bluuebunny/crossref_metadata_2025 huggingface dataset:
How precision medicine changes medical epistemology: A formative case from Norway
Authors: Vogt Henrik , Hofmann Bjørn
Published: January 2022

Rationale and Aims

Precision medicine (PM) raises a key question: How do we know what works when the number of people with a health problem becomes small or one (n = 1)? We here present a formative case from Norway. The Norwegian Board of Health Supervision was faced with a cancer patient, who had improved after treatment with a drug in the private health sector but was refused continued treatment in the public health service due to lack of clinical trial evidence. The Board overturned this decision, arguing that the drug had been unambiguously documented to work in the individual case. We aim to provide an in‐depth analysis of this case and The Board's decision and thereby to illustrate and elucidate key epistemological and ethical issues and developments in PM.

Method

We provide our analysis and discussion using tools of critical thinking and concepts from philosophy of science and medicine, such as uncertainty, evidence, forms of inference and causation. We also examine the case in light of the history of evidence‐based medicine (EBM).

Results and Discussion

The case reflects an epistemological shift in medicine where PM puts greater emphasis on evidence that arises in individual patients after the treatment is provided over pre‐existing population‐based evidence. PM may rely more heavily on abduction to decide what works and qualitative, rather than quantitative judgements. The case also illustrates a possible shift in the concept of causation from regularity accounts to mechanistic and process accounts. We discuss the ethical implications of a shift from more ‘traditional’ to ‘personalised EBM’.

Conclusion

A framework that is more based on abductions and evidence arising in the individual case has problems in creating quantifiable, reliable and generalisable evidence, and in promoting transparency and accountability. PM currently lacks clear criteria for deciding what works in an individual, posing ethical challenges.
Bioactive molecules from ciliates: Structure, activity, and applicative potential
Authors: Alimenti Claudio , Buonanno Federico , Di Giuseppe Graziano , Guella Graziano , Luporini Pierangelo , Ortenzi Claudio , Vallesi Adriana
Published: January 2022

Ciliates are a rich source of molecules synthesized to socialize, compete ecologically, and interact with prey and predators. Their isolation from laboratory cultures is often straightforward, permitting the study of their mechanisms of action and their assessment for applied research. This review focuses on three classes of these bioactive molecules: (i) water‐borne, cysteine‐rich proteins that are used as signaling pheromones in self/nonself recognition phenomena; (ii) cell membrane‐associated lipophilic terpenoids that are used in interspecies competitions for habitat colonization; (iii) cortical granule‐associated molecules of various chemical nature that primarily serve offence/defense functions.
Straightforward upriver migration to spawning sites by chum salmon Oncorhynchus keta homing to coastal short rivers in the Sanriku region
Authors: Nobata Shigenori , Sato Katsufumi , Houki Shouji , Ito Motohiro , Aoki Yoshinori , Kitagawa Takashi , Hyodo Susumu
Published: January 2022

In chum salmon (Oncorhynchus keta) homed to the Sanriku region, Japan, most of the fish are matured in bays and spawn near river mouths in coastal short rivers; therefore, their upriver migration is extremely short, but their behavioural characteristics have remained unknown. Upriver migration in the Otsuchi River, a typical coastal river, was evaluated from behavioural and physiological aspects. Homing salmon tracked in Otsuchi Bay held in the inner bay for less than 1 day to more than 10 days before river entry. The varied holding duration was negatively correlated with plasma 17α, 20β‐dihydroxy‐4‐pregnen‐3‐one (DHP) concentration, an indicator of maturation. After river entry, however, most fish were captured in weirs near the river mouths within 2 days regardless of the DHP concentration. Of the 34 fish released in the river, on the contrary, eighteen and five fish were seen next day in the main spawning sites located at c. 1.5 km upstream and in the branch creek, respectively, and 85% of the fish held position there until their death. The mean survival time of released fish was 5.8 days. Plasma DHP level suggested that preparations for spawning were already completed at the timing of the release. Taken together, homing salmon completed spawning preparation in the bay, and then they moved to their spawning sites immediately after river entry and spawned there during their short remaining life. This upriver migration contrasts with those of other populations, such as early migrants and long river migrants, whose maturation is completed during upriver migration.
Overdiagnosis of urinary tract infections by nursing home clinicians versus a clinical guideline
Authors: Kistler Christine E. , Wretman Christopher J. , Zimmerman Sheryl , Enyioha Chineme , Ward Kimberly , Farel Claire E. , Sloane Philip D. , Boynton Marcella H. , Beeber Anna S. , Preisser John S.
Published: January 2022

Purpose

To inform overprescribing and antibiotic stewardship in nursing homes (NHs), we examined the concordance between clinicians' (NH primary care providers and registered nurses) diagnosis of suspected UTI with a clinical guideline treated as the gold standard, and whether clinician characteristics were associated with diagnostic classification.

Methods

We conducted a cross‐sectional web‐based survey of a U.S. national convenience sample of NH clinicians. The survey included a discrete choice experiment with 19 randomly selected clinical scenarios of NH residents with possible UTIs. For each scenario, participants were asked if they thought a UTI was likely. Responses were compared to the guideline to determine the sensitivity and specificity of clinician judgment and performance indicators. Multivariable logistic mixed effects regression analysis of demographic, work, personality, and UTI knowledge/attitudes characteristics was conducted.

