Environmental eustress promotes liver regeneration through the sympathetic regulation of type 1 innate lymphoid cells to increase IL-22 in mice.

BACKGROUND AND AIMS: The liver has the unique ability of regeneration, which is extremely important for restoring homeostasis after liver injury. Although clinical observations have revealed an association between psychological stress and the liver, whether stress has a causal influence on the liver regeneration remains markedly less defined. APPROACH AND RESULTS: Rearing rodents in an enriched environment (EE) can induce eustress or positive psychological stress. Herein, EE-induced eustress was found to significantly enhance the ability of liver regeneration after partial hepatectomy or carbon tetrachloride-induced liver injury based on the more rapid restoration of liver/body weight ratio and the significantly increased number of proliferating hepatocytes in EE mice. Mechanistically, the cytokine array revealed that IL-22 was markedly increased in the regenerating liver in response to EE. Blockade of IL-22 signaling abrogated the enhanced liver regeneration induced by EE. Group 1 innate lymphoid cells (ILCs), including type 1 ILCs (ILC1s), have been identified as the major sources of IL-22 in the regenerating liver. EE housing led to a rapid accumulation of hepatic ILC1s after partial hepatectomy and the EE-induced enhancement of liver regeneration and elevation of IL-22 was nearly eliminated in ILC1-deficient Tbx21-/- mice. Chemical sympathectomy or blockade of ß-adrenergic signaling also abolished the effect of EE on ILC1s and attenuated the enhanced liver regeneration of EE-housed mice. CONCLUSION: The study findings support the brain-liver axis and suggest that environment-induced eustress promotes liver regeneration through the sympathetic nerve/ILC1/IL-22 axis.

Effect of the configuration mixing on the polarization and angular distribution of x-ray line emissions following electron-impact excitation of Ne-like ions.

We present a systematic theoretical study on the angular distribution and linear polarization of x-ray line emissions of neon-like ions following the electron-impact excitation from the ground state to the excited levels [(2p5)1/23d3/2]J=1, [(2p5)3/23d5/2]J=1, [(2p5)3/23d3/2]J=1, and [(2p5)1/23s]J=1. The cross sections are calculated by using the flexible atomic code under configuration-interaction plus many-body perturbation theory method. The angular distribution and linear polarization are obtained based on density matrix theory. Emphasis has been placed on the effect of the configuration mixing on the angular distribution and polarization. It has been proved that the strong mixing of configuration [(2p5)3/23d3/2]J=1 with configuration [(2p5)1/23s]J=1 can result in the abrupt change of Z-dependence of angular distribution and polarization. It indicates that angular distribution and polarization can be expected to serve as a tool for investigation of configuration mixing effect.

Open Quantum System Dynamics from Infinite Tensor Network Contraction.

Approaching the long-time dynamics of non-Markovian open quantum systems presents a challenging task if the bath is strongly coupled. Recent proposals address this problem through a representation of the so-called process tensor in terms of a tensor network. We show that for Gaussian environments highly efficient contraction to a matrix product operator (MPO) form can be achieved with infinite MPO evolution methods, leading to significant computational speed-up over existing proposals. The result structurally resembles open system evolution with carefully designed auxiliary degrees of freedom, as in hierarchical or pseudomode methods. Here, however, these degrees of freedom are generated automatically by the MPO evolution algorithm. Moreover, the semigroup form of the resulting propagator enables us to explore steady-state physics, such as phase transitions.

The effects of robot-assisted laparoscopic surgery with Trendelenburg position on short-term postoperative respiratory diaphragmatic function.

