bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Case study of polypharmacy-induced serotonin syndrome in a cancer patient
Authors: Zhu Andrew , Kuhnly Nicole , Chen Leon , Dulu Alina O. 
Published: July 2024

ABSTRACT
Polypharmacy in cancer care can be complex and detrimental, particularly among younger patients, who can be easily overlooked. This report showcases a 54-year-old woman with cancer, treated for dapsone-induced methemoglobinemia with methylene blue (MB), subsequently developing serotonin syndrome (SS) due to concurrent serotonin-active medications. This case highlights the critical impact of polypharmacy, emphasizing the necessity for acute care providers to diligently assess medication interactions, especially in emergencies. It underscores the importance of considering alternative treatments and the vigilant monitoring of symptoms indicative of adverse drug interactions to ensure patient safety and optimize outcomes in complex therapeutic scenarios.
A Quantitative Study of the Head Pitching Test for Lateral Canal BPPV
Authors: Califano Luigi , Martellucci Salvatore , Melillo Maria Grazia 
Published: July 2024

Objectives
Lateral semicircular canal BPPV (LSC-BPPV) is diagnosed with the Head Yaw Test (HYT) by observing nystagmus direction and comparing the nystagmus intensity on both sides according to Ewald’s laws. Head Pitching Test (HPT) is a diagnostic maneuver performed in the upright position by bending the patient’s head forward (bowing) and backward (leaning) and observing the evoked nystagmus. We aimed to assess the sensitivity of HPT in correctly diagnosing LSC-BPPV through the quantitative measurement of Bowing and Leaning nystagmus slow-phase velocity (SPV).

Methods
One hundred cases of LSC-BPPV were prospectively enrolled. HPT was performed, looking for pseudospontaneous, bowing, and leaning nystagmus. HYT was considered for the “final diagnosis.” HPT was defined as “diagnostic” if the nystagmus was present in at least one position, “undiagnostic” if no nystagmus was detectable. The direction and the SPV of nystagmus in all positions were analyzed and compared to determine the degree of agreement between HPT and HYT.

Outcomes
Sixty-four geotropic and 36 apogeotropic forms were diagnosed. HPT was diagnostic in 80 cases, with no difference between the two forms. According to Ewald’s laws, the direction of stronger nystagmus evoked by HPT agreed with the HYT results in 39/52 (75%) cases in geotropic forms and 21/28 (75%) cases in apogeotropic forms. The agreement between HPT and HYT was “substantial” considering all the cases and “almost complete” considering only the patients with diagnostic HPT.

Conclusion
Quantitative HPT is a valid test in diagnosing the affected side and form of LSC-BPPV, even if less reliable than HYT.
Amplitude Parameters Are Predictive of Hearing Preservation in a Randomized Controlled Trial of Intracochlear Electrocochleography During Cochlear Implant Surgery
Authors: Harris Michael S. , Koka Kanth , Thompson-Harvey Adam , Harvey Erin , Riggs William J. , Saleh Shaza , Holder Jordan T. , Dwyer Robert T. , Prentiss Sandra M. , Lefler Shannon M. , Kozlowski Kristin , Hiss Meghan M. , Ortmann Amanda J. , Nelson-Bakkum Erin R. , Büchner Andreas , Salcher Rolf , Harvey Steven A. , Hoffer Michael E. , Bohorquez Jorge E. , Alzhrani Farid , Alshihri Rana , Almuhawas Fida , Danner Christopher J. , Friedland David R. , Seidman Michael D. , Lenarz Thomas , Telischi Fred F. , Labadie Robert F. , Buchman Craig A. , Adunka Oliver F. 
Published: July 2024

