Miracle-dz/UniFAR-FTUs huggingface dataset:
CerS6 regulates cisplatin resistance in oral squamous cell carcinoma by altering mitochondrial fission and autophagy

Chemoresistance remains a challenge in the effective treatment of solid tumors, including oral squamous cell carcinoma (OSCC). Mitochondrial dynamics and autophagy have recently been implicated in the chemoresistance of cancer cells. The neutralization of ceramide is also associated with multidrug resistance, and ceramide synthase 6 (CerS6) is known to induce apoptosis. However, whether CerS6 regulates chemoresistance in OSCC is not clearly understood. Therefore, we investigated the role of CerS6 in the susceptibility of OSCC cells to cisplatin. In this study, we observed that cisplatin‐resistant OSCC cells process lower levels of fission‐state mitochondria and cell apoptosis than cisplatin‐sensitive cells, and autophagy was activated in cisplatin‐resistant OSCC cells. We found lower CerS6 expression in cisplatin‐resistant OSCC cells. Overexpression of CerS6 with lentivirus‐encoded CerS6 complementary DNA in cisplatin‐resistant OSCC cells increased cisplatin sensitivity. Overexpression of CerS6 enhanced mitochondrial fission and apoptosis and attenuated cisplatin‐induced autophagy in cisplatin‐resistant OSCC cells. Further investigation indicated that CerS6 might function through altering calpain expression to enhance cisplatin sensitivity. Cisplatin‐resistant OSCC cells xenografted onto a nude mouse model confirmed that CerS6 enhanced cisplatin chemotherapy sensitivity to reduce tumor volume. These data indicate that CerS6 could mediate an effective response to cisplatin in chemoresistant OSCC.
Condyle Fractures: Impact of Surgical and Conservative Approaches on Oral Health

Abstract The aim of this study is to assess the impact of oral health on the quality of life of patients who underwent conservative or surgical treatment for mandibular condylar fracture. A retrospective study was conducted, and 24 patients with condylar fracture were selected and underwent surgical or conservative treatment. Oral Health Impact Profile-14 (OHIP-14) was utilized to evaluate the patients. The angles of condylar fracture were measured in panoramic and Towne radiographs using the ImageJ software, and the results were compared to the results of the OHIP-14 questionnaire. Condylar fractures had a negative impact on the patients’ quality of life in pretreatment assessment. After conservative and surgical treatments, the condylar fracture had a low impact on the patients’ quality of life. Greater fracture alignment was obtained in patients treated by open reduction. A low level of correlation was observed between fracture alignment and changes in OHIP-14 of the patients studied. In conclusion, the study showed a significant improvement in the quality of life in the post-treatment period of the sample assessed. However, in patients selected for this study, no difference was found in the quality of life between the surgically and conservatively treated groups.
Expanding the fetal phenotype: Prenatal sonographic findings and perinatal outcomes in a cohort of patients with a confirmed 22q11.2 deletion syndrome

22q deletion syndrome (22q11.2DS) is most often correlated prenatally with congenital heart disease and or cleft palate. The extracardiac fetal phenotype associated with 22q11.2DS is not well described. We sought to review both the fetal cardiac and extracardiac findings associated with a cohort of cases ascertained prenatally, confirmed or suspected to have 22q11.2DS, born and cared for in one center. A retrospective chart review was performed on a total of 42 cases with confirmed 22q11.2DS to obtain prenatal findings, perinatal outcomes and diagnostic confirmation. The diagnosis was confirmed prenatally in 67% (28/42) and postnatally in 33% (14/42). The majority (81%) were associated with the standard LCR22A‐LCR22D deletion. 95% (40/42) of fetuses were prenatally diagnosed with congenital heart disease. Extracardiac findings were noted in 90% (38/42) of cases. Additional findings involved the central nervous system (38%), gastrointestinal (14%), genitourinary (16.6%), pulmonary (7%), skeletal (19%), facial dysmorphism (21%), small/hypoplastic thymus (26%), and polyhydramnios (30%). One patient was diagnosed prenatally with a bilateral cleft lip and cleft palate. No fetus was diagnosed with intrauterine growth restriction. The average gestational age at delivery was 38 weeks and average birth weight was 3,105 grams. Sixty‐two percentage were delivered vaginally and there were no fetal demises. A diagnosis of 22q11.2 deletion syndrome should be considered in all cases of prenatally diagnosed congenital heart disease, particularly when it is not isolated. Microarray is warranted in all cases of structural abnormalities diagnosed prenatally. Prenatal diagnosis of 22q11.2 syndrome can be used to counsel expectant parents regarding pregnancy outcome and guide neonatal management.
An integrative approach for the assessment of peritubular capillaritis extent and score in low-grade microvascular inflammation—associations with transplant glomerulopathy and graft loss

