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Abstract Breast cancer is the most common malignancy affecting women worldwide and is notable for its morphologic and biologic diversity, with varying risks of recurrence following treatment. The Oncotype DX Breast Recurrence Score test is an important predictive and prognostic genomic assay for estrogen receptor positive/HER2 negative breast cancer that guides therapeutic strategies; however, such tests can be expensive, delay care, and are not widely available. The aim of this study was to develop a multi-model approach integrating the analysis of whole-slide images and clinicopathologic data to predict their associated breast cancer recurrence risks and categorize these patients into two risk groups according to the predicted score: low-risk and high-risk. The proposed novel methodology uses convolutional neural networks for feature extraction and vision transformers for contextual aggregation, complemented by a logistic regression model that analyzes clinicopathologic data for classification into two risk categories. This method was trained and tested on 956 hematoxylin and eosin-stained whole-slide images of 950 ER+/HER2− breast cancer patients with corresponding clinicopathological features that had prior Oncotype DX testing. The model’s performance was evaluated using an internal test set of 192 patients from Dartmouth Health and an external test set of 405 patients from the University of Chicago. The multi-model approach achieved an AUC of 0.91 (95% CI: 0.87–0.95) on the internal set and an AUC of 0.84 (95% CI: 0.78–0.89) on the external cohort for predicting low- and high-breast cancer recurrence risk categories based on the Oncotype DX recurrence score. With further validation, the proposed methodology could provide an alternative to assist clinicians in personalizing treatment for breast cancer patients and potentially improving their outcomes.

ABSTRACT Introduction Data suggest malfunctioning mitochondria reduce oxidation and adenosine triphosphate (ATP) production, disrupting insulin signalling. Cytochrome c (CC), acylcarnitine (AC) and citrate synthase (CS) are essential components of the mitochondria machinery and can be used as reliable biomarkers of mitochondrial dysfunction. This study aimed to determine whether mitochondrial biomarkers (AC, CS and CC) are altered in individuals with type 2 diabetes mellitus (T2DM) and to examine the association between these biomarkers and insulin resistance. Methodology A cross‐sectional observational study that recruited 170 participants (88 with T2DM and 82 without DM) was conducted. Blood samples were collected from the recruits and analysed for levels of fasting glucose (FBG), AC, CS, CC, insulin, total cholesterol, triglycerides (TG), glycated haemoglobin (HbA1c) and magnesium. Blood pressure (BP) and anthropometric characteristics of participants were also taken. Appropriate formulas were used to determine %body fat, body mass index (BMI), waist‐to‐hip ratio (WHR), the homeostatic model assessment for insulin resistance (HOMA‐IR) and insulin sensitivity (HOMA‐β). Results Patients with T2DM had higher levels of CC, %body fat, FBG, TG, HbA1c, BMI and HOMA‐IR than controls (p

Abstract Aquaculture is a key component of Ghana's food system strategies, promoting sustainable animal protein production. Aquaculture complements traditional marine capture fisheries to close the gap between demand and supply. However, about one third of fish produced globally have been reported to go to waste yearly. Among the various cultured fish, the Nile tilapia Oreochromis niloticus is a predominant species. This study aimed to estimate the extent of Nile tilapia wastage by consumers in Ghana. A web‐based cross‐sectional consumer survey was designed to assess the parts of the tilapia consumers generally classified as edible or inedible, taking into account the three primary tilapia preparation methods. The study utilised a semi‐structured online questionnaire, gathering responses from 246 participants. The parts of Nile tilapia investigated included the flesh, fins, offal, head, scales, bones, and gill flaps/opercula. The analysis of consumed and wasted parts of Nile tilapias by weight showed that, on average, the flesh made up the majority of the fish at 55.26%, followed by the head at 26.46%, offal at 8.51%, scales at 3.10%, fins at 2.93%, bones at 2.76%, and operculum at 0.98%, which was the smallest component. The study concluded that approximately 30%–45% of waste is generated from Nile tilapia in the Ghanaian supply chain. Tilapia was widely consumed by all groups, with an average liking score of 7.69 ± 1.95 on a 10‐point hedonic scale. A significant association was found between gender and consumption patterns with females showing a higher degree of liking. There was a strong association between the method of preparation and consumption patterns; the fried parts were classified as more edible compared to those that were boiled or grilled. To reduce waste in the aquaculture industry, tilapia and other fishes could be processed in a way that various edible and inedible parts are sold separately.

Diarrhoea, which is a clinical manifestation of various illnesses, is frequently observed in dogs. Regrettably, many dog owners find it difficult to provide comprehensive case histories, primarily because of limited interaction with their canine companions. This study aimed to evaluate the potential of faecal biochemical analytes in detecting and characterizing acute diarrhoea in dogs. Sixty-two domestic dogs were selected using the proportionate stratified sample technique. A structured questionnaire was used to collect demographic and clinical data. Faecal stool specimens from the dogs were obtained using the colon flush technique. The specimens were taken through biochemical analysis to determine urea, creatinine, total bilirubin, total cholesterol, triglycerides, gamma-glutamyl transferase and uric acid levels. Results showed a significant association between the diarrhoea status of the participants and their age, weight, breed, body size, source of last diet, period of inappetence, and other gastrointestinal signs (p < 0.050, respectively). Dogs that had not eaten in at least three days were five times more likely (p < 0.05) to have diarrhoea. Furthermore, miniature breeds were about six times more likely to develop diarrhoea (p < 0.05). Of the seven selected biochemical parameters, total faecal cholesterol was the most predictive index in diagnosing acute diarrhoea in dogs, with a likelihood ratio of 6.5, and it was the most accurate in predicting defecation stooling frequency and texture. In summary, in situations of inadequate case histories, measuring total faecal cholesterol could assist veterinarians in detecting diarrhoea and predicting its faecal stooling texture and frequency in dogs.

