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Background: Heterogeneity in national SARS-CoV-2 infection surveillance capabilities may compromise global enumeration and tracking of COVID-19 cases and deaths and bias analyses of the pandemic's tolls. Taking account of heterogeneity in data completeness may thus help clarify analyses of the relationship between COVID-19 outcomes and standard preparedness measures. Methods: We examined country-level associations of pandemic preparedness capacities inventories, from the Global Health Security (GHS) Index and Joint External Evaluation (JEE), on SARS-CoV-2 infection and COVID-19 death data completion rates adjusted for income. Analyses were stratified by 100, 100–300, 300–500, and 500–700 days after the first reported case in each country. We subsequently reevaluated the relationship of pandemic preparedness on SARS-CoV-2 infection and age-standardized COVID-19 death rates adjusted for cross-country differentials in data completeness during the pre-vaccine era. Results: Every 10% increase in the GHS Index was associated with a 14.9% (95% confidence interval 8.34–21.8%) increase in SARS-CoV-2 infection completion rate and a 10.6% (5.91–15.4%) increase in the death completion rate during the entire observation period. Disease prevention (infections: β = 1.08 [1.05–1.10], deaths: β = 1.05 [1.04–1.07]), detection (infections: β = 1.04 [1.01–1.06], deaths: β = 1.03 [1.01–1.05]), response (infections: β = 1.06 [1.00–1.13], deaths: β = 1.05 [1.00–1.10]), health system (infections: β = 1.06 [1.03–1.10], deaths: β = 1.05 [1.03–1.07]), and risk environment (infections: β = 1.27 [1.15–1.41], deaths: β = 1.15 [1.08–1.23]) were associated with both data completeness outcomes. Effect sizes of GHS Index on infection completion (Low income: β = 1.18 [1.04–1.34], Lower Middle income: β = 1.41 [1.16–1.71]) and death completion rates (Low income: β = 1.19 [1.09–1.31], Lower Middle income: β = 1.25 [1.10–1.43]) were largest in LMICs. After adjustment for cross-country differences in data completeness, each 10% increase in the GHS Index was associated with a 13.5% (4.80–21.4%) decrease in SARS-CoV-2 infection rate at 100 days and a 9.10 (1.07–16.5%) decrease at 300 days. For age-standardized COVID-19 death rates, each 10% increase in the GHS Index was with a 15.7% (5.19–25.0%) decrease at 100 days and a 10.3% (− 0.00–19.5%) decrease at 300 days. Conclusions: Results support the pre-pandemic hypothesis that countries with greater pandemic preparedness capacities have larger SARS-CoV-2 infection and mortality data completeness rates and lower COVID-19 disease burdens. More high-quality data of COVID-19 impact based on direct measurement are needed. [ABSTRACT FROM AUTHOR]

Background: Atezolizumab, one of the immune checkpoint inhibitors, has been approved as an adjuvant treatment following resection and platinum‐based chemotherapy in patients with stage II–IIIA non‐small cell lung cancer with 1% or more programmed death ligand‐1 (PD‐L1) expression. The Food and Drug Administration (FDA) has approved SP263 as a companion diagnostic assay for adjuvant treatment with atezolizumab; however, in clinical practice, the 22C3 assay is most commonly used for advanced non‐small cell lung cancer. Therefore, our study aimed to compare two PD‐L1 assays, SP263 and 22C3, to evaluate whether 22C3 could replace SP263 when deciding whether to administer adjuvant atezolizumab. Methods: We retrospectively and prospectively analyzed 98 patients who underwent surgical resection at Kanagawa Cancer Center (Japan). An immunohistochemistry assay was performed for all the cases with both SP263 and 22C3. We statistically analyzed the concordance of PD‐L1 expression between SP263 and 22C3 assays. Results: The concordance between the two assays using Cohen's kappa was κ = 0.670 (95% CI: 0.522–0.818) at the 1% cutoff and κ = 0.796 (95% CI: 0.639–0.954) at the 50% cutoff. The Spearman correlation coefficient of 0.874 (p < 0.01) indicated high concordance. PD‐L1 expression with 22C3 resulted slightly higher than that with SP263. Conclusions: This study showed a high concordance of PD‐L1 expression with the SP263 and 22C3 assays. Further studies examining the therapeutic effects of adjuvant atezolizumab are required. [ABSTRACT FROM AUTHOR]

• In this study, we conducted a statistical analysis of foF2 and TEC data under both ionospheric quiet and disturbed conditions, employing the ionospheric slab thickness model. • The utilization of Kriging with external drift (KED) in generating maps has enhanced their realism. • The inclusion of foF2 data from the map's periphery has resulted in the overall stabilization of the map. • Based on our findings, we can conclude that the correlation distance between ionospheric characteristics should not exceed the range of 120–300 km. The importance of this study lies in its contribution to the field of ionospheric science, particularly in the monitoring and prediction of ionospheric parameters. This study focuses on comparing two techniques for spatio-temporal kriging of critical ionospheric parameters, namely the F2 layer critical frequency (foF2) and Total Electron Content (TEC), under both quiet and disturbed ionospheric conditions. The first technique, Ordinary Kriging (OK), relies solely on foF2 data, while the second technique, Kriging with External Drift (KED), incorporates the dynamic relationship between foF2 and TEC data to improve the interpolation process. This study demonstrates how KED, which utilizes dynamic secondary information, offers advantages over OK. By simultaneously monitoring the ionosphere from a single ionosonde station and collecting data from visible GPS satellites, KED enhances the accuracy of spatial structural analysis, enabling more precise estimations of ionospheric characteristics across interpolation grid nodes. The research highlights that the non-uniform distribution of ionosonde stations, especially in regions with limited foF2 data, can benefit from KED's incorporation of TEC data. Additionally, the study reveals the potential for improving TEC maps by assimilating foF2 data located at the periphery of the observation area. Furthermore, the paper discusses the determination of semivariogram structures for both foF2 and TEC data, emphasizing the spatial correlations between data points. These findings contribute to a better understanding of ionospheric behavior and the potential for enhanced ionospheric modeling. [ABSTRACT FROM AUTHOR]

Background: The overall survival (OS) for patients with recurrent glioma is meager. Also, the effect of radionecrosis and prognostic factors for recurrent glioma remains controversial. In this regard, developing effective predictive models and guiding clinical care is crucial for these patients. Methods: We screened patients with recurrent glioma after radiotherapy and those who received surgery between August 1, 2013, and December 31, 2020. Univariate and multivariate Cox regression analyses determined the independent prognostic factors affecting the prognosis of recurrent glioma. Moreover, nomograms were constructed to predict recurrent glioma risk and prognosis. Statistical methods were used to determine the prediction accuracy and discriminability of the nomogram prediction model based on the area under the curve (AUC), the C-index, the decision curve analysis (DCA), and the calibration curve. In order to distinguish high-risk and low-risk groups for OS, the X-Tile and Kaplan-Meier (K-M) survival curves were employed, and the nomogram prediction model was further validated by the X-Tile and K-M survival curves. Results: According to a Cox regression analysis, independent prognostic factors of recurrent glioma after radiotherapy with radionecrosis were World Health Organization (WHO) grade and gliosis percentage. We utilized a nomogram prediction model to analyze results visually. The C-index was 0.682 (95% CI: 0.616–0.748). According to receiver operating characteristic (ROC) analysis, calibration plots, and DCA, the nomogram prediction model was found to have a high-performance ability, and all patients were divided into low-risk and high-risk groups based on OS (P <.001). Conclusion: WHO grade and gliosis percentage are prognostic factors for recurrent glioma with radionecrosis, and a nomogram prediction model was established based on these two variables. Patients could be divided into high- and low-risk groups with different OS by this model, and it will provide individualized clinical decisions for future treatment. [ABSTRACT FROM AUTHOR]

Purpose: Facet joint degeneration (FJD) is a major cause of low back pain. Parathyroid hormone (PTH) (1–34) is commonly used to treat osteoporosis. However, little is known about its effects on FJD induced by estrogen deficiency. This study aims to investigate the effects of PTH (1–34) on FJD induced by estrogen deficiency and the underlying pathogenesis of the disease. Methods: Forty 3-month-old female Sprague-Dawley rats were randomly divided into four groups: 30 received bilateral ovariectomy (OVX) followed by 12 weeks of treatment with normal saline, PTH (1–34) or 17β-estradiol (E2), and 10 received sham surgery followed by administration of normal saline. Status and Wnt/β-catenin signaling activity in the cartilage and subchondral bone of the L4–L5 FJs and serum biomarkers were analyzed. Results: Administration of PTH (1–34) and E2 ameliorated cartilage lesions, and significantly decreased MMP-13 and caspase-3 levels and chondrocyte apoptosis. PTH (1–34) but not E2 significantly increased cartilage thickness, number of chondrocytes, and the expression of aggrecan. PTH (1–34) significantly improved microarchitecture parameters of subchondral bone, increased the expression of collagen I and osteocalcin, and decreased RANKL/OPG ratio. E2 treatment significantly increased the OPG level and decreased the RANKL/OPG ratio in the subchondral bone of ovariectomized rats, but it did not significantly improve the microarchitecture parameters of subchondral bone. Wnt3a and β-catenin expression was significantly reduced in the articular cartilage and subchondral bone in OVX rats, but PTH (1–34) could increase the expression of these proteins. E2 significantly increased the activity of Wnt/β-catenin pathway only in cartilage, but not in subchondral bone. The restoration of Wnt/β-catenin signaling had an obvious correlation with the improvement of some parameters associated with the FJs status. Conclusion: Wnt/β-catenin signaling may be a potential therapeutic target for FJD induced by estrogen deficiency. PTH (1–34) is effective in treating this disease with better efficacy than 17β-estradiol, and the efficacy may be attributed to its restoration of Wnt/β-catenin signaling. [ABSTRACT FROM AUTHOR]

Background: In bioinformatics, interactions are modelled as networks, based on graph models. Generally, these support a single-layer structure which incorporates a specific entity (i.e., node) and only one type of link (i.e., edge). However, real-world biological systems consisting of biological objects belonging to heterogeneous entities, and these operate and influence each other in multiple contexts, simultaneously. Usually, node similarities are investigated to assess the relatedness between biological objects in a network of interest, and node embeddings are widely used for studying novel interaction from a topological point of view. About that, the state-of-the-art presents several methods for evaluating the node similarity inside a given network, but methodologies able to evaluate similarities between pairs of nodes belonging to different networks are missing. The latter are crucial for studies that relate different biological networks, e.g., for Network Alignment or to evaluate the possible evolution of the interactions of a little-known network on the basis of a well-known one. Existing methods are ineffective in evaluating nodes outside their structure, even more so in the context of multilayer networks, in which the topic still exploits approaches adapted from static networks. In this paper, we presented pyMulSim, a novel method for computing the pairwise similarities between nodes belonging to different multilayer networks. It uses a Graph Isomorphism Network (GIN) for the representative learning of node features, that uses for processing the embeddings and computing the similarities between the pairs of nodes of different multilayer networks. Results: Our experimentation investigated the performance of our method. Results show that our method effectively evaluates the similarities between the biological objects of a source multilayer network to a target one, based on the analysis of the node embeddings. Results have been also assessed for different noise levels, also through statistical significance analyses properly performed for this purpose. Conclusions: PyMulSim is a novel method for computing the pairwise similarities between nodes belonging to different multilayer networks, by using a GIN for learning node embeddings. It has been evaluated both in terms of performance and validity, reporting a high degree of reliability. [ABSTRACT FROM AUTHOR]

