tbuckley/cabot-search huggingface dataset:
Survival time and its predictors in preterm infants in the post-discharge neonatal period: a prospective cohort study in Busoga Region, Uganda
Authors: Charles Opio, Richard Malumba, Joseph Kagaayi, Olufemi Ajumobi, Carol Kamya, Aggrey Mukose, Yeka Adoke, Angela Kisaakye, Peter Waiswa
Journal: The Lancet Global Health (2020)

BackgroundGlobally, out of 15 million babies born preterm every year, around 1 million will die. In Uganda, deaths in preterm infants make up 30% of all neonatal deaths. There is a paucity of information on the most critical time to conduct high-impact interventions among neonates born preterm especially after discharge from hospital. In this study, we determined the survival time to mortality and its predictors in preterm infants in the neonatal period after discharge from hospital.MethodsWe conducted a prospective cohort study in preterm infants in six district hospitals in Busoga Region, Uganda. Prematurity was confirmed using gestational age and birthweight. We assessed participants' background characteristics then followed them up prospectively until 28 days of life. We used Kaplan-Meier survival analysis to estimate survival probabilities while time-to-preterm mortality was described using the 5th percentile. We used Cox proportional hazards regression to determine predictors of survival.FindingsBetween June 1, 2017, and July 14, 2017, we recruited 128 preterm infants to the study. Mean gestational age was 4 days (SD 3) and mean birthweight was 1·8 kg (0·6). Overall, 8% (10/128) of preterm infants died; the 5th percentile survival time was 17 days. We noted a six-fold increase in hazard of mortality in preterm infants who did not have kangaroo mother care (KMC) compared with those who did (adjusted HR 6·4 [95%CI 1·7–24·5]), a five-fold increase in mortality hazard in preterm infants born to HIV-positive mothers compared with babies who had HIV-negative mothers (4·9 [1·1–22·2]); and a four-fold increase in the mortality hazard in preterm infants who were not exclusively breastfed compared with those who were exclusively breastfed (4·4 [1·1–18·3]).InterpretationTo reduce neonatal mortality in Uganda, we recommend follow-up care for preterm infants following hospital discharge, implementation of prevention of mother-to-child transmission of HIV, and exclusive breastfeeding of preterm babies.FundingEast Africa Preterm Birth Initiative sponsored by the Bill & Melinda Gates Foundation.
Abstract A17: Human papillomavirus type 16 and 18 viral loads as predictors associated with abnormal cervical cytology among women in Saudi Arabia
Authors: Dalia Obeid, Shihana Almatrrouk, Hadeel Khayat, Turfah Al-Muammer, Asma Tullbah, Ismail Albadawi, Mohammed Alahdal, Fatimah Alhamlan
Journal: Cancer Research (2020)

Abstract The present study aimed to screen for and genotype HPV among Saudi women; develop sensitive quantitative polymerase chain reaction (qPCR) assays to detect the viral load for the two most common HPV types, namely 16 and 18; and assess whether HPV viral load could be used as a marker for cervical abnormality and disease progression. This study examined 733 specimens (both formalin-fixed, paraffin-embedded specimens and PAP smear samples) from women who underwent cervical screening. The specimens and samples were processed for DNA extraction and then tested for HPV DNA. Approximately 165 specimens (18%) were positive for HPV. Those specimens were genotyped using a reverse line blotting hybridization assay. The results indicated that the most common HPV types detected were a single infection with HPV 16 (51%) or with HPV 18 (28%) followed by infections with multiple HPV types (~7%). A qPCR TaqMan assay developed in-house was used to determine the viral load for HPV genotypes 16 (n=80) and 18 (n=45). Viral loads for both HPV types were significantly associated with cervical cytology grade (P &amp;lt; 0.05). The odds ratio (OR) for the HPV 16 viral load was high for specimens with cervical cancer (OR, 18.8; 95% CI, 4.3–82.9) or for those with high-grade squamous intraepithelial lesions (OR, 14.7; 95% Cl, 2.43–88.49). For the HPV 18 viral load, the OR was significant only for specimens with cervical cancer (OR, 11.1; 95% Cl, 2.2–54.9). Logistic regression models for HPV 16 and for HPV 18 viral load levels were significant, with higher viral load associated with cervical abnormalities. These findings indicate that viral load is a predictor significantly associated with cytology abnormality in women who are positive for high-risk HPVs and suggest integrating a viral load test into current clinical screening practices for HPV-positive women. Citation Format: Dalia Obeid, Shihana Almatrrouk, Hadeel Khayat, Turfah Al-Muammer, Asma Tullbah, Ismail Albadawi, Mohammed Alahdal, Fatimah Alhamlan. Human papillomavirus type 16 and 18 viral loads as predictors associated with abnormal cervical cytology among women in Saudi Arabia [abstract]. In: Proceedings of the AACR Special Conference on the Microbiome, Viruses, and Cancer; 2020 Feb 21-24; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2020;80(8 Suppl):Abstract nr A17.
The Outcome of <i>Ex Vivo</i> TIL Expansion Is Highly Influenced by Spatial Heterogeneity of the Tumor T-Cell Repertoire and Differences in Intrinsic <i>In Vitro</i> Growth Capacity between T-Cell Clones
Authors: Isabel C. Poschke, Jessica C. Hassel, Aaron Rodriguez-Ehrenfried, Katharina A.M. Lindner, Ignacio Heras-Murillo, Lena M. Appel, Johanna Lehmann, Tanja Lövgren, Stina L. Wickström, Claudia Lauenstein, Jasmin Roth, Anna-Katharina König, John B.A.G. Haanen, Joost van den Berg, Rolf Kiessling, Frank Bergmann, Michael Flossdorf, Oliver Strobel, Rienk Offringa
Journal: Clinical Cancer Research (2020)

