bluuebunny/crossref_metadata_2025 huggingface dataset:
“At least we finally found out what it was”: Dementia diagnosis in minoritized populations
Authors: Blinka Marcela D. , Gundavarpu Sneha , Baker Dorcas , Thorpe Roland J. , Gallo Joseph J. , Samus Quincy M. , Amjad Halima
Published: March 2023

Background

Disparities in diagnosis persist among persons living with dementia (PLWD); most research on delayed diagnosis relies on medical records or administrative claims. This study aimed to identify factors that delay or facilitate dementia diagnoses in racial or ethnic minoritized PLWD and elicit care partner perspectives on timing and effects of diagnosis.

Methods

Maryland‐based participants cared for a PLWD age 60 or older, self‐identified as Black/African/African‐American, Asian, or Hispanic/Latino, and spoke English. Nineteen care partner in‐depth, semi‐structured interviews were conducted and analyzed using conventional qualitative content analysis methods.

Results

Biological, sociocultural, and environmental factors delayed dementia diagnosis. Memory loss was the most common early symptom, but the onset was often subtle or perceived as normal aging. Stigma and secrecy surrounding dementia influenced recognition and discussion of dementia among families and communities. Diagnoses were family‐initiated and started in primary care. Care partners were divided in their perceptions of diagnosis timeliness and whether earlier diagnosis would have changed outcomes. Family reactions to dementia diagnoses varied; most participants expressed a strong sentiment of service and duty to care for older family members. Participants overwhelmingly felt the benefits of obtaining a dementia diagnosis outweighed harms.

Conclusions

Numerous factors affect dementia diagnosis in racial and ethnic minoritized PLWD. Normalization of brain health discussions and systematic, proactive discussion and detection of dementia in primary care may address multilevel barriers and facilitators to diagnosis. Systems‐level and community‐led public health interventions may also help address disparities in brain health education and dementia diagnosis.
Differential SW16.1 allelic effects and genetic backgrounds contributed to increased seed weight after soybean domestication
Authors: Chen Xianlian , Liu Cheng , Guo Pengfei , Hao Xiaoshuai , Pan Yongpeng , Zhang Kai , Liu Wusheng , Zhao Lizhi , Luo Wei , He Jianbo , Su Yanzhu , Jin Ting , Jiang Fenfen , Wang Si , Liu Fangdong , Xie Rongzhou , Zhen Changgen , Han Wei , Xing Guangnan , Wang Wubin , Zhao Shancen , Li Yan , Gai Junyi
Published: March 2023

Although seed weight has increased following domestication from wild soybean (Glycine soja) to cultivated soybean (Glycine max), the genetic basis underlying this change is unclear. Using mapping populations derived from chromosome segment substitution lines of wild soybean, we identified SW16.1 as the causative gene underlying a major quantitative trait locus controlling seed weight. SW16.1 encodes a nucleus‐localized LIM domain‐containing protein. Importantly, the GsSW16.1 allele from wild soybean accession N24852 had a negative effect on seed weight, whereas the GmSW16.1 allele from cultivar NN1138‐2 had a positive effect. Gene expression network analysis, reverse‐transcription quantitative polymerase chain reaction, and promoter‐luciferase reporter transient expression assays suggested that SW16.1 regulates the transcription of MT4, a positive regulator of seed weight. The natural variations in SW16.1 and other known seed weight genes were analyzed in soybean germplasm. The SW16.1 polymorphism was associated with seed weight in 247 soybean accessions, showing much higher frequency of positive‐effect alleles in cultivated soybean than in wild soybean. Interestingly, gene allele matrix analysis of the known seed weight genes revealed that G. max has lost 38.5% of the G. soja alleles and that most of the lost alleles had negative effects on seed weight. Our results suggest that eliminating negative alleles from G. soja led to a higher frequency of positive alleles and changed genetic backgrounds in G. max, which contributed to larger seeds in cultivated soybean after domestication from wild soybean. Our findings provide new insights regarding soybean domestication and should assist current soybean breeding programs.
Explaining with Intentional Omissions
Authors: Kärki Kaisa
Published: March 2023

Determining the human activity that social processes consist in is a central task for the philosophy of the social sciences. This paper asks: which conception of agency arising from contemporary action theory is the most suitable for social science explanation? It is argued that a movement‐centered, Davidsonian picture of agency is not suitable for explaining certain social processes such as strikes and boycotts because, instead of intentional bodily movements, they are explained by the intentional omissions of agents. I propose that instead of intentional bodily movements, social processes are better explained by phenomena in which an agent is taking an active relation both to her mental or bodily processes as well as to what is happening around her. Thus, to fully explain social processes, a comprehensive theory of agency that can account for intentional actions and intentional omissions and a conception of agency that includes both materialist and volitionalist aspects is needed.
Constructing the Anti‐Vaxxer: Discursive analysis of public deliberations on childhood vaccination
Authors: White Jessica B. C. , O'Doherty Kieran C.
Published: March 2023

