bluuebunny/crossref_metadata_2025 huggingface dataset:
The X-ray point source population hosted by globular clusters in the elliptical galaxy NGC 4261
Authors: Nair Sneha , Dage Kristen C , Haggard Daryl , Kundu Arunav , Plotkin Richard M , Rhode Katherine L , Zepf Stephen E
Published: July 2023

Utilizing archival Chandra X-ray Observatory data and Hubble Space Telescope globular cluster catalogues, we probe the time-domain properties of the low mass X-ray binary population in the elliptical galaxy NGC 4261. Of the 98 unique X-ray sources identified in this study, 62 sources are within the optical field of view and, of those, 33 per cent are aligned with an optical cluster counterpart. We find twenty X-ray sources coincident with globular clusters; two are previously discovered ultra-luminous X-ray sources (ULXs) and eighteen are low mass X-ray binaries (GCLMXBs) with LX < 1039 erg s−1. ULXs are a heterogeneous class of extremely bright X-ray binaries (LX > 1039 erg s−1) and ULXs located in globular clusters (GCULXs) and may be indicators of black holes. Identifying these unusually X-ray bright sources and measuring their optical properties can provide valuable constraints on the progenitors of gravitational wave sources. We compare observations of these sources to the twenty previously studied GCULXs from five other early-type galaxies, and find that GCULXs in NGC 4261 are of similar colour and luminosity and do not significantly deviate from the rest of the sample in terms of distance from the galaxy centre or X-ray luminosity. Both the GCULX and GCLMXB populations of NGC 4261 show long-term variability; the former may have implications for fast radio bursts originating in globular clusters and the latter will likely introduce additional scatter into the low mass end of GCLMXB X-ray luminosity functions.
Clouds accreting from the IGM are not able to feed the star formation of low-redshift disc galaxies
Authors: Afruni Andrea , Pezzulli Gabriele , Fraternali Filippo , Grønnow Asger
Published: July 2023

Galactic halos accrete material from the intergalactic medium (IGM) and part of this accretion is expected to be in the form of cool (T ∼ 104 K) gas. A signature of this process could reside in the detection of numerous clouds in the circumgalactic medium (CGM). However, whether this material is able to accrete onto the galaxies and feed their star formation or, instead, evaporates into the CGM hot phase (corona, T ∼ 106 K), is not yet understood. Here, we investigate the evolution of cool CGM clouds accreted from the IGM and falling through the hot corona of low-redshift disc galaxies, using 3D high-resolution hydrodynamical simulations. We include the effects of gravity due to the dark matter halo, isotropic thermal conduction, radiative cooling, and an ionizing UV background. We explored different values of parameters such as the halo mass, coronal mass, initial cloud velocity and strength of the thermal conduction. We find that the clouds lose the vast majority of their mass at distances larger than half of the galaxy virial radius and are completely dissolved in the corona before reaching the central galaxy. Resolving the Field length with at least 5–7 cells is crucial to correctly capture the evolution of the infalling cool gas. Our results indicate that cool IGM accretion can not feed star formation in z ∼ 0 star-forming galaxies in halos with masses of 1011.9 M⊙ or above. This suggests that present-day massive star-forming galaxies can sustain their star formation only via the spontaneous or induced cooling of their hot corona.
Fuzzy dark matter in relativistic stars
Authors: Rezaei Zeinab
Published: July 2023

Fuzzy dark matter (FDM), a practical alternative to cold dark matter, can exist in compact stars. Here, applying the FDM equation of state (EoS) constrained by cosmic microwave background and large-scale structure data, we calculate the structure of relativistic stars in the presence of FDM. For this aim, the EoS for the visible matter in neutron stars, quark stars, and hybrid stars from the observational data are employed. A piecewise polytropic EoS constrained by the observational data of GW170817 and the data of six low-mass X-ray binaries with thermonuclear burst or the symmetry energy of the nuclear interaction describes the neutron star matter. For quark star matter, we apply the EoSs within the Bayesian statistical approach using the mass and radius measurements of PSR J0030+0451 from NICER. Employing the two-fluid formalism, we study the structure of FDM admixed relativistic stars.
Gravitational wave spectral synthesis
Authors: van Zeist Wouter G J , Eldridge J J , Tang Petra N
Published: July 2023

