bluuebunny/crossref_metadata_2025 huggingface dataset:
Running out of time: The case of patient advocacy for ovarian cancer patients' access to PARP inhibitors
Authors: Lindén Lisa
Published: October 2021

This article analyses patient advocacy for ovarian cancer patients' access to a group of new targeted cancer treatments, so‐called poly (adenosine diphosphate ribose) polymerase (PARP) inhibitors. Ovarian cancer is often detected in its advanced stages and has relatively poor survival rates. Based on ethnographic fieldwork with the Gynae Cancer Group, a Swedish patients' group, this article examines ovarian cancer patient advocates' engagement with biomedicine as a rarely considered topic in the social sciences. Adopting a modified version of the science and technology studies perspective on evidence‐based activism, I analyse how ovarian cancer patient advocates engage in the ‘epistemic activities’ of framing, producing and mobilising ‘credentialed’ and ‘experiential’ knowledge. I show how patient advocates, alone and together with professionals and the media, engage in epistemic activities to ‘act upon’ ovarian cancer patients' anticipated limited time and poor prognosis: patient advocates mobilise around PARP inhibitors as offering hope, access to these drugs as an urgent matter and ovarian cancer care as unequal. The article contributes to the sociological literature on novel cancer treatments and patient advocacy through its ethnographic tracing of cancer advocacy tropes and knowledge practices, centred on the temporal figure of ‘the patient running out of time’.
Maternal medicine: calling for improved research quality
Authors: Ovadia C , Nana M , Williamson C
Published: October 2021

Linked article: This is a mini commentary on Z Xu et al., pp. 367–377 in this issue. To view this article visit https://doi.org/10.1111/1471-0528.16968
Hobhouse, O'Connor and the Nottingham Election of 1847
Authors: Beckett John
Published: October 2021

At the general election in July 1847, to considerable surprise, the Nottingham electors rejected their two sitting Whig members in favour of Feargus O'Connor, the Chartist leader, and a free trade Conservative, John Walter. This article looks at how such a political upset occurred. It examines the political context of elections in the years leading to 1847 and at the contest itself, which ended with the return of O'Connor and the defeat of sitting MP, Sir John Cam Hobhouse. It also notes the political drift of Hobhouse, a leading radical during his time as MP for Westminster in the 1820s, to the point where he was an 1850s placeman. New evidence is brought forward from Hobhouse's own writings, which have previously been overlooked. Some of the broader issues relating to parliamentary reform in these years are also discussed, as well as the significance of O'Connor's electoral victory in enabling him to present the third Chartist petition in person in 1848.
‘Populist Constitutionalism’ and the Unionist Party during the 1911 House of Lords’ Crisis
Authors: Sayle Ben
Published: October 2021

This article reassesses the revolt against the 1911 Parliament Act by the ‘ditchers’ – the measure's diehard opponents in the house of lords. It shows that the ditchers had a clear and coherent platform on the constitution – referred to here as ‘populist constitutionalism’ – which sought to relegitimise aristocratic political power through the adoption of constitutional reforms including the introduction of referenda. This platform had evolved naturally from Lord Salisbury's ‘mandate theory’ that utilised the Unionist predominance in the second chamber to reject unpopular Liberal legislation. Where Salisbury had adopted a tactical, opportunistic perspective, however, populist constitutionalism was more programmatic. In contrast, Arthur Balfour, as Unionist leader, adopted a more cautious approach and avoided reform until his hand was forced by the constitutional crises of 1909–11. The ditchers, as part of the Edwardian ‘radical right’, were often frustrated with Balfour's refusal to advocate measures such as the referendum. This frustration reflected similar radical right criticisms of Balfour's leadership during the tariff reform debate. Hence the ditcher revolt represented the culmination of a decade of Unionist division over the Unionist platform, Balfour's leadership, and indeed the philosophical idea of Toryism itself.
Quantitative analysis and response surface modeling of important bitter compounds in chocolate made from cocoa beans with eight roast profiles across three origins
Authors: McClure Alan P. , Spinka Christine M. , Grün Ingolf U.
Published: October 2021

Eight different roast profiles for each of the three origins of cacao were prepared and made into unsweetened chocolate based upon an I‐Optimal response‐surface design for minimizing prediction variance. Quantitative chemical analysis of all chocolate treatments was performed with HPLC‐DAD on six important bitter compounds (i.e., theobromine, caffeine, epicatechin, catechin, procyanidin B2, and cyclo(Proline‐Valine)). Least‐squares linear modeling was then performed. Using derived linear models, response‐surface contour plots were produced to show predicted changes in the six bitter compounds over the entire experimental region. Significant and large decreases in concentration of epicatechin and procyanidin B2 were observed as roasting progressed, whereas for catechin and cyclo(Proline‐Valine), significant increases were observed. Small yet significant theobromine and caffeine concentration increases were also observed with roasting, likely due to moisture loss. Some significant differences were also found between the cacao origins for all bitter compound concentrations except for cyclo(Proline‐Valine), suggesting the importance of a survey encompassing a greater number of cacao origins in the future to obtain a more complete picture of the variation in bitter compounds in cacao due to origin.

