Diabetes now is the most common chronic disease in the world inducing heavy burden for the people's health. Based on this, diabetes research such as islet function has become a hot topic in medical institutes of the world. Today, in medical institutes, the conventional experiment platform in vitro is monolayer cell culture. However, with the development of micro- and nano-technologies, several microengineering methods have been developed to fabricate three-dimensional (3D) islet models in vitro which can better mimic the islet of pancreases in vivo. These in vitro islet models have shown better cell function than monolayer cells, indicating their great potential as better experimental platforms to elucidate islet behaviors under both physiological and pathological conditions, such as the molecular mechanisms of diabetes and clinical islet transplantation. In this review, we present the state-of-the-art advances in the microengineering methods for fabricating microscale islet models in vitro. We hope this will help researchers to better understand the progress in the engineering 3D islet models and their biomedical applications such as drug screening and islet transplantation.
Experimental findings indicate that in-situ chondrocytes die readily following impact loading, but remain essentially unaffected at low (non-impact) strain rates. This study was aimed at identifying possible causes for cell death in impact loading by quantifying chondrocyte mechanics when cartilage was subjected to a 5% nominal tissue strain at different strain rates. Multi-scale modelling techniques were used to simulate cartilage tissue and the corresponding chondrocytes residing in the tissue. Chondrocytes were modelled by accounting for the cell membrane, pericellular matrix and pericellular capsule. The results suggest that cell deformations, cell fluid pressures and fluid flow velocity through cells are highest at the highest (impact) strain rate, but they do not reach damaging levels. Tangential strain rates of the cell membrane were highest at the highest strain rate and were observed primarily in superficial tissue cells. Since cell death following impact loading occurs primarily in superficial zone cells, we speculate that cell death in impact loading is caused by the high tangential strain rates in the membrane of superficial zone cells causing membrane rupture and loss of cell content and integrity.
Papillary thyroid carcinoma is the most common thyroid malignancy and frequently metastasizes to regional lymph nodes. Occasionally, metastatic lymph nodes are palpable without the evidence of primary tumour. Papillary thyroid carcinoma of lateral neck cyst is a rare condition. It may arise from thyroid primary which underwent cystic degeneration or true malignant transformation of ectopic thyroid tissue. Herein, we reported two cases with preoperative diagnosis of benign lateral neck cyst but postoperative histopathological results showed primary papillary thyroid carcinoma. Ultrasonography and computed tomography of the neck in both cases showed no significant thyroid lesion. However, the patient in Case 2 was subjected for total thyroidectomy and histopathological results showed the origin of primary tumour. In conclusion, thorough investigations including total thyroidectomy are indicated in cases of papillary thyroid carcinoma of lateral neck cyst. This practice is to ensure that this type of thyroid cancer can be detected earlier because it has a very good prognosis if treated earlier.
Lumbar decompressive laminectomy is a standard treatment for degenerative lumbar spinal stenosis, but in some cases, can lead to iatrogenic spondylolysis and delayed segmental instability. Iatrogenic spondylolysis occurs in most cases in pars interarticularis, but rare cases have also been reported, pediculolysis in pedicle and laminolysis in lamina. Minimally invasive spine surgery (MIS) is known to have a low risk of developing these iatrogenic spondylolyses, and unilateral biportal endoscopy is the MIS that has been drawing attention. We present a case of a 72-year-old female who was diagnosed with L4-5 unstable non-isthmic spondylolisthesis and severe right central disc extrusion 10 weeks after UBE assisted unilateral laminotomy for bilateral decompression (ULBD) at the consecutive segments of L3-4 and L4-5. Pre-operative imaging studies revealed severe central stenosis without spondylolisthesis at L3-L4 and L4-L5 along with L4-L5 facet tropism. She was managed by anterior lumbar interbody fusion and cement augmented pedicle screw fixation, which resulted in the complete resolution of her clinical and neurologic symptoms.