ObjectiveTo prospectively evaluate the association between hearing preservation after cochlear implantation (CI) and intracochlear electrocochleography (ECochG) amplitude parameters.Study DesignMulti-institutional, prospective randomized clinical trial.SettingTen high-volume, tertiary care CI centers.PatientsAdults (n = 87) with sensorineural hearing loss meeting CI criteria (2018–2021) with audiometric thresholds of ≤80 dB HL at 500 Hz.MethodsParticipants were randomized to CI surgery with or without audible ECochG monitoring. Electrode arrays were inserted to the full-depth marker. Hearing preservation was determined by comparing pre-CI, unaided low-frequency (125-, 250-, and 500-Hz) pure-tone average (LF-PTA) to LF-PTA at CI activation. Three ECochG amplitude parameters were analyzed: 1) insertion track patterns, 2) magnitude of ECochG amplitude change, and 3) total number of ECochG amplitude drops.ResultsThe Type CC insertion track pattern, representing corrected drops in ECochG amplitude, was seen in 76% of cases with ECochG “on,” compared with 24% of cases with ECochG “off” (p= 0.003). The magnitude of ECochG signal drop was significantly correlated with the amount of LF-PTA change pre-CI and post-CI (p< 0.05). The mean number of amplitude drops during electrode insertion was significantly correlated with change in LF-PTA at activation and 3 months post-CI (p≤ 0.01).ConclusionsECochG amplitude parameters during CI surgery have important prognostic utility. Higher incidence of Type CC in ECochG “on” suggests that monitoring may be useful for surgeons in order to recover the ECochG signal and preventing potentially traumatic electrode–cochlear interactions.
A Population-based Study Investigating the Incidence of Human Papillomavirus–Associated and Human Papillomavirus–Independent Cervical Adenocarcinomas
Authors: Ben-Mussa Ali , Shah Rajeev , Rajendran Simon , McCluggage W. Glenn 
Published: July 2024

Cervical adenocarcinomas are now classified as human papillomavirus (HPV)-associated and HPV-independent types with the former being more common. However, population-based studies regarding the relative incidences of the 2 types are few. This study investigates the incidence of cervical adenocarcinomas in Northern Ireland (a country with a relatively stable population of ~1.8 million) over a recent 9-year period (2015–2023). Overall, there were 146 primary cervical adenocarcinomas, 130 HPV-associated (89%) and 16 HPV-independent (11%). The median age was 43 years (range: 24–82) for HPV-associated and 62.5 years (range: 31–84) for HPV-independent neoplasms; this was statistically significant (P < 0.001). The calculated age-adjusted incidence of the patients with HPV-associated and HPV-independent neoplasms was 1.68 and 0.20 per 100,000 person-years, respectively. The HPV-independent neoplasms were more often advanced stage at diagnosis; 97 of 130 (75.4%) of the HPV-associated cases were diagnosed at Stage I compared with 5 of 16 (31.3%) of the HPV-independent cases. The HPV-independent neoplasms were mostly gastric-type (56.3%) with smaller numbers of clear cells and mesonephric. Despite the relatively short follow-up, the mortality of patients with HPV-independent adenocarcinomas was significantly higher than patients with HPV-associated neoplasms (56.3% vs 5.4%) with a median survival of just over a year (13.2 mo) in the former for those who died.
Translation and Comprehensive Validation of the Hebrew Survey on Patient Safety Culture (HSOPS 2.0)
Authors: Ein-Gal Yaffa , Sela Roni , Arad Dana , Szyper Kravitz Martine , Hanhart Shuli , Goldschmidt Nethanel , Kedmi-Shahar Efrat , Bitan Yuval 
Published: July 2024

Objectives
The study aim was to create an updated valid translation into Hebrew of the AHRQ’s survey on patient safety culture for hospitals, version 2.0. It also suggested a supplementary section about workers’ safety. Comparable and valid measurement tools are important for national and international benchmarking of patient safety culture in hospitals.

Methods
The process was carried out by a designated committee according to AHRQ translation guidelines. Methodology included several translation cycles, 6 semistructured cognitive interviews with health workers, and a web-based pilot survey at 6 general hospitals. Main analyses included an exploratory factor analysis, a comparison of the differences in results between versions 1 and 2 of the survey to the differences reported by AHRQ, and content analysis of open-ended questions.

