bluuebunny/crossref_metadata_2025 huggingface dataset:
Sequencing individual genomes with recurrent genomic disorder deletions: an approach to characterize genes for autosomal recessive rare disease traits
Authors: Yuan Bo , Schulze Katharina V. , Assia Batzir Nurit , Sinson Jefferson , Dai Hongzheng , Zhu Wenmiao , Bocanegra Francia , Fong Chin-To , Holder Jimmy , Nguyen Joanne , Schaaf Christian P. , Yang Yaping , Bi Weimin , Eng Christine , Shaw Chad , Lupski James R. , Liu Pengfei
Published: September 2022

Background

In medical genetics, discovery and characterization of disease trait contributory genes and alleles depends on genetic reasoning, study design, and patient ascertainment; we suggest a segmental haploid genetics approach to enhance gene discovery and molecular diagnostics.

Methods

We constructed a genome-wide map for nonallelic homologous recombination (NAHR)-mediated recurrent genomic deletions and used this map to estimate population frequencies of NAHR deletions based on large-scale population cohorts and region-specific studies. We calculated recessive disease carrier burden using high-quality pathogenic or likely pathogenic variants from ClinVar and gnomAD. We developed a NIRD (NAHR deletion Impact to Recessive Disease) score for recessive disorders by quantifying the contribution of NAHR deletion to the overall allele load that enumerated all pairwise combinations of disease-causing alleles; we used a Punnett square approach based on an assumption of random mating. Literature mining was conducted to identify all reported patients with defects in a gene with a high NIRD score; meta-analysis was performed on these patients to estimate the representation of NAHR deletions in recessive traits from contemporary human genomics studies. Retrospective analyses of extant clinical exome sequencing (cES) were performed for novel rare recessive disease trait gene and allele discovery from individuals with NAHR deletions.

Results

We present novel genomic insights regarding the genome-wide impact of NAHR recurrent segmental variants on recessive disease burden; we demonstrate the utility of NAHR recurrent deletions to enhance discovery in the challenging context of autosomal recessive (AR) traits and biallelic variation. Computational results demonstrate new mutations mediated by NAHR, involving recurrent deletions at 30 genomic regions, likely drive recessive disease burden for over 74% of loci within these segmental deletions or at least 2% of loci genome-wide. Meta-analyses on 170 literature-reported patients implicate that NAHR deletions are depleted from the ascertained pool of AR trait alleles. Exome reanalysis of personal genomes from subjects harboring recurrent deletions uncovered new disease-contributing variants in genes including COX10, ERCC6, PRRT2, and OTUD7A.

Conclusions

Our results demonstrate that genomic sequencing of personal genomes with NAHR deletions could dramatically improve allele and gene discovery and enhance clinical molecular diagnosis. Moreover, results suggest NAHR events could potentially enable human haploid genetic screens as an approach to experimental inquiry into disease biology.
Altered methylation pattern in EXOC4 is associated with stroke outcome: an epigenome-wide association study
Authors: Cullell Natalia , Soriano-Tárraga Carolina , Gallego-Fábrega Cristina , Cárcel-Márquez Jara , Muiño Elena , Llucià-Carol Laia , Lledós Miquel , Esteller Manel , de Moura Manuel Castro , Montaner Joan , Rosell Anna , Delgado Pilar , Martí-Fábregas Joan , Krupinski Jerzy , Roquer Jaume , Jiménez-Conde Jordi , Fernández-Cadenas Israel
Published: September 2022

Background and purpose

The neurological course after stroke is highly variable and is determined by demographic, clinical and genetic factors. However, other heritable factors such as epigenetic DNA methylation could play a role in neurological changes after stroke.

Methods

We performed a three-stage epigenome-wide association study to evaluate DNA methylation associated with the difference between the National Institutes of Health Stroke Scale (NIHSS) at baseline and at discharge (ΔNIHSS) in ischaemic stroke patients. DNA methylation data in the Discovery (n = 643) and Replication (n = 62) Cohorts were interrogated with the 450 K and EPIC BeadChip. Nominal CpG sites from the Discovery (p value < 10–06) were also evaluated in a meta-analysis of the Discovery and Replication cohorts, using a random-fixed effect model. Metabolic pathway enrichment was calculated with methylGSA. We integrated the methylation data with 1305 plasma protein expression levels measured by SOMAscan in 46 subjects and measured RNA expression with RT-PCR in a subgroup of 13 subjects. Specific cell-type methylation was assessed using EpiDISH.

Results

The meta-analysis revealed an epigenome-wide significant association in EXOC4 (p value = 8.4 × 10–08) and in MERTK (p value = 1.56 × 10–07). Only the methylation in EXOC4 was also associated in the Discovery and in the Replication Cohorts (p value = 1.14 × 10–06 and p value = 1.3 × 10–02, respectively). EXOC4 methylation negatively correlated with the long-term outcome (coefficient = − 4.91) and showed a tendency towards a decrease in EXOC4 expression (rho = − 0.469, p value = 0.091). Pathway enrichment from the meta-analysis revealed significant associations related to the endocytosis and deubiquitination processes. Seventy-nine plasma proteins were differentially expressed in association with EXOC4 methylation. Pathway analysis of these proteins showed an enrichment in natural killer (NK) cell activation. The cell-type methylation analysis in blood also revealed a differential methylation in NK cells.

