bluuebunny/crossref_metadata_2025 huggingface dataset:
Multi‐level convergence of complex traits and the evolution of bioluminescence
Authors: Lau Emily S. , Oakley Todd H.
Published: December 2020

Evolutionary convergence provides natural opportunities to investigate how, when, and why novel traits evolve. Many convergent traits are complex, highlighting the importance of explicitly considering convergence at different levels of biological organization, or ‘multi‐level convergent evolution’. To investigate multi‐level convergent evolution, we propose a holistic and hierarchical framework that emphasizes breaking down traits into several functional modules. We begin by identifying long‐standing questions on the origins of complexity and the diverse evolutionary processes underlying phenotypic convergence to discuss how they can be addressed by examining convergent systems. We argue that bioluminescence, a complex trait that evolved dozens of times through either novel mechanisms or conserved toolkits, is particularly well suited for these studies. We present an updated estimate of at least 94 independent origins of bioluminescence across the tree of life, which we calculated by reviewing and summarizing all estimates of independent origins. Then, we use our framework to review the biology, chemistry, and evolution of bioluminescence, and for each biological level identify questions that arise from our systematic review. We focus on luminous organisms that use the shared luciferin substrates coelenterazine or vargulin to produce light because these organisms convergently evolved bioluminescent proteins that use the same luciferins to produce bioluminescence. Evolutionary convergence does not necessarily extend across biological levels, as exemplified by cases of conservation and disparity in biological functions, organs, cells, and molecules associated with bioluminescence systems. Investigating differences across bioluminescent organisms will address fundamental questions on predictability and contingency in convergent evolution. Lastly, we highlight unexplored areas of bioluminescence research and advances in sequencing and chemical techniques useful for developing bioluminescence as a model system for studying multi‐level convergent evolution.
Mining sick: Creatively unsettling normative narratives about industry, environment, extraction, and the health geographies of rural, remote, northern, and Indigenous communities in British Columbia
Authors: Aldred Terri‐Leigh , Alderfer‐Mumma Charis , de Leeuw Sarah , Farrales May , Greenwood Margo , Hoogeveen Dawn , O’Toole Ryan , Parkes Margot W. , Sloan Morgan Vanessa
Published: December 2020

Rural, remote, northern, and Indigenous communities on Turtle Island are routinely—as Cree Elder Willie Ermine says—pathologized. Social science and health scholarship, including scholarship by geographers, often constructs Indigenous human and physical geographies as unhealthy, diseased, vulnerable, and undergoing extraction. These constructions are not inaccurate: peoples and places beyond urban metropoles on Turtle Island live with higher burdens of poor health; Indigenous peoples face systemic violence and racism in colonial landscapes; rural, remote, northern, and Indigenous geographies are sites of industrial incursions; and many rural and remote geographies remain challenging for diverse Indigenous peoples. What, however, are the consequences of imagining and constructing people and places as “sick”? Constructions of “sick” geographies fulfill and extend settler (often European white) colonial narratives about othered geographies. Rural, remote, northern, and Indigenous geographies are discursively “mined” for narratives of sickness. This mining upholds a sense of health and wellness in southern, urban, Euro‐white‐settler imaginations. Drawing from multi‐year, relationship‐based, cross‐disciplinary qualitative community‐informed experiences, and anchored in feminist, anti‐colonial, and anti‐racist methodologies that guided creative and humanities‐informed stories, this paper concludes with different stories. It unsettles settler‐colonial powers reliant on constructing narratives about sickness in others and consequently reframes conversations about Indigenous well‐being and the environment.
Therapeutic inhibition of polo‐like kinases in anaplastic thyroid cancer
Authors: Lin Shu‐Fu , Yeh Chun‐Nan , Huang Yu‐Tung , Chou Ting‐Chao , Wong Richard J.
Published: December 2020

Polo‐like kinases (PLKs) are potent regulators of cell proliferation and cell survival. Polo‐like kinases are potential targets in the treatment of anaplastic thyroid cancer (ATC), a rare but deadly disease. The therapeutic effects of volasertib, a PLK inhibitor, was evaluated for the treatment of ATC either alone or in combination with sorafenib. Volasertib decreased cell viability in three ATC cell lines (8505C, 8305C, and KAT18) in a dose‐dependent manner. Volasertib caused ATC cells to accumulate in G2/M phase, activated caspase‐3 activity, and induced apoptosis. Combination therapy using volasertib and sorafenib in ATC cells showed mostly synergistic effects. In vivo studies revealed that combination therapy of volasertib and sorafenib was effective in the treatment of 8505C xenografts. Single‐agent volasertib treatment was sufficient to retard 8305C tumor growth. No substantial morbidity was observed in animals that received either single‐agent or combination treatment. These preclinical findings suggest that volasertib could be an effective drug in treating ATC.
Neutrophilic asthma features increased airway classical monocytes
Authors: Niessen Natalie M. , Baines Katherine J. , Simpson Jodie L. , Scott Hayley A. , Qin Ling , Gibson Peter G. , Fricker Michael
Published: December 2020

Background

Monocytes and macrophages are critical innate immune cells of the airways. Despite their differing functions, few clinical studies discriminate between them and little is known about their regulation in asthma.

