Ultrahigh-energy photons up to 1.4 petaelectronvolts from 12 γ-ray Galactic sources.

The extension of the cosmic-ray spectrum beyond 1 petaelectronvolt (PeV; 1015 electronvolts) indicates the existence of the so-called PeVatrons-cosmic-ray factories that accelerate particles to PeV energies. We need to locate and identify such objects to find the origin of Galactic cosmic rays1. The principal signature of both electron and proton PeVatrons is ultrahigh-energy (exceeding 100 TeV) γ radiation. Evidence of the presence of a proton PeVatron has been found in the Galactic Centre, according to the detection of a hard-spectrum radiation extending to 0.04 PeV (ref. 2). Although γ-rays with energies slightly higher than 0.1 PeV have been reported from a few objects in the Galactic plane3-6, unbiased identification and in-depth exploration of PeVatrons requires detection of γ-rays with energies well above 0.1 PeV. Here we report the detection of more than 530 photons at energies above 100 teraelectronvolts and up to 1.4 PeV from 12 ultrahigh-energy γ-ray sources with a statistical significance greater than seven standard deviations. Despite having several potential counterparts in their proximity, including pulsar wind nebulae, supernova remnants and star-forming regions, the PeVatrons responsible for the ultrahigh-energy γ-rays have not yet been firmly localized and identified (except for the Crab Nebula), leaving open the origin of these extreme accelerators.

Evidence for Chiral Wobbler in Nuclei.

Three ΔI=1 bands with the πg_{9/2}⊗νg_{9/2} configuration have been identified in _{35}^{74}Br_{39}. Angular distribution, linear polarization, and lifetime measurements were performed to determine the multipolarity, type, mixing ratio, and absolute transition probability of the transitions. By comparing these experimental observations with the corresponding fingerprints and the quantum particle rotor model calculations, the second and third lowest bands are, respectively, suggested as the chiral partner and one-phonon wobbling excitation built on the yrast band. The evidence indicates the first chiral wobbler in nuclei.

Measurements of All-Particle Energy Spectrum and Mean Logarithmic Mass of Cosmic Rays from 0.3 to 30 PeV with LHAASO-KM2A.

We present the measurements of all-particle energy spectrum and mean logarithmic mass of cosmic rays in the energy range of 0.3-30 PeV using data collected from LHAASO-KM2A between September 2021 and December 2022, which is based on a nearly composition-independent energy reconstruction method, achieving unprecedented accuracy. Our analysis reveals the position of the knee at 3.67±0.05±0.15 PeV. Below the knee, the spectral index is found to be -2.7413±0.0004±0.0050, while above the knee, it is -3.128±0.005±0.027, with the sharpness of the transition measured with a statistical error of 2%. The mean logarithmic mass of cosmic rays is almost heavier than helium in the whole measured energy range. It decreases from 1.7 at 0.3 PeV to 1.3 at 3 PeV, representing a 24% decline following a power law with an index of -0.1200±0.0003±0.0341. This is equivalent to an increase in abundance of light components. Above the knee, the mean logarithmic mass exhibits a power law trend towards heavier components, which is reversal to the behavior observed in the all-particle energy spectrum. Additionally, the knee position and the change in power-law index are approximately the same. These findings suggest that the knee observed in the all-particle spectrum corresponds to the knee of the light component, rather than the medium-heavy components.

Machine-learning-based performance comparison of two-dimensional (2D) and three-dimensional (3D) CT radiomics features for intracerebral haemorrhage expansion.

AIM: To investigate the value of non-contrast CT (NCCT)-based two-dimensional (2D) radiomics features in predicting haematoma expansion (HE) after spontaneous intracerebral haemorrhage (ICH) and compare its predictive ability with the three-dimensional (3D) signature. MATERIALS AND METHODS: Three hundred and seven ICH patients who received baseline NCCT within 6 h of ictus from two stroke centres were analysed retrospectively. 2D and 3D radiomics features were extracted in the manner of one-to-one correspondence. The 2D and 3D models were generated by four different machine-learning algorithms (regularised L1 logistic regression, decision tree, support vector machine and AdaBoost), and the receiver operating characteristic (ROC) curve was used to compare their predictive performance. A robustness analysis was performed according to baseline haematoma volume. RESULTS: Each feature type of 2D and 3D modalities used for subsequent analyses had excellent consistency (mean ICC >0.9). Among the different machine-learning algorithms, pairwise comparison showed no significant difference in both the training (mean area under the ROC curve [AUC] 0.858 versus 0.802, all p>0.05) and validation datasets (mean AUC 0.725 versus 0.678, all p>0.05), and the 10-fold cross-validation evaluation yielded similar results. The AUCs of the 2D and 3D models were comparable either in the binary or tertile volume analysis (all p>0.5). CONCLUSION: NCCT-derived 2D radiomics features exhibited acceptable and similar performance to the 3D features in predicting HE, and this comparability seemed unaffected by initial haematoma volume. The 2D signature may be preferred in future HE-related radiomic works given its compatibility with emergency condition of ICH.

