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BackgroundPain ratings reported by patients with cancer continue to increase, and numerous computer and phone apps for managing cancer-related pain have been developed recently; however, whether these apps effectively alleviate patients’ pain remains unknown. ObjectiveThis study aimed to comprehensively evaluate the role of mobile apps in the management of cancer pain. MethodsLiterature on the use of apps for cancer pain management and interventions, published before August 2019, was retrieved from the following databases: MEDLINE, Embase, Cochrane, CINAHL, Scopus, and PsycINFO. The effects of apps on cancer pain were evaluated using RevMan5.3 software, and the rates of adverse drug reactions were analyzed using the R Statistical Software Package 3.5.3. ResultsA total of 13 studies were selected for the analysis: 5 randomized controlled trials (RCTs), 4 before-after studies, 2 single-arm trials, 1 prospective cohort study, and 1 prospective descriptive study. The 5 RCTs reported data for 487 patients (240 patients in the intervention group and 247 patients in the control group), and the remaining studies reported data for 428 patients. We conducted a meta-analysis of the RCTs. According to the meta-analysis, apps can significantly reduce pain scores (mean difference [MD]=–0.50, 95% CI –0.94 to –0.07, I2=62%, P=.02). We then used apps that have an instant messaging module for subgroup analysis; these apps significantly reduced patients’ pain scores (MD=–0.67, 95% CI –1.06 to –0.28, I2=57%, P

Abstract Pressure dynamics can reflect the basic characteristics of fluid flow through underground porous formation. In this research, the oil–gas two-phase flow model for a double-porosity media formation with permeability-stress sensitivity was first established for three kinds of outer boundaries. The unified governing equation was deduced by utilizing the H function. The nonlinear mathematical model in consideration of permeability-stress sensitivity was linearized by implementing the canonical perturbation transformation and then solved by using the Laplace transformation. After that, a sequence of typical log–log curves of pressure dynamics influenced by various model parameters were plotted and analyzed. These curves reflect the typical characteristic of a V shape caused by the inter-porosity fluid flow from matrix toward natural fractures. Oil saturation and permeability-stress sensitivity coefficient have much influence on the pressure dynamics. Ultimately, the established model of oil–gas two-phase flow was validated through a well-test fitting interpretation for a real condensate gas well in a sandstone formation. This research can offer insights into the pressure dynamics dominated by the oil–gas two-phase flow in naturally fractured formations and the permeability-stress sensitivity effect.

Abstract Background The association of body mass index (BMI) with survival outcomes in patients with advanced non-small cell lung cancer (NSCLC) treated with first-line chemotherapy, immunotherapy, or chemoimmunotherapy is controversial. We aimed to investigate these associations, including associations in male and female patients specifically, in a multicenter cohort study. Methods We retrospectively analyzed data from seven cohorts comprising 7021 advanced non-small cell lung cancer patients who received chemotherapy (three cohorts), immunotherapy (two cohorts), and chemoimmunotherapy (two cohorts) from five data sources, including a de-identified nationwide (US-based) NSCLC clinico-genomic database and two randomized, double-blind, phase 3 clinical trials. BMI was categorized as underweight, normal weight, overweight, or obese. Underweight patients were excluded because of their small proportion. The primary endpoints were the associations between BMI and progression-free survival (PFS) and overall survival (OS) stratified by treatment type and sex, which were assessed using Kaplan–Meier methods and adjusted Cox modeling. Meta-analyses were performed to combine the adjusted hazard ratios. Results In the pooled analysis, obesity was significantly associated with improved OS in patients receiving chemotherapy (hazard ratios [HR] = 0.84, 95% confidence interval (CI) 0.76–0.93), but there was no association with PFS (HR = 0.91, 95% CI 0.82–1.02). The association of BMI with OS for patients receiving chemotherapy differed by sex, with an inverse association in men (HR = 0.74, 95% CI 0.64–0.84), but no association observed in women (HR = 0.96, 95% CI 0.81–1.13, Pinteraction = 0.018). No impact of BMI on OS or PFS was detected in patients receiving immunotherapy or chemoimmunotherapy. Obese patients had the lowest level of tumor mutational burden, similar level of programmed death-ligand 1 expression and ESTIMATE scores. Conclusions Obesity may be associated with an increased overall survival among male patients treated with chemotherapy, whereas not associated with the outcomes in patients treated with immunotherapy or chemoimmunotherapy.