Objective

We aimed to distinguish and quantify macrophages, monocytes and monocyte subsets in induced sputum and blood and examine their relationship with inflammatory and clinical features of asthma.

Methods

We applied flow cytometry to distinguish macrophages, monocytes and subsets in sputum and blood (n = 53; 45 asthma, 8 non‐asthma) and a second asthma sputum cohort (n = 26). Monocyte subsets were identified by surface CD14/CD16 (CD14++CD16− classical, CD14+CD16+ intermediate and CD14+CD16++ non‐classical monocytes). Surface CD206, a marker of monocyte tissue differentiation, was measured in sputum. Relationship to airway inflammatory phenotype (neutrophilic n = 9, eosinophilic n = 14, paucigranulocytic n = 22) and asthma severity (severe n = 12, non‐severe n = 33) was assessed.

Results

Flow cytometry‐ and microscope‐quantified sputum differential cell proportions were significantly correlated. Sputum macrophage number was reduced (p = .036), while classical monocyte proportion was increased in asthma vs non‐asthma (p = .032). Sputum classical monocyte number was significantly higher in neutrophilic vs paucigranulocytic asthma (p = .013). CD206− monocyte proportion and number were increased in neutrophilic vs eosinophilic asthma (p < .001, p = .013). Increased sputum classical and CD206− monocyte numbers in neutrophilic asthma were confirmed in the second cohort. Blood monocytes did not vary with airway inflammatory phenotype, but blood classical monocyte proportion and number were increased in severe vs non‐severe asthma (p = .022, p = .011).

Conclusion and Clinical relevance

Flow cytometry allowed distinction of sputum macrophages, monocytes and subsets, revealing compartment‐specific dysregulation of monocytes in asthma. We observed an increase in classical and CD206− monocytes in sputum in neutrophilic asthma, suggesting co‐recruitment of monocytes and neutrophils to the airways in asthma. Our data suggest further investigation of how airway monocyte dysregulation impacts on asthma‐related disease activity is merited.
Immune checkpoint expression on peripheral cytotoxic lymphocytes in cervical cancer patients: moving beyond the PD-1/PD-L1 axis
Authors: Solorzano-Ibarra F , Alejandre-Gonzalez A G , Ortiz-Lazareno P C , Bastidas-Ramirez B E , Zepeda-Moreno A , Tellez-Bañuelos M C , Banu N , Carrillo-Garibaldi O J , Chavira-Alvarado A , Bueno-Topete M R , del Toro-Arreola S , Haramati J
Published: December 2020

Immune checkpoint therapy to reverse natural killer (NK) and T cell exhaustion has emerged as a promising treatment in various cancers. While anti-programmed cell death 1 (PD-1) pembrolizumab has recently gained Food and Drug Administration (FDA) approval for use in recurrent or metastatic cervical cancer, other checkpoint molecules, such as T cell immunoreceptor with immunoglobulin (Ig) and immunoreceptor tyrosine-based inhibition motif (ITIM) domains (TIGIT) and T cell immunoglobulin and mucin-domain containing-3 (Tim-3), have yet to be fully explored in this disease. We report expression of TIGIT, Tim-3 and PD-1 on subsets of peripheral blood NK (CD56dim/negCD16bright/dim/neg and CD56brightCD16dim/neg) and T cells. The percentages of these cells were increased in women with cervical cancer and pre-malignant lesions. PD-1+ NK and T cells were likely to co-express TIGIT and/or Tim-3. These cells, with an apparently ‘exhausted’ phenotype, were augmented in patients. A subset of cells were also natural killer group 2 member D (NKG2D)- and DNAX accessory molecule 1 (DNAM-1)-positive. PD-1int and PD-1high T cells were notably increased in cervical cancer. Soluble programmed cell death ligand 1 (PD-L1) was higher in cancer patient blood versus healthy donors and we observed a positive correlation between sPD-L1 and PD-1+ T cells in women with low-grade lesions. Within the cancer group, there were no significant correlations between sPD-L1 levels and cervical cancer stage. However, when comparing cancer versus healthy donors, we observed an inverse association between sPD-L1 and total T cells and a correlation between sPD-L1 and CD56dim NK cells. Our results may show an overview of the immune response towards pre-cancerous lesions and cervical cancer, perhaps giving an early clue as to whom to administer blocking therapies. The increase of multiple checkpoint markers may aid in identifying patients uniquely responsive to combined antibody therapies.
IgG4 immunohistochemistry in Riedel's thyroiditis and the recommended criteria for diagnosis: A case series and literature review
Authors: Yu Yang , Liu Jumei , Yu Nan , Zhang Yang , Zhang Shuang , Li Ting , Gao Ying , Lu Guizhi , Zhang Junqing , Guo Xiaohui
Published: December 2020

Objective

Riedel’s thyroiditis (RT) is a very rare chronic fibrosing thyroiditis that is often associated with multifocal fibrosclerosis. Although the relationship of RT and IgG4‐related disease (IgG4‐RD) has been suggested, the expression of IgG and IgG4 in thyroid tissues of patients with RT has seldom been studied.

Design

A case series and literature review.

Patients and Measurements

We searched our hospital's pathology database and identified five cases of RT between 2000 and 2019. The expression levels of IgG4 and IgG in thyroid tissues were detected by immunohistochemistry. We also performed a literature search of the electronic databases PubMed/MEDLINE, Web of Science and China National Knowledge Internet (CNKI). Eight papers were included in this study.

