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Gliomas arising in the setting of neurofibromatosis type 1 (NF1) are heterogeneous, occurring from childhood through adulthood, can be histologically low-grade or high-grade, and follow an indolent or aggressive clinical course. Comprehensive profiling of genetic alterations beyond NF1 inactivation and epigenetic classification of these tumors remain limited. Through next-generation sequencing, copy number analysis, and DNA methylation profiling of gliomas from 47 NF1 patients, we identified 2 molecular subgroups of NF1-associated gliomas. The first harbored biallelic NF1 inactivation only, occurred primarily during childhood, followed a more indolent clinical course, and had a unique epigenetic signature for which we propose the terminology “pilocytic astrocytoma, arising in the setting of NF1”. The second subgroup harbored additional oncogenic alterations including CDKN2A homozygous deletion and ATRX mutation, occurred primarily during adulthood, followed a more aggressive clinical course, and was epigenetically diverse, with most tumors aligning with either high-grade astrocytoma with piloid features or various subclasses of IDH-wildtype glioblastoma. Several patients were treated with small molecule MEK inhibitors that resulted in stable disease or tumor regression when used as a single agent, but only in the context of those tumors with NF1 inactivation lacking additional oncogenic alterations. Together, these findings highlight recurrently altered pathways in NF1-associated gliomas and help inform targeted therapeutic strategies for this patient population.

Context.— Glioma is the most common primary brain tumor in adults. The diagnosis and grading of different pathological subtypes of glioma is essential in treatment planning and prognosis. Objective.— To propose a deep learning–based approach for the automated classification of glioma histopathology images. Two classification methods, the ensemble method based on 2 binary classifiers and the multiclass method using a single multiclass classifier, were implemented to classify glioma images into astrocytoma, oligodendroglioma, and glioblastoma, according to the 5th edition of the World Health Organization classification of central nervous system tumors, published in 2021. Design.— We tested 2 different deep neural network architectures (VGG19 and ResNet50) and extensively validated the proposed approach based on The Cancer Genome Atlas data set (n = 700). We also studied the effects of stain normalization and data augmentation on the glioma classification task. Results.— With the binary classifiers, our model could distinguish astrocytoma and oligodendroglioma (combined) from glioblastoma with an accuracy of 0.917 (area under the curve [AUC] = 0.976) and astrocytoma from oligodendroglioma (accuracy = 0.821, AUC score = 0.865). The multiclass method (accuracy = 0.861, AUC score = 0.961) outperformed the ensemble method (accuracy = 0.847, AUC = 0.933) with the best performance displayed by the ResNet50 architecture. Conclusions.— With the high performance of our model (>80%), the proposed method can assist pathologists and physicians to support examination and differential diagnosis of glioma histopathology images, with the aim to expedite personalized medical care.

In 2020–2021, the Boston Library Consortium (BLC) explored the potential for controlled digital lending (CDL) across the library consortium. Over the course of a year, the BLC's CDL Working Group engaged with internal stakeholders and external partners to develop a strategic vision for consortial CDL that received strong support from the BLC's Board of Directors. The group arrived at this vision through intensive collaboration, working closely as a group and engaging with the BLC's various membership communities while concurrently engaging with vendors and external entities to cross-pollinate ideas and co-create strategies. The BLC's resultant vision for consortial CDL is also predicated on powerful intra-consortial and inter-consortial collaborations to create the technologies for making CDL possible. This chapter is a case study of how this vision emerged and demonstrates its applicability to other types of consortial collaboration.

Triggering new stable macroscopic orders in materials by ultrafast optical or terahertz pump pulses is a difficult challenge, complicated by the interplay between multiscale microscopic mechanisms, and macroscopic excitation profiles in samples. In particular, the differences between the two types of excitations are still unclear. In this article, we compare the optical response on acoustic timescale of a V

In the scientific literature on innovation, there is a growing interest of researchers and academics in the analysis and discussion of the phenomenon of open innovation, as well as in the documentation of the contribution of empirical evidence of the capacities of the development of new products. However, little is known about the relationship between open innovation practices, new product development, and business performance, which is why there is a call from researchers, academics, and industry professionals, for future guidance, studies in the analysis and discussion of these three constructs through large samples that allow generalization of the results obtained, for which this research has the main objective of filling this gap in the literature through an extensive review of the literature. Likewise, a self-administered questionnaire was distributed to a sample of 460 manufacturing companies in Mexico, analyzing the data set through confirmatory factor analysis and structural equation models. The results obtained suggest that open innovation practices have significant positive effects on both the development of new products and the business performance of manufacturing companies in the automotive industry. JEL classification numbers: M31 Keywords: Open innovation practices, Product development, Firm performance, Manufacturing firms.

