tbuckley/cabot-search huggingface dataset:
&lt;i&gt;Lactobacillus&lt;/i&gt; attenuates progression of nonalcoholic fatty liver disease by lowering cholesterol and steatosis
Authors: Na Young Lee, Min Jea Shin, Gi Soo Youn, Sang Jun Yoon, Ye Rin Choi, Hyeong Seop Kim, Haripriya Gupta, Sang Hak Han, Byoung Kook Kim, Do Yup Lee, Tae Sik Park, Hotaik Sung, Byung Yong Kim, Ki Tae Suk
Journal: Clinical and Molecular Hepatology (2020)

Background/Aims: Nonalcoholic fatty liver disease (NAFLD) is closely related to gut-microbiome. There is a paucity of research on which strains of gut microbiota affect the progression of NAFLD. This study explored the NAFLD-associated microbiome in humans and the role of &lt;i&gt;Lactobacillus&lt;/i&gt; in the progression of NAFLD in mice.Methods: The gut microbiome was analyzed via next-generation sequencing in healthy people (n=37) and NAFLD patients with elevated liver enzymes (n=57). Six-week-old male C57BL/6J mice were separated into six groups (n=10 per group; normal, Western, and four Western diet + strains [10&lt;sup&gt;9&lt;/sup&gt; colony-forming units/g for 8 weeks; &lt;i&gt;L. acidophilus&lt;/i&gt;, &lt;i&gt;L. fermentum&lt;/i&gt;, &lt;i&gt;L. paracasei&lt;/i&gt;, and &lt;i&gt;L. plantarum&lt;/i&gt;]). Liver/body weight ratio, liver pathology, serum analysis, and metagenomics in the mice were examined.Results: Compared to healthy subjects (1.6±4.3), NAFLD patients showed an elevated &lt;i&gt;Firmicutes/Bacteroidetes&lt;/i&gt; ratio (25.0±29.0) and a reduced composition of Akkermansia and L. murinus (&lt;i&gt;P&lt;/i&gt;&lt;0.05). In the animal experiment, L. acidophilus group was associated with a significant reduction in liver/body weight ratio (5.5±0.4) compared to the Western group (6.2±0.6) (&lt;i&gt;P&lt;/i&gt;&lt;0.05). &lt;i&gt;L. acidophilus&lt;/i&gt; (41.0±8.6), &lt;i&gt;L. fermentum&lt;/i&gt; (44.3±12.6), and &lt;i&gt;L. plantarum&lt;/i&gt; (39.0±7.6) groups showed decreased cholesterol levels compared to the Western group (85.7±8.6) (&lt;i&gt;P&lt;/i&gt;&lt;0.05). In comparison of steatosis, &lt;i&gt;L. acidophilus&lt;/i&gt; (1.9±0.6), &lt;i&gt;L. plantarum&lt;/i&gt; (2.4±0.7), and &lt;i&gt;L. paracasei&lt;/i&gt; (2.0±0.9) groups showed significant improvement of steatosis compared to the Western group (2.6±0.5) (&lt;i&gt;P&lt;/i&gt;&lt;0.05).Conclusions: Ingestion of &lt;i&gt;Lactobacillus&lt;/i&gt;, such as &lt;i&gt;L. acidophilus&lt;/i&gt;, &lt;i&gt;L. fermentum&lt;/i&gt;, and &lt;i&gt;L. plantarum&lt;/i&gt;, ameliorates the progression of nonalcoholic steatosis by lowering cholesterol. The use of &lt;i&gt;Lactobacillus&lt;/i&gt; can be considered as a useful strategy for the treatment of NAFLD.
EPID-10. MITOCHONDRIAL DNA SEQUENCE VARIATION AND RISK OF GLIOMA
Authors: Claudine Samanic, Jamie Teer, Zachary Thompson, Jordan Creed, Louis Nabors, Sion Williams, Kathleen Egan
Journal: Neuro-Oncology (2020)