Practical Application

This research describes how roasting can be used to alter the concentration of bitter and sometimes astringent chemicals for several origins of cacao, which may be used to improve the sensory characteristics of dark chocolate.
Comparison of renal remission and relapse‐free rate in initial‐ and delayed‐onset lupus nephritis
Authors: Suzuki Eiji , Yashiro‐Furuya Makiko , Temmoku Jumpei , Fujita Yuya , Matsuoka Naoki , Hazama Momoko , Asano Tomoyuki , Sato Shuzo , Kobayashi Hiroko , Watanabe Hiroshi , Kanno Takashi , Migita Kiyoshi
Published: October 2021

Introduction

Lupus nephritis (LN) is a major manifestation of systemic lupus erythematosus (SLE) which contributes to significant morbidity and mortality. It is unclear whether the timing of LN onset influences renal outcome. This study aimed to investigate differences in clinical features—particularly the relapse‐free rate—in remission duration from induction therapies for LN and the onset timing of LN after the development of SLE.

Methods

We enrolled 66 LN patients from January 2004 to March 2020. We collected the following: demographic data, laboratory data, renal histology data, and LN induction therapy data. Renal remission and relapse‐free rates were calculated for each group.

Results

Patients were first divided into early remission group (achieved renal remission in <12 months [n = 44]) and others (n = 22). There were no significant differences in clinical data, treatments, and relapse‐free rate of LN. Patients were then divided into initial‐onset LN (<12 months after development of SLE [n = 49]) and delayed‐onset LN (≥12 months after development of SLE [n = 17]). Kaplan–Meier analysis showed that the relapse‐free rate was significantly higher in all patients with initial‐onset LN than those with delayed‐onset LN (P = .0094).

Conclusion

The relapse‐free rate was significantly higher in the initial‐onset LN group than the delayed‐onset LN group of patients with LN of various histopathological backgrounds. These data suggest that delayed‐onset LN is a risk factor for the relapse of LN.
Clinical suspicion of pancreatic cancer despite negative endoscopic ultrasound‐guided fine‐needle aspiration biopsy
Authors: Masuda Hiro , Kotecha Krishna , Maitra Rudra , Gill Anthony J. , Mittal Anubhav , Samra Jaswinder S.
Published: October 2021

Background

The early and accurate diagnosis of pancreatic ductal adenocarcinoma is vital for improving the efficacy of therapeutic interventions and to provide patients with the best chance of survival. While endoscopic ultrasound‐fine needle aspiration (EUS‐FNA) has been demonstrated to be a reliable and accurate diagnostic tool for solid pancreatic neoplasms, the ongoing management of patients with a high clinical suspicion for malignancy but with a negative EUS‐FNA biopsy result can prove a challenge.

Methods

We describe five patients from a single centre who presented for further work‐up of a pancreatic mass and/or imaging features concerning for a periampullary malignancy.

Results

All patients had at least one EUS‐FNA biopsy performed which returned no malignant cells on cytology. Despite these negative cytology results, all patients underwent further invasive investigation through upfront resection (pancreaticoduodenectomy) or extra‐pancreatic biopsy (laparoscopic biopsy of peritoneal nodule) due to worrisome features on imaging, biochemical factors and clinical presentation culminating in a high degree of suspicion for malignancy. The final tissue histopathological diagnosis in all patients was pancreatic ductal adenocarcinoma.

Conclusion

This case series highlights the important clinical findings, imaging and biochemical features which need to be considered in patients who have high suspicion for malignancy despite having a negative EUS‐FNA cytology result. In these patients with a high index of suspicion, surgical intervention through an upfront resection or further invasive investigation should not be delayed.
The impact of social norms on health‐related belief update
Authors: Vlasceanu Madalina , Coman Alin
Published: October 2021

People are constantly bombarded with information they could use to adjust their beliefs. Here, we are interested in exploring the impact of social norms on health‐related belief update. To investigate, we recruited a sample of 200 Princeton University students, who first rated the accuracy of a set of health statements (pre‐test). They were then provided with relevant evidence either in favor or against the initial statements, and were asked to rate how convincing each piece of evidence was. The evidence was randomly assigned to appear as normative or non‐normative, and anecdotal or scientific. Finally, participants rated the accuracy of the initial set of statements again (post‐test). The results show that participants rationally updated their beliefs more when the evidence was scientific compared to when it was anecdotal. More importantly to our primary inquiry, the results show that participants changed their beliefs more in line with the evidence when the evidence was portrayed as normative compared to when the evidence was portrayed as non‐normative, pointing to the impactful influence social norms have on health beliefs. Both effects were mediated by participants' subjective evaluation of the convincingness of the evidence, indicating the mechanism by which evidence is selectively incorporated into belief systems.
Credit frictions, selection into external finance and gains from trade
Authors: Unger Florian
Published: October 2021

This paper analyzes the effects of credit frictions in a trade model where heterogeneous firms select both into exporting and into two types of external finance. While small producers face stronger credit frictions and rely on bank finance, large firms have access to cheaper bond finance. The analysis shows that a bank credit shock leads to an increase in the share of firms that use bond finance. This selection effect is used to explain the observed decrease in bank finance relative to bond finance during the global financial crisis of 2007–2009. A calibration of the model to the crisis period documents that endogenous selection into external finance reduces the negative implications of credit frictions on product variety, exports and gains from trade.
Insights into the structure and drug design of benzimidazole derivatives targeting the epidermal growth factor receptor (EGFR)
Authors: Abdullah Mar’iyah Najihah , Ali Yousaf , Abd Hamid Shafida
Published: October 2021