In 2020–2021, the University of Connecticut (UConn) Library ceased more than 90% of its print journal subscriptions for the general collections. This decision was the outcome of a data-based review and cost-benefit analysis. Staff considered factors such as online availability, number of WorldCat holdings, scan-on-demand and interlibrary lending and borrowing activity, and hidden costs of storage and staff time for processing. Recorded usage proved all but nonexistent, with an annual average use of one per title. Additionally, print journals were inaccessible to patrons because of the closure of library stacks during the COVID-19 pandemic. We did not conduct an extensive qualitative review. UConn Library’s decisions broke new ground among U.S. research universities, which have winnowed their print subscriptions over the decades but rarely made a decisive break from print. This article will discuss the project, process, decisions, and data and will share UConn’s assessment strategies and criteria for reinstituting subscriptions. At stake was the principle that libraries must use their scarce resources effectively—at any scale. [ABSTRACT FROM AUTHOR] Copyright of Serials Review is the property of Routledge and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Fragile perinatal and fetal brains are the rule rather than the exception for developmental neuropathologists. Retrieving the fresh brain from the skull and examining early fetal, macerated or severely hydrocephalic brains after fixation can be a challenge. Textbooks on neurodevelopmental pathology mention these challenges to macroscopic examination of the developing central nervous system only in passing, but many perinatal pathologists recognize this diagnostic problem. We reviewed protocols and publications on the removal, fixation, slicing and sampling of these fetal- and perinatal brains. In addition, we describe a technique to facilitate the removal of severely hydrocephalic brains with very thin cerebral walls from the skull by replacing the intraventricular fluid with agar in-situ. Furthermore, we present a method for post-fixation pre-embedding in agar to facilitate slicing, macroscopic examination and sampling of fragile and macerated brains.

Introduction Silent corticotroph adenomas (SCA) are characterised by an absence of cortisol excess yet show positive immunostaining for T-Box transcription factor (TPIT) and frequently adrenocorticotropic hormone (ACTH). Patients with a SCA commonly present with symptoms of mass effect such as headache or visual compromise or are identified incidentally on imaging. SCAs are high risk according to the WHO 2017 classification scheme. Aim To assess our cohort of SCAs for differences in demographics, presenting symptoms and imaging results compared to other non-functioning pituitary adenomas (NFPA). Methods Surgically treated patients with NFPAs seen by endocrinology at an Australian Tertiary Centre between the years 2011-2021 were included in the analysis. SCA was diagnosed based on the absence of clinical and biochemical features of cortisol excess in combination with immunohistochemical staining including positive staining for ACTH. Other NFPA subtypes were defined by immunohistochemical staining and the absence of hormone overproduction. We compared demographic information, symptoms at presentation and tumour size as assessed by magnetic resonance imaging (MRI) between the SCA and all other NFPA groups. Where available, pre- and postoperative ACTH and cortisol levels were compared in the SCA and non-SCA groups. Results 31 patients were identified, 5 with SCA and 26 with other NFPA, all were macroadenomas. All 5 cases of SCA showed ACTH positivity, 2 of 5 cases were stained for TPIT, both were positive. Mean age at surgery for the SCA group was 50.8±10.9 years. Mean non-SCA age was 54.3±15.4 years. 3 of the 5 patients with SCA were women. The most frequent symptoms at presentation were headache (SCA: 40%; non-SCA 36%) and visual disturbances (SCA: 60%; non-SCA 68%). The mean maximal tumour diameter in the SCA group was 31.36±13.61 mm versus 24.65±6.80 mm in the non-SCA group on MRI. Cavernous sinus invasion was present in 60% of the SCA and 38.5% of the non-SCA group. In the SCA group pre-operative ACTH levels were 5.1±2.6 pmol/L (normal Conclusion In this retrospective comparison, compared to other NFPAs the SCA group showed younger age, more frequent headaches, less visual compromise, larger tumour size and increased cavernous sinus invasion. These findings are consistent with the known aggressiveness of SCAs. The reduction in ACTH levels postoperatively support the concept that SCAs produce inactive forms of ACTH. Although this is a small case series, there may be merit in monitoring for relative increases in ACTH levels in patients with a history of SCA. Presentation: No date and time listed

In our study, a measure of Mobile CRM (mCRM) is adapted and applied to salespeople in a business-to-business sales context. We propose a research model that integrates Technology Acceptance Model and DeLone and McLean’s IS success model to investigate the impact mCRM has on sales performance. Relationships with sales business process, traditional CRM use, collaboration and sales performance are conceptualized and tested. Results suggest that sales performance is highest when digital tools such as mCRM are supported by sales process. Results also suggest that mCRM impacts the relationship performance with customers when collaboration mediates the relationship. Overall, the research empirically demonstrates that mCRM plays an important role in traditional CRM adoption and in sales performance when sales process capabilities and collaboration are involved.

