bluuebunny/crossref_metadata_2025 huggingface dataset:
Spontaneous rupture of a mycotic splenic artery pseudoaneurysm secondary to histoplasmosis: a case report
Authors: Mirande Mitchell H. , Souza Dante L. S. , Thibodeaux Louis , Sutphin Cody
Published: June 2024

Background

A splenic artery pseudoaneurysm is a rare pathology that occurs mainly secondary to pancreatitis, abdominal trauma, peptic ulcers, pancreatic and gastric cancers, and infections. It is best diagnosed using computed tomography angiography and typically treated using endovascular embolization and, in some cases, open or laparoscopic surgery. In this report, we present a case of a ruptured mycotic splenic artery pseudoaneurysm containing Histoplasma capsulatum, which to our knowledge is the first case to report a mycotic splenic artery pseudoaneurysm of this nature.

Case presentation

We report a case of a 42-year-old white male with past medical history of Hepatitis C and IV drug abuse who presented to the Emergency Department with a 24-h history of severe diffuse abdominal pain. He was tachycardic and peritonitic on exam. Work-up demonstrated leukocytosis and lactic acidosis. Computed tomography of the abdomen and pelvis with intravenous contrast showed hemoperitoneum and active extravasation of contrast from the splenic artery into the splenic hilum, associated with a surrounding hematoma measuring 5.3 × 5.0 cm, concerning for ruptured splenic artery pseudoaneurysm. The patient was taken emergently for exploratory laparotomy, where a large intraperitoneal hematoma was evacuated. A ruptured splenic artery pseudoaneurysm was identified, isolated, and controlled, followed by completion splenectomy. Final pathology demonstrated a 3.0 × 1.3 × 0.3 cm pseudoaneurysm wall and a 14 × 9.5 × 5.5 cm spleen containing multiple necrotizing granulomata positive for the presence of Histoplasmosis species. The patient recovered appropriately and was discharged on post-operative day five.

Conclusions

This case demonstrates a successful approach to a ruptured mycotic splenic artery pseudoaneurysm resulting in a positive outcome. It is a unique case as it highlights, to our knowledge, the first report of splenic artery aneurysm secondary to Histoplasma capsulatum infection. This report helps further the understanding of the pathophysiology as well as the natural history of mycotic splenic pseudoaneurysms.
Asymmetric connectedness between conventional and Islamic cryptocurrencies: Evidence from good and bad volatility spillovers
Authors: Bouri Elie , Ghaemi Asl Mahdi , Darehshiri Sahar , Gabauer David
Published: June 2024

This paper examines the dynamics of the asymmetric volatility spillovers across four major cryptocurrencies comprising nearly 61% of cryptocurrency market capitalization and covering both conventional (Bitcoin and Ethereum) and Islamic (Stellar and Ripple) cryptocurrencies. Using a novel time-varying parameter vector autoregression (TVP-VAR) asymmetric connectedness approach combined with a high frequency (hourly) dataset ranging from 1st June 2018 to 22nd July 2022, we find that (i) good and bad spillovers are time-varying; (ii) bad volatility spillovers are more pronounced than good spillovers; (iii) a strong asymmetry in the volatility spillovers exists in the cryptocurrency market; and (iv) conventional cryptocurrencies dominate Islamic cryptocurrencies. Specifically, Ethereum is the major net transmitter of positive volatility spillovers while Stellar is the main net transmitter of negative volatility spillovers.
Column setting and text justification influence return-sweep eye movement behavior during Chinese multi-line reading
Authors: Wang Mengsi , Gill Donna E. , Judge Jeannie , Zang Chuanli , Bai Xuejun , Liversedge Simon P.
Published: June 2024

People regularly read multi-line texts in different formats and publishers, internationally, must decide how to present text to make reading most effective and efficient. Relatively few studies have examined multi-line reading, and fewer still Chinese multi-line reading. Here, we examined whether texts presented in single or double columns, and either left-justified or fully-justified affect Chinese reading. Text format had minimal influence on overall reading time; however, it significantly impacted return-sweeps (large saccades moving the eyes from the end of one line of text to the beginning of the next). Return-sweeps were launched and landed further away from margins and involved more corrective saccades in single- than double-column format. For left- compared to fully-justified format, return-sweeps were launched and landed closer to margins. More corrective saccades also occurred. Our results showed more efficient return-sweep behavior for fully- than left-justified text. Moreover, there were clear trade-off effects such that formats requiring increased numbers of shorter return-sweeps produced more accurate targeting and reduced numbers of corrective fixations, whereas formats requiring reduced numbers of longer return-sweeps caused less accurate targeting and an increased rate of corrective fixations. Overall, our results demonstrate that text formats substantially affect return-sweep eye movement behavior during Chinese reading without affecting efficiency and effectiveness, that is, the overall time it takes to read and understand the text.
Hydrogen sulfide activates calcium signaling to confer tolerance against selenium stress in Brassica rapa
Authors: Ye Xiefeng , Lu Haiyan , Xin Aijing , Liu Ruixian , Shi Zhiqi , Chen Jian , Yang Lifei
Published: June 2024

Background

Se (selenium) pollution is an emerging environmental concern. Excessive Se induces phytotoxicity. The endogenous H2S (hydrogen sulfide) was involved in plant adaptation to Se stress, but the signaling player of H2S remains unclear.

