bluuebunny/crossref_metadata_2025_split huggingface dataset:
Temsirolimus inhibits FSP1 enzyme activity to induce ferroptosis and restrain liver cancer progression
Authors: Tian Rui-Lin , Wang Tian-Xiang , Huang Zi-Xuan , Yang Zhen , Guan Kun-Liang , Xiong Yue , Wang Pu , Ye Dan 
Published: September 2024

Abstract
Ferroptosis is a non-apoptotic mode of cell death characterized by iron-dependent accumulation of lipid peroxidation. While lipid radical elimination reaction catalyzed by glutathione peroxidase 4 (GPX4) is a major anti-ferroptosis mechanism, inhibiting this pathway pharmaceutically shows promise as an anti-tumor strategy. However, certain tumor cells exhibit redundancy in lipid radical elimination pathways, rendering them unresponsive to GPX4 inhibitors. In this study, we conducted screens across different cancer cell lines and FDA-approved drugs, leading to the identification of temsirolimus in combination with the GPX4 inhibitor RSL3 as a potent inducer of ferroptosis in liver cancer cells. Mechanistically, temsirolimus sensitized liver cancer cells to ferroptosis by directly binding to and inhibiting ferroptosis suppressor protein 1 (FSP1) enzyme. Notably, while temsirolimus is recognized as a potent mTOR inhibitor, its ferroptosis-inducing effect is primarily attributed to its inhibition of FSP1 rather than mTOR activity. By performing in vitro colony formation assays and in vivo tumor xenograft models, we demonstrated that the combination of temsirolimus and RSL3 effectively suppressed liver tumor progression. This tumoricidal effect was associated with increased lipid peroxidation and induction of ferroptosis. In conclusion, our findings underscore the potential of combining multi-target ferroptosis-inducing agents to circumvent resistance to ferroptosis in liver cancer cells and highlight temsirolimus as a promising FSP1 inhibitor and ferroptosis inducer, which also deserves further investigation in translational medicine.
Phase separation of hnRNPA1 and TERRA regulates telomeric stability
Authors: Xu Ziyan , Liu Yongrui , Li Fudong , Yang Yi , Zhang Hong , Liu Xing , Xie Xin , Chen Xianjun , Shi Yunyu , Zhang Liang 
Published: September 2024

Abstract
Telomeres are repetitive DNA sequences and associated protein complexes located at the end of chromatin. As a result of the DNA replication ending issue, telomeric DNA shortens during each cell cycle. The shelterin protein complex caps telomeric ends and forms a high-order protein–DNA structure to protect telomeric DNA. The stability of telomeres is critical for cellular function and is related to the progression of many human diseases. Telomeric repeat-containing RNA (TERRA) is a noncoding RNA transcribed from telomeric DNA regions. TERRA plays an essential role in regulating and maintaining the stability of telomeres. Heterogeneous nuclear ribonucleoproteins (hnRNPs) are RNA-binding proteins associated with complex and diverse biological processes. HnRNPA1 can recognize both TERRA and telomeric DNA. Previous research reported that hnRNPA1, TERRA, and POT1, a component of the shelterin complex, worked coordinately and displaced replication protein A from telomeric ssDNA after DNA replication, promoting telomere capping to preserve genomic integrity. However, the detailed molecular mechanism has remained unclear for over twenty years. Our study revealed the molecular structure through which the hnRNPA1 UP1 domain interacts with TERRA. Through structural analysis, we identified critical residues on the interacting surface between UP1 and TERRA. Furthermore, we proved that nucleic acids significantly increase the phase separation ability of hnRNPA1 and disrupting the UP1–TERRA interaction extraordinarily affects hnRNPA1 droplet formation both in vitro and in vivo. Taken together, these data revealed the molecular mechanism of the droplet formation of hnRNPA1 and TERRA and the possible function of the droplets for maintaining genomic stability.
Surface sensitivity of atomic-resolution secondary electron imaging
Authors: Saitoh Koh , Oyobe Teppei , Igarashi Keisuke , Sato Takeshi , Matsumoto Hiroaki , Inada Hiromi , Endo Takahiko , Miyata Yasumitsu , Usami Rei , Takenobu Taishi 
Published: September 2024

