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The rapid integration of artificial intelligence (AI) into health professions education is revolutionizing traditional teaching methodologies and enhancing learning experiences. This study explores the use of generative AI to aid occupational therapy (OT) students in intervention planning. OT students often lack the background knowledge to generate a wide variety of interventions, spending excessive time on idea generation rather than clinical reasoning, practice skills, and patient care. AI can enhance creative ideation but students must still adhere to evidence-based practice, patient safety, and privacy standards. Students used ChatGPT v. 3.5 in a lecture and assignment to integrate generative AI into intervention planning. Students analyzed a case study, generated ideas with ChatGPT, selected interventions that aligned with the client’s needs, and provided a rationale. They conducted evidence-based searches and wrote an analysis on how the research influenced their decisions. The results demonstrate generative AI’s potential as a valuable tool for OT students, enhancing their comfort with AI and understanding of ethical and safety considerations. Qualitative feedback highlighted AI’s role in boosting efficiency and creativity in intervention planning, with most students expressing strong intent to use ChatGPT in clinical practice due to its ability to reduce cognitive load and generate innovative ideas. These findings suggest that integrating generative AI into the OT curriculum could enhance intervention planning and improve clinical readiness.

Abstract Background The Longshi Scale is a pictorial assessment tool for evaluating activities of daily living (ADL) in patients with stroke. The paper-based version presents challenges; thus, the WeChat version was created to enhance accessibility. Herein, we aimed to validate the inter-rater and test–retest reliabilities of the WeChat version of the Longshi Scale and explore its potential clinical applications. Methods We recruited 115 patients with stroke in the study. The ADL results of each patient were assessed using both the WeChat and paper-based version of the Longshi Scale; each evaluation was conducted by 28 health professionals and 115 caregivers separately. To explore the test–retest reliability of the WeChat version, 22 patients were randomly selected and re-evaluated by health professionals using the WeChat version. All evaluation criteria were recorded, and all evaluators were surveyed to indicate their preference between the two versions. Results Consistency between WeChat and the paper-based Longshi Scale was high for ADL scores by health professionals (ICC2,1 = 0.803–0.988) and caregivers (ICC2,1 = 0.845–0.983), as well as for degrees of disability (κw = 0.870 by professionals; κw = 0.800 by caregivers). Bland–Altman analysis showed no significant discrepancies. The WeChat version exhibited good test–retest reliability (κw = 0.880). The WeChat version showed similar inter-rater reliability in terms of the ADL score evaluated using the paper-based version (ICC2,1 = 0.781–0.941). The time to complete assessments did not differ significantly, although the WeChat version had a shorter information entry time (P

Introduction Major depressive disorder (MDD), the second leading cause of disability globally, is considered to be associated with a consequent deterioration in the quality of life and can lead to a major economic burden on medical service and suicide-related costs. Previous research has shown that acupuncture may be beneficial for treating MDD. However, there is a lack of rigorous evidence from previous studies comparing acupuncture with antidepressant medications. This study aims to assess the therapeutic potential of acupuncture in the management of depressive disorders.Methods and analysis A multicentre, randomised, participant-blind, sham-controlled, 2×2 factorial clinical trial, Acupuncture and Escitalopram for Treating Major Depression Clinical Study, aims to compare the efficacy of acupuncture versus escitalopram in treating depression. This study will be conducted at three hospitals in China, enrolling 260 patients with moderate-to-severe major depression, as defined by DSM-5 criteria and Hamilton Depression Rating Scale (HDRS-17) Scores above 17. Participants will be randomly assigned in equal proportions to one of four groups (acupuncture/escitalopram, sham acupuncture/escitalopram, acupuncture/placebo and sham acupuncture/placebo) and undergo 30 sessions across 10 weeks. The primary outcome is change in HDRS-17 Score and secondary outcomes include BDI, Clinical Global Impression, Generalised Anxiety Disorder-7 and Mini-Mental State Examination Scores, alongside potential biological markers.Ethics and dissemination Ethical approval for the study was granted by the Ethics Committees of the Seventh People’s Hospital of Shanghai University of Traditional Chinese Medicine (2023-7th-HIRB-020), Shanghai Mental Health Centre (2022–86) and Shanghai Pudong New Area Hospital of Traditional Chinese Medicine (2023–003). Informed consent will be obtained from all participants. The study’s findings are intended for publication in a scholarly journal.Trial registration NCT05901571.

Background & Aims: Recent studies demonstrated the importance of fibrosis in promoting an immunosuppressive liver microenvironment and thereby aggressive hepatocellular carcinoma (HCC) growth and resistance to immune checkpoint blockade (ICB), particularly via monocyte-to-monocytic myeloid-derived suppressor cell (M-MDSC) differentiation triggered by hepatic stellate cells (HSCs). We thus aimed to identify druggable targets in these immunosuppressive myeloid cells for HCC therapy. Methods: M-MDSC signature genes were identified by integrated transcriptomic analysis of a human HSC-monocyte culture system and tumor-surrounding fibrotic livers of patients with HCC. Mechanistic and functional studies were conducted using in vitro-generated and patient-derived M-MDSCs. The therapeutic efficacy of a M-MDSC targeting approach was determined in fibrosis-associated HCC mouse models. Results: We uncovered over-expression of protein phosphatase 1 regulatory subunit 15A (PPP1R15A), a myeloid cell-enriched endoplasmic reticulum stress modulator, in human M-MDSCs that correlated with poor prognosis and ICB non-responsiveness in patients with HCC. Blocking TGF-β signaling reduced PPP1R15A expression in HSC-induced M-MDSCs, whereas treatment of monocytes by TGF-β upregulated PPP1R15A, which in turn promoted ARG1 and S100A8/9 expression in M-MDSCs and reduced T-cell proliferation. Consistently, lentiviral-mediated knockdown of Ppp1r15a in vivo significantly reduced ARG1+S100A8/9+ M-MDSCs in fibrotic liver, leading to elevated intratumoral IFN-γ+GZMB+CD8+ T cells and enhanced anti-tumor efficacy of ICB. Notably, pharmacological inhibition of PPP1R15A by Sephin1 reduced the immunosuppressive potential but increased the maturation status of fibrotic HCC patient-derived M-MDSCs. Conclusions: PPP1R15A+ M-MDSC cells are involved in immunosuppression in HCC development and represent a novel potential target for therapies. Impact and implications: Our cross-species analysis has identified PPP1R15A as a therapeutic target governing the anti-T-cell activities of fibrosis-associated M-MDSCs (monocytic myeloid-derived suppressor cells). The results from the preclinical models show that specific inhibition of PPP1R15A can break the immunosuppressive barrier to restrict hepatocellular carcinoma growth and enhance the efficacy of immune checkpoint blockade. PPP1R15A may also function as a prognostic and/or predictive biomarker in patients with hepatocellular carcinoma.

