bluuebunny/crossref_metadata_2025 huggingface dataset:
Political Uncertainty and the Geographic Allocation of Credit: Evidence from Small Businesses
Authors: CERQUEIRO GERALDO , MÃO‐DE‐FERRO ANA , PENAS MARÍA FABIANA
Published: May 2024

We investigate how banks change the geographic distribution of their small business loan portfolio when they face political uncertainty in some of the states where they operate. Using exogenous variation in gubernatorial elections with binding term limits, we show that political uncertainty causes local banks to increase out‐of‐state lending to small firms, particularly those located in higher‐income areas. This effect follows a decrease in local lending and is stronger for banks that are more capital‐constrained. The increase in out‐of‐state credit leads to an increase in employment growth and net firm creation in sectors with larger capital needs.
Insight into the evolution of textural properties and juiciness of ready‐to‐eat chicken breasts upon different thermal sterilization: From the perspective of protein degradation
Authors: Liu Xiaoyan , Zhou Kai , Chen Bo , Xie Yong , Ma Yunhao , Zhou Hui , Xu Baocai
Published: May 2024

Texture deterioration of meat products upon high‐temperature sterilization is a pressing issue in the meat industry. This study evaluated the effect of different thermal sterilization temperatures on the textural and juiciness of ready‐to‐eat (RTE) chicken breast. In this study, by dynamically monitoring the texture and juiciness of chicken meat products during the process of thermal sterilization, it has been observed that excessively high sterilization temperatures (above 100°C) significantly diminish the shear force, springiness and water‐holding capacity of the products. Furthermore, from the perspective of myofibrillar protein degradation, molecular mechanisms have been elucidated, unveiling that the thermal sterilization treatment at 121°C/10 min triggers the degradation of myosin heavy chains and F‐actin, disrupting the lattice arrangement of myofilaments, compromising the integrity of sarcomeres, and resulting in an increase of approximately 40.66% in the myofibrillar fragmentation index, thus diminishing the quality characteristics of the products. This study unravels the underlying mechanisms governing the dynamic changes in quality of chicken meat products during the process of thermal sterilization, thereby providing theoretical guidance for the development of high‐quality chicken products.
Courts and democratic backsliding: A comparative perspective on the United States
Authors: Gardbaum Stephen
Published: May 2024

This article argues that courts in the United States are comparatively less likely to be captured than those of many other countries and more able to resist an authoritarian populist regime, but also somewhat more likely to facilitate democratic backsliding on their own account. In this way, they potentially could—and arguably already do—provide a relatively rare case of “abusive judicial review” by independent courts. The article also briefly considers whether the US experience provides any insights for the relationship of courts and democratic backsliding in other countries, and especially how the ability of courts to resist capture might be bolstered.
Serum bile acid change correlates with improvement in pruritus in patients with primary biliary cholangitis receiving linerixibat
Authors: Karatza Eleni , Swift Brandon , Carreño Fernando , Mukherjee Sumanta , Casillas Linda , Lennie Janelle , Fettiplace James , McLaughlin Megan M. , Kremer Andreas E.
Published: May 2024

Background & Aims

Total serum bile acid (TSBA) levels are elevated in patients with primary biliary cholangitis (PBC) and may mediate cholestatic pruritus. Linerixibat, an ileal bile acid transporter inhibitor, improved pruritus in patients with PBC. We explored the relationship between linerixibat dose, TSBA concentration, and pruritus.

Methods

Data from Phase 1/2 trials were used to develop a population kinetic‐pharmacodynamic model to characterize the linerixibat dose–TSBA relationship. Individual Bayesian parameter estimates for participants in the GLIMMER study were used to derive the area under the TSBA concentration curve over 24 h (AUC0–24). Time‐matched post hoc estimates of AUC0–24 were correlated with pruritus reported on a 0–10 numerical rating scale. Baseline TSBA concentration was correlated with change from baseline (ΔBL) in monthly itch score (MIS). ΔBL in model‐estimated TSBA AUC0–24 was correlated with time‐matched ΔBL in weekly itch score (WIS) or MIS.

Results

Linerixibat dose dependently reduced TSBA AUC0–24, reaching steady state after 5 days. Baseline TSBA levels in GLIMMER did not correlate with ΔBL in MIS. ΔBL in TSBA AUC0–24 correlated with improved WIS over 12 weeks of treatment (r = 0.52, p < 0.0001). Of participants with a ≥30% decrease in TSBA AUC0–24, 60% were pruritus responders (≥2‐point improvement in WIS from baseline).

Conclusions

Linerixibat treatment leads to rapid, dose‐dependent TSBA reductions. Baseline TSBA levels do not correlate with on‐treatment pruritus change, suggesting they do not predict linerixibat response. Change in TSBA AUC0–24 correlates significantly with, and can be predictive of, pruritus improvement in patients with PBC.
Protective effect of equol intake on bladder dysfunction in a rat model of bladder outlet obstruction
Authors: Miyazaki Nozomu , Katsura Ryota , Ozaki Chiaki , Suzutani Tatsuo
Published: May 2024

Objectives

This study evaluates the impact of equol, a metabolite of soy isoflavone, on bladder dysfunction in rats with bladder outlet obstruction (BOO). In addition, we investigate its potential as a neuroprotective agent for the obstructed bladder and discuss its applicability in managing overactive bladder (OAB).