Tyrosine kinase overexpression could result in an unfavourable consequence of cancer progression in the body. A number of kinase inhibitor drugs targeting various cancer‐related protein kinases have been developed and proven successful in clinical therapy. Benzimidazole is one of the most studied scaffolds in the search for effective anticancer drugs. The association of various functional groups and the structural design of the compounds may influence the binding towards the receptor. Despite numerous publications on the design, synthesis and biological assays of benzimidazole derivatives, their inhibitory activities against epidermal growth factor receptor (EGFR), a receptor tyrosine kinase (RTK), have not been specifically analysed. This review covers recent research reports on the anticancer activity of benzimidazole derivatives focusing on EGFR expression cell lines, based on their structure‐activity relationship study. We believe it would aid researchers to envision the challenges and explore benzimidazole's potentials as tyrosine kinase inhibitors.
Effect of subthreshold nanosecond laser on retinal structure and function in intermediate age‐related macular degeneration
Authors: Gunawan Josephine R. , Thiele Sarah H. , Isselmann Ben , Caruso Emily , Guymer Robyn H. , Luu Chi D.
Published: October 2021

Background

Subthreshold nanosecond laser (SNL) treatment has been studied as a potential intervention in intermediate age‐related macular degeneration (iAMD). This study investigated the effect of 100 SNL treatment spots on retinal structure and function.

Methods

A prospective single‐arm interventional pilot study. SNL treatment was delivered as 100 spots around the retinal vascular arcades of the study eye (worst visual acuity) in a single session in subjects with iAMD. Multimodal retinal imaging and dark‐adapted chromatic perimetry were performed at baseline and at 0.5, 3, 6 and 12 months post treatment. Post treatment changes in best corrected visual acuity (BCVA), retinal thickness, relative ellipsoid zone reflectivity (rEZR) and rod‐mediated functional parameters were compared to baseline.

Results

Twenty‐one subjects with iAMD were recruited. SNL treatment was associated with an increase in retinal thickness (p = 0.008) and decrease in rEZR (p < 0.001) at 2 weeks post laser. Recovery of retinal thickness and rEZR was observed at the 3‐month post laser visit. A gradual improvement in BCVA was observed after laser treatment. The mean change in BCVA between baseline and 12‐month visit was +1.9 ± 3.3 letters for the SNL treated eyes, compared to −0.4 ± 3.0 letters for the fellow eyes (p = 0.027). Rod‐mediated function improved at 3 months post laser (p < 0.001) and returned to the baseline levels at 12 months post treatment.

Conclusions

A single treatment with 100 SNL spots causes a short‐term change in retinal structure and improvement in retinal function that are apparent at 3 months post treatment.
The promise of exosome applications in treating central nervous system diseases
Authors: Mattingly Jared , Li Yuchen , Bihl Ji C. , Wang Jinju
Published: October 2021

Exosomes (EXs), a type of extracellular vesicles, are secreted from virtually all types of cells. EXs serve as cell‐to‐cell communicators by conveying proteins and nucleic acids with regulatory functions. Increasing evidence shows that EXs are implicated in the pathogenesis of central nervous system (CNS) diseases. Moreover, EXs have recently been highlighted as a new promising therapeutic strategy for in vivo delivery of nucleotides and drugs. Studies have revealed that infusion of EXs elicits beneficial effects on the CNS injury animal models. As compared to cell‐based therapy, EXs‐based therapy for CNS diseases has unique advantages, opening a new path for neurological medicine. In this review, we summarized the current state of knowledge of EXs, the roles and applications of EXs as a viable pathological biomarker, and EX‐based therapy for CNS diseases.
Role of tobacco exposure in the course of COVID‐19 disease and the impact of the disease on smoking behavior
Authors: Telatar Tahsin Gökhan , Karadoğan Dilek , Baykal Mehmet Halit , Yurtsever Burcu Aykanat
Published: October 2021

Background

The effect of COVID‐19 on smoking behavior is not fully known. Studies evaluating the link between smoking and COVID‐19 have controversial results. This study aims to evaluate patients' smoking status with COVID‐19 and the effect of COVID‐19 on smoking behavior.

Methods

Data were collected from 150 COVID‐19 patients with a positive polymerase chain reaction test for SARS‐CoV‐2 between 11 March 2020 and 15 May 2020 in Rize, Turkey. Patients were interviewed by phone calls 2 months after their recovery. After 9 months, a follow‐up was performed for those who quit smoking.

Results

Of the participants, 19 (12.7%) were current smokers before the COVID‐19 diagnosis, and 15 (78.9%) of them stated that they quit smoking after their diagnosis. After nine months of follow‐up, 11 of those 15 participants (57.8%) sustained abstinence.

Conclusion

Smoking cessation rates are high in people with COVID‐19. Besides, the frequency of sustaining abstinence in the long term was also high in these individuals. The COVID‐19 pandemic should be viewed as an open opportunity to strengthen and prioritize smoking cessation activities.
Hypoglycaemia: Still the main drawback of insulin 100 years on: “From man to mouse”
Authors: Merchant Heather J. , McNeilly Alison D.
Published: October 2021

One hundred years on from the initial discovery of insulin, we take this opportunity to reflect on the scientific discoveries that have improved so many lives. From its original crude form, insulin therapy has improved significantly over the past century. Despite this, hypoglycaemia remains an ever‐present fear for people with Type 1 diabetes. As such, it is essential that research now looks to minimise the frequency and severity of insulin‐induced hypoglycaemia and its complications, some of which can be life‐threatening. Over the last century, one thing that has become apparent is the success and need for translational diabetes research. From its origin in dogs, insulin treatment has revolutionised the lives of those with Type 1 diabetes through the coordinated effort of scientists and clinicians. In this review, we recount the more recent research that uses a mouse‐to‐man approach, specifically in hypoglycaemia research.
Immune profile and radiological characteristics of progressive multifocal leukoencephalopathy
Authors: Zeiner Pia S. , Mann Leonhard , Filipski Katharina , Starzetz Tatjana , Forster Marie‐Therese , Ronellenfitsch Michael W. , Steinbach Joachim P. , Mittelbronn Michel , Wagner Marlies , Harter Patrick N.
Published: October 2021

Background and purpose

Progressive multifocal leukoencephalopathy (PML) constitutes a severe disease with increasing incidence, mostly in the context of immunosuppressive therapies. A detailed understanding of immune response in PML appears critical for the treatment strategy. The aim was a comprehensive immunoprofiling and radiological characterization of magnetic resonance imaging (MRI) defined PML variants.

