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The rising cost of higher education has led parents, employers, and politicians to question the need for a college degree. Skills Infusion is a professional development program in which faculty review a course they teach to identify the career readiness competencies defined by the National Association of Colleges and Employers (NACE). The NACE competencies are skills that are expected by employers across all sectors of the economy. In addition to describing the Skills Infusion program, a description of how an information technology undergraduate program is expanding on the program to incorporate skills mapping to provide further evidence of accountability in higher education.

Brain metastases are an increasing global public health concern, even as survival rates improve for patients with metastatic disease. Both metastases and the sequelae of their treatment are key determinants of the inter-related priorities of patient survival, function, and quality of life, mandating a multidimensional approach to clinical care and research. At a virtual National Cancer Institute Workshop in September, 2022, key stakeholders convened to define research priorities to address the crucial areas of unmet need for patients with brain metastases to achieve meaningful advances in patient outcomes. This Policy Review outlines existing knowledge gaps, collaborative opportunities, and specific recommendations regarding consensus priorities and future directions in brain metastases research. Achieving major advances in research will require enhanced coordination between the ongoing efforts of individual organisations and consortia. Importantly, the continual and active engagement of patients and patient advocates will be necessary to ensure that the directionality of all efforts reflects what is most meaningful in the context of patient care.

The rapid growth of inexpensive and easily accessible communicating devices embedded into new or existing physical devices transform them into the intelligent devices that comprise the Internet of Things (IoT). The increasing use of these devices has attracted attention from various sectors, including consumer market, business, industry, health, government, education, research, and many others. In educational sectors, many institutions are exploring the advanced digital infrastructure applications to improve the learning and teaching abilities of the difficult subjects of Science, Technology, Engineering, and Mathematics (STEM). IoT devices in the classroom or in laboratory activities can enhance the learning process with innovative ideas to increase student motivation in much faster and effective ways. In addition to using IoT to enhance the educational process, IoT serves as an important topic of study. IoT education consists of diverse components including hardware, software, programming, and electronics. How IoT is incorporated into the curriculum is based on the programmatic objectives. For non-engineers, non-coders, and many others, IoT courses need to be designed and delivered in a different way than would be done with engineering, engineering technology, and computer science majors. This paper will discuss the use of widely available educational IoT kits that could be used for beginners or non-majors.

In the age of COVID-19, traditional teaching techniques are under scrutiny. Most concepts and labs in the area of information technology are intended to be taught face-to-face in labs using clusters and networking infrastructure. Simulation software's such as uCertify, Pearson online, etc.., are good alternative, but are not always a viable solution. Simulation software is used primarily to understand, remember, and apply the concepts rather than analyze evaluate and create the content. Due to unforeseen conditions during March 2020, educational institutions were required to shut down. In the middle of the semester, instructors had to determine how to complete the labs and final projects which are crucial to accomplishing the intended learning outcomes of their courses. A chosen alternative was to use Amazon AWS as a cloud platform to host the labs and projects. It was initially a challenge as students had not had the opportunity to learn how to work with AWS in advance. Training sessions were provided to help them understand how to deploy and connect virtual servers in AWS to build a virtual private cloud. Prior to the pandemic, students developed and deployed their labs and projects on a departmental cluster which was on-premise at the university. With AWS, it was challenging to design an architecture to host 19 services offered as a part of the project requirements for an organization network. This paper presents the scope of this project; the intended outcomes of the project, how students were able to implement the project requirements in the AWS environment; the intended learning outcomes; and the results of student surveys to assess the learning outcome of using AWS and traditional cluster.

Background/Objective: Celiac disease, an immune reaction to gluten causing nutrient malabsorption, and long-term glucocorticoid therapy adversely affect bone metabolism and increase fracture risk. Case Report: A patient with long-standing celiac disease on a strict gluten-free diet and long-term glucocorticoid therapy status post kidney transplant for Sjögren syndrome–induced interstitial nephritis presented for management of osteoporosis. Initial evaluation was notable for secondary hyperparathyroidism, which resolved after switching to a gluten-free calcium citrate supplement. Given normal serum total alkaline phosphatase (ALP) and parathyroid hormone (PTH), she began treatment of osteoporosis with abaloparatide. Two months later, she reported abrupt onset of diarrhea with significant weight loss. Biochemical investigation revealed a threefold increase in serum ALP level. As a precaution, abaloparatide was suspended, yet symptoms persisted with elevated ALP and PTH levels. Endoscopy revealed a celiac flare. The clinic-based pharmacist found that her pharmacy had inadvertently dispensed prednisone tablets containing wheat starch. A switch to a gluten-free formulation led to rapid resolution of the diarrhea with weight regain. Serum ALP and PTH levels normalized, and abaloparatide was resumed without biochemical abnormalities. Discussion: An unintended switch to a gluten-containing prednisone formulation resulted in uncontrolled celiac disease causing calcium malabsorption, secondary hyperparathyroidism, elevated ALP levels, and an interruption in osteoporosis therapy. Common supplements and drugs can be a hidden source of gluten. Collaboration with a clinic-based pharmacist enhances the detection and prevention of medication-induced adverse reactions. Conclusion: This case highlights the importance of a careful review of gluten-containing medications and supplements in patients with celiac disease.

