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Hydrogen can be used to reduce the concentration of reactive oxygen species (ROS), but its delivery to diseased tissues is challenging due to its low solubility. Here the authors develop a photosynthesis-inspired FRET nanocomplex to detect and scavenge local excess of ROS in the tissue using photocatalytic hydrogen production.

This study utilized semiconductor processing techniques to fabricate patterned silicon (Si) substrates with arrays of inverted pyramid-shaped micro-pits by etching. Molybdenum trioxide (MoO3) was then deposited on these patterned Si substrates using a thermal evaporation system, followed by two-stage sulfurization in a high-temperature furnace to grow MoS2 thin films consisting of only a few atomic layers. During the dropwise titration of Rhodamine 6G (R6G) solution, a longitudinal electric field was applied using a Keithley 2400 (Cleveland, OH, USA) source meter. Raman mapping revealed that under a 100 mV condition, the analyte R6G molecules were effectively confined within the pits. Due to its two-dimensional structure, MoS2 provides a high surface area and supports a surface-enhanced Raman scattering (SERS) charge transfer mechanism. The SERS results demonstrated that the intensity in the pits of the few-layer MoS2/patterned Si SERS substrate was approximately 274 times greater compared to planar Si, with a limit of detection reaching 10−5 M. The experimental results confirm that this method effectively resolves the issue of random distribution of analyte molecules during droplet evaporation, thereby enhancing detection sensitivity and stability.

This qualitative study aimed to investigate the effectiveness of community rehabilitation programs for children with developmental delays from the perspective of early intervention service providers in Taiwan. Adopting a single-case experimental design (ABM design), this study examined the immediate and sustained effects of interventions on individualized goals during baseline, intervention, and maintenance phases. Additionally, data from interviews with parents, special education teachers, and other participants were collected to understand the challenges and improvement strategies of community rehabilitation programs. Results revealed that community rehabilitation programs for children with developmental delays exhibited both immediate and sustained effectiveness. Challenges faced by parents and professionals differed, with parents having less contact and communication with administrative systems, while professionals experienced more pronounced implementation difficulties during interventions. Moreover, strategies for improving community rehabilitation programs for children with developmental delays should vary for parents and professionals to address inconsistencies in attitudes and strategies among parents and administrative obstacles encountered by professionals.

Abstract Objective This study evaluated the antitumor activity and safety of pemigatinib in previously treated Chinese patients with advanced cholangiocarcinoma and fibroblast growth factor receptor 2 (FGFR2) fusions or rearrangements. Background Pemigatinib provided clinical benefits for previously treated patients with cholangiocarcinoma carrying FGFR2 fusions or rearrangements and was approved for this indication in multiple countries. Methods In this ongoing, multicenter, single‐arm, phase II study, adult patients with locally advanced or metastatic cholangiocarcinoma carrying centrally confirmed FGFR2 fusions or rearrangements who had progressed on ≥1 systemic therapy received 13.5 mg oral pemigatinib once daily (3‐week cycle; 2 weeks on, 1 week off) until disease progression, unacceptable toxicity, or consent withdrawal. The primary endpoint was objective response rate (ORR) assessed by an independent radiology review committee. Results As of January 29, 2021, 31 patients were enrolled. The median follow‐up was 5.1 months (range, 1.5–9.3). Among 30 patients with FGFR2 fusions or rearrangements evaluated for efficacy, 15 patients achieved partial response (ORR, 50.0%; 95% confidence interval [CI], 31.3–68.7); 15 achieved stable disease, contributing to a disease control rate of 100% (95% CI, 88.4–100). The median time to response was 1.4 months (95% CI, 1.3–1.4), the median duration of response was not reached, and the median progression‐free survival was 6.3 months (95% CI, 4.9–not estimable [NE]). Eight (25.8%) of 31 patients had ≥grade 3 treatment‐emergent adverse events. Hyperphosphatemia, hypophosphatasemia, nail toxicities, and ocular disorders were mostly

