Common Form Research Articles

Mapping the diversity & transformative potential of approaches to sustainable just cities

How can cities be more sustainable and just? This question has guided a process of synthesizing insights from previously funded research and innovation projects that deal with approaches tackling urban sustainability and justice. As part of this process, a database in the form of a knowledge commons was developed to gather 40+ approaches: sets of interventions, actions, strategies, solutions or policies that address urban sustainability and justice. This paper reflects on what we can learn from this database of approaches from an urban transitions perspective, both by sharing the method we used to develop the database and by analysing the content of those approaches and what research has revealed in relation to them. Not only do we introduce our methodology of co-creating the database (Section 2) we also present its outcomes in terms of the interlinkages between sustainable and just cities in the identified approaches (Section 3), their transformative potential (Section 4) and which institutional logics are involved (Section 5). We conclude that in addressing sustainability challenges in cities, tensions and contradictions emerge between ecological sustainability on the one hand and inclusivity, recognition and equity on the other (Section 6). Based on the identified approaches, we find that issues linked to justice are frequently glossed over, implicitly addressed, and instrumentalized in favour of ecological improvements or profitability which causes serious implications for future urban research and innovation. In order to address this gap, we present four recommendations for city-makers and city-thinkers across the globe to integrate sustainability and justice at the urban level.

Decrypting the Pathological Pathways in IgA Nephropathy.

IgAN is the most common form of glomerulonephritis affecting 2000000 people annually. The disease ultimately progresses to chronic renal failure and ESRD. In this article, we focused on a comprehensive understanding of the pathogenesis of the disease and thus identifying different target proteins that could be essential in therapeutic approaches in the management of the disease. Aberrantly glycosylated IgA1 produced by the suppression of the enzyme β-1, 3 galactosyltransferase ultimately triggered the formation of IgG autoantibodies which form complexes with Gd-IgA1. The complex gets circulated through the blood vessels through monocytes and ultimately gets deposited in the glomerular mesangial cells via CD71 receptors present locally. This complex triggers the inflammatory pathways activating the alternate complement system, various types of T Cells, toll-like receptors, cytokines, and chemokines ultimately recruiting the phagocytic cells to eliminate the Gd-IgA complex. The inflammatory proteins cause severe mesangial and podocyte damage in the kidney which ultimately initiates the repair process following chronic inflammation by an important protein named TGFβ1.TGF β1 is an important protein produced during chronic inflammation mediating the repair process via various downstream transduction proteins and ultimately producing fibrotic proteins which help in the repair process but permanently damage the glomerular cells.

Predictive and Prognostic Biomarkers in Patients With Mycosis Fungoides and Sézary Syndrome (BIO-MUSE): Protocol for a Translational Study.

Cutaneous T-cell lymphoma (CTCL) is a rare group of lymphomas that primarily affects the skin. Mycosis fungoides (MF) is the most common form of CTCL and Sézary syndrome (SS) is more infrequent. Early stages (IA-IIA) have a favorable prognosis, while advanced stages (IIB-IVB) have a worse prognosis. Around 25% of patients with early stages of the disease will progress to advanced stages. Malignant skin-infiltrating T-cells in CTCL are accompanied by infiltrates of nonmalignant T-cells and other immune cells that produce cytokines that modulate the inflammation. Skin infection, often with Staphylococcus aureus, is frequent in advanced stages and can lead to sepsis and death. S. aureus has also been reported to contribute to the progression of the disease. Previous reports indicate a shift from Th1 to Th2 cytokine production and dysfunction of the skin barrier in CTCL. Treatment response is highly variable and often unpredictable, and there is a need for new predictive and prognostic biomarkers. This prospective translational study aims to identify prognostic biomarkers in the blood and skin of patients with MF and SS. The Predictive and Prognostic Biomarkers in Patients With MF and SS (BIO-MUSE) study aims to recruit 120 adult patients with MF or SS and a control group of 20 healthy volunteers. The treatments will be given according to clinical routine. The sampling of each patient will be performed every 3 months for 3 years. The blood samples will be analyzed for lactate dehydrogenase, immunoglobulin E, interleukins, thymus and activation-regulated chemokine, and lymphocyte subpopulations. The lymphoma microenvironment will be investigated through digital spatial profiling and single-cell RNA sequencing. Microbiological sampling and analysis of skin barrier function will be performed. The life quality parameters will be evaluated. The results will be evaluated by the stage of the disease. Patient inclusion started in 2021 and is still ongoing in 2023, with 18 patients and 20 healthy controls enrolled. The publication of selected translational findings before the publication of the main results of the trial is accepted. This study aims to investigate blood and skin with a focus on immune cells and the microbiological environment to identify potential new prognostic biomarkers in MF and SS. ClinicalTrials.gov NCT04904146; https://www.clinicaltrials.gov/study/NCT04904146. DERR1-10.2196/55723.