Results
A total of 483 returned questionnaires met the inclusion criterion of at least 70% completion of the questionnaire. The demographic distributions suggested this sample to be satisfactory representative. Cronbach’s alpha for the translated questionnaire was 0.95, meaning a high internal consistency between the survey items. An exploratory factor analysis revealed 8 underlying factors, and a secondary analysis further divided the first factor into 2 components. The factors structure generally resembled HSOPS 2.0 composite measures. Analyses of the new section about health workers’ safety showed high involvement and possible common themes.

Conclusions
The study demonstrated good psychometric properties—high reliability and validity of the new translated version of the questionnaire. This paper may serve other countries who wish to translate and adapt the safety culture survey to different languages.
Aurantiacibacter hainanensis sp. nov. and Qipengyuania zhejiangensis sp. nov., two novel Erythrobacteraceae species isolated from tidal flat sediments
Authors: Liu Wen-Jia , Zhang Yu , Cao Ke , Li Jia-Xi , Wen Yu-Qiao , Sun Cong , Xu Lin 
Published: July 2024

Two Gram-stain-negative, rod-shaped, non-motile, aerobic and carotenoid-producing strains, belonging to the family Erythrobacteraceae, designated as H149T and Z2T, were isolated from tidal flat sediment samples collected in Hainan and Zhejiang, PR China, respectively. Growth of strain H149T occurred at 15–42 °C, 0–10.0 % (w/v) NaCl, and pH 6.0–8.5, with the optima at 35–37 °C, 3.0–3.5 % (w/v) NaCl and pH 7.0. Strain Z2T grew at 15–37 °C, 0–6.0 % (w/v) NaCl, and pH 6.0–9.5, with the optima at 25–30 °C, 0.5–1.0 % (w/v) NaCl and pH 6.0–6.5. Ubiquinone-10 was the sole ubiquinone in two strains. The predominant cellular fatty acids of strain H149T were C16 : 0, summed feature 3 and summed feature 8, while those of strain Z2T were C17 : 1
ω6c, summed feature 3 and summed feature 8. Strains H149T and Z2T shared diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, phosphatidylcholine and sphingoglycolipid as major polar lipids. The 16S rRNA gene sequence identity analysis indicated that strain H149T had the highest sequence identity of 98.4 % with Aurantiacibacter odishensis KCTC 23981T, and strain Z2T had that of 98.2 % with Qipengyuania pacifica NZ-96T. Phylogenetic trees based on 16S rRNA gene and core-genome sequences revealed that strains H149T and Z2T formed two independent clades in the genera Aurantiacibacter and Qipengyuania, respectively. Strain H149T had average nucleotide identity values of 74.0–81.3 % and in silico DNA–DNA hybridization values of 18.5–23.1 % with Aurantiacibacter type strains, while strain Z2T had values of 73.3–78.7 % and 14.5–33.3 % with Qipengyuania type strains. The genomic DNA G+C contents of strains H149T and Z2T were 64.3 and 61.8 %, respectively. Based on the genetic, genomic, phylogenetic, physiological and chemotaxonomic results, strains H149T (=KCTC 8397T=MCCC 1K08920T) and Z2T (=KCTC 8396T=MCCC 1K08946T) are concluded to represent two novel Erythrobacteraceae species for which the names Aurantiacibacter hainanensis sp. nov. and Qipengyuania zhejiangensis sp. nov. are proposed, respectively.
Glioblastoma Neurovascular Progenitor Orchestrates Tumor Cell Type Diversity
Authors: Fazzari Elisa , Azizad Daria J. , Yu Kwanha , Ge Weihong , Li Matthew X. , Nano Patricia R. , Kan Ryan L. , Tum Hong A. , Tse Christopher , Bayley Nicholas A. , Haka Vjola , Cadet Dimitri , Perryman Travis , Soto Jose A. , Wick Brittney , Raleigh David R. , Crouch Elizabeth E. , Patel Kunal S. , Liau Linda M. , Deneen Benjamin , Nathanson David A. , Bhaduri Aparna 
Published: July 2024