[Application of "modified double pocket suture" pancreatoenterostomy in laparoscopic pancreatoduodenectomy].

Objective: The purpose of this study was to explore the value of the "improved double purse-string suture method" for pancreatojejunostomy in laparoscopic pancreaticoduodene-ctomy. Methods: The clinical data of 273 patients who underwent laparoscopic pancreaticoduode-nectomy in the Department of Hepatobiliary and Pancreatic Surgery of the First Hospital of Jilin University from January 2021 to May 2022 were retrospectively analyzed. According to the method of pancreaticoenteric anastomosis, the patients were divided into two groups: the "improved double purse-string suture method" group and the "Hong's one-stitch method" group. Results: The "improved double purse-string suture method" for pancreaticoenteric anastomosis was performed in a total of 189 patients, including 107 males and 82 females, with a mean age of (59.6±10.2) years. The "Hong's one-stitch method" group" was performed in a group of 84 patients, including 52 males and 32 females, with a mean age of (60.8±9.3) years.The results showed that the "improved double purse-string suture method" group had a lower incidence of postoperative pancreatic fistula (6.88% vs 8.33% for grade B fistula, and 1.58% vs 2.38% for grade C fistula) and a shorter anastomosis time [(25.25±4.73) min vs (25.76±6.71) min] than the "Hong's one-stitch method" group. There was no statistically significant difference between the two groups in terms of postoperative biliary fistula, abdominal bleeding, delayed gastric emptying, and other complications (P>0.05). Conclusion: The "improved double purse-string suture method" for pancreatojejunostomy is safe and feasible in laparoscopic pancreaticoduodenectomy.

[Risk factors for the occurrence of laryngopharyngeal reflux disease in the aged and the clinical characteristics of patients complicated with pneumonia].

Objective: To investigate the risk factors for the occurrence of laryngopharyngeal reflux disease in the aged, and to analyze the characteristics of patients with pneumonia. Methods: Patients who underwent 24-hour laryngopharyngeal pH monitoring from June 2020 to July 2022 and the positive patients of those who underwent 24-hour esophageal pH monitoring from March 2017 to July 2022 at the Second Medical Center of the PLA General Hospital were enrolled retrospectively. Positive results of 24-hour laryngopharyngeal reflux monitoring were in the laryngopharyngeal reflux group, and the negative results were in the non-laryngopharyngeal reflux group. Patients with pneumonia and simple gastroesophageal reflux disease were in the esophageal reflux pneumonia group, and patients with pneumonia and simple laryngopharyngeal reflux disease were in the laryngopharyngeal reflux pneumonia group. Patients' basic data, co-morbidities, drug use and relevant examination and test results were collected. Multivariate logistic regression analysis was used to analyze the risk factors of laryngopharyngeal reflux disease in the aged and its relationship with pneumonia. Results: A total of 80 patients with 24-hour laryngopharyngeal pH monitoring were enrolled finally, including 34 cases, all male, aged (73±12) years, in the laryngopharyngeal reflux group, and 46 cases [44 males, 2 females, aged (78±11) years] in the non-laryngopharyngeal reflux group. Multivariate logistic regression analysis showed that the risk factors of laryngopharyngeal reflux disease in the aged included age ≤70 years (OR=13.07, 95%CI: 2.53-67.68), body mass index (BMI) (OR=1.37, each additional 1 kg/m2, 95%CI: 1.03-1.83), use of antipsychotic drugs (OR=8.00, 95%CI: 1.40-45.73) and calcium channel blockers (OR=5.27, 95%CI: 1.13-24.53) (all P<0.05). The protective factors of the laryngopharyngeal reflux disease in the aged included antacids (OR=0.19, 95%CI: 0.04-0.90, P=0.035). The incidence of pneumonia was higher in the laryngopharyngeal reflux group compared with the non-laryngopharyngeal reflux group [44.1% (15/34) vs 21.7% (10/46), P=0.033]. The esophageal reflux pneumonia group included 32 cases [31 males and 1 females, aged (84±12) years]. The laryngopharyngeal reflux pneumonia group included 15 cases [ 15 males, aged (79±11) years]. Compared to the patients in the laryngopharyngeal reflux pneumonia group, the patients in the esophageal reflux pneumonia group had a longer course of antibiotics [(27.7±27.0) vs (14.6±13.9) days, P=0.034], a higher frequency of seizure frequency [(4.3±3.0) vs (1.8±1.5) times/year, P<0.001] and a higher maximal body temperature [(38.2±0.9) vs (37.6±1.1) ℃, P=0.037]. Conclusions: The risk factors of laryngopharyngeal reflux disease in the aged included age ≤70 years, higher BMI, use of antipsychotic drugs and calcium channel blockers. The incidence of pneumonia in laryngopharyngeal reflux disease is higher, but the condition of pneumonia is milder.

