bluuebunny/crossref_metadata_2025 huggingface dataset:
Perinatal post-mortem magnetic resonance imaging (MRI) of the central nervous system (CNS): a pictorial review
Authors: Pérez-Serrano Carlos , Bartolomé Álvaro , Bargalló Núria , Sebastià Carmen , Nadal Alfons , Gómez Olga , Oleaga Laura
Published: July 2021

Central nervous system (CNS) abnormalities cause approximately 32–37.7% of terminations of pregnancy (TOP). Autopsy is currently the gold standard for assessing dead foetuses and stillborn. However, it has limitations and is sometimes subject to parental rejection. Recent studies have described post-mortem foetal magnetic resonance imaging (MRI) as an alternative and even complementary to autopsy for CNS assessment. Radiologists now play a key role in the evaluation of perinatal deaths. Assessment of foetal CNS abnormalities is difficult, and interpretation of foetal studies requires familiarisation with normal and abnormal findings in post-mortem MRI studies as well as the strengths and limitations of the imaging studies. The purpose of this pictorial review is to report our experience in the post-mortem MRI evaluation of the CNS system, including a description of the protocol used, normal CNS findings related to post-mortem status, abnormal CNS findings in our sample, and the correlation of these findings with histopathological results.
Acute kidney injury with partial Fanconi syndrome in a patient with leptospirosis: a case report
Authors: Weiner Marc , Coen Matteo , Serratrice Jacques , Mavrakanas Thomas A. , Leidi Antonio
Published: July 2021

Background

Leptospirosis is an underdiagnosed bacterial infection with nonspecific symptoms, hence, a diagnostic challenge. Identifying a case of leptospirosis in Switzerland is uncommon. Although kidney complications are frequent in severe forms, including tubular dysfunction, observing this complication is rare in our country. We report the case of a patient with leptospirosis and kidney dysfunction, which was notable for proximal tubulopathy. This case report describes the diagnosis and management of this patient’s tubular dysfunction.

Case presentation

A 34-year-old Caucasian male known for alcohol and drug abuse presented to our emergency department suffering from severe pain in the lower limbs, jaundice, and fever with flu-like symptoms. Physical examination was not contributory. Blood tests showed cytopenia, elevated inflammatory markers, acute kidney injury, and altered liver function tests with predominant cholestasis. Urinalysis showed proteinuria and significant glycosuria without concomitant hyperglycemia. Leptospirosis was suspected and confirmed by both positive serum polymerase chain reaction and elevated immunoglobulin M for Leptospira interrogans. The patient was treated with intravenous amoxicillin–clavulanate and doxycycline for 7 days. After antibiotic treatment, symptoms disappeared, and kidney dysfunction completely resolved.

Conclusion

Our case focuses on the description of leptospirosis-related acute kidney injury with proximal tubular dysfunction, which is a rare finding in Switzerland.
EGR1 dysregulation defines an inflammatory and leukemic program in cell trajectory of human-aged hematopoietic stem cells (HSC)
Authors: Desterke Christophe , Bennaceur-Griscelli Annelise , Turhan Ali G.
Published: July 2021

Background

During aging, hematopoietic stem cells (HSC) lose progressively both their self-renewal and differentiation potential. The precise molecular mechanisms of this phenomenon are not well established. To uncover the molecular events underlying this event, we have performed a bioinformatics analysis of 650 single-cell transcriptomes.

Methods

Single-cell transcriptome analyses of expression heterogeneity, cell cycle, and cell trajectory in human cell compartment enriched in hematopoietic stem cell compartment were investigated in the bone marrow according to the age of the donors. Identification of aging-related nodules was identified by weighted correlation network analysis in this primitive compartment.

Results

The analysis of single-cell transcriptomes allowed to uncover a major upregulation of EGR1 in human-aged lineage−CD34+CD38− cells which present cell cycle dysregulation with reduction of G2/M phase according to less expression of CCND2 during S phase. EGR1 upregulation in aging hematopoietic stem cells was found to be independent of cell cycle phases and gender. EGR1 expression trajectory in aged HSC highlighted a signature enriched in hematopoietic and immune disorders with the best induction of AP-1 complex and quiescence regulators such as EGR1, BTG2, JUNB, and NR41A. Sonic Hedgehog-related TMEM107 transmembrane molecule followed also EGR1 cell trajectory. EGR1-dependent gene weighted network analysis in human HSC-associated IER2 target protein-specific regulators of PP2A activity, IL1B, TNFSF10 ligands, and CD69, SELP membrane molecules in old HSC module with immune and leukemogenic signature. In contrast, for young HSC which were found with different cell cycle phase progression, its specific module highlighted upregulation of HIF1A hypoxic factor, PDE4B immune marker, DRAK2 (STK17B) T cell apoptosis regulator, and MYADM myeloid-associated marker.

Conclusion

EGR1 was found to be connected to the aging of human HSC and highlighted a specific cell trajectory contributing to the dysregulation of an inflammatory and leukemia-related transcriptional program in aged human HSCs. EGR1 and its program were found to be connected to the aging of human HSC with dissociation of quiescence property and cell cycle phase progression in this primitive hematopoietic compartment.
Unresponsive thin endometrium caused by Asherman syndrome treated with umbilical cord mesenchymal stem cells on collagen scaffolds: a pilot study
Authors: Zhang Yanling , Shi Libing , Lin Xiaona , Zhou Feng , Xin Liaobing , Xu Wenzhi , Yu Huaying , Li Jing , Pan Mei , Pan Yibin , Dai Yongdong , Zhang Yinli , Shen Jia , Zhao Lijuan , Lu Min , Zhang Songying
Published: July 2021

Background

Unresponsive thin endometrium caused by Asherman syndrome (AS) is the major cause of uterine infertility. However, current therapies are ineffective. This study is to evaluate the effect of transplantation with collagen scaffold/umbilical cord mesenchymal stem cells (CS/UC-MSCs) on this refractory disease.

