Stem cell-based tissue engineering approaches are promising for bone repair and regeneration. Periodontal ligament stem cells (PDLSCs) are a promising cell source for tissue engineering, especially ...for maxillofacial bone and periodontal regeneration. Many studies have shown potent results
PDLSCs in bone regeneration. In this review, we describe recent cutting-edge researches on PDLSC-based bone regeneration and periodontal tissue regeneration.
An extensive search of the literature for papers related to PDLSCs-based bioactive constructs for bone tissue engineering was made on the databases of PubMed, Medline and Google Scholar. The papers were selected by three independent calibrated reviewers.
Multiple types of materials and scaffolds have been combined with PDLSCs, involving xeno genic bone graft, calcium phosphate materials and polymers. These PDLSC-based constructs exhibit the potential for bone and periodontal tissue regeneration. In addition, various osteo inductive agents and strategies have been applied with PDLSCs, including drugs, biologics, gene therapy, physical stimulation, scaffold modification, cell sheets and co-culture.
This review article demonstrates the great potential of PDLSCs-based bioactive constructs as a promising approach for bone and periodontal tissue regeneration.
To investigate the impact of a 5-year follow-up on the incidence of identified birth defects in children conceived using assisted reproductive technologies (ART).
A 5-year cohort study was performed ...in three ART centers from January 2013 to October 2018. 1,543 women with 1,985 infants who delivered successfully or underwent termination of pregnancy due to malformations were recruited in this study. Follow-up was conducted by phone interview, 7 days, 1 year, 3 years, and 5 years after birth. Collected data included whether one or more birth defects were diagnosed, the category of birth defects, and when the malformation was diagnosed. Cumulative incidence of birth defects and the loss to follow-up rate of each follow-up was compared.
According to the diagnostic criterion of birth defects, 111 cases of one or more birth defects were recorded, with a total of 117 birth defects after the 5-year follow-up. 0.2% (4/1,985) of birth defects were diagnosed before delivery; 2.7% (54/1,985) at 7 days; 5.0% (100/1,985) after 1 year; 5.5% (109/1,985) after 3 years; and 5.6% (111/1,985) after 5 years. 3.4% (4/117) of defects were diagnosed prenatally, 45.3% (53/117) of defects diagnosed within the first 7 days after delivery, 40.2% (47/117) diagnosed during 7 days to 1 year, and 9.4% (11/117) of defects diagnosed in 1-3 years after birth. The remaining 1.7% (2/117) of defects were diagnosed between the ages of 3 and 5 years. Among the 1,543 patients, 99.9% patients (1,542/1,543) responded to the telephone interview at 7 days after delivery; the response rate was 89.0% (1,373/1,543) at 1 year, 81% (1,250/1,543) at 3 years, and 64.5% (995/1,543) after 5 years.
We suggest that in ART, 1-year follow-up should be the minimum requirement and 3-year follow up the optimal length of follow-up that balances resource requirements with ascertainment completeness.
Recent years have witnessed a surge of investigations examining functional brain organization using resting-state functional connectivity MRI (rs-fcMRI). To date, this method has been used to examine ...systems organization in typical and atypical developing populations. While the majority of these investigations have focused on cortical-cortical interactions, cortical-subcortical interactions also mature into adulthood. Innovative work by Zhang et al. (2008) in adults have identified methods that utilize rs-fcMRI and known thalamo-cortical topographic segregation to identify functional boundaries in the thalamus that are remarkably similar to known thalamic nuclear grouping. However, despite thalamic nuclei being well formed early in development, the developmental trajectory of functional thalamo-cortical relations remains unexplored. Thalamic maps generated by rs-fcMRI are based on functional relationships, and should modify with the dynamic thalamo-cortical changes that occur throughout maturation. To examine this possibility, we employed a strategy as previously described by Zhang et al. to a sample of healthy children, adolescents, and adults. We found strengthening functional connectivity of the cortex with dorsal/anterior subdivisions of the thalamus, with greater connectivity observed in adults versus children. Temporal lobe connectivity with ventral/midline/posterior subdivisions of the thalamus weakened with age. Changes in sensory and motor thalamo-cortical interactions were also identified but were limited. These findings are consistent with known anatomical and physiological cortical-subcortical changes over development. The methods and developmental context provided here will be important for understanding how cortical-subcortical interactions relate to models of typically developing behavior and developmental neuropsychiatric disorders.
