tbuckley/cabot-search huggingface dataset:
Imaging the in vivo growth patterns of bacteria in human gut Microbiota
Authors: Liyuan Lin, Jia Song, Jian Li, Xiaolei Zuo, Hong Wei, Chaoyong Yang, Wei Wang
Journal: Gut Microbes (2021)

How to study the unculturable bacteria in the laboratory is one of the major challenges in human gut microbiota research. The resulting lack of microbiology knowledge of this "dark matter" greatly hinders further understanding of our gut microbiota. Here, to characterize the in vivo growth and division of human gut bacteria, we report the integrative use of STAMP (sequential tagging with D-amino acid–based metabolic probes) and fluorescence in situ hybridization (FISH) in a human microbiota-associated mouse model. After stable colonization of the human fecal microbiotas in germ-free mice, two fluorescent D-amino acid probes were sequentially administered by gavage, and the dually labeled peptidoglycan of the bacteria provided a chronological recording of their cell wall syntheses. Following taxonomic identification with FISH staining, the growth patterns of 32 species, including 5 currently unculturables, were identified. Surprisingly, we found that many bacterial species in the human microbiota were significantly shorter than those in the mouse gut microbiota. An imaging database for gut bacteria ̶ Microbiome Atlas was built for summarizing STAMP imaging of bacteria from different microbiotas, which can be contributed by the microbiota research community worldwide. This integrative imaging strategy and the database will promote our understanding of the bacterial cytology in gut microbiotas and facilitate communications among cellular microbiologists.
Advanced Closed-Loop Control System Improves Postprandial Glycemic Control Compared With a Hybrid Closed-Loop System Following Unannounced Meal
Authors: Jose Garcia-Tirado, Jenny L. Diaz, Rebeca Esquivel-Zuniga, Chaitanya L.K. Koravi, John P. Corbett, Martha Dawson, Christian Wakeman, Charlotte L. Barnett, Mary C. Oliveri, Helen Myers, Katie Krauthause, Marc D. Breton, Mark D. DeBoer
Journal: Diabetes Care (2021)

OBJECTIVE Meals are a major hurdle to glycemic control in type 1 diabetes (T1D). Our objective was to test a fully automated closed-loop control (CLC) system in the absence of announcement of carbohydrate ingestion among adolescents with T1D, who are known to commonly omit meal announcement. RESEARCH DESIGN AND METHODS Eighteen adolescents with T1D (age 15.6 ± 1.7 years; HbA1c 7.4 ± 1.5%; 9 females/9 males) participated in a randomized crossover clinical trial comparing our legacy hybrid CLC system (Unified Safety System Virginia [USS]-Virginia) with a novel fully automated CLC system (RocketAP) during two 46-h supervised admissions (each with one announced and one unannounced dinner), following 2 weeks of data collection. Primary outcome was the percentage time-in-range 70–180 mg/dL (TIR) following the unannounced meal, with secondary outcomes related to additional continuous glucose monitoring-based metrics. RESULTS Both TIR and time-in-tight-range 70–140 mg/dL (TTR) were significantly higher using RocketAP than using USS-Virginia during the 6 h following the unannounced meal (83% [interquartile range 64–93] vs. 53% [40–71]; P = 0.004 and 49% [41–59] vs. 27% [22–36]; P = 0.002, respectively), primarily driven by reduced time-above-range (TAR &amp;gt;180 mg/dL: 17% [1.3–34] vs. 47% [28–60]), with no increase in time-below-range (TBR &amp;lt;70 mg/dL: 0% median for both). RocketAP also improved control following the announced meal (mean difference TBR: −0.7%, TIR: +7%, TTR: +6%), overall (TIR: +5%, TAR: −5%, TTR: +8%), and overnight (TIR: +7%, TTR: +19%, TAR: −5%). RocketAP delivered less insulin overall (78 ± 23 units vs. 85 ± 20 units, P = 0.01). CONCLUSIONS A new fully automated CLC system with automatic prandial dosing was proven to be safe and feasible and outperformed our legacy USS-Virginia in an adolescent population with and without meal announcement.
26585 Baricitinib for the treatment of pediatric patients with moderate-to-severe atopic dermatitis
Authors: Amy Paller, Chia-Yu Chu, Chin-Yi Yang, Jonathan Janes, Apurva Prakash, Maria Jose Rueda, Sarah Stanley, Wen-Shuo Wu, Xin Zhang, Lawrence Eichenfield
Journal: Journal of the American Academy of Dermatology (2021)
Emerging role of natural products in cancer immunotherapy
Authors: Songtao Dong, Xiangnan Guo, Fei Han, Zhonggui He, Yongjun Wang
Journal: Acta Pharmaceutica Sinica B (2021)