Methods

The study was conducted in a hydroponic system with different chemicals added to the treatment solution. Fluorescent tracking was performed to detect endogenous signaling molecules in plant tissues. Physiological changes were determined based on pharmaceutics and histochemical experiments. Gene expression was analyzed using qRT-PCR. The data were summarized using hierarchical cluster and Pearson correlation analysis.

Results

Se stress inhibited B. rapa growth (e.g. root elongation, shoot height, and seedling fresh weight and dry weight) in both dose- and time-dependent manners, with approximately 50% of root growth inhibition occurred at 20 µM Se. Se stress induced ROS (reactive oxygen species) accumulation and oxidative injury in B. rapa. Se exposure resulted in the upregulation of LCDs (L-cysteine desulfhydrase) and DCDs (D-cysteine desulfhydrase) encoding enzymes for H2S production in B. rapa at early stage of Se exposure, followed by downregulation of these genes at late stage. This was consistent with the change of endogenous H2S in B. rapa. Enhancing endogenous H2S level with NaHS (H2S donor) stimulates endogenous Ca2+ in B. rapa upon Se exposure, accompanied the attenuation of growth inhibition, ROS accumulation, oxidative injury, and cell death. The beneficial effects of H2S on detoxifying Se were blocked by decreasing endogenous Ca2+ level with Ca2+ channel blocker or Ca2+ chelator. Finally, hierarchical cluster combined with correlation analysis revealed that Ca2+ might acted as downstream of H2S to confer Se tolerance in B. rapa.

Conclusion

Ca2+ was an important player of H2S in the regulation of plant physiological response upon Se stress. Such findings extend our knowledge of the mechanism for Se-induced phytotoxicity.

Graphical Abstract
MR imaging features of uterine necrosis following modified B-Lynch sutures: a case report
Authors: Thakur Shruti , Jhobta Anupam , Surya Mukesh , Tomar Ashwani
Published: June 2024

Background

B-Lynch braided compression sutures are applied as a lifesaving procedure to control atonic post-partum hemorrhage if the patient is not responding to uterotonics and other conservative methods. These sutures are applied to avoid hysterectomy so as to preserve fertility. However, if not applied properly, these can lead to a rare but serious complication of uterine necrosis secondary to uterine ischemia and sepsis. The patient then ends up in hysterectomy defeating the sole purpose of maintaining fertility for which the sutures were applied at the first place.

Case presentation

Here we describe a case of primipara who had caesarian section complicated by post-partum hemorrhage which was managed with modified B-Lynch compression sutures for achieving hemostasis. The patient presented three weeks post-procedure with signs and symptoms of inflammation and sepsis. The MR imaging revealed features of uterine necrosis. The patient underwent hysterectomy unwillingly as no other option was left to save her life. A detailed MR imaging of this case has been described given the scarcity of MR features of uterine necrosis following compressive sutures in medical literature.

Conclusions

The case is reported to make the clinicians aware of the possibility of such a dreaded complication following compressive sutures for post-partum hemorrhage and to emphasize on early and timely follow-up of such patients so that uterus could be salvaged.
Anti-Müllerian hormone (ovarian reserve) in rheumatoid arthritis patients: correlation with disease activity
Authors: Israel Traez , Saleh Hala Abdulhady , Ahmed Sahar Fathi , Gergius Youssy Saeed Eshak
Published: June 2024

Background

Rheumatoid arthritis is considered one of the most common chronic inflammatory autoimmune diseases that lead to affection of several joints, as well as extra-articular organ involvement.

Rheumatoid arthritis women tend to menopause somewhat earlier. This was attributed to primary ovarian insufficiency because of autoimmune disorders. Anti-Müllerian hormone is a marker used for evaluating preantral follicle reserve. It provides a very sensitive way to reflect the ovarian reserve and has become a crucial factor in determining it.

The study aimed to show the influence of rheumatoid arthritis and its activity on ovarian reserve assessed using anti-Müllerian hormone serum levels.

Results

Our cross-sectional study involved 30 rheumatoid arthritis female patients with an age range between 25 and 35 years. The Disease Activity Score (DAS 28-ESR) was used to assess the degree of disease activity. Serum level of anti-Müllerian hormone was determined using quantitative enzyme-linked immunosorbent assay and the correlation with the disease activity as well as with the medications the patients were receiving was analyzed. A statistically significant relation was found amid the disease activity and the anti-Müllerian hormone level. Serum levels of anti-Müllerian hormone were found less in cases with high disease activity than in low to moderate cases. Different medications had no effect on anti-Müllerian hormone levels.

