bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical efficacy of atezolizumab plus bevacizumab and chemotherapy inKRAS-mutated non-small cell lung cancer withSTK11,KEAP1,orTP53comutations: subgroup results from the phase III IMpower150 trial
Authors: West Howard Jack , McCleland Mark , Cappuzzo Federico , Reck Martin , Mok Tony SK , Jotte Robert M , Nishio Makoto , Kim Eugene , Morris Stefanie , Zou Wei , Shames David , Das Thakur Meghna , Shankar Geetha , Socinski Mark A 
Published: February 2022

BackgroundThe efficacy of atezolizumab (A) and/or bevacizumab (B) with carboplatin/paclitaxel (CP) chemotherapy was explored in the phase III, randomized IMpower150 study in patients with non-squamous non-small cell lung cancer (NSCLC) according toKRASmutations (mKRAS) and co-occurringSTK11,KEAP1,orTP53mutations.MethodsMutation status was determined by circulating tumor DNA next-generation sequencing. Overall survival (OS) and progression-free survival (PFS) were analyzed in a mutation-evaluable intention-to-treat population (MEP; n=920) and SP263 (programmed cell death ligand 1 (PD-L1)) biomarker-evaluable population (n=774).ResultsWithin the mKRASpopulation (24.5% of MEP), ABCP showed numerical improvements vs BCP in median OS (19.8 vs 9.9 months; HR 0.50; 95% CI 0.34 to 0.72) and PFS (8.1 vs 5.8 months; HR 0.42; 95% CI 0.29 to 0.61)—greater than with ACP (OS: 11.7 vs 9.9 months; HR 0.63; 95% CI 0.43 to 0.91; PFS: 4.8 vs 5.8 months; HR 0.80; 95% CI 0.56 to 1.13) vs BCP. Across PD-L1 subgroups in mKRASpatients, OS and PFS were longer with ABCP vs BCP, but OS with ACP was similar to BCP in PD-L1-low and PD-L1-negative subgroups. Conversely, inKRAS-WT patients, OS was longer with ACP than with ABCP or BCP across PD-L1 subgroups.KRASwas frequently comutated withSTK11,KEAP1,andTP53; these subgroups conferred different prognostic outcomes. Within the mKRASpopulation,STK11and/orKEAP1mutations were associated with inferior OS and PFS across treatments compared withSTK11-WT and/orKEAP1-WT. In mKRASpatients with co-occurring mSTK11and/or mKEAP1(44.9%) or mTP53(49.3%), survival was longer with ABCP than with ACP or BCP.ConclusionsThese analyses support previous findings of mutation ofSTK11and/orKEAP1as poor prognostic indicators. While clinical efficacy favored ABCP and ACP vs BCP in these mutational subgroups, survival benefits were greater in the mKRASandKEAP1-WT andSTK11-WT population vs mKRASand mKEAP1and mSTK11population, suggesting both prognostic and predictive effects. Overall, these results suggest that atezolizumab combined with bevacizumab and chemotherapy is an efficacious first-line treatment in metastatic NSCLC subgroups with mKRASand co-occurringSTK11and/orKEAP1orTP53mutations and/or high PD-L1 expression.
Neoantigen vaccine-induced CD4 T cells confer protective immunity in a mouse model of multiple myeloma through activation of CD8 T cells against non-vaccine, tumor-associated antigens
Authors: Bekri Selma , Rodney-Sandy Reunet , Gruenstein Diana , Mei Anna , Bogen Bjarne , Castle John , Levey Daniel , Cho Hearn Jay 
Published: February 2022

