with HBV with a baseline HBV VL ≥100 IU/mL may receive ICI safely, especially if they are on antiviral treatment.

We have demonstrated that the real-world performance of ICIs in advanced HCC appears comparable to that observed in clinical trials for HCC patients with CP A cirrhosis. While prognosis of patients with advanced HCC and CP B cirrhosis remains poor even with ICI, usage of ICI is likely to be safe. Patients with HBV with a baseline HBV VL ≥100 IU/mL may receive ICI safely, especially if they are on antiviral treatment.The evolution of tissue on a chip systems holds promise for mimicking the response of biological functionality of physiological systems. One important direction for tissue on a chip approaches are neuron-based systems that could mimic neurological responses and lessen the need for in vivo experimentation. For neural research, more attention has been devoted recently to understanding mechanics due to issues in areas such as traumatic brain injury (TBI) and pain, among others. To begin to address these areas, a 3D Nerve Integrated Tissue on a Chip (NITC) approach combined with a Mechanical Excitation Testbed (MET) System is developed to impose external mechanical stimulation toward more realistic physiological environments. PC12 cells differentiated with nerve growth factor, which were cultured in a controlled 3D scaffolds, are used. The cells are labeled in a 3D NITC system with Fluo-4-AM to examine their calcium response under mechanical stimulation synchronized with image capture. Understanding the neural responses to mechanical stimulation beyond 2D systems is very important for neurological studies and future personalized strategies. This work will have implications in a diversity of areas including tissue-on-a-chip systems, biomaterials, and neuromechanics.Intrinsically fluorescent poly(amidoamine) dendrimers (IF-PAMAM) are an emerging class of versatile nanoplatforms for in vitro tracking and bio-imaging. However, limited tissue penetration of their fluorescence and interference due to auto-fluorescence arising from biological tissues limit its application in vivo. Herein, a green IF-PAMAM (FGP) dendrimer is reported and its biocompatibility, circulation, biodistribution and potential role for traceable central nervous system (CNS)-targeted delivery in zebrafish is evaluated, exploring various routes of administration. Key features of FGP include visible light excitation (488 nm), high fluorescence signal intensity, superior photostability and low interference from tissue auto-fluorescence. After intravenous injection, FGP shows excellent imaging and tracking performance in zebrafish. Further conjugating FGP with transferrin (FGP-Tf) significantly increases its penetration through the blood-brain barrier (BBB) and prolongs its circulation in the blood stream. When administering through local intratissue microinjection, including intracranial and intrathecal injection in zebrafish, both FGP and FGP-Tf exhibit excellent tissue diffusion and effective cellular uptake in the brain and spinal cord, respectively. This makes FGP/FGP-Tf attractive for in vivo tracing when transporting to the CNS is desired. The work addresses some of the major shortcomings in IF-PAMAM and provides a promising application of these probes in the development of drug delivery in the CNS.

Several studies have suggested that polymorphisms within genes encoding T-lymphocyte immune regulating molecules CD28, CTLA-4, and ICOS, may alter the signaling process and subsequently could be involved in susceptibility to a broad spectrum of autoimmune diseases.

This study aimed to replicate associations between common polymorphisms in the 2q33.2 cluster and susceptibility to pemphigus foliaceus (PF) in the Tunisian population. We investigated seven polymorphisms rs3116496 and rs1879877 (CD28), rs231775, rs3087243, and (AT)

repeat (CTLA4); rs11889031 and rs10932029 (ICOS) in a case-control study which enrolled 106 Tunisian PF patients and 205 matched healthy controls.

We confirmed the associations with CTLA4((AT)

, p=0.00137, OR=3.96 and (AT)

, p=0.008, OR=5.22; respectively) and ICOS genes (rs10932029>CT, p=0.034, OR=2.12 and rs10932029>TT, p=0.04 and OR=0.41).

Our results indicate that susceptibility to PF is located in the proximal and the distal 3′ flanking region of the CTLA4/ICOS promoter. These findings may open avenues to the treatment of patients with biological drugs targeting CTLA4/ICOS molecules, in a personalized manner to achieve more effective treatment.

Our results indicate that susceptibility to PF is located in the proximal and the distal 3′ flanking region of the CTLA4/ICOS promoter. These findings may open avenues to the treatment of patients with biological drugs targeting CTLA4/ICOS molecules, in a personalized manner to achieve more effective treatment.Currently, there are no time-saving and cost-effective high-throughput screening methods for the evaluation of bacterial drug-resistance. In this study, a droplet microarray (DMA) system is established as a miniaturized platform for high-throughput screening of antibacterial compounds using the emerging, opportunistic human pathogen Pseudomonas aeruginosa (P. aeruginosa) as a target. Based on the differences in wettability of DMA slides, a rapid method for generating microarrays of nanoliter-sized droplets containing bacteria is developed. The bacterial growth in droplets is evaluated using fluorescence. The new method enables immediate screening with libraries of antibiotics. A novel simple colorimetric readout method compatible with the nanoliter size of the droplets is established. Furthermore, the drug-resistance of P. aeruginosa 49, a multi-resistant strain from an environmental isolate, is investigated. This study demonstrates the potential of the DMA platform for the rapid formation of microarrays of bacteria for high-throughput drug screening.For thousands of years, scientists have studied human anatomy by dissecting bodies. Our knowledge of their findings is limited, however, both by the subsequent loss of many of the oldest texts, and by a tendency toward a Eurocentric perspective in medicine. As a discipline, anatomy tends to be much more familiar with ancient Greek texts than with those from India, China, or Persia. Here, we show that the Mawangdui medical texts, entombed in the Mawangdui burial site in Changsha, China 168 BCE, are the oldest surviving anatomical atlas in the world. These medical texts both predate and inform the later acupuncture texts which have been the foundation for acupuncture practice in the subsequent two millennia. The skills necessary to interpret them are diverse, requiring the researcher firstly to read the original Chinese, and secondly to perform the anatomical investigations that allow a re-viewing of the structures that the texts refer to. Acupuncture meridians are considered to be esoteric in nature, but these texts are clearly descriptions of the physical body. As such, they represent a previously hidden chapter in the history of anatomy, and a new perspective on acupuncture.

