Tag: nevin manimala

Genome Med. 2023 Sep 18;15(1):72. doi: 10.1186/s13073-023-01218-y.

ABSTRACT

BACKGROUND: Novel immunotherapy combination therapies have improved outcomes for patients with hepatocellular carcinoma (HCC), but responses are limited to a subset of patients. Little is known about the inter- and intra-tumor heterogeneity in cellular signaling networks within the HCC tumor microenvironment (TME) that underlie responses to modern systemic therapy.

METHODS: We applied spatial transcriptomics (ST) profiling to characterize the tumor microenvironment in HCC resection specimens from a prospective clinical trial of neoadjuvant cabozantinib, a multi-tyrosine kinase inhibitor that primarily blocks VEGF, and nivolumab, a PD-1 inhibitor in which 5 out of 15 patients were found to have a pathologic response at the time of resection.

RESULTS: ST profiling demonstrated that the TME of responding tumors was enriched for immune cells and cancer-associated fibroblasts (CAF) with pro-inflammatory signaling relative to the non-responders. The enriched cancer-immune interactions in responding tumors are characterized by activation of the PAX5 module, a known regulator of B cell maturation, which colocalized with spots with increased B cell marker expression suggesting strong activity of these cells. HCC-CAF interactions were also enriched in the responding tumors and were associated with extracellular matrix (ECM) remodeling as there was high activation of FOS and JUN in CAFs adjacent to the tumor. The ECM remodeling is consistent with proliferative fibrosis in association with immune-mediated tumor regression. Among the patients with major pathologic responses, a single patient experienced early HCC recurrence. ST analysis of this clinical outlier demonstrated marked tumor heterogeneity, with a distinctive immune-poor tumor region that resembles the non-responding TME across patients and was characterized by HCC-CAF interactions and expression of cancer stem cell markers, potentially mediating early tumor immune escape and recurrence in this patient.

CONCLUSIONS: These data show that responses to modern systemic therapy in HCC are associated with distinctive molecular and cellular landscapes and provide new targets to enhance and prolong responses to systemic therapy in HCC.

PMID:37723590 | DOI:10.1186/s13073-023-01218-y

J Orthop Surg Res. 2023 Sep 18;18(1):697. doi: 10.1186/s13018-023-04208-3.

ABSTRACT

BACKGROUND: Currently, there is a lack of research investigating the feasibility of employing anterograde lag screw fixation through the iliac crest for minimally invasive percutaneous treatment of the posterior acetabular column, which encompasses retrograde and anterograde screw fixation in posterior acetabular lag screw fixation. And consequently, the purpose of this study was to examine the anatomical parameters of anterograde lag screw fixation of the posterior column of the pelvis through the iliac crest as well as to investigate the intraoperative fluoroscopy technique, to furnish a scientific rationale supporting the practical utilization of this method within clinical settings.

METHODS: In this study, pelvic CT data of 60 healthy adults, including 30 males and 30 females, were accumulated. The mimics 21.0 software was developed to reconstruct the three-dimensional pelvis model, simulate the anterograde lag screw fixation of the posterior column of the acetabulum through use of the iliac crest, and precisely identify the insertion point: Utilizing the widest iliac tubercle as the starting point, the insertion point was moved toward the anterior superior iliac spine by 1.0 cm at a time until it reached 4.0 cm. With a total of five insertion points, all oriented toward the lesser sciatic notch, the initial diameter of the virtual screw measured 5.0 mm, and it was progressively enlarged by 1.0 mm increments until reaching a final diameter of 8.0 mm. Besides, the longest lengths of virtual screws with distinct diameters at divergent entry points were measured and compared. At the same time, the intraoperative fluoroscopy technique for optimal access was analyzed.