South Asia is a demographically crucial, economically aspiring, and socio-culturally diverse region in the world. The region contributes to a large burden of surgically-treatable disease conditions. A large number of people in South Asia cannot access safe and affordable surgical, obstetric, trauma, and anesthesia (SOTA) care when in need. Yet, attention to the region in Global Surgery and Global Health is limited. Here, we assess the status of SOTA care in South Asia. We summarize the evidence on SOTA care indicators and planning. Region-wide, as well as country-specific challenges are highlighted. We also discuss potential directions—initiatives and innovations—toward addressing these challenges. Local partnerships, sustained research and advocacy efforts, and politics can be aligned with evidence-based policymaking and health planning to achieve equitable SOTA care access in the South Asian region under the South Asian Association for Regional Cooperation (SAARC).

BackgroundSurvivorship for those living with primary CNS cancers begins at diagnosis, continues throughout a person's life, and includes caregivers. Opportunities and challenges exist to advance survivorship care for those living with primary CNS cancers that necessitate stakeholder involvement.MethodsIn June 2021, NCI-CONNECT convened a two-day virtual workshop about survivorship care in neuro-oncology. Two expert panels provided key recommendations and five working groups considered critical questions to identify strengths, weaknesses, opportunities, and threats to the advancement of survivorship care and developed recommendations and action items.ResultsThe following action items emanated from the workshop: seek endorsement of meeting report from stakeholder organizations; address barriers in access to survivorship care and provider reimbursement; advance survivorship research through NIH and private grant support; develop a survivorship tool kit for providers, people living with primary CNS cancers and their caregivers; provide accessible educational content for neuro-oncology, neurology, and oncology community providers about survivorship care in neuro-oncology; and establish core competencies for survivorship care for neuro-oncology providers to be included in training and standardized exams.ConclusionsAction items aim to address access and reimbursement barriers, expand patient and provider education, develop core competencies, and support survivorship research through funding and other supports.

The quality of radiation therapy (RT) treatment plans directly affects the outcomes of clinical trials. KBP solutions have been utilized in RT plan quality assurance (QA). In this study, we evaluated the quality of RT plans for brain and head/neck cancers enrolled in multi-institutional clinical trials utilizing a KBP approach. The evaluation was conducted on 203 glioblastoma (GBM) patients enrolled in NRG-BN001 and 70 nasopharyngeal carcinoma (NPC) patients enrolled in NRG-HN001. For each trial, fifty high-quality photon plans were utilized to build a KBP photon model. A KBP proton model was generated using intensity-modulated proton therapy (IMPT) plans generated on 50 patients originally treated with photon RT. These models were then applied to generate KBP plans for the remaining patients, which were compared against the submitted plans for quality evaluation, including in terms of protocol compliance, target coverage, and organ-at-risk (OAR) doses. RT plans generated by the KBP models were demonstrated to have superior quality compared to the submitted plans. KBP IMPT plans can decrease the variation of proton plan quality and could possibly be used as a tool for developing improved plans in the future. Additionally, the KBP tool proved to be an effective instrument for RT plan QA in multi-center clinical trials.

With the lack of specific signs and symptoms, pancreatic ductal adenocarcinoma (PDAC) is often diagnosed at late metastatic stages, resulting in poor survival outcomes. Among various biomarkers, microRNA-21 (miR-21), a small non-coding RNA, is highly expressed in PDAC. By inhibiting regulatory proteins at the 3′ untranslated regions (UTR), miR-21 holds significant roles in PDAC cell proliferation, epithelial–mesenchymal transition, angiogenesis, as well as cancer invasion, metastasis, and resistance therapy. We conducted a systematic search across major databases for articles on miR-21 and pancreatic cancer mainly published within the last decade, focusing on their diagnostic, prognostic, therapeutic, and biological roles. This rigorous approach ensured a comprehensive review of miR-21’s multifaceted role in pancreatic cancers. In this review, we explore the current understandings and future directions regarding the regulation, diagnostic, prognostic, and therapeutic potential of targeting miR-21 in PDAC. This exhaustive review discusses the involvement of miR-21 in proliferation, epithelial–mesenchymal transition (EMT), apoptosis modulation, angiogenesis, and its role in therapy resistance. Also discussed in the review is the interplay between various molecular pathways that contribute to tumor progression, with specific reference to pancreatic ductal adenocarcinoma.