Methods

Eighteen male Sprague–Dawley rats were divided into three groups (six rats per group) during the rearing period. The Sham and C‐BOO groups received an equol‐free diet, while the E‐BOO group received equol supplementation (0.25 g/kg). At 8 weeks old, rats underwent BOO surgery, followed by continuous cystometry after 4 weeks of rearing. The urinary oxidative stress markers (8‐hydroxy‐2′‐deoxyguanosine and malondialdehyde) were measured, and the bladder histology was analyzed using hematoxylin–eosin, Masson's trichrome, and immunohistochemical staining (neurofilament heavy chain for myelinated nerves, peripherin for unmyelinated nerves, and malondialdehyde).

Results

Equol reduced BOO‐induced smooth muscle layer fibrosis, significantly prolonged the micturition interval (C‐BOO: 193 s, E‐BOO: 438 s) and increased the micturition volume (C‐BOO: 0.54 mL, E‐BOO: 1.02 mL) compared to the C‐BOO group. Equol inhibited the increase in urinary and bladder tissue malondialdehyde levels. While the C‐BOO group exhibited reduced peripherin alone positive nerve fibers within the smooth muscle layer, equol effectively attenuated this decline.

Conclusions

Equol reduces lipid peroxidation and smooth muscle layer fibrosis in the bladder and exhibited neuroprotective effects on bladder nerves (peripheral nerves) and prevented the development of bladder dysfunction associated with BOO in rats. Consumption of equol is promising for the prevention of OAB associated with BOO.
Forecasting Inflation with the New Keynesian Phillips Curve: Frequencies Matter*
Authors: Martins Manuel M. F. , Verona Fabio
Published: May 2024

We forecast US inflation with a new Keynesian Phillips curve (NKPC) in the frequency domain. Our method consists of decomposing the time series of inflation and its NKPC predictors into several frequency bands, forecasting separately each frequency component of inflation, and then summing up those forecasts to obtain the forecast for aggregate inflation. We find that (i) accurately forecasting the low frequency of inflation is, on average, crucial to successfully forecast inflation; (ii) our NKPC low‐frequency forecast model consistently and significantly outperforms the time‐series NKPC and standard benchmark models; (iii) the low frequencies of inflation expectations and unemployment are the key predictors; and (iv) optimally switching on / off the forecasts of each frequency components of inflation at each period allows to outstandingly track inflation and show that all frequencies of inflation matter.
Peritendinous Submembrane Access Technique for Management of Acute Ruptures of the Achilles Tendon: A Retrospective Study of 249 Cases
Authors: Huang Xin , Liu Jia‐Wei , Jiang Yu , Zhu Hong‐Wei , Hu Xing‐Xing , Wu Ke‐Jian , Wang Xiao‐Ning , Zhang Shuai
Published: May 2024

Objective

Percutaneous repair is an alternative to open surgical repair of the Achilles tendon with comparable, functional results and low re‐rupture and infection rates; however, sural nerve injury is a known complication. The purpose of this study is to design a new surgical procedure, the minimally invasive peritendinous submembrane access technique (MIS‐PSAT). It offers optimal results, with excellent functional outcomes, and with minimal soft tissue complications and sural nerve injury.

Methods

This retrospective study included 249 patients with acute closed Achilles tendon ruptures treated at our institution between 2009 and 2019. All patients underwent MIS‐PSAT at our institution and were followed up for 8–48 months. Functional evaluation was based on the Achilles tendon total rupture score (ATRS) and the American Orthopedic Foot and Ankle Society Ankle‐Hindfoot Scale (AOFAS‐AHS), associated with local complications and isokinetic tests.

Results

None of the patients had infection, necrosis, or sural nerve injury. Re‐rupture occurred in two cases. The average times to return to work and sports was 10.4 and 31.6 weeks, respectively. The average ATRS and AOFAS‐AHS scores were 90.2 and 95.7, respectively, with an excellent rate of 99.5%. Isokinetic tests showed that ankle function on the affected side was comparable with that on the healthy side (p > 0.05).

Conclusion

The MIS‐PSAT for acute Achilles tendon rupture is easy to perform with few complications. Importantly, the surgical technique reduces the risk of sural nerve injuries. Patients have high postoperative satisfaction, low re‐rupture rates, and muscle strength, and endurance can be restored to levels similar to those on the healthy side.
Occurrence and molecular characterization of Diaporthe eres causing stem canker on sweet cherry trees (Prunus avium) in northern China
Authors: Dai Qidong , Zhang Qijing , He Mingli , Ai Jiayin , Cai Feng
Published: May 2024

Sweet cherry (Prunus avium) is a commercially important species in China, experiencing a rapid increase in production. In June 2022, a severe infection, affecting more than 8% of sweet cherry trees, was observed on the Tetian cultivar in a 2–3‐year‐old orchard in Dalian City, northern China. Initially, spindle‐shaped brown disease spots formed on the surfaces of the branches. These spots continued to spread and merge, and the middle portion of the cankers sunk inward and gradually dried. Small black particles were found on the surface of the stems. The disease spread was more prevalent during the rainy season, leading to the withering of numerous branches and the death of the whole plant. Seven isolates, named lncy1‐1, lncy4‐1, lncy5‐1, lncy6‐1, lncy7‐1, lncy8‐1 and lncy9‐1, were obtained from 24 disease samples. Phylogenetic analysis based on three loci (rDNA ITS, TEF1 and TUB2) coupled with morphological identification confirmed that these seven isolates belong to Diaporthe eres. A representative isolate, lncy1‐1, was inoculated onto sweet cherry branches in a controlled environment, and showed that the isolate lncy1‐1 was pathogenic. The fungus isolated from diseased tissues was identified as D. eres based on morphological and molecular criteria. To the best of our knowledge, this is the first report of stem canker in sweet cherry caused by D. eres in China, which will promote disease management and expand the known host range of D. eres.
Protein Detection and Localization in Plant Cells Using Spot‐Tagging
Authors: Mentzelopoulou Andriani , Liu Chen , Moschou Panagiotis Nikolaou
Published: May 2024