In scientific research, assessing the impact and influence of authors is crucial for evaluating their scholarly contributions. Whereas in literature, multitudinous parameters have been developed to quantify the productivity and significance of researchers, including the publication count, citation count, well-known h index and its extensions and variations. However, with a plethora of available assessment metrics, it is vital to identify and prioritize the most effective metrics. To address the complexity of this task, we employ a powerful deep learning technique known as the Multi-Layer Perceptron (MLP) classifier for the classification and the ranking purposes. By leveraging the MLP's capacity to discern patterns within datasets, we assign importance scores to each parameter using the proposed modified recursive elimination technique. Based on the importance scores, we ranked these parameters. Furthermore, in this study, we put forth a comprehensive statistical analysis of the top-ranked author assessment parameters, encompassing a vast array of 64 distinct metrics. This analysis gives us treasured insights in between these parameters, shedding light on the potential correlations and dependencies that may affect assessment outcomes. In the statistical analysis, we combined these parameters by using seven well-known statistical methods, such as arithmetic means, harmonic means, geometric means etc. After combining the parameters, we sorted the list of each pair of parameters and analyzed the top 10, 50, and 100 records. During this analysis, we counted the occurrence of the award winners. For experimental proposes, data collection was done from the field of Mathematics. This dataset consists of 525 individuals who are yet to receive their awards along with 525 individuals who have been recognized as potential award winners by certain well known and prestigious scientific societies belonging to the fields' of mathematics in the last three decades. The results of this study revealed that, in ranking of the author assessment parameters, the normalized h index achieved the highest importance score as compared to the remaining sixty-three parameters. Furthermore, the statistical analysis results revealed that the Trigonometric Mean (TM) outperformed the other six statistical models. Moreover, based on the analysis of the parameters, specifically the M Quotient and FG index, it is evident that combining these parameters with any other parameter using various statistical models consistently produces excellent results in terms of the percentage score for returning awardees. [ABSTRACT FROM AUTHOR]

Introduction Material and Methods Results Conclusions Human papillomavirus (HPV) diagnosis has a considerable emotional and psychological impact on women. To evaluate the impairment this infection leads to regarding quality of life (QoL), several scales have been suggested, such as the human‐papillomavirus‐quality‐of‐life (HPV‐QoL) questionnaire. This has been validated for the Spanish population and measures the impact of HPV on health‐related‐quality‐of‐life (HR‐QoL). However, normative values are yet to be developed. Thus, the objective was to describe the population‐based norms of the HPV‐QoL for Spanish women aged 25–65 years and to test the questionnaire's construct validity.This was a cross‐sectional nationwide multicenter study. Women from outpatient clinics in Spain aged 25–65 years, with a diagnosis of past or active HPV infection were recruited. The central tendency, dispersion, and percentiles were calculated for the total score and its dimensions for each age group. Construct validity was tested by analyzing age groups and their correlations with other related scales (12‐Item General Health Questionnaire [GHQ‐12], Female Sexual Function Index [FSFI], and Hospital Anxiety and Depression Scale [HADS]).A total of 1352 women were included in the study. The norms showed moderate and significant coefficients of correlation with other related scales. Significant differences between age strata groups were found according to educational level, sexual dysfunction, sexual activity, mental deterioration, and severity of anxiety and depression symptoms (p < 0.001 in all cases). The total score differed significantly between the groups (p = 0.006). Significant differences in the contagiousness, health, and sexuality dimensions (p < 0.05) were found among the groups. It was seen that HPV infection impaired women's QoL. Dimensions within all test age groups (p < 0.001 in all cases) were significantly different, with the health dimension being the highest contributor to women's QoL impairment, whereas social well‐being was the main determinant of QoL.Population‐based norms for the novel HPV‐QoL questionnaire showed adequate validity and could be a useful tool for assessing the impact of QoL among women with HPV in Spain. [ABSTRACT FROM AUTHOR]

Background: In the realm of biomedical research, the growing volume, diversity and quantity of data has escalated the demand for statistical analysis as it is indispensable for synthesizing, interpreting, and publishing data. Hence the need for accessible analysis tools drastically increased. StatiCAL emerges as a user-friendly solution, enabling researchers to conduct basic analyses without necessitating extensive programming expertise. Results: StatiCAL includes divers functionalities: data management, visualization on variables and statistical analysis. Data management functionalities allow the user to freely add or remove variables, to select sub-population and to visualise selected data to better perform the analysis. With this tool, users can freely perform statistical analysis such as descriptive, graphical, univariate, and multivariate analysis. All of this can be performed without the need to learn R coding as the software is a graphical user interface where all the action can be performed by clicking a button. Conclusions: StatiCAL represents a valuable contribution to the field of biomedical research. By being open-access and by providing an intuitive interface with robust features, StatiCAL allow researchers to gain autonomy in conducting their projects. [ABSTRACT FROM AUTHOR]

Background: Although China has a long history of using insects as food and medicine and has developed numerous associated knowledge and practices, especially in its rural and mountainous areas, systematic surveys concerning this subject are limited. In-depth ethnobiological research is needed to compile a comprehensive database of edible and medicinal insects and record the associated knowledge of these food and medicinal resources. Methods: Data on edible and medicinal insects and associated knowledge about them were collected by interviewing 216 local villagers in a mountainous territory in southeast Guangxi Zhuang Autonomous Region, China. Results: Local villagers used at least 16 edible and 9 medicinal insects, of which 4 wasp species were used in both entomophagy and medicinal practices. Parapolybia varia, Polistes olivaceus, and Anomala chamaeleon were newly recorded edible insects in China. The wasps, Euconocephalus sp., Gryllotalpa orientalis, and Cyrtotrachelus longimanus, were preferred and culturally important edible insects. Populations of Euconocephalus sp. and G. orientalis were reported to have substantially decreased in recent years. Wasps and a bamboo bee were used to treat rheumatism, while cockroaches and antlions were used to treat common cold symptoms in infants. Insect-related knowledge was positively correlated with the interviewees' age. Conclusions: Villagers have accumulated considerable local and traditional knowledge of entomophagy and entomo-therapeutic practices. However, this knowledge is in danger of being lost, which highlights the urgent need to document this information. Edible insects enrich local diets, and a more sustainable supply (such as through insect farming) could maintain local entomophagy practices. Medicinal insects are a part of local folk medicine, and pharmacological and chemical techniques could be applied to identify various biologically active substances in these insects. [ABSTRACT FROM AUTHOR]

Background: A proportion of head and neck carcinomas (HNSCCs) are induced by high-risk human papillomaviruses (HPVs) and are associated with better patient outcomes compared to patients with HNSCCs related to tobacco and alcohol abuse. In the microenvironment of solid tumors, including HNSCCs, oxygen levels are often reduced, and a hypoxic state is induced. This can lead to a poor treatment response and a worse patient prognosis. One of the hypoxia-responsive genes is aspartate-β-hydroxylase (ASPH), whose activity promotes the growth, invasiveness, and metastasis of many types of solid tumors. Methods: In our study, HNSCC samples were analyzed for the expression of ASPH and selected endogenous hypoxia markers by real-time PCR and/or multiplex fluorescence immunohistochemistry. Results: Except for the EPAS1 gene, which had higher mRNA expression in the HPV-negative group of HNSCC (p < 0.05), we found no other differences in the expression of the tested genes that were related to HPV status. On the contrary, a statistically significantly higher number of cells producing ASPH (p < 0.0001), HIF1A (p < 0.0001), GLUT1 (p < 0.0001), and MMP13 (p < 0.05) proteins were detected in the HPV-positive tumor group than in the HPV-negative sample group. All the evaluated markers, except for MMP9/13, were more abundant in the tumor parenchyma than in the tumor stroma. The Cox proportional hazard models showed that increased numbers of cells with GLUT1 and HIF1A protein expression were positive prognostic markers for overall and disease-specific survival in patients independent of HPV tumor status. Conclusion: The study examined HNSCC samples and found that elevated ASPH and hypoxia marker proteins, typically associated with poor prognosis, may actually indicate active HPV infection, the strongest prognostic factor in HNSCC patients. In cases where HPV status is uncertain, increased expression of HIF1A and GLUT1 can serve as positive prognostic factors. [ABSTRACT FROM AUTHOR]

Background: Fragility fracture is common in the elderly. Osteoblast differentiation is essential for bone healing and regeneration. Expression pattern of long non-coding RNA MIAT during fracture healing was examined, and its role in osteoblast differentiation was investigated. Methods: 90 women with simple osteoporosis and 90 women with fragility fractures were included. Another 90 age-matched women were set as the control group. mRNA levels were tested using RT-qPCR. Cell viability was detected via CCK-8, and osteoblastic biomarkers, including ALP, OCN, Collagen I, and RUNX2 were tested via ELISA. The downstream miRNAs and genes targeted by MIAT were predicted by bioinformatics analysis, whose functions and pathways were annotated via GO and KEGG analysis. Results: Serum MIAT was upregulated in osteoporosis women with high accuracy of diagnostic efficacy. Serum MIAT was even elevated in the fragility fracture group, but decreased in a time manner after operation. MIAT knockdown promoted osteogenic proliferation and differentiation of MC3T3-E1, but the influences were reversed by miR-181a-5p inhibitor. A total of 137 overlapping target genes of miR-181a-5p were predicted based on the miRDB, TargetScan and microT datasets, which were mainly enriched for terms related to signaling pathways regulating pluripotency of stem cells, cellular senescence, and osteoclast differentiation. Conclusions: LncRNA MIAT serves as a promising biomarker for osteoporosis, and promotes osteogenic differentiation via targeting miR-181a-5p. [ABSTRACT FROM AUTHOR]