Background: : Pangdahai (matured, ripened, and dried seeds of Scaphium affine (Mast.) Pierre) is widely used in managing several diseases in countries like China, Vietnam, Japan, and India. This study evaluated the anti-inflammatory effects of the crude extracts (ethanol and aqueous) and isolated compounds of Pangdahai. Methods: : Xylene-induced ear edema in mice, carrageenan-induced paw edema in rats, and nitric oxide (NO) assay were used to evaluate and screen the crude extracts and isolated compounds from the ethanolic extracts of Pangdahai. TNF-α and IL-1β levels in the tissues of rat foot and ear were determined by ELISA. The cytotoxicity of the isolated compounds was also determined by MTT assay. Molecular docking studies using targets involved in the inflammatory process were also used to further evaluate the compounds. Results: : Both aqueous and ethanol extracts demonstrated significant anti-inflammatory effect and markedly attenuated vascular permeability in mice induced by acetic acid in a dose-independent manner. The ethanol extract also significantly inhibited levels of IL-1β and TNF-α. Four (4) compounds exhibited significant inhibitory effects on NO release without cytotoxicity on RAW 264.7 macrophage. These compounds also showed good binding affinities for COX-2, PLA2, IRAK-4 and NIK. Conclusions: This study validates, provides scientific evidence and justification for the use of the aqueous decoctions of Pangdahai in pharyngitis traditionally. (+) – Pinoresinol, tiliroside, Z-caffeic acid, and 3,4-dihydroxybenzoic acid (protocatechuic acid) isolated from Pangdahai showed anti-inflammatory activities, which might be responsible for the actions of Pangdahai. Tiliroside showed high binding affinity comparable to the native ligands of inflammatory mediators.

Abstract Efforts to discourage academic misconduct in online learning environments frequently include the use of remote proctoring services. While these services are relatively commonplace in undergraduate science courses, there are open questions about students’ remote assessment environments and their concerns related to remote proctoring services. Using a survey distributed to 11 undergraduate science courses engaging in remote instruction at three American, public, research-focused institutions during the spring of 2021, we found that the majority of undergraduate students reported testing in suboptimal environments. Students’ concerns about remote proctoring services were closely tied to technological difficulties, fear of being wrongfully accused of cheating, and negative impacts on mental health. Our results suggest that remote proctoring services can create and perpetuate inequitable assessment environments for students, and additional research is required to understand the efficacy of their intended purpose to prevent cheating. We also advocate for continued conversations about the broader social and institutional conditions that can pressure students into cheating. While changes to academic culture are difficult, these conversations are necessary for higher education to remain relevant in an increasingly technological world.

Abstract Objective Perilipin A is a common protein that coats lipid surfaces preventing them from being exposed to oxidative damage. Researchers have found little consistency in the relationship between perilipin A levels in the blood and body fat. This study was a cross-sectional observational that looked at circulating perilipin A levels and how they relate to metabolic health. Results The participants in this study were 86 individuals with a mean age of 45.5 ± 1.2 years. Multiple clinical and metabolic indicators (age, weight, BMI, total body fat mass, triglyceride, and HOMA-IR) were shown to be inversely associated with perilipin A levels (rho = − 0.32, − 0.37, − 0.40, − 0.45, − 0.33 and − 0.29; p

Abstract Background and Aims Cardiovascular diseases (CVDs) are among the leading causes of disability and early death in sub‐Saharan Africa. Most of the current blood tests for CVD diagnosis involve performing about three test profiles; often at additional cost to patients. C‐peptide, a cleavage product of proinsulin, is a promising marker that has the potential to serve as a proxy marker for diagnosing CVDs in resource‐poor settings. Methodology The study was an observational cross‐sectional one and involved 127 consenting persons diagnosed with CVD and 127 individuals without CVD. The socio‐demographic and clinical characteristics of participants were obtained. Blood levels of C‐peptide, fasting plasma glucose (FPG), total creatinine kinase (CK), creatine kinase myocardial bound (CKMB), lactate dehydrogenase (LDH), propeptide of brain natriuretic peptide (PBNP), Troponin T, lipids, and biomarkers of kidney and liver function were analyzed using ELISA and an automated analyzer. Insulin resistance was computed using the modified homeostatic model assessment (HOMA‐IR). Results The CVD Group had significantly higher levels of C‐peptide, CK, CKMB, troponin T, PBNP, FPG, HOMA‐IR, and several selected kidney, liver, and lipid parameters compared to the non‐CVD Group (p

Abstract Introduction Insulin resistance (IR) is one of the common chronic metabolic disorders in Africa and elsewhere. Accumulation of lipids in the body may be due to an imbalance in the metabolism of lipids, glucose and proteins. Ceramides are a sphingolipid class of lipids that are biologically active and vital in the production of more complex lipids. Circulating ceramides are thought to have a role in the development of obesity‐related IR, although the precise involvement remains unclear. Aim To investigate the impact of circulating ceramide on IR and body adiposity in people with and without type 2 diabetes mellitus (T2DM). Methodology The study was observational and cross‐sectional. There were a total of 84 volunteers with T2DM and 75 nondiabetics (control). The participants' ages, body mass indexes (BMI), waist circumferences, and blood pressure (BP) were among the clinical parameters assessed. Ceramide levels, fasting plasma glucose (FPG), lipids, basal insulin levels and glycated haemoglobin (HbA1c) were also measured. Additionally, the homeostatic model assessment for IR (HOMA‐IR) and beta cell function (HOMA‐β) were computed. Results T2DM and control participants had different mean values for anthropometric parameters, BP, FPG, HbA1c, lipids, insulin, HOMA‐IR, HOMA‐β and ceramide levels (p