Abstract
The surface sensitivity of high-resolution secondary electron (SE) imaging is examined using twisted bilayers of MoS2 stacked at an angle of 30°. High-resolution SE images of the twisted bilayer MoS2 show a honeycomb structure composed of Mo and S atoms, elucidating the monolayer structure of MoS2. Simultaneously captured annular dark-field scanning transmission electron microscope images from the same region show the projected structure of the two layers. That is, the SE images from the bilayer MoS2 selectively visualize the surface monolayer. It is noted that the SE yields from the surface monolayer are approximately three times higher than those from the second monolayer, likely attributable to attenuation when SEs emitted from the second layer traverse the surface layer. The surface sensitivity of high-resolution SE imaging is examined using twisted bilayers of MoS2 stacked at an angle of 30°. It was found that the SE images of the MoS2 bilayer visualize the surface monolayer approximately three times more intensely than the second monolayer.
Effect of chemotherapy and surgery timing on mortality in upper and lower extremity osteosarcoma
Authors: Danese Mark D , Groundland John S 
Published: September 2024

Abstract

Background
Surgery with neoadjuvant and adjuvant chemotherapy represents the standard of care for extremity osteosarcoma despite a lack of high-quality evidence for its use, and trial evidence that suggests upfront surgery may result in better outcomes. This study estimated the difference in overall survival for the standard of care (neoadjuvant first) vs upfront surgery first followed by adjuvant chemotherapy (surgery first).

Methods
Using Surveillance, Epidemiology, and End Results data, we identified patients aged 5-29 years diagnosed with a primary cancer of upper or lower extremity osteosarcoma between 2007 and 2019 who received surgery and chemotherapy. Our primary endpoint was the 5-year survival difference between the surgery first and neoadjuvant first groups.

Results
Adjusted 5-year survival was 74% for surgery first patients and 67% for neoadjuvant first patients, with a survival difference of 6.9% (95% confidence interval [CI] = −4.2% to 16.1%). In sensitivity analyses of 5-year survival, the results were consistent, showing a 6.8%-13.7% higher 5-year survival in surgery first patients. Statistically significant mortality risk factors included older age, larger tumor size, the type of resection (salvage vs amputation), and stage III-IV disease (vs stage I-II disease).

Conclusion
The evidence supporting neoadjuvant therapy in osteosarcoma care is weak. However, there is evidence that pausing chemotherapy in the perisurgical period might affect outcomes. Consequently, this study, and its consistency with the results from the only randomized trial to address this question, suggests that there is reason to revisit a prospective, randomized trial of osteosarcoma treatment regarding the timing of surgery and chemotherapy.
Influence of chronotype on sleep quality and menstrual regularity in nurses on monthly shift rotations
Authors: Peng Yu-Xuan , Chang Wen-Pei 
Published: September 2024

Abstract
Objectives: This study aimed to investigate factors that influence the sleep quality and menstrual cycles of female rotating-shift nurses.
Methods: A cross-sectional study was conducted in which 213 female rotating-shift nurses between the ages of 20 and 45 were recruited from a medical center in Taiwan from November 1, 2023, to December 31, 2023. Binary logistic regression analysis was performed with regard to sleep quality or menstrual cycle.
Results: Female rotating-shift nurses who perceived a higher level of stress (P &lt; .001), were late chronotypes (P = .020), or were working the night shift (P = .006) were more likely to have poor sleep quality. Late-type nurses working the day shift were more likely to have poor sleep quality than were early- and intermediate-type nurses (P &lt; .001). With regard to menstrual cycles, female rotating-shift nurses who perceived a higher level of stress (P = .008), were working the night shift (P &lt; .001), or had poor sleep quality (P = .001) were more likely to have irregular menstrual cycles. Late-type nurses working the day shift were more likely to have irregular menstrual cycles than were early- and intermediate-type nurses (P = .013).
Conclusions: A higher likelihood of poor sleep quality was found in female rotating-shift nurses when they perceived high levels of stress, and the interactions between chronotype and shift type could influence sleep quality. Shift type and the interactions between chronotype and shift type could also influence menstrual regularity.
Divide and Save: A Critical Care Air Transport Team Case With Prolonged Field Care
Authors: Brown Daniel J , Jeffries Jonathan , Broderick Joseph , Trager Jonathan , Cheney Mark , Clemons Melissa , Davis William T 
Published: September 2024

