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Basosquamous carcinoma (BSC) is a rare form of non-melanoma skin cancer with significant invasive and metastatic potential. This malignancy presents unique challenges in diagnostic and therapeutic options given its ambiguous clinical nature. While there are documented cases of BSC involving the aerodigestive tract and sun-exposed areas like the head and neck, cutaneous BSC in the gluteal and perineal regions remains quite rare. In this report, we provide an overview of the epidemiology, clinical presentation, treatment modalities, and prognosis of this disease. We describe a case of a 71-year-old female who presented for evaluation of a symptomatic right-sided cutaneous lesion in the inner gluteal and perineal region. Upfront surgical resection was pursued for both diagnostic and therapeutic purposes. Final pathology of the lesion revealed infiltrating BSC with negative margins. Although BSC typically presents in sun-exposed areas, the presentation in this patient in a non-sun-exposed area makes this presentation unusual. [ABSTRACT FROM AUTHOR]

Background Hearing loss is prevalent following ototoxic therapy for childhood cancer. Associations between hearing loss, self-perceived hearing handicap, and functional outcomes have not been examined in survivors. Methods Adult survivors treated with platinum or head and neck radiotherapy with hearing loss were recruited. A total of 237 survivors (median age at survey = 37.0 years [range = 30.0-45.0 years]; median = 29.1 years [range = 22.4-35.0 years] since diagnosis; median = 4.0 years [range = 2.9-7.7 years] from last audiogram to survey) completed the Hearing Handicap Inventory for Adults and questionnaires on social and emotional functioning and hearing aid use. Hearing loss severity was defined according to Chang criteria. Multivariable logistic regression models estimated odds ratios (ORs) and 95% confidence intervals (CIs) for associations between hearing loss, hearing handicap, functional outcomes, and hearing aid use with adjustment for sex, race, age at hearing loss diagnosis, and age at survey. Results Two-thirds of survivors had severe hearing loss, which was associated with increased likelihood of hearing handicap (mild-moderate handicap: OR = 2.72, 95% CI = 1.35 to 5.47; severe handicap: OR = 5.99, 95% CI = 2.72 to 13.18). Survivors with severe hearing handicap had an increased likelihood of social isolation (OR = 8.76, 95% CI = 3.62 to 21.20), depression (OR = 9.11, 95% CI = 3.46 to 24.02), anxiety (OR = 17.57, 95% CI = 3.77 to 81.84), reduced personal income (OR = 2.82, 95% CI = 1.46 to 5.43), and less than full-time employment (OR = 2.47, 95% CI = 1.30 to 4.70). Survivors who did not use a recommended hearing aid were twice as likely to have less than full-time employment (OR = 2.26, 95% CI = 1.10 to 4.61) and reduced personal income (OR = 2.24, 95% CI = 1.08 to 4.63) compared with survivors who wore a hearing aid. Conclusion Self-perceived hearing handicap beyond measured hearing loss is associated with reduced functional outcomes. Assessment of hearing handicap may facilitate targeted interventions in adult survivors with hearing loss. [ABSTRACT FROM AUTHOR]

The article discusses the relationship between cancer-related cognitive decline (CRCD) and Alzheimer's disease (AD). The study analyzed data from older women with nonmetastatic breast cancer and found that breast cancer survivors had lower attention, processing speed, and executive function scores compared to controls, but AD-related biomarkers were not associated with these scores. The article suggests that there may be biological connections between CRCD and AD, such as proinflammatory cytokines and reactive oxygen species, but more research is needed to understand the mechanisms. The findings have implications for drug development and intervention strategies for both conditions. [Extracted from the article]

