bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract LB507: Towards elucidating the role of RNA modifications in cancer by improving the quantitative accuracy of mass spectrometric profiling of RNA modifications
Authors: Chiu Norman H. , Simpson Jennifer H. , Fleming Renata L. , Teng Jian , Tannous Bakhos A.
Published: June 2022

The molecular structure of both coding and non-coding RNA is frequently altered by the enzymatic activity of either writer or eraser of RNA modifications. Since the RNA functions are dependent on its molecular structure, cellular activities that involve specific RNA molecule(s) can potentially be regulated by the reversible nature of RNA modifications. There are more than 140 known RNA modifications. Mass spectrometry is a proven technique for the identification of RNA modifications. However, due to the lack of ribonucleoside standards and biases in normalizing the level of RNA modifications, it remains a challenge to perform the quantitative analysis of multiple RNA modifications that may co-exist in a biological sample. Our group has recently developed a method for standard-free quantitative epitranscriptomic profiling (SqEP) that allows us using mass spectrometry to accurately determine the abundancy of each detectable RNA modification without using any ribonucleoside standards to calibrate the detection signals. Thus, the SqEP method can be used for the untargeted analysis of RNA modifications. It also allows us to directly compare the level of different RNA modifications that are detectable in an individual cell line. This is an important feature for studying the relationships between various RNA modifications. Using glioblastoma (GBM) as our model, the results from using the SqEP method to determine the level of specific RNA modifications in patient-derived GBM cell lines were shown to be more accurate than the existing methods, and complied with the gene expression data from GBM patients that are available in the Cancer Genome Atlas (TCGA) program.

Citation Format: Norman H. Chiu, Jennifer H. Simpson, Renata L. Fleming, Jian Teng, Bakhos A. Tannous. Towards elucidating the role of RNA modifications in cancer by improving the quantitative accuracy of mass spectrometric profiling of RNA modifications [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr LB507.
Abstract LB527: A novel dimeric small molecule-radio conjugate targeting fibroblast activation protein with high and prolonged tumor uptake
Authors: Cazzamalli Samuele , Galbiati Andrea , Zana Aureliano , Bocci Matilde , Millul Jacopo , Mock Jacqueline , Elsayed Abdullah , Neri Dario
Published: June 2022

Imaging procedures based on small molecule-radio conjugates targeting Fibroblast Activation Protein (FAP) are taking the spotlight in clinical practice for the diagnosis of a wide variety of cancer lesions. However, therapeutic applications of FAP-targeting radioligand therapeutics are limited by their short residence time in tumor lesions. We have recently described the discovery of OncoFAP, a novel ultra-high affinity ligand of FAP which has been already validated for PET imaging applications in more than twenty patients with solid tumors. In this abstract, we describe the development and in vivo characterization of BiOncoFAP, a dimeric FAP targeting small molecule based on OncoFAP. In particular, OncoFAP and BiOncoFAP displayed a superimposable affinity for recombinant human FAP (KD = 970 pM and 993 pM, respectively, measured by Fluorescence Polarization). Moreover, the two ligands exhibited a clear selectivity for the target, without significantly interacting with a wide panel of non-target proteins. BiOncoFAP was coupled to a DOTAGA chelator, suitable for radiolabeling with [177Lu]Lu for therapeutic applications. Cold [natLu]Lu-BiOncoFAP-DOTAGA showed an excellent stability in both mouse and human serum, with half-life longer than 5 days, supporting in vivo investigations. In a head-to-head in vivo biodistribution comparative study against [177Lu]Lu-OncoFAP-DOTAGA, [177Lu]Lu-BiOncoFAP-DOTAGA exhibited a more stable and prolonged residence time in FAP-positive tumors implanted in immunodeficient mice (~20% ID/g and ~200-to-1 tumor-to-blood ratio, 24 h after systemic administration). Notably, [177Lu]Lu-BiOncoFAP-DOTAGA did not significantly accumulate in healthy organs, thus showing an outstanding tumor-to-organ ratio (e.g., 12-to-1 tumor-to-kidney and 34-to-1 tumor-to-liver ratio, at the 24 h time point). These findings heighten BiOncoFAP as promising candidate for the development of anti-cancer radioligand therapeutics towards FAP-expressing tumor lesions.

Citation Format: Samuele Cazzamalli, Andrea Galbiati, Aureliano Zana, Matilde Bocci, Jacopo Millul, Jacqueline Mock, Abdullah Elsayed, Dario Neri. A novel dimeric small molecule-radio conjugate targeting fibroblast activation protein with high and prolonged tumor uptake [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr LB527.
Abstract LB530: A potent and selective small molecule antagonist of PD-L1 ABSK043 demonstrates significant anti-tumor efficacy in combination with other agents in preclinical models
Authors: Ying Haiyan , Zhang Yongxian , Yang Fei , Xin Wenqun , Song Jiaqi , Chen Zhui
Published: June 2022

Immunotherapy has revolutionized cancer treatment in the last decade. Several monoclonal PD-1 and PD-L1 antibodies have been approved for various cancers. Unlike antibodies, small molecule inhibitors may offer potential advantages in oral dosing, adjustable control of drug exposure, improved tumor penetration and many other aspects. Therefore, small molecule antagonist which can efficiently abolish interaction of PD-1 and PD-L1 may render a novel alternative treatment approach with potentially improved clinical benefits. ABSK043, an oral small molecule inhibitor of PD-L1 discovered by us, has entered into clinical Phase I in 2021. Preclinically, ABSK043 has shown significant tumor growth inhibition as a single agent in multiple models. To explore potential synergy of ABSK043 with other therapeutic agents, in vivo combination experiments were conducted.

