bluuebunny/crossref_metadata_2025_split huggingface dataset:
Duration of human papillomavirus persistence and its relationship with recurrent cervical dysplasia
Authors: Bogani Giorgio , Sopracordevole Francesco , Ciavattini Andrea , Vizza Enrico , Vercellini Paolo , Giannini Andrea , Ghezzi Fabio , Scambia Giovanni , Raspagliesi Francesco , Di Donato Violante ,   Italian Society of Colposcopy and Cervico-Vaginal Pathology (SICPCV); The Investigators of the Italian HPV study group (iHPV study group)
Published: July 2023

Objective
To evaluate how the duration of human papillomavirus (HPV) persistence influences the risk of developing recurrent high-grade cervical dysplasia (CIN2+).

Methods
Data of patients with persistent HPV infection (at least at 6 months) after primary conization were extracted from a multi-institutional Italian database, retrospectively. Kaplan–Meier and Cox proportional hazards models were used to evaluate associations between duration of HPV persistence with the 5-year risk of developing recurrent CIN2+.

Results
Overall, 545 patients met the inclusion criteria. Positive margins were detected in 160 (29.3%) patients. Overall, 247 (45.3%) and 123 (22.6%) patients had a documented infection from HPV16/18, and other high-risk HPV types. 187 (34.3%), 73 (13.4%), and 40 (7.3%) were diagnosed with persistent HPV infection at 12, 18, and 24 months, respectively. Patients with HPV persistence at 6 months experienced a risk of recurrence of 7.46%. Twelve-month HPV persistence strongly correlates with the risk of developing the recurrent disease (risk of recurrence: 13.1%). While, having HPV persistence >12 months did not correlate with an increased risk of recurrence (hazard ratio: 1.34 (95% confidence interval: 0.78–2.32); P = 0.336, log-rank test).

Conclusion
HPV persistence is one of the most important factors predicting the risk of CIN2+ recurrence. The risk of CIN2+ recurrence increased with the increase of HPV persistence for up to 1 year. The persistence of HPV after the first year does not appear as a risk factor.
Feasibility and Pilot Outcomes of the Move More @ Work Intervention Designed to Encourage Employees to be Physically Active for 2 Minutes After Every 30 Minutes of Sitting
Authors: Hargreaves Elaine A. , Shaw Sally , Scott Tessa , Calverley Jessica , Peddie Meredith C 
Published: July 2023

ObjectiveThe aim of the study is to evaluate the feasibility of a workplace intervention supporting employees to interrupt sitting time with short bouts of activity (termed an opportunity to move [OTM]).MethodsUsing an interrupted time series design, 58 sedentary employees provided baseline assessments of physical activity, health, and work-related outcomes and completed the 12-week intervention. Assessments were repeated immediately and 12 weeks after intervention. Focus groups explored intervention acceptability.ResultsAccelerometer data showed no change in the number of OTMs taken before to after intervention, while participants self-reported 62-69% intervention adherence. Physical activity at work, productivity, and musculoskeletal health improved but cardiometabolic health and psychological well-being did not. Intervention components were viewed favorably (pending amendments), but taking an OTM every 30 minutes was not feasible.ConclusionsThe Move More @ Work intervention has potential, but adaptations are required to increase adherence.
Elevated Body Mass Index Associated with Cerebrospinal Fluid Leak after Lateral Skull Base Surgery: A Systematic Review and Meta-analysis
Authors: Durrant Frederick G. , Warner Brendon K. , Nguyen Shaun A. , Sturm Joshua J. , Meyer Ted A. 
Published: July 2023

Objective
To determine if body mass index (BMI) increases the risk of cerebrospinal fluid (CSF) leak after lateral skull base surgery.

Data sources
CINAHL, PubMed, and Scopus were searched from January 2010 to September 2022 for articles published in English.

Study selection
Articles that reported BMI or obesity with and without CSF leaks after lateral skull base surgery were included.

Data extraction
Two reviewers (F.G.D. and B.K.W.) independently performed study screening, data extraction, and risk of bias assessment.