Conclusions

Rheumatoid arthritis high disease activity was linked to a diminished level of serum anti-Müllerian hormone.
Pure quasi-P-wave modeling and imaging using an approximated space-domain pseudo-differential operator in vertical transverse isotropy media
Authors: Qin Shanyuan , Yang Jidong , Huang Jianping , Tian Yiwei , Zhang Hao , Zhao Yang
Published: June 2024

Incorporating anisotropy in seismic modeling and imaging is important to produce the correct locations of subsurface reflectors. Traditional wave equations for quasi-P-wave in transverse isotropic media either suffer from S-wave artifacts or require complicated and expensive computation strategies. To mitigate this issue, we develop a novel pure quasi-P-wave equation with an approximated space-domain pseudo-differential operator in the vertical transverse isotropic (VTI) medium. For the pure quasi-P-wave equation, we first simplify it to an elliptical anisotropy equation with an additional pseudo-differential correction term. Then, we directly approximate the pseudo-differential term with a space-domain convolution operator that is calculated by solving a nonlinear inverse problem. Phase-velocity analysis and numerical modeling show that the new space-domain pseudo-differential operator has good accuracy in describing wave propagation in the VTI medium. In addition, it is more suitable for parallel computation with domain-decomposition than the Fourier transform, which is necessary for solving traditional pseudo-differential operators. Finally, we apply our quasi-P-wave propagator to reverse time migration to correct the anisotropic effects in seismic imaging. Numerical experiments for the benchmark models and a land survey demonstrate the feasibility and adaptability of our method.
Introduction to this special section: Subsurface uncertainty
Authors: Vyas Madhav , Lubo-Robles David , Walker Matt
Published: June 2024

Handling the nonuniqueness and ambiguity of geophysical inversion results is a major challenge in characterizing the subsurface. Geophysical inversion is the process of estimating the physical properties of the subsurface from the measured geophysical data, such as seismic, electromagnetic, gravity, or magnetic signals. However, there are often many different subsurface models that can fit the same data adequately well. Therefore, it is important to evaluate the uncertainty and reliability of the inverted models and integrate other sources of information, such as geologic, petrophysical, or geochemical data, to reduce uncertainty. Despite the industry's advances in recent decades, the number of subsurface outcomes that fall outside predicted ranges is disproportionate to the supposed certainty of those ranges. This leads to inefficient allocation of investment budgets, which is particularly painful due to the capital-intensive nature of the oil and gas industry.
Identifying imaging challenges for 1D and 3D geometric complexity (LG space)
Authors: Lau August , Gonzalez Alfonso
Published: June 2024

In some situations, it is difficult to image seismic data even when factors such as illumination, anisotropy, and attenuation are resolvable. An often-overlooked but dominant factor affecting imaging is the geometric complexity of subsurface reflectors. In some of these settings, we propose that geometric complexity plays a dominant role in the quality of seismic imaging. This has been documented in subsalt regions with poor image quality where 3D vertical seismic profiles (VSPs) are available. VSPs often demonstrate that there is good illumination below salt, but the complexity of the observed downgoing wave and diffractions cannot be simulated with smooth earth models. We use synthetic examples with high geometric complexity and no other complications to analyze the imaging process: a 2D sediment-salt model with rough salt-top topography, and a 1D model with complex reflectivity. In these models, it is difficult to estimate velocity, and it is challenging to image the data. These synthetic examples are useful to understand the limitations of imaging with smooth models, to create guidelines to identify geometric complexity in field data, and to develop possible mitigations to improve imaging. Further real data examples will be needed to test geometric complexity.
Invertible neural networks for uncertainty quantification in refraction tomography
Authors: Sun Yen , Williamson Paul
Published: June 2024

Uncertainty quantification (UQ) should be an essential ingredient of geophysical inversion because it measures the confidence in the results and enables the assessment of the value of information in the data. However, UQ using established methods ranges from very expensive to prohibitively costly, and estimating noise levels and integrating prior information is challenging, so it is not yet widely undertaken. In this paper, we explore the capabilities of a machine learning-based UQ tool known as the invertible neural network (INN) and focus on its application to a 2D tomography problem within a complex foothills environment. We propose a novel approach to handle realistic problem dimensions that uses variational autoencoders to compress the velocity model and data. The INN relates the respective latent spaces, significantly reducing memory requirements. Our findings reveal that this INN-based workflow can perform tomographic inversion while integrating an implicit prior in the form of a set of velocity models with pertinent features. Furthermore, we can address both epistemic and aleatoric uncertainties by adopting a deep ensemble strategy. This integrated approach yields plausible estimates of relative confidence in the inverted velocities, showcasing the potential of INN as a tool for UQ in geophysical inversion.
Seismic Soundoff: The secret to succeeding as a teacher
Authors: Geary Andrew
Published: June 2024

Roel Snieder discusses how to excel as a teacher (and professional) by using the Teaching with Heart practices. He discusses the importance of creating a more nurturing and loving educational environment. He also addresses the potential pitfalls of ego in teaching, the importance of seeing students as individuals with unique challenges and aspirations, and the delicate balance of maintaining professional boundaries while cultivating meaningful relationships.
Big Decisions on Small Cell Lung Cancer: A Focus on Clinical Care Updates and Patient Perspectives
Authors: Wang Xiao , Chiang Anne C.
Published: June 2024

