bluuebunny/crossref_metadata_2025_split huggingface dataset:
Microbiome-informed study of the mechanistic basis of methane inhibition by
Asparagopsis taxiformis
in dairy cattle
Authors: Indugu Nagaraju , Narayan Kapil , Stefenoni Hannah A. , Hennessy Meagan L. , Vecchiarelli Bonnie , Bender Joseph S. , Shah Reeti , Dai Grace , Garapati Satvik , Yarish Charles , Welchez Sergio C. , Räisänen Susanna E. , Wasson Derek , Lage Camila , Melgar Audino , Hristov Alexander N. , Pitta Dipti W. 
Published: July 2024

ABSTRACT

Copious amounts of methane, a major constituent of greenhouse gases currently driving climate change, are emitted by livestock, and efficient methods that curb such emissions are urgently needed to reduce global warming. When fed to cows, the red seaweed
Asparagopsis taxiformis
(AT) can reduce enteric methane emissions by up to 80%, but the achieved results can vary widely. Livestock produce methane as a byproduct of methanogenesis, which occurs during the breakdown of feed by microbes in the rumen. The ruminant microbiome is a diverse ecosystem comprising bacteria, protozoa, fungi, and archaea, and methanogenic archaea work synergistically with bacteria to produce methane. Here, we find that an effective reduction in methane emission by high-dose AT (0.5% dry matter intake) was associated with a reduction in methanol-utilizing
Methanosphaera
within the rumen, suggesting that they may play a greater role in methane formation than previously thought. However, a later spike in
Methanosphaera
suggested an acquired resistance, possibly via the reductive dehalogenation of bromoform. While we found that AT inhibition of methanogenesis indirectly impacted ruminal bacteria and fermentation pathways due to an increase in spared H
2
, we also found that an increase in butyrate synthesis was due to a direct effect of AT on butyrate-producing bacteria such as
Butyrivibrio
,
Moryella,
and
Eubacterium
. Together, our findings provide several novel insights into the impact of AT on both methane emissions and the microbiome, thereby elucidating additional pathways that may need to be targeted to maintain its inhibitory effects while preserving microbiome health and animal productivity.

IMPORTANCE

Livestock emits copious quantities of methane, a major constituent of the greenhouse gases currently driving climate change. Methanogens within the bovine rumen produce methane during the breakdown of feed. While the red seaweed
Asparagopsis taxiformis
(AT) can significantly reduce methane emissions when fed to cows, its effects appear short-lived. This study revealed that the effective reduction of methane emissions by AT was accompanied by the near-total elimination of methane-generating
Methanosphaera
. However,
Methanosphaera
populations subsequently rebounded due to their ability to inactivate bromoform, a major inhibitor of methane formation found in AT. This study presents novel findings on the contribution of
Methanosphaera
to ruminal methanogenesis, the mode of action of AT, and the possibility for complementing different strategies to effectively curb methane emissions.
The histamine receptor H1 acts as an alternative receptor for SARS-CoV-2
Authors: Yu Fei , Liu Xiaoqing , Ou Hailan , Li Xinyu , Liu Ruxin , Lv Xi , Xiao Shiqi , Hu Meilin , Liang Taizhen , Chen Tao , Wei Xuepeng , Zhang Zhenglai , Liu Sen , Liu Han , Zhu Yiqiang , Liu Guangyan , Tu Tianyong , Li Peiwen , Zhang Hui , Pan Ting , Ma Xiancai 
Published: July 2024

ABSTRACT

Numerous host factors, in addition to human angiotensin-converting enzyme 2 (hACE2), have been identified as coreceptors of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), demonstrating broad viral tropism and diversified druggable potential. We and others have found that antihistamine drugs, particularly histamine receptor H1 (HRH1) antagonists, potently inhibit SARS-CoV-2 infection. In this study, we provided compelling evidence that HRH1 acts as an alternative receptor for SARS-CoV-2 by directly binding to the viral spike protein. HRH1 also synergistically enhanced hACE2-dependent viral entry by interacting with hACE2. Antihistamine drugs effectively prevent viral infection by competitively binding to HRH1, thereby disrupting the interaction between the spike protein and its receptor. Multiple inhibition assays revealed that antihistamine drugs broadly inhibited the infection of various SARS-CoV-2 mutants with an average IC50 of 2.4 µM. The prophylactic function of these drugs was further confirmed by authentic SARS-CoV-2 infection assays and humanized mouse challenge experiments, demonstrating the therapeutic potential of antihistamine drugs for combating coronavirus disease 19.