Fluorescent labelling of proteins enables the determination of their spatiotemporal localization but, sometimes, it can perturb their activity, native localization, and functionality. Spot‐tag is a12‐amino acid peptide recognized by a single–domain nanobody and could potentially resolve the issues associated with large fluorescence tags due to its small size. Here, using as an example the microtubule motor CENTROMERIC PROTEIN E–RELATED KINESIN 7.3 (KIN7.3), we introduce the spot–tag for protein labelling in fixed and living plant cells. Spot–tagging and detection by an anti‐spot nanobody of ectopically expressed KIN7.3 did not interfere with its native localization. Most importantly, our spot‐tagging pipeline facilitated the localization of KIN7.3 much more rapidly and likely accurately than labelling with large fluorescent proteins or even immunolocalization approaches. We should, though, note some limitations we have not resolved yet. Spot–tagging is functional only in fixed cells; it is available only as two fluorophores and may create a noisy background during imaging. However, we foresee that, besides the limitations of this method, spot‐tagging will apply to many proteins, offsetting activity perturbations and low photon quantum yields of other protein‐tagging approaches.
Managing coopetitive innovation: sharing while protecting knowledge in separated project teams
Authors: Le Roy Frédéric , Fernandez Anne‐Sophie , Po‐Chang Lin
Published: May 2024

Existing research on coopetition acknowledges the dilemma companies face regarding sharing and protecting knowledge when developing coopetitive product innovation. To manage this dilemma, coopetitors can rely on two different organizational designs: the coopetitive project team (CPT) or the separated project team (SPT). The CPT fosters high knowledge sharing but creates uncertainty about knowledge protection. In contrast, the SPT limits the knowledge sharing but offers higher knowledge protection. While the CPT design has been studied in‐depth, the SPT design remains an underexplored black box. We know little about how knowledge is shared and protected within the SPT. To fill this gap, we conducted an ethnographic case study of a joint innovation project using SPT in the Chinese electric car industry. Our research shows how the SPT design manages the necessary knowledge sharing while protecting the knowledge. The project managers facilitate knowledge sharing by acting as the interface coordinator with the coopetitor, and the knowledge protection is guaranteed by a strict separation between the two coopetitors' operators. In SPT, the nature and the management of knowledge flows are not rigid but evolve according to the project stage.
Understanding Human Cognition Through Computational Modeling
Authors: Hsiao Janet Hui‐wen
Published: May 2024

One important goal of cognitive science is to understand the mind in terms of its representational and computational capacities, where computational modeling plays an essential role in providing theoretical explanations and predictions of human behavior and mental phenomena. In my research, I have been using computational modeling, together with behavioral experiments and cognitive neuroscience methods, to investigate the information processing mechanisms underlying learning and visual cognition in terms of perceptual representation and attention strategy. In perceptual representation, I have used neural network models to understand how the split architecture in the human visual system influences visual cognition, and to examine perceptual representation development as the results of expertise. In attention strategy, I have developed the Eye Movement analysis with Hidden Markov Models method for quantifying eye movement pattern and consistency using both spatial and temporal information, which has led to novel findings across disciplines not discoverable using traditional methods. By integrating it with deep neural networks (DNN), I have developed DNN+HMM to account for eye movement strategy learning in human visual cognition. The understanding of the human mind through computational modeling also facilitates research on artificial intelligence's (AI) comparability with human cognition, which can in turn help explainable AI systems infer humans’ belief on AI's operations and provide human‐centered explanations to enhance human−AI interaction and mutual understanding. Together, these demonstrate the essential role of computational modeling methods in providing theoretical accounts of the human mind as well as its interaction with its environment and AI systems.
Milnor–Wood inequality for klt varieties of general type and uniformization
Authors: Costantini Matteo , Greb Daniel
Published: May 2024

We generalize the definition of the Toledo invariant for representations of fundamental groups of smooth varieties of general type due to Koziarz and Maubon to the context of singular klt varieties, where the natural fundamental groups to consider are those of smooth loci. Assuming that the rank of the target Lie group is not greater than two, we show that the Toledo invariant satisfies a Milnor–Wood‐type inequality and we characterize the corresponding maximal representations.
Iwahori‐metaplectic duality
Authors: Brubaker Ben , Buciumas Valentin , Bump Daniel , Gustafsson Henrik P. A.
Published: May 2024

We construct a family of solvable lattice models whose partition functions include ‐adic Whittaker functions for general linear groups from two very different sources: from Iwahori‐fixed vectors and from metaplectic covers. Interpolating between them by Drinfeld twisting, we uncover unexpected relationships between Iwahori and metaplectic Whittaker functions. This leads to new Demazure operator recurrence relations for spherical metaplectic Whittaker functions. In prior work of the authors it was shown that the row transfer matrices of certain lattice models for spherical metaplectic Whittaker functions could be represented as ‘half‐vertex operators’ operating on the ‐Fock space of Kashiwara, Miwa and Stern. In this paper the same is shown for all the members of this more general family of lattice models including the one representing Iwahori Whittaker functions.
Poner el cuerpo: Beya (le viste la cara a Dios) como una genealogía de resistencia feminista en la Argentina del Siglo XX
Authors: Venturini María Ximena
Published: May 2024

