Study of pediatric appendicitis scores and management strategies: A prospective observational feasibility study.

OBJECTIVE: The objective was to investigate the feasibility of prospectively validating multiple clinical prediction scores (CPSs) for pediatric appendicitis in an Australian pediatric emergency department (ED). METHODS: A literature search was conducted to identify potential CPSs and a single-center prospective observational feasibility study was performed between November 2022 and May 2023 to evaluate the performance of identified CPSs. Children 5-15 years presenting with acute right-sided or generalized abdominal pain and clinician suspicion of appendicitis were included. CPSs were calculated by the study team from prospectively clinician-collected data and/or review of medical records. Accuracy of CPSs were assessed by area under the receiver operating characteristic curve (AUC) and proportions correctly identifiable as either low-risk or high-risk with the best performing CPS compared to clinician gestalt. Final diagnosis of appendicitis was confirmed on histopathology or by telephone/email follow-up for those discharged directly from ED. RESULTS: Thirty CPSs were identified in the literature search and 481 patients were enrolled in the study. A total of 150 (31.2%) patients underwent appendectomy with three (2.0%) having a normal appendix on histopathology. All identified CPSs were calculable for at least 50% of the patient cohort. The pediatric Appendicitis Risk Calculator for pediatric EDs (pARC-ED; n = 317) was the best performing CPS with AUC 0.90 (95% confidence interval [CI] 0.86-0.94) and specificity 99.0% (95% CI 96.4%-99.7%) in diagnosing high-risk cases and a misclassification rate of 4.5% for low-risk cases. CONCLUSIONS: The study identified 30 CPSs that could be validated in a majority of patients to compare their ability to assess risk of pediatric appendicitis. The pARC-ED had the highest predictive accuracy and can potentially assist in risk stratification of children with suspected appendicitis in pediatric EDs. A multicenter study is now under way to evaluate the potential of these CPSs in a broader range of EDs to aid clinical decision making in more varied settings.

Activin A as a potential biomarker for preserved ratio impaired spirometry (PRISm) and clinical outcomes in community-dwelling adults.

INTRODUCTION: This study endeavors to decipher the association between Activin A and PRISm, thereby addressing the potential of Activin A as a serum biomarker for early detection and long-term clinical outcome prediction of PRISm and subsequent all-cause mortality. METHODS: The study sample comprised middle-aged and older adults from the I-Lan Longitudinal Aging Study. Pulmonary function including forced vital capacity (FVC) and forced expiratory volume in one second (FEV1) were measured. Demographic data and laboratory data (including serum Activin A levels) were also collected. Multivariate logistic regression and Cox proportional hazards models were used to identify independent predictors of PRISm and all-cause mortality, respectively. RESULTS: Among 711 eligible participants, 34 % had PRISm. The risk of PRISm elevated with Activin A levels in group quartiles (adjusted odds ratio (aOR), Q2: 1.606 [95 % CI 0.972-2.652], p = 0.064, Q3: 2.666 [1.635-4.348], p < 0.001, Q4: 3.225 [1.965-5.293], p < 0.001). On the other hand, lower hemoglobin (aOR: 1.122, p = 0.041) and higher blood urea nitrogen (BUN) levels (aOR: 1.033, p = 0.048) were associated with increased risk of PRISm. In addition, the PRISm group had a higher all-cause mortality rate (non-PRISm 4.5% vs. PRISm 8.3 %, p = 0.038). Multivariate Cox models also identify a higher level of Activin A as a risk factor of all-cause mortality (aHR: 1.001 [1.000-1.003], p = 0.042). CONCLUSIONS: Higher Activin A quartiles were linked to increased risk of PRISm, along with lower hemoglobin and higher BUN levels. Additonally, elevated Activin A was a significant risk factor of all-cause mortality.

Do low skeletal muscle bulk and disturbed body fat mass impact tumor recurrence in stage I/II HCC undergoing surgery? An observational cohort study.