Public deliberation is a form of dialogue that allows members of the public to provide input on a policy issue. Public deliberation processes invite participants to engage with each other respectfully, learn about the topic and each other's perspectives, and then work together toward solutions to an issue that are broadly acceptable. In this article, we develop a discursive psychological analysis of public deliberation on the topic of childhood vaccination. In particular, we focus on how descriptions of a parent who did not have her children vaccinated were developed iteratively by a small group of deliberants; how these descriptions came to be accepted as factual; and how these descriptions came to be used to support normative claims about childhood vaccination. Our main argument is that we can develop a deeper understanding of deliberation processes if we understand participants' statements to be rhetorically organised. This is achieved by examining how descriptions of events or people that are relevant to the final conclusions of the group are developed in the course of deliberation; how they come to be accepted as factual and accurate by the group; and how they then become instrumental in supporting a final consensus position.
Prevalence and antibiotic resistance of Aeromonas schubertii causing internal white spot disease on snakehead fish, Channa striata, in the Mekong Delta, Vietnam
Authors: Pham Thi Hai Ha , Kim Do‐Hyung , Quach Van Cao Thi , Nguyen Phuong Thuy , Nguyen Thanh Luan
Published: March 2023

Snakehead, Channa striata, has a long history of invasion and associated negative impacts on the biodiversity of native aquatic organisms in the Mekong Delta. However, internal white spot disease caused by Aeromonas schubertii has a massive effect on the production of snakehead fish but also can spread to wild populations and to consumers. The aim of the study was to investigate the prevalence of multi‐antibiotic resistance (MAR) of A. schubertii isolated from snakehead fish cultured in several Mekong Delta fish farms, as well as its potential to spread throughout the infection season. Based on morphological and biochemical tests, as well as phylogenetic analysis of three housekeeping genes (16S rRNA, gyrB, and rpoD), isolates recovered from white nodules were strongly identified as A. schubertii. The antibiotic susceptibility testing revealed that all of the isolates (n = 25) were phenotypically multidrug‐resistant, with resistance to erythromycin (84%), rifampicin (84%), flumequine (88%), amoxicillin (96%), ciprofloxacin (92%), and florfenicol (92%). The multiple antibiotic resistance indices ranged from 0.33 to 0.92, with A. schubertii isolate As28 being resistant against 11 out of the 12 tested antibiotics. In particular, 15 MAR phenotypes (MARPs) were found in 25 isolates with 8 isolates (32%) commonly displaying MAR phenotypes against patterns of Ery–Rif–Flq–Aml–Cip–Flo, and four isolates (16%) expressing patterns of Ery–Rif–Nov–Flq–Aml–Cip–Flo. A hierarchical clustering analysis of their antibiotic‐resistant bacteria may indicate cross‐invasion between ponds/fish farms and its ability to survive in aquatic environments for long periods (at least 3 months). Our results suggest that the diversity of MARPs bacteria in snakehead represents a potential hazard to modifying the composition of native aquatic organisms, especially to consumers. To successfully manage C. striata in the future, several eco‐friendly techniques should be used to restrict the spread of A. schubertii inside the invaded habitat of the Mekong Delta river.
Acoustic ecology of terrestrial mammals: a new Signaller–Receiver Conceptual Framework
Authors: Stein Rachel M. , Rachlow Janet L.
Published: March 2023

Mammals use sound for a variety of purposes, such as detecting the presence of others and maintaining social bonds. Much research on mammalian acoustics has been focussed on marine mammals and bats; less has considered terrestrial species.

Our goal was to review knowledge about the role of acoustics in the behaviour and ecology of terrestrial mammals and to develop a conceptual framework that contextualises the knowledge. The purpose of the framework was to enable researchers to place their work in a broader understanding of the acoustics of terrestrial mammals, as well as to support them to articulate and explore new questions.

We conducted a keyword search in Web of Science and removed papers that did not meet our criteria, resulting in 228 reviewed papers. We scored these for keywords and used concept maps to identify broad patterns.

Of the 228 papers, 219 were focussed on acoustic communication. We therefore structured our Signaller–Receiver Conceptual Framework around factors that influence signallers (i.e. mammals producing sound) and receivers (i.e. mammals receiving sound). Factors that influence signallers were placed into two categories – those that influence call emission and those that influence call structure. Factors that influence receivers also fell into two categories – those that influence detection of sound and those that influence responses to sound. We added an additional receiver category – responses to sound. We present the framework in terms of five types of factors (environmental, social, morphological and physiological, state‐related factors, and other) and how they influence both signallers and receivers.

Our review is the first to detail the range of factors influencing acoustic ecology of terrestrial mammals, and our framework provides context for the articulation of hypotheses that integrate multiple factors, and so can help researchers place their work in a broader context.
A rare case of delayed complete lead dislodgement after deep septal pacing: A hidden risk of the specific procedure
Authors: Watanabe Ryo , Inden Yasuya , Yanagisawa Satoshi , Narita Yuji , Hiramatsu Kei , Yamauchi Ryota , Tsurumi Naoki , Suzuki Noriyuki , Shimojo Masafumi , Suga Kazumasa , Tsuji Yukiomi , Murohara Toyoaki
Published: March 2023

Deep septal ventricular pacing is a recently developed physiological pacing modality with good efficacy; however, it has a potential risk of unusual complications. Here, we report a patient with pacing failure and spontaneous, complete lead dislodgement after >2 years of deep septal pacing, possibly caused by systemic bacterial infection and specific lead behavior in the septal myocardium. This case report may implicate a hidden risk of unusual complications in deep septal pacing.
Pediatric chronic urticaria: Clinical and laboratory characteristics and factors linked to remission
Authors: Sandoval‐Ruballos Mónica , Domínguez Olga , Ortiz de Landazuri Iñaki , Gereda Daniella , Espinoza Cisneros Michelle , Quesada Sequeira Fabriella , Ramos Rodríguez Sandra Melissa , Machinena Adrianna , Piquer Mónica , Folqué María del Mar , Lozano Jaime , Jiménez‐Feijoo Rosa , Pascal Mariona , Alvaro‐Lozano Montserrat
Published: March 2023

Background

Chronic urticaria (CU) is defined as the occurrence of wheals/angioedema for ≥6 consecutive weeks. Until now, guidelines and publications addressing CU have focused mainly on adults. As a result, evidence and guidance in the pediatric population are scarce.

