tbuckley/cabot-search huggingface dataset:
Safety and immunogenicity of the ChAdOx1 nCoV-19 (AZD1222) vaccine against SARS-CoV-2 in people living with and without HIV in South Africa: an interim analysis of a randomised, double-blind, placebo-controlled, phase 1B/2A trial
Authors: Shabir A Madhi, Anthonet L Koen, Alane Izu, Lee Fairlie, Clare L Cutland, Vicky Baillie, Sherman D Padayachee, Keertan Dheda, Shaun L Barnabas, Qasim Ebrahim Bhorat, Carmen Briner, Parvinder K Aley, Sutika Bhikha, Tandile Hermanus, Elizea Horne, Aylin Jose, Prudence Kgagudi, Teresa Lambe, Masebole Masenya, Mduduzi Masilela, Nonhlanhla Mkhize, Andrew Moultrie, Christian K Mukendi, Thandeka Moyo-Gwete, Amit J Nana, Ayanda Nzimande, Faeezah Patel, Sarah Rhead, Carol Taoushanis, Asha Thombrayil, Samuel van Eck, Merryn Voysey, Tonya L Villafana, Johan Vekemans, Sarah C Gilbert, Andrew J Pollard, Penny L Moore, Gaurav Kwatra
Journal: The Lancet HIV (2021)

People living with HIV are at an increased risk of fatal outcome when admitted to hospital for severe COVID-19 compared with HIV-negative individuals. We aimed to assess safety and immunogenicity of the ChAdOx1 nCoV-19 (AZD1222) vaccine in people with HIV and HIV-negative individuals in South Africa.
Adverse health outcomes in vitamin D supplementation trials for depression: A systematic review
Authors: Karen S. van den Berg, Radboud M. Marijnissen, Rob H.S. van den Brink, Richard C. Oude Voshaar, Johanna M. Hegeman
Journal: Ageing Research Reviews (2021)

Vitamin D deficiency is a universal risk factor for adverse health outcomes. Since depression is consistently associated with low vitamin D levels as well as several adverse health outcomes, vitamin D supplementation may be especially relevant for depressed persons. This review examines the potential benefits of vitamin D for (somatic) health outcomes in randomised controlled supplementation trials for depression. Systematic literature search to assess whether adverse health outcomes, such as frailty, falls, or cognitive functioning, were included in vitamin D supplementation trials for depression, and whether these outcomes were affected by supplementation. The revised Cochrane tool for assessing risk of bias in randomised trials was used. Thirty-one trials were included. Adverse health outcomes were considered in five studies. Two studies reported some beneficial effect on an adverse health outcome. While depressed persons are at increased risk of vitamin D deficiency, supplementation trials hardly addressed the common negative health consequences of low vitamin D levels as secondary outcome measures. Well-designed trials of the effects of vitamin D supplementation in late-life depression should explore whether adverse health outcomes can be prevented or stabilised, and whether depression benefits from this improvement.
Airway remodeling and bronchodilator responses in asthma assessed by endobronchial optical coherence tomography
Authors: Zhu‐Quan Su, Zi‐Qing Zhou, Wei‐Jie Guan, Ming‐Yue Fan, Wan‐Yuan Rao, Yu Chen, Xiao‐Bo Chen, Chang‐Hao Zhong, Chun‐Li Tang, Shi‐Yue Li, Nan‐Shan Zhong
Journal: Allergy (2021)

Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Congenital Cytomegalovirus Infection Burden and Epidemiologic Risk Factors in Countries With Universal Screening
Authors: Paddy Ssentongo, Christine Hehnly, Patricia Birungi, Mikayla A. Roach, Jada Spady, Claudio Fronterre, Ming Wang, Laura E. Murray-Kolb, Laila Al-Shaar, Vernon M. Chinchilli, James R. Broach, Jessica E. Ericson, Steven J. Schiff
Journal: JAMA Network Open (2021)

