Socioeconomic status and physical activity disparities in older adults: Implications for COVID-19 related diabetes cognitive dysfunction.

Objectives: This study aims to investigate the influence of socioeconomic status (SES) on variations in physical activity (PA) levels and diabetes-related cognitive dysfunction and impairment amidst disruptions caused by the COVID-19 pandemic. Methods: With the sample of old population, comprising about 20 thousand from the Fact-Finding Survey on the Status of Senior Citizens (FSSSC) released by Ministry of Health and Welfare of South Korea in 2017 and 2020, we empirically tested the direct and indirect effects of SES on cognitive dysfunction using structural equation modeling (SEM). Two SEMs provided the comparison on the effects of COVID-19. Results: Household income had a negative impact on the likelihood of dementia diagnosis via PA related diabetes during the pandemic (p < 0.001), whereas no effects of household income on dementia diagnosis were found in 2017, due to no direct effect of PA on diabetes confirmation in 2017. The disparity in PA based on SES becomes more prominent among the older individuals during the pandemic (z = 11.7) than 2017 (z = 6.0), emphasizing the significance of PA in mitigating diabetes-induced cognitive dysfunction during the pandemic. SES affects access to PA, contributing to diabetes-induced cognitive dysfunctions in the older population with lower SES during the pandemic. Conclusion: PA may serve as a preventive measure against diabetes-induced cognitive dysfunction and dementia in the older population. Thorough investigation of these mechanisms is imperative to establish the role of PA in preventing diabetes-induced cognitive impairment, particularly among the older population with lower SES.

The effects of medial soft tissue release for varus deformity during medial open wedge supramalleolar osteotomy: a cadaveric study.

This study was performed to investigate the effects of fibular osteotomy and release of medial soft tissues including posterior tibial tendon (PTT), and deep deltoid ligaments, which act as medial stabilizing structures in medial open wedge SMO. Twelve fresh frozen human legs were obtained and disarticulated below the knee. Experiments were conducted in four steps. First, medial open wedge tibial osteotomy was performed. Second, fibular osteotomy was performed in an inferomedial direction at the same level as the tibial osteotomy. Third, the deep deltoid ligament was released from tibial attachments. Forth, total tenotomy of the PTT was performed behind the medial malleolus. After finishing each step, contact area and peak and mean pressures were measured in the tibiotalar and talofibular joints. Fibular osteotomy after medial open wedge SMO significantly decreased mean pressure in the tibiotalar joint, mean and peak pressures in the talofibular joint. Medial soft tissue release resulted in a remarkable lateral shift and decreased tibiotalar joint loading. However, no remarkable change was observed in the tibiotalar joint during releasing medial soft tissues. The overall peak pressure distribution tended to shift more laterally compared to the value of normal alignment. In conclusion, concomitant fibular osteotomy and release of the deltoid ligament and PTT provide a useful means of minimizing tibiotalar joint stress. Supplementary Information: The online version contains supplementary material available at 10.1007/s13534-024-00370-7.

Effects of Black and White Mulch on Mycelial Growth of Tuber Species in Korean Field Environment.

Truffles, belonging to the genus Tuber, are ectomycorrhizal (ECM) fungi that form underground ascocarps and primarily establish symbiosis with oaks and hazels. The cultivation of Tuber spp. involves transplanting inoculated seedlings that have formed ectomycorrhiza with Tuber species, with mulching being effective for truffle cultivation. In this study, we investigated the effects of mulching on the mycelial growth of four Tuber species (T. himalayense, T. koreanum, T. melanosporum, and T. borchii) in the Korean natural environment, highlighting the potential for Korea as a truffle cultivation site. We developed and tested species-specific primers for quantifying the soil mycelial biomass of Tuber spp. by qRT-PCR, determined the superior mulch color for mycelial growth, and identified the Tuber species exhibiting the highest growth rate in the Korean field environment. Our results demonstrated that white mulch significantly enhanced mycelial growth in Tuber species than black mulch, likely owing to its ability to maintain low soil temperatures, control weeds, and improve host plant growth. Among the Tuber species, T. himalayense showed the greatest growth potential in the Korean natural environment. Additionally, a significant and positive correlation was observed between the mycelial biomass of Tuber species and the growth of inoculated seedlings, as measured by the total stem length and the number of leaves, thereby indicating the importance of symbiosis between ECM fungi and host plants. This study provides valuable insights into truffle cultivation in Korea and highlights the potential of using white mulch to promote mycelial growth, thereby contributing essential data for understanding the appropriate environmental conditions for Tuber spp. cultivation in Korea. Further study is needed to assess the long-term impact of mulching and to explore the effectiveness of other mulching materials.

