Supporting Holistic Student Development Through Online Community Building

Faculty members abruptly transitioned to online course delivery during the COVID-19 public health crisis. Unfortunately, the isolation of learning online had the potential to damage students’ well-being during an already stressful pandemic. Furthermore, many faculty members had little experience with online modes of instruction and few effective strategies for building community online. This exploratory sequential mixed methods study uses data from 37 individual interviews with faculty across diverse disciplines, course evaluations from 13 of the 37 interview participants, and survey data from 347 faculty to answer the following research question: How did faculty foster a sense of community online to support students’ holistic well-being during the COVID pandemic? What strategies can faculty use to create community and foster well-being in online courses? Results show that successful strategies centered around intentional and purposeful course design, establishing clear expectations for faculty and students, and fostering supportive and trustworthy online learning environments

Nadir CA-125 level as prognosis indicator of high-grade serous ovarian cancer

PURPOSE: The capacity of nadir CA-125 levels to predict the prognosis of epithelial ovarian cancer remains controversial. This study aimed to explore whether the nadir CA-125 serum levels could predict the durations of overall survival (OS) and progression free survival (PFS) in patients with high-grade serous ovarian cancer (HG-SOC) from the USA and PRC. MATERIALS AND METHODS: A total of 616 HG-SOC patients from the MD Anderson Cancer Center (MDACC, USA) between 1990 and 2011 were retrospectively analyzed. The results of 262 cases from the Jiangsu Institute of Cancer Research (JICR, PRC) between 1992 and 2011 were used to validate the MDACC data. The CA-125 immunohistochemistry assay was performed on 280 tissue specimens. The Cox proportional hazards model and the log-rank test were used to assess the associations between the clinicopathological characteristics and duration of survival. RESULTS: The nadir CA-125 level was an independent predictor of OS and PFS (p < 0.01 for both) in the MDACC patients. Lower nadir CA-125 levels (≤10 U/mL) were associated with longer OS and PFS (median: 61.2 and 16.8 months with 95% CI: 52.0–72.4 and 14.0–19.6 months, respectively) than their counterparts with shorter OS and PFS (median: 49.2 and 10.5 months with 95% CI: 41.7–56.7 and 6.9–14.1 months, respectively). The nadir CA-125 levels in JICR patients were similarly independent when predicting the OS and PFS (p < 0.01 for both). Nadir CA-125 levels less than or equal to 10 U/mL were associated with longer OS and PFS (median: 59.9 and 15.5 months with 95% CI: 49.7–70.1 and 10.6–20.4 months, respectively), as compared with those more than 10 U/mL (median: 42.0 and 9.0 months with 95% CI: 34.4–49.7 and 6.6–11.2 months, respectively). Baseline serum CA-125 levels, but not the CA-125 expression in tissues, were associated with the OS and PFS of HG-SOC patients in the MDACC and JICR groups. However, these values were not independent. Nadir CA-125 levels were not associated with the tumor burden based on second-look surgery (p = 0.09). Patients who achieved a pathologic complete response had longer OS and PFS (median: 73.7 and 20.7 months with 95% CI: 63.7–83.7 and 9.5–31.9 months, respectively) than those with residual tumors (median: 34.6 and 10.6 months with 95% CI: 6.9–62.3 and 4.9–16.3 months, respectively). CONCLUSIONS: The nadir CA-125 level was an independent predictor of OS and PFS in HG-SOC patients. Further prospective studies are required to clinically optimize the chances for a complete clinical response of HG-SOC cases with higher CA-125 levels (>10 U/mL) at the end of primary treatment

Highly curved reflective W-shape and J-shape photonic hook induced by light interaction with partially coated microfluidic channels

Photonic hook (PH) is a new type of artificial self-bending beam focused by a dielectric particle-lens with a curved waist smaller than the wavelength, which has the potential to revolutionize mesoscale photonics in many applications, e.g., optical trapping, signal switching, imaging, etc. In this paper, we discover a new mechanism that the highly curved PHs can be realised by the light interaction with the fully or partially metal-coated microchannels. The generated W-shaped and J-shaped PHs have bending angles exceeding 80-degree. Compared to other PH setups, the proposed design has a larger range to flexibly control the bending angle through the coating process and can be easily integrated with the established microfluidic systems.Comment: 10 pages, 5 figure

Ultrasound-guided percutaneous implantation of rabbit VX2 carcinoma, using a coaxial technique and gelfoam pellet injection combination to establish a rabbit liver tumor model