In this work, we present in vivo combination results for ABSK043 with several therapeutic agents such as a VEGFR inhibitor axitinib, or carboplatin, a key component of the widely used CRC standard-of care chemotherapy treatment regimen, as well as other immune-oncology agents. These combinations demonstrated strong in vivo synergy in tumor mouse syngeneic models. Taken together, these data for the first time demonstrated combination synergy of a small molecule PD-L1 inhibitor with other agents and pave the road for potential clinical evaluation of combination treatment of ABSK043 with these agents in patients.

Citation Format: Haiyan Ying, Yongxian Zhang, Fei Yang, Wenqun Xin, Jiaqi Song, Zhui Chen. A potent and selective small molecule antagonist of PD-L1 ABSK043 demonstrates significant anti-tumor efficacy in combination with other agents in preclinical models [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr LB530.
Abstract LB537: CDK4/6 inhibition enhances oncolytic efficacy on refractory glioblastoma by potentiating tumor-selective cell killing and T cell activation
Authors: Guo Deyin , Xing Fan , Xiao Jingshu , liang Jiaming
Published: June 2022

Glioblastoma multiforme (GBM) is the most common and aggressive malignant primary brain tumor. Although oncolytic virus (OV) therapy has been proposed as a potential approach to treat GBM, the resistance is frequently observed because GBM cells are usually nonpermissive to OV. Here, we describe a dual-step drug screen for identifying chemical enhancers of oncolytic virus in GBM. An inhibitor of the cyclin-dependent kinases 4/6 (CDK4/6) was identified as the top enhancer from 1416 FDA-approved drugs, selectively increasing potency of the two OV strains, including VSVΔ51 and Zika virus. Mechanistically, CDK4/6 inhibition promoted the autophagic degradation of MAVS, resulting in impaired antiviral responses and enhanced tumor-selective replication of VSVΔ51 in vitro and in vivo. CDK4/6 inhibition cooperated with VSVΔ51 to induce severe DNA damage stress, leading to the amplification of oncolysis. In GBM xenograft models, combination treatment of CDK4/6 inhibitor and VSVΔ51 significantly inhibited the tumor growth and prolonged the survival time of tumor-bearing mice. Further investigation revealed that CDK4/6 inhibitor and VSVΔ51 synergistically induced the immunogenic cell death and boosted the anti-tumor immunity. Together, our study features a promising approach of treating aggressive GBM through the combination of CDK4/6 inhibitor with OV.

Citation Format: Deyin Guo, Fan Xing, Jingshu Xiao, Jiaming liang. CDK4/6 inhibition enhances oncolytic efficacy on refractory glioblastoma by potentiating tumor-selective cell killing and T cell activation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr LB537.
Abstract LB542: Overexpression of the short isoform of Brd4 in ovarian carcinoma leads to highly aggressive tumor phenotype
Authors: Drumond-Bock Ana Luiza , Wang Luyao , Wang Lin , Cybula Magdalena , Rostworowska Maria , Bieniasz Magdalena
Published: June 2022

High-grade serous ovarian carcinoma (HGSOC) is one of the deadliest types of cancer in the US. Occurrence of sporadic HGSOC is associated with high genomic instability, which causes amplification and deletion of several different genes. BRD4 is one of the most frequently amplified genes in ovarian carcinoma patients. BRD4 amplification leads to overexpression of BRD4 proteins including long and short BRD4 isoforms (BRD4-L and BRD4-S, respectively), and is associated with poor patient prognosis. Recently, it has been shown that the short isoform BRD4-S contributes to oncogenic properties of several tumor types; however, little is known about its role in ovarian cancer. Therefore, in order to interrogate the function of different BRD4 isoforms in HGSOC, we generated ovarian cancer cell lines stably overexpressing BRD4 isoforms (BRD4-L and BRD-S). Our data revealed that overexpression of BRD4-S in ovarian carcinoma cell lines induces a highly aggressive tumor phenotype in vitro and in vivo. Ovcar4-BRD4-S cells showed significantly higher cell proliferation rate and increased anchorage-independent growth when compared with parental cell lines. In addition, Ovcar4-BRD4-S presents a high level of DNA damage reflected by increased pH2AX foci. We also observed a disruption of cell cycle in Ovcar4-BRD4-S cells associated with a higher number of cells arrested in G2/M phase and increased population of polyploid cells. In vivo experiments demonstrated that BRD4-S expressing tumors grow significantly faster than parental tumors. BRD4-S overexpressing tumors are also very resistant to DNA-damage agents including standard of care platinum drugs. Finally, our preliminary drug screening demonstrated that Ovcar4-BRD4-S cells are highly sensitive to Wee1 inhibitor MK-1775. Furthermore, the combination of MK-1775 with paclitaxel synergistically increased the antitumor effect. In summary, our studies indicate that amplification of the BRD4 gene in HGSOC patients might lead to an increase in splicing of BRD4-S transcript, which in consequence promotes highly aggressive and platinum-resistant tumors. Precision therapies targeting BRD4 amplified tumors, such as Wee1 inhibitors in combination with paclitaxel hold great promise to improve ovarian cancer treatment and reduce chemotherapy resistance, which is a critical problem for eradication of this aggressive tumor.