Data synthesis
A total of 11 studies and 9,132 patients met inclusion criteria. Meta-analysis of mean difference (MD), odds ratio (OR), proportions, and risk ratio (RR) were calculated using RevMan 5.4 and MedCalc 20.110. BMI for patients with CSF leak after lateral skull base surgery (29.39 kg/m2, 95% confidence interval [CI] = 27.75 to 31.04) was significantly greater than BMI for patients without CSF leak after lateral skull base surgery (27.09 kg/m2, 95% CI = 26.16 to 28.01) with an MD of 2.21 kg/m2 (95% CI = 1.09 to 3.34, p = 0.0001). The proportion of patients with BMI ≥ 30 kg/m2 that had a CSF leak was 12.7%, and the proportion of patients with BMI < 30 kg/m2 (control) that had a CSF leak was 7.9%. The OR for CSF leak after lateral skull base surgery in patients with BMI ≥ 30 kg/m2 was 1.94 (95% CI = 1.40 to 2.68, p < 0.0001), and the RR was 1.82 (95% CI = 1.36 to 2.43, p < 0.0001).

Conclusion
Elevated BMI increases the risk of CSF leak after lateral skull base surgery.

Level of evidence
IIa.
Impact of Patient Frailty on Speech Recognition and Quality of Life Outcomes in Adult Cochlear Implant Users
Authors: Yuen Erick , Nguyen Shaun A. , Babb Emily , Wilkinson Rachel , Meyer Ted A. , McRackan Theodore R. 
Published: July 2023

Objective
The process of cochlear implantation (CI) and subsequent post-cochlear implant care is extensive and can be difficult to navigate for patients considered medically frail. This study investigates potential impact of patient frailty on speech recognition and quality of life outcomes after CI.

Study Design
Retrospective review of a prospectively maintained database.

Setting
Tertiary cochlear implant center.

Patients
Three hundred seventy adults undergoing CI for traditional bilateral hearing loss indication.

Interventions
None.

Main Outcome Measures
Comparison of pre-CI to 12-month post-CI change in consonant–nucleus–consonant phoneme/words, AzBio sentences in quiet/+10SNR, and Cochlear Implant Quality of Life (CIQOL)-35 Profile domain and global scores based on degree of patient frailty as assessed using the five-factor modified frailty index and Charlson Comorbidity Index.

Results
The average age at implantation was 65.4 years (±SD, 15.7; 19–94 years). Overall, there were minimal to absent and nonsignificant differences in speech recognition outcomes (consonant–nucleus–consonant phoneme/words, and AzBio sentences +10SNR) based on pre-CI patient frailty. The exception was less improvement in AzBio quiet sentence score in patients noted to be severely frail based on Charlson Comorbidity Index (57.1% vs. 35.2%, d = 0.7 [0.3, 1]). Similar findings were observed for CIQOL-35 Profile domain and global scores where no associations were found other than decreased improvement in the social domain in patients noted to be severely frail (21.7 vs. −0.3, d = 1 [0.4, 1.7]).

Conclusions
Although some differences in outcomes were noted based on cochlear implant user frailty, these were small and isolated to only a few outcome measures. Therefore, assuming the patient is medically safe for surgery, preoperative frailty should not dissuade clinicians from recommending CI.
Inducible mucosa-like differentiation of head and neck cancer cells drives the epigenetically determined loss of cell malignancy
Authors: Oppel Felix , Gendreizig Sarah , Martinez-Ruiz Laura , Florido Javier , López-Rodríguez Alba , Pabla Harkiren , Loganathan Lakshna , Hose Leonie , Kühnel Philipp , Schmidt Pascal , Schürmann Matthias , Neumann Judith Martha , Viyof Ful Flavian , Scholtz Lars Uwe , Ligum Dina , Brasch Frank , Niehaus Karsten , Escames Germaine , Busche Tobias , Kalinowski Jörn , Goon Peter , Sudhoff Holger 
Published: July 2023

