bluuebunny/crossref_metadata_2025 huggingface dataset:
LmRaC: a functionally extensible tool for LLM interrogation of user experimental results
Authors: Craig Douglas B , Drăghici Sorin
Published: November 2024

Motivation

Large Language Models (LLMs) have provided spectacular results across a wide variety of domains. However, persistent concerns about hallucination and fabrication of authoritative sources raise serious issues for their integral use in scientific research. Retrieval-augmented generation (RAG) is a technique for making data and documents, otherwise unavailable during training, available to the LLM for reasoning tasks. In addition to making dynamic and quantitative data available to the LLM, RAG provides the means by which to carefully control and trace source material, thereby ensuring results are accurate, complete, and authoritative.

Results

Here, we introduce LmRaC, an LLM-based tool capable of answering complex scientific questions in the context of a user’s own experimental results. LmRaC allows users to dynamically build domain specific knowledge-bases from PubMed sources (RAGdom). Answers are drawn solely from this RAG with citations to the paragraph level, virtually eliminating any chance of hallucination or fabrication. These answers can then be used to construct an experimental context (RAGexp) that, along with user supplied documents (e.g. design, protocols) and quantitative results, can be used to answer questions about the user’s specific experiment. Questions about quantitative experimental data are integral to LmRaC and are supported by a user-defined and functionally extensible REST API server (RAGfun).

Availability and implementation

Detailed documentation for LmRaC along with a sample REST API server for defining user functions can be found at https://github.com/dbcraig/LmRaC. The LmRaC web application image can be pulled from Docker Hub (https://hub.docker.com) as dbcraig/lmrac.
R3DMCS: a web server for visualizing structural variation in RNA motifs across experimental 3D structures from the same organism or across species
Authors: Appasamy Sri Devan , Zirbel Craig L
Published: November 2024

Motivation

The recent progress in RNA structure determination methods has resulted in a surge of newly solved RNA 3D structures. However, there is an absence of a user-friendly browser-based tool that can facilitate the comparison and visualization of RNA motifs across multiple 3D structures.

Results

We introduce R3DMCS, a web server that allows users to compare selected RNA nucleotides across all 3D structures of a given molecule from a given species, or across all 3D structures mapped to a single Rfam family. Starting from one instance of the motif, R3DMCS retrieves, aligns, annotates, organizes, and displays 3D coordinates of corresponding sets of nucleotides from other 3D structures. With R3DMCS, one can explore conformational changes of motifs due to 3D structures being solved in different functional states or different experimental conditions. One can also investigate conservation of 3D structure across species, or changes in 3D structure due to changes in sequence.

Availability and implementation

R3DMCS is open-source software and freely available at https://rna.bgsu.edu/correspondence/ and https://github.com/BGSU-RNA/RNA-3D-correspondence.
Resveratrol improves follicular development in PCOS rats by inhibiting the inflammatory response and pyroptosis of granulosa cells
Authors: Wei Huimei , Zhang Zhouxin , Zhang Shun , Wang Junli , Cui Xueying , Zhang Zhihan , Yu Jingjing , Lei Xiaocan , Xiuhong Zhuge , Huo Peng
Published: November 2024

Chronic inflammation is a key characteristic of polycystic ovary syndrome (PCOS) and is associated with follicular dysplasia in PCOS. PCOS patients treated with 1000 mg resveratrol (RES) daily for 3 months showed significant improvement in menstrual cycle regularity compared to the placebo group. This investigation explores potential impact of RES on a rat model of PCOS. Sprague–Dawley (SD) rats were subjected to a 30-day letrozole/high-fat diet interventions for PCOS model establishment, followed by RES intervention (20 mg/kg/d) for an additional 30 days. RES intervention mitigated obesity, estrous cycle irregularities, and ovulation disorders while decreasing serum testosterone and lipopolysaccharide (LPS) levels in PCOS rats. Concurrently, inflammatory markers (TNF-α, NLPR3, IL-6,) and pyroptosis-related markers (GSDMD, cleaved-Caspase-1, IL-1β, IL-18) were downregulated. Additionally, KGN cells (a human granulosa-like cell line) were treated with LPS and RES for in vitro assays. It was observed that RES (15 μM) significantly reduced ROS production and downregulated inflammatory cytokine expression in LPS-intervened KGN cells. Additionally, RES downregulated the expression levels of pyroptosis-related factors (GSDMD and cleaved-Caspase-1) and attenuated IL-18 and IL-1β secretion in LPS-induced KGN cells. Furthermore, RES intervention improved the pyroptosis-associated morphology of KGN cells after LPS treatment. In conclusion, RES may restore follicular development in PCOS rats by inhibiting inflammation and NLRP3/GSDMD/Caspase-1-mediated pyroptosis of ovarian granulosa cells, providing new insights into potential therapeutic approaches for PCOS.
Single-nucleus transcriptomics reveals disease- and pathology-specific signatures in α-synucleinopathies
Authors: Nido Gonzalo S , Castelli Martina , Mostafavi Sepideh , Rubiolo Anna , Shadad Omnia , Alves Guido , Tysnes Ole-Bjørn , Dölle Christian , Tzoulis Charalampos
Published: November 2024

α-synucleinopathies are progressive neurodegenerative disorders characterized by intracellular aggregation of α-synuclein, yet their molecular pathogenesis remains unknow. Here, we explore cell-specific changes in gene expression across different α-synucleinopathies. We perform single-nucleus RNA sequencing on nearly 300,000 nuclei from the prefrontal cortex of individuals with idiopathic Parkinson’s disease (iPD, n = 20), Parkinson’s disease caused by LRRK2 mutations (LRRK2-PD, n = 7), multiple system atrophy (MSA, n = 6) and healthy controls (n = 13).