Comparison of analgesic effectiveness between nefopam and propacetamol in living kidney donors following rectus sheath block after hand-assisted living donor nephrectomy: a prospective, randomized controlled trial.

BACKGROUND: Nefopam and propacetamol are the most commonly used analgesics in postoperative multimodal analgesic regimens. Distinct mechanisms are involved in each drug's anti-nociceptive effects. No studies have compared pain relief efficacy between the two drugs in patients undergoing transplantation surgery. Here, we investigated whether the administration of nefopam or propacetamol to healthy living kidney donors who underwent rectus sheath block (RSB) for parietal pain could reduce the subsequent opioid dose necessary to produce adequate analgesia. METHODS: This prospective, randomized controlled trial included 72 donors undergoing elective hand-assisted living donor nephrectomy into two groups: propacetamol (n = 36) and nefopam (n = 36). Intraoperative RSB was performed in all enrolled donors. The primary outcome was the total volume of intravenous opioid-based patient-controlled analgesia (PCA) used on postoperative day 1 (POD 1). Additionally, the Numeric Rating Scale scores for flank (visceral) and umbilicus (parietal) pain at rest and during coughing were compared, and the Korean adaptation of the Quality of Recovery-15 Questionnaire (QoR-15 K) was evaluated on POD 1. RESULTS: Both groups had similar preoperative and intraoperative characteristics. On POD 1, the total amount of PCA infusion was significantly lower in the nefopam group than in the propacetamol group (44.5 ± 19.3 mL vs. 70.2 ± 29.0 mL; p < 0.001). This group also reported lower pain scores at the flank and umbilical sites and required fewer rescue doses of fentanyl in the post-anesthesia care unit. However, pain scores and fentanyl consumption in the ward were comparable between groups. The QoR-15 K scores were similar between groups; there were substantial improvements in breathing, pain severity, and anxiety/depression levels in the nefopam group. The incidences of postoperative complications, including sweating and tachycardia, were similar between groups. CONCLUSION: Compared with propacetamol, nefopam provides a greater analgesic effect for visceral pain and enhances the effects of blocks that reduce the opioid requirement in living kidney donors with parietal pain managed by RSB. TRIAL REGISTRATION: The trial was registered prior to patient enrollment in the clinical trial database using the Clinical Research Information Service (registration no. KCT0007351 , Date of registration 03/06/2022).

Highly functional duodenal stent with photosensitizers enables photodynamic therapy for metabolic syndrome treatment: Feasibility and safety study in a porcine model.

Duodenal mucosal resurfacing (DMR) by thermal ablation of the duodenal mucosa is a minimally invasive endoscopic procedure for controlling metabolic syndrome (MS). However, thermal energy can cause adverse effects due to deep mucosal injury, necessitating an additional mucosal lifting process, which complicate the procedures. Therefore, we aimed to develop a similar procedure using non-thermal photodynamic therapy (PDT) for DMR using a highly functional metal stent covered with photosensitizers (PSs) to minimize the potential risks of thermal ablation injury. We developed a novel PS stent enabling the controlled release of radical oxygen species with specific structures to prevent stent migration and duodenal stricture after ablation and performed an animal study (n = 8) to demonstrate the feasibility and safety of PDT for DMR. The stents were placed for 7 days to prevent duodenal strictures after PDT. To confirm PDT efficacy, we stained for gastric inhibitory polypeptide (GIP) and glucose transporter isoform 1. The PS stents were deployed, and PDT was applied without evidence of duodenal stricture, pancreatitis, or hemorrhage in any of the pigs. Microscopic evaluation indicated apoptosis of the mucosal cells in the irradiated duodenum on days 7 and 14, which recovered after day 28. Immunohistochemistry revealed suppressed GIP expression in the mucosal wall of the irradiated duodenum. Endoscopic PDT for DMR using PS stents could be applied safely in a porcine model and may result in decreased GIP secretion, which is a crucial mechanism in MS treatment. Further clinical studies are required to explore its safety and efficacy in patients with MS.