INTRODUCTION: The influence of deranged body composition on stage I/II HCC after surgery remains undetermined. The current study aimed to investigate the impact of low skeletal muscle bulk and disturbed body fat mass on the recurrence outcome of stage I/II HCC patients undergoing liver resection. The associated metabolomic alterations were also assessed. METHODS: From 2012 to 2021, stage I and II HCC patients who underwent liver resection at our institute were retrospectively reviewed. Their preoperative body composition including skeletal muscle mass and body fat volume was measured by computed tomography (CT). The recurrence outcome was recorded and analyzed. The preoperative serum was collected and subjected to metabolomic analysis. RESULTS: A total of 450 stage I and II HCC patients were included in the current study. Among them, 76% were male and around 60% had HBV infection. After stratified by normal cutoff values obtained from a healthy cohort, 6.4% of stage I/II HCC patients were found to have a low psoas muscle index (PMI), 17.8% a high subcutaneous adipose tissue (SAT) index, and 27.8% a high visceral adipose tissue (VAT) index. Cox regression multivariate analysis further demonstrated that low PMI and high SAT index were independent prognostic factors for time-to-recurrence (TTR) after surgery. Metabolomic analysis discovered that free fatty acid ß-oxidation was enhanced in with low PMI or high SAT index. CONCLUSION: The current study demonstrated that reduced psoas muscle mass may impair while elevated SAT may prolong the TTR of stage I/II HCC patients undergoing liver resections. VAT, on the other hand, was not associated with recurrence outcome after surgery. Further studies are warranted to validate our findings.

Initial and corrective submovement encoding differences within primary motor cortex during precision reaching.

Precision reaching often requires corrective submovements to obtain the desired goal. Most studies of reaching have focused on single initial movements, and implied the cortical encoding model was the same for all submovements. However, corrective submovements may show different encoding patterns from the initial submovement with distinct patterns of activation across the population. Two rhesus macaques performed a precision center-out-task with small targets. Neural activity from single units in primary motor cortex and associated behavioral data were recorded to evaluate movement characteristics. Neural population data and individual neuronal firing rates identified with a peak finding algorithm to identify peaks in hand speed were examined for encoding differences between initial and corrective submovements. Individual neurons were fitted with a regression model that included the reach vector, position, and speed to predict firing rate. For both initial and corrective submovements, the largest effect remained movement direction. We observed a large subset changed their preferred direction greater than 45° between initial and corrective submovements. Neuronal depth of modulation also showed considerable variation when adjusted for movement speed. By utilizing principal component analysis, neural trajectories of initial and corrective submovements progressed through different neural subspaces. These findings all suggest that different neural encoding patterns exist for initial and corrective submovements within the cortex. We hypothesize that this variation in how neurons change to encode small, corrective submovements might allow for a larger portion of the neural space being used to encode a greater range of movements with varying amplitudes and levels of precision.

The distinct impacts of sarcopenic and dynapenic obesity on mortality in middle-aged and older adults based on different adiposity metrics: Results from I-Lan Longitudinal Aging Study.

BACKGROUND & AIMS: Sarcopenic obesity (SO) and dynapenic obesity (DO) represent two manifestations of excessive fat accumulation concurrent with compromised muscle mass and function, thereby necessitating an examination of their implications for health. This study aims to investigate the relationship between SO/DO and mortality, taking into account various adiposity measures and existing sarcopenia criteria, with further stratified analyses based on age and gender. METHODS: The study sample comprised 1779 older adults residing in the community from the I-Lan Longitudinal Aging Study (ILAS). Body composition was assessed via dual-energy X-ray absorptiometry. The diagnosis of sarcopenia was adhered to the 2019 consensus of the Asian Working Group for Sarcopenia, while adiposity was measured by waist circumference (WC), body mass index (BMI), and fat percentage. SO/DO was defined as the coexistence of sarcopenia/dynapenia and obesity. Multivariate Cox proportional hazard regression models were adopted to examine the association between SO or DO, defined by WC, BMI, fat percentage, and mortality. RESULTS: This 11-year follow-up study of 1779 participants aged 63.9 ± 9.2 years involved 15,068 person-years and 229 deaths. WC-defined SO (HR 1.9, 95% CI 1.1-3.3, p = 0.021) and WC-defined DO (HR 1.4, 95% CI 1.1-1.9, p = 0.022) significantly increased mortality risk, whereas definitions employing alternative adiposity metrics exhibited no statistical significance. WC-defined SO was associated with increased risk of mortality among middle-aged adults, while WC-defined DO was associated with increased risk of mortality among older adults. In sex-specific analysis, WC-defined DO was also associated with increased risk of mortality in men (HR 1.6, 95% CI 1.1-2.4, p = 0.019), while defined by other measurements showed no associations in both sexes. CONCLUSIONS: The study identified a significant link between SO/DO, defined by WC, and an 11-year mortality risk, advocating for WC-defined adiposity as an obesity measure and personalized interventions considering SO and DO's distinct impacts on mortality in middle-aged and older adults.