Overexpression of the epidermal growth factor receptor-related gene ErbB2 occurs in 18% to 25% of patients with breast cancer in Western countries and is associated with a poor prognosis. The prevalence of ErbB2-positive tumors in Asia is unclear, partly because data are limited. The objective of this review was to summarize the reported prevalence of ErbB2-positive tumors from a large sample of Asian patients and to examine ErbB2 assessment methods in Asia. From searches of MEDLINE, local language journals, and local and international conference proceedings as well as locoregional breast cancer experts' recommendations, the authors selected up to 5 studies each from India, Korea, Malaysia, the Philippines, Singapore, Taiwan, and Thailand that reported ErbB2 results based on assessment with immunohistochemistry (IHC) and/or fluorescence in situ hybridization (FISH). The reported prevalence of ErbB2-positive tumors in 22 studies on 24,671 patients, of whom 14,398 patients were assessed for ErbB2 status, varied widely (range, 6%-65%) as did the assessment methods used. Most studies (n=21) used IHC to assess ErbB2 status, but definitions for positivity varied. When robust assessment methods were used, the median prevalence was 19% based on strong IHC staining (IHC3+; n=9812 patients) and 25% based on FISH (n=681 patients). Data on the prevalence of ErbB2-positive breast cancer in Asia are limited. The current survey indicated that the prevalence in Asia may be similar to that in Western countries; thus, up to 1 in 4 Asian patients with breast cancer potentially could benefit from ErbB2-targeted treatment. A standard, reliable ErbB2 assessment method available to patients across Asia is urgently required.
Extracellular vesicles (EVs) derived from mesenchymal stem cells are promising nanotherapeutics in liver diseases due to their regenerative and immunomodulatory properties. Nevertheless, a concern has been raised regarding the rapid clearance of exogenous EVs by phagocytic cells. Here we explore the impact of protein corona on EVs derived from two culturing conditions in which specific proteins acquired from media were simultaneously adsorbed on the EV surface. Additionally, by incubating EVs with serum, simulating protein corona formation upon systemic delivery, further resolved protein corona-EV complex patterns were investigated. Our findings reveal the potential influences of corona composition on EVs under in vitro conditions and their in vivo kinetics. Our data suggest that bound albumin creates an EV signature that can retarget EVs from hepatic macrophages. This results in markedly improved cellular uptake by hepatocytes, liver sinusoidal endothelial cells and hepatic stellate cells. This phenomenon can be applied as a camouflage strategy by precoating EVs with albumin to fabricate the albumin-enriched protein corona-EV complex, enhancing non-phagocytic uptake in the liver. This work addresses a critical challenge facing intravenously administered EVs for liver therapy by tailoring the protein corona-EV complex for liver cell targeting and immune evasion.
Archaic admixture has had a substantial impact on human evolution with multiple events across different clades, including from extinct hominins such as Neanderthals and Denisovans into modern humans. In great apes, archaic admixture has been identified in chimpanzees and bonobos but the possibility of such events has not been explored in other species. Here, we address this question using high-coverage whole-genome sequences from all four extant gorilla subspecies, including six newly sequenced eastern gorillas from previously unsampled geographic regions. Using approximate Bayesian computation with neural networks to model the demographic history of gorillas, we find a signature of admixture from an archaic 'ghost' lineage into the common ancestor of eastern gorillas but not western gorillas. We infer that up to 3% of the genome of these individuals is introgressed from an archaic lineage that diverged more than 3 million years ago from the common ancestor of all extant gorillas. This introgression event took place before the split of mountain and eastern lowland gorillas, probably more than 40 thousand years ago and may have influenced perception of bitter taste in eastern gorillas. When comparing the introgression landscapes of gorillas, humans and bonobos, we find a consistent depletion of introgressed fragments on the X chromosome across these species. However, depletion in protein-coding content is not detectable in eastern gorillas, possibly as a consequence of stronger genetic drift in this species.