Background: The objective of this study was to evaluate the potential of zoledronic acid for reducing the incidence of cage subsidence and enhancing interbody fusion rates following oblique lumbar interbody fusion (OLIF) surgery, particularly as the first reported evidence of the role of zoledronic acid combined with OLIF. Methods: A retrospective analysis was conducted on data from 108 elderly patients treated for degenerative lumbar diseases using OLIF combined with bilateral pedicle screw fixation from January 2018 to December 2021. Patients were divided into the zoledronic acid (ZOL) group (43 patients, 67 surgical segments) and the control group (65 patients, 86 surgical segments). A comparative analysis of the radiographic and clinical outcomes between the groups was performed, employing univariate and multivariate regression analyses to explore the relationships between cage subsidence and the independent variables. Results: Radiographic outcomes, including anterior height, posterior height, disc height, coronal disc angle, foraminal height, and lumbar lordosis, were not significantly different between the two groups. Similarly, no statistically significant differences were noted in the back visual analog scale (VAS) scores and Oswestry Disability Index (ODI) scores between the groups. However, at the 1-year follow-up, the leg VAS score was lower in the ZOL group than in the control group (P = 0.028). The ZOL group demonstrated a notably lower cage subsidence rate (20.9%) than did the control group (43.0%) (P < 0.001). There was no significant difference in the interbody fusion rate between the ZOL group (93.0%) and the control group (90.8%). Non-use of zoledronic acid emerged as an independent risk factor for cage subsidence (OR = 6.047, P = 0.003), along with lower bone mineral density, lower postoperative anterior height, and concave endplate morphology. The model exhibited robust discriminative performance, with an area under the curve (AUC) of 0.872. Conclusion: The administration of zoledronic acid mitigates the risk of cage subsidence following OLIF combined with bilateral pedicle screw fixation in elderly patients; however, it does not improve the interbody fusion rate. [ABSTRACT FROM AUTHOR]

Background: Arthroscopic tuberoplasty is an optional technique for managing irreparable rotator cuff tears. However, there is a lack of studies investigating the resistance force during shoulder abduction in cases of irreparable rotator cuff tears and tuberoplasty. Hypotheses: In shoulders with irreparable rotator cuff tears, impingement between the greater tuberosity (GT) and acromion increases the resistance force during dynamic shoulder abduction. Tuberoplasty is hypothesized to reduce this resistance force by mitigating impingement. Study design: Controlled laboratory study. Methods: Eight cadaveric shoulders, with a mean age of 67.75 years (range, 63–72 years), were utilized. The testing sequence included intact rotator cuff condition, irreparable rotator cuff tears (IRCTs), burnishing tuberoplasty, and prosthesis tuberoplasty. Burnishing tuberoplasty refers to the process wherein osteophytes on the GT are removed using a bur, and the GT is subsequently trimmed to create a rounded surface that maintains continuity with the humeral head. Deltoid forces and actuator distances were recorded. The relationship between deltoid forces and actuator distance was graphically represented in an ascending curve. Data were collected at five points within each motion cycle, corresponding to actuator distances of 20 mm, 30 mm, 40 mm, 50 mm, and 60 mm. Results: In the intact rotator cuff condition, resistance forces at the five points were 34.25 ± 7.73 N, 53.75 ± 7.44 N, 82.50 ± 14.88 N, 136.25 ± 30.21 N, and 203.75 ± 30.68 N. In the IRCT testing cycle, resistance forces were 46.13 ± 7.72 N, 63.75 ± 10.61 N, 101.25 ± 9.91 N, 152.5 ± 21.21 N, and 231.25 ± 40.16 N. Burnishing tuberoplasty resulted in resistance forces of 32.25 ± 3.54 N, 51.25 ± 3.54 N, 75.00 ± 10.69 N, 115.00 ± 10.69 N, and 183.75 ± 25.04 N. Prosthesis tuberoplasty showed resistance forces of 29.88 ± 1.55 N, 49.88 ± 1.36 N, 73.75 ± 7.44 N, 112.50 ± 7.07 N, and 182.50 ± 19.09 N. Both forms of tuberoplasty significantly reduced resistance force compared to IRCTs. Prosthesis tuberoplasty further decreased resistance force due to a smooth surface, although the difference was not significant compared to burnishing tuberoplasty. Conclusion: Tuberoplasty effectively reduces resistance force during dynamic shoulder abduction in irreparable rotator cuff tears. Prosthesis tuberoplasty does not offer a significant advantage over burnishing tuberoplasty in reducing resistance force. Clinical Relevance: Tuberoplasty has the potential to decrease impingement, subsequently reducing resistance force during dynamic shoulder abduction, which may be beneficial in addressing conditions like pseudoparalysis. [ABSTRACT FROM AUTHOR]

Background: A negative attitude towards abortion among health care providers providing abortion services could be an obstacle even under a law, which permits abortion on request. Healthcare providers are expected to perform and be change agents of abortion services. However, little information is known about the attitude toward safe abortion among healthcare providers in Ethiopia. Objective: This study aimed to assess health care provider's attitudes towards safe abortion care and its associated factors at the public health facilities of Bahir Dar City, Northwest Ethiopia. Methods: A health facility-based cross-sectional study was employed from March 1 to 30/2021 among 416 health-care providers. The data were collected by computer-based generated simple random sampling technique, entered, coded, and cleaned using Epi data version 4.2 and analyzed using Statistical Package of Social Sciences version 25.0. Bivariate and multivariable logistic regression analyses were employed to estimate the crude and adjusted odds ratio with a confidence interval of 95% and a P-value of less than 0.05 considered statistically significant. Results: The response rate of the study was 99.3%, and 70.2% [95% CI: 65.6–74.6] of health-care providers had a favorable attitude towards safe abortion care. Multivariable analysis indicated that health care providers who are found in the age group of 25–29, 30–34, and ≥ 35 years [AOR = 3.34, 95% CI = 1.03–10.85], [AOR = 4.58, 95% CI = 1.33- 15.83] and [AOR = 5.30, 95% CI = 1.43–19.66] respectively, male health care providers [AOR = 3.20, 95% CI = 1.55–6.60], midwives [AOR = 6.50, 95% CI = 2.40–17.44], working at hospital [AOR = 4.77, 95% CI = 1.53–14.91], ever trained on safe abortion [AOR = 5.09, 95% CI = 2.29–11.32], practicing of an abortion procedure [AOR = 2.52, 95%, CI = 1.13–5.60], knowledge of abortion [AOR = 7.35, 95% CI = 3.23–16.71], awareness on revised abortion law [AOR = 6.44, 95% CI = 3.15–13.17] and need further legalization of abortion law [AOR = 11.78, 95% CI = 5.52–24.26] were associated with a favorable attitude towards safe abortion care. Conclusions: Healthcare providers who had a favorable attitude toward safe abortion care were relatively high compared to the previous studies. Age, sex, profession, workplace, training, knowledge, and practice-related factors were associated with a favorable attitude toward safe abortion. This study indicated that, a need for intervention to help improve the attitude of healthcare providers toward safe abortion care, especially for those working in the maternity care units. [ABSTRACT FROM AUTHOR]

Background: We aimed to compare the analgesic effects of intravenous ibuprofen to ketorolac after open abdominal hysterectomy. Methods: This randomized double-blinded controlled trial included adult women scheduled for elective open abdominal hysterectomy. Participants were randomized to receive either 30 mg ketorolac (n = 50) or 800 mg ibuprofen (n = 50) preoperatively, then every 8 h postoperatively for 24 h. All participants received paracetamol 1 gm/6 h. Rescue analgesic was given if the visual analogue scale (VAS) for pain assessment was > 3. The primary outcome was the mean postoperative dynamic VAS during the first 24 h. Secondary outcomes were static VAS, intraoperative fentanyl consumption, postoperative morphine consumption, time to independent movement, and patient's satisfaction. Results: Forty-six patients in the ibuprofen group and fifty patients in the ketorolac group were analyzed. The 24-h dynamic and static VAS were similar in the two groups. The median (quartiles) dynamic VAS was 1.1 (0.9, 1.9) in the ibuprofen group versus 1.0 (0.7, 1.3) in the ketorolac group, P-value = 0.116; and the median (quartiles) static VAS was 0.9 (0.6, 1.3) in the ibuprofen group versus 0.7 (0.4, 1.1) in the ketorolac group, P-value = 0.113. The intra- and postoperative analgesic requirements were also similar in the two groups. However, patient satisfaction was slightly higher in the ketorolac group than that in the ibuprofen group (median [quartiles]: 6 [5, 7] versus 5 [4, 7], respectively), P-value: 0.009. Conclusion: The two drugs, intravenous ibuprofen and ketorolac produced similar analgesic profile in patients undergoing open abdominal hysterectomy receiving multimodal analgesic regimen. NCT05610384, Date of registration: 09/11/2022 Clinical trial registration: ClinicalTrials.gov Identifier: NCT05610384. https://clinicaltrials.gov/ct2/show/NCT05610384 [ABSTRACT FROM AUTHOR]

Background: There is a lack of quantitative studies that specifically measure the association between the experience of pregnancy and unintended pregnancy. The present study aims to address the prevalence of unintended pregnancy and identify its predictors. Additionally, the study explores whether unintended pregnancy is associated with pregnancy uplifts and hassles. Methods: This cross-sectional study was conducted on 488 pregnant women between 20 to 40 weeks' gestation at the comprehensive health center in Tabriz City from February 2022 to January 2023. A cluster sampling method was used for sampling, and data were collected using socio-demographic questionnaires and the Pregnancy Experience Scale (PES). Descriptive statistics were used to describe the socio-demographic characteristics and the prevalence of unintended pregnancy. Binary logistic regression was employed to identify the predictors of pregnancy desirability. To examine the relationship between unintended pregnancy and pregnancy experience, an independent t-test was used for bivariate analysis, and a general linear model (GLM) was utilized for multivariate analysis, with control for potential confounding variables. Results: The prevalence of unintended pregnancies was 30.7% (24.3% unwanted pregnancies, and 6.4% mistimed pregnancies). The results of the binary logistic regression indicated that the lower age of both the woman and her spouse were significant predictors for unintended pregnancy (P < 0.05). Based on an independent t-test, the mean score for uplifts in women with unintended pregnancy was significantly lower than in women with intended pregnancy (mean difference (MD): -4.99; 95% confidence interval (CI): -5.96 to -4.02; p < 0.001), While the mean score of hassles in women with unintended pregnancy was significantly higher than women with intended pregnancy (MD: 2.92; 95% CI: 2.03 to 3.80; p < 0.001). The results of GLM showed that women who had unintended pregnancies had significantly lower scores for uplifts (B = -4.99; 95% CI: -5.96 to -4.03; P < 0.001) and higher scores for hassles (B = 2.92; 95% CI: 2.06 to 3.78; P < 0.001). Conclusions: The high prevalence of unintended pregnancies in Tabriz highlights the importance of targeted interventions to address this issue, considering the policy framework and unique challenges faced by women. Future studies should focus on developing context-specific interventions that effectively meet the needs of women with unintended pregnancies. Plain Language Summary: An unintended pregnancy is a pregnancy that occurs either when the woman did not intend to get pregnant at all or when she intended to get pregnant but became pregnant at an inappropriate time. This type of pregnancy can have negative effects on the physical and mental health of women during pregnancy and after delivery. So far, no study has investigated the relationship between the experience of pregnancy and unintended pregnancy, and the existing studies, which are qualitative and based on interviews, have examined women's experiences of unintended pregnancy. For the first time, our study examined the relationship between pregnancy experience and unintended pregnancy in 488 women using a valid questionnaire, the Pregnancy Experience Scale, which includes two parts: uplifts and hassles specific to pregnancy. Our findings showed that women who have an unintended pregnancy have a worse pregnancy experience in both uplifts and hassles specific to pregnancy. Also, limited studies have investigated the prevalence of unintended pregnancy in Iran, especially in the city of Tabriz in recent years. Our study, found this prevalence to be 30.7% in Tabriz, with 24.3% of women having no intention of getting pregnant and 6.4% of women experiencing pregnancy at an inappropriate time. The recommendation is to implement strategies to reduce unintended pregnancy rates and improve women's knowledge of fertility, sexuality, and contraception. [ABSTRACT FROM AUTHOR]