AbstractGlioblastoma (GBM) is the deadliest form of primary brain tumor with limited treatment options. Recent studies have profiled GBM tumor heterogeneity, revealing numerous axes of variation that explain the molecular and spatial features of the tumor. Here, we seek to bridge descriptive characterization of GBM cell type heterogeneity with the functional role of individual populations within the tumor. Our lens leverages a gene program-centric meta-atlas of published transcriptomic studies to identify commonalities between diverse tumors and cell types in order to decipher the mechanisms that drive them. This approach led to the discovery of a tumor-derived stem cell population with mixed vascular and neural stem cell features, termed a neurovascular progenitor (NVP). Followingin situvalidation and molecular characterization of NVP cells in GBM patient samples, we characterized their functionin vivo.Genetic depletion of NVP cells resulted in altered tumor cell composition, fewer cycling cells, and extended survival, underscoring their critical functional role. Clonal analysis of primary patient tumors in a human organoid tumor transplantation system demonstrated that the NVP has dual potency, generating both neuronal and vascular tumor cells. Although NVP cells comprise a small fraction of the tumor, these clonal analyses demonstrated that they strongly contribute to the total number of cycling cells in the tumor and generate a defined subset of the whole tumor. This study represents a paradigm by which cell type-specific interrogation of tumor populations can be used to study functional heterogeneity and therapeutically targetable vulnerabilities of GBM.
Aberration correction in long GRIN lens-based microendoscopes for extended field-of-view two-photon imaging in deep brain regions
Authors: Sattin Andrea , Nardin Chiara , Daste Simon , Moroni Monica , Reddy Innem , Liberale Carlo , Panzeri Stefano , Fleischmann Alexander , Fellin Tommaso 
Published: July 2024

AbstractTwo-photon (2P) fluorescence imaging through gradient index (GRIN) lens-based endoscopes is fundamental to investigate the functional properties of neural populations in deep brain circuits. However, GRIN lenses have intrinsic optical aberrations, which severely degrade their imaging performance. GRIN aberrations decrease the signal-to-noise ratio (SNR) and spatial resolution of fluorescence signals, especially in lateral portions of the field-of-view (FOV), leading to restricted FOV and smaller number of recorded neurons. This is especially relevant for GRIN lenses of several millimeters in length, which are needed to reach the deeper regions of the rodent brain. We have previously demonstrated a novel method to enlarge the FOV and improve the spatial resolution of two-photon microendoscopes based on GRIN lenses of length < 4.1 mm (Antonini et al. eLife 2020). However, previously developed microendoscopes were too short to reach the most ventral regions of the mouse brain. In this study, we combined optical simulations with fabrication of aspherical polymer microlenses through three-dimensional (3D) microprinting to correct for optical aberrations in long (length > 6 mm) GRIN lens-based microendoscopes (diameter, 500 µm). Long corrected microendoscopes had improved spatial resolution, enabling imaging in significantly enlarged FOVs. Moreover, using synthetic calcium data we showed that aberration correction enabled detection of cells with higher SNR of fluorescent signals and decreased cross-contamination between neurons. Finally, we applied long corrected microendoscopes to perform large-scale and high precision recordings of calcium signals in populations of neurons in the olfactory cortex, a brain region laying approximately 5 mm from the brain surface, of awake head-tethered mice. Long corrected microendoscopes are powerful new tools enabling population imaging with unprecedented large FOV and high spatial resolution in the most ventral regions of the mouse brain.
Dual host-bacterial gene expression to study pathogenesis and the regulation of virulence factors in tissue during respiratory infections
Authors: Di Marco Federico , Nicola Francesca , Giannese Francesca , Saliu Fabio , Tonon Giovanni , de Pretis Stefano , Cirillo Daniela M. , Lorè Nicola I. 
Published: July 2024