Methods

All biopsy‐confirmed PML patients (n = 15) treated in our department between January 2004 and July 2019 were retrospectively analysed. Data from MRI, histology as well as detailed clinical and outcome data were collected. The MRI‐defined variants of classical (cPML) and inflammatory (iPML) PML were discriminated based on the intensity of gadolinium enhancement. In these PML variants, intensity and localization (perivascular vs. parenchymal) of inflammation in MRI and histology as well as the cellular composition by immunohistochemistry were assessed. The size of the demyelinating lesions was correlated with immune cell infiltration.

Results

Patients with MRI‐defined iPML showed a stronger intensity of inflammation with an increased lymphocyte infiltration on histological level. Also, iPML was characterized by a predominantly perivascular inflammation. However, cPML patients also demonstrated certain inflammatory tissue alterations. Infiltration of CD163‐positive microglia and macrophage (M/M) subtypes correlated with PML lesion size.

Conclusions

The non‐invasive MRI‐based discrimination of PML variants allows for an estimation of inflammatory tissue alterations, although exhibiting limitations in MRI‐defined cPML. The association of a distinct phagocytic M/M subtype with the extent of demyelination might reflect disease progression.
A unifying hypothesis for the spawning migrations of temperate anguillid eels
Authors: Durif Caroline M. F. , Stockhausen Hans Hagen , Skiftesvik Anne Berit , Cresci Alessandro , Nyqvist Daniel , Browman Howard I.
Published: October 2021

Anguillid eels grow in freshwater but spawn in the open ocean. The cues that guide eels over long distances to the spawning area are unknown. The Earth's magnetic field can provide directional and positional information and is likely used by catadromous eels during their spawning migration; as magnetosensitivity and compass orientation have been reported in eels. To test whether this is theoretically possible, we compared the migratory routes of five species of temperate eels that undertake long migrations with the geomagnetic field of their distribution/spawning areas. We found that, regardless of the species and although routes are different between life stages, larvae of those species always drift along paths of increasing magnetic inclination and intensity, while adults follow reverse gradients. This is consistent with an imprinting/retracing hypothesis. We propose a general navigation mechanism based on larvae imprinting on a target magnetic intensity (or inclination) at the hatching area and on the intensity (or inclination) gradient during larval drift. Years later, adults retrace the magnetic route by following the gradient of decreasing total intensity (or inclination) values that occurs towards lower latitudes. As they reach the target value, adults switch to compass orientation to stay on the target isoline and reach the spawning area. The proposed mechanism fits for all temperate eels examined. Knowledge about navigational strategies of eels is important to evaluate the effectiveness of management strategies that involve stocking of juveniles displaced from one area to another to rebuild local populations.
Response of Amazonian forests to mid‐Holocene drought: A model‐data comparison
Authors: Smith Richard J. , Singarayer Joy S. , Mayle Francis E.
Published: October 2021

There is a major concern for the fate of Amazonia over the coming century in the face of anthropogenic climate change. A key area of uncertainty is the scale of rainforest dieback to be expected under a future, drier climate. In this study, we use the middle Holocene (ca. 6000 years before present) as an approximate analogue for a drier future, given that palaeoclimate data show much of Amazonia was significantly drier than present at this time. Here, we use an ensemble of climate and vegetation models to explore the sensitivity of Amazonian biomes to mid‐Holocene climate change. For this, we employ three dynamic vegetation models (JULES, IBIS, and SDGVM) forced by the bias‐corrected mid‐Holocene climate simulations from seven models that participated in the Palaeoclimate Modelling Intercomparison Project 3 (PMIP3). These model outputs are compared with a multi‐proxy palaeoecological dataset to gain a better understanding of where in Amazonia we have most confidence in the mid‐Holocene vegetation simulations. A robust feature of all simulations and palaeodata is that the central Amazonian rainforest biome is unaffected by mid‐Holocene drought. Greater divergence in mid‐Holocene simulations exists in ecotonal eastern and southern Amazonia. Vegetation models driven with climate models that simulate a drier mid‐Holocene (100–150 mm per year decrease) better capture the observed (palaeodata) tropical forest dieback in these areas. Based on the relationship between simulated rainfall decrease and vegetation change, we find indications that in southern Amazonia the rate of tropical forest dieback was ~125,000 km2 per 100 mm rainfall decrease in the mid‐Holocene. This provides a baseline sensitivity of tropical forests to drought for this region (without human‐driven changes to greenhouse gases, fire, and deforestation). We highlight the need for more palaeoecological and palaeoclimate data across lowland Amazonia to constrain model responses.
Haemostatic effect of adding tranexamic acid to emicizumab prophylaxis in severe haemophilia A: A preclinical study
Authors: Janbain Maissa , Enjolras Nathalie , Bolbos Radu , Brevet Marie , Bordet Jean‐Claude , Dargaud Yesim
Published: October 2021

Background

Patients with severe haemophilia have impaired haemostatic response, delayed clot formation and fibrin clots that are vulnerable to fibrinolysis. Emicizumab is a bispecific antibody that mimics activity of activated factor VIII (FVIII) and increases haemostatic capacity to the level of moderate‐to‐mild haemophilia, thereby used for prophylaxis. Regardless of the impressive clinical performance of emicizumab, breakthrough bleeds may still occur. We aimed to study, in FVIII knockout mice (FVIII‐KO), whether haemostasis is improved with the addition of tranexamic acid (TxAc) to emicizumab.

