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New oncology drugs undergo detailed review prior to public funding in a single-payer healthcare system. The aim of this study was to assess how cancer drug review times impact funding recommendations. Drugs reviewed by the pan-Canadian Oncology Drug Review (pCODR) between the years 2012 and 2020 were included. Data were collected including Health Canada approval dates, initial and final funding recommendations, treatment intent, drug class, clinical indications, and incremental cost-effectiveness ratios (ICER). Univariable and multivariable analyses were used to determine the association between funding recommendations and review times. Of the 164 applications submitted, 130 received a positive final recommendation. Median time from Health Canada (HC) approval to final recommendation was longer for drugs indicated for the treatment of gastrointestinal (GI) and lung cancer compared to breast, genitourinary (GU), and other tumours (205 vs. 198 vs. 111 vs. 129 vs. 181 days, respectively; Kruskal–Wallis p = 0.0312). Drugs with longer review times were more likely to receive a negative pCODR recommendation, even when adjusting for tumour type, drug class, and intent of therapy (157 vs. 298 days; Wilcoxon p = 0.0003, OR 1.002 95% CI [1.000–1.004].). There was no association between funding recommendation and tumour type or class of drug. The exploration of factors associated with variance in review times will be important in ensuring timely patient access to cancer drugs.

Abstract Background During the last decades, in patients with periodontitis, periodontal treatment has been shown to reduce the potential release of local and systemic biomarkers linked to an early risk of systemic inflammatory disorders. This study evaluated the efficacy of non-surgical-periodontal treatment (NSPT) on growth differentiation factor 15 (GDF-15) and related circulating biomarkers such as glutathione peroxidase 1 (GPx-1), c-reactive protein (hs-CRP), and surfactant protein D (SP-D) in periodontal patients and explored whether subjects who had high GDF-15 levels at baseline showed increased clinical benefits following NSPT at 6-months follow-up. Methods For this two-arm, parallel randomized clinical trial, patients with periodontitis were randomly allocated to receive quadrant scaling and root-planing (Q-SRP, n = 23, median age 51 years old) or full-mouth disinfection (FMD, n = 23, median age 50 years old) treatment. Clinical and periodontal parameters were recorded in all enrolled patients. The primary outcome was to analyse serum concentrations changes of GDF-15 and of GPx-1, hs-CRP, and SP-D at baseline and at 30, 90, and 180-days follow-up after NSPT through enzyme-linked immunosorbent assay (ELISA) and nephelometric assay techniques. Results In comparison with FMD, patients of the Q-SRP group showed a significant improvement in clinical periodontal parameters (p

Abstract Background The Bolton analysis is one of the commonly used tooth size analysis or diagnostic tools in deriving a treatment plan for orthodontic patients. Many studies have indicated and concluded that normal measurements for one group should not be considered normal for other ethnic groups. The aims and objectives of this study were to investigate the applicability of Bolton’s ratios in the orthodontic population of Malaysian main ethnics, Malay, Chinese, and Indians. Comparisons were made in terms of size and distribution of tooth size discrepancy in the Malaysian orthodontic population and the findings were converted in terms of millimeters. Methods Hundred fifty pre-orthodontic study casts comprised of 52 Malay, 54 Chinese, and 44 Indian patients were selected. Digital calipers (Fowler Pro-Max) linked to Hamilton Tooth Arch Software were used to measure the tooth width and ratios. Statistical analysis was carried out to test for gender differences (independent t-test), to identify the effects of malocclusion and ethnic groups (Two-way ANOVA), and to compare the means of the current study with Bolton’s standards (one sample t-test). Results This study showed that there was no significant difference between the genders of the sample of each ethnicity. There was no correlation found between ethnic groups and malocclusion classes. There was a significant difference when comparing Bolton values with the Malay sample for both ratios. It was found that more Malay subjects presented with maxillary excess contrary to Chinese and Indians who presented more maxillary deficiency for the anterior and overall ratio. Conclusion There was a significant difference found between the TSD of the three major ethnicities in Malaysia. The Bolton standards can be applied to Malaysian Chinese and Indians but not to Malays orthodontic populations for both anterior and overall ratios. Subsequently, a specific standard should be used for the Malays orthodontic population. It was found that more Malay subjects presented with maxillary excess contrary to Chinese and Indians who presented more maxillary deficiency for the anterior and overall ratio.

