bluuebunny/crossref_metadata_2025 huggingface dataset:
SMARCB1 regulates the hypoxic stress response in sickle cell trait
Authors: Soeung Melinda , Perelli Luigi , Chen Ziheng , Dondossola Eleonora , Ho I-Lin , Carbone Federica , Zhang Li , Khan Hania , Le Courtney N. , Zhu Cihui , Peoples Michael D. , Feng Ningping , Jiang Shan , Zacharias Niki Millward , Minelli Rosalba , Shapiro Daniel D. , Deem Angela K. , Gao Sisi , Cheng Emily H. , Lucchetti Donatella , Walker Cheryl L. , Carugo Alessandro , Giuliani Virginia , Heffernan Timothy P. , Viale Andrea , Tannir Nizar M. , Draetta Giulio F. , Msaouel Pavlos , Genovese Giannicola
Published: May 2023

Renal medullary carcinoma (RMC) is an aggressive kidney cancer that almost exclusively develops in individuals with sickle cell trait (SCT) and is always characterized by loss of the tumor suppressor
SMARCB1
. Because renal ischemia induced by red blood cell sickling exacerbates chronic renal medullary hypoxia in vivo, we investigated whether the loss of SMARCB1 confers a survival advantage under the setting of SCT. Hypoxic stress, which naturally occurs within the renal medulla, is elevated under the setting of SCT. Our findings showed that hypoxia-induced SMARCB1 degradation protected renal cells from hypoxic stress. SMARCB1 wild-type renal tumors exhibited lower levels of SMARCB1 and more aggressive growth in mice harboring the SCT mutation in human hemoglobin A (HbA) than in control mice harboring wild-type human HbA. Consistent with established clinical observations, SMARCB1-null renal tumors were refractory to hypoxia-inducing therapeutic inhibition of angiogenesis. Further, reconstitution of SMARCB1 restored renal tumor sensitivity to hypoxic stress in vitro and in vivo. Together, our results demonstrate a physiological role for SMARCB1 degradation in response to hypoxic stress, connect the renal medullary hypoxia induced by SCT with an increased risk of SMARCB1-negative RMC, and shed light into the mechanisms mediating the resistance of SMARCB1-null renal tumors against angiogenesis inhibition therapies.
Mechanically manipulating glymphatic transport by ultrasound combined with microbubbles
Authors: Ye Dezhuang , Chen Si , Liu Yajie , Weixel Charlotte , Hu Zhongtao , Yuan Jinyun , Chen Hong
Published: May 2023

The glymphatic system is a perivascular fluid transport system for waste clearance. Glymphatic transport is believed to be driven by the perivascular pumping effect created by the pulsation of the arterial wall caused by the cardiac cycle. Ultrasound sonication of circulating microbubbles (MBs) in the cerebral vasculature induces volumetric expansion and contraction of MBs that push and pull on the vessel wall to generate a MB pumping effect. The objective of this study was to evaluate whether glymphatic transport can be mechanically manipulated by focused ultrasound (FUS) sonication of MBs. The glymphatic pathway in intact mouse brains was studied using intranasal administration of fluorescently labeled albumin as fluid tracers, followed by FUS sonication at a deep brain target (thalamus) in the presence of intravenously injected MBs. Intracisternal magna injection, the conventional technique used in studying glymphatic transport, was employed to provide a comparative reference. Three-dimensional confocal microscopy imaging of optically cleared brain tissue revealed that FUS sonication enhanced the transport of fluorescently labeled albumin tracer in the perivascular space (PVS) along microvessels, primarily the arterioles. We also obtained evidence of FUS-enhanced penetration of the albumin tracer from the PVS into the interstitial space. This study revealed that ultrasound combined with circulating MBs could mechanically enhance glymphatic transport in the brain.
A formally certified end-to-end implementation of Shor’s factorization algorithm
Authors: Peng Yuxiang , Hietala Kesha , Tao Runzhou , Li Liyi , Rand Robert , Hicks Michael , Wu Xiaodi
Published: May 2023

Quantum computing technology may soon deliver revolutionary improvements in algorithmic performance, but it is useful only if computed answers are correct. While hardware-level decoherence errors have garnered significant attention, a less recognized obstacle to correctness is that of human programming errors—“bugs.” Techniques familiar to most programmers from the classical domain for avoiding, discovering, and diagnosing bugs do not easily transfer, at scale, to the quantum domain because of its unique characteristics. To address this problem, we have been working to adapt formal methods to quantum programming. With such methods, a programmer writes a mathematical specification alongside the program and semiautomatically proves the program correct with respect to it. The proof’s validity is automatically confirmed—certified—by a “proof assistant.” Formal methods have successfully yielded high-assurance classical software artifacts, and the underlying technology has produced certified proofs of major mathematical theorems. As a demonstration of the feasibility of applying formal methods to quantum programming, we present a formally certified end-to-end implementation of Shor’s prime factorization algorithm, developed as part of a framework for applying the certified approach to general applications. By leveraging our framework, one can significantly reduce the effects of human errors and obtain a high-assurance implementation of large-scale quantum applications in a principled way.
Targeted neurostimulation reverses a spatiotemporal biomarker of treatment-resistant depression
Authors: Mitra Anish , Raichle Marcus E. , Geoly Andrew D. , Kratter Ian H. , Williams Nolan R.
Published: May 2023

