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Abstract Background Cisplatin (CDDP) remains a key agent in the treatment of muscle-infiltrating bladder carcinoma (MIBC). However, a proportion of MIBC patients do not respond to chemotherapy, which may be caused by the increased repair of CDDP-induced DNA damage. The purpose of this study was to explore the prognostic value of proteins involved in nucleotide excision repair (NER) and translesion DNA synthesis (TLS) in MIBC patients. Methods This is a retrospective analysis of 86 MIBC patients. The XPA, XPF, XPG, ERCC1, POLI, POLH and REV3L proteins were stained in primary bladder tumors and their levels were analyzed both in the total cohort and in a subgroup with metastatic urothelial carcinoma (mUC) that received gemcitabine and CDDP as a first-line therapy. Both cohorts were divided by percentage of cancer cells stained positive for each protein into subgroups with high and low expression. In the same manner, the combined expression of NER (XPA + ERCC1 + XPF + XPG) and TLS (POLI + POLH + REV3L), as the whole pathways, was analyzed. Results Mortality was 89.5% at the median follow-up of 120.2 months. In the total cohort, patients with tumors stained positive for XPA, XPG and POLI had significantly worse overall survival (OS) compared to those with negative staining [hazard ratio (HR) = 0.60, 0.62 and 0.53, respectively]. Both XPG and POLI were independent prognostic factors in multivariate analyses (MVA). In addition, an increase in NER and TLS pathway expression was significantly associated with worse OS in the total cohort (HR = 0.54 and 0.60, respectively). In the mUC subgroup, high POLI expression was associated with significant deterioration of OS (HR = 0.56) in univariate analyses, and its independent prognostic value was shown in MVA. Conclusions Our study showed significant correlations between the tumor expression of XPG and POLI, as well as NER and TLS as the whole pathways, and inferior OS. Hence, they could constitute prognostic biomarkers and potentially promising therapeutic targets in MIBC. However, a prospective trial is required for further validation, thereby overcoming the limitations of this study.

We make two interventions in two evolving scholarly literatures. First, we show how fractal metaphors escape a recurring dichotomy in Christian pedagogical scholarship, the either/or of alienation from one's object of study versus union with it in "an act of love." Second, we try to replace recent interdisciplinary work's emphasis on "complexity" with "irreducibility." Fractals allow us to define these concepts and develop alternative "ways of knowing" with greater rigor. Both interventions bear directly on Christian formation, and so we derive five ways the Christian classroom can combat spiritual alienation and instead cultivate the "fractal imagination" of our students.

Abstract Background Germ cell tumours (GCTs) represent a highly curable malignity as they respond well to cisplatin (CDDP)-based chemotherapy. Nevertheless, a small proportion of GCT patients relapse or do not respond to therapy. As this might be caused by an increased capacity to repair CDDP-induced DNA damage, identification of DNA repair biomarkers predicting inadequate or aberrant response to CDDP, and thus poor prognosis for GCT patients, poses a challenge. The objective of this study is to examine the expression levels of the key nucleotide excision repair (NER) factors, XPA, ERCC1 and XPF, in GCT patients and cell lines. Methods Two hundred seven GCT patients’ specimens with sufficient follow-up clinical-pathological data and pairwise combinations of CDDP-resistant and -sensitive GCT cell lines were included. Immunohistochemistry was used to detect the ERCC1, XPF and XPA protein expression levels in GCT patients’ specimen and Western blot and qRT-PCR examined the protein and mRNA expression levels in GCT cell lines. Results GCT patients with low XPA expression had significantly better overall survival than patients with high expression (hazard ratio = 0.38, 95% confidence interval: 0.12–1.23, p = 0.0228). In addition, XPA expression was increased in the non-seminomatous histological subtype, IGCCCG poor prognosis group, increasing S stage, as well as the presence of lung, liver and non-pulmonary visceral metastases. Importantly, a correlation between inadequate or aberrant CDDP response and XPA expression found in GCT patients was also seen in GCT cell lines. Conclusions XPA expression is an additional independent prognostic biomarker for stratifying GCT patients, allowing for improvements in decision-making on treatment for those at high risk of refractoriness or relapse. In addition, it could represent a novel therapeutic target in GCTs.

Adolescence is a period of profound biopsychosocial development, with pubertally-driven neural reorganization as social demands increase in peer contexts. The explosive increase in social media access has fundamentally changed peer interactions among youth, creating an urgent need to understand its impact on neurobiological development and mental health. Extant literature indicates that using social media promotes social comparison and feedback seeking (SCFS) behaviors in youth, which portend increased risk for mental health disorders, but little is known about its impact on neurobiological development. We assessed social media behaviors, mental health symptoms, and spontaneous cortical activity using magnetoencephalography (MEG) in 80 typically developing youth (8–16 years) and tested how self-reported pubertal stage moderates their relationship. More mature adolescents who engaged in more SCFS showed weaker fusiform/parahippocampal alpha and medial prefrontal beta activity, and increased symptoms of anxiety and attention problems. Engaging in SCFS on social media during adolescence may thus relate to developmental differences in brain regions that undergo considerable development during puberty. These results are consistent with works indicating altered neurodevelopmental trajectories within association cortices surrounding the onset of many mental health disorders. Importantly, later pubertal stages may be most sensitive to the detrimental effects of social media use.