Methods

FVIII‐KO mice received prophylaxis with emicizumab or emicizumab+TxAc before trauma. FVIII‐KO mice were given emicizumab 1.5 mg/kg via IV injection. A second retro‐orbital IV injection containing human FIX and FX (both 100U/kg) was given 24 h later and 5 min before the tail amputation or knee trauma. After trauma‐induced knee joint bleeding, magnetic resonance imaging (MRI), and histological analysis were used to compare haemostatic efficacy of the two prophylactic strategies. Thrombin generation (TG) was measured and clots obtained with TG experiment were analysed by scanning electron microscopy.

Results

In FVIII‐KO mice, blood loss after tail clip was lower after prophylaxis with emicizumab+TxAc compared to emicizumab. MRI results and histological analysis of knee joints showed that the addition of TxAc significantly decreased joint bleeding. Fibrin fibre diameters of mice treated with emicizumab only was thicker than those who received combined prophylaxis with emicizumab+TxAc.

Conclusion

Our results suggest a potential benefit of TxAc when used in combination with emicizumab in prophylactic settings, especially in patients presenting breakthrough bleeds.
No overall impact on rate of weight gain with integrase inhibitor‐containing regimens in antiretroviral‐naïve adults
Authors: Burns James E. , Stirrup Oliver , Waters Laura , Dunn David , Gilson Richard , Pett Sarah L.
Published: October 2021

Objectives

Integrase strand transfer inhibitors (INSTIs) are commonplace in modern antiretroviral therapy (ART). Increased weight gain with their use is increasingly scrutinized. We evaluated weight changes in treatment‐naïve adults with HIV‐1 attending a UK centre who started regimens including raltegravir or dolutegravir.

Methods

A retrospective cohort study of adults prescribed an INSTI between January 2015 and March 2020 were categorized as having started an ART regimen containing raltegravir, dolutegravir, a protease inhibitor or a nonnucleoside reverse transcriptase inhibitor. Individuals with one or more weight measurement ≤ 5 years both pre‐ and post‐ART initiation, who started a three‐drug regimen with ≥ 6 months duration and achieved virological suppression (< 50 copies/mL) within 6 months were included. A random effects model with linear slope pre‐ and post‐ART was used, adjusting for age, gender, ethnicity, ART regimen, backbone and year of initiation.

Results

The cohort included 390 adults; 88.7% were male, 66.4% were of white ethnicity, their median age was 40 years, there was a median of six weight measurements, 2.2 years from diagnosis to ART initiation, 2.9 years from ART to the last weight measurement, and weight and body mass index at initiation were 75 kg and 24.1 kg/m2 respectively. Of these, 254 (65%) started an INSTI. The average pre‐ART rate of weight gain was 0.44 kg/year [95% confidence interval (CI): 0.19–0.70], increasing to 0.88 kg/year (0.63–1.10, p = 0.04) after ART initiation. Our adjusted model found no evidence of an association between ART regimen and rate of weight gain.

Conclusions

Weight increased in the cohort both pre‐ and post‐ART. We found no evidence of a higher rate of weight gain following ART initiation with an INSTI compared with other regimens.
Long‐term outcomes for children and adolescents with Kaposi sarcoma
Authors: Silverstein Allison , Kamiyango William , Villiera Jimmy , Peckham‐Gregory Erin C. , McAtee Casey L. , Scheurer Michael E. , Cox Carrie M. , Kovarik Carrie L. , Campbell Liane R. , Allen Carl E. , Mehta Parth S. , Kazembe Peter N. , Ozuah Nmazuo W. , El‐Mallawany Nader Kim
Published: October 2021

Objectives

Kaposi sarcoma (KS) is one of the most common childhood cancers in eastern and central Africa. It has become a treatable disease with increasing availability of antiretroviral therapy (ART) and chemotherapy. We aimed to fill the data gap in establishing whether long‐term survival is achievable for children in low‐income countries.

Methods

We retrospectively analysed data for children and adolescents aged ≤ 18.9 years diagnosed with HIV‐related or endemic KS from 2006 to 2015 who received standardized institutional treatment regimens utilizing chemotherapy plus ART (if HIV‐positive) at a tertiary care public hospital in Lilongwe, Malawi. Long‐term survival was analysed and mortality was associated with KS for those with refractory/progressive disease at the time of death.

Results

There were 207 children/adolescents with KS (90.8% HIV‐related); 36.7% were alive, 54.6% had died, and 8.7% had been lost to follow‐up. The median follow‐up time for survivors was 6.9 years (range 4.2–13.9 years). Death occurred at a median of 5.3 months after KS diagnosis (range 0.1–123 months). KS progression was associated with mortality for most (61%) early deaths (survival time of < 6 months); conversely, KS was associated with a minority (31%) of late‐onset deaths (after 24 months). The 7‐year overall survival was 37% [95% confidence interval (CI) 30–44%] and was higher for those diagnosed between 2011 and 2015 compared to 2006–2010: 42% (95% CI 33–51%) versus 29% (95% CI 20–39%), respectively (P = 0.01). Among the 66 HIV‐positive survivors, 58% were still on first‐line ART.