The suppression head impulse paradigm (SHIMP) involves suppression of the vestibulo-ocular reflex (VOR) and anticompensatory saccades generated thereof. SHIMP is gaining importance to understand vestibular compensation with its different parameters (VOR gain/peak saccadic velocity PSV/latency of saccades). SHIMP studies are emerging in adults, but pediatric studies have hardly been performed. This study is a retrospective case note audit over a period of 2 months in a tertiary pediatric vestibular center in the United Kingdom to investigate whether SHIMP is safe/robust to be used in children conforming to existing standards/norms in normal children and whether it yields any meaningful inferences in pediatric vestibular hypofunction. This is the largest pediatric SHIMP study to date. A total of 44 referred children (6–18 years, female children>male children) with a range of complaints from dizziness, imbalance, motor incoordination, postural instability, and hearing loss were included, and their SHIMP parameters were measured. All children underwent comprehensive functional/objective audiovestibular assessments. Two groups were defined—Group A with normal vestibular function and Group B with abnormal vestibular function. The normal population showed an average SHIMP VOR gain of 0.98+/−0.08 and latency of overt saccades at 215.68+/–46.16 milliseconds agreeing with published evidence. The PSV of overt saccades was 315.39+/−56.30/s, and there was a gain asymmetry of 7.42+/−4.68 between the sides. Statistically significant differences with moderate/large effect sizes were observed between the groups in terms of VOR gain and PSV but not in saccade latencies. Covert saccades were rare in SHIMP, while overt saccades were observed in 100% of children. VOR gain difference between the head impulse paradigm (HIMP) and the SHIMP was significant as well. We observed statistically significant differences in side asymmetry of VOR gain between the groups. Furthermore, we identified a group of children with cerebellar lesions where overt saccades in SHIMP were rather low in number. Further research is recommended to investigate pediatric PSV, asymmetry, and inability to generate overt saccades that may suggest useful means to assess compensation and central function. We conclude that SHIMP yields valuable information and is a safe, easy to perform, and a reliable test that should be used in children to supplement HIMP.

Bu-Shen-Yi-Qi granule (BSYQG), a Chinese herbal formula, has been used for the treatment of ischemic stroke with proven efficacy. The purpose of this study is to evaluate the therapeutic efficacy of BSYQG in neurovascular unit (NVU) and its mechanism of action on the thrombin expression in the cerebral ischemic/reperfusion (I/R) model. In the study, a rat model of I/R was established using middle cerebral artery occlusion operation (MCAO). Adult male Sprague–Dawley rats were divided into four groups (n = 36): sham-operation; I/R; I/R + BSYQG(6 g/kg/day), I/R + Argatroban (0.56 mg/ml). Apoptotic cells in the NVU were detected by doubling-labeling using TUNEL assay and immunofluorescence. The dynamics of thrombin expression was detected using immunofluorescence on both sides after I/R injury. Compared with I/R group the numbers and rates of neuronal apoptosis in BSYQG groups significantly decreased (P

Summary: Massive expansion of immature and suppressive myeloid cells is a common feature of malignant solid tumors. Over-expression of cyclin-dependent kinase 20, also known as cell cycle-related kinase (CCRK), in hepatocellular carcinoma (HCC) correlates with reduced patient survival and low immunotherapy responsiveness. Beyond tumor-intrinsic oncogenicity, here we demonstrated that CCRK is upregulated in myeloid cells in tumor-bearing mice and in patients with HCC. Intratumoral injection of Ccrk-knockdown myeloid-derived suppressor cells (MDSCs) increased tumor-infiltrating CD8+T cells and suppressed HCC tumorigenicity. Using an indel mutant transgenic model, we showed that Ccrk inactivation in myeloid cells conferred a mature phenotype with elevated IL-12 production, driving Th1 responses and CD8+T cell cytotoxicity to reduce orthotopic tumor growth and prolong survival. Mechanistically, CCRK activates STAT3/E4BP4 signaling in MDSCs to acquire immunosuppressive activity through transcriptional IL-10 induction and IL-12 suppression. Taken together, our findings unravel mechanistic insights into MDSC-mediated immunosuppression and offer a therapeutic kinase-target for cancer immunotherapy.

Objective: Traditionally, gallbladder is routinely removed during left hepatectomy even if there is no gallbladder pathology. However, adverse consequence after cholecystectomy, though rare, still occasionally occurs. This study aims to evaluate the feasibility of gallbladder preservation during robotic left hepatectomy. Methods: All consecutive robotic left hepatectomy cases between December 2010 and January 2022 in Prince of Wales Hospital, the Chinese University of Hong Kong were retrieved from a prospectively collected database. The gallbladder was preserved by moving the liver transection line just away from the gallbladder fossa. Patients were divided into two groups: gallbladder preservation (GBP) and non-gallbladder preservation (NGBP). Operative results and long-term outcomes were compared between these two groups. Results: There were 11 cases in the GBP group and 25 cases in the NGBP group. The two groups were comparable in terms of the patient demographics and disease characteristics. There was no operative mortality. There was no difference between the two groups in operative time (GBP 270 min vs. NGBP 332 min, p = 0.132), blood loss (GBP 50 mL vs. NGBP 150 mL, p = 0.115) or complication rate (GBP 27.3% vs. NGBP 24.0%, p > 0.999). There was also no difference in 5-year overall survival. In the GBP group, no patient developed specific symptoms or complications related to the preserved gallbladder. Follow-up ultrasound or computed tomography revealed a normal appearance of the preserved gallbladders except in one patient who developed a 3-mm gallbladder polyp. On the other hand, one (4%) patient in the NGBP group developed troublesome diarrhoea after surgery. Conclusion: Gallbladder preservation is safe and feasible during robotic left hepatectomy. The preserved gallbladder does not lead to any symptoms, while postcholecystectomy diarrhoea can be avoided.

Abstract Background To examine the extent to which financial impacts and community resources utilization are associated with pediatric feeding difficulties. We hypothesize that children with feeding difficulties will have more financial impacts and community resources utilization than children without feeding difficulties. Methods We conducted a secondary analysis of cross-sectional data from the 2017–2018 National Survey of Children’s Health (NSCH) regarding 14,960 children 0–5 years. NSCH utilized random sampling of families across the United States to collect nationally representative data. Outcomes included out-of-pocket costs, caregivers leaving a job due to the child’s health, food insufficiency, receival of food or cash assistance, and receival of special education and/or developmental services. We used a multivariable logistic regression controlling for sociodemographic factors to examine the associations of feeding difficulties with financial impacts and community resources utilization outcomes. Results Out of 14,690 respondents, children were a mean (SD) age of 2.53(0.03) years and 1.7% reported feeding difficulties. These children had higher odds of having out-of-pocket costs of ≥$1000 (OR: 3.01; 95% CI: 1.61, 5.62), having a caregiver that left a job due to their child’s health (OR: 3.16; 95% CI: 2.01, 4.98), experiencing food insufficiency (OR: 1.67; 95% CI: 1.03, 2.71), and receiving special education and/or developmental services (OR 3.98; 95% CI: 2.46, 6.45) than children without feeding difficulties. Conclusions Children with feeding difficulties are more likely to have financial impacts and community resources utilization than children without feeding difficulties. This information can be used to tailor interventions to improve family-centered care and outcomes for children.

Background and purposeHPV-associated or positive (HPV+) anal cancer patients may have better outcome compared to those with HPV negative (HPV−) disease. We report a planned interim analysis of a prospective registry study that tailors chemoradiation (CRT) for anal cancer according to HPV status.Materials and methodsHPV+ patients received de-escalated radiation doses of 45, 50.4 and 55.8 Gy, while HPV− received 50.4, 55.8 and 63 Gy for T1, T2 and T3/T4 disease respectively. Chemotherapy consisted of a single dose of mitomycin-C and oral capecitabine on days of RT. All patients were planned by VMAT following CT, PET/CT and MR simulation. This cohort (n = 24) had a minimum 24-month follow-up. Disease free survival (DFS) and local failure rates (LFR) were compared with 180 patients managed by standard CRT (2 cycles of mitomycin-C and 5-fluorouracil, radiation doses 50.4-63 Gy based on T-category) from 2011-2018. Propensity score comparison was performed using a retrospective to prospective 2 to 1 match based on tumor size and N-category.ResultsIn the HPV+ cohort (n = 20), there were 2 local failures. Two of 4 HPV− patients failed locally. The 30-month DFS and LFR were 79% and 17% respectively. Similar DFS and LFR were observed in the retrospective (80% and 15% respectively) and matched patients (76% and 16% respectively). No grade ≥3 neutropenia and febrile neutropenia were observed in the registry cohort whereas 19% and 14% respectively were seen in the retrospective patients.ConclusionDe-escalation of CRT for HPV+ anal cancer may result in decreased acute toxicities and similar cancer outcomes compared to standard CRT.