Introduction: Sexual risky behaviors, as defined by the World Health Organization, encompass a spectrum of sexual activities that heighten the likelihood of negative outcomes related to sexual and reproductive health. Despite the implementation of various healthcare programs and interventions, youths continue to encounter challenges in accessing reproductive health services. Consequently, they remain vulnerable to engaging in high-risk sexual behaviors; 50.36% of adolescents in Ethiopia. Therefore, this study was aimed to determine the prevalence of risky sexual behavior and associated factors among out-of-school Youths in Addis Ababa, Ethiopia; 2023. Methods: A community based cross sectional mixed methods study was conducted among 701 youths in Addis Ababa from September 1st to 30th, 2023. The quantitative data were collected through face to face interview using a pre-tested structured questionnaire, while qualitative data were gathered through in depth interviews and focus group discussions. For the quantitative study, the study samples were chosen using systematic sampling. Conversely, purposive sampling was employed for the qualitative study. Variables with P-value ≤ 0.25 in the bivariate analysis were considered as candidates for the multivariable analysis. Statistical significance was declared at a P-value less than 0.05. Results: The prevalence of risky sexual behavior among out of school students in Addis Ababa was 40.6% (95%CI: 36.8, 44.1). Age 15–19 years (AOR: 2.52; 95%CI: 1.61, 3.94), being female (AOR: 2.84; 95%CI: 1.93, 4.18), fathers who were unable to read and write (AOR: 4.13; 95%CI: 2.04, 8.37), alcohol consumption (AOR: 2.07; 95%CI: 1.33, 3.19), peer pressure (AOR: 2.59; 95%CI: 1.81, 3.72), live together with either of biological parent (AOR: 2.32; 95%CI: 1.52, 3.55), watching pornography (AOR: 2.10; 95%CI: 1.11, 3.97) and parental monitoring (AOR: 0.59; 95%CI: 0.39, 0.90) were factors associated with risky sexual behavior. Conclusion and recommendations: A lower prevalence of risky sexual behavior compared to prior research efforts. Age, gender, educational level of the husband, alcohol consumption, peer pressure, living arrangements, exposure to pornography, and family monitoring emerged as significant factors associated with risky sexual behavior. Therefore, government should prioritize strategies to reduce substance use, mitigate the impact of watching pornography, and enhance parent-youth connectedness. [ABSTRACT FROM AUTHOR]

Background: There is a lack of quantitative studies that specifically measure the association between the experience of pregnancy and unintended pregnancy. The present study aims to address the prevalence of unintended pregnancy and identify its predictors. Additionally, the study explores whether unintended pregnancy is associated with pregnancy uplifts and hassles. Methods: This cross-sectional study was conducted on 488 pregnant women between 20 to 40 weeks' gestation at the comprehensive health center in Tabriz City from February 2022 to January 2023. A cluster sampling method was used for sampling, and data were collected using socio-demographic questionnaires and the Pregnancy Experience Scale (PES). Descriptive statistics were used to describe the socio-demographic characteristics and the prevalence of unintended pregnancy. Binary logistic regression was employed to identify the predictors of pregnancy desirability. To examine the relationship between unintended pregnancy and pregnancy experience, an independent t-test was used for bivariate analysis, and a general linear model (GLM) was utilized for multivariate analysis, with control for potential confounding variables. Results: The prevalence of unintended pregnancies was 30.7% (24.3% unwanted pregnancies, and 6.4% mistimed pregnancies). The results of the binary logistic regression indicated that the lower age of both the woman and her spouse were significant predictors for unintended pregnancy (P < 0.05). Based on an independent t-test, the mean score for uplifts in women with unintended pregnancy was significantly lower than in women with intended pregnancy (mean difference (MD): -4.99; 95% confidence interval (CI): -5.96 to -4.02; p < 0.001), While the mean score of hassles in women with unintended pregnancy was significantly higher than women with intended pregnancy (MD: 2.92; 95% CI: 2.03 to 3.80; p < 0.001). The results of GLM showed that women who had unintended pregnancies had significantly lower scores for uplifts (B = -4.99; 95% CI: -5.96 to -4.03; P < 0.001) and higher scores for hassles (B = 2.92; 95% CI: 2.06 to 3.78; P < 0.001). Conclusions: The high prevalence of unintended pregnancies in Tabriz highlights the importance of targeted interventions to address this issue, considering the policy framework and unique challenges faced by women. Future studies should focus on developing context-specific interventions that effectively meet the needs of women with unintended pregnancies. Plain Language Summary: An unintended pregnancy is a pregnancy that occurs either when the woman did not intend to get pregnant at all or when she intended to get pregnant but became pregnant at an inappropriate time. This type of pregnancy can have negative effects on the physical and mental health of women during pregnancy and after delivery. So far, no study has investigated the relationship between the experience of pregnancy and unintended pregnancy, and the existing studies, which are qualitative and based on interviews, have examined women's experiences of unintended pregnancy. For the first time, our study examined the relationship between pregnancy experience and unintended pregnancy in 488 women using a valid questionnaire, the Pregnancy Experience Scale, which includes two parts: uplifts and hassles specific to pregnancy. Our findings showed that women who have an unintended pregnancy have a worse pregnancy experience in both uplifts and hassles specific to pregnancy. Also, limited studies have investigated the prevalence of unintended pregnancy in Iran, especially in the city of Tabriz in recent years. Our study, found this prevalence to be 30.7% in Tabriz, with 24.3% of women having no intention of getting pregnant and 6.4% of women experiencing pregnancy at an inappropriate time. The recommendation is to implement strategies to reduce unintended pregnancy rates and improve women's knowledge of fertility, sexuality, and contraception. [ABSTRACT FROM AUTHOR]

Background: Immunosuppression at intensive care unit (ICU) admission has been associated with a higher incidence of ICU-acquired infections, some of them related to opportunistic pathogens. However, the association of immunosuppression with the incidence, microbiology and outcomes of ICU-acquired bacterial bloodstream infections (BSI) has not been thoroughly investigated. Methods: Retrospective single-centered cohort study in France. All adult patients hospitalized in the ICU of Lille University-affiliated hospital for > 48 h between January 1st and December 31st, 2020, were included, regardless of their immune status. Immunosuppression was defined as active cancer or hematologic malignancy, neutropenia, hematopoietic stem cell and solid organ transplants, use of steroids or immunosuppressive drugs, human immunodeficiency virus infection and genetic immune deficiency. The primary objective was to compare the 28-day cumulative incidence of ICU-acquired bacterial BSI between immunocompromised and non-immunocompromised patients. Secondary objectives were to assess the microbiology and outcomes of ICU-acquired bacterial BSI in the two groups. Results: A total of 1313 patients (66.9% males, median age 62 years) were included. Among them, 271 (20.6%) were immunocompromised at ICU admission. Severity scores at admission, the use of invasive devices and antibiotic exposure during ICU stay were comparable between groups. Both prior to and after adjustment for pre‐specified baseline confounders, the 28-day cumulative incidence of ICU-acquired bacterial BSI was not statistically different between immunocompromised and non-immunocompromised patients. The distribution of bacteria was comparable between groups, with a majority of Gram-negative bacilli (~ 64.1%). The proportion of multidrug-resistant bacteria was also similar between groups. Occurrence of ICU-acquired bacterial BSI was associated with a longer ICU length-of-stay and a longer duration of invasive mechanical ventilation, with no significant association with mortality. Immune status did not modify the association between occurrence of ICU-acquired bacterial BSI and these outcomes. Conclusion: The 28-day cumulative incidence of ICU-acquired bacterial BSI was not statistically different between patients with and without immunosuppression at ICU admission. [ABSTRACT FROM AUTHOR]

Describing the structural complexity of seabeds is of primary importance for a number of geomorphological, hydrodynamical and ecological issues. Aiming to bring a decisive insight on the long-term development of a unified view, the present study reports on a comparative multi-site analysis of high resolution topography surveys in rough nearshore environments. The nine study sites have been selected to cover a wide variety of topographical features, including rocky and coral seabeds. The topography data has been processed to separate roughness and bathymetry-related terrain features, allowing to perform a comprehensive spectral and statistical analysis of each site. A series of roughness metrics have been tested to identify the most relevant estimators of the bottom roughness at each site. The spectral analysis highlights the systematic presence of a self-affine range of variable extension and spectral slope. The standard deviation of the seabed elevation varies from 0.04 to 0.77 m. The statistical and multi-scale analysis performed on the whole set of roughness metrics allows to identify connection between metrics and therefore to propose a reduced set of relevant roughness estimators. A more general emphasis is placed on the need to properly define a unified framework when reconstructing roughness statistics and bathymetry from fine seabed topographical data. [ABSTRACT FROM AUTHOR]

Background: Job crafting is defined as a series of proactive behaviors exhibited by employees in order to balance work resources and needs, which has a significant positive impact on the nurses. It is necessary to find the core factors that influence the job crafting, as emergency nurses deal with the most complex tasks, so as to improve their job satisfaction. Objectives: To investigate the core factors of job crafting among emergency nurses. Methods: A cross-sectional design was used in the study. A total of 255 nurses were recruited from two hospitals in Zhengzhou and Shenzhen, China in December 2021. 255 nurses completed an online questionnaire. Hierarchical regression models and fsQCA models were used to explore the factors influencing job crafting among emergency nurses and helped us to identify core factors. Results: The hierarchical regression model and the fsQCA model found that the occupational benefit, psychological empowerment, and research experience were the core factors affecting their job crafting. Job involvement was not significant in the regression model, but the QCA model indicated that it needs to be combined with other factors to impact on job crafting. The QCA model uncovered seven key conditional configurations that led to high and low job crafting among emergency nurses, explaining 80.0% of the results for high job crafting and 82.6% of the results for the low job crafting, respectively. Conclusions: The results of this study provide valuable insights into the job crafting experienced by emergency nurses. Junior emergency nurses should be granted a high level of psychological empowerment without assigning them overly complex tasks, such as research tasks, as these challenges can stop their job crafting. Intermediate and senior emergency nurses, on the other hand, can be assigned research tasks coupled with high psychological empowerment to enhance their job crafting. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to analyze the factors influencing glycemic control in patients with type 2 diabetes mellitus (T2DM). Methods: Baseline data, encompassing basic information, lifestyle habits, and treatment of 305 T2DM patients from March 2021 to January 2023, were collected and analyzed using SPSS 26.0 software. Results: Univariate and multivariate logistic regression analyses identified insulin therapy (OR = 2.233; 95%Cl = 1.013–4.520; P = 0.026) and regular clinic visits (OR = 0.567; 95%Cl = 0.330–0.973; P = 0.040) as independent factors influencing glycemic control. No observed interactions between the two variables were noted. Conclusion: History of insulin therapy and regular clinic visits were significantly and independently associated with glycated hemoglobin control in T2DM patients. Tailored interventions based on individual circumstances are recommended to optimize glycemic control. [ABSTRACT FROM AUTHOR]

