bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of Anti–PD-1 and Anti–CTLA-4 on the Human Immunodeficiency Virus (HIV) Reservoir in People Living With HIV With Cancer on Antiretroviral Therapy: The AIDS Malignancy Consortium 095 Study
Authors: Rasmussen Thomas A , Rajdev Lakshmi , Rhodes Ajantha , Dantanarayana Ashanti , Tennakoon Surekha , Chea Socheata , Spelman Tim , Lensing Shelly , Rutishauser Rachel , Bakkour Sonia , Busch Michael , Siliciano Janet D , Siliciano Robert F , Einstein Mark H , Dittmer Dirk P , Chiao Elizabeth , Deeks Steven G , Durand Christine , Lewin Sharon R
Published: February 2021

Background

Antibodies to programmed cell death 1 (PD-1) and cytotoxic T-lymphocyte–associated protein 4 (CTLA-4) may perturb human immunodeficiency virus (HIV) persistence during antiretroviral therapy (ART) by reversing HIV latency and/or boosting HIV-specific immunity, leading to clearance of infected cells. We tested this hypothesis in a clinical trial of anti–PD-1 alone or in combination with anti–CTLA-4 in people living with HIV (PLWH) and cancer.

Methods

This was a substudy of the AIDS Malignancy Consortium 095 Study. ART-suppressed PLWH with advanced malignancies were assigned to nivolumab (anti–PD-1) with or without ipilimumab (anti–CTLA-4). In samples obtained preinfusion and 1 and 7 days after the first and fourth doses of immune checkpoint blockade (ICB), we quantified cell-associated unspliced (CA-US) HIV RNA and HIV DNA. Plasma HIV RNA was quantified during the first treatment cycle. Quantitative viral outgrowth assay (QVOA) to estimate the frequency of replication-competent HIV was performed before and after ICB for participants with samples available.

Results

Of 40 participants, 33 received nivolumab and 7 nivolumab plus ipilimumab. Whereas CA-US HIV RNA did not change with nivolumab monotherapy, we detected a median 1.44-fold increase (interquartile range, 1.16–1.89) after the first dose of nivolumab and ipilimumab combination therapy (P = .031). There was no decrease in the frequency of cells containing replication-competent HIV, but in the 2 individuals on combination ICB for whom we had longitudinal QVOA, we detected decreases of 97% and 64% compared to baseline.

Conclusions

Anti–PD-1 alone showed no effect on HIV latency or the latent HIV reservoir, but the combination of anti–PD-1 and anti–CTL-4 induced a modest increase in CA-US HIV RNA and may potentially eliminate cells containing replication-competent HIV.

Clinical Trials Registration

NCT02408861.
The Impact of State Mask-Wearing Requirements on the Growth of Coronavirus Disease 2019 Cases, Hospitalizations, and Deaths in the United States
Authors: Rebeiro Peter F , Aronoff David M , Smith M Kevin
Published: February 2021

In ecologic analyses of US states, piecewise multivariable models showed lower case-rate slopes after implementation of mask requirements: −1.0% (95% confidence interval, −1.34% to −.57%) and −0.44% (−.86% to −.03%) per 100 000 per day in early- and late-adopter states, respectively, compared with never-adopter states. Our findings support statewide mask requirements to mitigate transmission of coronavirus disease 2019.
Battering Review Spam Through Ensemble Learning in Imbalanced Datasets
Authors: Khurshid Faisal , Zhu Yan , Hu Jie , Ahmad Muqeet , Ahmad Mushtaq
Published: February 2021

Nowadays, people’s buying or availing services decisions are subject to online available reviews/opinions. The authenticity of these reviews/opinions is dubious, as there exist many fake reviews posted to attain monetary benefits by promoting their own or demoting the competitor’s products or services known as review spam. Although the number of spam is relatively less than that of normal reviews in real-life, this class imbalance is a critical concern in review spam detection. The performance degrades when the classifier skew towards the majority class. Moreover, efficient feature selection is essentially needed for this issue. The purpose of this study is to develop a framework based on different effective feature selection along with data balancing techniques. Validation results show that our proposed framework commendably copes up with the review spam issue and a higher precision on the real-life dataset. Further, we tested the sensitivity of our proposed framework using both parametric and non-parametric tests and found it significant.
From organic and inorganic phosphates to valvular and vascular calcifications
Authors: Bäck Magnus , Michel Jean-Baptiste
Published: February 2021

Calcification of the arterial wall and valves is an important part of the pathophysiological process of peripheral and coronary atherosclerosis, aortic stenosis, ageing, diabetes, and chronic kidney disease. This review aims to better understand how extracellular phosphates and their ability to be retained as calcium phosphates on the extracellular matrix initiate the mineralization process of arteries and valves. In this context, the physiological process of bone mineralization remains a human model for pathological soft tissue mineralization. Soluble (ionized) calcium precipitation occurs on extracellular phosphates; either with inorganic or on exposed organic phosphates. Organic phosphates are classified as either structural (phospholipids, nucleic acids) or energetic (corresponding to phosphoryl transfer activities). Extracellular phosphates promote a phenotypic shift in vascular smooth muscle and valvular interstitial cells towards an osteoblast gene expression pattern, which provokes the active phase of mineralization. A line of defense systems protects arterial and valvular tissue calcifications. Given the major roles of phosphate in soft tissue calcification, phosphate mimetics, and/or prevention of phosphate dissipation represent novel potential therapeutic approaches for arterial and valvular calcification.
Electrophysiological and Behavioral Responses of Dasychira baibarana (Lepidoptera: Lymantriidae) to Tea Plant Volatiles
Authors: Magsi Fida Hussain , Luo Zongxiu , Zhao Yingjie , Li Zhaoqun , Cai Xiaoming , Bian Lei , Chen Zongmao
Published: February 2021