BackgroundCancer-associated neoantigens (neoAg) derived from tumor genomic sequencing and predictive algorithms for mutated peptides are a promising basis for therapeutic vaccines under investigation. Although these are generally designed to bind major histocompatibility complex class I and induce CD8 cytolytic T lymphocyte (CTL) activity, results from preclinical and clinical studies demonstrate that the majority of neoAg vaccines efficiently induce CD4 T helper (Th) responses but not CTL. Despite this, these vaccines have demonstrated clinical efficacy. Therefore, understanding the mechanisms of CD4 + T cell-mediated tumor protection is critical to optimizing this immunotherapeutic strategy.MethodsWe investigated this phenomenon in the mineral oil-induced plasmacytoma (MOPC).315.BM (MOPC315) mouse model of multiple myeloma, a malignancy of plasma cells. MOPC315 cells express in their lambda chain a unique tumor-specific neoAg, an idiotypic (Id) peptide. We generated a vaccine formulated with this Id peptide fused to a heat shock protein HSC70 binding (HSB) motif co-delivered with poly (I:C). The immunogenicity of the Id-vaccine was measured in splenocytes by ELISpot. Mice were challenged with MOPC315 cells and antitumor immunity was assessed by co-incubating splenocytes and bone marrow mononuclear cells derived from vaccinated mice and controls, with the Id antigen and irradiated MOPC315 cells. The frequency of activated CD4 and CD8 T cells and their phenotype were characterized by flow cytometry.ResultsId-vaccine efficiently induced antigen-specific CD4 Th activity and antitumor immunity, protecting mice from MOPC315 tumor growth. CD4 cytolytic activity was not detected under these conditions. Polyfunctional CD8 T cells homed to the bone marrow microenvironment of protected mice and preferentially expanded only when restimulated ex vivo with both Id peptide and MOPC315 cells. Protective activity was abrogated by depletion of either CD4 or CD8 lymphocytes.ConclusionThese results demonstrate that Id-HSB +poly (I:C) vaccine protects against MOPC315 growth by priming Id-specific CD4 Th cells that confer protection against tumor but are not directly cytotoxic. These data indicate that activation of CD8 CTL against MOPC315-associated antigens not present in the vaccine is one of the major mechanisms of tumor immunity.
Weak convergence of a collection of random functions defined by the eigenvectors of large dimensional random matrices
Authors: Silverstein Jack W. 
Published: February 2022

For each n, let [Formula: see text] be Haar distributed on the group of [Formula: see text] unitary matrices. Let [Formula: see text] denote orthogonal nonrandom unit vectors in [Formula: see text] and let [Formula: see text], [Formula: see text]. Define the following functions on [Formula: see text]: [Formula: see text], [Formula: see text], [Formula: see text]. Then it is proven that [Formula: see text], [Formula: see text], considered as random processes in [Formula: see text], converge weakly, as [Formula: see text], to [Formula: see text] independent copies of Brownian bridge. The same result holds for the [Formula: see text] processes in the real case, where [Formula: see text] is real orthogonal Haar distributed and [Formula: see text], with [Formula: see text] in [Formula: see text] and [Formula: see text] in [Formula: see text] replaced with [Formula: see text] and [Formula: see text], respectively. This latter result will be shown to hold for the matrix of eigenvectors of [Formula: see text] where [Formula: see text] is [Formula: see text] consisting of the entries of [Formula: see text], i.i.d. standardized and symmetrically distributed, with each [Formula: see text] and [Formula: see text] as [Formula: see text]. This result extends the result in [J. W. Silverstein, Ann. Probab. 18 (1990) 1174–1194]. These results are applied to the detection problem in sampling random vectors mostly made of noise and detecting whether the sample includes a nonrandom vector. The matrix [Formula: see text] is studied where [Formula: see text] is Hermitian or symmetric and nonnegative definite with either its matrix of eigenvectors being Haar distributed, or [Formula: see text], [Formula: see text] nonrandom and [Formula: see text] is a nonrandom unit vector. Results are derived on the distributional behavior of the inner product of vectors orthogonal to [Formula: see text] with the eigenvector associated with the largest eigenvalue of [Formula: see text]
Response to 1-Year Fixed-Regimen Bevacizumab Therapy in Treatment-Naïve DME Patients: Assessment by OCT Angiography
Authors: Hunt Magdalena , Teper Sławomir , Wylęgała Adam , Wylęgała Edward 
Published: February 2022

Purpose. To evaluate the effectiveness of intravitreal bevacizumab treatment in patients with diabetic macular edema (DME) by assessing retinal changes using optical coherence tomography angiography (OCT-A). Methods. This prospective study was performed in patients with treatment-naïve DME. The eyes of patients were imaged using a swept-source OCT system with a scan area of

6
×
6

mm. The DME patients with a central macular thickness (CMT) of ≥300 μm received nine bevacizumab injections within 12 months. The demographic, systemic, and ocular parameters, including the best-corrected visual acuity (BCVA), CMT, microaneurysm (MA) count, and foveal avascular zone (FAZ) area in both superficial capillary plexus (SCP) and deep capillary plexus (DCP), as well as vessel density in SCP, were assessed in the patients. In addition, the response (good or poor) of the DME eyes to bevacizumab treatment and the final visual acuity (BCVA of 75 letters) were analyzed. Results. Seventy-seven eyes of DME patients were subjected to the final analysis. Bevacizumab treatment reduced CMT from 425.06 μm (±77.15) to 350.25 μm (±82.04) and improved BCVA by about 8.61 letters (from 64.73 to 73.34) in the patients. The mean number of MAs in SCP decreased from