Small cell lung cancer (SCLC) is an uncommon, aggressive high-grade neuroendocrine carcinoma, associated with tobacco use. It is a highly chemosensitive disease that initially responds quickly to systemic therapy, although patients with SCLC tend to develop relapse. Although the landscape of SCLC treatment has remained stagnant for many decades, the field has seen notable advances in the past few years, including the use of immunotherapy, the development of further lines of systemic therapy, the refinement of thoracic and intracranial radiotherapy, and—most recently—the promise of more targeted therapies. Patients with SCLC also must face unique psychosocial burdens in their experience with their cancer, distinct from patients with other lung cancer. In this article, we review the latest literature and future directions in the management and investigation of SCLC, as well as the critical decisions that providers and patients must navigate in the current landscape. We also present the perspectives of several patients with SCLC in conjunction with this summary, to spotlight their individual journeys in the context of this challenging disease.
Access for adolescents and young adults with hard-to-cure cancer to PROFYLE: The pan-Canadian precision oncology pipeline.
Authors: Abbott Lesleigh S. , Grover Stephanie , Henning Jan-Willem , Oberoi Sapna , Malkin David
Published: June 2024

10012

Background: Cancer is the most common cause of disease-related death in children, adolescents and young adults (CAYA). Approximately, 1.5% of patients with cancer in Canada are adolescents and young adults (AYAs) (age 15-29). AYAs often present with advanced disease and limited access to clinical trials including genomic testing. The PRecision Oncology For Young peopLE (PROFYLE) national, collaborative program, was created to provide equitable access to molecular profiling to identify novel targeted treatment options for CAYA with hard-to-cure cancers. The AYA node of PROFYLE aims to enhance the inclusion of AYAs across Canada at pediatric and adult centers while raising awareness of improving cancer outcomes of this underserved population. Methods: Building upon 3 pre-existing regional precision oncology programs, PROFYLE was implemented as the first pan-Canadian precision oncology pipeline. The PROFYLE study is multi-centred, non-randomized, interventional, and qualitative. Inclusion criteria: ≤29y; treatment at a Canadian center; diagnosis of a hard-to-cure cancer. It includes genomic and transcriptomic sequencing of paired germline and cancer fresh/frozen samples. Actionable findings, potential targeted therapy options including available clinical trials, clarification of diagnosis, and genetic counseling recommendations are provided to the clinical care team. Results: To date, > 1,200 CAYA are included from all provinces. Of these, 33% were AYAs. Cancer diagnoses included: 47% sarcoma, 15% leukemia/lymphoma, 13% CNS tumor, 25% other. Of the AYAs enrolled, 53% had ≥1 significant tumour profiling finding (48% specific mutations/fusions; 6% DNA repair defect signature, hypermutation, microsatellite instability, chromosomal instability; 3% predictors of therapeutic resistance; 5% outliers in gene expression). 71% had potentially useful findings (15% diagnostic; 9% prognostic; 59% therapeutic; 2% etiologic; 15% cancer predisposition; 2% secondary germline; 0.5% pharmacogenetic). 23% had a pathogenic/likely pathogenic germline variant. 60% had ≥1 potentially actionable somatic alteration. 64% of clinicians indicated that molecular findings impacted clinical management (12% diagnostic; 6% prognostic, 60% therapeutic; 16% germline genetic). 24% indicated a change in treatment planning in response to these findings. Conclusions: The goal of developing a national precision oncology pipeline that provides equitable access to molecular profiling in a clinically relevant timeframe has been realized through the establishment of PROFYLE. Findings demonstrate that the sequencing platform provided medically informative results in the majority of enrolled AYAs. The success of PROFYLE underscores the importance of the continuing efforts to increase the access to this precision oncology initiative for all AYAs with cancer in Canada.
A multi-assay liquid biopsy approach to improve detection of bone and soft tissue sarcomas.
Authors: Najjar Deena , Lui LeeAnna , Battle Lauren , Dubin Robert , Zeldin Elizabeth , Applebaum Mark A. , Hayashi Masanori , Weiser Daniel A.
Published: June 2024

10019

Background: Bone and soft tissue sarcomas are among the most common extra-cranial solid tumors of childhood, yet advances in liquid biopsies lag behind what has been achieved across adult cancers. Solid tumors that lack recurrent genetic mutations or translocations, such as bone and soft tissue sarcomas, are more difficult to detect in circulation using established assays, such as ddPCR. We have developed a pipeline to analyze cell-free DNA (cfDNA) using two molecular profiling techniques that we hypothesized would improve detection of circulating tumor DNA at diagnosis for patients with bone and soft tissue sarcomas. Methods: cfDNA was isolated from plasma of patients with osteosarcoma (OS) (n = 36) and fusion-negative rhabdomyosarcoma (FN-RMS) (n = 7) at multiple timepoints. Methods for detecting tumor DNA in cfDNA included ultra-low coverage whole genome sequencing (ULC-WGS, 0.5x) and ultra-deep targeted sequencing (UDP, ~1000x) using a panel of 11 and 22 tumor-associated genes for OS and FN-RMS, respectively. ULC-WGS data underwent ichorCNA analysis to define percent tumor content of each sample. UDP analysis identified somatic variants through variant callers, Mutect2, Lancet, strelka, and DELLY2, with ClinVar to annotate and define tumor-specific variants in each sample. Combining ULC-WGS and UDP data, an integrated tumor score was developed and assessed in diagnostic samples. Results: 136 OS and 30 FN-RMS cfDNA samples were collected during the patients’ disease courses. Circulating tumor material was detected in 18/23 (78%) OS and7/7 (100%) FN-RMS samples at diagnosis. The most frequent copy number aberrations were seen in the region of chromosome 8q containing the cMYC gene. cMYC amplification was found in 11/23 (48%) of diagnostic OS samples and 2/7 (29%) of diagnostic FN-RMS samples. UDP analysis identified variants in 17/23 (73%) and 7/7 (100%) of diagnostic OS and FN-RMS samples respectively. The most commonly detected variants included TP53, BRCA2, MET, and BRAF. Of the 23 diagnostic OS samples, four had TP53 translocations. The integrated tumor score detected the presence of tumor associated material within diagnostic samples with a sensitivity of 25/30 (83%), compared to the sensitivity of ULC-WGS or UDP alone, which was 15/30 (50%) and 24/30 (80%) respectively. Conclusions: A multi-assay liquid biopsy has promise to improve disease detection and monitoring for patients with solid tumors that lack recurrent driver mutations. We plan to integrate additional molecular profiling technologies to improve the sensitivity and specificity of our cfDNA assays and aim to adapt our pipeline across additional cancers.
Phase I dose escalation and pharmacokinetics clinical trial of mitoxantrone hydrochloride liposome in children with relapsed and refractory solid tumors.
Authors: Huang Junting , Ji Mingqing , Li Hui , Wu Yanpeng , Cai Ruiqing , Wang Juan , Lu Suying , Zhu Jia , Sun Feifei , Zhen Zijun , Zhang Yizhuo
Published: June 2024

