cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.21976070
title: Supplementary Material for: Pathological complete response of metastatic clear cell renal carcinoma with pembrolizumab and axitinib: a case report and review of literature.

description: The role of cytoreductive nephrectomy has become unclear since the introduction of immunotherapy which is now the backbone of the treatment for metastatic renal cell carcinoma. Different combinations are used based on the prognosis. Achieving a complete response would be ideal and includes radiographic disappearance of lesions. However, there have been a few reported cases of pathological complete response with persistent radiographic evidence of cancer. The authors report a case of pathological complete response despite persistent radiographic evidence of residual disease in a patient with metastatic renal cell carcinoma treated with Pembrolizumab and Axitinib. The patient subsequently underwent cytoreductive nephrectomy after the 13th dose of Pembrolizumab. The resected mass consisted of scar tissue with no viable tumor cells seen on pathology. only scar tissue. This case reveals that persistent radiographic evidence of the tumor may be explained by scar tissue, challenging the role of cytoreductive nephrectomy in the era of immunotherapy.
DOI: 10.6084/m9.figshare.22041560
title: Supplementary Material for: Discrimination Exposure and Polygenic Risk for Obesity in Adulthood: Testing Gene-Environment Correlations and Interactions

description: Introduction: Exposure to discrimination has emerged as a risk factor for obesity. It remains unclear, however, whether the genotype of the individual can modulate the sensitivity or response to discrimination exposure (gene x environment interaction) or increase the likelihood of experiencing discrimination (gene-environment correlation). Methods: This was an observational study of 4,102 White/European Americans in the Health and Retirement Study with self-reported, biological assessments, and genotyped data from 2006 to 2014. Discrimination was operationalized using the average of nine Everyday Discrimination scale items. Polygenic risk scores (PRS) for body mass index (BMI) and waist circumference (WC) were calculated using the weighted sum of risk alleles based on studies conducted by the Genetic Investigation of Anthropometric Traits (GIANT) consortium. Results: We found that greater PRS-BMI were significantly associated with more reports of discrimination (β= 0.04 ± 0.02; p= 0.037). Further analysis showed that measured BMI partially mediated the association between PRS-BMI and discrimination. There was no evidence that the association between discrimination and BMI, or the association between discrimination and WC, differed by PRS-BMI or PRS-WC, respectively. Discussion/Conclusion: Our findings suggest that individuals with genetic liability for obesity may experience greater discrimination in their lifetime, consistent with a gene-environment correlation hypothesis. There was no evidence of a gene-environment interaction. More genome-wide association studies in diverse populations are needed to improve generalizability of study findings. In the meantime, prevention and clinical intervention efforts that seek to reduce exposure to all forms of discrimination may help reduce obesity at the population-level.
DOI: 10.6084/m9.figshare.22133897
title: Supplementary Material for: Two very rare cases of metastatic thymic carcinoma with Sjogren’s syndrome: A Case series

description: Thymic tumors are rare thoracic malignancies with thymic carcinoma accounting for approximately 12% of all thymic tumours compared to thymomas which account for approximately 86%. Unlike thymomas, it is very rare for thymic carcinomas to be associated with autoimmune disorders or paraneoplastic syndromes. When these phenomena do occur, the vast majority are myasthenia gravis, pure red cell aplasia or systemic lupus erythematous (SLE). Paraneoplastic Sjogren’s syndrome is a rare complication of thymic carcinoma, with only two cases previously reported. Here we present two cases of patients with metastatic thymic carcinoma who developed autoimmune phenomena consistent with Sjogren’s syndrome without classical symptoms prior to treatment. One patient opted for surveillance of their malignancy while the other underwent chemoimmunotherapy with favourable results. These case reports describe two distinctive clinical presentations of a rare paraneoplastic phenomenon.
DOI: 10.6084/m9.figshare.22193338
title: Supplementary Material for: A novel glycolysis-related signature for predicting the prognosis and immune infiltration of uveal melanoma

