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The atrocities committed by the Israeli government in Gaza have included the killing of nearly 2 000 health workers and tens of thousands of Palestinian civilians. Gaza's health workers deserve universal praise for their unwavering dedication to this population suffering under theIsraeli invader. The World Medical Association and the entire medical community have remained silent or have taken insufficientpositionsin support of these selfless individuals, and have.
Manual segmentation of the whole anterior visual pathway (aVP) from high-resolution magnetic resonance imaging (MRI) is time-consuming and prone to inter-rater variability. We developed and validated a fully automated deep learning framework, "aVP-seg," to perform rapid, multiclass segmentation of the optic nerves, chiasm, and optic tracts in healthy volunteers and multiple sclerosis (MS) patients. We developed and validated a cascaded two-stage three-dimensional convolutional neural network (principal segmentation + refinement) for automated multiclass segmentation of the aVP from 0.6-mm isotropic three-dimensional constructive interference in steady state (CISS) MRI. The model was trained and evaluated in 34 healthy controls and 46 MS patients. Ground truth was derived from manual segmentations by two expert radiologists. Spatial agreement metrics included Dice similarity coefficient (DSC), 95th percentile Hausdorff distance (HD95), and volumetric similarity. Agreement with the ground truth for the whole aVP was high (DSC 0.86 ± 0.03, mean ± standard deviation; 95% confidence interval (CI) 0.85-0.86). Boundary alignment was strong (HD95 1.18 mm ± 0.54; 95% CI 1.06-1.30) and volumetric similarity was high (0.96 ± 0.04; 95% CI 0.95-0.97). Accuracy was consistent for the left and right optic nerves (DSC 0.85-0.86 ± 0.05-0.04) and chiasm (DSC 0.83 ± 0.09), but lower for the left and right optic tracts (DSC 0.74-0.75 ± 0.07-0.07). The aVP-seg provided accurate, automated multiclass segmentation of the whole aVP from high-resolution CISS MRI. This tool may standardize and accelerate the extraction of quantitative biomarkers of aVP integrity in neuro-ophthalmic conditions. Automated multiclass segmentation of the entire anterior visual pathway enables standardized and reproducible preparation of MRI data for quantitative analysis. This approach facilitates future assessment of optic pathway involvement in MS and other neuro-ophthalmic disorders. aVP-seg enabled fully automated segmentation of the entire anterior visual pathway from high-resolution CISS MRI data. Automated segmentation reduces processing time and operator-dependent variability. aVP-seg shows robust performance across both healthy subjects and MS patients.
Conventional in vitro fertilization (IVF) outcome prediction is limited by static, single-endpoint analyses. We aimed to overcome this by using a multistate model to dissect the stage-specific and, crucially, the non-linear influence of endocrine factors across the entire pregnancy continuum in a large-scale cohort. We applied multistate regression models to a large cohort of 12,674 women undergoing their first fresh IVF cycle. This advanced method allowed us to analyze three sequential transitions (from infertility to biochemical pregnancy, from biochemical pregnancy to clinical pregnancy, and ultimately to live birth) and test for non-linear effects of baseline hormones, including anti-Müllerian hormone (AMH), luteinizing hormone (LH), and antral follicle count (AFC), on the hazard of success at each stage. The principal finding was a significant non-linear relationship between baseline AMH, LH, and AFC and pregnancy success (P < 0.05 for non-linearity). This directly challenges the "higher is better" paradigm, revealing that optimal hormonal "windows", not just maximum levels, are linked to clinical success. The multistate model further distinguished AMH and LH as robust predictors across all stages, while AFC's predictive power was confined to achieving initial pregnancy. The predictive value of baseline hormones in IVF is fundamentally non-linear. Our use of a multistate model demonstrates that while AMH and LH are consistent predictors for the entire pregnancy journey, their clinical interpretation must shift from a linear scale to identifying optimal ranges. This finding provides a more precise scientific basis to personalize ART treatment and improve live birth rates.
Real-time adaptive proton range verification systems based on produced neutrons require accurate information on their non-isotropic momentum distributions within seconds, for which general-purpose Monte Carlo (MC) methods are too computationally expensive. 
We therefore present a first study for a surrogate model based on Fourier Neural Operators (FNO) for fast prediction of angle- and energy-resolved proton transport and neutron production within proton therapy.