iPD and LRRK2-PD exhibit a largely overlapping cell type-specific signature, which is distinct from that of MSA, and includes an overall decrease of the transcriptional output in neurons. Notably, most of the differential expression signal in iPD and LRRK2-PD is concentrated in a specific deep cortical neuronal subtype expressing adrenoceptor alpha 2A. While most differentially expressed genes are highly cell type- and disease-specific, PDE10A is found consistently downregulated in most cortical neurons, and across all three diseases. Finally, exploiting the variable presence and/or severity of α-synuclein pathology in LRRK2-PD and iPD, we identify cell type-specific signatures associated with α-synuclein pathology, including a neuronal upregulation of the SNCA gene itself, encoding α-synuclein.

Our findings provide novel insights into the cell-specific transcriptional landscape of the α-synucleinopathy spectrum.
Cognition and maps of injury in small vessel disease: time to move on from the black and white era
Authors: O’Sullivan Michael
Published: November 2024

This scientific commentary refers to ‘Enhancing cognitive performance prediction by white matter hyperintensity connectivity assessment’ by Petersen et al. (https://doi.org/10.1093/brain/awae315).
A solitary cockade purpuric lesion in a pregnant woman
Authors: Sivakumar Aravind , Siddeswara Siddhartha , Badhe Bhawana , Kumari Rashmi
Published: November 2024

A pregnant woman presented to our dermatology department (Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Puducherry, India) with a solitary cockade purpuric lesion over the abdomen, present for 5 days.
Synthesis of bisphenol-A- and bio-based polyarylates via amorphous solid-state polymerization with fluoroalkyl diesters
Authors: Taniguchi Taihei , Okazoe Takashi , Matsuoka Shin-ichi , Suzuki Masato
Published: November 2024

Amorphous solid-sate polymerization was efficiently synthesized using bisphenol-A-based polyarylate and isosorbide- or isomannide-based polyarylates, which represent promising super engineering plastics. The prepolymers were synthesized through the solution polymerization of bis(1,1,1,3,3,3-hexafluoro-2-propyl) terephthalate and isophthalate with bisphenol-A, isosorbide, or isomannide, using 1,8-diazabicyclo[5.4.0]-7-undecene and 1,5-diazabicyclo[4.3.0]-5-nonene as catalysts. The obtained prepolymers were then heated incrementally from 40 to 180 °C in the solid state under vacuum conditions. The bisphenol-A-based polyarylate product derived from a mixture of bis(1,1,1,3,3,3-hexafluoro-2-propyl) terephthalate (25%) and bis(1,1,1,3,3,3-hexafluoro-2-propyl) isophthalate (75%) was amorphous, exhibiting a molecular weight of 63,000 and a glass transition temperature of 208 °C. Meanwhile, isomannide-based polyarylate, a novel bio-derived amorphous polymer prepared using a similar approach, exhibited the highest glass transition temperature of 179 °C among known isosorbide-based polymers. Overall, our amorphous solid-sate polymerization method proved to be more efficient compared with conventional solid-sate polymerization, which involves crystallization.
Electrocatalytic oxygen reduction on nitrogen-doped porous carbon spheres prepared with resorcinol–phenolsulfonic acid–formaldehyde mixed resins
Authors: Sakamoto Keisuke , Kinoshita Keisuke , Shiraishi Yasuhiro , Yoshida Koki , Hiramatsu Wataru , Tanaka Shunsuke , Hirai Takayuki
Published: November 2024

Resorcinol–phenolsulfonic acid–formaldehyde (RxPS1–xF) mixed resin spheres were prepared by using high-temperature hydrothermal synthesis. Pyrolysis of the resin spheres under a NH3 atmosphere produced small, porous, conductive N-doped carbon spheres. These carbon spheres promoted an electrocatalytic oxygen reduction reaction with almost 100% four-electron reduction selectivity and their performance was comparable to that of the state-of-the-art Pt/C catalyst.
Tuberculosis Preventive Treatment for Pregnant People With Human Immunodeficiency Virus in South Africa: A Modeling Analysis of Clinical Benefits and Risks
Authors: Rosen Linzy V , Thielking Acadia M , Dugdale Caitlin M , Montepiedra Grace , Kalk Emma , Kim Soyeon , LaCourse Sylvia M , Mathad Jyoti S , Freedberg Kenneth A , Horsburgh C Robert , Paltiel A David , Wood Robin , Ciaranello Andrea L , Reddy Krishna P
Published: November 2024

Background

Although prior studies of tuberculosis-preventive treatment (TPT) for pregnant people with human immunodeficiency virus (PPWH) report conflicting adverse pregnancy outcome (APO) risks, international guidelines recommend TPT for PPWH.

Methods

We used a microsimulation model to evaluate 5 TPT strategies among PPWH receiving antiretroviral therapy in South Africa: No TPT; 6 months of isoniazid (6H) or 3 months of isoniazid-rifapentine (3HP) during pregnancy (Immediate 6H or Immediate 3HP) or post partum (Deferred 6H or Deferred 3HP). The primary outcomes were maternal, fetal/infant, and combined deaths from causes potentially influenced by TPT (maternal tuberculosis, maternal hepatotoxicity, stillbirth, low birth weight [LBW], and infant tuberculosis). Tuberculosis during pregnancy confers 250% and 81% higher modeled risks of stillbirth and LBW, respectively. In lower-risk or higher-risk scenarios, immediate TPT confers 38% lower or 92% higher risks of stillbirth and 16% lower or 35% higher risks of LBW.

