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"Chen, Heng"
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New and Developing Therapies in Spinal Muscular Atrophy: From Genotype to Phenotype to Treatment and Where Do We Stand?
Spinal muscular atrophy (SMA) is a congenital neuromuscular disorder characterized by motor neuron loss, resulting in progressive weakness. SMA is notable in the health care community because it accounts for the most common cause of infant death resulting from a genetic defect. SMA is caused by low levels of the survival motor neuron protein (SMN) resulting from SMN1 gene mutations or deletions. However, patients always harbor various copies of SMN2, an almost identical but functionally deficient copy of the gene. A genotype–phenotype correlation suggests that SMN2 is a potent disease modifier for SMA, which also represents the primary target for potential therapies. Increasing comprehension of SMA pathophysiology, including the characterization of SMN1 and SMN2 genes and SMN protein functions, has led to the development of multiple therapeutic approaches. Until the end of 2016, no cure was available for SMA, and management consisted of supportive measures. Two breakthrough SMN-targeted treatments, either using antisense oligonucleotides (ASOs) or virus-mediated gene therapy, have recently been approved. These two novel therapeutics have a common objective: to increase the production of SMN protein in MNs and thereby improve motor function and survival. However, neither therapy currently provides a complete cure. Treating patients with SMA brings new responsibilities and unique dilemmas. As SMA is such a devastating disease, it is reasonable to assume that a unique therapeutic solution may not be sufficient. Current approaches under clinical investigation differ in administration routes, frequency of dosing, intrathecal versus systemic delivery, and mechanisms of action. Besides, emerging clinical trials evaluating the efficacy of either SMN-dependent or SMN-independent approaches are ongoing. This review aims to address the different knowledge gaps between genotype, phenotypes, and potential therapeutics.
Journal Article
Phillipsite and Al-tobermorite mineral cements produced through low-temperature water-rock reactions in Roman marine concrete
Pozzolanic reaction of volcanic ash with hydrated lime is thought to dominate the cementing fabric and durability of 2000-year-old Roman harbor concrete. Pliny the Elder, however, in first century CE emphasized rock-like cementitious processes involving volcanic ash (pulvis) \"that as soon as it comes into contact with the waves of the sea and is submerged becomes a single stone mass (fierem unum lapidem), impregnable to the waves and every day stronger\" (Naturalis Historia 35.166). Pozzolanic crystallization of Al-tobermorite, a rare, hydrothermal, calcium-silicate-hydrate mineral with cation exchange capabilities, has been previously recognized in relict lime clasts of the concrete. Synchrotron-based X-ray microdiffraction maps of cementitious microstructures in Baianus Sinus and Portus Neronis submarine breakwaters and a Portus Cosanus subaerial pier now reveal that Al-tobermorite also occurs in the leached perimeters of feldspar fragments, zeolitized pumice vesicles, and in situ phillipsite fabrics in relict pores. Production of alkaline pore fluids through dissolution-precipitation, cation-exchange and/or carbonation reactions with Campi Flegrei ash components, similar to processes in altered trachytic and basaltic tuffs, created multiple pathways to post-pozzolanic phillipsite and Al-tobermorite crystallization at ambient seawater and surface temperatures. Long-term chemical resilience of the concrete evidently relied on water-rock interactions, as Pliny the Elder inferred. Raman spectroscopic analyses of Baianus Sinus Al-tobermorite in diverse microstructural environments indicate a cross-linked structure with Al3+ substitution for Si4+ in Q3 tetrahedral sites, and suggest coupled [Al3++Na+] substitution and potential for cation exchange. The mineral fabrics provide a geoarchaeological prototype for developing cementitious processes through low-temperature rock-fluid interactions, subsequent to an initial phase of reaction with lime that defines the activity of natural pozzolans. These processes have relevance to carbonation reactions in storage reservoirs for CO2 in pyroclastic rocks, production of alkali-activated mineral cements in maritime concretes, and regenerative cementitious resilience in waste encapsulations using natural volcanic pozzolans.
Journal Article
The comparison between adenocarcinoma and squamous cell carcinoma in lung cancer patients
BackgroundThere are several studies comparing the difference between adenocarcinoma (AC) and squamous cell carcinoma (SqCC) of lung cancer. However, seldom studies compare the different overall survival (OS) between AC and SqCC at same clinical or pathological stage. The aim of the study was to investigate the 5-year OS between AC and SqCC groups.MethodsData were obtained from the Taiwan Society of Cancer Registry. There were 48,296 non-small cell lung cancer (NSCLC) patients analyzed between 2009 and 2014 in this retrospective study. We analyzed both the AC and SqCC groups by age, gender, smoking status, Charlson co-morbidity index (CCI) score, clinical TNM stage, pathological stage, tumor location, histologic grade, pleura invasion, performance status, treatment, stage-specific 5-year OS rate in each clinical stage I–IV and causes of death. We used propensity score matching to reduce the bias.ResultsThe AC and SqCC groups are significantly different in age, gender, smoking status, CCI score, clinical TNM stage, pathological stage, tumor location, histologic grade, pleura invasion, performance status, treatment, stage-specific 5-year OS rate in each clinical stage and causes of death (p < 0.0001). The stage-specific 5-year OS rates between AC and SqCC were 79% vs. 47% in stage I; 50% vs. 32% in stage II; 27% vs. 13% in stage III; 6% vs. 2% in stage IV, respectively (all p values < 0.0001).ConclusionsAC and SqCC have significantly different outcomes in lung cancer. We suggest that these two different cancers should be analyzed separately to provide more precise outcomes in the future.