Background Peritubular capillaritis (ptc), reported by the ptc score, is a major feature of kidney allograft rejection and microvascular inflammation (MVI). MVI sum scores (ptc + glomerulitis score ≥2) are accepted diagnostic surrogates of human leucocyte antigen (HLA)-antibody interaction. However, low-grade inflammation is common and ptc scores (number of leucocytes/capillary) may not mirror all aspects of ptc morphology. Recently we observed a relationship of the diffuse extent of ptc (inflammation of >50% of the renal cortex) with graft loss and significantly higher donor-specific antibody levels, suggesting potential inclusion of diffuse ptc as an additional surrogate of antibody-antigen interaction. Methods We sought to assess how a combination of ptc score and extent in low-grade inflammation (ptc1) affects transplant glomerulopathy (TG) and graft loss risk. Patients (n = 616) were assessed for MVI in first indication biopsies. Cases with a ptc score of 1 but diffuse extent (ptc1diffuse, g-score = 0, n = 26) were considered additional surrogates of HLA-antibody interaction and compared with MVI ≥2 and MVI <2. Results The ptc1diffuse and MVI score ≥2 subjects had worse graft survival (42% and 59%) compared with an MVI score <2 (70%) (P = 0.002). The incorporation of ptc1diffuse in the MVI score ≥2 increased the receiver operating characteristics curve for TG [area under the curve (AUC) 0.602; P = 0.008] compared with a Banff MVI score ≥2 (AUC 0.56; P = 0.12); cases with baseline TG were excluded. In multivariate analysis, ptc1diffuse remained independently related to TG (odds ratio 3.89; P = 0.008) and graft loss (hazard ratio 2.64; P = 0.001) even after inclusion of all rejection episodes. Conclusion An integrated view of ptc morphology including diffuse ptc in MVI is superior for TG and graft loss risk assessment.
Novel Bioinformatics Approach Identifies Transcriptional Profiles of Lineage-Specific Transposable Elements at Distinct Loci in the Human Dorsolateral Prefrontal Cortex

Abstract Expression of transposable elements (TE) is transiently activated during human preimplantation embryogenesis in a developmental stage- and cell type-specific manner and TE-mediated epigenetic regulation is intrinsically wired in developmental genetic networks in human embryos and embryonic stem cells. However, there are no systematic studies devoted to a comprehensive analysis of the TE transcriptome in human adult organs and tissues, including human neural tissues. To investigate TE expression in the human Dorsolateral Prefrontal Cortex (DLPFC), we developed and validated a straightforward analytical approach to chart quantitative genome-wide expression profiles of all annotated TE loci based on unambiguous mapping of discrete TE-encoded transcripts using a de novo assembly strategy. To initially evaluate the potential regulatory impact of DLPFC-expressed TE, we adopted a comparative evolutionary genomics approach across humans, primates, and rodents to document conservation patterns, lineage-specificity, and colocalizations with transcription factor binding sites mapped within primate- and human-specific TE. We identified 654,665 transcripts expressed from 477,507 distinct loci of different TE classes and families, the majority of which appear to have originated from primate-specific sequences. We discovered 4,687 human-specific and transcriptionally active TEs in DLPFC, of which the prominent majority (80.2%) appears spliced. Our analyses revealed significant associations of DLPFC-expressed TE with primate- and human-specific transcription factor binding sites, suggesting potential cross-talks of concordant regulatory functions. We identified 1,689 TEs differentially expressed in the DLPFC of Schizophrenia patients, a majority of which is located within introns of 1,137 protein-coding genes. Our findings imply that identified DLPFC-expressed TEs may affect human brain structures and functions following different evolutionary trajectories. On one side, hundreds of thousands of TEs maintained a remarkably high conservation for ∼8 My of primates’ evolution, suggesting that they are likely conveying evolutionary-constrained primate-specific regulatory functions. In parallel, thousands of transcriptionally active human-specific TE loci emerged more recently, suggesting that they could be relevant for human-specific behavioral or cognitive functions.
Developing a high‐throughput platform to direct adipogenic and osteogenic differentiation in adipose‐derived stem cells