[Clinical characteristics and associated factors of mild cognitive impairment in patients with common cardiovascular diseases].

Objective: To analyze the clinical characteristics of patients with common cardiovascular diseases (CVD, including hypertension, coronary heart disease, atrial fibrillation, and heart failure) combined with mild cognitive impairment (MCI) and explore the potential risk factors of MCI in patients with CVD. Methods: A total of 2 294 patients with common cardiovascular diseases who met the criteria at Cardiology Medical Center in Beijing Anzhen Hospital, Capital Medical University, from June 1, 2021, to January 5, 2022, were retrospectively included. The patients were divided into the normal cognitive function group (1 107 cases) and the MCI group (1 187 cases). Demographic information and CVD status were collected. The information of cognitive function were collected using the Montreal Cognitive Assessment (MoCA) and the Mini-Mental State Examination (MMSE) scales. The difference between normal cognitive function and MCI were compared and analyzed. The logistic regression analysis was used to explored risk factors of MCI in CVD patients. Results: A total of 2 294 patients aged (60.6±10.4) years were included, among whom there were 29.99% (688 cases) females. Compared with patients in the normal cognitive function group, patients in the MCI group were older [ (57.9±11.4) vs (63.1±8.9) years old, P<0.001], with a higher proportion of women [26.47% (293 cases) vs 33.28% (395 cases), P<0.001]; there was a higher proportion of patients suffering from hypertension in the MCI group [59.62% (660 cases) vs 64.62% (767 cases), P=0.014ï¼½, and more components of CVD [(1.68±0.62) vs (1.74±0.65) components, P=0.017]. The risk factors of MCI in patients with common CVD were increased age, increased depression score, combined with hypertension, and ≥3 common components of CVD, with OR (95%CI) of 1.043 (1.032-1.054), 1.021 (1.004-1.037), 1.151 (1.142-3.439), and 1.137 (1.023-1.797), respectively (all P values <0.05). Increasing education level was observed to be associated with reduced risk of MCI with OR (95%CI) of 0.319 (0.271-0.378) (P<0.05). Conclusions: The incidence of MCI was high in CVD patients. The risk factors of MCI in CVD patients included hypertension and≥3 common components of CVD.

[Research progress of vaccination status, efficacy and safety in children with tumor].

Malignant tumors in children are one of the most important diseases that threaten the health and quality of life of children and are the second most common cause of death in children.With the continuous improvement and progress of treatment technology, the long-term survival rate of children with tumor has been significantly improved, but both the disease itself and the treatment can impair the immune function of children, which makes them vulnerable to various infectious diseases and secondary serious complications, and even become a source of infection, endangering the health of others. Vaccination is the most cost-effective measure to prevent infectious diseases. For children with normal immune functions, the benefits of vaccination usually outweigh the disadvantages. However, there is a lack of detailed data on the vaccination situation, efficacy and safety of vaccine use for such immunocompromised tumor survivors, and there are no authoritative and uniform vaccination recommendations. This article reviewed and summarized the literature and consensus of some domestic and foreign scholars on current status of post-treatment vaccination status, efficacy and safety of vaccination for children with tumors after treatment, with the aim of providing a reference for the practice in this field in China.

[Application of 21-gene recurrence risk score in patients with breast cancer].

