bluuebunny/crossref_metadata_2025 huggingface dataset:
Trimethylamine
N
-oxide is a new plant molecule that promotes abiotic stress tolerance
Authors: Catalá Rafael , López-Cobollo Rosa , Berbís M. Álvaro , Jiménez-Barbero Jesús , Salinas Julio
Published: May 2021

TMAO functions as a protective osmolyte in plants, promoting abiotic stress tolerance.
Table-top extreme ultraviolet second harmonic generation
Authors: Helk Tobias , Berger Emma , Jamnuch Sasawat , Hoffmann Lars , Kabacinski Adeline , Gautier Julien , Tissandier Fabien , Goddet Jean-Philipe , Chang Hung-Tzu , Oh Juwon , Pemmaraju C. Das , Pascal Tod A. , Sebban Stephane , Spielmann Christian , Zuerch Michael
Published: May 2021

Second harmonic generation is demonstrated in the extreme ultraviolet with a table-top laser source.
Comparative evaluation of isogenic mesodermal and ectomesodermal chondrocytes from human iPSCs for cartilage regeneration
Authors: Lee Ming-Song , Stebbins Matthew J. , Jiao Hongli , Huang Hui-Ching , Leiferman Ellen M. , Walczak Brian E. , Palecek Sean P. , Shusta Eric V. , Li Wan-Ju
Published: May 2021

Inspired by how cartilage is developed, stem cell derivatives forming facial and articular cartilage are studied for joint repair.
Simplifying inverse materials design problems for fixed lattices with alchemical chirality
Authors: von Rudorff Guido Falk , von Lilienfeld O. Anatole
Published: May 2021

Alchemical chirality provides analytic expressions for new bonding rules and energy inequalities in chemical compound space.
Large-scale, robust mushroom-shaped nanochannel array membrane for ultrahigh osmotic energy conversion
Authors: Li Chao , Wen Liping , Sui Xin , Cheng Yiren , Gao Longcheng , Jiang Lei
Published: May 2021

A membrane with an ultrathin selective layer and ultrahigh pore density meets all the crucial demands for osmotic energy conversion.
Rapid imaging of special nuclear materials for nuclear nonproliferation and terrorism prevention
Authors: Petrović Jana , Göök Alf , Cederwall Bo
Published: May 2021

We introduce neutron-gamma emission tomography (NGET) for the 3D imaging of special nuclear materials (e.g. plutonium, uranium).
Cevipabulin-tubulin complex reveals a novel agent binding site on α-tubulin with tubulin degradation effect
Authors: Yang Jianhong , Yu Yamei , Li Yong , Yan Wei , Ye Haoyu , Niu Lu , Tang Minghai , Wang Zhoufeng , Yang Zhuang , Pei Heying , Wei Haoche , Zhao Min , Wen Jiaolin , Yang Linyu , Ouyang Liang , Wei Yuquan , Chen Qiang , Li Weimin , Chen Lijuan
Published: May 2021

A novel binding site on α-tubulin shows promise as a target for a new generation of anticancer drugs.
Na
v
1.7 target modulation and efficacy can be measured in nonhuman primate assays
Authors: Kraus Richard L. , Zhao Fuqiang , Pall Parul S. , Zhou Dan , Vardigan Joshua D. , Danziger Andrew , Li Yuxing , Daley Christopher , Ballard Jeanine E. , Clements Michelle K. , Klein Rebecca M. , Holahan Marie A. , Greshock Thomas J. , Kim Ronald M. , Layton Mark E. , Burgey Christopher S. , Serra Jordi , Henze Darrell A. , Houghton Andrea K.
Published: May 2021

Rhesus C-fiber microneurography, heat responsivity, and olfactory fMRI can be used as translatable biomarkers of Na
v
1.7 target modulation.
Cellular senescence inhibits renal regeneration after injury in mice, with senolytic treatment promoting repair
Authors: Mylonas Katie J. , O’Sullivan Eoin D. , Humphries Duncan , Baird David P. , Docherty Marie-Helena , Neely Sarah A. , Krimpenfort Paul J. , Melk Anette , Schmitt Roland , Ferreira-Gonzalez Sofia , Forbes Stuart J. , Hughes Jeremy , Ferenbach David A.
Published: May 2021

Senescent renal epithelia promote fibrosis and functional loss after injury, whereas depletion improves regeneration in aged or irradiated kidneys.
Dendritic cell targeting with Fc-enhanced CD40 antibody agonists induces durable antitumor immunity in humanized mouse models of bladder cancer
Authors: Garris Christopher S. , Wong Jeffrey L. , Ravetch Jeffrey V. , Knorr David A.
Published: May 2021

Fc-optimized CD40 agonist antibodies drive local and systemic immunity against bladder cancer in mice.
Preliminary Characterization of NP339, a Novel Polyarginine Peptide with Broad Antifungal Activity
Authors: Duncan Vanessa , Smith Daniel , Simpson Laura , Lovie Emma , Katvars Laura , Berge Leon , Robertson Jennifer , Smith Shane , Munro Carol , Mercer Derry , O’Neil Deborah
Published: May 2021

Fungi cause disease in nearly one billion individuals worldwide. Only three classes of antifungal agents are currently available in mainstream clinical use.
Complete Genome Sequences of Two Gammaproteobacterial Methanotrophs Isolated from a Mercury-Contaminated Stream
Authors: Kang-Yun Christina S. , Chang Jin , Brooks Scott C. , Gu Baohua , Semrau Jeremy D.
Published: May 2021