Abstract Malignant gliomas are the most common primary adult brain tumors, with poor prognosis and ill-defined etiology. Mitochondrial DNA (mtDNA) sequence variants and haplogroups have been linked with certain cancers, but research on glioma is lacking. We examined the association of germline mtDNA variants and haplogroups with glioma risk in 1,654 glioma cases and 1,065 controls from a US case-control study, and 427 glioma cases and 1,541 controls from the UK Biobank, all genotyped using the UKBiobank array with 276 tiled mtDNA variants. The analysis was restricted to participants of European ancestry, and risk of glioblastoma (GBM) and lower grade glioma (LGG) was examined separately. Distribution of mitochondrial haplogroups (H/HV,I,J,K,R,T,U,V,W,X) were similar in both study populations, with 46.4% and 48.1% of controls in the US and UK studies respectively, identified as H/HV, the most common haplogroup. In the US study there was an inverse association between haplogroup W and glioma (OR=0.43, 95%CI: 0.23–0.79) when compared with the H/HV haplogroup, which was not seen in the UK study (OR=1.10, 95%CI: 0.49–2.49). In the US study, a significant inverse association was observed with the previously reported mtDNA variant m.14798T &amp;gt; C (PMID: 31323957), resulting in the amino acid substitution F18L, for LGG (OR=0.73; 95%CI: 0.53–0.99) though not for GBM (OR=0.86; 95%CI: 0.66–1.11). In the UK study, the F18L substitution was associated with an increased risk of GBM (OR=1.48; 95%CI: 1.07–2.04), and no association was observed for LGG (OR=0.95; 95%CI: 0.53–1.68). Among cases in the US study with isocitrate dehydrogenase 1 (IDH1) status available (747 gliomas), a nonsignificant inverse association of the F18L substitution was observed in glioma cases with wild type (OR=0.72; 95%CI: 0.52–1.01) but not mutant (OR=1.08; 95%CI: 0.70–1.69) IDH1. No other common mtDNA variant (minor allele &amp;gt; 5%) was associated with glioma risk in either study. These associations merit further study.
Convergent Rewiring of the Virulence Regulatory Network Promotes Adaptation of <i>Ralstonia solanacearum</i> on Resistant Tomato
Authors: Rekha Gopalan-Nair, Marie-Françoise Jardinaud, Ludovic Legrand, David Landry, Xavier Barlet, Céline Lopez-Roques, Céline Vandecasteele, Olivier Bouchez, Stéphane Genin, Alice Guidot
Journal: Molecular Biology and Evolution (2020)

The evolutionary and adaptive potential of a pathogen is a key determinant for successful host colonization and proliferation but remains poorly known for most of the pathogens. Here, we used experimental evolution combined with phenotyping, genomics, and transcriptomics to estimate the adaptive potential of the bacterial plant pathogen Ralstonia solanacearum to overcome the quantitative resistance of the tomato cultivar Hawaii 7996. After serial passaging over 300 generations, we observed pathogen adaptation to within-plant environment of the resistant cultivar but no plant resistance breakdown. Genomic sequence analysis of the adapted clones revealed few genetic alterations, but we provide evidence that all but one were gain of function mutations. Transcriptomic analyses revealed that even if different adaptive events occurred in independently evolved clones, there is convergence toward a global rewiring of the virulence regulatory network as evidenced by largely overlapping gene expression profiles. A subset of four transcription regulators, including HrpB, the activator of the type 3 secretion system regulon and EfpR, a global regulator of virulence and metabolic functions, emerged as key nodes of this regulatory network that are frequently targeted to redirect the pathogen's physiology and improve its fitness in adverse conditions. Significant transcriptomic variations were also detected in evolved clones showing no genomic polymorphism, suggesting that epigenetic modifications regulate expression of some of the virulence network components and play a major role in adaptation as well.
RONC-24. PROTON THERAPY FOR PEDIATRIC EPENDYMOMA: MATURE OUTCOMES FROM THE UNIVERSITY OF FLORIDA AND MASSACHUSETTS GENERAL HOSPITAL
Authors: Daniel J Indelicato, Myrsini Ioakeim-Ioannidou, Julie Bradley, Raymond Mailhot-Vega, Christopher Morris, Nancy Tarbell, Torunn Yock, Shannon MacDonald
Journal: Neuro-Oncology (2020)