ABSTRACT
Critical care air transport teams (CCATTs) specialize in providing intensive medical and postoperative resuscitative care during air evacuations. In a 2014 mission, a seasoned CCATT was urgently deployed to evacuate 6 American service members with gunshot wounds. Despite only having 2 hours of premission preparation and no further injury or treatment details, CCATT secured additional equipment, medications, and blood supply. Upon arrival to a foreign nonmilitary hospital, they discovered that American ground commanders had lost trust in local medical capabilities. One patient experienced prolonged extremity tourniquet time and surgical delay. This led to acute renal failure, preventing immediate evacuation without continuous renal replacement therapy (CRRT). Deviating from the standard procedure, the CCATT obtained permission to split their team. The CCATT nurse attended 5 stabilized patients during unregulated critical care air transport with plans to swiftly return with CRRT equipment for the critical sixth patient. The physician and respiratory therapist remained at the foreign hospital for 2 days to provide prolonged field care. This case demonstrates the evolving mission scope of CCATT, which may encompass ground triage, prolonged field care, unregulated movement, and atypical CCATT equipment such as CRRT, occasionally necessitating a split team construct. To adapt to these evolving needs, updated policies and training now incorporate these diverse CCATT concepts, emphasizing the importance of flexibility in en route critical care missions.
MODEL&CO: exoplanet detection in angular differential imaging by learning across multiple observations
Authors: Bodrito Théo , Flasseur Olivier , Mairal Julien , Ponce Jean , Langlois Maud , Lagrange Anne-Marie 
Published: September 2024

ABSTRACT
Direct imaging of exoplanets is particularly challenging due to the high contrast between the planet and the star luminosities, and their small angular separation. In addition to tailored instrumental facilities implementing adaptive optics and coronagraphy, post-processing methods combining several images recorded in pupil tracking mode are needed to attenuate the nuisances corrupting the signals of interest. Most of these post-processing methods build a model of the nuisances from the target observations themselves, resulting in strongly limited detection sensitivity at short angular separations due to the lack of angular diversity. To address this issue, we propose to build the nuisance model from an archive of multiple observations by leveraging supervised deep learning techniques. The proposed approach casts the detection problem as a reconstruction task and captures the structure of the nuisance from two complementary representations of the data. Unlike methods inspired by reference differential imaging, the proposed model is highly non-linear and does not resort to explicit image-to-image similarity measurements and subtractions. The proposed approach also encompasses statistical modelling of learnable spatial features. The latter is beneficial to improve both the detection sensitivity and the robustness against heterogeneous data. We apply the proposed algorithm to several data sets from the VLT/SPHERE instrument, and demonstrate a superior precision-recall trade-off compared to the PACO algorithm. Interestingly, the gain is especially important when the diversity induced by ADI is the most limited, thus supporting the ability of the proposed approach to learn information across multiple observations.
Probing the energy and luminosity-dependent spectro-timing properties of RX J0440.9+4431 with AstroSat
Authors: Sharma Rahul , Mandal Manoj , Pal Sabyasachi , Paul Biswajit , Jaisawal G K , Ratheesh Ajay 
Published: September 2024

ABSTRACT
The Be/X-ray binary pulsar RX J0440.9+4431 went through a giant outburst in December 2022 with a peak flux of $\sim$2.3 Crab in 15–50 keV. We studied the broad-band timing and spectral properties of RX J0440.9+4431 using four AstroSat observations, where the source transited between subcritical and supercritical accretion regimes. Pulsations were detected significantly above 100 keV. The pulse profiles were found to be highly luminosity- and energy-dependent. A significant evolution in the pulse profile shape near the peak of the outburst indicates a possible change in the accretion mode and beaming patterns of RX J0440.9+4431. The rms pulsed fraction was luminosity- and energy-dependent, with a concave-like feature around 20–30 keV. The depth of this feature varied with luminosity, indicating changes in the accretion column height and proportion of reflected photons. The broad-band continuum spectra were best fitted with a two-component Comptonization model with a blackbody component or a two-blackbody component model with a thermal Comptonization component. A quasi-periodic oscillation (QPO) at 60 mHz was detected at a luminosity of $2.6 \times 10^{37}$ erg s$^{-1}$, which evolved into 42 mHz at $1.5 \times 10^{37}$ erg s$^{-1}$. The QPO rms were found to be energy dependent with an overall increasing trend with energy. For the first time, we found the QPO frequency varying with photon energy in an X-ray pulsar, which poses a challenge in explaining the QPO with current models such as the Keplarian and beat frequency model. Hence, more physically motivated models are required to understand the physical mechanism behind the mHz QPOs.
Long-term evolutionary links between the isolated neutron star populations
Authors: Gençali A A , Ertan Ü 
Published: September 2024