Results

According to immunohistochemistry, the numbers of IgG4+ plasma cells per high‐power field (HPF) of the five RT patients at our hospital were 80, 8, 50, 10 and 22, and the respective IgG4+/IgG+ ratios were 76%, 80%, 43%, 19% and 28%. In the literature, 15 RT patients with confirmed IgG4 and IgG immunohistochemical findings were identified. Only seven of them fulfilled the IgG4‐RD diagnostic criteria in terms of immunohistochemistry (IgG4+ > 10/HPF, IgG4+/IgG+ > 40%). In order to ensure that most RT cases can meet the IgG4 immunohistochemical criteria, an organ‐specific cut‐off value (≥10 IgG4+ plasma cells/HPF and ≥ an IgG4+/IgG ratio of 20%) was finally selected in our study.

Conclusion

Our findings of IgG4 expression in patients with RT suggest that a cut‐off of 10 IgG4+ plasma cells/HPF and an IgG4+/IgG ratio of 20% are more suitable diagnostic criteria for RT in IgG4‐RD.
Modelling Material Microstructure Using the Perlin Noise Function
Authors: Conde‐Rodríguez F. , García‐Fernández Á‐.L. , Torres J.C.
Published: December 2020

This paper introduces a precise and easy to use method for defining the microstructure of heterogeneous solids. This method is based on the concept of Heterogeneous Composite Bézier Hyperpatch, and allows to accurately represent the primary material proportions, as well as the size and shape of the material phases. The solid microstructure is modelled using two functions: a material distribution function (to compute the portion of the solid volume occupied by each primary material), and a modified Perlin noise function that determines the shape and size of each primary material phase.

With this method, the position and orientation of the solid in the modeling space does not affect the portion of its volume that is occupied by each primary material, nor the shape and size of the phases. However, the solid microstructure is coherently and automatically modified when the shape of the solid is edited. Regarding continuity, this method allows to define to which extent continuity (both in shape and material distribution) has to be preserved at the junction of the cells that compose the solid. This makes modeling geometrically complex figures very easy.
Improving povidone‐iodine and iodine preparations for patch testing
Authors: Forkel Susann , Beutner Caroline , Amschler Katharina , Schröder Silke Sabina , Schön Michael P. , Geier Johannes , Buhl Timo
Published: December 2020

Background

Allergy evaluation by patch testing with povidone‐iodine (PVP‐I) or iodine remains challenging, because current patch test preparations frequently lead to false‐positive or irritant skin reactions.

Objectives

To investigate different preparations for iodine patch tests and to assess their clinical relevance with repeated open application tests (ROATs).

Methods

We monocentrically analyzed 95 patients with suspected allergy to disinfectants in retrospect who underwent parallel iodine patch testing with four preparations: PVP‐I 2% aq., 5% aq., 10% aq., and iodine 0.5% pet.

Results

In 27 of 95 patients (28.4%), we found positive reactions to one of the four test preparations. After ROATs in 22 of these 27 positively tested individuals, only one patient was diagnosed with iodine allergy. In contrast, 31 of 95 patients (32.6%) showed irritant or questionable patch test reactions on day 2 (D2) and/or D3 and/or D7 to one or more test preparations. Testing with PVP‐I 2% aq. resulted in the lowest number of doubtful skin reactions while detecting the single allergic patient.

Conclusion

PVP‐I 2% aq. was found to be the optimal patch test preparation. In general, iodine allergy appears to be substantially overestimated, and positive patch test responses to iodine should prompt an urgent ROAT for confirmation before diagnosing iodine allergy.
Definition of large bowel obstruction by primary colorectal cancer: A systematic review
Authors: Veld Joyce V. , Beek Kim J. , Consten Esther C.J. , ter Borg Frank , van Westreenen Henderik L. , Bemelman Wilhelmus A. , van Hooft Jeanin E. , Tanis Pieter J.
Published: December 2020

Aim

Controversies on therapeutic strategy for large bowel obstruction by primary colorectal cancer mainly concern acute conditions, being essentially different from subacute obstruction. Clearly defining acute obstruction is important for design and interpretation of studies as well as for guidelines and daily practice. This systematic review aimed to evaluate definitions of obstruction by colorectal cancer in prospective studies.

Method

A systematic search was performed in PubMed, Embase and the Cochrane Library. Eligibility criteria included randomized or prospective observational design, publication between 2000 and 2019, and the inclusion of patients with an obstruction caused by colorectal cancer. Provided definitions of obstruction were extracted with assessment of common elements.

Results

A total of 16 randomized controlled trials (RCTs) and 99 prospective observational studies were included. Obstruction was specified as acute in 28 studies, complete/emergency in five, (sub)acute or similar terms in four and unspecified in 78. Five of 16 RCTs (31%) and 37 of 99 cohort studies (37%) provided a definition. The definitions included any combination of clinical symptoms, physical signs, endoscopic features and radiological imaging findings in 25 studies. The definition was only based on clinical symptoms in 11 and radiological imaging in six studies. Definitions included a radiological component in 100% of evaluable RCTs (5/5) vs. 54% of prospective observational studies (20/37, P = 0.07).