How Strategic Violence Distorts African Elections

Abstract: While violence is a common occurrence in African elections, most attention has been focused only on a handful of cases with extreme levels of fatal election violence. Not only are these cases unrepresentative of the African continent as a whole, but focusing narrowly on these cases is also misleading when trying to understand the broader role that electoral violence plays in contemporary African democracies. Far more pervasive is the non-fatal type of low-scale election violence, which has become a common form of electoral manipulation in African elections. While low-scale violence does not threaten national security, it is an effective form of manipulation with less severe consequences for perpetrating parties. The insidious effects of low-scale violence on political participation and the quality of elections are demonstrated in Zambia, where fear of violence has come to seriously erode the quality of democracy.

How can course design facilitate the development of teamwork skills for diligent students?

ABSTRACT Stakeholders emphasise that accounting graduates need excellent teamwork skills. Group work activities, included in the academic programme to develop teamwork skills, often lead to ‘free-riding’ by some students and disillusionment on the part of diligent students. Diligent students often prefer to work alone and could lack teamwork skills as a result. The aim of this study was to evaluate how course design can facilitate the development of teamwork skills for diligent students with negative perceptions on group work. Detailed perception data on how a certain group work activity affected diligent students’ teamwork skills were collected via in-depth interviews. Themes identified through thematic analysis were compared to existing literature to construct recommendations on structuring group work activities for diligent students. The recommendations indicate that a challenging assignment conducted by a small group of students, selected on some form of commonality, over a substantial period, with limited lecturer instructions, incorporating both online and in-person components, without formal peer assessment, is best suited to foster the trust that is essential in teamwork and leads to open communication and ultimately collaboration. Educators could employ these recommendations when designing group work activities, especially when they note negative perceptions regarding group work in diligent students.

Sex Differences in Epidemiological Distribution and Outcomes of Surgical Mitral Valve Disease.

Mitral valve (MV) disease is the most common form of valvular heart disease. Findings that indicate women have a higher risk for unfavorable outcomes than men remain controversial. This study aimed to determine the sex-based differences in epidemiological distributions and outcomes of surgery for MV disease.Methods and Results: Overall, 18,572 patients (45.3% women) who underwent MV surgery between 2001 and 2018 were included. Outcomes included in-hospital death and all-cause mortality during follow up. Subgroup analysis was conducted across different etiologies, including infective endocarditis (IE), degenerative, ischemic, and rheumatic mitral pathology. The overall MV repair rate was lower in women than in men (20.5% vs. 30.6%). After matching, 6,362 pairs (woman : man=1 : 1) of patients were analyzed. Women had a slightly higher risk for in-hospital death than men (10.8% vs. 9.8%; odds ratio [OR]: 1.11, 95% confidence interval [CI]: 0.99-1.24; P=0.075). Women tended to have a higher incidence of de novo dialysis (9.8% vs. 8.6%; P=0.022) and longer intensive care unit stay (8 days vs. 7.1 days; P<0.001). Women with IE had poorer in-hospital outcomes than men; however, there were no sex differences in terms of all-cause mortality. Sex-based differences of MV intervention still persist. Although long-term outcomes were comparable between sexes, women, especially those with IE, had worse perioperative outcomes than men.