Abstract Background The opioid epidemic continues to be associated with high numbers of fatalities in the USA and other countries, driven mainly by the inclusion of potent synthetic opioids in street drugs. Drug checking by means of various technologies is being increasingly implemented as a harm reduction strategy to inform users about constituent drugs in their street samples. We assessed how valued drug checking services (DCS) would be for opioid street drug users given the ubiquity of fentanyl and related analogs in the drug supply, the information they would most value from drug checking, and compared expected versus actual constituent drugs in collected samples. Methods A convenience sample of opioid street drug users (N = 118) was recruited from two syringe service exchange programs in Chicago between 2021 and 2022. We administered brief surveys asking about overdose history, whether fentanyl was their preferred opioid, and interest in DCS. We also collected drug samples and asked participants what drug(s) they expected were in the sample. Provided samples were analyzed using LC–MS technology and the results compared to their expected drugs. Results Participants reported an average of 4.4 lifetime overdoses (SD = 4.8, range = 0–20) and 1.1 (SD = 1.8, range = 0–10) past-year overdoses. A majority (92.1%) believed they had recently used drugs containing fentanyl whether intentionally or unintentionally. Opinions about the desirability of fentanyl were mixed with 56.1% indicating they did not and 38.0% indicating they did prefer fentanyl over other opioids, mainly heroin. Attitudes toward DCS indicated a general but not uniform receptiveness with a majority indicating interest in DCS though sizeable minorities believed DCS was “too much trouble” (25.2%) or there was “no point” in testing (35.4%). Participants were especially inaccurate identifying common cutting agents and potentiating drugs such as diphenhydramine in their samples (sensitivity = .17). Conclusions Results affirmed street drug users remain interested in using DCS to monitor their drugs and such services should be more widely available. Advanced checking technologies that provide information on the relative quantities and the different drugs present in a given sample available at point-of-care, would be most valuable but remain challenging to implement.

Introduction: Some cytokines, including asprosin and brain-derived neurotrophic factor (BDNF), are metabotropic factors, which play a role in the development of type 2 diabetes. This study aimed to determine the effect of aerobic interval training on the circulating levels of BDNF and asprosin in men with type 2 diabetes. Material & Methods: In this semi-experimental study, 20 men with type 2 diabetes were selected by random sampling and randomly divided into two experimental and control groups. Exercise training was performed for 12 weeks (three 60-90-min sessions of interval aerobic training). The obtained data were analyzed in SPSS software (version 26) through t-test and ANCOVA (P≤0.05). Findings: The results showed that after the training intervention, a significant decrease was observed in serum asprosin level (F=7.670; P=0.013), followed by a significant increase in serum levels of BDNF (F=7.585; P=0.014) in the training group, compared to the baseline values and the control group. Discussion & Conclusion: According to the results of the present study, it can be said that interval aerobic training has an effective role in controlling blood glycemic levels and the treatment of type 2 diabetes by reducing asprosin and increasing BDNF as two metabotropic cytokines.

This article investigates the role of the Israeli border in the process of criminalising Palestinians. Defining Israel in contrast to the Arab ‘terrorists’, waiting to attack, necessitates a grand, looming settler- colonial border and the sequestration of an entire population behind a manufactured prison. The justification for this form of border ‘control’ is made possible by the historic truths established by the West in the colonial era. The paper outlines this understanding of Arabs as a ‘bestial’, ‘bellicose’ group that thrives in conflict situations. It moves on to note that the consequence of this characterisation is the global, all-encompassing understanding of the Arab threat. It finally narrows the border wall down as an Israeli tool of segregation, justified by understandings of a racialised, ‘threatening Arab’. The Israeli ‘defence’ of its borders will be reimagined from a Southern perspective as an oppressive system of segregation justified by the ways in which Arabs have historically been constructed.