Conclusion

In this systematic review, the majority of prospective studies did not define obstruction by colorectal cancer and its urgency, whereas provided definitions varied hugely. Radiological confirmation seems to be an essential component in defining acute obstruction.
The Effect of Language‐Specific Characteristics on English and Japanese Speakers' Ability to Recall Number Information
Authors: Kirjavainen Minna , Kite Yuriko , Piasecki Anna E.
Published: December 2020

The current paper presents two experiments investigating the effect of presence versus absence of compulsory number marking in a native language on a speaker's ability to recall number information from photos. In Experiment 1, monolingual English and Japanese adults were shown a sequence of 110 photos after which they were asked questions about the photos. We found that the English participants showed a significantly higher accuracy rate for questions testing recall for number information when the correct answer was “2” (instead of “1”) than Japanese participants. In Experiment 2, English and Japanese adults engaged in the same task as in Experiment 1 with an addition that explored reasons for the results found in Experiment 1. The results of Experiment 2 were in line with the results of Experiment 1, but also suggested that the results could not be attributed to differences in guessing patterns between the two groups or the type of linguistic constructions used in the test situations. The current study suggests that native language affects speakers' ability to recall number information from scenes and thus provides evidence for the Whorfian hypothesis.
The sensory ecology of fear: African elephants show aversion to olfactory predator signals
Authors: Valenta Kim , Schmitt Melissa H. , Ayasse Manfred , Nevo Omer
Published: December 2020

Human–elephant conflict is a persistent problem across elephant home ranges, that results in economic damage to commercial and subsistence farmers, and physical harm and death to humans and elephants. This problem is likely to intensify with increased development, dwindling of natural habitats, and climate change‐driven environmental shifts. Various methods to mitigate human–elephant conflict have been employed, but to date these have been hampered by financial and logistical considerations. Based on the fact that African elephants are predated by lions and possess a remarkable sense of smell, we hypothesize that elephants are strongly averse to olfactory signals of lion presence, and that this can be utilized to create invisible barriers which elephants will not cross. We conducted a series of tests that show that lion dung is an effective deterrent of elephants. We conducted chemical analyses of lion dung and identified the main compounds. We then used synthetic mixtures containing these compounds, and show that they successfully elicit the deterrence effect, even in miniscule concentrations. These results indicate that elephants can be deterred using simple and low‐concentration mixtures based on available commercial products, that can be developed into products that offer a safe, sustainable, and cost‐effective method to mitigate human–elephant conflict.
Treating latent autoimmune diabetes in adults in the era of cardiovascular outcomes trials: Old dog should learn new tricks
Authors: Koufakis Theocharis , Vas Prashanth , Kotsa Kalliopi
Published: December 2020

Background

Latent autoimmune diabetes in adults (LADA) is characterised by pathophysiological and clinical heterogeneity. Hence, the optimal treatment strategy for this type of diabetes remains a clinical challenge.

Aim

To discuss the potential of a modern therapeutic approach for LADA in the context of the novel findings of cardiovascular outcomes trials and stress the controversies surrounding LADA and the barriers in the effective management of people with this type of diabetes.

Methods

We performed a literature search in major biomedical databases in order to retrieve relevant literature. The results of key studies, along with the authors' clinical experience and perspective, are summarised and discussed in this narrative, mini review article.

Results

Insulin remains the primary treatment choice in individuals with low C‐peptide levels. Although cardiovascular outcomes trials have mainly recruited participants with type 2 diabetes, recent data suggest that the cardiorenal protective properties of the new therapies are even present in people without diabetes and thus, the extrapolation of their results on LADA individuals sounds reasonable. Therefore, sodium–glucose co‐transporter 2 inhibitors (SGLT2is) and glucagon‐like peptide‐1 receptor agonists should be considered for the management of people with preserved insulin production being at high cardiovascular risk. The risk of diabetic ketoacidosis with SGLT2is requires increased vigilance by treating physicians.

Conclusions

Individualisation, preservation of beta‐cell mass and function and cardiorenal protection are the new challenges in LADA therapy.
Multiattempt Quizzes in an MBA‐Level Statistics Course
Authors: Robbins Thomas R.
Published: December 2020

Statistics is a difficult subject for many students, but it is also a requirement for most graduate‐level business programs. Mastery of difficult subject matter is achieved through repetition. In this article, we review the process for setting up a multiattempt quiz system in an MBA‐level introductory statistics course and investigate the impact it had on student behavior and learning. We analyzed a dataset of more than 3,000 quiz attempts to determine the impact repeated trials had on the time required to complete the quiz and the resulting score. We also examined the probability students will make an additional attempt and students’ bias for a round number score. We found that scores improved and that quiz duration times decreased with repetition. We also discovered that student's preference to achieve round number goals impacts their willingness to make additional attempts.
Phonophobia and brainstem excitability in migraine
Authors: Kalita Jayantee , Misra Usha K. , Bansal Robin
Published: December 2020

