genetic alterations and prognosis in EMPD.

Methods

A retrospective cohort study was carried out to analyse the data of patients with EMPD registered up to January 2024 in the Center for Cancer Genomics and Advanced Therapeutics database, a nationwide database that records clinical data and comprehensive genomic profiling (CGP) test results in Japan.

Results

A total of 167 patients with EMPD were recorded in the database, with CDKN2A loss being the most frequent genetic variant. Survival analysis was conducted on data from 127 patients. Survival from the initiation of chemotherapy was analysed, adjusting for length bias inherent in the database with the Kaplan–Meier estimator, an established method of adjustment. Patients with BRCA2-mutant tumours (n = 18) had a worse prognosis than those with BRCA2 wildtype (WT) tumours [n = 109; hazard ratio (HR) 2.97, 95% confidence interval (CI) 1.46–6.01 (P = 0.003)]. Additionally, patients in the CDKN2A mutant group (n = 72) had a significantly worse prognosis compared with those in the CDKN2A WT group [n = 55; HR 1.81, 95% CI 1.06–3.07 (P = 0.029)]. Most CDKN2A variants were pathogenic, primarily characterized by loss, while most BRCA2 variants were variants of uncertain significance. In the survival analysis of CGP enrolment based on Eastern Cooperative Oncology Group performance status (ECOG-PS), patients with an ECOG-PS of 1 at the time of CGP enrolment had a significantly poorer prognosis compared with those with an ECOG-PS of 0 (P = 0.034; median survival time 531 vs. 259 days).

Conclusions

A somatic CDKN2A variant, mainly exhibiting loss, may be associated with a poor prognosis in EMPD. Patients with EMPD with BRCA2-mutant disease might also have a worse prognosis. In addition, CGP testing before ECOG-PS deteriorates is preferable, considering that the observed median survival of individuals undergoing CGP tests in an ECOG-PS 1 condition was < 9 months.
Frailty using the Clinical Frailty Scale to predict short- and long-term adverse outcomes following emergency laparotomy: meta-analysis
Authors: Park Brittany , Alani Zena , Sulistio Edrick , Barazanchi Ahmed W H , Koea Jonathan , Vandal Alain , Hill Andrew G , MacCormick Andrew D
Published: August 2024

Background

Emergency laparotomy has high morbidity and mortality rates. Frailty assessment remains underutilized in this setting, in part due to time constraints and feasibility. The Clinical Frailty Scale has been identified as the most appropriate tool for frailty assessment in emergency laparotomy patients and is recommended for all older patients undergoing emergency laparotomy. The prognostic impact of measured frailty using the Clinical Frailty Scale on short- and long-term mortality and morbidity rates remains to be determined.

Methods

Observational cohort studies were identified by systematically searching Medline, Embase, Scopus and CENTRAL databases up to February 2024, comparing outcomes following emergency laparotomy for frail and non-frail participants defined according to the Clinical Frailty Scale. The primary outcomes were short- and long-term mortality rates. A random-effects model was created with pooling of effect estimates and a separate narrative synthesis was created. Risk of bias was assessed.

Results

Twelve articles comprising 5704 patients were included. Frailty prevalence was 25% in all patients and 32% in older adults (age ≥55 years). Older patients with frailty had a significantly greater risk of postoperative death (30-day mortality rate OR 3.84, 95% c.i. 2.90 to 5.09, 1-year mortality rate OR 3.03, 95% c.i. 2.17 to 4.23). Meta-regression revealed that variations in cut-off values to define frailty did not significantly affect the association with frailty and 30-day mortality rate. Frailty was associated with higher rates of major complications (OR 1.93, 95% c.i. 1.27 to 2.93) and discharge to an increased level of care.