Expert Consensus on the Application of Stem Cells in Psoriasis Research and Clinical Trials.

Psoriasis is an immune-mediated, chronic, relapsing, inflammatory, systemic disease induced by individual-environmental interactions, and is often lifelong because of the difficulty of treatment. In recent years, a variety of targeted therapies, including biologics, have improved the lesions and quality of life of most psoriasis patients, but they still do not address the problem of relapse and may be associated with decreased efficacy or adverse events such as infections over time. Therefore, there is an urgent need for breakthroughs in psoriasis treatment and in relapse-delaying and non-pharmacologic strategies, and stem cell therapy for psoriasis has emerged. In recent years, research on stem cell therapy for psoriasis has received a lot of attention, however, there is no reference standard as well as consensus in this field of research. Therefore, according to the latest consensus and guidelines, combined with relevant literature reports, clinical practice experience and the results of discussions with experts, this consensus specifies the types of stem cells commonly used in the treatment of psoriasis, the methods, dosages, and routes of stem cell therapy for psoriasis, as well as the clinical evaluations (efficacy and safety) of stem cell therapy for psoriasis. In addition, this consensus also provides normative standards for the processes of collection, preparation, preservation and quality control of stem cells and their related products, as well as recommendations for the management of stem cells during infusion for the treatment of psoriasis. This consensus provides the latest specific reference standards and practice guidelines for the field of stem cell therapy for psoriasis.

Dual protection by Bcp1 and Rkm1 ensures incorporation of uL14 into pre-60S ribosomal subunits.

Eukaryotic ribosomal proteins contain extended regions essential for translation coordination. Dedicated chaperones stabilize the associated ribosomal proteins. We identified Bcp1 as the chaperone of uL14 in Saccharomyces cerevisiae. Rkm1, the lysine methyltransferase of uL14, forms a ternary complex with Bcp1 and uL14 to protect uL14. Rkm1 is transported with uL14 by importins to the nucleus, and Bcp1 disassembles Rkm1 and importin from uL14 simultaneously in a RanGTP-independent manner. Molecular docking, guided by crosslinking mass spectrometry and validated by a low-resolution cryo-EM map, reveals the correlation between Bcp1, Rkm1, and uL14, demonstrating the protection model. In addition, the ternary complex also serves as a surveillance point, whereas incorrect uL14 is retained on Rkm1 and prevented from loading to the pre-60S ribosomal subunits. This study reveals the molecular mechanism of how uL14 is protected and quality checked by serial steps to ensure its safe delivery from the cytoplasm until its incorporation into the 60S ribosomal subunit.

How Do Plastic Surgery Program's Websites Feature Diversity and Inclusion Elements? An Analysis of 89 Integrated Plastic Surgery Programs' Websites.