Phonophobia in migraineurs may be due to lower hearing threshold (HT) and higher brainstem neuronal excitability. We report the correlation of phonophobia in migraineurs with HT, brain stem auditory evoked potential (BAEP) findings, and auditory triggers. Sixty‐one migraineurs and 101 controls were included for HT, of whom 59 migraineurs and 31 controls had BAEP studies. Clinical details, migraine triggers, and headache frequency were noted. Hearing threshold was measured, and amplitudes of waves I to V of BAEP studies were measured. Migraineurs had lower HT compared with controls (41.61 ± 5.25 versus 45.39 ± 6.26 dB; p < 0.001) especially in chronic migraine (40.24 ± 4.81; p < 0.001). Hearing threshold correlated with headache frequency (p < 0.05) and auditory, visual, and tactile (p < 0.05) triggers. Hearing threshold was lower during headache (p < 0.001). Wave II, III, and IV amplitudes of BAEP were higher in migraineurs than the controls. Wave II (p < 0.05) and III (p < 0.05) amplitudes correlated with HT. Migraineurs have lower HT, especially in those having chronic migraine, ictal HT recording, and multiple sensory triggers. Higher amplitudes of BAEP waves in migraineurs and their relationship with the frequency of headache and HT suggest the sensitization of brainstem auditory neurons.
Performance of different criteria for refractory myasthenia gravis
Authors: Tran Christopher , Biswas Aishani , Mendoza Meg , Katzberg Hans , Bril Vera , Barnett Carolina
Published: December 2020

Background and purpose

Defining refractory myasthenia gravis is important, as this can drive clinical decision making, for example, by escalating treatments in refractory individuals. There are several definitions of refractory myasthenia, and their performances have not been compared. Having valid and reliable criteria can help select patients in whom more aggressive treatments may be needed.

Methods

We applied five different refractory myasthenia criteria (Drachman, Mantegazza, Suh, the International Consensus Guideline (ICG), and the randomised controlled trial of eculizumab in refractory, anti‐acetylcholine receptor positive, generalised myasthenia gravis (REGAIN), to a cohort of 237 patients. We compared the proportion of refractory patients among different criteria and their scores on disease severity, fatigue, and quality‐of‐life (QoL) scales. We also assessed the agreement for each criterion between two trained assessors.

Results

The Drachman, Mantegazza, and Suh criteria resulted in high proportions of refractory individuals (40.1%, 39.2%, and 38.8%, respectively), compared with the ICG and REGAIN criteria (9.7% and 3.0%, respectively). Refractory patients by the ICG and REGAIN criteria had worse disease severity, QoL, and fatigue scores, compared with patients classified as refractory by other criteria. All criteria had high agreement between raters (between 70% and 100%).

Conclusions

There is high variability in the proportion of refractory myasthenia gravis patients depending on the criteria used, with ICG and REGAIN criteria capturing patients with worse disease severity. This reflects conceptual differences as to what refractory means. Further multicenter studies are needed to determine appropriate criteria for refractory myasthenia gravis.
Give Them Money: An Illustrative History of Forms of Reimagined Rehabilitation in Probation Practice in England and Wales
Authors: VANSTONE MAURICE
Published: December 2020

Traditionally, in its efforts to help people lead offence‐free lives, the probation service has focused on work aimed at changing the individual and there has been much less focus on the context of offending. Recent commentators have called for a reimagined definition of rehabilitative work that includes paying attention to the social context of offending. This article argues that this aspect of probation practice has been neglected and attempts to trace its history in order to draw out lessons that might inform the policies of the newly nationalised Service.
The relationship between excessive dietary fructose consumption and paediatric fatty liver disease
Authors: DiStefano Johanna K. , Shaibi Gabriel Q.
Published: December 2020

The global prevalence of non‐alcoholic fatty liver disease (NAFLD) in children and adolescents is escalating and currently represents the most common chronic liver disease in the paediatric population. NAFLD is associated with high daily caloric intake and sedentary behaviour, with excessive consumption of added sugar emerging as an important contributor to NAFLD risk in children. This is a particularly important factor for adolescents with obesity, who are the heaviest consumers of added sugar. Table sugar, or sucrose, is a disaccharide comprised of fructose and glucose, yet only fructose has been strongly linked to NAFLD pathogenesis largely due to the unique characteristics of its metabolism and detrimental effects on key metabolic pathways. To date, the relationship between excessive fructose intake and risk of NAFLD in children and adolescents remains incompletely understood, and it is not yet known whether fructose actually causes NAFLD or instead exacerbates hepatic fat accumulation and possible hepatocellular injury only within the context of cardiometabolic factors. The purpose of this review is to summarize recent studies linking fructose consumption with NAFLD in the paediatric population and integrate results from interventional studies of fructose restriction in children and adolescents on NAFLD and related metabolic markers. Given the overall positive impact of lifestyle modifications in the management of paediatric NAFLD, reduction of added sugar consumption may represent an important, early opportunity to mitigate or prevent NAFLD in high‐risk children and adolescents.
Impact of antiandrogen withdrawal syndrome in castration‐resistant prostate cancer patients treated with abiraterone or enzalutamide
Authors: Shiota Masaki , Machidori Asako , Abe Tatsuro , Monji Keisuke , Kashiwagi Eiji , Takeuchi Ario , Takahashi Ryosuke , Inokuchi Junichi , Yokomizo Akira , Naito Seiji , Eto Masatoshi
Published: December 2020

Objectives

To assess the impact of antiandrogen withdrawal syndrome after bicalutamide withdrawal in castration‐resistant prostate cancer patients treated with androgen receptor‐axis targeted agents.

