bluuebunny/crossref_metadata_2025 huggingface dataset:
Space use by semi‐free‐ranging cows on wetlands and its implication as a conservation management tool
Authors: Mirski Paweł
Published: August 2021

Wetlands are often exposed to reed and shrub expansion that dominate their heterogeneous landscape and threaten species inhabiting open wetlands. The alternative to heavy‐machine mowing is grazing, which should be carried out without fencing in high‐value protected areas. To evaluate the effectiveness of semi‐free‐ranging cattle in sustaining and restoring the open landscape of heterogeneous wetlands in Biebrza National Park, a herd of semi‐free‐ranging dairy cows was followed with a GPS tag. Cows freely grazed for 10.7 hours, on average, during the day and were taken to a cowshed at night. Each day the herd moved 10.2 km, on average (up to 23.5 km), but usually stayed in the radius of 3.5 km (up to 4.7 km) from the cowshed. The core foraging range (50% kernel) reached 46 ha (stock density reached 0.63 cow/ha), but the total foraging range (95% kernel) was a few times larger—208 ha (0.14 cow/ha). The cows used all available habitats (fen grasslands, hillocks, trees, and shrubs), but avoided reed in the late summer and autumn as well as afforested sites in spring. On the whole, reed expansion was suppressed in the cows' foraging range, while it still continued to increase on the outskirts of the study area, where cows did not regularly graze. It can be concluded that semi‐free‐ranging cattle can be used to effectively impede reed succession within a large wetland area.
Comparison of standard versus low‐dose valganciclovir regimens for cytomegalovirus prophylaxis in high‐risk liver transplant recipients
Authors: Bixby Alexandra L. , Fitzgerald Linda , Park Jeong M. , Kaul Daniel , Tischer Sarah
Published: August 2021

Purpose

The purpose of this study was to compare the safety and efficacy of two valganciclovir (VGCV) institutional dosing protocols for cytomegalovirus (CMV) prophylaxis in liver transplant (LT) recipients with CMV serotype donor +/recipient‐ (D+/R−).

Methods

This was a single‐center review of CMV D+/R− adult LT recipients who received VGCV 450 mg/day for 90 days (low‐dose) or VGCV 900 mg/day for 180 days (standard‐dose). The primary outcome was incidence of CMV disease at 1 year. Secondary outcomes included rates of CMV syndrome, end‐organ disease, breakthrough infection, and resistance. Neutropenia, early discontinuation of VGCV, growth colony stimulating factors use (G‐CSF), biopsy‐proven rejection (BPAR), graft loss, and death at 1 year were analyzed.

Results

Ninety‐six CMV D+/R− LT recipients were included. Although no difference in CMV disease was observed (low‐dose 26% vs. standard‐dose 23%, p = 0.71), 75% of CMV infections in the low‐dose group presented with end‐organ disease. Ganciclovir (GCV) resistance was observed only in the low‐dose group (n = 2). Significantly more patients in the standard‐dose group developed neutropenia (low‐dose 10% vs 60% standard‐dose, p < 0.001). In the standard‐dose group, 29% required early discontinuation of VGCV (vs. 5% in the low‐dose group, p < 0.001), and 20% were treated with G‐CSF. Both cohorts had similar rates of BPAR, graft loss, and death at 1 year.

Conclusions

VGCV 900 mg/day for 180 days had higher rates of hematologic adverse effects resulting in frequent treatment interruptions. However, the occurrence of two cases of GCV‐resistant CMV disease raises concerns about routinely using low‐dose VGCV prophylaxis.
Nonsurgical reduction of prolapsed colocolic intussusception in 2 puppies
Authors: Moores Alison L. , Urraca Carolina I. , de Sousa Ricardo J. R. , Jenkins Georgia , Anderson Davina M.
Published: August 2021

Objective

To describe the nonsurgical management of prolapsed colocolic intussusception in 2 puppies.

Case Summary

Two 3‐month‐old male intact puppies (Pug and Labrador Retriever) developed intussusceptions that had prolapsed from the anus after they had suffered from tenesmus with soft feces or diarrhea. Reduction of the prolapsed tissue was performed and colocolic intussusception was diagnosed ultrasonographically in 1 dog. Rectal manipulation and saline enema were performed in both dogs, and reduction of the intussusception was confirmed endoscopically or ultrasonographically. Bupivacaine and prednisolone foam enemas were administered to reduce tenesmus. Abdominal ultrasonography the following day in 1 dog confirmed a normal appearing colon. No further tenesmus was noted in 1 dog; the other had a brief rectal prolapse after an episode of tenesmus that was manually reduced. Intussusception had not recurred 4 months and 1 year following manual reduction procedures.

New or Unique Information Provided

This is the first report of successful nonsurgical management of colocolic intussusception in a companion animal. Nonsurgical management is a first‐line treatment of intussusception in children and could be considered in dogs with colocolic intussusception. Further investigation is required to define specific aspects, including rectal manipulation, saline enema, or anesthesia, that aid in resolution of this type of intussusception.
Prevalence of iron deficiency and red blood cell transfusions in surgical patients
Authors: Tonino Rik Paulus Bernardus , Wilson Michael , Zwaginga Jaap Jan , Schipperus Martin Roelof
Published: August 2021

Background and Objectives

While iron deficiency (ID) is the most common cause of anaemia, little is known about the prevalence and type of ID in preoperative surgical patients. The aims of the present study were to investigate the prevalence and types of ID in a large cohort of surgical patients, and how these are related to perioperative blood use after correction for confounders such as haemoglobin level.