Abstract Although many researchers of Parkinson’s disease (PD) have shifted their focus from the central nervous system (CNS) to the peripheral blood, a significant knowledge gap remains between PD severity and the peripheral immune response. In the current study, we aimed to map the peripheral immunity atlas in peripheral blood mononuclear cells (PBMCs) from PD patients and healthy controls using single-cell RNA sequencing (scRNA-seq). Our study employed scRNA-seq analysis to map the peripheral immunity atlas in PD by profiling PBMCs from PD-Early, PD-Late patients and matched controls. By enlarging the blood sample size, we validated the roles of NK cells in numerous immune-related biological processes. We also detected the infiltration of NK cells into the cerebral motor cortex as the disease progressed, using human brain sections, and elucidated the communication between the periphery and CNS and its implications for PD. As a result, cell subpopulation atlases in PBMCs from PD patients and healthy controls along with differentially expressed genes in NK cells were identified by scRNA-seq analysis, representing 6 major immune cell subsets among which NK cells declined in the progression of PD. We further validated NK cell reduction in increasing samples and found that they participated in numerous immune-related biological processes and infiltration into the cerebral motor cortex as the disease proceeded, evidencingd the close communication between the peripheral immune response and CNS. Strikingly, XCL2 positively correlated with PD severity, with good predictive performance of PD and specific expression in subclusters C2 and C5 of NK cells. All these findings delineated the critical role of peripheral immune response mediated by NK cells in the pathogenesis of PD. NK cell-specific XCL2 could be used as a diagnostic marker for treating PD. The indispensable function of NK cells and NK cell-specific molecular biomarkers highlighted the implication of the peripheral immune response in PD progression. Trial registration: ChiCTR, ChiCTR1900023975. Registered 20 June 2019 - Retrospectively registered, https://www.chictr.org.cn/showproj.html?proj=31035 .

Fibroblast growth factor receptor 1 (FGFR1) mutations are associated with congenital hypogonadotropic hypogonadism (CHH) through inheritance or spontaneous occurrence. We detected FGFR1 mutations in a Chinese cohort of 210 CHH patients at Peking Union Medical College Hospital (Beijing, China) using next-generation and Sanger sequencing. We assessed missense variant pathogenicity using six bioinformatics tools and compared clinical features and treatment outcomes between inherited and de novo mutation groups. Among 19 patients with FGFR1 mutations, three were recurrent, and 16 were novel variants. Sixteen of the novel mutations were likely pathogenic according to the American College of Medical Genetics and Genomics (ACMG) guidelines, with the prevalent P366L variant. The majority of FGFR1 mutations was inherited (57.9%), with frameshift mutations exclusive to the de novo mutation group. The inherited mutation group had a lower incidence of cryptorchidism, short stature, and skeletal deformities. In the inherited mutation group, luteinizing hormone (LH) levels were 0.5 IU l−1, follicle-stimulating hormone (FSH) levels were 1.0 IU l−1, and testosterone levels were 1.3 nmol l−1. In contrast, the de novo group had LH levels of 0.2 IU l−1, FSH levels of 0.5 IU l−1, and testosterone levels of 0.9 nmol l−1, indicating milder hypothalamus–pituitary–gonadal axis (HPGA) functional deficiency in the inherited group. The inherited mutation group showed a tendency toward higher spermatogenesis rates. In conclusion, this study underscores the predominance of inherited FGFR1 mutations and their association with milder HPGA dysfunction compared to de novo mutations, contributing to our understanding of the genetic and clinical aspects of FGFR1 mutations.