Conclusion

Frailty is significantly correlated with short- and long-term mortality rates following emergency laparotomy, as well as an adverse morbidity rate and functional outcomes. Identifying frailty using the Clinical Frailty Scale may aid in patient-centred decision-making and implementation of tailored care strategies for these ‘high-risk’ patients, with the aim of reducing adverse outcomes following emergency laparotomy.
Social Entrepreneurship in Social Work in Multicultural Societies: A Majority and Minority Lens
Authors: Nouman Hani , Choi Daniel Y
Published: August 2024

Despite the growing interest in social entrepreneurship in social work, the concept has not been examined from the perspective of majority and minority groups in multicultural societies. This study presents empirical evidence concerning factors that explain the entrepreneurial intention of social workers based on data from an extensive survey of social workers from the Jewish majority and the Arab minority in Israel. The findings revealed high levels of entrepreneurial intention amongst all the social workers, although it is lower amongst those from the minority group. Social workers from the majority group reported higher levels of openness to experience in the context of entrepreneurial intention and in extraversion compared to the minority group. Training for social entrepreneurship was identified as a key factor driving entrepreneurial intention.
Serum and CSF biomarkers in asymptomatic patients during primary HIV infection: a randomized study
Authors: Calcagno Andrea , Cusato Jessica , Cinque Paola , Marchetti Giulia , Bernasconi Davide , Trunfio Mattia , Bruzzesi Elena , Rusconi Stefano , Gabrieli Arianna , Muscatello Antonio , Antinori Andrea , Ripamonti Diego , Gulminetti Roberto , Antonucci Miriam , Nozza Silvia
Published: August 2024

It is debated whether CNS involvement begins during acute human immunodeficiency virus (HIV) infection in persons without meningitis/encephalitis and whether specific antiretroviral drugs or combinations would be beneficial.

Neurologically asymptomatic participants enrolled in a randomized and controlled study comparing three combination antiretroviral regimens (tenofovir alafenamide/emtricitabine plus dolutegravir; darunavir; or both) during primary HIV infection were enrolled. Serum and CSF were collected at baseline and at 12 and 48 (serum only) weeks after treatment initiation. Single molecule array was used to measure neurofilament light chain (NFL), total tau protein (Tau), brain-derived neurotrophic factor, glial fibrillary acidic protein (GFAP) and ubiquitin C-terminal hydrolase. We assessed the longitudinal change in biomarkers over time, in addition to the change in the prevalence of serum NFL concentrations above previously published age-adjusted cut-offs (7 pg/ml if 5–18 years, 10 pg/ml if 18–51 years, 15 pg/ml if 51–61 years, 20 pg/ml if 61–70 years and 35 pg/ml if >70 years).

Serum was available from 47 participants at all time points, and CSF was available from 13 participants at baseline and 7 at Week 12. We observed a significant direct serum-to-CSF correlation for NFL (ρ = 0.692, P = 0.009), GFAP (ρ = 0.659, P = 0.014) and brain-derived neurotrophic factor (ρ = 0.587, P = 0.045). Serum (ρ = 0.560, P = 0.046) and CSF NFL (ρ = 0.582, P = 0.037) concentrations were directly associated with CSF HIV RNA levels. We observed a significant decrease over time in serum NFL (P = 0.006) and GFAP (P = 0.006) but not in the other biomarkers. No significant difference was observed among the treatment arms. At baseline, serum and CSF age-adjusted NFL levels were above age-adjusted cut-offs in 23 (48.9%) and four participants (30.8%), respectively; considering serum NFL, this proportion was lower at Weeks 12 (31.9%, P = 0.057) and 48 (27.7%, P = 0.13).

A relevant proportion of neurologically asymptomatic participants had abnormal CSF and serum NFL levels during primary HIV infection. NFL and GFAP decreased in serum following combination antiretroviral therapy without significant differences among the treatment arms.
What does it mean to be queer in Wikidata? Practices of gender representation within a transnational online community
Authors: Melis Beatrice , Paolini Chiara , Fioravanti Marta , Metilli Daniele
Published: August 2024

The continuing digitization and datafication that our society is undergoing are having a significant impact on our daily lives, giving rise to new possibilities but also entailing significant risks for people who are discriminated against or marginalized. Queer communities are particularly affected by these processes; therefore, it is crucially relevant to research transnational digital projects that involve them. In the Wikidata Gender Diversity (WiGeDi) project, we are looking at practices of gender representation in the Wikidata knowledge base, a collaborative online project managed by a worldwide community. Working from the idea that gender is a complex social construct, we investigate how the Wikidata community has approached the complex issue of modeling and populating gender data, progressing from a very narrow interpretation of gender as a binary to a representation that is more inclusive of a multiplicity of gender identities.
Reproducing poverty through participation: examining the constraints of community development strategies in fostering empowerment and social change
Authors: Khan Shahzad , Eversole Robyn
Published: August 2024