Objective: To investigate the relationship between 21-gene recurrence risk score (21-Gene RS) and the prognosis and clinicopathological features of hormone receptor (HR) positive, HER2-negative early breast cancer patients who did not receive neoadjuvant therapy. Methods: A total of 469 patients with HR positive and HER2-negative early breast cancer who received surgical treatment in the First Affiliated Hospital, Zhejiang University School of Medicine from January 2014 to October 2017 were selected. Their clinicopathological data were retrospectively analyzed. Tumor tissue samples were collected from patients, and the expression of 21-gene was detected by reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR). The 21-Gene RS was calculated according to the Trial Assigning Individualized Options for Treatment (TAILORx) RS grouping and National Surgical Adjuvant Breast and Bowel Project B-20 (NSABP B-20) RS grouping principles. Patients were divided into low (21-Gene RS<11 or 21-Gene RS<18), intermediate (11≤21-Gene RS<26 or 18≤21-Gene RS<31) and high (21-Gene RS≥26 or 21-Gene RS≥31) risk groups, and the clinicopathological features and prognostic differences of patients in different risk groups were compared. Statistical data were compared by chi-square test. Survival analysis was performed using Kaplan-Meier curve analysis and the differences between groups were compared using Log-rank test. Multivariate analysis was conducted by COX regression analysis. Results: Based on TAILORx RS grouping, the proportions of low-risk, intermediate-risk and high-risk groups among the 469 patients were 18.8% (88/469), 48.2% (226/469) and 33.0% (155/469), respectively. Based on NSABP B-20 RS grouping, the proportion of low-risk, intermediate-risk and high-risk groups were 43.1% (202/469), 37.5% (176/469) and 19.4% (91/469), respectively. The association of 21-Gene RS with histological grading, luminal typing, Ki-67 expression, and chemotherapy and treatment modalities were statistically significant (P<0.05) regardless of TAILORx RS grouping or NSABP B-20 RS grouping. Kaplan-Meier survival curve suggested poor prognosis in high-risk group (P<0.05, Log-rank test). Multivariate COX regression analysis showed that surgical method and 21-Gene RS were risk factors affecting the prognosis of patients. Conclusions: 21-Gene RS is significantly associated with the prognosis of patients with HR-positive, HER2-negative, early-stage breast cancer not receiving neoadjuvant therapy, as well as with their clinicopathological characteristics such as patients' histologic grade, luminal typing, Ki-67 expression, and whether or not they are treated with chemotherapy or other treatment modalities.The 21-Gene RS threshold of 11 and 26 or 18 and 31 can be used to grade the prognosis in Chinese patients with early-stage breast cancer. More researches are needed to guide the selection of postoperative adjuvant therapy for patients with HR-positive and HER2-negative early-stage breast cancer.

[Comparison of ultrathin bronchoscopy with conventional bronchoscopy for the diagnostic value of peripheral pulmonary lesions].

Objective: To assess and compare the diagnostic efficacy of next-generation ultrathin bronchoscopy (UTB) and conventional bronchoscopy (CB), both combined with radial endobronchial ultrasound (r-EBUS), in the evaluation of peripheral pulmonary lesions (PPL). Methods: A cohort of 39 patients with PPL who underwent multimodal bronchoscopy at Dushu Lake Hospital, Soochow University, from June 1, 2021 to May 31, 2023 was consecutively enrolled. A single bronchoscopist performed multimodal bronchoscopies using CB (external diameter 4.9 mm or 5.9 mm, working channel diameter 2 or 3 mm, CB group) for transbronchial biopsy under r-EBUS guidance (rEBUS-TBLB), followed by UTB (external diameter 3 mm, working channel diameter 1.7 mm, UTB group) for transbronchial biopsy under r-EBUS guidance. Pathological findings and a 6-month clinical follow-up were used as the gold standard to compare the diagnostic yield of biopsy specimens, ultrasound characteristics, and localization rates of the two bronchoscope types. The aim was to evaluate the clinical application value of UTB combined with r-EBUS. Binary variables were analysed using the McNemar test for paired data. Continuous variables or ranked data were analysed using the Wilcoxon signed-rank test for paired data. Results: The diagnostic yields for UTB and CB groups were 66.67% (26/39) and 30.77% (12/39), respectively, with the UTB group significantly surpassing the CB group (χ2=10.56, P=0.001, 1-ß=0.968). r-EBUS with CB exhibited no visible lesion in 13 cases, adjacent to the lesion in 19 cases, and within the lesion in 7 cases.Substitution of UTB resulted in r-EBUS images changing from no visible lesion to adjacent to the lesion in 7 cases, from no visible lesion to within the lesion in 3 cases, and from adjacent to the lesion to within the lesion in 12 cases. The positioning of the r-EBUS probe in relation to the lesions improved significantly with UTB usage (Z=-4.46, P<0.001). Localization rates (number of patients with "within" or "adjacent to" the image/total number of patients) for UTB and CB were 92.30% (36/39) and 66.67% (26/39), respectively (χ2=8.10, P=0.002). UTB improved r-EBUS probe localization rates. The diagnostic yields of UTB were higher than CB for solid lesions, lesions>30 mm in diameter, non-upper lobar location, benign or malignant lesions and lesions with or without a bronchus sign. Conclusion: The UTB group demonstrated a significantly higher diagnostic yield than the CB group, providing superior r-EBUS probe images, and a significant diagnostic advantage for PPL.