Results

Immediate TPT would minimize deaths among PPWH. When TPT confers higher stillbirth and LBW risks, immediate TPT would produce the most combined maternal and fetal/infant deaths, even with low maternal CD4 cell count and high tuberculosis incidence. If immediate TPT yields a <4% or <20% increase in stillbirth or LBW, immediate TPT would produce fewer combined deaths than deferred TPT (sensitivity analysis range, <2%–22% and <11%–120%, respectively).

Conclusions

If APO risks are below identifiable thresholds, TPT during pregnancy could decrease combined maternal and fetal/infant deaths. Given uncertainty around isoniazid's risks, and the low threshold at which APO risks could outweigh benefits from tuberculosis deaths averted, studies of newer TPT regimens among PPWH are warranted to inform guidelines.
Prognostic implication of DPD quantification in transthyretin cardiac amyloidosis
Authors: Rettl René , Duca Franz , Kronberger Christina , Binder Christina , Willixhofer Robin , Ermolaev Nikita , Poledniczek Michael , Hofer Felix , Nitsche Christian , Hengstenberg Christian , Eslam Roza Badr , Kastner Johannes , Bergler-Klein Jutta , Hacker Marcus , Calabretta Raffaella , Kammerlander Andreas A
Published: November 2024

Aims

Quantification of cardiac [99mTc]-3,3-diphosphono-1,2-propanodicarboxylic acid (DPD) uptake enhances diagnostic capabilities and may facilitate prognostic stratification in patients with transthyretin cardiac amyloidosis (ATTR-CA). This study aimed to evaluate the association of quantitative left ventricular (LV) DPD uptake with myocardial structure and function, and their implications on outcome in ATTR-CA.

Methods and results

Consecutive ATTR-CA patients (n = 100) undergoing planar DPD scintigraphy with Perugini grade 2 or 3, alongside quantitative DPD single-photon emission computed tomography/computed tomography imaging and speckle-tracking echocardiography between 2019 and 2023, were included and divided into two cohorts based on median DPD retention index (low DPD uptake: ≤5.4, n = 50; high DPD uptake: >5.4, n = 50). The DPD retention index showed significant, albeit weak to modest, correlations with LV global longitudinal strain (LV-GLS: r = 0.366, P < 0.001), right ventricular free wall longitudinal strain (RV-FW-LS: r = 0.316, P = 0.002), LV diastolic function (E/e′ average: r = 0.304, P = 0.013), NT-proBNP (r = 0.332, P < 0.001), troponin T (r = 0.233, P = 0.022), 6 min walk distance (6MWD: r = −0.222, P = 0.033), and National Amyloidosis Centre (NAC) stage (r = 0.294, P = 0.003). ATTR-CA patients in the high DPD uptake cohort demonstrated more advanced disease severity regarding longitudinal cardiac function (LV-GLS: P = 0.012, RV-FW-LS: P = 0.036), LV diastolic function (E/e′ average: P = 0.035), cardiac biomarkers (NT-proBNP: P = 0.012, troponin T: P = 0.044), exercise capacity (6MWD: P = 0.035), and disease stage (NAC stage I: P = 0.045, III: P = 0.006), and experienced adverse outcomes compared with the low DPD uptake cohort [composite endpoint: all-cause death or heart failure hospitalization, HR: 2.873 (95% CI: 1.439–5.737), P = 0.003; DPD retention index: adjusted HR 1.221 (95% CI: 1.078–1.383), P = 0.002].

Conclusion

In ATTR-CA, enhanced quantitative LV DPD uptake indicates advanced disease severity and is associated with adverse outcome. DPD quantification may facilitate prognostic stratification when diagnosing patients with ATTR-CA.
Microfluidics for studying the deep underground biosphere: from applications to fundamentals
Authors: Morais Sandy , Vidal Emeline , Cario Anaïs , Marre Samuel , Ranchou-Peyruse Anthony
Published: November 2024

In this review, selected examples are presented to demonstrate how microfluidic approaches can be utilized for investigating microbial life from deep geological environments, both from practical and fundamental perspectives. Beginning with the definition of the deep underground biosphere and the conventional experimental techniques employed for these studies, the use of microfluidic systems for accessing critical parameters of deep life in geological environments at the microscale is subsequently addressed (high pressure, high temperature, low volume). Microfluidics can simulate a range of environmental conditions on a chip, enabling rapid and comprehensive studies of microbial behavior and interactions in subsurface ecosystems, such as simulations of porous systems, interactions among microbes/microbes/minerals, and gradient cultivation. Transparent microreactors allow real-time, noninvasive analysis of microbial activities (microscopy, Raman spectroscopy, FTIR microspectroscopy, etc.), providing detailed insights into biogeochemical processes and facilitating pore-scale analysis. Finally, the current challenges and opportunities to expand the use of microfluidic methodologies for studying and monitoring the deep biosphere in real time under deep underground conditions are discussed.
Communicating State Repression to the International Community: A Case Study of How China Frames Its Policies in Xinjiang Online
Authors: Villegas-Cruz Angel M
Published: November 2024