The genomes of
Methylomonas
sp. strain EFPC1 and
Methylococcus
sp. strain EFPC2 isolated from a mercury-contaminated stream in Oak Ridge Tennessee, were sequenced.
Complete Genome Sequence of Matlo Bat Lyssavirus
Authors: Grobler Colyn S. , Coertse Jessica , Markotter Wanda
Published: May 2021

The genus
Lyssavirus
includes rabies virus as well as multiple diverse and recently described novel species. Using next-generation sequencing technologies, we have obtained the whole-genome sequence of Matlo bat lyssavirus, which was isolated from a Natal long-fingered bat (
Miniopterus natalensis
) in South Africa.
Facies control on carbonate δ13C on the Great Bahama Bank
Authors: Geyman Emily C. , Maloof Adam C.
Published: May 2021

The carbon isotopic (δ13C) composition of shallow-water carbonates often is interpreted to reflect the δ13C of the global ocean and is used as a proxy for changes in the global carbon cycle. However, local platform processes, in addition to meteoric and marine diagenesis, may decouple carbonate δ13C from that of the global ocean. We present new δ13C measurements of benthic foraminifera, solitary corals, calcifying green algae, ooids, coated grains, and lime mud from the modern Great Bahama Bank. We find that vital effects, cross-shelf seawater chemistry gradients, and meteoric diagenesis produce carbonate with δ13C variability rivaling that of the past two billion years of Earth history. Leveraging Walther's Law, we illustrate how these local δ13C signals can find their way into the stratigraphic record of bulk carbonate.
Pityusa Patera, Mars: Structural analyses suggest a mega-caldera above a magma chamber at the crust-mantle interface
Authors: Bernhardt Hannes , Williams David A.
Published: May 2021

Pityusa Patera is the southernmost of four paterae in the 1.2 × 106 km2 wrinkle-ridged plains-dominated Malea Planum region of Mars. Based on their texture, morphology, and uniqueness to Pityusa Patera, we interpret layered, folded massifs as pyroclastic deposits emplaced during patera formation as a collapse caldera. Such deposits would not be expected in a previously suggested scenario of patera formation by subsidence from lithospheric loading. Our structural measurements and modeling indicate that the folding and high relief of the massifs resulted from ~1.3%–6.9% of shortening, which we show to be a reasonable value for a central plug sagging down into an assumed piston-type caldera. According to a previously published axisymmetric finite-element model, the extent of shortening structures on a caldera floor relative to its total diameter is controlled by the roof depth of the collapsed magma chamber beneath it, which would imply Pityusa Patera formed above a chamber at 57.5–69 km depth. We interpret this value to indicate a magma chamber at the crust-mantle interface, which is in agreement with crust-penetrating ring fractures and mantle flows expected from the formation of the Hellas basin. As such, the folded massifs in Pityusa Patera, which are partially superposed by ca. 3.8 Ga wrinkle-ridged plains, should consist of primordial mantle material, a theory that might be assessed by future hyperspectral observations. In conclusion, we do not favor a formation by load-induced lithospheric subsidence but suggest Pityusa Patera to be one of the oldest extant volcanic landforms on Mars and one of the largest calderas in the solar system, which makes the folded, likely mantle-derived deposits on its floor a prime target for future exploration.
Surface-wave tomography of the Emeishan large igneous province (China): Magma storage system, hidden hotspot track, and its impact on the Capitanian mass extinction
Authors: Liu Yiduo , Li Lun , van Wijk Jolante , Li Aibing , Fu Yuanyuan V.
Published: May 2021

Large igneous provinces (LIPs) are commonly associated with mass extinctions. However, the precise relations between LIPs and their impacts on biodiversity is enigmatic, given that they can be asynchronous. It has been proposed that the environmental impacts are primarily related to sill emplacement. Therefore, the structure of LIPs' magma storage system is critical because it dictates the occurrence and timing of mass extinction. We use surface-wave tomography to image the lithosphere under the Permian Emeishan large igneous province (ELIP) in southwestern China. We find a northeast-trending zone of high shear-wave velocity (Vs) and negative radial anisotropy (Vsv > Vsh; v and h are vertically and horizontally polarized S waves, respectively) in the crust and lithosphere. We rule out the possibilities of rifting or orogenesis to explain these seismic characteristics and interpret the seismic anomaly as a mafic-ultramafic, dike-dominated magma storage system of the ELIP. We further propose that the anomaly represents a hidden hotspot track that was emplaced before the ELIP eruption. A zone of higher velocity but less-negative radial anisotropy, on the hotspot track but to the northeast of the eruption center in the Panxi region, reflects an elevated proportion of sills emplaced at the incipient stage of the ELIP. Liberation of poisonous gases by the early sill intrusions explains why the mid-Capitanian global biota crisis preceded the peak ELIP eruption by 2–3 m.y.
Detrital-zircon analyses, provenance, and late Paleozoic sediment dispersal in the context of tectonic evolution of the Ouachita orogen
Authors: Thomas William A. , Gehrels George E. , Sundell Kurt E. , Romero Mariah C.
Published: May 2021