We study the Laser Interferometer Space Antenna (LISA) sources that arise from isolated binary evolution, and how these depend on age and metallicity, using model stellar populations from bpass. We model these as single-aged populations which are analogous to star clusters. We calculate the combined gravitational wave (GW) spectrum of all the binaries within these model clusters, including all types of compact binaries as well as those with living stars. These results allow us to evaluate the detectability of star clusters with LISA. We find at late times the dominant sources are WD–WD binaries by factors of 50–200, but at times between 108 and 109 yr we find a significant population of NS–WD and BH–WD binaries (2–40 per 106 M⊙), which is related to the treatment of mass transfer and common-envelope events in bpass, wherein mass transfer is relatively likely to be stable. Metallicity also has an effect on the GW spectrum and on the relative dominance of different types of binaries. Using the information about known star clusters will aid the identification of sky locations where one could expect LISA to find GW sources.
Observational predictions for Thorne–Żytkow objects
Authors: Farmer R , Renzo M , Götberg Y , Bellinger E , Justham S , de Mink S E
Published: July 2023

Thorne–Żytkow objects (TŻO) are potential end products of the merger of a neutron star with a non-degenerate star. In this work, we have computed the first grid of evolutionary models of TŻOs with the MESA stellar evolution code. With these models, we predict several observational properties of TŻOs, including their surface temperatures and luminosities, pulsation periods, and nucleosynthetic products. We expand the range of possible TŻO solutions to cover $3.45 \lesssim \rm {\log \left(T_{eff}/K\right)}\lesssim 3.65$ and $4.85 \lesssim \rm {\log \left(L/L_{\odot }\right)}\lesssim 5.5$. Due to the much higher densities our TŻOs reach compared to previous models, if TŻOs form we expect them to be stable over a larger mass range than previously predicted, without exhibiting a gap in their mass distribution. Using the GYRE stellar pulsation code we show that TŻOs should have fundamental pulsation periods of 1000–2000 d, and period ratios of ≈0.2–0.3. Models computed with a large 399 isotope fully coupled nuclear network show a nucleosynthetic signal that is different to previously predicted. We propose a new nucleosynthetic signal to determine a star’s status as a TŻO: the isotopologues $\mathrm{^{44}Ti} \rm {O}_2$ and $\mathrm{^{44}Ti} \rm {O}$, which will have a shift in their spectral features as compared to stable titanium-containing molecules. We find that in the local Universe (∼SMC metallicities and above) TŻOs show little heavy metal enrichment, potentially explaining the difficulty in finding TŻOs to-date.
The distribution of accretion rates as a diagnostic of protoplanetary disc evolution
Authors: Alexander Richard , Rosotti Giovanni , Armitage Philip J , Herczeg Gregory J , Manara Carlo F , Tabone Benoît
Published: July 2023

We show that the distribution of observed accretion rates is a powerful diagnostic of protoplanetary disc physics. Accretion due to turbulent (‘viscous’) transport of angular momentum results in a fundamentally different distribution of accretion rates than accretion driven by magnetized disc winds. We find that a homogeneous sample of ≳300 observed accretion rates would be sufficient to distinguish between these two mechanisms of disc accretion at high confidence, even for pessimistic assumptions. Current samples of T Tauri star accretion rates are not this large, and also suffer from significant inhomogeneity, so both viscous and wind-driven models are broadly consistent with the existing observations. If accretion is viscous, the observed accretion rates require low rates of disc photoevaporation (≲10−9 M⊙ yr−1). Uniform, homogeneous surveys of stellar accretion rates can therefore provide a clear answer to the long-standing question of how protoplanetary discs accrete.
Tidal dissipation due to the elliptical instability and turbulent viscosity in convection zones in rotating giant planets and stars
Authors: de Vries Nils B , Barker Adrian J , Hollerbach Rainer
Published: July 2023

Tidal dissipation in star–planet systems can occur through various mechanisms, among which is the elliptical instability. This acts on elliptically deformed equilibrium tidal flows in rotating fluid planets and stars, and excites inertial waves in convective regions if the dimensionless tidal amplitude (ϵ) is sufficiently large. We study its interaction with turbulent convection, and attempt to constrain the contributions of both elliptical instability and convection to tidal dissipation. For this, we perform an extensive suite of Cartesian hydrodynamical simulations of rotating Rayleigh–Bénard convection in a small patch of a planet. We find that tidal dissipation resulting from the elliptical instability, when it operates, is consistent with ϵ3, as in prior simulations without convection. Convective motions also act as an effective viscosity on large-scale tidal flows, resulting in continuous tidal dissipation (scaling as ϵ2). We derive scaling laws for the effective viscosity using (rotating) mixing-length theory, and find that they predict the turbulent quantities found in our simulations very well. In addition, we examine the reduction of the effective viscosity for fast tides, which we observe to scale with tidal frequency (ω) as ω−2. We evaluate our scaling laws using interior models of Hot Jupiters computed with mesa. We conclude that rotation reduces convective length-scales, velocities, and effective viscosities (though not in the fast tides regime). We estimate that elliptical instability is efficient for the shortest period Hot Jupiters, and that effective viscosity of turbulent convection is negligible in giant planets compared with inertial waves.
Taking the long view on short-run marginal emissions: how much carbon does flexibility and energy storage save?
Authors: Grunewald Phil , Aunedi Marko , Nosratabadi Seyyed Mostafa , Morstyn Thomas , Savelli Iacopo , Kumtepeli Volkan , Howey David
Published: July 2023