OBJECTIVE: To study how Pneumoperitoneum under Trendelenburg position for robot-assisted laparoscopic surgery impact the perioperative respiratory parameters, diagrammatic function, etc. METHODS: Patients undergoing robot-assisted laparoscopic surgery in the Trendelenburg position and patients undergoing general surgery in the supine position were selected. The subjects were divided into two groups according to the type of surgery: robot-assisted surgery group and general surgery group. ① Respiratory parameters such as lung compliance, oxygenation index, and airway pressure were recorded at 5 min after intubation, 1 and 2 h after pneumoperitoneum. ② Diaphragm excursion (DE) and diaphragm thickening fraction (DTF) were recorded before entering the operating room (T1), immediately after extubation (T2), 10 min after extubation (T3), and upon leaving the postanesthesia care unit (T4). ③ Peripheral venous blood (5 ml) was collected before surgery and 30 min after extubation and was analyzed by enzyme-linked immunosorbent assay to determine the serum concentration of Clara cell secretory protein 16 (CC16) and surfactant protein D (SP-D). RESULT: ① Compared with the general surgery group (N = 42), the robot-assisted surgery group (N = 46) presented a significantly higher airway pressure and lower lung compliance during the surgery(P < 0.001). ② In the robot-assisted surgery group, the DE significantly decreased after surgery (P < 0.001), which persisted until patients were discharged from the PACU (P < 0.001), whereas the DTF only showed a transient decrease postoperatively (P < 0.001) and returned to its preoperative levels at discharge (P = 0.115). In the general surgery group, the DE showed a transient decrease after surgery(P = 0.011) which recovered to the preoperative levels at discharge (P = 1). No significant difference in the DTF was observed among T1, T2, T3, and T4. ③ Both the general and robot-assisted surgery reduced the postoperative serum levels of SP-D (P < 0.05), while the robot-assisted surgery increased the postoperative levels of CC16 (P < 0.001). CONCLUSION: Robot-assisted laparoscopic surgery significantly impairs postoperative diaphragm function, which does not recover to preoperative levels at PACU discharge. Elevated levels of serum CC16 after surgery suggest potential lung injury. The adverse effects may be attributed to the prolonged Trendelenburg position and pneumoperitoneum during laparoscopic surgery.

Effectiveness of specialist nurse-led WeChat mini program management for disease control in asthma: A randomized controlled study.

BACKGROUND: Asthma is a common chronic respiratory disease in childhood, requiring effective management strategies. PURPOSE: This study aims to evaluate the effectiveness of a nurse-led WeChat Mini Program in managing asthma among children aged 6 to 11 years. METHODS: This randomized controlled trial adhered to the CONSORT checklist and was conducted at a tertiary hospital in China from January 2023 to August 2023. One hundred and eight children with asthma were randomly assigned to two groups, and 81 children completed the 6-month follow-up. All participants received asthma management from specialist nurses, including routine treatments such as inhaled corticosteroids. The experimental group also utilized the WeChat Mini Program for asthma management. Both groups underwent follow-up assessments at 3 and 6 months post-enrollment, which included the Childhood Asthma Control Test (C-ACT), asthma control levels, frequency of exacerbations, and lung function. RESULTS: At 3 and 6 months, the experimental group showed significantly higher C-ACT scores and a lower exacerbation frequency compared to the control group (p < 0.05). While Peak Expiratory Flow improved, Forced Expiratory Volume in 1 Second Percentage Predicted (FEV1%) and FEV1/FVC did not change significantly. CONCLUSIONS: The WeChat Mini Program significantly improved asthma control and reduced exacerbations but did not substantially enhance all lung function parameters. Further research is required to confirm its long-term effects. APPLICATION TO PRACTICE: Incorporating a specialist nurse-led digital management tool, such as the WeChat Mini Program, into standard pediatric asthma care may offer an effective management strategy.

Continuous Phase Transitions between Fractional Quantum Hall States and Symmetry-Protected Topological States.

We study quantum phase transitions in Bose-Fermi mixtures driven by interspecies interaction in the quantum Hall regime. In the absence of such an interaction, the bosons and fermions form their respective fractional quantum Hall (FQH) states at certain filling factors. A symmetry-protected topological (SPT) state is identified as the ground state for strong interspecies interaction. The phase transitions between them are proposed to be described by Chern-Simons-Higgs field theories. For a simple microscopic Hamiltonian, we present numerical evidence for the existence of the SPT state and a continuous transition to the FQH state. It is also found that the entanglement entropy between the bosons and fermions exhibits scaling behavior in the vicinity of this transition.