Methods

Eighteen infertile women with unresponsive thin endometrium, whose frozen–thawed embryo transfers (FETs) were cancelled due to reduced endometrial thickness (ET ≤ 5.5 mm), were enrolled in this before and after self-control prospective study. Hysteroscopic examination was performed to confirm no intrauterine adhesions, then twenty million UC-MSCs loaded onto a CS were transplanted into the uterine cavity in two consecutive menstrual cycles. Then uterine cavity was assessed through hysteroscopy after two transplants. FETs were performed in the following cycle. Pregnancy outcomes were followed up. Endometrial thickness, uterine receptivity and endometrial angiogenesis, proliferation and hormone response were compared before and after treatment.

Results

Sixteen patients completed the study. No treatment-related serious adverse events occurred. Three months after transplantation, the average ET increased from 4.08 ± 0.26 mm to 5.87 ± 0.77 mm (P < 0.001). Three of 15 patients after FET got pregnant, of whom 2 gave birth successfully and 1 had a miscarriage at 25 weeks’ gestation. One of 2 patients without FET had a natural pregnancy and gave birth normally after transplantation. Immunohistochemical analysis showed increased micro-vessel density, upregulated expression of Ki67, estrogen receptor alpha, and progesterone receptor, indicating an improvement in endometrial angiogenesis, proliferation, and response to hormones.

Conclusion

CS/UC-MSCs is a promising and potential approach for treating women with unresponsive thin endometrium caused by AS.

Trial registration

ClinicalTrials.gov NCT03724617. Registered on 26 October 2018—prospectively registered, https://register.clinicaltrials.gov/
Mesenchymal stem cell-derived extracellular vesicles as probable triggers of radiation-induced heart disease
Authors: Luo Lan , Yan Chen , Fuchi Naoki , Kodama Yukinobu , Zhang Xu , Shinji Goto , Miura Kiyonori , Sasaki Hitoshi , Li Tao-Sheng
Published: July 2021

Background

Radiation-induced heart disease has been reported, but the underlying mechanisms remain unclear. Mesenchymal stem cells (MSCs), also residing in the heart, are highly susceptible to radiation. We examined the hypothesis that the altered secretion of extracellular vesicles (EVs) from MSCs is the trigger of radiation-induced heart disease.

Methods

By exposing human placental tissue-derived MSCs to 5 Gy γ-rays, we then isolated EVs from the culture medium 48 h later and evaluated the changes in quantity and quality of EVs from MSCs after radiation exposure. The biological effects of EVs from irradiated MSCs on HUVECs and H9c2 cells were also examined.

Results

Although the amount and size distribution of EVs did not differ between the nonirradiated and irradiated MSCs, miRNA sequences indicated many upregulated or downregulated miRNAs in irradiated MSCs EVs. In vitro experiments using HUVEC and H9c2 cells showed that irradiated MSC-EVs decreased cell proliferation (P < 0.01), but increased cell apoptosis and DNA damage. Moreover, irradiated MSC-EVs impaired the HUVEC tube formation and induced calcium overload in H9c2 cells.

Conclusions

EVs released from irradiated MSCs show altered miRNA profiles and harmful effects on heart cells, which provides new insight into the mechanism of radiation-related heart disease risks.
Genome-wide analysis of protein–protein interactions and involvement of viral proteins in SARS-CoV-2 replication
Authors: Jiang Yiling , Tong Kuijie , Yao Roubin , Zhou Yuanze , Lin Hanwen , Du Liubing , Jin Yunyun , Cao Liu , Tan Jingquan , Zhang Xing-Ding , Guo Deyin , Pan Ji-An , Peng Xiaoxue
Published: July 2021

Background

Analysis of viral protein–protein interactions is an essential step to uncover the viral protein functions and the molecular mechanism for the assembly of a viral protein complex. We employed a mammalian two-hybrid system to screen all the viral proteins of SARS-CoV-2 for the protein–protein interactions.

Results

Our study detected 48 interactions, 14 of which were firstly reported here. Unlike Nsp1 of SARS-CoV, Nsp1 of SARS-CoV-2 has the most interacting partners among all the viral proteins and likely functions as a hub for the viral proteins. Five self-interactions were confirmed, and five interactions, Nsp1/Nsp3.1, Nsp3.1/N, Nsp3.2/Nsp12, Nsp10/Nsp14, and Nsp10/Nsp16, were determined to be positive bidirectionally. Using the replicon reporter system of SARS-CoV-2, we screened all viral Nsps for their impacts on the viral replication and revealed Nsp3.1, the N-terminus of Nsp3, significantly inhibited the replicon reporter gene expression. We found Nsp3 interacted with N through its acidic region at N-terminus, while N interacted with Nsp3 through its NTD, which is rich in the basic amino acids. Furthermore, using purified truncated N and Nsp3 proteins, we determined the direct interactions between Nsp3 and N protein.