Methods

The study cohort comprised 94 patients treated with abiraterone (n = 34) or enzalutamide (n = 60) as a first‐line androgen receptor‐axis targeted agent for castration‐resistant prostate cancer despite combined androgen blockade by castration with bicalutamide as the first‐line therapy. The association between clinicopathological factors (including antiandrogen withdrawal syndrome) and therapeutic outcome after using abiraterone and enzalutamide was investigated.

Results

The decline in the prostate‐specific antigen level after use of abiraterone or enzalutamide was comparable between patients with and without antiandrogen withdrawal syndrome. Antiandrogen withdrawal syndrome (hazard ratio 3.84, 95% confidence interval 1.29–11.45; P = 0.016) was associated with a higher risk of progression on multivariate analysis, but not all‐cause death after abiraterone use. Progression‐free survival and overall survival after enzalutamide use did not differ between patients with and without antiandrogen withdrawal syndrome.

Conclusions

The present data suggest a modest therapeutic efficacy of abiraterone in castration‐resistant prostate cancer patients with anti‐androgen withdrawal syndrome after bicalutamide withdrawal.
Trends in treatment outcomes for retractile testis in Japanese boys: A single‐center study
Authors: Hori Shunta , Aoki Katsuya , Nishimura Nobutaka , Morizawa Yosuke , Gotoh Daisuke , Fukui Shinji , Nakai Yasushi , Miyake Makito , Torimoto Kazumasa , Yoneda Tatsuo , Tanaka Nobumichi , Fujimoto Kiyohide
Published: December 2020

Objectives

To investigate the natural course of retractile testis by analyzing its prevalence and outcomes.

Methods

This retrospective study included 215 boys in whom retractile testis was diagnosed after reviewing the medical history and physical examinations of the patients. Orchiopexy was performed once the testis became undescended. We investigated the trends in the prevalence and outcomes of retractile testis and compared clinical factors between cases that resolved spontaneously and those that required orchiopexy.

Results

Of 215 boys, 145 were finally evaluated. The mean age at diagnosis was 2 years, and 100 boys were aged ≤2 years when they were hospitalized. Seventy‐three boys were referred to our institution through health examinations as babies. The condition improved spontaneously in 89 boys, while 43 boys underwent orchiopexy, and 13 boys remained under follow‐up. The follow‐up period between diagnosis and resolution was significantly longer in the spontaneous resolution group than in the surgical intervention group (P = 0.011). Bilateral retractile testis improved spontaneously in significantly more boys compared to unilateral retractile testis (P = 0.0010). Spontaneous resolution was observed in boys of all ages, but those diagnosed at ≤3 years of age had a significantly higher rate of spontaneous resolution compared to those who were diagnosed at >3 years of age (P = 0.0019).

Conclusions

Our findings suggest that retractile testis cannot be affirmed as a variant of normal testis. Performing examinations at a young age is critical for preventing misdiagnosis, screening failures, and unnecessary surgery.
Alemtuzumab mediates the CD39+ T‐regulatory cell response via CD23+ macrophages
Authors: Remez Lital , Ganelin‐Cohen Esther , Safina Dina , Hellmann Mark A , Lotan Itay , Bosak Noam , Buxbaum Chen , Vaknin Adi , Shifrin Alla , Rozenberg Ayal
Published: December 2020

Alemtuzumab (ALM) effectively prevents relapses of multiple sclerosis (MS). It causes lymphocyte depletion with subsequent enhancement of the T‐regulatory cell population. Direct administration of ALM to T cells causes cytolysis. However, the T cells may be indirectly affected by monocyte‐derived cells, which are resistant to ALM cytotoxicity. We aimed to examine whether ALM modulates monocytes and whether the crosstalk between monocytes and lymphocytes previously exposed to ALM would result in anti‐inflammatory effects. The CD14+ monocytes of 10 healthy controls and 10 MS (treatment naive) patients were isolated from peripheral blood mononuclear cells (PBMCs), exposed to ALM and reintroduced to PBMCs depleted of CD14+ cells. The macrophage profile was assessed and T‐cell markers were measured. ALM promoted M2 anti‐inflammatory phenotype as noted by an increased percentage in the populations of CD23+, CD83+ and CD163+ cells. The CD23+ cells were the most upregulated (7‐fold, P = 0.0002), and the observed effect was higher in patients with MS than in healthy subjects. ALM‐exposed macrophages increased the proportion of T‐regulatory cells, without affecting the proportion of T‐effector cells. Neutralizing the CD23+ monocytes with antibodies reversed the effect specifically on the CD4+CD39+ T‐regulatory cell subpopulation but not on the CD4+CD25hiCD127loFOXP3+ subpopulation. ALM induces the conversion of monocytes into anti‐inflammatory macrophages, which in turn promotes T‐regulatory cell enhancement, in a CD23‐dependent manner. These findings suggest that the mechanism of action of ALM is relevant to aspects of MS pathogenesis.
Polypharmacy and the use of low or limited value medications in advanced cancer
Authors: Haider Sana , Descallar Joseph , Moylan Eugene , Chua Wei
Published: December 2020

Background

Patients with advanced malignancy are often on medications for co‐morbidities, including those for primary or secondary prevention. The benefit from these medications can be limited and may result in adverse effects, interact with medications used for the malignancy or associated symptoms, increase pill burden and reduce quality of life.