Abstract Purpose: During our efforts to develop tumor-infiltrating lymphocyte (TIL) therapy to counter the devastating recurrence rate in patients with primary resectable pancreatic ductal adenocarcinoma (PDA), we found that PDA TILs can readily be expanded in vitro and that the majority of resulting TIL cultures show reactivity against the autologous tumor. However, the fraction of tumor-reactive T cells is low. We investigated to which extent this was related to the in vitro expansion. Experimental Design: We compared the clonal composition of TIL preparations before and after in vitro expansion using T-cell receptor (TCR) deep sequencing. Our findings for PDA were benchmarked to experiments with melanoma TILs. Results: We found that the TIL TCR repertoire changes dramatically during in vitro expansion, leading to loss of tumor- dominant T-cell clones and overgrowth by newly emerging T-cell clones that are barely detectable in the tumor. These changes are primarily driven by differences in the intrinsic in vitro expansion capacity of T-cell clones. Single-cell experiments showed an association between poor proliferative capacity and expression of markers related to antigen experience and dysfunction. Furthermore, we found that spatial heterogeneity of the TIL repertoire resulted in TCR repertoires that are greatly divergent between TIL cultures derived from distant tumor samples of the same patient. Conclusions: Culture-induced changes in clonal composition are likely to affect tumor reactivity of TIL preparations. TCR deep sequencing provides important insights into the factors that govern the outcome of in vitro TIL expansion and thereby a path toward optimization of the production of TIL preparations with high therapeutic efficacy. See related commentary by Lozano-Rabella and Gros, p. 4177
Impact assessment of non-pharmaceutical interventions against coronavirus disease 2019 and influenza in Hong Kong: an observational study
Authors: Benjamin J Cowling, Sheikh Taslim Ali, Tiffany W Y Ng, Tim K Tsang, Julian C M Li, Min Whui Fong, Qiuyan Liao, Mike YW Kwan, So Lun Lee, Susan S Chiu, Joseph T Wu, Peng Wu, Gabriel M Leung
Journal: The Lancet Public Health (2020)