AbstractBackgroundHuman papillomavirus-negative head and neck squamous cell carcinoma (HNSCC) is a highly malignant disease with high death rates that have remained substantially unaltered for decades. Therefore, new treatment approaches are urgently needed. Human papillomavirus-negative tumors harbor areas of terminally differentiated tissue that are characterized by cornification. Dissecting this intrinsic ability of HNSCC cells to irreversibly differentiate into non-malignant cells may have striking tumor-targeting potential.MethodsWe modeled the cornification of HNSCC cells in a primary spheroid model and analyzed the mechanisms underlying differentiation by RNA-seq and ATAC-seq. Results were verified by immunofluorescence using human HNSCC tissue of distinct anatomical locations.ResultsHNSCC cell differentiation was accompanied by cell adhesion, proliferation stop, diminished tumor-initiating potential in immunodeficient mice, and activation of a wound healing-associated signaling program. Small promoter accessibility increased despite overall chromatin closure. Differentiating cells upregulated KRT17 and cornification markers. Although KRT17 represents a basal stem-cell marker in normal mucosa, we confirm KRT17 to represent an early differentiation marker in HNSCC tissue and dysplastic mucosa. Cornification was observed to frequently surround necrotic and immune-infiltrated areas in human tumors, indicating an involvement of pro-inflammatory stimuli. Indeed, inflammatory mediators were found to activate the HNSCC cell differentiation program.ConclusionsDistinct cell differentiation states create a common tissue architecture in normal mucosa and HNSCCs. Our data demonstrate a loss of cell malignancy upon HNSCC cell differentiation, indicating that targeted differentiation approaches may be therapeutically valuable. Moreover, we describe KRT17 to be a candidate biomarker for HNSCC cell differentiation and early tumor detection.
Optical resolution is not the limiting factor for spatial precision of two-photon optogenetic photostimulation
Authors: Lees Robert M. , Pichler Bruno , Packer Adam M. 
Published: July 2023

AbstractTwo-photon optogenetics combines nonlinear excitation with noninvasive activation of neurons to enable manipulation of neural circuits with a high degree of spatial precision. Combined with two-photon population calcium imaging, these approaches comprise a flexible platform for all-optical interrogation of neural circuits. However, a multitude of optical and biological factors dictate the exact precision of this approachin vivo, where it is most usefully applied. Here, we carefully assessed how the optical factors determine the spatial precision of activation. We found that optical resolution is not the limiting factor of the spatial precision of two-photon optogenetic photostimulation, and by doing so, reveal the key factors to improve to achieve maximal precision. Our results enable future work to focus on the optimal factors by providing key insight from controlled experiments in a manner not previously reported. This research can be applied to advance the state-of-the-art of all-optical interrogation, extending the toolkit for neuroscience research to achieve spatiotemporal precision at the crucial levels at which neural circuits operate.
A Compound that Inhibits Glycolysis in Prostate Cancer Controls Growth of Advanced Prostate Cancer
Authors: Uo Takuma , Ojo Kayode K. , Sprenger Cynthia C. , Epilepsia Kathryn Soriano , Perera B. Gayani K. , Damodarasamy Mamatha , Sun Shihua , Kim Soojin , Hogan Hannah H. , Hulverson Matthew A. , Choi Ryan , Whitman Grant R. , Barrett Lynn K. , Michaels Samantha A. , Xu Linda H. , Sun Vicky L. , Arnold Samuel L.M. , Pang Haley J. , Nguyen Matthew M. , Vigil Anna-Lena B.G. , Kamat Varun , Sullivan Lucas B. , Sweet Ian R. , Vidadala Ram , Maly Dustin J. , Van Voorhis Wesley C. , Plymate Stephen R. 
Published: July 2023

ABSTRACTPurposeMetastatic castration-resistant prostate cancer remains incurable regardless of recent therapeutic advances. Prostate cancer tumors display highly glycolytic phenotypes as the cancer progresses. Non-specific inhibitors of glycolysis have not been utilized successfully for chemotherapy, because of their penchant to cause systemic toxicity. This study reports the preclinical activity, safety, and pharmacokinetics of a novel small molecule preclinical candidate, BKIDC-1553, with antiglycolytic activity.Experimental designWe tested a large battery of prostate cancer cell lines for inhibition of cell proliferation, in vitro. Cell cycle, metabolic and enzymatic assays were used to demonstrate their mechanism of action. A human PDX model implanted in mice and a human organoid were studied for sensitivity to our BKIDC preclinical candidate. A battery of pharmacokinetic experiments, absorption, distribution, metabolism, and excretion experiments, and in vitro and in vivo toxicology experiments were carried out to assess readiness for clinical trials.ResultsWe demonstrate a new class of small molecule inhibitors where antiglycolytic activity in prostate cancer cell lines is mediated through inhibition of hexokinase 2. These compounds display selective growth inhibition across multiple prostate cancer models. We describe a lead BKIDC-1553 that demonstrates promising activity in a preclinical xenograft model of advanced prostate cancer, equivalent to that of enzalutamide. BKIDC-1553 demonstrates safety and pharmacologic properties consistent with a compound that can be taken into human studies with expectations of a good safety margin and predicted dosing for efficacy.ConclusionThis work supports testing BKIDC-1553 and its derivatives in clinical trials for patients with advanced prostate cancer.
Yeast diversity in open agave fermentations across Mexico
Authors: Gallegos-Casillas Porfirio , García-Ortega Luis F. , Espinosa-Cantú Adriana , Torres-Lagunes Carolina G. , Avelar-Rivas J. Abraham , Cano-Ricardez Adrián , García-Acero Ángela M. , Ruiz-Castro Susana , Flores-Barraza Mayra , Castillo Alejandra , González-Zozaya Fernando , Delgado-Lemus América , Molina-Freaner Francisco , Jacques-Hernández Cuauhtémoc , Hernández-López Antonio , Delaye Luis , Aguirre-Dugua Xitlali , Kirchmayr Manuel R. , Morales Lucía , Mancera Eugenio , DeLuna Alexander 
Published: July 2023

