tbuckley/cabot-search huggingface dataset:
Technology-mediated communication with patients is a challenge for oncologists in the digitaland pandemic era and the winner is Whats App!
Authors: M. Torniai, G. Marcantognini, I. Fiordoliva, G. Mentrasti, V. Agostinelli, A. Pagliacci, R. Berardi, M. Caporossi
Journal: Clinical Cancer Research (2020)

Introduction: Since December 2019, coronavirus disease 2019 (COVID-19) has spread to every country, taking onpandemic proportions in few months  Physicians were asked to redefine ordinary hospital organization, reprogramming clinically differentiable activities  Materials and Methods: During the COVID pandemic our Institution was supported by a call center (CC, namedTOPS s r l ) to make a triage for cancer patients (pts) scheduled for follow-up in our outpatient clinics: C1 (dedicatedto female tumors), C2 (for gastrointestinal, urogenital, and thoracic tumors) and D1 (for tumors in over 5 years'follow-up)  We report preliminary data referred to the period 7th April-24th May, 2020  The activity was divided intotwo phases (F): April (F1) and May (F2)  In F2 pts were interviewed about their preferred visit modality  Physicalexamination was not postponed in case of clinical needs and first visits  Moreover, CC asked about programmedradiologic examinations and collected patients' feedback about the service  Results: A total of 587 pts have been contacted: 341 during F1 and 246 in F2  317/341 (93%) of the contacts in F1were successful  A gender-stratified analysis showed a majority of patients were female (72 4%)  The CC was ableto get in touch with 42 8% C1 pts, 34 6% C2 pts, and 22 6% D1 pts  During F2 246 pts (96 5%) of 255 planned wereefficiently contacted;female maintained the predominance (74 5%)  170 pts (69 1%) were scheduled in C1, 53 pts(21 5%) in C2, and 23 pts (9 4%) in D1  During F2, among the options provided 97 pts (39 4%) selected the phonecall, 142 pts (57 7%) decided for video chat (whatsapp), and 2 (0 8%) for video conference with a dedicated platform(google meet)  Only 5 pts (2 1%) expressed their intention to come to the hospital for examination  In 69 1% ofcases (170 pts) the programmed radiologic examinations were confirmed during the pandemic  According to somefavorable reports, the service was helpful in preserving continuum of care and preventing cancer pts from being leftaside in the emergency  Conclusions: This study show that cancer patients do appreciate technology-mediated follow-up visits, mainlyincluding video chat (whatsapp), and therefore we should take this into consideration  Furthermore, a dedicated CCmay be helpful to organize follow-up activities during COVID-19 and to strengthen the doctor-patient relationship insuch a critical moment
Multicenter randomized trial of endoscopic papillary large balloon dilation without sphincterotomy versus endoscopic sphincterotomy for removal of bile duct stones: MARVELOUS trial
Authors: Abdullah Emre Yıldırım, Buğra Tolga Konduk
Journal: Endoscopy (2021)

See also: Multicenter randomized trial of endoscopic papillary large balloon dilation without sphincterotomy versus endoscopic sphincterotomy for removal of bile duct stones: MARVELOUS trialEndoscopy 2020; 52(09): 736-744DOI: 10.1055/a-1145-3377
Mutational profile analysis and related outcomes in primary and metastatic pancreatic cancer (PC).
Authors: Abhinav Rohatgi, Aveena Desai, Alexander A. Hindenburg
Journal: Journal of Clinical Oncology (2021)