Universal Scaling of Klein Bottle Entropy near Conformal Critical Points.

We show that the Klein bottle entropy [H.-H. Tu, Phys. Rev. Lett. 119, 261603 (2017)PRLTAO0031-900710.1103/PhysRevLett.119.261603] for conformal field theories perturbed by a relevant operator is a universal function of the dimensionless coupling constant. The universal scaling of the Klein bottle entropy near criticality provides an efficient approach to extract the scaling dimension of lattice operators via data collapse. As paradigmatic examples, we validate the universal scaling of the Klein bottle entropy for Ising and Z_{3} parafermion conformal field theories with various perturbations using numerical simulation with continuous matrix product operator approach.

Risk Factors for Death Among the First 80 543 Coronavirus Disease 2019 (COVID-19) Cases in China: Relationships Between Age, Underlying Disease, Case Severity, and Region.

BACKGROUND: Knowledge of COVID-19 epidemiology remains incomplete and crucial questions persist. We aimed to examine risk factors for COVID-19 death. METHODS: A total of 80 543 COVID-19 cases reported in China, nationwide, through 8 April 2020 were included. Risk factors for death were investigated by Cox proportional hazards regression and stratified analyses. RESULTS: Overall national case-fatality ratio (CFR) was 5.64%. Risk factors for death were older age (≥80: adjusted hazard ratio, 12.58; 95% confidence interval, 6.78-23.33), presence of underlying disease (1.33; 1.19-1.49), worse case severity (severe: 3.86; 3.15-4.73; critical: 11.34; 9.22-13.95), and near-epicenter region (Hubei: 2.64; 2.11-3.30; Wuhan: 6.35; 5.04-8.00). CFR increased from 0.35% (30-39 years) to 18.21% (≥70 years) without underlying disease. Regardless of age, CFR increased from 2.50% for no underlying disease to 7.72% for 1, 13.99% for 2, and 21.99% for ≥3 underlying diseases. CFR increased with worse case severity from 2.80% (mild) to 12.51% (severe) and 48.60% (critical), regardless of region. Compared with other regions, CFR was much higher in Wuhan regardless of case severity (mild: 3.83% vs 0.14% in Hubei and 0.03% elsewhere; moderate: 4.60% vs 0.21% and 0.06%; severe: 15.92% vs 5.84% and 1.86%; and critical: 58.57% vs 49.80% and 18.39%). CONCLUSIONS: Older patients regardless of underlying disease and patients with underlying disease regardless of age were at elevated risk of death. Higher death rates near the outbreak epicenter and during the surge of cases reflect the deleterious effects of allowing health systems to become overwhelmed.

Application of a nomogram to radiomics labels in the treatment prediction scheme for lumbar disc herniation.

OBJECTIVE: To investigate and verify the efficiency and effectiveness of a nomogram based on radiomics labels in predicting the treatment of lumbar disc herniation (LDH). METHODS: By reviewing medical records that were analysed over the past three years, clinical and imaging data of 200 lumbar disc patients at the Affiliated Hospital of Jiangxi University of Traditional Chinese Medicine were obtained. The collected cases were randomly divided into a training group (n = 140) and a testing group (n = 60) at a ratio of 7:3. Two radiologists with experience in reading orthopaedics images independently segmented the ROIs. The whole intervertebral disc with the most obvious protrusion in the sagittal plane T2WI lumbar MRI as a mask (ROI) is sketched. The LASSO (Least Absolute Shrinkage And Selection Operator) algorithm was used to filter the features after extracting the radiomics features. The multivariate logistic regression model was used to construct a quantitative imaging Rad­Score for the selected features with nonzero coefficients. The radiomics labels and nomogram were evaluated using the receiver operating characteristic curve (ROC) and the area under the curve (AUC). The calibration curve was used to evaluate the consistency between the nomogram prediction and the actual treatment plan. The DCA decision curve was used to evaluate the clinical applicability of the nomogram. RESULT: Following feature extraction, 11 radiomics features were used to construct the radiomics label for predicting the treatment plan of LDH. A nomogram was then constructed. The AUC was 0.93 (95% CI: 0.90-0.97), with a sensitivity of 89%, a specificity of 91%, a positive predictive value of 92.7%, a negative predictive value of 89.4%, and an accuracy of 91%. The calibration curve showed that there was good consistency between the prediction and the actual observation. The DCA decision curve analysis showed that the nomogram of the imaging group has great potential for clinical application when the risk threshold is between 5 and 72%. CONCLUSION: A nomogram based on radiomics labels has good predictive value for the treatment of LDH and can be used as a reference for clinical decision-making.