Since December 2019 when COVID-19 was detected, it took the world by surprise in terms of spread and morbidity/mortality. The high rate of spread and casualties recorded from COVID-19 called for research in all directions to find ways to contain and reverse the incidences. It is against this background that this paper sought to measure the association of the socio-demographic factors in the hard-hit districts in Greater Accra and Ashanti to analyze its relationship with the novel COVID-19 virus. Data on COVID-19 cases from 35 Districts in both Greater Accra and Ashanti Regions were collected from the Ghana Health Service and population data from Ghana Statistical Service. Descriptive statistics and regression analysis were generated using R. We found that some socio-demographic variables have an association with COVID-19 infections. For example, age and religion especially Christianity and Islam pose risk to COVID-19. The population aged 15–64 was particularly at high risk of infections due to the high level of movement of this age group. We, therefore, recommend that places of congregation such as Churches and Mosques be targeted for vigorous sensitization on COVID-19 protocols and prevention. Also, districts with a high population between the ages of 15–64 should step sensitization efforts to educate their inhabitants on the need to reduce travel and related activities to curb the spread of the virus.

Abstract Lattice actions and amplitudes that perfectly mirror continuum physics are known as perfect discretizations. Such perfect discretizations naturally preserve the symmetries of the continuum. This is a key concern for general relativity, where diffeomorphism symmetry and dynamics are deeply connected, and diffeomorphisms play a crucial role in quantization. In this work we construct for the first time a perfect discretizations for four-dimensional linearized gravity. We show how the perfect discretizations lead to a straightforward construction of the one-loop quantum corrections for manifolds with boundary. This will also illustrate, that for manifolds with boundaries, gauge modes that affect the boundary, need to be taken into account. This work provides therefore an evaluation of the boundary action for the diffeomorphism modes for a general class of backgrounds.

Background/Aim: Depression-related aggression is linked to serotonin (5-HT) and dendritic spine alterations. Although Mallotus oppositifolius extract (MOE) has potential for reducing this effect, its specific role remains uncertain. Herein, we evaluated this potential and associated alterations in the brain.Methods: A standard resident-intruder model of para-chlorophenylalanine (pCPA)-induced depression-associated aggression in male ICR mice was used. The resident mice received pCPA (300 mg/kg, i. p.) for 3 consecutive days while saline-treated mice served as negative control. The pCPA aggressive mice were subsequently treated orally with either MOE (30, 100, 300 mg/kg), fluoxetine (20 mg/kg), tryptophan (20 mg/kg) or saline (untreated pCPA group) for 28 days. Locomotor activity was assessed using open field test. Serotonin (5-HT) levels in mice brain and phytochemical fingerprint of MOE were determined by high performance liquid chromatography (HPLC) while gas chromatography-mass spectrometry (GC-MS) was used to identify constituents of MOE. Dendritic spine density and morphology were evaluated using Golgi-Cox staining technique and analyzed with ImageJ and Reconstruct software.Results: Administration of pCPA induced aggressive behavior in mice, evidenced by increased attack behaviors (increased number and duration of attacks), which positively correlated with squeaking and tail rattling. MOE treatment significantly reduced these characteristics of aggression in comparison with vehicle (non-aggressive) and untreated pCPA groups (p < 0.001), and also reduced social exploration behavior. Although the behavioral effects of MOE were comparable to those of fluoxetine and tryptophan, these effects were quicker compared to fluoxetine and tryptophan. Additionally, MOE also markedly increased 5-HT concentration and dendritic spine density in the prefrontal cortex relative to vehicle and untreated pCPA groups (p < 0.05). Interestingly, these behavioral effects were produced without compromising locomotor activity. GC-MS analysis of the MOE identified 17 known compounds from different chemical classes with anti-inflammatory, antioxidant, neuroprotective and antidepressant activities, which may have contributed to its anti-aggressive effect.Conclusion: MOE decreased depression-associated aggressive behavior in mice via increased 5-HT concentration and dendritic spine density in the prefrontal cortex. The MOE-mediated effects were faster than those of fluoxetine and tryptophan. Our finding suggests that MOE may have clinical promise in decreasing aggressive and depressive behaviors.

Abstract Dielectric soil moisture probes can be used to obtain frequently logged field observations of volumetric water content, but because this is an indirect method, it is challenging to ensure that you have a suitable calibration relationship and parameters. Challenges are associated with (a) limitations in the probes’ ability to accurately measure the soil bulk dielectric constant and (b) limitations in obtaining reliable direct observations to calibrate the probe against, due to the spatial heterogeneity in the field. Furthermore, in soils that freeze, we do not have a robust approach to account for the effect of ice on the instrument. In this study, we propose a calibration relationship for all dielectric probes that is physically based, parsimonious, accounts for errors in the bulk dielectric constant, and quantifies the uncertainty in the liquid water content caused by the presence of ice. We show that our relationship has a better performance and more realistic parameter values than existing approaches. To calibrate a dielectric probe in the field, we show that it is necessary to account for spatial heterogeneity in samples taken for calibration. There is value in taking simultaneous measurements of the bulk dielectric constant (using the same dielectric probe as is being calibrated) and gravimetric samples for water content at a number of points in space. Taking too few samples is likely to be misinformative—we show that it is better to not calibrate the probe at all than to calibrate it with too few data points.