BackgroundNeuropathic pain (NP) is expected to increase due to the high risk of global population aging. Acupuncture has a definite clinical effect on NP. Therefore, a systematic review and meta-analysis were conducted to evaluate the effect on pain intensity and safety of acupuncture in patients with NP.MethodsAn encompassing search of specific authoritative databases in English, from their inception to 2022, was performed. The databases were as follows: Scopus, Ovid EMBASE, Ovid Cochrane Database of Systematic Reviews, Ovid Cochrane Central Register of Controlled Trials, Ovid MEDLINE(R) and Epub Ahead of Print, In-Process and Other Non-Indexed Citations, and Daily. All the randomized controlled trials regarding the acupuncture treatment of NP will be included. Methodological quality assessment of the included trials was assessed based on the risk of bias from the Cochrane handbook. A meta-analysis was performed for the main outcomes. In addition, sensitivity analysis, subgroup analysis, and funnel plot were also carried out.ResultsA total of 16 studies with 1,021 patients with NP were evaluated in a systematic review. According to the results of the overall meta-analysis in eight RCTs with 338 participants, the acupuncture group was better than the control group in improving changes in pain intensity (SMD −0.59, 95% CI: −0.95 to −0.23, P = 0.001). In subgroup analysis, five trials indicated that acupuncture was more effective in improving changes in pain intensity than sham acupuncture (SMD −0.54, 95% CI: −0.95 to −0.13, P = 0.01), two trials evaluated the effect on changes in pain intensity in the comparison of acupuncture and conventional treatments, no significant difference existed (SMD −0.61, 95% CI: −1.83 to 0.61, P = 0.33), and one trial compared acupuncture with blank control evaluating the effect of changes in pain intensity with a significant difference. Eleven studies mentioned the safety conditions and acupuncture-induced AEs were mild and reversible. Both the sensitivity analysis and funnel plot analysis showed that the meta-analysis was stable and irreversible without publication bias. The GRADE was rated as “very low.”ConclusionThe acupuncture group had higher effectiveness than sham intervention or blank control for changes in pain intensity, but there is no significant difference between acupuncture and conventional treatments in treating NP. The acupuncture-induced adverse events were mild and reversible. However, the interpretation of our results should be performed cautiously due to the low methodological quality of selected publications.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022306461.

Tumor invasion into the inferior vena cava (IVC) and hepatic vein (HV) is challenging in cancer surgery with curative intent. Appropriate techniques for venous reconstruction are essential. We have described in detail a novel technique of fashioning an interposition tube graft using the falciform ligament to reconstruct the IVC and HV. The falciform ligament maintains all the benefits of an autologous tissue graft, with the added advantage of its flexibility in customizing graft dimensions. Its use in IVC and HV reconstruction has rarely been reported. The short-term outcomes with this tube graft are promising.

PurposeIn this study, we aim to further evaluate the accuracy of ultrasound tracking for intra-fraction pancreatic tumor motion during radiotherapy by a phantom-based study.MethodsTwelve patients with pancreatic cancer who were treated with stereotactic body radiation therapy were enrolled in this study. The displacement points of the respiratory cycle were acquired from 4DCT and transferred to a motion platform to mimic realistic breathing movements in our phantom study. An ultrasound abdominal phantom was placed and fixed in the motion platform. The ground truth of phantom movement was recorded by tracking an optical tracker attached to this phantom. One tumor inside the phantom was the tracking target. In the evaluation of the results, the monitoring results from the ultrasound system were compared with the phantom motion results from the infrared camera. Differences between infrared monitoring motion and ultrasound tracking motion were analyzed by calculating the root-mean-square error.ResultsThe 82.2% ultrasound tracking motion was within a 0.5 mm difference value between ultrasound tracking displacement and infrared monitoring motion. 0.7% ultrasound tracking failed to track accurately (a difference value > 2.5 mm). These differences between ultrasound tracking motion and infrared monitored motion do not correlate with respiratory displacements, respiratory velocity, or respiratory acceleration by linear regression analysis.ConclusionsThe highly accurate monitoring results of this phantom study prove that the ultrasound tracking system may be a potential method for real-time monitoring targets, allowing more accurate delivery of radiation doses.

Background: Liver resection is an established treatment of choice for colorectal liver metastasis (CLM). However, the role of hepatectomy for non-colorectal liver metastasis (NCLM) is less clear. Patients and method: From 2004 to 2017, 264 patients received curative hepatectomy for NCLM (n = 28) and CLM (n = 236). Propensity score (PS) matching was performed between two groups, with respect to the significant confounding factors. Short-term and long-term outcomes were compared between PS matched groups. Univariate analysis was performed to identify prognostic factors affecting overall and recurrence-free survival. Results: After PS matching, there were 28 patients in NCLM group and 56 patients in CLM group. With a median follow-up of 34 months, there was no significant difference in 5-year overall survival rate between NCLM and CLM groups (62% vs. 39%) (P = 0.370). The 5-year recurrence-free survival rate was also comparable between NCLM and CLM groups (23% vs. 22%) (P = 0.707). Use of pre-operative systemic therapy (hazard ratio: 2.335, CI 1.157–4.712), multifocal tumors (hazard ratio: 1.777, CI 1.010–3.127), tumor size (hazard ratio: 1.135, CI 1.012–1.273), R1 resection (hazard ratio: 2.484, CI 1.194–5.169) and severe complications (hazard ratio: 6.507, CI 1.454–29.124), but not tumor type (NCLM vs. CLM), were associated with poor overall survival. Conclusion: Hepatectomy for NCLM can achieve similar oncological outcomes in selected patients as those with CLM. Significant prognostic factors were identified associating with worse overall survival.

Abstract Background Upper limb and hand motor dysfunction is one of the challenges in rehabilitation after cerebral ischemic stroke (CIS), and the clinical efficacy of rehabilitation needs to be improved. This study aims to combine Jin’s three-needle acupuncture (JTN) therapy with mirror therapy (MT) for hemiplegia after CIS, objectively evaluate the clinical effects and safety of JTN to treat upper limb dysfunction, and use functional magnetic resonance imaging (fMRI) of the brain to investigate the central mechanisms of the effects, which would provide a powerful evidence-based medical basis for further supporting the application of JTN combined with MT. Methods/design This trial will be a single-blind, randomized controlled study. Patients who meet the study criteria will be recruited and randomly assigned to either the combined treatment group (JTN+MT) or the JTN group. Both interventions will be conducted for 6 days per week and last for 4 weeks. The primary outcome will be the effective rate based on the Fugl–Meyer Assessment for Upper Extremity (FMA-UE). Other outcome measures will include scores on the motor assessment scale (MAS), action research arm test (ARAT), activities of daily living (ADL) scale, and fMRI analyses. For safety evaluation, adverse events will be observed and recorded. Discussion This study may help to identify the efficacy and safety of acupuncture combined with MT for upper limb dysfunction after CIS and explore the central mechanisms with brain fMRI. Trial registration Chinese Clinical Trial Registry ChiCTR-IOR-17012174 . Registered on 5 April 2017.