INTRODUCTION: Plastic surgery residency programs leverage their websites as platforms for promoting their commitment to diversity and inclusion to potential candidates. Medical students who are seeking residency positions, including individuals from underrepresented backgrounds, place significant importance on the alignment of program culture and diversity. The authors assessed how these programs showcased diversity and inclusion efforts on their websites. METHODS: The authors analyzed 89 plastic surgery integrated residency program websites for the presence of 12 elements, (1) nondiscrimination, (2) diversity and inclusion statement, (3) community resources, (4) extended resident biographies, (5) faculty biographies, (6) faculty photos, (7) resident photos, (8) additional financial resources for trainees, (9) wellness, (10) mental health resources, (11) health disparities/community engagement, and (12) presence of a diversity council. Additionally, we examined the presence of these 12 elements by geographic region (West, Midwest, South, and Northeast). Our analyzed use chi-squared, t-tests, and Mann-Whitney U; significance level was p = 0.005. The independent plastic surgery programs were excluded, considering their websites were combined with the integrated-residency programs. RESULTS: We reviewed 89 websites from February 9, 2024 until February 24, 2024 and on average had 6.32 ± 1.1 diversity and inclusion elements. Resident photos (n = 84, 94.4%), community resources (n = 55, 61.8%), faculty photos (n = 63, 70.8%), and additional financial resources for trainees (n = 56, 62.9%) were the most common. The least common diversity and inclusion elements were diversity councils (n = 12, 13.5%), wellness resources (n = 36, 40.4%), and diversity and inclusion statements (n = 42, 47.2%). The primary analysis revealed that programs with higher number of incoming positions (3 or more) (5.2 ± 1.8) had a significantly higher diversity and inclusion scores when compared to programs with lower number of incoming positions (3.6 ± 2.1) (p = 0.002). Furthermore, based on the geographic regions from the U.S. Census, there was no significant difference between geographic regions. CONCLUSIONS: Characterizing the number of program websites and quantifying the number of diversity elements on each site provide an opportunity for more residency programs to further commit to diversity and inclusion. Displaying different diversity and inclusive initiatives on program websites may attract more diverse applicants, particularly individuals from underrepresented populations in medicine.

Impact of chronic kidney disease on left atrial appendage occlusion: A meta-analysis of procedural outcomes and complications.

BACKGROUND: Patients with chronic kidney disease (CKD) experience atrial fibrillation more frequently. The balance of medical management for stroke prevention and bleeding events presents a challenging issue in CKD population. Left atrial appendage occlusion (LAAO) may be an effective solution for stroke prevention in patients who experience frequent bleeding with oral anticoagulants. However, the specific impact of CKD on the procedural success, complications, and outcomes of LAAO implantations remains underexplored. METHODS: We conducted a search of various databases for articles published before October 31, 2023. This search yielded 7 studies, comparing outcomes between CKD and non-CKD cohorts undergoing LAAO implantation. Our analysis focused on CHA2DS2-VASc scores, average eGFR, use of oral anticoagulants, procedural success rates, procedural complications, and associated outcomes. RESULTS: The meta-analysis included data from 2576 patients, with 1131 identified as having CKD. The CKD group also had higher CHA2DS2-VASc scores (4.7 ±â€…1.4 vs 4.0 ±â€…1.5; P < .001) and HAS-BLED scores (3.8 ±â€…1.1 vs 3.1 ±â€…1.0; P < .001) than the non-CKD group. CKD patients showed a nonreduction in procedural success rates and a nonsignificant increase in total complications. The risks of stroke and transient ischemic attack, major bleeding, and cardiovascular mortality were not significantly different between the 2 groups. However, a significantly lower rate of total mortality was observed in the non-CKD group (odds ratio: 0.43; 95% confidence interval, 0.32-0.60). CONCLUSION: While CKD is associated with a nonsignificant decrease in procedural success and a nonsignificant increase in complication risks, the outcomes of LAAO implantation are comparably favorable between CKD and non-CKD groups. Despite similar procedural outcomes, the CKD group exhibited a higher rate of all-cause mortality.

The Clinical Characteristics and Manifestation of Anxious Depression Among Patients With Major Depressive Disorders-Results From a Taiwan Multicenter Study.

