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BackgroundIntraoperative opioid use has a positive relationship with postoperative nausea and vomiting (PONV), and opioid-free anaesthesia (OFA) might reduce PONV. We investigated whether OFA compared with opioid-based anaesthesia would reduce PONV during the first 2 postoperative days among patients undergoing thoracoscopic lung resection.MethodsIn this randomised controlled trial, 120 adult patients were randomly assigned (1:1, stratified by sex) to receive either OFA with esketamine, dexmedetomidine, and sevoflurane, or opioid-based anaesthesia with sufentanil and sevoflurane. A surgical pleth index (SPI) of 20-50 was applied for intraoperative analgesia provision. All subjects received PONV prophylaxis (dexamethasone and ondansetron) and multimodal analgesia (flurbiprofen axetil, ropivacaine wound infiltration, and patient-controlled sufentanil). The primary outcome was the occurrence of PONV during the first 48 h after surgery.ResultsThe median age was 53 yr and 66.7% were female. Compared with opioid-based anaesthesia, OFA significantly reduced the incidence of PONV (15% vs 31.7%; odds ratio [OR]=0.38, 95% confidence interval [CI], 0.16-0.91; number needed to treat, 6; P=0.031). Secondary and safety outcomes were comparable between groups, except that OFA led to a lower rate of vomiting (OR=0.23, 95% CI, 0.08-0.77) and a longer length of PACU stay (median difference=15.5 min, 95% CI, 10-20 min). The effects of OFA on PONV did not differ in the prespecified subgroups of sex, smoking status, and PONV risk scores.ConclusionsIn the context of PONV prophylaxis and multimodal analgesia, SPI-guided opioid-free anaesthesia halved the incidence of PONV after thoracoscopic lung resection, although it was associated with a longer stay in the PACU.Clinical trial registrationChinese Clinical Trial Registry (ChiCTR2200059710).

Background Pandemic influenza virus is a public health issue, and the neuraminidase inhibitors (NIs) “Oseltamivir” and “Zanamivir” are effective treatments. While teenagers use NIs, there are concerns regarding neuropsychiatric adverse events (NPAEs). Aim We aimed to use the Taiwan National Health Insurance Research Database to identify the correlation between NPAEs and NIs use in teenagers aged 13–19 years. Methods The final population between 2000 and 2015 included in this study was 3698 individuals, with 2287 individuals having received “Oseltamivir” and “Zanamivir” (study cohort group) and 9148 individuals not receiving “Oseltamivir” and “Zanamivir” (comparison cohort group). We initially used a multivariate Cox regression analysis during the tracking period to determine the cumulative incidence of NPAEs. Results Our findings revealed no significant increase in the likelihood of developing NPAEs in the study group. The Kaplan–Meier survival curve demonstrated that individuals who received “Oseltamivir” and “Zanamivir” were not associated with statistically significantly increased NPAEs compared with controls (log-rank test, P = 0.724). Conclusion No more risk in comparison of the normal population in our study, and the safety of “Oseltamivir” and “Zanamivir” is established treatments for influenza.

Abstract Background Hypertensive disorders of pregnancy are among the leading causes of maternal mortality and morbidity in the U.S., with rates highest among birthing people who are Black, rural residents, and/or have low-income. Severe hypertension, in particular, increases risk of stroke and other serious pregnancy complications. To promote early detection and treatment of severe hypertension, the Alliance for Innovation on Maternal Health developed the Severe Hypertension During Pregnancy and Postpartum Period Safety Bundle (HTN Bundle). Multiple studies have demonstrated the HTN Bundle’s effectiveness in the inpatient setting. With funding from the National Heart, Lung, and Blood Institute, we engaged community partners to adapt the HTN Bundle for the outpatient setting (i.e., O-HTN Bundle) and planned for its implementation. In this paper, we describe the protocol for a study evaluating O-HTN Bundle implementation in 20 outpatient clinics serving Black, rural, and/or low-income populations. Methods This study is a hybrid type 3 effectiveness-implementation trial with a multiple baseline design. We will implement the O-HTN Bundle in three successive cohorts of clinics using a multicomponent implementation strategy to engage community partners (coalition, patient workgroup) and support clinics (training, facilitation, education materials, and simulations of severe hypertension events). To test the strategy, we will compare clinic fidelity to evidence-based guidelines for (a) patient education on hypertension and (b) blood pressure measurement technique, with repeated measures occurring before and after strategy receipt. We will also observe strategy effects on community- and clinic-level intermediate outcomes (community engagement, organizational readiness), implementation outcomes (reach, adoption, fidelity, maintenance), and effectiveness outcomes (receipt of guideline concordant care). Analyses will address whether outcomes are equitable across Black, rural, and/or low-income subgroups. Guided by the Consolidated Framework for Implementation Research 2.0, we will use mixed methods to identify adaptations and other determinants of implementation success. Discussion This study integrates community engagement and implementation science to promote equitable and timely response to severe HTN in the outpatient setting during pregnancy and postpartum. This is one of the first studies to implement an outpatient HTN Bundle and to use simulation as a strategy to reinforce team-based delivery of guideline concordant care. Trial registration This study was registered with ClinicalTrials.gov as “Testing Implementation Strategies to Support Clinic Fidelity to an Outpatient Hypertension Bundle (AC3HIEVE).” Registration number NCT06002165, August 21, 2023: https://clinicaltrials.gov/study/NCT06002165 .