Abstract Background The relationship between brain‐derived neurotrophic factor (BDNF) and depression is a hot topic in research as several results of preclinical and clinical studies have shown controversial results. Our meta‐analysis aims to evaluate and update the current status of peripheral BDNF with depression. Methods We performed a meta‐analysis by comprehensively searching PubMed and Web of Science for English‐language literature from inception to 1st of June 2020. The search terms included brain‐derived neurotrophic factor or BDNF in combination with depression, without year restriction. Using STATA software, data were pooled using a random‐effects model. Results In our literature search, 24 studies involving 1130 depressed patients and 1378 healthy individuals met our inclusion criteria. The results of our meta‐analysis showed that the peripheral levels of BDNF levels significantly decreased in depression than nondepressed healthy controls (SMD = −0.89, 95% CI = −1.41, −0.38, p

Background Individuals recovering from acute exacerbation of chronic obstructive pulmonary disease (AECOPD) are most likely to exhibit sedentary behaviour (SB) and low levels of physical activity (PA). This study seeks to explore their choices for adopting current patterns of SB and PA post AECOPD and add to current literature on stable COPD. Method A semi-structured interview, based on the broad framework of the Behaviour Change Wheel, was conducted on patients post AECOPD. A phenomenological approach was utilised inductively. Results Six participants were interviewed at their homes. Four major themes were identified: (1) low perceived capabilities for engaging in PA; (2) limited understanding on COPD and PA; (3) lack of translation of health knowledge and intentions into actions; and (4) poor adherence to movement-advice from physiotherapist. Conclusion Our findings revealed largely psychological and behavioural deficits influencing SB and PA in people post AECOPD, similar to those in stable COPD.

A national survey examined the implementation rates, barriers, challenges, and supports to implementation of two types of simulation (standardized patients and simulated environments) by entry-level occupational therapy education programs in the United States. It also sought to identify relationships between program characteristics and implementation of these types of simulation. An online survey inquiring about academic program characteristics and use of simulation was sent to all occupational therapy and occupational therapy assistant programs in the United States in 2017 prior to the implementation of the 2018 Accreditation Council for Occupational Therapy Education Standards and the onset of the COVID-19 Pandemic. Data were analyzed using both statistical and content analysis. There were 97 responses to the survey, with an approximate response rate of 23.8%. Thirty-eight percent of responses used standardized patients and 70% used simulated environments in their didactic coursework. Programs at private institutions were more likely to use standardized patients than programs at public institutions (Cramer’s V=0.229; p=0.024). Funding was the most cited support, challenge, and barrier to the use of standardized patients. Physical space was the most cited support and challenge for the use of simulated environments, with funding as the most cited barrier. Study results indicate that adequate funding, space, and potentially other resources are needed for successful implementation of these types of simulation. Future research should further study the barriers and supports to implementation of simulation by occupational therapy academic programs as well as further examination of implementation rates.

Purpose: Stereotactic ablative radiation therapy (SABR) for oligometastatic prostate cancer (OMPC) may improve clinical outcomes, but current challenges in intrafraction tracking of multiple small targets limits treatment accuracy. A biology-guided radiation therapy (BgRT) delivery system incorporating positron emission tomography (PET) detectors is being developed to use radiotracer uptake as a biologic fiducial for intrafraction tumor tracking to improve geometric accuracy. This study simulates prostate-specific membrane antigen (PSMA)-directed BgRT using a cohort from our phase II randomized trial of SABR in men with recurrent hormone sensitive OMPC and compares dose distributions to clinical SABR (CSABR). Methods and Materials: A research treatment planning system (RTPS) was used to replan 15 patients imaged with PSMA-targeted 18F-DCFPyL PET/computed tomography and previously treated with CSABR using conventional linear accelerators (linacs). The RTPS models a prototype ring-mounted linac incorporating PET and kilo-voltage computed tomography imaging subsystems and can be used to optimize BgRT plans, as well as research SABR (RSABR) plans, which use the prototype linac without radiotracer guidance. CSABR, RSABR, and BgRT plans were compared in terms of maximum planning target volume (PTV) dose (Dmax), mean dose to proximal organs at risk (DOAR), conformity index, as well as voxel-wise correlation of dose with PET specific uptake values to investigate possible dose-painting effects. Results: RSABR and BgRT plans resulted in mean ± standard deviation increases in Dmax of 4 ± 11% (P = .21) and 18 ± 15% (P < .001) and reductions in DOAR of –20 ± 19% (P

PurposePancreatic cancer is the fourth leading cause of cancer-related death, with a very low 5-year overall survival rate (OS). Radiation therapy (RT) together with dose escalation significantly increases the OS at 2 and 3 years. However, dose escalation is very limited due to the proximity of the duodenum. Hydrogel spacers are an effective way to reduce duodenal toxicity, but the complexity of the anatomy and the procedure makes the success and effectiveness of the spacer procedure highly uncertain. To provide a preoperative simulation of hydrogel spacers, we presented a patient-specific spacer simulator algorithm and used it to create a decision support system (DSS) to provide a preoperative optimal spacer location to maximize the spacer benefits.Materials and MethodsOur study was divided into three phases. In the validation phase, we evaluated the patient-specific spacer simulator algorithm (FEMOSSA) for the duodenal spacer using the dice similarity coefficient (DSC), overlap volume histogram (OVH), and radial nearest neighbor distance (RNND). For the simulation phase, we simulated four virtual spacer scenarios based on the location of the spacer in para-duodenal space. Next, stereotactic body radiation therapy (SBRT) plans were designed and dosimetrically analyzed. Finally, in the prediction phase, using the result of the simulation phase, we created a Bayesian DSS to predict the optimal spacer location and biological effective dose (BED).ResultsA realistic simulation of the spacer was achieved, reflected in a statistically significant increase in average target and duodenal DSC for the simulated spacer. Moreover, the small difference in average mean and 5th-percentile RNNDs (0.5 and 2.1 mm) and OVH thresholds (average of less than 0.75 mm) showed that the simulation attained similar separation as the real spacer. We found a spacer-location-independent decrease in duodenal V20Gy, a highly spacer-location-dependent change in V33Gy, and a strong correlation between L1cc and V33Gy. Finally, the Bayesian DSS predicted the change in BED with a root mean squared error of 3.6 Gys.ConclusionsA duodenal spacer simulator platform was developed and used to systematically study the dosimetric effect of spacer location. Further, L1cc is an informative anatomical feedback to guide the DSS to indicate the spacer efficacy, optimum location, and expected improvement.

The COVID-19 pandemic has caused a public health emergency in all sectors of society, including universities and other academic institutions. This study determined the seroprevalence of SARS-CoV-2 antibodies among administrators, faculty, staff, and students of a private tertiary academic institution in the Philippines over a 7 month period. It employed a serial cross-sectional method using qualitative and quantitative COVID-19 antibody test kits. A total of 1,318 participants were tested, showing 47.80% of the study population yielding IgG antibodies to SARS-CoV-2 virus. A general increase in seroprevalence was observed from June to December 2021, which coincided with the vaccine roll-out of the country. All brands yielded positive antibody formation, with mRNA vaccines having higher levels than other types of vaccines. A decreasing trend in IgG reactivity was found in vaccinated individuals after 1 to 6 months of completion of the 2 doses of the COVID-19 vaccine. Where possible, IgG and T-cell reactivity and/or neutralizing capacity against SAR-CoV-2 need to be monitored regardless of vaccine brand. Together with uptake of COVID-19 vaccines and boosters, other public health interventions such as wearing of masks and regular testing need to be continued for better protection. Effective communication is also needed to inform risks associated with activities across different settings. Investments in long-term measures such as air filtration and ventilation systems, and wastewater surveillance need to be made.