Cancer immunotherapy has become a new generation of anti-tumor treatment, but its indications still focus on several types of tumors that are sensitive to the immune system. Therefore, effective strategies that can expand its indications and enhance its efficiency become the key element for the further development of cancer immunotherapy. Natural products are reported to have this effect on cancer immunotherapy, including cancer vaccines, immune-check points inhibitors, and adoptive immune-cells therapy. And the mechanism of that is mainly attributed to the remodeling of the tumor-immunosuppressive microenvironment, which is the key factor that assists tumor to avoid the recognition and attack from immune system and cancer immunotherapy. Therefore, this review summarizes and concludes the natural products that reportedly improve cancer immunotherapy and investigates the mechanism. And we found that saponins, polysaccharides, and flavonoids are mainly three categories of natural products, which reflected significant effects combined with cancer immunotherapy through reversing the tumor-immunosuppressive microenvironment. Besides, this review also collected the studies about nano-technology used to improve the disadvantages of natural products. All of these studies showed the great potential of natural products in cancer immunotherapy.
Chiral mesoporous silica nano-screws as an efficient biomimetic oral drug delivery platform through multiple topological mechanisms
Authors: Yumei Wang, Jia Ke, Xianmou Guo, Kaijun Gou, Zhentao Sang, Yanbu Wang, Yan Bian, Sanming Li, Heran Li
Journal: Acta Pharmaceutica Sinica B (2021)

In the microscale, bacteria with helical body shapes have been reported to yield advantages in many bio-processes. In the human society, there are also wisdoms in knowing how to recognize and make use of helical shapes with multi-functionality. Herein, we designed atypical chiral mesoporous silica nano-screws (CMSWs) with ideal topological structures (e.g., small section area, relative rough surface, screw-like body with three-dimension chirality) and demonstrated that CMSWs displayed enhanced bio-adhesion, mucus-penetration and cellular uptake (contributed by the macropinocytosis and caveolae-mediated endocytosis pathways) abilities compared to the chiral mesoporous silica nanospheres (CMSSs) and chiral mesoporous silica nanorods (CMSRs), achieving extended retention duration in the gastrointestinal (GI) tract and superior adsorption in the blood circulation (up to 2.61- and 5.65-times in AUC). After doxorubicin (DOX) loading into CMSs, DOX@CMSWs exhibited controlled drug release manners with pH responsiveness in vitro. Orally administered DOX@CMSWs could efficiently overcome the intestinal epithelium barrier (IEB), and resulted in satisfactory oral bioavailability of DOX (up to 348%). CMSWs were also proved to exhibit good biocompatibility and unique biodegradability. These findings displayed superior ability of CMSWs in crossing IEB through multiple topological mechanisms and would provide useful information on the rational design of nano-drug delivery systems.
Now Is the Time for a Critical Conversation About the Reporting of Race and Ethnicity
Authors: John H. Stewart
Journal: JAMA Surgery (2021)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Surgery HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Surgery journal
Safety and unique pharmacokinetic profile of ARX788, a site-specific ADC, in heavily pretreated patients with HER2-overexpresing solid tumors: Results from two phase 1 clinical trials.
Authors: Sara A. Hurvitz, Haeseong Park, Sophia Frentzas, Catherine M. Shannon, Katharine Cuff, Richard Wilhelm Eek, George Thomas Budd, Amelia McCartney, Joyce O'Shaughnessy, Janice M. Lu, Jian Zhang, Dongmei Ji, Weina Shen, Matt Li, Jinchun Yan, Gang Xia, Yanping Ji, Sulan Yao, Gaozhun Xiong, Xichun Hu
Journal: Journal of Clinical Oncology (2021)

