Conversion of N-doped biochar from carotenoid-extracted Tetraselmis suecica and its application to produce supercapacitors.

Microalgae are one of the promising feedstocks for biorefinery, contributing significantly to net-zero emissions through carbon capture and utilization. However, the disposal of microalgal byproducts from the manufacturing process causes additional environmental pollution, thus, a new application strategy is required. In this study, the Tetraselmis suecica byproduct from the carotenoid extraction process was carbonized and converted into biochar. The converted biochar was proved to be nitrogen-doped biochar (NDB), up to 4.69%, with a specific surface area of 206.59 m2/g and was used as an electrode for a supercapacitor. The NDB electrode (NDB-E) in half-cell showed a maximum specific capacitance of 191 F/g. In a full-cell test, the NDB-E exhibited a high energy density of 7.396 Wh/kg and a high-power density of 18,100 W/kg, and maintained specific capacity of 95.5% after charge and discharge of 10,000 cycles. In conclusion, our study demonstrated that the carotenoid-extracted microalgal byproducts are a useful resource for the supercapacitor production. This approach is the first to convert T. suecica into active materials for supercapacitors.

Comparison of bilateral implantation of monofocal intraocular lenses with enhanced intermediate function targeting with - 2.00 D and emmetropia in moderate to high myopic Asian patients.

BACKGROUND: To investigate the outcomes of bilateral implantation of enhanced monofocal intraocular lenses (IOLs, ICB00) with a - 2.00 diopter (D) target in patients with moderate to high myopia and to compare the clinical outcomes of a - 2.00 D binocular target with an emmetropia target in patients who underwent cataract surgery. METHODS: In this retrospective study, we reviewed the medical records of patients who underwent uncomplicated phacoemulsification with ICB00 IOL implantation. Emmetropia (Group 1) and - 2.00 D (Group 2) were targeted in 60 and 20 eyes of 30 and 10 patients, respectively. Three months after surgery, uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), uncorrected intermediate visual acuity (UIVA), and uncorrected near visual acuity (UNVA) were measured. Defocus curves were measured under the photopic condition by intervals of 0.50 D from + 0.50 D to - 4.00 D. RESULTS: The postoperative binocular logMAR UDVA, UIVA, and UNVA were 0.01 ± 0.03, 0.08 ± 0.11, and 0.33 ± 0.15 in Group 1 and 0.31 ± 0.13, 0.04 ± 0.05, and 0.11 ± 0.07 in Group 2, respectively. Group 2 showed a significantly superior postoperative binocular UNVA (P = 0.027) and inferior binocular UDVA (P = 0.003) than Group 1. Binocular UIVA and CDVA did not significantly differ between the groups although UIVA was better in Group 2 than in Group 1. Near glasses were needed by 66% of Group 1 and 0% of Group 2. CONCLUSIONS: Bilateral implantation of ICB00 IOL with - 2.00 D of residual myopia is suitable for patients with moderate to high myopia to improve UDVA, UIVA, and UNVA.

Protecting our future: environmental hazards and children's health in the face of environmental threats: a comprehensive overview.

Children face the excitement of a changing world but also encounter environmental threats to their health that were neither known nor suspected several decades ago. Children are at particu-lar risk of exposure to pollutants that are widely dispersed in the air, water, and food. Children and adolescents are exposed to chemical, physical, and biological risks at home, in school, and elsewhere. Actions are needed to reduce these risks for children exposed to a series of envi-ronmental hazards. Exposure to a number of persistent environmental pollutants including air pollutants, endocrine disruptors, noise, electromagnetic waves, tobacco and other noxious sub-stances, heavy metals, and microplastics, is linked to damage to the nervous and immune sys-tems and affects reproductive function and development. Exposure to environmental hazards is responsible for several acute and chronic diseases that have replaced infectious diseases as the principal cause of illnesses and death during childhood. Children are disproportionately ex-posed to environmental toxicities. Children drink more water, eat more food, and breathe more frequently than adults. As a result, children have a substantially heavier exposure to toxins pre-sent in water, food, or air than adults. In addition, their hand-to-mouth behaviors and the fact that they live and play close to the ground make them more vulnerable than adults. Children undergo rapid growth and development processes that are easily disrupted. These systems are very delicate and cannot adequately repair the damage caused by environmental toxins. The first international development in children's environmental health was the Declaration of the Environment Leaders of the Eight on Children's Environmental Health by the Group of Eight. In 2002, the World Health Organization launched an initiative to improve children's environ-mental protection effort. Here, we review major environmental pollutants and related hazards among children and adolescents.