Approach: We treat the phantom and the proton beam's state as depth-evolving series, respectively of different materials, and of spatial, angular, and energy phase space density distributions. 
FNO models were trained to compute changes in proton distributions along with those of produced neutrons per unit of depth, and they were used auto-regressively to simulate the entire phantom.
For training and evaluation, two datasets of 47 MC simulations featuring different primary intensities were produced. Simulated geometries were extracted from a thoracic CT scan as series of laterally homogeneous materials.

Main Results: An average relative L2-norm error of 0.067 and 0.137 was achieved by the predicted proton and neutron distributions, respectively.
This corresponded to an average spatial gamma passing rate (2%, 2 mm) of 99.95% and 99.40%, and an average error in the mean of the longitudinal intensity distribution of 0.238 mm and 0.871 mm. Training with higher primary intensities improved neutron density metrics by up to 30%. 
Inference over depths of 40 cm at a resolution of 0.5 mm required on average 23.17 s per beam.

Significance: Our proton beam surrogate generates accurate phase space distributions of neutrons at MC-level accuracy within seconds, while demonstrating robust generalization with respect to irradiated geometry and beam characteristics. This first study is relevant for prototyping and operation of range verification systems and for other tasks such as neutron dose estimation, with methods being extendable to other kinds of secondary particles.
The aim of this study was to determine whether overall and time-specific patterns of hyperglycaemia, particularly soon after diagnosis, are associated with incident cancer in adults with newly diagnosed type 2 diabetes. We retrospectively analysed a territory-wide cohort of 52,926 Hong Kong Chinese people with newly diagnosed type 2 diabetes. We examined cancer risk across groups of individuals classified according to their time-weighted mean HbA1c over the entire follow-up period (n=49,978) or during specific early exposure periods (n=39,185). A weighted cumulative exposure model was used to determine the role of historical HbA1c exposures in cancer development (n=49,966). Among 49,978 individuals with newly diagnosed type 2 diabetes, 1758 cancer events occurred. Each 11 mmol/mol (1%) increase in time-weighted mean HbA1c was associated with a 27% relative higher risk of cancer at any site (HR 1.27; 95% CI 1.20, 1.33). Within the first 2 years after diagnosis, a time-weighted mean HbA1c ≥53 mmol/mol (≥7.0%) vs <53 mmol/mol (<7.0%) was associated with a 30-75% relative higher risk of cancer at any site, depending on the specific HbA1c category, even after adjusting for subsequent HbA1c. Longer durations of early exposure were associated with higher risk, reaching 51-213% in the first 5 years of exposure. Earlier high HbA1c exposures contributed more strongly to cancer risk than later exposures. A 11 mmol/mol (1%) HbA1c reduction at 1-2 years was associated with a 6% relative lower cancer risk over a hypothetical 10 year window (HR 0.94; 95% CI 0.91, 0.98), whereas reductions after 5 years showed no significant risk differences. Overall, hyperglycaemic exposure was associated with an elevated long-term cancer risk in type 2 diabetes. Notably, individuals who showed better glycaemic management soon after diagnosis exhibited a lower cancer risk than those whose glycaemic management improved later, despite comparable overall glycaemic burdens.
Gas injection is a fundamental process for hydrocarbon recovery, whereby gas is injected into the reservoir to maintain pressure and increase production of oil or gas. This study was conducted to investigate the optimization of gas injection, differentiating between the behavior of CO2 and N2, as a potential alternative to water in southern Iraqi fields (the Abu-Ghirab field, particularly) to overcome the water supply shortage as a result of climate change. Techlog, Petrel, and CMG software were utilized to examine the CO2 and N2 behaviour. The increased percentages (CO2 and N2 injection processes) in the oil production rate are 139.45 and 66.6%, respectively. The wells located near the fault section show the best water cut (approximately 18%) among all the wells. The water cut percentages are 520 and 380 for CO2 and N2 injection, respectively, pointing out that the water cut produced by the N2 injection process is higher than that of CO2 by percentage of 36.8. An acute increase in the gas-oil ratio by N2 injection (more than 40 times on average) could result. The wells far away from the fault region have the best performance of gas-oil ratio among all the wells. For the entire field, the oil production rate for the CO2 injection process shows a significant increase in both ultimate and maximum production compared to N2. This could be due to the specifications of crude oil. The sensitivity analysis of the results from CO2 injection for the Asmari formation in Abu-Ghirab for production/injection percentage and water cut shows that the water cut percentage will be acceptable during the first 9 years of the process, with concerns of economic issues due to increasing gas-oil ratio (GOR).