Tea black tussock moth, Dasychira baibarana (Matsumura) (Lepidoptera: Lymantriidae), is a devastating pest species of the tea plant in China. Here, we evaluated the responses of D. baibarana to tea plant volatiles using gas chromatography coupled electroantennographic detection (GC–EAD), eleclectroantennography (EAG), and a Y-tube olfactometer. In total, 11 of 18 analyzed compounds elicited GC–EAD responses from test insects. GC–EAD bio-active compounds were further investigated using EAG and behavioral responses. In the EAG analysis, male moths had significantly greater responses to four compounds [(Z)-3-hexenyl butyrate, (Z)-3-hexen-1-ol, ocimene and benzyl alcohol] than female moths. For females, maximum EAG amplitudes, were recorded in response to linalool, (Z)-3-hexenyl hexanoate and (Z)-jasmone. In EAG and behavioral bio-assays, the responses of both sexes were dose independent. In behavioral bio-assays male moths responding significantly to (Z)-3-hexen-1-ol, ocimene, (Z)-3-hexenyl butyrate, linalool, benzyl alcohol, and (Z)-jasmone at various concentrations. For females, significant behavioral responses were observed to (Z)-3-hexenyl hexanoate, followed by (Z)-jasmone, linalool, ocimene, and benzyl alcohol. However, neither sex was sensitive to 4 of the 11 tested compounds, phenyethyl alcohol, phenylacetonitrile, (E)-nerolidol, and indole. The present results showed that tea plant volatiles influenced the behavior of D. baibarana moths, which will greatly contribute in developing eco-friendly control strategies for D. baibarana, through the application of a blend of compounds that showed significant EAG and behavioral responses or a blend combined with female-produced sex pheromones.
Economic burden of patients living with heart disease in the last years of life in Australia: a retrospective analysis using linked data
Authors: Kularatna Sanjeewa , Senanayake Sameera , Parsonage William , Jun Deokhoon , McPhail Steven
Published: February 2021

Aims

People living with heart disease are at elevated risk of hospitalization during the last years of their life. The aim of this study was to describe hospitalization-related usage patterns, and associated cost burden, for patients living with heart disease in the last 6 years of their life.

Methods and results

The study was an observational cohort study, using routinely collected and linked data from hospital admission (HA), emergency department (ED) presentation and death registry data in Queensland, Australia. The study sample included 1000 randomly selected patients who died in 2017 due to any cause who had been living with heart disease for at least the prior 6 years. The two main outcomes of interest in this study were cost of HAs and cost of ED presentation in the last 6 years before death. Total cost was calculated as a sum of direct and overhead costs from each of the hospital presentations. The mean HA per patient in the sixth year, second year, and last year prior to death was 5.3, 6.6, and 7.5, respectively, with a similar pattern observed for ED presentations. The associated costs per patient from HA followed a similar trajectory increasing gradually from $17 711 in the sixth year to $26 658 in the second last year prior to death. A similar pattern was observed for ED presentation costs.

Conclusion

The large increase cost in the last year of life was primarily attributable to higher treatment cost per HA at end of life.
Impacts of stage 1 palliation and pre-Glenn pulmonary artery pressure on long-term outcomes after Fontan operation
Authors: Kido Takashi , Burri Melchior , Mayr Benedikt , Strbad Martina , Cleuziou Julie , Hager Alfred , Hörer Jürgen , Ono Masamichi
Published: February 2021

OBJECTIVES

The present study was aiming to determine whether high mean pulmonary artery pressure before bidirectional cavopulmonary shunt is a risk factor for late adverse events in patients with low pulmonary artery pressure before total cavopulmonary connection (TCPC).

METHODS

We retrospectively reviewed the medical records of all patients undergoing both bidirectional cavopulmonary shunt and TCPC with available cardiac catheterization data.

RESULTS

A total of 316 patients were included in this study. The patients were divided into 4 groups according to mean pulmonary pressure: those with pre-Glenn <16 mmHg and pre-Fontan <10 mmHg (Group LL, n = 124), those with pre-Glenn ≥16 mmHg and pre-Fontan <10 mmHg (Group HL, n = 61), those with pre-Glenn <16 mmHg and pre-Fontan ≥10 mmHg (Group LH, n = 66) and those with pre-Glenn ≥16 mmHg and pre-Fontan ≥10 mmHg (Group HH, n = 65). Group HL showed significantly higher rate of adverse events after TCPC than Group LL (P = 0.02). In univariate linear analysis, a history of atrial septectomy at stage 1 palliation was associated with low pre-Glenn mean pulmonary artery pressure (Coefficient B −1.38, 95% confidence interval −2.53 to −0.24; P = 0.02), while pulmonary artery banding was a significant risk factor for elevated pre-Fontan mean pulmonary artery pressure (Coefficient B 1.68, 95% confidence interval 0.81 to 2.56, P < 0.001).

CONCLUSIONS

High mean pulmonary artery pressure before bidirectional cavopulmoary shunt (≥16mmHg) remains a significant risk factor for adverse events after TCPC even though mean pulmonary artery pressure decreased below 10 mmHg before TCPC.
Surgical therapy of infective endocarditis following interventional or surgical pulmonary valve replacement
Authors: Gierlinger Gregor , Sames-Dolzer Eva , Kreuzer Michaela , Mair Roland , Zierer Andreas , Mair Rudolf
Published: February 2021

OBJECTIVES

Percutaneous pulmonary valve prostheses and right ventricle-to-pulmonary artery conduits are at risk for infective endocarditis (IE). In children and adults with a congenital heart disease, a pulmonary valve implant is frequently necessary. Prosthetic valve endocarditis is a conservatively barely manageable, serious life-threatening condition. We investigated the results of surgical pulmonary valve replacements in patients with IE.