Assessment of intraocular lens tilt and decentration after femtosecond laser-assisted and conventional cataract surgery at 12 months and beyond.

PURPOSE: To compare long-term intraocular lens (IOL) decentration and tilt following femtosecond laser-assisted cataract surgery (FLACS) and conventional surgery using swept-source anterior segment ocular coherence tomography (SS-ASOCT). METHODS: In this retrospective cross-sectional study, all patients underwent FLACS or conventional cataract surgery. Those with a minimum of 12-months follow-up since surgery were included. Patients with surgical complications were excluded. Demographics, preoperative ocular measurements (axial length, anterior chamber depth), and postoperative measurements [corrected distance visual acuity (CDVA), autorefraction, keratometry, IOL type] were collected. Postoperative IOL tilt and decentration were compared using SS-ASOCT between patients with FLACS and conventional cataract surgery. Subgroup analysis was conducted to analyze tilt and decentration by haptic type (single-piece vs. three-piece). RESULTS: A total of 188 eyes were included [110 (58.5%) in the FLACS group and 78 (41.5%) in the conventional group]. No differences were observed between the FLACS and conventional groups regarding preoperative parameters. FLACS resulted in less IOL decentration compared to conventional cataract surgery (170 µm vs. 240 µm, p = 0.002). No statistically significant differences were observed between the FLACS and conventional groups in the magnitude and axis of IOL tilt. Both groups had a trend of IOL tilt toward the inferotemporal aspects. Moreover, no difference regarding postoperative CDVA, spherical equivalent, and keratometric astigmatism was observed. CONCLUSIONS: FLACS resulted in significantly better long-term IOL centration than conventional surgery with manual capsulotomy. No significant difference in IOL tilt or postoperative CDVA was observed between FLACS and conventional cataract surgery.

Radio-opaque contrast agents for liver cancer targeting with KIM during radiation therapy (ROCK-RT): an observational feasibility study.

BACKGROUND: This observational study aims to establish the feasibility of using x-ray images of radio-opaque chemoembolisation deposits in patients as a method for real-time image-guided radiation therapy of hepatocellular carcinoma. METHODS: This study will recruit 50 hepatocellular carcinoma patients who have had or will have stereotactic ablative radiation therapy and have had transarterial chemoembolisation with a radio-opaque agent. X-ray and computed tomography images of the patients will be analysed retrospectively. Additionally, a deep learning method for real-time motion tracking will be developed. We hypothesise that: (i) deep learning software can be developed that will successfully track the contrast agent mass on two thirds of cone beam computed tomography (CBCT) projection and intra-treatment images (ii), the mean and standard deviation (mm) difference in the location of the mass between ground truth and deep learning detection are ≤ 2 mm and ≤ 3 mm respectively and (iii) statistical modelling of study data will predict tracking success in 85% of trial participants. DISCUSSION: Developing a real-time tracking method will enable increased targeting accuracy, without the need for additional invasive procedures to implant fiducial markers. TRIAL REGISTRATION: Registered to ClinicalTrials.gov (NCT05169177) 12th October 2021.

Randomized Immunogenicity Trial Comparing 2019-2020 Recombinant and Egg-Based Influenza Vaccines among Frequently Vaccinated Healthcare Personnel in Israel.