Exposure to microgravity is associated with stature increases, moderate-to-severe back/neck pain and elevated lumbar and cervical intervertebral disc (IVD) herniation risk post-flight. Whilst lumbar pathophysiology has been investigated, little attention has been placed on the cervical spine. Thus, the aim of this study was to determine the effect of 4 h of hyper-buoyancy flotation (HBF) and subsequent 15 min of upright 1 g exposure on stature, cervical IVD height, cervical muscle cross-sectional area (CSA) and thickness, passive cervical vertebral stiffness, and their association with stature changes and/or neck pain. To investigate this, 12 healthy volunteers (five male; 30.2 ± 7.2 years, 66.1 ± 11.7 kg, 173.4 ± 8.5 cm) participated. Stature was assessed at Pre HBF, after 4 h of supine HBF (Post HBF), and following 15 min of upright 1 g exposure (Post 1G). Cervical IVD height (C3-T1), longus colli and semispinalis cervicis CSA and thickness, passive vertebral stiffness (C2-L5), and neck pain were assessed at Pre HBF, HBF0, HBF2, HBF4 and Post 1G. Results indicated that 4 h HBF significantly increased stature (+1.6 ± 0.5 cm), which was partially reduced after acute 1 g exposure (-0.4 ± 0.3 cm). Cervical IVD height increased at all levels following HBF, with partial reversal at Post 1G, particularly in the lower cervical region. Longus colli and semispinalis cervicis CSA and thickness were unchanged. Passive vertebral stiffness significantly decreased (across the entire column and most regions) following HBF and was only partially restored after 1 g exposure. Neck pain increased during HBF and was reduced after 1 g exposure. No associations were observed between neck pain and stature or IVD changes. However, neck pain at HBF4 was positively correlated with mid-cervical vertebral stiffness (R = 0.587, P = 0.045). Overall, 4 h HBF induced mild neck pain, increased stature and cervical IVD height, all of which were partially reduced after 15 min of upright 1 g exposure. No changes in longus colli or semispinalis cervicis muscle thickness or CSA were observed. Passive cervical vertebral stiffness decreased following HBF and remained below baseline after 1 g exposure. A positive correlation between neck pain at HBF4 and mid-cervical vertebral stiffness suggests modulation of vertebral column stabilisation may contribute to symptoms. The lack of association between neck pain and IVD expansion suggests that vertebral flattening may play a role and therefore warrants direct evaluation with HBF and following spaceflight.
Hematopoietic stem cells (HSCs) housed within the bone marrow give rise to the full complement of blood and immune cells. Methods to expand HSCs ex vivo have traditionally relied on two-dimensional or liquid culture, but hydrogel approaches have been hypothesized to provide three-dimensional bone marrow-associated biophysical and biomolecular signals that may improve HSC expansion and maintenance ex vivo. Here, we describe a granular biomaterial approach to create a multicellular platform for HSC culture. By seeding HSCs amongst mesenchymal stromal cell (MSC)-laden hydrogel microspheres (microgels), we elish paracrine-mediated interactions between HSCs and hydrogel encapsulated MSCs. We provide support for the importance of microgel encapsulation for the emergence of niche-favorable MSC transcriptional profiles. We identify a common cell culture media strategy that accommodates MSC activity while avoiding the use of serum that typically induces differentiation of HSCs. We observe an MSC-density-dependent increase in maintenance of long-term repopulating HSCs in granular co-culture, and we identify significant depletion of long-term repopulating HSCs when both HSCs and MSCs are interstitially seeded in the granular matrix. Together, these findings establish a granular hydrogel co-culture model to examine the influence of MSC-HSC interactions on maintenance and expansion of HSCs in a defined three-dimensional engineered tissue. STATEMENT OF SIGNIFICANCE: Hematopoietic stem cells (HSCs) give rise to the entire blood and immune systems and are clinically relevant in the treatment of hematologic disorders. These stem cells reside primarily within bone marrow, the heterogeneity of which is difficult to capture without advances in tissue modeling approaches. HSCs are supported by a plethora of colocalized "niche" cells, including mesenchymal stromal cells (MSCs). In vitro culture of HSCs has primarily used either 2D substrates of large (bulk) hydrogels or scaffolds. This manuscript reports the use of gelatin-maleimide microgels to create a granular hydrogel co-culture to regulate multicellular interactions between HSCs and marrow-derived MSCs. This work contrasts with most granular hydrogel studies, which seed cells only within the interstitial space between particles. We show that encapsulation of MSCs within gelatin microgels forms a mosaic culture that enhances maintenance of co-cultured hematopoietic stem cells, forming a prototypical granular model of bone marrow paracrine signaling.
