bluuebunny/crossref_metadata_2025_split huggingface dataset:
Liposomal phytohemagglutinin: In vivo T‐cell activator as a novel pan‐cancer immunotherapy
Authors: Alhallak Kinan , Sun Jennifer , Muz Barbara , Jeske Amanda , O’Neal Julie , Ritchey Julie K. , Achilefu Samuel , DiPersio John F. , Azab Abdel Kareem 
Published: January 2022

AbstractImmunotherapy is an attractive approach for treating cancer. T‐cell engagers (TCEs) are a type of immunotherapy that are highly efficacious; however, they are challenged by weak T‐cell activation and short persistence. Therefore, alternative solutions to induce greater activation and persistence of T cells during TCE immunotherapy is needed. Methods to activate T cells include the use of lectins, such as phytohemagglutinin (PHA). PHA has not been used to activate T cells in vivo, for immunotherapy, due to its biological instability and toxicity. An approach to overcome the limitations of PHA while also preserving its function is needed. In this study, we report a liposomal PHA which increased PHA stability, reduced toxicity and performed as an immunotherapeutic that is able to activate T cells for the use in future cancer immunotherapies to circumvent current obstacles in immunosuppression and T‐cell exhaustion.
Analysis of the structure and function of the epidermal barrier in patients with ichthyoses—clinical and electron microscopical investigations
Authors: Fölster‐Holst R. , Naß C. , Dähnhardt‐Pfeiffer S. , Freitag‐Wolf S. 
Published: January 2022

AbstractBackgroundIchthyoses are pathogenetically characterized by a pronounced disorder of the epidermal barrier. Clinically, hyperkeratosis, severe scaling and erythroderma are present on the entire integument. The time‐consuming therapy includes daily baths and the application of skin care products to restore the epidermal barrier.Objectives and methodsTo enhance the knowledge about the structure and function of the epidermal barrier in ichthyoses, we conducted clinical, biophysical and electron microscopical measurements on 46 patients with ichthyoses, including autosomal recessive ichthyoses, keratinopathic ichthyoses, X‐chromosomal‐recessive ichthyosis and Netherton syndrome.ResultsThe patients displayed a significantly decreased skin hydration along with unexpectedly low transepidermal waterloss values. Electron microscopical examinations demonstrated a severe occlusion of the epidermis by lipid remnants of skin care products in the stratum corneum. We found decreased intercellular lipid lamellae and an increased undulation of the corneocyte membrane of all ichthyoses, mostly pronounced in Netherton syndrome. The lipid profiles of ichthyoses showed decreased esterified Ω‐hydroxy‐sphingosine (EOS) ceramide levels.ConclusionsThe results demonstrate the extent of the epidermal barrier disruption in ichthyoses. In combination with the knowledge about pathogenetic causes, individually improved therapeutic options can be derived from our results. In the future, the analyses of the organization of intercellular lipid lamellae and corneocyte membrane undulation will enable improved investigations of the epidermal barrier in ichthyoses and may be used to study and evaluate possible effects of topical skin preparations.
How precision medicine changes medical epistemology: A formative case from Norway
Authors: Vogt Henrik , Hofmann Bjørn 
Published: January 2022

AbstractRationale and AimsPrecision 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.MethodWe 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 DiscussionThe 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’.ConclusionA 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

AbstractCiliates 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

AbstractIn 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

AbstractPurposeTo 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.MethodsWe 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.ResultsOne 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).ConclusionsClinicians 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.
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

Summary

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.
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

SummaryWe 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

AbstractThe 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

AbstractPulmonary 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

AbstractE-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

AbstractAlthough 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.