Background: A Pain Plan was formulated for all patients undergoing elective spine surgery at our institution. It was based on prior opioid experiences and developed collaboratively between the patient and the surgeon at a preoperative clinic visit. Category 1 patients had no previous opioid experience, Category 2 patients had remote previous opioid experience with acceptable pain control and no side effects, Category 3 patients had remote previous opioid experience with unacceptable pain control and/or side effects, and Category 4 patients had opioid use leading up to surgery. Methods: This is a retrospective cohort study comparing adult patients within four different pain plan categories over one year (n = 313) to determine if categorization is predictive. Demographic data collected included age, gender, ASA class, BMI, smoking status, insurance status, substance abuse, and comorbid psychiatric diagnoses. Demographic factors between categories were compared and controlled for as covariates within analyses. Outcomes measures comprised self-reported pain scores and functional measurements, including inpatient opioid use, outpatient opioid prescription quantities, and postoperative healthcare utilization. Results: Inpatient and outpatient opioid use were statistically significant amongst the categories, with prescription quantities greatest in Category 4, followed by Categories 2, 3, and 1, respectively. There was no difference in LOS or complexity of communication encounters amongst any of the groups. Patient-reported pain scores showed statistically significant differences and followed the same trend as opioid quantities, 4, 2, 3, and 1. The number of communication encounters was significant exclusively for Category 3 vs. 4. Conclusions: The use of categorization in Pain Plan formation has been a helpful tool for postoperative pain management at our institution. Categorization is predictive of pain scores and opioid use after surgery, allowing the surgical team to tailor their care and counseling towards individual patients. In addition, the plan's collaborative nature enables patients to be involved in their pain management decisions while also setting limits and expectations.

Abstract Inquiry activities have become increasingly common in Ecology and Evolution courses, but the rapid shift to remote instruction for many faculty members in response to the COVID‐19 pandemic has created new challenges for maintaining these student‐centered activities in a distance learning format. Moving forward, many instructors will be asked to create flexible course structures that allow for a mix of different teaching modalities and will be looking for resources to support student inquiry in both online and in‐person settings. Here, we propose the use of data‐driven inquiry activities as a flexible option for offering students experiences to build career‐relevant skills and learn fundamental ecological concepts. We share lessons learned from our experiences teaching a two‐semester course‐based research experience in global change ecology that leverages publicly available datasets to engage students in broadly relevant scientific inquiry.

David C Metz,1 Eric Liu,2 Vijay N Joish,3 Lynn Huynh,4 Todor I Totev,4 Mei Sheng Duh,4 Kiernan Seth,3 Susan Giacalone,3 Pablo Lapuerta,3 Michael A Morse5 1Neuroendocrine Tumor Program at Penn Medicine, Philadelphia, PA 19104, USA; 2The Neuroendocrine Institute at Rocky Mountain Cancer Centers, Denver, CO 80218, USA; 3Lexicon Pharmaceuticals, Inc, The Woodlands, TX 77831, USA; 4Analysis Group, Boston, MA 02199, USA; 5Duke Cancer Institute, School of Medicine, Duke University, Durham, NC 27710, USACorrespondence: David C MetzNeuroendocrine Tumor Program at Penn Medicine, Perelman Center for Advanced Medicine, South Pavilion, 4th Floor, 3400 Civic Center Boulevard, Philadelphia, PA 19104, USATel +1 800 789 7366Email david.metz@pennmedicine.upenn.eduPurpose: The TELEACE study showed reductions in tumor size in patients with neuroendocrine tumors, receiving telotristat ethyl in US clinical practice. Here, we report progression-free survival, time to tumor progression, changes in carcinoid syndrome symptoms, and indictors of overall health.Patients and Methods: This was a retrospective, single arm, pre-post medical chart review of patients with locally advanced or metastatic neuroendocrine tumors and documented carcinoid syndrome receiving telotristat ethyl for at least 6 months. Patients with poorly differentiated tumors, mixed tumor types or conflicting clinical trial enrollment were excluded. Descriptive statistics, Kaplan–Meier and chi-square tests were used to evaluate PFS, tumor progression, changes in symptoms, body weight and ECOG performance status before and after telotristat ethyl initiation. Subgroup analyses were conducted in patients with the same pre- and post-telotristat ethyl background treatment.Results: Anonymized data for 200 patients were provided by 114 physicians; patients received telotristat ethyl for a median of 9 months. Median time to tumor progression was 39.8 months (IQR, 18.7– 39.8); most had no tumor progression at 6 (92%) and 12 months (87%). Median progression-free survival was 23.7 months (17.8– 39.8); most had progression-free survival at 6 (90%) and 12 months (80%). Results were consistent in the subgroup of 65 patients with the same pre/post background treatment. Nearly all patients had improved carcinoid syndrome symptoms, stable or improved weight and ECOG performance status.Conclusion: Patients showed improvements in clinical outcomes and indicators of overall health following treatment with telotristat ethyl in this exploratory pilot study, consistent with previously observed reductions in tumor size.Keywords: neuroendocrine tumors, carcinoid syndrome, telotristat ethyl, survival

Introduction: Current American Urological Association (AUA) Best Practice Statement recommends antibiotic prophylaxis for cystoscopy with manipulation, including stent removal; although no Level 1b trials explicitly address prophylaxis for stent removal. We sought to determine the efficacy of prophylactic antibiotics to prevent infectious complications after stent removal. Materials and Methods: Following institutional review board approval, patients undergoing removal of ureteral stent placed during stone surgery were recruited from July 2016 to March 2019. Patients were recruited at the time of stent removal and randomized to treatment (single dose 500 mg oral ciprofloxacin) or control group (no antibiotics). Telephone contact was attempted within 14 days of stent removal to assess for urinary tract infection (UTI) symptoms, antibiotic prescriptions, or Emergency Department visits. Primary outcome was UTI within 1 month of stent removal – defined by irritative voiding symptoms, fever or abdominal pain associated with positive urine culture (Ucx) (>100k colony-forming units/mL). Results: Seventy-seven patients were enrolled, with 58 meeting final inclusion criteria for the analysis (33 treatment, 25 controls). No differences were seen with clinical and demographic variables, except a higher body mass index in the treatment group (P = 0.007). Positive Ucx rate before stone surgery (16.7% vs. 11.8%, P = 0.819) and at the time of stent removal (16.0% vs. 11.1%, P = 0.648) was not significantly different in treatment versus control groups, respectively. Primary outcome: No patients in either cohort developed symptomatic culture-diagnosed UTI within 1 month of stent removal. Of patients with documented phone follow-up (treatment n = 29, control n = 22), only one patient (control) reported any positive response on phone survey. Conclusions: We found a low infectious complication rate regardless of antibiotic prophylaxis use during cystoscopic stent removal. The necessity of antibiotics during routine cystoscopic stent removal warrants possible reevaluation of the AUA best practice statement.