PURPOSEWe aimed to investigate the safety and tumor seeding rate of a coaxial implantation technique combined with injection of a gelfoam pellet in establishing a VX2 liver tumor model in rabbits.METHODSA VX2 liver tumor model was established in 60 male New Zealand white rabbits, which were randomly divided into 3 groups (20 in each group) based on implantation technique (all performed under ultrasound guidance): group A, single needle only; group B, single needle with injection of a gelfoam pellet; or group C, coaxial technique with injection of a gelfoam pellet. The rates of liver tumor formation and tumor seeding to extrahepatic tissues were compared 2 weeks after implantation. Data were also collected regarding procedure time, number of punctures, occurrence of complications, and mortality rate.RESULTSA VX2 liver tumor model was established in all 60 rabbits (100%, 60/60). Ectopic implantation rate was 70% (14/20) in group A, 35% (7/20) in group B, and 5% (1/20) in group C, with significant difference among the groups (p < 0.001). Post hoc analysis showed significant difference between group A and group C (p < 0.001). However, there were no significant differences between group B and group A or group C (p = 0.027, p = 0.048, respectively). There were no significant differences among the groups in terms of procedure time (p = 0.405) or number of punctures (p = 0.612). No complications or deaths occurred.CONCLUSIONA coaxial technique with injection of a gelfoam pellet is an effective and safe method for VX2 liver tumor implantation in rabbits, and this technique can reduce the risk of tumor seeding to the abdominal wall and omentum

Establishment and application of a rapid molecular diagnostic platform for the isothermal visual amplification of group B Streptococcus based on recombinase polymerase

With growing concerns about Group B streptococcal (GBS) infections and their adverse effects on perinatal pregnancies, including infection, premature delivery, neonatal septicemia, and meningitis, it is urgent to promote GBS screening at all pregnancy stages. The purpose of this study is to establish a device-independent, fast, sensitive, and visual GBS detection method. Taking advantage of the characteristics of the recombinase polymerase isothermal amplification (RPA), the activity of the nfo nuclease cleavage base analog (tetrahydrofuran, THF) site, and the advantages of visual reading of the lateral flow chromatography strip (LFS), a GBS detection method was developed. This method focused on the conservative region of the Christie–Atkins–Munch–Petersen factor encoded by the cfb gene, a virulence gene specific to GBS. Two forward primers, two biotin-labeled reverse primers, and one fluorescein isothiocyanate (FITC)-labeled and C3spacer-blocked probe were designed. The study involved optimizing the primer pair and probe combination, determining the optimal reaction temperature and time, evaluating specificity, analyzing detection limits, and testing the method on 87 vaginal swabs from perinatal pregnant women. The results showed that the visual detection method of GBS-RPA-LFS, using the cfb-F1/R2/P1 primer probe, could detect GBS within 15 min at the temperature ranging from 39°C to 42°C. Furthermore, the method specifically amplified only GBS, without cross-reacting with pathogens like Lactobacillus iners, Lactobacillus crispatus, Candida albicans, Listeria monocytogenes, Yersinia enterocolitica, Klebsiella Pneumoniae, Enterobacter cloacae, Citrobacter freundii, Vibrio alginolyticus, Vibrio parahaemolyticus, Salmonella typhimurium, Staphylococcus aureus, Pseudomonas aeruginosa, or Trichomonas vaginalis. It could detect a minimum of 100 copies per reaction. In clinical 98 samples of vaginal swabs from pregnant women, the agreement rate between the GBS-RPA-LFS method and TaqMan real-time fluorescence quantification method was 95.92%. In conclusion, this study successfully established a combined RPA and LFS GBS in situ detection platform, with short reaction time, high sensitivity, high specificity, portability, and device independence, providing a feasible strategy for clinical GBS screening

Design of experiment (DoE)-driven in vitro and in vivo uptake studies of exosomes for pancreatic cancer delivery enabled by copper-free click chemistry-based labelling

Exosomes (Exo)-based therapy holds promise for treatment of lethal pancreatic cancer (PC). Limited understanding of key factors affecting Exo uptake in PC cells restricts better design of Exo-based therapy. This work aims to study the uptake properties of different Exo by PC cells. Exo from pancreatic carcinoma, melanoma and non-cancer cell lines were isolated and characterised for yield, size, morphology and exosomal marker expression. Isolated Exo were fluorescently labelled using a novel in-house developed method based on copper-free click chemistry to enable intracellular tracking and uptake quantification in cells. Important factors influencing Exo uptake were initially predicted by Design of Experiments (DoE) approach to facilitate subsequent actual experimental investigations. Uptake of all Exo types by PC cells (PANC-1) showed time- and dose-dependence as predicted by the DoE model. PANC-1 cell-derived exosomes (PANC-1 Exo) showed significantly higher uptake in PANC-1 cells than that of other Exo types at the longest incubation time and highest Exo dose. In vivo biodistribution studies in subcutaneous tumour-bearing mice similarly showed favoured accumulation of PANC-1 Exo in self-tissue (i.e. PANC-1 tumour mass) over the more vascularised melanoma (B16-F10) tumours, suggesting intrinsic tropism of PC-derived Exo for their parent cells. This study provides a simple, universal and reliable surface modification approach via click chemistry for in vitro and in vivo exosome uptake studies and can serve as a basis for a rationalised design approach for pre-clinical Exo cancer therapies

Shared and differing functional connectivity abnormalities of the default mode network in mild cognitive impairment and Alzheimer's disease.