427 Background: PC has not been well molecularly characterized and there is an unmet need in our understanding of the biological properties of PC. One previous study has found that the presence of CDKN2A mutations is an independent negative prognostic OS indicator. We evaluated molecular analysis on tumor specimens to determine whether increased mutational burden affects survival. Methods: PDAC samples from patients seen at the NYU Perlmutter Cancer Center at Winthrop Oncology Hematology Associates between 2015-2020 were profiled using next generation sequencing through Foundation Cdx. Genomic data was correlated with mined clinical data. Pt outcomes were correlated with the presence of mutations defined in 3 categories: 3 or less mutations, 4 mutations, 5 or more mutations. Results: Our cohort (N = 81) included 42% men and 58% women. 55% percent had primary (localized and locally advanced) disease and 44% had stage IV disease. Genetic mutations were most commonly found in KRAS, CDKN2A, TP53, NOTCH, SMAD4. Mutations seen less frequently were BRAF, HER2, RB1, ARID1A, MTAP, MLL, BRCA2. 43% of pts had 3 or less mutations, 15% 4 mutations, 42% had 5 or more mutations. There was no difference in number of mutations present between primary vs metastatic cancers. Median PFS was 13.5 months and overall survival (OS) for all pts was 20.0 months. The OS in primary group was 26.1 mos while it was 12.4 mos in the metastatic group. Patients with 5+ mutations had a 1.5 mos decreased OS and a 10% decreased 24-mos OS%. When stratified by primary (localized) disease, there was an 8.3 mos decrease in the 5+ mutation group vs 3 mutation group. When stratified by metastatic disease at diagnosis, there was no appreciable difference in OS between mutational groups. Conclusions: In the primary PC cohort, increasing burden of gene alteration patterns from 3 to 5+ mutations is correlated with decreased overall survival. The effect did not extend to the metastatic group likely due to disease burden driving survival whereas in primary PC group, survival reflected the tumor biology. This suggests that as additional carcinogenic pathways (DNA repair, growth, apoptosis) are mutated, tumor biology becomes more aggressive. This study provides an impetus for mutational profiling in early stage pancreatic cancer. These findings can contribute to the use of molecular profiles for prognostication and further development of targeted therapies. [Table: see text]
Reply to Singh et al.
Authors: Gin-Ho Lo
Journal: Endoscopy (2021)

See also: A prospective, randomized trial of thrombin versus cyanoacrylate injection in the control of acute gastric variceal hemorrhageEndoscopy 2020; 52(07): 548-555DOI: 10.1055/a-1127-3170 See also: Thrombin or glue – you decideEndoscopy 2021; 53(02): 210-210DOI: 10.1055/a-1233-8902
High-resolution analysis of cell-state transitions in yeast suggests widespread transcriptional tuning by alternative starts
Authors: Minghao Chia, Cai Li, Sueli Marques, Vicente Pelechano, Nicholas M. Luscombe, Folkert J. van Werven
Journal: Genome biology (2021)

Abstract Background The start and end sites of messenger RNAs (TSSs and TESs) are highly regulated, often in a cell-type-specific manner. Yet the contribution of transcript diversity in regulating gene expression remains largely elusive. We perform an integrative analysis of multiple highly synchronized cell-fate transitions and quantitative genomic techniques in Saccharomyces cerevisiae to identify regulatory functions associated with transcribing alternative isoforms. Results Cell-fate transitions feature widespread elevated expression of alternative TSS and, to a lesser degree, TES usage. These dynamically regulated alternative TSSs are located mostly upstream of canonical TSSs, but also within gene bodies possibly encoding for protein isoforms. Increased upstream alternative TSS usage is linked to various effects on canonical TSS levels, which range from co-activation to repression. We identified two key features linked to these outcomes: an interplay between alternative and canonical promoter strengths, and distance between alternative and canonical TSSs. These two regulatory properties give a plausible explanation of how locally transcribed alternative TSSs control gene transcription. Additionally, we find that specific chromatin modifiers Set2, Set3, and FACT play an important role in mediating gene repression via alternative TSSs, further supporting that the act of upstream transcription drives the local changes in gene transcription. Conclusions The integrative analysis of multiple cell-fate transitions suggests the presence of a regulatory control system of alternative TSSs that is important for dynamic tuning of gene expression. Our work provides a framework for understanding how TSS heterogeneity governs eukaryotic gene expression, particularly during cell-fate changes.
Obesity-associated deficits in inhibitory control are phenocopied to mice through gut microbiota changes in one-carbon and aromatic amino acids metabolic pathways
Authors: María Arnoriaga-Rodríguez, Jordi Mayneris-Perxachs, Oren Contreras-Rodríguez, Aurelijus Burokas, Juan-Antonio Ortega-Sanchez, Gerard Blasco, Claudia Coll, Carles Biarnés, Anna Castells-Nobau, Josep Puig, Josep Garre-Olmo, Rafel Ramos, Salvador Pedraza, Ramon Brugada, Joan C Vilanova, Joaquín Serena, Jordi Barretina, Jordi Gich, Vicente Pérez-Brocal, Andrés Moya, Xavier Fernández-Real, Lluis Ramio-Torrentà, Reinald Pamplona, Joaquim Sol, Mariona Jové, Wifredo Ricart, Manuel Portero-Otin, Rafael Maldonado, Jose Manuel Fernández-Real
Journal: Gut (2021)