RESULTS: The cross-section from the iliac crest to the lesser sciatic notch was irregular, with multiple curved shapes. Furthermore, the diameter of the screw was determined by the anteroposterior radians and width of the iliac crest plate, while the screw length was determined by the curvature of the square body. On the condition that the screw diameter of the D channel (3.0 cm outward from the widest part of the iliac tubercle to the lesser sciatic notch) was 5 mm, 6 mm as well as 7 mm, the longest screw lengths were (145.6 ± 12.8) mm, (143.6 ± 14.4) mm and (139.9 ± 16.6) mm, correspondingly, indicating statistically substantial distinctions from other channels (P < 0.0001). Intraoperative fluoroscopy demonstrated that the C-arm machine was tilted (60.7 ± 2.9) ° to the iliac at the entrance position and perpendicular to the D-channel at the exit position.

CONCLUSION: It is possible to use the new channel to fix the posterior column of the acetabulum with an anterograde lag screw through the iliac crest. In specific, the channel is 3.0 cm outward from the widest part of the iliac tubercle to the lesser sciatic notch. Providing a wide channel, long screw insertion, and high safety, this technique offers a novel approach for minimally invasive treatment of posterior column fractures of the acetabulum.

PMID:37723587 | DOI:10.1186/s13018-023-04208-3

Genome Biol. 2023 Sep 18;24(1):209. doi: 10.1186/s13059-023-03045-1.

ABSTRACT

Identifying spatially variable genes (SVGs) is a key step in the analysis of spatially resolved transcriptomics data. SVGs provide biological insights by defining transcriptomic differences within tissues, which was previously unachievable using RNA-sequencing technologies. However, the increasing number of published tools designed to define SVG sets currently lack benchmarking methods to accurately assess performance. This study compares results of 6 purpose-built packages for SVG identification across 9 public and 5 simulated datasets and highlights discrepancies between results. Additional tools for generation of simulated data and development of benchmarking methods are required to improve methods for identifying SVGs.

PMID:37723583 | DOI:10.1186/s13059-023-03045-1

Reprod Biol Endocrinol. 2023 Sep 18;21(1):86. doi: 10.1186/s12958-023-01136-z.

ABSTRACT

BACKGROUND: In a true-natural cycle (t-NC), optimal progesterone (P₄) output from the corpus luteum is crucial for establishing and maintaining an intrauterine pregnancy. In a previous retrospective study, low P₄ levels (< 10 ng/mL) measured one day before warmed blastocyst transfer in t-NC were associated with significantly lower live-birth rates. In the current study, we aim to examine the relationship between patient, follicular-phase endocrine and ultrasonographic characteristics, and serum P₄ levels one day prior to warmed blastocyst transfer in t-NC.

METHOD: 178 consecutive women undergoing their first t-NC frozen embryo transfer (FET) between July 2017-August 2022 were included. Following serial ultrasonographic and endocrine monitoring, ovulation was documented by follicular collapse. Luteinized unruptured follicle (LUF) was diagnosed when there was no follicular collapse despite luteinizing-hormone surge (> 17 IU/L) and increased serum P₄ (> 1.5 ng/mL). FET was scheduled on follicular collapse + 5 or LH surge + 6 in LUF cycles. Primary outcome was serum P₄ on FET – 1.

RESULTS: Among the 178 patients, 86% (n = 153) experienced follicular collapse, while 14% (n = 25) had LUF. On FET-1, the median serum luteal P₄ level was 12.9 ng/mL (IQR: 9.3-17.2), ranging from 1.8 to 34.4 ng/mL. Linear stepwise regression revealed a negative correlation between body mass index (BMI) and LUF, and a positive correlation between follicular phase peak-E₂ and peak-P₄ levels with P₄ levels on FET-1. The ROC curve analyses to predict < 9.3 ng/mL (< 25th percentile) P₄ levels on FET-1 day showed AUC of 0.70 (95%CI 0.61-0.79) for BMI (cut-off: 23.85 kg/m²), 0.71 (95%CI 0.61-0.80) for follicular phase peak-P₄ levels (cut-off: 0.87 ng/mL), and 0.68 (95%CI 0.59-0.77) for follicular phase peak-E₂ levels (cut-off: 290.5 pg/mL). Combining all four independent parameters yielded an AUC of 0.80 (95%CI 0.72-0.88). The adjusted-odds ratio for having < 9.3 ng/mL P₄ levels on FET-1 day for patients with LUF compared to those with follicle collapse was 4.97 (95%CI 1.66-14.94).