New analyses for U-Pb ages and εHft values, along with previously published U-Pb ages, from Mississippian–Permian sandstones in synorogenic clastic wedges of the Ouachita foreland and nearby intracratonic basins support new interpretations of provenance and sediment dispersal along the southern Midcontinent of North America. Recently published U-Pb and Hf data from the Marathon foreland confirm a provenance in the accreted Coahuila terrane, which has distinctive Amazonia/Gondwana characteristics. Data from Pennsylvanian–Permian sandstones in the Fort Worth basin, along the southern arm of the Ouachita thrust belt, are nearly identical to those from the Marathon foreland, strongly indicating the same or a similar provenance. The accreted Sabine terrane, which is documented by geophysical data, is in close proximity to the Coahuila terrane, suggesting the two are parts of an originally larger Gondwanan terrane. The available data suggest that the Sabine terrane is a Gondwanan terrane that was the provenance of the detritus in the Fort Worth basin. Detrital-zircon data from Permian sandstones in the intracratonic Anadarko basin are very similar to those from the Fort Worth basin and Marathon foreland, indicating sediment dispersal from the Coahuila and/or Sabine terranes within the Ouachita orogen cratonward from the immediate forelands onto the southern craton. Similar, previously published data from the Permian basin suggest widespread distribution from the Ouachita orogen. In contrast to the other basins along the Ouachita-Marathon foreland, the Mississippian–Pennsylvanian sandstones in the Arkoma basin contain a more diverse distribution of detrital-zircon ages, indicating mixed dispersal pathways of sediment from multiple provenances. Some of the Arkoma sandstones have U-Pb age distributions like those of the Fort Worth and Marathon forelands. In contrast, other sandstones, especially those with paleocurrent and paleogeographic indicators of southward progradation of depositional systems onto the northern distal shelf of the Arkoma basin, have U-Pb age distributions and εHft values like those of the “Appalachian signature.” The combined data suggest a mixture of detritus from the proximal Sabine terrane/Ouachita orogenic belt with detritus routed through the Appalachian basin via the southern Illinois basin to the distal Arkoma basin. The Arkoma basin evidently marks the southwestern extent of Appalachian-derived detritus along the Ouachita-Marathon foreland and the transition southwestward to overfilled basins that spread detritus onto the southern craton from the Ouachita-Marathon orogen, including accreted Gondwanan terranes.
Dengue and hantavirus coinfection with good outcomes: a clinical case from Panama
Authors: Núñez-Samudio Virginia , Meza Martín , Landires Iván
Published: May 2021

Dengue and hantavirus are endemic in central Panama. We present a case report of a patient coinfected with dengue and hantavirus who presented overlapping clinical manifestations of both infections. The patient did not require intensive care—as it is commonplace during hantavirus pulmonary syndrome—and he had a good outcome. Patient’s care was positively impacted due to correct diagnosis of coinfection. This case highlights that in endemic areas, coinfection with dengue virus and hantavirus should be suspected. To the best of our knowledge, this case is the first documented case of coinfection with dengue virus and hantavirus in Central America.
Surgical corridors for congenital aural atresia with otogenic cerebellar abscess and lateral sinus thrombosis
Authors: Thangavel Saranya , Penubarthi Lokesh Kumar , Alexander Arun , Saxena Sunil Kumar
Published: May 2021

The following is a case report of an adolescent with mental retardation who had congenital aural atresia with contralateral congenital facial palsy. She developed multiple intracranial complications (cerebellar abscess and lateral sinus thrombosis) due to cholesteatoma. We managed her in a multidisciplinary approach. This report discusses case management, emphasising the meticulous intraoperative steps taken in identifying the landmarks and precautions adopted to avoid postoperative facial palsy and other complications.
Robot-assisted laparoscopic hysterectomy for endometrial cancer in a patient with Herlyn-Werner-Wunderlich syndrome
Authors: Kobayashi Misa , Kobayashi Hiroharu , Nakayama Satoru , Adachi Hiroshi
Published: May 2021

Herlyn-Werner-Wunderlich syndrome, a rare Mullerian duct anomaly, includes a triad of uterine didelphys, obstructed haemivagina and ipsilateral renal agenesis. A 58-year-old woman with Herlyn-Werner-Wunderlich syndrome, reported of recurrent genital bleeding for 9 years, was finally diagnosed with endometrial cancer. She had a history of vaginal septum resection and nephrectomy of atrophic right kidney. MRI demonstrated uterine didelphys, a tumour filling the left uterus and a cyst on the right lateral side of the uterus. Robot-assisted hysterectomy, including bilateral salpingo-oophorectomy and pelvic lymphadenectomy, was performed. As the cyst communicated with the right cervix, but not with the urinary tract, a Gartner duct cyst was diagnosed. Uncertain diagnosis and delay of treatment in endometrial cancer may occur in patients with Herlyn-Werner-Wunderlich syndrome. We should preoperatively fully evaluate the anatomy of the uterus and surrounding tissues and plan surgical procedures, especially in patients with urogenital malformations.
Recurrent transient loss of airway secondary to regurgitated pedunculated hypopharyngeal liposarcoma
Authors: Hickson Craig John , Ahmed Omar , Laycock Juliet , Hone Robert
Published: May 2021

We describe a rare case of hypopharyngeal liposarcoma with an atypical presentation. The patient presented with a 3-month history of intermittent, transient acute airway obstruction. In between episodes, he was asymptomatic. A pedunculated tumour originating in the postcricoid region was seen to be suspended into the oesophagus and intermittently regurgitated into the larynx to cause airway obstruction. The lesion was endoscopically removed and examined histologically to confirm the diagnosis. On-going management of rare lesions such as this should be through multidisciplinary team meetings at a tertiary sarcoma centre.
Subglottic ectopic thymus mimicking airway haemangioma
Authors: Konstantinidou Sevasti , Butler Colin R , Hartley Benjamin , Frauenfelder Claire
Published: May 2021