Gynecologic Cancer InterGroup CA125 response has a high negative predictive value for CHK1 inhibitor RECIST response in recurrent ovarian cancer.

We investigated the association of CA125 response with prognosis and RECIST response/progressive disease (PD) criteria in recurrent high grade serous ovarian cancer (HGSOC) patients treated with a cell cycle checkpoint kinase 1 inhibitor (CHK1i), prexasertib. 81 patients had measurable disease per RECISTv1.1, of which 72 and 70 were measurable by Gynecologic Cancer InterGroup (GCIG) CA125 response and PD criteria, respectively. Univariate and multivariate analyses showed that GCIG CA125 response (n = 32) is associated with improved progression-free survival (PFS) and overall survival (OS) compared to no GCIG CA125 response (n = 40) (median PFS 8.0 vs. 3.5 months [HR: 0.30, 95% CI: 0.18-0.51, p < 0.0001]; median OS 19.8 vs. 10.0 months [HR: 0.38, 95% CI: 0.23-0.64, p < 0.001]) independent of BRCA mutation status, platinum-sensitivity, previous PARP inhibitor therapy, ECOG performance status, and FIGO stage. Notably, GCIG CA125 response had a high negative predictive value (NPV: 93%, 95% CI: 80-98), but poor positive predictive value (PPV: 53%, 95% CI: 35-71) in predicting RECIST response. CA125 PD criteria also showed poor concordance with RECIST PD (PPV 56%, 95% CI: 40-71; NPV 33%, 95% CI: 17-54). Therefore, serum CA125 may be useful as a highly accessible prognostic and predictive biomarker to CHK1i therapy in recurrent HGSOC.

Sequential Comparison of Knee Muscle Strength after Anterior Cruciate Ligament Reconstruction between Hamstring Autograft and Tibialis Anterior Allograft: Propensity Score Matched Pair Analysis.

Among the graft options for anterior cruciate ligament reconstruction (ACLR), hamstring autografts are widely regarded as the preferred choice for primary ACLR among orthopedic surgeons worldwide. However, concerns persist regarding postoperative knee flexor weakness. We aimed to compare knee extensor and flexor strengths between hamstring autograft and tibialis anterior allograft groups in ACLR patients, who were propensity score-matched based on baseline characteristics. A retrospective analysis included 58 matched pairs who underwent isokinetic strength tests at 6 and 12 months post operation. Isokinetic muscle strength tests found no significant difference in knee extensor and flexor strength at 6 months post operation between the hamstring autograft and tibial anterior allograft groups. At 12 months, the hamstring autograft group exhibited significantly greater knee flexor deficit (total work and average power) compared to the allograft group, despite no differences in extensor strength or patient-reported outcomes. This study highlights the impact of hamstring autograft harvesting on muscle strength and recovery following ACLR in short-term period.

Combined Anterolateral Ligament Reconstruction Results in Better Knee Stability and More Satisfactory Subjective Outcomes in Non-Athlete Patients Undergoing Revision Anterior Cruciate Ligament Reconstruction.