Major depressive disorder (MDD) is widely hypothesized to result from disordered communication across brain-wide networks. Yet, prior resting-state-functional MRI (rs-fMRI) studies of MDD have studied zero-lag temporal synchrony (functional connectivity) in brain activity absent directional information. We utilize the recent discovery of stereotyped brain-wide directed signaling patterns in humans to investigate the relationship between directed rs-fMRI activity, MDD, and treatment response to FDA-approved neurostimulation paradigm termed Stanford neuromodulation therapy (SNT). We find that SNT over the left dorsolateral prefrontal cortex (DLPFC) induces directed signaling shifts in the left DLPFC and bilateral anterior cingulate cortex (ACC). Directional signaling shifts in the ACC, but not the DLPFC, predict improvement in depression symptoms, and moreover, pretreatment ACC signaling predicts both depression severity and the likelihood of SNT treatment response. Taken together, our findings suggest that ACC-based directed signaling patterns in rs-fMRI are a potential biomarker of MDD.
Reverse-QTY code design of active human serum albumin self-assembled amphiphilic nanoparticles for effective anti-tumor drug doxorubicin release in mice
Authors: Meng Run , Hao Shilei , Sun Changfa , Hou Zongkun , Hou Yao , Wang Lili , Deng Peiying , Deng Jia , Yang Yaying , Xia Haijian , Wang Bochu , Qing Rui , Zhang Shuguang
Published: May 2023

H
uman
s
erum
a
lbumin (HSA) is a highly water-soluble protein with 67% alpha-helix content and three distinct domains (I, II, and III). HSA offers a great promise in drug delivery with enhanced permeability and retention effect. But it is hindered by protein denaturation during drug entrapment or conjugation that result in distinct cellular transport pathways and reduction of biological activities. Here we report using a protein design approach named
r
everse-
QTY
(rQTY) code to convert specific hydrophilic alpha-helices to hydrophobic to alpha-helices. The designed HSA undergo self-assembly of well-ordered nanoparticles with highly biological actives. The hydrophilic amino acids, asparagine (N), glutamine (Q), threonine (T), and tyrosine (Y) in the helical B-subdomains of HSA were systematically replaced by hydrophobic leucine (L), valine (V), and phenylalanine (F). HSA
rQTY
nanoparticles exhibited efficient cellular internalization through the cell membrane albumin binding protein GP60, or SPARC (
s
ecreted
p
rotein,
a
cidic and
r
ich in
c
ysteine)-mediated pathways. The designed HSA
rQTY
variants displayed superior biological activities including: i) encapsulation of drug doxorubicin, ii) receptor-mediated cellular transport, iii) tumor cell targeting, and iv) antitumor efficiency compare to denatured HSA nanoparticles. HSA
rQTY
nanoparticles provided superior tumor targeting and antitumor therapeutic effects compared to the albumin nanoparticles fabricated by antisolvent precipitation method. We believe that the rQTY code is a robust platform for specific hydrophobic modification of functional hydrophilic proteins with clear-defined binding interfaces.
Cargo-selective and adaptive delivery of nucleic acid therapeutics by bola-amphiphilic dendrimers
Authors: Chen Jiaxuan , Zhu Dandan , Lian Baoping , Shi Kangjie , Chen Peng , Li Ying , Lin Wenyi , Ding Ling , Long Qiulin , Wang Yang , Laurini Erik , Lan Wenjun , Li Yun , Tintaru Aura , Ju Caoyun , Zhang Can , Pricl Sabrina , Iovanna Juan , Liu Xiaoxuan , Peng Ling
Published: May 2023

Nucleic acid therapeutics are becoming an important drug modality, offering the unique opportunity to address “undruggable” targets, respond rapidly to evolving pathogens, and treat diseases at the gene level for precision medicine. However, nucleic acid therapeutics have poor bioavailability and are chemolabile and enzymolabile, imposing the need for delivery vectors. Dendrimers, by virtue of their well-defined structure and cooperative multivalence, represent precision delivery systems. We synthesized and studied bola-amphiphilic dendrimers for cargo-selective and on-demand delivery of DNA and small interfering RNA (siRNA), both important nucleic acid therapeutics. Remarkably, superior performances were achieved for siRNA delivery with the second-generation dendrimer, yet for DNA delivery with the third generation. We systematically studied these dendrimers with regard to cargo binding, cellular uptake, endosomal release, and in vivo delivery. Differences in size both of the dendrimers and their nucleic acid cargos impacted the cooperative multivalent interactions for cargo binding and release, leading to cargo-adaptive and selective delivery. Moreover, both dendrimers harnessed the advantages of lipid and polymer vectors, while offering nanotechnology-based tumor targeting and redox-responsive cargo release. Notably, they allowed tumor- and cancer cell-specific delivery of siRNA and DNA therapeutics for effective treatment in different cancer models, including aggressive and metastatic malignancies, outperforming the currently available vectors. This study provides avenues to engineer tailor-made vectors for nucleic acid delivery and precision medicine.
Design of rigid protein–protein interaction inhibitors enables targeting of undruggable Mcl-1
Authors: Hargreaves David , Carbajo Rodrigo J. , Bodnarchuk Michael S. , Embrey Kevin , Rawlins Philip B. , Packer Martin , Degorce Sébastien L. , Hird Alexander W. , Johannes Jeffrey W. , Chiarparin Elisabetta , Schade Markus
Published: May 2023