Grid-scale electricity storage will play a crucial role in the transition of power systems towards zero carbon. During the transition, investments need to be channeled towards technologies and locations that enable zero carbon operation in the long term, while also delivering security of supply and value for money. We discuss metrics and market signals that are needed to guide this transition towards clean, secure and affordable solutions. Paradoxically, carbon metrics play an important role, but become less effective as a decision tool once the system approaches zero carbon. We critically assess the role of marginal and average emission and question the allocation of marginal emissions in systems where combinations of renewables and storage deliver flexibility. We conclude that, for strategic investments, short-term market signals may not always deliver sufficiently fast or far-sighted outcomes and operational decisions need to consider the merit order of demand as well as supply.
Higgs response and pair condensation energy in superfluid nuclei
Authors: Takahashi Kengo , Matsuda Yusuke , Matsuo Masayuki
Published: July 2023

The pairing correlation in nuclei causes a characteristic excitation, known as the pair vibration, which is populated by the pair transfer reactions. Here we introduce a new method of characterizing the pair vibration by employing an analogy to the Higgs mode, which emerges in infinite superconducting/superfluid systems as a collective vibrational mode associated with the amplitude oscillation of the Cooper pair condensate. The idea is formulated by defining a pair-transfer probe, the Higgs operator, and then describing the linear response and the strength function to this probe. We will show that the pair condensation energy in nuclei can be extracted with use of the strength sum and the static polarizability of the Higgs response. In order to demonstrate and validate the method, we perform numerical analysis for Sn isotopes based on the quasi-particle random phase approximation to the Skyrme–Hartree–Fock–Bogoliubov model. We discuss the possibility of applying this new scheme to pair-transfer experiments.
The influence of biological DMARDs on aseptic arthroplasty loosening: a retrospective cohort study
Authors: Schreiner Markus M , Straub Jennifer , Apprich Sebastian , Staats Kevin , Windhager Reinhard , Aletaha Daniel , Böhler Christoph
Published: July 2023

Objective

To investigate whether biological DMARDs affect the risk of aseptic loosening after total hip/knee arthroplasty (THA/TKA) in patients with RA.

Methods

We retrospectively identified all patients suffering from RA who underwent THA/TKA at our academic centre between 2002 and 2015 and linked them with an existing prospective observational RA database at our institution. The risk of aseptic loosening was estimated using radiological signs of component loosening (RCL). A time-dependent Cox regression analysis was used to compare the risk of implant loosening between patients treated with traditional DMARDS and biological DMARDs, or alternately both over time.

Results

A total of 155 consecutive total joint arthroplasties (TJAs) (103 TKA vs 52 THA) was retrospectively included in the study. Mean age at implantation was 59 ± 13 years. Mean follow-up time was 69 ± 43 months. Overall, 48 (31%) TJAs showed signs of RCL, with 28 (27.2%) RCLs occurring after TKA compared with 20 after THA (38.5%). A significant difference regarding the incidence of RCL between the traditional DMARDs group (39 cases of RCL, 35%) and the biological DMARDs group (nine cases of RCL, 21%) (P = 0.026) was observed using the log-rank test. This was also true when using a time-dependent Cox regression with therapy as well as arthroplasty location (hip vs knee) as variables (P = 0.0447).

Conclusion

Biological DMARDs may reduce the incidence of aseptic loosening after TJA in patients with RA compared with traditional DMARDs. This effect seems to be more pronounced after TKA than THA.
Effect of mindfulness on sexual self-efficacy and sexual satisfaction among Iranian postmenopausal women: a quasi-experimental study
Authors: Khazaeian Somayyeh , Navidian Ali , Rahiminezhad Maryam
Published: July 2023

Background

Menopause with anatomical, physiological, and psychological changes can affect sexual satisfaction and consequently the quality of life.

Aims

The study sought to evaluate the effects of mindfulness-based counseling on sexual self-efficacy and sexual satisfaction among Iranian postmenopausal women.