BACKGROUND: Trivalent inactivated influenza vaccine effectiveness was low in a prospective cohort of healthcare personnel (HCP) in Israel from 2016-2019. We conducted a randomized immunogenicity trial of quadrivalent recombinant influenza vaccine (RIV4) and standard-dose inactivated influenza vaccine (IIV4) among frequently and infrequently vaccinated previous cohort participants. METHODS: From October 2019 to January 2020, we enrolled and randomly allocated HCP from two Israeli hospitals to receive IIV4 or RIV4. Hemagglutination inhibition (HAI) antibody titers against 2019-2020 vaccine reference influenza viruses were compared between vaccine groups using geometric mean titer (GMT) ratios from sera collected one-month post-vaccination and by frequency of vaccination in the past 5 years (>2 versus ≤2). RESULTS: Among 415 HCP, the GMT ratio comparing RIV4 to IIV4 was 2.0 (95% confidence interval [CI] 1.7-2.7) for A(H1N1)pdm09, 1.6 (95% CI: 1.3-1.9) for A(H3N2), 1.8 (95% CI: 1.4-2.2) for B(Yamagata), and 1.1 (95% CI: 0.9-1.4) for B(Victoria). Similarly, RIV4 elicited higher HAI titers than IIV4 against all 2019-2020 vaccine reference viruses except B(Victoria) among infrequently and frequently vaccinated HCP (lower bound of GMT ratio 95% CIs ≥1.0). CONCLUSIONS: RIV4 had improved immunogenicity for influenza vaccine strains among both infrequent and frequent vaccinees compared to standard-dose IIV4.

Current peritonectomy practice during debulking surgery in patients with newly diagnosed advanced ovarian cancer: a Korean Gynecologic Oncology Group Study (KGOG 4004).

OBJECTIVE: Because of the possible therapeutic benefit of removing occult tumor cells, a source of recurrence and chemoresistance, total parietal peritonectomy (TPP) is an alternative treatment for advanced epithelial ovarian/fallopian tube/primary peritoneal cancer. Interventional studies comparing TPP with selective parietal peritonectomy (SPP) are in progress. Since surgeons skilled in TPP are essential for such trials to be conducted, this nationwide survey aimed to examine current peritonectomy practice among gynecologic oncologists in Korea. METHODS: A 17-item questionnaire, developed by a surgery committee and reviewed by the scientific review board of the Korean Gynecology Oncology Group (KGOG), was distributed to 144 KGOG members. The questionnaire was divided into 3 categories: respondent demographics, peritonectomy practice during primary debulking surgery (PDS), and peritonectomy practice during interval debulking surgery (IDS). RESULTS: We received 88 (61.1%) valid responses. Of the valid respondents, 98.9% and 93.8% performed SPP during PDS and IDS, respectively. Only 4.9% of the respondents performed TPP during IDS. Most respondents performed peritonectomy in cases where optimal postoperative outcomes were expected. Approximately 50.6% of the respondents had performed peritonectomy independently, while the others did so in cooperation with non-gynecologic surgeons. The primary reasons for not performing TPP were concerns about morbidity and uncertainty about the clinical benefits of the procedure. CONCLUSION: SPP is the predominant technique used in both PDS and IDS in Korea. A small percentage (4.9%) of gynecologic oncologists have performed TPP during IDS. Accordingly, a study regarding the feasibility of TPP should be conducted before proceeding with a prospective clinical trial.

Route to Enhancing Remote Epitaxy of Perovskite Complex Oxide Thin Films.

Remote epitaxy is taking center stage in creating freestanding complex oxide thin films with high crystallinity that could serve as an ideal building block for stacking artificial heterostructures with distinctive functionalities. However, there exist technical challenges, particularly in the remote epitaxy of perovskite oxides associated with their harsh growth environments, making the graphene interlayer difficult to survive. Transferred graphene, typically used for creating a remote epitaxy template, poses limitations in ensuring the yield of perovskite films, especially when pulsed laser deposition (PLD) growth is carried out, since graphene degradation can be easily observed. Here, we employ spectroscopic ellipsometry to determine the critical factors that damage the integrity of graphene during PLD by tracking the change in optical properties of graphene in situ. To mitigate the issues observed in the PLD process, we propose an alternative growth strategy based on molecular beam epitaxy to produce single-crystalline perovskite membranes.