The structure-based design of small-molecule inhibitors targeting protein–protein interactions (PPIs) remains a huge challenge as the drug must bind typically wide and shallow protein sites. A PPI target of high interest for hematological cancer therapy is myeloid cell leukemia 1 (Mcl-1), a prosurvival guardian protein from the Bcl-2 family. Despite being previously considered undruggable, seven small-molecule Mcl-1 inhibitors have recently entered clinical trials. Here, we report the crystal structure of the clinical-stage inhibitor AMG-176 bound to Mcl-1 and analyze its interaction along with clinical inhibitors AZD5991 and S64315. Our X-ray data reveal high plasticity of Mcl-1 and a remarkable ligand-induced pocket deepening. Nuclear Magnetic Resonance (NMR)-based free ligand conformer analysis demonstrates that such unprecedented induced fit is uniquely achieved by designing highly rigid inhibitors, preorganized in their bioactive conformation. By elucidating key chemistry design principles, this work provides a roadmap for targeting the largely untapped PPI class more successfully.
Astrocytic control of extracellular GABA drives circadian timekeeping in the suprachiasmatic nucleus
Authors: Patton Andrew P. , Morris Emma L. , McManus David , Wang Huan , Li Yulong , Chin Jason W. , Hastings Michael H.
Published: May 2023

The hypothalamic suprachiasmatic nucleus (SCN) is the master mammalian circadian clock. Its cell-autonomous timing mechanism, a transcriptional/translational feedback loop (TTFL), drives daily peaks of neuronal electrical activity, which in turn control circadian behavior. Intercellular signals, mediated by neuropeptides, synchronize and amplify TTFL and electrical rhythms across the circuit. SCN neurons are GABAergic, but the role of GABA in circuit-level timekeeping is unclear. How can a GABAergic circuit sustain circadian cycles of electrical activity, when such increased neuronal firing should become inhibitory to the network? To explore this paradox, we show that SCN slices expressing the GABA sensor iGABASnFR demonstrate a circadian oscillation of extracellular GABA ([GABA]
e
) that, counterintuitively, runs in antiphase to neuronal activity, with a prolonged peak in circadian night and a pronounced trough in circadian day. Resolving this unexpected relationship, we found that [GABA]
e
is regulated by GABA transporters (GATs), with uptake peaking during circadian day, hence the daytime trough and nighttime peak. This uptake is mediated by the astrocytically expressed transporter GAT3 (
Slc6a11
), expression of which is circadian-regulated, being elevated in daytime. Clearance of [GABA]
e
in circadian day facilitates neuronal firing and is necessary for circadian release of the neuropeptide vasoactive intestinal peptide, a critical regulator of TTFL and circuit-level rhythmicity. Finally, we show that genetic complementation of the astrocytic TTFL alone, in otherwise clockless SCN, is sufficient to drive [GABA]
e
rhythms and control network timekeeping. Thus, astrocytic clocks maintain the SCN circadian clockwork by temporally controlling GABAergic inhibition of SCN neurons.
Sequential absorption of two photons creates a bistable form of RubyACR responsible for its strong desensitization
Authors: Sineshchekov Oleg A. , Govorunova Elena G. , Li Hai , Wang Yumei , Spudich John L.
Published: May 2023

Channelrhodopsins with red-shifted absorption, rare in nature, are highly desired for optogenetics because light of longer wavelengths more deeply penetrates biological tissue. RubyACRs (Anion ChannelRhodopsins), a group of four closely related anion-conducting channelrhodopsins from thraustochytrid protists, are the most red-shifted channelrhodopsins known with absorption maxima up to 610 nm. Their photocurrents are large, as is typical of blue- and green-absorbing ACRs, but they rapidly decrease during continuous illumination (desensitization) and extremely slowly recover in the dark. Here, we show that long-lasting desensitization of RubyACRs results from photochemistry not observed in any previously studied channelrhodopsins. Absorption of a second photon by a photocycle intermediate with maximal absorption at 640 nm (P
640
) renders RubyACR bistable (i.e., very slowly interconvertible between two spectrally distinct forms). The photocycle of this bistable form involves long-lived nonconducting states (L
long
and M
long
), formation of which is the reason for long-lasting desensitization of RubyACR photocurrents. Both L
long
and M
long
are photoactive and convert to the initial unphotolyzed state upon blue or ultraviolet (UV) illumination, respectively. We show that desensitization of RubyACRs can be reduced or even eliminated by using ns laser flashes, trains of short light pulses instead of continuous illumination to avoid formation of L
long
and M
long
, or by application of pulses of blue light between pulses of red light to photoconvert L
long
to the initial unphotolyzed state.
Activation of P53 pathway contributes to
Xenopus
hybrid inviability
Authors: Shi Zhaoying , Liu Guanghui , Jiang Hao , Shi Songyuan , Zhang Xuan , Deng Yi , Chen Yonglong
Published: May 2023

Hybrid incompatibility as a kind of reproductive isolation contributes to speciation. The nucleocytoplasmic incompatibility between
Xenopus tropicalis
eggs and
Xenopus laevis
sperm (
t
e
×
l
s
) leads to specific loss of paternal chromosomes 3L and 4L. The hybrids die before gastrulation, of which the lethal causes remain largely unclear. Here, we show that the activation of the tumor suppressor protein P53 at late blastula stage contributes to this early lethality. We find that in stage 9 embryos, P53-binding motif is the most enriched one in the up-regulated Assay for Transposase-Accessible Chromatin with high-throughput sequencing (ATAC-seq) peaks between

t
e

×

l
s

and wild-type
X. tropicalis
controls, which correlates with an abrupt stabilization of P53 protein in
t
e
×
l
s
hybrids at stage 9. Inhibition of P53 activity via either
tp53
knockout or overexpression of a dominant-negative P53 mutant or Murine double minute 2 proto-oncogene (Mdm2), a negative regulator of P53, by mRNA injection can rescue the
t
e
×
l
s
early lethality. Our results suggest a causal function of P53 on hybrid lethality prior to gastrulation.
Impacts of Individual and Pair Housing on Calves
Authors: Mahendran Sophie
Published: May 2023