Background: Consensus has not yet been reached regarding combined anterior cruciate ligament reconstruction (ALLR) with revisional anterior cruciate ligament reconstruction (RACLR). We aimed to compare the clinical outcomes between patients who underwent isolated RACLR and those who underwent RACLR combined with ALLR. Methods: Between June 2010 and June 2021, 49 patients who underwent RACLR were retrospectively reviewed over a 24-month follow-up. Patients were categorized into the isolated RACLR (n = 37, group 1) or combined ALLR group (n = 12, group 2). Clinical outcomes were evaluated with several patient-reported outcome measures (PROMs) and minimal clinically important differences (MCIDs) for each PROM. The side-to-side difference (SSD) of the anterior instability was measured. The pivot-shift test was performed. Results: Baseline characteristics showed no differences between the groups. PROMs showed no significant differences between the groups at the 2-year follow-up. Group 2 was superior to group 1 in the MCID achievement rate for Lysholm knee and International Knee Documentation Committee (IKDC) subjective scores at 24 months postoperatively. At the final follow-up, the proportion of IKDC grade A in SSD for anterior laxity was higher in group 2 than in group 1 (58.3% versus [vs.] 18.3%, p = 0.009), and the proportion of pivot-shift grade 0 was also higher in group 2 (66.7% vs. 27.0%, p = 0.013). The "near return to activity" rate was also higher in group 2 than in group 1 (83.3% vs. 45.9%, p = 0.043). Conclusions: Combining ALLR with RACLR in non-athletes results in a higher proportion of patients with less mechanical graft failure and satisfactory clinical outcomes.

Shortcomings in the Evaluation of Blood Glucose Forecasting.

OBJECTIVE: Recent years have seen an increase in machine learning (ML)-based blood glucose (BG) forecasting models, with a growing emphasis on potential application to hybrid or closed-loop predictive glucose controllers. However, current approaches focus on evaluating the accuracy of these models using benchmark data generated under the behavior policy, which may differ significantly from the data the model may encounter in a control setting. This study challenges the efficacy of such evaluation approaches, demonstrating that they can fail to accurately capture an ML-based model's true performance in closed-loop control settings. METHODS: Forecast error measured using current evaluation approaches was compared to the control performance of two forecasters-a machine learning-based model (LSTM) and a rule-based model (Loop)-in silico when the forecasters were utilized with a model-based controller in a hybrid closed-loop setting. RESULTS: Under current evaluation standards, LSTM achieves a significantly lower (better) forecast error than Loop with a root mean squared error (RMSE) of 11.57 ±0.05 mg/dL vs. 18.46 ±0.07 mg/dL at the 30-minute prediction horizon. Yet in a control setting, LSTM led to significantly worse control performance with only 77.14% (IQR 66.57-84.03) time-in-range compared to 86.20% (IQR 78.28-91.21) for Loop. CONCLUSION: Prevailing evaluation methods can fail to accurately capture the forecaster's performance when utilized in closed-loop settings. SIGNIFICANCE: Our findings underscore the limitations of current evaluation standards and the need for alternative evaluation metrics and training strategies when developing BG forecasters for closed-loop control systems.

Effect of different bedding depths of rice hulls on growth performance and carcass traits of White Pekin ducks.

Duck meat is recognized as a healthier poultry product that contains higher amounts of unsaturated and essential fatty acids, iron, and excellent amounts of protein. It has been found to possess the ability to reduce low-density lipoprotein cholesterol and subsequently, blood pressure in the human body; and improve the immunity system. The current study investigated the appropriate bedding depths of rice hulls as a preferred bedding material by evaluating the growth performance and carcass traits of White Pekin ducks raised for 42 days. A total of 288 one-day-old White Pekin ducklings were randomly allotted to floor cages with one of four bedding depths at 4 cm, 8 cm, 12 cm, and 16 cm. Ducklings were fed standard duck starter (days 1-21) and finisher (days 22-42) diets. The birds were stocked at a rate of 6 birds/m2 with 6 replicates per treatment. Growth performance evaluation for the body weight, average daily gain, and average daily feed intake were measured to calculate the weekly feed conversion ratio. Breast, leg, and carcass yield were assessed as carcass traits. The muscle color and proximate composition were also analyzed for meat quality. Footpad dermatitis was also evaluated on day 42. Ducks reared on 16 cm bedding depth over the 42 days recorded higher (p < 0.05) body weight, average daily, average daily feed intake, and improved feed conversion ratios compared to other groups. The crude fat in breast meat also lowered (p < 0.05) in ducks reared at 16 cm (1.02%) when compared to ducks raised at 4 cm bedding depth (2.11%). Our results showed improved redness (p < 0.05) when the depth of bedding materials was elevated. Except for the breast meat fat, the dissimilar bedding depths did not affect (p < 0.05) the breast and leg meat composition, footpad dermatitis, and mortality for the current study. In conclusion, this study indicated that the bedding depths would directly or indirectly affect the growth performance and meat color of White Pekin ducks; and the bedding depth of rice hulls at 16 cm improved the growth performance of White Pekin ducks for 42 days.