Optimising PTV margins in oesophageal cancer radiotherapy: A modern radiotherapy planning, treatment delivery and verification approach - A single institutional analysis.

INTRODUCTION: Radiotherapy plays a key role in the multidisciplinary management of oesophageal cancers across neoadjuvant, definitive and palliative settings. Improved precision in radiotherapy planning and delivery techniques have allowed treating disease with tighter margins reducing toxicity. In this study, we examine the appropriateness of current practice in defining the planning target volume (PTV). METHODS: This is a single institutional retrospective study of patients who received radiotherapy for oesophageal cancers using volumetric modulated arc therapy (VMAT) during 2020. All cone-beam computerised tomography (CBCT) scans were reviewed to assess whether PTV expansions appropriately accounted for tumour motion and interfractional variation. RESULTS: Of the 27 patients, 2 (7%), 5 (19%) and 20 (74%) had cervical, thoracic and distal/gastro-oesophageal junction (GOJ) disease, respectively. 16 (59%) had adenocarcinoma and 9 (33%) had squamous cell carcinoma. 9 of 20 distal/GOJ patients were planned and treated according to the institutional stomach filling protocol. 521/528 (98.7%) CBCTs demonstrated adequate target coverage. Cervical, thoracic and GOJ regions demonstrated adequate target coverage in 57/58, 96/97 and 368/373 CBCTs with median PTV expansions of 5, 7 and 7 mm, respectively. In four patients with GOJ disease, CBCT review identified five episodes where the target volume was insufficiently covered during the treatment course. CONCLUSION: In this single institutional retrospective study, for the vast majority of patients, our institutional practice of defining PTV margins achieved satisfactory target treatment. The interfractional variations observed in patients with GOJ tumours due to target motion and variable gastric volume, highlights the role of further refinements to motion management techniques in this cohort.

Estimating Influenza Illnesses Averted by Year-Round and Seasonal Campaign Vaccination for Young Children, Kenya.

In Kenya, influenza virus circulates year-round, raising questions about optimum strategies for vaccination. Given national interest in introducing influenza vaccination for young children 6-23 months of age, we modeled total influenza-associated illnesses (inclusive of hospitalizations, outpatient illnesses, and non‒medically attended illnesses) averted by multiple potential vaccination strategies: year-round versus seasonal-campaign vaccination, and vaccination starting in April (Southern Hemisphere influenza vaccine availability) versus October (Northern Hemisphere availability). We modeled average vaccine effectiveness of 50% and annual vaccination coverage of 60%. In the introduction year, year-round vaccination averted 6,410 total illnesses when introduced in October and 7,202 illnesses when introduced in April, whereas seasonal-campaign vaccination averted 10,236 (October) to 11,612 (April) illnesses. In the year after introduction, both strategies averted comparable numbers of illnesses (10,831-10,868 for year-round, 10,175-11,282 for campaign). Campaign-style vaccination would likely have a greater effect during initial pediatric influenza vaccine introduction in Kenya; however, either strategy could achieve similar longer-term effects.

Tumour-directed radiotherapy as a successful bridge to curative chemotherapy in early stage Hodgkin's lymphoma-associated vanishing bile duct syndrome.

Hodgkin's lymphoma (HL)-associated vanishing bile duct syndrome (VBDS) is a paraneoplastic phenomenon leading to cholestasis, end-stage liver failure and potentially death, due to cholestatic liver dysfunction typically precluding the commencement of curative intent chemotherapy. A female in her 20s presented with pruritus, jaundice and cholestatic hepatitis on laboratory tests, confirmed as VBDS on liver biopsy. CT of the chest demonstrated a mediastinal mass and widespread cervical lymphadenopathy. The patient received 30.6 Gy in 17 fractions to the involved sites of disease which led to a marked improvement in liver function, allowing curative intent chemotherapy to be initiated. The patient achieved complete metabolic response and at the most recent follow-up she had no signs of recurrent disease and near-normal liver function tests. This demonstrates that tumour-directed radiotherapy can be used as a potential bridge to curative chemotherapy in early stage HL-associated VBDS.