<h3>Importance</h3> Congenital cytomegalovirus (cCMV) infection is the most common congenital infection and the leading acquired cause of developmental disabilities and sensorineural deafness, yet a reliable assessment of the infection burden is lacking. <h3>Objectives</h3> To estimate the birth prevalence of cCMV in low- and middle-income countries (LMICs) and high-income countries (HICs), characterize the rate by screening methods, and delineate associated risk factors of the infection. <h3>Data Sources</h3> MEDLINE/PubMed, Scopus, and Cochrane Database of Systematic Reviews databases were searched from January 1, 1960, to March 1, 2021, and a total of 1322 studies were identified. <h3>Study Selection</h3> Studies that provided data on the prevalence of cCMV derived from universal screening of infants younger than 3 weeks were included. Targeted screening studies were excluded. <h3>Data Extraction and Synthesis</h3> Preferred Reporting Items for Systematic Reviews and Meta-analyses guideline was followed. Extraction was performed independently by 3 reviewers. Quality was assessed using the Newcastle-Ottawa Scale for cohort studies. Random-effects meta-analysis was undertaken. Metaregression was conducted to evaluate the association of sociodemographic characteristics, maternal seroprevalence, population-level HIV prevalence, and screening methods with the prevalence of cCMV. <h3>Main Outcomes and Measures</h3> Birth prevalence of cCMV ascertained through universal screening of infants younger than 3 weeks for CMV from urine, saliva, or blood samples. <h3>Results</h3> Seventy-seven studies comprising 515 646 infants met the inclusion criteria from countries representative of each World Bank income level. The estimated pooled overall prevalence of cCMV was 0.67% (95% CI, 0.54%-0.83%). The pooled birth prevalence of cCMV was 3-fold greater in LMICs (1.42%; 95% CI, 0.97%-2.08%; n = 23 studies) than in HICs (0.48%; 95% CI, 0.40%-0.59%, n = 54 studies). Screening methods with blood samples demonstrated lower rates of cCMV than urine or saliva samples (odds ratio [OR], 0.38; 95% CI, 0.23-0.66). Higher maternal CMV seroprevalence (OR, 1.19; 95% CI, 1.11-1.28), higher population-level HIV prevalence (OR, 1.22; 95% CI, 1.05-1.40), lower socioeconomic status (OR, 3.03; 95% CI, 2.05-4.47), and younger mean maternal age (OR, 0.85; 95% CI, 0.78-0.92, older age was associated with lower rates) were associated with higher rates of cCMV. <h3>Conclusions and Relevance</h3> In this meta-analysis, LMICs appeared to incur the most significant infection burden. Lower rates of cCMV were reported by studies using only blood or serum as a screening method.
Post-migration acquisition of HIV: Estimates from four European countries, 2007 to 2016
Authors: Zheng Yin, Alison E Brown, Brian D Rice, Gaetano Marrone, Anders Sönnerborg, Barbara Suligoi, Andre Sasse, Dominique Van Beckhoven, Teymur Noori, Vincenza Regine, Valerie C Delpech
Journal: Eurosurveillance (2021)