IMPORTANCE
In addition to human angiotensin-converting enzyme 2, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can utilize alternative cofactors to facilitate viral entry. In this study, we discovered that histamine receptor H1 (HRH1) not only functions as an independent receptor for SARS-CoV-2 but also synergistically enhances ACE2-dependent viral entry by directly interacting with ACE2. Further studies have demonstrated that HRH1 facilitates the entry of SARS-CoV-2 by directly binding to the N-terminal domain of the spike protein. Conversely, antihistamine drugs, primarily HRH1 antagonists, can competitively bind to HRH1 and thereby prevent viral entry. These findings revealed that the administration of repurposable antihistamine drugs could be a therapeutic intervention to combat coronavirus disease 19.
mSphere of Influence: The power of observational research
Authors: Velle Katrina B. 
Published: July 2024

ABSTRACT

Katrina Velle is a cell biologist who uses microscopy to study amoebae. In this mSphere of Influence article, she reflects on how a classic paper on
Listeria
by Tilney and Portnoy made an impact on her by highlighting how much we can learn from simply looking at cells.
Reflections: enhancing critical thinking in science education by implementing philosophy elements into training
Authors: Ciubotariu Ilinca I. 
Published: July 2024

ABSTRACT

In this work, I describe the trajectory of philosophy and science as separate disciplines from their early days as quite overlapping fields to their clear divergence in the latest centuries. From personal experience, I discuss the benefits of exposure to philosophy and closely related courses in undergraduate studies and bring to the forefront the positive aspects of integrating philosophy of science courses in graduate science, technology, engineering, and mathematics (STEM) curriculum. I also briefly offer some additional steps institutions can take to foster unity between areas of science and philosophy by incorporating interdisciplinary activities.
Advancing equity in breast cancer care: natural language processing for analysing treatment outcomes in under-represented populations
Authors: Park Jung In , Park Jong Won , Zhang Kexin , Kim Doyop 
Published: July 2024

ObjectiveThe study aimed to develop natural language processing (NLP) algorithms to automate extracting patient-centred breast cancer treatment outcomes from clinical notes in electronic health records (EHRs), particularly for women from under-represented populations.MethodsThe study used clinical notes from 2010 to 2021 from a tertiary hospital in the USA. The notes were processed through various NLP techniques, including vectorisation methods (term frequency-inverse document frequency (TF-IDF), Word2Vec, Doc2Vec) and classification models (support vector classification, K-nearest neighbours (KNN), random forest (RF)). Feature selection and optimisation through random search and fivefold cross-validation were also conducted.ResultsThe study annotated 100 out of 1000 clinical notes, using 970 notes to build the text corpus. TF-IDF and Doc2Vec combined with RF showed the highest performance, while Word2Vec was less effective. RF classifier demonstrated the best performance, although with lower recall rates, suggesting more false negatives. KNN showed lower recall due to its sensitivity to data noise.DiscussionThe study highlights the significance of using NLP in analysing clinical notes to understand breast cancer treatment outcomes in under-represented populations. The TF-IDF and Doc2Vec models were more effective in capturing relevant information than Word2Vec. The study observed lower recall rates in RF models, attributed to the dataset’s imbalanced nature and the complexity of clinical notes.ConclusionThe study developed high-performing NLP pipeline to capture treatment outcomes for breast cancer in under-represented populations, demonstrating the importance of document-level vectorisation and ensemble methods in clinical notes analysis. The findings provide insights for more equitable healthcare strategies and show the potential for broader NLP applications in clinical settings.
How the COVID-19 pandemic affected infant vaccination trends in rural and urban communities in Ibadan, Nigeria: a cross-sectional study
Authors: Adegoke Awwal Adetunji , Balogun Folusho Mubowale 
Published: July 2024