10047

Background: Compared with solvent-based mitoxantrone, mitoxantrone hydrochloride liposome has been found to reduce bone marrow toxicity. This open-label, muti-center, single-arm phase I clinical trial aims to evaluate the safety and efficacy of mitoxantrone hydrochloride liposome in pediatric with solid tumors. Methods: The study was divided into Phase Ia and Ib. Phase Ia was the dose escalation study, with a "3+3" design. Patients received mitoxantrone hydrochloride liposome at three dose levels (16 mg/m2, 20mg/m2, 24mg/m2, d1) in combination with irinotecan (50mg/m2, d1-5) and vincristine (1.5mg/m2, d1) every 3 weeks. Pharmacokinetic studies were conducted simultaneously. The primary endpoint of Phase Ia was the maximum tolerated dose (MTD). In phase Ib, patients received the combination therapy of mitoxantrone hydrochloride liposome at the MTD dose. The primary endpoint of Phase Ib was the incidence and severity of hematological adverse events. Secondary endpoints in both phases included objective response rate (ORR), pharmacokinetic (PK) parameters, and others. Results: From October 2022 to January 2024, a total of 51 pediatric patients with relapsed and refractory solid tumors were enrolled, 28 patients in Phase Ia and 23 patients in Phase Ib. The median age was 10.0 years (range: 3, 21). All Patients could be evaluated for toxicity and 40 for efficacy. The MTD of mitoxantrone hydrochloride liposome was determined to be 24mg/m2. The results of pharmacokinetic analysis were not returned. Highest incidence of hematological and non-hematological adverse events (AEs) were anaemia (88.2%), diarrhea (84.3%). The newly found or aggravated TnIUtra, BNP value abnormality and lower LV function after medication were 4 (11.8%), 5 (14.3%) and 0 (0.0%), respectively. The overall ORR and DCR were 50.0% (95% CI: 33.8% - 66.2%) and 90.0% (95% CI: 76.3% -97.2%). 13 patients (25.0%) treated with mitoxantrone hydrochloride liposome combination regimen received the opportunity of surgery. Conclusions: The mitoxantrone hydrochloride liposome combination regimen has demonstrated an acceptable toxicity profile and promising clinical efficacy in pediatric patients with solid tumors, especially in sarcomas. Clinical trial information: NCT05620862 .
Central pathological review and molecular classification of medulloblastoma in countries with limited resources: A commitment to equitable access.
Authors: Epelman Sidnei , Carvalho Filho Neviçolino Pereira de , Purificação Filho Antonio Fernando da , Souza Filho Ronaldo Modesto de , Oliveira Renato de Paula Guedes de , Vieira Ana Glenda Santarosa , Rehder Roberta , Opazo Carlos Eduardo
Published: June 2024

10062

Background: Medulloblastoma, the most common malignant pediatric brain tumor, exhibits molecular heterogeneity influencing prognosis and treatment decisions. This study focuses on feasibility the pathological review and molecular classification with cost-effective methods. Methods: From December 2018 to November 2023, we analysed samples of patients referred to our laboratory. Data were collected on patient demographics (age, gender, origin), pathological review and specific medulloblastoma subtypes identified. The study was performed without costs for parents or institutions. Results: During the study period, 146 patients were included. The predominant age groups being 0 to 4 years (20.1%) and 5 to 9 years (36.1%) The mean age was 10.2 years. 55.6% of patients were female and 43.8% were male. Ninety-three patients were from Brazil and 7% from Latin America. Of the 117 samples that could be analyzed, 43% was classified as group 4, 37% were sonic hedgehog (SHH) group, 10% were group 3 and 4% were WNT group. Five percent of the samples had inconclusive results, with two patients had diagnoses other than medulloblastoma. Seventy percent of samples had a turnaround time for molecular classification results around 30 days. Conclusions: This study highlights the importance of central review pathology and molecular classification in medulloblastoma management. Our results emphasize the feasibility of centralized pathology review and molecular classification in countries with limited resources and provide equity for all patients. Based on this experience, we have expanded for other brain and pediatric tumors. Our effort contributes to ensuring that every patient benefits from the advancements in personalized medicine and this represents a real step to offer the same chances of cure for everyone.
The dose-response relationship between cumulative alkylating agent exposure and sperm concentration in adult survivors of childhood cancer: A report from the St. Jude Lifetime (SJLIFE) cohort study.
Authors: Green Daniel M. , Li Kendrick , Ke Raymond W. , Delaney Angela , Yu Christine , Xie Lu , Srivastava Deokumar , Kutteh Wiliam H , Ware Megan Elizabeth , Shelton Kyla C. , Taneja Siddhant , Ness Kirsten K. , Lucas John Thomas , Armstrong Gregory T. , Robison Leslie L. , Hudson Melissa M.
Published: June 2024