Social media has become increasingly important in shaping public vaccination views, especially since the COVID-19 outbreak. This paper uses bow-tie structure to analyse a temporal dataset of directed online social networks that represent the information exchange among anti-vaccination, pro-vaccination and neutral Facebook pages. Bow-tie structure decomposes a network into seven components, with two components, strongly connected component (SCC) and out-periphery component (OUT), emphasized in this paper: SCC is the largest strongly connected component, acting as an ‘information magnifier’, and OUT contains all nodes with a directed path from a node in SCC, acting as an ‘information creator’. We consistently observe statistically significant bow-tie structures with different dominant components for each vaccination group over time. In particular, the anti-vaccination group has a large OUT, and the pro-vaccination group has a large SCC. We further investigate changes in opinions over time, as measured by fan count variations, using agent-based simulations and machine learning models. Across both methods, accounting for bow-tie decomposition better reflects information flow differences among vaccination groups and improves our opinion dynamics prediction results. The modelling frameworks we consider can be applied to any multi-stance temporal network and could form a basis for exploring opinion dynamics using bow-tie structure in a wide range of applications.

Anti-D antibody is the most common cause of hemolytic disease of the newborn (HDN). Other antigens have emerged, causing significant damage to the newborn. We report a case of a 31-week dichorionic diamniotic twin born emergently to a mother with anti-C and anti-D antibodies who required multiple percutaneous umbilical cord blood sampling (PUBS) and transfusions. Extensive resuscitation at birth was required due to severe anemia, hypovolemia, and prematurity. Ensuing liver damage occurred with subsequent profound coagulopathy, transaminitis, and direct hyperbilirubinemia that required significant support. This patient developed several unique findings including the inability to monitor oxygen saturations due to dermal bilirubin deposits and staining of baby teeth. This case report highlights the importance of early identification of additional Rh antibodies due to concern for development of more severe forms of HDN.

Ellis-van Creveld syndrome (EVC), also known as chondroectodermal dysplasia, is a rare entity. It most commonly affects the tubular bones leading to dwarfism and a long trunk with ossification defects. Other presentations are wide hands and feet, dysplastic nails, thin hair, and cardiac malformations. An eight-year-old female patient presented to our tertiary care centre with complaints of short stature, abnormal dentition, and fatigue. The child’s parents were first-degree relatives. On radiological imaging, it was revealed that the patient had postaxial polydactyly, short stature, and genu valgum deformity along with mild cardiomegaly. All these features were indicative of Ellis-van Creveld syndrome. EVC is a rare clinical syndrome with a distinctive clinical presentation. It requires comprehensive radiological investigations and the management is best done with a multidisciplinary approach. Keywords: Cardiomegaly, Polydactyly, Ellis-van Creveld Syndrome.

Early in the pandemic, the spread of the emerging virus SARS-CoV-2 was causing mild illness lasting less than two weeks for most people, with a small proportion of people developing serious illness or death. However, as the pandemic progressed, many people reported suffering from symptoms for weeks or months after their initial infection. Persistence of COVID-19 symptoms beyond one month, or what is known as long COVID-19, is recognized as a risk of acute infection. Up to date, information on long COVID-19 among Jordanian patients has not been reported. Therefore, we sought to conduct this cross-sectional study utilizing a self-administered survey. The survey asks a series of questions regarding participant demographics, long COVID-19 symptoms, information about pre-existing medical history, supplements, vaccination history, and symptoms recorded after vaccination. Chi square analysis was conducted on 990 responders, and the results showed a significant correlation (P

Key Clinical Abstract Multidisciplinary treatment options can help provide good clinical outcomes if these are appropriately sequenced and carried out correctly. This case exemplifies interdisciplinary involvement to ensure the patient received an improved esthetic outcome. Abstract The presence of anterior diastemas may compromise the esthetics of a patient's smile, causing mental, and social trauma in many patients. After careful evaluation Periodontal, surgical, and prosthodontic treatments are sometimes required to ensure successful treatment outcomes using a multidisciplinary staged treatment approach. These approaches must be carefully planned to ensure timely treatment progress. Surgical intervention must be planned at the right point in treatment to ensure adequate healing before placement of esthetic restorations.