Abstract Background Programmed death-1 (PD-1) inhibitors are among the immunotherapies that have revolutionized our approach to treating several cancers. These novel agents act by blocking PD-1 receptor/PD-1 ligand interactions that would otherwise allow tumor cells to evade host immune destruction by inhibiting response of cytotoxic T-lymphocytes. They are overall well tolerated, though they have been associated with a constellation of immune mediated adverse events (irAEs). Case presentation We present a case of rare nivolumab mediated adverse events in a patient with nodular recurrence of melanoma. The patient presented with rhabdomyolysis and shortly thereafter developed a constellation of immune-mediated organ derangements. This case further demonstrates the utility and effectiveness of steroid therapy in the setting of irAEs despite our patient’s eventual poor clinical outcome. While PD-1 inhibitors have revolutionized the treatment of several cancers, they require vigilance by the clinician for early detection and treatment of uncommon but potentially fatal irAEs. Conclusions PD-1 inhibitors are now widely used in a multitude of cancer types including melanoma, advanced non-small cell lung cancer, metastatic renal cell carcinoma, and Hodgkin lymphoma amongst others. While these agents are often well tolerated, they are associated with a unique profile of immune-related toxicities that can cause significant morbidity and mortality. Education of both patients and healthcare providers is essential for diagnosis and treatment of these adverse events early in their course. This case highlights the uncommon but potentially serious PD-1-associated toxicity of myopathy and rhabdomyolysis along with other organ involvement and is directly applicable to use of these agents in patients with advanced cancers.

Abstract Background Thyroid dysfunction has not been previously reported in clinical trials of selective fibroblast growth factor receptor (FGFR) inhibitors including AZD4547. Herein, we report a case of worsening hypothyroidism in a patient with advanced urothelial cancer treated with AZD4547. Case presentation An 80-year-old Caucasian female with metastatic urothelial carcinoma failed first-line chemotherapy with gemcitabine and carboplatin and second-line treatment with atezolizumab, an inhibitor of programmed cell death ligand 1. She developed hypothyroidism at completion of atezolizumab treatment and responded to levothyroxine. Subsequently she was enrolled to a phase II study and received AZD4547 due to an actionable mutation at FGFR3 found in tumor biopsy. Two months later, she experienced recurrent hypothyroidism symptoms, and was hospitalized twice for small bowel obstruction. Her thyroid stimulating hormone level was significantly increased to 2957 uIU/mL (reference range 0.8–7.7 uIU/mL). Her levothyroxine dose was increased accordingly. Her thyroid function returned to normal 1 month afterwards, and small bowel obstruction did not recur. Conclusion Further reports and studies will be needed to confirm the relationship between AZD4547 and hypothyroidism. Based on this observation and possible mechanisms for thyroid dysfunction discussed in this paper, routine thyroid function monitoring in patients receiving FGFR inhibitor should be considered.

We developed genetic-epigenetic tissue mapping (GETMap) to determine the tissue composition of plasma DNA carrying genetic variants not present in the constitutional genome through comparing their methylation profiles with relevant tissues. We validated this approach by showing that, in pregnant women, circulating DNA carrying fetal-specific alleles was entirely placenta-derived. In lung transplant recipients, we showed that, at 72 hr after transplantation, the lung contributed only a median of 17% to the plasma DNA carrying donor-specific alleles, and hematopoietic cells contributed a median of 78%. In hepatocellular cancer patients, the liver was identified as the predominant source of plasma DNA carrying tumor-specific mutations. In a pregnant woman with lymphoma, plasma DNA molecules carrying cancer mutations and fetal-specific alleles were accurately shown to be derived from the lymphocytes and placenta, respectively. Analysis of tissue origin for plasma DNA carrying genetic variants is potentially useful for noninvasive prenatal testing, transplantation monitoring, and cancer screening.

With an increasing demand for telepractice services, the need for telepractice education is more important than ever. In addition to learning how to deliver these services, certain clinical and technological skills learned through telepractice apply more broadly to in-person care. Evaluating students’ abilities to master these skills is necessary to ensure clinical skill competence. We utilized self-efficacy ratings and self-reflections to determine student growth after hands-on telepractice training among nursing, occupational therapy, physical therapy, and speech-language pathology students. Students across disciplines demonstrated growth in all measured skill areas and reported overall increased confidence. Students with less prior telepractice experience reported greater increased confidence in seven measured competency areas than students with more prior telepractice experience. The number of completed sessions at the end of student placements was correlated with increased confidence for one measured skill area. Regardless of whether or not students had prior experience when starting their placement, as the number of telepractice sessions completed increased, thus did students’ confidence levels. The results of this study support telepractice as a viable clinical education tool for student growth and the use of self-efficacy and self-reflection as valuable tools for monitoring the effectiveness of telepractice clinical learning activities.

Photovoltaic (PV) panels must be equipped with a cooling system to increase their electrical output generation. Despite numerous publications on the fabrication of form-stable phase change material (FSPCM) for thermal energy storage application, studies on the usage of FSPCM for PV cooling are incredibly limited. In this work, the cooling performance of myristic acid FSPCM encapsulated with cross-linked nitrile rubber (NBR) was investigated. A fin heat sink (FHS) was employed to hold the FSPCM. The thermal performance of the FHS embedded with FSPCM (FHS-FSPCM) was preliminarily tested in an indoor setup. Results show that the FHS-FSPCM has a lower temperature distribution curve than the bare FHS, highlighting the increase in cooling capability of fabricated FSPCM. Field-testing of PV panels integrated with an FHS-FSPCM displayed that FSPCM manages to reduce the operating temperature of the panel by 4 to 15 °C and increase power output generation by 38.61%.

Background: Both microwave ablation (MWA) and radiofrequency ablation (RFA) are commonly employed local ablation techniques for malignant liver tumors. However, comparative data on long-term results between these two techniques is scarce in the literature. Methods: This is a retrospective comparative study between MWA and RFA for hepatocellular carcinoma (HCC) using surgical approach. Results: The MWA group consisted of 26 patients while the RFA group consisted of 47 case-matched patients. The two groups were comparable, except patients were older and their platelet count was lower in the MWA group. The median follow-up period was 47.5 months in MWA group and 52.9 months in RFA group (p = 0.322). There was no difference in 5-year overall survival (MWA 73.1%, RFA 46.3%, p = 0.082) and 5-year disease free survival (MWA 13.8%, RFA 14.6%, p = 0.736). When a subgroup analysis of tumors ≥ 3.5 cm was performed, there were 16 patients in the MWA group and 21 patients in the RFA group, the 5-year overall and disease-free survival were MWA 75.0%, RFA 28.6% (p = 0.022) and MWA 25.0%, RFA 4.8% (p = 0.207), respectively. Conclusion: MWA is comparable to RFA for HCC in terms of long-term outcomes. For tumors ≥ 3.5 cm, MWA is associated with a better overall 5-year survival.