Chemosensory scientists have been skeptical that reports of COVID-19 taste loss are genuine, in part because before COVID-19 taste loss was rare and often confused with smell loss. Therefore, to establish the predicted prevalence rate of taste loss in COVID-19 patients, we conducted a systematic review and meta-analysis of 376 papers published in 2020–2021, with 235 meeting all inclusion criteria. Drawing on previous studies and guided by early meta-analyses, we explored how methodological differences (direct vs. self-report measures) may affect these estimates. We hypothesized that direct measures of taste are at least as sensitive as those obtained by self-report and that the preponderance of evidence confirms taste loss is a symptom of COVID-19. The meta-analysis showed that, among 138,015 COVID-19-positive patients, 36.62% reported taste dysfunction (95% confidence interval: 33.02%–40.39%), and the prevalence estimates were slightly but not significantly higher from studies using direct (n = 15) versus self-report (n = 220) methodologies (Q = 1.73, df = 1, P = 0.1889). Generally, males reported lower rates of taste loss than did females, and taste loss was highest among middle-aged adults. Thus, taste loss is likely a bona fide symptom of COVID-19, meriting further research into the most appropriate direct methods to measure it and its underlying mechanisms. [ABSTRACT FROM AUTHOR]

It is estimated that 20%–67% of those with COVID-19 develop olfactory disorders, depending on the SARS-CoV-2 variant. However, there is an absence of quick, population-wide olfactory tests to screen for olfactory disorders. The purpose of this study was to provide a proof-of-concept that SCENTinel 1.1, a rapid, inexpensive, population-wide olfactory test, can discriminate between anosmia (total smell loss), hyposmia (reduced sense of smell), parosmia (distorted odor perception), and phantosmia (odor sensation without a source). Participants were mailed a SCENTinel 1.1 test, which measures odor detection, intensity, identification, and pleasantness, using one of 4 possible odors. Those who completed the test (N = 287) were divided into groups based on their self-reported olfactory function: quantitative olfactory disorder only (anosmia or hyposmia, N = 135), qualitative olfactory disorder only (parosmia and/or phantosmia; N = 86), and normosmia (normal sense of smell; N = 66). SCENTinel 1.1 accurately discriminates quantitative olfactory disorders, qualitative olfactory disorders, and normosmia groups. When olfactory disorders were assessed individually, SCENTinel 1.1 discriminates between hyposmia, parosmia, and anosmia. Participants with parosmia rated common odors less pleasant than those without parosmia. We provide proof-of-concept that SCENTinel 1.1, a rapid smell test, can discriminate quantitative and qualitative olfactory disorders, and is the only direct test to rapidly discriminate parosmia. [ABSTRACT FROM AUTHOR]

Many widely used psychophysical olfactory tests have limitations that can create barriers to adoption. For example, tests that measure the ability to identify odors may confound sensory performance with memory recall, verbal ability, and prior experience with the odor. Conversely, classic threshold-based tests avoid these issues, but are labor intensive. Additionally, many commercially available tests are slow and may require a trained administrator, making them impractical for use in situations where time is at a premium or self-administration is required. We tested the performance of the Adaptive Olfactory Measure of Threshold (ArOMa-T)—a novel odor detection threshold test that employs an adaptive Bayesian algorithm paired with a disposable odorant delivery card—in a non-clinical sample of individuals (n = 534) at the 2021 Twins Day Festival in Twinsburg, OH. Participants successfully completed the test in under 3 min with a false alarm rate of 7.5% and a test–retest reliability of 0.61. Odor detection thresholds differed by sex (~3.2-fold lower for females) and age (~8.7-fold lower for the youngest versus the oldest age group), consistent with prior studies. In an exploratory analysis, we failed to observe evidence of detection threshold differences between participants who reported a history of COVID-19 and matched controls who did not. We also found evidence for broad-sense heritability of odor detection thresholds. Together, this study suggests the ArOMa-T can determine odor detection thresholds. Additional validation studies are needed to confirm the value of ArOMa-T in clinical or field settings where rapid and portable assessment of olfactory function is needed. [ABSTRACT FROM AUTHOR]