In this conceptual analysis, we set out some of the negotiations and tensions that emerge when we try to build a shared understanding of water (in)security through the dual lenses of a feminist ethics of care and socio-ecological justice. We further reflect on how these theoretical lenses shape our work in practice—how do we actualise them in an international, interdisciplinary partnership? We actively seek to engage all our colleagues in how we understand the function of power and inequality in relation to the distribution of water resources and the ways in which intersectional inequalities shape access to, and availability of, water. We conclude that our international partnership will only add value to our understanding of water (in)security if we are able to identify not just how intersectional inequalities circumscribe differential access to water itself in a range of diverse contexts, but the ways socio-ecological justice and a feminist ethics of care are understood and in turn shape how we work together to achieve greater water security across diverse contexts.

Objective: Alveolar osteitis is a painful complication that often arises after tooth extraction, presenting a significant clinical challenge. It is imperative to gain a comprehensive understanding of both its occurrence and the contributing factors to enhance the quality of dental care. The aim of this study was to assess the frequency and prevalence of alveolar osteitis among patients and compare these variables based on demographic characteristics (age and sex), the number of teeth extractions, operator experience, health status, and smoking habits in the target population. Methods: This cross-sectional observational study was conducted from May 2019 to April 2020. It included all patients above 16 years of age, of both genders, who underwent permanent tooth extraction for various reasons. Patient demographics, smoking habits, health status, operating dental surgeon’s clinical experience, extraction technique, and the number of teeth extracted were recorded. Statistical analysis was performed using SPSS version 25. Chi-square test and regression analysis were used to assess differences between age, sex, smoking habit, dentist category, and the number of teeth extractions in relation to alveolar osteitis. Results: A total of 679 permanent tooth extractions were performed in 438 patients. Alveolar osteitis was observed in 107 cases (15.7%) following tooth extractions. Among these, 36 cases (33.6%) occurred in single tooth extraction cases, while 71 cases (66.4%) were present in patients with multiple extractions. Moreover, 67 cases (62.6%) of alveolar osteitis were found in cigarette smokers. In addition, 61 cases (57%) of dry sockets were reported after tooth extractions performed by dental interns, while 46 cases (43.0%) were noted in extractions performed by experienced dental surgeons and specialists. Conclusion: The study found a 15.7% incidence of alveolar osteitis in tooth extraction patients in the Al-Jouf region. Alveolar osteitis was more prevalent in males and the age group of 56–77 years. Multiple tooth extractions were associated with higher alveolar osteitis incidence, while operator inexperience increased post-extraction complication risks. In addition, a promising novel protocol and risk assessment scoring system have been devised which require further validation and future research.

In this paper, we will study a fractional-order SIR epidemic model with treatment cure rate. The paper starts with the investigation of some needed preliminaries related to fractional calculus. Next, we investigate the well-posedness of the fractional-order model in terms of positivity and boundedness of solution. Then, we give the basic reproduction number via the next generation matrix method. The model has two steady states, namely, the disease-free equilibrium and the endemic equilibrium. It was proven that when the basic reproduction number is less than unity, then, the disease-free-equilibrium is globally asymptotically stable. While, when the basic reproduction number is greater than unity, then the endemic-equilibrium is globally asymptotically stable. Numerical simulations are carried out in order to confirm the theoretical results. To this end, we will apply a numerical approach based on the fundamental theorem of fractional calculus and a three-step Lagrange polynomial interpolation technique. It is shown that any increase of the fractional order derivative leads to a decrease in the convergence speed towards the studied equilibrium.

Although data on livestock ownership are often collected at the household level, not all household members have the same rights over the livestock. In this paper, we investigate the gendered patterns of livestock ownership in smallholder households in Uganda using a unique data set with information on ownership, management, and decision-making across different types of livestock. Drawing on the bundle of rights frameworks, the analysis demonstrates the importance of going beyond analyses of ownership to also consider these other rights. We find that people who claim to be owners may not have the management or fructus rights. People also may have these latter rights without claiming ownership. We also find discrepancies in the responses from spouses; they provide different answers regarding who owns and has the rights over livestock. This suggests patterns of asymmetric information and potentially the hiding of animals from one’s spouse.