Results

One thousand seven hundred forty‐eight NH clinicians responded to 33,212 discrete choice scenarios; 867 (50%) were NH primary care providers and 881 (50%) were NH registered nurses, 39% were male, and the mean age was 45 years. Participants were uncertain about diagnosis in 30% of scenarios. Correct classification occurred for 66% of all scenarios (providers: 70%; nurses: 62%). Respondent judgment had a sensitivity of 78% (providers: 81%; nurses: 74%) and specificity of 54% (providers: 59%; nurses: 49%) compared to the clinical guideline. Adjusting for covariates in multivariable models, being a nurse and having higher closemindedness were associated higher odds of false positive UTI (odds ratio [OR] 1.61, p < 0.001; and OR 1.09, p = 0.039, respectively), although higher UTI knowledge and conscientiousness were associated with lower odds of false positive UTI ratings (OR 0.80, p < 0.001; OR 0.90, p = 0.005, respectively).

Conclusions

Clinicians tend to over‐diagnose urinary tract infections, necessitating systems‐based interventions to augment clinical decision‐making. Clinician type, UTI knowledge, and personality traits may also influence behavior and deserve further study.
Postracial Policing, “Mother Tongue” Sourcing, and Images of Singlish Standard
Authors: Babcock Joshua
Published: January 2022

After decades of denigration and targeting by the state, Singlish—or Singaporean Colloquial English—has come into its own as a “uniquely Singaporean” phenomenon (Wee 2018), both a source and site of projects of raciolinguistic value‐creation (Rosa and Flores 2017). Today, Singlish is often presented as emblematic of broader “racial harmony” among Singapore’s four official races, yet it has also become an arena for articulating and rejecting critiques of racialized Chinese‐Singaporean majoritarian privilege. This paper analyzes interviews with literary producers, public presentations by artists, and published mediatized texts in which Singlish comes into being as a site of ideological contestation. It describes two contrastive figures and the discourse registers through which they are materialized: first, postracial policing, voiced as an insistence that Singlish is sui generis, and second, “Mother Tongue” sourcing, voiced as an insistence on adherence, in spelling and pronunciation, to the racialized “Mother Tongue” varieties (and their racialized speakers) from which Singlish items are sourced. I argue that these two figures and enregistered positions co‐participate in the production of an image of standard: a felt sense of standard‐likeness that emerges as an effect of aesthetic textuality (Nakassis 2019), even in the absence of overt standardization projects.
I Am Whatever I Say I Am: The Salient Identity Content of U.S. Adolescents
Authors: Johnson Sara K. , Odjakjian Katharine , Park Yerin
Published: January 2022

Research about identity development has focused primarily on researcher‐chosen domains or overlooked content entirely. To investigate the content that is salient to adolescents, we analyzed responses to a shortened Twenty Statements Test (ten answers to the question, “Who am I?”) from 415 adolescents in the northeastern United States (Mage = 13.59 years; 63.7% girls, about 50% identified as White/European American). Inductive content analysis identified four Content codes (what the participants wrote: Personal, Social categories, Relationships, Self‐evaluation) and two Structure codes (how they wrote their statements: Qualifiers and Verb Tense). Content codes appeared in eight patterns, and there were between‐group differences in content and patterns. Results expand our understanding of adolescents’ identity content and demonstrate its complexity.
An aspartic protease 47 causes quantitative recessive resistance to rice black‐streaked dwarf virus disease and southern rice black‐streaked dwarf virus disease
Authors: Wang Zhaoyun , Zhou Lian , Lan Ying , Li Xuejuan , Wang Jian , Dong Jingfang , Guo Wei , Jing Dedao , Liu Qing , Zhang Shaohong , Liu Zhiyang , Shi Wenjuan , Yang Wu , Yang Tifeng , Sun Feng , Du Linlin , Fu Hua , Ma Yamei , Shao Yudong , Chen Luo , Li Jitong , Li Shuo , Fan Yongjian , Wang Yunyue , Leung Hei , Liu Bin , Zhou Yijun , Zhao Junliang , Zhou Tong
Published: January 2022

Rice black‐streaked dwarf virus disease (RBSDVD) and southern rice black‐streaked dwarf virus disease (SRBSDVD) are the most destructive viral diseases in rice. Progress is limited in breeding due to lack of resistance resource and inadequate knowledge on the underlying functional gene.

Using genome‐wide association study (GWAS), linkage disequilibrium (LD) decay analyses, RNA‐sequencing, and genome editing, we identified a highly RBSDVD‐resistant variety and its first functional gene.

A highly RBSDVD‐resistant variety W44 was identified through extensive evaluation of a diverse international rice panel. Seventeen quantitative trait loci (QTLs) were identified among which qRBSDV6‐1 had the largest phenotypic effect. It was finely mapped to a 0.8–1.2 Mb region on chromosome 6, with 62 annotated genes. Analysis of the candidate genes underlying qRBSDV6‐1 showed high expression of aspartic proteinase 47 (OsAP47) in a susceptible variety, W122, and a low resistance variety, W44. OsAP47 overexpressing lines exhibited significantly reduced resistance, while the knockout mutants exhibited significantly reduced SRBSDVD and RBSDVD severity. Furthermore, the resistant allele Hap1 of OsAP47 is almost exclusive to Indica, but rare in Japonica.