Regimes and their proxies seek to legitimize overt state repression abroad to avoid economic and reputational costs. Yet, few scholars have studied the international dimension of repression image management. I examine how countries communicate their repressive actions to the international community depending on the audience. Framing repression as a legitimate response to a credible threat (threat strategy) is more likely when communicating with countries facing higher levels of domestic threat. But due to in-group favoritism, when addressing in-group audiences of the repressed, governments are more likely to frame repression as necessary to protect the repressed (benevolent rule strategy). To test these claims, I collect 82,011 tweets about activities in Xinjiang published by eighty-eight Chinese diplomatic accounts from 2014 to 2020. The results suggest that regimes change their repression image management strategies depending on the audience. Chinese government accounts in countries with higher levels of domestic conflict are more likely to use the threat strategy than those in countries with lower levels of conflict, while those in countries with a similar in-group to Xinjiang (Muslim countries) are more likely to use the benevolent rule strategy than those in out-group states. This expands our understanding of the communication strategies of human rights-abusing regimes.
Establishment of a locally adaptive allele in multidimensional continuous space
Authors: Sakamoto Takahiro
Published: November 2024

Local adaptation is widely seen when species adapt to spatially heterogeneous environments. Although many theoretical studies have investigated the dynamics of local adaptation using 2-population models, there remains a need to extend the theoretical framework to continuous space settings, reflecting the real habitats of species. In this study, we use a multidimensional continuous space model and mathematically analyze the establishment process of local adaptation, with a specific emphasis on the relative roles of mutation and migration. First, the role of new mutations is evaluated by deriving the establishment probability of a locally adapted mutation using a branching process and a diffusion approximation. Next, the contribution of immigrants from a neighboring region with similar environmental conditions is considered. Theoretical predictions of the local adaptation rate agreed with the results of Wright–Fisher simulations in both mutation-driven and migration-driven cases. Evolutionary dynamics depend on several factors, including the strength of migration and selection, population density, habitat size, and spatial dimensions. These results offer a theoretical framework for assessing whether mutation or migration predominantly drives convergent local adaptation in spatially continuous environments in the presence of patchy regions with similar environmental conditions.
Allopolyploidy expanded gene content but not pangenomic variation in the hexaploid oilseed Camelina sativa
Authors: Bird Kevin A , Brock Jordan R , Grabowski Paul P , Harder Avril M , Healy Adam L , Shu Shengqiang , Barry Kerrie , Boston LoriBeth , Daum Christopher , Guo Jie , Lipzen Anna , Walstead Rachel , Grimwood Jane , Schmutz Jeremy , Lu Chaofu , Comai Luca , McKay John K , Pires J Chris , Edger Patrick P , Lovell John T , Kliebenstein Daniel J
Published: November 2024

Ancient whole-genome duplications are believed to facilitate novelty and adaptation by providing the raw fuel for new genes. However, it is unclear how recent whole-genome duplications may contribute to evolvability within recent polyploids. Hybridization accompanying some whole-genome duplications may combine divergent gene content among diploid species. Some theory and evidence suggest that polyploids have a greater accumulation and tolerance of gene presence–absence and genomic structural variation, but it is unclear to what extent either is true. To test how recent polyploidy may influence pangenomic variation, we sequenced, assembled, and annotated 12 complete, chromosome-scale genomes of Camelina sativa, an allohexaploid biofuel crop with 3 distinct subgenomes. Using pangenomic comparative analyses, we characterized gene presence–absence and genomic structural variation both within and between the subgenomes. We found over 75% of ortholog gene clusters are core in C. sativa and <10% of sequence space was affected by genomic structural rearrangements. In contrast, 19% of gene clusters were unique to one subgenome, and the majority of these were Camelina specific (no ortholog in Arabidopsis). We identified an inversion that may contribute to vernalization requirements in winter-type Camelina and an enrichment of Camelina-specific genes with enzymatic processes related to seed oil quality and Camelina's unique glucosinolate profile. Genes related to these traits exhibited little presence–absence variation. Our results reveal minimal pangenomic variation in this species and instead show how hybridization accompanied by whole-genome duplication may benefit polyploids by merging diverged gene content of different species.
Association of Low Muscle Strength With Incident Pneumonia in Older Patients With Heart Failure
Authors: Yamaguchi Kenta , Konishi Masaaki , Kagiyama Nobuyuki , Kasai Takatoshi , Kamiya Kentaro , Saito Hiroshi , Saito Kazuya , Maekawa Emi , Kitai Takeshi , Iwata Kentaro , Jujo Kentaro , Wada Hiroshi , Shinoda Satoru , Akiyama Eiichi , Momomura Shin-Ichi , Hibi Kiyoshi , Matsue Yuya
Published: November 2024

Background

Patients with heart failure (HF) are at an increased risk of developing pneumonia, leading to a high mortality. A decrease in muscle strength due to aging or concomitant disease may contribute to the development of pneumonia in older adults. We sought to investigate the relationship between low muscle strength and pneumonia incidence in older patients hospitalized for worsening HF.

Methods

We carried out a subanalysis of the FRAGILE-HF, a prospective multicenter observational study, including 1 266 consecutive older (≥65 years) patients hospitalized with HF (mean age 80.2 ± 7.8 years; 57.4% male; left ventricular ejection fraction 46% ± 17%) and information of incident pneumonia observed after discharge. Patients were followed up for 2 years post-discharge.