The flying agility demonstrated by dragonflies is accomplished by means of complex aerodynamic forces produced by flapping their four wings arranged in a tandem configuration. The current study presents a novel tandem flapping wing mechanism for a biomimetic air vehicle that was designed and manufactured to experimentally investigate the aerodynamic forces. By optimizing the configuration and using spatial network analysis, it is shown that the designed structure can flap the wings in a linear up–down stroke motion and is capable of maintaining good consistency and aerodynamic performance. Such a mechanism could be used in a future biomimetic micro air vehicle (BMAV) design. The mechanism uses an electromagnetic actuator to flap the wings with a variable beat frequency (30–210 Hz) at various angles of attack (−10°–20°). The results show that the tandem wings generate approximately 50% higher lift than the forewing or hindwing pairs acting alone. Tandem wings also improve stability, which could potentially allow hovering.

Abstract In magnetic systems, spin and exchange disorder can provide access to quantum criticality, frustration, and spin dynamics, but broad tunability of these responses and a deeper understanding of strong limit disorder are lacking. Here, it is demonstrated that high entropy oxides present a previously unexplored route to designing materials in which the presence of strong local compositional disorder may be exploited to generate tunable magnetic behaviors—from macroscopically ordered states to frustration‐driven dynamic spin interactions. Single‐crystal La(Cr0.2Mn0.2Fe0.2Co0.2Ni0.2)O3 films are used as a model system hosting a magnetic sublattice with a high degree of microstate disorder in the form of site‐to‐site spin and exchange type inhomogeneity. A classical Heisenberg model simplified to represent the highest probability microstates well describes how compositionally disordered systems can paradoxically host magnetic uniformity and demonstrates a path toward continuous control over ordering types and critical temperatures. Model‐predicted materials are synthesized and found to possess an incipient quantum critical point when magnetic ordering types are designed to be in direct competition, this leads to highly controllable exchange bias behaviors previously accessible only in intentionally designed bilayer heterojunctions.

Purpose Obesity can make bone marrow biopsy using manual landmarks as guidance technically challenging. This retrospective review was performed to assess the safety and technical success of performing bone marrow biopsies with computed tomography (CT)–guidance in obese patients. Materials and Methods This single-institution, retrospective study included 1,016 CT-guided bone marrow biopsies performed between 2009 and 2016. Thirty-four percent (n = 348) were performed in patients with a body mass index (BMI) of 30 kg/m2 or greater, and 7% (n = 75) were performed in patients with a BMI greater than 40 kg/m2. Demographic information, BMI, and complications were reviewed. The primary endpoint was technical success and procedurally related hemorrhagic complication. The electronic medical record was reviewed to identify procedural related hemorrhagic complications, Common Terminology Criteria for Adverse Events (CTCAE) Grade 3 or above. The complication rates in obese patients were compared with patients with a BMI less than 30 kg/m2. Results Biopsy was successfully performed in all patients. No biopsies resulted in a CTCAE Grade 3 or above complication. There was no difference in complication rate (0%) based on BMI. For patients with a BMI < 30 kg/m2, BMI ≥ 30 kg/m2, and BMI > 40 kg/m2, complications rates were 0% (95% confidence interval [CI]: 0–0.4%), 0% (95% CI: 0–0.9%), and 0% (95% CI: 0–4%), respectively. Conclusions CT-guided bone marrow biopsy in obese patients can be performed with a high rate of technical success and is safe. If patient body habitus limits the ability to palpate physical landmarks needed to perform bone marrow biopsy without image guidance, CT-guided bone marrow biopsy should be considered.

The interface between magnetic materials and topological insulators can drive the formation of exotic phases of matter and enable functionality through the manipulation of the strong spin polarized transport. Here, we report that the transport processes that rely on strong spin-momentum locking in the topological insulator Bi2Se3 are completely suppressed by scattering at a heterointerface with the kagome-lattice paramagnet, Co7Se8. Bi2Se3–Co7Se8–Bi2Se3 trilayer heterostructures were grown using molecular beam epitaxy, where magnetotransport measurements revealed a substantial suppression of the weak antilocalization effect for Co7Se8 at thicknesses as thin as a monolayer, indicating a strong dephasing mechanism. Bi2−xCoxSe3 films, in which Co is in a non-magnetic 3+ state, show weak antilocalization that survives to higher than x = 0.4, which, in comparison with the heterostructures, suggests that the unordered moments of Co2+ act as a far stronger dephasing element. This work highlights several important points regarding coherent transport processes involving spin-momentum locking in topological insulator interfaces and how magnetic materials can be integrated with topological materials to realize both exotic phases and novel device functionality.

A new class of ceramics, called entropy stabilized oxides, High Entropy Oxides (HEOs), multicomponent oxides, compositionally complex oxides, or polycation oxides, has generated considerable research interest since the first report in 2015. This multicomponent approach has created new opportunities for materials design and discovery. This Perspective will highlight some current research developments and possible applications while also providing an overview of the many successfully synthesized HEO systems to date. The polycation approach to composition development will be discussed along with a few case studies, challenges, and future possibilities afforded by this novel class of materials.