Chemosensory scientists have been skeptical that reports of COVID-19 taste loss are genuine, in part because before COVID-19 taste loss was rare and often confused with smell loss. Therefore, to establish the predicted prevalence rate of taste loss in COVID-19 patients, we conducted a systematic review and meta-analysis of 376 papers published in 2020–2021, with 241 meeting all inclusion criteria. Drawing on previous studies and guided by early meta-analyses, we explored how methodological differences (direct vs. self-report measures) may affect these estimates. We hypothesized that direct measures of taste are at least as sensitive as those obtained by self-report and that the preponderance of evidence confirms taste loss is a symptom of COVID-19. The meta-analysis showed that, among 138,897 COVID-19-positive patients, 39.2% reported taste dysfunction (95% confidence interval: 35.34%–43.12%), and the prevalence estimates were slightly but not significantly higher from studies using direct (n = 18) versus self-report (n = 223) methodologies (Q = 0.57, df = 1, P = 0.45). Generally, males reported lower rates of taste loss than did females, and taste loss was highest among middle-aged adults. Thus, taste loss is likely a bona fide symptom of COVID-19, meriting further research into the most appropriate direct methods to measure it and its underlying mechanisms. [ABSTRACT FROM AUTHOR]

Bone marrow is a hematopoietic site harboring multiple populations of myeloid cells in different stages of differentiation. Murine bone marrow eosinophils are traditionally identified by Siglec‐F(+) staining using flow cytometry, whereas neutrophils are characterized by Ly6G(+) expression. However, using flow cytometry to characterize bone marrow hematopoietic cells in wild‐type mice, we found substantial gray areas in identification of these cells. Siglec‐F(+) mature eosinophil population constituted only a minority of bone marrow Lin(+)CD45(+) pool (5%). A substantial population of Siglec‐F(−) cells was double positive for neutrophil marker Ly6G and eosinophil lineage marker, IL‐5Rα. This granulocyte population with mixed neutrophil and eosinophil characteristics is typically attributable to neutrophil pool based on neutral granule staining and expression of Ly6G and myeloid peroxidase. It is distinct from Lineage(−) myeloid progenitors or Siglec‐F(+)Ly6G(+) maturing eosinophil precursors, and can be accurately identified by Lineage(+) staining and positive expression of markers IL‐5Rα and Ly6G. At 15–50% of all CD45(+) hematopoietic cells in adult mice (percentage varies by sex and age), this is a surprisingly dominant population, which increases with age in both male and female mice. RNA‐seq characterization of these cells revealed a complex immune profile and the capacity to secrete constituents of the extracellular matrix. When sorted from bone marrow, these resident cells had neutrophilic phenotype but readily acquired all characteristics of eosinophils when cultured with G‐CSF or IL‐5, including expression of Siglec‐F and granular proteins (Epx, Mbp). Surprisingly, these cells were also able to differentiate into Ly6C(+) monocytes when cultured with M‐CSF. Herein described is the discovery of an unexpected hematopoietic flexibility of a dominant population of multipotent myeloid cells, typically categorized as neutrophils, but with the previously unknown plasticity to contribute to mature pools of eosinophils and monocytes. [ABSTRACT FROM AUTHOR]