Objective: There is no study on the relationship between triglyceride-glucose index (TyG index) and skeletal muscle mass in middle-aged and elderly C population. Therefore, the aim of the study is to investigate the relationship between the TyG index and weight-adjusted relative skeletal muscle index (RSMI) in middle-aged and elderly C population. Methods: We retrospectively studied 947 aged ⩾40 years subjects who got a routine medical examination in the Department of Geriatrics of R Hospital from May 2021 to March 2023. The RSMI was designed to evaluate skeletal muscle mass and calculated based on lean mass of the limbs(kg)/body weight(kg) × 100%. Skeletal muscle mass reduction was defined as a RSMI of 1-2 standard deviations (SD) below of healthy adults aged 30-49 years old. Considering the quartile groups of the TyG index, the subjects were assigned to 4 groups: Q1 (less than or equal to 8.171), Q2 (from 8.172 to 8.569), Q3 (from 8.570 to 8.992), and Q4 (greater than or equal to 8.993). Results: With TyG index increased, RSMI levels significantly reduced(P <.001). Spearman's correlation analysis showed that the TyG index was negatively correlated with RSMI in males (r = −0.320) and females (r = −0.240). The TyG index was positively correlated with body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), fasting plasma glucose (FPG), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) (P <.05). Besides, binary logistic regression analysis showed that the risk of developing reduced skeletal muscle mass in the group Q4 was 2.131 (95%CI:1.118-4.064) in males; and was 2.472 (95%CI:1.581-3.867) in females compared to the Q1 group. Conclusion: TyG index was negatively correlated with relative skeletal muscle index, and a higher TyG index was associated with the development of reduced skeletal muscle mass independently of other influencing factors. Therefore, the TyG index promises to be a predictor of skeletal muscle mass loss. [ABSTRACT FROM AUTHOR]

Background: Ankle fractures are frequent, and despite numerous publications on their treatment and outcome, there is a lack of precise data on the functional results in young, healthy and physically active patients. We hypothesized that patients who underwent open reduction and internal fixation (ORIF) for simple ankle fractures would have similar function compared to a healthy control group, whereas patients with complex fractures will have significant functional deficits. Furthermore, we postulate that there is a discrepancy between the radiological and the functional outcomes. Methods: A set of specific provocation tests was developed to evaluate the postoperative possibility of weight bearing, stop-and-go activities and range of motion. In combination with three questionnaires and a radiographic evaluation, the true functional outcome and the possibility of participating in sporting activities were investigated and compared with those of an age- and sex-matched control group. Results: A significant impairment was found in unilateral and simple ankle fractures. This impairment increased in tests including stop-and-go activities in combination with load bearing and with the complexity of the fractures. Concerning the subjective outcome, there was a significant adverse effect for daily activities without any difference in preoperative or postoperative sporting activity between the groups. No difference was found in the radiological assessment. Conclusions: Both simple and complex ankle fractures treated with ORIF have a significant and long-lasting impact on functional outcome in young and active patients. The radiological result is not associated with a good functional outcome. Trial registration: BASEC-Nr. 2018 − 01124. [ABSTRACT FROM AUTHOR]

Background: There are significant geographic inequities in COVID-19 case fatality rates (CFRs), and comprehensive understanding its country-level determinants in a global perspective is necessary. This study aims to quantify the country-specific risk of COVID-19 CFR and propose tailored response strategies, including vaccination strategies, in 156 countries. Methods: Cross-temporal and cross-country variations in COVID-19 CFR was identified using extreme gradient boosting (XGBoost) including 35 factors from seven dimensions in 156 countries from 28 January, 2020 to 31 January, 2022. SHapley Additive exPlanations (SHAP) was used to further clarify the clustering of countries by the key factors driving CFR and the effect of concurrent risk factors for each country. Increases in vaccination rates was simulated to illustrate the reduction of CFR in different classes of countries. Findings: Overall COVID-19 CFRs varied across countries from 28 Jan 2020 to 31 Jan 31 2022, ranging from 68 to 6373 per 100,000 population. During the COVID-19 pandemic, the determinants of CFRs first changed from health conditions to universal health coverage, and then to a multifactorial mixed effect dominated by vaccination. In the Omicron period, countries were divided into five classes according to risk determinants. Low vaccination-driven class (70 countries) mainly distributed in sub-Saharan Africa and Latin America, and include the majority of low-income countries (95.7%) with many concurrent risk factors. Aging-driven class (26 countries) mainly distributed in high-income European countries. High disease burden-driven class (32 countries) mainly distributed in Asia and North America. Low GDP-driven class (14 countries) are scattered across continents. Simulating a 5% increase in vaccination rate resulted in CFR reductions of 31.2% and 15.0% for the low vaccination-driven class and the high disease burden-driven class, respectively, with greater CFR reductions for countries with high overall risk (SHAP value > 0.1), but only 3.1% for the ageing-driven class. Conclusions: Evidence from this study suggests that geographic inequities in COVID-19 CFR is jointly determined by key and concurrent risks, and achieving a decreasing COVID-19 CFR requires more than increasing vaccination coverage, but rather targeted intervention strategies based on country-specific risks. [ABSTRACT FROM AUTHOR]

Lower extremity injuries are prevalent in military trainees, especially in female and older trainees. Modifiable factors that lead to higher injury risk in these subgroups are not clear. The purpose of this study was to identify whether external loading variables during military‐relevant tasks differ by age and sex in U.S. Army trainees. Data was collected on 915 trainees in the first week of Basic Combat Training. Participants performed running and ruck marching (walking with 18.1 kg pack) on a treadmill, as well as double‐/single‐leg drop landings. Variables included: vertical force loading rates, vertical stiffness, first peak vertical forces, peak vertical and resultant tibial accelerations. Comparisons were made between sexes and age groups (young, ≤19 years; middle, 20–24 years; older, ≥25 years). Significant main effects of sex were found, with females showing higher vertical loading rates during ruck marching, and peak tibial accelerations during running and ruck marching (p ≤ 0.03). Males showed higher vertical stiffness during running and peak vertical tibial accelerations during drop landings (p < 0.01). A main effect of age was found for vertical loading rates during running (p = 0.03), however no significant pairwise differences were found between age groups. These findings suggest that higher external loading may contribute to higher overall injury rates in female trainees. Further, higher stiffness during running may contribute to specific injuries, such as Achilles Tendinopathy, that are more prevalent in males. The lack of differences between age groups suggests that other factors contribute more to higher injury rates in older trainees. Highlights: Female trainees showed higher lower extremity loading during running and ruck marching that may predispose them to higher rates of musculoskeletal injury during initial‐entry training.Male trainees showed higher stiffness during running, which may relate to an increased risk of specific musculoskeletal injuries that are more prevalent in males, such as Achilles tendinopathy.Overall, older trainees did not show different lower extremity loading patterns compared to younger, suggesting that these factors are not related to the increased risk for musculoskeletal injury in older trainees. [ABSTRACT FROM AUTHOR]

Background: Quality-of-life metrics are increasingly important for oncological patients alongside traditional endpoints like mortality and disease progression. Statistical tools such as Win Ratio, Win Odds, and Net Benefit prioritize clinically significant outcomes using composite endpoints. In randomized trials, Win Statistics provide fair comparisons between treatment and control groups. However, their use in observational studies is complicated by confounding variables. Propensity score (PS) matching mitigates confounding variables but may reduce the sample size, affecting the power of win statistics analyses. Alternatively, PS matching can stratify samples, preserving the sample size. This study aims to assess the long-term impact of these methods on decision making, particularly in colorectal cancer patients. Methods: A motivating example involves a cohort of patients from the ReSARCh observational study (2016–2021) with locally advanced adenocarcinoma of the rectum, situated up to 12 cm from the anal verge. These patients underwent either a watch-and-wait approach (WW) or trans-anal local excision (LE). Win statistics compared the effects of WW and LE on a composite outcome (overall survival, recurrence, presence of ostomy, and rectum excision). For matched win statistics, we used robust inference techniques proposed by Matsouaka et al. (2022), and for stratified win statistics, we applied the method proposed by Dong et al. (2018). A simulation study assessed the coverage probability of matched and stratified win statistics in balanced and unbalanced groups, calculating how often the confidence intervals included the true values of WR, NB, and WO across 1000 simulations. Results: The results suggest a better efficacy of the LE approach when considering efficacy outcomes alone (WR: 0.47 (0.01 to 1.14); NB: −0.16 (−0.34 to 0.02); and WO: 0.73 (0.5 to 1.05)). However, when QoL outcomes are included in the analyses, the estimates are closer to 1 (WR: 0.87 (0.06 to 2.06); WO: 0.93 (0.61 to 1.4)) and to 0 (NB: −0.04 (−0.25 to 0.17)), indicating a negative impact of the treatment effect of LE regarding the presence of ostomy and the excision of the rectum. Moreover, based on the simulation study, our findings underscore the superior performance of matched compared to stratified win statistics in terms of coverage probability (matched WR: 97% vs. stratified WR: 33.3% in a high-imbalance setting; matched WR: 98% vs. stratified WR: 34.4% in a medium-imbalance setting; and matched WR: 99.2% vs. stratified WR: 37.4% in a low-imbalance setting). Conclusions: In conclusion, our study sheds light on the interpretation of the results of win statistics in terms of statistical significance, providing insights into the application of pairwise comparison in observational settings, promoting its use to improve outcomes for cancer patients. [ABSTRACT FROM AUTHOR]

