Category: Nevin Manimala

Oncologist. 2024 Feb 16:oyae021. doi: 10.1093/oncolo/oyae021. Online ahead of print.

ABSTRACT

BACKGROUND: As a newly identified subtype of HER2-negative tumors associated with a less favorable prognosis, it remains crucial to evaluate potential prognostic and predictive factors, particularly non-invasive biomarkers, for individuals with human epidermal growth factor 2 (HER2) low early-stage breast cancer (EBC). Multiple investigations have highlighted that HER2-negative patients with EBC exhibiting high homologous recombination deficiency (HRD) scores display lower rates of pathological complete response (PCR) to neoadjuvant chemotherapy (NAC). Nevertheless, no study to date has explored the correlation between HRD and the long-term prognosis in HER2-low patients with EBC.

PATIENTS AND METHODS: This retrospective observational study focuses on primary EBC sourced from The Cancer Genome Atlas dataset (TCGA). It reveals the gene mutation landscape in EBC with low HER2 expression and elucidates the tumor immune landscape across different HRD states. Utilizing bioinformatics analysis and Cox proportional models, along with the Kaplan-Meier method, the study assesses the correlation between HRD status and disease-specific survival (DSS), disease-free interval (DFI), and progression-free interval (PFI). Subgroup analyses were conducted to identify potential variations in the association between HRD and prognosis.

RESULTS: In the patients with HER2-low breast cancer, patients with homologous recombination related genes (HRRGs) defects had an HRD score about twice that of those without related genes mutations, and were at higher risk of acquiring ARID1A, ATM, and BRCA2 mutations. We also found that most immune cell abundances were significantly higher in EBC tumors with high HRD than in EBC tumors with low HRD or HRD-medium, particularly plasma B-cell abundance, CD8 T-cell abundance, and M1 macrophages. In addition, these tumors with HRD-high also appear to have significantly higher tumor immune scores and lower interstitial scores. Then, we analyzed the relationship between different HRD status and prognosis. There was statistical significance (P = .036 and P = .046, respectively) in DSS and PFI between the HRD-low and HRD-high groups, and patients with HRD-high EBC showed relatively poor survival outcomes. A medium HRD score (hazard ratio, HR = 2.15, 95% CI: 1.04-4.41, P = .038) was a significant risk factor for PFI. Hormone receptor positivity is an important factor in obtaining medium-high HRD score and poor prognosis.

CONCLUSION: Higher HRD scores were associated with poorer PFI outcomes, particularly in people with HR+/HER2-low. Varied HRD states exhibited distinctions in HRRGs and the tumor immune landscape. These insights have the potential to assist clinicians in promptly identifying high-risk groups and tailoring personalized treatments for patients with HER2-low EBC, aiming to enhance long-term outcomes.

PMID:38366907 | DOI:10.1093/oncolo/oyae021

Aesthet Surg J. 2024 Feb 16:sjae026. doi: 10.1093/asj/sjae026. Online ahead of print.

ABSTRACT

Liposuction is considered one of the most common procedures in plastic surgery. However, major postoperative complications such as visceral injury, fluid overload, and necrotizing fasciitis still occur. Likewise, minor complications such as ecchymosis, seromas, infections, and contour irregularities that do not threaten the life of the patient do generate significant dissatisfaction. Current evidence regarding the management of fibrosis after previous liposuction remains limited. The objective of this article is to standardize a management algorithm based on the extensive experience and successful results of the primary author. Patients who underwent secondary liposculpture between August 2022 and May 2023 were evaluated prospectively. Inclusion criteria: Women between 18 and 60 years, non-smokers, with a body mass index (BMI) <35 kg/m2, history of previous body contouring surgeries. Identification of the patient’s skin condition and subcutaneous lesions in the adipose tissue were obtained in detail. Statistical analysis of preoperative and postoperative medical photographs was also performed with Fiji Biological image analyzer. Photographic analysis showed a statistically significant difference between the areas affected by fibrosis from the preoperative photos compared to that from the postoperative ones (p<.001). The most frequent clinical findings were depressions in 99% of the women (74), followed by soft nodules in 95% (70), hard nodules in 81% (61), adherences in 47% (35), and finally, cutaneous bursas in 4%. Our classification system and management algorithm for fibrosis and contour irregularities is a safe and reliable tool and results were objectively verified, yielding statistically significant outcomes.