Less than 1% of all clinical trials are conducted in Africa. In 2019, only six of 26 oncology clinical trials conducted in Africa were conducted in countries with subjects of African ancestry. There are multiple barriers that hinder the conduct of cancer clinical trials in Africa. Time to trial activation (TTA) is the administrative and regulatory process required before a study can be activated—an important metric and often a major barrier for site selection. In Kenya, TTA involves review by Institutional Review Board (IRB), Pharmacy and Poisons Board, National Commission for Science, Technology and Innovation and Ministry of Health, all in a sequential fashion. We performed a prospective review of TTA for all clinical trials initiated and began enrolment at the Aga Khan University-Clinical Research Unit between June 2020 and November 2022. TTA was defined as total time from submission of study documents (to regulatory bodies) to site activation by the sponsor. A total of 12 studies were submitted for regulatory review. Eleven (nine industry sponsored and two investigator initiated) were approved for activation. Three were COVID-19-related studies and eight were non-COVID-19-related studies. Mean TTA for COVID-related studies was 80 days (range 40–120). Mean TTA for non-COVID-related studies was 259 days (range 190–399). This TTA difference was statistically significant (p=0.02). TTA remains a significant barrier to the efficient regulatory approval of and subsequent conduct of clinical trials in Africa. COVID-19 pandemic revealed that parallel processing and expedited review of clinical trials allows efficient TTA without compromising human subject safety or data integrity. These lessons need to be applied to all clinical trials in order for African sites to become competitive and contribute data from African patients to global knowledge.

Black root rot (BRR) caused by Lasiodiplodia theobromae is an alarming disease of mulberry that causes tremendous economic losses to sericulture farmers in India and China. Successful control of this disease can be attained by screening germplasm and identifying resistant sources. Seventy four diseased root samples were collected from farmer’s fields belonging to four major mulberry growing states of South India. Based on morpho-cultural and scanning electron microscopy studies, 57 fungal isolates were characterized and identified as L. theobromae. Phylogenetic analysis of concatenated internal transcribed spacer and β-tubulin sequences revealed variation of the representative 20 isolates of L. theobromae. Following the root dip method of inoculation, pathogenicity studies on susceptible mulberry genotypes (Victory-1 and Thailand male) recognized the virulent isolate MRR-142. Accordingly, MRR-142 isolate was used to evaluate resistance on a set of 45 diverse mulberry accessions. In the repeated experiments, the mulberry accession ME-0168 which is an Indonesian origin belonging to Morus latifolia was found to be highly resistant consistently against BRR. Eight accessions (G2, ME-0006, ME-0011, ME-0093, MI-0006, MI-0291, MI-0489, and MI-0501) were found to be resistant. These promising resistant resources may be exploited in mulberry breeding for developing BRR resistant varieties and to develop mapping populations which successively helps in the identification of molecular markers associated with BRR.

Purpose: Our objective was to report the quality of life (QoL) analysis and toxicity in patients with intermediate-risk prostate cancer treated with or without androgen deprivation therapy (ADT) in Proton Collaborative Group (PCG) GU003. Methods and Materials: Between 2012 and 2019, patients with intermediate-risk prostate cancer were enrolled. Patients were randomized to receive moderately hypofractionated proton beam therapy (PBT) to 70 Gy relative biologic effectiveness in 28 fractions to the prostate with or without 6 months of ADT. Expanded Prostate Cancer Index Composite, Short-Form 12, and the American Urological Association Symptom Index instruments were given at baseline and 3, 6, 12, 18, and 24 months after PBT. Toxicities were assessed according to Common Terminology Criteria for Adverse Events (version 4). Results: One hundred ten patients were randomized to PBT either with 6 months of ADT (n = 55) or without ADT (n = 55). The median follow-up was 32.4 months (range, 5.5-84.6). On average, 101 out of 110 (92%) patients filled out baseline QoL and patient-reported outcome surveys. The compliance was 84%, 82%, 64%, and 42% at 3, 6, 12, and 24 months, respectively. Baseline median American Urological Association Symptom Index was comparable between arms (6 [11%] ADT vs 5 [9%] no ADT, P = .359). Acute and late grade 2+ genitourinary and gastrointestinal toxicity were similar between arms. The ADT arm experienced a QoL decline of mean scores in the sexual (–16.1, P < .001) and hormonal (–6.3, P < .001) domains, with the largest time-specific hormonal differences at 3 (–13.8, P < .001) and 6 (–11.2, P < .001) months. The hormonal QoL domain returned to baseline 6 months after therapy. There was a trend to baseline in sexual function 6 months after completion of ADT. Conclusions: After 6 months of ADT, sexual and hormonal domains returned to baseline 6 months after completion of treatment for men with intermediate-risk prostate cancer.