Additional effects of herbal medicine combined with bisphosphonates for primary osteoporosis: a systematic review and meta-analysis.

Background: Osteoporosis (OP) is a significant medical issue associated with population aging. Recent research on herbal medicines (HMs) for OP has been increasing, with these therapies sometimes used in conjunction with bisphosphonates (BPs), the standard treatment for OP. We conducted a systematic review and meta-analysis to evaluate the effects of combining HMs with BPs on improving bone mineral density (BMD) in patients with primary OP. Methods: We searched nine databases-PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure Wanfang, KISS, Kmbase, Science On, and Oasis-up to 31 August 2023. We selected randomized controlled trials (RCTs) comparing BMD between HMs plus BPs and BPs alone in primary OP. A meta-analysis with BMD as the primary outcome was performed using RevMan version 5.4. Study quality and evidence certainty were assessed through Cochrane's risk of bias2 and GRADE. Results: Out of 43 RCTs involving 4,470 participants (mean age 65.8 ± 6.6 years), 35 RCTs with 3,693 participants were included in the meta-analysis. The combination of HMs and BPs was found to be more effective in improving BMD compared to BPs alone, with improvements of 0.10 g/cm2 at the lumbar spine (33 RCTs, 95% CI: 0.07-0.12, p < 0.001, I2 = 93%) and 0.08 g/cm2 at the femoral neck (20 RCTs, 95% CI: 0.05-0.12, p < 0.001, I2 = 94%), though this result was associated with high heterogeneity, high risk of bias, and very low certainty of evidence. Conclusion: Our data suggest the possibility that combining HMs with BPs may improve BMD in primary OP more effectively than using BPs alone. However, the results should be interpreted with caution due to the high heterogeneity and low quality of the studies included in the review. Therefore, further well-designed RCTs are needed to confirm these findings. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023392139.

Prognostic impact of intraoperative rupture in early-stage epithelial ovarian cancer: an ancillary study of GORILLA-3002.

OBJECTIVE: To evaluate whether intraoperative rupture affects oncological outcomes in patients with early-stage epithelial ovarian cancer (EOC). METHODS: A multicenter retrospective study was conducted on patients with early-stage EOC based on surgical and final pathological reports between 2007 and 2021. Oncologic outcomes were compared between the unruptured group (International Federation of Gynaecology and Obstetrics [FIGO] stage IA/IB) and ruptured group (FIGO stage IC1). The primary endpoint was progression-free survival (PFS). Propensity score matching (PSM) was performed to adjust for the imbalance in prognostic factors between the groups. RESULTS: Overall, 197 (58.3 %) patients comprised the unruptured group (FIGO stage IA/IB), and 141 (41.7 %) were in the intraoperatively ruptured group (FIGO stage IC1). No significant difference in the 5-year PFS was observed between the two groups before PSM (92.65 % vs. 92.80 %, P = 0.93). After PSM, the 5-year PFS showed a noticeable decrease in the ruptured group compared to the unruptured group, although this difference showed borderline statistical significance (96.90 % vs. 89.82 %, P = 0.061). This trend was particularly discernible in cases with aggressive tumor characteristics; intraoperative rupture remained an independent prognostic factor for shorter PFS in patients with high-grade histology (adjusted hazard ratio = 14.4, 95 % confidence interval = 2.8-74.1). CONCLUSIONS: Although not statistically significant, intraoperative rupture may negatively affect PFS in these patients after PSM. Therefore, rupture during surgery should be avoided as it can cause upstaging and unnecessary chemotherapy.

Decisive role of electrostatic interaction in rheological evolution of graphene oxide under ultrasonic fragmentation.

The aqueous dispersibility and processability of graphene oxide (GO) are pivotal for various applications, including the fluid assembly of macroscopic materials and nanofluidic systems. Despite the widespread utilization of ultrasonic treatment to achieve homogeneous dispersions, the rheological changes of GO during sonication have remained relatively unexplored, leading to conflicting research findings. In this study, we demonstrate that the viscoelastic evolution of GO can significantly differ under ultrasonic fragmentation depending on the balance between repulsion force and attraction force at the initial state before fragmentation. When electrostatic repulsion is in delicate equilibrium with attractive forces, gelation occurs under ultrasonic fragmentation, leading to increased viscosity under sonication. Conversely, when electrostatic repulsion predominates, viscosity decreases during sonication. This study reconciles conflicting observations on the rheological evolution of GO dispersions under ultrasonic fragmentation and provides valuable guidance and insights for the rheological engineering of GO colloidal systems.