Community participation is often heralded as a remedy to the disadvantages faced by marginalized people, with the assumption that it catalyses empowerment and social change. However, in development practice, this view may overlook the intricate power dynamics that reinforce marginalization and how they interplay within local communities and with external developers. This paper seeks to examine how power relations in and beyond the local level influence participatory community development initiatives and their potential to challenge or reinforce disadvantage. It focuses on the Rural Support Programmes Network’s much-touted ‘three-tier social mobilization strategy’ in Northwest Pakistan as a qualitative case study, using participant and non-participant observation, document analysis and semi-structured interviews.

Findings indicate that active participation by local people in community development processes does not always catalyse empowerment and social change. Without a deliberate reconfiguration of traditional exclusionary power relations, participation in community initiatives may simply perpetuate social exclusion for disadvantaged groups. Existing social structures allow traditionally powerful people to use participatory processes to reproduce and/or further reinforce their power and control via ‘strategic compliance’. The study concludes that community development programmes require a nuanced understanding of power dynamics and a deliberate effort to reconfigure those dynamics to foster meaningful engagement and empowerment of disadvantaged groups.
Repigmentation in facial vitiligo depends on the affected areas
Authors: Speeckaert Reinhart , Wang Lu , van Geel Nanja
Published: August 2024

It is currently not well documented whether the chance of repigmentation differs by location on the face. We conducted a retrospective analysis of 36 patients treated with topical treatment and methotrexate for facial vitiligo with or without additional phototherapy. Vitiligo on the forehead and temporal sides of the face was a good prognostic factor, whereas the broad areas around the eyes and mouth represent more treatment-resistant parts.
A large purplish swelling on the arm of a newborn
Authors: Ng Yean Joo , Lai Qi Ji , Albela Henrietta
Published: August 2024

We report a newborn girl with a large purplish swelling on her right arm. The diagnosis was established with imaging and a biopsy of the lesion.
Timing of Influenza Antiviral Therapy and Risk of Death in Adults Hospitalized With Influenza-Associated Pneumonia, Influenza Hospitalization Surveillance Network (FluSurv-NET), 2012–2019
Authors: Tenforde Mark W , Noah Kameela P , O’Halloran Alissa C , Kirley Pam Daily , Hoover Cora , Alden Nisha B , Armistead Isaac , Meek James , Yousey-Hindes Kimberly , Openo Kyle P , Witt Lucy S , Monroe Maya L , Ryan Patricia A , Falkowski Anna , Reeg Libby , Lynfield Ruth , McMahon Melissa , Hancock Emily B , Hoffman Marisa R , McGuire Suzanne , Spina Nancy L , Felsen Christina B , Gaitan Maria A , Lung Krista , Shiltz Eli , Thomas Ann , Schaffner William , Talbot H Keipp , Crossland Melanie T , Price Andrea , Masalovich Svetlana , Adams Katherine , Holstein Rachel , Sundaresan Devi , Uyeki Timothy M , Reed Carrie , Bozio Catherine H , Garg Shikha
Published: August 2024

Background

Pneumonia is common in adults hospitalized with laboratory-confirmed influenza, but the association between timeliness of influenza antiviral treatment and severe clinical outcomes in patients with influenza-associated pneumonia is not well characterized.

Methods

We included adults aged ≥18 years hospitalized with laboratory-confirmed influenza and a discharge diagnosis of pneumonia over 7 influenza seasons (2012–2019) sampled from a multistate population-based surveillance network. We evaluated 3 treatment groups based on timing of influenza antiviral initiation relative to admission date (day 0, day 1, days 2–5). Baseline characteristics and clinical outcomes were compared across groups using unweighted counts and weighted percentages accounting for the complex survey design. Logistic regression models were generated to evaluate the association between delayed treatment and 30-day all-cause mortality.