Background: Screening for chronic atrophic gastritis (CAG) is crucial for the prevention and early detection of gastric cancer. Endoscopy is the main method of CAG diagnosis, with high training requirements and limited accuracy, making it difficult to popularize. The study attempts to improve the positive rate and accuracy of CAG screening through non-invasive testing. Methods: A total of 2564 patients who underwent gastroscopy were included in this study. The results of gastroscopic evaluation, histological biopsy results (including H. pylori biopsy), urea breath test (UBT) results, serum pepsinogen, and testosterone were statistically analyzed. Results: We found significant differences in the diagnosis of CAG between endoscopy and histological biopsy. Pepsinogen II and pepsinogen I/II ratio were more useful for the diagnosis of CAG compared with pepsinogen I. The risk of CAG was increased when pepsinogen II exceeded 11.05 μg/L, and the pepsinogen I/II ratio was less than 3.75. CAG positivity was higher in patients with positive H. pylori infection on UBT screening. In addition, higher levels of testosterone, SHBG and HSD17B2, and lower level of GNRH1 were found in CAG mucosa. Patients with high serum testosterone had a higher risk of CAG. Conclusion: CAG screening should be combined with endoscopic evaluation, biopsy, and other non-invasive tests. Non-invasive tests include the combination of serum pepsinogen II protein and pepsinogen I/II ratio and high level of serum testosterone. UBT combined with serum pepsinogen testing may improve the positive rate of CAG and reduce gastric mucosal damage from multiple biopsies.

Affective states play a role in dietary behaviors. Yet, little research has studied within-subjects associations between affect and diet during pregnancy. We examined the acute bidirectional relationships between affect and food intake and moderation by pre-pregnancy body mass index (BMI) in low-income, Hispanic pregnant women using ecological momentary assessment (EMA). Women (N = 57) completed four days of EMA during their first trimester. Women responded to five random prompts per day about their current affect and past two-hour food intake. Higher positive affect (PA) or lower negative affect (NA) predicted greater likelihood of fruit/vegetable consumption in the next two hours in women with lower pre-pregnancy BMI and lower likelihood in women with higher pre-pregnancy BMI. Higher PA predicted less likelihood of fast food consumption in the next two hours in women with lower pre-pregnancy BMI and slightly higher likelihood in women with higher pre-pregnancy BMI. Women with lower pre-pregnancy BMI had higher PA when they reported consuming chips/fries in the past two hours, and women with higher pre-pregnancy BMI had lower PA when they reported consumption of chips/fries in the past two hours. Results showed differential relationships between affect and food intake as a function of pre-pregnancy BMI.

Objectives Recently studies demonstrated that adipose tissue can produce and release complement C3 and serum complement C3 levels were associated with diabetes mellitus, metabolic syndrome and non-alcoholic fatty liver disease (NAFLD). Thus, we plan to investigate the association of complement C3 levels and the presence of metabolic-associated fatty liver disease (MAFLD).Design Observational study with a cross-sectional sample.Setting This study surveyed 4729 participants in Zhejiang province, China.Participants 55 participants were excluded for acute infection and 1001 participants were excluded for lack of ultrasonography diagnoses and complete or partial absence of laboratory tests. The final sample size was 3673 participants.Outcome measures Spearman correlation analysis was used to examine the correlations between complement C3 levels and variables. Binary logistic regression was carried out to evaluate the association between complement C3 levels and the presence of MAFLD after adjustment for demographic and biochemical variables. Mediation effects were used to explore whether insulin resistance (IR), hyperlipidaemia and obesity mediated the association between complement C3 and MAFLD.Results Participants with MAFLD had higher complement C3 levels and complement C3 levels were closely associated with body mass index, waist circumference, alanine aminotransferase, aspartate aminotransferase, γ-glutamyl transpeptidase and homoeostasis model assessment (HOMA)-IR. The presence of MAFLD increased with the increase of complement C3 levels and the presence of MAFLD were highest in the HOMA-IR ≥2.5 participants. We found the OR and Cl of standardised C3 for MAFLD was 1.333 (1.185–1.500), each 1 SD increase in C3 would increase the presence of MAFLD by 33.3%, and obesity partly mediated the effect of complement C3 on the presence of MAFLD.Conclusions The present results suggest that complement C3 can be used as a risk factor for the presence of MAFLD after adjustment for confounding variables and obesity may partly mediate the effect of complement C3 on the presence of MAFLD.