Citation Format: Ana Luiza Drumond-Bock, Luyao Wang, Lin Wang, Magdalena Cybula, Maria Rostworowska, Magdalena Bieniasz. Overexpression of the short isoform of Brd4 in ovarian carcinoma leads to highly aggressive tumor phenotype [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr LB542.
Abstract LB544: Targeting adaptive metabolic program as a novel treatment approach for TKIs-failed ALK-positive NSCLCs
Authors: Lee You Won , Choi Hun Mi , Oh Seung Yeon , Lee Eun Ji , Pyo Kyoung-Ho , Kim Jae Hwan , Byeon Youngseon , Heo Seong Gu , Lim Sun Min , Hong Min Hee , Kim Chang Gon , Kim Hye Ryun , Yun Mi Ran , Cho Byoung Chul
Published: June 2022

Introduction: Acquired resistance to ALK-tyrosine kinase inhibitors (ALK-TKIs) treatment, particularly target-off resistance, remains a clinical challenge for ALK-rearranged non-small cell lung cancer (NSCLC). To explore novel vulnerabilities of ALK TKI-resistant cancer cells, we focused on their distinct metabolic pathways for growth and survival.

Experimental Design: To investigate metabolic pathways in resistance mechanisms, we generated ALK-TKIs -acquired-resistant in vitro/vivo models. We screened metabolite mechanisms using metabolite assay kit, Seahorse Extracellular Flux Analyzer, real-time PCR, western blot, RNA-seq in resistant models.

Results: Through an integrated transcriptomic and metabolic assay screening approach, we identified the enhanced reliance on glutamine metabolism in target-off ALK-TKIs-resistant cells. Specifically, resistant cells were characterized by upregulation of glutaminase 1 (GLS1), a mitochondrial enzyme hydrolyzing glutamine into glutamate, simultaneously with downregulation of mitochondrial oxidative phosphorylation (OXPHOS). We demonstrated that this metabolic state intensively accelerates glutaminolysis and subsequent mitochondrial glutamine-derived aspartate synthesis, resulting in TKI resistance by reinforcing antioxidant capacity with increase of NADPH and glutathione. Mechanistically, GLS1 inhibition elicited a marked reduction of cell growth with increase of reactive oxygen species (ROS) in resistant cells, which was restored by supplementation of exogenous aspartate. The antitumor activity of GLS1 inhibition against resistant tumor cells was further validated in in vivo experiments, patient-derived xenograft (PDX) and EML4-ALK transgenic mice. More importantly, glutaminase inhibitor CB-839 enhanced the therapeutic efficacy of anti-PD-L1 treatment in immune checkpoint blockade (ICB)-resistant EML4-ALK transgenic mice.

Conclusion: Our findings highlight a new metabolic vulnerability of ALK-TKIs resistant tumors and provide a rationale for targeting GLS1 as a potential treatment option to overcome ALK-TKIs resistance.

Citation Format: You Won Lee, Hun Mi Choi, Seung Yeon Oh, Eun Ji Lee, Kyoung-Ho Pyo, Jae Hwan Kim, Youngseon Byeon, Seong Gu Heo, Sun Min Lim, Min Hee Hong, Chang Gon Kim, Hye Ryun Kim, Mi Ran Yun, Byoung Chul Cho. Targeting adaptive metabolic program as a novel treatment approach for TKIs-failed ALK-positive NSCLCs [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr LB544.
Abstract LB562: L1-ATP8B1 exacerbated pathogenic high-level reduction-oxidation homeostasis to promote carcinogenesis in lung squamous cell carcinoma via affecting mitochondrial prohibitin 1 SUMOylation and increasing SLC1A5 expression
Authors: Yu Jinpu , Zhang Xiao , Zhang Rui , Sun Zeguo , Zhang Weijia
Published: June 2022

Long Interspersed Nuclear Element-1 (LINE-1, L1) plays important roles in carcinogenesis by forming L1 chimeric transcripts (LCTs) in somatic cells. However, the regulation and function of LCTs in lung squamous cell carcinoma (LUSC) remains unclear. Previously we identified L1-ATP8B1 as a prognostic LCT in LUSC. In this study we confirmed that L1-ATP8B1 was overexpressed in LUSC patients suffering from shorter survival and correlated with upregulation of LINE-1 ORF1, impaired expression of ATPase phospholipid transporting 8B1 (ATP8B1) and distinct mitochondria dysfunction in both TCGA dataset and TJMUCH cohort. Over-expression of L1-ATP8B1 in LUSC cell lines and xenograft-bearing mice promoted cell proliferation, migration and invasion in vitro and facilitated LUSC xenografts growth in vivo which could be attenuated by inhibiting LINE-1 activity via nevirapine (NVR). In addition, L1-ATP8B1 affected cardiolipin-dependent mitochondrial prohibitin 1 (PHB1) SUMOylation and increased GSH synthesis transporter protein SLC1A5 expression which produced excessive ROS and GSH to induce cellular high-level reduction-oxidation (REDOX) homeostasis. Interfering with REDOX homeostasis using antioxidant could inhibit L1-ATP8B1 overexpression, reverse L1-ATP8B1-related mitochondrial dysfunction and carcinogenesis. Furthermore, combined therapy of NVR and antioxidant dramatically abolished L1-ATP8B1-induced growth and metastasis of LUSC xenografts in vivo. In conclusion, we at the first time demonstrated metabolic disorder plays a vital role in LCTs-related carcinogenesis and L1-ATP8B1 promotes LUSC development and progression by exacerbating pathogenic high-level REDOX homeostasis, therefore L1-ATP8B1 is a promising prognostic biomarker and therapeutic target in LUSC.