Abstract Background and Aims Data on the safety and effectiveness of tenofovir alafenamide (TAF) plus peginterferon-alpha (Peg-IFN-α) in children with chronic hepatitis B (CHB) are lacking. The current study aimed to present the characteristics of four pediatric CHB patients who obtained a functional cure by using TAF and Peg-IFN-α. Methods In this case series study initiated in May 2019, ten children who had no clinical symptoms or signs received response-guided (HBV DNA undetectable, hepatitis B e antigen [HBeAg] loss or seroconversion, and hepatitis B surface antigen [HBsAg] loss or seroconversion) and functional cure-targeted (HBsAg loss or seroconversion) TAF (25 mg/d, orally) plus Peg-IFN-α-2b (180 µg/1.73m2, subcutaneously, once weekly) in combination (9/10) or sequential (1/10) therapy. The safety and effectiveness of these treatments were monitored. Results As of April 2024, four out of ten children obtained a functional cure after a mean of 31.5 months of treatment, and the other six children are still undergoing treatment. These four cured children, aged 2, 4, 8, and 6 years, were all HBeAg-positive and had alanine aminotransferase levels of 80, 47, 114, and 40 U/L; HBV DNA levels of 71200000, 93000000, 8220, and 96700000 IU/mL; and HBsAg levels of 39442.8, 15431.2, 22, and 33013.1 IU/mL, respectively. During treatment, all the children (10/10) experienced mild or moderate adverse events, including flu-like symptoms, anorexia, fatigue, and cytopenia. Notably, growth retardation (8/10) was the most significant adverse event; and it occurred in three cured children (3/4) treated with combination therapy and was present to a low degree in the other cured child (1/4) treated with sequential therapy. Fortunately, all three cured children recovered to or exceeded the normal growth levels at 9 months posttreatment. Conclusions TAF plus Peg-IFN-α-2b therapy is potentially safe and effective for pediatric CHB patients, which may provide important insights for future clinical practice and study designs targeting functional cures for children with CHB.

The in-situ TEM irradiation experiments of zirconium alloy were conducted at 573 K, 673 K, and 773 K utilizing a 400 keV Kr + single beam and a 400 keV Kr+ and 30 keV He + dual beam. The results show that a large number of dislocation loops have been characterized in the matrix of the zirconium alloy under irradiation. With increasing the irradiation damage dose, some dislocation loops have reacted with one another to form a larger dislocation loop, which has finally formed dislocation lines or other defect structures. In zirconium alloys irradiated with Kr + single beam and Kr+ and He + dual-beam radiation, the proportion of type dislocation loops with different Burgers vectors is essentially the same at low damage doses, but the proportion of interstitial type dislocation loops with the same Burgers vectors is obviously different. The amorphization of the second phase and the dissolution of the small-sized second phase were also pointed out. With the increase in temperature, the density of the dislocation loop in zirconium alloy gradually decreases, and the size of dislocation loop first increases and then decreases. Kr+ and He + dual beam irradiation increases the size of dislocation loops but decreases their density as compared with Kr + single beam irradiation.

Shengli exploration area in Junggar Basin is mainly located in the ultra-denudation zone， complex piedmont zone， and deep subsag zone around the basin. The conditions for oil and gas accumulation are complex， and exploration is difficult. In order to clarify the potential direction of key fields in Shengli exploration area and guide the optimization of the following oil and gas exploration deployment order， the next potential directions of each key field were analyzed on the basis of systematic summary of the exploration research progress of the sedimentation， reservoir， oil source correlation， transport system， hydrocarbon accumulation mode， as well as oil and gas enrichment control factors in the ultra-denudation zone field in the western margin of Junggar Basin， the deep field of the upper combination in the central area of Junggar Basin， the ultra-deep field of the lower combination in the central area of Junggar Basin， and the piedmont zone field in the northern margin and southeastern areas of Junggar Basin. The results show that the Jurassic-Cretaceous in Hashan area， the Neogene Shawan Formation in Chepaizi area， and the Carboniferous in Chepaizi area in the ultra-denudation zone in the western margin of the Junggar Basin， as well as the Jurassic Qigu Formation in Yongjin-Zhengshacun area and the Jurassic Sangonghe Formation in Moxizhuang area in the deep area of the upper combination in the central area of the Junggar Basin， are the main positions for increasing reserves and production in the future. The Permian Upper Wuerhe Formation-Triassic Karamay Formation in Well Zheng 10 area of Shawan Sag in the ultra-deep area of the lower combination in the central area of the Junggar Basin and the Permian Fengcheng Formation-Xiazijie Formation in Well Zhuangshen 1 area of the western sag of Well Pen 1 are the next important replacement positions. The parautochthonous nappe systems of the Hashan piedmont zone in the northern margin of the Junggar Basin and the southern and northern piedmont zones of Bogda Mountain in the southeastern margin of the Junggar Basin are the favorable positions to be explored continuously in the next step. The unconventional shale gas field in the deep Carboniferous strata of Shibei Sag and Shiqiantan Sag is a reserve position that needs to be actively prepared in the future. During the “14th-15th Five Year Planin 2021-2030” period， Shengli exploration area should be guided by the exploration concept of “focusing on the whole area， successfully exploring deep layers， emphasizing both conventional and unconventional oil and gas， and implementing coordinated promotion” and continuously and orderly promote exploration in various key fields of the basin.