1038 Background: ARX788 is a site-specific, homogeneous, and highly stable ADC. The payload AS269 is conjugated to the synthetic amino acids para-acetylphenylalanine (pAF) in a humanized anti-HER2 mAb. ARX788 demonstrated promising activity in HER2-positive, HER2-low, and T-DM1 resistant tumors in preclinical studies. Here we present the phase 1 clinical data evaluating the safety, antitumor activity, and PK of ARX788 in advanced solid tumors. Methods: The standard 3+3 design (0.33 - 1.5 mg/kg; Q3W or Q4W) is used to determine the MTD and/or RP2D in two phase 1 studies in HER2-positive solid tumors in U.S. and Australia (ACE-Pan tumor-01) and in HER2-positive breast cancers in China (ACE-Breast-01). The efficacy endpoints include ORR and DCR. Intensive PK sampling in first 3 cycles is performed to characterize serum PK profiles of ARX788, total Ab, and pAF-AS269. Results: 69 and 34 heavily pretreated patients received ARX788 monotherapy in the ACE-Breast-01 (median 6 prior lines of therapy) and ACE-Pan tumor-01 trial (including breast, gastric/GEJ, NSCLC, ovarian, urothelial, biliary track, endometrial, and salivary gland cancer) respectively. Dose escalation for both studies have been completed with no DLT reported. MTD has not been reached. ARX788 was generally well tolerated with most AEs being grade 1 or 2. The most common grade &gt;3 AEs include ocular AEs (5.7 %) and pneumonitis (4.3%) in the ACE-Breast-01 trial; pneumonitis (2.9%) and fatigue (2.9%) in the ACE-Pan tumor-01 trial. Low systemic toxicities in terms of the incidence rate and grade (as shown in table). No treatment-related death. In the 1.5 mg/kg cohort, ORR was 74% (14/19) and 67% (2/3) for ACE-Breast-01 and ACE-Pan tumor-01, respectively. DCR was 100%. Median DOR or median PFS has not been reached. PK profiles for total antibody and ARX788 were generally comparable across all dose levels. Mean T1/2 for ARX788 and total antibody had approximately 100 hours at the dose of 1.5 mg/kg. Serum pAF-AS269 concentrations peaked with a median time of 168 h. Serum exposure of pAF-AS269 was low with the Cmax and AUC at cycle 1 being approximately 0.1% and 0.18% of those for ARX788 on a molar basis, respectively. Conclusions: High stability of ARX788 and low serum exposure of pAF-AS269 may underlie the low systemic toxicity, which differentiates it from other ADCs. Clinical trial information: NCT032550070 .[Table: see text]
A Decision With Love
Authors: Kei Ouchi
Journal: JAMA Neurology (2021)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Neurology HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Neurology journal
Another Weak Link in the Electron Transport Chain: Variants in <i>SUCLG2</i> and Risk for Pheochromocytoma and Paraganglioma
Authors: Gina M Ney, Douglas R Stewart
Journal: JNCI Journal of the National Cancer Institute (2021)