Results

A total of 26 233 adults were sampled in the analysis. Median age was 71 years and most (92.2%) had ≥1 non-immunocompromising condition. Overall, 60.9% started antiviral treatment on day 0, 29.5% on day 1, and 9.7% on days 2–5 (median, 2 days). Baseline characteristics were similar across groups. Thirty-day mortality occurred in 7.5%, 8.5%, and 10.2% of patients who started treatment on day 0, day 1, and days 2–5, respectively. Compared to those treated on day 0, adjusted odds ratio for death was 1.14 (95% confidence interval [CI], 1.01–1.27) in those starting treatment on day 1 and 1.40 (95% CI, 1.17–1.66) in those starting on days 2–5.

Conclusions

Delayed initiation of antiviral treatment in patients hospitalized with influenza-associated pneumonia was associated with higher risk of death, highlighting the importance of timely initiation of antiviral treatment at admission.
Conspicuous consumption for social parity
Authors: Srikanth Chinmayi , Dey Shubhasis
Published: August 2024

Extant literature on status signalling primarily adopts Veblen’s theory of class to caste and racial identities. This study aimed at adopting a more suitable theoretical lens to examine status signalling that is more relevant not only for class identities, but also for other identities such as caste and racial identities. By viewing conspicuous consumption within the framework of the stigma-identity-threat model, the study analyses how socially disadvantaged groups in India respond to stigma through their consumption behaviour. Using data from two rounds of the India Human Development Survey, we study whether disadvantaged social groups embrace or distance themselves from their stigmatised identity. For the periods 2004–05 and 2011–12, we find that households from scheduled castes, scheduled tribes and other backward classes among caste groups, and Muslims among religious groups, tend to move away from their devalued identity. However, the manner in which this is done not only varies across these social groups but also across time. The study also finds that the material threshold that a social group needs to surpass in order to stop signalling status varies based on their position in the social hierarchy.
Machine Learning-Based Sample Misidentification Error Detection in Clinical Laboratory Tests: A Retrospective Multicenter Study
Authors: Seok Hyeon Seok , Yu Shinae , Shin Kyung-Hwa , Lee Woochang , Chun Sail , Kim Sollip , Shin Hangsik
Published: August 2024

Background

In clinical laboratories, the precision and sensitivity of autoverification technologies are crucial for ensuring reliable diagnostics. Conventional methods have limited sensitivity and applicability, making error detection challenging and reducing laboratory efficiency. This study introduces a machine learning (ML)-based autoverification technology to enhance tumor marker test error detection.

Methods

The effectiveness of various ML models was evaluated by analyzing a large data set of 397 751 for model training and internal validation and 215 339 for external validation. Sample misidentification was simulated by random shuffling error-free test results with a 1% error rate to achieve a real-world approximation. The ML models were developed with Bayesian optimization for tuning. Model validation was performed internally at the primary institution and externally at other institutions, comparing the ML models’ performance with conventional delta check methods.

Results

Deep neural networks and extreme gradient boosting achieved an area under the receiver operating characteristic curve of 0.834 to 0.903, outperforming that of conventional methods (0.705 to 0.816). External validation by 3 independent laboratories showed that the balanced accuracy of the ML model ranged from 0.760 to 0.836, outperforming the balanced accuracy of 0.670 to 0.773 of the conventional models.

Conclusions

This study addresses limitations regarding the sensitivity of current delta check methods for detection of sample misidentification errors and provides versatile models that mitigate the operational challenges faced by smaller laboratories. Our findings offer a pathway toward more efficient and reliable clinical laboratory testing.
Clinical Course of Bio Naive Ulcerative Colitis Patients Five Years After Initiation of Adalimumab in a Nationwide Cohort
Authors: Sundararajan Ramaswamy , Patel Manthankumar , Bahirwani Janak , Trivedi Chinmay , Mahmud Nadim , Khan Nabeel
Published: August 2024

Background

There is limited data on the long-term clinical outcomes of bio-naïve ulcerative colitis (UC) patients who are initiated on adalimumab (ADA). Our study aims to evaluate the clinical course of a nationwide cohort of bio naïve UC patients who were started on ADA, and then followed for 5 years after initiation of the drug.