Este artículo estudia la novela gráfica Beya (le viste la cara a Dios) (2013) de Iñaki Echeverría y Gabriela Cabezón Cámara, la cual narra el secuestro y la prostitución forzada de una mujer en el llamado conurbano bonaerense, en Argentina. El secuestro de la protagonista Beya se leerá a partir del concepto romano de homo sacer, tal y como señaló Giorgio Agamben en su obra homónima, el cual, en el mundo antiguo, representaba una vita nuda (‘vida desnuda’). Además, se analiza de qué manera la novela gráfica representa al cuerpo femenino como un espacio de resistencia y de contestación política ante el sistema patriarcal.
Orbital mechanics with the Global Positioning System
Authors: Baird William H. , Patton Kelly R.
Published: May 2024

The recent availability of relatively inexpensive dual-frequency receivers for signals from Global Navigation Satellite Systems (GNSS) provides access to ultra-precise, real-time data such as positions and velocities of dozens of satellites orbiting the Earth. We discuss how these data can be obtained, processed, and analyzed either with or without the actual purchase of a GNSS receiver. The positional information can be used to verify Kepler's three laws at lowest order as well as to reveal the presence of higher-order perturbations such as the oblateness of the Earth and the gravitational influences of the Sun and Moon on these satellites. The supplementary material includes both introductory laboratory exercises and Python scripts used to gather and process data suitable for intermediate courses.
Dynamics of a bouncing capsule: An impulse model vs a Hertzian model
Authors: Li Xinrui , Chen Guangyuan , Tee Ren Jie , Liu Jie Xu , Ong Christopher
Published: May 2024

A capsule-shaped object, unlike a sphere, can rebound to a higher height than it is dropped from if it has an initial spin. In this paper, we compare two quantitative models of this phenomenon: an impulse-based analytic model and a force-based Hertzian model. We experimentally studied the effects of impact angular velocity and contact angle on the capsule's rebounding velocity and angular velocity. Our experimental findings showed successful agreement with our Hertzian model but not with our impulse model. We attribute the comparative success of the Hertzian model to its intricate treatment of the slip–stick behavior of friction during the collision.
Mutual inductance between an infinite solenoid and a surrounding loop—A paradox resolved
Authors: Malcolm Ian C
Published: May 2024

Students may calculate the mutual inductance between an infinite solenoid and a surrounding circular loop using an incorrect method that yields the correct answer, causing frustration and confusion. A physical explanation for the agreement of the two methods is provided that is based on the translational symmetry of the solenoid. As a consequence, the conclusion generalizes to infinite uniform solenoids of arbitrary cross section.
A nuclear genome assembly of an extinct flightless bird, the little bush moa
Authors: Edwards Scott V. , Cloutier Alison , Cockburn Glenn , Driver Robert , Grayson Phil , Katoh Kazutaka , Baldwin Maude W. , Sackton Timothy B. , Baker Allan J.
Published: May 2024

We present a draft genome of the little bush moa (
Anomalopteryx didiformis
)—one of approximately nine species of extinct flightless birds from Aotearoa, New Zealand—using ancient DNA recovered from a fossil bone from the South Island. We recover a complete mitochondrial genome at 249.9× depth of coverage and almost 900 megabases of a male moa nuclear genome at ~4 to 5× coverage, with sequence contiguity sufficient to identify more than 85% of avian universal single-copy orthologs. We describe a diverse landscape of transposable elements and satellite repeats, estimate a long-term effective population size of ~240,000, identify a diverse suite of olfactory receptor genes and an opsin repertoire with sensitivity in the ultraviolet range, show that the wingless moa phenotype is likely not attributable to gene loss or pseudogenization, and identify potential function-altering coding sequence variants in moa that could be synthesized for future functional assays. This genomic resource should support further studies of avian evolution and morphological divergence.
Emergent tetragonality in a fundamentally orthorhombic material
Authors: Singh Anisha G. , Bachmann Maja D. , Sanchez Joshua J. , Pandey Akshat , Kapitulnik Aharon , Kim Jong Woo , Ryan Philip J. , Kivelson Steven A. , Fisher Ian R.
Published: May 2024

Symmetry plays a key role in determining the physical properties of materials. By Neumann’s principle, the properties of a material remain invariant under the symmetry operations of the space group to which the material belongs. Continuous phase transitions are associated with a spontaneous reduction in symmetry. Less common are examples where proximity to a continuous phase transition leads to an increase in symmetry. We find signatures of an emergent tetragonal symmetry close to a charge density wave (CDW) bicritical point in a fundamentally orthorhombic material, ErTe
3
, for which the two distinct CDW phase transitions are tuned via anisotropic strain. We first establish that tension along the
a
axis favors an abrupt rotation of the CDW wave vector from the
c
to
a
axis and infer the presence of a bicritical point where the two continuous phase transitions meet. We then observe a divergence of the nematic elastoresistivity approaching this putative bicritical point, indicating an emergent tetragonality in the critical behavior.
Polymer time crystal: Mechanical activation of reversible bonds by low-amplitude high frequency excitations
Authors: Heidari Maziar , Gaichies Théophile , Leibler Ludwik , Labousse Matthieu
Published: May 2024