METHODS

A total of 20 patients with congenital heart disease with the definite diagnosis of IE between March 2013 and July 2020 were included in this single institutional, retrospective review. Infected conduits were 11 Melody, 5 Contegra, 3 homografts and 1 Matrix P Plus. All of the infected prosthetic material was removed from the right ventricular outflow tract up to the pulmonary bifurcation. Pulmonary homografts were implanted after pulmonary root resection as right ventricle-to-pulmonary artery conduits.

RESULTS

All patients survived and were discharged infection-free. The mean time from the conduit implant to the operation for IE was 4.9 years [95% confidence interval (CI), 3.0–6.9]. The median intensive care unit stay was 3.0 days (95% CI, 2.0–4.7), and the median hospital time was 25.0 days (95% CI, 19.2–42.0). Median follow-up time was 204.5 days (range 30 days to 5 years) without death or recurrent endocarditis.

CONCLUSIONS

The surgical treatment of IE of percutaneous pulmonary valve prostheses and right ventricle-to-pulmonary artery conduits is a safe and effective therapeutic concept. Early surgical referral of patients with suspicion of IE should be pursued to avoid sequelae such as right ventricular failure, septic emboli, intracardiac expansion and antibiotic resistance.
Reporting, interpretation, and extrapolation issues (SPIN) in abstracts of orthodontic meta-analyses published from 2000 to 2020
Authors: Makou Olga , Eliades Theodore , Koletsi Despina
Published: February 2021

Aim

To assess the prevalence of and identify factors associated with SPIN in abstracts of orthodontic meta-analyses.

Materials and methods

Electronic search was performed within the contents of five orthodontic journals and the Cochrane Database of Systematic Reviews (CDSR) to identify meta-analyses of studies involving humans, from 1 January 2000 until 31 August 2020. Inclusion of SPIN in the abstract of meta-analyses, defined as misleading reporting, misleading interpretation, and inappropriate extrapolation of the findings, was documented. Extent of SPIN and associations with journal and year of publication, type of study, number of authors, continent of authorship, methodologist involvement, funding, and significance of the primary outcome were investigated.

Results

One hundred and nine meta-analyses were identified, with the highest proportion being published in the European Journal of Orthodontics (EJO: 31/109; 28.4%). Inclusion of SPIN, in at least one domain, was recorded in nearly half (53/109; 48.6%) of the studies, of which 30 (56.6%) included 2 or more domains of SPIN. Meta-analyses of observational studies presented 1.66 times higher risk for including SPIN in their abstracts compared with interventional ones [95% confidence intervals (CIs): 1.14, 2.40; P = 0.007], after adjusting for a number of predictors. Studies with a large number of authors (≥6) presented 1.76 times higher risk of SPIN (≥6 versus 1–3: 95% CIs: 1.04, 2.97; Wald test, P = 0.021), conditional on the pre-defined predictors.

Conclusions

Flaws in the reporting and interpretation of the findings of abstracts of meta-analyses, as framed by inclusion of SPIN are persistent in orthodontic research, being more prevalent in meta-analyses of observational studies. Consistent, multidirectional efforts should be endorsed to improve the quality of the disseminated research findings.
Is relational continuity of care as important to people as policy makers think? Preferences for continuity of care in primary care
Authors: Norwood Patricia , Correia Isabel , Heidenreich Sebastian , Veiga Paula , Watson Verity
Published: February 2021

Background

In 2005, the Portuguese government launched a Primary Care reform that aimed to reinforce continuity of care. After a promising start, the reform is still incomplete and continuity has been compromised by the lack of General Practice doctors.

Objective

This study evaluates public preferences for relational continuity of care alongside other attributes of Primary Care services in Portugal.

Methods

We use a discrete choice experiment (DCE) to evaluate preferences and estimate the population’s willingness to pay (WTP) for Primary Care attributes. We use a sequential, mixed-methods approach to develop a D-efficient fractional factorial design for the DCE. Five attributes were included in the DCE and there were 32 DCE choice sets. The data collection was conducted in 2014 and the final sample had 517 respondents. A random parameters multinomial logit was used to analyse the data.

Results

We find that respondents value relational continuity of care, but that the current focus of the Portuguese NHS on relational continuity at the expense of other attributes is too simplistic.

Conclusions

Relational continuity should be part of a broader policy that emphasizes person-centred care and considers the preferences of patients for Primary Care attributes.
In silico identification of key regulators instigating the pre-meiotic phase during respiration in Saccharomyces cerevisiae
Authors: Das Deepyaman , Sarkar Hironmoy , Podder Soumita
Published: February 2021