Conclusions

DNA methylation of EXOC4 is associated with a worse neurological course after stroke. The results indicate a potential modulation of pathways involving endocytosis and NK cells regulation.
Dramatic impacts on brain pathology, anxiety, and cognitive function in the knock-in APPNL-G-F mouse model of Alzheimer disease following long-term voluntary exercise
Authors: Mehla Jogender , Deibel Scott H. , Karem Hadil , Hossain Shakhawat , Lacoursiere Sean G. , Sutherland Robert J. , Mohajerani Majid H. , McDonald Robert J.
Published: September 2022

Background

An active lifestyle is associated with improved cognitive functions in aged people and may prevent or slow down the progression of various neurodegenerative diseases including Alzheimer’s disease (AD). To investigate these protective effects, male APPNL-G-F mice were exposed to long-term voluntary exercise.

Methods

Three-month-old AD mice were housed in a cage supplemented with a running wheel for 9 months for long-term exercise. At the age of 12 months, behavioral tests were completed for all groups. After completing behavioral testing, their brains were assessed for amyloid pathology, microgliosis, and cholinergic cells.

Results

The results showed that APPNL-G-F mice allowed to voluntarily exercise showed an improvement in cognitive functions. Furthermore, long-term exercise also improved anxiety in APPNL-G-F mice as assessed by measuring thigmotaxis in the Morris water task. We also found reductions in amyloid load and microgliosis, and a preservation of cholinergic cells in the brain of APPNL-G-F mice allowed to exercise in their home cages. These profound reductions in brain pathology associated with AD are likely responsible for the observed improvement of learning and memory functions following extensive and regular exercise.

Conclusion

These findings suggest the potential of physical exercise to mitigate the cognitive deficits in AD.
Immunoglobulin G4-related disease diagnosed by prostate biopsy: a case report
Authors: Aoki Shigeyuki , Morinaga Shingo , Kawai Naoki , Tanaka Haruna , Kanematsu Keiko , Tsuchiya Nanami , Nonomura Sayuri , Ozawa Akiko , Imai Rie , Takahashi Ryoko , Sawada Tomoko , Futamachi Ruriko , Yamada Yoshiaki
Published: September 2022

Background

Immunoglobulin G4-related disease is characterized by swelling of various organs throughout the body and nodules/hypertrophic lesions. However, its cause remains unknown. We report a case of immunoglobulin G4-related disease that was diagnosed based on the histopathological findings of prostate biopsy.

Case presentation

A 72-year-old Japanese man had been treated by a nearby doctor for hypertension, but subsequently developed lower urinary tract symptoms and was prescribed an α1 blocker for 1 year. However, the patient was subsequently referred to our department because his symptoms did not improve. Prostate-specific antigen was 1.258 ng/ml; however, the nodule was palpable in the right lobe on digital rectal examination, and magnetic resonance imaging suggested Prostate Imaging and Reporting and Data System category 3. Therefore, transrectal prostate needle biopsy (12 locations) under ultrasound was performed. Histopathological examination revealed no malignant findings, although infiltration of lymphocytes and plasma cells, and partial fibrosis were observed. No remarkable findings of obstructive phlebitis were observed. Immunoglobulin G4-related disease was suspected, and immunoglobulin and immunoglobulin G4 immunostaining was performed. Immunoglobulin G4 positive plasma cells were observed in a wide range, immunoglobulin G4 positive cells were noted at > 10 per high-power field, and the immunoglobulin G4 positive/immunoglobulin G positive cell ratio was > 40%. Serum immunoglobulin G4 levels were high at 1600 mg/dl. Enhanced abdominal computed tomography findings suggested periaortitis. Additionally, multiple lymphadenopathies were observed around the abdominal aorta. The patient was accordingly diagnosed with immunoglobulin G4-related disease definite, diagnosis group (definite). We proposed steroid treatment for periaortic soft tissue lesions and lower urinary tract symptoms; however, the patient was refused treatment. A computed tomography scan 6 months after diagnosis revealed no changes in the soft tissue lesions around the aorta. Follow-up computed tomography examinations will be performed every 6 months.

Conclusion

If immunoglobulin G4-related disease is suspected and a highly invasive examination is required for histopathological diagnosis, this can be performed by a relatively minimally invasive prostate biopsy for patients with lower urinary tract symptoms. Further evidence is needed to choose an optimal candidate for prostate biopsy for lower urinary tract symptoms patients with suspicion of immunoglobulin G4-related disease. For patients with lower urinary tract symptoms with immunoglobulin G4-related disease or a history, performing a prostate biopsy may avoid unnecessary treatment. However, if steroid therapy is ineffective, surgical treatment should be considered.
PICO entity extraction for preclinical animal literature
Authors: Wang Qianying , Liao Jing , Lapata Mirella , Macleod Malcolm
Published: September 2022

Background

Natural language processing could assist multiple tasks in systematic reviews to reduce workflow, including the extraction of PICO elements such as study populations, interventions, comparators and outcomes. The PICO framework provides a basis for the retrieval and selection for inclusion of evidence relevant to a specific systematic review question, and automatic approaches to PICO extraction have been developed particularly for reviews of clinical trial findings. Considering the difference between preclinical animal studies and clinical trials, developing separate approaches is necessary. Facilitating preclinical systematic reviews will inform the translation from preclinical to clinical research.