Citation Format: Jinpu Yu, Xiao Zhang, Rui Zhang, Zeguo Sun, Weijia Zhang. L1-ATP8B1 exacerbated pathogenic high-level reduction-oxidation homeostasis to promote carcinogenesis in lung squamous cell carcinoma via affecting mitochondrial prohibitin 1 SUMOylation and increasing SLC1A5 expression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr LB562.
Referral for Dietary Intervention in Celiac Disease Is Low among Gastroenterologists and Primary Care Providers
Authors: Venkateswaran Niranjani , Claxton Benjamin , Locke David , Baragona Allison , Lehman Erik B. , Dalessio Shannon , Clarke Kofi
Published: June 2022

Background: Strict adherence to a gluten-free diet is the only known effective treatment for celiac disease currently. Multiple organizations recommend follow-up with a dietitian and guideline-directed management after diagnosis. Few studies have evaluated follow-up post diagnosis. However, these do not include a systematic process for monitoring dietary referral among celiac disease patients. We sought to evaluate and compare the frequency of early dietary referral and guideline-directed preventive care and management for celiac disease patients managed by gastroenterologists and primary care providers. Methods: A retrospective chart review of celiac disease patients receiving care at a single tertiary care facility. Our primary outcome was to compare the frequency of dietary intervention between gastroenterologists and primary care providers in an outpatient setting after initial diagnosis. Multivariate analysis was performed to determine associated factors for referral for dietary intervention and recommended follow-up lab work. Results: 261 patients were included in the study, 81.6% were followed by gastroenterologist and only 51% were seen by a dietitian. Patients following up with gastroenterologists had higher odds of referral for dietary intervention on multivariate analysis (OR 3.29, p value <0.003). Only 16% of all patients completed appropriate guideline-directed follow-up care. Conclusions: Dietary intervention and follow-up of preventive care lab work were low in celiac disease patients. There is an opportunity for further education of both primary care providers and gastroenterologists on the importance of early dietary referral and appropriate medical management at follow-up.
Breast Cancer Patients Are at Increased Risk of Developing Uterine Serous Cancer: Implications for Counseling – A SEER Analysis
Authors: Nahshon Chen , Segev Yakir , Schmidt Meirav , Shulman Katerina , Lavie Ofer
Published: June 2022

Introduction: Several studies have investigated whether patients with prior breast cancer (BC) are at an increased risk for endometrial cancer (EC)/uterine serous cancer (USC). We aimed to study this relationship and analyze the effect of prior BC on the incidence and prognosis of USC patients. Methods: With permission of the Surveillance, Epidemiology, and End Results (SEER) program of the US National Cancer Institute, clinicopathological information of women diagnosed with BC and following USC were analyzed. The recorded data included age at diagnosis, stage of disease, cause of death, interval time between BC and USC diagnosis, and overall survival. Results: The SEER database included 10,021 patients with USC during the years 1975–2015. 698 (6.96%) of these patients had been previously diagnosed with BC. The incidence of USC in patients with BC history was 57 times higher than in women without BC history (p value <0.001). The incidence of USC did not differ between estrogen receptor (ER)-positive and ER-negative BC patients (p value 0.94). The mean survival of USC patients with previous BC history was 8 years (96 months, 95% CI: 85.7–106.2), shorter than in USC patients with no BC history, presenting a mean survival of 10.6 years (127 months, 95% CI: 124.0–130.8) (p value = 0.002). Conclusion: Our results highlight the relationship between BC and USC, suggesting an increased risk for USC among BC patients. This clinical association should be introduced to BC patients, and physicians should be alert to any EC presenting symptom in BC survivors.
Entre a dança e a arquitetura das mulheres Yawanawá: práticas espaciais indígenas na contemporaneidade
Authors: Mendo Pérez Maria Ayara
Published: June 2022

Este artigo visa observar transformações e permanências ocorridas nas práticas espaciais da população indígena Yawanawá. A intenção é pensar, junto com esse povo, caminhos que possam contribuir para o estudo das suas espacialidades e, assim, para a afirmação do saber indígena no âmbito acadêmico da arquitetura, de maneira que sejam visualizadas e reconstituídas as sabedorias e técnicas espaciais do saber-fazer ameríndio. As mulheres Yawanawá, que atualmente vivem conectadas aos fluxos econômicos e políticos de escala planetária, pensam, sonham e constroem arquiteturas contemporâneas no seu território. Elas materializam, cotidianamente, uma transgressão ao apagamento epistêmico do povo indígena, na medida em que circulam em seus corpos e ações estratégias políticas de (re)existência, de mutação e adaptação aos fluxos capitalistas, assentadas em sua cosmologia e em valores compartilhados entre si. Neste texto, trata-se de reivindicar a arquitetura contemporânea Yawanawá como locus de produção de saberes e conhecimentos de mútua implicação entre indígenas e não indígenas.
Ethical Considerations in Surgical Decompression for Stroke
Authors: Shlobin Nathan A. , Clark Jeffrey R. , Campbell Justin M. , Bernstein Mark , Jahromi Babak S. , Potts Matthew B.
Published: June 2022