Results suggest that OsAP47 knockout by editing is effective for improving RBSDVD and SRBSDVD resistance. This study provides genetic information for breeding resistant cultivars.
Fish resist temptation from junk food: state‐dependent diet choice in reproductive Atlantic codGadus morhuafacing seasonal fluxes of lipid‐rich prey
Authors: van Deurs Mikael , Persson Anders , Nilsson P. Anders , Jørgensen Christian
Published: January 2022

In ecological sciences, animal diets are often simplified to ‘resources' or ‘caloric quantities'. However, in the present study, we investigated the optimal foraging strategy of Atlantic codGadus morhuawhen both macro‐ and micro‐nutritional requirements are accounted for. Proteins cannot be synthesized from fatty acids, so the proteins for gonad development must come from other dietary sources. In addition, micronutrients are required in smaller quantities. For example, for cod, arachidonic acid (ARA) acts as a micronutrient precursor for prostaglandins, which is important for reproduction. We formulated a dynamic state‐dependent model to make predictions about optimal diet choice and foraging behavior. We applied the model to a case study in the strait between Denmark and Sweden. The model predicted that energy acquired from dietary protein should be twice that acquired from lipids, with a small increase in the lipid requirements when gonads are growing. The model also predicted that the ‘energy sparing effect of lipids' made it beneficial to engage in risky foraging activity to supplement a lean diet with a little bit of fat. When we constructed the model to also optimize ARA uptake, the cod consumed relatively more ARA‐rich crabs in the months prior to spawning, despite the otherwise poor energetic value of this prey. In support of the model predictions, field observations indicated that lipid stores reached a peak shortly after the arrival of the lipid‐rich migrating herring and the fatty acid signal of these herring were evident in the liver of nearly all cod. Three month later, only half of the cod contained the herring‐derived fatty acid signal, supporting the predicted shift in prey type prior to spawning. From these model predictions and field observations, we conclude that, also in the wild, nutritional requirements can be at least as important as pure energy acquisition.
Non‐native species drive biotic homogenization, but it depends on the realm, beta diversity facet and study design: a meta‐analytic systematic review
Authors: Petsch Danielle Katharine , Bertoncin Ana Paula dos Santos , Ortega Jean Carlo Gonçalves , Thomaz Sidinei Magela
Published: January 2022

While reducing the species richness of invaded communities is a well‐known consequence of biological invasions, non‐native species can also reduce variability between communities over time (i.e. beta diversity) in a process known as biotic homogenization. Although biotic homogenization due to non‐native species is a common topic of theoretical reviews, we believe no global meta‐analysis on the effect of non‐native species on beta diversity has been carried out yet. Here, we systematically show that non‐native species drive biotic homogenization, but it depends on the realm, beta diversity facet and study design. Biotic homogenization was more intense in marine and freshwater ecosystems than in terrestrial ecosystems. We also found that non‐native species reduced both taxonomic and phylogenetic beta diversity, but not the functional beta diversity. Finally, we observed more intense effects using ‘before versus after invasion' followed by ‘uninvaded versus invaded sites' while the effect size of studies using ‘communities associated with native versus non‐native species' did not differ from zero. Our findings highlight that non‐native species contribute to biotic homogenization as a prevalent pattern in communities worldwide, and that biodiversity conservation strategies should go beyond investigating the reduction in the number of species by also taking into account beta diversity in its multiple facets.
Development of an efficient marker‐free soybean transformation method using the novel bacterium Ochrobactrum haywardense H1
Authors: Cho Hyeon‐Je , Moy York , Rudnick Nathan A. , Klein Theodore M. , Yin Jiaming , Bolar Joy , Hendrick Carol , Beatty Mary , Castañeda Leandro , Kinney Anthony J. , Jones Todd J. , Chilcoat N. Doane
Published: January 2022

We have discovered a novel bacterium, Ochrobactrum haywardense H1 (Oh H1), which is capable of efficient plant transformation. Ochrobactrum is a new host for Agrobacterium‐derived vir and T‐DNA‐mediated transformation. Oh H1 is a unique, non‐phytopathogenic species, categorized as a BSL‐1 organism. We engineered Oh H1 with repurposed Agrobacterium virulence machinery and demonstrated Oh H1 can transform numerous dicot species and at least one monocot, sorghum. We generated a cysteine auxotrophic Oh H1‐8 strain containing a binary vector system. Oh H1‐8 produced transgenic soybean plants with an efficiency 1.6 times that of Agrobacterium strain AGL1 and 2.9 times that of LBA4404Thy‐. Oh H1‐8 successfully transformed several elite Corteva soybean varieties with T0 transformation frequency up to 35%. In addition to higher transformation efficiencies, Oh H1‐8 generated high‐quality, transgenic events with single‐copy, plasmid backbone‐free insertion at frequencies higher than AGL1. The SpcN selectable marker gene is excised using a heat shock‐inducible excision system resulting in marker‐free transgenic events. Approximately, 24.5% of the regenerated plants contained only a single copy of the transgene and contained no vector backbone. There were no statistically significant differences in yield comparing T3 null‐segregant lines to wild‐type controls. We have demonstrated that Oh H1‐8, combined with spectinomycin selection, is an efficient, rapid, marker‐free and yield‐neutral transformation system for elite soybean.
Competition and coopetition for two‐sided platforms
Authors: Cohen Maxime C. , Zhang Renyu
Published: January 2022