Materials and Methods

Data were retrospectively extracted from electronic case records of all patients who underwent elective surgery between September 2016 and November 2017 (n = 2711). Iron parameters, haemoglobin and details of perioperative red cell transfusions were collected.

Results

Of 2711 patients, 618 (22.8%) were iron deficient (= transferrin saturation [TSAT] < 16%) preoperatively, 173 (6.4% of the cohort) had an absolute iron deficiency (AID; TSAT < 16% and ferritin < 30 μg/L) and 445 (16.4%) had functional/mixed ID (TSAT < 16% and ferritin ≥ 30 μg/L). Corrected for Hb level, iron‐deficient patients received significantly more red cell units than patients without ID (p = 0.026). AID was not associated with a significantly higher incidence of transfusions (7.5% of patients transfused; p = 0.12 after correction for Hb) than patients without ID, whereas patients with functional/mixed deficiency did receive significantly more transfusions (6.1%; p = 0.021) as compared to patients without ID (1.7%).

Conclusion

Preoperative ID, in particular the functional/mixed type, was associated with a higher risk of receiving perioperative red cell transfusions as compared to patients without ID. Adequately treating ID might, therefore, reduce the need for perioperative red cell transfusions.
Caracterización de la gestión de la información contable en las Pymes comerciales de Ambato – Ecuador
Authors: Villacís Yank José Alfredo , Moreno Mejía Mario Alberto
Published: August 2021

La contabilidad en las empresas es el medio principal de información sobre la gestión empresarial. Los datos contables resumidos en los estados financieros permiten establecer los resultados de la gestión y proyectar escenarios futuros con base en el análisis proyectivo. La toma de decisiones operativas y estratégicas se basa en información, no obstante, la gerencia de las pequeñas y medianas empresas (Pymes) a menudo no brindan la importancia debida al análisis de los datos y asumen la función contable específicamente para cumplir disposiciones legales y reglamentarias o, a su vez, encargándole funciones adicionales de control. El objetivo de este artículo es constatar en las Pymes los criterios de calidad de la información y el uso de los datos contables, sintetizados en el balance general y el estado de resultados. Estos factores permiten clarificar la gestión de la información en la toma de decisiones como soporte de las actividades propias de los negocios.
Sistemas de informações contábeis: proposição de um modelo de avaliação dos fatores críticos de sucesso
Authors: Antonelli Ricardo Adriano , Bernardes Voese Simone , Ditzel Santos Gilson , Rufatto da Silva Marivânia
Published: August 2021

Esta pesquisa propõe um modelo composto por dez fatores críticos oriundos da literatura, e uma seleção de variáveis para avaliar o sucesso dos Sistemas de Informações Contábeis (SIC) nas Empresas Prestadoras de Serviços Contábeis (EPSC) do Brasil. A seleção das variáveis foi realizada seguindo o método Delphi em duas rodadas com 30 especialistas em SIC, contemplando empresas desenvolvedoras e usuários de SIC. Na primeira rodada, os especialistas sugeriram 75 variáveis críticas de sucesso e insucesso. Na segunda rodada, a partir das variáveis indicadas pela literatura e pelos especialistas (161), requisitou-se aos especialistas indicar as mais importantes, resultando em 74 variáveis distribuídas nos dez fatores que compõem o modelo teórico proposto. Destas, 41,9% não são originadas da literatura.
Ultradeep microaxicons in lithium niobate by focused Xe ion beam milling
Authors: Gorelick Sergey , de Marco Alex
Published: August 2021

Refractive axicons are conically shaped optical devices that are capable of generating nondiffracting Bessel-like beams over extended depths-of-focus (DOFs). In addition to the substantially longer DOF compared to those produced by parabolic focusing lenses, the axicons can generate beams with better resolution for the same form-factor of the optical element, e.g., its diameter and sag height. These properties make the axicons useful in numerous applications in imaging, particle trapping, and many others. Miniaturized refractive axicons or microaxicons are challenging to realize in hard substrates due to the lack of sufficiently precise and rapid fabrication technologies. Here, we report on the rapid fabrication of ultradeep microaxicons in lithium niobate using high-current focused Xe ion beam milling. Microaxicons with 230-μm diameter with ultradeep sag heights between 21 and 48 μm were milled using 200 nA of beam current. Furthermore, the microaxicons were milled in single-crystal lithium niobate—a material with a high refractive index of >2.2 but which inertness makes it a challenging material in microfabrication. The performance of the lenses was characterized by mapping the transmitted intensity at different positions. The measured spot sizes of the produced beams are in excellent agreement with the theoretical expectations and range from 750 down to 250 nm (∼λ/2) beam spot size for the shallowest and the deepest microaxicons in this study, respectively. The corresponding DOFs are from 500 down to ∼50 μm for the ultradeep microaxicon. The results verify the applicability of high-current milling with a focused Xe ion beam for the fabrication of high-performance optical elements.
Reevaluating the Impact of Epstein-Barr Virus Noncoding RNAs on the Interferon Response
Authors: Murphy Eain A.
Published: August 2021

The necessity of viruses to modulate the innate immune response often dictates the outcome of viral infection. As such, viruses encode many factors that undermine these potent antiviral responses.
Uncovering Divergence in Gene Expression Regulation in the Adaptation of Yeast to Nitrogen Scarcity
Authors: Villarroel Carlos A. , Bastías Macarena , Canessa Paulo , Cubillos Francisco A.
Published: August 2021