Glucose-6-phosphate dehydrogenase (G6PD) deficiency and variants of the UDP-glucuronosyltransferase 1A1 (UGT1A1) gene are the most common genetic causes of neonatal unconjugated hyperbilirubinemia (NUH). In this review, we searched PubMed for articles on the genetic causes of NUH published before December 31, 2022, and analyzed the data. On the basis of the results, we reached eight conclusions: (1) 37 mutations of the G6PD gene are associated with NUH; (2) the clinical manifestation of G6PD deficiency depends not only on ethnicity but also on the molecular mechanisms underlying the deficiency (and thus its severity); (3) of mutations in the UGT1A1 gene, homozygous c.−53A(TA)6TAA > A(TA)7TAA is the main cause of NUH in Caucasians and Africans, whereas homozygous c.211G > A is the main genetic cause of NUH in East Asians; (4) in Indonesian neonates, homozygous c.−3279T > G is the most common cause of NUH development, and neither c.−53 A(TA)6TAA > A(TA)7TAA nor c.211G > A causes it; (5) in breast-fed East Asian neonates, the TA7 repeat variant of the UGT1A1 gene protects against the development of NUH; (6) G6PD deficiency combined with homozygous c.211G > A variation of the UGT1A1 gene increases the risk of severe NUH; (7) in Pakistani and Caucasian patients with Crigler–Najjar syndrome type 2 (CN-2), point mutations of the UGT1A1 gene are widely distributed and frequently occur with variation at nucleotide −53, whereas in Asian patients with CN-2, compound homozygous variations in the coding region are frequently observed; and (8) records of G6PD deficiency and UGT1A1 variation status for a neonate offer useful pharmacogenomic information that can aid long-term care. These results indicate that timely diagnosis of NUH through molecular tests is crucial and that early initiation of treatment for the neonates and educational programs for their parents improves outcomes.

Abstract Oral squamous cell carcinoma (OSCC) is a prevalent cancer worldwide, exhibiting unique regional prevalence. Despite advancements in diagnostics and therapy, the 5-year survival rate for patients has seen limited improvement. A deeper understanding of OSCC pathogenesis, especially its molecular underpinnings, is essential for improving detection, prevention, and treatment. In this context, noncoding RNAs, such as circular RNAs (circRNAs), have gained recognition as crucial regulators and potential biomarkers in OSCC progression. Our study highlights the discovery of previously uncharacterized circRNAs, including a SNX5 gene-derived circRNA, circSNX5, through deep sequencing of OSCC patient tissue transcriptomes. We established circSNX5’s tumor-specific expression and its strong correlation with patient survival using structure-specific and quantitative PCR analyses. In vitro and in vivo experiments underscored circSNX5 RNA’s regulatory role in cancer growth and metastasis. Further, our omics profiling and functional assays revealed that ADAM10 is a critical effector in circSNX5-mediated cancer progression, with circSNX5 maintaining ADAM10 expression by sponging miR-323. This novel circRNA-miRNA-mRNA regulatory axis significantly contributes to oral cancer progression and malignancy. Moreover, we discovered that circSNX5 RNA is produced via noncanonical sequential back-splicing of pre-mRNA, a process negatively regulated by the RNA-binding protein STAU1. This finding adds a new dimension to our understanding of exonic circRNA biogenesis in the eukaryotic transcriptome. Collectively, our findings offer a detailed mechanistic dissection and functional interpretation of a novel circRNA, shedding light on the role of the noncoding transcriptome in cancer biology and potentially paving the way for innovative therapeutic strategies.