Boosting Photocatalytic Hydrogen Production by MOF-derived Metal Oxide Heterojunctions with a 10.0% Apparent Quantum Yield.

Photocatalytic hydrogen production offers an alternative pathway to establish a sustainable energy economy. While numerous photoactive materials exhibit potential for generating hydrogen from water, the synergy achieved by combining two different materials with complementary properties in the form of heterojunctions can significantly their photocatalytic activity. Our study describes the design and generation of the metal-organic framework-derived (MOF) metal oxide heterojunction composed of RuO2/N,S-TiO2. The RuO2/N,S-TiO2 is generated through the pyrolysis of MOFs, Ru- HKUST-1, and the amino-functionalized MIL-125-NH2. Among the various RuO2/N,S- TiO2 materials tested, the material characterized by the lowest RuO2 content, exhibited the highest hydrogen evolution rate, producing 10,761 µmol·hr-1·g-1 of hydrogen with an apparent quantum-yield of 10.0% in pure water. In addition to RuO2/N,S-TiO2, we generated two other MOF-derived metal-oxide heterojunctions, ZnO/N,S-TiO2 and In2O3/N,S-TiO2, leading to apparent quantum yields of 0.7% and 0.3%, respectively. The remarkable photocatalytic activity observed in RuO2/N,S-TiO2 is thought to be attributed to the synergistic effects arising from the combination of metallic properties inherent in the metal oxides, their band alignment, porosity, and surface properties inherited from the parent MOFs. The photocatalytic efficiency of RuO2/N,S-TiO2 was further demonstrated in actual water samples, producing hydrogen with a rate of 8,190 µmol·hr-1·g-1 in tap water.

Medical Students' Preferences on Practicing Intravenous Insertion on Each Other and Via Simulation.

SUMMARY STATEMENT: Medical students have traditionally practiced painful procedures such as intravenous (IV) line insertion on each other. Recently, there has been more emphasis on learning through simulation. Our study investigated students' attitudes regarding IV line insertion training, focusing on their anxiety, expectation to learn empathy, learning preference, and litigiousness. A 24-question survey was taken regarding anxiety and empathy when learning IV placement on each other versus on mannequins.Many students believed that they could learn empathy skills and better appreciate patient discomfort by learning IV placement through person-based practice. However, students who reported feeling anxious about having a student practice IV placement on them believed they were less likely to learn empathy through having a student practice IV insertion on them. The preferred method of learning painful procedures, such as IV placement, may be through a combination of simulation and person-based practice to mitigate anxiety while also enhancing empathy skills.

Comparison of the Rate of Concomitant Proximal Venous Stenosis between the Upper and Lower Extremities in Patients with Secondary Lymphedema Undergoing Lymphatico-venous Anastomosis.