Historically, coding variants were prioritized when searching for causal mechanisms driving adaptation of natural populations to stressful environments. However, the recent focus on noncoding variants demonstrated their ubiquitous role in adaptation.
Extracellular Vesicles in Teasing Apart Complex Plant-Microbiota Links: Implications for Microbiome-Based Biotechnology
Authors: Motaung Thabiso E. , Steenkamp Emma T.
Published: August 2021

Extracellular vesicles (EVs) are subcellular carriers of bioactive compounds with a complex array of functional effects on target cells. In mammals, circulating bodily fluid microbiota EVs (mbEVs) deliver cargo from source cells and adversely or favorably alter the physiology of the same source, neighboring, and distant recipient cells in an autocrine, paracrine, or endocrine fashion, respectively.
Giant Virus-Eukaryote Interactions as Ecological and Evolutionary Driving Forces
Authors: Ku Chuan
Published: August 2021

Giant DNA viruses of eukaryotes are notable for their extraordinary genome size and coding capacity. Once thought to be oddities in the virus world, these elusive microbes have turned out to be widely occurring in marine, freshwater, and terrestrial ecosystems and are commonly associated with diverse hosts, in particular microbial eukaryotes.
Deciphering Metabolic Currencies That Support Marine Microbial Networks
Authors: Durham Bryndan P.
Published: August 2021

Microbes are omnipresent in the biosphere and perform biological and chemical processes critical to ecosystem function, nutrient cycling, and global climate regulation. In the ocean, microbes constitute more than two-thirds of biomass with abundances reaching over one million microbial cells per milliliter of seawater.
The Split Personality of Beauveria bassiana: Understanding the Molecular Basis of Fungal Parasitism and Mutualism
Authors: Ortiz-Urquiza Almudena
Published: August 2021

Fungal pathogenicity toward insects has independently evolved several times, resulting in specialist and generalist pathogens, some of whom have maintained aspects of their previous lifestyles. Being able to grow as an endophyte (engaging in a mutualistic interaction with plants) or saprophyte (recycling nutrients back into the environment), the generalist (broad-host-range) fungus
Beauveria bassiana
does not need to rely on insect hosts to complete its life cycle.
Comparative Molecular and Immunoregulatory Analysis of Extracellular Vesicles from Candida albicans and Candida auris
Authors: Zamith-Miranda Daniel , Heyman Heino M. , Couvillion Sneha P. , Cordero Radames J. B. , Rodrigues Marcio L. , Nimrichter Leonardo , Casadevall Arturo , Amatuzzi Rafaela F. , Alves Lysangela R. , Nakayasu Ernesto S. , Nosanchuk Joshua D.
Published: August 2021

Candida auris
is a recently described multidrug-resistant pathogenic fungus that is responsible for outbreaks across the globe, particularly in the context of nosocomial infections. Its virulence factors and pathogenesis are poorly understood.
SubTap, a Versatile 3D Printed Platform for Eavesdropping on Extracellular Interactions
Authors: Birer-Williams Caroline M. C. , Chu Rosalie K. , Anderton Christopher R. , Wright Erik S.
Published: August 2021

Improvements in experimental techniques and instrumentation have led to the discovery that the microbiome plays an essential role in human and environmental health. Nevertheless, there remain major impediments to conducting large-scale interrogations of the microbiome in a high-throughput manner, particularly in the field of exometabolomics.
Supplemental Material: Identification of seasonal varves in the lower Pliocene Bouse Formation, lower Colorado River Valley, and implications for Colorado Plateau uplift
Authors: Spencer J.E. , al. et
Published: August 2021

Oxygen and carbon isotope analyses of laminated Bouse marl.
Examining the reach and exposure of a mobile phone-based training programme for frontline health workers (ASHAs) in 13 states across India
Authors: Bashingwa Jean Juste Harrisson , Shah Neha , Mohan Diwakar , Scott Kerry , Chamberlain Sara , Mulder Nicola , Rahul Sai , Arora Salil , Chakraborty Arpita , Ummer Osama , Ved Rajani , LeFevre Amnesty Elizabeth
Published: August 2021

Mobile phones are increasingly used to facilitate in-service training for frontline health workers (FLHWs). Mobile learning (mLearning) programmes have the potential to provide FLHWs with high quality, inexpensive, standardised learning at scale, and at the time and location of their choosing. However, further research is needed into FLHW engagement with mLearning content at scale, a factor which could influence knowledge and service delivery. Mobile Academy is an interactive voice response training course for FLHWs in India, which aims to improve interpersonal communication skills and refresh knowledge of preventative reproductive, maternal, neonatal and child health. FLHWs dial in to an audio course consisting of 11 chapters, each with a 4-question true/false quiz, resulting in a cumulative pass/fail score. In this paper, we analyse call data records from the national version of Mobile Academy to explore coverage, user engagement and completion. Over 158 596 Accredited Social Health Activists (ASHAs) initiated the national version, while 111 994 initiated the course on state-based platforms. Together, this represents 41% of the estimated total number of ASHAs registered in the government database across 13 states. Of those who initiated the national version, 81% completed it; and of those, over 99% passed. The initiation and completion rates varied by state, with Rajasthan having the highest initiation rate. Many ASHAs made multiple calls in the afternoons and evenings but called in for longer durations earlier in the day. Findings from this analysis provide important insights into the differential reach and uptake of the programme across states.
Barriers and facilitators to implementation of shared medical appointments in primary care for the management of long-term conditions: a systematic review and synthesis of qualitative studies
Authors: Graham Fiona , Tang Mei Yee , Jackson Katherine , Martin Helen , O'Donnell Amy , Ogunbayo Oladapo , Sniehotta Falko F , Kaner Eileen
Published: August 2021

Objective

To synthesise the published literature on practitioner, patient and carer views and experiences of shared medical appointments (SMAs) for the management of long-term conditions in primary care.

