tbuckley/cabot-search huggingface dataset:
Epidemiological trends of urinary tract infections, urolithiasis and benign prostatic hyperplasia in 203 countries and territories from 1990 to 2019
Authors: Cong Zhu, Dan-Qi Wang, Hao Zi, Qiao Huang, Jia-Min Gu, Lu-Yao Li, Xing-Pei Guo, Fei Li, Cheng Fang, Xiao-Dong Li, Xian-Tao Zeng
Journal: Military Medical Research (2021)

Urinary tract infections (UTI), urolithiasis, and benign prostatic hyperplasia (BPH) are three of the most common nonmalignant conditions in urology. However, there is still a lack of comprehensive and updated epidemiological data. This study aimed to investigate the disease burden of UTI, urolithiasis, and BPH in 203 countries and territories from 1990 to 2019.Data were extracted from the Global Burden of Disease 2019, including incident cases, deaths, disability-adjusted life-years (DALYs) and corresponding age-standardized rate (ASR) from 1990 to 2019. Estimated annual percentage changes (EAPC) were calculated to evaluate the trends of ASR. The associations between disease burden and social development degrees were analyzed using a sociodemographic index (SDI).Compared with 1990, the incident cases of UTI, urolithiasis, and BPH increased by 60.40%, 48.57%, and 105.70% in 2019, respectively. The age-standardized incidence rate (ASIR) of UTI increased (EAPC = 0.08), while urolithiasis (EAPC = - 0.83) and BPH (EAPC = - 0.03) decreased from 1990 to 2019. In 2019, the age-standardized mortality rate (ASMR) of UTI and urolithiasis were 3.13/100,000 and 0.17/100,000, respectively. BPH had the largest increase (110.56%) in DALYs in the past three decades, followed by UTI (68.89%) and urolithiasis (16.95%). The burden of UTI was mainly concentrated in South Asia and Tropical Latin America, while the burden of urolithiasis and BPH was recorded in Asia and Eastern Europe. Moreover, the ASIR and SDI of urolithiasis in high-SDI regions from 1990 to 2019 were negatively correlated, while the opposite trend was seen in low-SDI regions. In 2019, the ASIR of UTI in females was 3.59 times that of males, while the ASIR of urolithiasis in males was 1.96 times higher than that in females. The incidence was highest in the 30-34, 55-59, and 65-69 age groups among the UTI, urolithiasis, and BPH groups, respectively.Over the past three decades, the disease burden has increased for UTI but decreased for urolithiasis and BPH. The allocation of medical resources should be based more on the epidemiological characteristics and geographical distribution of diseases.
Abstract 10476: Patient Characteristics and Survival Outcomes of Cardiac Arrest in the Cardiac Catheterization Laboratory: Insights from Get with the Guidelines-Resuscitation Registry
Authors: Ahmed Elkaryoni, John J Lopez, Paul S Chan
Journal: Circulation (2021)