Background/purpose: Interproximal contact loss may lead to food impaction and result in subsequently periodontal complications. The purpose of this prospective study was to investigate the peri-implant parameters of posterior implant-supported single crowns (SCs) with and without mesial proximal contact loss after 2 years of follow-up. Material and methods: Twenty-six patients with a total of 40 posterior implant-supported SCs with mesial adjacent natural teeth were observed for 24 months after crown insertion. The mesial proximal contacts were assessed by dental floss, then were classified as tight, weak, and open contacts. The following peri-implant parameters were evaluated, including modified plaque index (MPI), modified gingival index (MGI), and probing depth (PD) were conducted at six sites per tooth (mesiofacail, midfacial, distofacial, mesiolingual, mid-lingual and distolingual) in the 6-, 12-, 18- and 24-month following visits. Furthermore, radiographs were taken regularly in 12- and 24-month recall sections for measuring the marginal bone loss (MBL). Results: At 12-month observation, the incidence rates of weak and open contacts were 22.5 % and 12.5 %; whereas after 24 months of clinical service, the rates came up with 12.9 % and 25.6 %, respectively. No significant differences were found between the tight, weak, and open contact groups in the parameters of MPI, MGI, or PD (P > 0.05) at 12- and 24-month follow-up. None of the mean differences of the peri-implant parameters: MPI, MGI, PD and MBL had significant differences between the tight, weak, and open contact groups after 1 and 2 years of clinical service (P > 0.05). Conclusion: The presence of open, weak, and tight mesial proximal contacts had no significant effects on the peri-implant tissue conditions.

Very light pseudoscalar fields, often referred to as axions, are compelling dark matter candidates and can potentially be detected through their coupling to the electromagnetic field. Recently a novel detection technique using the cosmic microwave background (CMB) was proposed, which relies on the fact that the axion field oscillates at a frequency equal to its mass in appropriate units, leading to a time-dependent birefringence. For appropriate oscillation periods this allows the axion field at the telescope to be detected via the induced sinusoidal oscillation of the CMB linear polarization. We search for this effect in two years of POLARBEAR data. We do not detect a signal, and place a median 95% upper limit of 0.65° on the sinusoid amplitude for oscillation frequencies between 0.02 days-1 and 0.45 days-1, which corresponds to axion masses between 9.6×10-22 eV and 2.2×10-20 eV. Under the assumptions that (1) the axion constitutes all the dark matter and (2) the axion field amplitude is a Rayleigh-distributed stochastic variable, this translates to a limit on the axion-photon coupling gφγ

BackgroundRegular physical activity is associated with improved quality of life in patients with inflammatory bowel diseases (IBDs), although much of the existing research is based on self-reported data. Wearable devices provide objective data on many rich physical activity dimensions including steps, duration, distance, and intensity. Little is known about how patients with IBDs engage in these varying dimensions of exercise and how it may influence their symptom and disease-specific patient-reported outcomes (PROs). ObjectiveThis study aims to (1) cluster physical activity patterns from consumer-grade wearable devices and (2) assess the relationship between the clusters and PROs in patients with IBDs. MethodsWe conducted a cross-sectional and longitudinal cohort study among adults with IBDs in the Crohn’s and Colitis Foundation IBD Partners cohort. Participants contribute physical activity data through smartphone apps or wearable devices in a bring-your-own-device model. Participants also complete biannual PRO questionnaires from the Patient-Reported Outcomes Measurement Information System short forms and IBD-specific questionnaires. K-means cluster analysis was used to generate physical activity clusters based on 3 key features: number of steps, duration of moderate to vigorous activity (minutes), and distance of activity (miles). Based on the clusters, we conducted a cross-sectional analysis to examine differences in mean questionnaire scores and participant characteristics using one-way ANOVA and chi-square tests. We also conducted a longitudinal analysis to examine individual cluster transitions among participants who completed multiple questionnaires, and mean differences in questionnaire scores were compared using 2-tailed paired sample t tests across 6-month periods. ResultsAmong 430 participants comprising 1255 six-week physical activity periods, we identified clusters of low (33.7%, n=423), moderate (46%, n=577), and high (20.3%, n=255) physical activity. Scores varied across clusters for depression (P=.004), pain interference (P