CONCLUSION: The BMI, LUF, peak-E_2, and peak-P₄ levels are independent predictors of low serum P₄ levels on FET-1 (< 25th percentile; <9.3 ng/ml) in t-NC FET cycles. Recognition of risk factors for low serum P₄ on FET-1 may permit a personalized approach for LPS in t-NC FET to maximize reproductive outcomes.

PMID:37723581 | DOI:10.1186/s12958-023-01136-z

Clin Respir J. 2023 Sep 18. doi: 10.1111/crj.13699. Online ahead of print.

ABSTRACT

BACKGROUND: Lymph node (LN) metastasis is crucial in non-small cell lung cancer (NSCLC) prognosis and treatment, but the TNM system lacks LN quantity consideration. Our goal is to investigate the role of positive LNs (nPLN) and positive LN rate (LNR) in overall survival (OS) and assess whether they offer higher value in prognostic assessment of NSCLC than N-stage.

METHODS: Patients were stratified into four subgroups using X-Tile software. Statistical analysis was conducted using the Kaplan-Meier method, univariate analysis, and multivariate Cox regression analysis. Model performance was evaluated using the Harrell consistency index (C-index), Akaike information criterion (AIC), and Bayesian information criterion (BIC). The prognostic performance of the nodal classification was validated using overall survival as the endpoint.

RESULTS: The survival curves demonstrate distinct disparities between each nPLN and LNR category. A pronounced trend toward deteriorating overall survival from N-PLN 1 to N-PLN 2+ was observed across all tumor size categories. However, the differences between each LNR category were only significant for tumors ≤3 cm and 5-7 cm. Notably, both nPLN and LNR classifications displayed a higher C-index, lower AIC, and lower BIC compared with the N staging. Furthermore, the LNR classification provided superior prognostic stratification when compared with the nPLN classification.

CONCLUSIONS: Our results demonstrate that nPLN and LNR classifications may offer improved prognostic performance compared with the current N classification for LN-positive NSCLC patients. Nonetheless, more studies are needed to assess the feasibility of incorporating these classifications into the next TNM staging system.

PMID:37723579 | DOI:10.1111/crj.13699

J Eat Disord. 2023 Sep 18;11(1):161. doi: 10.1186/s40337-023-00892-y.

ABSTRACT

BACKGROUND: Media has a reputation for painting a narrow, simplistic, sensationalized portrait of eating disorders. There is little analysis of how film and TV portray eating disorders nor the implications of this representation. This study fills that gap by comparing demographics of US film and TV characters since the 1980s to actual population demographics of people with eating disorders.

METHODS: We compiled a dataset of TV and movie characters with eating disorders and categorized characters’ gender, age, race/ethnicity, and sexual orientation. We narrowed the dataset to include only US media depictions to facilitate comparisons with empirical prevalence, resulting in a total of 66 characters over the period 1981 to 2022. We then compared the demographic characteristics of our sample to national statistics on eating disorder prevalence.

RESULTS: US media depictions of eating disorders overrepresented characters who were heterosexual (75.56%), White (84.85%), women (89.39%), and under age 30 (84.85%). This does not accurately reflect the populations experiencing eating disorders in the US.

CONCLUSIONS: Eating disorders have an image problem. TV and movies inaccurately portray them as primarily affecting heterosexual, White, women under age 30. Misrepresentation could fuel existing stigmas that inhibit individuals with eating disorders from seeking and receiving treatment. It could also perpetuate stereotypes that fuel misperceptions of the disease by medical providers, families, and policymakers. We recommend more accurate representation in the media to better reflect current demographics and increase awareness of the range of people who can experience eating disorders.

PMID:37723555 | DOI:10.1186/s40337-023-00892-y

Chin Neurosurg J. 2023 Sep 18;9(1):26. doi: 10.1186/s41016-023-00335-2.