3.51
±
2.07

to

2.31
±
1.15

(

p
<
0.001

) and in DCP from

17.12
±
11.56

to

12.21
±
6.99

(

p
<
0.001

), whereas the area of FAZ increased in SCP from

328.22
±
131.38

to

399.70
±
156.98

(

p
<
0.001

) and in DCP from

571.13
±
396.01

to

665.89
±
412.77

(

p
=
0.001

). The final BCVA letter score and CMT were statistically significant in both poor and good responders, as well as in

BCVA
<
75

and

BCVA
≥
75

groups. Conclusion. The fixed-regimen intravitreal bevacizumab therapy was effective in treating DME. Apart from noninvasive visualization of microvascular damage, OCT-A showed limited usefulness in predicting treatment response. Although the study showed that the number of MAs was significantly reduced during treatment, which is an OCT-A predictor of a good response to bevacizumab treatment at a 12-month visit, commonly observed artifacts may reduce the usefulness of OCT-A.
Person following control for a mobile robot based on color invariance corresponding to varying illumination
Authors: Oh-hara Shinsuke , Saito Kaoru , Fujimori Atsushi 
Published: February 2022

In this paper, we present a method of person following control for a mobile robot using visual information. Color information is often used for object tracking. Color information of objects varies greatly under illumination changing environment. In such conditions , the robot controlled by visu al information may lose sight of a person. In this paper, we consider a robust person following method by color invariance and image - based control. Color invariance show s robust features of colored objects in terms of changing illumination conditions . At f irst, we estimate the lowest positions of both feet of a tracked person through particle filters based on color invariances . Then, we control the velocity of the robot to track the person by using the image - based controller. Experimental results using a n a ctual robot demonstrate the effectiveness of the proposed method.
Prevalence of Burnout Syndrome in Physical Education Teachers
Authors: Souza Bruno Macedo , Leite Daniel Massote de Melo 
Published: February 2022

The objective was to verify the prevalence of Burnout Syndrome (BS) in Physical Education teachers from state schools in the metropolitan region of Belo Horizonte/MG. This is a cross-sectional study with a quantitative approach, its sample consisted of 47 teachers, being active in schools in the urban area, having at least 1 year of teaching in their current school. For data collection we used two instruments: a sociodemographic and labor questionnaire and the "Spanish Burnout Inventory", educational version (SBI-Ed). After analyzing the studies, it is clear that this was the first time that SBI was used in this professional class in Brazil. The results showed that the Physical Education teachers of the sample had Burnout, being 12.77% with the BS Profile 1 and 6.38% having the Profile 2. As initial results obtained from this sample demonstrates the need for longitudinal and epidemiological studies on this thematic, with a larger number of participants, to understand the possible consequences of people who have BS over the years; seen as a syndrome with several stages and processes for its prevalence.
Data final do Mecanismo de Anticítera
Authors: Bandeira Beatriz 
Published: February 2022

Este artigo apresenta as investigações de Carman (2017), que demonstram a data de 5 de março de 193 A.E.C., ou um mês anomalístico antes como sendo a última vez que a manivela do Mecanismo de Anticítera foi acionada, algum tempo antes do naufrágio. Para argumentar sua proposta este pesquisador considerou duas datas - ambas correspondentes ao ano de 205 A.E.C., - já obtidas a partir dos dados analisados nos mostradores posteriores do aparato; Metônico (parte superior) e Saros (parte inferior), alguns ponteiros identificados por tomografias computadorizadas, e restos de alguns dos fragmentos para fundamentar sua investigação.
Delayed Finalization of Sodium Targets in the United States May Cost Over 250 000 Lives by 2031
Authors: Song Jing , Brown Mhairi K. , Cobb Laura K. , Jacobson Michael F. , Ide Nicole , MacGregor Graham A. , He Feng J. 
Published: February 2022

Background:
The US Food and Drug Administration (FDA) proposed 2- and 10-year voluntary sodium-reduction targets for >150 packaged- and prepared-food categories in 2016 and finalized the short-term targets in 2021.

Methods:
We modeled the health benefits of implementing the newly finalized sodium targets, and the net health losses because of the 4.3-year delay in finalizing the sodium targets in different compliance scenarios in adults aged ≥30, using the National Health and Nutrition Examination Survey (NHANES) 2015 to 2016 cycle. The health impact was estimated by multiplying the projected reduction in population sodium intake by the annual health benefits resulting from every 1000-mg reduction in daily sodium intake.