The popular reductionist approach towards stem cell differentiation has identified an array of factors that can induce lineage‐specific differentiation. Whether these variables direct differentiation in a multivariable setting in the same way as a single‐variable setting is a question of interest. Polyacrylamide hydrogels of specific stiffness were microcontact printed with fibronectin in specific shapes and sizes to construct 54 different extracellular matrix types of defined stiffness, shape, and area. Three media types were also used to investigate the effect of both biomechanical and biochemical inducers of differentiation on adipose‐derived stem cells. Stiffness was found to be a significant regulator of both adipogenic (3 kPa) and osteogenic (35 kPa) differentiation across all conditions. Biochemically induced osteogenic differentiation occurred as well as increased osteogenesis on larger extracellular matrix areas (above 5,000 μm2). The absence of clear trends for all variables demonstrates the atypical expression patterns that arise when variables that may work competitively or synergistically are considered together in a single, high‐throughput system.
Integrin signaling downregulates filopodia during muscle–tendon attachment

ABSTRACT Cells need to sense their environment to ensure accurate targeting to specific destinations. This occurs in developing muscles, which need to attach to tendon cells before muscle contractions can begin. Elongating myotube tips form filopodia, which are presumed to have sensory roles, and are later suppressed upon building the attachment site. Here, we use live imaging and quantitative image analysis of lateral transverse (LT) myotubes in Drosophila to show that filopodia suppression occurs as a result of integrin signaling. Loss of the integrin subunits αPS2 and βPS (also known as If and Mys, respectively, in flies) increased filopodia number and length at stages when they are normally suppressed. Conversely, inducing integrin signaling, achieved by the expression of constitutively dimerised βPS cytoplasmic domain (diβ), prematurely suppressed filopodia. We discovered that the integrin signal is transmitted through the protein G protein-coupled receptor kinase interacting ArfGAP (Git) and its downstream kinase p21-activated kinase (Pak). Absence of these proteins causes profuse filopodia and prevents the filopodial inhibition mediated by diβ. Thus, integrin signaling terminates the exploratory behavior of myotubes seeking tendons, enabling the actin machinery to focus on forming a strong attachment and assembling the contractile apparatus. Summary: Integrins signal through Git and Pak to downregulate filopodia when muscles reach their target attachment site in Drosophila.
Mammalian dendritic regrowth: a new perspective on neural repair.

can be used to identify neuronal subclasses (including RGCs). Dendritic morphology is commonly assessed using measurements of dendrite length, area, branching, and Sholl analysis, which involves counting the number of intersections between dendrites and concentric rings centred at the soma. Dendritic arbours shrink and lose complexity, or degenerate, in injury and disease. Along with dendritic morphology, circuit function requires the structural and functional integrity of synaptic connections.
Trends in Bone Marrow Sampling and Core Biopsy Specimen Adequacy in the United States and Canada: A Multicenter Study