Subglottic haemangioma presents as progressive obstruction in the neonatal and infantile airway, with a soft lesion seen during endoscopy. Diagnosis is based on macroscopic findings, biopsy is not usually performed and propranolol is first-line treatment. In contrast, ectopic thymus is a rare differential diagnosis for subglottic mass made by histopathological examination after excision or autopsy. In this article, we present a case of an infant with a subglottic lesion with endoscopic features consistent with haemangioma. After initial clinical response to propranolol, the patient represented with progressive stridor no longer responding to therapy. Open excision of the lesion was performed, and histopathology revealed ectopic thymus tissue. In this case, ectopic thymus tissue mimicked the presentation of subglottic haemangioma, and confirmation bias persisted due to an apparent initial clinical response to treatment with propranolol. In cases of subglottic mass refractory to medical treatment, excision of the lesion should be considered.
Inborn error of immunity as the cause of recurrent pericarditis
Authors: Lucane Zane , Freidenberga Dace , Kurjane Natalja
Published: May 2021

Familial Mediterranean fever (FMF) is an autoinflammatory disease caused by a pyrin dysfunction, leading to uncontrolled interleukin-1 production that triggers the attacks. Here we report a case of a 36-year-old female patient repeatedly admitted to the cardiology ward with recurrent episodes of pericarditis, with intervals of 1 and 2 months between the episodes. During the attacks, chest pain and fever were the only symptoms. Following the administration of steroids and non-steroidal anti-inflammatory drugs, the patient became afebrile. She also had lymphoma and thyroid carcinoma in anamnesis essential for differential diagnosis. Laboratory tests for infection and autoimmune disease were all negative, and the positron emission tomography–CT scan did not reveal lymphoma relapse. Genetic testing revealed a mutation in theMEFVgene. It is very rare for pericarditis to be the first and only manifestation of FMF.
COVID-19-associated central retinal vein occlusion treated with oral aspirin
Authors: Venkatesh Ramesh , Reddy Nikitha Gurram , Agrawal Sameeksha , Pereira Arpitha
Published: May 2021

This is a case report of central retinal vein occlusion (CRVO) associated with COVID-19 treated with oral aspirin therapy. A 56-year-old woman reported decreased vision in her left eye. Her left eye vision was 6/18, N10. Anterior segment was within normal limits. Left eye fundus was suggestive of CRVO and macular oedema. Optical coherence tomography showed cystoid macular oedema and neurosensory detachment. Blood work-up revealed elevated D-dimer levels and erythrocyte sedimentation rate (ESR). She was started on treatment with low-dose aspirin 150 mg/day. After 1 month, her vision improved to 6/6, N6. Left eye fundus showed reduced retinal haemorrhages and complete resolution of macular oedema. Her repeat blood work-up showed reduced D-dimer and ESR levels. The patient was asked to be reviewed after 3 months. This case highlights that specific treatment for reducing the hypercoagulable state caused by COVID-19 with oral aspirin therapy can result in complete resolution of CRVO macular oedema.
Methodological frontiers in vaccine safety: qualifying available evidence for rare events, use of distributed data networks to monitor vaccine safety issues, and monitoring the safety of pregnancy interventions
Authors: Dodd Caitlin , Andrews Nick , Petousis-Harris Helen , Sturkenboom Miriam , Omer Saad B , Black Steven
Published: May 2021

While vaccines are rigorously tested for safety and efficacy in clinical trials, these trials do not include enough subjects to detect rare adverse events, and they generally exclude special populations such as pregnant women. It is therefore necessary to conduct postmarketing vaccine safety assessments using observational data sources. The study of rare events has been enabled in through large linked databases and distributed data networks, in combination with development of case-centred methods. Distributed data networks necessitate common protocols, definitions, data models and analytics and the processes of developing and employing these tools are rapidly evolving. Assessment of vaccine safety in pregnancy is complicated by physiological changes, the challenges of mother-child linkage and the need for long-term infant follow-up. Potential sources of bias including differential access to and utilisation of antenatal care, immortal time bias, seasonal timing of pregnancy and unmeasured determinants of pregnancy outcomes have yet to be fully explored. Available tools for assessment of evidence generated in postmarketing studies may downgrade evidence from observational data and prioritise evidence from randomised controlled trials. However, real-world evidence based on real-world data is increasingly being used for safety assessments, and new tools for evaluating real-world evidence have been developed. The future of vaccine safety surveillance, particularly for rare events and in special populations, comprises the use of big data in single countries as well as in collaborative networks. This move towards the use of real-world data requires continued development of methodologies to generate and assess real world evidence.
Estimation of long-term costs of postacute care in survivors of the methanol poisoning outbreak
Authors: Barták Miroslav , Rogalewicz Vladimír , Doubek Jaroslav , Šejvl Jaroslav , Petruželka Benjamin , Zakharov Sergey , Miovský Michal
Published: May 2021

Objectives

To fill the existing research gap related to long-term costs of postacute care in methanol poisoning survivors, healthcare cost for 6 years after the outbreak has been modelled and estimated.

Design

In a prospective longitudinal cohort study, data collected from 55 survivors of the Czech methanol mass poisoning outbreak in 2012 were collected in four rounds (5 months, then 2, 4 and 6 years after the discharge) in the General University Hospital in Prague according to the same predefined study protocol. The collected data were used to inform the cost model.

Setting and participants

All 83 patients discharged from a hospital poisoning treatment after the 2012 methanol outbreak were informed about the study and invited to participate. Fifty-five patients (66%) gave their written informed consent and were followed until their death or the last follow-up 6 years later. The costs were modelled from the Czech healthcare service (general health insurance) perspective.