[Analysis of risk factors associated with postoperative pancreatic fistula after robotic-assisted distal pancreatectomy].

Objective: To investigate pertinent risk factors for postoperative pancreatic fistula(POPF) after robotic-assisted distal pancreatectomy(RDP). Methods: This is a retrospective cohort study. Clinical data of 1 211 patients who underwent various methods of distal pancreatectomy at the Department of General Surgery,Ruijin Hospital,Shanghai Jiaotong University School of Medicine,between January 2021 and December 2023 were retrospectively collected. Among the study participants,440 cases were in the robot-assisted group(173 males and 267 females),with an age(M(IQR)) of 55(29)years;720 cases were in the open surgery group (390 males and 330 females),with an age of 64(15)years;and 51 cases were in the laparoscopic group(17 males and 34 females),with an age of 56(25)years. These 440 patients who underwent RDP were divided into two cohorts based on the presence of clinically relevant pancreatic fistulas(grades B and C). Univariate and multivariate analysis were performed on 27 factors related to POPF. Univariate analysis methods included independent sample t-test,Mann-Whitney U test,and χ2 test,while multivariate analysis utilized binary logistic regression. Results: After stratification by pathological type,there was no significant difference in the incidence of pancreatic fistula between the robot-assisted group and the open surgery group(benign tumor:χ2=1.200,P=0.952;malignant tumor:χ2=0.391,P=0.532). The surgical duration of the RDP group (Z1=15.113,P1<0.01; Z2=4.232, P2<0.01) was significantly shorter than that of the open surgery and laparoscopic groups,so as the intraoperative blood loss (Z1=12.530,P1<0.01;Z2=2.550,P2=0.032). Postoperative hospital stay in the RDP group was significantly shorter than that in the open surgery group (Z1=10.947, P1<0.01), but not different from that in the laparoscopic group (P2>0.05). All 440 patients underwent successful surgery,of which there was only 1 case who underwent a conversion to open surgery. A total of 104 patients(23.6%) developed clinically relevant pancreatic fistulas,and no perioperative mortality was observed. Univariate analysis revealed that 6 factors were associated with POPF after RDP: gender(χ2=12.048,P=0.001),history of smoking (χ2=6.327,P=0.012),history of alcohol consumption (χ2=17.597,P<0.01),manual pancreas division (χ2=9.839,P=0.002),early elevation of amylase in drainage fluid (Z=5.187,P<0.01),and delayed gastric emptying (χ2=4.485,P=0.034). No statistically significant association with POPF was found for the remaining factors(all P>0.05).The cut-off value for the early amylase level in the drainage fluid was determined to be 7 719.5 IU/ml,with an area under curve of 0.676 determined by receiver operating characteristic curve analysis. Binary logistic regression analysis identified a history of alcohol consumption(P=0.002,95%CI:0.112 to 0.623),manual pancreas division(P=0.001,95%CI:1.446 to 4.082),early amylase level of drainage fluid ≥7 719.5 IU/ml(P<0.01,95%CI:0.151 to 0.438),and delayed gastric emptying(P=0.020,95%CI:1.131 to 4.233) as independent risk factors for POPF of RDP. Conclusions: Patients with pancreatic body and tail tumors who receive RDP therapy are at increased risk of developing a pancreatic fistula if they have a history of alcohol consumption,manual pancreas division,early elevation of amylase in drainage fluid to ≥7 719.5 IU/ml, or delayed gastric emptying.

[Prognostic significance of textbook outcome in advanced gastric patients who underwent neoadjuvant chemotherapy followed by surgical resection].