ABSTRACT
We have investigated the evolutionary connections of the isolated neutron star (NS) populations including radio pulsars (RPs), anomalous X-ray pulsars (AXPs), soft gamma repeaters (SGRs), dim isolated NSs (XDINs), ‘high-magnetic field’ RPs (‘HBRPs’), central compact objects (CCOs), rotating radio transients (RRATs), and long-period pulsars (LPPs) in the fallback disc model. The model can reproduce these NS families as a natural outcome of different initial conditions (initial period, disc mass, and dipole moment, μ) with a continuous μ distribution in the $\sim 10^{27} - 5 \times 10^{30}$ G cm$^3$ range. Results of our simulations can be summarized as follows: (1) A fraction of ‘HBRPs’ with relatively high μ evolve into the persistent AXP/SGR properties, and subsequently become LPPs. (2) Persistent AXP/SGRs do not have evolutionary links with CCOs, XDINs, and RRATs. (3) For a wide range of μ, most RRATs evolve passing through RP or ‘HBRP’ properties during their early evolutionary phases. (4) A fraction of RRATs which have the highest estimated birth rate seem to be the progenitors of XDINs. (5) LPPs, whose existence was predicted by the fallback disc model, are the sources evolving in the late stage of evolution before the discs become inactive. These results provide concrete support to the ideas proposing evolutionary connections between the NS families to account for the ‘birth rate problem’, the discrepancy between the cumulative birth rate estimated for these systems and the core-collapse supernova rate.
Is WR 104 a face-on, colliding-wind binary?
Authors: Hill G M 
Published: September 2024

ABSTRACT
Two decades of extensive spectroscopic monitoring of WR 104 is used to confront what we think we understand about this iconic prototype of the dust-producing pinwheel stars. Convincing SB1 orbital solutions are obtained for both the WC9d star and its OB companion. The period ($241.54 \pm 0.14$ d) and circular orbit agree perfectly with results from modelling images of the rotating dust spiral. Contrary to those results though, the orbit is found to be significantly inclined instead of face-on. The two SB1 solutions each indicate $i \sim 45^{\circ }$ but could be as low as $\sim 34^{\circ }$. This result naturally provides an explanation for the long puzzling photometric and emission line strength variations but is difficult to reconcile with the imaging. Confirmation that colliding winds are present is found by the detection of variable excess emission in two of the lines where it would be most expected. The changing shapes of this excess emission are not perfectly phase-locked though, which will complicate future modelling.
Improvements in pain interference among geographically diverse adults with neurofibromatosis: Results from a fully powered randomized controlled trial
Authors: Hooker Julia E , Doorley James D , Greenberg Jonathan , Bakhshaie Jafar , Manglani Heena R , Briskin Ellie A , Vranceanu Ana-Maria 
Published: September 2024

Abstract

Background
Pain is prevalent among adults with neurofibromatoses (NF) and hinders quality of life. Pain management for NF is predominantly pharmacological and often ineffective. Psychosocial treatments improve pain outcomes in other chronic illness populations but have not been developed and tested in fully powered efficacy trials among adults with NF. Using data from a fully powered randomized clinical trial of an 8-week mind–body program (Relaxation Response Resiliency Program for NF [3RP-NF]) versus a health education control (HEP-NF), we examined (1) improvements in pain intensity and pain interference, and (2) mechanisms underlying improvements.

Methods
Participants (N = 210, Mage = 42.6, 73.4% female) were randomized to 3RP-NF versus HEP-NF. They completed measures of pain intensity, pain interference, and putative mechanisms (eg, mindfulness, coping, and social support) at baseline, post-intervention, 6-month, and 12-month follow-ups.

Results
There was a statistically significant change in pain interference over time F(3, 537.06) = 7.21, P &lt; .001, but not pain intensity. Neither group (3RP-NF vs. HEP-NF) nor the group-by-time interaction predicted change in pain interference. While the group-by-time interaction was not statistically significant across all time points, planned post-hoc analyses probing the interaction at specific time points revealed a statistically significant decrease in pain interference from baseline to post-intervention (P &lt; .001), which was sustained (ie, no subsequent change) from post-intervention through 6-month (P = 1.00) and 12-month follow-ups (P = 1.00) in the 3RP-NF group. The HEP-NF group had no significant changes in pain intensity or interference over time. The association between group (3RP-NF) and decreased pain interference from baseline to post-intervention was fully mediated by change in coping over the same period.