Abstract Retinal degeneration, a leading cause of irreversible low vision and blindness globally, can be partially addressed by retina prostheses which stimulate remaining neurons in the retina. However, existing electrode-based treatments are invasive, posing substantial risks to patients and healthcare providers. Here, we introduce a completely noninvasive ultrasonic retina prosthesis, featuring a customized ultrasound two-dimensional array which allows for simultaneous imaging and stimulation. With synchronous three-dimensional imaging guidance and auto-alignment technology, ultrasonic retina prosthesis can generate programmed ultrasound waves to dynamically and precisely form arbitrary wave patterns on the retina. Neuron responses in the brain’s visual center mirrored these patterns, evidencing successful artificial vision creation, which was further corroborated in behavior experiments. Quantitative analysis of the spatial-temporal resolution and field of view demonstrated advanced performance of ultrasonic retina prosthesis and elucidated the biophysical mechanism of retinal stimulation. As a noninvasive blindness prosthesis, ultrasonic retina prosthesis could lead to a more effective, widely acceptable treatment for blind patients. Its real-time imaging-guided stimulation strategy with a single ultrasound array, could also benefit ultrasound neurostimulation in other diseases.

Introduction: Older adults with dementia who are on multiple medications are more vulnerable to the use of potentially inappropriate medications (PIMs), which can significantly increase the risk of adverse events and drug-related problems. PIMs use is prevalent and varies among older adults with dementia or cognitive impairment (CI) attending memory clinics. However, the prevalence of PIMs, polypharmacy, and hyper-polypharmacy among older adults with dementia or CI who are attending memory clinics is not well understood. We will conduct a systematic review and meta-analyses to examine the overall estimate of the prevalence of the PIMs, polypharmacy, and hyper-polypharmacy use among older adults attending memory clinics, with dementia or CI. The secondary objective of this study will be to compile a list of commonly implicated PIMs and to investigate factors that may be associated with using PIMs in this population. Methods: Ovid MEDLINE, Ovid Embase, Scopus, Cochrane library, EBSCOhost CINAHL, and Ovid International Pharmaceutical Abstracts (IPA) will be systematically searched by a researcher (R.S.) with the help of a librarian (C.C.). All databases will be searched from inception to May 05, 2023. Cross-sectional, cohort, randomized clinical trials, quasi-experimental, and case-control studies will be included if they assess PIM’s use among older adults with dementia and/or CI. A step-by-step guide by Pai et al. [Natl Med J India. 2004;17(2):86–95] will be followed when conducting this systematic review (S.R.). The PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) checklist will be followed for reporting this SR. Conclusion: The findings from this SR/MA will identify the pooled prevalence of PIMs, providing a more precise estimate of the true prevalence of the PIMs, polypharmacy, hyper-polypharmacy in older adults with dementia or CI who are attending memory clinics at primary, secondary, or tertiary healthcare settings by considering the results of multiple studies.

Abstract Introduction Chronic non-infectious uveitis affecting the posterior segment (NIU-PS), which can be recurrent and persistent for numerous years, mainly affects people of working age and significantly increases the risk of visual impairment. This study aimed to investigate the cost-effectiveness of fluocinolone acetonide intravitreal (FAI) implant in the treatment of patients with chronic NIU-PS from the Chinese healthcare perspective. Methods A Markov model with a 2-week cycle was constructed from the perspective of the Chinese healthcare system over a lifetime time horizon. The model consists of four health states: on-treatment, treatment failure, blindness, and death. The outcomes for effectiveness were based on the Chinese real-world study (RWS). Utilities and mortality rates were derived from published literature and standard sources. Costs were determined from the MENET website, prices of medical service items at local providers, published literature, and expert surveys. Outcomes were measured in quality-adjusted life years (QALYs). Sensitivity analyses were performed to account for the impact of uncertainty. Results It was estimated that in the base case, the FAI implant provided 0.43 incremental QALYs compared with the limited current practice (LCP) at an additional cost of $7503.72 (¥50,575.05), resulting in an incremental cost-effectiveness ratio (ICER) of $17,373.49 (¥117,097.33) per QALY gained. Parameters related to utility emerged as the primary influencers on the outcomes. In probabilistic sensitivity analysis (PSA), considering the willingness-to-pay (WTP) threshold of $19,072 (¥128,547) and $38,145 (¥257,094), the FAI implant had 67.70% and 99.50% probability of being cost-effective, respectively. As demonstrated in the scenario analysis, if the FAI implant aligns its price reduction with the average rate from the 2023 negotiation of the National Reimbursement Drug List (NRDL), it would result in lower costs and represent an absolute advantage. Conclusions The FAI implant, which can effectively reduce the recurrence rate and maintain the incremental costs within the WTP limit, is likely to be cost-effective in treating chronic NIU-PS in China.