Background The assumption that migrants acquire human immunodeficiency virus (HIV) before migration, particularly those from high prevalence areas, is common. Aim We assessed the place of HIV acquisition of migrants diagnosed in four European countries using surveillance data. Methods Using CD4+ T-cell count trajectories modelled to account for seroconversion bias, we estimated infection year of newly HIV-diagnosed migrants residing in the United Kingdom (UK), Belgium, Sweden and Italy with a known arrival year and CD4+ T-cell count at diagnosis. Multivariate analyses identified predictors for post-migration acquisition. Results Between 2007 and 2016, migrants constituted 56% of people newly diagnosed with HIV in the UK, 62% in Belgium, 72% in Sweden and 29% in Italy. Of 23,595 migrants included, 60% were born in Africa and 70% acquired HIV heterosexually. An estimated 9,400 migrants (40%; interquartile range (IQR): 34–59) probably acquired HIV post-migration. This proportion was similar by risk group, sex and region of birth. Time since migration was a strong predictor of post-migration HIV acquisition: 91% (IQR: 87–95) among those arriving 10 or more years prior to diagnosis; 30% (IQR: 21–37) among those 1–5 years prior. Younger age at arrival was a predictor: 15–18 years (81%; IQR: 74–86), 19–25 years (53%; IQR: 45–63), 26–35 years (37%; IQR: 30–46) and 36 years and older (25%; IQR: 21–33). Conclusions Migrants, regardless of origin, sex and exposure to HIV are at risk of acquiring HIV post-migration to Europe. Alongside accessible HIV testing, prevention activities must target migrant communities.
Incidence of Type 1 Diabetes May Be Underestimated in the Chinese Population: Evidence From 21.7 Million People Between 2007 and 2017
Authors: Chang Liu, Ying-Chao Yuan, Mo-Ning Guo, Zhong Xin, Guan-Jie Chen, Amy R. Bentley, Lin Hua, Jian-Peng Zheng, Kenneth Ekoru, Jin-Kui Yang
Journal: Diabetes Care (2021)

OBJECTIVE Previous reports of the annual incidence of type 1 diabetes (T1D) in China were conducted using retrospective hospital cases, which may not reflect the reality. This longitudinal study estimated T1D incidence in a Chinese population of 21.7 million from 2007 to 2017. RESEARCH DESIGN AND METHODS A population-based registry of T1D was performed by the Beijing Municipal Health Commission Information Center. Annual incidence and 95% CIs were calculated by age group and sex. The association of sex with T1D incidence and predicted new cases of T1D were assessed using Poisson regression models. Annual percentage change and average annual percentage of change were assessed using Joinpoint regression. RESULTS Overall, there were 6,875 individuals who developed T1D from 2007 to 2017 in this population. T1D incidence (/100,000 persons) (95% CI) significantly increased from 2.72 (2.51, 2.93) in 2007 to 3.60 (3.38, 3.78) in 2017 (P &amp;lt; 0.001). The T1D onset peak was in the 10–14-year-old age group. While no significant trend was found in the 0–14- and 15–29-year-old age groups, T1D incidence markedly increased from 1.87 to 3.52 in the ≥30-year-old age group (P &amp;lt; 0.05). The prevalence of diabetic ketoacidosis at diagnosis was highest in the 0–4-year-old age group. We predicted new cases of T1D will increase 1.57-fold over the next decade. CONCLUSIONS T1D incidence in this large Chinese population is higher than has been reported previously. From 2007 to 2017, although the incidence peak was in the 10–14-year age group, the T1D incidence increased sharply in adults but not in youth.
Thrombopoietin level predicts response to treatment with romiplostim in chemotherapy‐induced thrombocytopenia
Authors: Andrew B. Song, Katayoon Goodarzi, Rebecca Karp Leaf, David J. Kuter, Hanny Al‐Samkari
Journal: American Journal of Hematology (2021)