Objective: To investigate the risk factors and prognostic value of the textbook outcome (TO) in patients with advanced gastric cancer (AGC) who underwent neoadjuvant chemotherapy followed by surgical resection. Methods: This is a retrospective cohort study. A total of 253 patients with AGC who underwent neoadjuvant chemotherapy combined with gastrectomy and D2 lymphadenectomy in the Department of Gastric Surgery, Fujian Medical University Union Hospital from January 2010 to December 2019 were retrospectively included. There were 195 males and 58 females, aged (60.3±10.0) years (range: 27 to 75 years). The patients were then divided into the TO group (n=168) and the non-TO group (n=85). Multivariate Logistic regression was used to analyze the independent predictors of TO. Univariate and multivariate Cox analysis were used to analyze independent prognosis factors for overall survival (OS) and disease-free survival (DFS). Propensity score matching was performed to balance the TO and non-TO groups, and the Kaplan-Meier method was used to calculate survival rates and draw survival curves. Results: Among the 253 patients, 168 patients (66.4%) achieved TO. The Eastern Cooperative Oncology Group score (OR=0.488, 95%CI: 0.278 to 0.856, P=0.012) and ypN stage (OR=0.626, 95%CI:0.488 to 0.805, P<0.01) were independently predictive of TO. Multivariate analysis revealed that TO was an independent risk factor for both OS (HR=0.662, 95%CI: 0.457 to 0.959,P=0.029) and DFS (HR=0.687, 95%CI: 0.483 to 0.976, P=0.036). After matching, the 5-year OS rate (42.2% vs. 27.8%) and the 5-year DFS rate (37.5% vs. 27.8%) were significantly higher in the TO group than in the non-TO group (both P<0.05). Furthermore, patients in the non-TO group benefited significantly from postoperative chemotherapy (both P<0.05), but those in the TO group did not (both P>0.05). Conclusion: TO is an independent prognosis factor in patients undergoing neoadjuvant chemotherapy and surgery for AGC and is associated with postoperative chemotherapy benefits.

[Research progress on pneumoconiosis markers based on multi-omics analysis].

The etiology of pneumoconiosis is relatively clear, but the pathogenic mechanism is not fully understood, and there is no effective cure for pneumoconiosis. Clarifying the pathogenesis of pneumoconiosis and exploring relevant markers can help screen high-risk groups of dust exposure, and relevant markers can also be used as targets to intervene in the process of pulmonary fibrosis. The in-depth development of genomics, transcriptomics and proteomics has provided a new way to discover more potential markers of pneumoconiosis. In the future, the combination of multi-omics and multi-stage interactive analysis can systematically and comprehensively identify key genes (proteins) , metabolites and metabolic pathways in the occurrence and development of pneumoconiosis, build a core regulatory network, and then screen out sensitive markers related to early diagnosis and treatment of pneumoconiosis. This article summarizes the research progress of pneumoconiosis markers from the perspective of multi-omics, hoping to provide more basic data for the early prevention and diagnosis of pneumoconiosis, pathogenesis research, and therapeutic intervention.

Measurement of Ultra-High-Energy Diffuse Gamma-Ray Emission of the Galactic Plane from 10 TeV to 1 PeV with LHAASO-KM2A.

The diffuse Galactic γ-ray emission, mainly produced via interactions between cosmic rays and the interstellar medium and/or radiation field, is a very important probe of the distribution, propagation, and interaction of cosmic rays in the Milky Way. In this Letter, we report the measurements of diffuse γ rays from the Galactic plane between 10 TeV and 1 PeV energies, with the square kilometer array of the Large High Altitude Air Shower Observatory (LHAASO). Diffuse emissions from the inner (15°10 TeV). The energy spectrum in the inner Galaxy regions can be described by a power-law function with an index of -2.99±0.04, which is different from the curved spectrum as expected from hadronic interactions between locally measured cosmic rays and the line-of-sight integrated gas content. Furthermore, the measured flux is higher by a factor of ∼3 than the prediction. A similar spectrum with an index of -2.99±0.07 is found in the outer Galaxy region, and the absolute flux for 10≲E≲60 TeV is again higher than the prediction for hadronic cosmic ray interactions. The latitude distributions of the diffuse emission are consistent with the gas distribution, while the longitude distributions show clear deviation from the gas distribution. The LHAASO measurements imply that either additional emission sources exist or cosmic ray intensities have spatial variations.

Asperosaponin VI Protects Against Bone Loss Due to Hindlimb Unloading in Skeletally Growing Mice Through Regulating Microbial Dysbiosis Altering the 5-HT Pathway.