PMID:38366902 | DOI:10.1093/asj/sjae026

Ann Work Expo Health. 2024 Feb 16:wxae005. doi: 10.1093/annweh/wxae005. Online ahead of print.

ABSTRACT

OBJECTIVE: Ensuring proper respirator fit for individuals remains a persistent challenge in occupational environments, yet there is limited knowledge about how respirators interact with the face to “‘fit.” Previous studies have attempted to understand the association between face dimensions and respirator fit using traditional head/face anthropometry not specifically tailored for respirators. The purpose of this study was to assess and compare the ability of filtering facepiece respirator (FFR)-specific face anthropometry with traditional head/face anthropometry in exploring the relationship between facial dimensions and the fit of FFR.

METHODS: The study utilized 3D face scans and quantitative fit factor scores from 56 participants to investigate the relationship between face anthropometry and FFR fit. Both FFR-specific and traditional anthropometric measurements were obtained through 3D anthropometric software. Intra-correlation of anthropometry was analyzed to evaluate the efficiency and effectiveness of FFR-specific and traditional anthropometry respectively. Principal component analysis (PCA) was conducted to test the usefulness of the PCA method for investigating various facial features. Logistic regression was used to develop fit association models by estimating the relationship between each face measurement set and the binary outcome of the fit test result. The prediction accuracy of the developed regression models was tested.

RESULTS: FFR-specific face anthropometry consists of a set of measurements that can inform the detailed facial shape associated with the FFRs more effectively than traditional head/face anthropometry. While PCA may have been effective in reducing the variable dimensions for the relatively large parts of the human body such as upper and lower bodies in previous literature, PCA results of FFR-specific and traditional anthropometry were inconsistent and insufficient to describe face dimensions with complex anatomy in a small-detailed area, suggesting that facial shape should be understood through a variety of approaches including statistical methods. Logistic regression analysis results confirmed that the association models of FFR-specific face anthropometry were significant with higher prediction accuracy and had a better model’s goodness of fit than those of traditional head/face anthropometry in 3 conditions inputting all measurements, all PC scores, or top 5 measurements from PCA.

CONCLUSIONS: The findings showed that the FFR fit association model enables an understanding of the detailed association between face and respirator fit and allows for the development of a system to predict respirator fit success or failure based on facial dimensions. Future research would include testing the validity of the model and FFR-specific measurement set on different respirator types, expanding the population set, and developing an integrated approach using automated and machine learning technologies to inform FFR selection for occupation workers and the general population.

PMID:38366891 | DOI:10.1093/annweh/wxae005

Phys Ther. 2024 Feb 16:pzae019. doi: 10.1093/ptj/pzae019. Online ahead of print.

ABSTRACT

OBJECTIVE: The objective of this study was to evaluate the efficacy of electrotherapy and manual therapy for the treatment of women with primary dysmenorrhea.

METHODS: Systematic searches were conducted in Scopus, Web of Science, PubMed, CINAHL, and MEDLINE. The articles must have been published in the last 10 years, had a sample exclusively of women with primary dysmenorrhea, had a randomized controlled trial design, and used interventions that included some form of manual therapy and/or electrotherapy techniques. Two reviewers independently screened articles for eligibility and extracted data. Difference in mean differences and their 95% CIs were calculated as the between-group difference in means divided by the pooled standard deviation. The I2 statistic was used to determine the degree of heterogeneity.

RESULTS: Twelve selected studies evaluated interventions, with 5 evaluating electrotherapy techniques and 7 evaluating manual therapy techniques. All studies analyzed identified improvements in pain intensity and meta-analysis confirmed their strong effect.

CONCLUSIONS: Manual therapy and electrotherapy are effective for the treatment of women with primary dysmenorrhea. Transcutaneous electrical nerve stimulation combined with thermotherapy and effleurage massage stands out for its effects on the intensity and duration of pain with the application of a few sessions and their long-term effects.