A range of public health measures have been implemented to suppress local transmission of coronavirus disease 2019 (COVID-19) in Hong Kong. We examined the effect of these interventions and behavioural changes of the public on the incidence of COVID-19, as well as on influenza virus infections, which might share some aspects of transmission dynamics with COVID-19.We analysed data on laboratory-confirmed COVID-19 cases, influenza surveillance data in outpatients of all ages, and influenza hospitalisations in children. We estimated the daily effective reproduction number (Rt) for COVID-19 and influenza A H1N1 to estimate changes in transmissibility over time. Attitudes towards COVID-19 and changes in population behaviours were reviewed through three telephone surveys done on Jan 20-23, Feb 11-14, and March 10-13, 2020.COVID-19 transmissibility measured by Rt has remained at approximately 1 for 8 weeks in Hong Kong. Influenza transmission declined substantially after the implementation of social distancing measures and changes in population behaviours in late January, with a 44% (95% CI 34-53%) reduction in transmissibility in the community, from an estimated Rt of 1·28 (95% CI 1·26-1·30) before the start of the school closures to 0·72 (0·70-0·74) during the closure weeks. Similarly, a 33% (24-43%) reduction in transmissibility was seen based on paediatric hospitalisation rates, from an Rt of 1·10 (1·06-1·12) before the start of the school closures to 0·73 (0·68-0·77) after school closures. Among respondents to the surveys, 74·5%, 97·5%, and 98·8% reported wearing masks when going out, and 61·3%, 90·2%, and 85·1% reported avoiding crowded places in surveys 1 (n=1008), 2 (n=1000), and 3 (n=1005), respectively.Our study shows that non-pharmaceutical interventions (including border restrictions, quarantine and isolation, distancing, and changes in population behaviour) were associated with reduced transmission of COVID-19 in Hong Kong, and are also likely to have substantially reduced influenza transmission in early February, 2020.Health and Medical Research Fund, Hong Kong.
Re: Shen et al.: Natural history of autosomal recessive Stargardt disease in untreated eyes: a systematic review and meta-analysis of study and individual level data (Ophthalmology. 2019;126:1288–1296)
Authors: Xiangrong Kong, Rupert W. Strauss, Beatriz Munoz, Sheila West, Janet Cheetham, Hendrik P.N. Scholl
Journal: Ophthalmology (2020)
All-Cause Mortality Among Children in the US Foster Care System, 2003-2016
Authors: Barbara H. Chaiyachati, Joanne N. Wood, Nandita Mitra, Krisda H. Chaiyachati
Journal: JAMA Pediatrics (2020)

This cross-sectional analysis uses data from the Adoption and Foster Care Analysis and Reporting System to investigate mortality rates among children in the US foster care system compared with those of the general population.
Prognostic factors and long‐term follow‐up of basiliximab for steroid‐refractory acute <scp>graft‐versus‐host disease</scp> : Updated experience from a large‐scale study
Authors: Si‐Ning Liu, Xiao‐Hui Zhang, Lan‐Ping Xu, Yu Wang, Chen‐Hua Yan, Huan Chen, Yu‐Hong Chen, Wei Han, Feng‐Rong Wang, Jing‐Zhi Wang, Kai‐Yan Liu, Xiao‐Jun Huang, Xiao‐Dong Mo
Journal: American Journal of Hematology (2020)

Acute graft-vs-host disease (aGVHD) is one of the most important causes of early mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT), particularly for those with steroid-refractory (SR)-aGVHD. We aimed to identify the prognostic factors and long-term clinical outcomes of basiliximab treatment for SR-aGVHD. Basiliximab was administered on days 1, 3, and 8, and repeated weekly until aGVHD was less than grade II, or patients showed no response after four doses. Out of 1498 patients receiving allo-HSCT, 230 patients with SR-aGVHD were enrolled. Grade III to IV aGVHD before basiliximab treatment significantly and independently predicted a poorer response to basiliximab in multivariate analysis. And, the cumulative incidence of overall response at 14 days, 28 days, and 56 days after treatment was 41.4% vs 23.1% (P = .023), 70.2% vs 43.6% (P = .002), and 80.1% vs 66.7% (P = .013), respectively. This was for those with grade II and grade III to IV aGVHD. Patients receiving more than four doses of basiliximab had higher rates of infections. The 4-year cumulative incidence of total and severe chronic GVHD after basiliximab treatment was 44.8% (95% CI 38.3%-51.3%) and 2.2% (95% CI 0.3%-4.1%), respectively. The 4-year cumulative incidence of relapse, non-relapse mortality, disease-free survival, and overall survival after basiliximab treatment was 11.3% (95% CI 7.2%-15.4%), 30.0% (95% CI 24.1%-35.9%), 58.7% (95% CI 52.3%-65.1%), and 61.7% (95% CI 55.4%-68.0%), respectively. Comorbidities before allo-HSCT and refined Minnesota aGVHD risk score at diagnosis had significant influences on long-term survival. Thus, basiliximab was a safe and effective treatment for patients with SR-aGVHD.
Correction to: Eculizumab: A Review in Neuromyelitis Optica Spectrum Disorder
Authors: James E. Frampton
Journal: Drugs (2020)

The article Eculizumab: A Review in Neuromyelitis Optica Spectrum Disorder, written by James E. Frampton, was originally published electronically in SpringerLink on 7 April 2020 without Open Access. After publication Alexion Pharmaceuticals, Inc., requested that the article be Open Choice to make the article an open access publication. Post-publication open access was funded by Alexion Pharmaceuticals, Inc.
Optic nerve ultrasonography has 94% sensitivity and 87% specificity for diagnosing increased intracranial pressure
Authors: Nicole Messenger, Christopher R. Carpenter
Journal: Annals of Internal Medicine (2020)