Methods

This study aims to describe clinical and laboratory findings in pediatric CU and to determine factors associated with remission.

Results

185 patients, 54% female, median age at onset of 8.8 years. Angioedema was present in almost half. The most common type of CU was chronic spontaneous urticaria (CSU) in 74%. At least one atopic comorbidity was found in almost a third (35%). In addition, 8% had an autoimmune disorder (exclusively in CSU) and 9% had a psychiatric condition. Basopenia was found in 67% and was more frequently associated with CSU. The basophil activation test (BAT) was positive in 40%. With regard to remission, being of male sex, angioedema absence, the absence of physical triggers, and eosinophil counts >0.51 × 109/L were associated with shorter CU duration.

Conclusion

Atopy is a common condition in pediatric CU. CSU is the most common type. Autoimmune comorbidities and basopenia were significantly more common in CSU. In addition, ours is one of the few studies, assessing BAT utility in the pediatric population, being positive in a relevant percentage (40%). BAT positivity was more frequent in CSU. Our results suggest that the absence of angioedema and physical triggers, male sex, and eosinophil counts >0.51 × 109/L appear to be associated with a better prognosis in terms of remission.
Long Non‐coding RNA H19‐Overexpressing Exosomes Ameliorate UVB‐Induced Photoaging by Upregulating SIRT1Via Sponging miR‐138
Authors: Gao Wei , Zhang Yue , Yuan Limin , Huang Fangzhou , Wang Yu‐shuai
Published: March 2023

UVB‐induced photoaging is characterized by wrinkle formation, slackness and senile plaques, affecting the health and beauty of human being. Our previous study revealed that exosomes derived from adipose‐derived stem cells (ADSCs) could efficiently alleviate UVB‐induced photodamage. However, the functional ingredients in exosomes were undefined. LncRNA H19, one of the well‐researched lncRNAs in exosomes, exhibits multiple physiological effects. This study aims to demonstrate the photo‐protective role of lncRNA H19 on skin photoaging in UVB‐irradiated human skin fibroblasts cells (HSFs) and Kunming mice. LncRNA H19‐overexpressing exosomes (H19‐Exo) were isolated from the supernatant of ADSCs infected with lncRNA H19‐loaded lentivirus. The results showed that H19‐Exo significantly inhibited MMPs production, DNA damage and ROS generation while enhancing procollagen type I synthesis in UVB‐irradiated HSFs. Meanwhile, H19‐Exo markedly reversed epidermal thickening and collagen degradation in UVB‐irradiated mice. Furthermore, luciferase reporter assays indicated that lncRNA H19 acted as a sponge for miR‐138 expression, and SIRT1 was targeted by miR‐138. Evidence from both in vitro and in vivo studies also revealed that H19‐Exo could enhance SIRT1 expression by knocking down miR‐138. In conclusion, lncRNA H19 served as a therapeutic candidate in treating UVB‐induced skin photoaging by upregulation of SIRT1 via miR‐138.
Credit market imperfection, lack of entrepreneurship and capital outflow from a developing economy
Authors: Marjit Sugata , Mishra Suryaprakash
Published: March 2023

This paper explores the impact of credit market imperfection on lack of demand for capital, trade, and capital flows in an economy with wealth heterogeneity. In particular, we look at the implications of wealth heterogeneity. We show that the low return of capital and lower output of credit‐intensive output in autarky may reflect lack of entrepreneurship and demand for credit due to wealth heterogeneity and eventually may lead to capital outflow from a capital‐scarce country. This is a different way of echoing the sentiment of the well–known Lucas paradox, which suggests that capital might flow from the poor to the rich countries. We also show the possibility of trade and capital flow being complements and not substitutes, as is usual in standard trade models driven by factor abundance.
Quantitative simulation of photothermal effect in laser therapy of hypertrophic scar
Authors: Shen Jin Cui , Liang Ya Ya , Li Wei
Published: March 2023

Background

Laser technology has been widely used in the treatment of hypertrophic scar (HPS). Due to the lack of effective quantitative relationship between laser doses and thermal effect of lesion tissue, the selection of laser doses in clinical laser treatment of HPS is blind, which cannot guarantee the best treatment effect.

Materials and methods

The photothermal model of HPS was established by using finite element method. The effects of laser dose parameters such as laser energy density, pulse width, and spot diameter on the thermal effects of laser treatment were analyzed. According to tissue temperature threshold and thermal damage degree of the simulation results, the optimal laser doses of HPS were selected for the laser treatment experiments of rabbit ear HPSs to verify the rationality of the quantitative photothermal model.