Results:
Under certain assumptions, the FDA’s finalization of the short-term targets in Oct 2021 and possible finalization of the long-term targets by April 2024 is projected to save up to 445 979 (95% CI, 17 349–787 352) lives in the coming 10 years. The net number of unnecessary deaths because of FDA’s delay is projected to be as high as 264 644 (95% CI, 10 295–467 215) according to our prediction.

Conclusions:
These findings highlight the enormous health costs due to the FDA’s delay in finalizing the sodium-reduction targets, and the great potential health benefits of industry compliance with the FDA’s finalization of its short- and long-term targets in the coming 10 years.
The experiences, perceptions, and support needs among family caregivers of patients with advanced cancer and eating problems: An integrative review
Authors: Hui-Lin Cheng , Ting Gan 
Published: February 2022

Background: Advanced cancer patients often present with numerous eating problems, posing a significant challenge for family caregivers during the provision of nutritional care. Aim: To systematically identify and synthesize empirical literature on the experiences, perceptions, and support needs of family caregivers of patients with advanced cancer and eating problems to ascertain directions for future research. Design: Integrative review guided by Whittemore and Knafl’s methodological framework. Data sources: Five electronic databases were searched from their inception to April 2021. Studies were eligible if they examined family caregivers’ perspectives and experiences when caring for their relatives with advanced cancer and eating problems and were primary quantitative, qualitative, and mixed-methods studies published in English-language peer-reviewed journals. The Mixed Methods Appraisal Tool was used to evaluate the quality of the studies. Results: Twenty-seven papers from 21 studies met the eligibility criteria and were included in this review. The included papers were mostly qualitative studies and were of moderate to high methodological quality. Three themes were identified: (a) multiple negative effects of advanced cancer patients’ eating problems; (b) coping responses in managing advanced cancer patients’ eating problems; and (c) unmet support needs in the provision of nutritional care. Conclusions: Research on the studied topic was descriptive and predominantly qualitative in nature. Quantitative research examining the impact of caregiving experiences in relation to food and eating in the context of advanced cancer patients is the first important step moving this research area forward.
Perpetration of Image-Based Sexual Abuse: Extent, Nature and Correlates in a Multi-Country Sample
Authors: Powell Anastasia , Scott Adrian J. , Flynn Asher , McCook Sarah 
Published: February 2022

Image-based sexual abuse (IBSA) is a form of technology-facilitated abuse in which intimate (nude or sexual) images of a person are taken, distributed, or threats are made to distribute the images, without a person’s consent. It is an increasingly criminalized form of sexual abuse, and yet little is known about the perpetrators of these harms, including the extent, relational nature and correlates of perpetration. This article reports on the first multi-country survey study to comprehensively investigate IBSA perpetration. An online panel survey of the general community (aged 16–64 years) in the United Kingdom (UK), Australia, and New Zealand (NZ) ( n = 6109) found that self-reported IBSA perpetration was relatively common, with one in six (17.5%, n = 1070) respondents engaging in at least one form of IBSA. Logistic regression analyses identified nine characteristics that significantly increased the odds of having engaged in IBSA perpetration during their lifetime, namely: residing in the NZ as opposed to the UK or Australia, being male, having disability/assistance needs, holding attitudes that minimize the harms and excuse the perpetrators of IBSA, engaging in online dating behaviors, engaging in sexual self-image behaviors, and experiencing IBSA victimization (images taken, images distributed, and images threatened). Policy and prevention implications of the findings, as well as directions for future research are discussed.
Retrospective Evaluation of Intrapleural Tissue Plasminogen Activator With or Without Dornase Alfa for the Treatment of Traumatic Retained Hemothorax: A 6-Year Experience
Authors: Janowak Christopher Francis , Becker Bradley Robert , Philpott Carolyn Dosen , Makley Amy Teres , Mueller Eric William , Droege Christopher Allen , Droege Molly Elizabeth 
Published: February 2022