Simple Summary: Multiparametric MRI with radiomics features derived from T2WI and ADC maps distinguished non-tumor regions from significant cancer and predicted the Gleason score using support vector machine (SVM) and random forest (RF) classification methods with tuned hyperparameters, as well as recursive feature elimination (RFE) and the least absolute shrinkage and selection operator (LASSO) feature selection methods. Successful application of a novel approach to machine learning incorporating recursive feature elimination combined with random forest and support vector classifiers allowed stratification of Gleeson scores in clinical cohorts at a sensitivity greater than 0.91. We developed a novel machine-learning algorithm to augment the clinical diagnosis of prostate cancer utilizing first and second-order texture analysis metrics in a novel application of machine-learning radiomics analysis. We successfully discriminated between significant prostate cancers versus non-tumor regions and provided accurate prediction between Gleason score cohorts with statistical sensitivity of 0.82, 0.81 and 0.91 in three separate pathology classifications. Tumor heterogeneity and prediction of the Gleason score were quantified using two feature selection approaches and two separate classifiers with tuned hyperparameters. There was a total of 71 patients analyzed in this study. Multiparametric MRI, incorporating T2WI and ADC maps, were used to derive radiomics features. Recursive feature elimination (RFE), the least absolute shrinkage and selection operator (LASSO), and two classification approaches, incorporating a support vector machine (SVM) (with randomized search) and random forest (RF) (with grid search), were utilized to differentiate between non-tumor regions and significant cancer while also predicting the Gleason score. In T2WI images, the RFE feature selection approach combined with RF and SVM classifiers outperformed LASSO with SVM and RF classifiers. The best performance was achieved by combining LASSO and SVM into a model that used both T2WI and ADC images. This model had an area under the curve (AUC) of 0.91. Radiomic features computed from ADC and T2WI images were used to predict three groups of Gleason score using two kinds of feature selection methods (RFE and LASSO), RF and SVM classifier models with tuned hyperparameters. Using combined sequences (T2WI and ADC map images) and combined radiomics (1st and GLCM features), LASSO, with a feature selection method with RF, was able to predict G3 with the highest sensitivity at a level AUC of 0.92. To predict G3 for single sequence (T2WI images) using GLCM features, LASSO with SVM achieved the highest sensitivity with an AUC of 0.92. [ABSTRACT FROM AUTHOR]

Simple Summary: Our findings confirm the role of developmental aspects in extracranial germ cell tumors (eGCTs). Strong associations between syndromes or congenital anomalies and eGCTs may hint at the need for research to identify potential causes and mechanisms. Strong effects were observed for Swyer and Currarino syndrome. The strengths of the associations emphasize the need for further elaboration on presently discussed pathophysiological mechanisms. For other suggested risk factors such as Klinefelter, Turner, and Down syndrome, the strength of risk appears to be substantially low and may be missed because of diagnostic bias for the first two or lack of power for the latter. A number of further syndromes were identified in single cases. Most of these pertain to girls. GCTs are developmental tumors and are likely to reflect ontogenetic and teratogenetic determinants. The objective of this study was to identify syndromes with or without congenital anomalies and non-syndromic defects as potential risk factors. Patients with extracranial GCTs (eGCTs) registered in MAKEI 96/MAHO 98 between 1996 and 2017 were included. According to Teilum's holistic concept, malignant and benign teratomas were registered. We used a case–control study design with Orphanet as a reference group for syndromic defects and the Mainz birth registry (EUROCAT) for congenital anomalies at birth. Co-occurring genetic syndromes and/or congenital anomalies were assessed accordingly. Odds ratios and 95% confidence intervals were calculated and p-values for Fisher's exact test with Bonferroni correction if needed. A strong association was confirmed for Swyer (OR 338.6, 95% CI 43.7–2623.6) and Currarino syndrome (OR 34.2, 95% CI 13.2–88.6). We additionally found 16 isolated cases of eGCT with a wide range of syndromes. However, these were not found to be significantly associated following Bonferroni correction. Most of these cases pertained to girls. Regarding non-syndromic defects, no association with eGCTs could be identified. In our study, we confirmed a strong association for Swyer and Currarino syndromes with additional congenital anomalies. [ABSTRACT FROM AUTHOR]

Simple Summary: The prognosis of PCa at diagnosis is assessed by classification systems that aim to group homogenous sets of patients. However, great heterogeneity exists within these risk groups, in terms of prognostic factors and treatment options. The aim of this study was to assess the prognostic impact and predictors of adverse tumor grade in very favorable low- and intermediate-risk prostate cancer patients treated with robot-assisted radical prostatectomy at a high-volume tertiary referral center. Objectives: To assess the prognostic impact and predictors of adverse tumor grade in very favorable low- and intermediate-risk prostate cancer (PCa) patients treated with robot-assisted radical prostatectomy (RARP). Methods: Data of low- and intermediate PCa risk-class patients were retrieved from a prospectively maintained institutional database. Adverse tumor grade was defined as pathology ISUP grade group > 2. Disease progression was defined as a biochemical recurrence event and/or local recurrence and/or distant metastases. Associations were assessed by Cox's proportional hazards and logistic regression model. Results: Between January 2013 and October 2020, the study evaluated a population of 289 patients, including 178 low-risk cases (61.1%) and 111 intermediate-risk subjects (38.4%); unfavorable tumor grade was detected in 82 cases (28.4%). PCa progression, which occurred in 29 patients (10%), was independently predicted by adverse tumor grade and biopsy ISUP grade group 2, with the former showing stronger associations (hazard ratio, HR = 4.478; 95% CI: 1.840–10.895; p = 0.001) than the latter (HR = 2.336; 95% CI: 1.057–5.164; p = 0.036). Older age and biopsy ISUP grade group 2 were independent clinical predictors of adverse tumor grade, associated with larger tumors that eventually presented non-organ-confined disease. Conclusions: In a very favorable PCa patient population, adverse tumor grade was an unfavorable prognostic factor for disease progression. Active surveillance in very favorable intermediate-risk patients is still a hazard, so molecular and genetic testing of biopsy specimens is needed. [ABSTRACT FROM AUTHOR]

Simple Summary: It is generally reported that the prognostic factors for ampulla of Vater cancer include T stage, N stage, and lymphovascular invasion and subtype, and the meaning of MUC stain is controversial. This retrospective study by the authors evaluated the significance of various MUC stains in AoV cancer using single-center clinicopathological data. The results showed that MUC5AC was significant for lymph node metastasis and was furthermore valuable as a prognostic factor for predicting overall survival. If this is evaluated in addition to the hematoxylin and eosin stain, which is commonly performed in preoperative biopsy, it is expected to be a method to select groups that require more extensive LN dissection and further prevent locoregional recurrence. Introduction: Mucins play a pivotal role in epithelial carcinogenesis; however, their role remains elusive in ampulla of Vater (AoV) cancer, regardless of histological subtype. Therefore, we investigated the clinical significance of MUC1, MUC2, MUC5AC, and MUC6 expression in AoV cancer. Methods: Using samples from 68 patients with AoV cancer, we performed immunohistochemical staining for MUC1, MUC2, MUC5AC, and MUC6 using a tissue microarray. Subsequently, we analyzed their expression patterns in relation to clinicopathological parameters and patient outcomes. Results: Of the patients, 98.5% exhibited positive expression for MUC1, while MUC2, MUC5AC, and MUC6 were expressed in 44.1%, 47.1%, and 41.2% of the patients, respectively. Correlation analyses between mucin expression and clinicopathological factors revealed no significant associations, except between MUC5AC expression and N stage. Univariate analysis demonstrated significant associations between MUC5AC expression and overall survival (OS). Multivariate analysis further confirmed that MUC5AC expression was a significant predictor of OS, along with the N stage. However, MUC5AC expression was not meaningfully associated with recurrence-free survival (RFS). The patients positive for MUC5AC expression had a considerably shorter OS than those with negative expression. Conclusions: Our study provides insights into the clinical impact of mucins on AoV cancer, regardless of the histological subtype. Although MUC1 expression is universal, MUC5AC expression is a significant prognostic indicator that correlates with lymph node metastasis and poor OS. These results emphasize the possible utility of MUC5AC as a biomarker for extensive lymph node dissection and the prognostic evaluation of patients with AoV cancer. [ABSTRACT FROM AUTHOR]

Simple Summary: Oral squamous cell carcinoma is a global health concern, particularly affecting the South Asian population. The South Asian community is among Canada's largest and most rapidly expanding minority groups. This study compared the outcomes of South Asian patients with oral squamous cell carcinoma to the general population at a Canadian cancer center. In total, 697 patients who underwent surgery for oral squamous cell carcinoma between 2009 and 2022 were evaluated, with South Asian patients constituting 9% of the cohort. Despite similar tumor characteristics and treatments, South Asian patients had double the risk of cancer recurrence and significantly worse survival compared to non-South Asian patients. Understanding the association between South Asian ethnicity and outcomes in OSCC is crucial for informing public health initiatives to meet the distinctive needs of this population, thus fostering a more inclusive and supportive environment. (1) Background: To compare oncologic outcomes of South Asian (SA) patients treated for oral squamous cell carcinoma (OSCC) to the general population. (2) Methods: Adult patients who underwent surgical resection of OSCC +/− adjuvant treatment between 2009 and 2022 (N = 697) at a regional cancer centre in Canada were included. SA patients, identified using a validated method, were compared to non-SA patients. Kaplan–Meier methods were used to compare the primary outcomes, disease-specific survival (DSS) and recurrence-free survival (RFS) across baseline univariate characteristics, including betel nut consumption. Median follow-up time was 36.4 months. Cox proportional hazard models were used to identify independent predictors of survival with significance set at p < 0.05. (3) Results: SA patients (9% of cohort, N = 64) were significantly younger and had lower rates of smoking and alcohol consumption compared to non-SA patients (p < 0.05). SA patients had a two-fold higher risk of recurrence and significantly worse disease-specific survival, even after adjusting for stage and high-risk features [RFS: HR 2.01 (1.28–3.14), DSS: HR 1.79 (1.12–2.88)]. The consumption of betel nut was not associated with outcomes. (4) Conclusions: SA patients had significantly worse oncologic outcomes, even after controlling for known predictors of poor prognosis. These findings are novel and can inform personalized treatment decisions and influence public health policies when managing patients with different ethnic backgrounds. [ABSTRACT FROM AUTHOR]

Simple Summary: The aim of this study was to elucidate whether osteopenia predicts clinicopathological findings in patients with hepatocellular carcinoma. Bone mineral density was assessed using computed tomography scan images taken within 3 months before surgery. The cutoff value of osteopenia was calculated using a threshold value of 160 Hounsfield units. The overall survival of osteopenia patients was shorter than that of non-osteopenia patients, regardless of gender. Osteopenia was an independent risk factor for overall survival and recurrence-free survival. The pathological factor associated with osteopenia was microvascular portal vein invasion. Background: Osteopenia is a well-known risk factor for survival in patients with hepatocellular carcinoma; however, it is unclear whether osteopenia can apply to both genders and how osteopenia is associated with cancer progression. The aim of this study was to elucidate whether osteopenia predicts reduced survival in regression models in both genders and whether osteopenia is associated with the pathological factors associated with reduced survival. Methods: This study included 188 consecutive patients who underwent hepatectomy. Bone mineral density was assessed using computed tomography (CT) scan images taken within 3 months before surgery. Non-contrast CT scan images at the level of the 11th thoracic vertebra were used. The cutoff value of osteopenia was calculated using a threshold value of 160 Hounsfield units. Overall survival (OS) curves and recurrence-free survival (RFS) were constructed using the Kaplan–Meier method, as was a log-rank test for survival. The hazard ratio and 95% confidence interval for overall survival were calculated using Cox's proportional hazard model. Results: In the regression analysis, age predicted bone mineral density. The association in females was greater than that in males. The OS and RFS of osteopenia patients were shorter than those for non-osteopenia patients. According to univariate and multivariate analyses, osteopenia was an independent risk factor for OS and RFS. The sole pathological factor associated with osteopenia was microvascular portal vein invasion. Conclusion: Models suggest that osteopenia may predict decreased OS and RFS in patients undergoing resection of hepatocellular carcinoma due to the mechanisms mediated via microvascular portal vein invasion. [ABSTRACT FROM AUTHOR]