Methods

This quasi-experimental study was conducted on 110 women who were assigned to an intervention group (n = 55) and a control group (n = 55). The intervention group received 8 sessions of mindfulness-based training and daily mindfulness exercises. Data collection tools included questionnaires of demographics and midwifery, sexual self-efficacy, and sexual satisfaction. They were completed before and 8 weeks after the intervention. The collected data were analyzed through a t test, a chi-square test, and repeated-measures analysis of variance.

Outcomes

Changes in sexual self-efficacy and sexual satisfaction scores were evaluated.

Results

The mindfulness-based intervention significantly improved sexual self-efficacy (F = 146.98, P = .000, ƞ2 = 0.576) and sexual satisfaction (F = 129.47, P = .000, ƞ2 = 0.545) over time. The mean scores of sexual self-efficacy (17.03 ± 2.08) and sexual satisfaction (87.94 ± 8.26) in the intervention group increased after the intervention as opposed to the mean scores of sexual self-efficacy (12.65 ± 1.70) and sexual satisfaction (76.61 ± 6.45) in the control group.

Clinical Implications

Mindfulness training can improve sexual self-efficacy and sexual satisfaction in postmenopausal women.

Strengths and Limitations

The intervention was implemented on a population of menopausal women in a culture in which the expression of sexual issues is taboo and has not been noticed in the past. The main limitation of this study was self-reporting, which may have affected the responses. The next limitation was the nonrandomized controlled design. Finally, the research sample included menopausal women who were heterosexual and married. Hence, the findings may not be generalizable to more diverse samples. In this study, psychological maladjustment or psychological distress was not analyzed. They should also be considered in future research.

Conclusion

According to the results, it is advisable to employ mindfulness-based intervention in routine care, because it can improve different aspects of menopausal women’s life.
Uterine defects and estradiol‐dependent development of oviductal diverticula in mice lacking the SMAD4 C‐terminal Mad homology 2 domain
Authors: Petit Fabrice G. , Kervarrec Christine , Allais‐Bonnet Aurélie , Evrard Bertrand , Chalmel Frédéric , Deng Chuxia , Jamin Soazik P.
Published: July 2023

In female mammals, the oviduct and uterus are essential sites for female and male gamete transport, fertilization, implantation, and maintenance of a successful pregnancy. To delineate the reproductive function of Mothers against decapentaplegic homolog 4 (Smad4), we specifically inactivated Smad4 in ovarian granulosa cells and, oviduct and uterine mesenchymal cells using the Amhr2‐cre mouse line. Deletion of exon 8 of Smad4 results in the production of an MH2‐truncated SMAD4 protein. These mutant mice are infertile due to the development of oviductal diverticula and defects during the implantation process. The ovaries are fully functional as demonstrated in an ovary transfer experiment. The development of oviductal diverticula occurs shortly after puberty and is dependent on estradiol. The diverticula interfere with sperm migration and embryo transit to the uterus, reducing the number of implantation sites. Analysis of the uterus shows that, even if implantation occurs, decidualization and vascularization are defective resulting in embryo resorption as early as the seventh day of pregnancy. Thus, Smad4 plays an important function in female reproduction by controlling the structural and functional integrity of the oviduct and uterus.
The role of intermittent fasting and the ketogenic diet in cancer disease: can they replace the Mediterranean diet?
Authors: Küçük Aleyna Nur , Çiftçi Seda
Published: July 2023

The prevalence of cancer is rising globally, and it is the second leading cause of death. Nutrition has an important influence on the risk of developing cancer. Moreover, changes in the gut microbiota are connected to the risk of developing cancer and are critical for sustaining immunity. Various studies have shown that intermittent fasting, ketogenic diet, and the Mediterranean diet are effective therapies in changing the intestinal microbiota, the prevention of cancer, and the improvement of tolerance to treatment in cancer patients. Although there is not enough evidence to show that the ketogenic diet is effective in changing the intestinal microbiota in a manner that could prevent cancer, intermittent fasting and the Mediterranean diet could positively affect composition of intestinal microbiota against cancer. In addition, the ketogenic diet, intermittent fasting, and the Mediterranean diet have the potential to stimulate anticarcinogenic pathways, and they might increase cancer patients’ quality of life according to scientific evidence. In this review, we represent and argue recent scientific data on relationship between intermittent fasting, the ketogenic diet, and the Mediterranean diet, intestinal microbiota, cancer prevention and cancer treatment.
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.
The role of lateral habenula NMDA receptors in tramadol-induced conditioning
Authors: Hajikarim-Hamedani Arman , Heidari Amirhossein , Sadat-Shirazi Mitra-Sadat , Mahboubi Sarah , Raminfard Samira , Khalifeh Solmaz , Zarrindast Mohammad-Reza
Published: July 2023