Results

The temperature rise and thermal damage degree of HPS following laser treatment were directly correlated to the laser doses, which grew with the increase of energy density and laser pulse width. For the different spot diameters, the temperature rise decreased with the increase of spot diameter, whereas the thermal damage degree worsened with the increase of spot diameter. Both simulation and experimental results show that the optimal treatment parameters of HPS were as follows: The laser energy density was 7.5 J/cm3, the pulse width was 4 ms, and the spot diameter was 7 mm.

Conclusion

The laser dose parameters optimized by the photothermal model have achieved good therapeutic effects in the rabbit ear HPS, indicating that the model can be used for quantitative evaluation of laser doses before clinical treatment.
Juggling Complexities
Authors: Taylor Peter J.
Published: March 2023

The three different engagements with my geographical ontology proposition each produce equally relevant additions to the argument. There are interesting discussions of data needs, geographical synthesis and confronting policy differences. Their common thread is recognition of the inherent complexities facing climate policy making.
Identification of a triatomine infected with Trypanosoma cruzi in an urban area of the state of Veracruz, Mexico: A comprehensive study
Authors: Ochoa‐Martínez Paulina , López‐Monteon Aracely , López‐Domínguez Jaime , Torres‐Montero Jesús , Alberto Domínguez‐Guillén Jorge , Ramos‐Ligonio Angel
Published: March 2023

Chagas disease, considered a neglected disease, was initially confined to rural localities in endemic areas; however, in recent years through the process of urbanization and migration of infected people, the disease is gaining importance in urban environments. The presence of the vector in urban areas in most cases is due to the passive transport of vectors, but recently, its presence seems to be linked to vector adaptation processes associated with climate change. This paper reports the occurrence of an infected triatomine in the peridomicile of a house in an urban area of Córdoba, Veracruz, Mexico, where the species found is described, the molecular characteristics and resistance to BZN and NFX of the Trypanosoma cruzi isolate obtained, as well as serological data of the dwelling inhabitants. These urban disease scenarios make it possible to generate new scientific knowledge and enable the creation of new control strategies for Chagas disease vectors.
Sets of special subvarieties of bounded degree
Authors: Urbanik David
Published: March 2023

Let $f : X \to S$ be a family of smooth projective algebraic varieties over a smooth connected quasi-projective base $S$, and let $\mathbb {V} = R^{2k} f_{*} \mathbb {Z}(k)$ be the integral variation of Hodge structure coming from degree $2k$ cohomology it induces. Associated to $\mathbb {V}$ one has the so-called Hodge locus$\textrm {HL}(S) \subset S$, which is a countable union of ‘special’ algebraic subvarieties of $S$ parametrizing those fibres of $\mathbb {V}$ possessing extra Hodge tensors (and so, conjecturally, those fibres of $f$ possessing extra algebraic cycles). The special subvarieties belong to a larger class of so-called weakly special subvarieties, which are subvarieties of $S$ maximal for their algebraic monodromy groups. For each positive integer $d$, we give an algorithm to compute the set of all weakly special subvarieties $Z \subset S$ of degree at most $d$ (with the degree taken relative to a choice of projective compactification $S \subset \overline {S}$ and very ample line bundle $\mathcal {L}$ on $\overline {S}$). As a corollary of our algorithm we prove conjectures of Daw–Ren and Daw–Javanpeykar–Kühne on the finiteness of sets of special and weakly special subvarieties of bounded degree.
The Effect of Contralateral Knee Neuromuscular Exercises on Static and Dynamic Balance, Knee Function, and Pain in Athletes Who Underwent Anterior Cruciate Ligament Reconstruction: A Single-Blind Randomized Controlled Trial
Authors: Karimijashni Motahareh , Sarvestani Fahimeh Kamali , Yoosefinejad Amin Kordi
Published: March 2023

Context: Contralateral training in the early stages after surgery can improve the balance of the reconstructed knee, which is impaired following anterior cruciate ligament reconstruction (ACLR). However, little is known about the neuromuscular cross exercise after ACLR. Objective: To investigate the effects of an 8-week cross exercise on balance and function of the reconstructed knee following ACLR. Design: A single-blind randomized clinical trial. Participants: Thirty athletic males who underwent ACLR were randomly divided into intervention (n = 15) and control groups (n = 15). Intervention: The intervention and control groups received a routine physiotherapy program. In addition, the intervention group performed neuromuscular exercises on the nonoperated limb. Outcome Measures: Before and 9 weeks after ACLR, dynamic and static balance, function, and pain in the reconstructed knee were measured by Star Excursion Balance Test (SEBT), stork balance stand test, balance error scoring system (BESS), Lysholm questionnaire, and visual analog scale. Data were analyzed by SPSS using 2-independent sample t test, paired t test, and analysis of covariance. Results: Between-group comparison showed that, contralateral knee neuromuscular exercises significantly increased in the reaching distance in SEBT in the anterior (P < .001), posterior (P < .001), posteromedial (P = .010), and posterolateral directions (P = .007), decreased the number of errors in 4 stance positions of BESS including single stance on the firm (P ≤ .001) and foam surface (P ≤ .001), and tandem stance on the firm (P = .028) and foam surface (P ≤ .001). It also increased the time of standing of the stork stand test (P = .044) and decreased the pain intensity (P = .014). Conclusion: Neuromuscular exercise of the nonsurgical knee could improve the dynamic and static balance, and pain in the early stages following ACLR in the surgical leg. These findings may be potentially valuable for current rehabilitation protocols.
CRISPR Screens Identify
Toxoplasma
Genes That Determine Parasite Fitness in Interferon Gamma-Stimulated Human Cells
Authors: Krishnamurthy Shruthi , Maru Parag , Wang Yifan , Bitew Mebratu A. , Mukhopadhyay Debanjan , Yamaryo-Botté Yoshiki , Paredes-Santos Tatiana C. , Sangaré Lamba O. , Swale Christopher , Botté Cyrille Y. , Saeij Jeroen P. J.
Published: March 2023