Stroke is a major cause of morbidity and mortality. Neurosurgical decompression is often considered for the treatment of malignant infarcts and intraparenchymal hemorrhages, but this treatment can be frought with ethical dilemmas. In this article, the authors outline the primary principles of bioethics and their application to stroke care, provide an overview of key ethical issues and special situations in the neurosurgical management of stroke, and highlight methods to improve ethical decision-making for patients with stroke. Understanding these ethical principles is essential for stroke care teams to deliver appropriate, timely, and ethical care to patients with stroke.
Brewing Tensions: The Colonial Gaze of the German–Namibian Publishing Industry
Authors: van der Hoog Tycho Alexander
Published: June 2022

The call to decolonize African Studies has a profound influence on the field, with varying degrees of success. This article addresses this topic in relation to the author’s personal experiences in the publishing industry in Namibia. By describing the attempt to publish a historical book about Namibian beer with a well-known German–Namibian publishing house, the lingering power of German–Namibian settler colonialism becomes clear. This article renders visible the power structures within the Namibian book market that perpetuates a whitewashed version of Namibian history and argues that decolonizing knowledge cannot succeed without paying attention to the (private) publishing industry.
The Vast Space in Which the Vertical Merger Guidelines Lived
Authors: Snyder Edward A.
Published: June 2022

The thesis of this article is that the gap left by the abandoned Vertical Merger Guidelines ( VMGs) is small, and that the gap should not be filled until a sound foundation for guidelines is built. The VMGs operated with a narrow scaffolding in a vast space of real-world decisions and a continuum of organizational forms. The illustrations in the VMGs were based on pricing models that show that anticompetitive exclusion may result from vertical mergers. But these models are incapable of generalization, and they do not account for investments, market uncertainty, contracting problems, information asymmetries, and governance issues. Perplexingly, the VMGs ignored research that considers such factors and illuminates a broad range of empirically verifiable efficiencies. The requisite foundation for effective vertical guidelines is not in place. Until it is developed, replacements will fail to screen vertical mergers that do not raise concerns and will not be of assistance when mergers are challenged. Antitrust scholars could advance the foundational work by developing authoritative briefs on topics such as anticompetitive exclusion, asset-specific investments, incomplete contracts and opportunistic behavior, information asymmetries and principal–agent problems, the purposes and effects of restrictive contracts, and the implications of network economies for the scope of firms.
Poland syndrome: a new classification system based on a retrospective analysis of 74 cases
Authors: Cabrera-Gonzalez Marisa , Gutierrez-de la Iglesia Diego , Fontecha Cesar G. , G. Garcia Rocio , Ortega-Centol Aritz , Perez-Lopez Laura M.
Published: June 2022

The aim of this study was to present a classification of Poland syndrome deformities, which we hypothesized was simple, valid, reliable and useful in planning surgery. We retrospectively reviewed 74 patients with Poland syndrome treated in our centre between 1990 and 2019 (inclusive). The proposed classification comprised six types of ascending severity and was based on clinical and radiological findings. Agreement with the frequently used but more complex Catena classification was substantial (kappa 0.70), and interobserver reliability was close to perfect (kappa 0.87). The severity of the deformities according to this classification correlated well with the number of surgeries performed, except for Type 5, in which the result of surgery often is disappointing, and in Type 6, that is beyond the reach of surgical treatment. We conclude that this classification is useful in planning surgery and in advising parents on the surgical strategy.

Level of evidence

III
The Concurrent OLSA Test: A Method for Speech Recognition in Multi-talker Situations at Fixed SNR
Authors: Heeren Jan , Nuesse Theresa , Latzel Matthias , Holube Inga , Hohmann Volker , Wagener Kirsten C. , Schulte Michael
Published: June 2022

A multi-talker paradigm is introduced that uses different attentional processes to adjust speech-recognition scores with the goal of conducting measurements at high signal-to-noise ratios (SNR). The basic idea is to simulate a group conversation with three talkers. Talkers alternately speak sentences of the German matrix test OLSA. Each time a sentence begins with the name “Kerstin” (call sign), the participant is addressed and instructed to repeat the last words of all sentences from that talker, until another talker begins a sentence with “Kerstin”. The alternation of the talkers is implemented with an adjustable overlap time that causes an overlap between the call sign “Kerstin” and the target words to be repeated. Thus, the two tasks of detecting “Kerstin” and repeating target words are to be done at the same time. The paradigm was tested with 22 young normal-hearing participants (YNH) for three overlap times (0.6 s, 0.8 s, 1.0 s). Results for these overlap times show significant differences, with median target word recognition scores of 88%, 82%, and 77%, respectively (including call-sign and dual-task effects). A comparison of the dual task with the corresponding single tasks suggests that the observed effects reflect an increased cognitive load.
Long-stemmed Hemiarthroplasty with Cerclage Wiring for the Treatment of Split-Head Fractures of the Proximal Humerus with Metaphyseal Extension: A Report of 2 Cases
Authors: Panagopoulos A. , Solou K. , Kouzelis A. , Papagiannis S. , Tatani I. , Kokkalis Z. T.
Published: June 2022

Introduction

Complex fractures of the proximal humerus with splitting-head component and metaphyseal propagation are very rare injuries that are difficult to treat. Preservation of the humeral head is always considered except in cases with severe comminution and compromised vascularity where shoulder hemiarthroplasty is an alternative option.

Case Report

We present two male patients, 57- and 62-years-old who sustained such a complex proximal humeral fracture after a high-energy injury. They both managed with long-stemmed shoulder hemiarthroplasty and cerclage wiring of the metaphyseal area. They both demonstrated good clinical and radiological outcome at 32- and 24-months postoperatively.