Aminoglycosides are broad-spectrum antibiotics used in the treatment of gram-negative bacterial infections. Due to their nephrotoxic and ototoxic potential (narrow therapeutic index), the use of aminoglycoside for clinical indications requires monitoring. The objective of this review was to identify relevant literature reporting liquid chromatographic methods for the bioanalysis of aminoglycosides in both preclinical and clinical settings/experiments. Data on liquid chromatographic methods were collected from articles in an online academic database (PubMed, Science Direct, Scopus, and Google Scholar). All 71 articles published from 1977 to 2020 were included in the review. Reversed-phase liquid chromatography was the most used method for the bioanalysis of aminoglycosides. Fluorescence or ultraviolet detection methods were mostly used from 1977 to 2002 (51 articles), while mass spectrometry was predominantly used as a detector from 2003 to 2020 (15 articles). Sixty-seven articles reported calibration ranges, which varied significantly for the various drugs assayed: some in the range of 0.1-0.5 ng/mL and others 1250-200000 ng/mL. Also, 61 articles reported R2 values (0.964-1.0) for almost all analytes under consideration. Sixty-three articles reported percent recoveries mostly between 61.0 % to 114.0 %, with only two articles reporting recoveries of 4.9 % and 36 %. Out of the 71 reviewed articles, 56 reported intermediate precision values ranging between 0.331 % to 19.76 %, which is within the acceptable limit of 20 %. This review will serve as a guide for research and/or routine clinical monitoring of aminoglycosides in biological matrices.

Background: There is limited information on the safety or efficacy of currently recommended antimalarial drugs in patients with sickle cell disease (SCD), a population predisposed to worse outcomes if affected by acute malaria. Artesunate-amodiaquine (ASAQ) is the first-line treatment for uncomplicated malaria (UM) in many malaria-endemic countries and is also used for treatment of UM in SCD patients. There is, however, no information to date, on the pharmacokinetics (PK) of amodiaquine or artesunate or the metabolites of these drugs in SCD patients. Objectives: This study sought to determine the PK of desethylamodiaquine (DEAQ), the main active metabolite of amodiaquine, among paediatric SCD patients with UM treated with artesunate-amodiaquine (ASAQ). Methods: Plasma concentration-time data (median DEAQ levels) of SCD children (n = 16) was initially compared with those of concurrently recruited non-SCD paediatric patients with acute UM (n = 13). A population PK modelling approach was then used to analyze plasma DEAQ concentrations obtained between 64 and 169 hours after oral administration of ASAQ in paediatric SCD patients with acute UM (n = 16). To improve PK modeling, DEAQ concentration-time data (n = 21) from SCD was merged with DEAQ concentration-time data (n = 169) of a historical paediatric population treated with ASAQ (n = 103) from the same study setting. Results: The median DEAQ concentrations on days 3 and 7 were comparatively lower in the SCD patients compared to the non-SCD patients. A two-compartment model best described the plasma DEAQ concentration-time data of the merged data (current SCD data and historical data). The estimated population clearance of DEAQ was higher in the SCD patients (67 L/h, 21% relative standard error (RSE) compared with the non-SCD population (15.5 L/h, 32% RSE). The central volume of distribution was larger in the SCD patients compared with the non-SCD patients (4400 L, 43% RSE vs. 368 L, 34% RSE). Conclusions: The data shows a tendency towards lower DEAQ concentration in SCD patients and the exploratory population PK estimates suggest altered DEAQ disposition in SCD patients with acute UM. These findings, which if confirmed, may reflect pathophysiological changes associated with SCD on DEAQ disposition, have implications for therapeutic response to amodiaquine in SCD patients. The limited number of recruited SCD patients and sparse sampling approach however, limits extrapolation of the data, and calls for further studies in a larger population. Key words: Clearance, Desethylamodiaquine, Sickle cell disease

Abstract Gravity is uniquely situated in between classical topological field theories and standard local field theories. This can be seen in the quasi-local nature of gravitational observables, but is nowhere more apparent than in gravity’s holographic formulation. Holography holds promise for simplifying computations in quantum gravity. While holographic descriptions of three-dimensional spacetimes and of spacetimes with a negative cosmological constant are well-developed, a complete boundary description of zero curvature, four-dimensional spacetime is not currently available. Building on previous work in three-dimensions, we provide a new route to four-dimensional holography and its boundary gravitons. Using Regge calculus linearized around a flat Euclidean background with the topology of a solid hyper-torus, we obtain the effective action for a dual boundary theory, which describes the dynamics of the boundary gravitons. Remarkably, in the continuum limit and at large radii this boundary theory is local and closely analogous to the corresponding result in three-dimensions. The boundary effective action has a degenerate kinetic term that leads to singularities in the one-loop partition function that are independent of the discretization. These results establish a rich boundary dynamics for four-dimensional flat holography.

Acute epididymo-orchitis is an inflammatory process caused by bacterial infection. Emphysematous epididymitis is an extremely rare manifestation characterized by gas within the epididymal tissues. We report a case of emphysematous epididymitis following hydrocelectomy in a patient with a history of spinal cord injury and chronic bacteriuria. The diagnosis was made by clinical and laboratory data with imaging demonstrating foci of gas within the epididymal structures. We hypothesize that intermittent catheterization may have contributed to bacterial translocation into the adjacent cord structures and development of infection. High level of suspicion leading to early diagnosis, aggressive antibiotics and adequate debridement are required.