Methods

We randomly selected 400 abstracts from the PubMed Central Open Access database which described in vivo animal research and manually annotated these with PICO phrases for Species, Strain, methods of Induction of disease model, Intervention, Comparator and Outcome. We developed a two-stage workflow for preclinical PICO extraction. Firstly we fine-tuned BERT with different pre-trained modules for PICO sentence classification. Then, after removing the text irrelevant to PICO features, we explored LSTM-, CRF- and BERT-based models for PICO entity recognition. We also explored a self-training approach because of the small training corpus.

Results

For PICO sentence classification, BERT models using all pre-trained modules achieved an F1 score of over 80%, and models pre-trained on PubMed abstracts achieved the highest F1 of 85%. For PICO entity recognition, fine-tuning BERT pre-trained on PubMed abstracts achieved an overall F1 of 71% and satisfactory F1 for Species (98%), Strain (70%), Intervention (70%) and Outcome (67%). The score of Induction and Comparator is less satisfactory, but F1 of Comparator can be improved to 50% by applying self-training.

Conclusions

Our study indicates that of the approaches tested, BERT pre-trained on PubMed abstracts is the best for both PICO sentence classification and PICO entity recognition in the preclinical abstracts. Self-training yields better performance for identifying comparators and strains.
Dyspnea after discharge from hospital due to pulmonary vein thrombosis after video-assisted left upper lobectomy: a case report
Authors: Kubo Ruiji , Hoshi Takuo , Shu Akae , Yamasaki Yuichiro
Published: September 2022

Background

Thrombus formation at the pulmonary vein transection site is more common in left upper lobectomy than other lobectomies. We report a case of dyspnea and contrast-enhanced computed tomography (CT) findings of pulmonary vein thrombosis after left upper lobectomy.

Case presentation

A 68-year-old man with left lung cancer underwent video-assisted thoracoscopic left upper lobectomy under general anesthesia with thoracic epidural analgesia. He had no postoperative complications and was discharged home on the 5th day postoperatively. He visited the outpatient clinic at 8 days after surgery because of dyspnea and underwent contrast-enhanced CT, which revealed a thrombus at the resected edge of the left upper pulmonary vein. Anticoagulation therapy was started. Thereafter, the thrombus shrank, and the patient’s dyspnea improved.

Conclusions

Left upper lobe resection is particularly associated with pulmonary venous thrombosis, and dyspnea due to pulmonary venous thrombus may develop late after surgery. Postoperative management methods such as anticoagulation and postoperative pain management should be reexamined.
Assessment of awareness and knowledge of schistosomiasis among school-aged children (6–13 years) in the Okavango Delta, Botswana
Authors: Gabaake Kebabonye P. , Phaladze Nthabiseng A. , Lucero-Prisno III Don Eliseo , Thakadu Olekae T.
Published: September 2022

Background

Schistosomiasis is a global health problem affecting 250 million people, with 90% in Sub-Saharan Africa. In Botswana, the burden is high in the Okavango delta because of the water channels. WHO recommends integrated measures, including access to clean water, sanitation, health education, and drugs to control and eliminate schistosomiasis. Gauging knowledge and awareness of schistosomiasis for School-Aged Children (SAC) is crucial. Our study aimed at assessing knowledge and awareness of schistosomiasis among SAC in the Okavango Delta.

Methods

A cross-sectional survey assessing awareness and knowledge of schistosomiasis in schools was conducted. 480 questionnaires were administered to gather demographic profiles, awareness, and knowledge of risky behaviors. Chi-square and descriptive analysis determined the differences in SAC`s awareness and knowledge levels based on localities, gender, age, and health education.

Results

The results showed a low awareness level, with only (42%) of respondents having heard about the disease and (52%) knowing its local name. Younger children from Sekondomboro (83%) and Samochima lacked awareness, while children from Mohembo (77%) and those who had health education (70%) demonstrated significant awareness levels (P ≤ 0.001). Seventy-two percent (72%) lacked knowledge of the cause and (95%) did not know the disease life-cycle. Children from Xakao (91%), (85%) Sepopa, and (75%) of younger children did not know haematuria is a symptom of the disease. Older and SAC with health education were more likely to know that swimming is a risk factor (P ≤ 0.001) and (P ≤ 0.05) respectively.

