Strong π-stacking causes unusually large anisotropic thermal expansion and thermochromism.

π-stacking in ground-state dimers/trimers/tetramers of N-butoxyphenyl(naphthalene)diimide (BNDI) exceeds 50 kcal ⋅ mol-1 in strength, drastically surpassing that for the *3[pyrene]2 excimer (∼30 kcal ⋅ mol-1; formal bond order = 1) and similar to other weak-to-moderate classical covalent bonds. Cooperative π-stacking in triclinic (BNDI-T) and monoclinic (BNDI-M) polymorphs effects unusually large linear thermal expansion coefficients (α a , α b , α c , ß) of (452, -16.8, -154, 273) × 10-6 ⋅ K-1 and (70.1, -44.7, 163, 177) × 10-6 ⋅ K-1, respectively. BNDI-T exhibits highly reversible thermochromism over a 300-K range, manifest by color changes from orange (ambient temperature) toward red (cryogenic temperatures) or yellow (375 K), with repeated thermal cycling sustained for over at least 2 y.

Rapidly Reversible Organic Crystalline Switch for Conversion of Heat into Mechanical Energy.

Solid-state thermoelastic behavior-a sudden exertion of an expansive or contractive physical force following a temperature change and phase transition in a solid-state compound-is rare in organic crystals, few are reversible systems, and most of these are limited to a dozen or so cycles before the crystal degrades or they reverse slowly over the course of many minutes or even hours. Comparable to thermosalience, wherein crystal phase changes induce energetic jumping, thermomorphism produces physical work via consistent and near-instantaneous predictable directional force. In this work, we show a fully reversible thermomorphic actuator that is stable at room temperature for multiple years and is capable of actuation for more than 200 cycles at near-ambient temperature. Specifically, the crystals shrink to 90% of their original length instantaneously upon heating beyond 45 °C and expand back to their original length upon cooling below 35 °C. Furthermore, the phase transition occurs instantaneously, with little obvious hysteresis, allowing us to create real-time actuating thermal fuses that cycle between on and off rapidly.

Protein Aggregation Capture on Microparticles Enables Multipurpose Proteomics Sample Preparation.

Universal proteomics sample preparation is challenging because of the high heterogeneity of biological samples. Here we describe a novel mechanism that exploits the inherent instability of denatured proteins for nonspecific immobilization on microparticles by protein aggregation capture. To demonstrate the general applicability of this mechanism, we analyzed phosphoproteomes, tissue proteomes, and interaction proteomes as well as dilute secretomes. The findings present a practical, sensitive and cost-effective proteomics sample preparation method.

DNA methylation effects on tetra-nucleosome compaction and aggregation.

DNA CpG methylation has been associated with chromatin compaction and gene silencing. Whether DNA methylation directly contributes to chromatin compaction remains an open question. In this study, we used fluorescence fluctuation spectroscopy (FFS) to evaluate the compaction and aggregation of tetra-nucleosomes containing specific CpG patterns and methylation levels. The compactness of both unmethylated and methylated tetra-nucleosomes is dependent on DNA sequences. Specifically, methylation of the CpG sites located in the central dyad and the major grooves of DNA seem to have opposite effects on modulating the compactness of tetra-nucleosomes. The interactions among tetra-nucleosomes, however, seem to be enhanced because of DNA methylation independent of sequence contexts. Our finding can shed light on understanding the role of DNA methylation in determining nucleosome positioning pattern and chromatin compactness.

Safety and Feasibility of Hippocampal Sparing Cranial Radiation in Pediatric and Adolescent Acute Lymphoblastic Leukemia Patients: A Prospective Study.