Two‐sided platforms have become omnipresent. In this context, firms compete not only for customers but also for flexible self‐scheduling workers who can work for multiple platforms. We consider a setting where two‐sided platforms simultaneously choose prices and wages to compete on both sides of the market. We assume that customers and workers each follow an endogenous generalized attraction model that accounts for network effects. In our model, the behavior of an agent depends not only on the price or wage set by the platforms, but also on the strategic interactions among agents on both sides of the market. We show that a unique equilibrium exists and that it can be computed using a tatônnement scheme. The proof technique for the competition between two‐sided platforms is not a simple extension of the traditional (one‐sided) setting and involves different arguments. Armed with this result, we study the impact of coopetition between two‐sided platforms, that is, the business strategy of cooperating with competitors. Motivated by recent practices in the ride‐sharing industry, we analyze a setting where two competing platforms engage in a profit sharing contract by introducing a new joint service. We show that a well‐designed profit sharing contract (e.g., under Nash bargaining) will benefit every party in the market (platforms, riders, and drivers), especially when the platforms are facing intensive competition on the demand side. However, if the platforms are facing intensive competition on the supply side, the coopetition partnership may hurt the profit of at least one platform.
Idebenone relieves the damage of heat stress on the maturation and developmental competence of porcine oocytes
Authors: Shi Xue‐Ying , Jin Xiao‐Hu , Lin Jing‐Yi , Sun Liang‐Zhen , Liu Xue , Zhang Tian‐Yu , Wang Mo‐Ran , Yue Shun‐Li , Zhou Jia‐Bo
Published: January 2022

The reproductive function of animals is often affected by climatic conditions. High‐temperature conditions can cause damage to oocyte maturation and embryonic development in a variety of ways. The purpose of this study was to prove that supplementation idebenone (IDB) to the maturation medium can improve the maturation and development of porcine oocytes after heat stress (HS). Porcine cumulus‐oocyte complexes (COCs) were cultured in the maturation medium with different concentrations of IDB (0, 0.1, 1 and 10 μM) for 44 hr at either 38.5°C or under the HS conditions. The cumulus oophorus expansion, nuclear maturation and blastocyst rate after parthenogenetic activation (PA) were measured. We found that HS (in vitro maturation 20–24 hr, 42°C) exposure significantly reduced cumulus expansion index and maturation rate of oocytes and the blastocyst rate of PA embryos, while IDB supplementation significantly improved oocyte maturation and development to the blastocysts stage after PA. Moreover, the addition of IDB decreased the intracellular level of ROS and increased GSH content, hence enhancing the antioxidant capacity of oocytes under HS. Meanwhile, IDB treatment also obviously improved the mitochondrial membrane potential and ATP synthesis of oocytes under HS conditions. Furthermore, IDB treatment increased the expression of GDF9 and BMP15 in IVM oocytes which attribute to improve the quality and outcome of IVM oocytes and the development competence of PA embryos in pigs. In summary, we demonstrated that IDB supplementation into the maturation medium exerted protective effects and improved the ability of maturation and developmental competence of porcine oocytes exposed to HS.
Pulmonary functional MRI: Detecting the structure–function pathologies that drive asthma symptoms and quality of life
Authors: Kooner Harkiran K. , McIntosh Marrissa J. , Desaigoudar Vedanth , Rayment Jonathan H. , Eddy Rachel L. , Driehuys Bastiaan , Parraga Grace
Published: January 2022

Pulmonary functional MRI (PfMRI) using inhaled hyperpolarized, radiation‐free gases (such as 3He and 129Xe) provides a way to directly visualize inhaled gas distribution and ventilation defects (or ventilation heterogeneity) in real time with high spatial (~mm3) resolution. Both gases enable quantitative measurement of terminal airway morphology, while 129Xe uniquely enables imaging the transfer of inhaled gas across the alveolar–capillary tissue barrier to the red blood cells. In patients with asthma, PfMRI abnormalities have been shown to reflect airway smooth muscle dysfunction, airway inflammation and remodelling, luminal occlusions and airway pruning. The method is rapid (8–15 s), cost‐effective (~$300/scan) and very well tolerated in patients, even in those who are very young or very ill, because unlike computed tomography (CT), positron emission tomography and single‐photon emission CT, there is no ionizing radiation and the examination takes only a few seconds. However, PfMRI is not without limitations, which include the requirement of complex image analysis, specialized equipment and additional training and quality control. We provide an overview of the three main applications of hyperpolarized noble gas MRI in asthma research including: (1) inhaled gas distribution or ventilation imaging, (2) alveolar microstructure and finally (3) gas transfer into the alveolar–capillary tissue space and from the tissue barrier into red blood cells in the pulmonary microvasculature. We highlight the evidence that supports a deeper understanding of the mechanisms of asthma worsening over time and the pathologies responsible for symptoms and disease control. We conclude with a summary of approaches that have the potential for integration into clinical workflows and that may be used to guide personalized treatment planning.
False Discovery Rate Control with E-values
Authors: Wang Ruodu , Ramdas Aaditya
Published: January 2022