Aortic aneurysms in children are rare and when present are usually caused by a connective tissue disorder. In this article, we present a case of multiple aortic aneurysms in an adolescent with a novel finding of a gene variation that is associated with aortic disease.

Introduction and Objectives. In recent years, there has been increasing utilization of single-use ureteroscopes albeit with few studies comparing the performance characteristics between these devices. We compared two commonly utilized single-use ureteroscopes in a porcine model. Methods. A female pig was placed under general anesthesia and positioned supine, and retrograde access to the renal collecting system was obtained. The LithoVue (Boston Scientific) and Uscope (Pusen Medical) were evaluated by three experienced surgeons, and each surgeon started with a new scope. The following parameters were compared between each ureteroscope: time for navigation to upper and lower pole calyces with and without implements (1.9 F basket, 200 μm laser fiber, and 365 μm laser fiber for upper only) in the working channel and subjective evaluations of maneuverability, irrigant flow through the scope, lever force, ergonomics, and scope optics. Results. Navigation to the lower pole calyx was significantly faster with LithoVue compared to Uscope when the working channel was empty (24.3 vs. 49.4 seconds, p

Babesia and Theileria are protozoan parasites belonging to the order piroplasmida, transmitted by hard ticks, and can cause diseases known as piroplasmosis. Human infections are usually asymptomatic, except in immuno-compromised persons who present malaria-like symptoms. Moreover, microscopically, the morphologies of Babesia and Theileria can resemble that of the malaria parasite, Plasmodium. In malaria-endemic areas with limited resources, these similarities can increase the possibility of misdiagnosing a patient as having malaria instead of piroplasmosis, which may further lead to inappropriate choice of disease management. This preliminary investigation aimed at detecting Babesia/Theileria in cattle, dogs and humans in some parts of Accra. Whole blood samples were taken from febrile cattle (n = 30) and dogs (n = 33), as well as humans diagnosed with malaria (n = 150). Blood samples of all study subjects were microscopically screened for possible presence of haemoparasites. Samples whose smears had features suggestive of possible piroplasmic infection were all given the label “suspected Babesia/Theileria-infected” samples. Nested polymerase chain reaction (PCR) was performed on extracted deoxyribonucelic acid (DNA) from all the “suspected” samples of cattle, dogs and humans, with primer sets that can detect 18S rRNA genes of Babesia/Theileria spp. In addition to this, amplification was performed on the “suspected” dog samples using the BcW-A/BcW-B primer set which detects the 18S rRNA genes of B. canis, while the BoF/BoR primer set which targets the rap-1 region of B. bovis and another primer set which detects the 18S rRNA genes of most bovine Babesia spp. (including B. divergens) were used on the suspected cattle samples. For the human samples, however, additional amplification was done on the extracted DNA using primers for the three other Babesia targeted (B. divergens, B. bovis and B. canis). Microscopy showed possible Babesia/Theileria infection suspected in all three groups of subjects in the following proportions: cattle (10/30; 33%), dogs (3/33; 9%) and humans (6/150; 4%). DNA from one-third of the “suspected” dog samples yielded amplification with Babesia canis primers. Moreover, a broad-detecting set of primers (that can amplify some Babesia and Theileria species) amplified DNA from nine (9/30; 30%) of the “suspected” cattle samples, but none from those of the humans. Although for this study conducted in the city, the Babesia/Theileria primers used did not amplify DNA from the six “suspected” human samples; the possibility of Babesia/Theileria infection in humans in other parts of the country cannot be overruled. There is therefore a need for further studies on possible emergence of human babesiosis/theileriosis in other parts of Ghana and sequencing for specific identification of any circulating strain.

Background: Ectopic fat deposition in obesity is associated with organ dysfunction; however, little is known about fat deposition within the lymphatic system and associated lymphatic dysfunction. Methods: One hundred fifty-five women who underwent routine screening mammography before and after a Roux-en-y gastric bypass or a sleeve gastrectomy were retrospectively reviewed and after excluding women without visible nodes both before and after bariatric surgery, 84 patients were included in the final analysis. Axillary lymph node size, patient weight in kilograms, body mass index, and a diagnosis of hypertension, type 2 diabetes, and dyslipidemia were evaluated before and after surgery. Binary linear regression models and Fischer’s exact test were used to evaluate the relationship between the size of fat-infiltrated axillary lymph nodes, patient age, change in patient weight, and diagnosis of hypertension, type 2 diabetes, and dyslipidemia. Results: Fat-infiltrated axillary lymph nodes demonstrated a statistically significant decrease in size after bariatric surgery with a mean decrease of 4.23 mm (95% CI: 3.23 to 5.2, p < 0.001). The resolution of dyslipidemia was associated with a decrease in lymph node size independent of weight loss (p = 0.006). Conclusions: Mammographically visualized fat-infiltrated axillary lymph nodes demonstrated a statistically significant decrease in size after bariatric surgery. The decrease in lymph node size was significantly associated with the resolution of dyslipidemia, independent of weight loss, age, and type of surgery.

The goal of our study was to track changes in student understanding of the central dogma of molecular biology before and after taking a genetics course. Concept maps require the ability to synthesize new information into existing knowledge frameworks, and so the hypothesis guiding this study was that student performance on concept maps reveals specific central dogma misconceptions gained, lost, and retained by students. Students in a genetics course completed pre- and posttest concept mapping tasks using terms related to the central dogma. Student maps increased in complexity and validity, indicating learning gains in both content and complexity of understanding. Changes in each of the 351 possible connections in the mapping task were tracked for each student. Our students did not retain much about the central dogma from their introductory biology courses, but they did move to more advanced levels of understanding by the end of the genetics course. The information they retained from their introductory courses focused on structural components (e.g., protein is made of amino acids) and not on overall mechanistic components (e.g., DNA comes before RNA, the ribosome makes protein). Students made the greatest gains in connections related to transcription, and they resolved the most prior misconceptions about translation. These concept-mapping tasks revealed that students are able to correct prior misconceptions about the central dogma during an intermediate-level genetics course. From these results, educators can design new classroom interventions to target those aspects of this foundational principle with which students have the most trouble.