Background: The characteristics and outcomes of in-hospital cardiac arrest (IHCA) in the cardiac catheterization laboratory (CCL) have not been well-described. We compared the characteristics and outcomes of patients with an IHCA in the CCL versus those in the operating room (OR) and the intensive care unit (ICU). Methods: Within the American Heart Association’s Get With the Guidelines-Resuscitation® registry, we identified patients 18 years of age or older with an IHCA in the CCL, OR, or ICU between 2000 and 2019. We compared rates of survival to discharge for patients in the CCL, OR, and ICU. Additionally, we examined predictors of survival to discharge for patients with IHCA in the CCL. Results: There were 6866, 5181, and 181,832 patients with an IHCA in the CCL, OR, and ICU, respectively. Patients with IHCAs in the CCL were more likely to have a shockable cardiac arrest rhythm as compared with those in the OR and ICU. Overall, 2614 (38.1%) patients with IHCA in the CCL survived to discharge, as compared with 30,833 (16.9%) from the ICU and 2096 (40.5%) from the OR. After adjustment for 27 patient and cardiac arrest factors, patients with IHCA in CCL were more likely to survive to discharge as compared with those with IHCA from the ICU (odds ratio, 1.37 [95% CI: 1.29-1.46], p&lt;0.001). In contrast, they were less likely to survive to discharge as compared with those with IHCA in the OR (odds ratio, 0.81 [95% CI: 0.69-0.94], p=0.006). Predictors of survival to discharge in patients with IHCA in the CCL included white race, pulseless ventricular tachycardia/fibrillation, and IHCA during normal hours and on weekdays, while having myocardial infarction during this or prior hospitalization was associated with less survival to discharge. (Table). Conclusion: IHCA in the CCL is not uncommon and has a lower survival rate as compared with IHCA in other procedural areas such as the OR. The reasons for this difference deserve further study given that response to IHCAs in both settings should be similar.
Quenching Epigenetic Drug Resistance Using Antihypoxic Microparticles in Glioblastoma Patient‐Derived Chips
Authors: Sewoom Baek, Seung Eun Yu, Yu‐Heng Deng, Yong‐Jae Lee, Dong Gue Lee, Surim Kim, Seonjin Yoon, Hye‐Seon Kim, Jeongeun Park, Chan Hee Lee, Jung Bok Lee, Hyun Joon Kong, Seok‐Gu Kang, Young Min Shin, Hak‐Joon Sung
Journal: Advanced Healthcare Materials (2021)

Glioblastoma (GBM) is one of the most intractable tumor types due to the progressive drug resistance upon tumor mass expansion. Incremental hypoxia inside the growing tumor mass drives epigenetic drug resistance by activating nongenetic repair of antiapoptotic DNA, which could be impaired by drug treatment. Hence, rescuing intertumor hypoxia by oxygen-generating microparticles may promote susceptibility to antitumor drugs. Moreover, a tumor-on-a-chip model enables user-specified alternation of clinic-derived samples. This study utilizes patient-derived glioblastoma tissue to generate cell spheroids with size variations in a 3D microchannel network chip (GBM chip). As the spheroid size increases, epigenetic drug resistance is promoted with inward hypoxia severance, as supported by the spheroid size-proportional expression of hypoxia-inducible factor-1a in the chip. Loading antihypoxia microparticles onto the spheroid surface significantly reduces drug resistance by silencing the expression of critical epigenetic factor, resulting in significantly decreased cell invasiveness. The results are confirmed in vitro using cell line and patient samples in the chip as well as chip implantation into a hypoxic hindlimb ischemia model in mice, which is an unprecedented approach in the field.
Recent Clinical Trials Insights into the Treatment of Primary Membranous Nephropathy
Authors: Jorge Rojas-Rivera, Fernando C. Fervenza, Alberto Ortiz
Journal: Drugs (2021)

Immunosuppressive therapy is mandatory for primary membranous nephropathy with persistent nephrotic proteinuria or anti-phospholipase A2 receptor antibodies, reduced kidney function, or another risk factor for progression. Rituximab has demonstrated efficacy for proteinuria remission compared with renin-angiotensin system blockade or cyclosporine in two well-powered randomized controlled trials. More recently, STARMEN showed that alternating glucocorticoid-cyclophosphamide is superior to sequential tacrolimus-rituximab for proteinuria remission, although it was associated with a higher risk of non-serious adverse events. However, sequential tacrolimus-rituximab involved delayed lower dose rituximab and was the worst-performing rituximab regimen among those tested in randomized clinical trials. The RI-CYCLO pilot study did not demonstrate superiority of glucocorticoid-cyclophosphamide over rituximab and found no difference in adverse events. Overall, STARMEN and RI-CYCLO confirmed the efficacy of glucocorticoid-cyclophosphamide in patients with high-risk membranous nephropathy and the role of rituximab as a valid alternative. However, none of the trials tested an optimized rituximab protocol involving a second rituximab cycle before declaring treatment failure. Calcineurin inhibitors should be considered third-line drugs and sequential use of calcineurin inhibitor rituximab did not add over rituximab-only regimens. We critically review recent randomized controlled trials, propose a research agenda, and call for multinational pragmatic trials that enroll patients at referral centers to address unmet research needs.
Latent class analysis identification of prurigo nodularis comorbidity phenotypes
Authors: Shannon Wongvibulsin, Varsha Parthasarathy, Vartan Pahalyants, William Murphy, Nishadh Sutaria, Youkyung S. Roh, Zachary A. Bordeaux, Junwen Deng, Matthew T. Taylor, Yevgeniy R. Semenov, Shawn G. Kwatra
Journal: British Journal of Dermatology (2021)