Conclusions

Our findings provided a basis for understanding the functions of coronavirus proteins and supported the potential of interactions as the target for antiviral drug development.
Dexibuprofen ameliorates peripheral and central risk factors associated with Alzheimer’s disease in metabolically stressed APPswe/PS1dE9 mice
Authors: Ettcheto Miren , Sánchez-Lopez Elena , Cano Amanda , Carrasco Marina , Herrera Katherine , Manzine Patricia R. , Espinosa-Jimenez Triana , Busquets Oriol , Verdaguer Ester , Olloquequi Jordi , Auladell Carme , Folch Jaume , Camins Antoni
Published: July 2021

Background

Several studies stablished a relationship between metabolic disturbances and Alzheimer´s disease (AD) where inflammation plays a pivotal role. However, mechanisms involved still remain unclear. In the present study, we aimed to evaluate central and peripheral effects of dexibuprofen (DXI) in the progression of AD in APPswe/PS1dE9 (APP/PS1) female mice, a familial AD model, fed with high fat diet (HFD). Animals were fed either with conventional chow or with HFD, from their weaning until their sacrifice, at 6 months. Moreover, mice were divided into subgroups to which were administered drinking water or water supplemented with DXI (20 mg kg−1 d−1) for 3 months. Before sacrifice, body weight, intraperitoneal glucose and insulin tolerance test (IP-ITT) were performed to evaluate peripheral parameters and also behavioral tests to determine cognitive decline. Moreover, molecular studies such as Western blot and RT-PCR were carried out in liver to confirm metabolic effects and in hippocampus to analyze several pathways considered hallmarks in AD.

Results

Our studies demonstrate that DXI improved metabolic alterations observed in transgenic animals fed with HFD in vivo, data in accordance with those obtained at molecular level. Moreover, an improvement of cognitive decline and neuroinflammation among other alterations associated with AD were observed such as beta-amyloid plaque accumulation and unfolded protein response.

Conclusions

Collectively, evidence suggest that chronic administration of DXI prevents the progression of AD through the regulation of inflammation which contribute to improve hallmarks of this pathology. Thus, this compound could constitute a novel therapeutic approach in the treatment of AD in a combined therapy.
Exosomal delivery of therapeutic modulators through the blood–brain barrier; promise and pitfalls
Authors: Heidarzadeh Morteza , Gürsoy-Özdemir Yasemin , Kaya Mehmet , Eslami Abriz Aysan , Zarebkohan Amir , Rahbarghazi Reza , Sokullu Emel
Published: July 2021

Nowadays, a large population around the world, especially the elderly, suffers from neurological inflammatory and degenerative disorders/diseases. Current drug delivery strategies are facing different challenges because of the presence of the BBB, which limits the transport of various substances and cells to brain parenchyma. Additionally, the low rate of successful cell transplantation to the brain injury sites leads to efforts to find alternative therapies. Stem cell byproducts such as exosomes are touted as natural nano-drug carriers with 50–100 nm in diameter. These nano-sized particles could harbor and transfer a plethora of therapeutic agents and biological cargos to the brain. These nanoparticles would offer a solution to maintain paracrine cell-to-cell communications under healthy and inflammatory conditions. The main question is that the existence of the intact BBB could limit exosomal trafficking. Does BBB possess some molecular mechanisms that facilitate the exosomal delivery compared to the circulating cell? Although preliminary studies have shown that exosomes could cross the BBB, the exact molecular mechanism(s) beyond this phenomenon remains unclear. In this review, we tried to compile some facts about exosome delivery through the BBB and propose some mechanisms that regulate exosomal cross in pathological and physiological conditions.
Changes in ecosystem service values strongly influenced by human activities in contrasting agro-ecological environments
Authors: Berihun Mulatu Liyew , Tsunekawa Atsushi , Haregeweyn Nigussie , Tsubo Mitsuru , Fenta Ayele Almaw
Published: July 2021

Background

Evaluating the impacts of land-use/land-cover (LULC) changes on ecosystem service values (ESVs) is essential for sustainable use and management of ecosystems. In this study, we evaluated the impact of human activity driven LULC changes on ESVs over the period 1982–2016/17 in contrasting agro-ecological environments: Guder (highland), Aba Gerima (midland), and Debatie (lowland) watersheds of the Upper Blue Nile basin, Ethiopia.

Results

During the study period, the continuous expansion of cultivated land at the expense of natural vegetation (bushland, forest, and grazing land) severely reduced the total ESV by about US$ 58 thousand (35%) in Aba Gerima and US$ 31 thousand (29%) in Debatie watersheds. In contrast, the unprecedented expansion of plantations, mainly through the planting of Acacia decurrens, led, from 2006, to a ESV rebound by about US$ 71 thousand (54%) in Guder watershed, after it had decreased by about US$ 61 thousand (32%) between 1982 and 2006. The reduction in natural forest area was the major contributor to the loss of total ESV in the study watersheds, ranging from US$ 31 thousand (63%) in Debatie to US$ 96.9 thousand (70%) in Guder between 1982 and 2016/17. On an area-specific basis, LULC changes reduced the average ESV from US$ 560 ha−1 year−1 (1982) in Guder to US$ 306 ha−1 year−1 (2017) in Debatie watersheds. Specific ESVs such as provisioning (mainly as food production) and regulating services (mainly as erosion control and climate regulation) accounted for most of the total ESVs estimated for the study watersheds.