Conclusion

We report the functional and radiological outcomes of two cases of a rare proximal humeral fracture's pattern - combination of splitting-head and metaphyseal comminution – that were managed with long-stemmed hemiarthroplasty and cerclage wire and demonstrated good midterm clinical outcome.
Conservative management of urethral prolapse in African girls: a report of 15 cases
Authors: Seck Ndeye Fatou , Ndoye Ndeye Aby , Zeng Florent Tshibwid A , Diop Mame Bounama , Cissé Lissoune , Wellé Ibrahima Bocar , Sagna Aloïse , Ngom Gabriel
Published: June 2022

Background

Urethral prolapse is a rare disease, mainly occurring in African prepubertal girls. Its etiology remains unclear; however, some risk factors have been reported. The diagnosis is made clinically. The treatment can be conservative or surgical.

Methods

We report our experience in the service of pediatric surgery at Albert Royer National Children’s Hospital Centre. We conducted a retrospective descriptive cross-sectional study, on which considered patients were managed for urethral prolapse in our service from 2014 to 2019.

Results

Our study has included 15 girls whose mean age was 4.08 years (1.17–10). Two risk factors (chronic cough and constipation) were found in 20%. Genital hemorrhage was the main symptom (73.3%), and suspicion of sexual abuse was documented in 13.3%. The clinical finding was classical (donut-shaped vulvar mass) in all patients. All patients underwent conservative management, which was successful in 73.3%. Patients with failed conservative management were treated surgically by resection of the prolapsed mucosa on a Foley catheter. No complication was reported after surgical treatment, and after a 13-month mean follow-up, no recurrence was reported in all patients.

Conclusions

Conservative management is an efficient option for urethral prolapse. It has the advantage of avoiding general anesthesia with its potential complications and restricted availability in sub-Saharan Africa. Surgical management should be reserved for failed conservative management.
Risk of selection bias assessment in the NINDS rt-PA stroke study
Authors: Garg Ravi , Mickenautsch Steffen
Published: June 2022

Objectives

The NINDS rt-PA Stroke Study is frequently cited in support of alteplase for acute ischemic stroke within 3 h of symptom onset. Multiple post-hoc reanalyses of this trial have been published to adjust for a baseline imbalance in stroke severity. We performed a risk of selection bias assessment and reanalyzed trial data to determine if the etiology of this baseline imbalance was more likely due to random chance or randomization errors.

Methods

A risk of selection bias assessment was conducted using signaling questions from the Cochrane Risk of Bias 2 (ROB 2) tool. Four sensitivity analyses were conducted on the trial data based on the randomization process: assessment of imbalances in allocation in unique strata; adherence to a pre-specified restriction on randomization between time strata at each randomization center; assessment of differences in baseline computed tomography (CT) results in unique strata; and comparison of baseline characteristics between allocation groups within each time strata. A multivariable logistic regression model was used to compare reported treatment effects with revised treatment effects after adjustment of baseline imbalances identified in the sensitivity analyses.

Results

Based on criteria from the ROB 2 tool, the risk of bias arising from the randomization process was high. Sensitivity analyses found 11 of 16 unique strata deviated from the expected 1:1 allocation ratio. Three randomization centers violated an apriori rule regarding a maximum difference in allocation between the time strata. Three unique strata had imbalances in baseline CT results that prognostically favored alteplase. Four imbalances in baseline characteristics were identified in the 91–180-min time stratum that all prognostically favored alteplase and were consistent with a larger alteplase treatment effect size compared to the 0–90-min time stratum. After adjustments for baseline imbalances, all reported treatment effects were reduced. Three out of seven originally positive reported results were revised to non-significant.

Conclusion

This risk of selection bias assessment revealed a high risk of selection bias in the NINDS rt-PA Stroke Study. Sensitivity analyses conducted based on the randomization process supported this assessment. Baseline imbalances in the trial were more likely due to randomization errors than random chance. Adjusted analyses accounting for baseline imbalances revealed a reduction in reported treatment effects supporting the presence of selection bias in the trial. Treatment decisions and guideline recommendations based on the original treatment effect reported in the NINDS rt-PA Stroke Study should be done cautiously.
The effect of HPV DNA and p16 status on the prognosis of patients with hypopharyngeal carcinoma: a meta-analysis
Authors: Shi Jinfeng , Wang Ling , Yao Nan , Sun Le , Hu Wenyu , Li Xiaotong , Yang Yixue , Wang Yusheng , Zhu Wei , Li Bo
Published: June 2022

Objective

To evaluate whether the presence of human papillomavirus (HPV) DNA and p16 might be associated with better prognosis in patients with hypopharyngeal carcinoma (HPC), especially on overall survival (OS) and disease-free survival (DFS).

Method

PubMed, the Cochrane Library, the Web of Science and EMBASE were searched from inception to April 2021 to search for HPV DNA- and p16-related prognostic articles on HPC. Meta-analysis was performed on the selected articles according to the inclusion and exclusion criteria. Publication bias was assessed for the included studies with Egger’s test. All studies were analyzed by using Stata 16.0 statistical software.

Results

A total of 18 studies were included, including 12 HPV DNA studies and 11 p16 studies. Meta-analysis showed that HPV DNA positivity was a strong prognostic factor for improved OS in patients with HPC, with a pooled hazard ratio (HR) of 0.61 (95% CI, 0.54–0.69), but there was no statistically significant difference in DFS (HR, 0.60; 95% CI, 0.31–1.16). Patients with p16-positive tumors had better OS (HR, 0.66; 95% CI, 0.49–0.89) and DFS (HR, 0.59; 95% CI, 0.44–0.78) than patients with p16-negative tumors.