ABSTRACTYeasts are a diverse group of fungal microorganisms that are widely used to produce fermented foods and beverages. In Mexico, open fermentations are used to obtain spirits from agave plants. Despite the prevalence of this traditional practice throughout the country, yeasts have only been isolated and studied from a limited number of distilleries. To systematically describe the diversity of yeast species from open agave fermentations, here we generate the YMX.1.0 culture collection by isolating 4,524 strains from 68 sites in diverse climatic, geographical, and biological contexts. We used MALDI-TOF mass spectrometry for taxonomic classification and a subset of the strains was verified by ITS and D1/D2 sequencing. The most abundant species isolated from all producing regions wereSaccharomyces cerevisiae,Pichia kudriavzevii,Pichia manshurica, andKluyveromyces marxianus. Despite the great diversity of environmental conditions and production practices the composition of yeast communities remained largely homogeneous throughout locations and fermentation stages, even if less abundant but commonly occurring yeasts were considered. Furthermore, ITS and D1/D2 sequencing revealed two candidate new species of Saccharomycetales. To explore the intraspecific variation of the yeasts from agave fermentations, we conducted genome sequencing on four isolates of the non-conventional yeastKazachstania humilis. The genomes of these four strains were considerably distinct from other genomes of the same species, suggesting that they belong to a different population. Our work contributes to the understanding and conservation of an open fermentation system of great cultural and economic importance, providing a valuable resource to study the biology and genetic diversity of microorganisms living at the interface of natural and human-associated environments.TAKE AWAYWe isolated and identified 4,524 yeast strains from open agave fermentations in Mexico.Yeast communities remained largely homogeneous throughout diverse locations.Kazachstania humilisgenomes differed significantly from isolates in other regions of the world.We report two candidate new species related to thePichiaclade.
A machine learning toolbox for the analysis of sharp-wave ripples reveal common features across species
Authors: Navas-Olive Andrea , Rubio Adrian , Abbaspoor Saman , Hoffman Kari L. , de la Prida Liset M 
Published: July 2023

AbstractThe study of sharp-wave ripples (SWRs) has advanced our understanding of memory function, and their alteration in neurological conditions such as epilepsy and Alzheimer’s disease is considered a biomarker of dysfunction. SWRs exhibit diverse waveforms and properties that cannot be fully characterized by spectral methods alone. Here, we describe a toolbox of machine learning (ML) models for automatic detection and analysis of SWRs. The ML architectures, which resulted from a crowdsourced hackathon, are able to capture a wealth of SWR features recorded in the dorsal hippocampus of mice. When applied to data from the macaque hippocampus, these models were able to generalize detection and revealed shared SWR properties across species. We hereby provide a user-friendly open-source toolbox for model use and extension, which can help to accelerate and standardize SWR research, lowering the threshold for its adoption in biomedical applications.
Postsynaptic frequency filters shaped by the interplay of synaptic short-term plasticity and cellular time scales
Authors: Mondal Yugarshi , Benito Guillermo Villanueva , Pena Rodrigo F. O. , Rotstein Horacio G. 
Published: July 2023