Conclusions
Participation in the 3RP-NF is associated with sustained improvement in pain interference. Improvement occurred through increased coping.

Trial Registration
ClinicalTrials.gov Identifier: NCT03406208

Trial Registration URL
https://clinicaltrials.gov/study/NCT03406208
Clinical Manifestations and Outcomes in Adults Hospitalized With Respiratory Syncytial Virus and Influenza a/B: A Multicenter Observational Cohort Study
Authors: Clausen Clara Lundetoft , Egeskov-Cavling Amanda Marie , Hayder Noor , Sejdic Adin , Roed Casper , Gitz Holler Jon , Nielsen Lene , Eiberg Mads Frederik , Rezahosseini Omid , Østergaard Christian , Harboe Zitta Barrella , Fischer Thea K , Benfield Thomas , Lindegaard Birgitte 
Published: September 2024

Abstract

Background
Respiratory syncytial virus (RSV) and influenza cause significant health challenges, particularly for individuals with comorbid conditions and older adults. However, information on the clinical manifestations and outcomes of adults hospitalized with RSV in Europe remains limited.

Methods
This multicenter observational cohort study of adults hospitalized with RSV or influenza A or B from March 2016 to April 2020 investigated the clinical manifestations, mortality risk factors, and association with 90-day mortality rates by logistic regression analysis after adjustment for covariates.

Results
Of 988 patients hospitalized with either virus, 353 had RSV, 347 had influenza A, and 288 had influenza B infection. Patients with RSV, compared with those with influenza A or B, were more likely to have comorbid conditions (83% for RSV vs 72% for influenza A [P = .03] and 74% for influenza B [P = .001]) or pneumonia (41% vs 29% [P = .03] and 24% [P &lt; .001], respectively). After adjustment for covariates, RSV infection was associated with an increased all-cause mortality rate within 90 days compared with influenza B (odds ratio, 2.16 [95% confidence interval, 1.20–3.87]; P = .01) but not influenza A (1.38 [.84–2.29]; P = .21). Increasing age and present pneumonia were identified as independent mortality risk factors in patients with RSV.

Conclusions
Older adults hospitalized with RSV infections are at a higher risk of dying within 90 days of hospitalization than patients admitted with influenza B but at a similar risk as those admitted with influenza A, emphasizing the detrimental effects and severity of older patients being infected with RSV. Our findings underscore the need for strategic testing and vaccination approaches to mitigate the impact of RSV among older adults.
Cerebrospinal Fluid Lactate Levels as a Prognostic Indicator in Patients With Cryptococcal Meningitis Who Are HIV Negative: A Retrospective Cohort Study
Authors: Tsai Yu-Chi , Chen Yao-Shen , Yao Cai-Sin , Chang Ren-In , Wang Ning-Chi , Chen Jui-Kuang 
Published: September 2024

Abstract

Background
Cryptococcal meningitis (CM) is a severe central nervous system infection. In patients with HIV infections and coexisting CM, elevated baseline cerebrospinal fluid (CSF) lactate levels can predict increased mortality. However, the CSF lactate level's significance in patients with CM who are HIV negative remains unclear, necessitating further investigation to elucidate the potential distinctions and enhance patient management. This study investigated the significance of CSF lactate levels in patients with CM who were HIV negative.

Methods
This retrospective study utilized data from the clinical databases of patients who underwent lumbar punctures at a medical center in Kaohsiung City, southern Taiwan. Demographic data, CSF lactate levels, routine CSF analyses, and hematologic and neurologic findings were evaluated. The optimal CSF lactate threshold value was determined by the Youden index.

Results
This retrospective study included 70 patients with CM, among whom 44 (63%) and 26 (37%) tested negative and positive for HIV, respectively. The group without HIV exhibited higher CSF lactate levels, with an optimal CSF lactate cutoff point of 7.935 mmol/L for predicting 90-day mortality, resulting in significant predictive accuracies (area under the curve, 0.755; sensitivity, 57.1%; specificity, 100%); this value was an independent mortality predictor in patients who were HIV negative. In patients with CM who were HIV negative, CSF lactate levels ≥7.935 mmol/L correlated with higher mortality rates but without statistical significance. All patients with CM who were HIV negative and had CSF lactate levels ≥7.935 mmol/L died within 3 months of admission.

Conclusions
Patients with CM who were HIV negative had elevated CSF lactate levels that correlated with adverse outcomes, enabling early identification of high-risk individuals.