bluuebunny/crossref_metadata_2025 huggingface dataset:
The Efficacy of Whole Blood Resuscitation During Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA) to Mitigate Post-occlusion Circulatory Collapse: A Translational Model in Large Swine
Authors: Newberry Ryan K , Paredes R Madelaine , Barnard Ed B G , Redman Theodore T , Arana Allyson A , Maddry Joseph K , Glaser Jacob J , Rall Jason M
Published: June 2024

Introduction

Uncontrolled torso hemorrhage is the primary cause of potentially survivable deaths on the battlefield. Zone 1 Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA), in conjunction with damage control resuscitation, may be an effective management strategy for these patients in the prehospital or austere phase of their care. However, the effect of whole blood (WB) transfusion during REBOA on post-occlusion circulatory collapse is not fully understood.

Materials and Methods

Yorkshire male swine (n = 6 per group, 70–90 kg) underwent a 40% volume-controlled hemorrhage. After a 10-minute hemorrhagic shock period, a REBOA balloon was inflated in Zone 1. Fifteen minutes after inflation, 0, 1, or 3 units (450 mL/unit) of autologous WB was infused through the left jugular vein. Thirty minutes after initial balloon inflation, the balloon was deflated slowly over 3 minutes. Following deflation, normal saline was administered (up to 3,000 mL) and swine were observed for 2 hours. Survival (primary outcome), hemodynamics, and blood gas values were compared among groups. Statistical significance was determined by log-rank test, one-way ANOVA, and repeated measures ANOVA.

Results

Survival rates were comparable between groups (P = .345) with 66% of control, 33% of the one-unit animals, and 50% of the 3-unit animals survived until the end of the study. Following WB infusion, both the 1-unit and the 3-unit groups had significantly higher blood pressure (P < .01), pulmonary artery pressure (P < .01), and carotid artery flow (P < .01) compared to the control group.

Conclusions

WB transfusion during Zone 1 REBOA was not associated with increased short-term survival in this large animal model of severe hemorrhage. We observed no signal that WB transfusion may mitigate post-occlusion circulatory collapse. However, there was evidence of supra-normal blood pressures during WB transfusion.
Glucagon-Like Peptide-1 Receptor Agonists and Sodium Glucose Cotransporter-2 Inhibitors and Cardiorespiratory Fitness Interaction
Authors: Ni David , Kokkinos Peter , Nylen Eric S
Published: June 2024

Introduction

Cardiorespiratory fitness (CRF) is a stronger predictor of mortality than traditional risk factors and is a neglected vital sign of health. Enhanced fitness is a cornerstone in diabetes management and is most often delivered concurrently with pharmacological agents, which can have an opposing impact, as has been reported with metformin. Considering the rapid evolution of diabetes medications with improved cardiovascular outcomes, such as glucagon-like peptide-1 receptor agonists and sodium glucose cotransporter-2 inhibitors, it is of importance to consider the influence of these vis-a-vis effects on CRF.

Materials and Methods

Combining the words glucagon-like peptide-1 receptor agonists and sodium glucose cotransporter-2 inhibitors with cardiorespiratory fitness, an online search was done using PubMed, Embase, Scopus, Web of Science, Scientific Electronic Library Online, and Cochrane.

Results

There were only a few randomized controlled studies that included CRF, and the results were mostly neutral. A handful of smaller studies detected improved CRF using sodium glucose cotransporter-2 inhibitors in patients with congestive heart failure.

Conclusions

Since CRF is a superior prognosticator for cardiovascular outcomes and both medications can cause lean muscle mass loss, the current review highlights the paucity of relevant interactive analysis.
Cost Removed! Do Different Factors Influence Motivation for Vasectomy Reversal When Cost Is Not an Issue?
Authors: Maloney Trevor J , Swargaloganathan Piragash , Hawksworth Dorota J
Published: June 2024

Introduction

Vasectomy is a relatively common procedure performed for the purposes of sterilization; however, up to 6% of men that undergo vasectomy wish for its reversal at some point. Few studies have examined the motivation behind vasectomy reversal (VR), especially within special populations, such as the U.S. Military. The aim of this study was to examine the motivations of U.S. Military service members (SMs) who opted for VR surgery, considering their unique access to free health care.

Materials and Methods

We conducted a retrospective record review of microsurgical VRs performed by a single surgeon (DJH) between January 2020 and May 2023. We evaluated patient’s age at which vasectomy was performed, age at VR, reasons for seeking VR surgical care, number of children fathered before the vasectomy, and the age of the current partner.

Results

A total of 106 patients underwent VR during the study period, and 102 of them had their medical records available for review. The average age at the time of vasectomy was 31.3 years, while the average age at VR was 40.2 years. The average spousal age at the time of seeking VR was 34.8 years. Before undergoing vasectomy, the men had fathered an average of 2.7 children. Most men were enlisted members of the military (68) and of all service branches, Army represented the greatest number (50). The vast majority of men (76) cited having a new partner after divorce as the primary motivation for seeking VR. Within this group, 57 were remarried, 15 were in a new relationship, 3 were newly engaged, and 1 desired fertility for future relationships. Additionally, 21 sought VR to have more children with the same spouse. Among them, motivating factors included changes to financial status and improvement in partner’s health condition. A minority of patients (2) desired VR due to post vasectomy pain syndrome or religious beliefs.