Objectives: To compare and evaluate the bond durability, surface morphology, and remineralization of the adhesive layer with newer adhesive systems modified with novel bioactive nanoparticles. Methodology: Bonding agents evaluated in this study include (a) Conventional dentin bonding agent (CN-DBA) (b) Nanohydroxyapatite (nanoHAP) incorporated dentin bonding agent (NH DBA); (c) Silica doped nanohydroxyapatite (Si nanoHAP) incorporated dentin bonding agent (Si NH DBA). A total of 104 human dentin discs (5 mm × 5 mm × 2 mm) were sectioned. Elemental analysis (Ca/P ratio) and surface morphology of the adhesive layer with different dentin adhesives were evaluated under scanning electron microscopy with energy-dispersive X-ray analysis after speculated storage time of 1 day and 6 months. Microshear bond strength of adhesive restorations with different dentin adhesives was evaluated under universal testing machine and fractographic analysis under scanning electron microscope after speculated storage time of 1 day and 6 months. The results were analyzed using analysis of variance and post hoc analysis. Results: Si-NH-DBA showed highest mean microshear bond strength for both 1 day and 6 months, which was significantly higher compared to conventional nanofilled dentin bonding agent (CN-DBA) and NH-DBA. Si-NH-DBA group showed only 10% reduction in bond strength after 6 months, which was less compared to that of other groups. Similarly, Si-NH-DBA showed higher remineralization with stellate-shaped crystals at the adhesive layer after 6 months with hydrolytic resistant hybrid layer, compared to CN-DBA and NH-DBA. Conclusion: Silica-doped nanohydroxyapatite proved its efficiency on bond stability, remineralization, and hydrolytic resistance when incorporated into dentin bonding agents because of its bioactivity and carbonate-containing apatite-forming ability.

PURPOSE: Proton therapy can allow for superior avoidance of normal tissues. A widespread consensus has been reached that proton therapy should be used for patients with curable pediatric brain tumor to avoid critical central nervous system structures. Brainstem necrosis is a potentially devastating, but rare, complication of radiation. Recent reports of brainstem necrosis after proton therapy have raised concerns over the potential biological differences among radiation modalities. We have summarized findings from the National Cancer Institute Workshop on Proton Therapy for Children convened in May 2016 to examine brainstem injury. METHODS AND MATERIALS: Twenty-seven physicians, physicists, and researchers from 17 institutions with expertise met to discuss this issue. The definition of brainstem injury, imaging of this entity, clinical experience with photons and photons, and potential biological differences among these radiation modalities were thoroughly discussed and reviewed. The 3 largest US pediatric proton therapy centers collectively summarized the incidence of symptomatic brainstem injury and physics details (planning, dosimetry, delivery) for 671 children with focal posterior fossa tumors treated with protons from 2006 to 2016. RESULTS: The average rate of symptomatic brainstem toxicity from the 3 largest US pediatric proton centers was 2.38%. The actuarial rate of grade ≥2 brainstem toxicity was successfully reduced from 12.7% to 0% at 1 center after adopting modified radiation guidelines. Guidelines for treatment planning and current consensus brainstem constraints for proton therapy are presented. The current knowledge regarding linear energy transfer (LET) and its relationship to relative biological effectiveness (RBE) are defined. We review the current state of LET-based planning. CONCLUSIONS: Brainstem injury is a rare complication of radiation therapy for both photons and protons. Substantial dosimetric data have been collected for brainstem injury after proton therapy, and established guidelines to allow for safe delivery of proton radiation have been defined. Increased capability exists to incorporate LET optimization; however, further research is needed to fully explore the capabilities of LET- and RBE-based planning.