Reversible supramolecular bonds play an important role in materials science and in biological systems. The equilibrium between open and closed bonds and the association rate can be controlled thermally, chemically, by mechanical pulling, by ultrasound, or by catalysts. In practice, these intrinsic equilibrium methods either suffer from a limited range of tunability or may damage the material. Here, we present a nonequilibrium strategy that exploits the dissipative properties of the system to control and change the dynamic properties of sacrificial and reversible networks. We show theoretically and numerically how high-frequency mechanical oscillations of very low amplitude can open or close bonds. This mechanism indicates how reversible bonds could alleviate mechanical fatigue of materials especially at low temperatures where they are fragile. In another area, it suggests that the system can be actively modified by the application of ultrasound to induce gel-fluid transitions and to activate or deactivate adhesion properties.
A mechanically robust and facile shape morphing using tensile-induced buckling
Authors: An Siqi , Cao Yajun , Jiang Hanqing
Published: May 2024

Inspired by the adaptive mechanisms observed in biological organisms, shape-morphing soft structures have emerged as promising platforms for many applications. In this study, we present a shape-morphing strategy to overcome existing limitations of the intricate fabrication process and the lack of mechanical robustness against mechanical perturbations. Our method uses tensile-induced buckling, achieved by attaching restraining strips to a stretchable substrate. When the substrate is stretched, the stiffness mismatch between the restraining strips and the substrate, and the Poisson’s effect on the substrate cause the restraining strips to buckle, thereby transforming initially flat shapes into intricate three-dimensional (3D) configurations. Guided by an inverse design method, we demonstrate the capability to achieve complicated and diverse 3D shapes. Leveraging shape morphing, we further develop soft grippers exhibiting outstanding universality, high grasping efficiencies, and exceptional durability. Our proposed shape-morphing strategy is scalable and material-independent, holding notable potential for applications in soft robotics, haptics, and biomedical devices.
Rice’s trajectory from wild to domesticated in East Asia
Authors: Zhang Jianping , Jiang Leping , Yu Lupeng , Huan Xiujia , Zhou Liping , Wang Changsheng , Jin Jianhui , Zuo Xinxin , Wu Naiqin , Zhao Zhijun , Sun Hanlong , Yu Zhaoyuan , Zhang Guoping , Zhu Jiangping , Wu Zhenlei , Dong Yajie , Fan Baoshuo , Shen Caiming , Lu Houyuan
Published: May 2024

Rice (
Oryza sativa
) serves as a staple food for more than one-third of the global population. However, its journey from a wild gathered food to domestication remains enigmatic, sparking ongoing debates in the biological and anthropological fields. Here, we present evidence of rice phytoliths sampled from two archaeological sites in China, Shangshan and Hehuashan, near the lower reaches of the Yangtze River. We demonstrate the growth of wild rice at least 100,000 years before present, its initial exploitation as a gathered resource at about 24,000 years before present, its predomestication cultivation at about 13,000 years before present, and eventually its domestication at about 11,000 years before present. These developmental stages illuminate a protracted process of rice domestication in East Asia and extend the continuous records of cereal evolution beyond the Fertile Crescent.
Reversible male contraception by targeted inhibition of serine/threonine kinase 33
Authors: Ku Angela F. , Sharma Kiran L. , Ta Hai Minh , Sutton Courtney M. , Bohren Kurt M. , Wang Yong , Chamakuri Srinivas , Chen Ruihong , Hakenjos John M. , Jimmidi Ravikumar , Kent Katarzyna , Li Feng , Li Jian-Yuan , Ma Lang , Madasu Chandrashekhar , Palaniappan Murugesan , Palmer Stephen S. , Qin Xuan , Robers Matthew B. , Sankaran Banumathi , Tan Zhi , Vasquez Yasmin M. , Wang Jian , Wilkinson Jennifer , Yu Zhifeng , Ye Qiuji , Young Damian W. , Teng Mingxing , Kim Choel , Matzuk Martin M.
Published: May 2024

Men or mice with homozygous serine/threonine kinase 33 (
STK33
) mutations are sterile owing to defective sperm morphology and motility. To chemically evaluate STK33 for male contraception with STK33-specific inhibitors, we screened our multibillion-compound collection of DNA-encoded chemical libraries, uncovered potent STK33-specific inhibitors, determined the STK33 kinase domain structure bound with a truncated hit CDD-2211, and generated an optimized hit CDD-2807 that demonstrates nanomolar cellular potency (half-maximal inhibitory concentration = 9.2 nanomolar) and favorable metabolic stability. In mice, CDD-2807 exhibited no toxicity, efficiently crossed the blood-testis barrier, did not accumulate in brain, and induced a reversible contraceptive effect that phenocopied genetic
STK33
perturbations without altering testis size. Thus, STK33 is a chemically validated, nonhormonal contraceptive target, and CDD-2807 is an effective tool compound.
The cesarean section, in context
Invisible Labor: The Untold Story of the Cesarean Section
Rachel Somerstein
Ecco, 2024. 336 pp.
Authors: Mulder Tara
Published: May 2024

A journalist confronts the often unseen elements that influence birthing practices
Medical forecasting
Authors: Topol Eric J.
Published: May 2024

“AI-Powered Forecasting” was recently on the

cover of
Science

, highlighting
a new deep learning model
for much faster and more accurate weather forecasting. Known as GraphCast, it outperformed the gold-standard system and had an accuracy of 99.7% for tropospheric predictions, the most important forecasting region that is closest to Earth’s surface. Better warnings for extreme weather events such as hurricanes and cyclones will help save lives. The parallel in medicine is forecasting specific, actionable, high risk for individuals to prevent diseases or severe acute events. But we don’t have a gold standard for predicting health outcomes. That is hopefully about to change.
Decoding the Brain
Authors: Nusinovich Yevgeniya
Published: May 2024