E-values have gained attention as potential alternatives to p-values as measures of uncertainty, significance and evidence. In brief, e-values are realized by random variables with expectation at most one under the null; examples include betting scores, (point null) Bayes factors, likelihood ratios and stopped supermartingales. We design a natural analogue of the Benjamini-Hochberg (BH) procedure for false discovery rate (FDR) control that utilizes e-values, called the e-BH procedure, and compare it with the standard procedure for p-values. One of our central results is that, unlike the usual BH procedure, the e-BH procedure controls the FDR at the desired level—with no correction—for any dependence structure between the e-values. We illustrate that the new procedure is convenient in various settings of complicated dependence, structured and post-selection hypotheses, and multi-armed bandit problems. Moreover, the BH procedure is a special case of the e-BH procedure through calibration between p-values and e-values. Overall, the e-BH procedure is a novel, powerful and general tool for multiple testing under dependence, that is complementary to the BH procedure, each being an appropriate choice in different applications.
Willingness to pay for COVID‐19 test and vaccine in South Africa and Ghana: A contingent valuation study
Authors: Ayifah Rebecca Nana Yaa , Ayifah Emmanuel
Published: January 2022

Although from a public health perspective, governments are expected to finance the cost of testing and vaccination against the COVID‐19 pandemic, most African countries do not have the resources to do these. Individuals' willingness to pay (WTP) for COVID‐19 testing and vaccination is thus crucial. We employ the Contingent Valuation Method to assess WTP for COVID‐19 testing and vaccine and also investigate factors associated with WTP in South Africa and Ghana. On average, respondents in South Africa are willing to pay US$16.29 for COVID‐19 testing, whereas those in Ghana are willing to pay US$9.69. In terms of the COVID‐19 vaccine, South Africans are willing to pay twice (US$41.83) as high as the amount Ghanaians are willing to pay (US$20.36). The results from the probit and tobit estimations on factors associated with WTP show that WTP for COVID‐19 testing and vaccine are correlated with income, education, employment, gender, having tested for COVID‐19, travel experience, and low satisfaction with the government's COVID‐19 measures. These findings suggest that the private sector can play a crucial role in COVID‐19 testing and the deployment of COVID‐19 vaccines because people are willing to pay. However, there may be a need for subsidisation for the poor.
Risk factors associated with unsuccessful tuberculosis treatment outcomes in Hunan Province, China
Authors: Gilmour Beth , Xu Zuhui , Bai Liqiong , Alene Kefyalew Addis , Clements Archie C. A.
Published: January 2022

Objectives

Globally, China has the third highest number of tuberculosis (TB) cases despite high rates (85.6%) of effective treatment coverage. Identifying risk factors associated with unsuccessful treatment outcomes is an important component of maximising the efficacy of TB control programmes.

Methods

Retrospective cohort study to evaluate the outcomes of 306,860 drug‐susceptible TB patients who underwent treatment in Hunan Province, China between 2013 and 2018. Univariable and multivariable logistic regression models were used to identify factors associated with unsuccessful TB treatment outcomes.

Results

A successful treatment outcome was recorded for 98.6% of patients, defined as the sum of patients who were cured (36.2%) and completed treatment (62.4%). An unsuccessful treatment outcome was recorded for 1.8% of patients, defined as the sum of treatment failure (1.1%), deaths (0.5%) and lost to follow up (0.2%). The odds of an unsuccessful treatment outcome showed an increasing trend in more recent years of registration (2018 adjusted odds ratio (AOR): 1.43; 95% Confidence Interval (CI) 1.31, 1.57 relative to 2013). Other significant risk factors were male sex (AOR: 1.17; 95% CI 1.10, 1.25); increasing age (AOR:1.02 per year increase; 95% CI 1.02,1.02); being severely ill (AOR: 1.50; 95% CI 1.33, 1.70); having a history of TB treatment (AOR: 2.93; 95% CI 2.69, 3.20); not being under systematic management (AOR: 16.10 (14.49, 17.88) and treatment regimens that differed from full course management.

Conclusions

The increasing likelihood of an unsuccessful treatment outcome over time necessitates the need for further research.
Prolonged twice‐daily administration of oclacitinib for the control of canine atopic dermatitis: a retrospective study of 53 client‐owned atopic dogs
Authors: Denti Daria , Caldin Marco , Ventura Laura , De Lucia Michela
Published: January 2022

Background

Oclacitinib administered at the licensed dose twice daily for two weeks and then once daily as required is recommended for the treatment of atopic dogs. In some cases, the once‐daily regimen is insufficient to control the clinical signs.

Objectives

To provide preliminary safety and efficacy data on the prolonged twice‐daily administration of oclacitinib in atopic dogs.

Animals

Fifty‐three client‐owned atopic dogs.

Methods and materials

The medical records of dogs with atopic dermatitis treated with oclacitinib twice daily for more than two weeks were reviewed retrospectively. Animal details, treatment dose and duration, concurrent diseases, adjunctive medications and possible adverse events were recorded. Treatment efficacy was assessed retrospectively and, when available, the selected blood parameters before and during the treatment were compared. Statistical analyses of the collected data were performed.

Results

The median treatment duration was 113 days. Excellent‐to‐good efficacy was observed in 38 dogs (72%), including 24 of 33 dogs that failed to respond to the once‐daily regimen. Eight dogs showed a poor response despite the addition of systemic glucocorticoids. Pyoderma, gastrointestinal signs and otitis externa were the most frequent adverse events recorded whilst on treatment. Blood tests performed in 35 dogs showed slightly decreased leucocyte, neutrophil, eosinophil and monocyte counts that remained within the reference ranges in most cases. Three dogs developed hypercholesterolemia.