Like higher eukaryotes, diploid MATa/MATα budding yeasts can undergo both mitosis and meiosis. Although the potential reason for their phase switching is elucidated by two consecutive processes, i.e. transition from fermentation (mitotic growth) to respiration in glucose-deficient media and then complete shift to meiotic phase in combined nitrogen- and glucose-starved media, the genomic interactions and regulatory cascade operating this drive remain elusive. Here, we aim to explore the regulatory cross-talk that mediates the phase transition. We have hypothesized that pre-growth in glucose-starved condition (yeast extract–peptone–acetate media) not only causes switch from fermentation to respiration but also prepares them for meiosis via a myriad of signaling events regulated by transcription factors (TFs). We have identified 23 putative TFs from integrated protein–protein interaction and gene regulatory network that were reconstructed from predicted and experimentally validated data. A total of six TFs (Xbp1p, Abf1p, Cbf1p, Ste12p, Reb1p and Gcn4p) are found to be highly connected in the network and involved in the cross-talk between respiration and cellular preparation for meiosis. We have identified Abf1p and Adr1p as the master regulators of the integrated network. This study in yeast will help to decipher the pre-meiotic initiation that occurs in higher eukaryotes.
Multifrequency inversion of global ambient seismic sources
Authors: Ermert L A , Sager K , Nissen-Meyer T , Fichtner A
Published: February 2021

We develop and apply a method to constrain the space- and frequency-dependent location of ambient noise sources. This is based on ambient noise cross-correlation inversion using numerical wavefield simulations, which honour 3-D crustal and mantle structure, ocean loading and finite-frequency effects. In the frequency range from 3 to 20 mHz, our results constrain the global source distribution of the Earth’s hum, averaged over the Southern Hemisphere winter season of 9 yr. During Southern Hemisphere winter, the dominant sources are largely confined to the Southern Hemisphere, the most prominent exception being the Izu-Bonin-Mariana arc, which is the most active source region between 12 and 20 mHz. Generally, strong hum sources seem to be associated with either coastlines or bathymetric highs. In contrast, deep ocean basins are devoid of hum sources. While being based on the relatively small number of STS-1 broad-band stations that have been recording continuously from 2004 to 2013, our results demonstrate the practical feasibility of a frequency-dependent noise source inversion that accounts for the complexities of 3-D wave propagation. It may thereby improve full-waveform ambient noise inversions and our understanding of the physics of noise generation.
Deciphering the structural attributes of protein–heparan sulfate interactions using chemo-enzymatic approaches and NMR spectroscopy
Authors: Préchoux Aurélie , Simorre Jean-Pierre , Lortat-Jacob Hugues , Laguri Cédric
Published: February 2021

Heparan sulfates (HS) is a polysaccharide found at the cell surface, where it mediates interactions with hundreds of proteins and regulates major pathophysiological processes. HS is highly heterogeneous and structurally complex and examples that define their structure–activity relationships remain limited. Here, in order to characterize a protein–HS interface and define the corresponding saccharide-binding domain, we present a chemo-enzymatic approach that generates 13C-labeled HS-based oligosaccharide structures. Nuclear magnetic resonance (NMR) spectroscopy, which efficiently discriminates between important or redundant chemical groups in the oligosaccharides, is employed to characterize these molecules alone and in interaction with proteins. Using chemokines as model system, docking based on NMR data on both proteins and oligosaccharides enable the identification of the structural determinant involved in the complex. This study shows that both the position of the sulfo groups along the chain and their mode of presentation, rather than their overall number, are key determinant and further points out the usefulness of these 13C-labeled oligosaccharides in obtaining detailed structural information on HS–protein complexes.
Who will drop out of voluntary social health insurance? Evidence from the New Cooperative Medical Scheme in China
Authors: Xu Mingming , Yang Wei
Published: February 2021

Although public voluntary health insurance (VHI) has been adopted in many low- and middle-income countries to improve access to care for the population, a common issue with VHI is its high dropout rate. Using the New Cooperative Medical Scheme (NCMS)—a public VHI in China—as a case study, this article employs a fixed-effects negative binomial regression model combining the difference-in-difference-in-differences approach and multivariate distance matching to examine the factors associated with dropping out and the impact of dropout on outpatient care utilization among middle-aged and older people in rural China. Drawing data from the China Health and Retirement Longitudinal Study, our results showed that healthy people, vulnerable people and people who use less healthcare tended to drop out. Dropout had a significant negative impact on outpatient care utilization, especially for those with worse health statuses and those living in poorer provinces. We also found that the impact of dropout on outpatient utilization was more pronounced at secondary and tertiary hospitals than at primary care clinics. We urge policymakers to rethink the design of the NCMS by waiving premiums for the most vulnerable people.
The Highland Society of London, material culture and the development of Scottish military identity, 1798–1817
Authors: Watt Patrick
Published: February 2021

The image of the Highland soldier as a brave, loyal warrior was central to nineteenth-century notions of Scottish national identity. This article uses material culture evidence alongside traditional archival sources to provide an interdisciplinary explanation of how the military dimension of Scottish identity was shaped in the early nineteenth century. It finds that it was the responses of the Highland Society of London to Scottish battlefield valour – rather than the actions themselves – that created the enduring popular perception of the Highland soldier as a desirable national symbol and as an icon of empire.
Integrative analyses of scRNA-seq and scATAC-seq reveal CXCL14 as a key regulator of lymph node metastasis in breast cancer
Authors: Xu Kun , Zhang Wenwen , Wang Cong , Hu Longfei , Wang Runtian , Wang Cenzhu , Tang Lin , Zhou Guohua , Zou Bingjie , Xie Hui , Tang Jinhai , Guan Xiaoxiang
Published: February 2021