We evaluated the efficacy and safety of laparoscopic ureterolithotomy (LPU) for the treatment of large proximal ureteric stone.

A retrospective multicenter analysis for patients with solitary impacted proximal ureteric stone ≥15 mm who underwent LPU from 2016 to 2019 was performed. Primary outcome was to estimate the stone-free rate (SFR). SFR was defined as absence of residual stones on postoperative computed tomography scan. Secondary outcome was to assess the perioperative outcomes, as well as to review literature data of randomized controlled trials and meta-analyses comparing LPU to other treatment options.

Forty-four patients were included in our study. Mean stone size was 22.9 ± 5.8 mm and median follow-up was 14 months. Three patients had previous abdominal surgery, one patient had severe degree of scoliosis and six patients failed primary therapy. All stones were extracted successfully (SFR = 100%) without need of auxiliary treatments. Mean operative time and estimated blood loss were 86.6 ± 14ral stones, LPU should be advised as the procedure that has the higher SFR, lower auxiliary treatments, and comparable complication rates to other treatments.The development of in vitro assays for 3D microenvironments is essential for understanding cell migration processes. A 3D-printed in vitro competitive radial device is developed to identify preferred Matrigel concentration for glioblastoma migration. Melt electrowriting (MEW) is used to fabricate the structural device with defined and intricate radial structures that are filled with Matrigel. Controlling the printing path is necessary to account for the distance lag in the molten jet, the applied electric field, and the continuous direct-writing nature of MEW. Circular printing below a diameter threshold results in substantial inward tilting of the MEW fiber wall. An eight-chamber radial device with a diameter of 9.4 mm is printed. Four different concentrations of Matrigel are dispensed into the radial chambers. Glioblastoma cells are seeded into the center and grow into all chambers within 8 days. The cell spreading area demonstrates that 6 and 8 mg mL-1 of Matrigel are preferred over 2 and 4 mg mL-1 . Furthermore, topographical cues via the MEW fiber wall are observed to promote migration even further away from the cell seeding depot. Previous studies implement MEW to fabricate cell invasive scaffolds whereas here it is applied to 3D-print in vitro tools to study cell migration.

This study sought to investigate how glycemia and ketonemia variations during two ketogenic diet protocols affect appetite, executive functions, and mood in young women with overweight.

Fifty healthy young females with overweight were randomly assigned to (1) a ketogenic diet without any restriction on energy intake, (2) a commercial energy-restricted ketogenic Mediterranean diet, and (3) an energy-restricted Mediterranean diet for 10 days. A visual analogue scale was used to test appetite, and one mood test and two cognitive tasks (working memory and inhibition control) were performed. Moreover, body composition, fasting blood glucose, and β-hydroxybutyrate (BHB) were measured.

A positive correlation was found between glycemia and appetite (P = 0.019), unfullness score (P =  0.001), and desire to eat (P = 0.030) (pre- and postdiet levels). Postdiet BHB levels showed a positive correlation with fullness score (P = 0.002) and a negative correlation with appetite (P = 0.022) and desire to eat (P = 0.009). A positive correlation was found between prediet levels of glycemia and reaction times in the go-trials of the executive function test (P = 0.018). Postdiet BHB level showed a negative correlation with the accuracy of the no-go trials (P = 0.027).

Ketogenic diets, compared with a Mediterranean diet, have a greater effect in terms of appetite reduction but might affect inhibition functions.

Ketogenic diets, compared with a Mediterranean diet, have a greater effect in terms of appetite reduction but might affect inhibition functions.Cryopreserved tissues are increasingly needed in biomedical applications. However, successful cryopreservation is generally only reported for thin tissues (≤1 mm). This work presents several innovations to reduce cryoprotectant (CPA) toxicity and improve tissue cryopreservation, including 1) improved tissue warming rates through radiofrequency metal form and field optimization and 2) an experimentally verified predictive model to optimize CPA loading and rewarming to reduce toxicity. CPA loading is studied by microcomputed tomography (µCT) imaging, rewarming by thermal measurements, and modeling, and viability is measured after loading and/or cryopreservation by alamarBlue and histology. Loading conditions for three common CPA cocktails (6, 8.4, and 9.3 m) are designed, and then fast cooling and metal forms rewarming (up to 2000 °C min-1 ) achieve ≥90% viability in cryopreserved 1-2 mm arteries with various CPAs. Despite high viability by alamarBlue, histology shows subtle changes after cryopreservation suggesting some degree of cell damage especially in the central portions of thicker arteries up to 2 mm.