Commercially available smell tests are primarily used in research or in-depth clinical evaluations and are too costly and time-consuming for population surveillance in health emergencies like COVID-19. To address this need, we developed the SCENTinel 1.0 test, which rapidly evaluates 3 olfactory functions: detection, intensity, and identification. We tested whether self-administering the SCENTinel 1.0 test discriminates between individuals with self-reported smell loss and those with average smell ability (normosmic individuals) and provides performance comparable to the validated and standardized NIH Toolbox Odor Identification Test in normosmic individuals. Using Bayesian linear models and prognostic classification algorithms, we compared the SCENTinel 1.0 performance of a group of self-reported anosmic individuals (N = 111, 47 ± 13 years old, F = 71%) and normosmic individuals (N = 154, 47 ± 14 years old, F = 74%) as well as individuals reporting other smell disorders (such as hyposmia or parosmia; N = 42, 55 ± 10 years old, F = 67%). Ninety-four percent of normosmic individuals met our SCENTinel 1.0 accuracy criteria compared with only 10% of anosmic individuals and 64% of individuals with other smell disorders. Overall performance on SCENTinel 1.0 predicted belonging to the normosmic group better than identification or detection alone (vs. anosmic: AUC = 0.95, specificity = 0.94). Odor intensity provided the best single-feature predictor to classify normosmic individuals. Among normosmic individuals, 92% met the accuracy criteria at both SCENTinel 1.0 and the NIH Toolbox Odor Identification Test. SCENTinel 1.0 is a practical test able to discriminate individuals with smell loss and will likely be useful in many clinical situations, including COVID-19 symptom screening. [ABSTRACT FROM AUTHOR]

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), has currently infected over 6.5 million people worldwide. In response to the pandemic, numerous studies have tried to identify the causes and symptoms of the disease. Emerging evidence supports recently acquired anosmia (complete loss of smell) and hyposmia (partial loss of smell) as symptoms of COVID-19, but studies of olfactory dysfunction show a wide range of prevalence from 5% to 98%. We undertook a search of Pubmed/Medline and Google Scholar with the keywords "COVID-19," "smell," and/or "olfaction." We included any study that quantified smell loss (anosmia and hyposmia) as a symptom of COVID-19. Studies were grouped and compared based on the type of method used to measure smell loss—subjective measures, such as self-reported smell loss, versus objective measures using rated stimuli—to determine if prevalence differed by method type. For each study, 95% confidence intervals (CIs) were calculated from point estimates of olfactory disturbances. We identified 34 articles quantifying anosmia as a symptom of COVID-19 (6 objective and 28 subjective), collected from cases identified from January 16 to April 30, 2020. The pooled prevalence estimate of smell loss was 77% when assessed through objective measurements (95% CI of 61.4–89.2%) and 44% with subjective measurements (95% CI of 32.2–57.0%). Objective measures are a more sensitive method to identify smell loss as a result of infection with SARS-CoV-2; the use of subjective measures, while expedient during the early stages of the pandemic, underestimates the true prevalence of smell loss. [ABSTRACT FROM AUTHOR]

Eosinophils are often cited as playing roles in wound healing and epithelial remodeling; however, the exact triggers and mechanisms of such activity remain poorly understood. Eosinophils show the remarkable capacity to partner with coagulation, which is a highly conserved biologic system evolved to protect an organism from injury by promoting hemostasis and tissue repair. Eosinophils contribute directly by producing key factors in coagulation (tissue factor, thrombin) and fibrinolysis (plasminogen). Moreover, they have been shown to interact with other players in these cascades, such as fibrinogen and the urokinase‐type plasminogen activator/urokinase‐type plasminogen activator receptor system, which further promotes coagulation and fibrinolysis. Although primarily thought of in the contexts of blood clotting and vascular repair, coagulation and fibrinolytic systems play key roles within tissue, in particular during epithelial injury and remodeling. Chronic inflammation and remodeling frequently associate with pro‐thrombotic and pro‐coagulation state. There is a striking association between eosinophils and dysregulated coagulation in animal models and human disease. This review will examine the mechanistic links between eosinophils and the coagulation system in the context of epithelial injury and repair, as well as evidence for this interaction in heart disease, type 2 inflammatory diseases, and cancer. Collectively, multiple emerging studies summarized in this review elucidate an overlooked, but potentially fundamental, biologic mechanism to engage eosinophils in processes of epithelial injury and repair. [ABSTRACT FROM AUTHOR]