ABSTRACT

BACKGROUND: To describe and report the efficacy and safety of MR-guided laser interstitial thermal therapy (MRgLITT) in the treatment of drug-resistant epilepsy.

METHODS: A retrospective review of all MRgLITT procedures in our hospital was performed. All procedures were performed using a surgical laser ablation system. Demographic and outcome data were compiled and analyzed.

RESULTS: A total of 19 patients underwent MRgLITT procedures from June 2021 to November 2021. The average age at surgery was 18.1 years (3-61.4 years). The average length of hospitalization post-surgery was 4.95 days (4-7 days). Surgical substrates included 8 patients with hypothalamic hamartomas, 5 with medial temporal lobe epilepsy, 3 with deep focal cortical dysplasia, 1 with tuberous sclerosis, 1 with a cavernous malformation, and 1 with Lennox-Gastaut syndrome who underwent anterior corpus callosotomy. Complications occurred in three patients. After an average follow-up of 1 year, 6 patients were seizure-free (Engel I, 31.6%), 1 had significant seizure control (Engel II, 5.3%), 7 had seizure control (Engel III, 36.8%), and 5 had no improvement in their seizures (Engel IV, 26.3%). Fisher’s exact tests did not reveal statistical significance for the association between Engel class outcome and epileptic disease.

CONCLUSION: This study confirmed that MRgLITT, as a method for treating drug-resistant epilepsy, is minimally invasive, safe, and efficient and that it can reduce the incidence of surgery-related complications.

PMID:37723550 | DOI:10.1186/s41016-023-00335-2

BMC Med Educ. 2023 Sep 18;23(1):673. doi: 10.1186/s12909-023-04604-7.

ABSTRACT

BACKGROUND: Academics and clinicians are exposed to significant workload pressures and are at a high risk of stress and burnout.

OBJECTIVES: This study aimed to examine the relationship between burnout and emotional intelligence (EI) by comparing and corelating burnout and EI scores among academics and clinicians against several factors.

METHODS: In this cross-sectional study, academics and clinicians at King Saud University and King Saud University Medical City and Affiliated Hospitals were invited to complete anonymous questionnaires: Maslach Burnout Inventory-Human Services Survey and the Trait Emotional Intelligence Questionnaire Short Form. The collected data were analyzed using the SPSS software for descriptive studies, group comparisons, regression analyses, and Pearson’s (r) correlation tests.

RESULTS: Study participants included 126 individuals (men = 65, 51.6%; women = 61, 48.4%). Of these, 65% were Saudi nationals and 35% were expatriates, and 76 were academics while 50 were clinicians. The mean (minimum to maximum) burnout total score was 55 ± 18.9 (8 to 97) and the global TEIQue-SF score ranged between 2.8 and 6.7 (5.04 ± 0.7). Burnout scores varied between departments and were higher among younger participants and non-Saudis. Age had a small direct correlation with self-control (r = .17, p = .05), and there was no statistically significant correlation with other EI factors. However, there was a moderate inverse correlation between age and emotional exhaustion (EE) (r = -0.33, p < 0.0001), and a small inverse correlation with depersonalization (DP) (r = -0.21, p = 0.02). T-tests demonstrated a statistically significant difference in EI factor “emotionality” among Saudis (5.2 ± .8) and non-Saudis (4.9 ± .8) (t124 = 2.2, p = 0.03), and for burnout subscales, there was a statistically significant difference in DP among Saudis (6.4 ± 4.8) and non-Saudis (8.5 ± 5.6), (p = 0.03). Moderate (r = -0.3, p = 0.01) and weak (r = -0.2, p = 0.05) negative correlations were found between EI factors and burnout subscales (EE, DP).

CONCLUSION: This study confirmed an inverse relationship between burnout and EI scores among academics and clinicians. The findings suggest the need for introducing measures and implementing a system for early detection of burnout among staff and providing support to enhance EI and requisite care for those undergoing burnout episodes.