AbstractCo-localization of spatial transcriptome information of host and pathogen can revolutionize our understanding of microbial pathogenesis. Here, we aimed to demonstrate that customized bacterial probes can be successfully used to identify host-pathogen interactions in formalin-fixed-paraffin-embedded (FFPE) tissues by probe-based spatial transcriptomics technology. We analyzed the spatial gene expression of bacterial transcripts with the host transcriptomic profile in murine lung tissue chronically infected withMycobacterium abscessusembedded in agar beads. Customized mycobacterial probes were designed for the constitutively expressedrpoBgene (an RNA polymerase β subunit) and the virulence factor precursorlsr2, modulated by oxidative stress. We found a correlation between therpoBexpression, bacterial abundance in the airways, and an increased expression oflsr2virulence factor in lung tissue with high oxidative stress. Overall, we demonstrate the potential of dual bacterial and host gene expression assay in FFPE tissues, paving the way for the simultaneous detection of host and bacterial transcriptomes in pathological tissues.
CIB2 as a Ca2+Sensor for Auditory Mechano-Electrical Transduction and Linked to Genetic-Heterogeneity ofTMC1in Hearing Loss
Authors: Wu Shaoxuan , Lin Lin , Hu Qiaoyu , Yao Xuebo , Wang Hongyang , Liu Shuang , Liu Qingling , Xi Yuehui , Lin Yuzhe , Gong Jianqiao , Hu Ruixing , Zhan Wei , Luo Yi , He Guang , Liu Zhijun , Xiong Wei , Wang Qiuju , Xu Zhigang , Bai Fang , Lu Qing 
Published: July 2024

SummaryNon-syndromic sensorineural hearing loss is characterized by genetic heterogeneity, leading to potential clinical misdiagnosis.TMC1, a unique causative gene associated with deafness, exhibits variants with autosomal dominant and recessive inheritance patterns.TMC1codes for the transmembrane channel-like 1 (TMC1), a key component of the mechano-electrical transduction (MET) machinery for hearing. However, the molecular mechanism of Ca2+regulation in MET, which is essential for sound perception, remains unclear. CIB2, another MET component associated with deafness, can bind with calcium and may play a role in MET gating. Our study reveals that the TMC1-CIB2 complex undergoes a Ca2+-induced conformational change, highlighting the crucial role of Ca2+in MET. We identified a vertebrate-specific binding site on TMC1, named CR3, that interacts withapoCIB2, with the binding interface linked to hearing loss. Using an in-vivo animal model, we demonstrated that disruption of the calcium-sensing site of CIB2 perturbs the MET channel conductivity, confirming its role as a Ca2+sensor for MET. Additionally, after systematically analyzing the hearing-loss variants, we observed that dominant mutations of TMC1 are often located near the ion pore or at the binding interfaces with the Ca2+sensor CIB2. This provides a detailed mechanism of the genetic heterogeneity ofTMC1in hearing loss at an atomic level.
Spatiotemporal dispersion of DENV1 genotype V in western Colombia
Authors: Rojas-Gallardo Diana , Ferrell Tyshawn , Escobar Paula , Lopez Diego , Giraldo Beatriz , Restrepo-Chica Juliana , Jimenez-Posada Erika , Martinez-Gutierrez Marlen , Ruiz-Sáenz Julian , Key Autum , Shariatzadeh Nima , Khosravi Dara , Martinez Megan A. , Bombin Andrei , Waggoner Jesse J. , Osorio Jorge E. , Neufeldt Christopher J , Collins Matthew H , Cardona-Ospina Jaime A. , Piantadosi Anne 
Published: July 2024

