Browse Articles

Exploratory associations between radiographic findings and metadata-derived proxies of 90-day follow-up in 112,120 ChestX-ray14 radiographs

Abstract Chest radiography is widely used as an initial imaging modality. However, how specific findings relate to subsequent care or follow-up actions remains unclear. Prior studies have rarely examined follow-up actions, and potential sex-specific differences have been understudied. We analyzed 112,120 frontal chest radiographs from the NIH ChestX-ray14 dataset (63,340 male, 48,780 female). Images were labeled with 14 findings using a natural language processing (NLP) pipeline applied to reports. We modeled a metadata-derived proxy of 90-day follow-up using logistic regression, including sex-stratified analyses and interaction testing, with models adjusted for sex. Robustness was assessed through sensitivity analyses (30/60/180-day windows), patient-level clustering, and false discovery rate (FDR) adjustment. The strongest associations with proxy follow-up were observed for pulmonary edema (OR 10.6, 95% CI 8.5–13.2), pneumothorax (OR 7.6, 95% CI 6.7–8.6), and pleural effusion (OR 4.0, 95% CI 3.8–4.3). Interactions between sex and specific findings were modest but reached statistical significance for atelectasis ( P  = 0.003), pneumothorax ( P  = 0.0083), and emphysema ( P  = 0.0238). Radiographic findings were associated with metadata-derived proxy follow-up, but residual confounding from unmeasured factors (e.g., age, comorbidities, clinical context) likely remains. Sex-specific effects were statistically significant but small, and not clinically meaningful. Results should therefore be interpreted strictly as hypothesis-generating signals, not as causal evidence or clinically directive guidance.

A conformal piezoelectric microsystem for demographic-adaptive and calibration-free cuffless blood pressure monitoring

Abstract Frequent recalibration poses a significant challenge to the accuracy and reliability of current cuffless blood pressure (BP) monitoring devices, especially in long-term use. Here, we introduce a conformal and stretchable piezoelectric microsystem (CSPM) combined with a demographic-adaptive BP estimation model, enabling calibration-free, continuous BP tracking with accuracy comparable to cuff-based medical devices. The CSPM integrates an ultrasound transducer array for vessel diameter waveform recording and two pulse waveform (PWF) sensors with cavity-enhanced piezoelectric thin films for precise pulse wave detection, enabling simultaneous measurement of pulse wave velocity (PWV) and vessel diameter in the same localized vascular area. Leveraging real-time PWV and vessel diameter inputs, our BP algorithm employs a demographic feature learning module for broad population applicability and a time decay compensation strategy to address minor slippage and measurement shifts, enabling the acquisition of individual BP values without calibration. This innovation effectively addresses key challenges in population recalibration and multimodal integration, enabling stable long-term continuous BP tracking, achieving mean absolute errors of 5.22 mmHg for systolic BP and 4.57 mmHg for diastolic BP.

TGFBR2 coordinates the endometrial response to estrogen, regulating endometrial hyperplasia and fertility

Proper endometrial function is critical for establishing and maintaining healthy pregnancies, as well as preventing the pathogenesis of conditions such as endometrial hyperplasia and endometrial cancer. The TGFβ signaling pathway regulates key aspects of endometrial biology, although the direct effects of many individual receptors remain unstudied. In this study, we characterize the role of TGFβR2 within the endometrium using a progesterone receptor-cre conditional knock-out mouse model ( Tgfbr2 flox/flox ; Pg r cre/+ ; “ Tgfbr2 cKO”). We found that conditional deletion of TGFβR2 resulted in female infertility, endometrial hyperplasia, altered estrogen and progesterone response, and, only in bred females, reproductive tract tumors. Pregnancy abnormalities in these females began in the prereceptive and implantation stages and compounded throughout gestation, presenting errors in decidualization, immune cell invasion, and early spiral artery formation. Tgfbr2 cKO females had endometrial epithelial hyperplasia at 13 to 14 wk of age, with a significant and region-specific reduction in glandular FOXA2 expression. While this hyperplasia did not advance to malignancy in virgin females, Tgfbr2 cKO females continuously bred for 6 mo all presented with reproductive tract tumors at the time of collection. Mechanistically, we show signaling via TGFβR2 attenuates estrogen signaling while bolstering progesterone signaling in the endometrial epithelium. By integrating ER and SMAD4 genome-wide binding studies with transcriptomic datasets, we demonstrate that both ER and SMAD4 are required for Pgr transcription. In this study, we highlight the importance of TGFβR2 in endometrial function and female fertility and shed light on the potential involvement of TGFβ signaling in estrogen and progesterone response regulation during early pregnancy.