Design

Systematic review of qualitative primary studies.

Methods

A systematic search was conducted using MEDLINE (Ovid), PsycINFO (Ovid), CINAHL (EBSCOhost), Web of Science, Social Science Premium Collection (Proquest) and Scopus (SciVerse) from database starting dates to June 2019. Practitioner, patient and carer perspectives were coded separately. Deductive coding using a framework approach was followed by thematic analysis and narrative synthesis. Quality assessment was conducted using the Critical Appraisal Skills Programme for qualitative studies.

Results

We identified 18 unique studies that reported practitioner (n=11), patient (n=14) and/or carer perspectivs(n=3). Practitioners reported benefits of SMAs including scope for comprehensive patient-led care, peer support, less repetition and improved efficiency compared with 1:1 care. Barriers included administrative challenges and resistance from patients and colleagues, largely due to uncertainties and unclear expectations. Skilled facilitators, tailoring of SMAs to patient groups, leadership support and teamwork were reported to be important for successful delivery. Patients’ reported experiences were largely positive with the SMAs considered a supportive environment in which to share and learn about self-care, though the need for good facilitation was recognised. Reports of carer experience were limited but included improved communication between carer and patient.

Conclusion

There is insufficient evidence to indicate whether views and experiences vary between staff, medical condition and/or patient characteristics. Participant experiences may be subject to reporting bias. Policies and guidance regarding best practice need to be developed with consideration given to resource requirements. Further research is needed to capture views about wider and co-occurring conditions, to hear from those without SMA experience and to understand which groups of patients and practitioners should be brought together in an SMA for best effect.

PROSPERO registration number

CRD42019141893.
Relationship between weight retention at 6 weeks postpartum and the risk of large-for-gestational age birth in a second pregnancy in China: a retrospective cohort study
Authors: Liu Jing , Song Guang , Zhao Ge , Meng Tao
Published: August 2021

Objective

We aimed to investigate the association between weight retention at 6 weeks postpartum after the first pregnancy and large-for-gestational age (LGA) risk in a subsequent pregnancy.

Study design

A retrospective cohort study.

Setting

A tertiary hospital of China.

Participants

5950 Chinese singleton pregnancies that delivered their second singletons between 28 and 42 weeks of gestation.

Outcomes measures

We calculated the weight retention at 6 weeks postpartum after the first pregnancy (the body mass index (BMI) at 6 weeks after the first birth minus the prepregnant BMI of the first pregnancy) and the gestational weight gain in the second pregnancy. We used the logistic regression to obtain adjusted OR. We determined the relationship between maternal BMI change at 6 weeks after the first pregnancy and LGA risk in the second pregnancy.

Results

Relative to other categories of BMI change at 6 weeks postpartum, women who gained ≥3 kg/m2compared with the prepregnancy BMI were at increased LGA risk. The stratified analysis showed that LGA risk was increased in the second pregnancy in underweight and normal weight women who gained ≥3 kg/m2when using remain stable women as the reference group (OR=3.35, 95% CI 1.11 to 10.12 for underweight women; OR=2.23, 95% CI 1.43 to 3.45 for normal weight women) at 6 weeks postpartum. For the women who gained ≥3 kg/m2at 6 weeks postpartum, LGA risk was increased in normal weight women with an adequate (OR=3.21, 95% CI 1.10 to 9.33) and excessive (OR=2.62, 95% CI 1.02 to 6.76) gestational weight in the second pregnancy when using obese women as the reference.

Conclusion

Postpartum weight retention at 6 weeks after the first pregnancy provides us a new early window to identify LGA risk in a subsequent pregnancy and allows us to implement primary preventative strategies.
What is the extent of COVID-19 vaccine hesitancy in Bangladesh? A cross-sectional rapid national survey
Authors: Ali Mohammad , Hossain Ahmed
Published: August 2021

Objectives

To assess COVID-19 vaccine hesitancy in Bangladesh and identify population subgroups with higher odds of vaccine hesitancy.

Design

A nationally representative cross-sectional survey was used for this study. Descriptive analyses helped to compute vaccine hesitancy proportions and compare them across groups. Multiple logistic regression analyses were performed to compute the adjusted OR.

Setting

Bangladesh.

Participants

A total of 1134 participants from the general population, aged 18 years and above participated in this study.

Outcome measures

Prevalence and predictors of vaccine hesitancy.

Results

Of the total participants, 32.5% showed COVID-19 vaccine hesitancy. Hesitancy was high among respondents who were men, over 60, unemployed, from low-income families, from central Bangladesh, including Dhaka, living in rented houses, tobacco users, politically affiliated, doubtful of the vaccine’s efficacy for Bangladeshis and those who did not have any physical illnesses in the past year. In the multiple logistic regression models, transgender respondents (adjusted OR, AOR=3.62), married individuals (AOR=1.49), tobacco users (AOR=1.33), those who had not experienced any physical illnesses in the past year (AOR=1.49), those with political affiliations with opposition parties (AOR=1.48), those who believed COVID-19 vaccines would not be effective for Bangladeshis (AOR=3.20), and those who were slightly concerned (AOR=2.87) or not concerned at all (AOR=7.45) about themselves or a family member getting infected with COVID-19 in the next year were significantly associated with vaccine hesitancy (p<0.05).