description: Introduction As the most common aggressive intraocular cancer in adults, uveal melanoma (UVM) threatens the survival and vision of many people. Glycolysis is a novel hallmark of cancer, but the role of glycolysis-related genes in UVM prognosis remains unknown. The purpose of the study was to establish a glycolysis-related gene signature (GRGS) to predict UVM prognosis. Methods Raw data were obtained from TCGA-UVM and GSE22138 datasets. The GRGS was established by univariate, LASSO and multivariate Cox regression analyses. Kaplan‒Meier survival and time-dependent receiver operating characteristic curves were used to evaluate the predictive ability of the GRGS. The relationships of the GRGS with infiltrating immune cell levels and mutations were analyzed with CIBERSORT and maftools. Results A novel GRGS (risk score = 0.690861*ISG20 +0.070991*MET -0.227520*SDC2 +0.690223*FBP1 +0.048008*CLN6-0.128520* SDC3) was developed for predicting UVM prognosis. The GRGS had robust predictive stability in UVM. Enrichment annotation suggested that the high-risk group had stronger adaptive immune responses and that the low-risk group had more innate immune cell infiltration. Moreover, BAP1 mutation was related to high risk, and SF3B1 mutation was related to low risk. Conclusions This study developed and validated a novel GRGS to predict UVM prognosis and immune infiltration. The signature revealed an association between glycolysis-related genes and the tumor microenvironment, providing new insights into the role of glycolysis in UVM.
DOI: 10.6084/m9.figshare.22211989
title: Supplementary Material for: Human-centered design study to inform traceback cascade genetic testing programs at three integrated health systems

description: Introduction: A traceback genetic testing program for ovarian cancer has the potential to identify individuals with hereditary breast and ovarian cancer and their relatives. Successful implementation depends on understanding and addressing the experiences, barriers, and preferences of the people served. Methods: We conducted a remote, human-centered design research study of people with ovarian, fallopian tube, or peritoneal cancer (probands) and people with a family history of ovarian cancer (relatives) at three integrated health systems between May and September 2021. Participants completed activities to elicit their preferences about ovarian cancer genetic testing messaging, and to design their ideal experience receiving an invitation to participate in genetic testing. Interview data were analyzed using a rapid thematic analysis approach. Results: We interviewed 70 participants and identified five preferred experiences for a traceback program. Participants strongly prefer discussing genetic testing with their doctor but are comfortable discussing with other clinicians. The most highly preferred experience for both probands and relatives was to discuss with a knowledgeable clinician who can answer questions, followed by directed (sent directly to specific people) or passive (shared in a public area) communication. Repeated contact was acceptable for reminders. Discussion/Conclusion: Participants were open to receiving information about traceback genetic testing and recognized its value. Participants preferred discussing genetic testing with a trusted clinician. Directed communication was preferable to passive communication. Other valued information included how genetic tests help their family and the cost of genetic testing. These findings are informing traceback cascade genetic testing programs at all three sites.
DOI: 10.6084/m9.figshare.22219426
title: Supplementary Material for: Current management of patients with RPE65 mutation-associated Inherited Retinal Degenerations (RPE65-IRD) in Europe. Results of a 2 years follow-up multinational survey

description: Introduction: To evaluate the current management of RPE65-biallelic mutation-associated inherited retinal degeneration (RPE65-IRD) in Europe since market authorization of Voretigene Neparvovec (VN, LuxturnaTM) in 2018. By July 2022, over 200 patients have been treated outside the USA, of whom about 90% in Europe. We conducted among all centers of the European Vision Institute Clinical Research Network (EVICR.net) and health care providers (HCPs) of the European Reference Network dedicated to Rare Eye Diseases (ERN-Eye) the second multinational survey on management of IRDs in Europe elaborated by EVICR.net with a special focus on RPE65-IRD. Methods: An electronic survey questionnaire with 48 questions specifically addressing RPE65-IRD (2019 survey 35) was developed and sent by June 2021 to 95 EVICR.net centers and 40 ERN-EYE HCPs and affiliated members. Of note, 11 centers are members of both networks. Statistical analysis was performed with Excel and R. Results: The overall response rate was 44% (55/124); 26 centers follow RPE65 biallelic mutation-associated IRD patients. By June 2021, 8/26 centers have treated 57 RPE65-IRD cases (1 – 19/center, median 6), and 43 planned for treatment (range 0 – 10/center, median 6). The overall age range was 3 – 52 years, and on average 22% of the patients did not (yet) qualify for treatment (range 2 – 60%/center, median 15%). Main reasons were too advanced (range 0-100, median 75%) or mild disease (range 0-100, median 0). Eighty-three percent of centers (10/12) that follow RPE65 mutation-associated IRD patients treated with VN participate in the PERCEIVE registry (EUPAS31153, http://www.encepp.eu/encepp/viewResource.htm?id=37005). Quality of life and full field stimulus test (FST) improvements had the highest scores of the survey-reported outcome parameters in VN treatment follow-up. Discussion/Conclusion: This second multinational survey on management of RPE65-IRD by EVICR.net centers and ERN-Eye HCPs in Europe indicates that RPE65-IRD might be diagnosed more reliably in 2021 compared to 2019. By June 2021, 8/26 centers reported detailed results including VN treatment. Main reasons for non-treatment were too advanced or mild disease, followed by absence of two class 4 or 5 mutations on both alleles, or because of a too young age. Patient satisfaction with treatment was estimated to be high by 50% of the centers.
DOI: 10.6084/m9.figshare.22242079
title: Supplementary Material for: Idiopathic Acroosteolysis: A Novel Cutaneous Sign Can Help Identify the Condition Early