OBJECTIVE: Anxious depression is a prevalent characteristic observed in Asian psychiatric patients diagnosed with major depressive disorder (MDD). This study aims to investigate the prevalence and clinical presentation of anxious depression in Taiwanese individuals diagnosed with MDD. METHODS: We recruited psychiatric outpatients aged over 18 who had been diagnosed with MDD through clinical interviews. This recruitment took place at five hospitals located in northern Taiwan. We gathered baseline clinical and demographic information from the participants. Anxious depression was identified using a threshold of an anxiety/somatization factor score ≥7 on the 21-item Hamilton Rating Scale for Depression (HAM-D). RESULTS: In our study of 399 patients (84.21% female), 64.16% met the criteria for anxious depression. They tended to be older, married, less educated, with more children, and an older age of onset. Anxious depression patients had higher HAM-D and Clinical Global Impression-Severity scale score, more panic disorder (without agoraphobia), and exhibited symptoms like agitation, irritability, concentration difficulties, psychological and somatic anxiety, somatic complaints, hypochondriasis, weight loss, and increased insight. Surprisingly, their suicide rates did not significantly differ from non-anxious depression patients. This highlights the importance of recognizing and addressing these unique characteristics. CONCLUSION: Our study findings unveiled that the prevalence of anxious depression among Taiwanese outpatients diagnosed with MDD was lower compared to inpatients but substantially higher than the reported rates in European countries and the United States. Furthermore, patients with anxious depression exhibited a greater occurrence of somatic symptoms.

The crosstalk between copper-induced oxidative stress and cuproptosis: a novel potential anticancer paradigm.

Copper is a crucial trace element that plays a role in various pathophysiological processes in the human body. Copper also acts as a transition metal involved in redox reactions, contributing to the generation of reactive oxygen species (ROS). Under prolonged and increased ROS levels, oxidative stress occurs, which has been implicated in different types of regulated cell death. The recent discovery of cuproptosis, a copper-dependent regulated cell death pathway that is distinct from other known regulated cell death forms, has raised interest to researchers in the field of cancer therapy. Herein, the present work aims to outline the current understanding of cuproptosis, with an emphasis on its anticancer activities through the interplay with copper-induced oxidative stress, thereby providing new ideas for therapeutic approaches targeting modes of cell death in the future.

Enhancement noise margin and delay time performance of novel punch-through nMOS for single-carrier CMOS.

In this paper, we propose the use of punch-through nMOS (PTnMOS) as an alternative to pMOS in complementary metal oxide semiconductor (CMOS) circuits. According to the TCAD simulation results, PTnMOS exhibit sub-threshold characteristics similar to those of pMOS and can be formed by simply changing the doping concentration of the source and drain. Without the need for sizing, which solves the area occupation problem caused by the need to increase the width of pMOS due to insufficient hole mobility. In addition, we compose a PTnMOS and nMOS without sizing to form a single-carrier CMOS in which only electrons are transmitted, and We extract its performance for comparison with conventional CMOS (Wp/Wn = 1). The results indicate that single-carrier CMOS has symmetric noise margin and 29% faster delay time compared to conventional CMOS (Wp/Wn = 1). If III-V or II-VI group materials could be applied to single-carrier CMOS, not only could costs be reduced and wafer area occupancy minimized, but also significant improvements in the performance and bandwidth application of microwave circuits could be achieved.

Does autoimmune disease impair the survival of hepatocellular carcinoma patients undergoing liver resection? A multi-institutional observational study.

BACKGROUND: Patients with autoimmune diseases (AD) generally carry an increased risk of developing cancer. However, the effect of AD in hepatocellular carcinoma (HCC) patients receiving surgical treatment is uncertain. The present study aimed to investigate the potential influence of AD on the survival of HCC patients undergoing hepatectomies. METHODS: Operated HCC patients were identified from the Chang Gung Research Database, and the survival outcomes of HCC patients with or without AD were analyzed ad compared. Cox regression model was performed to identify significant risk factors associated with disease recurrence and mortality. RESULTS: From 2002 to 2018, a total of 5532 patients underwent hepatectomy for their HCC. Among them, 229 patients were identified to have AD and 5303 were not. After excluding cases who died within 30 days of surgery, the estimated median overall survival (OS) was 43.8 months in the AD (+) group and 47.4 months in the AD (-) group (P = 0.367). The median liver-specific survival and disease-free survival (DFS) were also comparable between the two groups. After Cox regression multivariate analysis, the presence of AD did not lead to a higher risk of all-cause mortality, liver-specific mortality, or disease recurrence. CONCLUSION: Our study demonstrated that autoimmune disease does not impair the OS and DFS of HCC patients undergoing liver resections. AD itself is not a risk factor for tumor recurrence after surgery. Patients eligible for liver resections, as a result, should be considered for surgery irrespective of the presence of AD. Further studies are mandatory to validate our findings.