Results

A total of 88 patients (7.0%) developed pneumonia after discharge, with an incidence of 42.7 per 1 000 person-years. A total of 893 patients with low muscle strength, defined as handgrip strength <28 kg for men and <18 kg for women according to international criteria, were more likely to develop pneumonia than those with normal muscle strength (p < .001; log-rank test). Low muscle strength was a significant predictor of incident pneumonia (adjusted hazard ratio with 95% confidence interval: 2.65 [1.31–5.35], p = .007). Furthermore, the mortality rates were 43.2% in patients who developed pneumonia and 19.3% in those who did not, indicating a heightened risk of death following the onset of pneumonia (adjusted hazard ratio: 4.25 [2.91–6.19], p < .001).

Conclusions

In older patients hospitalized for HF, low muscle strength was associated with incident pneumonia after discharge.
Two dimensions of product modularity and innovation: the case of R&D teams
Authors: Martinez Martin Daniel , de Leeuw Tim , Haefliger Stefan
Published: November 2024

This study investigates the relationship between product modularity and innovation in 101 research and development (R&D) teams. The key contribution and the departure from prior empirical work consists in bringing into relation multidimensional operationalizations of these two concepts. Product modularity is composed of standardization and reconfigurability and innovation of novelty and efficiency. The literature provides arguments for both negative and positive relationships between standardization and the two types of innovation, while positive relationships are argued for product reconfigurability. The empirical findings corroborate most of the theorizing, although negative relationships are found for standardization. This study contributes to the literature by unpacking the understanding of the concept of product modularity in R&D organizations since the multidimensional approach resolves some of the ambiguity from previous studies. The modularity literature long called for studies to empirically investigate product modularity in more than one dimension implying a number of theoretical implications discussed here.
Elucidating the augmented resistance profile of Scedosporium/Lomentospora species to azoles in a cystic fibrosis mimic environment
Authors: Mello Thaís P , Ramos Lívia S , Andrade Valter V , Torres-Santos Eduardo Caio , Lackner Michaela , Branquinha Marta H , Santos André L S
Published: November 2024

Background

Scedosporium/Lomentospora species are ranked as the second most frequently isolated filamentous fungi from cystic fibrosis (CF) patients. Previously, we demonstrated that the minimum inhibitory concentration (MIC) for voriconazole and posaconazole increased when performed on a mucin-containing synthetic CF sputum medium (SCFM) compared to the standard medium, RPMI-1640. In this study, we have expanded the MIC comparison to four additional azoles and investigated characteristics linked to azole resistance in Scedosporium apiospermum, Scedosporium minutisporum, Scedosporium aurantiacum and Lomentospora prolificans.

Methods

MIC was assayed by CLSI protocol, efflux pump activity was assessed by rhodamine 6G and sterols were analysed by gas chromatography-mass spectrometry (GC-MS).

Results

Overall, MICs for fluconazole, itraconazole, voriconazole, posaconazole, miconazole and ketoconazole increased by least 2-fold when susceptibility tests were performed using SCFM compared to RPMI. The activity of efflux pumps was similar in both media; however, in RPMI, but not in SCFM, the activity was induced by voriconazole and fluconazole. Additionally, MICs for those antifungals decreased more noticeably in SCFM than in RPMI in the presence of the efflux pump inhibitor PaβN. The SCFM-grown cells presented fewer sterols in their composition, and consequently higher membrane fluidity, than RPMI-grown cells. GC-MS analysis demonstrated a remodulation in the sterol profile in SCFM- compared to RPMI-grown cells. Accordingly, when the MIC assay was performed in the presence of the membrane stressor NaCl (3%), the susceptibility to voriconazole and fluconazole increased more in SCFM- than RPMI-grown cells.

Conclusions

Scedosporium/Lomentospora species undergo cellular adaptations in SCFM that favours their growth in face of the challenges imposed by azole antifungals.
Clinical impact of ceftazidime/avibactam on the treatment of suspected or proven infections in a large cohort of patients with haematological malignancies: a multicentre observational real-world study
Authors: Tumbarello Mario , Giuliano Gabriele , Criscuolo Marianna , Del Principe Maria Ilaria , Papayannidis Cristina , Fracchiolla Nicola Stefano , Dargenio Michela , Cefalo Mariagiovanna , Nadali Gianpaolo , Candoni Anna , Buquicchio Caterina , Marchesi Francesco , Picardi Marco , Lessi Federica , Piedimonte Monica , Prezioso Lucia , Piccini Matteo , Cattaneo Chiara , Busca Alessandro , Brunetti Sara , Buzzatti Elisa , Dedola Alessandra , Sciumé Mariarita , Di Renzo Nicola , Cesini Laura , Vatteroni Alessandra , Raffaelli Francesca , Pagano Livio
Published: November 2024

Objectives

To evaluate clinical impact of ceftazidime/avibactam on treating infections due to MDR Gram-negative bacteria in patients with haematological malignancies (HMs).

Methods

We conducted a retrospective, observational study at 17 Italian haematological wards that included patients with HMs receiving ceftazidime/avibactam for the treatment of suspected or proven infections. The primary endpoint was all-cause mortality 30 days after infection onset. Secondary endpoints included the development of in vitro ceftazidime/avibactam resistance, adverse reactions and infection relapse.

Results

Of 198 patients enrolled, 66 had fever of unknown origin and 132 had microbiologically proven infections (MPIs). Enterobacterales were responsible for 98 MPIs, with KPC producers accounting for 75% of these, and carbapenem-resistant Pseudomonas aeruginosa caused 25% of MPIs. The overall 30-day mortality rate was 17.7%. Infection relapse occurred in four patients with MPI. Patients who died within 30 days of infection onset tended to have pre-existing cerebrovascular diseases, a Charlson Comorbidity Index > 4 and septic shock at infection onset and had received inadequate initial antibiotic therapy. Thirty-day mortality was independently associated with septic shock at infection onset and inappropriate initial antibiotic therapy.