Simple Summary: Mutation of the SMARCB1 gene can cause one of the most aggressive and lethal cancers of early childhood and infancy, malignant rhabdoid tumor (MRT). Despite the standard multimodal therapy (resection, conventional chemotherapy, and radiotherapy), the outlook for young children with MRT is poor. For infants, the disease can also preclude the use of radiotherapy. Numerous experimental treatments explore epigenetic mechanisms, but the DNA damage response has not yet been extensively evaluated as a therapeutic approach for MRT. We report a new therapeutic strategy for SMARCB1-deficient MRTs, combining PARP1 inhibition and DNA damage induction. The observed synergy between the PEGylated PARP1 inhibitor talazoparib (PEG~TLZ) and the DNA alkylating agent temozolomide (TMZ) may lead to improved therapeutic strategies for patients with this challenging cancer. We identified a new potential biomarker of response to PEG~TLZ+TMZ, O6-methylguanine methyltransferase (MGMT), and uncovered dysregulated signaling pathways involved in the response. Additionally, we elucidated the pro-survival role of SMARCB1 loss in MRT cells. Malignant rhabdoid tumors (MRTs) are among the most aggressive and treatment-resistant malignancies affecting infants, originating in the kidney, brain, liver, and soft tissues. The 5-year event-free survival rate for these cancers is a mere 20%. In nearly all cases of MRT, the SMARCB1 gene (occasionally SMARCA4)—a pivotal component of the SWI/SNF chromatin remodeling complex—is homozygously deleted, although the precise etiology of these tumors remains unknown. While young patients with localized MRT generally show improved outcomes, especially those who are older and have early-stage disease, the overall prognosis remains poor despite optimal standard treatments. This highlights the urgent need for more effective treatment strategies. We investigated the antitumor activity of a PARP1 inhibitor (talazoparib, TLZ) combined with a DNA alkylating agent (temozolomide, TMZ) in MRT xenograft models. PARP1 is a widely targeted molecule in cancer treatment and, beyond its role in DNA repair, it participates in transcriptional regulation by recruiting chromatin remodeling complexes to modulate DNA accessibility for RNA polymerases. To widen the therapeutic window of the drug combination, we employed PEGylated TLZ (PEG~TLZ), which has been reported to reduce systemic toxicity through slow drug release. Remarkably, our findings indicate that five out of six MRT xenografts exhibited an objective response to PEG~TLZ+TMZ therapy. Significantly, the loss of SMARCB1 was found to confer a protective effect, correlating with higher expression levels of DNA damage and repair proteins in SMARCB1-deficient MRT cells. Additionally, we identified MGMT as a potential biomarker indicative of in vivo MRT response to PEG~TLZ+TMZ therapy. Moreover, our analysis revealed alterations in signaling pathways associated with the observed antitumor efficacy. This study presents a novel and efficacious therapeutic approach for MRT, along with a promising candidate biomarker for predicting tumor response. [ABSTRACT FROM AUTHOR]

Simple Summary: Telomerase reverse transcriptase promoter (TERTp) mutation is commonly observed in brain tumors and are known to contribute to the acquisition of immortality in tumors via maintaining telomere length. In this study, we aimed to investigate the prognostic impact of several known prognostic factors, including TERTp mutations, in 528 adult-type diffuse gliomas classified according to the 2021 WHO criteria. Our data showed that TERTp mutation status had a significant impact on prognosis in the combined group of glioblastoma, IDH-wildtype and astrocytoma, IDH-mutant, but was not a predictor of prognosis within any individual tumor groups. We also showed that several known clinicopathologic factors have different prognostic significance depending on the type of tumor. This supports the need for systematic tumor diagnosis based on molecular pathology classification and indicates that multiple factors, not just TERTp mutation status, should be considered in the prognosis of tumors. Mutation in the telomerase reverse transcriptase promoter (TERTp)is commonly observed in various malignancies, such as central nervous system (CNS) tumors, malignant melanoma, bladder cancer, and thyroid carcinoma. These mutations are recognized as significant poor prognostic factors for these tumors. In this investigation, a total of 528 cases of adult-type diffuse gliomas diagnosed at a single institution were reclassified according to the 2021 WHO classifications of CNS tumors, 5th edition (WHO2021). The study analyzed clinicopathological and genetic features, including TERTp mutations in each tumor. The impact of known prognostic factors on patient outcomes was analyzed through Kaplan–Meier survival and Cox regression analysis. TERTp mutations were predominantly identified in 94.1% of oligodendrogliomas (ODG), followed by 66.3% in glioblastoma, IDH-wildtype (GBM-IDHwt), and 9.2% of astrocytomas, IDH-mutant (A-IDHm). When considering A-IDHm and GBM as astrocytic tumors (Group 1) and ODGs (Group 2), TERTp mutations emerged as a significant adverse prognostic factor (p = 0.013) in Group 1. However, within each GBM-IDHwt and A-IDHm, the presence of TERTp mutations did not significantly impact patient prognosis (p = 0.215 and 0.268, respectively). Due to the high frequency of TERTp mutations in Group 2 (ODG) and their consistent prolonged survival, a statistical analysis to evaluate their impact on overall survival was deemed impractical. When considering MGMTp status, the combined TERTp-mutated and MGMTp-unmethylated group exhibited the worst prognosis in OS (p = 0.018) and PFS (p = 0.034) of GBM. This study confirmed that the classification of tumors according to the WHO2021 criteria effectively reflected prognosis. Both uni- and multivariate analyses in GBM, age, MGMTp methylation, and CDKN2A/B homozygous deletion were statistically significant prognostic factors while in univariate analysis in A-IDHm, grade 4, the Ki-67 index and MYCN amplifications were statistically significant prognostic factors. This study suggests that it is important to classify and manage tumors based on their genetic characteristics in adult-type diffuse gliomas. [ABSTRACT FROM AUTHOR]

Simple Summary: Spatial characteristics, including cell morphology and spatial distribution patterns, hold potential prognostic value in melanoma. This study builds on existing research by exploring these spatial factors through a computational pipeline, including both univariate and multivariate Cox proportional hazards models, supplemented by rigorous cross-validation techniques. Our findings reveal that spatial and morphological features can potentially enhance the prognostication of melanoma, supporting their integration into standard prognostic models. We also discuss potential limitations and outline directions for future research. In this study, the prognostic value of cellular morphology and spatial configurations in melanoma has been examined, aiming to complement traditional prognostic indicators like mitotic activity and tumor thickness. Through a computational pipeline using machine learning and deep learning methods, we quantified nuclei sizes within different spatial regions and analyzed their prognostic significance using univariate and multivariate Cox models. Nuclei sizes in the invasive band demonstrated a significant hazard ratio (HR) of 1.1 (95% CI: 1.03, 1.18). Similarly, the nuclei sizes of tumor cells and Ki67 S100 co-positive cells in the invasive band achieved HRs of 1.07 (95% CI: 1.02, 1.13) and 1.09 (95% CI: 1.04, 1.16), respectively. Our findings reveal that nuclei sizes, particularly in the invasive band, are potentially prognostic factors. Correlation analyses further demonstrated a meaningful relationship between cellular morphology and tumor progression, notably showing that nuclei size within the invasive band correlates substantially with tumor thickness. These results suggest the potential of integrating spatial and morphological analyses into melanoma prognostication. [ABSTRACT FROM AUTHOR]

Simple Summary: Different immunotherapy combinations improved prognosis for advanced non-oncogene driven NSCLC, but they were not directly compared. The aim of our study is to present the real-world data for 122 patients treated at the Institute of Oncology in Cluj-Napoca with three different consecutive immunotherapy combinations (dual immunotherapy—18 patients, dual immunotherapy plus short course chemotherapy—33 patients, mono-immunotherapy plus full course chemotherapy—71 patients). Efficacy results using different immunotherapy combination strategies were in line with those from the registration trials, with 22.2 months median overall survival and 49% actuarial 2-year survival. Results were not significantly different between the three protocols. Older age, impaired performance status, corticotherapy in the first month of immunotherapy, and >3.81 neutrophils to lymphocytes ratio were independent unfavorable prognostic factors in the multivariate survival analysis. Long-term data are available for the dual immunotherapy cohorts, with 30.5% and 18.8% of patients alive at 5 years. Purpose. Different combination modalities between an anti-PD-1/PD-L1 agent and a platinum-based chemotherapy or another checkpoint inhibitor (with or without a short course or full course of a platinum doublet) proved superior to chemotherapy alone in multiple clinical trials, but these strategies were not directly compared. The aim of this study is to report the real-world data results with different immunotherapy combinations in a series of patients treated in consecutive cohorts at the Ion Chiricuță Oncology Institute. Methods. A total of 122 patients were successively enrolled in three cohorts: (1A) nivolumab + ipilimumab (18 patients), (1B) nivolumab + ipilimumab + short-course chemotherapy (33 patients), and (2) pembrolizumab plus full-course chemotherapy (71 patients). Endpoints included overall survival (OS), progression-free survival (PFS), objective response (ORR), and univariate and multivariate exploratory analysis of prognostic factors. RESULTS. Median follow-up in the consecutive cohorts 1A, 1B, and 2 was 83 versus 59 versus 14.2 months. Median OS and PFS for all patients were 22.2 and 11.5 months, respectively, and 2-year actuarial OS and PFS were 49% and 35%, respectively. For the nivolumab + ipilimumab (cohorts 1A and 1B) versus pembrolizumab combinations (cohort 2), median OS was 14 vs. 24.8 months (p = 0.18) and 2-year actuarial survival 42% vs. 53%; median PFS was 8.6 vs. 12.7 months (p = 0.41) and 2-year actuarial PFS 34% vs. 35%; response rates were 33.3% vs. 47.9% (p = 0.22). Older age, impaired PS (2 versus 0–1), corticotherapy in the first month of immunotherapy, and >3.81 neutrophils to lymphocytes ratio were independent unfavorable prognostic factors in the multivariate analysis of survival (limited to 2 years follow-up). The 5-year long-term survival was 30.5% and 18.8% for cohorts 1A and 1B, respectively (not enough follow-up for cohort 2). Conclusions. Efficacy results using different immunotherapy combination strategies were promising and not significantly different between protocols at 2 years. Real-world efficacy and long-term results in our series were in line with those reported in the corresponding registration trials. [ABSTRACT FROM AUTHOR]