Category: Midfoot/Forefoot Introduction/Purpose: Müller Weiss disease is becoming increasingly recognized and is of unknown etiology. Maceria et al. formulated a classification based upon the Méary-Tomeno talo-first metatarsal angle and coined the term ‘paradoxical pes planus varus’ proposing hallmark deformities. Acknowledging there is no gold standard for treatment, various surgical modalities have been advocated in the literature e.g. isolated lateral displacement calcaneal osteotomy as sole treatment. The question subsequently arises; which joints to fuse in Muller-Weiss disease? Although no consciences prevails, one must postulate fusion should include those affected. For the purpose of establishing an algorithm in the surgical treatment of Muller-Weiss disease, we therefore set out to study its clinical and radiographic features, including pathoanatomy and metabolism as determined by SPECT- CT. Methods: We studied 63 consecutive feet presenting with Muller-Weiss disease (15 to 86 years, 18 men, 26 women). History and examination by consultant in all cases. Plain radiographs included standing anteroposterior both ankles, hindfoot alignment views, lateral standing of both ankles and feet, medial oblique both feet and dorsoplantar standing and SPECT-CT. Surgery performed on significantly symptomatic feet unresponsive to minimum of six months conservative measures. Méary’s talo-first metatarsal angles measured. On dorsoplantar radiographs the anteroposterior thickness of the navicular was measured at each naviculo-cuneiform joint perpendicular to transverse axis of the medial pole of the navicular. The percentage compression was calculated at each joint and the degree of extrusion of the medial pole. Hindfoot alignment measured using method of Saltzmann. Study approved by our local research and ethics department and in accordance with General Data Protection Regulation guidelines. Statistical analysis was performed using SPSS software. Results: Using R2 coefficient of determination we found no correlation at any level between extrusion and the degree of compression. With respect to hindfoot alignment and Méarys angle there was no significant correlation (R2=0.003) Shapiro-Wilk test demonstrates a normal distribution of extrusion in both unilateral and bilateral cases. In 95.2% of unilateral cases extrusion significantly greater on affected side (P

Category: Ankle, Ankle Arthritis Introduction/Purpose: The optimal management of severe ankle arthritis is still debated. Some maintain that arthrodesis is the reference standard. However, with appropriately selected patients modern Total Ankle Replacements (TAR) can offer good to excellent patient reported outcomes. First generation TARs were highly constrained and prone to accelerated wear, loosening and subsidence and failure. Subsequent reincarnations have led to the development of reduced constraint, mobile bearing prostheses with reliance on ligamentous balancing. New generation TARs report 10-year survival of up to 89%, however many studies are from design centres and not uniformly replicated elsewhere. The largest long-term Hintegra TAR study is from a designer’s centre, reporting 84% survival at 10 years. This paper reports multicentre results on the intermediate (6 years +) outcomes of the Hintegra TAR. Methods: TARs performed by two senior consultant surgeons from 30/03/2004-18/01/2013 were reviewed. Prospective review of patients included; review of current and or new symptoms, an updated past medical history, AOFAS Hindfoot scores and radiological imaging. We used the AOFAS hindfoot score for our functional assessment as it validated and also the most frequently cited scoring system in the literature. Radiographs were reviewed for loosening and this was defined by a validated assessment method with a suitably low inter-observer variability. In our study all images were reviewed by at least two authors for a consensus opinion. The Charlson Comorbidity Index (CCI) was utilised to evaluate and risk stratify co-morbidities and their influence on other illnesses and surgical outcomes. This study was considered to be service evaluation by our local research and ethics department and approved in accordance with General Data Protection Regulation guidelines. Statistical analysis was performed using SPSS software. Results: 62 TARs were performed on 58 patients. Excluding the deceased (n=9) and patients lost to follow up (n=1), mean follow up was 12years 3months. AOFAS score did not decline with age of TAR (Spearman Rho co-efficient 0.339). During the first 4 years Hintegra TARs were performed 11/23 (48%) patients underwent additional surgery highlighting the already published learning curve with TAR. 5-year and 10-year survival was 84% (52/62) and 71% respectively (27/38). Predictors for revision included obesity with a BMI>30 versus those with a BMI of 18.5-25 (Chi-Sq P-value 0.006) and previous smoking history (Chi-Sq P-value 0.027). No association was found between CCI scores and revision (One-way ANOVA P-value 0.4). Interestingly lower ASA scores were significantly more likely to require revision (One-way ANOVA P-value 0.034). Conclusion: The Hintegra Total Ankle Replacement offers good sustained pain relief and function. 71% of implants were retained with an average AOFAS score of 78 (36-100 range) after 10 years. We do recommend caution in patients who are obese, smokers, ex-smokers and those with a high functional demand. We stress the importance of achieving correct alignment of the TAR to maximise longevity. There is a steep learning curve when performing a TAR and we would suggest operating with another experienced surgeon for at least the first 20 cases.

The images generated during radiation oncology treatments provide a valuable resource to conduct analysis for personalized therapy, outcomes prediction, and treatment margin optimization. Deformable image registration (DIR) is an essential tool in analyzing these images. We are enhancing and examining DIR with the contributions of this paper: 1) implementing and investigating a cloud and graphic processing unit (GPU) accelerated DIR solution and 2) assessing the accuracy and flexibility of that solution on planning computed tomography (CT) with cone-beam CT (CBCT). Registering planning CTs and CBCTs aids in monitoring tumors, tracking body changes, and assuring that the treatment is executed as planned. This provides significant information not only on the level of a single patient, but also for an oncology department. However, traditional methods for DIR are usually time-consuming, and manual intervention is sometimes required even for a single registration. In this paper, we present a cloud-based solution in order to increase the data analysis throughput, so that treatment tracking results may be delivered at the time of care. We assess our solution in terms of accuracy and flexibility compared with a commercial tool registering CT with CBCT. The latency of a previously reported mutual information-based DIR algorithm was improved with GPUs for a single registration. This registration consists of rigid registration followed by volume subdivision-based nonrigid registration. In this paper, the throughput of the system was accelerated on the cloud for hundreds of data analysis pairs. Nine clinical cases of head and neck cancer patients were utilized to quantitatively evaluate the accuracy and throughput. Target registration error (TRE) and structural similarity index were utilized as evaluation metrics for registration accuracy. The total computation time consisting of preprocessing the data, running the registration, and analyzing the results was used to evaluate the system throughput. Evaluation showed that the average TRE for GPU-accelerated DIR for each of the nine patients was from 1.99 to 3.39 mm, which is lower than the voxel dimension. The total processing time for 282 pairs on an Amazon Web Services cloud consisting of 20 GPU enabled nodes took less than an hour. Beyond the original registration, the cloud resources also included automatic registration quality checks with minimal impact to timing. Clinical data were utilized in quantitative evaluations, and the results showed that the presented method holds great potential for many high-impact clinical applications in radiation oncology, including adaptive radio therapy, patient outcomes prediction, and treatment margin optimization.

Severe radiation-related lymphopenia is common and associated with decreased survival in patients with several solid tumors. As the mechanisms underlying systemic lymphopenia are poorly understood, we developed an animal model to study the effects of brain radiation on lymphocytes and cytokines. C57 BL/6 and BALB/c mice received focal brain irradiation (4 Gy x 10 fractions or 2 Gy x 30 fractions). Weekly total lymphocyte counts (TLC), lymphocyte subsets and cytokines in blood and lymph nodes were measured. Non-irradiated lymph nodes were collected and examined before, during, and after radiation. We found that systemic TLC decreased rapidly irrespective of mouse strain or radiation schedule. 4 Gy x 10 resulted in a 42% and 75% & 70% and 49% TLC reduction in C57 BL/6 and BALB/c mice respectively. 2 Gy x 30 caused a 70% / 49% decrease in TLC in C57 BL/6 and BALB/c. Similar trends were seen for total T cells, CD4+, regulatory T and CD8+ cells. Changes in lymph node architecture and cellular composition correlated with the development of systemic lymphopenia. Three weeks after radiation, TLC returned to 60–80% of baseline, preceded by increased IL-7 levels in the lymph nodes. Focal brain radiation in mice results in significant systemic lymphodepletion.