Bioluminescent tools have been used for decades to image processes in complex tissues and preclinical models. However, few distinct probes are available to probe multicellular interactions. We and others are addressing this limitation by engineering new luciferases that can selectively process synthetic luciferin analogues. In this work, we explored naphthylamino luciferins as orthogonal bioluminescent probes. Three analogues were prepared using an optimized synthetic route. The luciferins were found to be robust emitters with native luciferase in vitro and in cellulo. We further screened the analogues against libraries of luciferase mutants to identify unique enzyme-substrate pairs. The new probes can be used in conjunction with existing bioluminescent tools for multi-component imaging.

The genetic basis of Lewy body dementia (LBD) is not well understood. Here, we performed whole-genome sequencing in large cohorts of LBD cases and neurologically healthy controls to study the genetic architecture of this understudied form of dementia, and to generate a resource for the scientific community. Genome-wide association analysis identified five independent risk loci, whereas genome-wide gene-aggregation tests implicated mutations in the gene GBA. Genetic risk scores demonstrate that LBD shares risk profiles and pathways with Alzheimer's disease and Parkinson's disease, providing a deeper molecular understanding of the complex genetic architecture of this age-related neurodegenerative condition.

BACKGROUND. Disease due to dengue viruses is a growing global health threat, causing 100-400 million cases annually. An ideal dengue vaccine should demonstrate durable protection against all 4 serotypes in phase III efficacy trials, however the lack of circulating serotypes may lead to incomplete efficacy data. Controlled human infection models help downselect vaccine candidates and supply critical data to supplement efficacy trials. We evaluated the efficacy of a leading live-attenuated tetravalent dengue vaccine candidate, TV005, against infection with a newly established dengue serotype 3 or an established serotype 2 challenge virus. METHODS. Two randomized, controlled clinical trials were performed. In study 1, a total of 42 participants received TV005 or placebo (n = 21 each), and 6 months later, all were challenged with dengue 2 virus (rDEN2[DELTA]30) at a dose of 103 PFU. In study 2, a total of 23 participants received TV005 and 20 received placebo, and 6 months later, all were challenged with 104 PFU dengue 3 virus (rDEN3[DELTA]30). The study participants were closely monitored for safety, viremia, and immunologic responses. Infection, measured by post-challenge viremia, and the occurrence of rash and neutropenia were the primary endpoints. Secondary endpoints included safety, immunologic, and virologic profiles following vaccination with TV005 and subsequent challenge with the rDEN2[DELTA]30 or rDEN3[DELTA]30 strain. RESULTS. TV005 was well tolerated and protected all vaccinated volunteers from viremia with DENV2 or DENV3 (none infected in either group). Placebo recipients had post-challenge viremia (100% in study 1, 85% in study 2), and all experienced rash following challenge with either serotype. CONCLUSIONS. TV005 is a leading tetravalent dengue vaccine candidate that fully protected against infection with DENV2 and DENV3 in an established controlled human infection model. TRIAL REGISTRATION. ClinicalTrials.gov NCT02317900 and NCT02873260. FUNDING. Intramural Research Program, NIH (contract HHSN272200900010C)., Introduction Dengue viruses are estimated to cause 100-400 million symptomatic illnesses each year, with a significant and expanding burden of severe disease and mortality in both endemic populations and travelers [...]

It's after 10 p.m. when I finally land in San Juan and my friend Luis Othoniel Rosa picks me up so we can drive two hours west along Puerto Rico's [...]