Epidemiologic Analysis of Efforts to Achieve and Sustain Malaria Elimination along the China-Myanmar Border.

Malaria cases have dramatically declined in China along the Myanmar border, attributed mainly to adoption of the 1-3-7 surveillance and response approach. No indigenous cases have been reported in China since 2017. Counties in the middle and southern part of the border area have a higher risk for malaria importation and reestablishment after elimination.

Characterization of pfmdr1, pfcrt, pfK13, pfubp1, and pfap2mu in Travelers Returning from Africa with Plasmodium falciparum Infections Reported in China from 2014 to 2018.

The artemisinin-based combination therapies (ACTs) used to treat Plasmodium falciparum in Africa are threatened by the emergence of parasites in Asia that carry variants of the Kelch 13 (K13) locus with delayed clearance in response to ACTs. Single nucleotide polymorphisms (SNPs) in other molecular markers, such as ap2mu and ubp1, were associated with artemisinin resistance in rodent malaria and clinical failure in African malaria patients. Here, we characterized the polymorphisms in pfmdr1, pfcrt, pfK13, pfubp1, and pfap2mu among African isolates reported in Shandong and Guangxi provinces in China. Among 144 patients with P. falciparum returning from Africa from 2014 to 2018, pfmdr1 N86Y (8.3%) and pfcrt K76T (2.1%) were the major mutant alleles. The most common genotype for pfcrt was I74E75T76 (8.3%), followed by E75T76 (2.1%). For K13 polymorphisms, a limited number of mutated alleles were observed, and A578S was the most frequently detected allele in 3 isolates (2.1%). A total of 27.1% (20/144) of the isolates were found to contain pfubp1 mutations, including 6 nonsynonymous and 2 synonymous mutations. The pfubp1 genotypes associated with artemisinin resistance were D1525E (10.4%) and E1528D (8.3%). Furthermore, 11 SNPs were identified in pfap2mu, and S160N was the major polymorphism (4.2%). Additionally, 4 different types of insertions were found in pfap2mu, and the codon AAT, encoding aspartic acid, was more frequently observed at codons 226 (18.8%) and 326 (10.7%). Moreover, 4 different types of insertions were observed in pfubp1 at codon 1520, which was the most common (6.3%). These findings indicate a certain degree of variation in other potential molecular markers, such as pfubp1 and pfap2mu, and their roles in either the parasite's mechanism of resistance or the mode of action should be evaluated or elucidated further.

Trimethylamine N-oxide is associated with coronary atherosclerotic burden in non-ST-segment myocardial infarction patients: SZ-NSTEMI prospective cohort study.