ObjectivesThis study compared the infant vaccination trends a year before and a year after the onset of the COVID-19 pandemic in selected urban and rural communities in Ibadan, Nigeria.DesignThis was a cross-sectional study in which data were extracted from infant vaccination records.SettingTwo rural and three urban vaccination centres in primary health clinics at Ibadan Southeast and Olúyòlé local government areas, respectively.ParticipantsInfant vaccination records 1 year before and 1 year after the onset of the COVID-19 pandemic (March 2019–February 2020 and March 2020–February 2021, respectively).Outcome measuresTimeliness of vaccination (vaccination taken within 2 weeks of appointment) and vaccination completion according to the Nigerian routine infant vaccination schedule.Results2000 vaccination records were included in the study (1013 (50.6%) for male infants). 840 (42.0%) of the records were from the rural immunisation clinics. There were 1194 (59.7%) and 806 (40.3%) records from before and after the onset of the COVID-19 pandemic, respectively. Before the pandemic, birth dose vaccines were timelier among infants from urban communities, while vaccines given at 6 weeks were timelier in the rural areas. Following the onset of the pandemic, the rural communities had a higher proportion of infants with timelier and complete vaccination except for the birth dose vaccines. Overall, there was higher vaccination completion before the pandemic, and this was higher in the rural compared with the urban communities both before (54.8% vs 11.7%) and after (23.6% vs 1.0%) the onset of the pandemic.ConclusionsA decline in infant vaccination uptake, timeliness and completion persisted 1 year after the COVID-19 pandemic onset, and urban communities were more affected. More efforts are required to ensure optimal infant vaccination, especially in urban communities, to forestall outbreaks of vaccine-preventable diseases.
Just-in-time adaptive interventions for adolescent and young adult health and well-being: protocol for a systematic review
Authors: Guan Kathleen W , Adlung Christopher , Keijsers Loes , Smit Crystal R , Vreeker Annabel , Thalassinou Eva , van Roekel Eeske , de Reuver Mark , Figueroa Caroline A 
Published: July 2024

IntroductionHealth behaviours such as exercise and diet strongly influence well-being and disease risk, providing the opportunity for interventions tailored to diverse individual contexts. Precise behaviour interventions are critical during adolescence and young adulthood (ages 10–25), a formative period shaping lifelong well-being. We will conduct a systematic review of just-in-time adaptive interventions (JITAIs) for health behaviour and well-being in adolescents and young adults (AYAs). A JITAI is an emerging digital health design that provides precise health support by monitoring and adjusting to individual, specific and evolving contexts in real time. Despite demonstrated potential, no published reviews have explored how JITAIs can dynamically adapt to intersectional health factors of diverse AYAs. We will identify the JITAIs’ distal and proximal outcomes and their tailoring mechanisms, and report their effectiveness. We will also explore studies’ considerations of health equity. This will form a comprehensive assessment of JITAIs and their role in promoting health behaviours of AYAs. We will integrate evidence to guide the development and implementation of precise, effective and equitable digital health interventions for AYAs.Methods and analysisIn adherence to Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines, we will conduct a systematic search across multiple databases, including CENTRAL, MEDLINE and WHO Global Index Medicus. We will include peer-reviewed studies on JITAIs targeting health of AYAs in multiple languages. Two independent reviewers will conduct screening and data extraction of study and participant characteristics, JITAI designs, health outcome measures and equity considerations. We will provide a narrative synthesis of findings and, if data allows, conduct a meta-analysis.Ethics and disseminationAs we will not collect primary data, we do not require ethical approval. We will disseminate the review findings through peer-reviewed journal publication, conferences and stakeholder meetings to inform participatory research.PROSPERO registration numberCRD42023473117.
Temporal trends and cohort variations of gender-specific major depressive disorders incidence in China: analysis based on the age-period-cohort-interaction model
Authors: Hu Xiyuan , Guo Chao 
Published: July 2024