Simple Summary: Microsatellite instability (MSI) is a hallmark of colorectal cancer (CRC) that is present in 10–15% of all patients with this condition. MSI results from the inactivation of the mismatch repair (MMR) pathway in tumors due to germline MMR mutations, known as Lynch syndrome or sporadic epigenetic gene silencing, leading to an increased mutation rate and genomic instability. In this study, we assessed the utility of the polymerase chain reaction (PCR)-based molecular method as an alternative to immunohistochemistry for determining MSI status in formalin-fixed paraffin-embedded tissues and investigated the clinicopathological significance and prognostic value of MSI in CRC. We found that patients with MSI-high (i.e., high MSI) had better overall and disease-free survival than those with microsatellite stability, and this result was significant in patients with right-sided CRC. Our results demonstrate that PCR-based MSI detection may serve as a useful prognostic predictor in patients with CRC and may have clinical value in the management of these patients. Given the crucial predictive implications of microsatellite instability (MSI) in colorectal cancer (CRC), MSI screening is commonly performed in those with and at risk for CRC. Here, we compared results from immunohistochemistry (IHC) and the droplet digital PCR (ddPCR) MSI assay on formalin-fixed paraffin-embedded tumor samples from 48 patients who underwent surgery for colon and rectal cancer by calculating Cohen's kappa measurement (k), revealing high agreement between the methods (k = 0.915). We performed Kaplan–Meier survival analyses and univariate and multivariate Cox regression to assess the prognostic significance of ddPCR-based MSI and to identify clinicopathological features associated with CRC outcome. Patients with MSI-high had better overall survival (OS; p = 0.038) and disease-free survival (DFS; p = 0.049) than those with microsatellite stability (MSS). When stratified by primary tumor location, right-sided CRC patients with MSI-high showed improved DFS, relative to those with MSS (p < 0.001), but left-sided CRC patients did not. In multivariate analyses, MSI-high was associated with improved OS (hazard ratio (HR) = 0.221, 95% confidence interval (CI): 0.026–0.870, p = 0.042), whereas the loss of DNA mismatch repair protein MutL homolog 1 (MLH1) expression was associated with worse OS (HR = 0.133, 95% CI: 0.001–1.152, p = 0.049). Our results suggest ddPCR is a promising tool for MSI detection. Given the opposing effects of MSI-high and MLH1 loss on OS, both ddPCR and IHC may be complementary for the prognostic assessment of CRC. [ABSTRACT FROM AUTHOR]

Simple Summary: Juvenile nasopharyngeal angiofibroma (JNA) presents a therapeutic challenge in its advanced stages due to the close proximity to critical structures at the skull base. While radiotherapy is an effective treatment alternative, radiation-induced complications due to dose deposition in healthy tissue remain a major concern. Particle radiotherapy offers a high degree of conformality, and notably, helium ions present a promising treatment option due to their favorable biophysical characteristics between protons and carbon ions, supporting their reconsideration for clinical application. We retrospectively designed helium ion therapy (HRT) plans for all patients previously treated with proton therapy (PRT) at the Heidelberg Ion-Beam Therapy Center. Our findings indicate potential dosimetric advantages of HRT over PRT for advanced JNA, suggesting enhanced target coverage along with reduced dose deposition in healthy tissue, thereby potentially mitigating acute and late-term complications, including secondary neoplasms. This is particularly important given the benign nature of JNA and the patients' young age. Helium ion therapy (HRT) is a promising modality for the treatment of pediatric tumors and those located close to critical structures due to the favorable biophysical properties of helium ions. This in silico study aimed to explore the potential benefits of HRT in advanced juvenile nasopharyngeal angiofibroma (JNA) compared to proton therapy (PRT). We assessed 11 consecutive patients previously treated with PRT for JNA in a definitive or postoperative setting with a relative biological effectiveness (RBE) weighted dose of 45 Gy (RBE) in 25 fractions at the Heidelberg Ion-Beam Therapy Center. HRT plans were designed retrospectively for dosimetric comparisons and risk assessments of radiation-induced complications. HRT led to enhanced target coverage in all patients, along with sparing of critical organs at risk, including a reduction in the brain integral dose by approximately 27%. In terms of estimated risks of radiation-induced complications, HRT led to a reduction in ocular toxicity, cataract development, xerostomia, tinnitus, alopecia and delayed recall. Similarly, HRT led to reduced estimated risks of radiation-induced secondary neoplasms, with a mean excess absolute risk reduction of approximately 30% for secondary CNS malignancies. HRT is a promising modality for advanced JNA, with the potential for enhanced sparing of healthy tissue and thus reduced radiation-induced acute and long-term complications. [ABSTRACT FROM AUTHOR]

Simple Summary: This research investigates the challenge of drug resistance in non-small cell lung carcinoma (NSCLC) and how certain drugs, namely, tyrosine kinase inhibitors (TKIs), can induce multidrug resistance (MDR). This study aims to understand how patient-derived NSCLC cells respond to different TKIs and how genetic variations in patients may influence this response. The analysis of the efficacy of TKIs and their influence on the expression of specific markers associated with MDR shows that they elicit a different response in different NSCLC cells. Genetic alterations in signaling pathways associated with drug resistance likely contribute to the differential responses to TKIs. These findings underscore the importance of considering individual genetic profiles and performing thorough sensitivity testing to develop effective treatment strategies, particularly in the early stages of NSCLC, and highlight the potential for personalized cancer therapies. The impact of tyrosine kinase inhibitors (TKIs) on multidrug resistance (MDR) in non-small cell lung carcinoma (NSCLC) is a critical aspect of cancer therapy. While TKIs effectively target specific signaling pathways of cancer cells, they can also act as substrates for ABC transporters, potentially triggering MDR. The aim of our study was to evaluate the response of 17 patient-derived NSCLC cultures to 10 commonly prescribed TKIs and to correlate these responses with patient mutational profiles. Using an ex vivo immunofluorescence assay, we analyzed the expression of the MDR markers ABCB1, ABCC1, and ABCG2, and correlated these data with the genetic profiles of patients for a functional diagnostic approach. NSCLC cultures responded differently to TKIs, with erlotinib showing good efficacy regardless of mutation burden or EGFR status. However, the modulation of MDR mechanisms by erlotinib, such as increased ABCG2 expression, highlights the challenges associated with erlotinib treatment. Other TKIs showed limited efficacy, highlighting the variability of response in NSCLC. Genetic alterations in signaling pathways associated with drug resistance and sensitivity, including TP53 mutations, likely contributed to the variable responses to TKIs. The relationships between ABC transporter expression, gene alterations, and response to TKIs did not show consistent patterns. Our results suggest that in addition to mutational status, performing functional sensitivity screening is critical for identifying appropriate treatment strategies with TKIs. These results underscore the importance of considering drug sensitivity, off-target effects, MDR risks, and patient-specific genetic profiles when optimizing NSCLC treatment and highlight the potential for personalized approaches, especially in early stages. [ABSTRACT FROM AUTHOR]

Simple Summary: This study assessed the overall complications in 169 patients treated for extremity soft tissue sarcomas (ESTS) with a multimodal treatment involving radiotherapy and surgery. Risk factors for complications were identified, including postoperative, acute, and chronic radiotherapy-related complications, aiming to optimize treatment strategies to reduce morbidity. Multimodal treatment of ESTSs demonstrated excellent tolerance, with manageable side effects. Introduction: Soft tissue sarcomas of the extremities (ESTSs) pose significant challenges in treatment and management due to their diverse nature and potential complications. This study aimed to assess complications associated with multimodal treatments involving surgery and radiotherapy (RT) and to identify potential risk factors. Methods: We retrospectively analyzed nonmetastatic ESTS patients treated with surgery and pre- or post-operative RT between 2007 and 2020 in Strasbourg, France. Complications, including wound complications (WCs), lymphedema, acute and chronic RT-related complications, and fractures, were meticulously evaluated. Results: A total of 169 patients diagnosed with localized ESTSs were included, with a median age of 64 years (range 21–94 years). ESTSs primarily occurred proximally (74.6%) and in the lower limbs (71%). The median follow-up was 5.5 years. WCs occurred in 22.5% of patients, with proximal and lower extremity tumors being significant risk factors. Acute RT-related complications included radiodermatitis, with grade ≥ 2 occurring in 43.1% of patients, which was associated with superficial tumors. Three patients had an edema grade ≥ 2. Chronic complications included telangiectasias (21.7%) and fibrosis (38.7%), with higher rates associated with larger PTVs and higher RT doses, respectively. Fractures occurred in 5 patients, mainly in the tibia (40%). Conclusions: Multimodal treatment of ESTSs demonstrated excellent tolerance, with manageable side effects. Numerous risk factors have been highlighted, providing insights for optimizing treatment strategies and enhancing patient care in this rare disease. [ABSTRACT FROM AUTHOR]

Regions densely populated with archaeological monuments pose significant challenges for construction investors and archaeologists during the planning stages of major construction projects. Recognising the archaeological potential of these areas is crucial for planning effective rescue excavations, which have become a standard procedure in construction. This study explores the utility of non-invasive prospection techniques, including artefact field surveys, multispectral imaging, and magnetic surveys, in assessing the area chosen for the I/16 Slaný–Velvary road construction. We specifically focused on the contributions these methods make towards understanding the archaeological context of the proposed construction site. The findings from the magnetic survey were compared with the results of actual archaeological excavations. Through manual visual analysis and statistical spatial correlation, we assessed the effectiveness of the magnetic survey. The ability of magnetic survey to locate different types of archaeological objects proved to be dependent on various factors. The variability of the environmental setting, particularly pedological and geological conditions, is essential. However, the modern anthropogenic impact and the very nature of individual archaeological objects, especially their dimensions, also play an essential role. [ABSTRACT FROM AUTHOR]

The statistical significance of a clinical trial analysis result is determined by a mathematical calculation and probability based on null hypothesis significance testing. However, statistical significance does not always align with meaningful clinical effects; thus, assigning clinical relevance to statistical significance is unreasonable. A statistical result incorporating a clinically meaningful difference is a better approach to present statistical significance. Thus, the minimal clinically important difference (MCID), which requires integrating minimum clinically relevant changes from the early stages of research design, has been introduced. As a follow-up to the previous statistical round article on P values, confidence intervals, and effect sizes, in this article, we present hands-on examples of MCID and various effect sizes and discuss the terms statistical significance and clinical relevance, including cautions regarding their use. [ABSTRACT FROM AUTHOR]