Toxoplasma
infection causes serious complications in immunocompromised individuals and in the developing fetus. During infection, certain immune cells release a protein called interferon gamma that activates cells to destroy the parasite or inhibit its growth.
Essential Role of WetA, but No Role of VosA, in Asexual Development, Conidial Maturation and Insect Pathogenicity of Metarhizium
robertsii
Authors: Zhang Jin-Guan , Zhang Ke , Xu Si-Yuan , Ying Sheng-Hua , Feng Ming-Guang
Published: March 2023

WetA and VosA regulate conidiation and conidial maturation required for the life cycle of
Beauveria bassiana,
like they do in
Aspergillus,
but remain functionally unexplored in
Metarhizium
robertsii
, another hypocrealean pathogen considered to have evolved insect pathogenicity ~130 million years later than
B.
bassiana
. This study reveals a similar role of WetA ortholog in asexual development, conidial maturation, and insect pathogenicity, and also its distinctive role in mediating some other conidial maturation-related cellular events, but has functional redundancy of VosA in
M. robertsii
.
Landscape of Exhausted T Cells in Tuberculosis Revealed by Single-Cell Sequencing
Authors: Pan Jiahui , Zhang Xinyue , Xu Jianting , Chang Zecheng , Xin Zhuoyuan , Wang Guoqing
Published: March 2023

Identifying the changes in immune cells in response to infection can provide a better understanding of the effects of
Mycobacterium tuberculosis
on the host immune system. We performed single-cell RNA-sequencing analysis of CD4
+
T and CD8
+
T cells isolated from peripheral blood mononuclear cells of healthy individuals and patients with tuberculosis to reveal the cellular characteristics.
Metabolic Versatility of the FamilyHalieaceaeRevealed by the Genomics of Novel Cultured Isolates
Authors: Li Shan-Hui , Kang Ilnam , Cho Jang-Cheon
Published: March 2023

Although the familyHalieaceae(OM60/NOR5 clade) is an abundant and cosmopolitan clade widely found in coastal seas and involved in interactions with phytoplankton, a limited number of cultured isolates are available. In this study, we isolated six pure culturedHalieaceaestrains from coastal seawaters and performed a comparative physiological and genomic analysis to give insights into the phylogeny and metabolic potential of this family.
Association between Intestinal Colonization and Extraintestinal Infection with Carbapenem-Resistant Klebsiella pneumoniae in Children
Authors: Du Qingqing , Xu Qi , Pan Fen , Shi Yingying , Yu Fangyuan , Zhang Tiandong , Jiang Jie , Liu Wenxin , Pan Xiaozhou , Han Dingding , Zhang Hong
Published: March 2023

Carbapenem-resistant
Klebsiella pneumoniae
(CRKP) causes an increasing number of nosocomial infections, which can be life-threatening, as carbapenems are last-resort antibiotics.
K. pneumoniae
is part of the healthy human microbiome, and this provides a potential advantage for infection. This study demonstrated that CRKP intestinal colonization is strongly linked to extraintestinal infection, based on the evidence given by whole-genome sequencing data and phenotypic assays of antimicrobial resistance and virulence.
Vascular Endothelial Growth Factor A Contributes to Increased Mammalian Respiratory Epithelial Permeability Induced by Pasteurella multocida Infection
Authors: Lin Lin , Yang Jie , Zhang Dajun , Lv Qingjie , Wang Fei , Liu Peng , Wang Mixue , Shi Congcong , Huang Xi , Liang Wan , Tan Chen , Wang Xiangru , Chen Huanchun , Wilson Brenda A. , Wu Bin , Peng Zhong
Published: March 2023

The mammalian respiratory epithelium forms the first line of defense against infections with
P. multocida
, an important zoonotic respiratory pathogen. In this study, we found that
P. multocida
infection increased respiratory epithelial permeability and promoted the induction of the HIF-1α–VEGFA axis in both mouse and murine cell models.
Antifungal Peptide SP1 Damages Polysaccharide Capsule of Cryptococcus neoformans and Enhances Phagocytosis of Macrophages
Authors: Liu Yan , Zhang Yang , Zhao Xi , Lu Weilai , Zhong Yuxin , Fu Yu V.
Published: March 2023

C. neoformans
is an opportunistic pathogen that causes invasive infections with a high mortality rate. Currently, the clinical drugs available for the treatment of cryptococcosis are limited to amphotericin B, azoles, and flucytosine.
Systematic Effects in the Measurement of the Lifetime of the Neutron in Magnetic Traps of Ultracold Neutrons
Authors: Ezhov V. F. , Ryabov V. L.
Published: March 2023