Evaluating Immunologic and Illness Outcomes of SARS-CoV-2 Infection in Vaccinated and Unvaccinated Children Aged ≥ 5 Years, in a Multisite Longitudinal Cohort.

Hybrid immunity, as a result of infection and vaccination to SARS-CoV-2, has been well studied in adults but limited evidence is available in children. We evaluated the antibody responses to primary SARS-CoV-2 infection among vaccinated and unvaccinated children aged ≥ 5 years. METHODS: A longitudinal cohort study of children aged ≥ 5 was conducted during August 2021-August 2022, at sites in Arizona, Texas, Utah, and Florida. Children submitted weekly nasal swabs for PCR testing and provided sera 14-59 days after PCR-confirmed SARS-CoV-2 infection. Antibodies were measured by ELISA against the receptor-binding domain (RBD) and S2 domain of ancestral Spike (WA1), in addition to Omicron (BA.2) RBD, following infection in children, with and without prior monovalent ancestral mRNA COVID-19 vaccination. RESULTS: Among the 257 participants aged 5 to 18 years, 166 (65%) had received at least two mRNA COVID-19 vaccine doses ≥ 14 days prior to infection. Of these, 53 occurred during Delta predominance, with 37 (70%) unvaccinated at the time of infection. The remaining 204 infections occurred during Omicron predominance, with 53 (26%) participants unvaccinated. After adjusting for weight, age, symptomatic infection, and gender, significantly higher mean RBD AUC values were observed among the vaccinated group compared to the unvaccinated group for both WA1 and Omicron (p < 0.0001). A smaller percentage of vaccinated children reported fever during illness, with 55 (33%) reporting fever compared to 44 (48%) unvaccinated children reporting fever (p = 0.021). CONCLUSIONS: Children with vaccine-induced immunity at the time of SARS-CoV-2 infection had higher antibody levels during convalescence and experienced less fever compared to unvaccinated children during infection.

Effects of combined intense pulsed light and cyclosporine 0.05% eyedrops in ocular surface matrix metalloproteinase-9 levels in patients with moderate-to-severe MGD.

To investigate the changes in meibomian gland dysfunction (MGD) and tear matrix metalloproteinase-9 (MMP-9) levels in patients with moderate-to-severe MGD after combined treatment with intense pulsed light (IPL) therapy and cyclosporine 0.05%. Thirty-six patients concurrently treated with IPL and cyclosporine 0.05% ophthalmic drops were retrospectively enrolled. Tear break up time (TBUT), corneal and conjunctival staining scores, Schirmer test, and ocular surface disease index (OSDI) questionnaire responses were recorded. Meibum quality, consistency, and eyelid margin telangiectasia were evaluated. MMP-9 levels were examined by the positivity and signal intensity of red lines (scored 0-4). IPL was performed four times with a vascular filter at 2-week intervals, followed by a 1-month follow-up after treatment cessation. Immediately after each IPL treatment, gentle meibomian gland expression was performed in both the upper and lower eyelids using meibomian gland expressor forceps. TBUT (1.88 ± 1.02 s to 3.12 ± 1.08 s, p < 0.001), corneal and conjunctival staining (6.19 ± 2.11 to 3.12 ± 1.89, p < 0.001), Oxford staining grade (2.66 ± 0.89 to 1.35 ± 0.76, p < 0.001), and OSDI (52.97 ± 21.86 to 36.36 ± 22.45, p < 0.001) scores significantly improved after the combined treatment. Meibum quality, consistency and lid margin telangiectasia showed significant post-treatment improvement in both the upper and lower eyelids. MMP-9 positivity showed a significant decrease (97-69%, p = 0.026) with a reduction in signal intensity (2.72 ± 0.87 to 2.09 ± 0.95, p = 0.011). The combination of IPL therapy and 0.05% cyclosporine eye drops effectively treats moderate-to-severe MGD by reducing symptoms and signs of MGD and by decreasing ocular surface MMP-9-associated inflammation.