Conclusions

Given the high prevalence of COVID-19 vaccine hesitancy, in order to guarantee that COVID-19 vaccinations are widely distributed, the government and public health experts must be prepared to handle vaccine hesitancy and increase vaccine awareness among potential recipients. To address these issues and support COVID-19 immunisation programs, evidence-based educational and policy-level initiatives must be undertaken especially for the poor, older and chronically diseased individuals.
Sex disparity in subsequent outcomes in survivors of coronary heart disease
Authors: Akyea Ralph Kwame , Kontopantelis Evangelos , Kai Joe , Weng Stephen F , Patel Riyaz S , Asselbergs Folkert W , Qureshi Nadeem
Published: August 2021

Objective

Evidence on sex differences in outcomes after developing coronary heart disease (CHD) has focused on recurrent CHD, all-cause mortality or revascularisation. We assessed sex disparities in subsequent major adverse cardiovascular events (MACE) in adults surviving their first-time CHD.

Methods

Using a population-based cohort obtained from the Clinical Practice Research Datalink (CPRD GOLD) linked to hospitalisation and death records in the UK, we identified 143 702 adults (aged ≥18 years) between 1 January 1998 and 31 December 2017 with no prior history of MACE. MACE outcome was a composite of recurrent CHD, stroke, peripheral vascular disease, heart failure and cardiovascular-related mortality. Multivariable models (Cox and competing risks regressions) were used to assess differences between sexes.

Results

There were 143 702 adults with any incident CHD (either angina, myocardial infarction or coronary revascularisation). Women (n=63 078, 43.9%) were older than men (median age, 73 vs 66 years). First subsequent MACE outcome was observed in 91 706 (63.8%). Women had a significantly lower risk of MACE (hazard ratio (HR), 0.68 (95% CI 0.67 to 0.69); sub-hazard ratio (HRsd), 0.71 (0.70 to 0.72), respectively) and recurrent CHD (n=66 543, 46.3%) (HR, 0.60 (0.59 to 0.61); HRsd, 0.62 (0.61 to 0.63)) when compared with men after incident CHD. However, women had a significantly higher risk of stroke (n=5740, 4.0%) (HR, 1.26 (1.19 to 1.33); HRsd, 1.32 (1.25 to 1.39)), heart failure (n=7905, 5.5%) (HR, 1.09 (1.04 to 1.15); HRsd, 1.13 (1.07 to 1.18)) and all-cause mortality (n=29 503, 20.5%) (HR, 1.05 (1.02 to 1.07); HRsd, 1.11 (1.08 to 1.13)).

Conclusions

After incident CHD, women have lower risk of composite MACE and recurrent CHD outcomes but higher risk of stroke, heart failure, and all-cause mortality compared with men.
Reference standards for gene fusion molecular assays on cytological samples: an international validation study
Authors: Malapelle Umberto , Pepe Francesco , Pisapia Pasquale , Altimari Annalisa , Bellevicine Claudio , Brunnström Hans , Bruno Rossella , Büttner Reinhard , Cirnes Luis , De Andrea Carlos E , de Biase Dario , Dumur Catherine I , Ericson Lindquist Kajsa , Fontanini Gabriella , Gautiero Eugenio , Gentien David , Hofman Paul , Hofman Veronique , Iaccarino Antonino , Lozano Maria Dolores , Mayo-de-Las-Casas Clara , Merkelbach-Bruse Sabine , Pagni Fabio , Roman Ruth , Schmitt Fernando C , Siemanowski Janna , Roy-Chowdhuri Sinchita , Tallini Giovanni , Tresserra Francesc , Vander Borght Sara , Vielh Philippe , Vigliar Elena , Vita Giulia Anna Carmen , Weynand Birgit , Rosell Rafael , Molina Vila Miguel Angel , Troncone Giancarlo
Published: August 2021

Aims

Gene fusions assays are key for personalised treatments of advanced human cancers. Their implementation on cytological material requires a preliminary validation that may make use of cell line slides mimicking cytological samples. In this international multi-institutional study, gene fusion reference standards were developed and validated.

Methods

Cell lines harbouringEML4(13)–ALK(20) andSLC34A2(4)–ROS1(32) gene fusions were adopted to prepare reference standards. Eight laboratories (five adopting amplicon-based and three hybridisation-based platforms) received, at different dilution points two sets of slides (slide A 50.0%, slide B 25.0%, slide C 12.5% and slide D wild type) stained by Papanicolaou (Pap) and May Grunwald Giemsa (MGG). Analysis was carried out on a total of 64 slides.

Results

Four (50.0%) out of eight laboratories reported results on all slides and dilution points. While 12 (37.5%) out of 32 MGG slides were inadequate, 27 (84.4%) out of 32 Pap slides produced libraries adequate for variant calling. The laboratories using hybridisation-based platforms showed the highest rate of inadequate results (13/24 slides, 54.2%). Conversely, only 10.0% (4/40 slides) of inadequate results were reported by laboratories adopting amplicon-based platforms.

Conclusions

Reference standards in cytological format yield better results when Pap staining and processed by amplicon-based assays. Further investigation is required to optimise these standards for MGG stained cells and for hybridisation-based approaches.
Phase II study of durvalumab plus tremelimumab as therapy for patients with previously treated anti-PD-1/PD-L1 resistant stage IV squamous cell lung cancer (Lung-MAP substudy S1400F, NCT03373760)
Authors: Leighl Natasha B , Redman Mary W , Rizvi Naiyer , Hirsch Fred R , Mack Philip C , Schwartz Lawrence H , Wade James L , Irvin William J , Reddy Sreekanth C , Crawford Jeffrey , Bradley Jeffrey D , Stinchcombe Thomas E , Ramalingam Suresh S , Miao Jieling , Minichiello Katherine , Herbst Roy S , Papadimitrakopoulou Vassiliki A , Kelly Karen , Gandara David R
Published: August 2021

Introduction

S1400F is a non-match substudy of Lung Cancer Master Protocol (Lung-MAP) evaluating the immunotherapy combination of durvalumab and tremelimumab to overcome resistance to anti-programmed death ligand 1 (PD-(L)1) therapy in patients with advanced squamous lung carcinoma (sq non-small-cell lung cancer (NSCLC)).