Abstract OBJECTIVE Report long-term efficacy and toxicity of proton therapy for pediatric ependymoma. MATERIALS AND METHODS Between 2000–2017, 318 children with nonmetastatic grade II/III intracranial ependymoma received proton therapy at Massachusetts General Hospital and the University of Florida. Median age was 3.5 years (range, 0.7–21.3 years); 56% were male. Most (69%) tumors were in the posterior fossa and classified as WHO grade III (64%). Eighty-four percent had a gross total or near total tumor resection before radiotherapy and 30% received chemotherapy. Median radiation dose was 55.8 CGE (range, 50.4–59.4 CGE). RESULTS Median follow-up was 6 years (range, 0.6–19.2 years). Seven-year local control, progression-free survival, and overall survival rates were 77.1% (95% CI 71.7–81.7%), 64.4% (95% CI 58.6–69.8%), and 82% (76.9–86.2%), respectively. Subtotal resection was associated with inferior local control (60% vs 80%; p&amp;lt;0.01), progression-free survival (49% vs 67%; p&amp;lt;0.01), and overall survival (69% vs 84%; p&amp;lt;0.05). Male gender was associated with inferior progression-free (59% vs 71%; p&amp;lt;0.01) and overall survival (77% vs 89%; p&amp;lt;0.05). Twenty patients (6.2%) require hearing aids; of these, 12/20 received cisplatin. Grade 3+ brainstem toxicity rate was 1.6% and more common in patients who received &amp;gt;54 CGE. The rate of second malignancy was 0.9%. CONCLUSION Proton therapy offers commensurate disease control to modern photon therapy without unexpected toxicity. The high rate of long-term survival justifies efforts to reduce radiation exposure in this young population with brain tumors. Independent of modality, this large series confirms extent of resection as the most important modifiable factor for survival.
CTNI-08. A PHASE 1–2 CLINICAL TRIAL OF EO1001, A NOVEL IRREVERSIBLE PAN-ErbB INHIBITOR WITH PROMISING BRAIN PENETRATION
Authors: Helen Wheeler, Jeffrey Bacha, Dennis Brown, Sarath Kanekal, Neil Sankar, Ian Nisbet, Kathy Skoff, Wang Shen, Wang ZhenZhong, Harry Pedersen
Journal: Neuro-Oncology (2020)

Abstract Mutations causing errant ErbB activation are implicated in many cancers, including tumors correlated with high incidence of CNS metastasis. ErbB family member “crosstalk” is associated with rapid development acquired resistance to ErbB TKIs, particularly in advanced disease. The development of agents targeting multiple ErbB receptors has shown promise but has been limited by toxicity and poor brain penetration. EO1001 is a first-in-class, oral, brain penetrating, irreversible pan-ErbB inhibitor. Preclinical data suggests a favorable pharmacokinetic and safety profile and promising activity against ErbB-driven cancers in patient-derived xenograft models. EO1001 is being advanced into first-in-man studies under the Australia Clinical Trials Notification (CTN) scheme (ANZCTR Reg.#ACTRN12320000589343p). METHODS: Adult patients with confirmed ErbB-positive cancer, including patients with CNS involvement, who have progressed after standard of care therapy, with adequate bone marrow, renal and liver function are eligible. Toxicity is assessed by NCI CCTCAEv5 and tumor response is assessed by RECISTv1.1. CNS exposure is evaluated in in select patients with confirmed CNS disease involvement via CSF collection. An accelerated dose-escalation design is employed. One subject per dose cohort will be recruited until drug related toxicity (≥ G2) is observed, after which dose escalation will revert to a 3 + 3 design to determine the maximum tolerated dose (MTD). DOSE ESCALATION: Cycle 1: Patients will receive a single dose EO1001 on day 1 and single dose pharmacokinetics will be performed. Beginning on day 8, EO1001 will be administered once daily for 21 days; multi-dose pharmacokinetics will be performed. Cycles 2–6: Oral EO1001 will be administered once daily in continuous 28-day cycles for up to 20 weeks. MTD EXPANSION: Oral EO1001 will be administered once daily at the MTD in continuous 28-day cycles for up to 6 cycles (24 weeks). An update on the progress of this trial will be presented.
CBIO-23. PROXIMITY-DEPENDENT BIOTIN IDENTIFICATION (BIOID2) INDICATES MEMBRANE TRAFFICKING AND VESICLE TRANSPORT AS A POTENTIAL NOVEL FUNCTION OF EXTRACELLULAR SIGNAL-REGULATED KINASE 5 (ERK5)
Authors: Ann-Catherine Stanton, Antonius Koller, Robert Koncar, Brian Golbourn, Katharine Halligan, Matthew Halbert, Stephen Mack, Ian Pollack, Sameer Agnihotri
Journal: Neuro-Oncology (2020)