AbstractNeuronal frequency filters can be thought of as constituent building blocks underlying the ability of neuronal systems to process information, generate rhythms and perform computations. How neuronal filters are generated by the concerted activity of a multiplicity of processes (e.g., electric circuit, history-dependent) and interacting time scales within and across levels of neuronal network organization is poorly understood. In this paper, we use mathematical modeling, numerical simulations and analytical calculations of the postsynaptic response to presynaptic spike trains to address this issue in a basic feedforward network motif in the presence of synaptic short-term plasticity (STP, depression and facilitation). The network motif consists of a presynaptic spike-train, a postsynaptic passive cell, and an excitatory (AMPA) chemical synapse. The dynamics of each network component are controlled by one or more time scales. We explain the mechanisms by which the participating time scales shape the neuronal filters at the (i) synaptic update level (the target of the synaptic variable in response to presynaptic spikes), which is shaped by STP, (ii) the synaptic level, and (iii) the postsynaptic membrane potential (PSP) level. We focus on three metrics that gives rise to three types of profiles (curves of the corresponding metrics as a function of the spike-train input frequency or firing rate): (i) peak profiles, (ii) peak-to-trough amplitude profiles, and (iii) phase profiles. The effects of STP are present at the synaptic update level and are communicated to the synaptic level where they interact with the synaptic time scales. The PSP filters result from the interaction between these variables and time scales and the biophysical properties and time scales of the postsynaptic cell. Band-pass filters (BPFs) result from a combination of low-pass filters (LPFs) and high-pass filters (HPFs) operating at the same or different levels of organization. PSP BPFs can be inherited from the synaptic level (STP-mediated BPFs) or they can be generated across levels of organization due to the interaction between (i) a synaptic LPF and the PSP summation-mediated HPF (PSP peaks), and (ii) a synaptic HPF and the PSP summation-mediated LPF (PSP amplitude). These types of BPFs persist in response to more realistic presynaptic spike trains: jittered (randomly perturbed) periodic spike trains and Poisson-distributed spike trains. The response variability is frequency-dependent and is controlled by STP in a non-monotonic frequency manner. The results and and lessons learned from the investigation of this basic network motif are a necessary step for the construction of a framework to analyze the mechanisms of generation of neuronal filters in networks with more complex architectures and a variety of interacting cellular, synaptic and plasticity time scales.
RNA structure and multiple weak interactions balance the interplay between RNA binding and phase separation of SARS-CoV-2 nucleocapsid
Authors: Estelle Aidan B , Forsythe Heather M , Yu Zhen , Hughes Kaitlyn , Lasher Brittany , Allen Patrick , Reardon Patrick , Hendrix David A , Barbar Elisar J 
Published: July 2023

AbstractThe nucleocapsid (N) protein of SARS-CoV-2 binds viral RNA, condensing it inside the virion, and phase separating with RNA to form liquid-liquid condensates. There is little consensus on what differentiates sequence-independent N-RNA interactions in the virion or in liquid droplets from those with specific genomic RNA motifs necessary for viral function inside infected cells. To identify the RNA structures and the N domains responsible for specific interactions and phase separation, we use the first 1000nt of viral RNA and short RNA segments designed as models for single-stranded and paired RNA. Binding affinities estimated from fluorescence anisotropy of these RNAs to the two folded domains of N (the NTD and CTD) and comparison to full-length N demonstrate that the NTD binds preferentially to single-stranded RNA, and while it is the primary RNA binding site, it is not essential to phase separation. Nuclear magnetic resonance spectroscopy identifies two RNA binding sites on the NTD: a previously characterized site and an additional although weaker RNA-binding face that becomes prominent when binding to the primary site is weak, such as with dsRNA or a binding-impaired mutant. Phase separation assays of nucleocapsid domains with different RNA structures support a model where multiple weak interactions, such as with the CTD or the NTD’s secondary face promote phase separation, while strong, specific interactions do not. These studies indicate that both strong and multivalent weak N-RNA interactions underlie the multifunctional abilities of N.SignificanceThe nucleocapsid protein of the SARS-CoV-2 coronavirus binds to viral RNA, both to protect and condense it inside the viral particle and to facilitate viral transcription inside infected host cells. Evidence suggests that variations in RNA structure impact how and where it binds to the nucleocapsid, but these differences are not well understood at a structural level. Using nuclear magnetic resonance spectroscopy, we examine the interactions between each folded domain of the nucleocapsid and different RNA structures. Binding affinities and NMR chemical shift profiles demonstrate that binding between the N-terminal domain and single stranded RNA is driven by strong interactions at a specific site, while multiple weak nonspecific interactions at newly discovered sites lead to phase separation and RNA condensation.