10066

Background: Male survivors of childhood cancer treated with alkylating agents (AA) are at risk for azoospermia; however, the long-term dose-response relationship is unknown. Methods: Of the 685 male SJLIFE participants treated with AA but no radiation therapy, 387 (56.5%) provided an evaluable semen sample (mean age at diagnosis: 8.3 years, mean age at evaluation: 28.6 years, and mean years from diagnosis to evaluation: 20.3 years). 73 had one or more subsequent semen analyses (median interval between semen analyses 5.4 years; interquartile range 4.2 – 6.6 years). Survivors were categorized as azoospermia, oligospermia (sperm concentration > 0 and < 15 million/ml), or normospermia (sperm concentration ≥ 15 million/ml). AA exposure was estimated using the cyclophosphamide equivalent dose (CED). Risks were estimated using the odds ratio (OR) and 95% confidence intervals (CI) from multinomial logistic regression analyses. Results: Among survivors 22.5% had azoospermia, 26.6% oligospermia, and 50.9% normospermia (Table). Motility and progressive motility were not associated with increasing CED categories among normospermic or oligospermic participants. Multinomial logistic regression including CED, age at diagnosis and at follow-up demonstrated that, for each 1,000 mg/m2 increase in CED, the odds of azoospermia increased by 1.14 (95% CI 1.09, 1.20), and the odds of azoospermia and oligospermia increased by 1.22 (95% CI, 1.14, 1.30). Azoospermia and oligospermia were best distinguished from normospermia using a CED cutoff of 7,000 mg/m2 based on the Youden Index. Nearly all participants initially identified with azoospermia (24 out of 25) maintained this diagnosis upon later evaluation. Conclusions: Nearly half of adult childhood cancer survivors who received alkylating agents without radiation therapy experience impaired sperm production, either low sperm count (oligospermia) or no sperm at all (azoospermia). The association increases with increasing CED. Recovery of spermatogenesis is unlikely among those who present azoospermic. CED = 7,000 mg/m2 is the optimal cutoff for differentiating risk for oligo- or azoospermia from normospermia. [Table: see text]
AMH levels after initial cycles of chemotherapy in female adolescents with Ewing sarcoma and implications for preservation of fertility.
Authors: Xu Jie , Sun Xin , Liu Kuisheng , Xie Lu , Shi Jingtian , Tang Xiaodong
Published: June 2024

10067

Background: Anti-Müllerian hormone (AMH) has been recommended as the primary surveillance modality for evaluation of ovarian insufficiency in females. Patients with Ewing sarcoma receive VDC-IE chemotherapy which is estimated high risk of gonadotoxic injury. Previous studies have shown that only a small part of female patients with Ewing sarcoma show signs of ovarian recovery during long-term follow-up, similar to those treated with SCT or abdominal radiotherapy. Time to start preservation of fertility should be defined in this group of patients. Methods: In this observational study, we prospectively investigated AMH as a measure of ovarian function in female adolescents (less than 18 years old) with Ewing sarcoma who received initial chemotherapy in our hospital. Patients previously treated with systemic treatment were excluded. Serum levels of AMH were measured at the laboratory of Peking University People’s Hospital. Blood samples were collected at the first day of the initial two cycles of VDC-IE treatment, before local therapy including surgical resection and radial radiation, and at the end of chemotherapy. All statistical analyses were performed using SPSS 19.0 version. Results: A total of 53 female adolescents with Ewing sarcoma who received initial chemotherapy in our hospital were analyzed from February 1, 2021 to December 31, 2023, including 35 patients aging from 6 to 12 (group 1), 18 patients aging from 12 to 18 (group 2). 255 blood samples from unique time points were measured. The baseline mean AMH were 4.16 (90% CI, 1.88 – 9.42) ng/mL in all patients, 3.58 (90% CI, 1.40 – 6.91) ng/mL for group1 and 5.28 (90% CI, 3.10 – 9.48) ng/mL for group 2. The mean AMH level after first cycle of chemotherapy was 0.43 (90% CI, 0.03 – 0.81) ng/mL in all patients, 0.40 (90% CI, 0.03 – 0.69) ng/mL and 0.47 (90% CI, 0.12 – 1.09) ng/mL for each group at a mean time of 16.5 days after initial chemotherapy. The mean AMH level before local therapy was 0.17 (90% CI, 0.03 – 0.37) ng/mL and 0.07 (90% CI, 0.01 – 0.32) ng/mL at the end of chemotherapy. Conclusions: Female adolescents with Ewing sarcoma treated by VDC-IE regimen showed a rapid reduction of AMH after initial cycles. Methods for preservation of fertility should be implemented as soon as possible but not at the same time of local therapy.
The frequency of HER2-low breast cancer among BRCA1, BRCA2, and PALB2 mutation carriers.
Authors: Goldblatt Lindsay , Coutifaris Paulina , Shah Payal Deepak
Published: June 2024