A cell-by-cell look at neuropsychiatric diseases
Communication breakdown
Authors: Leslie Mitch
Published: May 2024

Faulty messaging between organs could make us old
U.S. blocks funding for pandemic research group
Authors: Kaiser Jocelyn
Published: May 2024

EcoHealth Alliance mishandled grant that helped fund virus studies in China, officials say
Selective depletion of HBV-infected hepatocytes by class A capsid assembly modulators requires high levels of intrahepatic HBV core protein
Authors: Kornyeyev Dmytro , Song Zhijuan , Eng Stacey , Soulette Cameron , Ramirez Ricardo , Tang Jennifer , Yue Qin , Subramanian Raju , Zaboli Shiva , Moon Christina , Tam Jane , Brodbeck Jens , Aggarwal Abhishek , Diehl Lauri , Fletcher Simon P. , Hyrina Anastasia , Holdorf Meghan M. , Burdette Dara
Published: May 2024

Capsid assembly mediated by hepatitis B virus (HBV) core protein (HBc) is an essential part of the HBV replication cycle, which is the target for different classes of capsid assembly modulators (CAMs). While both CAM-A (“aberrant”) and CAM-E (“empty”) disrupt nucleocapsid assembly and reduce extracellular HBV DNA, CAM-As can also reduce extracellular HBV surface antigen (HBsAg) by triggering apoptosis of HBV-infected cells in preclinical mouse models. However, there have not been substantial HBsAg declines in chronic hepatitis B (CHB) patients treated with CAM-As to date. To investigate this disconnect, we characterized the antiviral activity of tool CAM compounds in HBV-infected primary human hepatocytes (PHHs), as well as in HBV-infected human liver chimeric mice and mice transduced with adeno-associated virus-HBV. Mechanistic studies in HBV-infected PHH revealed that CAM-A, but not CAM-E, induced a dose-dependent aggregation of HBc in the nucleus which is negatively regulated by the ubiquitin-binding protein p62. We confirmed that CAM-A, but not CAM-E, induced HBc-positive cell death in both mouse models via induction of apoptotic and inflammatory pathways and demonstrated that the degree of HBV-positive cell loss was positively correlated with intrahepatic HBc levels. Importantly, we determined that there is a significantly lower level of HBc per hepatocyte in CHB patient liver biopsies than in either of the HBV mouse models. Taken together, these data confirm that CAM-As have a unique secondary mechanism with the potential to kill HBc-positive hepatocytes. However, this secondary mechanism appears to require higher intrahepatic HBc levels than is typically observed in CHB patients, thereby limiting the therapeutic potential.
In defense of children’s brain: reshuffling the laboratory toolbox for the diagnosis of congenital toxoplasmosis
Authors: Montoya Jose G.
Published: May 2024

For decades, an immunosorbent agglutination assay (ISAGA) has been considered the gold standard method for the detection of
Toxoplasma gondii
-specific IgM in infants for the diagnosis of congenital toxoplasmosis (CT). The Toxoplasma IgM ISAGA was consistently reported as having superior sensitivity. Unfortunately, the commercial kit for the detection of Toxoplasma IgM ISAGA will no longer be available in 2024 and alternatives will only be available at a handful of reference laboratories as in-house or laboratory-developed tests. In a recent study, S. Arkhis, C. Rouges, N. Dahane, H. Guegan, et al. (J Clin Microbiol 62:e01222-23, 2024,
https://doi.org/10.1128/jcm.01222-23
), reported that the performance of the PLATELIA Toxo IgM was comparable to that of the ISAGA method for the diagnosis of CT. A second study revealing similar results supports the PLATELIA Toxo IgM as the new gold standard for the detection of
T. gondii
-specific IgM in infants. Although the laboratory toolbox for CT diagnosis has been reshuffled successfully, it is by universally implementing all available serological and molecular tools at the earliest possible time during gestation that we can best defend children’s brain from the potential harm caused by trans-placentally transmitted
T. gondii
.
Phages enhance both phytopathogen density control and rhizosphere microbiome suppressiveness
Authors: Wang Xiaofang , Wang Shuo , Huang Mingcong , He Yilin , Guo Saisai , Yang Keming , Wang Ningqi , Sun Tianyu , Yang Hongwu , Yang Tianjie , Xu Yangchun , Shen Qirong , Friman Ville-Petri , Wei Zhong
Published: May 2024

Bacteriophages, viruses that specifically target plant pathogenic bacteria, have emerged as a promising alternative to traditional agrochemicals. However, it remains unclear how phages should be applied to achieve efficient pathogen biocontrol and to what extent their efficacy is shaped by indirect interactions with the resident microbiota. Here, we tested if the phage biocontrol efficacy of
Ralstonia solanacearum
phytopathogenic bacterium can be improved by increasing the phage cocktail application frequency and if the phage efficacy is affected by pathogen-suppressing bacteria already present in the rhizosphere. We find that increasing phage application frequency improves
R. solanacearum
density control, leading to a clear reduction in bacterial wilt disease in both greenhouse and field experiments with tomato. The high phage application frequency also increased the diversity of resident rhizosphere microbiota and enriched several bacterial taxa that were associated with the reduction in pathogen densities. Interestingly, these taxa often belonged to
Actinobacteria
known for antibiotics production and soil suppressiveness. To test if they could have had secondary effects on
R. solanacearum
biocontrol, we isolated Actinobacteria from
Nocardia
and
Streptomyces
genera and tested their suppressiveness to the pathogen
in vitro
and
in planta
. We found that these taxa could clearly inhibit
R. solanacearum
growth and constrain bacterial wilt disease, especially when combined with the phage cocktail. Together, our findings unravel an undiscovered benefit of phage therapy, where phages trigger a second line of defense by the pathogen-suppressing bacteria that already exist in resident microbial communities.