Abstract INTRODUCTION Pediatric High-Grade Gliomas (PHGG), which include Diffuse Midline Gliomas (DMG), are a leading cause of brain tumor death in children. Our recent work has identified extracellular signal-regulated kinase 5 (ERK5) as a critical mediator of cell survival in DMG, as ERK5 knockdown decreases cell proliferation and extends survival time in orthotopic xenograft mice. Further investigation into the structure of ERK5 shows that it has a kinase domain and, unlike other ERKs, a transactivation domain, and both are important for promoting cell proliferation. HYPOTHESIS AND METHODS We hypothesize that identifying interactors and substrates of ERK5 could identify clinically actionable proteins and provide a more mechanistic insight into ERK5 in the progression of PHGGS. To determine protein–protein associations (PPAs), we employed the proximity-dependent biotin identification (BioID2) method and generated inducible ERK5-BioID2 and ERK2-BioID2 constructs to overcome barriers of conventional screening methods for PPAs. ERK2, similar in structure but much more studied than ERK5, was used as a comparison. Using DIPG lines as proof of principle, we performed streptavidin pull down assays for putative biotinylated ERK PPA and followed with mass spectrometry to identify the ERK2 and ERK5 interactomes. RESULTS Using data-dependent acquisition (DDA), we identified several unique and common interactors of ERK5 compared to ERK2. Through STRING network and pathway analysis, we identified a novel function of ERK5 with respect to membrane trafficking and vesicle transport. Identification of interactors with ERK5 may lead to effective therapeutic combinations. Our current work is focused on validating these interactions and the function of ERK5 in these biological processes. CONCLUSIONS Currently, ERK5 is not as understood as ERK1 or ERK2. Identification of interactors and substrates of ERK5 will further our understanding of PHGG biology, and may lead to identifying druggable targets and pathways.
Therapeutic Potential of an Antibody Targeting the Cleaved Form of Mutant Calreticulin in Myeloproliferative Neoplasms
Authors: Yoshihiko Kihara, Marito Araki, Misa Imai, Yosuke Mori, Mei Horino, Satoko Ogata, Syunpei Yoshikawa, Teppei Taguchi, Nami Masubuchi, Yo Mabuchi, Yinjie Yang, Yasutaka Fukuda, Soji Morishita, Takehiro Suzuki, Naoshi Domae, Motoyuki Shimonaka, Chihiro Akazawa, Akimichi Ohsaka, Norio Komatsu
Journal: Blood (2020)
A cyclic peptide retards the proliferation of DU145 prostate cancer cells in vitro and in vivo through inhibition of FGFR2
Authors: Yibo Zhang, Man Ouyang, Hailong Wang, Bihui Zhang, Wenhua Guang, Ruiwu Liu, Xiaocen Li, Tsung‐Chieh Shih, Zhixin Li, Jieqiong Cao, Qiling Meng, Zijian Su, Jinshao Ye, Feng Liu, An Hong, Xiaojia Chen
Journal: MedComm (2020)

In malignancies, fibroblast growth factor receptors (FGFRs) signaling is reinforced through overexpression of fibroblast growth factors (FGFs) or their receptors. FGFR2 has been proposed as a target for cancer therapy, because both the expression and activation of FGFR2 are boosted in various malignant carcinomas. Although several chemicals have been designed against FGFR2, they did not exhibit enough specificity and might bring potential accumulated toxicity. In this study, we developed an epitope peptide (P5) and its cyclic derivative (DcP5) based on the structure of FGF2 to limit the activation of FGFR2. The anticancer activities of P5 and DcP5 were examined in vitro and in vivo. Our results demonstrated that P5 significantly inhibited the cell proliferation in FGFR2-dependent manner in DU145 cells and retarded tumor growth in DU145 xenograft model with negligible toxicity toward normal organs. Further investigations found that the Gln4 and Glu6 residues of P5 bind to FGFR2 to abolish its activation. Moreover, we developed the P5 cyclic derivative, DcP5, which achieved reinforced stability and anticancer activity in vivo. Our findings suggest P5 and its cyclic derivative DcP5 as potential candidates for anticancer therapy.
B Cell-Derived Induced Pluripotent Stem Cells Are Useful for Determining the Cellular Origin of Abnormal B Cells in Multiple Myeloma
Authors: Aki Yanagi, Fumihiko Kawamura, Makoto Inaki, Atsushi Katafuchi, Yukari Yanai, Yu Abe, Naohiro Tsuyama, Misaki Sugai, Mitsunori Higuchi, Satoshi Muto, Takumi Yamaura, Hiroyuki Suzuki, Hideyoshi Noji, Shinichi Suzuki, Yoshida A Mitsuaki, Megumi Sasatani, Kenji Kamiya, Masafumi Onodera, Akira Sakai
Journal: Blood (2017)
Platelet-derived microvesicles induce calcium oscillations and promote VSMC migration <i>via</i> TRPV4
Authors: Shan-Shan Li, Shuang Gao, Yi Chen, Han Bao, Zi-Tong Li, Qing-Ping Yao, Ji-Ting Liu, Yingxiao Wang, Ying-Xin Qi
Journal: Theranostics (2020)