Abstract 6750: Validation of a platform to develop new dendritic cell vaccines for cancer immunotherapy

Abstract Osteosarcoma is the most common malignant form of bone cancer that generally causes patients to die of pulmonary metastasis. If detected before the tumor has metastasized, osteosarcoma has a 75% survival at 5 years after the conventional therapy with surgery and chemotherapy. However, most osteosarcomas are high-grade tumors that grow quickly and spread before being detected, lowering patient survival to 20%. Our unique protocol using the human platelet lysate PLTMax® allows establishing tumor cell lines without genetically modifying cells and with minimal genetic drift. The use of PLTMax® and allogeneic tumor cell cultures has proven to be a major advantage for the generation of large amounts of rich tumor antigen libraries for dendritic cell (DC) vaccines. This protocol was used in an autologous dendritic cell/allogeneic tumor lysate vaccine developed at the Mayo Clinic and licensed to Mill Creek Life Sciences (MCLS) to treat newly diagnosed glioblastoma (GBM), which normally has a poor survival rate at only 2%. The technology was used in a phase I clinical trial (MC1272) performed at the Mayo Clinic. The clinical outcomes proved over a 10 time increase in survival rate of patients that received the DC vaccine after the conventional therapy, providing over 20% three-year survival rate. Our technology differs from other clinically used DC vaccines in three primary ways: a) Highly efficient cell line establishment: The unique method for generating tumor cell lines uses Mill Creek Life Sciences’ PLTMax®, a media supplement derived from human platelets. PLTMax® more closely mimics the native microenvironment of tumors and is used to reduce genetic drift and senescence. b) High genetic fidelity: GBM tumor cells expanded via PLTMax® maintain genetic fidelity and TAA expression—a feat that has not been previously achieved by any other GBM cell culture method. c) Reduction of treatment delays and inclusion of all patients that qualify for treatment: Because we will use allogeneic tumor cell lines, we will be able to avoid delays in treatment caused by the time required to culture autologous tumor cell lines, and all patients may receive treatment without exclusion. Through our preliminary work we transferred the technology from a labor-intensive, small-scale approach, to an automated scalable system. Our ultimate goal is to apply this strategy to not only osteosarcoma, but also several other tumor types to validate it as a platform. Like osteosarcoma, there are other therapy-refractory cancers that we believe can benefit from the use of our platform technology, through the use of DC vaccines that offer an immune response against a wider panel of tumor antigens. Citation Format: Vanesa Alonso-Camino, William Mirsch. Validation of a platform to develop new dendritic cell vaccines for cancer immunotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6750.

Abstract 7117: Convection enhanced delivery of a novel ATR inhibitor synergizes with systemic lomustine for improved treatment of glioblastoma

Abstract Developing effective strategies for treating glioblastoma (GBM), the most common and aggressive form of brain cancer, has been a long-standing challenge. Despite rigorous treatment regimens including surgical resection with concomitant radiotherapy and chemotherapy, the prognosis for this disease remains poor, largely due to tumor recurrence, resistance to conventional therapeutics, pharmacokinetic and brain delivery challenges, and dose-limiting toxicities of existing therapies. The DNA damage response and DNA repair mechanisms such as the ataxia telangiectasia and Rad3-related (ATR) pathway are key mediators of therapeutic responses, and recent studies have shown that targeting DNA repair proteins alongside standard-of-care options is a promising anti-tumor strategy. Here, we employ a combination approach using a next-generation macrocyclic ATR inhibitor, ATRIN-333, to sensitize GBM tumors to alkylators. We establish the potency of ATRIN-333 and report a robust synergistic interaction between it and the alkylator lomustine in GBM cell-based assays and in a murine flank tumor model. This combinatorial treatment was then applied to a mouse intracranial tumor model, where we utilized a convection enhanced delivery (CED) system combined with nanoparticle technology for direct intracranial administration of ATRIN-333. ATRIN-333 was successfully encapsulated into a novel polymeric nanoparticle formulation using poly(ethylene glycol)-co-poly(ethylene brassylate-co-dioxanone) (PEG-EB-co-DO). CED of both free and encapsulated ATRIN-333 potently sensitized intracranial GBM tumors to low-dose (5 mg/kg) systemically-delivered lomustine, reducing tumor size and conferring a substantial survival benefit compared to cohorts treated with lomustine or the ATR inhibitor alone. The combination approach was well tolerated by the mice, with no hematological toxicity observed as assessed by bone marrow analysis and blood cell counts. Our results demonstrate that ATR inhibitor/lomustine combination therapy, used in conjunction with a CED platform, is a powerful avenue for GBM treatment and a viable option for potential clinical implementation. Note: AJ and TL contributed equally to this work. Citation Format: Alexander Josowitz, Teresa Lee, Ranjini K. Sundaram, Jinal Pothupitiya, Eric J. Brown, Amrita Sule, Jason Beckta, Yongheng Wang, Joseph Vacca, Oren Gilad, Ranjit S. Bindra, W Mark Saltzman. Convection enhanced delivery of a novel ATR inhibitor synergizes with systemic lomustine for improved treatment of glioblastoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7117.