Purpose: Hippocampal volume (HV) is an established predicting factor for neurocognitive function (NCF) in neurodegenerative disease. Whether the same phenomenon exists with hippocampal-avoidant whole brain radiation therapy is not known; therefore, we assessed the association of baseline HV with NCF among patients enrolled on RTOG 0933. Methods and Materials: Hippocampal volume and total brain volume were calculated from the radiation therapy plan. Hippocampal volume was correlated with baseline and 4-month NCF scores (Hopkins Verbal Learning Test–Revised [HVLT-R] Total Recall [TR], Immediate Recognition, and Delayed Recall [DR]) using Pearson correlation. Deterioration in NCF was defined per the primary endpoint of RTOG 0933(mean 4-month relative decline in HVLT-R DR). Comparisons between patients with deteriorated and nondeteriorated NCF were made using the Wilcoxon test. Results: Forty-two patients were evaluable. The median age was 56.5 years (range, 28-83 years), and 81% had a class II recursive partitioning analysis. The median total, right, and left HVs were 5.4 cm3 (range, 1.9-7.4 cm3), 2.8 cm3 (range, 0.9-4.0 cm3), and 2.7 cm3 (range, 1.0-3.7 cm3), respectively. The median total brain volume was 1343 cm3 (range, 1120.5-1738.8 cm3). For all measures of corrected HV, increasing HV was associated with higher baseline HVLT-R TR and DR scores (ρ: range, 0.35-0.40; P-value range, .009-.024) and 4-month TR and DR scores (ρ: range, 0.29-0.40; P-value range, .009-.04), with the exception of right HV and 4-month DR scores (ρ: 0.29; P = .059). There was no significant association between HV and NCF change between baseline and 4 months. Fourteen patients (33.3%) developed NCF deterioration per the primary endpoint of RTOG 0933. There was no significant difference in HV between patients with deteriorated and nondeteriorated NCF, although in all instances, patients with deteriorated NCF had numerically lower HV. Conclusions: Larger HV was positively associated with improved performance on baseline and 4-month HVLT-R TR and DR scores in patients with brain metastases undergoing hippocampal-avoidant whole brain radiation therapy but was not associated with a change in NCF.

Oxidative stress (OS)-induced mitochondrial damage is a risk factor for primary open-angle glaucoma (POAG). Mitochondria-targeted novel antioxidant therapies could unearth promising drug candidates for the management of POAG. Previously, our dual-acting hybrid molecule SA-2 with nitric oxide-donating and antioxidant activity reduced intraocular pressure and improved aqueous humor outflow in rodent eyes. Here, we examined the mechanistic role of SA-2 in trabecular meshwork (TM) cells in vitro and measured the activity of intracellular antioxidant enzymes during OS. Primary human TM cells isolated from normal (hNTM) or glaucomatous (hGTM) post-mortem donors and transformed glaucomatous TM cells (GTM-3) were used for in vitro assays. We examined the effect of SA-2 on oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) in vitro using Seahorse Analyzer with or without the oxidant, tert-butyl hydroperoxide (TBHP) treatment. Concentrations of total antioxidant enzymes, catalase (CAT), malondialdehyde (MDA), and glutathione peroxidase (GPx) were measured. We observed significant protection of both hNTM and hGTM cells from TBHP-induced cell death by SA-2. Antioxidant enzymes were elevated in SA-2-treated cells compared to TBHP-treated cells. In addition, SA-2 demonstrated an increase in mitochondrial metabolic parameters. Altogether, SA-2 protected both normal and glaucomatous TM cells from OS via increasing mitochondrial energy parameters and the activity of antioxidant enzymes.

CNS metastases are often terminal for cancer patients and occur at an approximately 10-fold higher rate than primary CNS tumors. The incidence of these tumors is approximately 70,000–400,000 cases annually in the US. Advances that have occurred over the past two decades have led to more personalized treatment approaches. Newer surgical and radiation techniques, as well as targeted and immune therapies, have enanled patient to live longer, thus increasing the risk for the development of CNS, brain, and leptomeningeal metastases (BM and LM). Patients who develop CNS metastases have often been heavily treated, and options for future treatment could best be addressed by multidisciplinary teams. Studies have indicated that patients with brain metastases have improved survival outcomes when cared for in high-volume academic institutions using multidisciplinary teams. This manuscript discusses a multidisciplinary approach for both parenchymal brain metastases as well as leptomeningeal metastases implemented in three academic institutions. Additionally, with the increasing development of healthcare systems, we discuss optimizing the management of CNS metastases across healthcare systems and integrating basic and translational science into our clinical care to further improve outcomes. This paper summarizes the existing therapeutic approaches to the treatment of BM and LM and discusses novel and emerging approaches to optimizing access to neuro-oncologic care while simultaneously integrating multidisciplinary teams in the care of patients with BM and LM.

Abstract The circadian clock is a cellular mechanism that synchronizes various biological processes with respect to the time of the day. While much progress has been made characterizing the molecular mechanisms underlying this clock, it is less clear how external light cues influence the dynamics of the core clock mechanism and thereby entrain it with the light–dark cycle. Zebrafish-derived cell cultures possess clocks that are directly light-entrainable, thus providing an attractive laboratory model for circadian entrainment. Here, we have developed a stochastic oscillator model of the zebrafish circadian clock, which accounts for the core clock negative feedback loop, light input, and the proliferation of single-cell oscillator noise into population-level luminescence recordings. The model accurately predicts the entrainment dynamics observed in bioluminescent clock reporter assays upon exposure to a wide range of lighting conditions. Furthermore, we have applied the model to obtain refitted parameter sets for cell cultures exposed to a variety of pharmacological treatments and predict changes in single-cell oscillator parameters. Our work paves the way for model-based, large-scale screens for genetic or pharmacologically-induced modifications to the entrainment of circadian clock function.