Abstract Background South Africa bears a large HIV burden with 7.8 million people with HIV (PWH). However, due to suboptimal antiretroviral therapy (ART) adherence and retention in care, only 66% of PWH in South Africa are virally suppressed. Standard care only allows for suboptimal adherence detection when routine testing indicates unsuppressed virus. Several adherence interventions are known to improve HIV outcomes, yet few are implemented in routinely due to the resources required. Therefore, determining scalable evidence-based adherence support interventions for resource-limited settings (RLS) is a priority. The multiphase optimization strategy (MOST) framework allows for simultaneous evaluation of multiple intervention components and their interactions. We propose to use MOST to identify the intervention combination with the highest levels of efficacy and cost-effectiveness that is feasible and acceptable in primary care clinics in Cape Town. Methods We will employ a fractional factorial design to identify the most promising intervention components for inclusion in a multi-component intervention package to be tested in a future randomized controlled trial. We will recruit 512 participants initiating ART between March 2022 and February 2024 in three Cape Town clinics and evaluate acceptability, feasibility, and cost-effectiveness of intervention combinations. Participants will be randomized to one of 16 conditions with different combinations of three adherence monitoring components: rapid outreach following (1) unsuppressed virus, (2) missed pharmacy refill collection, and/or (3) missed doses as detected by an electronic adherence monitoring device; and two adherence support components: (1) weekly check-in texts and (2) enhanced peer support. We will assess viral suppression (

Abstract Background Suubi is an evidenced based multi-component intervention that targets psychosocial and economic hardships to improve ART adherence, viral suppression, mental health, family financial stability, and family cohesion for adolescents living with HIV (ALHIV) in Uganda. Suubi was originally tested as a combined package of four components: 1) Financial Literacy Training; 2) incentivized matched Youth Savings Accounts with income-generating activities; 3) a manualized and visual-based intervention for ART adherence and stigma reduction; and 4) engagement with HIV treatment-experienced role models. However, it is unknown if each component in Suubi had a positive effect, how the components interacted, or if fewer components could have produced equivalent effects. Hence, the overall goal of this new study is to identify the most impactful and sustainable economic and psychosocial components across 48 health clinics in Uganda. Methods A total of 576 ALHIV (aged 11–17 years at enrollment) will be recruited from 48 clinics and each clinic will be randomized to one of 16 study conditions. Each condition represents every possible combination of the 4 components noted above. Assessments will be conducted at baseline, 12, 24, 36 and 48- months post-intervention initiation. Using the multi-phase optimization strategy (MOST), we will identify the optimal combination of components and associated costs for viral suppression, as well as test key mediators and moderators of the component-viral suppression relationship. Discussion The study is a shift in the paradigm of research to use new thinking to build/un-pack highly efficacious interventions that lead to new scientific knowledge in terms of understanding what drives an intervention’s success and how to iterate on them in ways that are more efficient, affordable and scalable. The study advances intervention science for HIV care outcomes globally. Trial Registration This project was registered at clinicaltrials.gov (NCT05600621) on October, 31, 2022. https://clinicaltrials.gov/ct2/show/NCT05600621

Introduction: Glucose transporter type 4 (GLUT4) is a membrane glucose transporter that is influenced by insulin signaling and muscle contraction. The aim of the present study was to review the function of GLUT4 in normal conditions and insulin resistance, as well as the role of exercise training on the kinetics of GLUT4 in skeletal muscles. In the present study, by searching for sports keywords; exercise; sports adaptations; glucose transporter; absorption of glucose; glucose transporter type 4; type 2 diabetes; insulin signaling; and insulin resistance was searched from electronic databases of related articles until November 2022 and entered into the study. Conclusion: Due to the pathological factors of type 2 diabetes, skeletal muscles are disturbed in the delivery, absorption, and metabolism of glucose; pathological disorders of muscle tissue affect insulin signaling and the quantity and function of GLUT4. In the present review, it was found that an exercise training session initiated the GLUT4 gene expression and protein production and its transfer from intracellular stores to sarcolemma; this effect of local exercise was related to muscle contraction. GLUT4 gene and protein expression increased in response to regular exercise and led to an increase in the total level of GLUT4 protein in skeletal muscles; furthermore, regular exercise has improve insulin signaling and, as a result, improved muscle efficiency for blood glucose collection. Considering the role of physical activity on muscle function in blood glucose collection, one of the treatment goals in type 2 diabetes is maintaining muscle mass, increasing muscle mass and also increasing muscle function (muscle quality).