Alzheimer's disease (AD) and mild cognitive impairment (MCI) both show abnormal resting-state functional connectivity (rsFC) of default mode network (DMN), but it is unclear to what extent these abnormalities are shared. Therefore, we performed a comprehensive meta-analysis, including 31 MCI studies and 20 AD studies. MCI patients, compared to controls, showed decreased within-DMN rsFC in bilateral medial prefrontal cortex/anterior cingulate cortex (mPFC/ACC), precuneus/posterior cingulate cortex (PCC), right temporal lobes, and left angular gyrus and increased rsFC between DMN and left inferior temporal gyrus. AD patients, compared to controls, showed decreased rsFC within DMN in bilateral mPFC/ACC and precuneus/PCC and between DMN and left inferior occipital gyrus and increased rsFC between DMN and right dorsolateral prefrontal cortex. Conjunction analysis showed shared decreased rsFC in mPFC/ACC and precuneus/PCC. Compared to MCI, AD had decreased rsFC in left precuneus/PCC and between DMN and left inferior occipital gyrus and increased rsFC in right temporal lobes. MCI and AD share a decreased within-DMN rsFC likely underpinning episodic memory deficits and neuropsychiatric symptoms, but differ in DMN rsFC alterations likely related to impairments in other cognitive domains such as language, vision, and execution. This may throw light on neuropathological mechanisms in these two stages of dementia

Membrane radiolabelling of exosomes for comparative biodistribution analysis in immunocompetent and immunodeficient mice – a novel and universal approach

Extracellular vesicles, in particular exosomes, have recently gained interest as novel drug delivery vectors due to their biological origin and inherent intercellular biomolecule delivery capability. An in-depth knowledge of their in vivo biodistribution is therefore essential. This work aimed to develop a novel, reliable and universal method to radiolabel exosomes to study their in vivo biodistribution. Methods: Melanoma (B16F10) cells were cultured in bioreactor flasks to increase exosome yield. B16F10-derived exosomes (ExoB₁₆) were isolated using ultracentrfugation onto a single sucrose cushion, and were characterised for size, yield, purity, exosomal markers and morphology using Nanoparticle Tracking Analysis (NTA), protein measurements, flow cytometry and electron microscopy. ExoB₁₆ were radiolabelled using 2 different approaches – intraluminal labelling (entrapment of ¹¹¹Indium via tropolone shuttling); and membrane labelling (chelation of ¹¹¹Indium via covalently attached bifunctional chelator DTPA-anhydride). Labelling efficiency and stability was assessed using gel filtration and thin layer chromatography. Melanoma-bearing immunocompetent (C57BL/6) and immunodeficient (NSG) mice were injected intravenously with radiolabelled ExoB₁₆ (1x10¹¹ particles/mouse) followed by metabolic cages study, whole body SPECT-CT imaging and ex vivo gamma counting at 1, 4 and 24 h post-injection. Results: Membrane-labelled ExoB₁₆ showed superior radiolabelling efficiency and radiochemical stability (19.2 ± 4.53 % and 80.4 ± 1.6 % respectively) compared to the intraluminal-labelled exosomes (4.73 ± 0.39 % and 14.21 ± 2.76 % respectively). Using the membrane-labelling approach, the in vivo biodistribution of ExoB₁₆ in melanoma-bearing C57Bl/6 mice was carried out, and was found to accumulate primarily in the liver and spleen (~56% and ~38% ID/gT respectively), followed by the kidneys (~3% ID/gT). ExoB₁₆ showed minimal tumour i.e. self-tissue accumulation (~0.7% ID/gT). The membrane-labelling approach was also used to study ExoB₁₆ biodistribution in melanoma-bearing immunocompromised (NSG) mice, to compare with that in the immunocompetent C57Bl/6 mice. Similar biodistribution profile was observed in both C57BL/6 and NSG mice, where prominent accumulation was seen in liver and spleen, apart from the significantly lower tumour accumulation observed in the NSG mice (~0.3% ID/gT). Conclusion: Membrane radiolabelling of exosomes is a reliable approach that allows for accurate live imaging and quantitative biodistribution studies to be performed on potentially all exosome types without engineering parent cells