Neuroblastoma accounts for >15% of cancer-associated mortalities of children in the USA. Despite aggressive treatment regimens, the long-term survival for these children remains

Neuroblastoma is the cause of >15% of cancer-associated mortality in children in the USA. Despite aggressive treatment regimens, the long-term survival rate for these children remains at

Brain metastases are the most common intracranial neoplasm and are seen in upwards of 10-30% of patients with cancer. For decades, whole brain radiation therapy (WBRT) was the mainstay of treatment in these patients. While WBRT is associated with excellent rates of intracranial tumor control, studies have demonstrated a lack of survival benefit, and WBRT is associated with higher rates of cognitive deterioration and detrimental effects on quality of life. In recent years, strategies to mitigate this risk, such as the incorporation of memantine and hippocampal avoidance have been employed with improved results. Furthermore, stereotactic radiosurgery (SRS) has emerged as an appealing treatment option over the last decade in the management of brain metastases and is associated with superior cognitive preservation and quality of life when compared to WBRT. This review article evaluates the pathogenesis and impact of cranial irradiation on cognition in patients with brain metastases, as well as current and future risk mitigation techniques.

• Myocardial flow reserve (MFR) on positron emission tomography longitudinally declines over time after heart transplantation and is prognostic for adverse post-transplant events. • Cardiometabolic risk factors, allograft rejection and cytomegalovirus infection are associated with reduced MFR and, therefore, the development and progression of cardiac allograft vasculopathy. • The use of moderate- to high-intensity statin therapy is associated with a higher MFR, and escalation of statin intensity may reduce the incidence of cardiac allograft vasculopathy. Positron emission tomography (PET) myocardial flow reserve (MFR) is a noninvasive method of detecting cardiac allograft vasculopathy in recipients of heart transplants (HTs). There are limited data on longitudinal change and predictors of MFR following HT. We conducted a retrospective analysis of HT recipients undergoing PET myocardial perfusion imaging at an academic center. Multivariable linear and Cox regression models were constructed to identify longitudinal trends, predictors and the prognostic value of MFR after HT. Of HT recipients, 183 underwent 658 PET studies. The average MFR was 2.34 ± 0.70. MFR initially increased during the first 3 years following HT (+ 0.12 per year; P = 0.01) before beginning to decline at an annual rate of -0.06 per year (P < 0.001). MFR declines preceding acute rejection and improves after treatment. Treatment with mammalian target of rapamycin (mTOR) inhibitors (37.2%) slowed the rate of annual MFR decline (P = 0.03). Higher-intensity statin therapy was associated with improved MFR. Longer time post-transplant (P < 0.001), hypertension (P < 0.001), chronic kidney disease (P < 0.001), diabetes mellitus (P = 0.038), antibody-mediated rejection (P = 0.040), and cytomegalovirus infection (P = 0.034) were associated with reduced MFR. Reduced MFR (HR: 7.6, 95% CI: 4.4–13.4; P < 0.001) and PET-defined ischemia (HR: 2.3, 95% CI: 1.4–3.9; P < 0.001) were associated with a higher risk of the composite outcome of mortality, retransplantation, heart failure hospitalization, acute coronary syndrome, or revascularization. MFR declines after the third post-transplant year and is prognostic for cardiovascular events. Cardiometabolic risk-factor modification and treatment with higher-intensity statin therapy and mechanistic target of rapamycin inhibitors are associated with a higher MFR. [Display omitted] [ABSTRACT FROM AUTHOR]

Abstract Background Proton therapy is a promising advancement in radiation oncology especially in terms of reducing normal tissue toxicity, although it is currently expensive and of limited availability. Here we estimated the individual quality of life benefit and cost-effectiveness of proton therapy in patients with oropharyngeal cancer treated with definitive radiation therapy (RT), as a decision-making tool for treatment individualization. Methods and materials Normal tissue complication probability models were used to estimate the risk of dysphagia, esophagitis, hypothyroidism, xerostomia and oral mucositis for 33 patients, comparing delivered photon intensity-modulated RT (IMRT) plans to intensity-modulated proton therapy (IMPT) plans. Quality-adjusted life years (QALYs) lost were calculated for each complication while accounting for patient-specific conditional survival probability and assigning quality-adjustment factors based on complication severity. Cost-effectiveness was modeled based on upfront costs of IMPT and IMRT, and the cost of acute and/or long-term management of treatment complications. Uncertainties in all model parameters and sensitivity analyses were included through Monte Carlo sampling. Results The incremental cost-effectiveness ratios (ICERs) showed considerable variability in the cost of QALYs spared between patients, with median $361,405/QALY for all patients, varying from $54,477/QALY to $1,508,845/QALY between individual patients. Proton therapy was more likely to be cost-effective for patients with p16-positive tumors ($234,201/QALY), compared to p16-negative tumors ($516,297/QALY). For patients with p16-positive tumors treated with comprehensive nodal irradiation, proton therapy is estimated to be cost-effective in ≥ 50% of sampled cases for 8/9 patients at $500,000/QALY, compared to 6/24 patients who either have p16-negative tumors or receive unilateral neck irradiation. Conclusions Proton therapy cost-effectiveness varies greatly among oropharyngeal cancer patients, and highlights the importance of individualized decision-making. Although the upfront cost, societal willingness to pay and healthcare administration can vary greatly among different countries, identifying patients for whom proton therapy will have the greatest benefit can optimize resource allocation and inform prospective clinical trial design.