In this issue of the Journal, Hadrava Vanova and colleagues (1) provide evidence that germline variation encoding SUCLG2, a beta subunit of succinyl-CoA ligase, a hetero-dimeric enzyme involved in mitochondrial metabolism, predisposes individuals to pheochromocytoma and paraganglioma (PPGL).In the analysis, 352 individuals with pheochromocytoma and/or paraganglioma evaluated at the National Institutes of Health underwent sequencing of blood leukocyte DNA, and of these, 15 (4.2%) harbored 1 of 8 variants (7 missense) in SUCLG2 and no known pathogenic germline variants in other PPGL genes.Mechanistically, the authors provide data that show SUCLG2 variants result in succinate dehydrogenase (SDH) dysregulation and suggest that such variants alter metabolic programs that favor cancer development, similar to what is seen in SDH deficiency.These observations, if replicated, add SUCLG2 to the growing list of known genes in which pathogenic germline variation increases risk for PPGL development because of dysregulation of cellular metabolism.Changes in cellular metabolism have been a defining feature of cancer since the 1920s, when Otto Warburg observed that cancer cells use aerobic glycolysis preferentially over mitochondrial pathways (2).Since then, numerous seminal discoveries have linked metabolic reprogramming to nearly every facet of cancer development and metastasis.Early transforming somatic mutations in KRAS and TP53 result in favorable bioenergetics to promote tumorigenesis, epigenetic dysregulation, and genomic instability (3-6).When tumor growth is established, profound microenvironmental changes occur that sustain immune escape and tumor proliferation despite local nutrient depletion (7-9).Furthermore, the predominant bioenergetic processes within an individual tumor cell help determine its metastatic potential (10).Thus, cell metabolism provides critical biochemical messengers that create an environment favorable for cancer initiation, survival, and spread.Illustratively, individuals with pathogenic germline variants in metabolic enzymes are at increased risk of developing cancers, such as pheochromocytoma, renal cell carcinoma, and gastrointestinal stromal tumors (11).Pathogenic germline variants are found in genes of the SDH family (SDHA, SDHB, SDHC, and SDHD) in approximately
Abnormal amyloid beta metabolism in systemic abnormalities and Alzheimer’s pathology: Insights and therapeutic approaches from periphery
Authors: Rahat Ullah, Tae Ju Park, Xu Huang, Myeong Ok Kim
Journal: Ageing Research Reviews (2021)

Alzheimer's disease (AD) is an age-associated, multifactorial neurodegenerative disorder that is incurable. Despite recent success in treatments that partially improve symptomatic relief, they have failed in most clinical trials. Re-holding AD for accurate diagnosis and treatment is widely known as a challenging task. Lack of knowledge of basic molecular pathogenesis might be a possible reason for ineffective AD treatment. Historically, a majority of therapy-based studies have investigated the role of amyloid-β (Aβ peptide) in the central nervous system (CNS), whereas less is known about Aβ peptide in the periphery in AD. In this review, we provide a comprehensive summary of the current understanding of Aβ peptide metabolism (anabolism and catabolism) in the brain and periphery. We show that the abnormal metabolism of Aβ peptide is significantly linked with central-brain and peripheral abnormalities; the interaction between peripheral Aβ peptide metabolism and peripheral abnormalities affects central-brain Aβ peptide metabolism, suggesting the existence of significant communication between these two pathways of Aβ peptide metabolism. This close interaction between the central brain and periphery in abnormal Aβ peptide metabolism plays a key role in the development and progression of AD. In conclusion, we need to obtain a full understanding of the dynamic roles of Aβ peptide at the molecular level in both the brain and periphery in relation to the pathology of AD. This will not only provide new information regarding the complex disease pathology, but also offer potential new clues to improve therapeutic strategies and diagnostic biomarkers for the successful treatment of AD.
Anuric Kidney Failure in a Patient With Metastatic Melanoma
Authors: Avani M. Kolla, George Jour, Janice M. Mehnert
Journal: JAMA Oncology (2021)

A 53-year-old man with stage IV melanoma with metastatic disease to the spine and brain presents with acute abdominal pain in the setting of rapidly rising lactic acid dehydrogenase levels. What is your diagnosis?
26590 Design and rationale of Effisayil 1, a Phase II, multicenter, randomized, double-blind, placebo-controlled trial of spesolimab in patients with generalized pustular psoriasis with an acute flare
Authors: Siew Eng Choon, Mark G. Lebwohl, Slaheddine Marrakchi, A. David Burden, Tsen-Fang Tsai, Akimichi Morita, Alexander A. Navarini, Hongjie Deng, Christian Thoma, Hervé Bachelez
Journal: Journal of the American Academy of Dermatology (2021)
27473 Worldwide survey shows that atopic dermatitis in children is associated with a negative impact on their families
Authors: Sébastien Barbarot, Jonathan I. Silverberg, Eric L. Simpson, Stephan Weidinger, Ashish Bansal, Ana B. Rossi, Lysel Brignoli, Tarek Mnif, Grece Saba, Dimittri Delevry, Puneet Mahajan
Journal: Journal of the American Academy of Dermatology (2021)
Placental dysfunction and impaired fetal growth: a relationship with bronchopulmonary dysplasia and pulmonary hypertension
Authors: Karen Young, Ilene Sosenko, Nelson Claure
Journal: Thorax (2021)