Aberration corrections for quasi-conformal transformation optics-based reflectors

Abstract Efficiency limitations of flat reflector antennas designed using quasi-conformal transformation optics are examined along with mechanisms to improve performance over wide bandwidths (> 2.5:1). Specifically, the aperture efficiency constraints are shown to be a result of phase aberrations induced by the approximate nature of the quasi-conformal transformation used to create an isotropic, non-magnetic structure. The aberrations are drastically reduced by introducing a simple curved surface into the domain prior to the transformation. This technique noticeably improves performance without increasing the size of the resulting device. Ultimately, this methodology allows for flat reflectors designed via quasi-conformal transformation optics to operate over wider bandwidths (up to 10:1) than with standard transformations.

Hydrothermal alteration of Ryugu from a disruptive impact recorded in a returned sample

Abstract Samples returned from C-type asteroid (162173) Ryugu by JAXA’s Hayabusa2 spacecraft provide material free of terrestrial alteration for analysis. Previous work shows that Ryugu was aqueously altered below 100 °C under neutral to alkaline fluid conditions. Such low-temperature alteration was unexpected based on spacecraft observations which indicated that Ryugu’s surface may be thermally altered. Here we show that sulfides in a single particle (A0016) returned by the Hayabusa2 mission are unlike any previously described from Ryugu. The presence and compositions of violarite, pyrite, chalcopyrite, pentlandite, and Fe-depleted pyrrhotite grains provide direct evidence for hydrothermal alteration between 230 to 400 °C under highly oxidizing and acidic fluid conditions. We hypothesize that A0016 was near to the site of a large impact that disrupted Ryugu’s precursor parent body.

Machine learning enables de novo multiepitope design of <i>Plasmodium falciparum</i> circumsporozoite protein to target trimeric L9 antibody

Currently approved vaccines for the prevention of malaria provide only partial protection against disease due to high variability in the quality of induced antibodies. These vaccines present the unstructured central repeat region, as well as the C-terminal domain, of the circumsporozoite protein ( Pf CSP) of the malaria parasite, Plasmodium falciparum [K. L. Williams et al ., Nat. Med. 30 ,1–13 (2024)]. A recently discovered protective monoclonal antibody, L9, recognizes three structured copies of the Pf CSP minor repeat. Similarly to other highly potent antimalarial antibodies, L9 relies on critical homotypic interactions between antibodies for its high protective efficacy [P. Tripathi et al. , Structure 31 , 480–491.e4 (2023); G. M. Martin et al. , Nat. Commun. 14 ,2815 (2023)]. Here, we report the design of antigens scaffolding one copy of Pf CSP’s minor repeat capable of binding L9. To design antigens capable of presenting multiple, structure-based epitopes in one scaffold, we developed a machine learning– driven structural antigen design pipeline, MESODID, tailored to focus on multiepitope vaccine targets. We use this pipeline to design multiple scaffolds that present three copies of the Pf CSP minor repeat. A 3.6 Å cryo-EM structure of our top design, minor repeat targeting immunogen (M-TIM), demonstrates that M-TIM successfully orients three copies of L9, effectively recapitulating its critical homotypic interactions. The wide prevalence of repeated epitopes in key vaccine targets, such as HIV-1 Envelope, SARS-CoV-2 spike, and Influenza Hemagglutinin, suggests that MESODID will have broad utility in creating antigens that incorporate such epitopes, offering a powerful approach to developing vaccines against a range of challenging infections, including malaria.

Application of SBR-MFC process in wastewater treatment at high-altitude areas of Xizang: research on MPC voltage boosting and stabilization strategies

Geminin inhibits DNA replication licensing by sterically blocking CDT1-MCM2 interactions

Abstract DNA replication is tightly regulated to occur once per cell cycle, with the MCM2-7 helicase loaded onto replication origins only during G1-phase. In higher eukaryotes, geminin negatively regulates this process during S-, G2- and M-phases by binding the essential licensing factor CDT1. Although geminin’s function is crucial for genomic stability, its inhibitory mechanism remains elusive. Here, we utilise a fully reconstituted human DNA replication licensing assay to dissect geminin’s role. AlphaFold modelling provides structural insights into an N-terminal CDT1-binding helix of geminin, which proves essential for inhibition. Structural docking of the CDT1-geminin complex into the ORC-CDC6-CDT1-MCM2-7 (OCCM) assembly shows that geminin’s long coiled-coil domain sterically clashes with the MCM2 C-terminus, rather than directly blocking CDT1 binding to ORC-CDC6-MCM2-7. Shortening the coiled-coil preserves geminin dimerisation and CDT1 binding but abolishes inhibition, confirming its mechanistic role. Surprisingly, geminin is not able to fully inhibit DNA licensing. However, CDK1/2-cyclin A can partially inhibit DNA licensing and, in conjunction with geminin, result in a complete block. These findings uncover geminin’s steric inhibitory mechanism and suggest that a dual CDK-geminin axis controls human DNA replication.