Conclusions

Although respondents from four schools demonstrated some level of awareness of the disease, and knowledge of risky behaviors, the study showed a lack of in-depth knowledge on the life-cycle and cause of the diseases. We, therefore, recommend the implementation of an integrated approach to health education and improvement in access to clean water and sanitation in all study areas.
PUMD: a PU learning-based malicious domain detection framework
Authors: Fan Zhaoshan , Wang Qing , Jiao Haoran , Liu Junrong , Cui Zelin , Liu Song , Liu Yuling
Published: October 2022

Domain name system (DNS), as one of the most critical internet infrastructure, has been abused by various cyber attacks. Current malicious domain detection capabilities are limited by insufficient credible label information, severe class imbalance, and incompact distribution of domain samples in different malicious activities. This paper proposes a malicious domain detection framework named PUMD, which innovatively introduces Positive and Unlabeled (PU) learning solution to solve the problem of insufficient label information, adopts customized sample weight to improve the impact of class imbalance, and effectively constructs evidence features based on resource overlapping to reduce the intra-class distance of malicious samples. Besides, a feature selection strategy based on permutation importance and binning is proposed to screen the most informative detection features. Finally, we conduct experiments on the open source real DNS traffic dataset provided by QI-ANXIN Technology Group to evaluate the PUMD framework’s ability to capture potential command and control (C&C) domains for malicious activities. The experimental results prove that PUMD can achieve the best detection performance under different label frequencies and class imbalance ratios.
Ultrasound-guided vacuum-assisted excision biopsy in breast fibroadenomas: an Egyptian center experience
Authors: Soliman Ahmed Hassan
Published: September 2022

Background

Benign breast tumors although classified as benign lesions but excising them remain a troublesome problem. Surgical excision for benign breast lesions frightens most of female population suffering from such a problem, which created an urgency to search for a safe and effective alternative. My aim was to assess the efficacy of vacuum-assisted biopsy (VAB) excision system for the removal of benign breast lesions in terms of complete excision rate and incidence of complications.

Results

Twenty-three female patients with 29 twenty-nine lesions were included in our study. Mean age was 33 years (19–52 years). The incidence of complete excision was 100% in follow-up with 3 drop outs. The largest diameter of the tumors ranged from 1.2 to 3.3 cm. Rate of occurrence of complications in form of intra-procedural pain, 69% of our patients experienced mild intra-procedural pain with visual analog pain scale (VAS) score (1–3).21% experienced moderate pain with VAS score (4–6).8% experienced no pain. Patients who developed post procedural ecchymosis were 17% while hematoma group of patients were 10% of total number of patients.

Conclusions

The study showed that the use of vacuum-assisted biopsy excision system could provide a safe method for complete excision of fibroadenomas, with low rate of complications as incomplete excision, pain, and hematoma formation.
Anti-inflammatory and antioxidant effect of Moringa oleifera against bisphenol-A-induced hepatotoxicity
Authors: Abd-Elnaby Yasmin A. , ElSayed Ibrahim E. , AbdEldaim Mabrouk A. , Badr Eman A. , Abdelhafez Mona M. , Elmadbouh Ibrahim
Published: September 2022

Background

Non-pharmacological exposure or pharmacological drug-induced hepatic injury is the most common cause of hepatotoxicity. This study was conducted to evaluate the effect of Moringa oleifera leaf extract against bisphenol-A (BPA)-induced hepatic toxicity in rats.

Methods

Rats (n=56) were randomized into 7 groups (8 rats/each). Control groups: rats received olive oil or Moringa oleifera (400mg/kg) orally for 42 days. Hepatotoxicity groups: rats received BPA (50mg/kg BW) orally in a 1-ml olive oil for 42 days. Reversal groups: rats received Moringa oleifera (200 or 400mg/kg) and BPA (50mg/kg BW) for 42 days. Preventive groups: rats received Moringa oleifera (200 or 400mg/kg) for 30 days followed by BPA (50mg/kg BW) for 14 days. At the end of the experiments, blood samples were collected for glucose and liver function assay, while the liver tissue samples were collected and homogenated for measuring the inflammatory/oxidant and antioxidant markers.

Results

Rats with BPA-induced hepatotoxicity have significantly increased serum aspartate transaminase (AST), alanine transaminase (ALT), and glucose; liver lysate malondialdehyde (MDA); tumor necrosis factor (TNF-α); and macrophage migrating inhibitory factor (MIF) but significantly decreased levels of liver lysate reduced glutathione (GSH) and total antioxidant capacity (TAC) levels. The administration of Moringa oleifera (especially 400mg/kg BW) in both reversal and preventive groups ameliorate the toxic effects of BPA in rats, as it decreased the activities of AST, ALT, glucose, MDA, TNF-α, and MIF levels and increased the antioxidant levels of GSH and TAC.

Conclusion

Moringa oleifera has hepatoprotective effects against BPA-induced liver damage through the regulation of antioxidants and inflammatory biomarkers.
Iatrogenic massive hemorrhagic edema of the tongue: a case report
Authors: Kyriaki Vallianou , Fani Saini , Jiannis Hajiioannou
Published: September 2022

Background

Lingual edema is usually the result of infectious etiology, angioedema, and less commonly of traumatic etiology.

As for the therapeutic approach, the first priority excluding airway compromise or ensuring airway safety. Antibiotic treatment should be administered for tongue swelling of inflammatory etiology while standard therapy with epinephrine, steroids, and antihistamines is recommended for cases of anaphylaxis. In addition, in case of injury causing lingual edema, one of the treatment options is surgical intervention.

Aim of work

The aim of our work is to present a rare and simultaneously instructive case of traumatic hemorrhagic edema of the tongue, leading to airway obstruction.

Case presentation

We report a case of hemorrhagic traumatic lingual edema, initially without symptoms of upper airway obstruction on admission. However, immediate intervention and airway securing was necessary due to rapid growth of the edema.