Conclusions and clinical relevance

Prolonged twice‐daily administration of oclacitinib generally was well‐tolerated and was effective in most of the treated dogs. Regular clinical evaluation and blood tests are advisable for this treatment regimen.
Effects of dual chelation therapy with deferasirox and deferoxamine in patients with beta thalassaemia major
Authors: Zargari Ahmad , Wu Simon , Greenway Anthea , Cheng Ken , Kaplan Zane
Published: January 2022

Background and Objectives

Patients with thalassaemia experience complications related to iron overload. In Australia currently, the two main options for iron chelation are deferasirox and deferoxamine. Optimal iron chelation using monotherapy can be limited due to toxicity or tolerability. Dual chelation therapy (DCT) may provide more aggressive iron chelation.

Material and Methods

A retrospective, observational study was performed on a state‐wide referral centre for patients receiving red cell transfusions for haemoglobinopathies (Monash Health, Australia). All patients prescribed DCT were identified using a local pharmacy dispensing database and were included in the study. Pre‐DCT initiation and post‐DCT completion were correlated with serum ferritin, cardiac iron loading (based on MRI T2* measurements) and liver iron content (LIC) using Wilcoxon signed‐rank test.

Results

A total of 18 patients (12 adults, 6 children) were identified as receiving DCT. All patients received a combination of deferasirox and deferoxamine. The median duration of therapy was 23 months (range 2–73). Median serum ferritin reduced by 42% (p = 0.004) and there was a 76% reduction in LIC (p = 0.062). No significant changes were seen in cardiac iron loading.

Conclusion

DCT over a prolonged period is effective at reducing serum ferritin and may contribute to improvement in liver iron loading.
Small-Molecule Mn Antioxidants in Caenorhabditis elegans and Deinococcus radiodurans Supplant MnSOD Enzymes during Aging and Irradiation
Authors: Gaidamakova Elena K. , Sharma Ajay , Matrosova Vera Y. , Grichenko Olga , Volpe Robert P. , Tkavc Rok , Conze Isabel H. , Klimenkova Polina , Balygina Irina , Horne William H. , Gostinčar Cene , Chen Xiao , Makarova Kira S. , Shuryak Igor , Srinivasan Chandra , Jackson-Thompson Belinda , Hoffman Brian M. , Daly Michael J.
Published: January 2022

The current theory of cellular defense against oxidative damage identifies antioxidant enzymes as primary defenders against ROS, with MnSOD being the preeminent superoxide (O
2
•−
) scavenger. However, MnSOD is shown to be dispensable both for radiation resistance and longevity in model organisms, the bacterium
Deinococcus radiodurans
and the nematode
Caenorhabditis elegans
.
Cleavage-Polyadenylation Factor Cft1 and SPX Domain Proteins Are Agents of Inositol Pyrophosphate Toxicosis in Fission Yeast
Authors: Schwer Beate , Garg Angad , Sanchez Ana M. , Bernstein Mindy A. , Benjamin Bradley , Shuman Stewart
Published: January 2022

Impeding the catabolism of the inositol pyrophosphate (IPP) signaling molecule IP8 is cytotoxic to fission yeast. Here, by performing a genetic suppressor screen, we identified several cellular proteins required for IPP toxicosis.
Tailoring Escherichia coli Chemotactic Sensing towards Cadmium by Computational Redesign of Ribose-Binding Protein
Authors: Li Hengyi , Zhang Changsheng , Chen Xi , You Hantian , Lai Luhua
Published: January 2022

Cadmium pollution is one of the major environmental problems due to excessive release and accumulation. New technologies that can auto-detect cadmium ions with good biocompatibility are in urgent need.
Intestinal Microbiota and Host Cooperate for Adaptation as a Hologenome
Authors: Zhou Hao , Yang Lingyu , Ding Jinmei , Dai Ronghua , He Chuan , Xu Ke , Luo Lingxiao , Xiao Lu , Zheng Yuming , Han Chengxiao , Akinyemi Fisayo T. , Honaker Christa F. , Zhang Yan , Siegel Paul B. , Meng He
Published: January 2022

The hologenome concept has broadened our perspectives for studying host-microbe coevolution. The multiomic analyses reported here involved two lines of chickens, from a common founder population, that had undergone long-term selection for high (HWS) or low (LWS) 56-day body weight.
Guideline for feedback of individual genetic research findings for genomics research in Africa
Authors: Matimba Alice , Ali Stuart , Littler Katherine , Madden Ebony , Marshall Patricia , McCurdy Sheryl , Nembaware Victoria , Rodriguez Laura , Seeley Janet , Tindana Paulina , Yakubu Aminu , de Vries Jantina
Published: January 2022

As human genomics research in Africa continues to generate large amounts of data, ethical issues arise regarding how actionable genetic information is shared with research participants. The Human Heredity and Health in Africa Consortium (H3Africa) Ethics and Community Engagement Working group acknowledged the need for such guidance, identified key issues and principles relevant to genomics research in Africa and developed a practical guideline for consideration of feeding back individual genetic results of health importance in African research projects. This included a decision flowchart, providing a logical framework to assist in decision-making and planning for human genomics research projects. Although presented in the context of the H3Africa Consortium, we believe the principles described, and the decision flowchart presented here is applicable more broadly in African genomics research.
Cultural influences on physical activity and exercise beliefs in patients with chronic kidney disease: ‘The Culture-CKD Study’—a qualitative study
Authors: Mayes Juliet , Castle Ellen M. , Greenwood James , Ormandy Paula , Howe P David , Greenwood Sharlene A.
Published: January 2022

Objectives

This study used a mixed-method approach to explore cultural and ethnic influences on the perception of, and decision to engage with or not to engage with, physical activity and exercise therapy in patients with chronic kidney disease (CKD).