BackgroundMajor depressive disorders (MDDs) impose substantial burdens on individuals and society; however, further detailed analysis is still needed for its long-term trends.AimsThis study aimed to analyse the gender-specific temporal trends and cohort variations of MDD incidence among Chinese residents over the past three decades.MethodsEmploying the age-period-cohort-interaction model and leveraging data from the Global Burden of Disease Study 2019, this research identified and analysed incidence trends of MDD among Chinese males and females aged 5–94 years from 1990 to 2019 across three dimensions, encompassing age, period and birth cohort.ResultsThe analysis reveals age-related effects, indicating heightened MDD risk among adolescents and older adults. Specifically, individuals entering the older adulthood at the age of 65–69 significantly increased the risk of MDD by 64.9%. People aged 90–94 years witnessed a 105.4% increase in MDD risk for the overall population, with females and males in this age group experiencing a 75.1% and 103.4% increase, respectively. In terms of period effects, the risk of MDD displayed a decline from 1990 to 1994, followed by a rebound in 2008. Cohort effects demonstrated diverse generational patterns, with generation I and generation III manifesting opposing ‘age-as-level’ trends. Generation II and generation IV exhibited ‘cumulative disadvantage’ and ‘cumulative advantage’ patterns, respectively. Age effects indicated an overall higher risk of MDD incidence in females, while cohort effects showed greater variations of MDD incidence among females.ConclusionsThe study underscores the substantial effects of age, period and cohort on MDD across genders in China. Priority interventions targeting vulnerable populations, including children, adolescents, older adults, females and the post-millennium birth cohort, are crucial to mitigate the impact of MDD.
Trends in educational inequalities in smoking-attributable mortality and their impact on changes in general mortality inequalities: evidence from England and Wales, Finland, and Italy (Turin)
Authors: Van Hemelrijck Wanda Monika Johanna , Kunst Anton E , Sizer Alison , Martikainen Pekka , Zengarini Nicolas , Costa Giuseppe , Janssen Fanny 
Published: July 2024

BackgroundSocioeconomic mortality inequalities are persistent in Europe but have been changing over time. Smoking is a known contributor to inequality levels, but knowledge about its impact on time trends in inequalities is sparse.MethodsWe studied trends in educational inequalities in smoking-attributable mortality (SAM) and assessed their impact on general mortality inequality trends in England and Wales (E&W), Finland, and Italy (Turin) from 1972 to 2017. We used yearly individually linked all-cause and lung cancer mortality data by educational level and sex for individuals aged 30 and older. SAM was indirectly estimated using the Preston-Glei-Wilmoth method. We calculated the slope index of inequality (SII) and performed segmented regression on SIIs for all-cause, smoking and non-SAM to identify phases in inequality trends. The impact of SAM on all-cause mortality inequality trends was estimated by comparing changes in SII for all-cause with non-SAM.ResultsInequalities in SAM generally declined among males and increased among females, except in Italy. Among males in E&W and Finland, SAM contributed 93% and 76% to declining absolute all-cause mortality inequalities, but this contribution varied over time. Among males in Italy, SAM drove the 1976–1992 increase in all-cause mortality inequalities. Among females in Finland, increasing inequalities in SAM hampered larger declines in mortality inequalities.ConclusionOur findings demonstrate that differing education-specific SAM trends by country and sex result in different inequality trends, and consequent contributions of SAM on educational mortality inequalities. The following decades of the smoking epidemic could increase educational mortality inequalities among Finnish and Italian women.
Bendamustine is a safe and effective lymphodepletion agent for axicabtagene ciloleucel in patients with refractory or relapsed large B-cell lymphoma
Authors: Bharadwaj Sushma , Lau Eric , Hamilton Mark P , Goyal Anmol , Srinagesh Hrishi , Jensen Alexandria , Lee Dasom , Mallampet Jayasindhu , Elkordy Sarah , Syal Shriya , Patil Sunita , Latchford Theresa , Sahaf Bita , Arai Sally , Johnston Laura J , Lowsky Robert , Negrin Robert , Rezvani Andrew R , Shizuru Judith , Meyer Everett H , Shiraz Parveen , Mikkilineni Lekha , Weng Wen-Kai , Smith Melody , Sidana Surbhi , Muffly Lori , Maecker Holden T , Frank Matthew J , Mackall Crystal , Miklos David , Dahiya Saurabh 
Published: July 2024