Trimethylamine N-oxide (TMAO) is reported to accelerate atherosclerosis and the development of adverse cardiac outcomes. Relationship between coronary atherosclerotic burden and TMAO has been examined in stable coronary artery disease and ST-segment elevation myocardial infarction, but not in non-ST-segment elevation myocardial infarction (NSTEMI). We examined the association between TMAO and coronary atherosclerotic burden in NSTEMI. In this prospective cohort study, two groups including NSTEMI (n = 73) and age-sex matched Healthy (n = 35) individuals were enrolled between 2019 and 2020. Coronary atherosclerotic burden was stratified based on the number of diseased coronary vessels and clinical risk scores including SYNTAX and GENSINI. Fasting plasma TMAO was measured by isotope dilution high-performance liquid chromatography. The median plasma TMAO levels were significantly higher in the NSTEMI group than in the Healthy group, respectively (0.59 µM; interquartile range [IQR]: 0.43-0.78 versus 0.42 µM; IQR: 0.33-0.64; P = 0.006). Within the NSTEMI group, higher TMAO levels were observed in the multivessel disease (MVD) versus single vessel disease (P = 0.002), and intermediate-high risk (score ≥ 23) versus low risk (score < 23) of SYNTAX (P = 0.003) and GENSINI (P = 0.005). TMAO level remained an independent predictor of MVD (odds ratio [OR]: 5.94, P = 0.005), intermediate-high risk SYNTAX (OR: 3.61, P = 0.013) and GENSINI scores (OR: 4.60, P = 0.008) following adjustment for traditional risk factors. Receiver operating characteristic curve (AUC) analysis for TMAO predicted MVD (AUC: 0.73, 95% confidence interval [Cl]: 0.60-0.86, P = 0.002), intermediate-high SYNTAX score (AUC: 0.70, 95% Cl: 0.58-0.82, P = 0.003) and GENSINI score (AUC: 0.70, 95% Cl: 0.57-0.83, P = 0.005). In all, TMAO levels are independently associated with high coronary atherosclerotic burden in NSTEMI.

Characterization of hepatitis B virus DNA integration patterns in intrahepatic cholangiocarcinoma.

AIM: Hepatitis B virus (HBV) integration is one of the mechanisms contributing to hepatocellular carcinoma (HCC) development. However, the status of HBV integration in intrahepatic cholangiocarcinoma (ICC) is poorly understood. This study aims to characterize the viral integration in HBV-related ICC. METHODS: The presence of HBV S and C gene in ICCs and the paratumor tissue was determined by polymerase chain reaction direct sequencing. Hepatitis B virus integration was detected by a high-throughput capture sequencing method. The expression analysis of the genes targeted by HBV in ICC was undertaken in The Cancer Genome Atlas dataset. RESULTS: Hepatitis B virus S and/or C gene fragments were detected in 71.43% (10/14) ICCs and 57.14% (8/14) paratumor tissues. Using the high-throughput capture sequencing approach, 139 and 183 HBV integration breakpoints were identified from seven ICC and seven paired paratumor tissues, respectively. Seven genes (TERT, CEACAM20, SPATA18, TRERF1, ZNF23, LINC01449, and LINC00486) were recurrently targeted by HBV-DNA in different ICC tissues or different cell populations of the same tissue. TERT, which is the most preferential HBV target gene in HCC, was found to be repeatedly interrupted by HBV-DNA in three different ICC tissues. Based on The Cancer Genome Atlas dataset, TERT, as well as three other HBV recurrently targeted genes (SPATA18, TRERF1, and ZNF23), showed differential expression levels between ICC and para-ICC tissues. CONCLUSIONS: Taken together, HBV integration is a common event in HBV-related ICC. The HBV recurrent integration genes identified from this study, such as TERT, provide new clues for further research on the causative link between HBV infection and ICC.

Long-term endoscopic submucosal dissection with postoperative lung injury: a case report.

BACKGROUND: Endoscopic submucosal dissection (ESD) has been recognized as a safe and minimally invasive technique for the removal of early gastric cancer. Here, we describe a case of extended-duration ESD for a gastric tumor associated with intraoperative perforation and bleeding. Unfortunately, the patient developed acute lung injury (ALI) after the operation. CASE PRESENTATION: A 72-year-old woman received ESD for a gastric tumor under general anesthesia. Preoperatively, endoscopic ultrasonography (EUS) showed a 3.1 × 3.5 cm hypoechoic, well-defined mass at the junction of the antrum and body of the stomach on the greater curvature, originating in the muscularis propria layer. During the ESD procedure, when the submucosal mass was stripped, it was found to be closely adhered to the muscular layer and serosa layer, and a full-thickness incision was performed. The abdominal cavity was gradually filled with carbon dioxide gas, and abdominal puncture was performed to reduce intra-abdominal hypertension (IAH). Because the mass adhered to the greater omentum and there was more bleeding during the operation, a long duration of hemostasis and suturing of the wound was required. The whole operation lasted nearly 9 h, and total blood loss was 800 ml. After surgery, acute lung injury was suspected, and the patient was sent to the intensive care unit (ICU) for further treatment. CONCLUSIONS: The operation time of ESD and IAH caused by perforation are closely related to a poor prognosis. We should pay attention to the impact of operation time on patients and improve awareness regarding protecting important organ functions.