IMPACT: Manual therapy techniques and electrotherapy methods reduce the pain intensity of women with primary dysmenorrhea. Quality of life and degree of anxiety improved significantly with manual therapy interventions. Transcutaneous electrical nerve stimulation combined with thermotherapy and effleurage massage are the interventions with which positive effects were achieved with fewer sessions.

PMID:38366860 | DOI:10.1093/ptj/pzae019

Sleep. 2024 Feb 16:zsae048. doi: 10.1093/sleep/zsae048. Online ahead of print.

ABSTRACT

STUDY OBJECTIVES: Sleep disturbances are common in adolescence and associated with a host of negative outcomes. Here we assess associations between multifaceted sleep disturbances and a broad set of psychological, cognitive, and demographic variables using a data-driven approach, canonical correlation analysis (CCA).

METHODS: Baseline data from 9,093 participants from the Adolescent Brain Cognitive Development℠ (ABCD) Study were examined using CCA, a multivariate statistical approach that identifies many-to-many associations between two sets of variables by finding combinations for each set of variables that maximize their correlation. We combined CCA with leave-one-site-out cross-validation across ABCD sites to examine the robustness of results and generalizability to new participants. The statistical significance of canonical correlations was determined by non-parametric permutation tests that accounted for twin, family, and site structure. To assess the stability of the associations identified at baseline, CCA was repeated using two-year follow-up data from 4,247 ABCD Study participants.

RESULTS: Two significant sets of associations were identified: 1) difficulty initiating and maintaining sleep and excessive daytime somnolence were strongly linked to nearly all domains of psychopathology (r-squared = 0.36, p < .0001); 2) sleep breathing disorders were linked to BMI and African American/Black race (r-squared = 0.08, p < .0001). These associations generalized to unseen participants at all 22 ABCD sites and were replicated using two-year follow-up data.

CONCLUSIONS: These findings underscore interwoven links between sleep disturbances in early adolescence and psychological, social, and demographic factors.

PMID:38366843 | DOI:10.1093/sleep/zsae048

Inflamm Bowel Dis. 2024 Feb 16:izae010. doi: 10.1093/ibd/izae010. Online ahead of print.

ABSTRACT

BACKGROUND: Patterns of health services utilization among children with inflammatory bowel disease (IBD) are important to understand as the number of children with IBD continues to increase. We compared health services utilization and surgery among children diagnosed <10 years of age (Paris classification: A1a) and between 10 and <16 years of age (A1b).

METHODS: Incident cases of IBD diagnosed <16 years of age were identified using validated algorithms from deterministically linked health administrative data in 5 Canadian provinces (Alberta, Manitoba, Nova Scotia, Ontario, Quebec) to conduct a retrospective cohort study. We compared the frequency of IBD-specific outpatient visits, emergency department visits, and hospitalizations across age groups (A1a vs A1b [reference]) using negative binomial regression. The risk of surgery was compared across age groups using Cox proportional hazards models. Models were adjusted for sex, rural/urban residence location, and mean neighborhood income quintile. Province-specific estimates were pooled using random-effects meta-analysis.

RESULTS: Among the 1165 (65.7% Crohn’s) children with IBD included in our study, there were no age differences in the frequency of hospitalizations (rate ratio [RR], 0.88; 95% confidence interval [CI], 0.74-1.06) or outpatient visits (RR, 0.95; 95% CI, 0.78-1.16). A1a children had fewer emergency department visits (RR, 0.70; 95% CI, 0.50-0.97) and were less likely to require a Crohn’s-related surgery (hazard ratio, 0.49; 95% CI, 0.26-0.92). The risk of colectomy was similar among children with ulcerative colitis in both age groups (hazard ratio, 0.71; 95% CI, 0.49-1.01).

CONCLUSIONS: Patterns of health services utilization are generally similar when comparing children diagnosed across age groups.

PMID:38366807 | DOI:10.1093/ibd/izae010

Brief Bioinform. 2024 Jan 22;25(2):bbae039. doi: 10.1093/bib/bbae039.