BackgroundFludarabine in combination with cyclophosphamide (FC) is the standard lymphodepletion regimen for CAR T-cell therapy (CAR T). A national fludarabine shortage in 2022 necessitated the exploration of alternative regimens with many centers employing single-agent bendamustine as lymphodepletion despite a lack of clinical safety and efficacy data. To fill this gap in the literature, we evaluated the safety, efficacy, and expansion kinetics of bendamustine as lymphodepletion prior to axicabtagene ciloleucel (axi-cel) therapy.Methods84 consecutive patients with relapsed or refractory large B-cell lymphoma treated with axi-cel and managed with a uniform toxicity management plan at Stanford University were studied. 27 patients received alternative lymphodepletion with bendamustine while 57 received FC.ResultsBest complete response rates were similar (73.7% for FC and 74% for bendamustine, p=0.28) and there was no significant difference in 12-month progression-free survival or overall survival estimates (p=0.17 and p=0.62, respectively). The frequency of high-grade cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome was similar in both the cohorts. Bendamustine cohort experienced lower proportions of hematological toxicities and antibiotic use for neutropenic fever. Immune reconstitution, as measured by quantitative assessment of cellular immunity, was better in bendamustine cohort as compared with FC cohort. CAR T expansion as measured by peak expansion and area under the curve for expansion was comparable between cohorts.ConclusionsBendamustine is a safe and effective alternative lymphodepletion conditioning for axi-cel with lower early hematological toxicity and favorable immune reconstitution.
Mapping the complexity and diversity of tertiary lymphoid structures in primary and peritoneal metastatic gastric cancer
Authors: Groen-van Schooten Tessa S , Franco Fernandez Rosalia , van Grieken Nicole C T , Bos Emma N , Seidel Jens , Saris Job , Martínez-Ciarpaglini Carolina , Fleitas Tania C , Thommen Daniela S , de Gruijl Tanja D , Grootjans Joep , Derks Sarah 
Published: July 2024

BackgroundTertiary lymphoid structures (TLSs) are thought to stimulate antitumor immunity and positively impact prognosis and response to immune checkpoint blockade. In gastric cancers (GCs), however, TLSs are predominantly found in GC with poor prognosis and limited treatment response. We, therefore, hypothesize that immune cell composition and function of TLS depends on tumor location and the tumor immune environment.MethodsSpatial transcriptomics and immunohistochemistry were used to characterize the phenotype of CD45+immune cells inside and outside of TLS using archival resection specimens from GC primary tumors and peritoneal metastases.ResultsWe identified significant intrapatient and interpatient diversity of the cellular composition and maturation status of TLS in GC. Tumor location (primary vs metastatic site) accounted for the majority of differences in TLS maturity, as TLS in peritoneal metastases were predominantly immature. This was associated with higher levels of tumor-infiltrating macrophages and Tregs and less plasma cells compared with tumors with mature TLS. Furthermore, mature TLSs were characterized by overexpression of antitumor immune pathways such as B cell-related pathways, MHC class II antigen presentation while immature TLS were associated with protumor pathways, including T cell exhaustion and enhancement of DNA repair pathways in the corresponding cancer.ConclusionThe observation that GC-derived peritoneal metastases often contain immature TLS which are associated with immune suppressive regulatory tumor-infiltrating leucocytes, is in keeping with the lack of response to immune checkpoint blockade and the poor prognostic features of peritoneal metastatic GC, which needs to be taken into account when optimizing immunomodulatory strategies for metastatic GC.