Abstract Background Medication management capacity is a crucial component of medication adherence, particularly among older adults. Various factors, including physical abilities, cognitive functions, sensory capabilities, motivational, and environmental factors, influence older adults' ability to manage medications. It is, therefore, crucial to identify appropriate tools that allow clinicians to determine which factors may impact medication management capacity and, consequently, nonadherence to medications. Purpose 1)To identify tools that measure physical, cognitive, sensory (vision, hearing, touch), motivational, and environmental barriers to medication self-management in older adults, and 2) to understand the extent to which these tools assess various barriers. Methods The scoping review was conducted using Arksey and O'Malley's scoping review framework and the PRISMA Extension for Scoping Reviews checklist. In June 2022, the relevant literature was identified by searching PubMed (MEDLINE), Ovid Embase, Ovid IPA, EBSCOhost CINAHL, APA PsycINFO, and Scopus. Results and discussion In total, 7235 studies were identified. Following the removal of duplicates, 4607 articles were screened by title and abstract, of which 4253 did not meet the inclusion criteria. Three reviewers reviewed the full texts of the remaining 354 articles; among them, 41 articles, 4 theses and 1 conference abstract met the inclusion criteria. From the included studies, 44 tools were identified that measured a combination of physical, cognitive, sensory, motivational, and environmental barriers (n=19) or only cognition (n=13), vision (n=5), environmental factors (n=3), auditory (n=1), and motivational factors (n=1). The review also examined the psychometric properties of the identified tools and found that most of them had reported validity and reliability data. Several tools have demonstrated promise in assessing a combination of barriers with validity and reliability. These tools include the Self-Medication Assessment Tool (SMAT), ManageMed Screening (MMS), Self-Medication Risk Assessment Tool (RAT), HOME-Rx revised, and Medication Management Ability Assessment (MMAA). Conclusion This scoping review identified 44 validated tools to measure various challenges that older adults encounter with medication management. However, no tool measures all five barriers (physical, cognitive, sensory, motivational, and environmental) to medication-taking at home. Therefore, utilizing a combination of tools would be most appropriate to measure these different aspects comprehensively. Further research is needed to develop a new comprehensive tool that simultaneously measures various barriers to medication self-management.

Abstract Background The workplace can play an important role in shaping the eating behaviors of U.S. adults. Unfortunately, foods obtained in the workplace tend to be low in nutritional quality. Questions remain about the best way to approach the promotion of healthy food purchases among employees and to what extent health promotion activities should be tailored to the demographic characteristics of the employees. The purpose of this study was to (1) assess the nutritional quality of lunchtime meal purchases by employees in cafeterias of a large organization, (2) examine associations between lunchtime meal quality selection and the demographic characteristics of employees, and (3) determine the healthfulness of foods and beverages offered in the cafeterias of this organization. Methods A cross-sectional analysis was conducted using secondary data from a food labeling study implemented in three worksite cafeterias. Demographic data was collected via surveys and meal data was collected using a photo capture system for 378 participants. The Healthy Eating Index 2015 (HEI-2015) was used to determine meal quality and a total score for the menu of options available in the cafeterias during the study period. Summary statistics were generated, and the analysis of variance (ANOVA) was used to compare the HEI-2015 scores between groups. Results The mean HEI-2015 total score for the menu items offered (n = 1,229) in the cafeteria during the study period was 63.1 (SD = 1.83). The mean HEI-2015 score for individual lunchtime meal observations (n = 378) was 47.1 (SD = 6.8). In general, HEI-2015 total scores were higher for non-smokers, individuals who self-identified as Asian, had higher physical activity levels, scored higher on numeracy and literacy assessments, and reported higher education levels, incomes, and health status. Conclusions The overall HEI-2015 scores indicate that the menu of options offered in the cafeterias and individual meal selections did not align with the Dietary Guidelines for Americans, and there were significant associations between average lunchtime meal quality scores and several demographic characteristics. These results suggest that healthy eating promotion activities in workplaces may need to be tailored to the demographic characteristics of the employees, and efforts to improve the food environment in the workplace could improve meal quality for all employees.