Since its discovery in 2007, we have seen the lives of patients diagnosed with advanced anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancers (NSCLC) transform with the advent of molecular therapies with first-, second-, and third-generation ALK inhibitors now available in the clinic. Despite great gains in patient survival now measured in years and preserved quality of life with targeted therapies, drug resistance is unfortunately inevitably encountered in this rare and unique molecular subset of lung cancer, and patients will eventually succumb to the disease. As these patients are often young, fit, and never smokers, the clinical and scientific communities have aligned to expedite drug development and access. Drug resistance profiling and further strategies are being explored through clinical trials, including the evaluation of specific drug sequencing and combinations to overcome such resistance and promote patient longevity. The cases of this report focus on precision medicine and aim to portray the pertinent aspects to consider when treating ALK-rearranged NSCLC in 2020, an ever-shifting space. By way of case examples, this report offers valuable information to the treating clinician, including the evolution of systemic treatments and the management of oligo-progression and multisite drug resistance. With the maturation of real-world data, we are fortunate to be experiencing quality and length of life for patients with this disease surpassing prior expectations in advanced lung cancer. Key Points This report focuses on the importance of genetic analysis of serial biopsies to capture the dynamic therapeutic vulnerabilities of a patient's tumor, providing a perspective on the complexity of ALK tyrosine kinase inhibitor (ALKi) treatment sequencing. These case examples contribute to the literature on ALK-rearranged and oncogene addicted non-small cell lung cancer (NSCLC), providing a framework for care in the clinic. In oligo-progressive disease, local ablative therapy and continuation of ALKi postprogression should be considered with potential for sustained disease control. ALK G1202R kinase domain mutations (KDM), highly prevalent at resistance to second-generation ALKi resistances, may emerge in non-EML4-ALK variant 3 cases and is sensitive to third-generation lorlatinib. When in compound with one or more ALK KDMs, resistance to lorlatinib is expected. In the case of rampantly progressive disease, rebiopsy and redefining biology in a timely manner may be informative.

Indiastat aggregates socioeconomic statistical data about India from 2000 to the present. Data are browsable by economic sector, state, and region. Visitors can view, print, or download data tables in spreadsheet, word processing, and web formats. Available statistics should add value for global business research, and Indiastat is the sole globally accessible source for much of this content. On the other hand, the product has a cumbersome user interface, poor searchability, and steep pricing. While the content may trump these concerns for institutions with specialized academic programs and research areas, most academic libraries will continue to rely on free statistical data provided by the Indian government and international nongovernmental organizations.

Accessibility of library electronic resources is a must. Its importance derives from professional ethics of librarianship, rising total costs of acquisition, and mounting legal challenges to colleg...

Morphological differences in the dentate gyrus (DG) have been reported in sudden unexpected deaths in infancy (SUDI), with the feature of focal granule cell (GC) bilamination (FGCB) reported as increased in unexplained SUDI, including sudden infant death syndrome (SIDS), compared with explained SUDI (eSUDI). However, it remains to be determined how these morphologies relate to each other and their extent along the anteroposterior length. This retrospective study evaluated the prevalence of FGCB, single or clustered ectopic GCs, granule cell dispersion (GCD), heterotopia, hyperconvolution, gaps, thinning, blood vessel dissection (BVD), and cuffing (BV cuffing), in an Australian SUDI cohort, and compared the prevalence of these features in eSUDI and unexplained SUDI. We analyzed 850 formalin-fixed paraffin-embedded serial and subserial sections of the hippocampus at the level of the lateral geniculate nucleus from 90 infants, and identified GCD in 97% of infants, single ectopic cells, hyperconvolution, thinning, and BVD in 60%-80%, heterotopia in 36%, gaps, clusters of ectopic cells and BV cuffing in 9%–15%, and FGCB in 18%. These features are clustered within 3–5 serial sections. The presence of FGCB correlated with single ectopic GCs and hyperconvolution. There were no differences in the prevalence of these features between unexplained SUDI (n = 74) and eSUDI (n = 16). Our findings highlight that DG morphological features are highly localized, extending 14–35 µm at their focal location(s) along the anteroposterior length. Consequently, multiple sections along the longitudinal extent are required to identify them. No feature differentiated SUDI from eSUDI in our cohort, thus we cannot conclude that any of these features are abnormal and it remains to be determined their functional significance.