BACKGROUND: Concomitant iatrogenic proximal venous stenosis increases venous pressure and can be a risk factor for unfavorable outcomes of lymphaticovenular anastomosis (LVA) in extremities with secondary lymphedema. This study investigated the frequency and relevant factors of venous stenosis in patients diagnosed with secondary lymphedema who underwent LVA. METHODS: Patients who underwent preoperative computed tomographic venography (CTV) and LVA for secondary lymphedema of the extremities from October 2018 to March 2022 were included. The incidence of proximal venous stenosis in the affected limb on preoperative CTV and the rate of endovascular intervention were compared between upper and lower extremities. Factors affecting proximal venous stenosis were identified through multivariable analysis using independent variables, including patient age, body mass index, comorbidities, smoking history, radiation therapy, duration of lymphedema, and location of lymphedema. RESULTS: A total of 211 patients were analyzed, including 83 patients with upper extremity and 128 patients with lower extremity lymphedema. The incidence of proximal venous stenosis in the preoperative CTV was 32.5% and 7.8% in upper extremity, and lower extremity lymphedema, respectively (p < 0.001). The incidence of venous stenosis requiring endovascular intervention was significantly higher in the upper extremity compared to the lower extremity (16.9 % vs. 6.3 %, p = 0.014). In multivariable analysis, risk factors affecting incidence of venous stenosis requiring endovascular intervention was the patient age (p = 0.007) and upper extremity (p = 0.009). CONCLUSIONS: Preoperative evaluation and treatment of venous stenosis in extremities with secondary lymphedema are necessary before LVA surgery, particularly in upper extremity lymphedema.

Direct observation of twisted stacking domains in the van der Waals magnet CrI3.

Van der Waals (vdW) stacking is a powerful technique to achieve desired properties in condensed matter systems through layer-by-layer crystal engineering. A remarkable example is the control over the twist angle between artificially-stacked vdW crystals, enabling the realization of unconventional phenomena in moiré structures ranging from superconductivity to strongly correlated magnetism. Here, we report the appearance of unusual 120° twisted faults in vdW magnet CrI3 crystals. In exfoliated samples, we observe vertical twisted domains with a thickness below 10 nm. The size and distribution of twisted domains strongly depend on the sample preparation methods, with as-synthesized unexfoliated samples showing tenfold thicker domains than exfoliated samples. Cooling induces changes in the relative populations among different twisting domains, rather than the previously assumed structural phase transition to the rhombohedral stacking. The stacking disorder induced by sample fabrication processes may explain the unresolved thickness-dependent magnetic coupling observed in CrI3.

An Extensive Study of the Influence of Key Flow Variables on Printed Line Quality Outcomes during Aerosol Jet Printing Using Coupled Three-Dimensional Numerical Models.

A three-dimensional (3D) numerical model was developed to explore the intricate aerodynamic mechanisms associated with aerosol jet printing (AJP). The proposed approach integrates computational fluid dynamics and discrete phase modeling, offering a comprehensive understanding of the deposition mechanisms of the AJP process. Initially, numerical solutions of the governing equations were obtained under the assumptions of compressible and laminar flows, facilitating an analysis of certain key flow variables, in this case, the sheath gas flow rate and carrier gas flow rate across the fluid domain. Subsequently, incorporating a Lagrangian discrete phase model allowed a detailed examination of the droplet behavior after nozzle ejection, considering the influence of the Saffman lift force. Finally, experiments were performed to elucidate the influence of key flow variables on the printed width. Generally, the measured printed line morphology and corresponding line electrical performance exhibited close conformity with the numerical model, demonstrating that the proposed numerical model is important for making well-informed decisions during process optimization.

Clinical evaluation of a one-piece polyetheretherketone removable partial denture fabricated using a novel digital workflow: A self-controlled clinical trial.