Calf rearing is a large financial cost to farms, with particular importance for dairy heifer replacements where the forward investment does not receive any pay-back for 3 to 4 years. Ensuring the critical pre-weaning phase is carried out optimally and understanding the impact that housing has on this time are important. Historically, individual calf housing has been used to reduce disease transmission between calves, but there is limited evidence that pair housing has any detrimental impact on this. Instead, research over the past decade has served to highlight the range of benefits that pair housing can provide. Pair-housed calves start to eat concentrates at an earlier age and in greater amounts, although this does not always translate to increased growth rates during the pre-weaning period. Pair housing allows calves to start forming social relationships, which can have a calming effect in stressful situations and can improve behaviour when heifers enter the milking herd. Additionally, calves housed with others have increased play behaviours, which is a positive indicator of well-being. This growing body of evidence suggests that pair housing of calves results in overall better health and welfare compared to individual housing; therefore, practitioners should help encourage farmers to move towards this housing type.

Information

© The Author 2023
CLASPs stabilize the pre-catastrophe intermediate state between microtubule growth and shrinkage
Authors: Lawrence Elizabeth J. , Chatterjee Saptarshi , Zanic Marija
Published: May 2023

Cytoplasmic linker-associated proteins (CLASPs) regulate microtubules in fundamental cellular processes. CLASPs stabilize dynamic microtubules by suppressing microtubule catastrophe and promoting rescue, the switch-like transitions between growth and shrinkage. How CLASPs specifically modulate microtubule transitions is not understood. Here, we investigate the effects of CLASPs on the pre-catastrophe intermediate state of microtubule dynamics, employing distinct microtubule substrates to mimic the intermediate state. Surprisingly, we find that CLASP1 promotes the depolymerization of stabilized microtubules in the presence of GTP, but not in the absence of nucleotide. This activity is also observed for CLASP2 family members and a minimal TOG2-domain construct. Conversely, we find that CLASP1 stabilizes unstable microtubules upon tubulin dilution in the presence of GTP. Strikingly, our results reveal that CLASP1 drives microtubule substrates with vastly different inherent stabilities into the same slowly depolymerizing state in a nucleotide-dependent manner. We interpret this state as the pre-catastrophe intermediate state. Therefore, we conclude that CLASPs suppress microtubule catastrophe by stabilizing the intermediate state between growth and shrinkage.
Real-time control applications of JET heterodyne radiometer electron temperature profiles using ICRH
Authors: Cappelli M. , Cardinali A. , Zerbini M. , Pucella G. , Giovannozzi E. , JET contributors
Published: May 2023

The Real Time ECE data processing has been recently implemented at JET, by using a cross calibration between the Martin-Puplett interferometer (also known as Michelson) measurements and the Heterodyne faster data. The applicability of RT control with ICRH has been discussed in recent works. In particular, in case of a hollow electron temperature profile, central ICRF heating could be applied to restore temperature peaking. In this work a study about the possibility of controlling the electron temperature profile by using ICRH

as an actuator, with inputs from ECE measurements, is described. The ICRH is here used for the optimization of the plasma ramp-down, in order to correct the end of the discharge and avoid the plasma disruption, though a similar approach could also be proposed to improve the plasma performances during the flat top. Preliminary results have been obtained on the physical and logical feasibility of using ICRH in a real-time control loop. A database of good pulses in identifiable conditions has been compiled and validated by covering the main experiments both in the baseline and hybrid scenarios. Such scenarios have been simulated, for a selected numbers of discharges, using the full-wave propagation solver TORIC-SSQLFP, in order to establish the ICRH power deposition profiles to be used to locally restore a peaked electron temperature profile.
Physical design and multi-physics analysis of a 200 MHz continuous wave radio frequency quadrupole accelerator for a proton accelerator facility
Authors: Zhang Z.Y. , Ma W. , Yuan N. , Sun Y.B. , Ge Y.L. , Zou Z.P. , Zhang Z.L. , Zou L.P. , Yang Z. , Lu L.
Published: May 2023

Based on the platform of a proton accelerator facility, a 200 MHz high intensity continuous wave (CW) radio frequency quadrupole (RFQ) accelerator has been designed at the Sino-French Institute of Nuclear Engineering and Technology of Sun Yat-Sen University, China. Employing the conventional four-vane structure, the RFQ can accelerate 20 mA proton beam from 20 keV to 2.5 MeV. In the beam dynamics design, the simulated transmission efficiency reaches 99.5% and the vane length is less than 4 m. In the electromagnetic design, for the long-term stable operation, Pi-mode Stabilizer Loops (PISLs) are utilized to achieve more than 10 MHz mode frequency separation and to decrease the effects of dipole modes. The 48 tuners are optimized to provide a range of ± 2 MHz frequency tuning. Additionally, the undercuts are optimized to ensure a good field flatness along the longitudinal direction. Based on the coolant channel design, the multi-physics analysis is performed to investigate the deformation and stress resulting from the dissipation of RF power within the cavity, as well as determine the temperature tuning coefficients of the coolants within the vane and wall. The entire design and analysis of PAFA-RFQ has been completed, and the scheme of the design can also be applied to the design of other RFQ cavities.
On the noise generation and unsteady performance of combined heaving and pitching foils
Authors: Wagenhoffer Nathan , Moored Keith W , Jaworski Justin W
Published: May 2023