Torque-generating units of the bacterial flagellar motor are rotary motors

Escherichia coli swims using helical flagellar filaments driven at their base by a rotary motor. Torque-generating “stator” units drive the bacterial flagellar motor by transmitting mechanical power to a cytoplasmic “rotor,” the C-ring. Each stator unit is a proton-conducting heteromer. A central dimer of two MotB proteins anchors to the cell wall. A surrounding pentamer of five MotA proteins transmits mechanical power to the C-ring. This asymmetrical 5:2 structure is consistent with rotation as the mechanism of torque generation. Here, we test the hypothesis that the MotA 5 MotB 2 stator units are rotary motors themselves and interact with the rotor like intermeshed gearwheels, where rotation of the C-ring is directly coupled to MotA 5 rotation around the MotB 2 . We used in vivo polarized photobleaching microscopy. When a subset of fluorescent domains inside a multimer is rapidly photobleached by a strong pulse of polarized light, the induced polarization-dependent fluorescence of unbleached domains becomes a reporter of angular orientation. We applied polarized photobleaching microscopy to tethered cells rotating by single flagellar motors. We probed fluorescently labeled MotA pentamer and MotB dimer calibrated to motor rotation. The MotB dimer rotates at the same angular speed as the cell body, consistent with its anchor to the cell wall. The MotA pentamer rotates ∼ 6.2 × faster than the flagellar motor, revealing the gear ratio between stator and rotor.

Colloidal stability and controlled release of Au@SiO₂ and Ag@SiO₂ core–shell nanostructures from biopolymer-based hydrogels

Gate tuning of coupled electronic and structural phase transition in atomically thin Ta2NiSe5

Correction for Yuan et al., Oil–water interfaces drive gold precipitation via microdroplet chemistry in thermal geological systems

Surrogate measurement of traffic safety with insights from pavement condition, sensor fusion, and machine learning

Fragment-based discovery enables direct targeting of the melanoma oncogene MITF

Oxidative pentose phosphate pathway is required for T cell activation and antitumor immunity

Glucose is catabolized by two major metabolic pathways, glycolysis and the oxidative pentose phosphate pathway (oxPPP). The oxPPP generates nicotinamide adenine dinucleotide phosphate (NADPH) at two steps, glucose-6-phosphate dehydrogenase (G6PD), the most common enzyme deficiency in humans, and 6-phosphogluconate dehydrogenase (PGD). Previous literature suggests that G6PD supports but PGD limits T cell–mediated immunity. Here, we use T cell–specific knockout mouse models to show that both enzymes are required for antitumor immunity and response to immunotherapy. PGD knockout depletes mature T cells systemically, while G6PD loss does not reduce basal T cell populations but results in apoptosis upon activation. Such apoptosis is not reversed by major downstream products of the oxPPP, including antioxidants, nucleosides, or fatty acids. Instead, T cells are partially rescued by removal of media cystine, whose reduction requires NADPH. G6PD loss induces an oxidative stress response that upregulates cystine import, which together with low NADPH leads to fatal disulfide stress. Overall, these results highlight an essential role for the oxidative pentose phosphate pathway in cystine homeostasis and T cell–mediated immunity.

Effect of neuromuscular electrical stimulation on diastasis recti abdominis

Multimodal mass spectrometry imaging for plaque- and region-specific neurolipidomics in Alzheimer’s disease mouse models

Correction for Sachdev et al., Reversal of <i>C9orf72</i> mutation-induced transcriptional dysregulation and pathology in cultured human neurons by allele-specific excision

Dynamic vehicular channel characteristics analysis and TDL modeling in different scenarios

Prime editing of the β1 adrenoceptor in the brain restores physiological REM sleep in a mouse model of Alzheimer’s disease

Abstract Prime editing offers versatile genome modifications with therapeutic potential; yet its use to modulate neural circuitry remains underexplored. Here, we used adeno-associated viral vectors to deliver prime editors into the mouse brain and introduced the naturally occurring Adrb1 A187V variant of the β1-adrenergic receptor, linked to short sleep in humans and mice. Editing reached up to 28.1% in the cortex six months after intracerebroventricular injection and increased excitability of β1-noradrenergic neurons. This enhanced wake-associated behaviors, including home cage activity, locomotion, exploration, and recognition memory, while reducing slow wave activity (SWA) during non-rapid eye movement (NREM) sleep indicating reduced build-up of sleep pressure during active phases. In a mouse model of Alzheimer’s disease, Adrb1 A187V installation restored physiological REM sleep and again reduced NREM sleep SWA following spontaneous activity. Together, these findings demonstrate the feasibility of prime editing for reprogramming genetic circuits in the brain and reveal beneficial effects of the Adrb1 A187V variant on activity and sleep regulation.