description: Acro-osteolysis (AO) is a rare condition characterized by resorption of the distal phalanges of the fingers and/or toes. It can be familial, idiopathic (IAO), occupational, or secondary. Other authors suggest a classification into primary (genetic disorders, lysosomal storage disorders) or secondary AO. Various skin and nail changes have been reported in this condition. However, the cutaneous change on the affected digit(s)/toe(s) during the natural course of AO has been poorly documented. A 5-year-old girl presented with a 3-month history of a distinct transverse boundary between normal skin proximally and affected crusted skin overlying osteolysis distally (‘split’ sign) on the plantar surface of the third toe. This boundary gradually elongated circumferentially to involve the dorsal surface. The mother gave a similar history of a delimitation line on the 2nd, 4th and 5th toes of the right foot with a duration of 3 months, one year, and two years, respectively, that disappeared before she noticed a shortening of those toes. X-rays revealed partial resorption of the terminal phalanx of the third toe and several lytic changes in the middle and terminal phalanx of the second, fourth, and fifth toes. The clinical features, radiology findings and a work-up that helped rule out conditions associated with AO (secondary AO) helped establish the diagnosis of IAO in our patient. This case study highlights that the natural course of IAO includes distinct skin findings, such as the ‘split’ sign that we describe. This sign can help identify the condition early.
DOI: 10.6084/m9.figshare.22249837
title: Supplementary Material for: Chromosome 18 loss of heterozygosity in small intestinal neuroendocrine tumours: Multi-omic and tumour composition analyses

description: Background: Small intestinal neuroendocrine tumours (siNETs) are rare neoplasms which present with low mutational burden and can be subtyped based on copy number variation (CNV). Currently, siNETs can be molecularly classified as having chromosome 18 loss of heterozygosity (18LOH), multiple CNVs (MultiCNV), or no CNVs. 18LOH tumours have better progression free survival when compared to MultiCNV and NoCNV tumours, however the mechanism underlying this is unknown, and clinical practice does not currently consider CNV status. Methods: Here, we use genome-wide tumour DNA methylation (n=54) and gene expression (n=20 matched to DNA methylation) to better understand how gene regulation varies by 18LOH status. We then use multiple cell deconvolution methods to analyse how cell composition varies between 18LOH status, and determine potential associations with progression free survival. Results: We identified 27,464 differentially methylated CpG sites and 12 differentially expressed genes between 18LOH and non-18LOH (MultiCNV + NoCNV) siNETs. Although few differentially expressed genes were identified, these genes were highly enriched with the differentially methylated CpG sites compared to the rest of the genome. We identified differences in tumour micro-environment between 18LOH and non-18LOH tumours, including CD14+ infiltration in a subset of non-18LOH tumours which had the poorest clinical outcomes. Conclusions: We identify a small number of genes which appear to be linked to the 18LOH status of siNETs, and find evidence of potential epigenetic dysregulation of these genes. We also find a potential prognostic marker for worse progression free outcomes in the form of higher CD14 infiltration in non-18LOH siNETs.
DOI: 10.6084/m9.figshare.22270147
title: Supplementary Material for: Bioenergy Treatment for Improving Well-Being: A Meta-Analysis