Diffuse leptomeningeal glioneuronal tumours (DLGNT) represent rare enigmatic CNS tumours of childhood. Most patients with this disease share common radiological and histopathological features but the clinical course of this disease is variable. A radiological hallmark of this disease is widespread leptomeningeal enhancement that may involve the entire neuroaxis with predilection for the posterior fossa and spine. The classic pathologic features include low- to moderate-density cellular lesions with OLIG2 expression and evidence of ‘oligodendroglioma-like’ appearance. The MAPK/ERK signaling pathway has recently been reported as a potential driver of tumourigenesis in up to 80% of DLGNT with KIAA1549:BRAF fusions being the most common event seen. Until now, limited analysis of the biological drivers of tumourigenesis has been undertaken via targeted profiling, chromosomal analysis and immunohistochemistry. Our study represents the first examples of comprehensive genomic sequencing in DLGNT and shows that it is not only feasible but crucial to our understanding of this rare disease. Moreover, we demonstrate that DLGNT may be more genomically complex than single-event MAPK/ERK signaling pathway tumours. Supplementary Information The online version contains supplementary material available at 10.1186/s40478-021-01248-w.

Background Translating outcomes achieved by clinical trials into routine care is crucial to improving outcomes of glioblastoma (GBM). This study examines the extent to which an advance in treatment for GBM has translated into meaningful, population-level survival benefits in New South Wales (NSW), Australia. Methods This retrospective cohort study used linked population-based cancer registry, admitted patient, and mortality datasets. The cohort (n = 2604) included NSW residents aged ≥18 years with a histologically confirmed GBM and a surgical resection between July 2001 and December 2012. The study outcome was all-cause survival, examined using multivariable proportional hazard models. The main study factor was period of surgery, categorized into 4 periods corresponding to different eras in temozolomide (TMZ) use. Survival was examined over time by age (≤70 and >70 years) and for a subcohort selected to approximate the seminal European Organisation for Research and Treatment of Cancer (Stupp) protocol trial cohort. TMZ use was estimated using aggregate prescription claims data. Results Median survival in 2001-2003, 2004-2006, 2007-2009, and 2010-2012 was 7.4, 9.0, 9.8, and 10.6 months, and risk-adjusted 2-year survival was 8.2%, 13.8%, 15.5%, and 18.3%, respectively. Survival improved for those aged ≤70 years and those aged >70 years. In the proxy trial subcohort, median and 2-year survival were 14.3 months and 27.3%, respectively. The volume of TMZ prescribed annually increased rapidly from 2005. Conclusions Introduction of TMZ into standard care in 2005 coincided with improvements in survival and a rapid increase in TMZ prescribing. Optimization of care has continued to improve survival of people with GBM in subsequent years.

This article draws on a case study at the University of Connecticut Library to present best practices for managing license documents as well as tracking and communicating terms of use and performan...

Purpose: The current study explores the latest generation of the workforce, Generation Z/Millennial cusp, and the loyalty concerns hiring managers’ experience. The authors explore how the character...

The brainstem has been a focus of sudden infant death syndrome (SIDS) research with amassing evidence of increased neuronal apoptosis. The present study extends the scope of brain regions examined and determines associations with known SIDS risk factors. Immunohistochemical expression of cell death markers, active caspase-3 and TUNEL, was studied in 37 defined brain regions in infants (aged 1–12 months) who died suddenly and unexpectedly (SUDI). A semi-quantitative mean score of marker expression was derived for each region and scores compared between three SUDI subgroups: explained SUDI (eSUDI; n = 7), SIDS I (n = 8) and SIDS II (n = 13). In eSUDI, active caspase-3 scores were highest in several nuclei of the rostral medulla, and lowest in the hypothalamus and cerebellar grey matter (GM). TUNEL was highest in regions of the hippocampus and basal ganglia, and lowest in the thalamus and cerebellar GM. TUNEL scores were higher in SIDS II compared to eSUDI in the amygdala (p = 0.03) and 5/9 nuclei in the rostral medulla (p = 0.04 − 0.01), and higher in SIDS II compared to SIDS I in the amygdala (p