The role of the lateral habenula (LHb) as a hub for receiving and relaying signals from the limbic system to serotonergic, dopaminergic, and norepinephrinergic regions in the brainstem makes this area a critical region in the control of reward and addiction. Behavioral evidence reveals the vital role of the LHb in negative symptoms during withdrawal. In this investigation, we study the role of the LHb N-Methyl D-Aspartate receptor (NMDAR) in the modulation of tramadol reward. Male adult Wistar rats were used in this study. The effect of intra-LHb micro-injection of NMDAR agonist (NMDA, 0.1, 0.5, 2 µg/rat) and antagonist (D-AP5, 0.1, 0.5, 1 µg/rat) was evaluated in conditioned place preference (CPP) paradigm. The obtained results showed that intra-LHb administration of NMDA induced place aversion dose-dependently, while blockade of NMDAR in the LHb using D-AP5 micro-injection led to an increased preference score in the CPP task. Co-administration of NMDA (0.5 µg/rat) with tramadol (4 mg/kg) reduced preference score, while co-administration of D-AP5 (0.5 µg/rat) with a non-effective dose of tramadol (1 mg/kg) potentiate the rewarding effect of tramadol. LHb receives inputs from the limbic system and projects to the monoaminergic nuclei in the brainstem. It has been declared that NMDAR is expressed in LHb, and as obtained data revealed, these receptors could modulate the rewarding effect of tramadol. Therefore, NMDA receptors in the LHb might be a new target for modulating tramadol abuse.
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

Objective

The 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]).

Methods

Using 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.

Results

Accelerometer 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.

Conclusions

The 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.
Design and validation of a PCR screen for γ-butyrolactone-like regulatory systems in Streptomyces
Authors: Waschulin Valentin , Borsetto Chiara , Corre Christophe , Wellington Elizabeth M.
Published: July 2023

γ-butyrolactone and related signalling systems are found in Streptomyces and other actinobacteria where they control the production of specialised metabolites such as antibiotics. Genetic manipulation of these regulatory systems therefore leads to changes in the specialised metabolite profile of a strain and has been used to activate previously silent specialised metabolite gene clusters. However, there is no easy way to assess the presence of γ-butyrolactone-like systems in Streptomyces strains without whole genome sequencing. We have therefore developed and tested a PCR screen that is able to detect homologs of the commonly co-located butenolide synthase and γ-butyrolactone receptor genes. This PCR screen could be employed for the screening of strain libraries to detect signalling systems without the necessity for whole genome sequencing.
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

Background

Human 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.

Methods

We 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.

Results

HNSCC 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.

Conclusions

Distinct 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

Two-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

Purpose

Metastatic 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 design

We 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.

Results

We 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.

Conclusion

This 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

Yeasts 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 AWAY

We 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

The 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

Neuronal 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

The 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.

Significance

The 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.
Sociodemographic and health-related differences in undiagnosed hypertension in the Health Survey for England 2015-2019
Authors: Campbell Emma , Macey Ellie , Shine Chris , Nafilyan Vahé , Clark Nathan Cadogan , Pawelek Piotr , Ward Isobel , Hughes Andrew , Raleigh Veena , Banerjee Amitava , Finning Katie
Published: July 2023

Background

Hypertension is a leading cause of morbidity and mortality worldwide, yet a substantial proportion of cases are undiagnosed. Understanding the scale of undiagnosed hypertension and identifying groups most at risk is important to inform approaches to detection.

Methods

We used data from the 2015 to 2019 Health Survey for England, an annual, cross-sectional, nationally representative survey. Undiagnosed hypertension was defined by a measured blood pressure of 140/90mmHg or above but no history of diagnosis. Age-adjusted prevalence of undiagnosed hypertension was estimated across sociodemographic and health-related characteristics. To assess the independent association between undiagnosed hypertension and each characteristic, we fitted a logistic regression model adjusted for sociodemographic factors.

Findings

An estimated 30.7% (29.0-32.4%) of men and 27.6% (26.1-29.1%) of women with hypertension were undiagnosed. Younger age, lower Body Mass Index, and better self-reported general health were associated with an increased likelihood of hypertension being undiagnosed for men and women. Living in rural areas and in regions outside of London and the East of England were also associated with an increased likelihood of hypertension being undiagnosed for men, as were being married or in a civil partnership and having higher educational qualifications for women.

Interpretation

Hypertension is commonly undiagnosed, and some of the groups less at risk of hypertension are most likely to be undiagnosed. Given the high lifetime risk of hypertension and its strong links with morbidity and mortality, our findings suggest a need for greater awareness of the potential for undiagnosed hypertension, including among those typically considered ‘low risk’.