PURPOSE: To explore the clinical application of one-piece polyetheretherketone (PEEK) removable partial dentures (RPDs) fabricated using a novel digital workflow and to evaluate their weights and fits in vivo and patient satisfaction. MATERIALS AND METHODS: Fifteen cases with posterior partially edentulous situations were selected, and each patient received two types of RPDs, including a novel digital workflow (test group) and a conventional workflow (control group). For the test group, one-piece RPDs were designed through three-dimensional (3D) methods by scanning stone casts and fabricated by milling PEEK discs. Each RPD was weighed. The gaps between the oral tissue and RPDs in each group were duplicated using a polyvinylsiloxane (PVS) replica and measured by 3D analysis. A visual analog scale (VAS) was used to evaluate the patient's satisfaction. Paired t-tests were used to compare the differences in the weight, the gaps of each RPD, and VAS values between the two groups. One-way analysis of variance tests was used to compare the differences in the gap among different components in each group. RESULTS: The RPD in the test group weighed less than that in the control group (p < 0.01). No statistically significant differences in the gaps of denture bases and rests (p > 0.05) were found between the two groups, but the gaps of major connectors in the test group were significantly smaller than in the control group (p < 0.05). The VAS scores for comfortableness and masticatory efficiency were not significantly different between the two groups (p > 0.05) but the scores for the aesthetic appearance of the clasps in the test group were significantly higher than that in the control group (p < 0.05). CONCLUSIONS: One-piece PEEK RPDs manufactured using a novel digital workflow weighed less than conventional RPDs and exhibited a clinically acceptable internal fit. Although the aesthetic appearance of the PEEK clasps was superior to the control, there is still room for improvement.

Real-world outcomes of patients with resected stage III melanoma treated with adjuvant therapies.

BACKGROUND: Both immunotherapy (IO) and targeted therapy (TT) are used as adjuvant (adj) treatment for stage III melanoma, however, data describing real-world outcomes are limited. In addition, a significant proportion of patients relapse, for whom best management is unclear. The aim of our study was to assess the efficacy, and safety of adj anti-PD1 IO and TT in a real-world cohort of patients with resected stage III melanoma, and further delineate patterns of recurrence and treatment strategies. METHODS: We retrospectively analyzed 130 patients who received adj therapy (100 anti-PD1 IO and 30 TT). RESULTS: At a median follow-up of 30 months, median relapse-free survival (RFS) was 24.6 (95% CI, 17-not reached [NR]) versus 64 (95% CI, 29.5-NR) months for the TT and IO groups, respectively (p = 0.26). Median overall survival (OS) was NR for either subgroup. At data cutoff, 77% and 82% of patients in TT and IO arms were alive. A higher number of grade ≥3 treatment-related adverse events (AEs) were noted in the IO group (11% vs. 3%), however, a higher proportion of patients permanently discontinued adj therapy in the TT group (43% vs. 11%) due to toxicity. Strategies at relapse and outcomes were variable based on location and timing of recurrence. A significant number of patients who relapsed after adj IO received a second round of IO. Among them, patients who were off adj IO at relapse had superior second median RFS (mRFS2), compared to those who relapsed while on adj IO; mRFS2 was NR versus 5.1 months (95% CI, 2.5-NR), respectively, p = 0.02. CONCLUSION: In summary, both TT and IO yielded prolonged RFS in a real-world setting, however, longer follow-up is needed to determine any potential OS benefit. Adj therapy, particularly TT, may not be as well tolerated as suggested in clinical trials, with lower completion rates (59% vs. 74%) in a real-life setting. Overall, patients who relapse during adj therapy have poor outcomes, while patients who relapse after discontinuation of adj IO therapy appear to benefit from IO re-treatment.

Risk of avascular necrosis in patients with inflammatory bowel disease: Insights from a nationwide cohort study and the impact of corticosteroid use.

BACKGROUND AND AIM: Corticosteroid use is a risk factor for avascular necrosis (AVN) and inflammatory bowel disease (IBD) patients are often exposed to higher corticosteroid usage. We investigated the epidemiology and risk factors of AVN in a nationwide population-based cohort of IBD patients. METHODS: Patients newly diagnosed with IBD were identified, and sex- and age-matched participants from the general population were selected in a 1:3 IBD:non-IBD ratio. We investigated newly diagnosed AVN and assessed the incidence rates and risk of AVN with multivariate Cox regression models. RESULTS: During the median follow-up period of 7.22±3.85 years, 357 (0.62 %) were newly diagnosed with AVN. The risk of AVN was higher in IBD (aHR = 1.42, 95 % CI: 1.25-1.62). Ulcerative colitis (UC) patients showed a particularly elevated risk of developing AVN. IBD patients with higher cumulative corticosteroid intake and exposed to a mean prednisolone-equivalent daily dose>20 mg for >1 month were at higher risk of AVN. In Crohn's disease (CD), longer exposure time to >20 mg prednisolone-equivalent presented a trend in increased risk. CONCLUSION: AVN risk was higher in IBD than in those without, particularly in UC and corticosteroid use in IBD could pose a crucial role. These underscore the importance of considering the AVN etiological factors, particularly corticosteroid use.