Conclusions

Our study provides further evidence about the effectiveness of ceftazidime/avibactam in treating infections in patients with HMs.
How to validate UV-C based air cleaners using viruses containing aerosols in a test room
Authors: Kramer Bernd , Warschat Daniela , Meepool Anna , Muranyi Peter
Published: November 2024

Aims

UV-C based air cleaners may reduce the transmission of infectious diseases. However, microbiological validation is necessary to quantify their efficiency. In this study, the stability of aerosolized bacteriophages for validation purposes was investigated in a test room, before a UV-C based air cleaner was exemplarily evaluated regarding the inactivation of airborne bacteriophages.

Methods and results

The bacteriophage Phi6 was selected as virus surrogate and aerosolized in a room of 30 m³ volume. The recovery of infectious bacteriophages was first analyzed under variation of the relative humidity (20%–55% RH) and sampling time. The aerosol studies showed that a low humidity between 20% RH and 30% RH provides a high and stable recovery of bacteriophages Phi6 over 1 h. However, with increasing humidity, the number of infectious airborne bacteriophages Phi6 decreased significantly. At 50% RH, the recovery of Phi6 was 4 orders of magnitude lower compared to 20% RH. The validation of a UV-C based air cleaner was then demonstrated in the test room whereat the decline of infectious airborne bacteriophages was recorded over time. The nonenveloped bacteriophage MS2 was used as a reference. The validation results were significantly different for Phi6 when the humidity in the test room was either 40% RH or 30% RH, whereas comparable results were obtained for MS2 at both humidities.

Conclusion

A rising humidity in the test room caused a significant decline in the recovery of infectious airborne bacteriophages Phi6. The result of a quantitative validation of UV-C based air cleaners may therefore be affected by the respective humidity.
Research for all: building a diverse researcher community for the All of Us Research Program
Authors: Baskir Rubin , Lee Minnkyong , McMaster Sydney J , Lee Jessica , Blackburne-Proctor Faith , Azuine Romuladus , Mack Nakia , Schully Sheri D , Mendoza Martin , Sanchez Janeth , Crosby Yong , Zumba Erica , Hahn Michael , Aspaas Naomi , Elmi Ahmed , Alerté Shanté , Stewart Elizabeth , Wilfong Danielle , Doherty Meag , Farrell Margaret M , Hébert Grace B , Hood Sula , Thomas Cheryl M , Murray Debra D , Lee Brendan , Stark Louisa A , Lewis Megan A , Uhrig Jen D , Bartlett Laura R , Rico Edgar Gil , Falcón Adolph , Cohn Elizabeth , Lunn Mitchell R , Obedin-Maliver Juno , Cottler Linda , Eder Milton , Randal Fornessa T , Karnes Jason , Lemieux KiTani , Lemieux Nelson , Lemieux Nelson , Bradley Lilanta , Tepp Ronnie , Wilson Meredith , Rodriguez Monica , Lunt Chris , Watson Karriem
Published: November 2024

Objectives

The NIH All of Us Research Program (All of Us) is engaging a diverse community of more than 10 000 registered researchers using a robust engagement ecosystem model. We describe strategies used to build an ecosystem that attracts and supports a diverse and inclusive researcher community to use the All of Us dataset and provide metrics on All of Us researcher usage growth.

Materials and Methods

Researcher audiences and diversity categories were defined to guide a strategy. A researcher engagement strategy was codeveloped with program partners to support a researcher engagement ecosystem. An adapted ecological model guided the ecosystem to address multiple levels of influence to support All of Us data use. Statistics from the All of Us Researcher Workbench demographic survey describe trends in researchers’ and institutional use of the Workbench and publication numbers.

Results

From 2022 to 2024, some 13 partner organizations and their subawardees conducted outreach, built capacity, or supported researchers and institutions in using the data. Trends indicate that Workbench registrations and use have increased over time, including among researchers underrepresented in the biomedical workforce. Data Use and Registration Agreements from minority-serving institutions also increased.

Discussion

All of Us built a diverse, inclusive, and growing research community via intentional engagement with researchers and via partnerships to address systemic data access issues. Future programs will provide additional support to researchers and institutions to ameliorate All of Us data use challenges.

Conclusion

The approach described helps address structural inequities in the biomedical research field to advance health equity.
A systematic review and meta-analysis of the effects of probiotics on bone outcomes in rodent models
Authors: Yumol Jenalyn L , Gittings William , de Souza Russell J , Ward Wendy E
Published: November 2024