Introduction: The current Coronavirus Disease-19 (COVID-19) pandemic is considered as one of the most serious public health crises which caused more than 1.62 million deaths from October 2020 to November 2020. Acute respiratory failure is leading cause of death followed by sepsis, cardiac failure and haemorrhage. Since the pathological findings are diverse in COVID-19 and majority of studies in literature were by open autopsy; the present study was done using percutaneous core needle biopsy. Postmortem lung biopsies are rather easy and quick to perform and decrease the infective risk caused by full autopsies. This could be an essential tool for diagnosis, surveillance and research. Aim: To study the pathological features of lung in COVID-19 deceased patients by postmortem. Materials and Methods: This cross-sectional study was conducted in the Department of Pulmonary Medicine, Dr. Pinnamaneni Siddhartha Institute of Medical Sciences and Research Foundation, Vijayawada, Andhra Pradesh, India from October 2020 to November 2020. In present study, postmortem percutaneous core needle biopsies from lung were performed within two hours of death from eight deceased patients who died of COVID-19. Clinical history, inflammatory markers and treatment details were collected from case sheets, biopsy was done, specimen was collected and sent for pathological examination. Data was presented in the descriptive form for each variable. Results: Out of eight cases, five were men and three were women with a mean age of 54.12 years. Majority of patients presented with complaints of shortness of breath and fever. Hypertension, type 2 diabetes mellitus, obesity, hypothyroidism, history of pulmonary tuberculosis were the co-morbidities noticed. Four biopsies presented acute lung injury with hyaline membrane changes, Diffuse Alveolar Damage (DAD) with hyaline membrane was seen in two cases, squamous metaplasia was seen in two cases and acute lung injury with organising pneumonia was seen in two cases. Conclusion: Postmortem lung biopsies are safe, easy to perform and provide insights of possible undergoing pathology of the disease with regard to clinical presentation.

Neuroblastoma (NB) is the most common extra-cranial solid tumor in children and despite aggressive therapy survival rates remain low. One of the contributing factors for low survival rates is aggressive tumor angiogenesis, which is known to increase due to radiation, one of the standard therapies for neuroblastoma. Therefore, targeting tumor angiogenesis can be a viable add-on therapy for the treatment of neuroblastomas. In the present study, we demonstrate that overexpression of secreted protein acidic and rich in cysteine (SPARC) suppresses radiation induced angiogenesis in SK-N‑BE(2) and NB1691 neuroblastoma cells. We observed that overexpression of SPARC in SK-N-BE(2) and NB1691 cells reduced radiation induced angiogenesis in an in vivo mouse dorsal skin model and an ex vivo chicken CAM (chorioallantoic-membrane) model and also reduced tumor size in subcutaneous mouse tumor models of NB. We also observed that SPARC overexpression reduces VEGF-A expression, in SK-N-BE(2) and NB1691 NB cells via miR-410, a VEGF-A targeting microRNA. SPARC overexpression alone or in combination with miR-410 and radiation was shown to be effective at reducing angiogenesis. Moreover, addition of miR-410 inhibitors reversed SPARC mediated inhibition of VEGF-A in NB1691 cells but not in SK-N-BE(2) NB cells. In conclusion, the present study demonstrates that the overexpression of SPARC in combination with radiation reduced tumor angiogenesis by downregulating VEGF-A via miR-410.