description: <b><i>Background:</i></b> Bioenergy treatment devices for self-treatment with the aim to improve well-being are widely available, have become popular, and are used by a rather large number of persons. Yet, a systematic analysis of the assumed effect of these devices has not yet been conducted. We meta-analyzed eight very similar studies of the Healy device to assess the joint effect size. <b><i>Method:</i></b> Eight studies with similar designs, some active controlled and some wait-list controlled, testing the Healy bioenergy device, were meta-analyzed. They were conducted by the producer of the device for quality assurance and further development of the application. An additional literature search revealed no additional, independent studies. <b><i>Result:</i></b> The overall effect size across studies, combining all active arms and averaging outcome measures, is Hedge’s g = 0.757 (random effects model, <i>I</i><sup>2</sup> = 85.8; <i>z</i> = 6.57; <i>p</i> &lt; 0.0001). The stronger active intervention against control yields a heterogeneous <i>g</i> = 0.825 (random effects, <i>I</i><sup>2</sup> = 82.5; <i>z</i> = 7.77; <i>p</i> &lt; 0.0001). Active treatments against each other result in a significant <i>g</i> = 0.29 (fixed effects, <i>I</i><sup>2</sup> = 0.0; <i>z</i> = 8.34; <i>p</i> &lt; 0.0001). <b><i>Discussion:</i></b> The highest effect sizes are produced by a measure of coherence, followed by the WHO5 well-being questionnaire, the Perceived Stress Scale, with the Measure Your Own Medical Outcome Profile, resulting in the smallest effect size. Heterogeneity can be partially explained by the type of control, with active control producing smaller and wait-list control producing larger outcomes. Another source of heterogeneity is the sequencing of studies. Effect sizes grew for three studies, which were similar, and then fell and remained very similar for the rest of the studies. A limitation of this analysis is the fact that all studies were conducted by the R and D Department of the producer of the device. <b><i>Conclusion:</i></b> In this meta-analysis, the Healy device showed considerable effects, improving general well-being in healthy individuals. Nonetheless, an independent confirmation of these findings would be desirable. Moreover, the potential mechanisms of effect of the bioenergy device remain unclear, and further studies addressing this research question are warranted.
DOI: 10.6084/m9.figshare.22284412
title: Supplementary Material for: Recurrent TAPO with Long-term Afatinib: A Case Report

description: Afatinib is the second generation EGFR-TKI. Recently, transient asymptomatic pulmonary opacity (TAPO) was reported in EGFR-mutation harboring NSCLC receiving osimertinib. However, TAPO related to other EGFR-TKI has not been reported. Here, we reported a case of TAPO related to afatinib in lung adenocarcinoma harboring EGFR mutation. A 64-year-old male had the diagnosis of stage IV (The 7th edition of the staging system by Union for International Cancer Control) lung adenocarcinoma habering EGFR del 19 mutation. He received afatinib 40mg per day from May, 2015. Partial response was achieved, though the dose was reduced to 30mg per day due to grade 3 rash. In January 2016, CT showed ground glass opacity in the right middle lobe, which resolved spontaneously two weeks later. He had no symptom and laboratory findings were not remarkable. Thereafter, recurrent GGO were revealed with chest CT, but all opacity improved without any medication (ie corticosteroids) or stopping afatinib. Therefore, we diagnosed a series of opacity as recurrent TAPO with afatinib. TAPO could occur with EGFR-TKI other than osimertinib. Further study is needed to establish the management of new opacity suggesting TAPO under EGFR-TKI treatment.
DOI: 10.6084/m9.figshare.22340971
title: Supplementary Material for: A metastatic breast tumor of an appendiceal signet ring cell carcinoma