AbstractDengue virus (DENV) is a significant public health concern in Colombia, with increased transmission of DENV type 1 (DENV-1) in the departments of Risaralda and Valle del Cauca in the Central-West region of the country following a large outbreak in 2019. However, little is known about the source, genetic diversity, and evolution of circulating viruses. We obtained plasma samples from individuals with acute DENV infection and analyzed DENV-1 genetic diversity, phylodynamics, and phylogeography. We found that most viruses belonged to DENV-1 genotype V, and phylogenetic analysis revealed three distinct clades, each of which was most closely related to viruses from neighboring departments of Colombia sampled over the last 5-10 years. Thus, the 2019 outbreak and subsequent DENV-1 circulation was not due to the introduction of a new lineage but rather reflected local DENV-1V dispersion and evolution. We identified amino acid positions under positive selection in structural proteins and NS1, which may have a role in immune evasion and pathogenesis. Overall, our analysis of DENV1 genotype V diversity, evolution and spread within Colombia highlights the important role of genomic surveillance in understanding virus dynamics during endemic circulation and outbreaks.
Precious3GPT: Multimodal Multi-Species Multi-Omics Multi-Tissue Transformer for Aging Research and Drug Discovery
Authors: Galkin Fedor , Naumov Vladimir , Pushkov Stefan , Sidorenko Denis , Urban Anatoly , Zagirova Diana , Alawi Khadija M. , Aliper Alex , Gumerov Ruslan , Kalashnikov Aleksandr , Mukba Sabina , Pogorelskaya Aleksandra , Ren Feng , Shneyderman Anastasia , Tang Qiuqiong , Xiao Deyong , Tyshkovskiy Alexander , Ying Kejun , Gladyshev Vadim N. , Zhavoronkov Alex 
Published: July 2024

AbstractWe present a multimodal multi-species multi-omics multi-tissue transformer for aging research and drug discovery capable of performing multiple tasks such as age prediction across species, target discovery, tissue, sex, and disease sample classification, drug sensitivity prediction, replication of omics response and prediction of biological and phenotypic response to compound treatment. This model combines textual, tabular, and knowledge graph-derived representations of biological experiments to provide insights into molecular-level biological processes. We demonstrate that P3GPT has developed an intuition for the interactions between compounds, pathologies, and gene regulation in the context of multiple species and tissues. In these areas, it outperforms existing LLMs and we highlight its utility in diverse case studies. P3GPT is a general model that may be used as a target identification tool, aging clock, digital laboratory, and scientific assistant. The model is intended as a community resource available open source as well as via a Discord server.
A combination of the geroprotectors trametinib and rapamycin is more effective than either drug alone
Authors: Gkioni Lisonia , Nespital Tobias , Monzó Carolina , Bali Jitin , Nassr Taim , Cremer Anna Lena , Beyer Andreas , Backes Heiko , Grönke Sebastian , Partridge Linda 
Published: July 2024

AbstractGenetic suppression of activity of the insulin/IGF/mTORC1/Ras network can ameliorate the effects of ageing in animals. The network provides multiple drug targets because of its role in metabolic disease and cancer, and these are candidates for repurposing for geroprotection. For instance, inhibition of the activity of the mTORC1 complex by rapamycin can extend lifespan in multiple organisms including mice, with early indications of efficacy in humans. Trametinib inhibits MEKs in the Ras pathway and can extend lifespan inDrosophila. However, it is not yet known if trametinib alone or in combination with rapamycin can extend mouse lifespan or improve health at older ages. We assessed survival and health indices of female and male mice treated with trametinib or rapamycin alone, or with the two in combination at the same doses. Trametinib treatment extended lifespan in both sexes, while its combination with rapamycin caused further, additive prolongation. Combination treatment reduced liver tumours in both sexes and spleen tumours in males, and ameliorated the age-related increase in brain glucose uptake. There was a striking reduction in inflammation in the brain, kidney, spleen and muscle with combination treatment, accompanied by reduced circulating levels of pro-inflammatory cytokines. Trametinib alone is therefore geroprotective in mice, but combined trametinib and rapamycin treatment is more geroprotective than treatment with either drug alone, suggesting immediate translational potential for humans.