Aims

To evaluate the proportion of patients with advanced malignancy that were continued on low or limited value medications and identify the factors associated with this. We also sought to determine how prevalent polypharmacy was within this group of patients and the factors associated with this.

Methods

A retrospective chart review was conducted of patients with incurable malignancy admitted under medical oncology at Liverpool Hospital over a 90‐day period. Demographic variables, co‐morbidities, disease related parameters and medications were reviewed. Criteria were established to identify low or limited value medications.

Results

Seventy‐eight patients were identified between September and December 2018. Thirty‐day mortality was 33%. Sixty‐five percent of the cohort was on five or more medications and 24% on 10 or more. One low or limited value medication was reported in 36% and 20% were on two or more. Age ≤60 years was associated with a risk of being on at least one unnecessary medication. Patients with fewer co‐morbidities and those in their last 3 months of life were significantly less likely to have polypharmacy. Nine percent of the cohort was on three or more antihypertensives and 6% of patients were on three or more oral hypoglycaemics.

Conclusion

Polypharmacy and continued prescribing of low or limited value medications was identified in a high proportion of patients. Further studies are needed to assess the impact of continuing these medications, as well as investigation of patient and physician attitudes towards de‐escalation.
Work harder or aim lower? Overconfidence and belief updating in the classroom
Authors: Nicholls Nicky , Romm Aylit T.
Published: December 2020

Building on recent lab experiments on belief updating, this study uses a university‐based field experiment to investigate behaviour change together with the updating of beliefs in response to feedback in a real‐life context. Postgraduate students predict their performance expectations for a core degree course in a probability distribution format where correct expectations are incentivised using a quadratic scoring rule. Behaviour, in the form of weekly time spent on the course, is also reported. Students then receive feedback in the form of graded tests and assignments, following which they repeat both the prediction exercise and the behaviour reporting. Cognitive dissonance theory predicts that where beliefs and performance feedback do not align, people will either change their beliefs to better conform to received feedback or change their behaviour so that performance better approximates their beliefs. In line with findings from lab experiments, results show that beliefs adjust to better predict true performance when feedback is received. Beliefs also become more precise (lower variance) with feedback. Evidence of behaviour change (time spent on the course) in response to feedback is also noted. The latter finding might account for some of the incomplete adjustment of beliefs often noted in the literature.
Severe Ovarian Hyperstimulation Syndrome with Minimal Ovarian Enlargement: A Case Report
Authors: Shand Karen L. , Haines Christopher J. , Loong Edward P. L.
Published: December 2020

Abstract

Severe ovarian hyperstimulation syndrome is an uncommon but potentially lethal complication of treatment with in vitro fertilization and other assisted reproductive technologies. We describe such a case which was atypical in that ascites and hydrothorax occurred despite the absence of ovarian enlargment. Whilst the pathophysiology of the syndrome remains unclear, the clinician must remain alert to the possibility of such an unusual presentation of this syndrome.
Assessment of Follicular Maturity by Follicular Diameter and Fluid Volume in a Program of in vitro Fertilization and Embryo Transfer
Authors: Nataprawira Dudy S. , Harada Tasuku , Sekijima Akio , Mio Yasuyuki , Terakawa Naoki
Published: December 2020

Abstract

We compared the assessment of follicular maturity by follicular diameter or follicular fluid (FF) volume and the subsequent fertilization and cleavage of the oocytes in 36 patients who had ovarian stimulation performed for in vitro fertilization and embryo transfer (IVF‐ET). All patients received clomiphene citrate and human menopausal gonadotropin. The daily growth of follicles was assessed ultrasonically for 6 consecutive days before oocyte collection. The follicular diameter was found to be well correlated with the volume of follicular fluid. There were no significant differences among the dominant, second, and third follicles in the rates of oocyte recovery, maturation, fertilization, or cleavage. The rates of oocyte maturation and fertilization in FF volumes of 5.1 to 7.0 ml were significantly higher than in volumes of 1.1 to 5.0 ml, but the cleavage rates were similar. A smaller percentage of embryos developed to the four‐cell stage when the oocytes were recovered from follicles with volumes of 1.1 to 3.0 ml. These observations suggest that follicular volume is a good parameter for judging the maturity of oocytes. It is also suggested that, although the oocytes of small follicles can be fertilized and cleaved, oocytes from larger follicles may have a better developmental capacity.
Investigating the relationship between organizational justice, job satisfaction, and intention to leave the nursing profession: A cross‐sectional study
Authors: Zahednezhad Hosein , Hoseini Mohammad Ali , Ebadi Abbas , Farokhnezhad Afshar Pouya , Ghanei Gheshlagh Reza
Published: December 2020

Aims

This study aims to test a hypothetical model linking various dimensions of organizational justice to the job satisfaction and nurses' intention to leave the profession based on the theoretical assumptions of the Alexander model of voluntary turnover.

Design

A cross‐sectional survey.