The potentially different genetics and epigenetics in the primary tumors and metastases affect the efficacy of treatment in breast cancer patients. Nevertheless, the cellular and molecular mechanisms of breast cancer lymph node metastasis still remain elusive. Here, we employed single-cell RNA sequencing to acquire the transcriptomic profiles of individual cells from primary tumors, negative lymph nodes (NLs) and positive lymph nodes (PLs). We also performed a single-cell assay for transposase-accessible chromatin (ATAC) sequencing (scATAC-seq) of the positive and NL samples to get the chromatin accessibility profile. We identified a novel cell subpopulation with an abnormally high expression level of CXCL14 in the PL of breast cancer patients. Cell trajectory analysis also revealed that CXCL14 was increased expressed in the late pseudo-time. Moreover, based on a tissue microarray of 55 patients and the Oncomine database, we validated that CXCL14 expression was significantly higher in breast cancer patients with lymph node metastasis. Furthermore, scATAC-seq identified several transcription factors that may be potential regulation factors for the lymph node metastasis of breast cancer. Thus, our findings will improve our current understanding of the mechanism for lymph node metastasis, and they are potentially valuable in providing novel prognosis markers for the lymphatic metastasis of breast cancer.
Blood metal levels after minimally invasive repair of pectus excavatum
Authors: Torre Michele , Genova Gaia Luca , Calevo Maria Grazia , Wong Michela , Raso Maria , Barco Sebastiano , Di Gaudio Francesca , Cangemi Giuliana
Published: February 2021

OBJECTIVES

Minimally invasive repair of pectus excavatum (MIRPE) is the most popular surgical approach for paediatric patients with pectus excavatum. A substernal stainless still bar is inserted and left in place for 3 years and then removed. Our goal was to investigate blood metal levels after MIRPE and to correlate them with surgical details, such as the numbers of bars and stabilizers and the length of time the bar was in place.

METHODS

Blood levels of iron, chromium, manganese, molybdenum and nickel were analysed in 130 teenagers (108 boys and 22 girls) who had MIRPE using inductively coupled plasma mass spectrometry. A total of 62 patients were operated on using MIRPE (study group) and 68 patients were evaluated at implant time (control group). Differences between the numbers of bars implanted and the presence or absence of stabilizers were also considered.

RESULTS

Significant increases in the levels of abnormal chromium were found in patients in the study group compared with the controls (P = 0.02). When we compared the group of patients with 2 or more bars with the group with 1 bar, the percentage of patients with a value above the threshold increased by 29 (P = 0.05). A significant increase in chromium levels was observed in patients with stabilizers (P = 0.03). Above-threshold levels of molybdenum were found in 5.1% of patients in the control group, but the number was not statistically significant (P = 0.09).

CONCLUSIONS

We demonstrated that stainless steel devices used in MIRPE can elevate blood metal levels in paediatric patients. Moreover, we demonstrated that the use of metal stabilizers is associated with higher metal levels, probably due to increased dispersion.
Etiology and Diagnosis of Pelvic Inflammatory Disease: Looking Beyond Gonorrhea and Chlamydia
Authors: Mitchell Caroline M , Anyalechi Gloria E , Cohen Craig R , Haggerty Catherine L , Manhart Lisa E , Hillier Sharon L
Published: February 2021

Pelvic inflammatory disease (PID) is a clinical syndrome that has been associated with a wide range of potential causal pathogens. Three broad groups of organisms have been isolated from the genital tract of people with PID: sexually transmitted organisms such as Neisseria gonorrhoeae, Chlamydia trachomatis, Mycoplasma genitalium, and Trichomonas vaginalis; bacterial vaginosis (BV)-associated species and genera such as Atopobium vaginae, Sneathia, and Megasphaera; and genera and species usually associated with the gastrointestinal or respiratory tracts such as Bacteroides, Escherichia coli, Streptococcus, or Haemophilus influenza. Although PID is often considered to be synonymous with gonorrhea or chlamydia, these pathogens are found in only one quarter to one third of people with PID, suggesting that broader screening and diagnostic and treatment strategies need to be considered to reduce the burden of PID and its associated sequelae.
Long-Term Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infectiousness Among Three Immunocompromised Patients: From Prolonged Viral Shedding to SARS-CoV-2 Superinfection
Authors: Tarhini Hassan , Recoing Amélie , Bridier-nahmias Antoine , Rahi Mayda , Lambert Céleste , Martres Pascale , Lucet Jean-Christophe , Rioux Christophe , Bouzid Donia , Lebourgeois Samuel , Descamps Diane , Yazdanpanah Yazdan , Le Hingrat Quentin , Lescure François-Xavier , Visseaux Benoit
Published: February 2021

Background

Guidelines for stopping coronavirus disease 2019 patient isolation are mainly symptom-based, with isolation for 10 to 20 days depending on their condition.

Methods

In this study, we describe 3 deeply immunocompromised patients, each with different clinical evolutions. We observed (1) the patients’ epidemiological, clinical, and serological data, (2) infectiousness using viral culture, and (3) viral mutations accumulated over time.

Results

Asymptomatic carriage, symptom resolution, or superinfection with a second severe acute respiratory syndrome coronavirus 2 strain were observed, all leading to prolonged infectious viral shedding for several months.