Conclusions

Our study demonstrates that the primary driver for seeking VR surgical care among SMs was the desire for fertility with a new partner, which correlates with trends in the civilian sector. Approximately 20% of the men cited the wish to have more children with the same partner as their motivation. Non-fertility reasons, such as religious beliefs and post vasectomy pain syndrome, were also observed, albeit less frequently.
SPT-SZ MCMF: an extension of the SPT-SZ catalogue over the DES region
Authors: Klein M , Mohr J J , Bocquet S , Aguena M , Allen S W , Alves O , Ansarinejad B , Ashby M L N , Bacon D , Bayliss M , Benson B A , Bleem L E , Brodwin M , Brooks D , Bulbul E , Burke D L , Canning R E A , Carlstrom J E , Rosell A Carnero , Carretero J , Chang C L , Conselice C , Costanzi M , Crites A T , da Costa L N , Pereira M E S , Davis T M , De Vicente J , Desai S , de Haan T , Dobbs M A , Doel P , Ferrero I , Flores A M , Frieman J , George E M , Giannini G , Gladders M D , Gonzalez A H , Grandis S , Gruen D , Gruendl R A , Gutierrez G , Halverson N W , Hinton S R , Holder G P , Hollowood D L , Holzapfel W L , Honscheid K , Hrubes J D , Huang N , James D J , Khullar G , Kim K , Knox L , Kraft R , Kéruzoré F , Lee A T , Luong-Van D , Mahler G , Mantz A , Marrone D P , Marshall J L , McDonald M , McMahon J J , Mena-Fernández J , Menanteau F , Meyer S S , Miquel R , Myles J , Padin S , Pieres A , Plazas Malagón A A , Pryke C , Reichardt C L , Reil K , Roberson J , Romer A K , Romero C , Ruhl J E , Saliwanchik B R , Salvati L , Sanchez E , Saro A , Schaffer K K , Schrabback T , Schubnell M , Sevilla-Noarbe I , Sharon K , Shirokoff E , Smith M , Somboonpanyakul T , Stalder B , Stanford S A , Stark A A , Strazzullo V , Suchyta E , Swanson M E C , Tarle G , To C , Vanderlinde K , Vieira J D , von der Linden A , Weaverdyck N , Williamson R , Wiseman P , Young M
Published: June 2024

We present an extension to a Sunyaev–Zel’dovich Effect (SZE) selected cluster catalogue based on observations from the South Pole Telescope (SPT); this catalogue extends to lower signal to noise than the previous SPT–SZ catalogue and therefore includes lower mass clusters. Optically derived redshifts, centres, richnesses, and morphological parameters together with catalogue contamination and completeness statistics are extracted using the multicomponent matched filter (MCMF) algorithm applied to the S/N > 4 SPT–SZ candidate list and the Dark Energy Survey (DES) photometric galaxy catalogue. The main catalogue contains 811 sources above S/N = 4, has 91  per cent purity, and is 95 per cent complete with respect to the original SZE selection. It contains in total 50 per cent more clusters and twice as many clusters above z = 0.8 in comparison to the original SPT-SZ sample. The MCMF algorithm allows us to define subsamples of the desired purity with traceable impact on catalogue completeness. As an example, we provide two subsamples with S/N > 4.25 and S/N > 4.5 for which the sample contamination and cleaning-induced incompleteness are both as low as the expected Poisson noise for samples of their size. The subsample with S/N > 4.5 has 98 per cent purity and 96 per cent completeness and is part of our new combined SPT cluster and DES weak-lensing cosmological analysis. We measure the number of false detections in the SPT-SZ candidate list as function of S/N, finding that it follows that expected from assuming Gaussian noise, but with a lower amplitude compared to previous estimates from simulations.
The MOSDEF survey: properties of warm ionized outflows at z = 1.4–3.8
Authors: Weldon Andrew , Reddy Naveen A , Coil Alison L , Shapley Alice E , Siana Brian , Price Sedona H , Kriek Mariska , Mobasher Bahram , Song Zhiyuan , Wozniak Michael A
Published: June 2024

We use the large spectroscopic data set of the MOSFIRE Deep Evolution Field survey to investigate the kinematics and energetics of ionized gas outflows. Using a sample of 598 star-forming galaxies at redshift 1.4 < z < 3.8, we decompose [O iii] and $\rm {H}\,\alpha$ emission lines into narrow and broad components, finding significant detections of broad components in 10 per cent of the sample. The ionized outflow velocity from individual galaxies appears independent of galaxy properties, such as stellar mass, star formation rate (SFR), and SFR surface density (ΣSFR). Adopting a simple outflow model, we estimate the mass-, energy-, and momentum-loading factors of the ionized outflows, finding modest values with averages of 0.33, 0.04, and 0.22, respectively. The larger momentum- than energy-loading factors, for the adopted physical parameters, imply that these ionized outflows are primarily momentum driven. We further find a marginal correlation (2.5σ) between the mass-loading factor and stellar mass in agreement with predictions by simulations, scaling as ηm$\propto M_{\star }^{-0.45}$. This shallow scaling relation is consistent with these ionized outflows being driven by a combination of mechanical energy generated by supernovae explosions and radiation pressure acting on dusty material. In a majority of galaxies, the outflowing material does not appear to have sufficient velocity to escape the gravitational potential of their host, likely recycling back at later times. Together, these results suggest that the ionized outflows traced by nebular emission lines are negligible, with the bulk of mass and energy carried out in other gaseous phases.
Plasma lensing interpretation of FRB 20201124A bursts at the end of September 2021
Authors: Chen Xuechun , Hu Bin , Wang Pei , Zheng Wenwen , Li Di , Er Xinzhong
Published: June 2024