Abstract Soil extractable nitrate, ammonium, and organic nitrogen (N) are essential N sources supporting primary productivity and regulating species composition of terrestrial plants. However, it remains unclear how plants utilize these N sources and how surface-earth environments regulate plant N utilization. Here, we establish a framework to analyze observational data of natural N isotopes in plants and soils globally, we quantify fractional contributions of soil nitrate (f NO3-), ammonium (f NH4+), and organic N (f EON) to plant-used N in soils. We find that mean annual temperature (MAT), not mean annual precipitation or atmospheric N deposition, regulates global variations of f NO3-, f NH4+, and f EON. The f NO3- increases with MAT, reaching 46% at 28.5 °C. The f NH4+ also increases with MAT, achieving a maximum of 46% at 14.4 °C, showing a decline as temperatures further increase. Meanwhile, the f EON gradually decreases with MAT, stabilizing at about 20% when the MAT exceeds 15 °C. These results clarify global plant N-use patterns and reveal temperature rather than human N loading as a key regulator, which should be considered in evaluating influences of global changes on terrestrial ecosystems.

Abstract Callosobruchus maculatus is one of the most competitive stored grain pests, which causes a great loss to agricultural economy. However, due to an inadequacy of high-quality reference genome, the molecular mechanisms for olfactory and hypoxic adaptations to stored environments are unknown and require to be revealed urgently, which will contribute to the detection and prevention of the invasive pests C. maculatus. Here, we presented a high-quality chromosome-level genome of C. maculatus based on Illumina, Nanopore and Hi-C sequencing data. The total size was 1.2 Gb, and 65.17% (797.47 Mb) of it was identified to be repeat sequences. Among assembled chromosomes, chromosome 10 was considered the X chromosome according to the evidence of reads coverage and homologous genes among species. The current version of high-quality genome provides preferable data resources for the adaptive evolution research of C. maculatus.

Abstract Sciatic nerve injury (SNI) is a common type of peripheral nerve injury typically resulting from trauma, such as contusion, sharp force injuries, drug injections, pelvic fractures, or hip dislocations. It leads to both sensory and motor dysfunctions, characterized by pain, numbness, loss of sensation, muscle atrophy, reduced muscle tone, and limb paralysis. These symptoms can significantly diminish a patient’s quality of life. Following SNI, Wallerian degeneration occurs, which activates various signaling pathways, inflammatory factors, and epigenetic regulators. Despite the availability of several surgical and nonsurgical treatments, their effectiveness remains suboptimal. Exosomes are extracellular vesicles with diameters ranging from 30 to 150 nm, originating from the endoplasmic reticulum. They play a crucial role in facilitating intercellular communication and have emerged as highly promising vehicles for drug delivery. Increasing evidence supports the significant potential of exosomes in repairing SNI. This review delves into the pathological progression of SNI, techniques for generating exosomes, the molecular mechanisms behind SNI recovery with exosomes, the effectiveness of combining exosomes with other approaches for SNI repair, and the changes and future outlook for utilizing exosomes in SNI recovery.