Journal Article
From network biology to immunity: potential longitudinal biomarkers for targeting the network topology of the HIV reservoir
In the “omics” era, studies often utilize large-scale datasets, eliciting the overall functional machinery of a network’s organization. In this context, determining how to read the enormous number of interactions in a network is imperative to comprehend its functional organization. Topology is the principal attribute of any network; as such, topological properties help to elucidate the roles of entities and represent a network’s behavior. In this review, I showcase the foundational concepts involved in graph theory, which form the basis of network biology, and exemplify the application of this conceptual framework to bridge the connection between the task-evoked functional genome network of the HIV reservoir. Furthermore, I point out potential longitudinal biomarkers identified using network-based analysis and systematically compare them with other potential biomarkers identified based on experimental research with longitudinal clinical samples.
Journal Article
On conformal blocks, crossing kernels and multi-variable hypergeometric functions
A
bstract
In this note, we present an alternative representation of the conformal block with external scalars in general spacetime dimensions in terms of a
finite
summation over Appell fourth hypergeometric function
F
4. We also construct its generalization to the non-local primary exchange operator with continuous spin and its corresponding Mellin representation which are relevant for Lorentzian spacetime. Using these results we apply the Lorentzian inversion formula to compute the so-called crossing kernel in general spacetime dimensions, the resultant expression can be written as a double infinite summation over certain Kampé de Fériet hypergeometric functions with the correct double trace operator singularity structures. We also include some complementary computations in AdS space, demonstrating the orthogonality of conformal blocks and performing the decompositions.
Journal Article
Efficacy, Chemical Constituents, and Pharmacological Actions of Radix Paeoniae Rubra and Radix Paeoniae Alba
Radix Paeoniae Rubra and Radix Paeoniae Alba are the different characteristic forms of Paeonia lactiflora Pall. They are widely used as traditional Chinese medicines in clinical practices. This study analyzes the development history, efficacy, chemical compositions, and pharmacological effects of Radix Paeoniae Rubra and Radix Paeoniae Alba , and explores the causes of the similarities and differences of these two amalgams. It provides a basis for the clinical application of these two Chinese medicinal materials, and lays a foundation for further study of the pharmacological effects and the quality identification of Paeonia lactiflora Pall as it applies to traditional Chinese medicine.
Journal Article
A lexical network approach to second language development
This study investigates lexical development in second language (L2) learning from the perspective of complex dynamic system theory (CDST) using a complex network method. Based on authentic written output texts from L2 Chinese learners of different proficiency levels and language backgrounds, we successfully differentiate between different proficiency levels using a bi-gram lexical network model at a corpus level. A more in-depth investigation reveals that when compared to traditional lexical complexity indices, such as average word length and hapax legomena percentage (though
Guiraud
proves to be a robust predictor), the lexical network indices, such as network density and network clusters, provide a more profound understanding of L2 proficiency distinctions and a more precise approximation of the target language. Moreover, our findings illuminate the consistent manifestation of complex network characteristics within L2 Chinese lexical networks across all proficiency levels. Additionally, word association features, encompassing more than just word frequency information, provide comprehensive properties of the interlanguage system, as supported by their information gain values. We argue that studies within the CDST framework should integrate both lexical frequency and lexical network features to gain a comprehensive understanding of L2 lexical development.
Journal Article
Role of Galectins in Tumors and in Clinical Immunotherapy
Galectins are glycan-binding proteins that contain one or two carbohydrate domains and mediate multiple biological functions. By analyzing clinical tumor samples, the abnormal expression of galectins is known to be linked to the development, progression and metastasis of cancers. Galectins also have diverse functions on different immune cells that either promote inflammation or dampen T cell-mediated immune responses, depending on cognate receptors on target cells. Thus, tumor-derived galectins can have bifunctional effects on tumor and immune cells. This review focuses on the biological effects of galectin-1, galectin-3 and galectin-9 in various cancers and discusses anticancer therapies that target these molecules.
Journal Article
Superconformal block from holographic geometry
A
bstract
We explicitly construct the holographic dual configuration for the four dimensional
N
= 4 superconformal block containing half-BPS scalar primary operators by considering its full
AdS
5
× S
5
dual geometry. We extend the embedding space formalism and the related Harmonic analysis to general
d
-dimensional sphere
S
d
, and obtain precisely the
R
-symmetry contribution to the half-BPS scalar superconformal blocks, which we refer as “
R
-symmetry block”. We also observe that the
R
-symmetry quadratic Casimir operator can be mapped to BC
2
Calogero-Sutherland system Hamiltonian, such that
R
-symmetry block is in terms identified as its bound state wave function.
Journal Article