Background: schistosomiasis is a neglected tropical disease caused by helminths of the genus Schistosoma. The disease has a worldwide distribution, with more cases occurring in Africa. Urogenital schistosomiasis caused by S. haematobium with its associated morbidity is prevalent in many areas of Ghana. Praziquantel is still the recommended drug of choice for schistosomiasis treatment, although a number of studies have reported sub-therapeutic effects and associated treatment failure. The current study, therefore, assessed whether persistent schistosomiasis, with its associated morbidity among children living in endemic areas within the Greater Accra Region of Ghana, is as a result of reinfection or suspected praziquantel resistance. Methodology: this was a longitudinal study involving a baseline and follow-up sampling after praziquantel treatment. Urine samples were collected from school children (whose parents had also consented) for the detection of S. haematobium ova using a sedimentation technique. The morbidity parameters were examined with urine chemistry strips, as well as microscopy. Viability was assessed using a modified hatchability technique, vital staining (0.4% trypan blue and 1% neutral red) and fluorescent (Hoechst 33258) microscopy. Infected individuals were treated with a single dose of praziquantel (40mg/kg). Resampling to determine reinfection was done sixth months post-treatment, after evidence of total egg clearance. For possible resistance assessment, egg counts and viability testing were conducted on the positive samples at the baseline, as well as weekly post-treatment follow-ups for 12 weeks. Results: out of the 420 school children sampled, 77 were initially positive but, after the sixth month sampling for reinfection assessment, eight out of the initial positives were infected again, giving a reinfection percentage of 10.4%. No suspected praziquantel resistance was recorded in the 21 positives detected out of the 360 sampled for suspected resistance assessment. The egg reduction rate increased weekly in the follow-up samples with a gradual reduction in the egg count. The study also recorded a gradual decrease in the percentage of live eggs after the first week; with all viability testing methods used complimenting each other. The morbidity parameters (proteinuria, haematuria and pyuria) changed between the baseline and post-treatment samples, eventually reducing to zero. Conclusions: the outcome of this study suggests that the persistent schistosomiasis, with its associated morbidity observed in these endemic communities, is not likely to be as a result of praziquantel resistance, but reinfection. Even though there was no suspected resistance observed in the study, there remains the need to continuously intensify the monitoring of praziquantel in other endemic communities.

Freshwater aquatic systems are biogeochemical hotspots, with heterotrophic bacteria rapidly cycling the compounds that pass through them. P is a key nutrient that controls primary production in many freshwater ecosystems and is important for understanding eutrophication in lakes. Previous work has often focused on the dynamics of inorganic phosphorus and its impact on primary production, however, the role of nutrients bound in more complex organic forms (such as dissolved organic phosphorus, DOP) in supporting primary production and harmful algal blooms has been neglected. Here, we quantify the bioavailability of dissolved organic carbon (DOC) and DOP in 27 aquatic systems across the Upper Midwest United States. Using exponential decay models, long-term nutrient degradation assays revealed that decay constants for DOP ranged from −0.001 per day to −0.12 per day with a median value of −0.01 per day. These rates were geographically variable and were as high or higher than DOC decay constants, which ranged from −0.003 per day to −0.024 per day with a median value of −0.01 per day. Additionally, total bioavailability of DOP ranged from 0 to 100% with a median value of 78% of the DOP pool, demonstrating that DOP bioavailability was highly variable across systems. In contrast, bioavailable DOC was more tightly constrained with values ranging from 4.37 to 53.81% of the total DOC pool with a median value of 24.95%. DOP bioavailability was negatively correlated with the DOC:DOP of the organic matter pool, suggesting that bioavailable DOP is drawn down in systems that are more likely to be P limited. Finally, we show that including estimates of DOC and DOP bioavailability reduces estimates of elemental imbalance experienced by aquatic bacteria.

Course-based undergraduate research experiences (CUREs) are a type of laboratory learning environment associated with a science course, in which undergraduates participate in novel research. According to Auchincloss et al. (CBE Life Sci Educ 2104; 13:29–40), CUREs are distinct from other laboratory learning environments because they possess five core design components, and while national calls to improve STEM education have led to an increase in CURE programs nationally, less work has specifically focused on which core components are critical to achieving desired student outcomes. Here we use a backward elimination experimental design to test the importance of two CURE components for a population of non-biology majors: the experience of discovery and the production of data broadly relevant to the scientific or local community. We found nonsignificant impacts of either laboratory component on students’ academic performance, science self-efficacy, sense of project ownership, and perceived value of the laboratory experience. Our results challenge the assumption that all core components of CUREs are essential to achieve positive student outcomes when applied at scale.

Engaging interested students in field-based research experiences is imperative for cultivating interest in field science and preparing students for a career in field-based science. Here we provide a framework for completing meaningful, authentic course-based research in a five-week field course. Student research outcomes and feedback suggest that a five-week course can provide students a significant research experience that not only develops student interest in pursuing field research, but also improvements in their science-process skills. By using this course-based model, we intend to make field-based research experiences accessible to a broader range of students, increasing the opportunities for all students to explore this dimension of scientific research.