Mass is a defining property of particles, shaping their fundamental nature and interactions. In condensed matter systems, the effective mass of electrons has long been regarded as a key factor influencing material properties, including their transport and optical responses. In this work, we challenge this conventional wisdom by unveiling a mass-invariant universal optical conductivity, purely derived from quantum geometry, in quadratic band-touching semimetals. Specifically, the optical conductivity simplifies to [Formula: see text], independent of effective mass and other band structure details, where [Formula: see text] represents the maximum Hilbert-Schmidt quantum distance. Furthermore, under time-reversal and rotational symmetries, [Formula: see text] is restricted to discrete values of 0 or 1, leading to a quantized universal optical conductivity. We also use first-principles calculations to demonstrate the mass-invariant universal optical conductivity across multiple materials, including bilayer graphene, monolayer bismuth, monolayer kagome palladium thiophosphate, and other realistic material candidates. Our work establishes a previously unidentified class of universal quantities in quantum materials entirely governed by quantum geometry.
Radiotherapy (RT) achieves excellent local control (LC) in early-stage glottic cancer (ESGC); however, treatment-related edema or necrosis may necessitate tracheostomy and adversely affect quality of life. We compared tracheostomy rates and oncologic outcomes between whole-larynx radiotherapy (WLRT) and vocal cord-only radiotherapy (VC-RT) in patients with ESGC. We retrospectively analyzed 247 patients with Tis-T2 glottic cancer treated with definitive RT (2007-2023) at two Middle Eastern centers. Patients received WLRT (n = 166) or VC-RT (n = 81). The primary endpoint was a tracheostomy rate (TR) ≥6 months after RT for non-recurrent airway compromise. Secondary endpoints included 3-year local failure (LF) and overall survival (OS). TR and LF rates were analyzed using cumulative incidence with death as a competing risk, whereas OS was estimated using the Kaplan-Meier method. The median age was 59 years; 97.6% of patients were men and 78.9% were smokers. The median follow-up among surviving patients was 38.2 months (range 1.6-194 months). The median potential follow-up for the entire cohort, estimated by the reverse Kaplan-Meier method, was 45.3 months. VC-RT patients more frequently had cT2 disease (22.2% vs. 5.4%, p < 0.001) and received accelerated fractionation (19.8% vs. 7.2%, p = 0.0069). Overall, 20 of 247 patients (8%) required tracheostomy without recurrence. Edema-related tracheostomy occurred exclusively in WLRT patients (14.2% vs. 0% with VC-RT; p < 0.001). Tracheostomy was reversed in 8/20 patients (40%) after a median of 13.4 months. The 3-year LF rates were 7.6% with VC-RT and 11.6% with WLRT (p = 0.18), and OS was 93.3% and 89.5% (p = 0.16), respectively. VC-RT reduces the risk of tracheostomy without compromising oncologic outcomes.