Background: Intrapleural fibrinolytic instillation is second-line treatment for retained hemothorax. Dornase alfa (DNase) has demonstrated efficacy in parapneumonic effusion, but the lack of deoxyribonucleoproteins limits direct extrapolation to traumatic retained hemothorax treatment. Objective: This study evaluated the effectiveness of intrapleural tissue plasminogen activator (tPA) with and without DNase in the treatment of retained traumatic hemothorax. Methods: This retrospective cohort study included patients aged 16 years and older admitted to a level 1 trauma center from January 2013 through July 2019 with retained hemothorax and one or more intrapleural tPA instillations. Exclusion criteria were tPA for other indications or concomitant empyema. The primary endpoint was treatment failure defined as the need for operative intervention. Results: Fifty patients were included (tPA alone: 28; tPA with DNase: 22). Baseline characteristics were similar between groups, including time to diagnosis (6.5 [interquartile range (IQR), 4-15.5] days vs 6 [IQR, 6.3-10.8] days, P = 0.52). Median tPA dose per treatment (6 [IQR, 6-6.4] mg vs 10 [IQR, 8.4-10] mg, P < 0.001) and cumulative tPA (18 [IQR, 6.5-24] mg vs 30 [IQR, 29.5-40], P < 0.001) dose were significantly lower in the tPA alone group. Treatment failure was similar between groups. Chest tube output, retained hemothorax reduction, and bleeding incidences were similar between groups. Multivariate logistic regression demonstrated no significant risk factors for treatment failure. Conclusions and Relevance: Dornase alfa added to tPA may not reduce the need for operation to treat retained hemothorax. Further studies should be directed at optimal tPA dose determination and economic impact of inappropriate DNase use.
Association of Delayed Surgery for Ankle Fractures and Patient-Reported Outcomes
Authors: Pilskog Kristian , Gote Teresa Brnic , Odland Heid Elin Johannessen , Fjeldsgaard Knut Andreas , Dale Håvard , Inderhaug Eivind , Fevang Jonas Meling 
Published: February 2022

Background: Several studies probe the association between prolonged time to surgery and postoperative complications in ankle fractures, but little is known about how a longer wait time affects clinical outcomes. The present study aims to assess the association between time from injury to surgery and patient-reported outcomes after operative treatment of severe ankle fractures. Method: Patients treated operatively for low-energy ankle fractures that also involve the posterior malleolus from 2014 to 2016 were included. Patient charts were reviewed for patient demographics, type of trauma, fracture characteristics, treatment given, and complications. Ankle function was evaluated on a follow-up visit by clinical examination, radiographs, and patient-reported outcome measures (Self-Reported Foot and Ankle Score [SEFAS], RAND-36, visual analog scale [VAS] of Pain, VAS of Satisfaction). We compared patients treated within 1 week to those treated later than a week from injury for analyses. Results: Follow-up visits of 130 patients were performed at mean 26 (SD 9) months after surgery. Patient demographics and fracture characteristics were similar between groups. Mean SEFAS was 34 (SD 10) in patients treated later than a week from injury vs 38 (SD 9) in those treated earlier ( P = .012). Patients operated on later than 7 days from injury reported more pain ( P = .008) and lower satisfaction than those treated earlier ( P = .016). Conclusion: In this retrospective patient series of low-energy ankle fractures with posterior malleolar fragments, we found that waiting >7 days for definitive surgery was associated with poorer clinical outcomes and more pain compared with those who had surgery earlier. Level of Evidence: Level III, retrospective comparative study.
Atopy, allergen sensitization and development of hypersensitivity reactions to paclitaxel
Authors: González-Díaz Sandra Nora , Canel-Paredes Alejandra , Macías-Weinmann Alejandra , Vidal-Gutiérrez Oscar , Villarreal-González Rosalaura Virginia 
Published: February 2022

Background Paclitaxel is a chemotherapeutic agent used in the treatment of multiple types of malignant tumors which was discovered from the Taxus brevofilia tree. In some patients, anaphylaxis develops during the first exposure to paclitaxel, suggesting that primary sensitization may have occurred through hidden or unidentified allergens that produce cross-reactivity. Skin testing may be useful in identifying sensitization to these allergens. Atopy has also been reported in patients with hypersensitivity reactions (HSR) to paclitaxel. The aim of this study is to evaluate the association between atopy and sensitization to allergens with the development of immediate HSR to paclitaxel. Methods Skin prick tests (SPT) for environmental and food allergens were applied to 76 patients recently diagnosed with cancer. A SPT to paclitaxel was applied and if negative, an intradermal test was performed. After paclitaxel's infusion, the development of immediate HSR was observed. Results Of 76 skin tests, 43% of patients had allergen sensitization and 57% did not. HSR occurred in 12.1% and 11.6% of each group, respectively. Five percent of patients tested positive to paclitaxel and only one had an immediate HSR. Eighty-nine percent of patients who developed an HSR had a family or personal history of atopy. Conclusions Sensitization to environmental or food allergens does not appear to be a risk factor for the development of immediate HSR to paclitaxel, suggesting that there are other non-IgE-mediated immunologic mechanisms responsible for their development, however, a personal and family history of atopy increases 8x the risk of developing anaphylaxis.