Rhizobacterial syntrophy between a helper and a beneficiary promotes tomato plant health.

Microbial interactions impact the functioning of microbial communities. However, microbial interactions within host-associated communities remain poorly understood. Here, we report that the beneficiary rhizobacterium Niallia sp. RD1 requires the helper Pseudomonas putida H3 for bacterial growth and beneficial interactions with the plant host. In the absence of the helper H3 strain, the Niallia sp. RD1 strain exhibited weak respiration and elongated cell morphology without forming bacterial colonies. A transposon mutant of H3 in a gene encoding succinate-semialdehyde dehydrogenase displayed much attenuated support of RD1 colony formation. Through the subsequent addition of succinate to the media, we found that succinate serves as a public good that supports RD1 growth. Comparative genome analysis highlighted that RD1 lacked the gene for sufficient succinate, suggesting its evolution as a beneficiary of succinate biosynthesis. The syntrophic interaction between RD1 and H3 efficiently protected tomato plants from bacterial wilt and promoted tomato growth. The addition of succinate to the medium restored complex II-dependent respiration in RD1 and facilitated the cultivation of various bacterial isolates from the rhizosphere. Taken together, we delineate energy auxotrophic beneficiaries ubiquitous in the microbial community, and these beneficiaries could benefit host plants with the aid of helpers in the rhizosphere.

De novo missense variants in HDAC3 leading to epigenetic machinery dysfunction are associated with a variable neurodevelopmental disorder.

Histone deacetylase 3 (HDAC3) is a crucial epigenetic modulator essential for various developmental and physiological functions. Although its dysfunction is increasingly recognized in abnormal phenotypes, to our knowledge, there have been no established reports of human diseases directly linked to HDAC3 dysfunction. Using trio exome sequencing and extensive phenotypic analysis, we correlated heterozygous de novo variants in HDAC3 with a neurodevelopmental disorder having variable clinical presentations, frequently associated with intellectual disability, developmental delay, epilepsy, and musculoskeletal abnormalities. In a cohort of six individuals, we identified missense variants in HDAC3 (c.277G>A [p.Asp93Asn], c.328G>A [p.Ala110Thr], c.601C>T [p.Pro201Ser], c. 797T>C [p.Leu266Ser], c.799G>A [p.Gly267Ser], and c.1075C>T [p.Arg359Cys]), all located in evolutionarily conserved sites and confirmed as de novo. Experimental studies identified defective deacetylation activity in the p.Asp93Asn, p.Pro201Ser, p.Leu266Ser, and p.Gly267Ser variants, positioned near the enzymatic pocket. In addition, proteomic analysis employing co-immunoprecipitation revealed that the disrupted interactions with molecules involved in the CoREST and NCoR complexes, particularly in the p.Ala110Thr variant, consist of a central pathogenic mechanism. Moreover, immunofluorescence analysis showed diminished nuclear to cytoplasmic fluorescence ratio in the p.Ala110Thr, p.Gly267Ser, and p.Arg359Cys variants, indicating impaired nuclear localization. Taken together, our study highlights that de novo missense variants in HDAC3 are associated with a broad spectrum of neurodevelopmental disorders, which emphasizes the complex role of HDAC3 in histone deacetylase activity, multi-protein complex interactions, and nuclear localization for proper physiological functions. These insights open new avenues for understanding the molecular mechanisms of HDAC3-related disorders and may inform future therapeutic strategies.