ABSTRACT

The evolution in single-cell RNA sequencing (scRNA-seq) technology has opened a new avenue for researchers to inspect cellular heterogeneity with single-cell precision. One crucial aspect of this technology is cell-type annotation, which is fundamental for any subsequent analysis in single-cell data mining. Recently, the scientific community has seen a surge in the development of automatic annotation methods aimed at this task. However, these methods generally operate at a steady-state total cell-type capacity, significantly restricting the cell annotation systems’capacity for continuous knowledge acquisition. Furthermore, creating a unified scRNA-seq annotation system remains challenged by the need to progressively expand its understanding of ever-increasing cell-type concepts derived from a continuous data stream. In response to these challenges, this paper presents a novel and challenging setting for annotation, namely cell-type incremental annotation. This concept is designed to perpetually enhance cell-type knowledge, gleaned from continuously incoming data. This task encounters difficulty with data stream samples that can only be observed once, leading to catastrophic forgetting. To address this problem, we introduce our breakthrough methodology termed scEVOLVE, an incremental annotation method. This innovative approach is built upon the methodology of contrastive sample replay combined with the fundamental principle of partition confidence maximization. Specifically, we initially retain and replay sections of the old data in each subsequent training phase, then establish a unique prototypical learning objective to mitigate the cell-type imbalance problem, as an alternative to using cross-entropy. To effectively emulate a model that trains concurrently with complete data, we introduce a cell-type decorrelation strategy that efficiently scatters feature representations of each cell type uniformly. We constructed the scEVOLVE framework with simplicity and ease of integration into most deep softmax-based single-cell annotation methods. Thorough experiments conducted on a range of meticulously constructed benchmarks consistently prove that our methodology can incrementally learn numerous cell types over an extended period, outperforming other strategies that fail quickly. As far as our knowledge extends, this is the first attempt to propose and formulate an end-to-end algorithm framework to address this new, practical task. Additionally, scEVOLVE, coded in Python using the Pytorch machine-learning library, is freely accessible at https://github.com/aimeeyaoyao/scEVOLVE.

PMID:38366803 | DOI:10.1093/bib/bbae039

Acta Obstet Gynecol Scand. 2024 Feb 17. doi: 10.1111/aogs.14804. Online ahead of print.

ABSTRACT

INTRODUCTION: Team-based learning (TBL) is a well-established active teaching method which has been shown to have pedagogical advantages in some areas such as business education and preclinical disciplines in undergraduate medical education. Increasingly, it has been adapted to clinical disciplines. However, its superiority over conventional learning methods used in clinical years of medical school remains unclear. The aim of this study was to compare TBL with traditional seminars delivered in small group interactive learning (SIL) format in terms of knowledge acquisition and retention, satisfaction and engagement of undergraduate medical students during the 6-week obstetrics and gynecology clerkship.

MATERIAL AND METHODS: The study was conducted at Karolinska Institutet, a medical university in Sweden, and had a prospective, crossover design. All fifth-year medical students attending the obstetrics and gynecology clerkship, at four different teaching hospitals in Stockholm (approximately 40 students per site), in the Autumn semester of 2022 were invited to participate. Two seminars (one in obstetrics and one in gynecology) were designed and delivered in two different formats, ie TBL and SIL. The student:teacher ratio was approximately 10:1 in the traditional SIL seminars and 20:1 in the TBL. All TBL seminars were facilitated by a single teacher who had been trained and certified in TBL. Student knowledge acquisition and retention were assessed by final examination scores, and the engagement and satisfaction were assessed by questionnaires. For the TBL seminars, individual and team readiness assurance tests were also performed and evaluated.

RESULTS: Of 148 students participating in the classrooms, 132 answered the questionnaires. No statistically significant differences were observed between TBL and SIL methods with regard to student knowledge acquisition and retention, engagement and satisfaction.

CONCLUSIONS: We found no differences in student learning outcomes or satisfaction using TBL or SIL methods. However, as TBL had a double the student to teacher ratio as compared with SIL, in settings where teachers are scarce and suitable rooms are available for TBL sessions, the method may be beneficial in reducing faculty workload without compromising students’ learning outcomes.

PMID:38366801 | DOI:10.1111/aogs.14804

J Viral Hepat. 2024 Feb 17. doi: 10.1111/jvh.13930. Online ahead of print.