Characterization of hepatitis B virus infection and viral DNA integration in non-Hodgkin lymphoma.

Hepatitis B virus (HBV) infection has been reported to be associated with non-Hodgkin lymphoma (NHL). However, the evidence is limited to the seroepidemiological study. There is a lack of evidence showing the HBV infection and integration in NHL cells. Here, we reported that in the Shanghai area, the positive rates of serum HBsAg (OR: 3.11; 95% CI: 2.20-4.41) and HBeAg (OR: 3.99; 95% CI: 1.73-9.91) were significantly higher in patients with NHL. HBsAg, HBcAg and HBV DNA were detected in 34.4%, 45.2% and 47.0% of the NHL tissues, respectively. Furthermore, by using a high-throughput viral integration detection approach (HIVID), integrated HBV DNA was identified from 50% (6/12) HBV-related NHL tissues. There were a total of 313 HBV integration sites isolated from the NHL tissues, among which four protein-coding genes (FAT2, SETX, ITGA10 and CD63) were interrupted by HBV DNA in their exons. Seven HBV preferential target genes (ANKS1B, HDAC4, EGFLAM, MAN1C1, XKR6, ZBTB38 and CCDC91) showed significantly altered expression levels in NHL, suggesting a potential role of these genes in NHL development. Taken together, HBV integration is a common phenomenon in NHL. This finding opens up a new direction of research into the mechanistic link between HBV infection and NHL.

Prevalence of Plasmodium falciparum Kelch 13 (PfK13) and Ubiquitin-Specific Protease 1 (pfubp1) Gene Polymorphisms in Returning Travelers from Africa Reported in Eastern China.

Delayed clearance of Plasmodium falciparum by artemisinin-based combination therapies (ACTs) has already been observed for African isolates. Here, we aimed to investigate the prevalence, among travelers returning from African countries, of polymorphisms in two genes correlated with delayed parasite clearance (encoding P. falciparum Kelch 13 [PfK13] and ubiquitin-specific protease 1 [pfubp1]) reported in eastern China and to provide baseline data for antimalarial drug resistance (ART) surveillance and evaluation. A total of 153 filter paper blood spots collected in 2017-2019 from patients with uncomplicated P. falciparum cases in Anhui and Shandong Provinces were included in this study. Among them, 3.3% (5/153) of the isolates carried PfK13 mutations, and 3 of them harbored the same synonymous mutation, C469C. A total of 13.1% (20/153) of the isolates were found to contain pfubp1 mutations, and all were nonsynonymous. The pfubp1 genotypes associated with ART that occurred in this study included E1528D (6.5% [10/153]) and D1525E (2.6% [4/153]). However, a high prevalence of the previously unreported mutation E1531D (5.9% [9/153]) was also detected. In addition, two types of deletions (encoding KID and KIE, respectively) and two types of insertions (encoding KYE and KYDKYD, respectively) were found in 16 isolates and 6 isolates, respectively. This study showed limited variation in PfK13 among travelers returning from African countries and suggested other potential molecular markers, such as pfubp1, for use in the surveillance of African isolates in ACT susceptibility studies. Further clinical trial research is under way to investigate these PfK13 and pfubp1 mutations, as well as other candidate molecular markers, and their roles in delaying parasite clearance.

Continuous Matrix Product Operator Approach to Finite Temperature Quantum States.