Source Citation Koziarz A, Sne N, Kegel F, et al. Bedside optic nerve ultrasonography for diagnosing increased intracranial pressure: a systematic review and meta-analysis. Ann Intern Med. 2019;171:896-905. 31739316
An unfortunate surgical twist?
Authors: Radj Cally, Antoine Khalil, Rym Zaïmi, Pierre Magdeleinat, Damien Contou
Journal: Thorax (2020)

<h3>Abstract</h3> A pattern in which nucleotide transitions are favored several-fold over transversions is common in molecular evolution. When this pattern occurs among amino acid replacements, explanations often invoke an effect of selection, on the grounds that transitions are more conservative in their effects on proteins. However, the underlying hypothesis of conservative transitions has never been tested directly. Here we assess support for this hypothesis using direct evidence: the fitness effects of mutations in actual proteins, measured via individual or paired growth experiments. We assembled data from 8 published studies, ranging in size from 24 to 757 single-nucleotide mutations that change an amino acid. Every study has the statistical power to reveal significant effects of amino acid exchangeability, and most studies have the power to discern a binary conservative-vs-radical distinction. However, only one study suggests that transitions are significantly more conservative than transversions. In the combined set of 1239 replacements, the chance that a transition is more conservative than a transversion is 53 % (95 % confidence interval, 50 % to 56 %), compared to the null expectation of 50 %. We show that this effect is not large compared to that of most biochemical factors, and is not large enough to explain the several-fold bias observed in evolution. In short, available data have the power to verify the “conservative transitions” hypothesis if true, but suggest instead that selection on proteins plays at best a minor role in the observed bias.
Fungal Trans-kingdom Dynamics Linked to Responsiveness to Fecal Microbiota Transplantation (FMT) Therapy in Ulcerative Colitis
Authors: Irina Leonardi, Sudarshan Paramsothy, Itai Doron, Alexa Semon, Nadeem O. Kaakoush, Jose C. Clemente, Jeremiah J. Faith, Thomas J. Borody, Hazel M. Mitchell, Jean-Frederic Colombel, Michael A. Kamm, Iliyan D. Iliev
Journal: Cell Host & Microbe (2020)
TCRs with segment TRAV9‐2 or a CDR3 histidine are overrepresented among nickel‐specific CD4+ T cells
Authors: Marina Aparicio‐Soto, Franziska Riedel, Melanie Leddermann, Petra Bacher, Alexander Scheffold, Heiner Kuhl, Bernd Timmermann, Dmitriy M. Chudakov, Sonja Molin, Margitta Worm, Guido Heine, Hermann‐Josef Thierse, Andreas Luch, Katherina Siewert
Journal: Allergy (2020)

Nickel is the most frequent cause of T cell-mediated allergic contact dermatitis worldwide. In vitro, CD4+ T cells from all donors respond to nickel but the involved αβ T cell receptor (TCR) repertoire has not been comprehensively analyzed.We introduce CD154 (CD40L) upregulation as a fast, unbiased, and quantitative method to detect nickel-specific CD4+ T cells ex vivo in blood of clinically characterized allergic and non allergic donors. Naïve (CCR7+ CD45RA+) and memory (not naïve) CD154+ CD4+ T cells were analyzed by flow cytometry after 5 hours of stimulation with 200 µmol/L NiSO4 ., TCR α- and β-chains of sorted nickel-specific and control cells were studied by high-throughput sequencing.Stimulation of PBMCs with NiSO4 induced CD154 expression on ~0.1% (mean) of naïve and memory CD4+ T cells. In allergic donors with recent positive patch test, memory frequencies further increased ~13-fold and were associated with markers of in vivo activation. CD154 expression was TCR-mediated since single clones could be specifically restimulated. Among nickel-specific CD4+ T cells of allergic and non allergic donors, TCRs expressing the α-chain segment TRAV9-2 or a histidine in their α- or β-chain complementarity determining region 3 (CDR3) were highly overrepresented.Induced CD154 expression represents a reliable method to study nickel-specific CD4+ T cells. TCRs with particular features respond in all donors, while strongly increased blood frequencies indicate nickel allergy for some donors. Our approach may be extended to other contact allergens for the further development of diagnostic and predictive in vitro tests.
HLA-corrected tumor mutation burden and homologous recombination deficiency for the prediction of response to PD-(L)1 blockade in advanced non-small-cell lung cancer patients
Authors: J.H. Shim, H.S. Kim, H. Cha, S. Kim, T.M. Kim, V. Anagnostou, Y.-L. Choi, H.A. Jung, J.-M. Sun, J.S. Ahn, M.-J. Ahn, K. Park, W.-Y. Park, S.-H. Lee
Journal: Annals of Oncology (2020)