Introduction Acute lymphoblastic leukemia (ALL) constitutes a significant portion of pediatric malignancies, with central nervous system (CNS) relapse posing a considerable threat to patient outcomes. While cranial radiation therapy (CRT) has been utilized to mitigate CNS relapse, it is associated with neurocognitive (NC) side effects. This study explores the feasibility and safety of using volumetric arc therapy (VMAT) with hippocampal sparing (HS) during cranial radiation therapy for ALL patients, aiming to reduce these side effects. Methodology This prospective observational study included pediatric and young adult patients with ALL who were in remission. HS was achieved using VMAT, and NC assessments were performed at baseline, six months, one year, and, to a limited extent, four years posttreatment. Results VMAT enabled precise hippocampal-sparing CRT with minimal dose to the hippocampus. Dosimetric analysis revealed that patients receiving 18 Gy had mean doses to planning target volume (PTV) and bilateral hippocampus of 18.9 and 9 Gy, respectively. Those receiving 12 Gy had corresponding doses of 13.3 and 7 Gy, respectively. Conformity and homogeneity indices were 0.9 and 0.1, and no brain relapses were observed among the patients in this study. NC assessments demonstrated no decline in intelligence quotient (IQ) scores over time, while only a subset of patients could be assessed at the four-year mark; telephone interviews suggested no significant cognitive decline. Conclusions This study highlights the potential of VMAT with HS as a promising approach to CRT for ALL patients in reducing the risk of NC side effects. The absence of brain relapses and preservation of NC function are encouraging findings, though larger studies are necessary to establish conclusive evidence.

Noninvasive Ventilation or CPAP in the Initial Treatment Phase of Small Infants With Respiratory Failure.

BACKGROUND: Respiratory failure in infants is a common reason for admission to the pediatric ICU (PICU). Although high-flow nasal cannula (HFNC) is the preferred first-line treatment at our institution, some infants require CPAP or noninvasive ventilation (NIV). Here we report our experience using CPAP/NIV in infants < 10 kg. METHODS: We conducted a retrospective review of infants < 10 kg treated with CPAP/NIV in our PICUs between July 2017-May 2021 in the initial phase of treatment. Demographic, support type and settings, vital signs, pulse oximetry, and intubation data were extracted from the electronic health record. We compared subjects successfully treated with CPAP/NIV with those who required intubation. RESULTS: We studied 62 subjects with median (interquartile range) age 96 [6.5-308] d and weight 4.5 (3.4-6.6) kg. Of these, 22 (35%) required intubation. There were no significant differences in demographics, medical history, primary interface, pre-CPAP/NIV support, and device used to deliver CPAP/NIV. HFNC was used in 57 (92%) subjects before escalation to CPAP/NIV. Subjects who failed CPAP/NIV were less likely to have bronchiolitis (27% vs 60%, P = .040), less likely to be discharged from the hospital to home (68% vs 93%, P = .02), had a longer median hospital length of stay (LOS) (26.9 [21-50.5] d vs 10.4 [5.6-28.4] d, P = .002), and longer median ICU LOS (14.6 [7.9-25.2] d vs 5.8 [3.8-12.4] d, P = .004). Initial vital signs and FIO2 were similar, but SpO2 was lower and FIO2 higher at 6 h and 12 h after support initiation for subjects who failed CPAP/NIV. Initial CPAP/NIV settings were similar, but subjects who failed CPAP/NIV had higher maximum and final inspiratory/expiratory pressure. CONCLUSIONS: Most infants who failed initial HFNC support were successfully managed without intubation using NIV or CPAP. Bronchiolitis was associated with a lower rate of CPAP/NIV failure, whereas lower SpO2 and higher FIO2 levels were associated with higher rates of intubation.

Empyema with pleuropulmonary mucormycosis.

Pleuropulmonary mucormycosis is relatively rare disease and that too localised disease is very rare but has got better prognosis. Maintaining a high level of suspicion is important in right clinical setting with pleuropulmonary involvement that fails to antibacterial agent either clinically or radiologically.

Noninvasive Ventilation or CPAP for Postextubation Support in Small Infants.