More than five decades ago, Northway et al 1 described the clinical, radiological and pathological features of a chronic lung disease in preterm infants characterised by lung emphysema, fibrosis, pulmonary vascular remodelling and cardiac hypertrophy.1 At that time, this chronic lung disease of prematurity, which they named bronchopulmonary dysplasia (BPD), was thought to occur as a consequence of postnatal events, including severe respiratory distress syndrome, oxygen toxicity and volutrauma.1 Despite improvements in neonatal care, postnatal adverse exposures continue to be important factors in BPD pathogenesis. Emerging evidence also suggests that pulmonary outcomes after preterm birth are likely determined not only by postnatal factors but also by the in utero environment.

Male gender, white race, smoking, hypertension and infection have all been linked to increased BPD susceptibility. In addition, growing evidence suggests that fetal growth restriction (FGR) is a major risk factor for BPD.2 Abnormal placentation resulting in impaired placental perfusion is one of the most frequent causes of early FGR (<32 weeks gestational age) and preeclampsia. In the French EPIPAGE-2 study of preterm infants <32 weeks gestation, the risk of moderate/severe BPD was more than sixfold higher in FGR infants.3 Importantly, FGR has also been linked …
Association of Tourette Syndrome and Chronic Tic Disorder With Cervical Spine Disorders and Related Neurological Complications
Authors: Josef Isung, Kayoko Isomura, Henrik Larsson, Anna Sidorchuk, Lorena Fernández de la Cruz, David Mataix-Cols
Journal: JAMA Neurology (2021)

Severe forms of Tourette syndrome or chronic tic disorder (TS/CTD) may involve repeated head jerking. Isolated case reports have described a spectrum of severe neck disorders in individuals with TS/CTD. However, the nature and prevalence of cervical spine disorders in TS/CTD are unknown.To establish if TS/CTD are associated with an increased risk of cervical spine disorders and related neurological complications compared with individuals from the general population.All individuals born from 1973 to 2013 and living in Sweden between 1997 and 2013 were identified. Individuals with a record of TS/CTD diagnosed in specialist settings were matched on age, sex, and county of birth with 10 unexposed individuals randomly selected from the general population. Cox proportional hazards regression models were used to estimate the risk of vascular and nonvascular cervical spine disorders among exposed individuals, compared with unexposed individuals. Models were adjusted for other known causes of cervical spine injury. Data were analyzed from March 19 to May 16, 2021.International Statistical Classification of Diseases and Related Health Problems, Tenth Revision diagnoses of TS/CTD in the Swedish National Patient Register.Records of cervical vascular disorders (ie, aneurysm, cerebral infarction, transitory cerebral ischemia) and cervical nonvascular disorders (ie, spondylosis, cervical disc disorders, fractures of the cervical spine, cervicalgia) and cervical surgeries. Covariates included rheumatic disorders, traffic injuries, fall- or sport-related injuries, and attention-deficit/hyperactivity disorder comorbidity.A total of 6791 individuals with TS/CTD were identified (5238 [77.1%] were male; median [interquartile] age at first diagnosis, 15.6 [11.4-23.7] years) and matched to 67 910 unexposed individuals. Exposed individuals had a 39% increased risk of any cervical spine disorder (adjusted hazard ratio, 1.39; 95% CI, 1.22-1.59). Adjusted hazard ratios for cervical vascular and nonvascular disorders were 1.57 (95% CI, 1.16-2.13) and 1.38 (95% CI, 1.19-1.60), respectively. Risks were similar among men and women.Individuals with severe TS/CTD are at increased risk of cervical spine disorders. These outcomes are relatively rare but may lead to persistent disability in some individuals and thus require close monitoring to facilitate early interventions.