Evidence is required on the relative effectiveness of sulphonylureas, dipeptidyl peptidase-4 inhibitors or sodium-glucose cotransporter 2 inhibitors added to metformin for people with type 2 diabetes mellitus. To assess disparities in the initiation of second-line antidiabetic treatments prescribed among people with type 2 diabetes mellitus in England according to ethnicity and social deprivation. To compare the effectiveness of sulphonylureas, dipeptidyl peptidase-4 inhibitors and sodium-glucose cotransporter 2 inhibitors added to metformin for people with type 2 diabetes mellitus who require second-line treatment in routine clinical practice. To examine heterogeneity in the comparative short-term (12 months) effectiveness of sulphonylureas versus dipeptidyl peptidase-4 inhibitors combined with metformin on levels of glycated haemoglobin across the entire target population and subpopulations of decision-making relevance. To assess the comparative effectiveness of sulphonylureas, dipeptidyl peptidase-4 inhibitors or sodium-glucose cotransporter 2 inhibitors added to metformin according to individual risk-factor profiles of multiple long-term conditions. To calibrate the RAPIDS microsimulation model to UK data and then use the resultant RAPIDS-UK model to predict probabilities of long-term complications for people with type 2 diabetes mellitus in England after second-line treatment with sulphonylureas, dipeptidyl peptidase-4 inhibitors or sodium-glucose cotransporter 2 inhibitors added to metformin. We included adults with type 2 diabetes mellitus who initiated second-line antidiabetic treatment with sulphonylureas, dipeptidyl peptidase-4 inhibitors or sodium-glucose cotransporter 2 inhibitors added to metformin monotherapy. We used data from the Clinical Practice Research Datalink linked to Hospital Episode Statistics and the Office of National Statistics. We applied target trial emulation and instrumental variable analyses to reduce the risks of biases, including confounding. The primary outcome was change in mean glycated haemoglobin (mmol/mol) at 1-year follow-up. Secondary outcomes: change in mean body mass index, systolic blood pressure, estimated glomerular filtration rate and time to major adverse kidney event, major adverse cardiovascular event, heart failure hospitalisation, eye disease, amputation and all-cause mortality. We assessed treatment effect heterogeneity according to multiple long-term conditions. We used a microsimulation model to report the impact on long-term complications. After the instrumental variable analysis, the mean 95% confidence interval differences in glycated haemoglobin change between baseline and 1 year were: -2.5 mmol/mol (-3.7 to -1.3) for sodium-glucose cotransporter 2 inhibitors versus sulphonylureas, and -3.2 mmol/mol (-4.6 to -1.8) for sodium-glucose cotransporter 2 inhibitors versus dipeptidyl peptidase-4 inhibitors. Sodium-glucose cotransporter 2 inhibitors were more effective in reducing body mass index and systolic blood pressure compared to either sulphonylureas or dipeptidyl peptidase-4 inhibitors. Sodium-glucose cotransporter 2 inhibitors were also more effective at reducing mean glycated haemoglobin at 2-year follow-up, at reducing body mass index and systolic blood pressure at 1- and 2-year follow-ups and at reducing the hazards of heart failure hospitalisation (vs. dipeptidyl peptidase-4 inhibitors) and ≥ 40% decline in estimated glomerular filtration rate (vs. sulphonylureas). We did not find evidence of treatment effect heterogeneity by baseline cardiovascular disease status or multiple long-term condition profiles. The microsimulation model found that sodium-glucose cotransporter 2 inhibitors led to lower predicted incidence of end-stage kidney disease, heart failure and eye disease. Public and patient involvement translation workshop participants provided valuable insights on how best to share our findings. We could only partially evaluate the main instrumental variable assumptions. We found that sodium-glucose cotransporter 2 inhibitors were better than dipeptidyl peptidase-4 inhibitors and sulphonylureas at improving important risk factors and at reducing the risk of complications among a general population of people with type 2 diabetes mellitus. Newer antidiabetic treatments should be evaluated. This synopsis presents independent research funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme as award number NIHR128490. In the United Kingdom, around 4 million people have been diagnosed with type 2 diabetes, which causes high levels of sugar (glucose) in the blood. Most people start treatment with a drug called metformin, but some will later need to take additional drugs when metformin is not effective enough. We do not know drugs are best to use with metformin. We looked at the health care information routinely collected about people with type 2 diabetes when they use the National Health Service. We used the information collected between 2015 and 2021 to investigate which treatments worked best. We included 75,739 people in our study, all of whom received one of the three drug types below in addition to metformin: sulphonylureas (e.g. Diamicron) dipeptidyl peptidase-4 inhibitors (e.g. Januvia) sodium–glucose cotransporter 2 inhibitors (e.g. Forxiga). There was a lot of variation across different groups of general practices in the treatment they prescribed. We found that sodium–glucose cotransporter 2 inhibitors were more effective than sulphonylureas or dipeptidyl peptidase-4 inhibitors in reducing blood sugar levels, body mass index and blood pressure and preventing hospitalisation due to heart failure. For other outcomes (like preventing or delaying heart attack, stroke or death), there was no clear difference between drug types. Our results show that using sodium–glucose cotransporter 2 inhibitors alongside metformin may help patients manage some of the common symptoms and side effects of their diabetes. However, some of these effects are quite small. There will be people whose personal circumstances mean that the drug they are taking works especially well for them. Where we did not see a significant difference between drug types, this may be because we did not have data for enough people over a long enough period.