Then, as long as patient was hemodynamically stable and airway patency was ensured, the diagnosis of iatrogenic tongue hematoma was confirmed. The challenge was to decide the appropriate treatment for the patient. Following, she was taken for 24 h to the ICU due to lactic acidosis while the bleeding was treated conservatively.

Afterward, she was transferred to the clinic, hemodynamically stable, and was discharged uneventfully.

Conclusions

Hemorrhagic edema of the tongue may become a life-threatening condition. Its rapid growth can lead to obstruction of the upper respiratory way; therefore, special wariness in its management is required. Treatment can be conservative or surgical, depending on the size and tendency of hematoma to increase.
Conformal optical black hole for cavity
Authors: Ba Qingtao , Zhou Yangyang , Li Jue , Xiao Wen , Ye Longfang , Liu Yineng , Chen Jin-hui , Chen Huanyang
Published: September 2022

Whispering-gallery-mode (WGM) cavity is important for exploring physics of strong light-matter interaction. Yet it suffers from the notorious radiation loss universally due to the light tunneling effect through the curved boundary. In this work, we propose and demonstrate an optical black hole (OBH) cavity based on transformation optics. The radiation loss of all WGMs in the ideal OBH cavity is completely inhibited by an infinite wide potential barrier. Besides, the WGM field in the OBH cladding is revealed to follow $$1/r^\alpha$$

1
/

r
α

decay rule based on conformal mapping, which is fundamentally different from the conventional Hankel-function distributions in a homogeneous cavity. Experimentally, a truncated OBH cavity is achieved based on the effective medium theory, and both the Q-factor enhancement and tightly confined WGM fields are measured in the microwave spectra which agree well with the theoretical results. The circular OBH cavity is further applied to the arbitrary-shaped cavities including single-core and multi-core structures with high-Q factor via the conformal mapping. The OBH cavity design strategy can be generalized to resonant modes of various wave systems, such as acoustic and elastic waves, and finds applications in energy harvesting and optoelectronics.
Seismic Soundoff: What geophysicists and engineers need to know about DAS
Authors: Geary Andrew
Published: October 2022

In this episode, Mark Willis discusses his Distinguished Instructor Short Course, “Distributed acoustic sensing for seismic measurements — What geophysicists and engineers need to know.” Willis helps attendees build intuition and understanding of the value, limitations, and applications of distributed acoustic sensing (DAS) seismic technology. Hear the full episode at https://seg.org/podcast/post/15802 .
Meaningful measures for advanced cancer: Building a measure set to promote goal-concordant care.
Authors: McNiff Landrum Kristen K. , Ross Tom , Andiel Corinna , Eaton Keith D. , Edge Stephen B. , George Marina C. , Lakin Joshua , Morse Denise , Papio Joseph , Plank Wendy , Thacker Lauren , Thompson Emily , Zachariah Finly , Kolosky Jack
Published: September 2022

210

Background: Research suggests that patients with advanced cancer do not reliably receive care consistent with their goals and values, indicating an important gap. While experts promote measurement of ‘goal concordant care’ this construct is difficult to measure due to definitional and data complexity. The 10 cancer hospitals of the Alliance of Dedicated Cancer Centers (ADCC) have collaboratively implemented interventions to improve goal concordant care and create a wholistic measure set through the Improving Goal Concordant Care (IGCC) Initiative. Methods: ADCC launched the 3 year initiative in 2020. Oncology, palliative care and quality experts completed conceptual work prior to launch including identifying core intervention components, specific aims and potential measures. Following an environmental scan, a workgroup brainstormed relevant measures, then applied feasibility and priority ratings. Patient/family advisors provided guidance. In 2020, a measure panel initiated technical development, using existing specifications as feasible. Claims-based measures were modeled. Following alpha testing, quarterly data submission of selected measures began in 2022. Results: During the conceptual phase, the workgroup identified 60 measures. 19 measures remained following the prioritization and feasibility rating; 14 have been tested and implemented to date (Table). A stakeholder (e.g., patients, physicians, administrators) assessment regarding each measure’s value in assessing quality and usefulness for improvement is in progress. Conclusions: In support of IGCC, we created a set of measures to assess progress towards achieving goal-concordant care. This measure set is intended to be useful in any cancer setting.[Table: see text]
Real-world practice patterns in multidisciplinary squamous cell carcinoma care at community oncology centers.
Authors: Kirkwood John M. , Krakowski Andrew C. , Carter Jeffrey D. , Heggen Cherilyn , McKinnon Kelly E.
Published: September 2022