When radio photons propagate through a non-uniform electron density volume, the plasma lensing effect can induce an extreme magnification to the observed flux at certain frequencies. Because the plasma lens acts as a diverging lens, it can extremely suppress the observed flux when aligned with the source. These two properties can theoretically cause a highly magnified fast radio burst (FRB) to become faint or even disappear for a period of time. In this paper, we interpret that the significant increase in burst counts followed by a sudden quenching in FRB 20201124A in September 2021 can be attributed to plasma lensing. Based on the one-dimensional Gaussian lens model, we search for double main-peak structures in the spectra just before its extinction on 2021 September 29. After the de-dispersion and de-scintillation procedures, we find eight bursts with double main-peaks at stable positions. There are three parameters in our modelling, the height N0, width a of the lens and its distance DLS to the source. We reformulate them as a combined parameter ${P}_0 \propto \left(\frac{a}{\mathrm{au}}\right)\sqrt{\frac{\mathrm{kpc}}{D_{\mathrm{LS}}} \frac{\mathrm{pc}\mathrm{cm}^{-3}}{N_0} }$. The frequency spectra can give an accurate estimation of P0 corresponding to $\left(\frac{a}{\mathrm{au}}\right)\sqrt{\frac{\mathrm{kpc}}{D_{\mathrm{LS}}} \frac{\mathrm{pc}\mathrm{cm}^{-3}}{N_0} } \approx 28.118$, while the time of arrival only give a relatively loose constraint on a2/DLS. Comparing with the observation dynamic spectra, we suggest that for a plasma lens in host galaxy, e.g. DLS ≈ 1 kpc, the width of lens can not be larger than 40 au. At last, we estimate the relative transverse motion velocity between the lens and source, $v\approx 98\left(\frac{a}{\mathrm{au}}\right)\mathrm{km\,s^{-1}}$.
Radiative properties of plasmoids and plasmoid mergers in magnetic reconnection
Authors: Zhang Haocheng , Dong Lingyi , Giannios Dimitrios
Published: June 2024

Magnetic reconnection is often considered as the primary particle acceleration mechanism in a magnetized blazar zone environment. The majority of radiation in the reconnection layer comes from plasmoids and their mergers. In particular, plasmoid mergers can produce strong multiwavelength flares and major variations in synchrotron polarization signatures. However, radiative properties of plasmoid mergers have not been well explored due to difficulties in tracking the merging processes. Here we use an image processing method that combines the magnetic vector potential and density to identify isolated and merging plasmoids. We find that this method can clearly distinguish radiation contributions from isolated plasmoids, merging plasmoids, and the primary current sheet of reconnection. This new method enables us to study the radiative properties of plasmoids and mergers statistically. Our results show that isolated plasmoids have similar emissivity regardless of their sizes, and they generally have non-zero polarization degree (PD) due to their quasi-circular shape. Flares due to plasmoid mergers have relative amplitudes that are antiproportional to the size ratio of the plasmoids participating in the mergers. Finally, only mergers between plasmoids of comparable sizes (width ratio ≲5) can lead to significant spectral hardening and polarization angle (PA) variations; the amplitude of the PA variations is between 0 and 180° and has a mean value of 90°. Our analyses on 2D simulations can pave the way for future analyses and machine learning techniques on radiative properties of 3D magnetic reconnection simulations.
Astrophysical parameter inference on accreting white dwarf binaries using gravitational waves
Authors: Yi Sophia , Lau Shu Yan , Yagi Kent , Arras Phil
Published: June 2024

Accreting binary white dwarf systems are among the sources expected to emanate gravitational waves that the Laser Interferometer Space Antenna (LISA) will detect. We investigate how accurately the binary parameters may be measured from LISA observations. We complement previous studies by performing our parameter estimation on binaries containing a low-mass donor with a thick, hydrogen-rich envelope. The evolution is followed from the early, pre-period minimum stage, in which the donor is non-degenerate, to a later, post-period minimum stage with a largely degenerate donor. We present expressions for the gravitational-wave amplitude, frequency, and frequency derivative in terms of white dwarf parameters (masses, donor radius, etc.), where binary evolution is driven by gravitational-wave radiation and accretion torques, and the donor radius and logarithmic change in radius (ηd) due to mass-loss are treated as model parameters. We then perform a Fisher analysis to reveal the accuracy of parameter measurements, using models from Modules for Experiments in Stellar Astrophysics (mesa) to estimate realistic fiducial values at which we evaluate the measurement errors. We find that the donor radius can be measured relatively well with LISA observations alone, while we can further measure the individual masses if we have an independent measurement of the luminosity distance from electromagnetic observations. When applied to the parameters of the recently discovered white dwarf binary ZTF J0127+5258, our Fisher analysis suggests that we will be able to constrain the system’s individual masses and donor radius using LISA’s observations, given Zwicky Transient Facility’s (ZTF’s) measurement of the luminosity distance.
Predictions for CO emission and the CO-to-H2 conversion factor in galaxy simulations with non-equilibrium chemistry
Authors: Thompson Oliver A , Richings Alexander J , Gibson Brad K , Faucher-Giguère Claude-André , Feldmann Robert , Hayward Christopher C
Published: June 2024