Abstract Chemotherapy‐induced thrombocytopenia (CIT) is a common complication of cancer treatment. Evidence has emerged supporting use of romiplostim to treat CIT but predicting clinical response to romiplostim is not possible. To determine utility of endogenous thrombopoietin (TPO) as a biomarker of romiplostim response, we performed an observational cohort study of patients with CIT and known baseline TPO levels receiving romiplostim. For weekly on‐romiplostim platelet (Plt) count assessment, clinical response was defined as Plt ≥ 75 × 10 9 /L and ≥ 30 × 10 9 /L above pretreatment baseline. Overall, moderate, and superior classes of treatment response were defined based on fraction of Plt assessments meeting clinical response criteria (&gt; 0, ≥ 0.6, and ≥ 0.8, respectively). Sixty‐three patients with CIT were included; median age was 62 years, 41.3% were female, and median (IQR) romiplostim treatment duration was 14 (4–38) weeks. Median (IQR) TPO was lower in patients achieving moderate response to romiplostim vs those who did not, 234 (135–1085) pg/mL vs 665 (244–1970) pg/mL ( p = .034) and lower still in patients achieving superior response vs those who did not, 212 (91–690) pg/mL versus 559 (173–1851) pg/mL ( p = .023). Negative correlations were found between TPO level and baseline Plt and TPO level and response fraction. A positive correlation was found between TPO level and lowest effective romiplostim dose. In receiver operating characteristic (ROC) analysis, optimally discriminant TPO level thresholds (as defined by Youden's Index) were ≤ 457 pg/mL for moderate response and ≤ 260 pg/mL for superior response. In conclusion, TPO levels predict response to romiplostim in CIT, with lower levels predicting improved probability and depth of response.
Reply
Authors: Abdul Rahman Hakeem, Ashwin Rammohan, Mukul Vij, Mohamed Rela
Journal: Hepatology (2021)

We thank Varghese et al. for the interest shown in our article. Their assumptions are nonetheless fractious and factually erroneous, necessitating clarification. The findings of post-liver transplant (LT) allograft biopsies in our cohort of yellow phosphorus (YP) toxin-related liver injury (TLI) was unlike anything observed in other causes of post-LT early allograft dysfunction (EAD).
Phase Ia study of CBP-1008, a bi-specific ligand drug conjugate targeting FRα and TRPV6, in patients with advanced solid tumors.
Authors: Jifang Gong, Xichun Hu, Jian Zhang, Yiqun Du, Robert Huang, Yan Teng, Wei Tan, Lin Shen
Journal: Journal of Clinical Oncology (2021)

3077 Background: CBP-1008 is a first-in-class bi-specific ligand drug conjugate targeting folate receptor α (FRα) and vanilloid subfamily member 6 of transient receptor potential channels (TRPV6) with a high potency tublin inhibitor payload, monomethyl auristatin E (MMAE). A first-in-human, multicenter, phase I study of CBP-1008 (NCT 04740398) is ongoing, and we herein report the preliminary result of part A which is to evaluate the safety, tolerability, pharmacokinetics, and antitumor activity of CBP-1008 in solid tumors. Methods: Dose escalation commenced in single-patient cohorts for the first 2 planned dose levels and then followed by a standard 3 + 3 scheme. CBP-1008 was administered as intravenous infusion at escalating doses (0.015, 0.03, 0.12, 0.15, and 0.18 mg/kg). The primary endpoints were to determine the safety and maximum tolerated dose (MTD). Adverse events (AEs) and dose-limiting toxicities (DLTs) were evaluated. Results: Eighteen patients with advanced solid tumors who had failed multiple systemic treatment regimens were enrolled. The diseases include colorectal cancer (n = 7), breast cancer (n = 5), non-small cell lung cancer (n = 2), ovarian cancer (n = 2), adrenocortical carcinoma (n = 1), and follicular dendritic cell sarcoma (n = 1). The DLTs observed included grade 4 hypophosphatemia (0.15 mg/kg), grade 4 neutropenia (0.12, 0.15, and 0.18 mg/kg), grade 4 febrile neutropenia (FN) (0.18 mg/kg), grade 3 hyperglycemia (0.15 mg/kg), and grade 3 alanine aminotransferase (ALT) elevation (0.18 mg/kg). The most common all grade AEs suspected to be drug-related were fever (83.3%, totally limited to grade 1-2), aspartate aminotransferase (AST) elevation (72.2%, 5.6% evaluated as grade 3-4), leukopenia (66.7%, 27.8% as grade 3-4), neutropenia (66.7%, 38.9% as grade 3-4) and hypohemoglobinemia (55.6%, 5.6% as grade 3-4), with no drug-related deaths. MTD is estimated between 0.15 mg/kg and 0.18 mg/kg Q2W. Best overall response was partial response (PR) in 1 patient at 0.18 mg/kg and 4 patients (22.2%) achieved stable disease (SD). Responses occurred in patients with FRα and/or TRPV6 -positive expression advanced solid tumors. Conclusions: CBP-1008 has demonstrated acceptable safety profile. Tumor response correlating with dosing and FRα/TRPV6 receptor expression levels has been well observed. Clinical trial information: 04740398.
Stable softening bioelectronics: A paradigm for chronically viable ester-free neural interfaces such as spinal cord stimulation implants
Authors: Aldo Garcia-Sandoval, Edgar Guerrero, Seyed Mahmoud Hosseini, Pedro E. Rocha-Flores, Rashed Rihani, Bryan J. Black, Ajay Pal, Jason B. Carmel, Joseph J. Pancrazio, Walter E. Voit
Journal: Biomaterials (2021)
A Hospital-Wide Intervention to Improve Compliance With TNM Cancer Staging Documentation
Authors: Jason H. Lee, Tariq Mohamed, Celia Ramsey, Jihoon Kim, Shelly Kane, Kathryn A. Gold, Farhoud Faraji, Joseph A. Califano
Journal: Journal of the National Comprehensive Cancer Network (2021)