Abstract 5943: Development of a SMART theranostic agent for precision pancreatic cancer therapeutics

Abstract Pancreatic cancer is predicted to emerge as the second leading cause of cancer-related deaths in the United States by 2030. Pancreatic ductal adenocarcinoma (PDAC) - the most common form of pancreatic cancer - is often diagnosed as metastatic disease and has demonstrated the least improvement in overall survival over the last three decades with incidence rising by 0.5% to 1.0% per year due in part to lack of effective and tumor-selective treatment strategies. One approach to reduce host toxicity is the development of novel molecules and innovative therapeutic approaches that are nontoxic to normal cells but can be activated only under tumor-specific conditions for lethality, which we coined as SMART (Selective Method of Activation for Response in Tumors) therapeutic agents. We utilized explicit properties and biomarkers present in PDAC tumors but not in normal tissues to develop a SMART DNA-damaging anti-cancer agent with both therapeutic and diagnostic (theranostic) activities. We evaluated the tumoricidal effect of our SMART agent using long-term survival assays in PDAC cell lines and 3D co-culture spheroids, as well as in tumor xenograft model studies in mice. We also tested the ability of our SMART agent to treat, detect/diagnose (via click chemistry), and identify critical resistance mechanisms (via proteomics) as a single agent or as a chemosensitizer with predictive tumor biomarkers for tumor-selective therapeutic response. We found that our SMART small molecule induces tumor-selective lethal effects as a monotherapy or in combination with DNA repair inhibitors or small molecules known to generate hydrogen peroxide (H2O2) in a tumor-selective manner for activation. Using “click” chemistry, we detected and quantified the incorporation of our SMART small molecule as a DNA-damaging agent via flow cytometry that correlated with therapeutic response, which is a feature that could facilitate the stratification, treatment monitoring, and management of patients with pancreatic cancers. We also found that our SMART agent is less toxic and more effective as a monotherapy than cisplatin in PDAC cell line-derived xenograft studies in mice. Overall, our novel SMART theranostic agent could provide a significant advancement as they are preferentially activated under tumor-specific conditions to induce tumor-selective therapeutic response. Furthermore, the diagnostic component our SMART agent could provide oncologists with essential information to make rapid clinical decisions on treatment strategies. Our SMART agent is also remarkably versatile as it can be utilized as a chemosensitizer or as a chemical probe to identify targetable vulnerabilities to potentiate its therapeutic effects at lower doses. Citation Format: Edward A. Motea, Jarrett J. Smith, Oluwasijibomi Ketiku. Development of a SMART theranostic agent for precision pancreatic cancer therapeutics [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5943.

The challenges in diagnosing isolated epididymal tuberculosis (TB) in an adolescent male: a case report

BackgroundGenitourinary tuberculosis (GUTB) is a common form of extrapulmonary TB (EPTB) in children. An example of GUTB is epididymal TB, which usually presents unspecific chronic clinical manifestations. Definitive diagnosis can be conducted based on bacteriologic confirmation and histopathologic results, but this is challenging due to the paucibacillary nature of EPTB. Therefore, we reported the challenges in diagnosing isolated epididymal TB in an adolescent male.Case presentationA 16-year-old male presented to respirology clinic with painful swelling of the left scrotum for 3 months before visiting to the hospital. The symptoms were associated with persistent coughing for 2 months, and physical examination of the left scrotum showed swelling accompanied by cardinal signs. A palpable hard mass was found on the left scrotum, with firm borders, measuring 7 × 4 cm. Laboratory examination and tumor markers were within normal limits, although leukocyturia was found, and the urine culture was negative. Genital ultrasound (US) showed epididymitis sinistra with septal hydrocele, while magnetic resonance imaging (MRI) indicated inhomogeneous left epididymitis with bilateral inguinal lymph node enlargement. Although TB evaluation presented a negative purified protein derivative (PPD) test and bacteriologic examination, chest X-ray (CXR) showed perihilar lymphadenopathy. Based on the clinical and radiologic results suggesting TB, the patient was diagnosed with isolated epididymal TB and received quadruple antituberculosis therapy (ATT) for 6 months. After treatment, the left testicle size started to shrink and was equal to the right testicle, also, there were no signs of inflammation, the body weight increased by 5 kg, and cough disappeared. Sperm analysis at the end of treatment indicated teratozoospermia, which was subsequently treated by the urologic surgery department.ConclusionsBiopsy and bacteriologic confirmation for TB epididymitis were challenging to perform in the clinical setting. Epididymal TB should be considered in adolescent males with complaints of chronic scrotal swelling and pain. Clinical judgment based on history taking, physical examination, and radiologic features supporting TB features could be helpful in accurate and fast diagnosis for favorable outcome.