Conclusions

This study suggests that the presence of HPV DNA leads to better OS in patients with HPC, and the presence of p16 also corresponds to better OS and DFS. Our results provide up-to-date evidence to clinicians and researchers. Larger studies adjusting for prognostic factors are needed in subsequent studies.
MiR-335 promotes corneal neovascularization by Targeting EGFR
Authors: Qian Jingjing , Yu Junbo , Zhu Xi , Liang Shu
Published: June 2022

Background

Corneal neovascularization (CRNV) is a severe threat to the vision of people. MicroRNA-335 (miR-335) has the function of facilitating angiogenesis. However, whether miR-335 regulates the progression of CRNV remains unclear.

Methods

The miR-335 expressions in CRNV rats induced by corneal suture and HUVECs induced by b-FGF were detected by quantitative real-time PCR. For the miR-335 function, wound healing and tube formation assays were performed. For the miR-335 mechanism, a dual-luciferase reporter gene assay was conducted. Besides, for the epidermal growth factor receptor (EGFR) function, Cell Counting Kit-8 and wound healing assays were performed. Meanwhile, the rescue assay was used to assess the miR-335/EGFR function in the migration and angiogenesis of b-FGF-treated HUVECs.

Results

Functionally, the miR-335 knockdown weakened the migration and angiogenesis of b-FGF-treated HUVECs, while the miR-335 overexpression showed an opposite trend. Mechanistically, miR-335 interacted with EGFR and negatively regulated the expression of EGFR. The rescue assay illustrated that miR-335 regulated the migration and angiogenesis of b-FGF-treated HUVECs through EGFR.

Conclusions

In general, our data confirmed that miR-335 facilitated the process of CRNV by targeting EGFR.
Radial distraction may reduce the incidence of ulnar-sided wrist pain in ulna-plus morphology intraoperatively following distal radius fractures fixation
Authors: Ma Hsuan-Hsiao , Huang Hui-Kuang , Yin Cheng-Yu , Huang Yi-Chao , Chang Ming-Chau , Wang Jung-Pan
Published: June 2022

Introduction

Fixed-angle plate fixation can be an effective treatment for distal radius fractures (DRFs). However, patients with existing ulnar positive variance might be at risk of developing symptoms of ulnar-sided wrist pain (USWP). Ulnar shortening osteotomy (USO) is one of the main treatment options for USWP. We hypothesized that a limited radial distraction at the fracture site at the time of surgery for DRF would be functionally equivalent to an indirect USO and that if this were done in a patient with an ulnar plus morphology it could potentially decrease the risk of USWP.

Methods

This retrospective study was conducted at a single institution and all the surgeries were performed by single surgeon. A total of 136 patients (92 women and 44 men) with a mean age of 55 years were enrolled with 57 patients in the distraction group (from 2014 to 2017) and 79 patients (from 2011 to 2013) in the non-distraction group. Patients were assessed USWP. Functional outcomes were assessed using the Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire, Visual Analogue Scale (VAS) for pain, grip strength, and range of motion for the wrist.

Results

The mean follow-up was 37.9 months (range, 28–61 months). The radiographs at postoperative 2-year follow-ups showed the mean ulnar positive variance was 1.3 mm (range, 1–2 mm) in the distraction group and 3.5 mm (range, 2-5 mm) in the non-distraction group. The average of the distraction length was 2.32 mm (range, 2–3 mm). At the 2-year follow-ups, USWP presented in 7% (four patients) in the distraction group, which was significantly less than the incidence of 28% (22 patients) in the non-distraction group. The distraction group exhibited significantly better DASH scores and grip strength and less subsequent ulnar-shortening osteotomy for ulnar-sided wrist pain.

Conclusions

The radial distraction procedure performed during DRFs fixation could possibly reduce the occurrence of postoperative USWP and improve the functional outcomes.

Level of evidence

Level III, Therapeutic.
Effect of the knee replacement surgery on activity level based on ActivPAL: a systematic review and meta-analysis study
Authors: Alfatafta Huda , Alfatafta Mahmoud , Onchonga David , Hammoud Sahar , Khatatbeh Haitham , Zhang Lu , Boncz Imre , Lohner Szimonetta , Molics Bálint
Published: June 2022

Background

The knee replacement (KR) surgery aims to restore the activity level and reduce the risk of experiencing disabilities. The outcomes of this surgery are evaluated mainly with subjective tools or low validity objective tools. However, the effect of the surgery on activity level using high validity objective accelerometer is still in question.

Methods

A systematic review and meta-analysis were conducted to evaluate the benefit of KR surgery alone to enhance physical activity recommendations based on high validity accelerometer. Two independent reviewers evaluated five electronic databases (Cochrane-Central-Register-of-Controlled Trials, EMBASE, PubMed, Web of Science, and Scopus) to find relative studies between January 2000 and October 2021. The quality assessments and risk of bias assessments were examined.

Results

Three articles were included with 202 participants (86 males, 116 females), with an average age of 64 years and an average 32 kg/m2 body mass index. The results found that the number of steps was significantly improved up to 36.35 and 45.5% after 6-months and 1-year of the surgery, respectively. However, these changes did not meet the recommended activity level guideline and could be related to the patients’ health status and their activity level before the surgery. No significant changes were seen in sedentary time, standing time, and upright time after 6-months and 1-year follow-ups. Heterogeneity among studies was low to moderate (0–63%).