Our ability to trace the star-forming molecular gas is important to our understanding of the Universe. We can trace this gas using CO emission, converting the observed CO intensity into the H$_2$ gas mass of the region using the CO-to-H$_2$ conversion factor ($X_{\rm{{\small CO}}}$). In this paper, we use simulations to study the conversion factor and the molecular gas within galaxies. We analysed a suite of simulations of isolated disc galaxies, ranging from dwarfs to Milky Way-mass galaxies, that were run using the fire-2 subgrid models coupled to the chimes non-equilibrium chemistry solver. We use the non-equilibrium abundances from the simulations, and we also compare to results using abundances assuming equilibrium, which we calculate from the simulation in post-processing. Our non-equilibrium simulations are able to reproduce the relation between CO and H$_2$ column densities, and the relation between $X_{\rm{{\small CO}}}$ and metallicity, seen within observations of the Milky Way. We also compare to the xCOLD GASS survey, and find agreement with their data to our predicted CO luminosities at fixed star formation rate. We also find the multivariate function used by xCOLD GASS overpredicts the H$_2$ mass for our simulations, motivating us to suggest an alternative multivariate function of our fitting, though we caution that this fitting is uncertain due to the limited range of galaxy conditions covered by our simulations. We also find that the non-equilibrium chemistry has little effect on the conversion factor (<5 per cent) for our high-mass galaxies, though still affects the H$_2$ mass and $L_{\rm{{\small CO}}}$ by $\approx$25  per cent.
Emergence of red, star-forming galaxies (red misfits) in a ΛCDM universe
Authors: Manuwal Aditya
Published: June 2024

We investigate the formation of red misfits (RM) using a cosmological, hydrodynamical simulation from the eagle project. Similar to observations, the RM possess less dust, higher stellar metallicities, and older stellar populations compared to blue, star-forming galaxies (BA) at the same $M_\star$. Lagrangian particle-tracking reveals that the older ages of RM have resulted from a combined effect of higher star formation efficiency (SFE), and the earlier onset and faster net depletion of their interstellar medium (ISM). For the centrals, the latter was partially due to higher efficiency of escape from ISM, driven by stronger stellar and/or active galactic nucleus feedback (depending on the mass). There was an additional contribution to this escape from gas stripping for satellite RM, as suggested by the higher group masses ($\gtrsim 0.5$ dex) and $\mathrm{H_2}/\mathrm{H}\, {\rm{\small I}}$ ratios ($\gtrsim 0.3$ dex). Moreover, accretion of circumgalactic gas (CGM) on to the galaxy has been less efficient for the satellites. On the metallicity front, the offsets are largely due to the disparity in SFE, causing varying degrees of enrichment through the mass transfers associated with stellar winds and supernovae. We ascribe this SFE disparity to the lower specific angular momentum (j) of freshly accreted CGM for RM, which ultimately manifested in the ISM kinematics due to interactions with cooling flows. The impact on $j_{\rm ism}$ was further intensified by poorer alignment with the flow’s $\vec{j}$, particularly for the satellites. Our results illuminate potential origins of RM, and motivate further exploration of this peculiar class through a synergy between observations and simulations.
Efficient activation of hundreds of LTR12C elements reveals cis-regulatory function determined by distinct epigenetic mechanisms
Authors: Ohtani Hitoshi , Liu Minmin , Liang Gangning , Jang H Josh , Jones Peter A
Published: June 2024

Long terminal repeats (LTRs), which often contain promoter and enhancer sequences of intact endogenous retroviruses (ERVs), are known to be co-opted as cis-regulatory elements for fine-tuning host-coding gene expression. Since LTRs are mainly silenced by the deposition of repressive epigenetic marks, substantial activation of LTRs has been found in human cells after treatment with epigenetic inhibitors. Although the LTR12C family makes up the majority of ERVs activated by epigenetic inhibitors, how these epigenetically and transcriptionally activated LTR12C elements can regulate the host-coding gene expression remains unclear due to genome-wide alteration of transcriptional changes after epigenetic inhibitor treatments. Here, we specifically transactivated >600 LTR12C elements by using single guide RNA-based dCas9-SunTag-VP64, a site-specific targeting CRISPR activation (CRISPRa) system, with minimal off-target events. Interestingly, most of the transactivated LTR12C elements acquired the H3K27ac-marked enhancer feature, while only 20% were co-marked with promoter-associated H3K4me3 modifications. The enrichment of the H3K4me3 signal was intricately associated with downstream regions of LTR12C, such as internal regions of intact ERV9 or other types of retrotransposons. Here, we leverage an optimized CRISPRa system to identify two distinct epigenetic signatures that define LTR12C transcriptional activation, which modulate the expression of proximal protein-coding genes.
HDAC4 influences the DNA damage response and counteracts senescence by assembling with HDAC1/HDAC2 to control H2BK120 acetylation and homology-directed repair
Authors: Di Giorgio Eros , Dalla Emiliano , Tolotto Vanessa , D’Este Francesca , Paluvai Harikrishnareddy , Ranzino Liliana , Brancolini Claudio
Published: June 2024