Conclusions

Understanding underlying mechanisms and frequency of prolonged infectiousness is crucial to adapt current guidelines and strengthen the use of systematic polymerase chain reaction testing before stopping isolation in immunocompromised populations.
Tenofovir disoproxil fumarate and emtricitabine maintenance strategy in virologically controlled adults with low HIV-1 DNA: 48 week results from a randomized, open-label, non-inferiority trial
Authors: Prazuck Thierry , Verdon Renaud , Le Moal Gwenaël , Ajana Faïza , Bernard Louis , Sunder Simon , Roncato-Saberan Mariam , Ponscarme Diane , Etienne Manuel , Viard Jean-Paul , Pasdeloup Thierry , Darasteanu Iuliana , Pialoux Gilles , de la Blanchardière Arnaud , Avettand-Fènoël Véronique , Parienti Jean-Jacques , Hocqueloux Laurent ,   the TRULIGHT Study Team, Fourmy Adeline , Mureau Elody , Juteau Nathalie , Giraudeau Bruno , Dargere Sylvie , Michon Jocelyn , Baldoli Aurélie
Published: February 2021

Objectives

Low HIV reservoirs may be associated with viral suppression under a lower number of antiretroviral drugs. We investigated tenofovir disoproxil fumarate/emtricitabine as a maintenance strategy in people living with HIV (PLHIV) with low HIV-DNA.

Methods

TRULIGHT (NCT02302547) was a multicentre, open-label, randomized trial comparing a simplification to tenofovir disoproxil fumarate/emtricitabine versus a triple regimen continuation (tenofovir disoproxil fumarate/emtricitabine with a third agent, control arm) in virologically suppressed adults with HIV-DNA <2.7 log10 copies/106 PBMCs and no prior virological failure (VF). The primary endpoint (non-inferiority margin 12%) was the percentage of participants with a plasma viral load (pVL) <50 copies/mL in ITT (Snapshot approach) and PP analyses at Week 48 (W48).

Results

Of the 326 participants screened, 223 (68%) were randomized to the tenofovir disoproxil fumarate/emtricitabine arm (n = 113) or control arm (n = 110). At W48, the tenofovir disoproxil fumarate/emtricitabine and control arms maintained a pVL < 50 copies/mL in 100/113 (88.5%) and 100/110 (90.9%) participants, respectively (ITT difference 2.4%, 95% CI –5.9 to 10.7; PP difference 3.4%, 95% CI –4.2 to 11.0). Six VFs occurred in the tenofovir disoproxil fumarate/emtricitabine arm (two with emerging mutations M184V and K65R) versus two in the control arm (ITT difference 3.5%, 95% CI –1.9 to 9.4). All VFs were resuppressed after treatment modification.

Conclusions

Although non-inferiority was shown, simplification to tenofovir disoproxil fumarate/emtricitabine should not be used for most PLHIV because of a low risk of VF with resistance.
A landscape survey of planned SMART/HL7 bulk FHIR data access API implementations and tools
Authors: Jones James , Gottlieb Daniel , Mandel Joshua C , Ignatov Vladimir , Ellis Alyssa , Kubick Wayne , Mandl Kenneth D
Published: February 2021

The Office of National Coordinator for Health Information Technology final rule implementing the interoperability and information blocking provisions of the 21st Century Cures Act requires support for two SMART (Substitutable Medical Applications, Reusable Technologies) application programming interfaces (APIs) and instantiates Health Level Seven International (HL7) Fast Healthcare Interoperability Resources (FHIR) as a lingua franca for health data. We sought to assess the current state and near-term plans for the SMART/HL7 Bulk FHIR Access API implementation across organizations including electronic health record vendors, cloud vendors, public health contractors, research institutions, payors, FHIR tooling developers, and other purveyors of health information technology platforms. We learned that many organizations not required through regulation to use standardized bulk data are rapidly implementing the API for a wide array of use cases. This may portend an unprecedented level of standardized population-level health data exchange that will support an apps and analytics ecosystem. Feedback from early adopters on the API’s limitations and unsolved problems in the space of population health are highlighted.
Terbinafine-Induced Acute Generalized Exanthematous Pustulosis
Authors: Correia Bernardo , Costa Joana , Egipto Paula , Reis Pedro
Published: February 2021

Severe cutaneous adverse drug reactions are uncommon but potentially critical clinical situations demanding prompt diagnosis and treatment. We report a rare and severe case of terbinafine-induced acute generalized pustulosis. The patient was directly referred to a Burn Unit where she underwent diagnostic confirmation, systemic supportive care, and wound care treatments. Clinical and histopathological differential diagnosis of severe cutaneous adverse drug reactions is fundamental due to their significantly different management and prognosis.
Vision and Ocular Surface Salvage in Extreme Postburn Cicatricial Ectropion With Infectious Exposure Keratitis
Authors: Behera Geeta , Sangaraju Suneel , Meethale Thiruvoth Friji , Kasturi Nirupama , Babu Krishna Ramesh
Published: February 2021

Prevention and early management of postburn cicatricial ectropion is the best strategy to avoid ocular complications, with poor visual prognosis in extreme cases. A 51-year-old man presented with diminution of vision and absolute inability to close both eyes, 3 months after thermal burn injuries to face, upper limbs, and trunk. His best corrected visual acuity (BCVA) was 1/60 in BE. He had bilateral extremely severe ectropion involving both upper and lower lids with complete inability to close the eyes. The ensuing exposure keratitis developed secondary infection by Methicillin-resistant Staphylococcus aureus (MRSA) in the right eye and multidrug-resistant Pseudomonas aeruginosa in the left eye. His extreme ectropion prevented infection healing, so its release and full-thickness skin grafting was done when partial resolution of infection was noted. After 3 months, he had moderate residual ectropion in BE; vascularized corneal scar in the inferior part of the right eye (BCVA:20/40) and adherent leucoma in left eye (BCVA:HM). Prioritizing ectropion surgery in our extreme case for infection control, facilitated corneal healing. Our case highlights the extreme consequences of not taking preventive measures or of managing incident ectropion following thermal injury to the face.
Revocation of an EUTM: the relevant time for determining the five-year period of non-use is the filing date of the counterclaim
Authors: Bergazov Marie-Sophie , Basire Yann
Published: February 2021

Court of Justice of the European Union, Husqvarna AB v Lidl Digital International GmbH & Co. KG, C-607/19, 17 December 2020 ECLI:EU:C:2020:1044

In case of a counterclaim for revocation of an EU trade mark, the relevant date for assessing the five-year period of use is the date on which the counterclaim was filed.
Medical Financial Hardship in Survivors of Adolescent and Young Adult Cancer in the United States
Authors: Lu Amy D , Zheng Zhiyuan , Han Xuesong , Qi Ruowen , Zhao Jingxuan , Yabroff K Robin , Nathan Paul C
Published: February 2021

Background

Cancer and its treatment can result in lifelong medical financial hardship, which we aimed to describe among adult survivors of adolescent and young adult (AYA) cancers in the United States.