Bicolor Tuning and Hyper-Reflective Color Switching Based on Two Stacked Cholesteric Liquid Crystal Cells with Asymmetric Electrothermal Optical Responses.

We propose a double-cell cholesteric liquid crystal (CLC) device composed of a left-handed (LH) CLC cell with a pair of sheet electrodes and a right-handed (RH) CLC cell with a tri-electrode configuration characterized by a sheet electrode on the top and an interdigitated electrode on the bottom substrates. Bi-reflected color tuning and hyper-reflective color switching are revealed from this cell stack via the electrothermal control of the central wavelengths of the LH- and RH-bandgaps by voltage-induced pseudo-dielectric heating. The two CLCs are thermally sensitive and exhibit overlapped bandgaps in the field-off state with nearly identical temperature dependence, resulting in a hyper-reflective color at 720 nm at 23.4 °C and 380 nm at 29.8 °C. Upon the application of 4 Vrms at 2 MHz across the stacked device to induce pseudo-dielectric heating, two reflective colors can be resolved due to asymmetrical temperature elevations. Accordingly, the difference in wavelength between the two colors increases with increasing voltage through a series cell connection, while maintaining approximately constant via a parallel connection. This study provides a feasible pathway to developing a multifunctional device with electrothermally tunable bi-reflected and hyper-reflective states based on two conventional cell geometries, which is promising for lasers and color-related display applications.

Pd and Pt Complexes of Benzo-Fused Dipyrrins: Synthesis, Structure, Electrochemical, and Optical Properties.

Benzo-fused dipyrrins are π-extended analogs of conventional dipyrrins, which exhibit bathochromically shifted absorption and possess the synthetic capability to bind various metal ions. We aimed to investigate the synthetic potential of benzo-fused dipyrrins in the complexation with transition metals. Two new complexes with Pd2+ and Pt2+ were synthesized and characterized. X-ray crystallography reveals that both complexes exhibit a zigzag geometry with square planar coordination of the central metal. The Pd2+ complex possesses a very weak fluorescence at 665 nm, while the Pt2+ complex is completely nonemissive. Transient absorption spectroscopy confirmed triplet excited state formation for both complexes; however, they are short-lived and no phosphorescence was observed even at 77K. DFT calculations support the experimental observation, revealing the existence of the low-lying ligand-metal charge-transfer (LMCT) triplet state acting as an energy sink.

Sex-specific implications of inflammation in covert cerebral small vessel disease.

BACKGROUND: The relationship between inflammation and covert cerebral small vessel disease (SVD) with regards to sex difference has received limited attention in research. We aim to unravel the intricate associations between inflammation and covert SVD, while also scrutinizing potential sex-based differences in these connections. METHODS: Non-stroke/dementia-free study population was from the I-Lan longitudinal Aging Study. Severity and etiology of SVD were assessed by 3T-MRI in each participant. Systemic and vascular inflammatory-status was determined by the circulatory levels of high-sensitivity C-reactive protein (hsCRP) and homocysteine, respectively. Sex-specific multivariate logistic regression to calculate odds ratios (ORs) and interaction models to scrutinize women-to-men ratios of ORs (RORs) were used to evaluate the potential impact of sex on the associations between inflammatory factors and SVD. RESULTS: Overall, 708 participants (62.19 ± 8.51 years; 392 women) were included. Only women had significant associations between homocysteine levels and covert SVD, particularly in arteriosclerosis/lipohyalinosis SVD (ORs[95%CI]: 1.14[1.03-1.27] and 1.15[1.05-1.27] for more severe and arteriosclerosis/lipohyalinosis SVD, respectively). Furthermore, higher circulatory levels of homocysteine were associated with a greater risk of covert SVD in women compared to men, as evidenced by the RORs [95%CI]: 1.14[1.01-1.29] and 1.14[1.02-1.28] for more severe and arteriosclerosis/lipohyalinosis SVD, respectively. No significant associations were found between circulatory hsCRP levels and SVD in either sex. CONCLUSION: Circulatory homocysteine is associated with covert SVD of arteriosclerosis/lipohyalinosis solely in women. The intricacies underlying the sex-specific effects of homocysteine on SVD at the preclinical stage warrant further investigations, potentially leading to personalized/tailored managements. TRIAL REGISTRATION: Not applicable.