BACKGROUND: Infants with a high risk of extubation failure are often treated with noninvasive ventilation (NIV) or CPAP, but data on the role of these support modalities following extubation are sparse. This report describes our experience using NIV or CPAP to support infants following extubation in our pediatric ICUs (PICUs). METHODS: We performed a retrospective study of children < 10 kg receiving postextubation NIV or CPAP in our PICUs. Data on demographics, medical history, type of support, vital signs, pulse oximetry, near-infrared spectroscopy (NIRS), gas exchange, support settings, and re-intubation were extracted from the electronic medical record. Support was classified as prophylactic if planned before extubation and rescue if initiated within 24 h of extubation. We compared successfully extubated and re-intubated subjects using chi-square test for categorical variables and Mann-Whitney test for continuous variables. RESULTS: We studied 51 subjects, median age 44 (interquartile range 0.5-242) d and weight 3.7 (3-4.9) kg. There were no demographic differences between groups, except those re-intubated were more likely to have had cardiac surgery prior to admission (0% vs 14%, P = .040). NIV was used in 31 (61%) and CPAP in 20 (39%) subjects. Prophylactic support was initiated in 25 subjects (49%), whereas rescue support was needed in 26 subjects (51%). Twenty-two subjects (43%) required re-intubation. Re-intubation rate was higher for rescue support (58% vs 28%, P = .032). Subjects with a pH < 7.35 (4.3% vs 42.0%, P = .003) and lower somatic NIRS (39 [24-56] vs 62 [46-72], P = .02) were more likely to be re-intubated. The inspiratory positive airway pressure, expiratory positive airway pressure, and FIO2 were higher in subjects who required re-intubation. CONCLUSIONS: NIV or CPAP use was associated with a re-intubation rate of 43% in a heterogeneous sample of high-risk infants. Acidosis, cardiac surgery, higher FIO2 , lower somatic NIRS, higher support settings, and application of rescue support were associated with the need for re-intubation.

Timing of Treatment Outcomes and Risk Factors for Failure of BPAP in Patients Hospitalized for COPD Exacerbation.

BACKGROUND: Patients hospitalized for COPD exacerbation have an increased risk of mortality, particularly among those who fail bi-level positive airway pressure (BPAP) for hypercapnic respiratory failure subsequently requiring invasive mechanical ventilation. Therefore, we sought to investigate the treatment course of BPAP and factors associated with BPAP treatment failure. METHODS: We performed a retrospective cohort study using real-world evidence to investigate subjects with COPD who were treated with BPAP during a hospitalization for COPD exacerbation. Treatment outcomes were defined within 7 d from BPAP initiation as either failure, persistent, or success. Failure was defined as death or progression to invasive ventilation. Persistent was defined as receiving BPAP during hospital day 7. Success was defined as liberation from BPAP prior to hospital day 7 and not meeting criteria for failure. Unadjusted multinomial logistic regression models were used to examine the association between BPAP treatment outcomes and 17 recipient characteristics. RESULTS: Among the 427 clinical encounters, 78% were successful, 10% were persistent, and 12% experienced failure. The median time to failure and success was 8 h and 16 h, respectively. Increasing age, body mass index (BMI), bicarbonate level, and creatinine level were significantly associated with either BPAP treatment failure, persistent treatment, or both. CONCLUSIONS: The first 8 h following initiation of BPAP is a critical time period where patients are at high risk for life-threatening decompensation. Careful consideration should be given to increasing age, BMI, bicarbonate level, and creatinine level as these factors were associated with BPAP treatment failure or persistent treatment.

Targeting mutant p53-R248W reactivates WT p53 function and alters the onco-metabolic profile.

TP53 is the most commonly mutated gene in cancer, and gain-of-function mutations have wide-ranging effects. Efforts to reactivate wild-type p53 function and inhibit mutant functions have been complicated by the variety of TP53 mutations. Identified from a screen, the NSC59984 compound has been shown to restore activity to mutant p53 in colorectal cancer cells. Here, we investigated its effects on esophageal adenocarcinoma cells with specific p53 hot-spot mutations. NSC59984 treatment of cells reactivated p53 transcriptional regulation, inducing mitochondrial intrinsic apoptosis. Analysis of its effects on cellular metabolism demonstrated increased utilization of the pentose phosphate pathway and inhibition of glycolysis at the fructose-1,6-bisphosphate to fructose 6-phosphate junction. Furthermore, treatment of cells with NSC59984 increased reactive oxygen species production and decreased glutathione levels; these effects were enhanced by the addition of buthionine sulfoximine and inhibited by N-acetyl cysteine. We found that the effects of NSC59984 were substantially greater in cells harboring the p53 R248W mutation. Overall, these findings demonstrate p53-dependent effects of NSC59984 on cellular metabolism, with increased activity in cells harboring the p53 R248W mutation. This research highlights the importance of defining the mutational status of a particular cancer to create a patient-centric strategy for the treatment of p53-driven cancers.

A comparative immunohistochemical analysis of cortactin in orthokeratinized odontogenic cyst (OOC), sporadic odontogenic keratocyst (OKC), and syndromic OKC.