Summary: Background: Rectal neoplasm is one of the most common malignancies worldwide. Screening programs for rectal neoplasm result in early diagnosis and a decrease in disease-related mortality and morbidity. In selected patients, early rectal cancer may be treated with local excision. Owing to poor exposure during conventional transanal excision, transanal minimally invasive surgery (TAMIS) was developed, and TAMIS is feasible for the local excision of selected rectal neoplasms. However, the limited range of motion is a major disadvantage of this operation. Therefore, robotic TAMIS was developed to resolve this issue. This paper describes the surgical outcomes of robotic TAMIS for selected rectal tumors. Methods: The eligibility criteria for robotic TAMIS were as follows: benign neoplasms, early malignancy, complete remission after concurrent chemoradiotherapy, lesions located in the middle or lower rectum, and a lesion size of less than 5 cm. To gain access to the anal canal, a transanal access platform was used, and the da Vinci robotic system was mounted for surgery. Patient characteristics and surgical outcomes were recoded. Results: A total of 23 patients were included, and the median tumor size was 2.5 cm (range: 1.1–4.5 cm) on average. The median tumor location was 5 cm (range: 2–8 cm) from the anal verge. The median length of hospital stay was 3 days (range: 1–10 days). No intraoperative complications were reported, and no patient readmission occurred. The median follow-up period was 9.6 months. No recurrent lesion was found in the follow-up period. Conclusion: Based on the short-term results, robotic TAMIS is a feasible and safe technique for the local excision of selected rectal neoplasms. Keywords: Robotic, Selected rectal neoplasms, Transanal minimally invasive surgery

Background: The percentage of female medical students has been significant elevating worldwide. The demographic shift is expected to influence the proportion of male versus female surgeons soon. The objective of this study was to evaluate the gender differences in the acquisition of robotic suturing skills. Methods: We compared the robotic suturing performance between 39 male and 19 female medical students. We separated the training into two parts: phase I, involving virtual reality (VR) robotic simulation, and phase II, involving robotic dry-laboratory simulation training. Participants first conducted step-by-step exercises on the VR robotic simulator and then the robotic skin-suturing pad using the da Vinci robot. Results: The metric analysis of the VR task “suture sponge” showed that female students required less time (difference: −170.7 seconds, 95% CI: −247.4 to −94.0) and had fewer errors (error difference: −50, 95% CI: −74.2 to −25.8) to complete the suture sponge exercise compared to male students. Moreover, female students completed more stitches than male students (differences in mean stitch achieved: .35; 95% CI: .06 to .65). However, there was no difference in the quality scores of stitches by gender (p = 0.85). Conclusion: Female medical students performed better in the VR task of suture spongy and achieved more stitches than male students with the da Vinci system despite no difference in robotic suture quality by gender. Because this is the first study comparing gender performance on a robotic platform, further studies are required to investigate if different training approaches will affect the performance by gender. Keywords: Robotic surgery, Simulation, Gender difference, Virtual reality, Medical education

Abstract Background Aberrant expression of the RON receptor tyrosine kinase is a pathogenic feature and a validated drug target in various types of cancers. Currently, therapeutic antibodies targeting RON for cancer therapy are under intensive evaluation. Here we report the development and validation of a novel humanized anti-RON antibody-drug conjugate for cancer therapy. Methods Antibody humanization was achieved by grafting sequences of complementarity-determining regions from mouse monoclonal antibody Zt/g4 into human IgG1/κ acceptor frameworks. The selected humanized Zt/g4 subclone H1L3 was conjugated with monomethyl auristatin E using a dipeptide linker to form H-Zt/g4-MMAE. Pharmacokinetic analysis of H-Zt/g4-MMAE was determined using hydrophobic interaction chromatography and a MMAE ADC ELISA kit. Biochemical and biological assays were used for measuring RON expression, internalization, cell viability and death. Therapeutic efficacies of H-Zt/g4-MMAE were validated in vivo using three pancreatic cancer xenograft models. Toxicological activities of H-Zt/g4-MMAE were determined in mouse and cynomolgus monkey. Results H-Zt/g4-MMAE had a drug to antibody ratio of 3.77:1 and was highly stable in human plasma with a dissociation rate less than 5% within a 20 day period. H-Zt/g4-MMAE displayed a favorable pharmacokinetic profile in both mouse and cynomolgus monkey. In vitro, H-Zt/g4-MMAE induced RON internalization, which results in killing of pancreatic cancer cells with IC50 values at 10–20 nM. In vivo, H-Zt/g4-MMAE inhibited pancreatic cancer xenograft growth with tumoristatic concentrations at 1~3 mg/kg bodyweight. Significantly, H-Zt/g4-MMAE eradicated tumors across multiple xenograft models regardless their chemoresistant and metastatic statuses. Moreover, H-Zt/g4-MMAE inhibited and eradicated xenografts mediated by pancreatic cancer stem-like cells and by primary cells from patient-derived tumors. Toxicologically, H-Zt/g4-MMAE is well tolerated in mice up to 60 mg/kg. In cynomolgus monkey, H-Zt/g4-MMAE up to 30 mg/kg had a manageable and reversible toxicity profile. Conclusions H-Zt/g4-MMAE is superior in eradication of pancreatic cancer xenografts with favorable pharmacokinetic profiles and manageable toxicological activities. These findings warrant the transition of H-Zt/g4-MMAE into clinical trials in the future.