Access to DNA is the first level of control in regulating gene transcription, a control that is also critical for maintaining DNA integrity. Cellular senescence is characterized by profound transcriptional rearrangements and accumulation of DNA lesions. Here, we discovered an epigenetic complex between HDAC4 and HDAC1/HDAC2 that is involved in the erase of H2BK120 acetylation. The HDAC4/HDAC1/HDAC2 complex modulates the efficiency of DNA repair by homologous recombination, through dynamic deacetylation of H2BK120. Deficiency of HDAC4 leads to accumulation of H2BK120ac, impaired recruitment of BRCA1 and CtIP to the site of lesions, accumulation of damaged DNA and senescence. In senescent cells this complex is disassembled because of increased proteasomal degradation of HDAC4. Forced expression of HDAC4 during RAS-induced senescence reduces the genomic spread of γH2AX. It also affects H2BK120ac levels, which are increased in DNA-damaged regions that accumulate during RAS-induced senescence. In summary, degradation of HDAC4 during senescence causes the accumulation of damaged DNA and contributes to the activation of the transcriptional program controlled by super-enhancers that maintains senescence.
The impact of mRNA poly(A) tail length on eukaryotic translation stages
Authors: Biziaev Nikita , Shuvalov Alexey , Salman Ali , Egorova Tatiana , Shuvalova Ekaterina , Alkalaeva Elena
Published: June 2024

The poly(A) tail plays an important role in maintaining mRNA stability and influences translation efficiency via binding with PABP. However, the impact of poly(A) tail length on mRNA translation remains incompletely understood. This study explores the effects of poly(A) tail length on human translation. We determined the translation rates in cell lysates using mRNAs with different poly(A) tails. Cap-dependent translation was stimulated by the poly(A) tail, however, it was largely independent of poly(A) tail length, with an exception observed in the case of the 75 nt poly(A) tail. Conversely, cap-independent translation displayed a positive correlation with poly(A) tail length. Examination of translation stages uncovered the dependence of initiation and termination on the presence of the poly(A) tail, but the efficiency of initiation remained unaffected by poly(A) tail extension. Further study unveiled that increased binding of eRFs to the ribosome with the poly(A) tail extension induced more efficient hydrolysis of peptidyl-tRNA. Building upon these findings, we propose a crucial role for the 75 nt poly(A) tail in orchestrating the formation of a double closed-loop mRNA structure within human cells which couples the initiation and termination phases of translation.
Comparative analysis and classification of highly divergent mouse rDNA units based on their intergenic spacer (IGS) variability
Authors: Kim Jung-Hyun , Nagaraja Ramaiah , Ogurtsov Alexey Y , Noskov Vladimir N , Liskovykh Mikhail , Lee Hee-Sheung , Hori Yutaro , Kobayashi Takehiko , Hunter Kent , Schlessinger David , Kouprina Natalay , Shabalina Svetlana A , Larionov Vladimir
Published: June 2024

Ribosomal DNA (rDNA) repeat units are organized into tandem clusters in eukaryotic cells. In mice, these clusters are located on at least eight chromosomes and show extensive variation in the number of repeats between mouse genomes. To analyze intra- and inter-genomic variation of mouse rDNA repeats, we selectively isolated 25 individual rDNA units using Transformation-Associated Recombination (TAR) cloning. Long-read sequencing and subsequent comparative sequence analysis revealed that each full-length unit comprises an intergenic spacer (IGS) and a ∼13.4 kb long transcribed region encoding the three rRNAs, but with substantial variability in rDNA unit size, ranging from ∼35 to ∼46 kb. Within the transcribed regions of rDNA units, we found 209 variants, 70 of which are in external transcribed spacers (ETSs); but the rDNA size differences are driven primarily by IGS size heterogeneity, due to indels containing repetitive elements and some functional signals such as enhancers. Further evolutionary analysis categorized rDNA units into distinct clusters with characteristic IGS lengths; numbers of enhancers; and presence/absence of two common SNPs in promoter regions, one of which is located within promoter (p)RNA and may influence pRNA folding stability. These characteristic features of IGSs also correlated significantly with 5′ETS variant patterns described previously and associated with differential expression of rDNA units. Our results suggest that variant rDNA units are differentially regulated and open a route to investigate the role of rDNA variation on nucleolar formation and possible associations with pathology.
Oral phosphate binders and incident osteoporotic fracture in patients on dialysis
Authors: Kim Ji Eun , Park Jina , Jang Yunyoung , Kang Eunjeong , Kim Yong Chul , Kim Dong Ki , Joo Kwon Wook , Kim Yon Su , Lee Hajeong
Published: June 2024

Background

End-stage kidney disease (ESKD) has an elevated risk of osteoporotic fractures in relation to mineral and bone disorder (MBD) as well as conventional risks of osteoporosis. We investigated the association between oral phosphate binders, the mainstay of MBD treatment, and osteoporotic fracture in dialysis patients.

Methods

We obtained data from the National Health Insurance database for incident dialysis patients without a history of osteoporotic fractures. Participants were categorized into four groups based on their initial 1-year prescription profiles: calcium-based phosphate binder (CBPB), non-calcium-based phosphate binder (NCBPB), both CBPB and NCBPB (mixed), and non-phosphate binder (non-user) groups. The primary outcome was the occurrence of new-onset osteoporotic fractures after 1 year of dialysis. Secondary outcomes included cardiovascular events and mortality.

Results

Out of 69 368 incident dialysis patients, 22 326, 5020, 2853 and 39 169 were included in the CBPB, NCBPB, mixed and non-user groups, respectively. The overall risk of osteoporotic fractures was lower in patients taking any phosphate binders compared with non-users. Specifically, only the CBPB group showed a reduced risk of vertebral [adjusted hazard ratio (aHR) 0.83 (0.76–0.92)], hip [aHR 0.81 (0.74–0.89)] and distal radius [aHR 0.88 (0.78–0.99)] fractures compared with non-users. This relationship presented in a time-dependent manner with fracture risk reduction in patients taking CBPB for 3–6 months [aHR 0.9 (0.83–0.99)] and ≥6 months [aHR 0.83 (0.78–0.89)], compared with those using CBPB for <3 months. Additionally, only the CBPB group had a lower risk of MACE, cardiac arrest and ventricular arrhythmia than non-users. All phosphorus binder groups showed a reduced mortality risk compared with non-users.