Methods

Patients with previously treated sqNSCLC with disease progression after anti-PD-(L)1 monotherapy, who did not qualify for any active molecularly targeted Lung-MAP substudies, were eligible. Patients received tremelimumab 75 mg plus durvalumab 1500 mg once every 28 days for four cycles then durvalumab alone every 28 days until disease progression. The primary endpoint was the objective response rate (RECIST V.1.1). Primary and acquired resistance cohorts, defined as disease progression within 24 weeks versus ≥24 weeks of starting prior anti-PD-(L)1 therapy, were analyzed separately and an interim analysis for futility was planned after 20 patients in each cohort were evaluable for response.

Results

A total of 58 eligible patients received drug, 28 with primary resistance and 30 with acquired resistance to anti-PD-(L)1 monotherapy. Grade ≥3 adverse events at least possibly related to treatment were seen in 20 (34%) patients. The response rate in the primary resistance cohort was 7% (95% CI 0% to 17%), with one complete and one partial response. No responses were seen in the acquired resistance cohort. In the primary and resistance cohorts the median progression-free survival was 2.0 months (95% CI 1.6 to 3.0) and 2.1 months (95% CI 1.6 to 3.2), respectively, and overall survival was 7.7 months (95% CI 4.0 to 12.0) and 7.6 months (95% CI 5.3 to 10.2), respectively.

Conclusion

Durvalumab plus tremelimumab had minimal activity in patients with advanced sqNSCLC progressing on prior anti-PD-1 therapy.

Trial registration number

NCT03373760.
Nomogram to predict the outcomes of patients with microsatellite instability-high metastatic colorectal cancer receiving immune checkpoint inhibitors
Authors: Pietrantonio Filippo , Lonardi Sara , Corti Francesca , Infante Gabriele , Elez Maria Elena , Fakih Marwan , Jayachandran Priya , Shah Aakash Tushar , Salati Massimiliano , Fenocchio Elisabetta , Salvatore Lisa , Curigliano Giuseppe , Cremolini Chiara , Ambrosini Margherita , Ros Javier , Intini Rossana , Nappo Floriana , Damian Silvia , Morano Federica , Fucà Giovanni , Overman Michael , Miceli Rosalba
Published: August 2021

Background

The efficacy of immune checkpoint inhibitors (ICIs) in patients with microsatellite instability (MSI)-high metastatic colorectal cancer (mCRC) is unprecedented. A relevant proportion of subjects achieving durable disease control may be considered potentially ‘cured’, as opposed to patients experiencing primary ICI refractoriness or short-term clinical benefit. We developed and externally validated a nomogram to estimate the progression-free survival (PFS) and the time-independent event-free probability (EFP) in patients with MSI-high mCRC receiving ICIs.

Methods

The PFS and EFP were estimated using a cure model fitted on a developing set of 163 patients and validated on a set of 146 patients with MSI-high mCRC receiving anti-programmed death (ligand)1 (PD-(L)1) ± anticytotoxic T-lymphocyte antigen 4 (CTLA-4) agents. A total of 23 putative prognostic factors were chosen and then selected using a random survival forest (RSF). The model performance in estimating PFS probability was evaluated by assessing calibration (internally—developing set and externally—validating set) and quantifying the discriminative ability (Harrell C index).

Results

RFS selected five variables: ICI type (anti-PD-(L)1 monotherapy vs anti-CTLA-4 combo), ECOG PS (0 vs >0), neutrophil-to-lymphocyte ratio (≤3 vs >3), platelet count, and prior treatment lines. As both in the developing and validation series most PFS events occurred within 12 months, this was chosen as cut-point for PFS prediction. The combination of the selected variables allowed estimation of the 12-month PFS (focused on patients with low chance of being cured) and the EFP (focused on patients likely to be event-free at a certain point of their follow-up). ICI type was significantly associated with disease control, as patients receiving the anti-CTLA-4-combination experienced the best outcomes. The calibration of PFS predictions was good both in the developing and validating sets. The median value of the EFP (46%) allowed segregation of two prognostic groups in both the developing (PFS HR=3.73, 95% CI 2.25 to 6.18; p<0.0001) and validating (PFS HR=1.86, 95% CI 1.07 to 3.23; p=0.0269) sets.

Conclusions

A nomogram based on five easily assessable variables including ICI treatment was built to estimate the outcomes of patients with MSI-high mCRC, with the potential to assist clinicians in their clinical practice. The web-based system ‘MSI mCRC Cure’ was released.
Use of a sheathless 8-French balloon guide catheter (Walrus) through the radial artery for mechanical thrombectomy: technique and case series
Authors: Dossani Rimal H , Waqas Muhammad , Monteiro Andre , Cappuzzo Justin M , Almayman Faisal , Snyder Kenneth V , Levy Elad I , Siddiqui Adnan H , Davies Jason M
Published: August 2021

Background

The effectiveness of transradial stroke thrombectomy has been limited by guide catheter size and lack of good balloon options. In this study we describe our technique for the use of a sheathless 8-French balloon guide catheter (Walrus) through radial access and present our initial clinical experience.