Possible systematic effects in experimental measurements of the lifetime of the neutron using magneto-gravitational traps to store ultracold neutrons have been discussed. Methods for the online detection of possible losses, including depolarization losses and a small heating of neutrons stored in a trap, have been proposed.
Theoretical Foundations of Quantum Spectral-Domain Optical Coherence Tomography with Frequency Scanning
Authors: Ushakov N. A. , Makovetskaya T. A. , Markvart A. A. , Liokumovich L. B.
Published: March 2023

A quantum spectral-domain optical coherence tomography technique based on the control of the joint spectral amplitude of a biphoton has been developed. An analytical expression for a quantum spectral-domain optical coherence tomography signal has been obtained in the case of a Gaussian joint spectral amplitude. The effect of the shape of the joint spectral amplitude of the biphoton on the resulting interference signal has been analyzed. The possibility of improving the quality of the interference signal by controlling the parameters of the joint spectral amplitude has been considered. It has been shown theoretically that the proposed approach provides a higher longitudinal spatial resolution than other optical coherence tomography techniques.
Magnetic Field Effect on the Formation of Ultracold Plasma
Authors: Bronin S. Ya. , Vikhrov E. V. , Zelener B. B. , Zelener B. V.
Published: March 2023

The molecular dynamics method is used to simulate the formation of ultracold plasma under continuous ionizing irradiation in a quadrupole magnetic field with the gradient of the magnetic field along the axis of symmetry equal to 0, 30, 150, and 500 G/cm. An increase in the magnetic field promotes an increase in the plasma density owing to the trapping of some part of fast electrons by the quadrupole magnetic field.
Treatment-induced diabetes neuropathy: description of singular clinical signs to reach a prompt diagnosis
Authors: Guisado Vasco Pablo , Llanero-Luque ­Marcos , Cano-Megías Marta , Cortés-Berdonces María
Published: March 2023

A 23-year-old woman diagnosed with type 1 diabetes mellitus in 2011 came to our outpatient office because of an inability to walk correctly. She was under a basal bolus insulin regimen. In the summer of 2016, she experienced a rapid improvement in her glycaemic control. A few weeks later, she started to complain of a severe burning pain in the soles of her feet (pain score 10/10). Neither macrovascular nor microvascular complications were detected. The patient was forced to walk barefoot due to an intense pain using shoes or socks and used to soak her feet in water for several hours daily. She also developed severe intolerance to environmental heat, both indoors and outdoors. A diagnosis of treatment-induced diabetic neuropathy was made. The patient was admitted to a general ward to start pain therapy. After a 6-month course of different neuropathic pain drugs, the patient was able to walk autonomously again.
Potential impact on cost-effectiveness estimates of using immature survival data: a case study based on transcatheter edge-to-edge repair (TEER) used for patients with severe mitral regurgitation at high surgical risk
Authors: Connock Martin , Auguste Peter , Capelle Aude , Hénaine Anna-Maria , Obadia Jean-François , Armoiry Xavier
Published: March 2023

Objective

To review the survival modelling used in cost-effectiveness studies evaluating an interventional procedure and to discuss implications for decision-makers.

Design

A case study of three economic evaluations that each used immature data from the EVEREST II High Surgical Risk (HSR) Study of transcatheter edge-to-edge repair (TEER) for patients with severe mitral regurgitation (MR) who were at high risk of surgery.

Setting

Estimation of patient survival in cost-effectiveness studies.

Participants

The EVEREST II HSR Study included 78 patients who had TEER of the mitral valve using the MitraClip device and a retrospectively identified control group of 36 patients who received medical management and were followed up for 12 months. Observed survival (TEER arm only) was updated at 5 years.

Results

Two studies used 12-month observed mortality from EVEREST II HSR to model survival over lifetime horizons. Observed and modelled survival were associated with considerable uncertainty due to short follow-up and small numbers of participants. Modelling control patients’ survival required an approximate 10-fold extrapolation based on 12-month observation of only 38 patients. Observed 5-year survival in the TEER group differed from that less mature follow-up suggesting that survival modelling based on shorter follow-up was unsatisfactory. No public domain data for the control group are available beyond 12-month follow-up so meaningful estimates using mature data for both arms are currently not possible. A third study developed survival models using incompletely reported transitions between MR grades in EVEREST II HSR and mortality rates observed for different MR grades derived from a study in an unrelated population.

Conclusions

Modelling survival in such small samples followed up for only 12 months is associated with great uncertainty, and cost-effectiveness results based on these analyses should be viewed as premature and used cautiously in reimbursement decisions.
Healthcare providers’ perceptions and expectations of video-assisted debriefing of real-life obstetrical emergencies: a qualitative study from Denmark
Authors: Rosvig Lena Have , Lou Stina , Hvidman Lone , Manser Tanja , Uldbjerg Niels , Kierkegaard Ole , Brogaard Lise
Published: March 2023

Objectives

Video-assisted debriefing (VAD) of real-life obstetrical emergencies provides an opportunity to improve quality of care, but is rarely used in clinical practice. A barrier for implementation is the expected mental reservations among healthcare providers. The aim of this study was to explore healthcare providers’ perceptions and expectations of VAD of real-life events.

Setting

Participants were recruited from two Labour and Delivery Units in Denmark. In both units, VAD of real-life obstetrical emergencies had never been conducted.

Participants

22 healthcare providers (10 physicians, 9 midwives and 3 nursing assistants). During the study period (August–October 2021), semi-structured, individual interviews were conducted. Interviews were analysed using thematic analysis.