PMID:37723529 | DOI:10.1186/s12909-023-04604-7

Hum Resour Health. 2023 Sep 18;21(1):76. doi: 10.1186/s12960-023-00862-0.

ABSTRACT

BACKGROUND: Healthcare workers (HCWs) are essential resources, and their health and wellbeing are key not only for offering constant and useful care facilities to clients, but also for maintaining the safety of the workforce and patients. The risk of severe mental health problems among HCWs may have increased during large outbreaks of COVID-19. To evaluate the psychosocial status and risk perception of HCWs who participated in treating COVID-19 patients in Northern Iran, we performed a web-based cross-sectional study.

METHODS: The web-based cross-sectional design was applied between June 27 and September 2, 2021. Using convenience sampling, 637 HCWs were recruited from hospitals in Northern Iran (Mazandaran). The HCWs completed self-report questionnaires that included a sociodemographic information form, the 12-item General Health Questionnaire, Impact of the Event Scale-Revised, Risk Perception Questionnaire, and Anxiety Stress Scale-21. The data were analyzed via descriptive and inferential statistics and univariate/multivariate logistic regression to assess the risk factors linked to each psychosocial consequence.

RESULTS: The results reveal that the COVID-19 pandemic had an adverse psychosocial influence on HCWs, which was already apparent 1.5 years after the crisis began. Based on the results, 71.6%, 55.6%, and 32.3% of HCWs reported having anxiety, depression, and stress symptoms, respectively, since the outbreak of this disease. The logistic regression models displayed that marital status, having children, and working hours with patients were all risk factors of psychosocial impairment.

CONCLUSIONS: The outbreak of COVID-19 can be considered an important experience of a bio-disaster resulting in a significant rate of psychiatric problems in HCWs. There is a need for designing and promoting supportive programs to help HCWs cope and to improve their psychosocial state, and the present study has detected for whom psychosocial support may be effective and practical 1.5 years after the primary outbreak. Moreover, detecting and managing concerns and reducing infection-related embarrassment/stigma are essential for improving HCWs’ mental health.

PMID:37723512 | DOI:10.1186/s12960-023-00862-0

BMC Oral Health. 2023 Sep 18;23(1):673. doi: 10.1186/s12903-023-03377-1.

ABSTRACT

BACKGROUND: The aim of this study was to evaluate the effect of thermal and mechanical cyclic aging using a mastication simulator on push-out bond strength of mandibular premolars obturated with AH Plus and BioRoot RCS root canal sealers.

METHODS: With REVO-S files up to SU/0.06 taper, 48 single-rooted premolar teeth were instrumented. The teeth were randomly divided into two main groups (n = 24) based on the two root canal sealers used (AH Plus and BioRoot RCS). All teeth were obturated with h matched-taper single-cone. Each main group was then subdivided into three subgroups (A, B, and C) (n = 8). Group A served as the negative control group (no-thermocycling aging). While groups B and C were subjected to thermal changes in a thermocycler machine (15,000 and 30,000 thermal cycles, respectively), followed by two different dynamic loading periods, 3 × 10⁵ and 6 × 10⁵ in a masticatory simulator with a nominal load of 5 kg at 1.2 Hz which represent roughly 1½ and 3 years of clinical function respectively. 2 mm slice at 3 levels, apical, middle, and coronal, to obtain 3 sections were prepared and subjected to push-out test using a universal testing machine. Statistical analysis was performed using analysis of variance (ANOVA) followed by a Tukey post hoc comparisons test and an independent T-test. A significance level of 5% was used.

RESULTS: After thermal-mechanical cyclic aging, the two root canal sealers showed a significantly decreased in push-out bond strength (p < 0.05), however, AH Plus had significantly higher bond strength values than BioRoot RCS after cycling aging.

CONCLUSIONS: It could be concluded that thermal-mechanical cyclic aging had a significant impact on the outcome of the dislodgment resistance of AH Plus and BioRoot RCS.

PMID:37723511 | DOI:10.1186/s12903-023-03377-1