IMPORTANCE

Ralstonia solanacearum
is a highly destructive plant-pathogenic bacterium with the ability to cause bacterial wilt in several crucial crop plants. Given the limitations of conventional chemical control methods, the use of bacterial viruses (phages) has been explored as an alternative biological control strategy. In this study, we show that increasing the phage application frequency can improve the density control of
R. solanacearum
, leading to a significant reduction in bacterial wilt disease. Furthermore, we found that repeated phage application increased the diversity of rhizosphere microbiota and specifically enriched Actinobacterial taxa that showed synergistic pathogen suppression when combined with phages due to resource and interference competition. Together, our study unravels an undiscovered benefit of phages, where phages trigger a second line of defense by the pathogen-suppressing bacteria present in resident microbial communities. Phage therapies could, hence, potentially be tailored according to host microbiota composition to unlock the pre-existing benefits provided by resident microbiota.
Complete genome sequence of
Imperialibacter roseus
strain P4
T
Authors: Tizabi Daniela , Bachvaroff Tsvetan , Hill Russell T.
Published: May 2024

Imperialibacter roseus
strain P4
T
is a bacterial strain isolated from Permian groundwater. The complete genome of
Imperialibacter roseus
strain P4
T
was sequenced to reveal a single circular chromosome of 6,747,663 bp with a GC content of 46.5%.
Lactobacillus-
derived protoporphyrin IX and SCFAs regulate the fiber size via glucose metabolism in the skeletal muscle of chickens
Authors: Cai Liyuan , Wang Xinkai , Zhu Xiaoyan , Xu Yunzheng , Qin Wenxia , Ren Jing , Jiang Qin , Yan Xianghua
Published: May 2024

The gut microbiota contributes to skeletal muscle energy metabolism and is an indirect factor affecting meat quality. However, the role of specific gut microbes in energy metabolism and fiber size of skeletal muscle in chickens remains largely unknown. In this study, we first performed cecal microbiota transplantation from Chinese indigenous Jingyuan chickens (JY) to Arbor Acres chickens (AA), to determine the effects of microbiota on skeletal muscle fiber and energy metabolism. Then, we used metagenomics, gas chromatography, and metabolomics analysis to identify functional microbes. Finally, we validated the role of these functional microbes in regulating the fiber size via glucose metabolism in the skeletal muscle of chickens through feeding experiments. The results showed that the skeletal muscle characteristics of AA after microbiota transplantation tended to be consistent with that of JY, as the fiber diameter was significantly increased, and glucose metabolism level was significantly enhanced in the pectoralis muscle.
L. plantarum
,
L. ingluviei
,
L. salivarius,
and their mixture could increase the production of the microbial metabolites protoporphyrin IX and short-chain fatty acids, therefore increasing the expression levels of genes related to the oxidative fiber type (
MyHC SM
and
MyHC FRM
), mitochondrial function (
Tfam
and
CoxVa
), and glucose metabolism (
PFK
,
PK
,
PDH
,
IDH
, and
SDH
), thereby increasing the fiber diameter and density. These three
Lactobacillus
species could be promising probiotics to improve the meat quality of chicken.

IMPORTANCE

This study revealed that the
L. plantarum, L. ingluviei
, and
L. salivarius
could enhance the production of protoporphyrin IX and short-chain fatty acids in the cecum of chickens, improving glucose metabolism, and finally cause the increase in fiber diameter and density of skeletal muscle. These three microbes could be potential probiotic candidates to regulate glucose metabolism in skeletal muscle to improve the meat quality of chicken in broiler production.
Strigolactones shape the assembly of root-associated microbiota in response to phosphorus availability
Authors: Chen Pubo , Huang Pingliang , Yu Haiyang , Yu Huang , Xie Weicheng , Wang Yuehua , Zhou Yu , Chen Li , Zhang Meng , Yao Ruifeng
Published: May 2024

Plants rely on strigolactones (SLs) to regulate their development and form symbiotic relationships with microbes as part of the adaptive phosphorus (P) efficiency strategies. However, the impact of SLs on root-associated microbial communities in response to P availability remains unknown. Here, root microbiota of SL biosynthesis (
max3-11
) and perception (
d14-1
) were compared to wild-type Col-0 plants under different P concentrations. Using high-throughput sequencing, the relationship between SLs, P concentrations, and the root-associated microbiota was investigated to reveal the variation in microbial diversity, composition, and interaction. Plant genotypes and P availability played important but different roles in shaping the root-associated microbial community. Importantly, SLs were found to attract
Acinetobacter
in low P conditions, which included an isolated CP-2 (
Acinetobacter soli
) that could promote plant growth in cocultivation experiments. Moreover, SLs could change the topologic structure within co-occurrence networks and increase the number of keystone taxa (e.g., Rhizobiaceae and Acidobacteriaceae) to enhance microbial community stability. This study reveals the key role of SLs in mediating root-associated microbiota interactions.