Osteoporosis is a complex multifactorial disease that can lead to an increased risk of fracture. However, selective and effective osteoporosis drugs are still lacking. We showed that Asperosaponin VI (AVI) has the implications to be further developed as an alternative supplement for the prevention and treatment of bone loss. AVI has been found to have beneficial effects on metabolic diseases such as bone loss, obesity, and atherosclerosis. Our study was designed to determine the effect and mechanism of action of AVI against bone loss through regulating microbial dysbiosis. A hindlimb unloading mouse model was established to determine the effect of AVI on bone microarchitecture, gut microbiota, and serum metabolites. Eighteen female C57BL/6 J mice were divided into three groups: control, hindlimb unloading with vehicle (HLU), and hindlimb unloading treated with AVI (HLU-AVI, 200 mg/kg/day). AVI was administrated orally for 4 weeks. The results demonstrated that AVI improved the bone microstructure by reversing the decrease in bone volume fraction and trabecular number, and the increase in trabecular separation and structure model index of cancellous bone in hindlimb suspension mice. The results of 16sRNA gene sequencing suggested that the therapeutic effect of AVI on bone loss may be achieved through it regulating the gut microbiota, especially certain specific microorganisms. Combined with the analysis of ELISA, immunohistochemistry, and serum metabolome results, it could be speculated that AVI played an important role in adjusting the balance of bone metabolism by influencing specific flora such as Clostridium and its metabolites to regulate the 5-hydroxytryptophan pathway. The study explored the novel mechanism of AVI against osteoporosis, and has implications for the further development of AVI as an alternative supplement for the prevention and treatment of bone loss.

The Role of Mobility in the Dynamics of the COVID-19 Epidemic in Andalusia.

Metapopulation models have been a popular tool for the study of epidemic spread over a network of highly populated nodes (cities, provinces, countries) and have been extensively used in the context of the ongoing COVID-19 pandemic. In the present work, we revisit such a model, bearing a particular case example in mind, namely that of the region of Andalusia in Spain during the period of the summer-fall of 2020 (i.e., between the first and second pandemic waves). Our aim is to consider the possibility of incorporation of mobility across the province nodes focusing on mobile-phone time-dependent data, but also discussing the comparison for our case example with a gravity model, as well as with the dynamics in the absence of mobility. Our main finding is that mobility is key toward a quantitative understanding of the emergence of the second wave of the pandemic and that the most accurate way to capture it involves dynamic (rather than static) inclusion of time-dependent mobility matrices based on cell-phone data. Alternatives bearing no mobility are unable to capture the trends revealed by the data in the context of the metapopulation model considered herein.

Measurement of oesophageal hiatus surface area by multiplanar reconstruction of MDCT: relationship with lower oesophageal sphincter pressure and acid reflux.

AIM: To evaluate the relationship between oesophageal hiatus surface area (OHSA) and gastro-oesophageal reflux disease (GERD). MATERIALS AND METHODS: Patients who underwent 24-h pH monitoring, oesophageal high-resolution manometry, and upper abdominal contrast-enhanced multidetector computed tomography (MDCT) during 2014-2021 were enrolled. Patients with a hiatus hernia (HH) on MDCT or who had a history of gastro-oesophageal surgery were excluded. Multiplanar reconstruction (MPR) of the MDCT image was used for the measurement of OHSA. Correlations of OHSA with acid exposure time (AET) and lower oesophageal sphincter (LOS) pressure of all patients were analysed. RESULTS: Seventy-eight patients were included in the study. OHSA was much less in the AET <4% group than in the AET >6% group (1.61 ± 0.42 versus 2.09 ± 0.55 cm2, p<0.001). Correlation analysis reveals that OHSA correlated positively with AET (correlation coefficient = 0.47, p<0.001). Receiver operating characteristic (ROC) curve analysis reveals that OHSA can significantly distinguish patients in different groups divided by AET (area under the ROC curve [AUC] = 0.76, 95% confidence interval [CI]: 0.63-0.90). OHSA was not related to LOS pressure (correlation coefficient = -0.268, p=0.051). There was no difference in OHSA between the low LOS pressure group and the normal LOS pressure group (1.84 ± 0.61 versus 1.74 ± 0.50 cm2, p=0.52). CONCLUSIONS: OHSA significantly correlated with AET but has no relationship with LOS pressure. It may be an independent risk factor of GERD.

Predictive value of DEEPVESSEL-fractional flow reserve and quantitative plaque analysis based on coronary CT angiography for major adverse cardiac events.