10509

Background: Human epidermal growth factor 2 (HER2) expression in breast cancer (BC) has historically been characterized as negative (0 or 1+ by immunohistochemistry (IHC); 2+ by IHC and not amplified by in-situ hybridization, ISH) or positive (2+ by IHC and amplified by ISH or 3+ by IHC). Recently developed therapies highlight the importance of identifying tumors that are HER2-low (IHC 1+, or 2+ with negative ISH). A minority of BC associated with germline BRCA1, BRCA2( BRCA1/2) or PALB2pathogenic variants (PV) are HER2-positive, but the proportion of BRCA1/2- and PALB2-associated HER2-negative BC that are HER2-low and may benefit from novel HER2-low therapies is unknown.This study aims to retrospectively identify the frequency of HER2-low BC in BRCA1/2 and PALB2 mutation carriers whose cancers were identified as HER2-negative. Methods: We conducted a retrospective chart review of 170 patients diagnosed with HER2-negative BC in the context of a BRCA1/2or PALB2PV at the University of Pennsylvania from 2003 to 2023. Genomic and cancer-specific characteristics including variant classification and receptor status were collected and are descriptively reported. Results: 170 individuals with BRCA1/2 or PALB2 PV developed 190 HER2-negative BC. Forty-seven percent of primary tumors that had been identified as HER2-negative were HER2-low (39% of BRCA1-, 56% of BRCA2-,60% of PALB2-associated BC; see Table). 17 individuals had 17 metastatic site biopsy reports available for review. Of these, 10 (59%) were HER2-low (1 BRCA1-, 8 BRCA2-, and 1 PALB2-associated). 6 of 17 (35%) individuals had discordant HER2 status in primary and metastatic samples; in all cases, the primary tumor was HER2 IHC 0 and the metastatic site was HER2-low. Conclusions: Despite the lower frequency of conventionally HER2-positive BC among individuals with BRCA1/ 2and PALB2PVs, the proportion of these BC that have low HER2 expression is substantial and similar to that of sporadic breast cancer. Discordance in HER2 status between primary and metastatic samples is observed. Individuals with BRCA1/2and PALB2HER2-negative BC may benefit from therapies for HER2-low BC; reevaluation of HER2 status on metastatic samples may identify additional candidates for such therapies. [Table: see text]
Perceptions of non-disclosure of results in clinical trial designs for multicancer detection tests.
Authors: Samimi Goli , Temkin Sarah M. , Weil Carol J. , Han Paul KJ , LeeVan Elyse , Rubinstein Wendy S. , Swigart Tessa , Caban Sarah , Dent Katherine , Minasian Lori M.
Published: June 2024

10546

Background: Multi-cancer detection tests (MCDs) are blood-based tests designed to detect multiple cancers. The National Cancer Institute (NCI) is planning a pilot study to ascertain the feasibility of recruitment and the necessary infrastructure, clinical workflow, and diagnostic pathways for conducting a large clinical trial to assess whether cancer screening using MCDs reduces cancer mortality. In preparation for these activities, the NCI conducted a qualitative focus group study with primary care physicians (PCPs) and laypersons to explore the acceptability of alternative MCD trial designs, including the disclosure vs. non-disclosure of MCD test results to study participants. Methods: Focus groups were conducted with convenience samples of PCPs (6 groups, N=45) and laypersons (4 groups, N=88) by a consumer research firm. Interviews used both open-ended questions and specific prompts to explore participants’ perceptions of alternative clinical trial designs. Interviews were audio-recorded and transcribed, and qualitative thematic analysis of interview transcripts was conducted to identify emergent themes. Results: In general, PCPs and laypersons reported a willingness to refer or participate in an MCD trial regardless of design, with the understanding that clear and transparent information would be provided in the consent process. However, both groups expressed concern with a trial design in which patients in the control arm would not receive their MCD test results—a design that would allow a marked reduction in sample size and time necessary to assess a mortality endpoint. PCPs noted that although this design might be ethically acceptable due to current clinical equipoise about MCD testing, they expressed concern about mistrust among patients and medical-legal liability. Laypersons had difficulty understanding the rationale for non-disclosure of MCD test results during a trial, and concerns about the ethics of non-disclosure. Some participants felt more comfortable if return of value with other information was included as part of routine study procedures. Participants were more comfortable with an alternative design involving delayed testing of stored blood samples from the control group after trial completion. PCPs also expressed concern about increased workloads if their patients enrolled. Conclusions: PCPs and laypersons had generally positive reactions to a trial to investigate diagnostic performance, pathways, and outcomes of MCDs. Concerns about study designs involving non-disclosure of results might be managed through return of value strategies, careful education, and clear communication of the benefits and risks of MCDs.
Increasing cancer-related mortality and demographic disparities in young adults in the United States between 1999 and 2020.
Authors: Didier Alexander James , Fahoury Alan , Nandwani Swamroop , Campbell Andrew , Batten Macelyn , Sutton Jeffrey M.
Published: June 2024