Background Inhibitory control (IC) is critical to keep long-term goals in everyday life. Bidirectional relationships between IC deficits and obesity are behind unhealthy eating and physical exercise habits. Methods We studied gut microbiome composition and functionality, and plasma and faecal metabolomics in association with cognitive tests evaluating inhibitory control (Stroop test) and brain structure in a discovery (n=156), both cross-sectionally and longitudinally, and in an independent replication cohort (n=970). Faecal microbiota transplantation (FMT) in mice evaluated the impact on reversal learning and medial prefrontal cortex (mPFC) transcriptomics. Results An interplay among IC, brain structure (in humans) and mPFC transcriptomics (in mice), plasma/faecal metabolomics and the gut metagenome was found. Obesity-dependent alterations in one-carbon metabolism, tryptophan and histidine pathways were associated with IC in the two independent cohorts. Bacterial functions linked to one-carbon metabolism ( thyX,dut, exodeoxyribonuclease V), and the anterior cingulate cortex volume were associated with IC, cross-sectionally and longitudinally. FMT from individuals with obesity led to alterations in mice reversal learning. In an independent FMT experiment, human donor’s bacterial functions related to IC deficits were associated with mPFC expression of one-carbon metabolism-related genes of recipient’s mice. Conclusion These results highlight the importance of targeting obesity-related impulsive behaviour through the induction of gut microbiota shifts.
Plasma ACE2 activity is persistently elevated following SARS-CoV-2 infection: implications for COVID-19 pathogenesis and consequences
Authors: Sheila K. Patel, Jennifer A. Juno, Wen Shi Lee, Kathleen M. Wragg, P. Mark Hogarth, Stephen J. Kent, Louise M. Burrell
Journal: European Respiratory Journal (2021)

<b>Plasma ACE2 activity is persistently elevated in patients after COVID-19 infection. Larger studies are needed to determine if this identifies people at risk of prolonged illness following COVID-19.</b>https://bit.ly/2XQlrYF
Targeting the AnxA1/Fpr2/ALX pathway regulates neutrophil function, promoting thromboinflammation resolution in sickle cell disease
Authors: Junaid Ansari, Elena Y. Senchenkova, Shantel A. Vital, Zaki Al-Yafeai, Gaganpreet Kaur, Erica M. Sparkenbaugh, A. Wayne Orr, Rafal Pawlinski, Robert P. Hebbel, D. Neil Granger, Paul Kubes, Felicity N. E. Gavins
Journal: Blood (2021)
Serine Biosynthesis Is a Metabolic Vulnerability in IDH2-Driven Breast Cancer Progression
Authors: Georgina D. Barnabas, Joo Sang Lee, Tamar Shami, Michal Harel, Lir Beck, Michael Selitrennik, Livnat Jerby-Arnon, Neta Erez, Eytan Ruppin, Tamar Geiger
Journal: Cancer Research (2021)

Abstract Cancer-specific metabolic phenotypes and their vulnerabilities represent a viable area of cancer research. In this study, we explored the association of breast cancer subtypes with different metabolic phenotypes and identified isocitrate dehydrogenase 2 (IDH2) as a key player in triple-negative breast cancer (TNBC) and HER2. Functional assays combined with mass spectrometry–based analyses revealed the oncogenic role of IDH2 in cell proliferation, anchorage-independent growth, glycolysis, mitochondrial respiration, and antioxidant defense. Genome-scale metabolic modeling identified phosphoglycerate dehydrogenase (PHGDH) and phosphoserine aminotransferase (PSAT1) as the synthetic dosage lethal (SDL) partners of IDH2. In agreement, CRISPR-Cas9 knockout of PHGDH and PSAT1 showed the essentiality of serine biosynthesis proteins in IDH2-high cells. The clinical significance of the SDL interaction was supported by patients with IDH2-high/PHGDH-low tumors, who exhibited longer survival than patients with IDH2-high/PHGDH-high tumors. Furthermore, PHGDH inhibitors were effective in treating IDH2-high cells in vitro and in vivo. Altogether, our study creates a new link between two known cancer regulators and emphasizes PHGDH as a promising target for TNBC with IDH2 overexpression. Significance: These findings highlight the metabolic dependence of IDH2 on the serine biosynthesis pathway, adding an important layer to the connection between TCA cycle and glycolysis, which can be translated into novel targeted therapies.
At the Cusp — Reimagining Infective Endocarditis Care amid the Opioid Epidemic
Authors: Michael A. Incze
Journal: New England Journal of Medicine (2021)

Interview with Dr. Michael Incze on building multidisciplinary care teams for endocarditis and reducing stigma related to substance use. (07:55)Download The opioid epidemic has transformed the epidemiology of infective endocarditis. Treatment models focused on managing acute complications could be expanded to encompass substance use disorder treatment, intensive case management, supportive housing, and primary care.
Post hoc analysis in patients (pts) with unresectable hepatocellular carcinoma (uHCC) who progressed to Child-Pugh B (CPB) liver function in the phase III REFLECT study of lenvatinib (LEN).
Authors: Jasmine Huynh, May Thet Cho, Edward Jae-Hoon Kim, Min Ren, Carol Robbins, Carlos Amaya-Chanaga, Arndt Vogel
Journal: Journal of Clinical Oncology (2021)