A simulated design for a temperature-compensated voltage sensor based on photonic crystal fiber (PCF) infiltrated with liquid crystal and ethanol is presented in this paper. The holes distributed across the transverse section of the PCF provide two channels for mode coupling between the liquid crystal or ethanol and the fiber core. The couplings are both calculated accurately and explored theoretically using the finite element method (FEM). The influence of voltage on the alignment of the liquid crystal molecules and confinement loss of the fiber mode are studied. Liquid crystal molecules rotate which changes its properties as the voltage changes. As the characteristics of the liquid crystal will be affected by temperature, therefore, we further fill using ethanol, which is merely sensitive to temperature, into one hole of the PCF to realize temperature compensation. The simulated results show that the sensitivity is up to 1.29977 nm/V with the temperature of 25 °C when the voltage ranges from 365 to 565 V. The standard deviation of the wavelength difference is less than 2 nm within the temperature adjustment from 25 to 50 °C for temperature compensation. The impacts of the construction parameters of the PCF on sensing performances of this voltage sensor are also analyzed in this paper.

Background: Given the unprecedented nature of the COVID-19 pandemic, it is important to understand how those with eating disorders (EDs) are affected by the pandemic. Using data from the Understanding America Study (UAS), we examined the association between EDs and mental health and how the relationship changed over time across the months following the institution of virus containment procedures (e.g., social distancing, quarantine). Method: The analytic sample consisted of 7137 adults (Mage =50.58 years; SD =16.10) who completed surveys between waves 1–11 of the UAS study. Participants self-reported ED diagnosis (i.e., yes, no, or unsure) and completed self-report measures of psychological distress, perceived stress, and loneliness. Multilevel models were used to compare trajectories of psychological distress, perceived stress, and loneliness among ED groups. Results: Individuals with EDs and unsure EDs had higher levels of psychological distress, perceived stress, and loneliness compared to those without EDs. Those unsure about their EDs showed initial decreases in perceived stress and loneliness but started increasing again after some time. Levels of loneliness among those with EDs increased initially but later began to decrease; individuals with EDs showed steady decreases in perceived stress. Limitations: Type, severity, and duration of EDs were unspecified in the self-reported measure of EDs, which could differentiate the trajectories of outcomes. Conclusions: Intervention is crucial for mitigating mental health problems among those with a history of ED symptoms during COVID-19. Further, results showed that individuals who are unsure about their ED status may be experiencing more fluctuation in mental health across the pandemic.

Cylindrical waveguides have a wide range of applications in photonic integrated circuits because of lower transmission losses. This paper proposes a directional coupler composed of a cylindrical silicon nanowire waveguide and a metal-based cylindrical hybrid plasmon waveguide. The coupling characteristics of the coupler are analyzed theoretically and are also simulated using the finite-difference time-domain method. The results show that the coupler can operate effectively with a relatively short coupling length, displaying low insertion loss, and a high coupling efficiency and extinction ratio. This study also shows how the TM mode in the plasmon waveguide can be excited with the TE mode of the dielectric waveguide. This directional coupler has a potential application in signal exchanging and mode switching between the dielectric and plasmon waveguides in photonic integrated circuits.