Accurate oncologic staging meeting clinical practice guidelines is essential for guideline adherence, quality assessment, and survival outcomes. However, timely and uniform documentation in the electronic health record (EHR) at the time of diagnosis is a challenge for providers. This quality improvement project aimed to increase provider compliance of timely clinical TNM (cTNM) or pathologic TNM (pTNM) staging for newly diagnosed oncologic patients.Providers in the following site-specific oncologic teams were included: head and neck, skin, breast, genitourinary, gastrointestinal, lung and thoracic, gynecologic, colorectal, and bone marrow transplant. Interventions to facilitate timely cTNM and pTNM staging included standardized EHR-based workflows, learning modules, stakeholder meetings, and individualized provider training sessions. For most teams, staging was considered compliant if it was completed in the EHR within the first 7 days of the calendar month after the date of the patient visit. Factors associated with staging compliance were analyzed using logistic regression models.From January 1, 2014, to December 31, 2018, 7,787 preintervention and 5,152 postintervention new patient visits occurred. During the preintervention period, staging was compliant in 5.6% of patients compared with 67.4% of patients after intervention (P<.001). In the final month of the postintervention period, the overall staging compliance rate was 78.1%. At most recent tracking, staging compliance was 95%, 97%, and 93% in December 2019, January 2020, and February 2020, respectively. Logistic regression found that increasing years of provider experience was associated with decreased staging compliance.High rates of staging compliance in complex multidisciplinary academic oncologic practice models can be achieved via comprehensive quality improvement and structured initiatives. This approach serves as a model for improving oncologic documentation systems to facilitate clinical decision-making and multidisciplinary coordination of care.
Humoral and cellular immune responses in SARS-CoV-2 mRNA-vaccinated patients with cancer
Authors: Mario Mairhofer, Lea Kausche, Sabine Kaltenbrunner, Riad Ghanem, Maike Stegemann, Katharina Klein, Maria Pammer, Isabella Rauscher, Helmut J.F. Salzer, Stefan Doppler, Anna Habringer, Christian Paar, Susanne Kimeswenger, Wolfram Hoetzenecker, Bernd Lamprecht, Soyoung Lee, Clemens A. Schmitt
Journal: Cancer Cell (2021)
26941 The prognostic value of inositol polyphosphate 5-phosphatase in cutaneous squamous cell carcinoma in a random sampling representative of the general population
Authors: Aaron R. Mangold, Meera H. Patel, Caitlin M. Brumfiel, Kevin J. Severson, Richard J. Butterfield, Nan Zhang, Steven A. Nelson, David J. DiCaudo, Mark R. Pittelkow, Aleksander Sekulic
Journal: Journal of the American Academy of Dermatology (2021)
Effect of Low-Intensity vs High-Intensity Walking Exercise on Walk Distance in Patients With Peripheral Artery Disease
Authors: Eduardo C. Costa, Gabriel G. Cucato, Raphael M. Ritti-Dias
Journal: JAMA (2021)