Conclusions

In most cases, the total and specific ESVs of the watersheds were negatively associated with the population growth, which in turn was positively associated with the expansion of cultivated land over the study period. In Guder, however, ESVs were positively associated with population growth, especially after 2012. This is mainly due to the expansion of Acacia decurrens plantations. Our results suggest, therefore, that future policy measures and directions should focus on improving vegetation cover through planting multipurpose trees such as Acacia decurrens to prevent future loss of ESV in the midland and lowland regions of the Upper Blue Nile basin and beyond. However, caution must be taken during plantation of invasive species as they may have undesirable consequences.
Improving the knowledge of plant potential biodiversity-ecosystem services links using maps at the regional level in Southern Patagonia
Authors: Rosas Yamina Micaela , Peri Pablo L. , Lencinas María Vanessa , Lasagno Romina , Martínez Pastur Guillermo J.
Published: July 2021

Background

Biodiversity supports multiple ecosystem services, whereas species loss endangers the provision of many services and affects ecosystem resilience and resistance capacity. The increase of remote sensing techniques allows to estimate biodiversity and ecosystem services supply at the landscape level in areas with low available data (e.g. Southern Patagonia). This paper evaluates the potential biodiversity and how it links with ecosystem services, based on vascular plant species across eight ecological areas. We also evaluated the habitat plant requirements and their relation with natural gradients. A total of 977 plots were used to develop habitat suitability maps based on an environmental niche factor analysis of 15 more important indicator species for each ecological area (n = 53 species) using 40 explanatory variables. Finally, these maps were combined into a single potential biodiversity map, which was linked with environmental variables and ecosystem services supply. For comparisons, data were extracted and compared through analyses of variance.

Results

The plant habitat requirements varied greatly among the different ecological areas, and it was possible to define groups according to its specialization and marginality indexes. The potential biodiversity map allowed us to detect coldspots in the western mountains and hotspots in southern and eastern areas. Higher biodiversity was associated to higher temperatures and normalized difference vegetation index, while lower biodiversity was related to elevation and rainfall. Potential biodiversity was closely associated with supporting and provisioning ecosystem services in shrublands and grasslands in the humid steppe, while the lowest values were related to cultural ecosystem services in Nothofagus forests.

Conclusions

The present study showed that plant species present remarkable differences in spatial distributions and ecological requirements, being a useful proxy for potential biodiversity modelling. Potential biodiversity values change across ecological areas allowing to identify hotspots and coldspots, a useful tool for landscape management and conservation strategies. In addition, links with ecosystem services detect potential synergies and trade-offs, where areas with the lowest potential biodiversity are related to cultural ecosystem services (e.g. aesthetic values) and areas with the greatest potential biodiversity showed threats related to productive activities (e.g. livestock).
Materials and techniques used for the “Vienna Moamin”: multianalytical investigation of a book about hunting with falcons from the thirteenth century
Authors: Vetter Wilfried , Frühmann Bernadette , Cappa Federica , Schreiner Manfred
Published: July 2021

A multianalytical approach was used to characterize the materials in the “Vienna Moamin”, an outstanding richly illustrated manuscript from the late thirteenth century, which was made in Italy and is now kept in the Kunsthistorisches Museum Wien. The investigations were carried out with a non-invasive approach by using complementary techniques, such as X-ray fluorescence (XRF), reflection Fourier transform infrared spectroscopy (rFTIR), Raman spectroscopy, and fiber optic reflectance spectroscopy (FORS). In addition, XRF scans were performed in two areas which yielded chemical maps showing the elemental distribution. The results revealed that typical materials from the medieval times were applied for the manuscript. Calcium carbonate on the parchment surface indicated a dehairing process with lime and/or whitening with chalk. Two different iron gall inks were detected in the main text and marginal notes, and vermilion was used for rubrication. The color palette included azurite, a green colorant composed of orpiment and indigo, yellow ochre, brown iron oxide pigments, minium, vermilion, brazilwood lake, and carbon black. Moreover, mosaic gold was detected in gold-beige hues. Lead white was identified for white areas and fine decoration lines, as well as in mixture with blue and red pigments for light color shades. No reliable information could be obtained concerning the binding media. Two differing application techniques for gold leaf were detected, which correspond with stylistic differences: either on gypsum or chalk preparation layers. Furthermore, calcium soap contents in certain colors were determined only on one folio with unique characteristics. The XRF scans of two historiated initials revealed that similar materials were applied in both cases and provided further valuable information about the painting technique. The results obtained enabled to gain insights into Italian thirteenth century manuscript production techniques and to characterize the used materials. The investigations showed the importance of scanning XRF for the elucidation of painting techniques, but also the demand of scanning devices utilizing compound specific analytical techniques such as rFTIR.
Application of a cashew-based oxime in extracting Ni, Mn and Co from aqueous solution
Authors: Phan Chi M. , Hoang Son A. , Vu Son H. , Nguyen Hoang M. , Nguyen Cuong V. , Hyde Anita E. , Yusa Shin-ichi
Published: July 2021

Background

Cashew nut shell is a by-product of cashew (Anacardium occidentale) production, which is abundant in many developing countries. Cashew nut shell liquor (CNSL) contains a functional chemical, cardanol, which can be converted into a hydroxyoxime. The hydroxyoximes are expensive reagents for metal extraction.

Methods

CNSL-based oxime was synthesized and used to extract Ni, Co, and Mn from aqueous solutions. The extraction potential was compared against a commercial extractant (LIX 860N).