Methods

This was a retrospective case series of consecutive patients who underwent mechanical thrombectomy for large vessel occlusion using the sheathless catheter over a period of 3 months. Clinical characteristics, procedural details, reperfusion success (modified Thrombolysis in Cerebral Infarction (mTICI) 2b–3 grade), first-pass effect (FPE; mTICI reperfusion grade 2c or 3 with a single pass), access site complications and clinical improvement at discharge were recorded. A descriptive analysis was performed.

Results

Among the 10 patients in the series, median age was 77 years (IQR 75–79) and three were women. All patients had a baseline modified Rankin Scale score ≤2. Median admission National Institutes of Health Stroke Scale (NIHSS) score was 12.5 (IQR 9–16). Four patients received intravenous alteplase before mechanical thrombectomy. Eight patients had M1 occlusion and two had proximal M2 occlusion. The median radial artery diameter was 2.5 mm (IQR 2.5–2.7). Successful reperfusion was achieved in all patients. FPE was achieved in six patients. No access site-related complications or post-procedural intracranial hemorrhages occurred. All patients had improvement in NIHSS score at discharge.

Conclusions

The use of this sheathless catheter for transradial access was safe and feasible. The technique can potentially improve the outcomes of transradial access for stroke intervention.
Interventional and surgical management of internal jugular venous stenosis: a narrative review
Authors: Pang Sharon , Kolarich Andrew R , Brinjikji Waleed , Nakaji Peter , Hepworth Ed , Hui Ferdinand
Published: August 2021

Background

A small subset of patients with presumed idiopathic intracranial hypertension are found to have isolated internal jugular vein stenosis (IJVS).

Objective

To review the current interventions used in patients who present with intracranial hypertension secondary to IJVS.

Methods

In December 2020, we performed a literature search on Pubmed/Medline and Scopus databases for original articles studying surgical and endovascular interventions used for intracranial hypertension in the setting of internal jugular vein stenosis. No date, patient population, or study type was excluded.

Results

All studies that included at least one case in which a surgical or endovascular intervention was used to treat IJVS were included. Selection criteria for patients varied, most commonly defined by identification of compression of the internal jugular vein. The 17 studies included in this review ranged from case reports to large single-center cohort studies. The most used surgical intervention was styloidectomy. Styloidectomy had an overall better outcome success rate (79%) than angioplasty/stenting (66%). No complications were recorded in any of the surgical cases analyzed. Outcome measures varied, but all studies recorded clinical symptoms of the patients.

Conclusion

Few current large cohort studies analyze surgical and endovascular interventions for patients with IJVS. Notably, the most common intervention is styloidectomy, followed by internal jugular vein stenting. By understanding the trends and experience of interventionalists and surgeons, more focused and larger studies can be performed to determine effective strategies with the best clinical outcomes.
Safety and efficacy of tenecteplase versus alteplase in patients with acute ischaemic stroke (TRACE): a multicentre, randomised, open label, blinded-endpoint (PROBE) controlled phase II study
Authors: Li Shuya , Pan Yuesong , Wang Ziran , Liang Zhigang , Chen Huisheng , Wang Dong , Sui Yi , Zhao Xingquan , Wang Yilong , Du WanLiang , Zheng Huaguang , Wang Yongjun
Published: August 2021

Background

Tenecteplase (TNK) possesses several pharmacological characteristics superior to conventional alteplase (rt-PA), with well-established safety and efficacy profile in Caucasians. There exists controversy over the optimal dose of intravenous rt-PA for East Asians with acute ischaemic stroke (AIS). Current study aimed to determine the safety dose range of recombinant human TNK tissue-type plasminogen activator (rhTNK-tPA) for patients with AIS in China.

Methods

This multicentre, prospective, randomised, open-label, blinded end-point, phase II study compared three tiers of 0.1, 0.25, 0.32 mg/kg rhTNK-tPA (to a maximum of 40 mg) with standard 0.9 mg/kg rt-PA (to a maximum of 90 mg) in patients who were eligible for intravenous thrombolysis. The safety outcome were symptomatic intracranial haemorrhage (sICH) within 36 hours.

Results

Between May 2018 and February 2020, 240 patients were randomly assigned to four group, 4 of whom did not receive study treatment. The intention-to-treat analysis included 236 patients. There was no difference in the improvement on National Institutes of Health Stroke Scale at day 14 in the 3 tiers and control group (63.3%, 77.2%, 66.7% vs 62.7%). The number of sICH was 3 of 60 (5.0%) in the 0.1 mg/kg group, none in the 0.25 mg/kg group, 2 of 60 (3.3%) in the 0.32 mg/kg group and 1 (1.7%) of 59 in the rt-PA group. There were no significant between-group differences in severe adverse events.

Conclusions

Similar to the Caucasians, rhTNK-tPA was well tolerated in Chinese patients with AIS at all doses administered within 3 hours of symptom onset. The dose-efficacy profile of rhTNK-tPA needs to be established with future investigations.