The FLUXNET2015 dataset provides ecosystem-scale data on CO2, water, and energy exchange between the biosphere and the atmosphere, and other meteorological and biological measurements, from 212 sites around the globe (over 1500 site-years, up to and including year 2014). These sites, independently managed and operated, voluntarily contributed their data to create global datasets. Data were quality controlled and processed using uniform methods, to improve consistency and intercomparability across sites. The dataset is already being used in a number of applications, including ecophysiology studies, remote sensing studies, and development of ecosystem and Earth system models. FLUXNET2015 includes derived-data products, such as gap-filled time series, ecosystem respiration and photosynthetic uptake estimates, estimation of uncertainties, and metadata about the measurements, presented for the first time in this paper. In addition, 206 of these sites are for the first time distributed under a Creative Commons (CC-BY 4.0) license. This paper details this enhanced dataset and the processing methods, now made available as open-source codes, making the dataset more accessible, transparent, and reproducible.
The dependence of the ratio between the B_{s}^{0} and B^{+} hadron production fractions, f_{s}/f_{u}, on the transverse momentum (p_{T}) and rapidity of the B mesons is studied using the decay channels B_{s}^{0}→J/ψϕ and B^{+}→J/ψK^{+}. The analysis uses a data sample of proton-proton collisions at a center-of-mass energy of 13 TeV, collected by the CMS experiment in 2018 and corresponding to an integrated luminosity of 61.6 fb^{-1}. The f_{s}/f_{u} ratio is observed to depend on the B p_{T} and to be consistent with becoming asymptotically constant at large p_{T}. No rapidity dependence is observed. The ratio of the B^{0} to B^{+} meson production fractions, f_{d}/f_{u}, is also measured, for the first time in proton-proton collisions, using the B^{0}→J/ψK^{*0} decay channel. The result is found to be within 1 standard deviation of unity and independent of p_{T} and rapidity, as expected from isospin invariance.
We present an observation of photon-photon production of τ lepton pairs in ultraperipheral lead-lead collisions. The measurement is based on a data sample with an integrated luminosity of 404 μb^{-1} collected by the CMS experiment at a center-of-mass energy per nucleon pair of sqrt[s_{NN}]=5.02 TeV. The γγ→τ^{+}τ^{-} process is observed for τ^{+}τ^{-} events with a muon and three charged hadrons in the final state. The measured fiducial cross section is σ(γγ→τ^{+}τ^{-})=4.8±0.6(stat)±0.5(syst) μb, where the second (third) term corresponds to the statistical (systematic) uncertainty in σ(γγ→τ^{+}τ^{-}) in agreement with leading-order QED predictions. Using σ(γγ→τ^{+}τ^{-}), we estimate a model-dependent value of the anomalous magnetic moment of the τ lepton of a_{τ}=0.001_{-0.089}^{+0.055}.
The first search exploiting the vector boson fusion process to probe heavy Majorana neutrinos and the Weinberg operator at the LHC is presented. The search is performed in the same-sign dimuon final state using a proton-proton collision dataset recorded at sqrt[s]=13 TeV, collected with the CMS detector and corresponding to a total integrated luminosity of 138 fb^{-1}. The results are found to agree with the predictions of the standard model. For heavy Majorana neutrinos, constraints on the squared mixing element between the muon and the heavy neutrino are derived in the heavy neutrino mass range 50 GeV-25 TeV; for masses above 650 GeV these are the most stringent constraints from searches at the LHC to date. A first test of the Weinberg operator at colliders provides an observed upper limit at 95% confidence level on the effective μμ Majorana neutrino mass of 10.8 GeV.
A search for nonresonant Higgs boson (H) pair production via gluon and vector boson (V) fusion is performed in the four-bottom-quark final state, using proton-proton collision data at 13 TeV corresponding to 138 fb^{-1} collected by the CMS experiment at the LHC. The analysis targets Lorentz-boosted H pairs identified using a graph neural network. It constrains the strengths relative to the standard model of the H self-coupling and the quartic VVHH couplings, κ_{2V}, excluding κ_{2V}=0 for the first time, with a significance of 6.3 standard deviations when other H couplings are fixed to their standard model values.