Abnormal migration of vascular smooth muscle cells (VSMCs) from the media to the interior is a critical process during the intimal restenosis caused by vascular injury. Here, we determined the role of platelet-derived microvesicles (PMVs) released by activated platelets in VSMC migration.
MBCL-01. METHYLATION PROFILING OF PEDIATRIC MEDULLOBLASTOMA IN SAUDI ARABIA IN A CLINICAL SETTING PERMITS SUB-CLASSIFICATION AND REVEALS NEW OUTCOME PREDICTIONS
Authors: Musa Alharbi, Nahla Mobark, Ali Abdullah O Balbaid, Yara Bashawri, Leen Abu Safieh, Albandary Alowayn, Rasha Alaljelaify, Mariam AlSaeed, Amal Almutairi, Fatmah Alqubaishi, Ebtehal Alsolm, Maqsood Ahmad, Ayman Al-Banyan, Fahad E Alotabi, Matija Snuderl, Malak Abedalthagafi
Journal: Neuro-Oncology (2020)

Abstract Medulloblastoma (MB) is the most common childhood malignant brain tumor. DNA methylation profiling has rapidly advanced our understanding of MB pathogenesis at the molecular level, MBs can be sub-grouped according to methylation patterns from FPPE samples into Wingless (WNT-MB), Sonic Hedgehog (SHH-MB), Group 3 (G3) and Group 4 (G4) WNT-MB and SHH-MB subgroups are characterized by gain-of function mutations that activate oncogenic cell signalling whilst G3/G4 tumors show recurrent chromosomal alterations. each subgroup has distinct clinical outcomes, the ability to subgroup SA-FPPE samples holds significant prognostic and therapeutic value. We performed the first assessment of MB-DNA methylation patterns in Saudi Arabian SA cohort using archival biopsy materials (FPPE n=49). Of the 41 materials available for methylation assessments, 39 could be classified into the major DNA methylation subgroups (SHH, WNT, G3 and G4). Methylation analysis was able to reclassify tumors that could not be sub-grouped through NGS testing, highlighting its improved accuracy for MB molecular classifications. Independent assessments demonstrate clinical relationships of the subgroups, exemplified by the high survival rates observed for WNT tumors. Surprisingly, the G4 subgroup did not conform to previously identified phenotypes, with a high prevalence in females, high metastatic rates and a large number of tumor-associated deaths. DNA methylation profiling enables the robust sub-classification of four disease sub-groups in SA-MB patients. Moreover, the incorporation of DNA methylation biomarkers can significantly improve current disease-risk stratification schemes, particularly concerning the identification of aggressive G4 tumors. These findings have important implications for future clinical disease management in MB cases across the Arab world.
RONC-20. RECURRENT HIGH-GRADE ASTROBLASTOMA TREATED WITH STEREOTACTIC RADIOTHERAPY
Authors: Shota Nishimoto, Yu Kawanishi, Shohei Fujita, Toshio Yawata, Tetsuya Ueba
Journal: Neuro-Oncology (2020)

Abstract INTRODUCTION Astroblastoma is a rare, mostly supratentorial glial tumor, occurring predominantly in children and young adults. However, treatment strategies have not yet been established for this rare disease. CASE PRESENTATION A 6-year-old male presented with headache and nausea. CT and MR imaging revealed a left frontal mass lesion with slight edema and macrocalcifications. Gross tumor resection was performed. Histological examination found neoplastic cells with astroblastic characteristics, and a striking perivascular array of pseudorosettes. The final diagnosis was high-grade astroblastoma. MR imaging 13 months after surgery suggested local recurrence and enlargement was found 3 months later. Stereotactic radiotherapy (SRT) was performed. MR imaging after SRT showed enhanced cyst formation around the tumor bed, suggesting tumor recurrence. However, 11C-methionine PET revealed radiation necrosis. The last follow-up MR imaging 15 months after SRT showed no further recurrence. CONCLUSION Astroblastoma is rare, so no optimal management is known. SRT may be effective to treat recurrent astroblastomas. 11C-methionine PET/CT is useful for the differentiation from radiation necrosis.
Sixty seconds on . . . JVT
Authors: Zosia Kmietowicz
Journal: BMJ (2020)