Trial registration number

NCT04676659.
An experimental approach for crown to whole-canopy defoliation in forests
Authors: Fahey Robert T. , Tanzer Danielle N. , Alveshere Brandon C. , Atkins Jeff W. , Gough Christopher M. , Hardiman Brady S.
Published: August 2021

Canopy defoliation is an important source of disturbance in forest ecosystems that has rarely been represented in large-scale manipulation experiments. Scalable crown to canopy level experimental defoliation is needed to disentangle the effects of variable intensity, timing, and frequency on forest structure, function, and mortality. We present a novel pressure-washing-based defoliation method that can be implemented at the canopy-scale, throughout the canopy volume, targeted to individual leaves or trees, and completed within a timeframe of hours or days. Pressure washing proved successful at producing consistent leaf-level and whole-canopy defoliation, with 10%–20% reduction in leaf area index and consistent leaf surface area removal across branches and species. This method allows for stand-scale experimentation on defoliation disturbance in forested ecosystems and has the potential for broad application. Studies utilizing this standardized method could promote mechanistic understanding of defoliation effects on ecosystem structure and function and development of synthetic understanding across forest types, ecoregions, and defoliation sources.
Radial growth responses of post oak (Quercus stellata) to climate variability and management in southeastern Oklahoma, USA
Authors: Adhikari Arjun , Masters Ronald E. , Adams Henry D. , Will Rodney E.
Published: August 2021

We investigated radial growth of post oak (Quercus stellata Wangenh.) growing in a range of stand structures (forest to savanna) created in 1984 by different harvesting, thinning, and prescribed fire intervals. We related ring width index (RWI) to monthly and seasonal climate variables and time since fire to assess impacts of climate variability and interactions with management on radial growth. The RWI of all treatments was positively correlated to minimum daily temperature the previous September and precipitation late spring and early summer the current year, and negatively correlated to maximum daily temperatures and drought index late spring – early summer. June weather was most strongly correlated in four of five treatments. While stand structure affected absolute diameter growth, the RWI of savanna and forest stands responded similarly to climate variability, and low intensity prescribed fire did not influence RWI. On average, a 100 mm reduction in June precipitation decreased RWI by 7%, a 1 °C increase in previous-year September daily minimum temperature increased RWI by 3.5%, and a 1 °C increase in June maximum daily temperature decreased RWI by 3.7%. Therefore, negative effects of drought and warmer spring and summer temperatures may be reduced by a longer growing season under warmer climate scenarios. However, management did not appear to influence RWI.
Low Power, Wide Range Synthesizer for 534 MHz–18.56 GHz Band with FoM of − 192.45 dBc/Hz
Authors: Sharma Gaurav Kumar , Johar Arun Kishor , Boolchandani D.
Published: August 2021

A wide range frequency synthesizer is designed with the help of dual voltage tunable Differential Ring Oscillator (DRO). Frequency ranging from 534[Formula: see text]MHz to 18.56[Formula: see text]GHz can be generated using the proposed synthesizer. As proposed circuit utilizes dual voltage tunable DRO, a select input is provided to control the output frequency range. Logic low value (0[Formula: see text]V) of select input generates frequencies from 534[Formula: see text]MHz to 5.08[Formula: see text]GHz whereas logic high value (1.1[Formula: see text]V) of select input enables the frequency generation in the range of 5.08[Formula: see text]GHz to 18.56[Formula: see text]GHz. This work utilizes a single charge pump and single loop filter along with charge pump and bias control circuit. Proposed circuit is designed in GPDK 45-nm CMOS technology with supply voltage of 1.1[Formula: see text]V. Power consumption of the proposed circuits is 2.88[Formula: see text]mW while generating frequency of 7.84[Formula: see text]GHz. Proposed synthesizer demonstrates Figure of Merit (FoM2) of [Formula: see text][Formula: see text]dBc/Hz at this frequency. Because of such a wide spectrum, this synthesizer is well suited in the field of satellite communication, GPS and navigation.
A Poynting theorem formulation for the gravitational wave stress pseudo tensor
Authors: Balbus Steven A.
Published: August 2021

A very simple and physical derivation of the conservation equation for the propagation of gravitational radiation is presented. The formulation is exact. The result takes the readily recognisable and intuitive form of a Poynting-style equation, in which the outward propagation of stress energy is directly related to the volumetric equivalent of a radiation reaction force acting back upon the sources, including the purely gravitational contribution to the sources. Upon averaging, the emergent pseudo tensor for the gravitational radiation is in exact agreement with that found by much more labour-intensive methods.
PROPORTIONAL EFFECT IN SbSi/N-DOPED GRAPHENE NANOCOMPOSITE PREPARATION FOR HIGH-PERFORMANCE LITHIUM-ION BATTERIES
Authors: MAHAMAI NARUEPHON , AUTTHAWONG THANAPHAT , YU AISHUI , SARAKONSRI THAPANEE
Published: August 2021

Lithium-ion batteries (LIBs) have become commercialized technologies for the modern and future world, but commercial batteries using graphite still have a low specific capacity and are concerned with safety issues. Silicon (Si) and antimony (Sb) nanocomposites have the tendency to be synthesized as high-energy-density anode materials which can be a solution for the above-mentioned problems. This work reported the synthesis methods and characterization of Sb and Si composited with nitrogen-doped graphene (SbSi/NrGO) by facile chemical method and thermal treatment. Si was obtained by magnesiothermic reduction of SiO2 derived from rice husk, waste from the agricultural process. To study the phases, particle distributions, and morphologies, all prepared composites were characterized. In this experiment, the phase compositions were confirmed as [Formula: see text]-Si, [Formula: see text]-Si, SiC, Sb, and shifted peaks of expanded C which were caused by NrGO synthesis. Interestingly, a good distribution of Si and Sb particles on the NrGO surface was obtained in 15Sb15Si/NrGO composition. It could be due to appropriate Sb and Si contents on the NrGO surface area in composite materials. Morphological identification of synthesized products represented the Sb and Si particles in nanoscale dispersed on thin wrinkled-paper NrGO. These results suggested that the synthesis method in this paper is appropriate to prepare SbSi/NrGO nanocomposites to be used as high-performance anode materials in high-performance LIBs for advanced applications.