261

Background: As the incidence of cutaneous squamous cell carcinoma (cSCC) continues to rise and newer systemic therapies become available, coordination of care between dermatologists and oncologists will be vital to provide quality, patient-centered care. Methods: Between 8/17/2020 and 11/30/2020, we surveyed dermatology team members (n = 50) and oncology team members (n = 54) at 5 community oncology practices to assess current practices, challenges/barriers, and areas for improvement in multidisciplinary care of cSCC. Providers then participated in audit/feedback educational sessions and developed action plans to address identified gaps. Results: A majority of providers (72%) reported “very low” or “low” levels of care coordination between oncology and dermatology teams (5-point Likert scale). The three main barriers identified by dermatology/oncology teams included lack of relationship to other specialties (36%/47%), lack of multidisciplinary tumor board (30%/36%), and difficulty with patient navigation to follow-up and monitoring (44%/29%). In addition, lack of administrative support (30%/47%), lack of time (54%/42%), and high case load (32%/16%) hindered multidisciplinary tumor board meetings. Overall, dermatology teams reported lower confidence in making treatment decisions for patients with advanced cSCC compared to oncology teams. Specific strategies were identified to bridge these gaps and improve cSCC care including improving electronic communication, coordinating treatment plans with multidisciplinary teams, integrating educational seminars between oncologists and dermatologists, and finding better multimodality therapeutic options. Conclusions: These findings reveal important challenges in multidisciplinary care of cSCC in community oncology clinics. The identified gaps may inform future implementation science initiatives, and represent key opportunities for improvement in cSCC patient care.[Table: see text]
A novel cannabis education clinic for patients with cancer: Patient characteristics from initial visit.
Authors: Zylla Dylan M. , Jax Sarah , Schmiechen Katherine , Jelle Katie , Gilmore Grace
Published: September 2022

298

Background: Patients with cancer express growing interest in using cannabis to alleviate symptoms and want information from their oncology care teams. However, most oncology clinicians report insufficient knowledge to discuss potential benefits and risks of cannabis with patients. Methods: We created the Cannabis and Cancer Research and Education Clinic (CanCaRE) to educate patients interested in cannabis use through 1:1 video consultations with an oncology advanced practice clinician. We also developed an electronic registry built in REDCap that tracks outcomes including NCI PRO-CTCAE symptom questionnaires. All patients receive an intake survey with questions about their diagnosis, cancer treatments, current symptom burden, cannabis use history, and current medications. Results: During the first 18 months of the CanCaRE clinic, 103 of the 130 patients seen for consultation completed the intake survey. All 16 of our clinic’s medical oncologists had at least one patient receive a consultation. Patients had diverse cancer diagnoses (breast (19%), gynecologic (15%), lung (11%), pancreas (11%)) and were more often white (84%), not currently using cannabis (74%), and female (60%), with a median age of 64 (range 26-92). Most respondents (41%) had stage IV disease with the remaining 32% stage I-III (28% unknown). Table outlines symptom burden at time of initial CanCaRE consultation. The percentage of patients using medications for symptoms was high; non-opioid analgesics (81%), antiemetics (52%), anxiety/depression meds (52%), sleep meds (39%), and opioids (30%). The most common initial cannabis product recommendation included an oral tablet/solution (2.5mg THC/2.5mg CBD) twice daily as well as a THC-dominant vaporizer (3-5mg THC per puff) as needed. Conclusions: The development of a cannabis clinic to provide patients with cancer personalized education and dosing guidance is novel and helps serve an unmet need. Patients have diverse cancer histories and express a high level of symptom burden. Patients and oncology care teams report high satisfaction with our clinic model. Initial cannabis dosing recommendations used a “start low, go slow” titration plan. Analysis has begun on cannabis use patterns and changes in symptoms/concomitant medications to further tailor recommendations that are safe, effective, and cost-efficient. Exploring ways to expand this clinic model to other cancer centers is underway.[Table: see text]
Do clinical pathways impede provider workflow: A provider efficiency analysis of time spent using an EHR-embedded clinical decision support tool.
Authors: Maniago Rebecca , Miao Jennifer , Jou Stephanie , Calip Gregory Sampang , Huda Shawn , Shulman Lawrence N. , Bange Erin Mary , Singh Aditi Puri , Davella Christopher
Published: September 2022

381

Background: With the growing complexity and cost of cancer care, adoption of oncology pathway tools as clinical decision support (CDS) has increased at the point of care. These tools have been shown to improve care quality, reduce variations in care and reduce healthcare costs. Flatiron Assist (FA) is a customizable CDS tool that is embedded in the electronic health record (EHR) to facilitate selection and documentation of National Comprehensive Cancer Network (NCCN) guideline concordant cancer treatment regimens. The time burden of engaging with CDS tools is a top concern for clinicians and often limits uptake of these tools. However, data on the actual time spent utilizing these tools in clinical practice is limited. Our study reports on the time spent by clinicians in various oncology practices, utilizing and ordering cancer treatment regimens with a CDS tool. Methods: We reviewed all completed sessions in FA from July 23, 2021 to May 23, 2022 by 878 prescribers at 24 academic and community oncology centers. Sessions that were part of an electronic prior authorization pilot program were excluded for purposes of standardization. Session length was defined as the time from the completion of application launch to application exit. For prescribers who completed over 20 sessions, we compared the mean sessions lengths of user’s initial sessions (#1-10) to subsequent sessions (#11-20) using paired t tests. We also determined the total number of potential CDS tool sessions per user per week. Results: All 14,394 CDS tool sessions were analyzed during the 10 month observation period. Median session length was 42 seconds (95th percentile, 253 seconds or 4.2 minutes). The average number of treatment orders placed was 5 per week per provider. Table shows the median session length across the 9 most commonly treated cancers. For the 31 prescribers who started using FA during the study and completed more than 20 sessions, the mean (SD) session length decreased from 95.2 (11.8) seconds in sessions #1-10 to 71.0 (6.0) seconds in sessions #11-20 (two-sided P = 0.034). Conclusions: Utilization of FA as a CDS tool to provide guideline concordant care is feasible and adds less than 4 minutes/week on average to a provider’s workflow. When used effectively, it can integrate seamlessly into provider workflows across academic and community practices without disruptive increases in time or effort of cancer treatment regimen ordering. Future studies are needed to evaluate the impact of product improvements, content changes, and electronic prior authorization integrations on time in this workflow.[Table: see text]
Liquid biopsy detection of tumor shed in cancers for which molecular profiling is best practice.
Authors: Kasi Pashtoon Murtaza , Weipert Caroline , Kaylor Julie
Published: September 2022