10569

Background: The global rise in cancer incidence in the young adult population (≤ 45 years), particularly in obesity-related cancers, is of growing concern. As the demographic afflicted by cancer expands beyond traditional boundaries, a nuanced understanding of the unique characteristics and challenges specific to young adults is imperative for developing interventions that address their distinct needs. In this study, we characterize cancer mortality rates in the young adult population to assess for emerging trends and cancer burden in the United States. Methods: The Centers for Disease Control database was queried for all underlying causes of death due to cancer (ICD 10 codes C00-C97) between 1999 and 2020. Malignancies that primarily affect the elderly, such as prostate and multiple myeloma, were excluded. Age-adjusted mortality (AAMR) rates per 100,000 people were extracted for adult patients between 25 and 44 years of age. AAMR was assessed by demographic and clinical variables, including race, geographic density, sex, and primary site. Joinpoint trend analysis was used to identify the presence of statistically significant temporal trends. Average annual percent change (AAPC) was considered statistically significant if p < 0.05. Results: Between 1999 and 2020, 366,478 cancer-related deaths occurred in young adults in the United States. The overall AAMR was 20.7, decreasing from 24.8 in 1999 to 17.5 in 2020 at a rate of -1.6% annually (p<0.05). However, increasing mortality was seen in a number of primary sites, including uterine cancer with an increase of 2.6% annually (p<0.05) and colorectal cancer with an increase of 0.8% annually (p<0.05). Overall AAMR was highest for non-Hispanic Black individuals at 28.3, 29% higher than the next highest group (non-Hispanic White) at 21.2 and almost double that of non-Hispanic Asians at 14.7. Individuals residing in rural populations experienced the highest AAMRs at 24.3 and the slowest rates of decrease at -1.6% annually (p<0.05), compared with urban individuals whose AAMR was 19.8 with a decrease of -1.9% annually (p<0.05). Primary sites with the highest AAMRs included breast (3.1), lung (2.1), and colorectal (1.8) cancers. Conclusions: The current study sheds light on the evolving landscape of cancer mortality among young adults in the United States. The overall decrease in age-adjusted mortality rates is promising, reflecting advancements in cancer care and prevention strategies. However, the alarming increase in mortality rates for specific cancer types, such as uterine and colorectal cancers, underscores the need for targeted interventions and heightened awareness, especially in at-risk populations. The identified racial and geographic disparities further emphasize the importance of implementing tailored approaches to address the unique challenges faced by diverse populations.
Statewide burden of cancer attributable to alcohol use in the United States in the last three decades, projections of deaths to 2040: A benchmarking study.
Authors: Potluri Geethika , Obulareddy Sri Usha Jeevani , Koyani Himanshu Bharatkumar , Gadhiya Dhruvkumar , Markandu Keethanshan , Maddineni Kavya , Adedara Victor O , Parisapogu Anusha , Desai Hardik Dineshbhai , Patel Rushin , Zakia Ummul Barakat , Bramwell Colleen
Published: June 2024

10575

Background: Cancer stands as the 2nd leading cause of deaths and disability in the United States (US), and among the numerous contributing factors, modifiable risk factors play a significant role in exacerbating this burden. Within the spectrum of cancers, alcohol consumption ranks as the second leading attributable cause of death, as per the Global Burden of Disease Cancer Attributable Risk Factor Study. Methods: Employing the GBD protocol, we conducted an estimation of deaths, disability-adjusted life years (DALYs) attributable to cancer caused by alcohol consumption in the US. This comprehensive analysis was stratified by age, gender, year, and geographical location throughout the US, from 1990 to 2019. To project future trends, we utilized time-series regression techniques to forecast deaths until the year 2040. Results: The total number of cancer-related deaths in the US surged from 19,898 (95%UI: 17,791-22,149) in 1990 to 34,455 (30,542-38,388) in 2019. Concurrently, DALYs increased from 532,533 (480,249-586,646) in 1990 to 854,351 (764,549-949,378) in 2019, and YLLs rose from 501,639 (452,446- 554,400) in 1990 to 802,493 (717,123-891,789) in 2019. The highest annual percentage change (APC) in ASR for mortality was observed in West Virginia, with a 32% increase, followed by Tennessee at 27%. Conversely, the District of Columbia witnessed the most significant decrease, with a 30% reduction from 1990 to 2019. In terms of DALYs rates, the highest increases were observed in West Virginia (27%) and Oklahoma (21%). Males bore a greater overall burden compared to females, with an APC in deaths of 97% vs 40% and an APC in DALYs of 87% vs 26%. The highest number of deaths occurred in the 60-64 age group, with 5,228 cases in 2019, while DALYs reached 154,034 in the same year. Projections indicate that the total number of deaths is expected to increase by 49,230 by the year 2040. Conclusions: In 2019, cancer-related deaths attributed to alcohol use represented 4.42% of all cancer mortality cases. From both a public health and clinician perspective, the study's results highlight the urgent need for comprehensive strategies to address the growing burden of cancer associated with alcohol use. Efforts should focus on prevention, early intervention, and support for individuals struggling with alcohol-related cancer risks. [Table: see text]