The present study investigates the characteristics of long-term PM10 pollution in the proximity of Afşin-Elbistan lignite-fired thermal power plant complex, one of Türkiye's largest coal-based energy production regions. Daily measurements obtained from the Elbistan monitoring station are analyzed from 2011 to 2024 using descriptive statistics, exceedance analysis for annual and monthly data, and Air Quality Index-Integrated Innovative Trend Analysis (AQI-ITA). The obtained results show that the annual average PM10 concentration values exceed the national limit for the whole period and are several-fold higher than the WHO guideline value. In addition, the lowest annual averages are recorded in 2020 and 2022, while the highest annual averages are found in 2017 and 2018. For some years, the number of days when the daily limit is exceeded approaches the total number of days in the year. High PM10 concentration values are registered in winter months due to emissions related to lignite combustion and residential heating. According to AQI-ITA results, the trendless behavior dominates the process under analysis at low and moderate concentration values, while increasing trends occur at high pollution values in winter and autumn. Overall, PM10 pollution in Elbistan can be considered persistent during the entire period under consideration and may be influenced by the nearby energy production complex, residential heating activities, and various environmental factors. Therefore, further improvements in air quality management policies are also expected to contribute to more effective pollution control in the region.
The utility and availability of ultrasound (US) are increasing. While US has traditionally not been performed on the esophagus, as the entire length of the esophagus cannot be optimally viewed, it does allow for visualization of the cervical and intraabdominal esophagus. There is growing evidence that esophageal US can be useful in clinical esophagology. This review summarizes the current knowledge concerning esophageal US in various esophageal disorders. Studies of achalasia patients have shown that US can distinguish patients with achalasia from health controls and esophagogastric cancer patients. US may be helpful as a screening test for esophageal varices in cirrhotic patients as esophageal wall thickness has been shown to correlate with the presence of varices. US has also been shown to identify the presence of esophageal foreign bodies in case reports in both the adult and pediatric population. In infants, numerous studies have shown its utility in diagnosing GERD and its correlation with pH study results, although the data in adults is less convincing. Taken together, these results suggest that there is a role for US-a non-invasive, cost-effective, and widely-available test-in evaluating esophageal disorders. Despite these promising results, it does not appear that esophageal US is frequently used in clinical practice. Barriers to its implementation, including the availability of US and the training required, are discussed, along with the lack of standardized US protocols, equipment, and normal values. Future high-quality studies on the utility of US in esophageal disorders are warranted and will accelerate the implementation of this promising technology.
A self-powered photoelectrochemical (PEC) sensor based on an In2O3/Ag2S heterojunction was successfully developed for the highly sensitive monitoring of tetracycline (TC) traces in water matrices. Benefiting from superior intrinsic optoelectronic properties, hexagonal tubular In2O3 was initially synthesized via a solvothermal reflux-heating route followed by thermal calcination. Subsequently, the In2O3/Ag2S heterojunction was fabricated through an in situ growth strategy, yielding a remarkably amplified photoelectric response and a robust, stable initial photocurrent driven entirely by internal potential. Under optimized operational parameters, the developed sensor delivered a wide linear detection range spanning from 1 nM to 1 mM, coupled with an ultra-low detection limit of 0.87 nM. Moreover, the sensing platform demonstrated outstanding long-term stability, rapid transient response, robust anti-interference selectivity, and satisfactory reproducibility. Crucially, by integrating a dedicated microcontroller-based hardware module, device portability was successfully realized, offering a viable blueprint for the decentralization of PEC instrumentation. Although the current hardware prototype remains at a preliminary stage, this work establishes a rigorous and practical fundamental framework for low-cost, on-site antibiotic field screening.
The pyrochlore iridates R2Ir2O7have emerged as a unique playground for exploring exotic quantum phenomena arising from the intricate interplay of strong spin-orbit coupling, electron correlations, and geometric frustration. While bulk crystals of these materials have revealed a rich landscape of correlated and topological states, recent breakthroughs in epitaxial thin-film synthesis and heterostructure engineering unlocked an entirely new dimension of discovery. This brief Perspective reviews recent advancements highlighting how new tuning knobs such as dimensional confinement, epitaxial strain, and interfacial coupling can be used to manipulate the delicate balance of competing interactions. We discuss several key discoveries enabled by this approach including the realization of the magnetic Weyl semimetal phase in (111) oriented films, strain-engineered magnetic multipolar orders, the emergence of a chiral spin liquid-like state in the quasi-2D limit, and the discovery of novel electronically anisotropic states at interfaces between pyrochlore iridates and other quantum materials, such as spin ice pyrochlores. These findings showcase that low-dimensional pyrochlore iridates provide ample opportunities for both theory and experiment to unravel, control and ultimately design novel quantum states of matter. We conclude by outlining key open questions and future directions ranging from the synthesis of new heterostructures to the application of advanced probes and the exploration of non-equilibrium phenomena.