Conclusions

Long‐term survival is possible for pediatric KS in low‐resource settings. Despite better survival in more recent years, there remains room for improvement.
The success rate of interphase fluorescence in situ hybridization in plasma cell disorders can be improved using unconventional sources of plasma cells
Authors: Panakkal Vandana , Rana Sonia , Rathore Shailja , Anshu Anshu , Balakrishnan Anand , Singh Charanpreet , Jandial Aditya , Sachdeva Man Updesh Singh , Varma Neelam , Lad Deepesh , Malhotra Pankaj , Sreedharanunni Sreejesh
Published: October 2021

Background

Immunomagnetic cell sorting (IMCS) is a preferred technique for the enrichment of plasma cells (PC) before fluorescence in situ hybridization (FISH). Here, we share our real‐world experience regarding the success rate of IMCS, its limitations, and the utility of alternate sources to obtain a successful FISH in various PC disorders.

Materials and Methods

A retrospective analysis was performed in patients with a PC neoplasm, who underwent bone marrow (BM) examination, and FISH testing over 30 months. In all cases with an unsuccessful IMCS, an attempt was made to identify the cause of failure.

Results

Immunomagnetic cell sorting of PCs was successful in 395/450 cases (87.8%; 77/98 cases (78.6%) with <10% PCs and 318/352 (90.3%) with ≥10% PCs in BM aspirate; P = .003). Among cases with unsuccessful IMCS (<10% PCs; n = 21 and ≥10% PCs; n = 34), an alternate source could be used successfully in 34 (62%) patients and includes air‐dried trephine biopsy imprint smears (n = 28) with aggregates or sheets of PCs, fine‐needle aspiration smears/biopsy from plasmacytoma (n = 5), and ascitic fluid (n = 1). 284/395 (71.9%) patients with successful IMCS and all 34 cases with an alternate source of PCs showed at least one cytogenetic abnormality on four‐probe FISH.

Conclusion

Variations in the sample quality together with significant variation in the number of PCs between BM aspirate and the trephine biopsy imprint smears/biopsy reduce the success rate of IMCS in a real‐world scenario and necessitate utilization of patient‐specific alternate sources of PCs like a trephine biopsy imprint or cytology smears from extramedullary sources for successful FISH testing in PC neoplasms.
Tensions experienced by teachers of Dutch culturally diverse senior secondary vocational education and training: An exploratory study
Authors: Tielman Kennedy , Wesselink Renate , den Brok Perry
Published: October 2021

Senior secondary vocational education and training (SSVET) is highly culturally diverse, with a majority of students having an immigrant background. Teachers in culturally diverse classes are more often confronted with tensions in their daily practice and they are uncertain of how to manage these tensions. This exploratory study investigated what value‐based tensions teachers encountered when teaching in culturally diverse SSVET classes. Furthermore, the reported tensions by teachers were examined in terms of (inadequate) knowledge, skills and (hindering) attitudes as a possible cause to deal effectively with the experienced tensions. We collected interview data from 16 SSVET teachers from five schools, each with more than 60% of students with immigrant backgrounds. The results showed that most of the value‐based tensions that the SSVET teachers encountered were related to the intercultural loaded values diversity and respect. Next to tensions related to values also found in prior research, teachers additionally reported tensions with regard to professional ethics & stance of students, which seems unique to SSVET. Most experienced tensions were perceived as being caused by self‐reported lack of skills. Less often, teachers experienced a shortage of knowledge or hindering attitudes when faced with these tensions in culturally diverse SSVET classes.
Clinical significance of the secondary pedicle amputation of the repair of distal defects with pedicled axial flap
Authors: Zhang Xinling , Ding Pengbing , Wang Guanhuier , Chen Yujie , Yang Xin , Zhao Zhenmin , Bi Hongsen
Published: October 2021

We aimed to explore the clinical significance of the secondary pedicle amputation of the repair of distal defects with pedicled axial flap. Five patients who underwent pedicled axial flap transfer to repair a large area of skin and soft tissue defects in our hospital were included in this retrospective study. Detailed information including general data and clinical data, such as preoperative complication, type of primary wound, the distance between the primary wound and the donor site (cm), postoperative complications, and types of axial flap were collected. The patients had good joint movement at 6 months after pedicle amputation. At 48 hours after transplantation, except for the last patient (NO.5), there were no obvious complications such as blood supply disorder, infection, and incision dehiscence of the patients, and the flaps survived well. Just after pedicle amputation, 3 and 6 months after pedicle amputation, the flaps survived well with good local morphology. Forty‐eight hours after operation, part of the distal flap in the last patient (NO.5) was necrotic. After 6 months of pedicle amputation, part of the flap was transferred to the distal wound again. At 6 months after pedicle amputation, these patients could accept local scars even though the scar of the last patient was obvious. The secondary pedicle amputation of the repair of distal defects with axial flap could avoid the compression of the vascular pedicle in the subcutaneous tunnel between the donor site and the primary wound, which may ensure the bold supply and increase the survival rate of the flap.
The relationship between crystal structure and modified microwave dielectric properties of Ca3SnSi2‐xGexO9 ceramics
Authors: Du Kang , Yin Chang‐Zhi , Guo Yan‐Bo , Wang Xiao‐Chuan , Lu Wen‐Zhong , Ta Shi‐Wo , Hu Chun‐Yuan , Lei Wen
Published: October 2021