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Coiled-Coil Domain: Uncoiling Tumor Suppression by BRCA1
Authors: Arun P. Mishra, Sounak Sahu, Shyam K. Sharan
Journal: Cancer Research (2021)

The coiled-coil domain of BRCA1 is essential for its interaction with partner and localizer of BRCA2 (PALB2). In mice, loss of this interaction is known to result in Fanconi anemia-associated phenotypes. In a study published in this issue of Cancer Research, Pulver and colleagues from the Jonkers lab have generated a mouse model with a leucine to proline change in codon 1363 in the coiled-coil domain of BRCA1 (Brca1LP ), which disrupts its binding with PALB2. Unlike the previously reported viable coiled-coil defective mice, homozygous Brca1LP/LP mutant mice die during embryogenesis. The authors examined the role of the BRCA1/PALB2 interaction on mammary tumorigenesis and reported increased incidence of mammary tumors that are carcinosarcomas or sarcomatoids, unlike the adenocarcinomas that are characteristic mammary tumor types associated with loss of Brca1 and Trp53 in mice. The findings reveal the relevance of the coiled-coil domain in mammary tumor suppression by BRCA1.See related article by Pulver et al., p. 6171.
Correction to: Low expression of TRAF3IP2-AS1 promotes progression of NONO-TFE3 translocation renal cell carcinoma by stimulating N6-methyladenosine of PARP1 mRNA and downregulating PTEN
Authors: Lei Yang, Yi Chen, Ning Liu, QianCheng Shi, Xiaodong Han, Weidong Gan, Dongmei Li
Journal: Journal of Hematology & Oncology (2021)
Virulence factors perforate the pathogen-containing vacuole to signal efferocytosis
Authors: Hirotaka Hiyoshi, Bevin C. English, Vladimir E. Diaz-Ochoa, Tamding Wangdi, Lillian F. Zhang, Miako Sakaguchi, Takeshi Haneda, Renée M. Tsolis, Andreas J. Bäumler
Journal: Cell Host & Microbe (2021)