Main outcome measures

Long-term national budget impact of the methanol poisoning outbreak, frequencies of sequelae and their average costs.

Results

The postacute cost analysis concentrated on visual and neurological sequelae that were shown to be dominant. Collected data were used to create process maps portraying gradual changes in long-term sequelae over time. Individual process maps were created for the central nervous system, peripheral nervous system, sequelae detected during eye examinations and sequelae concerning the visual evoked potentials. Based on the process maps the costs of the postacute outpatient care were estimated.

Conclusions

In 2013–2019 the highest costs per patient related to postacute care were found in the first year; the average costs decreased afterwards, and remained almost constant for the rest of the studied period of time. These costs per patient ranged from CZK4142 in 2013 to CZK1845 in 2018, when they raised to CZK2519 in 2019 again.
Mobility study of young women who exchange sex for money or commodities using Google Maps and qualitative methods in Kampala, Uganda
Authors: King Rachel , Muhanguzi Eva , Nakitto Miriam , Mirembe Miriam , Kasujja Francis Xavier , Bagiire Daniel , Seeley Janet
Published: May 2021

Objectives

We aimed to assess mobility patterns and reasons for high mobility among young women engaged in sex work within a randomised controlled trial to gauge how mobility may hinder access to health services and enhance HIV risk in a highly vulnerable population.

Setting

Participants were recruited from a clinic in Kampala, Uganda set up for women at high risk of HIV infection.

Participants

Adolescent girls and young women engaged in sex for money and/or commodities are at particular risk in countries with high HIV prevalence and high fertility rates. High mobility increases exposure to HIV risk. Women participants were eligible for the parent study if aged 15–24 years, HIV negative and engaged in sex work. For this substudy, 34 qualitative interviews were held with 14 sex workers (6 HIV positive, 8 HIV negative), 6 health worker/policy makers, 3 peer educators, 5 ‘queen mothers’ and 6 male partners

Measures

Participants used Google Maps to identify work venues at 12-month and 18-month study visits. We also conducted 34 interviews on mobility with: high-risk women, male partners, health workers and sex-worker managers. Topics included: distance, frequency and reasons for mobility. We used Python software to analyse mapping data.

Results

Interviews found in depth narratives describing lack of education and employment opportunities, violence, lack of agency, social, sexual and familial support networks and poverty as a complex web of reasons for high mobility among young sex workers.

Conclusions

Young women at high risk are highly mobile. Reasons for mobility impact access and retention to health services and research activities. Strategies to improve retention in care should be cognisant and tailored to suit mobility patterns.

Trial registration number

NCT03203200.
Cost-effectiveness of home versus hospital management of children at onset of type 1 diabetes: the DECIDE randomised controlled trial
Authors: McCarroll Zoe , Townson Julia , Pickles Timothy , Gregory John W , Playle Rebecca , Robling Michael , Hughes Dyfrig A
Published: May 2021

Objective

The aim of this economic evaluation was to assess whether home management could represent a cost-effective strategy in the patient pathway of type 1 diabetes (T1D). This is based on the Delivering Early Care In Diabetes Evaluation trial (ISRCTN78114042), which compared home versus hospital management from diagnosis in childhood diabetes and found no statistically significant difference in glycaemic control at 24 months.

Design

Cost-effectiveness analysis alongside a randomised controlled trial.

Setting

Eight paediatric diabetes centres in England, Wales and Northern Ireland.

Participants

203 clinically well children aged under 17 years, with newly diagnosed T1D and their carers.

Outcome measures

The base-case analysis adopted n National Health Service (NHS) perspective. A scenario analysis assessed costs from a broader societal perspective. The incremental cost-effectiveness ratio (ICER), expressed as cost per mmol/mol reduction in glycated haemoglobin (HbA1c), was based on the mean difference in costs between the home and hospital groups, divided by mean differences in effectiveness (HbA1c). Uncertainty was considered in terms of the probability of cost-effectiveness.

Results

At 24 months postintervention, the base-case analysis showed a difference in costs between home and hospital, in favour of home management (mean difference −£2,217; 95% CI −£2825 to −£1,609; p<0.001). Home care dominated, with an ICER of £7434 (saved) per mmol/mol reduction of HbA1c. The results of the scenario analysis also favoured home management. The greatest driver of cost differences was hospitalisation during the initiation period.

Conclusions

Home management from diagnosis of children with T1D who are medically stable represents a less costly approach for the NHS in the UK, without impacting clinical effectiveness.

Trial registration number

ISRCTN78114042.
Clinical, behavioural and social factors associated with racial disparities in COVID-19 patients from an integrated healthcare system in Georgia: a retrospective cohort study
Authors: Lobelo Felipe , Bienvenida Alan , Leung Serena , Mbanya Armand , Leslie Elizabeth , Koplan Kate , Shin Sangmin Ryan
Published: May 2021

Objectives

To identify sociodemographic, clinical and behavioural drivers of racial disparities and their association with clinical outcomes among Kaiser Permanente Georgia (KPGA) members with COVID-19.

Design

Retrospective cohort of patients with COVID-19 seen from 3 March to 29 October 2020. We described the distribution of underlying comorbidities, quality of care metrics, demographic and social determinants of health (SDOH) indicators across race groups. We also described clinical outcomes in hospitalised patients including length of stay, intensive care unit (ICU) admission, readmission and mortality. We performed multivariable analyses for hospitalisation risk among all patients with COVID-19 and stratifyied by race and sex.

Setting

KPGA, an integrated healthcare system.