Design

Qualitative research was conducted through the use of semistructured interviews and focus groups. Self-reported physical activity levels were measured using the General Practice Physical Activity Questionnaire (GPPAQ), and self-efficacy for exercise with Bandura’s Self-Efficacy for Exercise Scale.

Setting

This study was conducted in a non-clinical setting of a single National Health Service Hospital Trust between April 2018 and July 2019.

Participants

Participants >18 years of age with a diagnosis of CKD, from black African, black Caribbean, South Asian or white ethnicity were eligible for the study. 84 patients with a diagnosis of CKD (stages 2–5), aged 25–79 (mean age 57) were recruited. Semistructured interviews (n=20) and six single-sex, ethnic-specific focus group discussions were undertaken (n=36).

Outcomes

Primary outcome was to explore the perceptions, attitudes and values about exercise and physical activity in different ethnic groups through qualitative interviews, analysed using an inductive thematic analysis approach. Questionnaires were analysed using Pearson correlation to determine if there was a significant relationship between the self-efficacy and GPPAQ levels.

Results

Qualitative analysis provided four primary themes: I am who I am, Change of identity, Influences to physical activity and exercise and Support and education. Quantitative analysis using Pearson correlation revealed a significant correlation between GPPAQ levels of activity and self-efficacy to regulate exercise behaviour (r=−0.40, p=0.001).

Conclusion

Understanding the cultural, attitudes and beliefs of individuals with CKD from a variety of ethnic backgrounds is complex. Understanding of patients’ experiences, thoughts and beliefs may be of relevance to clinicians when designing CKD exercise services.

Trial registration number

NCT03709212; Pre-results.
Factors associated with peritraumatic stress symptoms among the frontline healthcare workers during the outbreak of COVID-19 in China
Authors: Qi Xinye , Wang Jiahui , Liu Jingjing , Amporfro Daniel Adjei , Wang Kexin , Liu Huan , Shah Saleh , Wu Qunhong , Hao Yanhua
Published: January 2022

Objectives

This study aimed to examine the prevalence of peritraumatic stress symptoms (PTSSs), perceived threat, social support and factors contributing to clinically significant PTSS among frontline COVID-19 healthcare workers (HCWs) in China.

Design and setting

An online survey through self-administered questionnaires was conducted from 18 February to 4 March 2020, during the outbreak of COVID-19.

Outcomes measures

PTSS was assessed using the post-traumatic stress disorder (PTSD) self-rating scale. Demographic and socioeconomic characteristics, self-reported health, physical/psychological symptoms, perceived threat from frontline work and perceived social support were investigated. Multivariable line regression analysis distinguished factors associated with HCWs’ PTSS scores.

Results

A total of 676 (58.1%) HCWs have shown clinically significant high levels of PTSS. Only 441 (37.9%) self-reported good health. Most had physical symptom(s) (915 (78.7%)), psychological symptom(s) (906 (77.9%)), inability to vent emotions (284 (24.4%)), emotional exhaustion (666 (57.3%)) and 1037 (89.2%) needed professional respect. Moreover, social support received was less than expected, and the receipt of psychological services/help scored the lowest (3.11±1.73). Combined psychological and physical symptoms, difficulty in releasing tension and venting emotions timely, fear of infection, emotional exhaustion and depersonalisation are significantly associated with PTSS scores among frontline HCWs. Working ≥8 hours, having the senior professional title, self-reported health, enjoying perfect protection and control measures, economic subsidy and control policy on reducing discriminatory practices are negatively correlated with PTSS scores.

Conclusions

During the outbreak of COVID-19, frontline HCWs experienced clinically significant high levels of PTSS and heavy workload, and the emergency resulted in their inadequate psychosocial support. If this is left unchecked, HCWs have a higher risk of developing PTSD. Early detection, identification and person-directed, targeted multidisciplinary interventions should be undertaken to address various influencing factors. Comprehensive measures, including setting up emotional release channels, as well as providing psychological and social support intervention for HCWs globally, are highly recommended.
Recognition of intracranial hypertension using handheld optical coherence tomography in children (RIO Study): a diagnostic accuracy study protocol
Authors: Rufai Sohaib R , Jeelani Noor ul Owase , Bowman Richard , Bunce Catey , Proudlock Frank A , Gottlob Irene
Published: January 2022

Introduction

Paediatric intracranial hypertension (IH) is a rare but serious condition that can pose deleterious effects on the brain and vision. Estimating intracranial pressure (ICP) in children is difficult. Gold standard direct ICP measurement is invasive and carries risk. It is impractical to routinely perform direct ICP measurements over time for all children at risk of IH. This study proposes to assess the diagnostic accuracy of handheld optical coherence tomography (OCT), a non-invasive ocular imaging method, to detect IH in children.