Results

All metals were successfully extracted with pH0.5between 4 and 6. The loaded organic phase was subsequently stripped with an acidic solution. The extraction efficiency and pH0.5of the CNSL-based extractant were similar to a commercial phenol-oxime extractant. The metals were stripped from the loaded organic phase with a recovery rate of 95% at a pH of 1.

Conclusions

Cashew-based cardanol can be used to economically produce an oxime in a simple process. The naturally-based oxime has the economic potential to sustainably recover valuable metals from spent lithium-ion batteries.

Graphic abstract
Excessive anterior tibial translation in the contralateral uninjured limb is significantly associated with ramp lesion in anterior cruciate ligament injury
Authors: Asai Kazuki , Nakase Junsuke , Yoshimizu Rikuto , Kimura Mitsuhiro , Tsuchiya Hiroyuki
Published: July 2021

Purpose

This study aimed to evaluate the excessive anterior tibial translation (ATT) and muscle strength of patients with ramp lesions. We hypothesised that the higher ATT, lower hamstring-to-quadriceps (HQ) ratio, and higher flexion peak torque influenced by semimembranosus would be associated with ramp lesions.

Methods

One hundred and twenty-one patients who underwent anterior cruciate ligament (ACL) reconstruction were retrospectively evaluated. Clinical evaluation included ATT of the contralateral uninjured limb measured using a KT-1000 arthrometer, the knee flexor and extensor muscle strength of the contralateral uninjured limb at 60°/s and 180°/s of an angular velocity measured using an isokinetic dynamometer, and HQ ratio at 60°/s and 180°/s during the preoperative state. Binary stepwise logistic regression analysis was performed to evaluate the risk factors of ramp lesions.

Results

Ramp lesions were found in 27 cases of ACL injuries (27/121, 22.3%). Male sex (odds ratio [OR], 2.913; 95% confidence interval [CI], 1.090–7.787; P = 0.033), longer time between injury to surgery (OR, 2.225; 95% CI, 1.074–4.608; P = 0.031), and higher ATT in the contralateral uninjured limb (OR, 1.502; 95% CI, 1.046–2.159; P = 0.028) were indicated as the independent risk factors of the presence of ramp lesion associated with an ACL injury.

Conclusions

Male sex, longer period from injury to surgery, and higher ATT in the contralateral uninjured limb were significantly associated with ramp lesion. These findings are advantageous for identifying patients with a greater risk of developing a ramp lesion with an ACL injury in the clinical setting.

Level of evidence

Level IV
Reporting on patient and public involvement (PPI) in research publications: using the GRIPP2 checklists with lay co-researchers
Authors: Jones Julia , Cowe Marion , Marks Sue , McAllister Tony , Mendoza Alex , Ponniah Carole , Wythe Helena , Mathie Elspeth
Published: July 2021

Background

Patient and public involvement (PPI) in health and social care research is considered important internationally, with increasing evidence that PPI improves the quality, relevance and outcomes of research. There has been a growth in research publications that describe PPI in the research process, but the frequency and detail of PPI reporting varies considerably. This paper reports on a collaborative study that aimed to describe the extent of PPI in publications from research funded by the Collaboration for Leadership in Applied Health Research and Care (CLAHRC) in the East of England (EoE), part of the National Institute of Health Research (NIHR) in England (2014–2019).

Methods

A descriptive study of all research publications (1st January 2014 to 31st October 2017) funded by the NIHR CLAHRC EoE. Members of the Public Involvement in Research group (PIRg), at the University of Hertfordshire, were actively involved, with four PIRg co-researchers. We used an internationally recognised reporting checklist for PPI called the GRIPP2 (Guidance for Reporting Involvement of Patients and the Public, Version 2) to guide the reviewing process.

Results

Out of 148 research papers identified, 16 (14%) reported some aspect of PPI activity and were included for review. Ten of the publications (63%) acknowledged the contributions of PPI individuals and/or groups and five had PPI co-authors. There was considerable variation in the PPI reported in the publications, with some ‘missed opportunities’ to provide detail of PPI undertaken. The perspectives of the co-researchers shaped the reporting of the results from this study. The co-researchers found the GRIPP2-SF (short form) to be useful, but the GRIPP2-LF (long form) was considered over complicated and not user-friendly.

Conclusions

This is one of the first studies to involve lay co-researchers in the review of PPI reporting using the GRIPP2 reporting checklists (GRIPP2-SF and GRIPP2-LF). We make recommendations for a revised version of the GRIPP2-SF, with clearer instructions and three additional sections to record whether PPI is reported in the abstract or key words, in the acknowledgements section, and whether there are PPI co-authors. We also recommend the provision of training and support for patient and public peer reviewers.
Conceptualising and constructing ‘diversity’ through experiences of public and patient involvement in health research
Authors: Reynolds Joanna , Ogden Margaret , Beresford Ruth
Published: July 2021

Background

Increasing the accessibility of public and patient involvement (PPI) in health research for people from diverse backgrounds is important for ensuring all voices are heard and represented. Critiques of PPI being dominated by ‘the usual suspects’ reflect concerns over the barriers to involvement in PPI faced by people from minority groups or non-professional backgrounds. Yet, what has received less attention is how undertaking PPI work might produce diverse experiences, potentially shaping the motivation and capacity of people from different backgrounds to continue in PPI.

Methods

We conducted qualitative research to explore experiences of the health research PPI field in the UK and to understand how these might shape the accessibility of PPI for people of diverse backgrounds. We conducted in-depth and follow-up interviews with five PPI contributors with experience of multiple health research projects, and a focus group with nine people in professional roles relating to PPI. Interview data were analysed using a narrative approach, and then combined with the focus group data for thematic analysis.