Introduction: Opioid overprescription after surgery results in a surplus of tablets that become available for diversion and abuse. This study aims to describe opioid consumption after common elective outpatient cosmetic surgeries to provide a reference for surgeons and deter preemptive overprescription. Secondary endpoints were risk factors for increased opioid use after cosmetic surgery and the influence of helium plasma technology (Renuvion; Apyx Medical Corporation, Clearwater, Florida) on postoperative opioid consumption. Materials and Methods: Patients completed a preoperative survey on the day of surgery and a postoperative survey 14 to 21 days after surgery. Data regarding procedure type, demographics, quantity of prescribed opioids, pain experience, amount of opioids consumed, and supplementation with over-the-counter pain medications or alternative therapies were collected. Results: Two hundred sixty-six patients were included. On average, 28 opioid pills were prescribed, and 13.8 pills were consumed across all cosmetic surgery types. Procedure type, body mass index, ethnicity, prior surgical history, and the incorporation of helium plasma technology did not influence opioid consumptions postoperatively. Patients with a surgical complication had a statistically significant higher opioid use than those without a surgical complication ( P = .0397). Conclusions: Patients in our study required on average about half of the opioids prescribed during the immediate postoperative period. Means of opioids consumed per cosmetic surgery category are described and can serve as a reference for cosmetic surgeons.

In about half of all patients with a suspected monogenic disease, genomic investigations fail to identify the diagnosis. A contributing factor is the difficulty with repetitive regions of the genome, such as those generated by segmental duplications. TheWhole exome, whole genome and long-read DNA sequencing techniques combined with studies of RNA and quantitative proteomics were used to investigate 17 subjects from 16 unrelated families with suspected mitochondrial disease.We report six differentAustralian NHMRC, US Department of Defense, Japanese AMED and JSPS agencies, Australian Genomics Health Alliance and Australian Mito Foundation.

Summary Background In about half of all patients with a suspected monogenic disease, genomic investigations fail to identify the diagnosis. A contributing factor is the difficulty with repetitive regions of the genome, such as those generated by segmental duplications. The ATAD3 locus is one such region in which recessive deletions and dominant duplications have recently been reported to cause lethal perinatal mitochondrial diseases characterized by pontocerebellar hypoplasia or cardiomyopathy, respectively. Methods Whole-exome, whole-genome, and long-read DNA sequencing techniques combined with studies of RNA and quantitative proteomics were used to investigate 17 subjects from 16 unrelated families with suspected mitochondrial disease. Findings We report 6 different de novo duplications in the ATAD3 gene locus causing a distinctive presentation, including lethal perinatal cardiomyopathy, persistent hyperlactacidemia, and frequently, corneal clouding or cataracts and encephalopathy. The recurrent 68-kb ATAD3 duplications are identifiable from genome and exome sequencing but usually missed by microarrays. The ATAD3 duplications result in the formation of identical chimeric ATAD3A/ATAD3C proteins, altered ATAD3 complexes, and a striking reduction in mitochondrial oxidative phosphorylation complex I and its activity in heart tissue. Conclusions ATAD3 duplications appear to act in a dominant-negative manner and the de novo inheritance infers a low recurrence risk for families, unlike most pediatric mitochondrial diseases. More than 350 genes underlie mitochondrial diseases. In our experience, the ATAD3 locus is now one of the five most common causes of nuclear-encoded pediatric mitochondrial disease, but the repetitive nature of the locus means ATAD3 diagnoses may be frequently missed by current genomic strategies. Funding Australian NHMRC, US Department of Defense, US National Institutes of Health, Japanese AMED and JSPS agencies, Australian Genomics Health Alliance, and Australian Mito Foundation.

Background Pediatric high-grade glioma is a devastating diagnosis. There has been no improvement in outcomes for several decades, with few children surviving 2 years postdiagnosis. Research progress has been hampered by a lack of tumor samples, which can be used to develop and test novel therapies. Postmortem tumor donations are therefore a valuable opportunity to collect tissue. In this study, we explored Australian parents’ experiences of donating their child’s tumor for research after their child had died. Methods We collected qualitative data from 11 bereaved parents who consented to donate samples of their child’s high-grade glioma for research postmortem. We asked parents about their perceived benefits/burdens of the autopsy, recommendations for improving consent discussions, and decision regret. Results Parents hoped that their donation would help to find a cure for future children with high-grade glioma. They described feeling comforted knowing that their child’s suffering may help others. Some parents also felt that the donation would help them better understand their child’s tumor. Although some parents described discomfort about procedures leading up to the autopsy, parents reported minimal regret regarding their decision to donate their child’s tumor. Parents provided recommendations to improve consent discussions, such as providing more information about the autopsy logistics and why the donation was needed. Conclusion Parents consented to autopsy for altruistic reasons, although donation may also assist parents in their grieving. There is a strong need to improve access to tumor donations for any family who wishes to donate.