Incidence of laboratory-confirmed influenza and RSV and associated presenteeism and absenteeism among healthcare personnel, Israel, influenza seasons 2016 to 2019.

BackgroundHealthcare personnel (HCP) are at high risk for respiratory infections through occupational exposure to respiratory viruses.AimWe used data from a prospective influenza vaccine effectiveness study in HCP to quantify the incidence of acute respiratory infections (ARI) and their associated presenteeism and absenteeism.MethodsAt the start and end of each season, HCP at two Israeli hospitals provided serum to screen for antibodies to influenza virus using the haemagglutination inhibition assay. During the season, active monitoring for the development of ARI symptoms was conducted twice a week by RT-PCR testing of nasal swabs for influenza and respiratory syncytial virus (RSV). Workplace presenteeism and absenteeism were documented. We calculated incidences of influenza- and RSV-associated ARI and applied sampling weights to make estimates representative of the source population.ResultsThe median age of 2,505 participating HCP was 41 years, and 70% were female. Incidence was 9.1 per 100 person-seasons (95% CI: 5.8-14.2) for RT-PCR-confirmed influenza and 2.5 per 100 person-seasons (95% CI: 0.9-7.1) for RSV illness. Each season, 18-23% of unvaccinated and influenza-negative HCP seroconverted. The incidence of seroconversion or RT-PCR-confirmed influenza was 27.5 per 100 person-seasons (95% CI: 17.8-42.5). Work during illness occurred in 92% (95% CI: 91-93) of ARI episodes, absence from work in 38% (95% CI: 36-40).ConclusionInfluenza virus and RSV infections and associated presenteeism and absenteeism were common among HCP. Improving vaccination uptake among HCP, infection control, and encouraging sick HCP to stay home are important strategies to reduce ARI incidence and decrease the risk of in-hospital transmission.

A randomized phase II study of secondary cytoreductive surgery in patients with relapsed ovarian cancer who have progressed on a PARP inhibitor as first-line maintenance therapy: the SOCCER-P study (KGOG 3067/JGOG 3036/APGOT-OV11).

BACKGROUND: Although two recent phase III randomized controlled trials showed survival benefits of undergoing secondary cytoreductive surgery for an initial relapse of ovarian cancer, patients who received a poly-ADP ribose polymerase inhibitor (PARPi) as the first-line maintenance treatment, which is currently the standard treatment for advanced ovarian cancer, were not included in those trials. Therefore, determining an optimal treatment strategy, including secondary cytoreductive surgery, in patients whose cancer progresses even with PARPi treatment, is needed. PRIMARY OBJECTIVE: To determine whether secondary cytoreductive surgery is beneficial in patients who have progressed on PARPi maintenance treatment. STUDY HYPOTHESIS: Secondary cytoreductive surgery followed by chemotherapy is superior to chemotherapy alone for patients who have progressed on PARPi maintenance treatment. TRIAL DESIGN: The SOCCER-P study is a multicenter randomized phase II clinical trial. Patients who meet the eligibility criteria will be randomized to either undergo secondary cytoreductive surgery and subsequent platinum-based chemotherapy plus or minus bevacizumab, or to receive platinum-based chemotherapy plus or minus bevacizumab alone. Patients randomly allocated to the surgery group will undergo secondary cytoreductive surgery followed by six cycles of a physician's choice of platinum-based chemotherapy once they have recovered from surgery. MAJOR INCLUSION/EXCLUSION CRITERIA: The major inclusion criteria are as follows: first recurrence of disease with treatment-free interval from last platinum dose (TFIp) ≥6 months and progression during PARPi maintenance or treatment-free interval from last PARPi therapy (TFIPARPi) <3 months. The major exclusion criteria are as follows: >1 line of prior chemotherapy, TFIp <6 months, and radiological signs suggesting metastases not accessible to surgical removal (complete resection is deemed not possible). PRIMARY ENDPOINT: Progression-free survival. SAMPLE SIZE: 124 patients. ESTIMATED DATES FOR COMPLETING ACCRUAL AND PRESENTING RESULTS: Accrual completion approximately the end of 2026 and the results are expected after 2 years of follow-up in 2029. TRIAL REGISTRATION: NCT05704621.