Objectives: As Spanish-speaking parents face many barriers to care, we sought to: (1) understand HIT experiences and preferences; (2) pilot test a tablet/navigator intervention; (3) understand HIT uses and barriers. Methods: Prospective, uncontrolled, non-randomized, pilot intervention examining facilitated access to a patient portal for Spanish-speaking parents. Parents were recruited from pediatric specialty clinics in an academic center. Parents received an electronic tablet pre-populated with health resources, plus 2 telephone calls from a navigator. Surveys assessed HIT perceptions/use; portal activation was assessed through electronic records. Results: Twenty-five Spanish-speaking parents were enrolled. All parents wished they knew more about their child's health and that doctors knew them better. Most parents endorsed interest in HIT, however only 12% activated portals. Post-intervention, there were non-significant increases in using portals to make appointments, receive reminders, send/receive messages, and view labs/instructions. Uses of study tablets included video visits (56%), health/COVID information (16%), and schoolwork (16%). Innovation: Spanish-speaking parents express high interest in HIT. Provision of tablets may augment electronic capacity and facilitate video visits. Greater Spanish-language support is needed for Spanish-speaking parents to meaningfully use portals.

BackgroundDepressive symptoms are common among patients with lung cancer. We aimed to assess the effects of esketamine on postoperative depressive symptoms after thoracoscopic lung cancer surgery.MethodsIn this randomized, double-blind, placebo-controlled trial, 156 patients undergoing thoracoscopic lung cancer surgery were randomly allocated in a 1:1 ratio to receive intravenous esketamine (intraoperatively and in patient-controlled analgesia until 48 h postoperatively) or normal saline placebo. The primary outcome was the proportion of patients with depressive symptoms at 1 month postoperatively, assessed using the Beck Depression Inventory-II (BDI-II). Secondary outcomes included depressive symptoms at 48 h postoperatively, hospital discharge and 3 months postoperatively, BDI-II scores, anxious symptoms, Beck Anxiety Inventory scores, Quality of Recovery-15 (QoR-15) scores, and 1- and 3-month mortality.Main resultsA total of 151 patients (75 in the esketamine group and 76 in the normal saline group) completed the 1-month follow-up. The esketamine group had a significantly lower incidence of depressive symptoms at 1 month compared to the normal saline group (1.3% vs. 11.8%; risk difference = -10.5, 95%CI = -19.6% to -0.49%; p = 0.018). After excluding patients without lung cancer diagnosis, the incidence of depressive symptoms was also lower in the esketamine group (1.4% vs. 12.2%; risk difference = -10.8, 95%CI = -20.2% to -0.52%; p = 0.018). The secondary outcomes were similar between groups, except that the esketamine group had higher QoR-15 scores at 1 month postoperatively (median difference = 2; 95%CI = 0 to 5; p = 0.048). The independent risk factors for depressive symptoms were hypertension (odds ratio = 6.75, 95%CI = 1.13 to 40.31; p = 0.036) and preoperative anxious symptoms (odds ratio = 23.83, 95%CI = 3.41 to 166.33; p = 0.001).ConclusionPerioperative administration of esketamine reduced the incidence of depressive symptoms at 1 month after thoracoscopic lung cancer surgery. History of hypertension and preoperative anxious symptoms were independent risk factors for depressive symptoms.Clinical trial registration: Chinese Clinical Trial Registry http://www.chictr.org.cn, Identifier (ChiCTR2100046194).