Participants

5712 patients who all had laboratory-confirmed COVID-19. Of them, 57.8% were female, 58.4% black, 29.5% white, 8.5% Hispanic and 3.6% Asian.

Results

Black patients had the highest proportions of living in neighborhoods under the federal poverty line (12.4%) and in more deprived locations (neighbourhood deprivation index=0.4). Overall, 14.4% (n=827) of this cohort was hospitalised. Asian patients had the highest rates of ICU admission (53.1%) and mechanical ventilation (21.9%). Among all patients, Hispanics (adjusted 1.60, 95% CI (1.08, 2.37)), blacks (1.43 (1.13, 1.83)), age in years (1.03 (1.02, 1.04)) and living in a zip code with high unemployment (1.08 (1.03, 1.13)) were associated with higher odds of hospitalisation. COVID-19 patients with chronic obstructive pulmonary disease (2.59 (1.67, 4.02)), chronic heart failure (1.79 (1.31, 2.45)), immunocompromised (1.77 (1.16, 2.70)), with glycated haemoglobin >8% (1.68 (1.19, 2.38)), depression (1.60 (1.24, 2.06)), hypertension (1.5 (1.21, 1.87)) and physical inactivity (1.25 (1.03, 1.51)) had higher odds of hospitalisation.

Conclusions

Black and Hispanic KPGA patients were at higher odds of hospitalisation, but not mortality, compared with other race groups. Beyond previously reported sociodemographics and comorbidities, factors such as quality of care, lifestyle behaviours and SDOH indicators should be considered when designing and implementing interventions to reduce COVID-19 racial disparities.
Consensus-based approach to managing opioids, including opioid misuse and opioid use disorder, in patients with serious illness: protocol for a modified Delphi process
Authors: King Caroline , Arnold Robert , Dao Emily , Kapo Jennifer , Liebschutz Jane , Meier Diane , Paice Judith , Ritchie Christine , Czajkowski Kristen , Khodyakov Dmitry , Merlin Jessica
Published: May 2021

Introduction

Management of opioid misuse and opioid use disorder (OUD) among individuals with serious illness is an important yet understudied issue. Palliative care clinicians caring for individuals with serious illness, many of whom may live for months or years, describe a complex tension between weighing the benefits of opioids, which are considered a cornerstone of pain management in serious illness, and serious opioid-related harms like opioid misuse and OUD. And yet, little literature exists to inform the management of opioid misuse and OUDs among individuals with serious illness. Our objective is to provide evidence-based management guidance to clinicians caring for individuals with serious illness who develop opioid misuse or OUD.

Methods and analysis

We chose a modified Delphi approach, which is appropriate when empirical evidence is lacking and expert input must be used to shape clinical guidance. We sought to recruit 60 clinicians with expertise in palliative care, addiction or both to participate in this study. We created seven patient cases that capture important management challenges in individuals with serious illness prescribed opioid therapy. We used ExpertLens, an online platform for conducting modified Delphi panels. Participants completed three rounds of data collection. In round 1, they rated and commented on the appropriateness of management choices for cases. In round 2, participants reviewed and discussed their own and other participants’ round 1 numerical responses and comments. In round 3 (currently ongoing), participants again reviewed rounds 1 and 2, and are allowed to change their final numerical responses. We used ExpertLens to automatically identify whether there is consensus, or disagreement, among responses in panels. Only round 3 responses will be used to assess final consensus and disagreement.

Ethics and dissemination

This project received ethical approval from the University of Pittsburgh’s Institutional Review Board (study 19110301) and the RAND Institutional Research Board (study 2020-0142). Guidance from this work will be disseminated through national stakeholder networks to gain buy-in and endorsement. This study will also form the basis of an implementation toolkit for clinicians caring for individuals with serious illness who are at risk of opioid misuse or OUD.
From screen time to the digital level of analysis: a scoping review of measures for digital media use in children and adolescents
Authors: Browne Dillon Thomas , May Shealyn S , Colucci Laura , Hurst-Della Pietra Pamela , Christakis Dimitri , Asamoah Tracy , Hale Lauren , Delrahim-Howlett Katia , Emond Jennifer A , Fiks Alexander G , Madigan Sheri , Perlman Greg , Rumpf Hans-Jürgen , Thompson Darcy , Uzzo Stephen , Stapleton Jackie , Neville Ross , Prime Heather
Published: May 2021

Objectives

This scoping review aims to facilitate psychometric developments in the field of digital media usage and well-being in young people by (1) identifying core concepts in the area of “screen time” and digital media use in children, adolescents, and young adults, (2) synthesising existing research paradigms and measurement tools that quantify these dimensions, and (3) highlighting important areas of need to guide future measure development.

Design

A scoping review of 140 sources (126 database, 14 grey literature) published between 2014 and 2019 yielded 162 measurement tools across a range of domains, users, and cultures. Database sources from Ovid MEDLINE, PsycINFO and Scopus were extracted, in addition to grey literature obtained from knowledge experts and organisations relevant to digital media use in children. To be included, the source had to: (1) be an empirical investigation or present original research, (2) investigate a sample/target population that included children or young persons between the ages of 0 and 25 years of age, and (3) include at least one assessment method for measuring digital media use. Reviews, editorials, letters, comments and animal model studies were all excluded.

Measures

Basic information, level of risk of bias, study setting, paradigm, data type, digital media type, device, usage characteristics, applications or websites, sample characteristics, recruitment methods, measurement tool information, reliability and validity.