Primary and secondary outcome measures

A qualitative description of healthcare providers’ perceptions and expectations of VAD of real-life events.

Results

Three major themes were identified: (1)Video-assisted debriefing (VAD) as an opportunity for learning:All participants expected VAD to provide an opportunity for learning and improving patient care. All participants expected the video to provide a ‘bigger picture’, by showing ‘what was actually done’ instead of ‘what we believed was done’. (2)Video-assisted debriefing (VAD) as a cause for concern:The primary concern for all participants was the risk of being exposed as less competent. Participants were concerned that being confronted with every minor detail of their clinical practice would enhance their self-criticalness. (3)Preconditions for video-assisted debriefing (VAD):Participants emphasised the importance of organisational support from management. In addition, creating a safe environment for VAD, for example, by using only expert debriefers was considered an essential precondition for successful implementation.

Conclusions

The risk of being exposed as less competent was a barrier towards VAD of real-life events. However, the majority found the educational benefits to outweigh the risk of being exposed.
Intravenousferric carboxymaltoseversus oral ferrous sulfate replacement in elderly patients after acute non-variceal gastrointestinal bleeding (FIERCE): protocol of a multicentre, open-label, randomised controlled trial
Authors: Teutsch Brigitta , Váncsa Szilárd , Farkas Nelli , Szakács Zsolt , Vörhendi Nóra , Boros Eszter , Szabó Imre , Hágendorn Roland , Alizadeh Hussain , Hegyi Péter , Erőss Bálint
Published: March 2023

Introduction

Acute gastrointestinal bleeding (GIB) is a life-threatening emergency with a critical economic burden. As a result of bleeding, anaemia often requires intravenous or oral iron supplementation. Elderly patients are even more prone to untoward outcomes after hospital discharge if iron supplementation is inefficient. There is a gap in current guidelines on which supplementation route clinicians should choose. We aim to investigate the effect of one dose of intravenous iron therapy versus 3-month oral iron administration on anaemia in an elderly population.

Methods and analysis

The FIERCE study is an open-label, randomised controlled, two-armed trial. At least 48 hours after the acute non-variceal GIB treatment, patients will be recruited in participating centres. A random sequence generator will allocate the participants to group A (intravenous ferric carboxymaltose, 1000 mg) or group B (oral ferrous sulfate (FS), ca. 200 mg every day) with an allocation ratio of 1:1 on the day of the planned discharge from the hospital. Randomisation will be stratified for participating centres and the need for transfusion within the same hospitalisation before recruitment to the trial. Quality of life assessment, functional measurement and laboratory tests will be performed at baseline, 1 and 3 months±7 days after enrolment to the trial. The primary endpoint is a composite endpoint, including all-cause mortality, anaemia-associated unplanned emergency visit and anaemia-associated unplanned hospital admission within 3 months of enrolment in the trial.

Ethics and dissemination

The study has been approved by the relevant organisation, the Scientific and Research Ethics Committee of the Hungarian Medical Research Council (46395-5/2021/EÜIG). We will disseminate our results to the medical community and will publish our results in peer-reviewed journals.

Trial registration

The trial has been registered at ClinicalTrials.gov (NCT05060731).
Prevalence of myocardial fibrosis among patients living with HIV and factors associated with a higher prevalence rate: protocol for a systematic review and meta-analysis
Authors: Shoar Saeed , Dao Calvin D , Higgason Noel M , Shoar Nasrin
Published: March 2023

Introduction

HIV infection is an established risk factor for the development of cardiovascular diseases. Although increasing evidence implicates a higher prevalence of myocardial fibrosis (MF) among patients living with HIV (PLWH) compared with the HIV-negative population, there is a paucity of knowledge regarding its determinants and factors associated with higher odds of MF development. We aim to perform a systematic review to estimate the prevalence of MF among PLWH. Additionally, we will determine the factors associated with higher odds of MF among PLWH compared with the HIV-negative population.

Methods

A systematic review will be performed by consulting the Cochrane handbook for systematic reviews of interventional studies reporting a confirmed diagnosis of MF among PLWH. Articles will be eligible if they provide the prevalence of MF among PLWH and HIV-negative populations or the odds ratio (OR) and 95% confidence interval (CI) of MF development in relation to HIV. Depending on the quality of the data and the heterogeneity among the included studies, a random-effects or fixed-effects model will be used to pool and compare the ORs of MF among PLWH and HIV-negative population. Factors associated with higher odds of MF in relation to HIV will also be determined.

Ethics and dissemination

Ethical approval and obtaining informed consent are not required for this systematic review as it does not use individual patients’ data. Results of this study will be published in a peer-reviewed medical journal.
CD47 expression is critical for CAR T-cell survival in vivo
Authors: Beckett Alex N , Chockley Peter , Pruett-Miller Shondra M , Nguyen Phuong , Vogel Peter , Sheppard Heather , Krenciute Giedre , Gottschalk Stephen , DeRenzo Christopher
Published: March 2023

Background

CD47 is an attractive immunotherapeutic target because it is highly expressed on multiple solid tumors. However, CD47 is also expressed on T cells. Limited studies have evaluated CD47-chimeric antigen receptor (CAR) T cells, and the role of CD47 in CAR T-cell function remains largely unknown.