Panax quinquefolius L. is a perennial medicinal herb particularly vulnerable to recurring cold stress throughout its life cycle. The GRAS family constitutes a class of plant-specific transcription factors with pivotal functions in growth, development, and environmental adaptation. Nevertheless, a comprehensive characterization of the GRAS transcription factor family in P. quinquefolius remains lacking. A total of 123 PqGRAS members were identified and classified into 13 subfamilies. Transcriptomic profiling implicated that the PAT1 and DELLA subfamilies likely play pivotal roles in integrating multiple environmental and hormonal signals to coordinate complex stress-adaptive responses in P. quinquefolius. Notably, PqGRAS086 (PAT1 subfamily) was significantly upregulated under both cold and methyl jasmonate (MeJA) treatments. Within the 2,000 bp upstream promoter of PqGRAS086, MeJA-responsive regulatory elements were enriched, whereas low-temperature-responsive elements were entirely absent. Phylogenetic analysis further revealed that PqGRAS086 clustered with VaPAT1, PtrPAT1, and ZjCIGR1, which have been demonstrated to play a positive regulatory role in enhancing plant cold tolerance. RT-qPCR analysis further demonstrated that exogenous MeJA enhanced PqGRAS086 expression during cold exposure, suggesting indirect involvement of PqGRAS086 in cold stress through the JA signaling pathway. This study provides the first genome-wide characterization of GRAS genes in P. quinquefolius and identifies PqGRAS086 as a candidate target for future functional studies and molecular breeding.
To evaluate associations between pterygium size parameters and corneal refractive properties and higher-order aberrations (HOAs). In 41 patients with unilateral pterygium, thickness, length, and width were measured by anterior segment optical coherence tomography(AS-OCT). Corneal refractive parameters, irregularity indices, and HOAs were assessed using Pentacam HR. Correlation analyses evaluated relationships between pterygium dimensions and corneal parameters. Pterygium length and width significantly correlated with multiple corneal parameters in the 3-7 mm zone. Moderate correlations were found with K1 (length: |r| = 0.376-0.473; width: |r| = 0.361-0.415; all p < 0.05), and stronger correlations with corneal astigmatism (length: r = 0.582-0.642; width: r = 0.529-0.581; all p < 0.001) and irregularity indices (ISV, IVA, IHD) (length: r = 0.623-0.637; width: r = 0.566-0.596; all p < 0.001). Length positively correlated with total, third-, and fourth-order HOA RMS across the anterior and posterior surface, and entire cornea (r = 0.455-0.691, p < 0.05), primarily driven by vertical trefoil, vertical coma, and tetrafoil. Width also correlated with anterior and total corneal HOAs (r = 0.519 to 0.645, p < 0.05). Posterior surface correlations for width were weaker (r = 0.313 to 0.472, p < 0.05) but remained significant for total RMS, third-order RMS, and several specific aberrations. Pterygium length and width are key parameters associated with deteriorated corneal refractive status, irregularity, and HOAs. Width, being easily standardized, serves as a practical indicator for predicting pterygium-induced visual quality deterioration.