Non-Alcoholic Fatty Liver Disease May Be a Risk Factor for Liver Metastasis After Radical Surgery for Colorectal Cancer: A Retrospective Study.

Distant metastasis develops in approximately one-third of patients with colorectal cancer (CRC) who undergo radical surgery, and colorectal liver metastasis (CRLM) is the most common form of distant metastasis in CRC. Hepatectomy is the only potentially curative treatment for CRLM, but few patients with metastatic CRC meet the criteria for this radical resection, and the 5-year survival rate is poor. Identifying risk factors for CRLM is critical. Non-alcoholic fatty liver disease (NAFLD) is an independent risk factor for CRC. However, the effect of NAFLD on CRC liver metastasis after radical surgery remains unclear. Therefore, we examined the impact of NAFLD-associated hepatic fibrosis on liver metastasis after radical surgery for CRC. We retrospectively analyzed data from 388 patients who underwent curative surgery for CRC at our hospital between April 2008 and March 2015. The patients' clinical results, surgical procedures, postoperative course, and pathological and survival data were collected from the hospital records. The NAFLD fibrosis score was calculated and used to divide the patients into two groups (NAFLD and non-NAFLD). Recurrence was observed in 83/388 (21.4%) patients after a mean follow-up of 65.6 ± 15.1months. Twenty-five patients had liver metastasis: 8 in the NAFLD group (8/45; 17.8%) and 17 in the non-NALFD group (17/343; 5.0%) (p = 0.004). Liver metastasis-free survival was significantly worse in the NAFLD than non-NAFLD group (p < 0.001). NAFLD and cancer stage were independent risk factors for liver metastasis recurrence. NAFLD may be a risk factor for liver metastasis in patients with CRC who undergo curative surgery.

Intimate Partner Sexual Violence: An Exploratory Study on Sexual Victimization Profiles Among Survivors of Intimate Partner Violence in France.

Intimate partner sexual violence (IPSV) is a common form of intimate partner violence (IPV). This study aimed to (a) identify a typology of intimate partner sexual victimization among French women victims of IPV on the basis of the frequency of various forms of sexual violence and (b) evaluate whether these profiles differ in several clinical characteristics. A total of 93 women consulting a specialized hospital service were recruited. Cluster analyses suggested four profiles: highly frequent rapes (5.4%), predominant sexual coercion (20.4%), medium frequency of all forms (20.4%), and low frequency of all forms (19.4%). Further person-centered research focusing on IPSV is warranted.

The clinical benefits of sodium-glucose cotransporter type 2 inhibitors in people with gout.

Gout is the most common form of inflammatory arthritis worldwide and is characterized by painful recurrent flares of inflammatory arthritis that are associated with a transiently increased risk of adverse cardiovascular events. Furthermore, gout is associated with multiple cardiometabolic-renal comorbidities such as type 2 diabetes, chronic kidney disease and cardiovascular disease. These comorbidities, potentially combined with gout flare-related inflammation, contribute to persistent premature mortality in gout, independently of serum urate concentrations and traditional cardiovascular risk factors. Although better implementation of standard gout care could improve gout outcomes, deliberate efforts to address the cardiovascular risk in patients with gout are likely to berequired to reduce mortality. Sodium-glucose cotransporter type 2 (SGLT2) inhibitors are approved for multiple indications owing to their ability to lower the risk of all-cause and cardiovascular death, hospitalizations for heart failure and chronic kidney disease progression, making them an attractive treatment option for gout. These medications have also been shown to lower serum urate concentrations, the causal culprit in gout risk, and are associated with a reduced risk of incident and recurrent gout, potentially owing to their purported anti-inflammatory effects. Thus, SGLT2 inhibition could simultaneously address both the symptoms of gout and its comorbidities.