Methods

We identified adult (aged ≥18 years) survivors of AYA cancers (diagnosed ages 15-39 years) and adults without a cancer history from the 2010-2018 National Health Interview Surveys. Proportions of respondents reporting measures in different hardship domains (material [eg, problems paying bills], psychological [eg, distress], and behavioral [eg, forgoing care due to cost]) were compared between groups using multivariable logistic regression models and hardship intensity (cooccurrence of hardship domains) using ordinal logistic regression. Cost-related changes in prescription medication use were assessed separately.

Results

A total of 2588 AYA cancer survivors (median = 31 [interquartile range = 26-35] years at diagnosis; 75.0% more than 6 years and 50.0% more than 16 years since diagnosis) and 256 964 adults without a cancer history were identified. Survivors were more likely to report at least 1 hardship measure in material (36.7% vs 27.7%, P < .001) and behavioral (28.4% vs 21.2%, P < .001) domains, hardship in all 3 domains (13.1% vs 8.7%, P < .001), and at least 1 cost-related prescription medication nonadherence (13.7% vs 10.3%, P = .001) behavior.

Conclusions

Adult survivors of AYA cancers are more likely to experience medical financial hardship across multiple domains compared with adults without a cancer history. Health-care providers must recognize this inequity and its impact on survivors’ health, and multifaceted interventions are necessary to address underlying causes.
Weapons from the South: Democratization, Civil Society, and Brazil's Arms Exports
Authors: de Moraes Rodrigo Fracalossi
Published: February 2021

What explains the existence of humanitarian concerns in decisions involving arms transfers? This paper examines the potential influence of democratization and civil society activities on arms transfer policies and practice through a case study on Brazil. Brazil's re-democratization in 1985 provides an opportunity to test whether a change of regime type influences arms export behavior and whether civil society groups can influence it in newly democratized countries. Based on evidence collected mainly through archival research at Brazil's Ministry of Foreign Affairs and semi-structured interviews, this paper argues that transitioning to democracy had an immediate effect on arms transfer policies and practice in Brazil. After the end of Brazil's military regime, arms export policies and practice changed due mainly to reputational concerns: a stricter arms control could provide reputational gains to Brazil in an international norm environment where liberal values were perceived to be cascading. In addition to this immediate effect, democratic institutions created better conditions for the emergence of civil society groups campaigning for a stricter arms control, which emerged in the late 1990s. The paper studies a campaign and network led by the civil society group Viva Rio, which led to the introduction of a stricter policy on arms sales to most Latin American and Caribbean countries. These findings imply that democratization has both short- and long-term effects on arms transfers and that democratic institutions can influence state behavior regarding arms transfers even in countries with little tradition of civil society groups working with arms control.
Outcomes of patients with nasopharyngeal carcinoma treated with intensity-modulated radiotherapy
Authors: Yeh Shyh-An , Hwang Tzer-Zen , Wang Chih-Chun , Yang Chuen-Chien , Lien Ching-Feng , Wang Chien-Chung , Hsu Tun-Yen , Hsu Ruey-Feng , Shih Yu-Chen , Huang Yaw-Chang , Hsieh Meng-Che , Gau Jhy-Shyan , Chang Liyun , Lee Tsair-Fwu
Published: February 2021

Nasopharyngeal cancer shows a good response to intensity-modulated radiotherapy. However, there is no clear evidence for the benefits of routine use of image-guided radiotherapy. The purpose of this study was to perform a retrospective investigation of the treatment outcomes, treatment-related complications and prognostic factors for nasopharyngeal cancer treated with intensity-modulated radiotherapy and image-guided radiotherapy techniques. Retrospective analysis was performed on 326 consecutive nasopharyngeal cancer patients treated between 2004 and 2015. Potentially significant patient-related and treatment-related variables were analyzed. Radiation-related complications were recorded. The 5-year overall survival and disease-free survival rates of these patients were 77.9% and 70.5%, respectively. Age, AJCC (American Joint Committee on Cancer) stage, retropharyngeal lymphadenopathy, treatment interruption and body mass index were independent prognostic factors for overall survival. Age, AJCC stage, retropharyngeal lymphadenopathy, image-guided radiotherapy and body mass index were independent prognostic factors for disease-free survival. In conclusion, intensity-modulated radiotherapy significantly improves the treatment outcomes of nasopharyngeal cancer. With the aid of image-guided radiotherapy, the advantage of intensity-modulated radiotherapy might be further amplified.
Intrapulmonary solitary fibrous tumour: a case report
Authors: Horikiri Akie , Tsubochi Hiroyoshi , Mizukoshi Natsuki , Myobatake Ryota , Sakurai Hidetaka , Shibano Tomoki , Kanai Yoshihiko , Yamamoto Shinichi
Published: February 2021