•Only a few studies have investigated the reasons for effective dewatering at optimum dosages from the perspective of understanding changes in the internal and external microstructure of the floc ...when treated with polymers.•Effective dewatering occurs at optimum dosage because two different characteristic zones of reduced porosity and open channels, respectively develop in the floc microstructure indicating that this arrangement could have led to an effective squeeze-out of water from the pores.•Optimum dosage also leads to effective dewatering due to flocs formed in the size range of 10–50 μm and 50–150 μm having reduced re-flocculation tendencies.
Synthetic polymeric flocculants such as anionic polyacrylamides are widely used for dewatering mature fine tailings (MFT) generated from oil sands mining operations. Many studies have investigated the effects of polymer properties on dewatering efficiency. However, only a few studies have investigated the reasons for effective dewatering at optimum dosages from the perspective of understanding changes in the internal and external microstructure of the floc. In MFT, clay solids are dispersed in brine (along with trace amounts of bitumen) and are known to have a house-of-card like microstructural arrangement due to electrostatic stabilization. In this study, we investigated why there is maximum dewatering in the specific polyacrylamide (PAM) polymer-MFT system at optimum dosage. To understand this, we investigated the morphological changes in the house-of-cards microstructure in terms of porosity and floc density when flocculated at different polymer dosages as well as the corresponding floc strength, size, and re-flocculation tendencies. SEM imaging results showed that at the optimum dosage of 1000 ppm the internal floc microstructure had two different characteristic zones of reduced porosity and open channels, respectively, indicating that this arrangement could have led to an effective squeeze-out of water from the pores. Focused Beam Reflectance Microscopy results indicated that optimum dosage leads to effective dewatering due to flocs formed in the size range of 10–50 μm and 50–150 μm having reduced re-flocculation tendencies. Optimum dosage resulted in the least number of flocs and the reduction of flocs in the size range of 10–50 μm and < 10 μm was maximum while the corresponding increase of flocs in the size range of 50–150 μm was maximum as compared to other dosages. Additionally, the flocs at optimum dosage did not change in number for a given size range of flocs even after 1-hour stirring indicating strong floc formation. These observations are specific for the particular pairing and could form a basis for investigating other polymer-tailing systems.
Summary
Plant establishment requires the formation and development of an extensive root system with architecture modulated by complex genetic networks.
Here, we report the identification of the ...PtrXB38 gene as an expression quantitative trait loci (eQTL) hotspot, mapped using 390 leaf and 444 xylem Populus trichocarpa transcriptomes. Among predicted targets of this trans‐eQTL were genes involved in plant hormone responses and root development.
Overexpression of PtrXB38 in Populus led to significant increases in callusing and formation of both stem‐born roots and base‐born adventitious roots. Omics studies revealed that genes and proteins controlling auxin transport and signaling were involved in PtrXB38‐mediated adventitious root formation. Protein–protein interaction assays indicated that PtrXB38 interacts with components of endosomal sorting complexes required for transport machinery, implying that PtrXB38‐regulated root development may be mediated by regulating endocytosis pathway.
Taken together, this work identified a crucial root development regulator and sheds light on the discovery of other plant developmental regulators through combining eQTL mapping and omics approaches.
Purpose
This study assessed the impact of adherence to guidelines-recommended diagnostic testing on treatment selection and overall survival (OS) in patients with diffuse large B-cell lymphoma ...(DLBCL) initiated on rituximab-based first line of treatment (1-LOT).
Methods
This retrospective cohort study used a nationwide electronic health record-derived de-identified database, including diagnostic testing information on immunohistochemistry (IHC), fluorescence in situ hybridization (FISH) and karyotype analysis that were abstracted from pathology reports or clinical visit notes, where available. The study included patients above 18 years old who were diagnosed with DLBCL between January 2011 and December 2019 and initiated on rituximab-based 1-LOT. Patients were classified into ‘non-adherence,’ ‘partial-adherence’ and ‘complete-adherence’ groups according to the evidence/documentation of a confirmed known result for IHC and molecular profiling tests (FISH and karyotyping) on a selection of the markers prior to the initiation of 1-LOT. Logistic regression was used to evaluate associations of adherence to diagnostic testing with 1-LOT between R-CHOP and other rituximab-based regimens. Median OS after the start of rituximab-based 1-LOT was calculated using the Kaplan–Meier method. Multivariable-adjusted Cox proportional hazards regression was used to assess the risk of all-cause death after initiation of 1-LOT by the degrees of adherence to guidelines-recommended diagnostic testing.