Results

The structure, organisation and relationships of health research in the UK all shape PPI experiences in ways that can intersect the different backgrounds and identities of contributors, and can pose barriers to involvement and motivation for some. Navigating processes for claiming expenses can be frustrating particularly for people from lower-income backgrounds or with additional needs, and short-term research can undermine relationships of trust between contributors and professionals. Pressure on PPI coordinators to find ‘more diverse’ contributors can also undermine ongoing relationships with contributors, and how their inputs are valued.

Conclusions

To increase diversity within PPI, and to ensure that people of different backgrounds are supported and motivated to continue in PPI, changes are needed in the wider health research infrastructure in the UK. More resources are required to support relationships of trust over time between contributors and professionals, and to ensure the unique circumstances of each contributor are accommodated within and across PPI roles. Finally, critical reflection on the pressure in PPI to seek ‘more diverse’ contributors is needed, to understand the impacts of this on those already involved.
Developing standardized patient-based cases for communication training: lessons learned from training residents to communicate diagnostic uncertainty
Authors: Papanagnou Dimitrios , Klein Matthew R. , Zhang Xiao Chi , Cameron Kenzie A. , Doty Amanda , McCarthy Danielle M. , Rising Kristin L. , Salzman David H.
Published: July 2021

Health professions education has benefitted from standardized patient (SP) programs to develop and refine communication and interpersonal skills in trainees. Effective case design is essential to ensure an SP encounter successfully meets learning objectives that are focused on communication skills. Creative, well-designed case scenarios offer learners the opportunity to engage in complex patient encounters, while challenging them to address the personal and emotional contexts in which their patients are situated. Therefore, prior to considering the practical execution of the patient encounter, educators will first need a clear and structured strategy for writing, organizing, and developing cases. The authors reflect on lessons learned in developing standardized patient-based cases to train learners to communicate to patients during times of diagnostic uncertainty, and provide suggestions to develop a set of simulation cases that are both standardized and diverse. Key steps and workflow processes that can assist educators with case design are introduced. The authors review the need to increase awareness of and mitigate existing norms and implicit biases, while maximizing variation in patient diversity. Opportunities to leverage the breadth of emotional dispositions of the SP and the affective domain of a clinical encounter are also discussed as a means to guide future case development and maximize the value of a case for its respective learning outcomes.
Physicochemical compatibility studies of triclosan and flurbiprofen with excipients of pharmaceutical formulation using binary, ternary, and multi-combination approach
Authors: Aminu Nafiu , Chan Siok-Yee , Mumuni Momoh A. , Umar Nura Muhammad , Tanko Nuhu , Zauro Sirajo Abubakar , Aminu Abdulmalik , Toh Seok-Ming
Published: July 2021

Background

The aim of the study was to evaluate the suitability of triclosan (TCS) and flurbiprofen (FLB) with poly-ε-caprolactone (PCL), chitosan (CS), and Kolliphor® P188 (KP) for possible application in the design of nano-formulations.

Results

Differential scanning calorimetry (DSC), X-ray powder diffraction (XRPD), and scanning electron microscopy (SEM) revealed the physical characteristics of the various sample compositions without any apparent interaction. The Fourier transform infrared spectroscopy (FTIR)’s spectra of the physical mixtures showed their characteristic absorption bands with broadening and overlapping of bands in some instances, but no appearance of new bands was observed.

Conclusion

The study revealed the physical form stability of the evaluated components after the storage period and lack of definite pharmaceutical incompatibility between them. Thus, the selected drugs and excipients could be used for the development of pharmaceutical nano-formulations.
Safety, Efficacy, and Pharmacodynamics of Tremelimumab Plus Durvalumab for Patients With Unresectable Hepatocellular Carcinoma: Randomized Expansion of a Phase I/II Study
Authors: Kelley Robin Kate , Sangro Bruno , Harris William , Ikeda Masafumi , Okusaka Takuji , Kang Yoon-Koo , Qin Shukui , Tai David W.-M. , Lim Ho Yeong , Yau Thomas , Yong Wei-Peng , Cheng Ann-Lii , Gasbarrini Antonio , Damian Silvia , Bruix Jordi , Borad Mitesh , Bendell Johanna , Kim Tae-You , Standifer Nathan , He Philip , Makowsky Mallory , Negro Alejandra , Kudo Masatoshi , Abou-Alfa Ghassan K.
Published: July 2021

PURPOSE

This phase I/II study evaluated tremelimumab (anticytotoxic T-lymphocyte–associated antigen-4 monoclonal antibody) and durvalumab (antiprogrammed death ligand-1 monoclonal antibody) as monotherapies and in combination for patients with unresectable hepatocellular carcinoma (HCC), including a novel regimen featuring a single, priming dose of tremelimumab (ClinicalTrials.gov identifier: NCT02519348 ).

PATIENTS AND METHODS

Patients with HCC who had progressed on, were intolerant to, or refused sorafenib were randomly assigned to receive T300 + D (tremelimumab 300 mg plus durvalumab 1,500 mg [one dose each during the first cycle] followed by durvalumab 1,500 mg once every 4 weeks), durvalumab monotherapy (1,500 mg once every 4 weeks), tremelimumab monotherapy (750 mg once every 4 weeks [seven doses] and then once every 12 weeks), or T75 + D (tremelimumab 75 mg once every 4 weeks plus durvalumab 1,500 mg once every 4 weeks [four doses] followed by durvalumab 1,500 mg once every 4 weeks). Safety was the primary end point. Secondary end points included objective response rate (ORR) by Response Evaluation Criteria in Solid Tumors v1.1 and overall survival; exploratory end points included circulating lymphocyte profiles.