Conclusions

Our findings indicate that the using phosphate binders in ESKD patients is lowers the risk of osteoporotic fractures. Notably, those taking CBPB had a reduced risk without increasing cardiovascular events or mortality compared with non-users.
NRG-BN002: Phase I study of ipilimumab, nivolumab, and the combination in patients with newly diagnosed glioblastoma
Authors: Sloan Andrew E , Winter Kathryn , Gilbert Mark R , Aldape Kenneth , Choi Serah , Wen Patrick Y , Butowski Nicholas , Iwamoto Fabio M , Raval Raju R , Voloschin Alfredo D , Kamiya-Matsuoka Carlos , Won Minhee , Mehta Minesh P
Published: June 2024

Background

Immune checkpoint inhibitors (ICIs) have efficacy in several solid tumors but limited efficacy in glioblastoma (GBM). This study evaluated the safety of anti-CTLA-4 and anti-PD-1 ICIs alone or in combination in newly diagnosed GBM after completion of standard radiochemotherapy with the subsequent intent to test combinatorial ICIs in this setting.

Methods

The primary endpoint was dose-limiting toxicity (DLT) for adults with unifocal, supratentorial newly diagnosed GBM after resection and chemoradiation. Ipilimumab and nivolumab were tested separately and in combination with a planned expansion cohort dependent upon DLT results.

Results

Thirty-two patients were enrolled at 9 institutions: 6 to each DLT assessment cohort and 14 to the expansion cohort. Median age: 55 years, 67.7% male, 83.9% White. Treatment was well tolerated with 16% Grade 4 events; the combination did not have unexpectedly increased toxicity, with no Grade 5 events. One DLT was seen in each single-agent treatment; none were observed in the combination, leading to expanded accrual of the combined treatment. The median follow-up was 19.6 months. For all patients receiving combination treatment, median overall survival (OS) and progression-free survival (PFS) were 20.7 and 16.1 months, respectively.

Conclusions

IPI and NIVO are safe and tolerable with toxicities similar to those noted with other cancers when given in combination with adjuvant temozolomide for newly diagnosed GBM. Combination IPI + NIVO is not substantially more toxic than single agents. These results support a subsequent efficacy trial to test the combination of ICIs in Phase II/III for patients with newly diagnosed GBM.

ClinicalTrials.gov Registration

NCT02311920
Polygenic and Socioeconomic Contributions to Nicotine Use and Cardiometabolic Health in Early Mid-Life
Authors: Lippert Adam M , Corsi Daniel J , Kim Rockli , Wedow Robbee , Kim Jinho , Taddess Beza , Subramanian S V
Published: June 2024

Introduction

Early mid-life is marked by accumulating risks for cardiometabolic illness linked to health-risk behaviors like nicotine use. Identifying polygenic indices (PGI) has enriched scientific understanding of the cumulative genetic contributions to behavioral and cardiometabolic health, though few studies have assessed these associations alongside socioeconomic (SES) and lifestyle factors.

Aims and Methods

Drawing on data from 2337 individuals from the United States participating in the National Longitudinal Study of Adolescent to Adult Health, the current study assesses the fraction of variance in five related outcomes—use of conventional and electronic cigarettes, body mass index (BMI), waist circumference, and glycosylated hemoglobin (A1c)—explained by PGI, SES, and lifestyle.

Results

Regression models on African ancestry (AA) and European ancestry (EA) subsamples reveal that the fraction of variance explained by PGI ranges across outcomes. While adjusting for sex and age, PGI explained 3.5%, 2.2%, and 0% in the AA subsample of variability in BMI, waist circumference, and A1c, respectively (in the EA subsample these figures were 7.7%, 9.4%, and 1.3%). The proportion of variance explained by PGI in nicotine-use outcomes is also variable. Results further indicate that PGI and SES are generally complementary, accounting for more variance in the outcomes when modeled together versus separately.

Conclusions

PGI are gaining attention in population health surveillance, but polygenic variability might not align clearly with health differences in populations or surpass SES as a fundamental cause of health disparities. We discuss future steps in integrating PGI and SES to refine population health prediction rules.

Implications

Study findings point to the complementary relationship of PGI and socioeconomic indicators in explaining population variance in nicotine outcomes and cardiometabolic wellness. Population health surveillance and prediction rules would benefit from the combination of information from both polygenic and socioeconomic risks. Additionally, the risk for electronic cigarette use among users of conventional cigarettes may have a genetic component tied to the cumulative genetic propensity for heavy smoking. Further research on PGI for vaping is needed.
Native Aortic Valve Endocarditis Caused by Scopulariopsis Species: Case Report, Considerations for Management, and Review of Literature
Authors: Imam Sabrina , Kaperak Christopher J , Hozain Ahmed E , Qin Hecong , Nguyen Cynthia T , Sudhindra Praveen , Jeevanandam Valluvan , Landon Emily
Published: June 2024