Background: A previous phase 1 dose-escalation study in Taiwan indicated CAN008 (asunercept) with standard concurrent chemoradiotherapy (CCRT) improved progression-free survival (PFS) in newly diagnosed glioblastoma (GBM) patients. This study evaluates the efficacy of CAN008 in promoting overall survival (OS) and identifies genetic alterations associated with treatment responses. Methods: We compared OS of 5-year follow-ups from 9 evaluable CAN008 cohort patients (6 received high-dose and 3 received low-dose) to a historical Taiwanese GBM cohort with 164 newly diagnosed patients. CAN008 treatment response-associated genetic alterations were identified by whole-exome sequencing and comparing variant differences between response groups. Associations among patient survival, tumor mutational burden (TMB), and genetic alterations were analyzed using CAN008 cohort and TCGA-GBM dataset. Results: OS for high-dose CAN008 patients at 2 and 5 years was 83% and 67%, respectively, and 40.1% and 8.8% for the historical GBM cohort, respectively. Better OS was observed in the high-dose CAN008 cohort (without reaching the median survival) than the historical GBM cohort (median OS: 20 months; p = 0.0103). Five high-dose CAN008 patients were divided into good and poor response groups based on their PFS. A higher variant count and TMB were observed in good response patients, whereas no significant association was observed between TMB and patient survival in the newly diagnosed TCGA-GBM dataset, suggesting TMB may modulate patient CAN008 response. Conclusion: CAN008 combined with standard CCRT treatment prolonged the PFS and OS of newly diagnosed GBM patients compared to standard therapy alone. Higher treatment efficacy was associated with higher TMB.

Optimizing tillage practices to improve crop yield and crop water productivity (CWP) is essential for promoting sustainable dryland agriculture. This meta-analysis used the water supply during the growing season (WS, total soil water storage at sowing time, and growing-season precipitation) instead of mean annual precipitation (MAP), to assess the effects of different tillage practices on the yield and CWP of winter wheat and spring maize in northern China. The results showed that WS had a stronger correlation with crop yield than MAP, especially for winter wheat. Compared with conventional tillage, no-tillage combined with straw mulching (SM) increased winter yield by 36.56 % and CWP by 17.93 % when WS ≤ 650 mm, and subsoiling tillage increased winter wheat yield by 21.17 % and CWP by 9.29 % in winter wheat yield when WS > 650 mm. SM and subsoiling tillage performed better in regions with higher mean annual temperature (MAT) than that with lower MAT. For spring maize, no tillage, no-tillage combined with plastic film mulching (PM), subsoiling tillage and rotary tillage significantly increased yield and CWP under different WS conditions and the highest effect was showed in PM under higher WS condition; meanwhile, PM and subsoiling tillage performed good under various temperature conditions, while rotary tillage performed better in areas with lower temperature. Thus, the recommended tillage practice for spring maize is PM in northeast China, and subsoiling tillage in north-central and northwest China; for winter wheat, subsoiling tillage is recommended for north-central China, and SM is recommended for northwest China. Taken together, our results indicate that it is more accurate to use WS rather than the MAP to evaluate appropriate tillage practices in drylands. Furthermore, WS can also replace MAP for yield estimation and prediction.

Background: Patients with poor glycemic control are at increased risk of postoperative complications. Hemoglobin A 1c (HbA 1c ) has traditionally been used to assess preoperative glycemic control, but with limitations. More recently, fructosamine has been tested preoperatively in patients undergoing elective total joint arthroplasty. This study aims to assess whether preoperative serum fructosamine can be used to avoid adverse outcomes in patients undergoing foot and ankle surgery. Methods: This was a retrospective chart review of all patients who underwent foot and ankle surgeries at 2 level 1 trauma centers from January 2020 to December 2021. Of those, 305 patients were tested for HbA 1c and fructosamine levels preoperatively. Adverse outcomes were assessed over 30 and 90 days. Outcomes of interest were surgical site infection, wound dehiscence, unplanned return to the operating room, unplanned readmission, and death. Data were analyzed using independent 2-sample t tests. A mixed effects model was used for multivariate analysis. P values less than .05 were considered statistically significant. Results: Preoperative serum fructosamine was significantly higher ( P = .029) in those with complications within 90 days compared to those without. The mean preoperative fructosamine level was 269.2 µmol/L (SD = 58.85) in those who did have a complication vs 247.2 µmol/L (SD = 53.95) in those who did not. Clinically significant fructosamine threshold was determined using 2 different methods. Fructosamine was found to be non-inferior to HbA 1c in accurately predicting postoperative complications. Conclusion: Fructosamine is a serum marker that reflects nearer term glycemic control than HbA 1c . Elevation in preoperative fructosamine is associated with increased perioperative complications after foot and ankle surgery within 90 days. Preoperative fructosamine may be used in patient optimization and risk stratification when determining candidacy and timing for elective foot and ankle surgeries. Level of evidence: Level III, retrospective cohort study.