Emerging evidence demonstrates an opportunity for using probiotics to support bone health, but findings in humans are limited. This systematic review investigated if probiotic supplementation improves bone mineral density (BMD) and bone structure in rodent models compared to no supplementation. Studies (n = 71) examining the effect of oral consumption of any probiotic strain on BMD or bone structure in rodents were included. Meta-analyses were conducted separately by study model (intact, ovariectomized) and bone site (femur, tibia, spine) to determine the probiotic effect (standardized mean difference, SMD) on volumetric BMD (vBMD), bone volume fraction (BV/TV), and cortical thickness (Ct.Th). Reasons for heterogeneity were explored (probiotic genus, sex, type of rodent). In intact rodents, probiotics resulted in greater vBMD (SMD = 0.43, 95% CI [0.13, 0.74], I2 = 3%, p < 0.05) and higher BV/TV (SMD = 0.63, 95% CI [0.25, 1.02], I2 = 57%, p < 0.05) at the femur without changes in cortical bone structure. In ovariectomized models, probiotic supplementation resulted in greater vBMD (femur: SMD = 1.28, 95% CI [1.01, 1.55], I2 = 3%, p < 0.05; tibia: SMD = 1.29, 95% CI [0.52, 2.05], I2 = 67%, p < 0.05; and spine: SMD = 1.47, 95% CI [0.97, 1.97], I2 = 26%, p < 0.05) as well as higher BV/TV (femur: SMD = 1.16, 95% CI [0.80, 1.52], I2 = 56%, p < 0.05; tibia: SMD = 2.13, 95% CI [1.09, 3.17], I2 = 79%, p < 0.05; spine: SMD = 2.04, 95% CI [1.17, 2.90], I2 = 76%, p < 0.05) and Ct.Th at the tibia (SMD = 2.35; 95% CI [0.72, 3.97], I2 = 82%, p < .0.05) but not at the femur versus control. The syntheses support probiotics as a strategy to improve bone outcomes in rodent models.
Postharvest CO2 treatment and cold storage for Drosophila suzukii (Diptera: Drosophilidae) fruit infestation control
Authors: Cvelbar Weber Nika , Modic Špela , Žigon Primož , Razinger Jaka
Published: November 2024

The invasive pest, spotted wing drosophila (Drosophila suzukii (Matsumura, 1931) or SWD), damages various soft-skinned fruits, severely impacting orchards and vineyards economically. Current sorting practices in commercial production may overlook early-stage SWD infestations, as visible signs take a few days to appear. Our study focused on managing SWD infesting fruits (blueberry, cherry, and raspberry) without visible signs using an artificial atmosphere with elevated CO2 and low temperature. We hypothesized that these factors affect SWD survival and possibly interact, with potential variations among different soft- or stone-fruit species or varieties. High CO2 concentrations and cold storage both negatively affected SWD development. A 24-h 100% CO2 fumigation, without cold storage, significantly reduced SWD infestations in all 3 fruit species studied. On the other hand, 10% CO2 without cold storage did not cause a significant infestation reduction in cherries. Cold storage alone was too slow to be considered effective. Concurrent low-temperature treatment and CO2 treatment reduced the insecticidal efficacy of CO2 fumigation. Optimal fruit sanitation was achieved with a 3-h 100% CO2 treatment at ambient temperature before cold storage. Raspberries were the most suitable host for SWD development, with over a 5-fold higher SWD development compared to blueberries and over 50 times more than in cherries. We discussed the observed interactions between CO2 fumigation and chilling and suggested a simple postharvest SWD management protocol using optimal CO2 levels, exposure times, and chilling periods—achievable without complex equipment.
Knocking on a Locked Door: Assessing Canada’s Response to Attacks Against Human Rights Defenders
Authors: Francescone Kirsten , Rankin Lisa
Published: November 2024

For over two decades, Canadian corporations have been the subject of severe allegations of human rights and environmental violations related to the forced imposition of their operations abroad. Despite the growing consensus within the literature and international governance community that Canadian corporations—especially within the extractive sector—are serial perpetrators of grave human rights violations and despite Canada’s international legal obligations, at present there are very little ‘hard law’ mechanisms available to hold corporations to account. Whereas much literature has been dedicated to how Canadian corporations are facilitated by advocacy and lobbying efforts at the level of Canadian embassies in home-state-countries, much less studied is how these same state actors work towards protecting and preventing human rights defenders from harm. In this article we critically analyse the implementation of the Canadian government’s Voices at Risk guidelines (2016) from the perspective of two Canadian human rights advocacy Civil Society Organizations (CSOs) supporting communities in Guatemala, drawing from email and verbal communications as well as Access to Information Requests from 2016 to 2021 regarding the Escobal mine. We assess the usefulness of advocacy at the level of embassies as a way of protecting defenders and demonstrate that, in our experience, calls for support to defenders were ignored. We argue that, within the context of foreign policy which prioritizes trade and investment over all other government policies and wherein corporate violence is met with impunity, current Canadian policies aimed at protecting human rights defenders are essentially useless as an advocacy strategy.
SMARTboost Learning for Tabular Data
Authors: Giordani Paolo
Published: November 2024

We introduce SMARTboost (boosting of symmetric smooth additive regression trees), an extension of gradient boosting machines with improved accuracy when the underlying function is smooth or the sample small or noisy. In extensive simulations, we find that the combination of smooth symmetric trees and of carefully designed priors gives SMARTboost a large edge (in comparison with XGBoost and BART) on data generated by the most common parametric models in econometrics, and on a variety of other smooth functions. XGBoost outperforms SMARTboost only when the sample is large, and the underlying function is highly discontinuous. SMARTboost’s performance is illustrated in two applications to global equity returns and realized volatility prediction.
Impact of anomalous ocean warming on the abundance and foraging habits of the California Sea Lion (Zalophus californianus) from the San Benito Archipelago in the Mexican Pacific
Authors: Rodríguez-Martínez María Isabel , Moreno-Sánchez Xchel G , Moncayo-Estrada Rodrigo , Elorriaga-Verplancken Fernando R
Published: November 2024