Results

Significant variability in nomenclature surrounding problematic use and criteria for identifying clinical impairment was discovered. Moreover, there was a paucity of measures in key domains, including tools for young children, whole families, disadvantaged groups, and for certain patterns and types of usage.

Conclusion

This knowledge synthesis exercise highlights the need for the widespread development and implementation of comprehensive, multi-method, multilevel, and multi-informant measurement suites.
Genomic profiling of advanced cervical cancer to predict response to programmed death-1 inhibitor combination therapy: a secondary analysis of the CLAP trial
Authors: Huang Xin , He Minjun , Peng Hongyu , Tong Chongjie , Liu Zhimin , Zhang Xiaolong , Shao Yang , Zhu Dongqin , Zhang Junli , Yin Jiani C , Yang Fan , Lan Chunyan
Published: May 2021

Background

The Camrelizumab Plus Apatinib in Patients with Advanced Cervical Cancer trial was a single-arm, phase II study that showed promising activity of the programmed death-1 (PD-1) inhibitor camrelizumab plus the vascular endothelial growth factor receptor-2 inhibitor apatinib in patients with advanced cervical cancer. However, the predictive biomarkers for treatment outcomes are unknown. In this study, we aimed to identify potential predictors of treatment response in PD-1 inhibitor combination therapy.

Methods

Genomic profiling was performed on patients with available biopsy or surgical samples by targeted next-generation sequencing of 425 cancer-related genes in this preplanned, secondary analysis. Somatic alterations, including all non-synonymous mutations, and tumor mutational burden (TMB) were assessed for their predictive values in objective response rate, progression-free survival (PFS), and overall survival (OS).

Results

A subset of 32 patients was included in this analysis. Top altered genes includedPIK3CA(43.8%),STK11(25%),FBXW7(15.6%), andPTEN(15.6%). The PI3K/AKT pathway was among the most frequently dysregulated pathways, and its genetic alterations were identified in 68.8% of patients.PIK3CA(PFS HR 0.33, p=0.05; OS HR 0.23, p=0.04) andPTEN(PFS HR 3.71e-09, p=0.05; OS HR 3.64e-09, p=0.08) alterations were associated with improved outcomes. PI3K/AKT pathway genetic alterations showed improved predictive power compared with eitherPIK3CAorPTENalterations alone (PFS HR 0.33, p=0.03; OS HR 0.25, p=0.02), whileERBB3mutations (PFS HR 34.9, p<0.001; OS HR 19.8, p<0.001) correlated with poor survival. TMB-high (≥5 mut/Mb) was associated with prolonged PFS (HR 0.26, p<0.01) and OS (HR 0.31, p=0.05). Multivariate analysis showedERBB3mutations (PFS p=0.01, OS p<0.001), PD-L1 positive (PFS p=0.01, OS p=0.05), and high TMB (PFS p=0.01, OS p=0.05) remained significantly associated with survival.

Conclusions

We uncovered that genetic alterations inPIK3CA,PTEN,ERBB3, and PI3K/AKT pathway, as well as TMB, could be novel predictive biomarkers in patients with cervical cancer treated with PD-1 inhibitor combination therapy.

Trial registration number

NCT03816553.
Anti-pituitary antibodies and susceptible human leukocyte antigen alleles as predictive biomarkers for pituitary dysfunction induced by immune checkpoint inhibitors
Authors: Kobayashi Tomoko , Iwama Shintaro , Sugiyama Daisuke , Yasuda Yoshinori , Okuji Takayuki , Ito Masaaki , Ito Sachiko , Sugiyama Mariko , Onoue Takeshi , Takagi Hiroshi , Hagiwara Daisuke , Ito Yoshihiro , Suga Hidetaka , Banno Ryoichi , Nishikawa Hiroyoshi , Arima Hiroshi
Published: May 2021

Background

Pituitary dysfunction is a life-threatening immune-related adverse event (irAE) induced by immune checkpoint inhibitors (ICIs). To date, it is not possible to identify patients who may develop pituitary irAEs prior to ICI treatment. The aim of this study was to characterize the predisposition for ICI-induced pituitary irAEs by analyzing anti-pituitary antibodies (APAs) and human leukocyte antigens (HLAs).

Methods

In this case–control study, APAs and HLA alleles were analyzed in 62 patients (17 who developed ICI-induced isolated adrenocorticotropic hormone deficiency (ICI-IAD), 5 who developed ICI-induced hypophysitis (ICI-H) and 40 who did not develop pituitary irAEs) treated with ICIs between November 2, 2015, and March 31, 2020, at Nagoya University Hospital. The main outcome measures in this study were the association between the development of pituitary irAEs with APAs at baseline and after treatment and HLA alleles.

Results

Eleven of 17 (64.7%) patients who developed ICI-IAD had APAs at baseline, whereas APAs were positive only in 1 of 40 (2.5%) control patients. Although APAs were negative at baseline in all patients who developed ICI-H, they had become positive before the onset of ICI-H in 3 of 4 patients several weeks after ipilimumab administration. At the onset of ICI-IAD and ICI-H, APAs were positive in 15 of 17 (88.2%) and 4 of 5 (80%) patients, respectively. The prevalence of HLA-Cw12, HLA-DR15, HLA-DQ7, and HLA-DPw9 was significantly higher in patients with ICI-IAD, whereas that of HLA-Cw12 and HLA-DR15 was significantly higher in patients with ICI-H than in controls.

Conclusions

This study showed distinct and overlapped patterns of APAs and HLA alleles between ICI-IAD and ICI-H. Our findings also showed that positive APAs at baseline and after treatment, together with susceptible HLA alleles, could become predictive biomarkers for ICI-IAD and ICI-H, respectively.