Abstract: Eosinophils play homeostatic roles in different tissues and are found in several organs at a homeostatic baseline, though their tissue numbers increase significantly in development and disease. The morphological, phenotypical, and functional plasticity of recruited eosinophils are influenced by the dynamic tissue microenvironment changes between homeostatic, morphogenetic, and disease states. Activity of the epithelial‐mesenchymal interface, extracellular matrix, hormonal inputs, metabolic state of the environment, as well as epithelial and mesenchymal‐derived innate cytokines and growth factors all have the potential to regulate the attraction, retention, in situ hematopoiesis, phenotype, and function of eosinophils. This review examines the reciprocal relationship between eosinophils and such tissue factors, specifically addressing: (1) tissue microenvironments associated with the presence and activity of eosinophils; (2) non‐immune tissue ligands regulatory for eosinophil accumulation, hematopoiesis, phenotype, and function (with an emphasis on the extracellular matrix and epithelial–mesenchymal interface); (3) the contribution of eosinophils to regulating tissue biology; (4) eosinophil phenotypic heterogeneity in different tissue microenvironments, classifying eosinophils as progenitors, steady state eosinophils, and Type 1 and 2 activated phenotypes. An appreciation of eosinophil regulation by non‐immune tissue factors is necessary for completing the picture of eosinophil immune activation and understanding the functional contribution of these cells to development, homeostasis, and disease. [ABSTRACT FROM AUTHOR]

A letter to the editor of the journal "Chemical Senses" acknowledges concerns about overestimating taste loss as a symptom of COVID-19. The overestimate may have been due to including studies that used unvalidated sensory tests and had biased participant selection. The authors of the letter admit to including six biased studies and have removed them from the analysis, with no change in the outcomes or conclusions. They also mention the importance of including studies with validated methods in future meta-analyses. [Extracted from the article]

Genomic stability, stress response, and nutrient signaling all play critical, evolutionarily conserved roles in lifespan determination. However, the molecular mechanisms coordinating these processes with longevity remain unresolved. Here we investigate the involvement of the yeast anaphase promoting complex (APC) in longevity. The APC governs passage through M and G1 via ubiquitin-dependent targeting of substrate proteins and is associated with cancer and premature aging when defective. Our twohybrid screen utilizing Apc5 as bait recovered the lifespan determinant Fob1 as prey. Fob1 is unstable specifically in G1, cycles throughout the cell cycle in a manner similar to Clb2 (an APC target), and is stabilized in APC (apc5CA) and proteasome (rpn10Δ) mutants. Deletion of FOB1 increased replicative lifespan (RLS) in wild type (WT), apc5CA, and apc10Δ cells, and suppressed apc5CA cell cycle progression and rDNA recombination defects. Alternatively, increased FOB1 expression decreased RLS in WT cells, but did not reduce the already short apc5CA RLS, suggesting an epistatic interaction between apc5CA and fob1Δ. Mutation to a putative L-Box (Fob1E420V), a Destruction Box-like motif, abolished Fob1 modifications, stabilized the protein, and increased rDNA recombination. Our work provides a mechanistic role played by the APC to promote replicative longevity and genomic stability in yeast. [ABSTRACT FROM AUTHOR]