A transient two-dimensional acoustic boundary element solver is coupled to a potential flow boundary element solver via Powell’s acoustic analogy to determine the acoustic emission of isolated hydrofoils performing biologically-inspired motions. The flow-acoustic boundary element framework is validated against experimental and asymptotic solutions for the noise produced by canonical vortex-body interactions. The numerical framework then characterizes the noise production of an oscillating foil, which is a simple representation of a fish caudal fin. A rigid NACA 0012 hydrofoil is subjected to combined heaving and pitching motions for Strouhal numbers (

0.03
<

S
t

<
1

) based on peak-to-peak amplitudes and chord-based reduced frequencies (

0.125
<

f

∗

<
1

) that span the parameter space of many swimming fish species. A dipolar acoustic directivity is found for all motions, frequencies, and amplitudes considered, and the peak noise level increases with both the reduced frequency and the Strouhal number. A combined heaving and pitching motion produces less noise than either a purely pitching or purely heaving foil at a fixed reduced frequency and amplitude of motion. Correlations of the lift and power coefficients with the peak root-mean-square acoustic pressure levels are determined, which could be utilized to develop long-range, quiet swimmers.
Poly(vinyl alcohol)-gelatin crosslinked by silane-functionalized guanidyl-hydroxyurethane oligomer as contact-killing non-leaching antibacterial wound dressings
Authors: Babaahmadi Masoud , Yeganeh Hamid
Published: May 2023

The present work aims to prepare efficient wound dressing with noncytotoxicity, proper mechanical strength, and the ability to preserve a hygienic environment over wounded skin tissue. To fulfill this goal, the synthesis of a novel silane crosslinking agent with antibacterial guanidinium chloride functional group is considered. The resulting reagent was applied to make a series of film-type stable crosslinked networks composed of poly(vinyl alcohol) and gelatin. The potential protection of wounds from external forces was confirmed, as these films had a very good tensile strength (16–31 MPa) and good elongation (54%–101%) under dry conditions. The good dimensional strength of dressings was preserved after hydration with simulated wound exudates. Based on the calculated fluid handling capacity of the prepared dressings (2.43–3.54 g 10−1cm−2d−1), they were suitable for treating wounds with ‘light’ to ‘moderate’ exudate volume. All the prepared dressings showed very good biocompatibility, as determined by the high viability of fibroblast cells directly contacted with dressing (over 80%) or leachates extracted from them (over 90%). In addition, dressings functionalized with guanidinium groups could effectively kill representative gram-positive and gram-negative bacterial strains.
Unraveling the pertinence of drought indices in the changing climate
Authors: Singh Gauranshi Raj , Dhanya C T , Chakravorty Aniket
Published: May 2023

The increasing divergence/disagreement between the meteorological drought indicators, majorly due to the changing climate conditions, has disputed their pertinency in the monitoring and modeling of drought events. In the present study, we attempted to quantify the divergence between widely used drought indices such as the standardized precipitation index (SPI), standardized precipitation evapotranspiration index (SPEI), and the newly developed standardized net precipitation index (SNEPI) and traced the evolution of this divergence/disagreement. A persistent presence of enhanced dry extremes in the annual divergence of SPEI with SPI and SNEPI was observed, which raises doubts about the utility of traditional drought indices in capturing the changing climatic characteristics. The seasonal dispersion of this annual divergence revealed a strong, spatiotemporally dominant, signal of dryness in the monsoon season by SNEPI, which SPEI failed to unravel. Furthermore, the attribution analysis revealed that the SPI-SPEI disagreements evolved under the influence of the shortwave radiative fluxes. In addition to that, the divergence between SPEI and SNEPI, is driven by the characteristics of wet spells, with the relationship strengthening in the monsoon season and tropical climate zones. All these findings caution us to evaluate the need to incorporate the changing precipitation characteristics before deploying drought indices in operational uses, especially in tropical climate zones.
Enhancing surface adhesion of polytetrafluoroethylene induced by two-step in-situ treatment with radiofrequency capacitively coupled Ar/Ar+CH4+NH3 plasma
Authors: LU Manting , HE Yi , LIU Xue , HUANG Jiamin , ZHANG Jiawei , MA Xiaoping , XIN Yu
Published: May 2023

Although some progress in plasma modification of the polytetrafluoroethylene (PTFE) surface has been made recently, its adhesion strength still needs to be further improved. In this work, the surface of a PTFE sample was treated with a two-step in-situ method. Firstly, the PTFE surface was treated with capacitively coupled Ar plasma to improve its mechanical interlocking performance; then, Ar+NH3+CH4 plasma was used to deposit an a-CN
x
:H cross-linking layer on the PTFE surface to improve the molecular bonding ability. After treatment, a high specific surface area of 2.20 and a low F/C ratio of 0.32 were achieved on the PTFE surface. Its surface free energy was increased significantly and its maximum adhesion strength reached 77.1 N·10 mm−1, which is 56% higher than that of the single-step Ar plasma-treated sample and 32% higher than that of the single-step Ar+CH4+NH3 plasma-treated sample.
Update: Cellulite Therapies and Optimizing Treatment Combinations
Authors: Dhillon Rummit K , Dayan Steven H , Hexsel Doris , Shridharani Sachin , Chilukuri Suneel , LaTowsky Brenda , Fabi Sabrina Guillen
Published: May 2023

Cellulite in the proximal lower extremities is a reported concern among many adult females. The unsightly appearance of cellulite leads many affected individuals to seek treatment by trained specialists. The objective of this review is to provide the reader with an update on new and innovative therapies for cellulite including various treatment combinations to maximize therapeutic outcomes, and strategies for minimizing adverse events. The availability of new technologies and the results from recent clinical trials provide additional tools and data to consider when creating treatment plans for cellulite patients. This update to previous treatment recommendations is based on the most recent developments in cellulite management including the personal experiences of the authors with an emphasis on injectable enzymes, acoustic subcision, targeted verifiable subcision, and biostimulators. Formal clinical studies are warranted to compare various treatment modalities and further investigate combination regimens.