Intracellular pathogens commonly reside within macrophages to find shelter from humoral defenses, but host cell death can expose them to the extracellular milieu. We find intracellular pathogens solve this dilemma by using virulence factors to generate a complement-dependent find-me signal that initiates uptake by a new phagocyte through efferocytosis. During macrophage death, Salmonella uses a type III secretion system to perforate the membrane of the pathogen-containing vacuole (PCV), thereby triggering complement deposition on bacteria entrapped in pore-induced intracellular traps (PITs). In turn, complement activation signals neutrophil efferocytosis, a process that shelters intracellular bacteria from the respiratory burst. Similarly, Brucella employs its type IV secretion system to perforate the PCV membrane, which induces complement deposition on bacteria entrapped in PITs. Collectively, this work identifies virulence factor-induced perforation of the PCV as a strategy of intracellular pathogens to generate a find-me signal for efferocytosis.
94P Patient-reported outcomes (PROs) following sintilimab (sint) plus pemetrexed (pem) and platinum (plt) based chemotherapy as first-line therapy for locally advanced or metastatic nonsquamous NSCLC: A randomized, double-blind, phase III study (Orient-11)
Authors: J. Fang, Y. Zhao, B. Han, G. Chen, Z. Yang, M. Bi, L. Zhang, C. Molife, Y. Zhao, L. Zhang
Journal: Annals of Oncology (2021)
Risk of Hepatocellular Carcinoma in Patients With Indeterminate (LI-RADS 3) Liver Observations
Authors: Ashwini Arvind, Sagar Joshi, Timothy Zaki, Daniel Burkholder, Neehar D. Parikh, Amit G. Singal, Sruthi Yekkaluri, Takeshi Yokoo, David Fetzer, Travis Browning, Nicole E. Rich, Gaurav Khatri, Hao Zhu, Yujin Hoshida, Jorge A. Marrero, Adam C. Yopp, Purva Gopal, Carrie Manwaring
Journal: Clinical Gastroenterology and Hepatology (2021)
Anthrax toxins regulate pain signaling and can deliver molecular cargoes into ANTXR2+ DRG sensory neurons
Authors: Nicole J. Yang, Jörg Isensee, Dylan V. Neel, Andreza U. Quadros, Han-Xiong Bear Zhang, Justas Lauzadis, Sai Man Liu, Stephanie Shiers, Andreea Belu, Shilpa Palan, Sandra Marlin, Jacquie Maignel, Angela Kennedy-Curran, Victoria S. Tong, Mahtab Moayeri, Pascal Röderer, Anja Nitzsche, Mike Lu, Bradley L. Pentelute, Oliver Brüstle, Vineeta Tripathi, Keith A. Foster, Theodore J. Price, R. John Collier, Stephen H. Leppla, Michelino Puopolo, Bruce P. Bean, Thiago M. Cunha, Tim Hucho, Isaac M. Chiu
Journal: Nature Neuroscience (2021)
Abstract 11939: Can Live Video Streaming From Bystander's Smartphone Improve the Quality of Chest Compressions in Real Out-of-Hospital Cardiac Arrest?
Authors: Gitte Linderoth, Oscar Rosenkrantz, Freddy Lippert, Doris Oestergaard, Annette K Ersbøll, Christian S Meyhoff, Fredrik Folke, Helle C Christensen
Journal: Circulation (2021)

Introduction: Good quality of cardiopulmonary resuscitation (CPR) provided by bystanders is important for the outcome in out-of-hospital cardiac arrest (OHCA). A live video stream from the bystander’s smartphone to the medical dispatcher might improve the quality of chest compressions performed during CPR. Methods: At the Copenhagen Emergency Medical Services in Denmark, the medical dispatcher can add a live video to the emergency call. In case of OHCA, the medical dispatcher guides bystanders in dispatcher-assisted CPR (DA-CPR). After initiating chest compressions, the medical dispatcher can add live video streaming. A cohort study was conducted with an evaluation of performed chest compressions from the video footage before and after the dispatcher used the video to instruct CPR (video-instructed DA-CPR). Correct chest compressions were defined according to European Resuscitation Council Guidelines. Results: CPR was provided with a live video stream in 52 OHCA calls, in which 90 bystanders performed chest compressions. Thirty OHCA occurred at a public location, and more than four bystanders were present in 32 (62%) cases. In 26 cases, chest compressions were performed by more than one bystander. Eight (9%) bystanders performed correct chest compressions before video-instructed DA-CPR. For the bystanders first initiating insufficient CPR improvements were observed for: hand placement 58% (n=17/29), compressions rate 73% (n=17/21), and compressions depth 62% (n=19/31) following video-instructed DA-CPR. For the second bystander providing CPR (n=26) improvements were still observed for: hand placement 57% (n=4/7), compressions rate 73% (N=8/11), and compressions depth 53% (n=11/21) following video-instructed DA-CPR. For the third and fourth bystander (n=10), providing CPR improvements were seen for: hand placement 100% (n=2/2), compressions rate 50 % (n=2/4), and compressions depth 60% (n=3/5). Eighteen bystanders had a chest compressions performance measurement that could not be observed. Conclusions: A live video from the bystander`s smartphone to the medical dispatcher could improve the quality of chest compressions in CPR, and guidance seems important not just for the first bystander but for all bystanders performing CPR.
Efficacy and Safety of Parsaclisib in Patients with Relapsed or Refractory Follicular Lymphoma: Primary Analysis from a Phase 2 Study (CITADEL-203)
Authors: Ryan C. Lynch, Abraham Avigdor, Matthew S McKinney, Shankara Paneesha, Björn Wahlin, John S Hrom, David Cunningham, Nicholas Morley, Miguel Canales, Mariana Bastos-Oreiro, David Belada, Liliana Devizzi, Fred Zheng, Douglas J DeMarini, Wei Jiang, Marek Trněný
Journal: Blood (2021)
Resveratrol ameliorates polycystic ovary syndrome via transzonal projections within oocyte-granulosa cell communication
Authors: Mingyue Chen, Chengyong He, Kongyang Zhu, Zihan Chen, Zixiao Meng, Xiaoming Jiang, Jiali Cai, Chunyan Yang, Zhenghong Zuo
Journal: Theranostics (2021)