Immune checkpoint inhibitors (ICIs) have been shown to be beneficial for some patients with advanced non-small-cell lung cancer (NSCLC). However, the underlying mechanisms mediating the limited response to ICIs remain unclear.We carried out whole-exome sequencing on 198 advanced NSCLC tumors that had been sampled before anti-programmed cell death 1 (anti-PD-1)/programmed death-ligand 1 (PD-L1) therapy. Detailed clinical characteristics were collected on these patients. We designed a new method to estimate human leukocyte antigen (HLA)-corrected tumor mutation burden (TMB), a modification which considers the loss of heterozygosity of HLA from conventional TMB. We carried out external validation of our findings utilizing 89 NSCLC samples and 110 melanoma samples from two independent cohorts of immunotherapy-treated patients.Homology-dependent recombination deficiency was identified in 37 patients (18.7%) and was associated with longer progression-free survival (PFS; P = 0.049). Using the HLA-corrected TMB, non-responders to ICIs were identified, despite having a high TMB (top 25%). Ten patients (21.3% of the high TMB group) were reclassified from the high TMB group into the low TMB group. The objective response rate (ORR), PFS, and overall survival (OS) were all lower in these patients compared with those of the high TMB group (ORR: 20% versus 59%, P = 0.0363; PFS: hazard ratio = 2.91, P = 0.007; OS: hazard ratio = 3.43, P = 0.004). Multivariate analyses showed that high HLA-corrected TMB was associated with a significant survival advantage (hazard ratio = 0.44, P = 0.015), whereas high conventional TMB was not associated with a survival advantage (hazard ratio = 0.63, P = 0.118). Applying this approach to the independent cohorts of 89 NSCLC patients and 110 melanoma patients, TMB-based survival prediction was significantly improved.HLA-corrected TMB can reconcile the observed disparity in relationships between TMB and ICI responses, and is of predictive and prognostic value for ICI therapies.
Immune involvement of the contralateral hemisphere in a glioblastoma mouse model
Authors: Matheus H W Crommentuijn, Sjoerd T T Schetters, Sophie A Dusoswa, Laura J W Kruijssen, Juan J Garcia-Vallejo, Yvette van Kooyk
Journal: Journal for ImmunoTherapy of Cancer (2020)

Background Glioblastoma (GBM) is the most common and deadliest form of brain cancer in adults. Standard treatment, consisting of surgery and radiochemotherapy, only provides a modest survival benefit and is incapable of combating infiltrating GBM cells in other parts of the brain. New therapies in clinical trials, such as anti-programmed cell death 1 immunotherapy, have so far shown limited success in GBM. Moreover, it is unclear how the growth of GBM suppresses the immune system locally at the site of the brain tumor or if distant sites of tumor cell migration are also involved. Invasive GBM cells in brain tissue beyond the primary tumor limit the use of surgery, thus immunotherapy could be beneficial if activated/suppressed immune cells are present in the contralateral hemisphere. Methods Here, we used a syngeneic orthotopic GL26 GBM mouse model and multiparameter fluorescence-activated cell sorting analysis to study the phenotype of resident and infiltrating immune cells in both the brain tumor hemisphere and contralateral hemisphere. Results We show that lymphoid cells, including tumor antigen-specific CD8 + tumor-infiltrating lymphocytes (TILs) are present in the tumor and are characterized by a tolerogenic phenotype based on high immune checkpoint expression. Massive infiltration of myeloid cells is observed, expressing immune checkpoint ligands, suggesting an immune-dependent coinhibitory axis limiting TIL responses. Surprisingly, these phenotypes are paralleled in the contralateral hemisphere, showing that infiltrating immune cells are also present at distant sites, expressing key immune checkpoints and immune checkpoint ligands. Conclusion Whole-brain analysis indicates active immune involvement throughout the brain, both at the site of the primary tumor and in the contralateral hemisphere. Using the right combination and timing, immune checkpoint blockade could have the potential to activate immune cells at the site of the brain tumor and at distant sites, thereby also targeting diffusely infiltrating GBM cells.
Association of Postnatal Cytomegalovirus Infection With Head Growth—Reply
Authors: Kristin E. D. Weimer, Sallie R. Permar, Rachel G. Greenberg
Journal: JAMA Pediatrics (2020)

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