We present the first case of native aortic valve endocarditis caused by Scopulariopsis. Intraoperative images and videos from valve replacement surgery illustrate the severity of fungal endocarditis. This case demonstrates the aggressive presentation of left-sided fungal endocarditis, highlights challenges with treating highly resistant fungi, and considers the potential utility of olorofim.
Testing the TTG–Metabasite Connection in the Southern Superior Province: an Integrated Geochemical, Isotopic, and Petrogenetic Modelling Approach
Authors: Kendrick Jillian , Duguet Manuel , Kirkland Christopher L , Liebmann Janne , Moser Desmond E , Vervoort Jeffrey D , Yakymchuk Chris
Published: June 2024

Archean cratons are dominated by tonalite–trondhjemite–granodiorite (TTG) suites, the products of crustal differentiation that formed early continental crust. These rocks may have been primarily generated by partial melting of hydrated basaltic crust in a variety of settings including subduction zones or the deep lithosphere. Sources are mainly inferred from examination of TTGs alone, as potential source rocks are rarely exposed. In the southern Superior Province, Canada, the Kapuskasing Uplift exposes an important crustal cross-section with upper- to middle-crustal TTGs and lower-crustal metabasites, which show evidence of having produced trondhjemitic anatectic melt. Here, we test the hypothesis that these metabasites were the source of the Mesoarchean to Neoarchean TTGs in the Kapuskasing Uplift by combining phase equilibrium and melt trace element modelling with whole-rock and zircon Lu–Hf isotope analysis and geochronology (garnet Lu–Hf and zircon U–Pb) of metabasic samples. By comparison of the results with existing data from TTGs in the Kapuskasing Uplift, we determined that the metabasites are plausible source rocks for the TTGs. The Lu–Hf systematics of the metabasites and TTGs are the most robust evidence of a genetic connection. Modelling results support an increase in TTG source depth over time. New geochronological data constrain partial melting of metabasite and crystallization of anatectic melt between ca. 2685 Ma and ca. 2600 Ma, coeval with crystallization of only the youngest TTGs. Overall, these results indicate a complex history of intracrustal differentiation in the Kapuskasing Uplift, with partial melting of two isotopically distinct lower-crustal metabasic sources at different times and depths.
Cross-cultural adaptation and psychometric validation of the French version of the Defense and Veterans Pain Rating Scale for acute and chronic pain: a prospective clinical study
Authors: Safran Szilard Laszlo , Follonier David , Weber Eric , Vayne-Bossert Petra , Ahrendts Ulrike , Rehberg-Klug Benno
Published: June 2024

Background

Pain assessment and proper evaluation of pain are prerequisites for treatment of acute and chronic pain. Until now, most evaluations have used only resting pain intensity and a unidimensional scale, although multidimensional pain assessment and especially assessment of functional pain impact on activities are recommended. The Defense and Veterans Pain Rating Scale (DVPRS) permits this multidimensional assessment, but no validated French translation exists.

Objectives

To validate the French translation of the multidimensional DVPRS, called the Functional Pain Scale (FPS), in multiple settings of acute and chronic pain.

Study design

Prospective observational study.

Setting

Two large hospitals in the French-speaking region of Switzerland.

Methods

We recruited 232 patients from February 2022 to January 2023. Patients with acute or chronic pain in different settings received a paper questionnaire with both a numerical rating scale (NRS) and the FPS and a customized evaluation questionnaire. Correlation between the FPS and NRS, psychometric properties, and patient preferences were analyzed.

Results

Correlation between the FPS and NRS was high for the whole group of 232 patients, as well for all subgroups. The multi-item FPS scale showed excellent internal consistency. A large majority of patients, even those >75 years of age, preferred the FPS over the NRS and stated that the FPS was easy to use.

Conclusions

The study confirms that the French translation of the DVPRS (the FPS) is a valid measurement instrument for acute and chronic pain evaluation in a wide range of patient groups and is easy for patients to use.

Trial registration

ClinicalTrials.gov ID: NCT05307380.
Containing the COVID-19 Pandemic Under an External Threat: A Case Study of Taiwan
Authors: Tsai Chia-hung , Lin Shane Hsuan-yu
Published: June 2024

Given the global reach of the COVID-19 pandemic, external factors play a critical role in containing its spread and prompt questions about how such threats affect a country's response. Taiwan has received recognition for its effective management of the early stages of the pandemic, but faced significant international obstruction, especially from China. This study examines the relationship between Taiwanese citizens' trust in China and their satisfaction with the government’s COVID-19 policies by analyzing data from six rounds of the Taiwan Election and Democratization Study (TEDS) conducted between 2020 and 2022. This research reveals that public opinion about China can significantly influence people’s satisfaction with domestic policies, particularly during crises like pandemics. Thus, factors beyond national borders can influence public satisfaction with public health policies. The findings contribute to existing literature on shaping public opinion under external threats and have broader implications for China's impact on Taiwan’s domestic politics.
Probing New Physics in Light of Recent Developments in b → c ℓ v Transitions
Authors: Yasmeen Tahira , Ahmed Ishtiaq , Shafaq Saba , Arslan Muhammad , Aslam Muhammad Jamil
Published: June 2024