Rationale: Polycystic ovary syndrome (PCOS) is closely linked to follicular dysplasia and impaired bidirectional oocyte-granulosa cell (GC) communication. Given that PCOS is a heterogeneous, multifactorial endocrine disorder, it is important to clarify the pathophysiology of this ovarian disease and identify a specific treatment. Methods: We generated PCOS rat models based on neonatal tributyltin (TBT) exposure and studied the therapeutic effect and mechanism of resveratrol (RSV), a natural plant polyphenol. Transcriptome analysis was conducted to screen the significantly changed pathways, and a series of experiments, such as quantitative real-time polymerase chain reaction (PCR), Western blot and phalloidin staining, were performed in rat ovaries. We also observed similar changes in human PCOS samples using Gene Expression Omnibus (GEO) database analysis and quantitative real-time PCR. Results: We first found that injury to transzonal projections (TZPs), which are specialized filopodia that mediate oocyte-GC communication in follicles, may play an important role in the etiology of PCOS. We successfully established PCOS rat models using TBT and found that overexpressed calcium-/calmodulin-dependent protein kinase II beta (CaMKIIβ) inhibited TZP assembly. In addition, TZP disruption and CAMK2B upregulation were also observed in samples from PCOS patients. Moreover, we demonstrated that RSV potently ameliorated ovarian failure and estrus cycle disorder through TZP recovery via increased cytoplasmic calcium levels and excessive phosphorylation of CaMKIIβ. Conclusions: Our data indicated that upregulation of CaMKIIβ may play a critical role in regulating TZP assembly and may be involved in the pathogenesis of PCOS associated with ovarian dysfunction. Investigation of TZPs and RSV as potent CaMKIIβ activators provides new insight and a therapeutic target for PCOS, which is helpful for improving female reproduction.
Reply to Keenan <i>et al.</i>: Obstructive Sleep Apnea Symptom Subtypes and Cardiovascular Risk: Conflicting Evidence to an Important Question
Authors: Wojciech Trzepizur, Margaux Blanchard, AbdelKebir Sabil, Chloé Gervès-Pinquié, Frédéric Gagnadoux
Journal: American Journal of Respiratory and Critical Care Medicine (2021)
Suppression of mutant C9orf72 expression by a potent mixed backbone antisense oligonucleotide
Authors: Hélène Tran, Michael P. Moazami, Huiya Yang, Diane McKenna-Yasek, Catherine L. Douthwright, Courtney Pinto, Jake Metterville, Minwook Shin, Nitasha Sanil, Craig Dooley, Ajit Puri, Alexandra Weiss, Nicholas Wightman, Heather Gray-Edwards, Miklos Marosfoi, Robert M. King, Thomas Kenderdine, Daniele Fabris, Robert Bowser, Jonathan K. Watts, Robert H. Brown
Journal: Nature Medicine (2021)
Adaptive Dosing of Nivolumab + Ipilimumab Immunotherapy Based Upon Early, Interim Radiographic Assessment in Advanced Melanoma (The ADAPT-IT Study)
Authors: Michael A. Postow, Debra A. Goldman, Alexander N. Shoushtari, Allison Betof Warner, Margaret K. Callahan, Parisa Momtaz, James W. Smithy, Ellesa Naito, Marina K. Cugliari, Vladislav Raber, Omar Eton, Suresh G. Nair, Katherine S. Panageas, Jedd D. Wolchok, Paul B. Chapman
Journal: Journal of Clinical Oncology (2021)