Elemental homeostasis has been largely characterized using three important elements that were part of the Redfield ratio (i.e., carbon: nitrogen: phosphorus). These efforts have revealed substantial diversity in homeostasis among taxonomic groups and even within populations. Understanding the evolutionary basis, and ecological consequences of such diversity is a central challenge. Here, we propose that a more complete understanding of homeostasis necessitates the consideration of other elements beyond C, N, and P. Specifically, we posit that physiological complexity underlying maintenance of elemental homeostasis along a single elemental axis impacts processing of other elements, thus altering elemental homeostasis along other axes. Indeed, transcriptomic studies in a wide variety of organisms have found that individuals differentially express significant proportions of the genome in response to variability in supply stoichiometry in order to maintain varying levels of homeostasis. We review the literature from the emergent field of ionomics that has established the consequences of such physiological trade-offs on the content of the entire suite of elements in an individual. Further, we present experimental data on bacteria exhibiting divergent phosphorus homeostasis phenotypes demonstrating the fundamental interconnectedness among elemental quotas. These observations suggest that physiological adjustments can lead to unexpected patterns in biomass stoichiometry, such as correlated changes among suites of non-limiting microelements in response to limitation by macroelements. Including the entire suite of elements that comprise biomass will foster improved quantitative understanding of the links between chemical cycles and the physiology of organisms.

Background: Amikacin exhibits marked pharmacokinetic (PK) variability and is commonly used in combination with other drugs in the treatment of neonatal sepsis. There is a paucity of amikacin PK information in neonates from low-resource settings. Objectives: To determine the PK parameters of amikacin, and explore the influence of selected covariates, including coadministration with aminophylline, on amikacin disposition in neonates of African origin. Methods: Neonates with suspected sepsis admitted to an intensive care unit in Accra, Ghana, and treated with amikacin (15 mg/kg loading followed by 7.5 mg/kg every 12 hours), were recruited. Serum amikacin concentration was measured at specified times after treatment initiation and analyzed using a population PK modeling approach. Results: A total of 419 serum concentrations were available for 247 neonates. Mean (SD) trough amikacin concentration (from samples collected 30 minutes before the fourth dose) among term (n = 25), and preterm (

In this work we construct holographic boundary theories for linearized 3D gravity, for a general family of finite or quasi-local boundaries. These boundary theories are directly derived from the dynamics of 3D gravity by computing the effective action for a geometric boundary observable, which measures the geodesic length from a given boundary point to some center in the bulk manifold. We identify the general form for these boundary theories and find that these are Liouville-like with a coupling to the boundary Ricci scalar. This is illustrated with various examples, which each offer interesting insights into the structure of holographic boundary theories.

In 2018, the Endourology Disease Group for Excellence (EDGE) published a prospective trial comparing dusting versus basketing during ureteroscopy. One hundred fifty-nine patients were included in the original analysis, which found no difference in stone-free rate at 3 months. We report the intermediate and long-term outcomes of patients included in the original trial. Two analyses were performed. At 1-year, a retrospective chart review was performed, and data collected on stone episodes, Emergency Department (ED) visits, hospital admissions and surgical interventions. To obtain long-term outcomes, the four sites with the largest initial accrual were included in a second phase of data collection with updated analyses. The patients from those sites were contacted, re-consented, and data were collected on stone surgical interventions, stone episodes, stone recurrences on imaging, emergency department (ED) visits, and hospital admissions for stone-related care since their original procedure. One-year follow-up data were collected in 111 of the original 159 (69.8%) patients from the nine sites. There were no statistically significant differences in the number of painful episodes, ED visits, hospital admissions, or surgical interventions. 94 patients from four sites were included in the long-term analysis. There were no statistically significant differences in surgical interventions, painful stone episodes, stone recurrence on imaging, ED visits or hospitalizations for stone-related events between the two groups. Long-term outcomes of dusting versus basketing during ureteroscopy indicate that there are no significant differences in clinical outcomes between the two surgical modalities.

Introduction and Objective: Guidelines from the American Urological Association (AUA) and American College of Radiology (ACR) recommend that patients with suspected nephrolithiasis undergo low-dose CT of the kidney, ureter, and bladder (LD CT KUB) as opposed to higher dose conventional imaging. We hypothesized that even at institutions with established LD protocols, higher dose imaging is common. Materials and Methods: We identified four academic medical centers where LD CT KUB protocols were implemented to yield an effective dose (EDose) consistent with national guidelines. Fifty consecutive adult patients who underwent CT KUB specifically for the evaluation of nephrolithiasis were retrospectively reviewed at each site. Patient age, sex, body mass index (BMI), imaging location, and EDose (millisieverts [mSv]) were recorded. Results: Two hundred patients with a mean age of 54 years were identified. Forty-six patients (23%) underwent CT KUB with an EDose ≤4 mSv, accounting for 10% to 48% of each institution's cohort. One hundred sixteen patients had a BMI

Spondylolysis of the lumbar spine has traditionally been treated using a variety of techniques ranging from conservative care to fusion. Direct repair of the defect may be utilized in young adult patients without significant disc degeneration and lumbar instability. We used minimally invasive techniques to place pars interarticularis screws with the use of an intraoperative CT scanner in three young adults, including two athletes. This technique is a modification of the original procedure in 1970 by Buck, and it offers the advantage of minimal muscle dissection and optimal screw trajectory. There were no intra- or postoperative complications. The detailed operative procedure and the postoperative course along with a brief review of pars interarticularis defect treatment are discussed.

Efforts to discourage academic misconduct in online learning environments frequently include the use of remote proctoring services. While these services are relatively commonplace in undergraduate science courses, there are open questions about students' remote assessment environments and their concerns related to remote proctoring services. Using a survey distributed to 11 undergraduate science courses engaging in remote instruction at three American, public, research-focused institutions during the spring of 2021, we found that the majority of undergraduate students reported testing in suboptimal environments. Students' concerns about remote proctoring services were closely tied to technological difficulties, fear of being wrongfully accused of cheating, and negative impacts on mental health. Our results suggest that remote proctoring services can create and perpetuate inequitable assessment environments for students, and additional research is required to understand the efficacy of their intended purpose to prevent cheating. We also advocate for continued conversations about the broader social and institutional conditions that can pressure students into cheating. While changes to academic culture are difficult, these conversations are necessary for higher education to remain relevant in an increasingly technological world.