Current guideline-recommended screening for pulmonary hypertension in patients with systemic sclerosis has not been evaluated in systemic lupus erythematosus (SLE), which is disproportionately prevalent in Asians. This multicentre, cross-sectional screening study aims to study the prevalence of pulmonary hypertension among SLE patients using these guidelines, and identify independent predictors and develop a prediction model for pulmonary hypertension in SLE patients. SLE patients from participating centres will undergo an echocardiography- and biomarker-based pulmonary hypertension screening procedure as in the DETECT study. Standard right heart catheterisation will be provided to patients with intermediate or high echocardiographic probability of pulmonary hypertension. Those with low echocardiographic probability will rescreen within 1 year. The primary measure will be the diagnosis and types of pulmonary hypertension and prevalence of pulmonary hypertension in SLE patients. The secondary measures will be the predictors and prediction models for pulmonary hypertension in SLE patients. The estimated sample size is approximately 895 participants. The results of the SOPHIE study will be an important contribution to the literature of SLE-related pulmonary hypertension and may be immediately translatable to real clinical practice. Ultimately, this study will provide the necessary evidence for establishing universal guidelines for screening of pulmonary hypertension in SLE patients.

Acupuncture has been widely used in China to treat neurological diseases including Alzheimer’s disease (AD). However, its mechanism remains unclear. In the present study, eighty healthy Wistar rats were divided into a normal control group (n=15) and premodel group (n=65). Forty-five rats that met the criteria for the AD model were then randomly divided into the model group (MG), the nonacupoint group (NG), and the acupoint group (AG). All rats received positron emission tomography (PET) scanning, and the images were analyzed with Statistical Parametric Mapping 8.0. MG exhibited hypometabolism in the olfactory bulb, insular cortex, orbital cortex, prelimbic cortex, striatum, parietal association cortex, visual cortex, cingulate gyrus, and retrosplenial cortex. AG exhibited prominent and extensive hypermetabolism in the thalamus, hypothalamus, bed nucleus of the stria terminalis, cerebral peduncle, midbrain tegmentum, and pontine tegmentum compared to NG. These results demonstrated that acupuncturing at GV24 and bilateral GB13 acupoints may improve the learning and memory abilities of the AD rats, probably via altering cerebral glucose metabolism (CGM) in the hypothalamus, thalamus, and brain stem. The observed effects of acupuncture may be caused by regulating the distribution of certain kinds of neurotransmitters and enhancing synaptic plasticity.

The patella usually dislocates laterally. Less commonly, intra-articular dislocation occurs about either the vertical or horizontal axis. Patellar fractures are generally transverse with varying degrees of comminution, and less frequently vertical in the sagittal plane. We present a 9-year follow-up of a previously undescribed coronal patellar fracture associated with vertical axis dislocation of the patella. The mechanism of this severe injury is described. Keywords: Trauma, Coronal patellar fracture, Vertical axis patellar dislocation, Mechanism of injury

OBJECTIVES/SPECIFIC AIMS: Hepatitis C virus (HCV) has a high prevalence among individuals in jail and prisons. Access to HCV treatment has been restricted in jails and prisons. We hypothesized that HCV infection in inmates would be associated with increased mortality in people who were hospitalized while incarcerated. METHODS/STUDY POPULATION: We created and then linked a database of people who were incarcerated and admitted at Lemuel Shattuck Hospital (2004, 2008, 2011) to the Massachusetts Vital Statistic Registry (updated through end of 2015). Death was classified using the Automatic Classification of Medical Entry Death Code. The primary outcome of interest was mortality within 1 year of hospitalization, and the secondary outcome was mortality at any time. The primary indicator of interest was HCV, defined as the presence of the ICD-9 code for HCV on discharge. Covariates included in univariate and multivariate modeling included age, year of admission, and race/ethnicity classified as: White, Black, Hispanic or Other (i.e., Asian, Native American, Multi-Racial, or No answer). RESULTS/ANTICIPATED RESULTS: Of the 1,541 hospital admissions, 21% had HCV, and 57% were white, 22% black, 8% Hispanic and 12% other. Of the 273 total deaths (18% of cohort), 82 deaths occurred within 1 year of hospitalization (5.3% of the entire cohort, 30% of all deaths). The primary cause of death was vascular (21%), followed by chronic liver disease (18%), cancer (17%), overdose/suicide/trauma (19%), pulmonary (7%) and infection (6%). People with HCV were more likely to die of chronic liver disease (40% vs 7%, p

Background: During the COVID-19 outbreak, most Chinese college students were home-quarantined to prevent the spread of the virus. COVID-19-associated impact has been shown to be a risk factor for the development of post-traumatic symptoms disorder (PTSD). However, little is known about the psychological processes that mediate this association. This study investigated the association between COVID-19-associated impact and PTSD and examined whether past stressful events, psychological resilience, and social support have mediating effects on this association. Methods: The 12,397 valid responses from 31cities in China via an online survey assessed PTSD symptoms, past stressful events, psychological resilience, social support and social-demographic variables. AMOS was used to test the hypotheses of mediating effects. Results: On the 39th day of the declared COVID-19 epidemic in China, 6.75% of the surveyed sample showed PTSD symptoms. A positive mediating effect of past stressful events was found between COVID-19-associated impact and PTSD, whereas psychological resilience and social support had negative mediating effects. The fit indices for the path model were found to be significant (β = 0.28, p < 0.001), COVID-19-associated impact indirectly affects the risk of PTSD through mediating pathways (past stressful events → psychological resilience → social support) on PTSD. Conclusions: Attention should be paid to the effects of past stressful events of Chinese college students who were home-quarantined during the COVID-19 epidemic, and strategies should also be implemented to improve social support and develop psychological resilience. Trial registration: The study was approved by the ethics committee of the Southwest Minzu University. [ABSTRACT FROM AUTHOR]

Radiation therapy typically begins with the acquisition of a CT scan of the patient for planning, followed by multiple days where radiation is delivered according to the plan. This requires that the patient be reproducibly positioned (set up) on the radiation therapy device (linear accelerator) such that the radiation beams pass through the target. Modern linear accelerators provide cone-beam computed tomography (CBCT) imaging, but this does not provide sufficient contrast to discriminate many abdominal soft-tissue targets and therefore patient setup is often done by aligning bony anatomy or implanted fiducials. Ultrasound (US) can be used to both assist with patient setup and to provide real-time monitoring of soft-tissue targets. One challenge, however, is that the ultrasound probe contact pressure can deform the target area and cause discrepancies with the treatment plan. Another challenge is that radiation therapists typically do not have ultrasound experience and therefore cannot easily find the target in the US image. We propose cooperative control strategies to address both challenges. First, we use cooperative control with virtual fixtures (VFs) to enable acquisition of a planning CT that includes the soft-tissue deformation. Then, for the patient setup during the treatment sessions, we propose to use real-time US image feedback to dynamically update the VFs; this co-manipulation strategy provides haptic cues that guide the therapist to correctly place the US probe. A phantom study is performed to demonstrate that the co-manipulation strategy enables inexperienced operators to quickly and accurately place the probe on a phantom to reproduce a desired reference image. This is a necessary step for patient setup and, by reproducing the reference image, creates soft-tissue deformations that are consistent with the treatment plan, thereby enabling real-time monitoring during treatment delivery.