Nivolumab + ipilimumab (nivo + ipi) is highly efficacious but has high toxicity. Standard treatment in advanced melanoma is four doses of nivo + ipi followed by nivo alone. Whether four doses of nivo + ipi are needed is unclear.The Adaptively Dosed ImmunoTherapy Trial (ADAPT-IT) study (NCT03122522) is a multicenter, single-arm phase II clinical trial. Patients received two doses of nivo (1 mg/kg) + ipi (3 mg/kg) followed by a computed tomography scan at week 6. Patients without new lesions or index lesion tumor growth of > 4% had protocol-defined early favorable antitumor effect (FATE) and ceased nivo + ipi, transitioning to nivo monotherapy. Patients without FATE at week 6 received the standard third and fourth doses of nivo + ipi followed by nivo monotherapy. The primary end point was response rate by RECIST 1.1 at week 12. Secondary end points included additional efficacy assessments and safety.Sixty patients were enrolled; 41 patients (68%) had FATE at week 6 and met criteria for stopping nivo + ipi. Best overall response rates by RECIST at week 12 or any time afterward were 48% (95% CI, 35 to 62) and 58% (95% CI, 45 to 71), respectively. With a median follow-up of 25 months, the estimated 18-month progression-free survival and overall survival are 52% and 80%, respectively. Fifty seven percent of patients had grade 3-5 treatment-related toxicity.The efficacy and toxicity of standard four dose nivo + ipi induction therapy in melanoma is likely driven by the first two doses. An interim computed tomography scan after two doses guided cessation of combination dosing and identified almost all responders. Longer follow-up and further study are needed to fully understand the implications of a shortened induction course of nivo + ipi.
Uterine Uptake of 68Ga-FAPI-04 in Uterine Pathology and Physiology
Authors: Xiao Zhang, Wenyu Song, Chunxia Qin, Yangmeihui Song, Fang Liu, Fan Hu, Xiaoli Lan
Journal: Clinical Nuclear Medicine (2021)

68Ga-labeled fibroblast activation protein inhibitor (68Ga-FAPI-04) has been useful in the imaging of desmoplastic reaction in different tumors. As we have found that most female patients showed avid uterine uptake of 68Ga-FAPI-04, we sought to further investigate the pathological and physiological uptake of 68Ga-FAPI-04 characteristics in the uterus.We reviewed the image data of female patients who had undergone 68Ga-FAPI-04 PET/MRI at our institute between May 22, 2020, and June 21, 2021. The characteristics of uterine uptake and clinical information were collected. The uterus with and without malignancy were compared. We further analyzed the relationship of age, uterus size, gynecological history, and 18F-FDG uptake (if performed) with 68Ga-FAPI-04 uptake.Seventy-seven patients were included in this study. Much higher cervical 68Ga-FAPI-04 accumulation was noticed in cervical cancer patients than in normal cases, and 37 more metastases were found in 68Ga-FAPI-04 PET than that in 18F-FDG. Uterine body malignancies displayed different uptake features. Two cases with the metastases to uterine body showed relative lower 68Ga-FAPI-04 activity compared with their normal uteri. Of 67 patients without malignancy, lower 68Ga-FAPI-04 uptake was noted in postmenopausal women than in reproductive and perimenopausal patients. The invasive operation or hysteromyoma may increase 68Ga-FAPI-04 uptake.68Ga-FAPI-04 PET might be a promising method in cervical cancers. However, physiological uptake may limit its diagnostic value in uterine body malignancy. It should be noticed that the metastatic lesion in the uterus may show relative lower uptake of 68Ga-FAPI-04 compared with the rest of the uterus. Age, fibroids, and uterine volume may influence 68Ga-FAPI-04 uptake in the uterus. More patients with various uterine diseases could be involved to provide more differential diagnostic information.