Ca3SnSi2‐xGexO9 (0 ≤ x ≤ 0.8) and (1–y) Ca3SnSi1.6Ge0.4O9 – y CaSnSiO5 – 2 wt% LiF (y = 0.4 and 0.5) microwave dielectric ceramics were prepared by traditional solid‐state reaction through sintering at 1250°C–1425°C for 5 h and at 875°C for 2 h, respectively. Ge4+ replaced Si4+, and Ca3SnSi2‐xGexO9 (0 ≤ x ≤ 0.4) solid solutions were obtained. At 0.1 ≤ x ≤ 0.4, the Ge4+ substitution for Si4+ decreased the sintering temperature of Ca3SnSi2‐xGexO9 from 1425 to 1300°C, the SnO6 octahedral distortions, and the average CaO7 decahedral distortions, which affected the τf value. The large average decahedral distortions corresponded with nearer‐zero τf values at Ca3SnSi2‐xGexO9 (0.1 ≤ x ≤ 0.4) ceramics. The τf value and sintering temperature of Ca3SnSi2‐xGexO9 (x = 0.4) ceramic were adjusted to near‐zero by CaSnSiO5 and decreased to 875°C upon the addition of 2 wt% LiF. The (1 – y) Ca3SnSi1.6Ge0.4O9 – y CaSnSiO5 – 2 wt% LiF (y = 0.5) ceramic sintered at 875°C for 2 h exhibited good microwave dielectric properties: εr = 10.3, Q × f = 14 300 GHz (at 12.2 GHz), and τf = ‒5.8 ppm/°C.
Decreased selectivity during mate choice in a small‐sized population of a long‐lived seabird
Authors: Bried Joël , Andris Malvina , Dubois Marie‐Pierre , Jarne Philippe
Published: October 2021

As biparental care is crucial for breeding success in Procellariiformes seabirds (i.e. albatrosses and petrels), these species are expected to be choosy during pair formation. However, the choice of partners is limited in small‐sized populations, which might lead to random pairing. In Procellariiformes, the consequences of such limitations for mating strategies have been examined in a single species. Here, we studied mate choice in another Procellariiforme, Bulwer's petrelBulweria bulwerii, in the Azores (ca 70 breeding pairs), where the species has suffered a dramatic population decline. We based our approach on both a 11‐year demographic survey (capture–mark–recapture) and a genetic approach (microsatellites, n = 127 individuals). The genetic data suggest that this small population is not inbred and did not experience a genetic bottleneck. Moreover, pairing occurred randomly with respect to genetic relatedness, we detected no extrapair parentage (n = 35 offspring), and pair fecundity was unrelated to relatedness between partners. From our demographic survey, we detected no assortative mating with respect to body measurements and breeding experience and observed very few divorces, most of which were probably forced. This contrasts with the pattern previously observed in the much larger population from the Selvagens archipelago (assortative mating with respect to bill size and high divorce rate). We suggest that the Bulwer's petrels from the Azores pair with any available partner and retain it as long as possible despite the fact that reproductive performance did not improve with pair common experience, possibly to avoid skipping breeding years in case of divorce. We recommend determining whether decreased choosiness during mate choice also occurs in reduced populations of other Procellariiform species. This might have implications for the conservation of small threatened seabird populations.
NUDT15 polymorphism and NT5C2 and PRPS1 mutations influence thiopurine sensitivity in acute lymphoblastic leukaemia cells
Authors: Somazu Shinpei , Tanaka Yoichi , Tamai Minori , Watanabe Atsushi , Kagami Keiko , Abe Masako , Harama Daisuke , Shinohara Tamao , Akahane Koshi , Goi Kumiko , Sugita Kanji , Moriyama Takaya , Yang Jun , Goto Hiroaki , Minegishi Masayoshi , Iwamoto Shotaro , Takita Junko , Inukai Takeshi
Published: October 2021

In chemotherapy for childhood acute lymphoblastic leukaemia (ALL), maintenance therapy consisting of oral daily mercaptopurine and weekly methotrexate is important. NUDT15 variant genotype is reportedly highly associated with severe myelosuppression during maintenance therapy, particularly in Asian and Hispanic populations. It has also been demonstrated that acquired somatic mutations of the NT5C2 and PRPS1 genes, which are involved in thiopurine metabolism, are detectable in a portion of relapsed childhood ALL. To directly confirm the significance of the NUDT15 variant genotype and NT5C2 and PRPS1 mutations in thiopurine sensitivity of leukaemia cells in the intrinsic genes, we investigated 84 B‐cell precursor‐ALL (BCP‐ALL) cell lines. Three and 14 cell lines had homozygous and heterozygous variant diplotypes of the NUDT15 gene, respectively, while 4 and 2 cell lines that were exclusively established from the samples at relapse had the NT5C2 and PRPS1 mutations, respectively. Both NUDT15 variant genotype and NT5C2 and PRPS1 mutations were significantly associated with DNA‐incorporated thioguanine levels after exposure to thioguanine at therapeutic concentration. Considering the continuous exposure during the maintenance therapy, we evaluated in vitro mercaptopurine sensitivity after 7‐day exposure. Mercaptopurine concentrations lethal to 50% of the leukaemia cells were comparable to therapeutic serum concentration of mercaptopurine. Both NUDT15 variant genotype and NT5C2 and PRPS1 mutations were significantly associated with mercaptopurine sensitivity in 83 BCP‐ALL and 23 T‐ALL cell lines. The present study provides direct evidence to support the general principle showing that both inherited genotype and somatically acquired mutation are crucially implicated in the drug sensitivity of leukaemia cells.
miRNA‐34b/c regulates mucus secretion in RSV‐infected airway epithelial cells by targeting FGFR1
Authors: Li Wenkai , Du Xizi , Yang Yu , Yuan Lin , Yang Ming , Qin Ling , Wang Leyuan , Zhou Kai , Xiang Yang , Qu Xiangping , Liu Huijun , Qin Xiaoqun , Xiao Gelei , Liu Chi
Published: October 2021