To the Editor We read with great interest the seminal study conducted by Dr McDermott and colleagues1 that investigated the effect of walking exercise intensity on the ambulatory function of patients with peripheral artery disease (PAD).
P-113 FIGHT-302: Phase 3 study of first-line pemigatinib vs gemcitabine + cisplatin for cholangiocarcinoma with FGFR2 fusions or rearrangement
Authors: T. Bekaii-Saab, J. Valle, E. Van Cutsem, L. Rimassa, J. Furuse, T. Ioka, T. Macarulla, J. Bridgewater, H. Wasan, M. Borad, A. Vogel, C. Lihou, H. Zhen, P. Jiang, P. Langmuir, D. Melisi
Journal: Annals of Oncology (2021)
Usefulness of Tricuspid Annular Plane Systolic Excursion as the Index of Right Ventricular Performance to Detect Low Stroke Index
Authors: Mukai Kentaro, Mizuno Tomofumi, Nakano Yusuke, Niwa Toru, Wakabayashi Hirokazu, Watanabe Atsushi, Andoh Hirohiko, Waseda Katsuhisa, Fukuta Motoyuki, Takashima Hiroaki, Amano Tetsuya
Journal: Circulation (2016)
Has the Current Oncology Value Paradigm Forgotten Patients’ Time?
Authors: Adam Fundytus, Vinay Prasad, Christopher M. Booth
Journal: JAMA Oncology (2021)

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Biology and pathology of the uterine microenvironment and its natural killer cells
Authors: Fuyan Wang, Anita Ellen Qualls, Laia Marques-Fernandez, Francesco Colucci
Journal: Cellular and Molecular Immunology (2021)

Tissues are the new frontier of discoveries in immunology. Cells of the immune system are an integral part of tissue physiology and immunity. Determining how immune cells inhabit, housekeep, and defend gut, lung, brain, liver, uterus, and other organs helps revealing the intimate details of tissue physiology and may offer new therapeutic targets to treat pathologies. The uterine microenvironment modulates the development and function of innate lymphoid cells [ILC, largely represented by natural killer (NK) cells], macrophages, T cells, and dendritic cells. These immune cells, in turn, contribute to tissue homeostasis. Regulated by ovarian hormones, the human uterine mucosa (endometrium) undergoes ~400 monthly cycles of breakdown and regeneration from menarche to menopause, with its fibroblasts, glands, blood vessels, and immune cells remodeling the tissue into the transient decidua. Even more transformative changes occur upon blastocyst implantation. Before the placenta is formed, the endometrial glands feed the embryo by histiotrophic nutrition while the uterine spiral arteries are stripped of their endothelial layer and smooth muscle actin. This arterial remodeling is carried out by invading fetal trophoblast and maternal immune cells, chiefly uterine NK (uNK) cells, which also assist fetal growth. The transformed arteries no longer respond to maternal stimuli and meet the increasing demands of the growing fetus. This review focuses on how the everchanging uterine microenvironment affects uNK cells and how uNK cells regulate homeostasis of the decidua, placenta development, and fetal growth. Determining these pathways will help understand the causes of major pregnancy complications.
SARS-CoV-2 infection of islet β cells: Evidence and implications
Authors: Amy L. Clark, Raghavendra G. Mirmira
Journal: Cell Reports Medicine (2021)

The health of insulin-producing β cells is critical for normoglycemia. Wu et al.1 and Tang et al.2 provide evidence in vitro that β cells can be infected by SARS-CoV-2 virus, possibly contributing to worsening hyperglycemia seen during the COVID-19 pandemic.