Liver transplantation for advanced hepatocellular carcinoma: Controversy over portal vein tumor thrombosis.

Liver transplantation (LT) is considered the ideal treatment for hepatocellular carcinoma (HCC) concurrent with underlying cirrhotic liver disease. As well-known, LT for HCC based on the Milan criteria has shown satisfactory outcomes. However, numerous expanded transplantation criteria were proposed to benefit more patients for LT and showed comparable survivals as well. In addition, a modest expansion of transplantation criteria for HCC may be acceptable on the basis of the consensus within the transplantation community. Nonetheless, LT in patients with advanced HCC and portal vein tumor thrombosis (PVTT) recently has received attention and has been reported by many transplantation centers despite being contraindicated. Of those, the LT outcomes in certain HCC patients with PVTT were favorable. Additionally, the advancement of multimodality treatments and the evolution of systemic therapies have emerged as promising therapeutic options for downstaging advanced HCC prior to LT. Somehow, advanced HCC with PVTT could be downstaged to become eligible for LT through these multidisciplinary approaches. Although the available evidence of LT for HCC with PVTT is limited, it is hoped that LT may soon be more widely indicated for these patients. Nevertheless, several unknown factors associated with LT for HCC remain to be explored. Herein, this review aimed to update the developments in LT for patients with advanced HCC.

Manipulating the Crosstalk between Cancer and Immunosuppressive Cells with Phototherapeutic Gold-Nanohut for Reprogramming Tumor Microenvironment.

Photoimmunotherapy faces challenges due to insufficient intratumoral accumulation of photothermal agents and the reversion of the cancer-immunity cycle during treatment. In this study, an anti-PD-L1-immobilized magnetic gold nanohut, AuNH-2-Ab, with photoresponsive, thermosensitive, and immunomodulatory properties to effectively suppress the growth of primary tumors, elevate immunogenic cell death (ICD) levels, reverse the tumor immune microenvironment (TIME), and consequently inhibit metastases are developed. AuNH-2-Ab achieves high tumor accumulation (9.54% injected dose) following systemic administration, allowing the modulation of hyperthermia dose of over 50 °C in the tumor. By optimizing the hyperthermia dose, AuNH-2-Ab simultaneously target and eliminate cancer cells and tumor-associated macrophages, thereby activating potent antitumor immunity without being compromised by immunosuppressive elements. Hyperthermia/pH induced morphological transformation of AuNH-2-Ab involving the detachment of the surface antibody for in situ PD-L1 inhibition, and exposure of the inner fucoidan layer for natural killer (NK) cell activation. This precision photoimmunotherapy approach reprograms the TIME, significantly prolongs survival in a murine hepatocellular carcinoma model (Hep55.1c), and harnesses the synergistic effects of ICD production and checkpoint inhibitors by utilizing a single nanoplatform.

Scalable electron tomography for connectomics.

We demonstrate limited-tilt, serial section electron tomography (ET), which can non-destructively map brain circuits over large 3D volumes and reveal high-resolution, supramolecular details within subvolumes of interest. We show accelerated ET imaging of thick sections (>500 nm) with the capacity to resolve key features of neuronal circuits including chemical synapses, endocytic structures, and gap junctions. Furthermore, we systematically assessed how imaging parameters affect image quality and speed to enable connectomic-scale projects.