For the above challenges to be met, it will be important for the field of injury epidemiology to move from the largely descriptive studies that have predominated in the literature to the application of more rigorous analytical methods for defining the underlying casual patterns of injury. Studies focusing on the descriptive epidemiology of injury have and will continue to serve the field well, perhaps even more so than in other fields, since the proximal etiology of injuries (i.e., acute exposure to physical agents such as mechanical energy) is well known. However, major new advances in the prevention of injuries will continue to require a more analytical approach to understanding the complex array of factors that influence the incidence, severity, and outcomes of injury. At the same time, it will be important for investigators in this field to conduct rigorous evaluations of new interventions to better inform the establishment of programs and policies. These evaluations must include assessments of both the effectiveness and the costs of the intervention. For example, in a recently published systematic review of 10 different strategies for preventing motor vehicle injuries, 54,708 papers and reports were identified in the literature but only 161 met the initial screening criteria for inclusion in the published review (44). Of these, a much smaller number were randomized controlled trials or well executed controlled time series trials. Major advancements in the prevention and control of injuries will continue to rely on effective collaborations between epidemiologists and scientists from other disciplines, including the behavioral sciences, sociology, criminology, law, engineering, and biomechanics. Only through truly collaborative efforts across these disciplines will we be able to establish a foundation for cost-effective interventions. For example, understanding the principles of injury mechanics and the physical and physiologic responses of the human body to the impact of injury is fundamental to the study of injury causation (6). While significant advances have been made in this regard, more work needs to be done. The biomechanics of head injury are still not well understood, yet head injuries account for nearly 50 percent of all injury deaths and remain the leading cause of both injury death and disability among children and young adults. Animal and human cadaver research combined with rapidly evolving techniques of computerized modeling will continue to play a critical role in increasing our understanding of injury mechanisms. At the same time, the development of effective interventions is dependent on a better understanding of the role of behavior in injury causation and prevention (45). We know, for example, that the use of personal protective devices such as seat belts, car seats, and bicycle helmets reduces injury risk and that these behaviors can be influenced through educational, behavioral, and legislative strategies (46-49). Interventions addressing individuals at risk can be enhanced by additional research into risk perception, risk-taking, and behavioral responses to safety improvements. However, behavioral strategies may also be used effectively with key decision-makers who design and manufacture products and who pass and implement laws that affect the injury risk of entire populations; more research is needed to understand and influence the process of behavior change in these groups (50). The importance of injury as a major public health problem worldwide was highlighted in the seminal report "The Global Burden of Disease" (25). Worldwide, injuries account for approximately one in eight deaths among males and one in 14 deaths among females (51). Motor vehicle injuries alone constitute the ninth leading cause of disease burden as measured by the number of associated disability-adjusted life years (25). By the year 2020, motor vehicle injuries are projected to increase in rank to third. (ABSTRACT TRUNCATED) [ABSTRACT FROM AUTHOR]

A further development of the displacement cardiograph has made possible the recording of left atrial and posterior left ventricle movements. A displacement cardiograph sensing element and an ECG electrode were built into a silicon tube to form an oesophageal probe. Records taken at various oesophageal levels have been recovered. Fourteen baboons were examined. Reproducible results of left atrial and posterior left ventricle movements were seen. The technique appears to be harmless and is easily performed. [ABSTRACT FROM PUBLISHER]

Background Ovarian cancer remains a leading cause of death from gynecological malignancies. Race, socioeconomic status (SES), and access to health care are important predictors of quality treatment and survival. We provide a systematic review and meta-analysis on the role of these predictors on disparities in ovarian cancer treatment and mortality. Methods Using the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, we searched PubMed, EMBASE, and Scopus for relevant articles published between January 2000 and March 2017. We selected studies published in the United States that evaluated the role of race, SES, or health-care access on disparities in ovarian cancer treatment or survival. Pooled relative risk (RR) and 95% confidence intervals (CIs) were calculated for each outcome using a random-effects model. Results A total of 41 studies met the inclusion criteria for systematic review. In meta-analysis, there was a 25% decrease (RR = 0.75, 95% CI = 0.66 to 0.84) in receipt of adherent ovarian cancer treatment and 18% increased risk (RR = 1.18, 95% CI = 1.11 to 1.26) of mortality for blacks compared to whites. Receipt of adherent ovarian cancer treatment was 15% lower (RR = 0.85, 95% CI = 0.77 to 0.94) in the lowest vs highest SES group and 30% lower (RR = 0.70, 95% CI = 0.58 to 0.85) among patients at lower vs higher hospital volumes. Conclusion We found consistent and strong evidence for continued lack of quality ovarian cancer treatment and higher mortality among ovarian cancer patients who are black, are of low SES, and/or have poor access to care. Interventions focused on these groups targeting specific barriers to care are needed to reduce disparities in ovarian cancer treatment and mortality. [ABSTRACT FROM AUTHOR]