Solitary fibrous tumours (SFTs) mainly originate from the visceral pleura and may protrude to the thoracic cavity, but intrapulmonary SFTs are extremely rare. We describe a rare case of SFT arising in the right lung of an 83-year-old man who underwent surgical excision. Chest computed tomography (CT) revealed a 10-mm tumour in the lower lobe of the right lung. The size of tumour gradually increased and reached 17 mm 2 years after the first radiologic examination. Considering the possibility of malignancy, wedge resection of the right lower lobe was performed via video-assisted thoracic surgery. Microscopically, the tumour consisted mainly of spindle-shaped cells. Immunohistochemical staining indicated the tumour was positive for CD34, STAT6, vimentin and bcl-2, but negative for cytokeratins, D2–40 and S-100. Based on the histological findings, the tumour was diagnosed as SFT. The patient has been in good health for 6 months since the surgery.
Cytoreductive surgical resection of a rare pulmonary artery intimal sarcoma involving the pulmonary valve and right ventricle: a case report
Authors: Williams Michael L , Tan Charis , Misfeld Martin , Yan Tristan D
Published: February 2021

Pulmonary artery intimal sarcoma (PAIS) is an extremely rare malignant tumour. It is often misdiagnosed as chronic pulmonary thromboembolism. We describe a complex case in a 70-year-old man with PAIS extending into his right ventricle undergoing salvage cytoreductive surgical resection utilizing bivalirudin for cardiopulmonary bypass anticoagulation due to heparin-induced thrombocytopenia and thrombosis syndrome. The prognosis for PAIS is extremely poor, with a median survival of 1.5 months without surgical resection. Cytoreductive surgical debulking can improve the median survival time to 17 months. The main aim of palliative surgical resection is to improve ventilation–perfusion mismatch and prevent haemodynamic collapse.
Typhoid and paratyphoid fever: a clinical seminar
Authors: Manesh Abi , Meltzer Eyal , Jin Celina , Britto Carl , Deodhar Divya , Radha Sneha , Schwartz Eli , Rupali Priscilla
Published: February 2021

Rationale for review: Enteric fever (EF) caused by Salmonella enterica subspecies enterica serovar Typhi (Salmonella Typhi) and S. Paratyphi (Salmonella Paratyphi) remains an important cause of infectious morbidity and mortality in many low-income countries and, therefore, still poses a major infectious risk for travellers to endemic countries.

Main findings: Although the global burden of EF has decreased over the past two decades, prevalence of EF remains high in Asia and Africa, with the highest prevalence reported from the Indian subcontinent. These statistics are mirrored by data on travel-related EF. Widespread and increasing antimicrobial resistance has narrowed treatment options for travel-related EF. Ceftriaxone- and azithromycin-based therapies are commonly used, even with the emergence of extremely drug-resistant typhoid in Pakistan. Preventive measures among locals and travellers include provision of safe food and water and vaccination. Food and water precautions offer limited protection, and the efficacy of Salmonella Typhi vaccines is only moderate signifying the need for travellers to be extra cautious.

Recommendations: Improvement in the diagnosis of typhoid with high degree of clinical suspicion, better diagnostic assays, early and accurate detection of resistance, therapy with appropriate drugs, improvements in hygiene and sanitation with provision of safe drinking water in endemic areas and vaccination among travellers as well as in the endemic population are keys to controlling typhoid. While typhoid vaccines are recommended for travellers to high-risk areas, moderate efficacy and inability to protect against Salmonella Paratyphi are limitations to bear in mind. Improved Salmonella Typhi vaccines and vaccines against Salmonella Paratyphi A are required.
Fatal outcomes of imported dengue fever in adult travelers from non-endemic areas are associated with primary infections
Authors: Huits Ralph , Schwartz Eli
Published: February 2021

Background

The case-fatality rate of dengue in travelers is low. Secondary dengue virus (DENV) infections are considered a risk factor for fatal outcome in endemic populations; however, the impact of secondary infections on mortality in travelers has not been studied systematically. We performed a descriptive analysis of case reports of dengue fatalities in travelers.

Methods

We searched Medline for clinical case reports, using the free terms and MeSH headings: ‘Dengue’ OR ‘Severe Dengue’ AND ‘Travel-Related Illness’ OR ‘travel’ AND ‘Mortality’ OR ‘Fatal Outcome’. We analyzed case reports of fatal dengue in returning travelers published from 1995 to 2020, with the objective to detail risk factors for dengue mortality in this population. We verified the authors’ classifications of primary or secondary dengue infections; infections were considered as primary by absence of anti-DENV immunoglobulin (Ig)G or by IgM-to-IgG ratios greater than or equal to 1.8 in the first 7 days post symptom onset.

Results

We identified nine detailed reports of dengue with fatal outcome among travelers from non-endemic countries. Eight fatalities were female. The median age was 32 years (range 21–63). Out of nine fatal cases, seven travelers had a primary DENV infection, one had a secondary infection and, in one, these data were not reported. The infecting DENV serotypes were DENV-1 (n = 2), DENV-2 (n = 2) and DENV-3 (n = 3); DENV-1 or 2 (n = 1) and in one case, the serotype could not be determined.

Conclusions

Dengue-related deaths in travelers are rare. Most dengue cases in travelers are primary infections. Contrary to prevailing conceptions, we found that fatal outcomes of dengue in travelers from non-endemic countries were reported mainly with primary DENV infections. We alert health care providers that primary DENV infections are not always harmless and that in adult travelers from non-endemic countries, primary infections may contribute more to dengue-related mortality than secondary infections.