Experimental studies of the observables associated with $b \rightarrow c$ transitions in semileptonic B-meson decays at BaBar, Belle, and LHCb have shown some deviations from the Standard Model predictions, consequently providing a handy tool to probe the possible new physics (NP). In this context, we first revisit the impact of recent measurements of $R({D^{(*)}})$ and $R(\Lambda _c)$ on the parametric space of the NP scenarios. In addition, we include the $R(J/\psi )$ data in the analysis and find that their influence on the best-fit point and the parametric space is mild. Using the recent HFLAV data, after validating the well established sum rule of $R(\Lambda _c)$, we derive a similar sum rule for $R(J/\psi )$. Furthermore, according to the updated data, we modify the correlation among the different observables, giving us their interesting interdependence. Finally, to discriminate the various NP scenarios, we plot the different angular observables and their ratios for $B \rightarrow D^{*} \tau \nu _\tau$ against the transfer momentum square $\left(q^2\right)$, using the $1\sigma$ and $2\sigma$ parametric space of considered NP scenarios. By implementing the collider bounds on NP Wilson coefficients (WCs), we find that the parametric space of some NP WCs is significantly restrained. To see the clear influence of NP on the amplitude of the angular observables, we also calculate their numerical values in different $q^2$ bins and show them through bar plots. We hope that their precise measurements will help to discriminate various NP scenarios.
Effect of implementing an effective farrowing accommodation hygiene routine on clinical cases of disease, medication usage, and growth in suckling and weaned pigs
Authors: Halpin Keely M , Lawlor Peadar G , Arnaud Elisa A , Teixé-Roig Júlia , O’ Doherty John V , Sweeney Torres , O’ Brien Triona M , Gardiner Gillian E
Published: June 2024

The few studies that have evaluated hygiene routines in farrowing accommodation to date have focused on pathogen elimination from pens, with little attention paid to pig growth and no information provided on pig health or medication usage. This study aimed to determine if implementation of an optimized farrowing accommodation hygiene routine could improve pig health and growth and reduce medication usage pre- and post-weaning (PW). Forty seven sows were blocked on parity, previous litter size and body weight and assigned to two treatments: T1) Basic hygiene: cold water washing only with minimal drying time; T2) Optimized hygiene: use of detergent and a chlorocresol-based disinfectant with a 6-d drying time. Total bacterial counts (TBC), Enterobacteriaceae counts and adenosine triphosphate (ATP) swabs were obtained from different areas within the farrowing pens. Pig growth and medication usage were monitored from birth to slaughter and carcass data were obtained at slaughter. On entry of sows to the farrowing pens, TBC and Enterobacteriaceae counts and ATP concentrations were lower on pen surfaces subjected to the optimized compared to the basic hygiene routine (P < 0.05). Pre-weaning diarrhea prevalence was lower in pigs born into optimal compared to basic hygiene pens (0 vs. 22%; P < 0.001). The number of clinical cases of disease and injections administered to piglets per litter was 75% and 79% less for the optimized compared to the basic hygiene routine, respectively (P < 0.001). This led to reductions of 77% (P < 0.001) and 75% (P < 0.01), respectively in the volume of antibiotics and anti-inflammatories administered per litter in the optimized hygiene group. Pigs from the optimized hygiene treatment were also heavier at weaning (P < 0.01) and their average daily gain (ADG) was higher from day 21 to weaning and days 22 to 49 PW (P < 0.05). However, these growth improvements did not carry through to the finisher period. In conclusion, implementation of an optimized hygiene routine reduced the bacterial load in farrowing pens, leading to a reduction in diarrhea and clinical cases of disease and therefore, medication usage, in suckling pigs. Pig growth was also improved during the suckling and early PW periods. Based on the results, an easily implementable farrowing room hygiene protocol with demonstrable benefits for pig health, growth, and welfare can be provided to farmers.
Responses of Wheat (Triticum aestivum) Constitutively Expressing Four Different Monolignol Biosynthetic Genes to Fusarium Head Blight Caused by Fusarium graminearum
Authors: Funnell-Harris Deanna L. , Sattler Scott E. , Dill-Macky Ruth , Wegulo Stephen N. , Duray Zachary T. , O'Neill Patrick M. , Gries Tammy , Masterson Steven D. , Graybosch Robert A. , Mitchell Robert B.
Published: June 2024

The Fusarium head blight (FHB) pathogen Fusarium graminearum produces the trichothecene mycotoxin deoxynivalenol and reduces wheat yield and grain quality. Spring wheat ( Triticum aestivum) genotype CB037 was transformed with constitutive expression (CE) constructs containing sorghum ( Sorghum bicolor) genes encoding monolignol biosynthetic enzymes caffeoyl coenzyme A (CoA) 3- O-methyltransferase ( SbCCoAOMT), 4-coumarate-CoA ligase ( Sb4CL), or coumaroyl shikimate 3-hydroxylase ( SbC3′H) or monolignol pathway transcriptional activator SbMyb60. Spring wheats were screened for type I (resistance to initial infection, using spray inoculations) and type II (resistance to spread within the spike, using single-floret inoculations) resistances in the field (spray) and greenhouse (spray and single floret). Following field inoculations, disease index, percentage of Fusarium-damaged kernels (FDK), and deoxynivalenol measurements of CE plants were similar to or greater than those of CB037. For greenhouse inoculations, the area under the disease progress curve (AUDPC) and FDK were determined. Following screens, focus was placed on two each of SbC3′H and SbCCoAOMT CE lines because of trends toward a decreased AUDPC and FDK observed following single-floret inoculations. These four lines were as susceptible as CB037 following spray inoculations. However, single-floret inoculations showed that these CE lines had a significantly reduced AUDPC ( P < 0.01) and FDK ( P ≤ 0.02) compared with CB037, indicating improved type II resistance. None of these CE lines had increased acid detergent lignin compared with CB037, indicating that lignin concentration may not be a major factor in FHB resistance. The SbC3′H and SbCCoAOMT CE lines are valuable for investigating phenylpropanoid-based resistance to FHB.