Preventive repression: Protest policing in New Delhi

ABSTRACT States view protests as disruptive and police them. Scholarship points to selective policing of protests that endanger law and order as well as those organized by minority groups. A common form of protest policing in cities is requiring protestors to obtain permits in advance. We use interviews with protestors and the police in New Delhi to examine their perception of protest policing. We test these perceptions empirically using an original dataset of 4,921 protest applications submitted to the Delhi police between 2016 and 2019. We find that the rejection of protest applications is driven by the disruptive threat that they pose rather than the identity of the protesting group. However, the police disproportionately flag protest applications by religious minorities for threat assessment. A postcolonial police force, which privileges preservation of order over its other functions, regularly curtails the democratic freedom to protest.

Acquired Forms of Fibroblast Growth Factor 23-Related Hypophosphatemic Osteomalacia.

Fibroblast growth factor 23 (FGF23) is a pivotal humoral factor for the regulation of serum phosphate levels and was first identified in patients with autosomal dominant hypophosphatemic rickets and tumor-induced osteomalacia (TIO), the most common form of acquired FGF23-related hypophosphatemic rickets/osteomalacia (FGF23rHR). After the identification of FGF23, many other inherited and acquired forms of FGF23rHR were reported. In this review article, the detailed features of each acquired FGF23rHR are discussed, including TIO, ectopic FGF23 syndrome with malignancy, fibrous dysplasia/McCune-Albright syndrome, Schimmelpenning- Feuerstein-Mims syndrome/cutaneous skeletal hypophosphatemia syndrome, intravenous iron preparation-induced FGF23rHR, alcohol consumption-induced FGF23rHR, and post-kidney transplantation hypophosphatemia. Then, an approach for the differential diagnosis and therapeutic options for each disorder are concisely introduced. Currently, the majority of endocrinologists might only consider TIO when encountering patients with acquired FGF23rHR; an adequate differential diagnosis can reduce medical costs and invasive procedures such as positron emission tomography/computed tomography and venous sampling to identify FGF23-producing tumors. Furthermore, some acquired FGF23rHRs, such as intravenous iron preparation/alcohol consumption-induced FGF23rHR, require only cessation of drugs or alcohol to achieve full recovery from osteomalacia.

Zinner syndrome: A rarer variant of a rare syndrome

Zinner syndrome, characterized by the combination of absent unilateral kidney, obstructed ejaculatory duct on the same side, and cysts in the seminal vesicle, represents a rare congenital malformation of the mesonephric duct. Its symptoms are often vague, ranging from urinary discomfort to painful ejaculation and infertility, making it difficult to diagnose without imaging. In this report, we discuss a less common form of Zinner syndrome identified through diagnostic imaging.

Racial and ethnic bias in letters of recommendation in academic medicine: a systematic review.

Letters of recommendations (LORs) are key components of academic medicine applications. Given that bias against students and trainees underrepresented in medicine (UIM) has been demonstrated across assessment, achievement, and advancement domains, the authors reviewed studies on LORs to assess racial, ethnic, and UIM differences in LORs. Standardized LORs (SLORs), an increasingly common form of LORs, were also assessed for racial and ethnic differences. A systematic review was conducted for English-language studies that assessed racial or ethnic differences in LORs in academic medicine published from database inception to July 16, 2023. Studies evaluating SLORs underwent data abstraction to evaluate their impact on the given race or ethnicity comparison and outcome variables. Twenty-three studies describing 19,012 applicants and 41,925 LORs were included. Nineteen studies (82.6%) assessed LORs for residency, 4 (17.4%) assessed LORs for fellowship, and none evaluated employment or promotion. Fifteen of 17 studies (88.2%) assessing linguistic differences reported a significant difference in a particular race or ethnicity comparison. Of the 7 studies assessing agentic language (e.g., "strong," "confident"), 1 study found fewer agentic terms used for Black and Latinx applicants, and 1 study reported higher agency scores for Asian applicants and applicants of races other than White. There were mixed results for the use of communal and grindstone language in UIM and non-UIM comparisons. Among 6 studies, 4 (66.7%) reported that standout language (e.g., "exceptional," "outstanding") was less likely to be ascribed to UIM applicants. Doubt-raising language was more frequently used for UIM trainees. When SLORs and unstructured LORs were compared, fewer linguistic differences were found in SLORs. There is a moderate bias against UIM candidates in the domains of linguistic differences, doubt-raising language, and topics discussed in LORs, which has implications for perceptions of competence and ability in the high-stakes residency and fellowship application process.