Methods and analysis

This is a prospective study evaluating the diagnostic accuracy of handheld OCT for IH in at risk children. Inclusion criteria include clinical and/or genetic diagnosis of craniosynostosis, idiopathic intracranial hypertension, space occupying lesion or other conditions association with IH and age 0–18 years old. Exclusion criteria include patients older than 18 years of age and/or absence of condition placing the child at risk of IH. The primary outcome measures are handheld OCT and 48-hour ICP assessments, which will be used for diagnostic accuracy testing (sensitivity, specificity, positive predictive value, negative predictive value and accuracy). Main secondary outcome measures include visual acuity, fundoscopic examination, contrast sensitivity, visual field testing and visual evoked potentials, wherever possible.

Ethics and dissemination

Ethical approval was granted for this study by the East Midlands Nottingham 2 Research Ethics committee (UOL0348/IRAS 105137). Our findings will be disseminated through presentation at relevant meetings, peer-reviewed publication and via the popular media.

Trial registration number

ISRCTN52858719
Characterising common challenges faced by parental caregivers of children with type 1 diabetes mellitus in mainland China: a qualitative study
Authors: Tong Huijuan , Qiu Feng , Fan Ling
Published: January 2022

Objectives

The mental state of parental caregivers affects outcomes in children with type 1 diabetes mellitus (T1DM). This study aimed to qualitatively examine perception of common challenges among parental caregivers of children with T1DM.

Setting

Semistructured interviews 45–60 min long were conducted with parental caregivers of children with T1DM. Interview recordings were transcribed and coded in NVivo V.11.0 to observe emergent themes.

Participants

Eligible T1DM caregiving parents (parent(s) and/or legal guardian(s)) were identified from caregivers attending visits with children hospitalised or assessed in the Pediatric Neuroendocrinology Department of Shengjing Hospital, China Medical University in Shenyang from January 2018 to June 2019.

Primary and secondary outcome measures

Not applicable.

Results

A total of 20 T1DM caregiving parents were interviewed, aged 30–53 years, including 7 fathers and 13 mothers, with their children whose mean age was 10.6±2.45 years. Content analysis revealed 5 major themes with 13 subthemes, including persistent psychological stress (catastrophic emotions, emotional distress and altered self-efficacy), family function change (altered family life patterns and changes in parental role/function), challenges in daily management (technical challenges, emotional regulation, parent–child conflict and transition of care autonomy from parent to child), financial burden (cost burden of treatment and altered family economics), and lack of social support (social activity limitations and insufficient support system).

Conclusions

The period of emotional disturbance during initial diagnosis, psychological stresses of long-term caregiving, and conflict emerging from transition from parental to child responsibility all can cause psychological response detrimental to parental caregivers and children with T1DM. This work provides compelling evidence for the role of assessment and intervention in parental caregivers’ psychological and emotional well-being in diabetes care, as well as for the necessity of improved social and school support for children with T1DM in China.
Feasibility of delivering and evaluating stratified care integrated with telehealth (‘Rapid Stratified Telehealth’) for patients with low back pain: protocol for a feasibility and pilot randomised controlled trial
Authors: Zadro Joshua R , Needs Christopher , Foster Nadine E , Martens David , Coombs Danielle M , Machado Gustavo C , Adams Cameron , Han Christopher S , Maher Christopher G
Published: January 2022

Introduction

Long waiting time is an important barrier to accessing recommended care for low back pain (LBP) in Australia’s public health system. This study describes the protocol for a randomised controlled trial (RCT) that aims to establish the feasibility of delivering and evaluating stratified care integrated with telehealth (‘Rapid Stratified Telehealth’), which aims to reduce waiting times for LBP.

Methods and analysis

We will conduct a single-centre feasibility and pilot RCT with nested qualitative interviews. Sixty participants with LBP newly referred to a hospital outpatient clinic will be randomised to receive Rapid Stratified Telehealth or usual care. Rapid Stratified Telehealth involves matching the mode and type of care to participants’ risk of persistent disabling pain (using the Keele STarT MSK Tool) and presence of potential radiculopathy. ‘Low risk’ patients are matched to one session of advice over the telephone, ‘medium risk’ to telehealth physiotherapy plus App-based exercises, ‘high risk’ to telehealth physiotherapy, App-based exercises, and an online pain education programme, and ‘potential radiculopathy’ fast tracked to usual in-person care. Primary outcomes include the feasibility of delivering Rapid Stratified Telehealth (ie, acceptability assessed through interviews with clinicians and patients, intervention fidelity, appointment duration, App useability and online pain education programme usage) and evaluating Rapid Stratified Telehealth in a future trial (ie, recruitment rates, consent rates, lost to follow-up and missing data). Secondary outcomes include waiting times, number of appointments, intervention and healthcare costs, clinical outcomes (pain, function, quality of life, satisfaction), healthcare use and adverse events (AEs). Quantitative analyses will be descriptive and inform a future adequately-powered RCT. Interview data will be analysed using thematic analysis.

Ethics and dissemination

This study has received approval from the Ethics Review Committee (RPAH Zone: X21-0221). Results will be published in peer-reviewed journals and presented at conferences.

Trial registration number

ACTRN12621001104842.