Objectives To assess bone marrow (BM) sampling in academic medical centers. Methods Data from 6,374 BM samples obtained in 32 centers in 2001 and 2011, including core length (CL), were analyzed. Results BM included a biopsy (BMB; 93%) specimen, aspirate (BMA; 92%) specimen, or both (83%). The median (SD) CL was 12 (8.5) mm, and evaluable marrow was 9 (7.6) mm. Tissue contraction due to processing was 15%. BMB specimens were longer in adults younger than 60 years, men, and bilateral, staging, and baseline samples. Only 4% of BMB and 2% of BMB/BMA samples were deemed inadequate for diagnosis. BM for plasma cell dyscrasias, nonphysician operators, and ancillary studies usage increased, while bilateral sampling decreased over the decade. BM-related quality assurance programs are infrequent. Conclusions CL is shorter than recommended and varies with patient age and sex, clinical circumstances, and center experience. While pathologists render diagnoses on most cases irrespective of CL, BMB yield improvement is desirable.
A Gratuitous Grace: The Influence of Religious Set and Intent on the Psychedelic Experience

ABSTRACT Psychedelic drugs, or entheogens, have been used for religious purposes among various cultures for thousands of years. Recently, these substances have caught the attention of Westerners for many reasons, including their propensity to induce mystical experiences. This study examined the relationship between religion and having mystical experiences. A total of 119 participants were drawn from psychedelic-related websites and asked to complete an anonymous online questionnaire containing items regarding history of psychedelic use, set and setting for psychedelic use, and a measure for mystical experiences. A majority of respondents were White males who displayed at least some level of post-secondary education. The findings indicated that respondents who used psychedelics for specifically religious purposes, as well as those who identified with a religion, were more likely to score higher on the Mysticism Scale than those who did not.
A New Criterion for Pediatric AKI Based on the Reference Change Value of Serum Creatinine.

BACKGROUND Current definitions of AKI do not take into account serum creatinine's high variability in children. METHODS We analyzed data from 156,075 hospitalized children with at least two creatinine tests within 30 days. We estimated reference change value (RCV) of creatinine on the basis of age and initial creatinine level in children without kidney disease or known AKI risk, and we used these data to develop a model for detecting pediatric AKI on the basis of RCV of creatinine. We defined pediatric AKI according to pediatric reference change value optimized for AKI in children (pROCK) as creatinine increase beyond RCV of creatinine, which was estimated as the greater of 20 μmol/L or 30% of the initial creatinine level. RESULTS Of 102,817 children with at least two serum creatinine tests within 7 days, 5432 (5.3%) had AKI as defined by pROCK compared with 15,647 (15.2%) and 10,446 (10.2%) as defined by pediatric RIFLE (pRIFLE) and Kidney Disease Improving Global Outcomes (KDIGO), respectively. Children with pROCK-defined AKI had significantly increased risk of death (hazard ratio, 3.56; 95% confidence interval, 3.15 to 4.04) compared with those without AKI. About 66% of patients with pRIFLE-defined AKI and 51% of patients with KDIGO-defined AKI, mostly children with initial creatinine level of <30 μmol/L, were reclassified as non-AKI by pROCK, and mortality risk in these children was comparable with risk in those without AKI by all definitions. CONCLUSIONS pROCK criterion improves detection of "true" AKI in children compared with earlier definitions that may lead to pediatric AKI overdiagnosis.
Involvement of calvarial stem cells in healing: A regional analysis of large cranial defects

Large craniofacial defects present a substantial clinical challenge that often requires the use of osteoconductive matrices and osteoinductive cues (i.e., bone morphogenetic proteins [BMP2]) to augment healing. While these methods have improved clinical outcomes, a better understanding of how the osteogenic fronts surrounding the defect, the underlying dura mater, and the cranial suture area contribute to healing may lead to more targeted therapies to enhance bone regeneration. We hypothesized that healing within a large bone defect will be precipitated from cells within the remaining or available suture mesenchyme abutting the edges of a murine critical sized defect. To investigate this hypothesis, 39 adult, wild‐type mice were randomly arranged into groups (9 or 10 per group) by time (4 and 8 weeks) and treatment (control, acellular collagen sponge alone, or acellular collagen sponge loaded with a clinically relevant scaled dosage of BMP2). The skulls were then subjected to microcomputed tomography and histological analysis to assess bone regeneration in regions of interest within the defect area. A regional assessment of healing indicated that BMP2 drives greater healing than control and that healing emanates from the surgical margin, particularly from the margin associated with undisrupted suture mesenchyme. Though BMP2 treatment drove an increase in cell presence within the healing defect, there was no regional orientation of craniofacial stem cells or vascularity. Overall, these data reinforce that osteoconductive matrices in conjunction with osteoinductive peptides result in better healing of large calvarial defects. This healing is characterized as emanating from the surgical margin where there is an abundant supply of vasculature and progenitor cells.
Cost-effectiveness and economies of scale of a mass radio campaign to promote household life-saving practices in Burkina Faso