ABSTRACT

The emergency department (ED) has increasingly become an important public health partner in non-targeted hepatitis C virus (HCV) testing and referral to care efforts. HCV has traditionally been an infection associated with the Baby Boomer generation; however, recent exacerbation of the opioid epidemic has resulted in a growing number of younger cohorts, namely Millennials, also impacted by HCV. Examination of this age-related demographic shift, including subsequent linkage success and linkage barriers, from the perspective of an ED-based testing and linkage programme may have implications for future population and health systems interventions. A retrospective descriptive chart review was performed, inclusive of data from August 2015 through December 2020. We compared the quantity of positive HCV screening antibody (Ab) and confirmatory (RNA) tests and further considered linkage rates and correlative demographics (e.g. gender, race). Patient barriers to HCV care linkage (e.g. substance misuse, lack of health insurance, homelessness) were also evaluated. The data set was disaggregated by birth cohort to include Silent Generation (SG) (1928-45), Baby Boomer (BB) (1946-64), Generation X (Gen X) (1965-80), Millennial (1981-96) and Generation Z (1997-2012). Descriptive statistics and chi-square analysis were performed. Overall, 83,817 patients were tested for HCV (50.6% of eligible); 6187 (7.4%) were HCV Ab positive, and 2665 were HCV RNA positive (3.2%). RNA-positive individuals were more likely to be white (70.4%) and male (67.7%); generational distribution was similar (BB 33.3%, Gen X 32.0% and Millennials 32.7%). Amongst Ab-positive patients, white (45.5%), male (47.2%) and Millennial (49.7%) individuals were most likely to be RNA-positive. Overall, 28.1% of the RNA-positive cohort successfully linked to care; linkage to care rates were significantly higher in older generations (38.1% in BB vs. 17.8% in Millennials) (p < .00001). Over 90% were identified as having at least one linkage to care barrier. Younger generations (Gen X and Millennials) were disproportionately impacted by linkage barriers, including incarceration, lack of health insurance, history of mental health and substance use disorders, as well as history of or active injection drug use (IDU) (p < .00001). Older generations (SG and BB) were more likely to be impacted by competing medical comorbidities (p < .00001). The ED population represents a particularly vulnerable, at-risk cohort with a high prevalence of HCV and linkage to care barriers. While past HCV-specific recommendations and interventions have focused on Baby Boomers, this data suggests that younger generations, including Gen X and Millennials, are increasingly affected by HCV and face disparate social risk and social need factors which impede definitive care linkage and treatment.

PMID:38366787 | DOI:10.1111/jvh.13930

J Obstet Gynaecol Res. 2024 Feb 17. doi: 10.1111/jog.15906. Online ahead of print.

ABSTRACT

AIM: To estimate the incidence of abruption in first births and recurrence in the subsequent birth in patients of a large US-based integrated health care system.

METHODS: Retrospective population-based cohort study of patients with first two consecutive singleton births using data from the Kaiser-Permanente South California health care system who delivered over a period of 30 years (1991-2021), using longitudinally linked electronic health records. ICD-9/ICD-10 codes “641.20” and “O45.x” identified placental abruption. We calculated the incidence and rates of abruption in first and second pregnancies. We used logistic regression to estimate the adjusted odds ratios (aOR) for abruption in second pregnancies in patients with and without abruptions in their first pregnancies.

RESULTS: Of the 126 264 patients with first two consecutive singleton births over the period, 805 had abruptions in their first births, and 861 in their second births. Rates of abruption in first and second births were 0.63% and 0.68%, respectively. Twenty-seven patients had abruptions in both first and second births. Rates of abruption in the second birth among individuals with and without previous placental abruption were 3.35% and 0.66%, respectively, giving an approximately five-fold increased odds of abruption in a second pregnancy in individuals who had abruption in their first birth when compared with those who did not have placental abruption in their first birth (aOR: 4.95, 95% confidence interval: 3.35-7.31, p < 0.00001). Interpregnancy interval had no statistically significant association with recurrence.

CONCLUSION: Abruption in a first birth is associated with an approximately five-fold increased odds of abruption in a second birth.

PMID:38366767 | DOI:10.1111/jog.15906