The California sea lion (Zalophus californianus; CSL) reflects environmental conditions of the Northeastern Pacific, where resource availability was importantly reduced for different taxa during climatic variations such as the North Pacific heatwave (The Blob 2014 to 2015) or El Niño 2015 to 2016 due to the effect of these anomalies on primary productivity. Our objective was to determine the abundance and foraging habits of CSLs from the San Benito Archipelago (Mexican Pacific) in a period (2013 to 2019) that involved warm anomalies. Annual counts were conducted by sex/age classes; scats were sampled to identify the main prey consumed; and pup fur (maternal foraging indicators) was collected for analysis of δ13C and δ15N. The prey importance index (PII) and trophic level were calculated and the Siber assessment in R was used to estimate isotopic niches. Colony abundance decreased by approximately 50% from 2013 to 2019. Values of δ13C showed significant interannual differences (P < 0.001) with more negative values (−17.2‰ to −16.7‰) from 2015 onwards, indicating offshore foraging habits. Significant interannual differences (P < 0.001) were found for δ15N, with a declining trend (20.4‰ to 19.07‰), and a difference of more than 1‰ between 2013 and 2019, evidencing a probable shift of foraging grounds toward higher latitudes. Based on the PII, Strongylura exilis (30%), Merluccius productus (24%), Ommastrephes bartramii (10%), and Sardinops sagax (10%) were the most important prey, showing significant interannual differences (P < 0.001). CSLs had a mean trophic level of 4.89, with a slight increasing trend toward the end of the period. Dietary plasticity was found in CSLs, possibly caused by environmental changes that modified prey availability and led to variations in foraging grounds, and consequently in the colony abundance over time.
The Eastern Fox Squirrel (Sciurus niger) exhibits minimal patterns of phylogeography across native and introduced sites
Authors: Armstrong Noah , Klure Dylan M , Greenhalgh Robert , Stapleton Tess E , Dearing M Denise
Published: November 2024

Introduced species are one of the leading causes of declining global biodiversity and result in many billions of dollars of losses to the bioeconomy worldwide. Introduced species have become increasingly common due to globalization and climate change, and population genetics is a useful tool for the management of such species. The Eastern Fox Squirrel (Sciurus niger) is a highly successful invader that was introduced to many states in western North America throughout the 20th century. We used low-pass whole genome sequencing to evaluate phylogeographic structure across native and introduced ranges of this species and identify the putative number and geographic sources of introductions in California and Utah. We found minimal patterns of phylogeographic structure, consistent with recent range and population expansion since the Last Glacial Maximum. Additionally, we found evidence for multiple mitochondrial haplotypes in California and only 1 haplotype in Utah, which suggests that fox squirrels in California were sourced from multiple introduction events while those in Utah were likely sourced from a single event. Genomic resources generated in this study will be useful for future conservation efforts in this species and will assist with the ongoing management of its introductions across western North America.
A different sense of place: care and curation in the university
Authors: Thompson Christiane
Published: November 2024

The aim of this article is to explore the spatial constitution of the university today, its relation to Bildung in the university, and the way that changes of the universities are conceptually articulated or even programmatically demanded. In the first part of the article, the concept of the so-called ‘non-places’ advanced by the French ethnologist Marc Augé is used in order to set a conceptual framework for reflecting on the place of the university. In the second part of the article, it is demonstrated that the university is currently being reshaped as a non-place and more specifically, as a transit lounge. Using the example of Minerva University, it is shown how mobilization, optimization, and functionalization of learning become dominant at the expense of forming its own place. In the third part of the article, the relations between Bildung and place are reflected on following Ronald Barnett’s ecological approach of the university. In this approach, care and curation are central, as is shown in the final part of the article.
Towards black methods in research with refugees
Authors: Rashid Mariam
Published: November 2024

Critical approaches to forced displacement and migration studies gesture towards methodologies and theoretical orientations that are contextualized within the complex socialities of refuge lifeworlds and ways of being. This article offers methodological approaches that account for the forces of displacement as well as the layered and textured experiences of forcibly displaced people. Turning to black studies and black feminist thought, the article examines how forcibly displaced people navigate and contest resettlement processes in the USA. Thinking with empirical material from a research study engaging with forcibly displaced interlocutors from East and Central Africa and refugee resettlement personnel, the article illuminates critical methods of interpreting the experiences of refugees and forms of resettlement through the lenses of black studies and black feminist thought.
Complex postoperative ureterovaginal and vesicovaginal fistula following a non-oncological hysterectomy: a report of a challenging complication
Authors: Tzelepis Konstantinos , Giannakodimos Ilias , Samara Athina A , Kotanidis Christos , Tsiapakidou Sofia , Janho Michel , Koutras Antonios , Sotiriou Sotirios
Published: November 2024

In a quarter of patients with ureterovaginal fistula (UVF), a concurrent associated vesicovaginal fistula (VVF) can also be found. An increased clinical suspicion should be arised in cases of urinary vaginal discharge accompanied with unilateral flank pain following a gynecological procedure. A 43-year-old female patient diagnosed with a complex postoperative UVF and VVF following a total hysterectomy. After an unsuccessful initial conservative approach with the placement of a nephrostomy tube, an ureterocystotomy with antireflux reimplantation of the ureter was decided. The patient experienced an uneventful postoperative period and a year later, the patient remains asymptomatic without any evidence of fistula recurrent. Our case reports the relatively rare presence of a concurrent postoperative complex UVF and VVF formation in order to rise clinical suspicion in clinicians regarding the diagnostic approach and optimal management.