O6-methylguanine DNA methyltransferase (MGMT), a DNA repair enzyme, has been reported in some congenital malformations, but it is less frequently reported in neural tube defects. This study investigated MGMT mRNA expression and methylation levels in the early embryo and in different embryonic stages, as well as the relationship between MGMT and neural tube defects. Spina bifida aperta was induced in rats by a single intragastric administration of all-trans retinoic acid on embryonic day (E) 10, whereas normal control rats received the same amount of olive oil on the same embryonic day. DNA damage was assessed by detecting γ-H2A.X in spina bifida aperta rats. Real time-polymerase chain reaction was used to examine mRNA expression of MGMT in normal control and spina bifida aperta rats. In normal controls, the MGMT mRNA expression decreased with increasing embryonic days, and was remarkably reduced from E11 to E14, reaching a minimum at E18. In the spina bifida aperta model, γ-H2A.X protein expression was increased, and mRNA expression of MGMT was markedly decreased on E14, E16, and E18. Bisulfite sequencing polymerase chain reaction for MGMT promoter methylation demonstrated that almost all CpG sites in the MGMT promoter remained unmethylated in both spina bifida aperta rats and normal controls, and there was no significant difference in methylation level between the two groups on either E14 or E18. Our results show that DNA damage occurs in spina bifida aperta rats. The mRNA expression of MGMT is downregulated, and this downregulation is independent of promoter DNA methylation.

Background and Aims: The best treatment modalities for elderly patients with stage I–II HCC (hepatocellular carcinoma) remain controversial in an era of a shortage of liver donors.Methods: From the SEER database (Surveillance, Epidemiology, and End Results program), 2,371 elderly patients were sampled as Cohort 1. OS (Overall Survival) and CSS (Cancer-Specific Survival) were compared between the Non-surgery and Surgery groups. A stratification analysis in a CSS Cox model was also conducted among sub-groups, and propensity score matching was performed to generate Cohort 2 (746 pairs), reducing the influences of confounders.Results: For Cohort 1, the median follow-up times of the Non-surgery and Surgery groups were 11 months (95% CI, confidence interval: 9.74–12.26) vs. 49 months (44.80–53.21) in OS, and 14 months (12.33–15.67) vs. 74 months (64.74–83.26) in CSS, respectively. In the stratification analysis, for the elderly patients (age >= 70 years), Larger Resection was associated with a higher HR (hazard ratio) than Segmental Resection: 0.30 (95% CI, confidence interval: 0.22–0.41) vs. 0.29 (0.21–0.38) in 70–74 year-olds; 0.26 (0.18–0.38) vs. 0.23 (0.16–0.32) in 75–79 year-olds; 0.32 (0.21–0.49) vs. 0.21 (0.13–0.32) in those 80+ years old. For Cohort 2, a similar result could be seen in the CSS Cox forest plot. The HRs of Larger Resection and Segmental Resection were 0.27 (0.21–0.33) and 0.25 (0.20–0.31), respectively.Conclusions: It is cautiously recommended that, when liver transplantation is not available, segmental or wedge liver resection is the better treatment choice for elderly patients with stage I–II HCC (AJCC edition 6), especially those over 70 years old, compared with other surgeries, based on the SEER data.

Abstract Background This study aimed to investigate the efficacy and safety of drug eluting beads transarterial chemoembolization (DEB-TACE) treatment by CalliSpheres® in Chinese patients with hepatocellular carcinoma (HCC) as well as the predicting factors for response. Methods 99 patients with HCC were consecutively enrolled in this study. All participants were treated by CalliSpheres® DEB-TACE. Clinical response was evaluated according to modified Response Evaluation Criteria in Solid Tumors (mRECIST) criteria. Common Terminology Criteria for Adverse Events (CTCAE) was used to assess the adverse events and liver dysfunction during and after the operation. Results Post treatment, 16 patients (16.2%) achieved CR and 59 (59.6%) achieved PR, the ORR was 75.8%. Subgroup analysis showed that patients with higher BCLC stage were of worse CR and ORR rates, and the CR as well as ORR between patients with cTACE history and patients without cTACE history were similar. Univariate logistic regression analysis displayed that number of nodules > 3, higher BCLC stage and previous cTACE might be correlated with worse ORR but with no statistical significance. As to liver function, CTCAE grades of laboratory indexes for liver function were increased at 1 week compared to baseline and recovered to the baseline grades at 1–3 months post operation. Besides, most of the common adverse events were light and moderate in our study. Conclusions In conclusion, DEB-TACE by CalliSpheres® was efficient and well tolerated in Chinese HCC patients, and BCLC stage, number of nodules and cTACE history were possibly correlated with treatment response.