Introduction Child health promotion through mass media has not been rigorously evaluated for cost-effectiveness in low-income and middle-income countries. We assessed the cost-effectiveness of a mass radio campaign on health-seeking behaviours for child survival within a trial in Burkina Faso and at national scale. Methods We collected provider cost data prospectively alongside a 35-month cluster randomised trial in rural Burkina Faso in 2012–2015. Out-of-pocket costs of care-seeking were estimated through a household survey. We modelled intervention effects on child survival based on increased care-seeking and estimated the intervention’s incremental cost-effectiveness ratio (ICER) in terms of the cost per disability-adjusted life year (DALY) averted versus current practice. Model uncertainty was gauged using one-way and probabilistic sensitivity analyses. We projected the ICER of national-scale implementation in five sub-Saharan countries with differing media structures. All costs are in 2015 USD. Results The provider cost of the campaign was $7 749 128 ($9 146 101 including household costs). The campaign broadcast radio spots 74 480 times and 4610 2-hour shows through seven local radio stations, reaching approximately 2.4 million people including 620 000 direct beneficiaries (pregnant women and children under five). It resulted in an average estimated 24% increase in care-seeking for children under five and a 7% reduction in child mortality per year. The ICER was estimated at $94 ($111 including household costs (95% CI −38 to 320)). The projected provider cost per DALY averted of a national level campaign in Burkina Faso, Burundi, Malawi, Mozambique and Niger in 2018–2020, varied between $7 in Malawi to $27 in Burundi. Conclusion This study suggests that mass-media campaigns can be very cost-effective in improving child survival in areas with high media penetration and can potentially benefit from considerable economies of scale. Trial registration number NCT01517230; Results.
Metallothionein‐1 suppresses rheumatoid arthritis pathogenesis by shifting the Th17/Treg balance

It is now well accepted that an imbalance between the Th17 and regulatory T‐cell responses is closely associated with the development of rheumatoid arthritis (RA). However, the precise regulatory mechanism for the differentiation of Th17 and Treg in RA is not well characterized. The present study showed that metallothionein‐1 (MT‐1), which is a low molecular weight protein that is involved in the detoxification of heavy metals and scavenging of free radicals, was upregulated in RA. Furthermore, the synovial inflammation and pathologic symptoms in collagen‐induced arthritis and collagen antibody‐induced arthritis mice were significantly suppressed when MT‐1 was expressed intraarticularly. Further investigation revealed that MT‐1 inhibited the differentiation of Th17 cells but enhanced that of Treg cells. Furthermore, it markedly decreased both STAT3 and RAR‐related orphan receptor gamma t (RORγt) expression in vitro and in vivo. Collectively, our studies demonstrated that MT‐1 might manifest as a protein involved in immunosuppression of RA pathogenesis by shifting Th17/Treg balance and may prove to be a potential therapeutic target for RA autoimmune diseases.
American Diabetes Association 78th Scientific Sessions

Martin J. Kurian, Ann M. Carracher, and Kelly L. Close are of Close Concerns (http://www.closeconcerns.com), a healthcare information company focused exclusively on diabetes and obesity care. Close Concerns publishes Closer Look, a periodical that brings together news and insights in these areas. Each month, the Journal of Diabetes includes this News feature, in which Kurian, Carracher, and Close review the latest developments relevant to researchers and clinicians.