In order for underwater wireless sensor networks to communicate more efficiently, MAC protocols are needed to control the use of acoustic channels. With the high propagation delay and the limited bandwidth available on the acoustic channel, a specially designed MAC protocol is needed for UWASN (Underwater Acoustic Sensor Networks). In this research, the adaptation of Cooperative MAC for underwater (CoopMAC-U) will be further studied to test the protocol performance. In the previous research, CoopMAC-U was simulated yet the fairness of the transmission was not simulated and tested. In this research, CoopMAC-U will be studied further and improved. The simulation result shows that the Improved CoopMAC-U protocol produces better-normalized throughput than the initial version of CoopMAC-U. The protocol is also proven that it is backward compatible between conventional mode and cooperative mode. For offered load greater than 0.2, both the initial version of CoopMAC-U and the Improved CoopMAC-U result in stagnant normalized throughputs but the improved ones double the value of the initial version.

We previously reported on the experimental validation of several in silico-predicted glioma biomarkers (e.g., Plexin-B2 (PLXNB2), SLIT3, and Spondin-1 (SPON1)) that were found to be higher in human high-grade gliomas (HGGs). In this study, we validated their therapeutic potential by investigating antibody therapies against these three biomarkers in a preclinical mouse GL261 high-grade glioma model. Efficacies for antibody therapies against these biomarkers were assessed by survival and tumor volumes, biomarker expressions, cell invasion and proliferation, and bioinformatics gene/protein associations. Antibodies against PLXNB2, SLIT3, or SPON1 were effective in significantly reducing tumor volumes and increasing animal survival. With immunohistochemistry (IHC), these biomarkers were highly expressed in human HGGs, as well as in mice tumors. From IHC, CD44v6 was significantly decreased for all three antibody treatments, compared to UT GL261 tumors. Bioinformatics suggested that targeting either PLXNB2 or SPON1 may have a major effect on HGG cell migration and invasion (validated with CD44v6 IHC), whereas targeting SLIT3, in addition to affecting cell invasion, may also affect cell proliferation (not validated with Ki67 IHC). These results indicate that targeting these three biomarkers could add to the therapeutic arsenal against high-grade gliomas and that antibodies against them could be considered for clinical translation.

The complex, bis(N,N-diethyl-4-methyl-4-piperazine-1-carboxamide) tetrakis(isothiocyanato-κN)cobalt(II) (N,N-diethyl-4-methyl-4-piperazine-1-carboxamide = diethylcarbamazine), (C10H22N3O)2[Co(NCS)4], is presented. This complex is a blue precipitate, insoluble in water but soluble in organic solvents, that is formed from the reaction of diethylcarbamazine citrate, a protonated tertiary amine, with cobalt(II) and thiocyanate. This reaction, in the form of the Scott test, is a common presumptive test for cocaine hydrochloride. The known cobalt compound, [K2Co(NCS)4]·3H2O, has a deep-blue coloration due to the tetrahedral [Co(NCS)4]2− that is also present in the ion pair with bulky amines, and is similar to the color of other tetrahedral cobalt(II) complex ions, such as [CoCl4]2−. The structure is consistent with a previous proposal that a hydrophobic ion pair formed between [Co(NCS)4]2− and two protonated molecules of cocaine is responsible for the blue hydrophobic products formed by cocaine in the Scott test.

We examined the role of repeat expansions in the pathogenesis of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) by analyzing whole-genome sequence data from 2,442 FTD/ALS patients, 2,599 Lewy body dementia (LBD) patients, and 3,158 neurologically healthy subjects. Pathogenic expansions (range, 40-64 CAG repeats) in the huntingtin (HTT) gene were found in three (0.12%) patients diagnosed with pure FTD/ALS syndromes but were not present in the LBD or healthy cohorts. We replicated our findings in an independent collection of 3,674 FTD/ALS patients. Postmortem evaluations of two patients revealed the classical TDP-43 pathology of FTD/ALS, as well as huntingtin-positive, ubiquitin-positive aggregates in the frontal cortex. The neostriatal atrophy that pathologically defines Huntington's disease was absent in both cases. Our findings reveal an etiological relationship between HTT repeat expansions and FTD/ALS syndromes and indicate that genetic screening of FTD/ALS patients for HTT repeat expansions should be considered.