Level of Evidence: 5
Betelgeuse: a review
Authors: Wheeler J Craig , Chatzopoulos Emmanouil
Published: May 2023

Was Betelgeuse once in a binary star system? What causes it to vary over a vast range of timescales? Why did it dim dramatically in 2020? When and how will it explode? J. Craig Wheeler and Manos Chatzopoulos present a host of challenges to both observers and theorists.
Future UK solar system science
Authors: de Moortel Ineke , Eastwood Jonathan , Bridges John , Burchell Maerk , Elseworth Yvonne , Imber Suzie , King Ashley , Morton Richard
Published: May 2023

A new Roadmap for Solar System Research in the UK has been published, and the Solar System Advisory Panel report on the processes involved in updating the previous iteration
Space on the line
Authors: Patterson Cameron
Published: May 2023

Cameron Patterson explains how, in these days of the complex interdependence of technologies, the Sun presents a decided threat to your train journey – and a great deal more besides
scAnno: a deconvolution strategy-based automatic cell type annotation tool for single-cell RNA-sequencing data sets
Authors: Liu Hongjia , Li Huamei , Sharma Amit , Huang Wenjuan , Pan Duo , Gu Yu , Lin Lu , Sun Xiao , Liu Hongde
Published: May 2023

Undoubtedly, single-cell RNA sequencing (scRNA-seq) has changed the research landscape by providing insights into heterogeneous, complex and rare cell populations. Given that more such data sets will become available in the near future, their accurate assessment with compatible and robust models for cell type annotation is a prerequisite. Considering this, herein, we developed scAnno (scRNA-seq data annotation), an automated annotation tool for scRNA-seq data sets primarily based on the single-cell cluster levels, using a joint deconvolution strategy and logistic regression. We explicitly constructed a reference profile for human (30 cell types and 50 human tissues) and a reference profile for mouse (26 cell types and 50 mouse tissues) to support this novel methodology (scAnno). scAnno offers a possibility to obtain genes with high expression and specificity in a given cell type as cell type-specific genes (marker genes) by combining co-expression genes with seed genes as a core. Of importance, scAnno can accurately identify cell type-specific genes based on cell type reference expression profiles without any prior information. Particularly, in the peripheral blood mononuclear cell data set, the marker genes identified by scAnno showed cell type-specific expression, and the majority of marker genes matched exactly with those included in the CellMarker database. Besides validating the flexibility and interpretability of scAnno in identifying marker genes, we also proved its superiority in cell type annotation over other cell type annotation tools (SingleR, scPred, CHETAH and scmap-cluster) through internal validation of data sets (average annotation accuracy: 99.05%) and cross-platform data sets (average annotation accuracy: 95.56%). Taken together, we established the first novel methodology that utilizes a deconvolution strategy for automated cell typing and is capable of being a significant application in broader scRNA-seq analysis. scAnno is available at https://github.com/liuhong-jia/scAnno.
Chasing the Hat
Authors: Mahon Daryl
Published: May 2023

I was sitting in the hall where the graduation of my master’s degree was taking place in 2016 and noted to my wife that I would like one of those hats that are worn by the university faculty in recognition that they have completed advanced studies to doctorate level. To even have such an aspiration is something I am grateful for because as you are about to read, the script for my life was not meant to unfold in this way. The following account is adapted from the prologue of an unpublished autobiography I penned in early 2019. In many ways, I am happy that it is unpublished, not just due to the anxiety I feel about another person reading it, but also because my story is still unfolding. The chasing of the hat then puts my story into context in a broader sense, based on what I imagine the hat to represent, the challenges that I have had to overcome and the journey that I am on towards attaining it.
‘You Just Treat me like a Human Being’: Using Lived Experience to (Re)imagine Boundary Practices in mental health settings
Authors: Sinclair Aimee , Mahboub Lyn , Gillieatt Sue , Fernandes Christina
Published: May 2023

The personal/professional dichotomy, present within dominant notions of professional boundaries, is an ongoing source of tension within social work. Peer workers, given their positioning as both service users and workers, are uniquely placed to contribute to pre-existing efforts in unsettling this dichotomy. Our analysis, informed by dialogic sharing and theorising with fifteen peer support workers, alongside post-humanist and critical mental health approaches, considers the oppressive effects of enacting a personal/professional dichotomy within mental health settings, and conversely, the emancipatory potential of unsettling the dichotomy. Rather than conceptualising such events as boundary ‘crossings’, ‘incursions’ or ‘transgressions’, we suggest (re)imagining professional boundaries as multiple, enacted through ever-shifting socio-material relations. Our analysis supports pre-existing calls for a relational ethic of social work and highlights how lived experience and post-humanism can support the discipline’s commitment to anti-oppressive practices. We recommend further research, informed by lived experience, to explore the complex relations that constitute boundary practices and their effects for both social workers and service users.
Why Didn’t Anyone Understand? Why Didn’t Anyone Ever Stand in the Way? Detecting Child Abuse in Out-of-Home care Setting: The Role of Safeguard and Protection Systems and Social Workers
Authors: Aversa Giuseppe , Filistrucchi Petra
Published: May 2023