Methods

Here, we describe the development of CD47-CAR T cells derived from a high affinity signal regulatory protein α variant CV1, which binds CD47. CV1-CAR T cells were generated from human peripheral blood mononuclear cells and evaluated in vitro and in vivo. The role of CD47 in CAR T-cell function was examined by knocking out CD47 in T cells followed by downstream functional analyses.

Results

While CV1-CAR T cells are specific and exhibit potent activity in vitro they lacked antitumor activity in xenograft models. Mechanistic studies revealed CV1-CAR T cells downregulate CD47 to overcome fratricide, but CD47 loss resulted in their failure to expand and persist in vivo. This effect was not limited to CV1-CAR T cells, since CD47 knockout CAR T cells targeting another solid tumor antigen exhibited the same in vivo fate. Further, CD47 knockout T cells were sensitive to macrophage-mediated phagocytosis.

Conclusions

These findings highlight that CD47 expression is critical for CAR T-cell survival in vivo and is a ‘sine qua non’ for successful adoptive T-cell therapy.
Society for Immunotherapy of Cancer (SITC) consensus definitions for resistance to combinations of immune checkpoint inhibitors
Authors: Kluger Harriet , Barrett J Carl , Gainor Justin F , Hamid Omid , Hurwitz Michael , LaVallee Theresa , Moss Rebecca A , Zappasodi Roberta , Sullivan Ryan J , Tawbi Hussein , Sharon Elad
Published: March 2023

Immunotherapy is the standard of care for several cancers and the field continues to advance at a rapid pace, with novel combinations leading to indications in an increasing number of disease settings. Durable responses and long-term survival with immunotherapy have been demonstrated in some patients, though lack of initial benefit and recurrence after extended disease control remain major hurdles for the field. Many new combination regimens are in development for patients whose disease progressed on initial immunotherapy. To guide clinical trial design and support analyses of emerging molecular and cellular data surrounding mechanisms of resistance, the Society for Immunotherapy of Cancer (SITC) previously generated consensus clinical definitions for resistance to single-agent anti-PD-1 immune checkpoint inhibitors (ICIs) in three distinct scenarios: primary resistance, secondary resistance, and progression after treatment discontinuation. An unmet need still exists, however, for definitions of resistance to ICI-based combinations, which represent an expanding frontier in the immunotherapy treatment landscape. In 2021, SITC convened a workshop including stakeholders from academia, industry, and government to develop consensus definitions for resistance to ICI-based combination regimens for improved outcome assessment, trial design and drug development. This manuscript reports the minimum drug exposure requirements and time frame for progression that define resistance in both the metastatic setting and the perioperative setting, as well as key caveats and areas for future research with ICI/ICI combinations. Definitions for resistance to ICIs in combination with chemotherapy and targeted therapy will be published in companion volumes to this paper.
Teenager and the transplant: how the case of William Verden highlights action is needed to optimise equitable access to organs for patients with impaired decision-making
Authors: Venter Bonnie , Ruck Keene Alexander , Cronin Antonia J
Published: March 2023

In February 2022, the Court of Protection was faced with the question of whether a kidney transplant was in the best interests of William Verden. The case highlighted the legal, ethical and clinical complexities of treating potential kidney transplant patients with impaired decision-making. Above all, it exposed the potential risk of discrimination on the basis of disability when treatment decisions in relation to potential kidney recipients with impaired capacity are being made. In this paper, we draw on the Verden case to (1) examine the role of the Court of Protection in cases relating to patients with impaired decision-making capacity who require a transplant, (2) to highlight the lack of empirical data on patients who have faced inequitable access to transplant and (3) highlight the shortcomings of the existing legal and regulatory framework in England and Wales guiding clinical decision making for patients in William’s position. We consequently argue that there is a clear need for action to ensure equitable access to transplant for those in William’s position. Furthermore, we suggest that there is a responsibility incumbent on policy makers and clinicians alike to develop a meaningful, and meaningfully operational, framework centred on preventing discrimination against potential organ recipients based on their decision-making capacity.
Multiphase lattice Boltzmann modeling of cyclic water retention behavior in unsaturated sand based on X-ray computed tomography
Authors: Wang Qiuyu , Milatz Marius , Hosseini Reihaneh , Kumar Krishna
Published: March 2023

The water retention curve (WRC) defines the relationship between matric suction and saturation and is a key function for determining the hydro-mechanical behavior of unsaturated soils. We investigate possible microscopic origins of the water retention behavior of granular soils using both computed tomography (CT) experiment and multiphase lattice Boltzmann Method (LBM). We conduct a CT experiment on Hamburg sand to obtain its WRC and then run LBM simulations based on the CT grain skeleton. The multiphase LBM simulations capture the hysteresis and pore-scale behaviors of WRC observed in the CT experiment. Using LBM, we observe that the spatial distribution and morphology of gas clusters varies between drainage and imbibition paths and is the underlying source of the hysteresis. During drainage, gas clusters congregate at the grain surface; the local suction increases when gas clusters enter through small pore openings and decreases when gas clusters enter through large pore openings. Whereas, during imbibition, gas clusters disperse in the liquid, the local suction decreases uniformly. Large pores empty first during drainage and small pores fill first during imbibition. The pore-based WRC shows that an increase in pore size causes a decrease in suction during drainage and imbibition, and an increase in hysteresis.