412

Background: Technology and innovation in genomic profiling provides an opportunity to improve the outcomes of advanced solid cancer patients including some cancer agnostic approved therapies, and biomarker analysis is recommended within NCCN guidelines for 15 solid cancers. Tissue-based molecular profiling may not be efficient or feasible for many patients due to factors such as fitness for procedure, timeliness to treatment, and sample exhaustion, leading to healthcare disparities. Despite robust validation and regulatory approval for use in genomic profiling across all advanced solid tumors, circulating tumor DNA (ctDNA) or “liquid biopsy” is included within NCCN guidelines for 9 solid cancers. The utility of ctDNA based profiling in additional cancers for which molecular analysis is recommended is contingent upon the ability to reliably detect tumor shed and biomarkers of interest. Methods: Results were analyzed for a large nationwide cohort over 40,000 patients seen across community and academic settings receiving Guardant360 CDx or Guardant360 (Guardant Health, Redwood City, CA) in a 6-month window to evaluate detection of ctDNA, or tumor shed, among cancers for which guidelines do and do not currently include liquid biopsy. Results: Tumor shed was detected in 83%-92% (median 89%) of cancers for which guidelines include liquid biopsy, and 73%-94% (median 88%) for those without guideline inclusion for liquid biopsy. The detection of tumor shed was similar among cancer types with and without liquid biopsy inclusion in guidelines (p value = 0.5014; two-tailed t-test). Conclusions: The non-invasive nature of liquid biopsy, rapid turnaround, and sufficient tumor shed (as shown by results of this study) further support the inclusion of liquid biopsy in NCCN guidelines when molecular profiling is indicated. For tumors where it may replace the need for tissue biopsy acquisition, a plasma-first approach incorporating a liquid biopsy can reduce the financial toxicity as it would be more efficient and cost-effective.[Table: see text]
Financial Hardship in Adult Survivors of Childhood Cancer in the Era After Implementation of the Affordable Care Act: A Report From the Childhood Cancer Survivor Study
Authors: Nathan Paul C. , Huang I-Chan , Chen Yan , Henderson Tara O. , Park Elyse R. , Kirchhoff Anne C. , Robison Leslie L. , Krull Kevin , Leisenring Wendy , Armstrong Gregory T. , Conti Rena M. , Yasui Yutaka , Yabroff K. Robin
Published: September 2022

PURPOSE

To estimate the prevalence of financial hardship among adult survivors of childhood cancer compared with siblings and identify sociodemographic, cancer diagnosis, and treatment correlates of hardship among survivors in the era after implementation of the Affordable Care Act.

METHODS

A total of 3,555 long-term (≥ 5 years) survivors of childhood cancer and 956 siblings who completed a survey administered in 2017-2019 were identified from the Childhood Cancer Survivor Study. Financial hardship was measured by 21 survey items derived from US national surveys that had been previously cognitively tested and fielded. Principal component analysis (PCA) identified domains of hardship. Multiple linear regression examined the association of standardized domain scores (ie, scores divided by standard deviation) with cancer and treatment history and sociodemographic characteristics among survivors.

RESULTS

Survivors were more likely than siblings to report hardship in ≥ 1 item (63.4% v 53.7%, P < .001). They were more likely to report being sent to debt collection (29.9% v 22.3%), problems paying medical bills (20.7% v 12.8%), foregoing needed medical care (14.1% v 7.8%), and worry/stress about paying their rent/mortgage (33.6% v 23.2%) or having enough money to buy nutritious meals (26.8% v 15.5%); all P < .001. Survivors reported greater hardship than siblings in all three domains identified by principal component analysis: behavioral hardship (mean standardized domain score 0.51 v 0.35), material hardship/financial sacrifices (0.64 v 0.46), and psychological hardship (0.69 v 0.44), all P < .001. Sociodemographic (eg, <college education, without private insurance) and treatment factors (eg, received ≥ 250 mg/m2 anthracycline chemotherapy, or chest radiation) were statistically significantly associated with increased hardship.