In diabetic peripheral neuropathy, offloading high-plantar-pressure areas using statically offloaded customized insoles or expensive sensors and actuators are commonly-followed treatment procedures. In this article, we propose the concept of dynamically self-offloading therapeutic footwear that operates mechanically without using sensors and actuators. We achieve this by using an array of snapping arches. When a load higher than a bespoke value is applied, these arches enter negative-stiffness regime and offload the high-pressure region by snapping to a different shape. They again return to their initial shape when the load disappears. Thus, they serve as both sensors and actuators that get actuated by person’s body weight. We present an analytical method to compute the switching load and the switchback time of such arches and use them to customize the footwear according to the person’s body weight, gait speed, and foot size. We identify the high-pressure regions from the clinical data and place the arches such that these high-pressure regions get dynamically offloaded, and the pressure gets redistributed to other regions. We considered 200 kPa as a limiting pressure to prevent the prolonged effects of high plantar pressure. To check the efficacy of the concept, a complete 3D-printed prototype made of thermoplastic polyurethane was tested and compared with barefoot and in-shoe plantar pressure for subjects recruited at a clinical facility. We notice that the self-offloading insole shows the plantar pressure reduction at all the foot regions, and significant offloading of 57% is observed at the forefoot region.

BackgroundLow dose radiation therapy (LDRT) has been used for non-malignant conditions since early 1900s based on the ability of single fractions between 50-150 cGy to inhibit cellular proliferation. Given scarcity of resources, poor access to vaccines and medical therapies within low and middle income countries, there is an urgent need to identify other cost-effective alternatives in management of COVID-19 pneumonia. We conducted a pilot phase Ib/II investigator-initiated clinical trial to assess the safety, feasibility, and toxicity of LDRT in patients with severe COVID-19 pneumonia at the Aga Khan University Hospital in Nairobi, Kenya. Additionally, we also assessed clinical benefit in terms of improvement in oxygenation at day 3 following LDRT and the ability to avoid mechanical ventilation at day 7 post LDRT.MethodsPatients with both polymerase chain reaction (PCR) and high-resolution computer tomogram (HRCT) confirmed severe COVID-19 pneumonia, not improving on conventional therapy including Dexamethasone and with increasing oxygen requirement were enrolled in the study. Patients on mechanical ventilation were excluded. Eligible patients received a single 100cGy fraction to the whole lung. In the absence of any dose limiting toxicity the study proposed to treat a total of 10 patients. The primary endpoints were to assess the safety/feasibility, and toxicity within the first 24 hours post LDRT. The secondary endpoints were to assess efficacy of LDRT at Day 3, 7, 14 and 28 post LDRT.ResultsTen patients were treated with LDRT. All (100%) of patients were able to complete LDRT without treatment related SAE within the first 24 hours post treatment. None of the patients treated with LDRT experienced any acute toxicity as defined by change in clinical and respiratory status at 24hr following LDRT. Majority (90%) of patients avoided mechanical ventilation within 7 days of LDRT. Four patients (40%) demonstrated at least 25% improvement in oxygen requirements within 3 days. Six patients (60%) were discharged and remained off oxygen, whereas four progressed and died (1 due to sepsis and 3 in cytokine storm). Median time to discharge (n = 6) was 16.5 days and median time to death (n = 4) was 11.0 days. Patients who ultimately died showed elevated inflammatory markers including Ferritin, CRP and D-dimers as compared to those who were discharged alive.ConclusionLDRT was feasible, safe and shows promise in the management of severe COVID-19 pneumonia including in patients progressing on conventional systemic treatment. Additional phase II trials are warranted to identify patients most likely to benefit from LDRT.

The current study intended to improve the disintegration potential of paper mill sludge through alkyl polyglycoside-coupled disperser disintegration. The sludge biomass was fed to the disperser disintegration and a maximum solubilization of 6% was attained at the specific energy input of 4729.24 kJ/kg TS. Solubilization was further enhanced by coupling the optimum disperser condition with varying dosage of alkyl polyglycoside. The maximum solubilization of 11% and suspended solid (SS) reduction of 8.42% were achieved at the disperser rpm, time, and surfactant dosage of 12,000, 30 min, and 12 μL. The alkyl polyglycoside-coupled disperser disintegration showed a higher biogas production of 125.1 mL/gCOD, compared to the disperser-alone disintegration (70.1 mL/gCOD) and control (36.1 mL/gCOD).

The objective of this study was to evaluate the effect of surfactant on disperser homogenization pretreatment for macroalgae (Ulva intestinalis) to enhance biogas production. The macroalgae are subjected to surfactant coupled disperser pretreatment, which enhanced the liquefaction and improved the biomethane production. The outcome of this study revealed that 10,000 rpm at 20 min with a specific energy input of 1748.352 kJ/ kg total solids (TS) are the optimum conditions for surfactant disperser pretreatment (SDP), which resulted in the liquefaction rate of 20.08% with soluble organics release of 1215 mg/L and showed a better result than disperser pretreatment (DP) with a liquefaction rate of 14%. Biomethane production through the SDP method was found to be 0.2 g chemical oxygen demand (COD)/g COD, which was higher than DP (0.11 g COD/g COD). SDP was identified to be a synergetic pretreatment method with an energy ratio and net profit of about 0.91 and 104.04 United States dollars (USD)/ton, respectively.