No, this has nothing to do with blood clots—but it’s certainly sent some people’s blood pressure soaring. We’re talking about Jonathan Van-Tam (JVT), deputy chief medical officer (CMO) for England, who is a new entry in Grazia magazine’s Chart of Lust, five places above Hollywood heartthrob Matthew McConaughey.

You’re right, and JVT loves nothing more than a transport metaphor to explain the complexities of the covid-19 pandemic. Referring to the imminence of a vaccine, he adopted …
Solitary Femoral Nodal Metastasis Identified With 68Ga–Prostate-Specific Membrane Antigen PET/CT
Authors: Luke Hilliar, Joshua Wei Liang Yip, Veronica Chi Ken Wong, Ken Le, Robert Mansberg
Journal: Clinical Nuclear Medicine (2020)

A 66-year-old man was referred for a 68Ga-prostate-specific membrane antigen (PSMA) PET/CT scan for primary staging of Gleason 8 prostatic adenocarcinoma. The PET/CT images confirmed PSMA activity in the bilateral prostatic apex in keeping with the known malignancy. An intensely PSMA-avid focus was also noted in a nonenlarged right femoral lymph node with no evidence of PSMA-avid metastatic disease elsewhere. Subsequent core biopsy and histopathology confirmed a solitary metastatic focus of prostatic adenocarcinoma in a right femoral lymph node.
EPCT-18. PHASE 0/I STUDY OF GM-CSF AND INTRATHECAL TRASTUZUMAB IN CHILDREN WITH RECURRENT POSTERIOR FOSSA EPENDYMOMA
Authors: Kathleen Dorris, Melissa Widener, Vladimir Amani, Andrew Donson, Debra Schissel, Jessica Carson, Ashley Mettetal, Dominique Ramirez, Daniel Gustafson, Todd Hankinson, Michael Handler, Margaret Macy, Nicholas Foreman
Journal: Neuro-Oncology (2020)

Abstract BACKGROUND Posterior fossa ependymoma (PF EPN) is a pediatric central nervous system malignancy that has a poor outcome to standard therapeutic approaches. The majority of PF EPN tumors have increased HER2 expression. Trastuzumab is a monoclonal antibody that targets HER2, and sargramostim (GM-CSF) stimulates hematopoietic progenitor cell proliferation. The combination of trastuzumab and GM-CSF has been shown to trigger antibody-dependent cell cytotoxicity in vitro in PF EPN cell lines. METHODS Children aged 1–21 years with relapsed PF EPN and no ventriculoperitoneal shunt or CSF obstruction are eligible for the Phase 0/I institutional trial at Children’s Hospital Colorado. Stratum 1 involves IT trastuzumab and subcutaneous (subQ) GM-CSF prior to standard-of-care surgical resection. Stratum 2 involves a 3 + 3 phase I design with serial IT trastuzumab doses, each preceded by three days of GM-CSF, to establish the MTD for IT trastuzumab. RESULTS Trastuzumab was detected in a sufficient number of tumors after presurgical IT delivery in Stratum 1 to open Stratum 2. Four patients (75% female) have been enrolled in Stratum 2 at trastuzumab Dose Level 1. Median age at enrollment is 9.8 years (range, 3.5–20.2 years). Preliminary CSF pharmacokinetic analysis demonstrated detectable trastuzumab up to 14 days after IT doses. No dose-limiting toxicities have occurred. Two patients progressed on therapy (median, 4 cycles). One patient is progression-free at 18 months off therapy. One patient remains on study therapy. CONCLUSIONS IT trastuzumab penetrates PF EPN tumor tissue. Stratum 2 remains open to accrual at Dose Level 2.
A Young Man With Generalized Muscle Weakness and a Peculiar Electrocardiogram
Authors: Dinkar Bhasin, Rahul Kumar, Anunay Gupta
Journal: JAMA Internal Medicine (2020)

This case report describes the electrocardiographic findings of a man in his 20s who presented with acute-onset, bilateral lower-limb weakness and less severe upper-limb weakness a day after performing physical activity.