A search for the standard model (SM) Higgs boson (H) produced with transverse momentum (p_{T}) greater than 450 GeV and decaying to a charm quark-antiquark (cc[over ¯]) pair is presented. The search is performed using proton-proton collision data collected at sqrt[s]=13 TeV by the CMS experiment at the LHC, corresponding to an integrated luminosity of 138 fb^{-1}. Boosted H→cc[over ¯] decay products are reconstructed as a single large-radius jet and identified using a deep neural network charm tagging technique. The method is validated by measuring the Z→cc[over ¯] decay process, which is observed in association with jets at high p_{T} for the first time with a signal strength of 1.00_{-0.14}^{+0.17}(syst)±0.08(theo)±0.06(stat), defined as the ratio of the observed process rate to the SM expectation. The observed (expected) upper limit on σ(H)B(H→cc[over ¯]) is set at 47 (39) times the SM prediction at 95% confidence level.
We present the first direct search for exotic Higgs boson decays H→AA, A→γγ in events with two photonlike objects. The hypothetical particle A is a low-mass spin-0 particle decaying promptly to a merged diphoton reconstructed as a single photonlike object. We analyze the data collected by the CMS experiment at sqrt[s]=13 TeV corresponding to an integrated luminosity of 136 fb^{-1}. No excess above the estimated background is found. We set upper limits on the branching fraction B(H→AA→4γ) of (0.9-3.3)×10^{-3} at 95% confidence level for masses of A in the range 0.1-1.2 GeV.
The first observation of the production of W^{±}W^{±} bosons from double parton scattering processes using same-sign electron-muon and dimuon events in proton-proton collisions is reported. The data sample corresponds to an integrated luminosity of 138 fb^{-1} recorded at a center-of-mass energy of 13 TeV using the CMS detector at the CERN LHC. Multivariate discriminants are used to distinguish the signal process from the main backgrounds. A binned maximum likelihood fit is performed to extract the signal cross section. The measured cross section for production of same-sign W bosons decaying leptonically is 80.7±11.2(stat) _{-8.6}^{+9.5}(syst)±12.1(model) fb, whereas the measured fiducial cross section is 6.28±0.81(stat)±0.69(syst)±0.37(model) fb. The observed significance of the signal is 6.2 standard deviations above the background-only hypothesis.
A search for the rare η→μ^{+}μ^{-}μ^{+}μ^{-} double-Dalitz decay is performed using a sample of proton-proton collisions, collected by the CMS experiment at the CERN LHC with high-rate muon triggers during 2017 and 2018 and corresponding to an integrated luminosity of 101 fb^{-1}. A signal having a statistical significance well in excess of 5 standard deviations is observed. Using the η→μ^{+}μ^{-} decay as normalization, the branching fraction B(η→μ^{+}μ^{-}μ^{+}μ^{-})=[5.0±0.8(stat)±0.7(syst)±0.7(B_{2μ})]×10^{-9} is measured, where the last term is the uncertainty in the normalization channel branching fraction. This work achieves an improved precision of over 5 orders of magnitude compared to previous results, leading to the first measurement of this branching fraction, which is found to agree with theoretical predictions.
A search for decays to invisible particles of Higgs bosons produced in association with a top-antitop quark pair or a vector boson, which both decay to a fully hadronic final state, has been performed using proton-proton collision data collected at s=13TeV by the CMS experiment at the LHC, corresponding to an integrated luminosity of 138fb-1. The 95% confidence level upper limit set on the branching fraction of the 125GeV Higgs boson to invisible particles, B(H→inv), is 0.54 (0.39 expected), assuming standard model production cross sections. The results of this analysis are combined with previous B(H→inv) searches carried out at s=7, 8, and 13TeV in complementary production modes. The combined upper limit at 95% confidence level on B(H→inv) is 0.15 (0.08 expected).