Methods

We conducted a retrospective cohort study using the US Veteran Affairs Healthcare System (VAHS). Bio naïve UC patients were followed for 5 years after initiation of ADA. The primary outcome was to determine the time to discontinuation of ADA and if patients achieved endoscopic remission by the end of follow-up.

Results

A total of 387 patients were included among whom 193 (49.87%) had pancolitis. The highest rate of ADA discontinuation was within the first year, with the elderly having a higher rate of discontinuation (HR 1.67, 95% CI: 1.14–2.45) and those on concomitant immunomodulators having a lower rate of discontinuation (HR 0.70, 95% CI: 0.48–1.03). In total, 125 (32.30%) patients remained on ADA at the end of their maximum follow-up. 54 (43.90%) achieved endoscopic remission.

Conclusion

Among bio-naive UC patients who were started on ADA, a third were still on the drug at the end of 5 years and half had endoscopic remission. The rate of discontinuation was highest within the first year of initiation, but patients continued to stop the drug over the course of follow-up.
Smooth muscle-specific deletion of cellular communication network factor 2 causes severe aorta malformation and atherosclerosis
Authors: Larsen Jannik H , Hegelund Julie S , Pedersen Matilde K , Andersson Cecilie M , Lindegaard Caroline A , Hansen Didde R , Stubbe Jane , Lindholt Jes S , Hansen Camilla S , Grentzmann Andrietta , Bloksgaard Maria , Jensen Boye L , Rodriguez-Díez Raúl R , Ruiz-Ortega Marta , Albinsson Sebastian , Pasterkamp Gerard , Mokry Michal , Leask Andrew , Goldschmeding Roel , Pilecki Bartosz , Sorensen Grith L , Pyke Charles , Overgaard Martin , Beck Hans C , Ketelhuth Daniel F J , Rasmussen Lars M , Steffensen Lasse B
Published: August 2024

Aims

Cellular communication network factor 2 (CCN2) is a matricellular protein implicated in fibrotic diseases, with ongoing clinical trials evaluating anti-CCN2-based therapies. By uncovering CCN2 as abundantly expressed in non-diseased artery tissue, this study aimed to investigate the hypothesis that CCN2 plays a pivotal role in maintaining smooth muscle cell (SMC) phenotype and protection against atherosclerosis.

Methods and results

Global- and SMC-specific Ccn2 knockout mouse models were employed to demonstrate that Ccn2 deficiency leads to SMC de-differentiation, medial thickening, and aorta elongation under normolipidaemic conditions. Inducing hyperlipidaemia in both models resulted in severe aorta malformation and a 17-fold increase in atherosclerosis formation. Lipid-rich lesions developed at sites of the vasculature typically protected from atherosclerosis development by laminar blood flow, covering 90% of aortas and extending to other vessels, including coronary arteries. Evaluation at earlier time points revealed medial lipid accumulation as a lesion-initiating event. Fluorescently labelled LDL injection followed by confocal microscopy showed increased LDL retention in the medial layer of Ccn2 knockout aortas, likely attributed to marked proteoglycan enrichment of the medial extracellular matrix. Analyses leveraging data from the Athero-Express study cohort indicated the relevance of CCN2 in established human lesions, as CCN2 correlated with SMC marker transcripts across 654 transcriptomically profiled carotid plaques. These findings were substantiated through in situ hybridization showing CCN2 expression predominantly in the fibrous cap.

Conclusion

This study identifies CCN2 as a major constituent of the normal artery wall, critical in regulating SMC differentiation and aorta integrity and possessing a protective role against atherosclerosis development. These findings underscore the need for further investigation into the potential effects of anti-CCN2-based therapies on the vasculature.
Complete pathologic response in esophageal adenocarcinoma: does it make a difference?
Authors: Donato Britton B , Campany Megan E , Brady Justin T , Jenkins J Asher , Armstrong Valerie , Butterfield Richard , Reck dos Santos Pedro , D’Cunha Jonathan
Published: August 2024