A randomised controlled trial of Standard Of Care versus RadioAblaTion in Early Stage HepatoCellular Carcinoma (SOCRATES HCC).

BACKGROUND: Therapeutic options for early-stage hepatocellular carcinoma (HCC) in individual patients can be limited by tumor and location, liver dysfunction and comorbidities. Many patients with early-stage HCC do not receive curative-intent therapies. Stereotactic ablative body radiotherapy (SABR) has emerged as an effective, non-invasive HCC treatment option, however, randomized evidence for SABR in the first line setting is lacking. METHODS: Trans-Tasman Radiation Oncology Group (TROG) 21.07 SOCRATES-HCC is a phase II, prospective, randomised trial comparing SABR to other current standard of care therapies for patients with a solitary HCC ≤ 8 cm, ineligible for surgical resection or transplantation. The study is divided into 2 cohorts. Cohort 1 will compromise 118 patients with tumors ≤ 3 cm eligible for thermal ablation randomly assigned (1:1 ratio) to thermal ablation or SABR. Cohort 2 will comprise 100 patients with tumors > 3 cm up to 8 cm in size, or tumors ≤ 3 cm ineligible for thermal ablation, randomly assigned (1:1 ratio) to SABR or best other standard of care therapy including transarterial therapies. The primary objective is to determine whether SABR results in superior freedom from local progression (FFLP) at 2 years compared to thermal ablation in cohort 1 and compared to best standard of care therapy in cohort 2. Secondary endpoints include progression free survival, overall survival, adverse events, patient reported outcomes and health economic analyses. DISCUSSION: The SOCRATES-HCC study will provide the first randomized, multicentre evaluation of the efficacy, safety and cost effectiveness of SABR versus other standard of care therapies in the first line treatment of unresectable, early-stage HCC. It is a broad, multicentre collaboration between hepatology, interventional radiology and radiation oncology groups around Australia, coordinated by TROG Cancer Research. TRIAL REGISTRATION: anzctr.org.au, ACTRN12621001444875, registered 21 October 2021.

Asparagine Dependency Is a Targetable Metabolic Vulnerability in TP53-Altered Castration-Resistant Prostate Cancer.

TP53 tumor suppressor is frequently altered in lethal, castration-resistant prostate cancer (CRPC). However, to date there are no effective treatments that specifically target TP53 alterations. Using transcriptomic and metabolomic analyses, we have shown here that TP53-altered prostate cancer exhibits an increased dependency on asparagine (Asn) and overexpresses Asn synthetase (ASNS), the enzyme catalyzing the synthesis of Asn. Mechanistically, the loss or mutation of TP53 transcriptionally activated ASNS expression, directly and via mTORC1-mediated ATF4 induction, driving de novo Asn biosynthesis to support CRPC growth. TP53-altered CRPC cells were sensitive to Asn restriction by knockdown of ASNS or L-asparaginase treatment to deplete the intracellular and extracellular sources of Asn, respectively, and cell viability was rescued by Asn addition. Notably, pharmacological inhibition of intracellular Asn biosynthesis using a glutaminase inhibitor and depletion of extracellular Asn with L-asparaginase significantly reduced Asn production and effectively impaired CRPC growth. This study highlights the significance of ASNS-mediated metabolic adaptation as a synthetic vulnerability in CRPC with TP53 alterations, providing a rationale for targeting Asn production to treat these lethal prostate cancers. Significance: TP53-mutated castration-resistant prostate cancer is dependent on asparagine biosynthesis due to upregulation of ASNS and can be therapeutically targeted by approaches that deplete intracellular and extracellular asparagine.