The issue of institutional abuse (IA) in out-of-home care services is a difficult one, which we struggle to think about and which is slow to find attention and recognition: the victims are those children who, after experiencing maltreatment and abuse in the family, still suffer violence in the residential care services that should protect them. It represents the failure of the public system in protecting children, and it is often the result of institutions and professionals who allow, collude, cover, justify and minimise violence against children. Starting from a recent and paradigmatic Italian story and from the contribution of experience and thought of those who, as the first author, survived it, as well as from the analysis of the existing literature, this article examines the specific characteristics and dynamics of IA that motivate the extreme difficulty of its emergence. This article aims to improve professionals’ awareness concerning the phenomenon and their responsibilities in the prevention and early detection. For professionals and services to see institutional maltreatment implies questioning themselves, their own methodological tools and their own professional practices, as well as opening themselves to the concrete possibility of being able—at least—to make serious mistakes.
The amyloid cascade hypothesis: an updated critical review
Authors: Kepp Kasper P , Robakis Nikolaos K , Høilund-Carlsen Poul F , Sensi Stefano L , Vissel Bryce
Published: May 2023

Results from recent clinical trials of antibodies that target amyloid-β (Aβ) for Alzheimer’s disease have created excitement and have been heralded as corroboration of the amyloid cascade hypothesis. However, while Aβ may contribute to disease, genetic, clinical, imaging and biochemical data suggest a more complex aetiology.

Here we review the history and weaknesses of the amyloid cascade hypothesis in view of the new evidence obtained from clinical trials of anti-amyloid antibodies. These trials indicate that the treatments have either no or uncertain clinical effect on cognition. Despite the importance of amyloid in the definition of Alzheimer’s disease, we argue that the data point to Aβ playing a minor aetiological role.

We also discuss data suggesting that the concerted activity of many pathogenic factors contribute to Alzheimer’s disease and propose that evolving multi-factor disease models will better underpin the search for more effective strategies to treat the disease.
In-hospital complications associated with pulmonary vein isolation with adjunctive lesions: the NCDR AFib Ablation Registry
Authors: Darden Douglas , Aldaas Omar , Du Chengan , Munir Muhammad Bilal , Feld Gregory K , Pothineni Naga Venkata K , Gopinathannair Rakesh , Lakkireddy Dhanunjaya , Curtis Jeptha P , Freeman James V , Akar Joseph G , Hsu Jonathan C
Published: May 2023

Aims

No prior study has been adequately powered to evaluate real-world safety outcomes in those receiving adjunctive ablation lesions beyond pulmonary vein isolation (PVI). We sought to evaluate characteristics and in-hospital complications among patients undergoing PVI with and without adjunctive lesions.

Methods and results

Patients in the National Cardiovascular Data Registry AFib Ablation Registry undergoing first-time atrial fibrillation (AF) ablation between 2016 and 2020 were identified and stratified into paroxysmal (PAF) and persistent AF, and separated into PVI only, PVI + cavotricuspid isthmus (CTI) ablation, and PVI + adjunctive (superior vena cava isolation, coronary sinus, vein of Marshall, atypical atrial flutter lines, other). Adjusted odds of adverse events were calculated using multivariable logistic regression. A total of 50 937 patients [PAF: 30 551 (60%), persistent AF: 20 386 (40%)] were included. Among those with PAF, there were no differences in the adjusted odds of complications between PVI + CTI or PVI + adjunctive when compared with PVI only. Among persistent AF, PVI + adjunctive was associated with a higher risk of any complication [3.0 vs. 4.5%, odds ratio (OR) 1.30, 95% confidence interval (CI) 1.07–1.58] and major complication (0.8 vs. 1.4%, OR 1.56, 95% CI 1.10–2.21), while no differences were observed in PVI + CTI compared with PVI only. Overall, there was high heterogeneity in adjunctive lesion type, and those receiving adjunctive lesions had a higher comorbidity burden.

Conclusion

Additional CTI ablation was common without an increased risk of complications. Adjunctive lesions other than CTI are commonly performed in those with more comorbidities and were associated with an increased risk of complications in persistent AF, although the current analysis is limited by high heterogeneity in adjunctive lesion set type.
Effectiveness of non-interruptive nudge interventions in electronic health records to improve the delivery of care in hospitals: a systematic review
Authors: Raban Magdalena Z , Gates Peter J , Gamboa Sarah , Gonzalez Gabriela , Westbrook Johanna I
Published: May 2023

Objectives

To describe the application of nudges within electronic health records (EHRs) and their effects on inpatient care delivery, and identify design features that support effective decision-making without the use of interruptive alerts.

Materials and methods

We searched Medline, Embase, and PsychInfo (in January 2022) for randomized controlled trials, interrupted time-series and before–after studies reporting effects of nudge interventions embedded in hospital EHRs to improve care. Nudge interventions were identified at full-text review, using a pre-existing classification. Interventions using interruptive alerts were excluded. Risk of bias was assessed using the ROBINS-I tool (Risk of Bias in Non-randomized Studies of Interventions) for non-randomized studies or the Cochrane Effective Practice and Organization of Care Group methodology for randomized trials. Study results were summarized narratively.