Advancements in neoadjuvant regimens for esophageal adenocarcinoma have enabled some patients to achieve complete pathologic response at time of esophagectomy. There are currently limited data detailing this trend or the implications of complete pathologic response on survival. The National Cancer Database was used to identify 16,169 patients with esophageal adenocarcinoma that received trimodal therapy including esophagectomy between 2006 and 2020. Of these, 11.4% had complete pathologic response at esophagectomy. Patient factors, staging characteristics, and survival trends were evaluated. In patients diagnosed between 2016 and 2020, the rate of complete pathologic response was 17.5%. Female sex (OR 1.295, 95% CI 1.134–1.481, p = 0.0001), Black race (OR 1.729, 95% CI 1.362–2.196, p = 0.0002), Hispanic ethnicity (OR 1.418, 95% CI 1.073–1.875, p = 0.0141), and later era of diagnosis (2016–2020 OR 2.898, 95% CI 2.508–3.349, p < 0.0001) were independent predictors of complete pathologic response. Clinical stage II disease was associated with an increased probability of complete pathologic response (OR 1.492, 95% CI 1.19–1.871) while clinical stage III disease had a decreased probability of complete pathologic response (OR 0.762, 95% CI 0.621–0.936, p < 0.0001). Complete pathologic response conveyed a strong survival benefit, with a median survival of 86.4 months (95% CI 73.9–102.1) versus 30.7 months (95% CI 29.8–31.7, p < 0.0001) in those without complete pathologic response. Four-year median survival was also higher in those with complete pathologic response (63.3%, 95% CI 60.8–66.0% vs. 39.2%, 95% CI 38.4–40.1%, p < 0.0001). In summary, complete pathologic response is associated with a profound survival advantage in patients with esophageal adenocarcinoma. Such knowledge carries implications for patient counseling, prognostication, and surveillance and demonstrates a need for improved identification of complete clinical response prior to esophagectomy.
The chicken or the egg? Mycoplasma pneumoniae complicated by left ventricle thrombus and anterior myocardial infarction: a case report
Authors: Balac Nina , Nelson Kyle F , Naib Tara , El-Eshmawi Ahmed , Goldman Martin E
Published: August 2024

Background

Mycoplasma pneumoniae can be associated with extrapulmonary manifestations, including vasculitis, myocarditis, and thrombosis. In rare cases, it has also been implicated in intracardiac thrombus formation.

Case Summary

A previously healthy 25-year-old male presented with worsening abdominal pain, an episode of acute chest pain, new lightheadedness, and gait instability in the setting of M. pneumoniae. Initial blood tests were notable for mild coagulopathy, thrombocytosis, transaminitis, and elevated high-sensitivity troponin. Further, workup revealed systematic emboli to the cerebellum, kidneys, spleen, anterior myocardial infarction, and a left ventricular multilobular mural mass. Due to the unknown composition of the mass with concern for further embolic events, the patient underwent successful surgical excision with the mass ultimately defined as a thrombus. Hypercoagulable workup was notably inconclusive and intraoperative myocardial biopsies revealed organizing infarction without inflammation or healed myocarditis. Post-operative course was complicated by left ventricular dysfunction and acute kidney injury, both with eventual improvement. Patient has remained on guideline-directed medical therapy and prophylactic anticoagulation.

Discussion

We presume that the formation of the ventricular thrombus in this case was a result of transient thrombophilia in the setting of M. pneumonia resulting in coronary obstruction and subsequent myocardial injury. This case underscores the challenge of determining the pathophysiological sequence of events in patients with mycoplasma who develop systemic embolism and the management of a large residual thrombus, particularly in regard to surgical consideration.
Successful treatment of acute left main coronary artery disease with a drug-coated balloon under left ventricular unloading using Impella: a case report
Authors: Kamada Kazuhiro , Joko Kensuke , Otaka Naoya , Matsusaka Hidenori , Morishige Kunio
Published: August 2024

Background

Although the efficacy and safety of drug-coated balloons (DCBs) for acute left main coronary artery (LMCA) disease have not yet been proven, stentless percutaneous coronary intervention with a DCB is preferred for patients with high bleeding risk requiring a shorter duration of dual antiplatelet therapy. Mechanical circulatory support may improve haemodynamics in patients with cardiogenic shock caused by acute LMCA disease.