Results
In total, 3730 patients with DLBCL who initiated on rituximab-based 1-LOT were included. No association was found between adherence to guidelines-recommended diagnostic testing and treatment selection of 1-LOT for R-CHOP versus other rituximab-based regimens. Patients with a higher degree of adherence to guidelines-recommended diagnostic testing survived longer (median OS at 5.1, 6.9 and 7.1 years for ‘non-adherence,’ ‘partial-adherence’ and ‘complete-adherence’ groups, respectively log-rank
p
< 0.001) and had a decreased mortality risk (multivariable-adjusted hazard ratio with 95% confidence intervals at 0.83 0.70–0.99 for ‘partial-adherence’ and 0.77 0.64–0.91 for ‘complete-adherence’ groups, respectively).
Conclusion
Patients’ adherence to guidelines-recommended diagnostic testing were associated with better survival benefit, reinforcing the need for adoption of diagnostic testing guidelines in routine clinical care.
IgE-mediated anaphylaxis is an acute life-threatening systemic reaction to allergens, including certain foods and venoms. Anaphylaxis is triggered when blood-borne allergens activate IgE-bound ...perivascular mast cells (MCs) throughout the body, causing an extensive systemic release of MC mediators. Through precipitating vasodilatation and vascular leakage, these mediators are believed to trigger a sharp drop in blood pressure in humans and in core body temperature in animals. We report that the IgE/MC-mediated drop in body temperature in mice associated with anaphylaxis also requires the body's thermoregulatory neural circuit. This circuit is activated when granule-borne chymase from MCs is deposited on proximal TRPV1
sensory neurons and stimulates them via protease-activated receptor-1. This triggers the activation of the body's thermoregulatory neural network, which rapidly attenuates brown adipose tissue thermogenesis to cause hypothermia. Mice deficient in either chymase or TRPV1 exhibited limited IgE-mediated anaphylaxis, and, in wild-type mice, anaphylaxis could be recapitulated simply by systemically activating TRPV1
sensory neurons. Thus, in addition to their well-known effects on the vasculature, MC products, especially chymase, promote IgE-mediated anaphylaxis by activating the thermoregulatory neural circuit.
The rate of isolated locoregional recurrence after surgery for pancreatic adenocarcinoma (PDAC) approaches 25%. Ablative radiation therapy (A-RT) has improved outcomes for locally advanced disease in ...the primary setting. We sought to evaluate the outcomes of salvage A-RT for isolated locoregional recurrence and examine the relationship between subsequent patterns of failure, radiation dose, and treatment volume.
: We conducted a retrospective analysis of all consecutive participants who underwent A-RT for an isolated locoregional recurrence of PDAC after prior surgery at our institution between 2016 and 2021. Treatment consisted of ablative dose (BED10 98-100 Gy) to the gross disease with an additional prophylactic low dose (BED10 < 50 Gy), with the elective volume covering a 1.5 cm isotropic expansion around the gross disease and the circumference of the involved vessels. Local and locoregional failure (LF and LRF, respectively) estimated by the cumulative incidence function with competing risks, distant metastasis-free and overall survival (DMFS and OS, respectively) estimated by the Kaplan-Meier method, and toxicities scored by CTCAE v5.0 are reported. Location of recurrence was mapped to the dose region on the initial radiation plan.
: Among 65 participants (of whom two had two A-RT courses), the median age was 67 (range 37-87) years, 36 (55%) were male, and 53 (82%) had undergone pancreaticoduodenectomy with a median disease-free interval to locoregional recurrence of 16 (range, 6-71) months. Twenty-seven participants (42%) received chemotherapy prior to A-RT. With a median follow-up of 35 months (95%CI, 26-56 months) from diagnosis of recurrence, 24-month OS and DMFS were 57% (95%CI, 46-72%) and 22% (95%CI, 14-37%), respectively, while 24-month cumulative incidence of in-field LF and total LRF were 28% (95%CI, 17-40%) and 36% (95%CI 24-48%), respectively. First failure after A-RT was distant in 35 patients (53.8%), locoregional in 12 patients (18.5%), and synchronous distant and locoregional in 10 patients (15.4%). Most locoregional failures occurred in elective low-dose volumes. Acute and chronic grade 3-4 toxicities were noted in 1 (1.5%) and 5 patients (7.5%), respectively.
: Salvage A-RT achieves favorable OS and local control outcomes in participants with an isolated locoregional recurrence of PDAC after surgical resection. Consideration should be given to extending high-dose fields to include adjacent segments of at-risk vessels beyond direct contact with the gross disease.
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