The average intake of dietary fibers known to beneficially modulate the gut microbiota is below recommendations in high-income countries. This study aimed to evaluate the gut effects of resistant dextrin in healthy male adults with normal weight, consuming high (≥ 25 g/day; HF) or low (≤15 g/day; LF) levels of fiber as part of their usual diet. In this randomized, double-blind, placebo-controlled trial, participants received either 15 g/day of resistant dextrin (NUTRIOSE® soluble fiber) or a placebo (maltodextrin) for 4 weeks. Gut microbiota composition, and especially the relative abundance of the Parabacteroides genus, gut microbiota function, fecal parameters [pH, short chain fatty acids (SCFAs) and secretory IgA], and stool frequency and consistency, were assessed. Overall, 124 subjects were recruited, 62 in each treatment arm; 57 in HF, 67 in LF; age: 36.2 ± 11.6 years. The mean relative abundance of Parabacteroides at baseline was similar in the LF (1.5%) and HF (1.3%) subgroups. It increased with the active supplementation and remained stable with the placebo, both in the entire population (5.5% vs. 1.4%; p < 0.0001) and in the subgroups of dietary fiber intake (HF: 5.5% vs. 1.5%; LF: 5.5% vs. 1.3%; p < 0.0001), then returned to baseline levels 2 weeks later. Among Parabacteroides, P. distasonis showed the highest abundance in the active arm as compared to placebo (2.6% vs. 0.5%; p < 0.0001). The Bacillota phylum was less abundant (tendency) at the end of intervention (55.4% vs. 59.0%; p = 0.0545). Conversely, several species from the Clostridium genus were more abundant. From a functional perspective, resistant dextrin intake tended to increase bacterial genes involved in α- and β-glucosidase activities, and to decrease those involved in propionate production, especially in the HF subgroup. No treatment effect (p > 0.05) was found on pH, SCFAs, IgA, stool consistency and frequency. The tested resistant dextrin was effective in modulating the gut microbiota after four weeks of supplementation in healthy male volunteers, favoring the Parabacteroides genus and several related species (especially P. distasonis). The treatment effect was observed in both subgroups of dietary fiber intake, and was even more pronounced in the high-intake subgroup. https://clinicaltrials.gov/, identifier NCT05105425.
Rapid detection of airborne bacteria is crucial for preventing disease transmission and safeguarding public health. However, conventional methods for bioaerosol collection and detection often rely on complex and expensive equipment with low integration and automation, limiting their use for real-time applications. Herein, a dual-function 3D-printed cyclonic collector/reactor-integrated colorimetric biosensor was innovatively developed for the collection, separation, and detection of airborne bacteria. This platform incorporated a custom-designed wet cyclone, which served as a bioaerosol collector and an immunoassay reactor by utilizing the cyclonic vortex for simultaneous bioaerosol collection and active mixing with immunoreagents. Airborne bacteria were first collected into the phosphate-buffered saline at a flow rate of 12 L/min, followed by pumping the immunomagnetic nanoparticles (MNPs) and palladium/platinum (Pd/Pt) nanozymes. Then, the flow rate was changed to 5 L/min within the wet cyclone to facilitate the mixing for forming MNP-bacteria-nanozyme sandwich complexes. After magnetic separation, a colorless mixture of 3,3',5,5'-tetramethylbenzidine (TMB) and hydrogen peroxide (H2O2) was pumped to resuspend these complexes, which were catalyzed by the Pd/Pt nanozymes on the complexes to produce the blue TMBox. The resulting absorbance was finally measured by a self-developed portable microreader, which showed high consistency with the traditional microplate reader. The entire processes, from bioaerosol collection to detection, were automatically controlled via a microcontroller, minimizing manual operation and cross-contamination risks. This platform was demonstrated to complete the airborne bacteria detection in 2.0 h with a detection limit of 459 CFU/m3. This highly integrated platform offers a promising tool for rapid and automated detection of bioaerosols.
This case series evaluates the outcome of a functional presurgical infant orthopedic approach (Fun-PSIO) using a combined 2- and 3-dimensional morphometric assessment based on the anatomic landmarks described by Mazaheri and Botticelli. Grounded in the biological and biomechanical principles of functional maxillary orthopedics (FMO), customized intraoral devices (Fun-Plates) incorporate externally carved acrylic grooves that create a textured surface designed to elicit a tactile-proprioceptive response from the tongue. This neuromuscular stimulation may enhance tongue activity and guide maxillary segment growth and alignment before cheilorhinoplasty. Conducted in low-resource settings, 5 consecutive infants with unilateral cleft lip and palate treated from birth were evaluated at 2 treatment stages. Quantitative analyses indicated reductions in alveolar and palatal cleft widths along the entire cleft extension, with a parallel reduction of the palatal cleft-including the mid- and posterior regions-together with increases in maxillary width and length and a trend toward prevention of T-shaped residual defects. These findings suggest that this functional presurgical approach may contribute to a more favorable surgical field for primary repair, particularly by promoting a parallel palatal cleft configuration along its entire extent, including the posterior region, thereby facilitating tension-reduced closure in infants with unilateral cleft lip and palate.