Methods

This study was conducted on 317 inpatient ward nurses of six teaching hospitals in Tehran, Iran during 1 September 2017–14 November 2018. Clinical nurses were recruited by a multistage random sampling. Data were collected using structured questionnaires of organizational justice, job satisfaction, and nurses' intention to leave. Data were analysed by structural equation modelling using Amos 22 statistical program.

Results

The structural equation model demonstrated adequate fit and the hypothesized correlations were partially supported. The findings suggested that the distributive justice (p < .001; β = 0.24) and interactional justice (p < .001; β = 0.44) could indirectly affect the nurses' intention to leave the nursing profession via the direct impact on job satisfaction, while job satisfaction had a significant, negative effect on the nurses' intention to leave (p < .001; β = −0.71).

Conclusions

According to the results, the model fit was acceptable, suggesting the validity of the final model. Furthermore, distributive and interactional justice could reduce the intention to leave the nursing profession by influencing the job satisfaction of the clinical nurses.

Impact

This was one of the first studies to determine the aspects of justice that must be further emphasized by healthcare managers to increase the job satisfaction of nurses and their retention in healthcare systems. The findings indicated that fair interactions have a greater impact on job satisfaction and retention of nurses than procedural and distributive justice. The results of this study provide valuable references for nursing managers to increase the job satisfaction of nurses and their retention in healthcare settings.
The relationship between adverse interpersonal experiences and self‐esteem in people with intellectual disabilities: The role of shame, self‐compassion and social support
Authors: Davies Lauren , Randle‐Phillips Cathy , Russell Ailsa , Delaney Claire
Published: December 2020

Background

People with intellectual disabilities are reported to have low self‐esteem and to experience high rates of adverse interpersonal experiences (AIEs). This study aimed to investigate whether shame and self‐compassion mediate the relationship between AIEs and self‐esteem for people with intellectual disabilities and whether perceived social support moderates this relationship.

Method

This study employed a cross‐sectional design, involving between‐group comparisons. Forty‐seven people with intellectual disabilities and 50 people without intellectual disabilities completed self‐report questionnaires measuring shame, self‐compassion, self‐esteem, early AIEs and social support.

Results

Shame and self‐compassion were found to mediate the relationship between AIEs and self‐esteem for people with intellectual disabilities. There was no evidence for a moderating effect of social support and no difference between groups in shame or self‐compassion.

Conclusions

The findings suggest shame and self‐compassion are important concepts for people with intellectual disabilities. Clinical and research implications are discussed.
Knowledge and attitude toward mental health and mental health problems among secondary school students in Jordan
Authors: AlAzzam Manar , Abuhammad Sawsan
Published: December 2020

Objective

Examine secondary school students' knowledge and attitude about mental health, mental health problems, and interacting with people with mental health problems.

Methods

A survey was carried out with 500 students in secondary schools in the northern area of Jordan.

Results

A variance in knowledge and attitude was predicted by the regression model. Family income, having a family member with a mental disorder, and experience with people with mental health problems were the major predictors of knowledge about and attitude toward interacting with people with mental health problems.

Conclusion

The results indicate that secondary school students have low knowledge about mental health problems and people with mental health problems. Moreover, they have a negative attitude toward interacting with people with mental health problems. Hence, there is a strong need to better educate young people about mental health and the diverse types of mental health problems that exist, as well as to help them to develop a more constructive and appropriate attitude.

Implications for Practice

Improving the scope of the school curriculum on topics relating to people with mental health problems would help students to make more objective evaluations of people with mental health problems.
A simple pacing maneuver to unmask an epicardial connection involving the right‐sided pulmonary veins
Authors: Hasebe Hideyuki , Yoshida Kentaro , Nogami Akihiko , Furuyashiki Yoshitaka , Hanaki Yuichi , Baba Masako , Ieda Masaki
Published: December 2020

Introduction

An epicardial connection (EC) between the right‐sided pulmonary venous (PV) carina and right atrium (RA) is one of the mechanisms for which carinal ablation is required for right‐sided PV isolation. The purpose of the study was to devise a simple pacing maneuver to differentiate an EC from a residual conduction gap on the antral ablation line during radiofrequency catheter ablation.

Methods and Results

This study included 133 consecutive patients. After one round of ablation, electrograms at the posterior antrum outside the ablation line were recorded during sinus rhythm (SR) and coronary sinus (CS) pacing, and intervals between the antral and PV potentials were measured in each rhythm. The ΔintervalSR‐CS was calculated as the difference between the interval during SR and that during CS pacing. Presence of an EC was confirmed by observation of a RA posterior wall breakthrough during right‐sided PV pacing, which was then targeted for ablation. Patients with nonachievement of first‐pass isolation (N = 35) and with PV reconnection during the procedure (N = 9) were classified into the EC‐group (N = 20) and gap‐group (N=24), respectively. The prevalence of carina breakthrough during SR was higher in the EC‐group than the gap‐group (18 [95%] vs. 1 [4%] patients, p < .0001). The ΔintervalSR‐CS was larger in the EC‐group versus gap‐group (71 [interquartile range, 57–97] vs. 6 [2–9] ms, p < .0001). In all patients with an EC, RA ablation resulted in delay (32 [20–40] ms) (N = 15) or elimination of PV potentials (N = 5).

Conclusion

An EC can be efficiently discriminated from a conduction gap by a simple pacing maneuver.