RESULTS

A total of 332 patients were enrolled (T300 + D, n = 75; durvalumab, n = 104; tremelimumab, n = 69; and T75 + D, n = 84). Tolerability was acceptable across arms, with grade ≥ 3 treatment-related adverse events occurring in 37.8%, 20.8%, 43.5%, and 24.4%, respectively. Confirmed ORRs (95% CI) were 24.0% (14.9 to 35.3), 10.6% (5.4 to 18.1), 7.2% (2.4 to 16.1), and 9.5% (4.2 to 17.9), respectively. An early expansion of CD8+ lymphocytes was associated with response across arms, with highest proliferating CD8+ lymphocyte levels occurring in the T300 + D arm. The median (95% CI) overall survival was 18.7 (10.8 to 27.3), 13.6 (8.7 to 17.6), 15.1 (11.3 to 20.5), and 11.3 (8.4 to 15.0) months in the T300 + D, durvalumab, tremelimumab, and T75 + D arms, respectively.

CONCLUSION

All regimens were found to be tolerable and clinically active; however, the T300 + D regimen demonstrated the most encouraging benefit-risk profile. The unique pharmacodynamic activity and association with ORR of the T300 + D regimen further support its continued evaluation in HCC.
Impact of Pain on Employment and Financial Outcomes Among Cancer Survivors
Authors: Halpern Michael T. , de Moor Janet S. , Yabroff K. Robin
Published: July 2021

PURPOSE

Although pain is a frequently reported symptom among individuals with cancer, there is limited information on the impact of pain on employment or financial outcomes. This study used nationally representative data to examine the role of pain levels on employment and financial outcomes.

METHODS

We used data from the 2016-2017 Medical Expenditure Panel Survey Experiences with Cancer Survivorship Supplement to identify 1,213 adults diagnosed with cancer. Multivariable logistic regression analyses were used to examine association of pain levels and self-reported employment and financial outcomes.

RESULTS

Approximately 43% of adults with a cancer history reported no pain, 29% mild pain, 18% moderate pain, and 10% severe pain over the past 7 days. Compared with those reporting no pain, individuals reporting any pain had significantly increased likelihood of adverse employment outcomes including early retirement, feeling less productive, and staying at a job because of concerns about losing insurance. Individuals with any pain (compared with no pain) also had significantly increased likelihood of adverse financial outcomes including borrowing money or going into debt, inability to cover medical costs, and worrying about paying medical bills. For both employment and financial outcomes, there were dose-response relationships, with worse outcomes generally associated with greater pain levels.

CONCLUSION

Pain is frequently associated with adverse employment and financial outcomes among cancer survivors, and greater pain is associated with worse outcomes. Better assessment of pain severity among survivors and implementation of strategies to assist with employment and financial objectives may be important steps to enhance patient-centered care.
Practice Patterns and Variability in Intraoperative Opioid Utilization: A Report From the Multicenter Perioperative Outcomes Group
Authors: Naik Bhiken I. , Kuck Kai , Saager Leif , Kheterpal Sachin , Domino Karen B. , Posner Karen L. , Sinha Anik , Stuart Ami , Brummett Chad M. , Durieux Marcel E. , Vaughn Michelle T. , Pace Nathan L. ,   the MPOG EOS Investigator Group
Published: July 2021

BACKGROUND:

Opioids remain the primary mode of analgesia intraoperatively. There are limited data on how patient, procedural, and institutional characteristics influence intraoperative opioid administration. The aim of this retrospective, longitudinal study from 2012 to 2016 was to assess how intraoperative opioid dosing varies by patient and clinical care factors and across multiple institutions over time.

METHODS:

Demographic, surgical procedural, anesthetic technique, and intraoperative analgesia data as putative variables of intraoperative opioid utilization were collected from 10 institutions. Log parenteral morphine equivalents (PME) was modeled in a multivariable linear regression model as a function of 15 covariates: 3 continuous covariates (age, anesthesia duration, year) and 12 factor covariates (peripheral block, neuraxial block, general anesthesia, emergency status, race, sex, remifentanil infusion, major surgery, American Society of Anesthesiologists [ASA] physical status, non-opioid analgesic count, Multicenter Perioperative Outcomes Group [MPOG] institution, surgery category). One interaction (year by MPOG institution) was included in the model. The regression model adjusted simultaneously for all included variables. Comparison of levels within a factor were reported as a ratio of medians with 95% credible intervals (CrI).

RESULTS:

A total of 1,104,324 cases between January 2012 and December 2016 were analyzed. The median (interquartile range) PME and standardized by weight PME per case for the study period were 15 (10–28) mg and 200 (111–347) μg/kg, respectively. As estimated in the multivariable model, there was a sustained decrease in opioid use (mean, 95% CrI) dropping from 152 (151–153) μg/kg in 2012 to 129 (129–130) μg/kg in 2016. The percent of variability in PME due to institution was 25.6% (24.8%–26.5%). Less opioids were prescribed in men (130 [129–130] μg/kg) than women (144 [143–145] μg/kg). The men to women PME ratio was 0.90 (0.89–0.90). There was substantial variability in PME administration among institutions, with the lowest being 80 (79–81) μg/kg and the highest being 186 (184–187) μg/kg; this is a PME ratio of 0.43 (0.42–0.43).