We present an algorithm for studying quantum systems at finite temperature using continuous matrix product operator representation. The approach handles both short-range and long-range interactions in the thermodynamic limit without incurring any time discretization error. Moreover, the approach provides direct access to physical observables including the specific heat, local susceptibility, and local spectral functions. After verifying the method using the prototypical quantum XXZ chains, we apply it to quantum Ising models with power-law decaying interactions and on the infinite cylinder, respectively. The approach offers predictions that are relevant to experiments in quantum simulators and the nuclear magnetic resonance spin-lattice relaxation rate.

Tensor Network Representations of Parton Wave Functions.

Tensor network states and parton wave functions are two pivotal methods for studying quantum many-body systems. This work connects these two subjects as we demonstrate that a variety of parton wave functions, such as projected Fermi sea and projected fermionic or bosonic paired states, can be represented exactly as tensor networks. The results can be compressed into matrix product states with moderate bond dimensions so various physical quantities can be computed efficiently. For the projected Fermi sea, we develop an excellent compression scheme with high fidelity using maximally localized Wannier orbitals. Numerical calculations on two parton wave functions demonstrate that our method exceeds commonly adopted Monte Carlo methods in some aspects. It produces energy and correlation function with very high accuracy that is difficult to achieve using Monte Carlo method. The entanglement measures that were almost impossible to compute before can also be obtained easily using our method.

Fractionalized Fermionic Quantum Criticality in Spin-Orbital Mott Insulators.

We study transitions between topological phases featuring emergent fractionalized excitations in two-dimensional models for Mott insulators with spin and orbital degrees of freedom. The models realize fermionic quantum critical points in fractionalized Gross-Neveu* universality classes in (2+1) dimensions. They are characterized by the same set of critical exponents as their ordinary Gross-Neveu counterparts, but feature a different energy spectrum, reflecting the nontrivial topology of the adjacent phases. We exemplify this in a square-lattice model, for which an exact mapping to a t-V model of spinless fermions allows us to make use of large-scale numerical results, as well as in a honeycomb-lattice model, for which we employ ε-expansion and large-N methods to estimate the critical behavior. Our results are potentially relevant for Mott insulators with d^{1} electronic configurations and strong spin-orbit coupling, or for twisted bilayer structures of Kitaev materials.

Noninvasive Prenatal Testing for Trisomies 21, 18, and 13, Sex Chromosome Aneuploidies, and Microdeletions in Average-Risk Pregnancies: A Cost-Effectiveness Analysis.

OBJECTIVE: The cost effectiveness of noninvasive prenatal testing (NIPT) has been established for high-risk pregnancies but remains unclear for pregnancies at other risk levels. The aim was to assess the cost effectiveness of NIPT in average-risk pregnancies from the perspective of a provincial public payer in Canada. METHODS: A model was developed to compare traditional prenatal screening (TPS), NIPT as a second-tier test (performed only after a positive TPS result), and NIPT as a first-tier test (performed instead of TPS) for trisomies 21, 18, and 13; sex chromosome aneuploidies; and microdeletions in a hypothetical annual population cohort of average-risk pregnancies (142 000 to 148,000) in Ontario, Canada. A probabilistic analysis was conducted with 5000 repetitions. RESULTS: Compared with TPS, NIPT as a second-tier test detected more affected fetuses with trisomies 21, 18, and 13 (188 vs. 158), substantially reduced the number of diagnostic tests (i.e., chorionic villus sampling and amniocentesis) performed (660 vs. 3107), and reduced the cost of prenatal screening ($26.7 million vs. $27.6 million) annually. Compared with second-tier NIPT, first-tier NIPT detected an additional 80 cases of trisomies 21, 18, and 13 at an additional cost of $33 million. The incremental cost per additional affected fetus detected was $412 411. Extending first-tier NIPT to include testing for sex chromosome aneuploidies and 22q11.2 deletion would increase the total screening cost. CONCLUSIONS: NIPT as a second-tier test is cost-saving compared with TPS alone. Compared with second-tier NIPT, first-tier NIPT detects more cases of chromosomal anomalies but at a substantially higher cost.