Trial registration number

UMIN000019024.
Empiric antifungals do not decrease the risk for organ space infection in patients with perforated peptic ulcer
Authors: Barmparas Galinos , Alhaj Saleh Adel , Huang Raymond , Eaton Barbara C , Bruns Brandon R , Raines Alexander , Bryant Cressilee , Crane Christopher E , Scherer Elizabeth P , Schroeppel Thomas J , Moskowitz Eliza , Regner Justin L , Frazee Richard , Campion Eric M , Bartley Matthew , Mortus Jared R , Ward Jeremy , Margulies Daniel R , Dissanaike Sharmila
Published: May 2021

Introduction

Infection control in patients with perforated peptic ulcers (PPU) commonly includes empiric antifungals (AF). We investigated the variation in the use of empiric AF and explored the association between their use and the subsequent development of organ space infection (OSI).

Methods

This was a secondary analysis of a multicenter, case–control study of patients treated for PPU at nine institutions between 2011 and 2018. Microbiology and utilization of empiric AF, defined as AF administered within 24 hours from the index surgery, were recorded. Patients who received empiric AF were compared with those who did not. The primary outcome was OSI and secondary outcome was OSI with growth ofCandidaspp. A logistic regression was used to adjust for differences between the two cohorts.

Results

A total of 554 patients underwent a surgical procedure for PPU and had available timing of AF administration. The median age was 57 years and 61% were male. Laparoscopy was used in 24% and omental patch was the most common procedure performed (78%). Overall, 239 (43%) received empiric AF. There was a large variation in the use of empiric AF among participating centers, ranging from 25% to 68%. The overall incidence of OSI was 14% (77/554) and was similar for patients who did or did not receive empiric AF. The adjusted OR for development of OSI for patients who received empiric AF was 1.04 (95% CI 0.64 to 1.70), adjusted p=0.86. The overall incidence of OSI with growth ofCandidaspp was 5% and was similar for both groups (adjusted OR 1.29, 95% CI 0.59 to 2.84, adjusted p=0.53).

Conclusion

For patients undergoing surgery for PPU, the use of empiric AF did not yield any significant clinical advantage in preventing OSI, even those due toCandidaspp. Use of empiric AF in this setting is unnecessary.

Study type

Original article, case series.

Level of evidence

III.
Quantum electrodynamics with self-conjugated equations with spinor wave functions for fermion fields
Authors: Neznamov V. P. , Shemarulin V. E.
Published: May 2021

Quantum electrodynamics (QED) with self-conjugated equations with spinor wave functions for fermion fields is considered. In the low order of the perturbation theory, matrix elements of some of QED physical processes are calculated. The final results coincide with cross-sections calculated in the standard QED. The self-energy of an electron and amplitudes of processes associated with determination of the anomalous magnetic moment of an electron and Lamb shift are calculated. These results agree with the results in the standard QED. Distinctive feature of the developed theory is the fact that only states with positive energies are present in the intermediate virtual states in the calculations of the electron self-energy, anomalous magnetic moment of an electron and Lamb shift. Besides, in equations, masses of particles and antiparticles have the opposite signs.
Comment on: “Lorentz transformation of a charge-current density and ‘relativistic polarization’ of a moving current loop”
Authors: Franklin Jerrold
Published: May 2021

We show that the attack on my paper, “Complete Lorentz transformation of a charge-current density,” by Kholmetskii, Missevitch, and Yarman in their paper, “Lorentz transformation of a charge-current density and ‘relativistic polarization’ of a moving current loop” is based on completely erroneous assumptions and equations.
Geology and petroleum prospectivity of the Sea of Hebrides Basin and Minch Basin, offshore NW Scotland
Authors: Fyfe Laura-Jane C. , Schofield Nick , Holford Simon , Hartley Adrian , Heafford Adrian , Muirhead David , Howell John
Published: May 2021

The Sea of Hebrides Basin and Minch Basin are late Paleozoic–Mesozoic rift basins located to the NW of the Scottish mainland. The basins were the target of small-scale petroleum exploration from the late 1960s to the early 1990s, with a total of three wells drilled within the two basins between 1989 and 1991. Although no commercially viable petroleum discoveries were made, numerous petroleum shows were identified within both basins, including a gas show within the Upper Glen 1 well in Lower Jurassic limestones. Organic-rich shales have been identified throughout the Jurassic succession within the Sea of Hebrides Basin, with one Middle Jurassic (Bajocian–Bathonian) shale exhibiting a total organic carbon content of up to 15 wt%. The focus of this study is to review the historical petroleum exploration within these basins, and to evaluate whether the conclusions drawn in the early 1990s of a lack of prospectivity remains the case. This was undertaken by analysis of seismic reflection data, gravity and aeromagnetic data, and sedimentological data from both onshore and offshore wells, boreholes and previously published studies. The key findings from our study suggest that there is a low probability of commercially sized petroleum accumulations within either the Sea of Hebrides Basin or the Minch Basin. Ineffective source rocks, likely to be due to low maturities (due to lack of burial) and the fact that the encountered Jurassic and Permian–Triassic reservoirs are of poor quality (low porosity and permeability), has led to our interpretation of future exploration being high risk, with any potential accumulations being small in size. While petroleum accumulations are unlikely within the basin, applying the knowledge obtained from this study could provide additional datasets and insight into petroleum exploration within other NE Atlantic margin basins, such as the Rockall Trough and the Faroe–Shetland Basin.