CONCLUSIONS:

We observed a reduction in intraoperative opioid administration over time, with variability in dose ranging between sexes and by procedure type. Furthermore, there was substantial variability in opioid use between institutions even when adjusting for multiple variables.
Pre-notification and personalisation of text-messages to retain participants in a smoking cessation pregnancy RCT: an embedded randomised factorial trial
Authors: Coleman Elizabeth , Whitemore Rachel , Clark Laura , Daykin Karen , Clark Miranda
Published: July 2021

Background: 

Low response rates in randomised controlled trials can compromise the reliability of the results, so ways to boost retention are often implemented. Although there is evidence to suggest that sending a text message to participants increases retention, there is little evidence around the timing or personalisation of these messages. 

Methods: 

A two-by-two factorial SWAT (study within a trial) was embedded within the MiQuit-3 trial, looking at smoking cessation within pregnant smokers. Participants who reached their 36-week gestational follow-up were randomised to receive a personalised or non-personalised text message, either one week or one day prior to the telephone follow-up. Primary outcomes were completion rate of questionnaire via telephone. Secondary outcomes included: completion rate via any method, time to completion, and number of reminders required. 

Results 

In total 194 participants were randomised into the SWAT; 50 to personalised early text, 47 to personalised late text, 50 to non-personalised early text, and 47 to non-personalised late text. There was no evidence that timing of the text message (early: one week before; or late: one day before) had an effect on any of the outcomes. There was evidence that a personalised text would result in fewer completions via telephone compared with a non-personalised text (adjusted OR 0.44, 95% CI 0.22–0.87, p=0.02). However, there was no evidence to show that personalisation or not was better for any of the secondary outcomes. 

Conclusion 

Timing of the text message does not appear to influence the retention of participants. Personalisation of a text message may be detrimental to retention; however, more SWATs should be undertaken in this field.
Prevalence and predictors of multimorbidity among immigrant Asian Indian women residing in Sydney Australia: A cross-sectional study
Authors: O'Callaghan Cathy , Yadav Uday , Natarajan Sudha , Srinivasan Saroja , Fernandez Ritin
Published: July 2021

Abstract

Background: There has been a rise in multimorbidity as people age and technology advances which is challenging for health systems. Multimorbidity prevalence varies globally due to various biological and social risk factors which can be accentuated or mitigated for populations in migration. This study investigated the prevalence and predictors of multimorbidity amongst a group of migrant Asian Indian women living in Australia.

Methods: A cross-sectional descriptive study design using convenience sampling investigated the multimorbidity risk factors among first generation migrant Asian Indian women in Australia.  This study was part of a larger study titled “Measuring Acculturation and Psychological Health of Senior Indian Women Living in Australia” that was conducted in Sydney, Australia. Data were collected using validated instruments as well as investigator developed questions. Women completed questionnaire surveys either by themselves or through the assistance of bilingual coordinators as English was not their first language.

Results: 26% of the participants had one chronic condition and 74% had multimorbidities. The prevalence of individual conditions included cardiovascular disease 67.0%, osteoarthritis 57.6%, depression 37.4%, diabetes 31.5%, chronic respiratory conditions 10.8%, cancer 4.9% and nephrological problems 1.47%. In the unadjusted model, factors such as increasing age, education level, employment status, living arrangements, low physical activity, and elements of acculturative stress were significantly associated with multimorbidity. Multi-variable analysis identified the acculturative stress factor of threat to ethnic identity as a predictor of multimorbidity.

Conclusion:  Identifying the key determinants of multimorbidity in older adults from a migrant community with pre-existing risk factors can assist with the development of culturally appropriate strategies to identify people at risk of health conditions and to mitigate the health effects of acculturative stress.
Proficiency-based progression intern training to reduce critical blood sampling errors including ‘wrong blood in tube’
Authors: O' Herlihy Noirin , Griffin Sarah , Gaffney Robert , Henn Patrick , Khashan Ali S , Ring Mary , Gallagher Anthony , Cahill Mary R
Published: July 2021

Background: Blood sampling errors including ‘wrong blood in tube’ (WBIT) may have adverse effects on clinical outcomes. WBIT errors occur when the blood sample in the tube is not that of the patient identified on the label. This study aims to determine the effect of proficiency-based progression (PBP) training in phlebotomy on the rate of blood sampling errors (including WBIT).

Methods: A non-randomised controlled trial compared the blood sampling error rate of 43 historical controls who had not undergone PBP training in 2016 to 44 PBP trained interventional groups in 2017. In 2018, the PBP training programme was implemented and the blood sampling error rate of 46 interns was compared to the 43 historical controls in 2016. Data analysis was performed using logistic regression analysis adjusting for sample timing.

Results: In 2016, 43 interns had a total blood sample error rate of 2.4%, compared to 44 interns in 2017, who had error rate of 1.2% (adjusted OR=0.50, 95% CI 0.36-0.70; <0.01). In 2018, 46 interns had an error rate of 1.9% (adjusted OR=0.89, 95% CI 0.65-1.21; p=0.46) when compared to the 2016 historical controls. There were three WBITs in 2016, three WBITs in 2017 and five WBITs in 2018. 

Conclusions: The study demonstrates that PBP training in phlebotomy has the potential to reduce blood sampling errors.

Trial registration number: NCT03577561