Case summary

A 74-year-old man diagnosed with acute congestive heart failure underwent emergency coronary angiography (CAG) at our hospital owing to ischaemic changes on the electrocardiogram (ECG), indicating acute LMCA disease. Coronary angiography revealed severe LMCA ostial stenosis. Immediately after CAG, mechanical circulatory support was initiated using Impella CP® for haemodynamic collapse with abrupt ST-segment elevation in the precordial leads. The haemodynamics stabilized with a dramatic improvement in the ECG. We treated the culprit ostial lesion with inflation of a cutting balloon followed by DCB delivery because of an episode of haematochezia. Subsequently, his cardiac function recovered fully.

Discussion

A case of acute LMCA disease was successfully treated with a DCB under haemodynamic support using Impella CP. The left ventricular (LV) unloading with Impella was indicated to contribute to stable haemodynamics, even during long inflation with the DCB, and the immediate recovery of LV function. Haemodynamic support using Impella may be effective, especially in cases requiring repeated and longer inflation of balloon catheters accompanied by extensive myocardial ischaemia.
Life's Essential 8 and the risk of cardiovascular disease: a systematic review and meta-analysis
Authors: Sebastian Sneha Annie , Shah Yash , Paul Haris , Arsene Camelia
Published: August 2024

Aims

The benefits of achieving optimal cardiovascular health (CVH) through Life's Simple 7 (LS7) are well-documented across diverse populations. In this study, we assess the updated metrics, Life's Essential 8 (LE8), and its association with long-term cardiovascular disease (CVD) outcomes and mortality.

Methods and results

We conducted a comprehensive systematic review, searching PubMed, Google Scholar, Cochrane Library, and ScienceDirect from January 2022 until June 2024, focusing on studies that specifically assessed the impact of LE8 on CVH. The statistical analysis used RevMan 5.4 and applied a random effects model to synthesize hazard ratios (HRs) for primary and secondary outcomes. This study is registered in PROSPERO (CRD42024558493). Our final analysis comprised 34 observational studies, encompassing 1 786 664 participants aged 18–80 years, with an average follow-up of approximately 11.6 years. Pooled analysis revealed a statistically significant decrease in the risk of CVD among individuals with higher LE8 scores compared with those with lower scores, with an HR of 0.47 (95% CI: 0.39–0.56, P < 0.00001). Higher LE8 scores were also associated with significant reductions in both all-cause mortality (HR: 0.54, 95% CI: 0.43–0.69, P < 0.00001) and CVD-related mortality (HR: 0.37, 95% CI: 0.26–0.52, P < 0.00001. Moreover, individuals with high LE8 scores have a 56% lower risk of coronary heart disease and a 48% lower risk of stroke.

Conclusion

LE8 has a strong inverse association with CVD risk and mortality, with higher LE8 scores corresponding to significantly lower risk levels.
Candida species-specific colonization in the healthy and impaired human gastrointestinal tract as simulated using the Mucosal Ileum-SHIME® model
Authors: Marsaux Benoît , Moens Frédéric , Vandevijver Gies , Marzorati Massimo , van de Wiele Tom
Published: August 2024

Candida species primarily exist as harmless commensals in the gastrointestinal tract of warm-blooded animals. However, they can also cause life-threatening infections, which are often associated with gut microbial dysbiosis. Identifying the microbial actors that restrict Candida to commensalism remains a significant challenge. In vitro models could enable a mechanistic study of the interactions between Candida and simulated colon microbiomes. Therefore, this study aimed to elucidate the spatial and temporal colonization kinetics of specific Candida, including C. albicans, C. tropicalis, and C. parapsilosis, and their relative Nakaseomyces glabratus, by using an adapted SHIME® model, simulating the ileum, and proximal and distal colons. We monitored fungal and bacterial colonization kinetics under conditions of eubiosis (commensal lifestyle) and antibiotic-induced dysbiosis (pathogenic lifestyle). Our findings highlighted the variability in the colonization potential of Candida species across different intestinal regions. The ileum compartment proved to be the most favourable environment for C. albicans and C. parapsilosis under conditions of eubiosis. Antibiotic-induced dysbiosis resulted in resurgence of opportunistic Candida species, especially C. tropicalis and C. albicans. Future research should focus on identifying specific bacterial species influencing Candida colonization resistance and explore the long-term effects of antibiotics on the mycobiome and bacteriome.