Cerebral visual impairment: genetic diagnoses and phenotypic associations

BackgroundCerebral visual impairment (CVI) is the most common form of paediatric visual impairment in developed countries. CVI can arise from a host of genetic or acquired causes, but there has...

Prevalence and antimicrobial-resistant patterns of Pseudomonas aeruginosa among burn patients attending Yekatit 12 Hospital Medical College in Addis Ababa, Ethiopia.

Burns are one of the most common forms of trauma globally. P. aeruginosa plays a prominent role as an etiological agent among burn patients. There is a paucity of information about the prevalence and antimicrobial resistance patterns of P. aeruginosa among burn patients in Ethiopia. Hence, this study was designed to assess the prevalence and antimicrobial-resistant patterns of P. aeruginosa among burn patients attending Yekatit 12 Hospital Medical College in Addis Ababa, Ethiopia. Hospital-based cross-sectional study was conducted at Yekatit 12 Hospital Medical College among burn patients from November 2020 to April 2021. Identification of P. aeruginosa was performed using Culture, Biochemical tests, and, Gram staining. Antimicrobial resistance testing was done using the Kirby-Bauer disc diffusion method. Logistic regression was computed to determine associated factors. From 210 burn wound cultures, 27 (12.86%) were found positive for P. aeruginosa. All the isolates showed greater than 70% susceptibility to the tested antibiotics except Gentamycin, Ceftazidime, and, Ciprofloxacin. In addition, 33.33% of P. aeruginosa isolates were multidrug-resistant. Admission type, Hospital stay time and Total body surface area (TBSA) had a statistically significant association (all with P-value <0.05) with the acquisition of P. aeruginosa infection. Overall, the prevalence of P. aeruginosa isolates among burn patients is almost 13%. Most P. aeruginosa isolates were sensitive to Imipenem, while they were most resistant to Gentamycin. One-third of P. aeruginosa were multidrug-resistant. This suggests the need to monitor the treatment of infection with the pathogen to limit the possibility of the emergence of multidrug-resistant isolates in burn centers.

Neuropathological stage-dependent proteome mapping of the olfactory tract in Alzheimer's disease: From early olfactory-related omics signatures to computational repurposing of drug candidates.

Alzheimer's disease (AD) is the most common form of dementia, characterized by an early olfactory dysfunction, progressive memory loss, and behavioral deterioration. Albeit substantial progress has been made in characterizing AD-associated molecular and cellular events, there is an unmet clinical need for new therapies. In this study, olfactory tract proteotyping performed in controls and AD subjects (n = 17/group) showed a Braak stage-dependent proteostatic impairment accompanied by the progressive modulation of amyloid precursor protein and tau functional interactomes. To implement a computational repurposing of drug candidates with the capacity to reverse early AD-related olfactory omics signatures (OMSs), we generated a consensual OMSs database compiling differential omics datasets obtained by mass-spectrometry or RNA-sequencing derived from initial AD across the olfactory axis. Using the Connectivity Map-based drug repurposing approach, PKC, EGFR, Aurora kinase, Glycogen synthase kinase, and CDK inhibitors were the top pharmacologic classes capable to restore multiple OMSs, whereas compounds with targeted activity to inhibit PI3K, Insulin-like growth factor 1 (IGF-1), microtubules, and Polo-like kinase (PLK) represented a family of drugs with detrimental potential to induce olfactory AD-associated gene expression changes. To validate the potential therapeutic effects of the proposed drugs, in vitro assays were performed. These validation experiments revealed that pretreatment of human neuron-like SH-SY5Y cells with the EGFR inhibitor AG-1478 showed a neuroprotective effect against hydrogen peroxide-induced damage while the pretreatment with the Aurora kinase inhibitor Reversine reduced amyloid-beta (Aβ)-induced neurotoxicity. Taken together, our data pointed out that OMSs may be useful as substrates for drug repurposing to propose novel neuroprotective treatments against AD.