298 Background: The treatment landscape for pts with uHCC has recently expanded. However, there is an unmet need for effective treatment options in CPB pts. LEN is approved first-line in uHCC based on the REFLECT study (Child-Pugh A [CPA] pts were allowed, per inclusion criteria). In a prior analysis of REFLECT, pts treated with LEN benefited irrespective of baseline liver function (ALBI grade 1 or 2; Child-Pugh score 5 or 6). To determine outcomes in pts with reduced liver function, we report a post hoc analysis of key efficacy and safety results in LEN-treated pts from REFLECT who progressed to CPB and those who did not within the first 8 weeks of treatment. Methods: In REFLECT, pts with uHCC were randomized 1:1 to LEN (per bodyweight: 12 mg/day for ≥60 kg; 8 mg/day for &lt; 60 kg) or sorafenib (400 mg twice daily) in 28-day cycles. This analysis assessed ORR. Landmark analyses (starting at week 8) of PFS, time-to-progression (TTP), and OS in CPB pts and in pts who remained CPA at 8 weeks post-randomization were also conducted. Tumors were assessed by mRECIST by independent imaging review. Safety was also assessed from baseline. Results: This subgroup analysis included LEN-treated pts (n = 60) who progressed to CPB within the first 8 weeks of treatment (CPB pts) and 413 pts who did not (CPA pts). At baseline, 26.7% and 73.1% of pts had an ALBI grade of 1 and 73.3% and 26.9% of pts had an ALBI grade of 2 in CPB and CPA pts, respectively. ORR was 28.3% (95% CI 16.9–39.7) for CPB pts and 42.9% (95% CI 38.1–47.6) for CPA pts. A landmark analysis showed a median PFS of 3.7 mos (95% CI 1.8–7.4) for CPB pts and 6.5 mos (95% CI 5.6–7.4) for CPA pts from the week 8 timepoint. Landmark analyses at week 8 also showed that the median TTP was 5.6 mos (95% CI 3.5–9.3) for CPB pts and 7.3 mos (95% CI 5.6–7.4) for CPA pts; the median OS was 6.8 mos (95% CI 2.6–10.3) for CPB pts and 13.3 mos (95% CI 11.6–16.1) for CPA pts per week 8 landmark analyses. As expected, efficacy appeared to be greater in CPA pts versus CPB pts; however, OS of 6.8 months in CPB pts after the week 8 landmark is notable. Moreover, median duration of treatment was 3.2 mos for CPB pts and 6.9 mos for CPA pts, thereby suggesting CPB pts can remain on LEN. The incidence of grade ≥3 treatment-related AEs (TRAEs) was 71.7% in CPB pts and 54.7% in CPA pts. TRAEs leading to discontinuation occurred in 18.3% of CPB pts and 7.5% of CPA pts. Conclusions: In this post hoc analysis of pts in REFLECT, we examine the key efficacy and safety results for LEN-treated pts who progressed to CPB by week 8. This post hoc analysis is limited by its descriptive nature; however, the results indicate that further study of LEN in CPB pts with uHCC is warranted. Clinical trial information: NCT01761266.
Impact of COVID-19 on Cervical Cancer Screening Rates Among Women Aged 21–65 Years in a Large Integrated Health Care System — Southern California, January 1–September 30, 2019, and January 1–September 30, 2020
Authors: Maureen J. Miller, Lanfang Xu, Jin Qin, Erin E. Hahn, Quyen Ngo-Metzger, Brian Mittman, Devansu Tewari, Melissa Hodeib, Patricia Wride, Mona Saraiya, Chun R. Chao
Journal: MMWR Morbidity and Mortality Weekly Report (2021)