Respiratory syncytial virus (RSV) infection in airway epithelial cells is the main cause of bronchiolitis in children. Excessive mucus secretion is one of the primary symbols in RSV related lower respiratory tract infections (RSV‐related LRTI). However, the pathological processes of mucus hypersecretion in RSV‐infected airway epithelial cells remains unclear. The current study explores the involvement of miR‐34b/miR‐34c in mucus hypersecretion in RSV‐infected airway epithelial cells by targeting FGFR1. First, miR‐34b/miR‐34c and FGFR1 mRNA were quantified by qPCR in throat swab samples and cell lines, respectively. Then, the luciferase reporters’ assay was designed to verify the direct binding between FGFR1 and miR‐34b/miR‐34c. Finally, the involvement of AP‐1 signalling was assessed by western blot. This study identified that miR‐34b/miR‐34c was involved in c‐Jun‐regulated MUC5AC production by targeting FGFR1 in RSV‐infected airway epithelial cells. These results provide some useful insights into the molecular mechanisms of mucus hypersecretion which may also bring new potential strategies to improve mucus hypersecretion in RSV disease.
Testing potential mechanisms of conspecific sperm precedence in Drosophila pseudoobscura
Authors: Peckenpaugh Brooke , Castillo Dean M. , Moyle Leonie C.
Published: October 2021

Drosophila pseudoobscura females that co‐occur with sister species D. persimilis show elevated fertilization by conspecific sperm when they mate with both a heterospecific and a conspecific male. This phenomenon, known as conspecific sperm precedence (CSP), has evolved as a mechanism to avoid maladaptive hybridization with D. persimilis. In this study, we assessed pericopulatory (during mating) and postcopulatory (after mating) traits in crosses with sympatric or allopatric D. pseudoobscura females and conspecific or heterospecific males to evaluate potential mechanisms of CSP in this system. We observed shorter copulation duration in crosses with sympatric females, but found no difference in quantity of sperm transferred or female reproductive tract toxicity between sympatry and allopatry. Our data show some support for the hypothesis that parasperm, a short, sterile sperm morph, can protect fertile eusperm from the D. pseudoobscura female reproductive tract, though it is unclear how this might affect patterns of sperm use in sympatry vs. allopatry. Overall, these results suggest that copulation duration could potentially contribute to the elevated CSP observed in sympatry.
Spontaneous twin anemia‐polycythemia sequence from two donors to one recipient in a monochorionic triamniotic pregnancy: Case report and review of the literature
Authors: Pena Burgos Eva Manuela , Regojo Zapata Rita María , Turiel Miranda Miriam , Antolín Alvarado Eugenia , De la Calle María
Published: October 2021

Monochorionic triamniotic (MCTA) pregnancies present a high number of complications, mainly due to the presence of unbalanced vascular anastomoses, such as twin anemia‐polycythemia sequence (TAPS). Previous reported cases related to TAPS are in twin pregnancies or only affect the monochorionic component of dichorionic triamniotic (DCTA) pregnancies. We report an exceptional case, the only one reported as far as we know, of a MCTA pregnancy that developed a TAPS in which the three triplets are implicated, from two donors to one recipient. The pregnancy had been previously sonographically diagnosed as DCTA pregnancy and this could not explain the clinical results. The pathological study of the placenta showed the presence of three monochorionic dividing membranes, a congested area in the recipient parenchyma and two non‐congested areas in the donor's parenchyma that confirmed the clinical findings. Pathological study of multiple placentas should always be done because it provides understanding of pregnancy complications.
Beyond Co‐Location: Development of a School Health Integration Measure*
Authors: Ferenchak Kenny S. , Trieu Sang Leng , Franco Rosina , Jackson Nicholas J. , Dudovitz Rebecca
Published: October 2021

BACKGROUND

School‐based health centers (SBHCs) can integrate health and educational services to achieve common goals of student wellness and success. As no method exists to quantify the degree of integration for clinics and partner schools, this study aimed to design such a measure.

METHODS

Measure items were drafted from the literature. Eleven school health experts from Los Angeles, CA, used a modified Delphi method to reach consensus around items for inclusion in a School Health Integration Measure (SHIM), evaluating each on its appropriateness, substantivity, and feasibility. Twenty‐eight staff at 17 SBHC campuses pilot tested the SHIM to examine its psychometric properties.

RESULTS

From 36 items, the expert panel utilized 4 rounds to reach consensus on 12 items across 5 domains: health authority, integrated programming, marketing and recruitment, shared outcomes, and staff collaboration. In the SHIM pilot, scores ranged from 2.25 to 5 (possible 1‐5, mean 3.53). The measure had high internal consistency (alpha = 0.9385) and was associated with participants' general assessment of integration at their sites (p = .001).

CONCLUSIONS

The SHIM provides a new tool to quantify health and educational service integration at SBHC sites, drive practice improvement, and test whether integration leads to better student outcomes.