Results

We included 18 studies evaluating 24 EHR nudges. An improvement in care delivery was reported for 79.2% (n = 19; 95% CI, 59.5–90.8) of nudges. Nudges applied were from 5 of 9 possible nudge categories: change choice defaults (n = 9), make information visible (n = 6), change range or composition of options (n = 5), provide reminders (n = 2), and change option-related effort (n = 2). Only one study had a low risk of bias. Nudges targeted ordering of medications, laboratory tests, imaging, and appropriateness of care. Few studies evaluated long-term effects.

Discussion

Nudges in EHRs can improve care delivery. Future work could explore a wider range of nudges and evaluate long-term effects.

Conclusion

Nudges can be implemented in EHRs to improve care delivery within current system capabilities; however, as with all digital interventions, careful consideration of the sociotechnical system is crucial to enhance their effectiveness.
Short communication: Analysis of the nasal microbiota in newly received feedlot heifers according to subsequent incidence of bovine respiratory disease
Authors: Pickett Autumn T , Cooke Reinaldo F , Bicalho Rodrigo , Gouvea Vinicius N
Published: May 2023

This study compared the relative abundance of bacteria in the nasal cavity of high-risk beef heifers at feedlot arrival according to subsequent incidence of bovine respiratory disease (BRD). Angus-influenced heifers (n = 76) were transported for 1,100 km (11 h) to the feedlot (day −1). At feedlot arrival (day 0), heifers were weighed [shrunk body weight (BW) = 234 ± 15 kg] and a nasal cavity swab collected for microbiota analysis. Heifers were ranked by arrival BW and allocated into 6 pens on day 1 where they remained until day 55. Heifers were evaluated daily for BRD signs (days 0 to 55), and a final shrunk BW was recorded on day 56 (16-h feed and water deprivation). Heifers were classified according to number of antimicrobial treatments for BRD received (0, 1, or ≥2), or according to time of the first incidence of BRD signs (no incidence [NOBRD], early incidence [EARLY; 4.1 ± 0.1 d, ranging from 3 to 6 d], or late incidence [LATE; 18.5 ± 9.6 d, ranging from 10 to 28 d]). Average daily gain decreased linearly (P = 0.04) according to number of BRD treatments, and was less (P = 0.04) in LATE and tended (P = 0.08) to be less in EARLY compared with NOBRD. The abundance of the Tenericutes phylum increased linearly (P < 0.01), while the abundance of other phyla (e.g., Firmicutes and Bacteroidetes) decreased linearly (P ≤ 0.05) and phyla diversity tended to decrease linearly (P = 0.10) according to number of BRD treatments. Heifers classified as EARLY had greater (P = 0.01) abundance of Tenericutes compared with NOBRD, whereas Tenericutes abundance in LATE heifers was intermediate and did not differ (P = 0.22) compared with EARLY and NOBRD. The abundance of Mycoplasma genus increased linearly (P < 0.01) while the abundance of other genera (e.g., Corynebacterium and Blautia) and genera diversity decreased linearly (P ≤ 0.03) according to number of BRD treatments. Heifers classified as EARLY had greater (P = 0.01) abundance of Mycoplasma and reduced (P = 0.01) genera diversity compared with NOBRD, and values noted in LATE heifers for these variables were intermediate and not different (P ≥ 0.27) compared with EARLY and NOBRD. Hence, heifers that developed BRD during the experiment had altered nasal microbiota at arrival compared with heifers that remained healthy, particularly increased prevalence of Tenericutes and Mycoplasma. Such differences in nasal microbiota were heightened in heifers that developed BRD shortly after arrival, or that required multiple antimicrobial treatments.
44 Higher Out-of-pocket Expenses are Associated with Worse Health-Related Quality of Life in Burn Survivors
Authors: Holan Cole , Carrougher Gretchen , Stewart Barclay , Gibran Nicole , Orton Caitlin , Sheckter Clifford
Published: May 2023

Introduction

The care required to recover serious burn injuries is costly. In the US, these costs are often borne by patients. Examining the relationship between out-of-pocket (OOP) costs and health-related quality of life (HRQL) is important to support burn survivors.

Methods

Financial data from a regional burn center were merged with data in the Burn Model System (BMS) National Database. HRQL outcomes included VA-Rand 12 (VR-12) physical component summary (PCS) and mental component summary (MCS) scores. Participant surveys were conducted at 6-, 12-, and 24-months post-injury. VR-12 scores were evaluated using generalized linear models and adjusted for potential confounders (age, sex, insurance/payer, self-identified race/ethnicity, measures of burn injury severity).

Results

644 participants were included, of which 13% (84) had OOP costs. The percentage of participants with OOP costs was 34% for commercial/private, 22% for Medicare, 8% for other, 4% for self-pay, and 0% for workers’ compensation and Medicaid. For participants with OOP expenses, median payments were $875 with an IQR of $368 - 1,728. In addition to markers of burn injury severity, OOP costs were negatively associated with PCS scores at 6-months (coefficient -0.002, p< 0.001) and 12-months post-injury (coefficient -0.001, p=0.004). There were no significant associations with PCS scores at 24 months post-injury or MCS scores at any interval.

Conclusions

Participants with commercial/private or Medicare payer had higher financial liability than other payers. Higher OOP expenses were negatively associated with physical HRQL for at least 12 months after injury.

Applicability of Research to Practice

Financial toxicity is a real phenomenon in burn survivors. Burn care providers should be attuned to their patients' finances and spending and connect them with resources when appropriate.