OBJECTIVES: To evaluate and compare the immunohistochemical expression of cortactin in the epithelial lining of orthokeratinized odontogenic cyst (OOC), sporadic odontogenic keratocyst (OKC), and syndromic OKC. METHODS: Formalin-fixed paraffin-embedded tissue blocks of histopathologically diagnosed cases of OOC, OKC, syndromic OKC, normal buccal mucosa (NBM), and oral squamous cell carcinoma (OSCC) were examined for immunohistochemical expression of cortactin. Clear brown cytoplasmic and membranous staining was considered positive. RESULTS: A statistically significant difference was observed between OOC and syndromic OKC (p < 0.001), as well as between sporadic OKC and syndromic OKC (p < 0.001). Although not statistically significant, the expression of cortactin was slightly higher in the basal layer of NBM (mean = 0.47), OOC (mean = 0.27), sporadic OKC (mean = 0.47) syndromic OKC (mean = 1.53), and OSCC (mean = 0.67) than in the parabasal layers of NBM (mean = 0.27), OOC (mean = 0.20), sporadic OKC (mean = 0.47), syndromic OKC (mean = 1.27), and OSCC (mean = 0.60). CONCLUSION: The expression of cortactin in the basal layer may suggest the formation of invadopodia in the basal layer where the invasion mechanism occurs. This finding is further supported by the higher localization of cortactin in areas of epithelial budding and daughter cysts in syndromic OKC, thereby reaffirming its possible association with recurrence.

Proteomics-Based Comparative Mapping of the Secretomes of Human Brown and White Adipocytes Reveals EPDR1 as a Novel Batokine.

Adipokines secreted from white adipose tissue play a role in metabolic crosstalk and homeostasis, whereas the brown adipose secretome is less explored. We performed high-sensitivity mass-spectrometry-based proteomics on the cell media of human adipocytes derived from the supraclavicular brown adipose and from the subcutaneous white adipose depots of adult humans. We identified 471 potentially secreted proteins covering interesting categories such as hormones, growth factors, extracellular matrix proteins, and proteins of the complement system, which were differentially regulated between brown and white adipocytes. A total of 101 proteins were exclusively quantified in brown adipocytes, and among these was ependymin-related protein 1 (EPDR1). EPDR1 was detected in human plasma, and functional studies suggested a role for EPDR1 in thermogenic determination during adipogenesis. In conclusion, we report substantial differences between the secretomes of brown and white human adipocytes and identify novel candidate batokines that can be important regulators of human metabolism.

Oncogenes and pathway identification using filter-based approaches between various carcinoma types in lung.

Lung cancer accounts for the most cancer-related deaths. The identification of cancer-associated genes and the related pathways are essential to prevent many types of cancer. In this paper, a more systematic approach is considered. First, we did pathway analysis using Hyper Geometric Distribution (HGD) and significantly overrepresented sets of reactions were identified. Second, feature-selection-based Particle Swarm Optimisation (PSO), Information Gain (IG) and the Biomarker Identifier (BMI) for the identification of different types of lung cancer were used. We also evaluated PSO and developed a new method to determine the BMI thresholds to prioritize genes. We were able to identify sets of key genes that can be found in several pathways. Experimental results show that our method simplifies features effectively and obtains higher classification accuracy than the other methods from the literature.

Child survival--the survival of a perinate.

PIP: While there is indeed an increasing awareness and a feeling for immediately improving the presently available health care to an expectant mother and her newborn, it must be questioned whether it is feasible in India to do so in the time and with the resources available. The task appears to be as gigantic and formidable as the gap between what is desirable and what is available is wide. It is further compounded by the fact that while several strategies have been suggested, hardly any have been attempted at operational level or demonstrated to be replicable. The choice therefore, remains either to leave the situation as it is and hope that with time things will improve, or to make an earnest and concerted effort to accept the challenge and improve the situation. An approach that is practical, acceptable, cost effective, and within means for adoption will have to be made. It is of paramount importance to realize that in a country the size of India, with diversity in all spheres of life, it would be imprudent to think of a single common approach. It would thus be necessary to 1st identify the local problem, do a situational analysis, and then to prioritize problems to prioritively use the available resources. However, a general plan of action can be suggested for implementation. This would include: 1) community awareness; 2) delivery of perinatal and neonatal care; training and reorientation; 4) prevention of low birth weight; and 4) health education.^ieng