Conclusion

Knee replacement surgery is an effective treatment for improving patients’ quality of life with severe knee injuries. However, various factors impact the success of surgical and achieving maximum benefit of the surgery. One factor, sedentary time, can be reduced by implementing pre-and post-surgery exercise or physical activity recommendations. Further studies are needed to understand the benefit of surgery with or without rehabilitation assessed using high validity monitors.
EGFR-targeted fluorescent imaging using the da Vinci® Firefly™ camera for gallbladder cancer
Authors: Choi Jung Ha , Kang Chang Moo , Park Jeong Youp
Published: June 2022

Background

Fluorescent imaging may aid with the precise diagnosis and treatment of patients with gallbladder cancer. In this study, we sought to demonstrate whether the da Vinci® surgical system and Firefly™ camera could detect EGFR-targeted fluorescent images in orthotopic mouse models of gallbladder cancer.

Methods

An orthotopic mouse model of gallbladder cancer was created by injecting NOZ gallbladder cancer cells mixed with Matrigel into the gallbladder. In vivo imaging of subcutaneous and orthotopic gallbladder tumors was performed after the injection of DyLight 650- or 800-conjugated EGFR antibody.

Results

Western blotting, flow cytometry, and confocal microscopy showed the presence of EGFR in NOZ cells, but not in HEK293 cells. Subcutaneous NOZ cell tumors fluoresced after injection with fluorescent EGFR antibody, but subcutaneous HEK293 tumors did not. Fluorescent EGFR antibody made orthotopic NOZ tumors fluoresce, with an intensity stronger than that in the surrounding normal tissues. Histochemical examination confirmed the location of the tumors inside the gallbladder and adjacent liver parenchyma. Fluorescent signal was also detected in orthotopic gallbladder tumors with Firefly™ camera.

Conclusion

Our study showed that fluorescent EGFR antibodies and the Firefly camera in the da Vinci system can detect fluorescing gallbladder tumors, which demonstrates their potential use for molecular imaging-based prevision surgery in the near future.
Effect of shifting cultivation and fallow on soil quality index in Mokokchung district, Nagaland, India
Authors: Temjen Wati , Singh Maibam Romeo , Ajungla Tali
Published: June 2022

Background

Shifting cultivation is a major agriculture practice in the Nagaland state of India. This study examines the effect of shifting cultivation and the length of the fallow period on soil quality index (SQI). Four sites were selected for the study, viz., a shifting cultivation site (SCS), a 3-year-old fallow land (FL-3), a 7-year-old fallow land (FL-7), and a 12-year-old fallow land (FL-12). Soil parameters were recorded seasonally and SQI was calculated from the minimum data set.

Results

With the increase in the fallow period, the values of conductivity, soil organic carbon, available nitrogen, available phosphorus, exchangeable potassium, moisture, clay, and cation exchange capacity of soil increased. Meanwhile, soil pH and bulk density decreased with fallow duration. The additive SQIa values were in the order SCS < FL-3 < FL-12 < FL-7; meanwhile, the weighted SQIw values were in the order SCS < FL-3 < FL-7 < FL-12. It is also observed that the SQI value decreases with the increase in soil depth under both the weighted and additive indexes. SCS with the lowest SQI value reflects the reduced soil organic carbon (SOC) and macronutrients. Increased SOC levels in site FL-12 (2.88–3.94%) may be one reason for its higher SQI value.

Conclusions

Our study highlights that unsustainable practices of shifting cultivation and reduction in the fallow period negatively affect soil quality. Furthermore, the study also recommends the use of the weighted method of SQI as it agrees with the reports of land use causing alteration in the soil quality. Our findings may be utilized to quickly access and disseminate information to the stakeholders and aid in constructing local soil quality index maps of the region. There is an urgent need for a rapid, cost and resource-efficient soil quality assessment and SQI may be one tool that achieves this goal.
Alone against the danger: a study of the routine precautions taken by voluntary sex workers to avoid victimisation
Authors: Molnar Lorena , Aebi Marcelo F.
Published: June 2022

This article explores the routine precautions taken by sex workers (SW) in Switzerland, a country in which sex work is a legal activity. It is based on approximately 1100 h of non-systematic participant observation spread over 18 months and 14 semi-structured interviews with indoor and outdoor SW. The findings show that SW use a series of routine precautions that overlap with the situational prevention techniques for increasing perpetrators’ efforts or their perception of the risk of offending, reducing the rewards of the crime, and decreasing the provocations and perpetrators’ excuses. Future tests of the efficacy of these routine precautions could help developing specific situational crime prevention techniques for deterring offences against SW.
Dispatches to the Dead: Delegation, Consumption, and Mischievous Pleasure (Thinking with Robert Pfaller in the So-called Present)
Authors: Steintrager James A. , Chow Rey
Published: June 2022

For the past twenty years or so, the Austrian cultural theorist Robert Pfaller has been positing and analyzing the concepts of “interpassivity” (as opposed to interactivity) and the delegation of enjoyment both in sacred rituals and in relation to various media of reproduction (such as video recorders and photocopiers). Steintrager and Chow argue that Pfaller's insights into delegation as a key and understudied feature of media ecologies are particularly relevant today, as delegation of various activities has intensified. However, the latest media and technologies, which gather so much information about us that we end up in a state of informational debt, pose a challenge to his thesis that delegation is an unconscious strategy for seeking relief from the onslaught of images, commodities, and information.