description: A 54-year-old woman with pseudomyxoma peritonei from an appendiceal signet ring cell carcinoma was referred to our hospital. Right massive effusion with cytology-proven malignant cells was controlled with thoracentesis. Pathological study after intraperitoneal (IP) chemotherapy, hyperthermic IP chemotherapy, and cytoreductive surgery showed no malignant cells in the abdomen except for the appendix and greater omentum. Although the patient noticed a right breast mass, mammography (MMG) showed no abnormality. Ultrasonography (US) showed right breast masses consisting of hypo- and hyper-echoic areas without clear tumor margins. Magnetic resonance imaging (MRI) with contrast medium showed multiple lesions showing persistent enhancement pattern. Pathological study of the vacuum-assisted biopsy specimen showed signet ring cells growing in diffuse, trabecular, and linear fashions, leading to the diagnosis of metastatic breast tumors from the appendiceal signet ring cell carcinoma. Positron emission tomography (PET) / computed tomography (CT) showed no fluorodeoxyglucose uptake in the breasts. The patient was treated with simple mastectomy for local control. Pathological study of the resected breast showed predominant localization of the metastatic breast tumors deep in the mammary gland and lymphovascular invasion. Metastatic breast tumors from appendiceal signet ring cell carcinomas are extremely rare and can sometimes be difficult to be detected with mammography and PET/CT. General surgeon should note that appendiceal signet ring cell carcinomas can metastasize to the breast, presumably through lymphatic permeation from malignant pleural effusion, without abnormal MMG and PET/CT findings.
DOI: 10.6084/m9.figshare.22341076
title: Supplementary Material for: Real-world outcomes of ranibizumab treatment in French patients with visual impairment due to Macular Edema secondary to Retinal Vein Occlusion: 24-month results from the BOREAL-RVO study.

description: Introduction Information about real-world ranibizumab use is needed to optimize treatment of macular edema secondary to retinal vein occlusion (RVO). The BOREAL-RVO study assessed treatment use, effectiveness and safety of 24-month treatment with ranibizumab 0.5 mg in patients with visual impairment due to macular edema secondary to RVO in a real-world setting. Methods This was a multicenter, post-authorization, observational study in France, including patients starting ranibizumab for RVO. Primary endpoint was mean change from baseline in best-corrected visual acuity (BCVA) at Month 6. Secondary endpoints were mean changes from baseline in BCVA at Month 24 and central retinal thickness (CRT) at Months 6 and 24, and treatment use in real-world setting. Results 226 branch RVO (BRVO) and 196 central RVO (CRVO) patients were enrolled; 71.7% and 70.9% completed the 24-month follow-up, respectively. In BRVO, mean (SD) baseline BCVA was 55.2 (18.7) letters, with gains of 14.3 (13.7), 14.1 (16.5), 13.0 (17.5) and 11.4 (20.1) letters at Months 3, 6, 12 and 24. In CRVO, mean (SD) baseline BCVA was 40.4 (25.6) letters, with gains of 16.0 (21.2), 9.5 (25.4), 9.2 (27.7) and 8.3 (23.8) letters at Months 3, 6, 12 and 24. At Month 24, 52% of BRVO and 41% of CRVO patients had gains of 15 or more letters. In BRVO, mean (SD) CRT values at baseline and Months 3, 6, 12 and 24 were 550 (175), 315 (104), 343 (122), 335 (137) and 340 (105) μm. In CRVO, mean (SD) CRT values at baseline and Months 3, 6, 12 and 24 were 643 (217), 327 (152), 400 (203), 379 (175) and 348 (161) μm. On average, BRVO patients had 3.8 injections for 6.9 visits by Month 6, and 7.2 injections for 19.7 visits by Month 24. CRVO patients had 2.7 injections for 4.2 visits by Month 6, and 7.1 injections for 21.1 visits by Month 24. Factors predictive of better BCVA gain at Month 6 were age under 60 at baseline, lower baseline BCVA and BCVA gain at Month 3. There were no new safety findings. Conclusion Major improvements in BCVA and CRT were observed at Month 3 after the induction phase, and then was sustained up to Month 24, with a slight decrease, probably due to under-treatment. This study demonstrated ranibizumab to be a safe and effective treatment for BRVO and CRVO in the real-world setting, although more regular or pro-active treatment could further improve outcomes.
DOI: 10.6084/m9.figshare.22353637
title: Supplementary Material for: Brain-only metastasis and 10-year survival after curative gastric cancer resection: a case report

description: Gastric cancer (GC) usually metastasizes to locoregional lymph nodes, the peritoneum causing ascites, or to the liver and lungs, but rarely to the brain. Few cases of brain-only GC metastases have been reported, and the prognosis is very poor. We present a case of brain-only metastasis 2 years after curative GC surgery and chemotherapy, who visited the ER due to a headache. The patient underwent operative tumor resection of the brain with additional chemotherapy and is still alive and disease free 10-years after initial curative treatment. This case shows that as brain-only metastasis may have a better prognosis than that of systemic metastasis, aggressive treatment with radiotherapy or surgery with chemotherapy may be needed.