On March 19, 2020, the governor of California issued a statewide stay-at-home order to contain the spread of SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19).* The order reduced accessibility to and patient attendance at outpatient medical visits,† including preventive services such as cervical cancer screening. In-person clinic visits increased when California reopened essential businesses on June 12, 2020.§ Electronic medical records of approximately 1.5 million women served by Kaiser Permanente Southern California (KPSC), a large integrated health care system, were examined to assess cervical cancer screening rates before, during, and after the stay-at-home order. KPSC policy is to screen women aged 21-29 years every 3 years with cervical cytology alone (Papanicolaou [Pap] test); those aged 30-65 years were screened every 5 years with human papillomavirus (HPV) testing and cytology (cotesting) through July 15, 2020, and after July 15, 2020, with HPV testing alone, consistent with the latest recommendations from U.S. Preventive Services Task Force.¶ Compared with the 2019 baseline, cervical cancer screening rates decreased substantially during the stay-at-home order. Among women aged 21-29 years, cervical cytology screening rates per 100 person-months declined 78%. Among women aged 30-65 years, HPV test screening rates per 100 person-months decreased 82%. After the stay-at-home order was lifted, screening rates returned to near baseline, which might have been aided by aspects of KPSC's integrated, organized screening program (e.g., reminder systems and tracking persons lost to follow-up). As the pandemic continues, groups at higher risk for developing cervical cancers and precancers should be evaluated first. Ensuring that women receive preventive services, including cancer screening and appropriate follow-up in a safe and timely manner, remains important.
<i>Nras</i> <i>Q61R/+</i> and <i>Kras</i> <i>−/−</i> cooperate to downregulate Rasgrp1 and promote lympho-myeloid leukemia in early T-cell precursors
Authors: Zhi Wen, Grant Yun, Alexander Hebert, Guangyao Kong, Erik A. Ranheim, Remington Finn, Adhithi Rajagoplan, Shuyi Li, Yun Zhou, Mei Yu, Alisa Damnernsawad, Jeroen P. Roose, Joshua J. Coon, Renren Wen, Demin Wang, Jing Zhang
Journal: Blood (2021)
NICE recommends new CAR-T treatment for lymphoma for some patients on NHS
Authors: Elisabeth Mahase
Journal: BMJ (2021)

Some patients with relapsed or refractory mantle cell lymphoma will now be able to access a new CAR-T treatment, which uses their own re-engineered white blood cells to attack cancer cells, through the NHS.1

The new treatment has been made available after recommendation from the National Institute for Health and Care Excellence (NICE). The guidance, issued on 19 January, says that Tecartus (also known as autologous anti-CD19-transduced CD3+) can be …
Parkinson Disease (Japanese Version)
Authors: Houman Homayoun
Journal: Annals of Internal Medicine (2018)

In the Clinic4 September 2018Parkinson Disease (Japanese Version)Correction(s) for this article:CorrectionsNov 2022Correction: Japanese Translations of In the ClinicFREEHouman Homayoun, MDHouman Homayoun, MDUniversity of Pittsburgh Medical Center, Pittsburgh, Pennsylvania (H.H.)Author, Article, and Disclosure Informationhttps://doi.org/10.7326/IsTranslatedFrom_AITC201809040_Japanese SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Editors' Note: This article (available in PDF format) is the translated Japanese version of In the Clinic: Parkinson Disease (Homayoun H. Parkinson Disease. Ann Intern Med. 2018;169:ITC33-ITC48. doi:10.7326/AITC201809040). Author, Article, and Disclosure InformationAffiliations: University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania (H.H.)Correction: This article was updated on 1 November 2022 to remove the glossary of terms, which was not present on the original publication, and to indicate the translators of the article.Acknowledgment: The author thanks Kelvin L. Chou, MD, author of the previous version of this In the Clinic.Funding Source: American College of Physicians.Disclosures: Dr. Homayoun, ACP Contributing Author, reports personal fees (honoraria) from AbbVie and Medtronic. Disclosures can also be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M18-0853.With the assistance of additional physician writers, the editors of Annals of Internal Medicine develop In the Clinic using MKSAP and other resources of the American College of Physicians.In the Clinic does not necessarily represent official ACP clinical policy. For ACP clinical guidelines, please go to https://www.acponline.org/clinical_information/guidelines/. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoParkinson Disease Houman Homayoun Correction: Japanese Translations of In the Clinic Metrics Cited byCorrection: Japanese Translations of In the ClinicPlasma miR-153 and miR-223 Levels as Potential Biomarkers in Parkinson's Disease 4 September 2018Volume 169, Issue 5Page: JITC33-JITC48 ePublished: 19 January 2021 Issue Published: 4 September 2018 Copyright & PermissionsCopyright © 2018 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Intrusion Through the Fragile Back Door: Immature Plaque Microvessels as Entry Portals for Leukocytes and Erythrocytes in Atherosclerosis**Editorials published in the Journal of the American College of Cardiologyreflect the views of the authors and do not necessarily represent the views of JACCor the American College of Cardiology.
Authors: Sebastian F. Mause, Christian Weber
Journal: Journal of the American College of Cardiology (2009)