AIM: To investigate the predictive value of the combination of DEEPVESSEL-fractional flow reserve (DVFFR) and quantitative plaque analysis using coronary computed tomographic angiography (CCTA) for major adverse cardiac events (MACE). METHOD: In this retrospective study, data from 69 vessels from 58 consecutive patients were collected. These patients who underwent coronary angiography (CAG) with DVFFR were divided into MACE-positive and MACE-negative groups. DVFFR measurements were obtained from CCTA images acquired before CAG, and an FFR or DVFFR value ≤ 0.80 was considered haemodynamically significant. CCTA images were analysed quantitatively using automated software to obtain the following indices: total plaque volume (TPV) and burden (TPB), calcified plaque volume (CPV) and burden (CPB), non-calcified plaque volume (NCPV) and burden (NCPB), low-attenuation plaque (LAP), minimum lumen area (MLA), stenosis grade (SG) and lesion length (LL). Univariate and multivariate logistic regression, correlation, and receiver operating characteristic (ROC) analyses were used for statistical analysis. RESULTS: DVFFR was highly correlated with invasive FFR (R=0.728), and the Bland-Altman plot showed good agreement between DVFFR and FFR (95% CI: -0.109-0.087) on a per-vessel level. DVFFR showed a high diagnostic performance in identifying abnormal haemodynamic vessels, with an area under the ROC curve (AUC) of 0.984. In multivariate analysis, the following biomarkers were predictors of MACE: DVFFR ≤ 0.8, SG, TPB, NCPB, and LL values. The combination of the above independent risk factors yielded the most valuable prediction for MACE (AUC:0.888). CONCLUSIONS: DVFFR was highly correlated with FFR with satisfactory diagnostic accuracy. DVFFR, together with plaque analysis indices, yielded valuable predictions for MACE.

RESOLVE-based radiomics in cervical cancer: improved image quality means better feature reproducibility?

AIM: To compare the reproducibility of apparent diffusion coefficient (ADC)-based radiomic features between readout-segmented echo-planar diffusion-weighted imaging (RESOLVE) and single-shot echo-planar diffusion-weighted imaging (SS-EPI DWI) in cervical cancer. MATERIALS AND METHODS: The RESOLVE and SS-EPI DWI images of 36 patients with histopathologically confirmed cervical cancer were collected retrospectively. Two observers independently delineated the whole tumour on RESOLVE and SS-EPI DWI, and then copied them to the corresponding ADC maps. Shape, first-order, and texture features were extracted from ADC maps in the original and filtered (Laplacian of Gaussian [LoG] and wavelet) images. Thereafter, 1,316 features were generated in each RESOLVE and SS-EPI DWI, respectively. The reproducibility of radiomic features was assessed using intraclass correlation coefficient (ICC). RESULTS: In the original images, RESOLVE showed 92.86%, 66.67%, and 86.67% of features with excellent reproducibility in shape, first-order, and texture features, while SS-EPI DWI showed 85.71%, 72.22%, and 60% of features with excellent reproducibility, respectively. In the LoG and wavelet filtered images, RESOLVE had 56.77% and 65.32% of features with excellent reproducibility and SS-EPI DWI had 44.95% and 61.96% of features with excellent reproducibility, respectively. CONCLUSION: Compared with SS-EPI DWI, the feature reproducibility of RESOLVE was better in cervical cancer, especially for texture features. The filtered images cannot improve the feature reproducibility compared with the original images for both SS-EPI DWI and RESOLVE.

Radiomics nomogram integrating intratumoural and peritumoural features to predict lymph node metastasis and prognosis in clinical stage IA non-small cell lung cancer: a two-centre study.

AIM: To investigate the value of a radiomics nomogram integrating intratumoural and peritumoural features in predicting lymph node metastasis and overall survival (OS) in patients with clinical stage IA non-small-cell lung cancer (NSCLC). MATERIALS AND METHODS: This study retrospectively enrolled 199 patients (training cohort: 71 patients from Affiliated Tumour Hospital of Nantong University; internal validation cohort: 46 patients from Affiliated Tumour Hospital of Nantong University; external validation cohort: 82 patients from the public database). CT radiomics models were constructed based on four volumes of interest: gross tumour volume (GTV), gross and 3 mm peritumoural volume (GPTV3), gross and 6 mm peritumoural volume (GPTV6), and gross and 9 mm peritumoural volume (GPTV9). The optimal radiomics signature was further combined with independent clinical predictors to develop a nomogram. Univariable and multivariable Cox regression analysis were applied to determine the relationship between factors and OS. RESULTS: GPTV6 radiomics yielded better performance than GTV, GPTV3, and, GPTV9 radiomics in the training (area under the curve [AUC], 0.81), internal validation (AUC, 0.79), and external validation cohorts (AUC, 0.71), respectively. The nomogram integrating GPTV6 radiomics and spiculation improved predictive ability, with AUCs of 0.85, 0.80, and 0.74 in three cohorts, respectively. Pathological lymph node metastasis, nomogram-predicted lymph node metastasis, and pleural indentation were independent risk predictors of OS (p<0.05). CONCLUSIONS: The nomogram integrating GPTV6 radiomics features and independent clinical predictors performed well in predicting lymph node metastasis and prognosis in patients with clinical stage IA NSCLC.