CONCLUSION

Survivors of childhood cancer were more likely to experience financial hardship than siblings. Correlates of hardship can inform survivorship care guidelines and intervention strategies.
Tristan’s Origins
Authors: Boitani Giulia
Published: September 2022

The initial section of the thirteenth-century Tristan en prose has been the subject of multiple critical investigations, mostly devoted to identifying its teleological purpose or figurative function in relation to the rest of the romance. This article proposes to reframe the question by reading the narrative of incest that dominates the “prehistory” of the prose Tristan against two key concepts that inform Michel Foucault’s 1971 essay “Nietzsche, la généalogie, l’histoire.” First, Foucault’s focus on the succession of discursive formations allows for a reinterpretation of the “guerre des récits” that traverses the Tristan: within this critical framework, Foucault’s work on judicial forms permits the identification of the points of emergence of new power/knowledge relationships within the prehistory, with the advent of ecclesiastical authority embodied by Saint Augustine and affirmed in the context of the saint’s public ordeal. Second, Foucault’s reading of the body as the surface of inscription of such discursive conflicts sheds light on the ways in which the saint’s discourse rewrites the bodies of the two protagonists, Apollo and Chelinde, and frames them within the lines of lineage. However, once Augustine’s narrative of “origin” is reinscribed in its discursive context, it clearly appears as purposefully chimeric. Because Tristan’s Arimathean lineage is founded on the revelation of Apollo and Chelinde’s incest, the very idea of unbroken continuity and ordered descent within genealogy is revealed as an illusion: it is a genealogical stemma that only exists in virtue of an archetypal error—the “bad grammar” of incest.
Optimal Public Debt with Life Cycle Motives
Authors: Peterman William B. , Sager Erick
Published: September 2022

This paper determines optimal public debt in a life cycle model with incomplete markets that matches the empirically observed variation in consumption, labor, and savings. We find that public savings—not public debt—equal to 168 percent of output is optimal, primarily due to the influence of the life cycle on household decision-making. By inducing a lower interest rate, public savings slow consumption and leisure growth over an average household’s lifetime, and the resulting flatter allocation of lifetime consumption and leisure improves welfare. These life cycle welfare benefits are large—on net, they outweigh the transitional costs from a tax-financed public debt elimination. (JEL D15, D52, E21, E43, E62, G51, H63)
Monetary Policy and Liquidity Constraints: Evidence from the Euro Area
Authors: Almgren Mattias , Gallegos José-Elías , Kramer John , Lima Ricardo
Published: September 2022

We quantify the relationship between the response of output to monetary policy shocks and the share of liquidity-constrained households. We do so in the context of the euro area, using a Local Projections Instrumental Variables estimation. We construct an instrument for changes in interest rates from changes in overnight indexed swap rates in a narrow time window around ECB announcements. Monetary policy shocks have heterogeneous effects on output across countries. Using micro data, we show that the elasticity of output to monetary policy shocks is larger in countries that have a larger fraction of households that are liquidity constrained. (JEL E23, E43, E52, F33, F45, G51)
Neo-Fisherian Policies and Liquidity Traps
Authors: Bilbiie Florin O.
Published: September 2022

Liquidity traps can be either fundamental or confidence-driven. In a simple, unified New Keynesian framework, I provide the analytical condition for the latter’s prevalence: enough shock persistence and endogenous intertemporal amplification of future (“news”) shocks, making income effects dominate substitution effects. The same condition allows neo-Fisherian effects (expansionary-inflationary interest rate increases), which are thus inherent in confidence traps. Several monetary and fiscal policies (forward guidance, interest rate increases, public spending, labor tax cuts) have diametrically opposed effects according to the trap variety. This duality provides testable implications to disentangle between trap types; that is essential, for optimal policies are also conflicting across trap varieties. (JEL E12, E31, E32, E43, E52, E62)
The adverse effects of long-term exposure to anticholinergics among people with intellectual disabilities: a scoping review
Authors: Al Shuhaimi Lamya , Henman Martin , McCallion Philip , McCarron Mary , O'Dwyer Maire
Published: September 2022

Background: Older adults with intellectual disability are exposed to a higher anticholinergic burden compared to general older adults. This is due to a higher rate of both mental and neurological disorders among people with intellectual disability. The use of medications with a high anticholinergic burden is associated with adverse effects including daytime dozing, constipation and higher dependence level in the Barthel index for measuring activities of daily living. This scoping review aims to map and examine the existing research on physical and cognitive adverse effects associated with the long-term impact of anticholinergics among people with intellectual disabilities.

Methods: The search was conducted in: PubMed, Cochrane library, EMBASE, Medline, Science Direct, CINAHL Complete and PsycINFO. Preliminary studies, grey literature, and conference papers were searched in related electronic databases. The search terms included terms related to ‘anticholinergic’, ‘long-term exposure’, ‘intellectual disability’ and ‘adverse drug reaction’ with Boolean operator ‘and’. Studies with at least three months’ exposure to anticholinergics were included. The search was restricted to research papers on people with intellectual disability aged 40 or over and publication in the English language only. Initially, it was conducted in May and June 2021 and covered the publication period between 1970 and 2021. It was re-run in October 2021.

Results: The conducted search provided 509 records of publications and grey literature. Duplicates were removed using EndNote 20 and resulted in 432 remaining records. Then, 426 further records were excluded because they were deemed irrelevant, or non-longitudinal studies or conducted on different populations. Only six full articles were retrieved to assess their eligibility and all were excluded due to different study populations. This resulted in no studies meeting the stated inclusion criteria.

Conclusions: Further research is urgently required to examine the long-term adverse effects associated with higher anticholinergic scores among older people with intellectual disability.