IMPORTANCE

Strigolactones (SLs) play a crucial role in plant development and their symbiotic relationships with microbes, particularly in adapting to phosphorus levels. Using high-throughput sequencing, we compared the root microbiota of plants with SL biosynthesis and perception mutants to wild-type plants under different phosphorus concentrations. These results found that SLs can attract beneficial microbes in low phosphorus conditions to enhance plant growth. Additionally, SLs affect microbial network structures, increasing the stability of microbial communities. This study highlights the key role of SLs in shaping root-associated microbial interactions, especially in response to phosphorus availability.
Supplemental Material: High-pressure, low-temperature metamorphism preserved in the Indus-Yarlung suture zone of the eastern Himalaya: Overprinting at amphibolite facies and comparison with occurrences in the western Himalaya
Authors: Li Wangchao , Yin Changqing , et al.
Published: May 2024

Description of supplemental figure, analytical and phase equilibria modeling methods.
Supplemental Material: High-pressure, low-temperature metamorphism preserved in the Indus-Yarlung suture zone of the eastern Himalaya: Overprinting at amphibolite facies, and comparison with occurrences in the western Himalaya
Authors: Li Wangchao , Yin Changqing , et al.
Published: May 2024

Description of supplemental figure, analytical and phase equilibria modeling methods.
Popliteal venous access for renal replacement therapy in a critically ill patient with central access failure
Authors: Hamed Muhanad Omer , Abdelmagid Mohanad , Ahmed Mohannad
Published: May 2024

A woman in her 80s was admitted to the emergency department with an acute infective exacerbation of chronic obstructive pulmonary disease and type 2 respiratory failure, culminating in cardiac arrest for 2 min. She was successfully resuscitated, connected to a mechanical ventilator and subsequently transferred to the intensive care unit. Later in her hospital stay, the patient underwent a tracheostomy following prolonged intubation.

During this period, she developed septic shock with complications, including acute kidney injury, metabolic acidosis and volume overload. As a result, the nephrologist recommended emergency haemodialysis. Initially, a left femoral haemodialysis catheter was established but had to be withdrawn a few days later due to the development of deep vein thrombosis (DVT). A left internal jugular catheter was then inserted but was removed after 5 days due to another DVT. It was subsequently replaced with a central line for vasopressor support.

A Doppler scan revealed a large thrombus in the right internal jugular vein, extending to the area just above the superior vena cava. A similar thrombus was detected in the left internal jugular vein, with weak blood flow observed in both the right and left subclavian veins. Although the subclavian vein flows were deemed adequate, there was unsatisfactory blood flow through the catheter after insertion, rendering it unsuitable for haemodialysis.

Due to an earlier central line-related infection, the right femoral site exhibited signs of infection and the presence of a pus pocket, making it unsuitable for haemodialysis access. To address this, the right popliteal vein was chosen for catheterisation using a 20-cm, 12 French catheter, the longest available catheter in the country at the time. The patient was placed in a prone position, and the catheter was smoothly inserted with ultrasound guidance, resulting in good flow. Subsequent haemodialysis sessions were carried out regularly.
Epidural analgesia during labour and severe maternal morbidity: population based study
Authors: Kearns Rachel J , Kyzayeva Aizhan , Halliday Lucy O E , Lawlor Deborah A , Shaw Martin , Nelson Scott M
Published: May 2024

Objectives

To determine the effect of labour epidural on severe maternal morbidity (SMM) and to explore whether this effect might be greater in women with a medical indication for epidural analgesia during labour, or with preterm labour.

Design

Population based study.

Setting

All NHS hospitals in Scotland.

Participants

567 216 women in labour at 24+0 to 42+6 weeks’ gestation between 1 January 2007 and 31 December 2019, delivering vaginally or through unplanned caesarean section.

Main outcome measures

The primary outcome was SMM, defined as the presence of ≥1 of 21 conditions used by the US Centers for Disease Control and Prevention (CDC) as criteria for SMM, or a critical care admission, with either occurring at any point from date of delivery to 42 days post partum (described as SMM). Secondary outcomes included a composite of ≥1 of the 21 CDC conditions and critical care admission (SMM plus critical care admission), and respiratory morbidity.

Results

Of the 567 216 women, 125 024 (22.0%) had epidural analgesia during labour. SMM occurred in 2412 women (4.3 per 1000 births, 95% confidence interval (CI) 4.1 to 4.4). Epidural analgesia was associated with a reduction in SMM (adjusted relative risk 0.65, 95% CI 0.50 to 0.85), SMM plus critical care admission (0.46, 0.29 to 0.73), and respiratory morbidity (0.42, 0.16 to 1.15), although the last of these was underpowered and had wide confidence intervals. Greater risk reductions in SMM were detected among women with a medical indication for epidural analgesia (0.50, 0.34 to 0.72) compared with those with no such indication (0.67, 0.43 to 1.03; P<0.001 for difference). More marked reductions in SMM were seen in women delivering preterm (0.53, 0.37 to 0.76) compared with those delivering at term or post term (1.09, 0.98 to 1.21; P<0.001 for difference). The observed reduced risk of SMM with epidural analgesia was increasingly noticeable as gestational age at birth decreased in the whole cohort, and in women with a medical indication for epidural analgesia.

Conclusion

Epidural analgesia during labour was associated with a 35% reduction in SMM, and showed a more pronounced effect in women with medical indications for epidural analgesia and with preterm births. Expanding access to epidural analgesia for all women during labour, and particularly for those at greatest risk, could improve maternal health.