Ricin exhibits well characterized ribotoxic actions that lead to the inhibition of protein synthesis and the phosphorylation of stress activated protein kinases (SAPKs). Proinflammatory effects of ricin are thought to be caused by upregulation of genes encoding proinflammatory transcripts as a result of the activation of c-Jun N-terminal kinase (JNK) and p38 MAPK. We reported previously that macrophages and interleukin-1β (IL-1β) signaling are required for murine host immune responses to ricin delivered to the lungs. Here we report that ricin-mediated IL-1β release from bone-marrow derived macrophages is dependent on the NALP3 inflammasome, a scaffolding complex that mediates pro-IL-1β cleavage to active IL-1β by caspase-1. Release of IL-1β from macrophages was suppressed by the reactive oxygen species (ROS) scavenger N-acetyl cysteine (NAC) and high extracellular K+, which are two agents known to inhibit NALP3/cryopyrin/CIAS1 inflammasome formation. By employing inhibitors of p38 MAPK and JNK, we demonstrated that ricin-mediated release of IL-1β was enhanced, rather than suppressed, by inhibition of SAPK phosphorylation. In contrast, proteasomal inhibitors bortezomib and MG-132 completely suppressed ricin-induced IL-1β release from macrophages. These data suggest that ricin-mediated translational inhibition itself, by fostering the disappearance of labile protein(s) that normally suppress inflammasome formation, may constitute the mechanism underlying IL-1-dependent inflammatory signaling by ricin.

Huntington's disease (HD) is an inherited progressive neurodegenerative disorder resulting from CAG repeat expansion in the gene that encodes for the protein huntingtin. To identify neuroprotective compound (s) that can slow down disease progression and can be administered long term with few side effects in Huntington's disease, we investigated the effect of sertraline, a selective serotonin reuptake inhibitor (SSRI) which has been shown to upregulate BDNF levels in rodent brains. We report here that in HD mice sertraline increased BDNF levels, preserved chaperone protein HSP70 and Bcl-2 levels in brains, attenuated the progression of brain atrophy and behavioral abnormalities and thereby increased survival. Sertraline also enhanced neurogenesis, which appeared to be responsible for mediating the beneficial effects of sertraline in HD mice. Additionally, the effective levels of sertraline are comparable to the safe levels achievable in humans. The findings suggest that sertraline is a potential candidate for treatment of HD patients.

We aimed to evaluate the role of elevated perioperative alanine aminotransferase (ALT) as a surrogate marker of hepatitis activity in determining the risk of recurrence and survival in hepatitis B-related hepatocellular carcinoma (HCC) after curative hepatectomy. METHODS: A retrospective review of the hepatectomy database was performed and 142 patients were found who had hepatitis B-related HCC from January 2001 to March 2006. Their ALT levels preoperatively and 1 month, 3 months, and 6 months postoperatively were recorded. The risk factors for recurrence and prognostic factors of survival were analysed. RESULTS: An elevated perioperative ALT level (p = 0.021), multiple tumour nodules in the resected specimen (p < 0.001), and a tumour size greater than 5 cm (p = 0.001) were significant independent risk factors for tumour recurrence. The latter two factors were also independent prognostic factors for overall survival and disease-free survival. An elevated ALT level was an independent prognostic factor for disease-free survival (p = 0.025). CONCLUSION: An elevated perioperative ALT level, which reflects increased hepatitis activity, is an independent risk factor for intrahepatic recurrence of hepatitis B-related HCC. It is also associated with a poorer disease-free survival rate.

Fatigue is a major debilitating symptom after stroke. The biological mechanisms underlying poststroke fatigue (PFS) are unknown. We hypothesized that PSF is associated with an alteration in the balance between Th17 and Treg cells. To test this hypothesis we assessed fatigue in 30 stroke survivors using the Fatigue Scale for Motor and Cognitive Functions (FSMC). Peripheral blood was collected for assessment of Th17 and Treg cell populations and measurement of interleukin-10 (IL-10). Participants were dichotomized into severe fatigue n=14 and low-moderate fatigue n=16 groups by K-mean cluster analysis of FSMC scores. There were no group differences in age, gender, stroke type, stroke severity, or time since stroke. Stroke survivors in the severe fatigue group reported greater anxiety p=0.004 and depression p=0.001 than in the low-moderate fatigue group. The ratio of Th17 to Treg cells was significantly increased in the severe fatigue group relative to the mild-moderate fatigue group p=0.035. Serum levels of IL-10 negatively correlated withTh17/Treg ratio (r=-0.408, p=0.025). Our preliminary findings suggest that an imbalance in the Th17/Treg ratio is associated with the severity of PSF.

Activating epidermal growth factor receptor (EGFR) mutations in metastatic non-small cell lung cancer (NSCLC) are associated with a high response rate to EGFR tyrosine kinase inhibitor (TKI). The current guidelines recommend routine EGFR mutational analysis prior to initiating first line systemic therapy. The clinical characteristics including smoking status, histologic type, sex and ethnicity are known to be associated with the incidence of EGFR mutations. We retrospectively analyzed 277 patients with metastatic NSCLC within Kaiser Permanente Northern California (KPNC); among these patients, 83 were positive for EGFR mutations. We performed both univariate and multivariable logistic regressions to identify predictors of EGFR mutations. We found that histologic grade was significantly associated with the incidence of EGFR mutation, regardless of ethnicity, sex and smoking status. In grade I (well differentiated) and II (moderately differentiated), histology was associated with significantly higher incidence of EGFR mutations compared to grade II–III (moderate-to-poorly differentiated) and III (poorly differentiated). Ever-smokers with grade III lung adenocarcinoma had 1.8% incidence of EGFR mutations. This study indicates that histologic grade is a predictive factor for the incidence of EGFR mutations and suggests that for patients with grade II–III or III lung adenocarcinoma, prompt initiation of first-line chemotherapy or immunotherapy is appropriate while awaiting results of EGFR mutational analysis, particularly for patients with history of smoking.

Persistent hyperkinetic circulation after liver transplantation has been described in humans, but similar changes have not been well characterized in the rat model. This study aimed to investigate the hemodynamics of the systemic and splanchnic circulations in both arterialized and nonarterialized hepatic allografts. Orthotopic liver transplantation was performed in four groups of Sprague-Dawley rats. Group A comprised sham-operated rats with hepatic artery ligation that did not receive transplants; group B comprised rats that received transplants without arterialization; group C comprised sham-operated rats with intact hepatic artery that did not receive transplants; and group D comprised rats that received transplants with arterialization. Blood flow measurements were performed three weeks after the surgical procedure, using the radioactive microsphere method. The results showed that rats that received transplants exhibited a significantly higher cardiac index and lower systemic vascular resistance than the control rats. Splanchnic hyperemia was also present with increased mesenteric blood flow. However, there was no difference in hemodynamics between rats that received arterialized transplants and those that received nonarterialized transplants. Arterial collateral vessels from adjacent tissues were observed in the nonarterialized grafts; this was confirmed histologically. It is concluded that rats that undergo orthotopic liver transplantation exhibit hyperdynamic circulation, regardless of the arterial reconstruction procedure, possibly due to extensive collateral formation in the hepatosplanchnic circulation.