Background/Aims: Pancreatic cancer is an aggressive malignancy as a result of highly metastatic potential. The current study was carried out to alter the expression of LINC01121 in pancreatic cancer, with the aim of elucidating its effects on the biological processes of cell proliferation, migration, invasion, and apoptosis. We hypothesized that both the GLP1R gene and cAMP/PKA signaling pathway participate in the aforementioned process. Methods: Microarray data (GSE14245, GSE27890 and GSE16515) and annotating probe files linked to pancreatic cancer were downloaded through the GEO database. The Multi Experiment Matrix (MEM) site was used to predict the target gene of lncRNA. Both pancreatic cancer tissues (n = 56) and paracancerous tissues (n = 45) were collected from patients diagnosed with pancreatic cancer. Immunohistochemistry was applied to identify the positive expression rate of GLP1R protein. Isolated pancreatic cancer cells and PANC-1 cells were independently classified into the blank, negative control (NC), LINC01121 vector, siRNA-LINC01121, siRNA-GLP1R and siRNA-LINC01121 + siRNA-GLP1R groups. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) and Western blot analysis were applied to detect the expressions of LINC01121, GLP1R, cAMP, PKA, CREB, Bcl-2, Bad and PCNA. Cell proliferation, migration, invasion, cycle progression, and apoptosis were examined by MTT assay, scratch test, Transwell assay and flow cytometry analyses of Annexin V-FITC/PI staining. Results: Observations were made indicating that LINC01121 was highly expressed, while low expressions of GLP1R in pancreatic cancer were detected based on microarray data, which was largely in consistent with the data collected of LINC01121 and GLP1R within the tissues. The target prediction program and luciferase activity analysis was testament to the notion suggesting that GLP1R was indeed a target of LINC01121. In contrast to the blank and NC groups, the LINC01121 vector group exhibited increased expressions of LINC01121; decreased mRNA and protein levels of GLP1R, Bad, cAMP, and PKA; increased protein levels of CREB, Bcl-2, PCNA, p-PKA and p-CREB; increased cell proliferation, migration and invasion; and decreased cell apoptosis. There was no significant difference detected among the blank, NC, and siRNA-LINC01121 + siRNA-GLP1R groups, except that decreased LINC01121 expression was determined in the siRNA-LINC01121 + siRNA-GLP1R group. Parallel data were observed in the pancreatic cancer cells and PANC-1 cells. Conclusion: The current study presents evidence indicating that LINC01121 might inhibit apoptosis while acting to promote proliferation, migration, and invasion of pancreatic cancer cells, supplementing the stance held that LINC01121 functions as a tumor promoter by means of its involvement in the process of translational repression of the GLP1R and inhibition of the cAMP/PKA signaling pathway.

Nucleoplasmin (Npm) is an abundant histone chaperone in vertebrate oocytes and embryos. During embryogenesis, regulation of Npm histone binding is critical for its function in storing and releasing maternal histones to establish and maintain the zygotic epigenome. Here, we demonstrate that Xenopus laevis Npm post-translational modifications (PTMs) specific to the oocyte and egg promote either histone deposition or sequestration, respectively. Mass spectrometry and Npm phosphomimetic mutations used in chromatin assembly assays identified hyperphosphorylation on the N-terminal tail as a critical regulator for sequestration. C-terminal tail phosphorylation and PRMT5-catalyzed arginine methylation enhance nucleosome assembly by promoting histone interaction with the second acidic tract of Npm. Electron microscopy reconstructions of Npm and TTLL4 activity toward the C-terminal tail demonstrate that oocyte- and egg-specific PTMs cause Npm conformational changes. Our results reveal that PTMs regulate Npm chaperoning activity by modulating Npm conformation and Npm-histone interaction, leading to histone sequestration in the egg.

Following publication of the original article [1], the author reported two errors in the authors affiliations: