bluuebunny/crossref_metadata_2025 huggingface dataset:
Selection of highly responsive T cell receptors by an analysis combining the expression of multiple markers
Authors: Thi Viet Ha My , Hamana Hiroshi , Shitaoka Kiyomi , Hayee Abdul , Kobayashi Eiji , Yoshikawa Toshiaki , Nakatsura Tetsuya , Saikawa Reiko , Sato Eri , Osawa Mitsujiro , Hitoshi Yasumichi , Son Dang Tung , Ozawa Tatsuhiko , Kishi Hiroyuki
Published: March 2023

The clinical success of T cell receptor (TCR) gene–transduced T (TCR‐T) cell therapy is expected as one of the next‐generation immunotherapies for cancer, in which the selection of TCRs with high functional avidity (high‐functional TCRs) is important. One widely used approach to select high‐functional TCRs is a comparison of the EC50 values of TCRs, which involves laborious experiments. Therefore, the establishment of a simpler method to select high‐functional TCRs is desired. We herein attempted to establish a simple method to select high‐functional TCRs based on the expression of T cell activation markers using the mouse T cell line BW5147.3 (BW). We examined relationships between the EC50 values of TCRs in interleukin‐2 production and the expression levels of TCR activation markers on BW cells. In TCR‐expressing BW cells stimulated with antigenic peptides, the CD69, CD137, and PD‐1 expression was differentially induced by various doses of peptides. An analysis of TCRs derived from the tumor‐infiltrating lymphocytes of murine melanoma and peripheral blood T cells of hepatocellular carcinoma patients treated with a peptide vaccination revealed that an analysis combining CD69, CD137, and PD‐1 expression levels in BW cells stimulated with a single dose of an antigenic peptide selected high‐functional TCRs with functional avidity assessed by EC50 values. Our method facilitates the section of high‐functional TCRs among tumor‐reacting TCRs, which will promote TCR‐T cell therapy. The stimulation of BW cells expressing objective TCRs with a single dose of antigenic peptides and analysis combining the expression of CD69, CD137, and PD‐1 allows us to select highly responsive TCRs.
Efficacy and safety of empagliflozin in combination with insulin in Chinese patients with type 2 diabetes and insufficient glycaemic control: A phase III, randomized, double‐blind, placebo‐controlled, parallel study
Authors: Ji Linong , Lu Yibin , Li Qifu , Fu Liujun , Luo Yong , Lei Tao , Li Ling , Ye Shandong , Shi Bimin , Li Xiyan , Meinicke Thomas
Published: March 2023

Aim

To evaluate the efficacy and safety of empagliflozin in combination with insulin ± oral antidiabetic drugs (OADs) over 24 weeks, in Chinese patients with type 2 diabetes (T2D) who had insufficient glycaemic control.

Materials and Methods

This was a randomized, double‐blind, placebo‐controlled, parallel group, multicentre phase III study. Adult patients with T2D and insufficient glycaemic control who received insulin ± up to two OADs were randomized (1:1:1) to receive empagliflozin 10 or 25 mg, or placebo for 24 weeks. The primary endpoint was change from baseline in HbA1c at week 24.

Results

Of 219 randomized patients, 73 patients were in each treatment group; baseline characteristics were comparable among the groups. There was a significantly larger decrease from baseline in HbA1c (adjusted mean treatment difference −0.99 and −0.98 for in the empagliflozin 10 and 25 mg groups, respectively; P < .0001) with both doses of empagliflozin than with placebo. There were also significantly larger decreases from baseline in fasting plasma glucose, 2‐hour postprandial glucose and body weight with both empagliflozin doses than with placebo. Among patients in the empagliflozin 10 mg, 25 mg and placebo groups, 17.8%, 9.6% and 11.0% reported confirmed hypoglycaemic events, respectively (nominal P = .2422 and .7661 in the empagliflozin 10 and 25 mg groups, respectively), and no Clinical Events Committee‐confirmed diabetic ketoacidosis events were reported.

Conclusions

In Chinese patients with T2D, empagliflozin combined with insulin ± OADs improved glycaemic control and was well tolerated, without an increased risk of hypoglycaemia.
Effects of glucagon‐like peptide‐1 receptor agonists on major coronary events in patients with type 2 diabetes
Authors: Guo Xueyuan , Sang Caihua , Tang Ribo , Jiang Chenxi , Li Songnan , Liu Nian , Long Deyong , Du Xin , Dong Jianzeng , Ma Changsheng
Published: March 2023

Aims

To perform a meta‐analysis to assess the effects of glucagon‐like peptide‐1 receptor agonists (GLP‐1RAs) on major coronary events, including myocardial infarction (MI), unstable angina and coronary revascularization, in patients with type 2 diabetes mellitus (T2DM).

Materials and methods

We systematically searched the PubMed, CENTRAL, EMBASE and clinicaltrial.gov databases to seek eligible studies with a cardiovascular endpoint comparing GLP‐1RAs with a placebo in T2DM patients. Odds ratio (ORs) and 95% confidence intervals (CIs) were calculated for the outcomes.

Results

Nine studies, with a total of 64 236 patients, were included. GLP‐1RA treatment reduced fatal and nonfatal MI by 8% (OR 0.92, 95% CI 0.86–0.99; P = 0.02, I2 = 39%). The reduction reached 15% in human‐based GLP‐1RA‐treated patients. Similarly, once‐weekly GLP‐1RA treatment reduced the risk of MI by 13%. In contrast, GLP‐1RA treatment did not reduce the risk of hospitalization for unstable angina (OR 1.11, 95% CI 0.97–1.28; P = 0.13, I2 = 21%). GLP‐1RAs exhibited a tendency to lower the risk of coronary revascularization (OR 0.95, 95% CI 0.89–1.02; P = 0.15, I2 = 22%), but without statistical significance. Human‐based GLP‐1RAs decreased the risk by 11%.

Conclusions

In high‐risk patients with T2DM, GLP‐1RAs were associated with a decrease in MI, especially the human‐based and once‐weekly GLP‐1RAs. No benefit was seen for hospitalization for unstable angina or coronary revascularization. Further research is urgently needed to ascertain improvements in coronary events.
Phylogenetic and morphological analyses of Japanese Aquarius water strider, with a new synonym
Authors: Hiraishi Naoki , Suzuki Tomoya , Matsushima Ryosuke , Ohba Shin‐ya
Published: March 2023

The genus Aquarius, of the subfamily Gerrinae, was formerly divided into two species and one subspecies in Japan (A. paludum paludum, A. paludum amamiensis and A. elongatus, respectively). Aquarius haliplous Yasunaga et al. 2018 has recently been described as a new species, which occurs in brackish waters of Nagasaki Prefecture and is found sympatrically with the widely distributed species, A. p. paludum. However, they are considered to be speciated, with no cross‐breeding. In this study, molecular phylogenetic and morphological analyses were undertaken using the mitochondrial DNA COI (529 bp) and nuclear DNA histone H3 (314 bp) gene regions to investigate the genetic and morphological differentiation in the genus Aquarius, including A. haliplous, throughout Japan (including the islands). The results show that, unlike A. p. paludum, A. p. amamiensis and A. haliplous, A. elongatus displays substantial genetic differentiation. Considering that, although morphological differences exist in the antennae of A. p. paludum and A. p. amamiensis, A. haliplous has no clear genetic or morphological difference from A. p. paludum, and hence cannot be classified as a distinct species. Therefore, we propose that A. haliplous be synonymized with A. paludum.
The family law detection of overall risk screen (FL‐DOORS): Utility as a repeated measure for assessing change in family violence risk over time
Authors: Booth Anna T. , Wright Bradley J. , Pearce Heather , Ralfs Claire , McIntosh Jennifer E.
Published: March 2023

Conflicted parental separation is associated with risks to safety and wellbeing for all family members. The Family Law DOORS (FL‐DOORS; Detection of Overall Risk Screen) is a standardized screening framework to assist identification, evaluation, and response to family safety risks. The FL‐DOORS has previously been validated in two large Australian samples (N = 6089) and found fit‐for‐purpose as an indicator of family violence and wellbeing risks in separated families. Now, using pilot data from a community mediation context, we examine its utility as a repeated measure for detecting change in safety and wellbeing over time. A pilot cohort of 67 parents engaged in a mediation service for parenting and/or property disputes completed the FL‐DOORS at intake (T1) and approximately 8 weeks later (T2). We assessed T1‐T2 change scores and correlations in change between variables and used MANOVA to determine if clusters of related scales discriminated change across time. Findings support the psychometric capacity of the FL‐DOORS for use as a repeated measure in risk monitoring. We also note possible effects of this early screening process for reducing risk prior to engagement in mediation input. We discuss implementation utility for family law services to monitor change in risk type and magnitude over time.
Phenotypic plasticity increases exposure to extreme climatic events that reduce individual fitness
Authors: Regan Charlotte E. , Sheldon Ben C.
Published: March 2023

Climate models, and empirical observations, suggest that anthropogenic climate change is leading to changes in the occurrence and severity of extreme climatic events (ECEs). Effects of changes in mean climate on phenology, movement, and demography in animal and plant populations are well documented. In contrast, work exploring the impacts of ECEs on natural populations is less common, at least partially due to the challenges of obtaining sufficient data to study such rare events. Here, we assess the effect of changes in ECE patterns in a long‐term study of great tits, near Oxford, over a 56‐year period between 1965 and 2020. We document marked changes in the frequency of temperature ECEs, with cold ECEs being twice as frequent in the 1960s than at present, and hot ECEs being ~three times more frequent between 2010 and 2020 than in the 1960s. While the effect of single ECEs was generally quite small, we show that increased exposure to ECEs often reduces reproductive output, and that in some cases the effect of different types of ECE is synergistic. We further show that long‐term temporal changes in phenology, resulting from phenotypic plasticity, lead to an elevated risk of exposure to low temperature ECEs early in reproduction, and hence suggest that changes in ECE exposure may act as a cost of plasticity. Overall, our analyses reveal a complex set of risks of exposure and effects as ECE patterns change and highlight the importance of considering responses to changes in both mean climate and extreme events. Patterns in exposure and effects of ECEs on natural populations remain underexplored and continued work will be vital to establish the impacts of ECEs on populations in a changing climate.
Long‐term population decline of a genetically homogeneous continental‐wide top Arctic predator
Authors: Gousy‐Leblanc Marianne , Therrien Jean‐François , Broquet Thomas , Rioux Delphine , Curt‐Grand‐Gaudin Nadine , Tissot Nathalie , Tissot Sophie , Szabo Ildiko , Wilson Laurie , Evans Jack T. , Bowes Victoria , Gauthier Gilles , Wiebe Karen L. , Yannic Glenn , Lecomte Nicolas
Published: March 2023

Genetic analysis can provide valuable information for conservation programmes by unravelling the demographic trajectory of populations, estimating effective population size or inferring genetic differentiation between populations. Here, we investigated the genetic differentiation within Snowy Owls Bubo scandiacus in North America, a species identified as vulnerable by the IUCN, to (1) quantify connectivity among wintering areas, (2) evaluate current genetic diversity and effective population size, and (3) infer changes in the historical effective population size changes from the last millennia to the recent past. The Snowy Owl, a highly mobile top predator, breeds across the Arctic tundra, a region especially sensitive to current climate change. Using single‐nucleotide polymorphism (SNP)‐based analyses on Snowy Owls sampled across the North American non‐breeding range, we found an absence of genetic differentiation among individuals located up to 4650 km apart. Our results suggest high genetic intermixing and effective dispersal at the continental scale despite documented philopatry to non‐breeding sites in winter. Reconstructing the population demographic indicated that North American Snowy Owls have been steadily declining since the Last Glacial Maximum c. 20 000 years ago, and concurrently with global increases in temperature. Conservation programmes should now consider North American Snowy Owls a single, genetically homogeneous continental‐wide population which is probably sensitive to the long‐term global warming occurring since the Last Glacial Maximum.
In situ measurement of combustion wave propagation during combustion synthesis of α‐Si3N4 powder
Authors: Wang Liang , Yang Zengchao , Li Jiangtao
Published: March 2023

α‐Si3N4 powder was prepared by combustion synthesis method. The propagation characteristics of combustion wave were investigated by thermocouple temperature measurement and “resistance—combustion wave displacement response device.” The results show that the combustion reaction takes place in a narrow area, and there is a maximum temperature gradient of 180°C/mm in the combustion front. The “resistance—combustion wave displacement response device” was innovatively used to realize the in situ measurement of combustion wave propagation process. The test results showed the pulse combustion mode in which the combustion front took 10 s as a cycle, and the quantitative data of Si–N2 discrete combustion characteristics were obtained for the first time.
Phylogeography of Solomon Islands blossom bats reflects oceanic divides and Pleistocene connections
Authors: Lavery Tyrone H. , DeCicco Lucas H. , Olson Karen V. , Holland Piokera S. , Moyle Robert G.
Published: March 2023

Aim

Periodic lowering of sea levels and formation of land bridges can reshape phylogeographic patterns of insular biotas. Using archipelago‐wide sampling, we aimed to test if phylogeography of an old‐endemic bat lineage reflected Pleistocene land bridges.

Location

Solomon Islands and Papua New Guinea.

Taxon

MelonycterisandNesonycterisbats (Pteropodidae).

Methods

We sequenced genome‐wide RADseq data for 49 specimens from 15 islands. We assessed phylogenetic relationships using maximum likelihood inRAxMLand quartet‐based methods inSVDquartets, population structure usingStructure, and admixture using maximum likelihood methods inTreeMix. We tested for genetic and geographic distance correlations using distance‐based redundancy analyses (dbRDA), identifying best‐fit models using stepwise model selection.

Results

Phylogenetic analyses identified fiveNesonycterisclades corresponding to Greater Bukida, Guadalcanal, Makira, Malaita and New Georgia group. Makira samples were sister to remainingNesonycteris.Structureidentified four populations: New IrelandMelonycteris melanops; andNesonycterisfrom Greater Bukida (including Guadalcanal); Malaita and Makira; and New Georgia group. Genetic backgrounds of Mono, Ngella and Guadalcanal separated from remaining Greater Bukida islands. Makira and Malaita separated into two populations. New Georgia group lacked structure, and genetic and geographic distances were not correlated. The best‐fit geographic distance models forNesonycterisand a Greater Bukida subset were least shore‐to‐shore distance; and Euclidean and least‐cost distances respectively.

Main Conclusions

Influences of modern and Pleistocene island isolation and connectivity were evident in the overall Phylogeography ofNesonycteris. The lack of structure or geographic distance correlations within the New Georgia group indicated all islands were interconnected during the Last Glacial Maximum or contemporary oceanic divides are ineffective barriers. Conversely, genetic divergence across Greater Bukida islands reflected land‐bridge constrained dispersal. A Makira clade sister to allNesonycterispossibly indicates an origin on Makira. Alternately it reflects Makira's long‐isolated geographic status, as similar results exist for a range of taxa.
Myopathic changes caused by protein aggregates in adult‐onset spinal muscular atrophy
Authors: Yamashita Satoshi , Nagatoshi Akihito , Takeuchi Yosuke , Nishino Ichizo , Ueda Mitsuharu
Published: March 2023

Spinal muscular atrophy (SMA), an autosomal‐recessive lower motor neuron disease, causes progressive proximal muscle waste and weakness. It remains unclear whether myopathic changes are involved in pathogenesis. We encountered a patient with adult‐onset SMA caused by a homozygous deletion in exon 7 of the survival motor neuron 1 (SMN1) gene who had had four copies of SMN2 exon 7. Muscle biopsy showed neurogenic features of groups of atrophic fibers, fiber‐type grouping, and pyknotic nuclear clumps associated with fibers with rimmed vacuoles. Immunohistochemistry revealed sarcoplasmic aggregates of phosphorylated TDP‐43 and p62 but not SMN. This study demonstrated myopathic changes with the accumulation of phosphorylated p62 and TDP‐43 in the muscles of a patient with SMA, suggesting that abnormal protein aggregation may be involved in myopathic pathology.
Utricularia ochroleuca and U. minor new‐found in nutrient‐poor waters of northern Greece
Authors: Bergmeier Erwin
Published: March 2023

Nutrient‐poor waters with small Utricularia species have been unknown in most of southern Europe and the Balkans. All the more notable are occurrences of Utricularia ochroleuca and Utricularia minor in north Greece. The records presented in this paper extend the known southeast European distribution boundaries of both species southward, and constitute U. ochroleuca a new species to Greece and southern Europe. U. ochroleuca was found in small peaty pools and seepage sites with base‐poor water within subalpine fens and headwaters, U. minor in very shallow base‐containing waters of spring brooks in upper montane ophiolite environments. The plant species composition of the Utricularia vegetation and its habitats are described. The pertinent vegetation types – Utricularietum ochroleucae and Scorpidio‐Utricularietum, respectively, as well as their higher‐ranking syntaxa – are new to Greece and the Balkans. The vegetation with U. ochroleuca forms part of the Annex I habitat type 3160 of the EU Habitats Directive, which is also new to Greece. Nature conservation status and management conditions of the detected plant communities and habitats with Utricularia in northern Greece are discussed.
The normativity of gender
Authors: Cosker‐Rowland Rach
Published: March 2023

There are important similarities between moral thought and talk and thought and talk about gender: disagreements about gender, like disagreements about morality, seem to be intractable and to outstrip descriptive agreement; and it seems coherent to reject any definition of what it is to be a woman in terms of particular social, biological, or other descriptive features, just as it seems coherent to reject any definition of what it is to be good or right in terms of any set of descriptive properties. These similarities give us reason to investigate the idea that, like moral thought and talk, gender thought and talk is inherently normative. This paper proposes a normative account of gender thought and talk in terms of fitting treatment. On this fitting treatment account, to judge that A is gender G is just to judge that it is fitting to treat A as a G. This account is a descriptive or hermeneutical account of our gender thought and talk rather than an ameliorative account of our gender concepts or a metaphysical account of gender properties in social metaphysics. This paper argues that other descriptive accounts of gender thought and talk face problems that the fitting treatment account overcomes.
Functional and MRI Outcomes After In Situ Repair Versus Tear Completion Before Repair of Bursal‐Side Partial‐Thickness Rotator Cuff Tears
Authors: Zhuo Hongwu , Pan Ling , Li Jian
Published: March 2023

Objective

The optimal repair method for bursal‐side partial‐thickness rotator cuff tears (PTRCTs) involving >50% of the thickness remains a controversial topic. The study was aimed to compare the functional and magnetic resonance imaging (MRI) outcomes after in situ repair or tear completion before repair of bursal‐side PTRCTs.

Methods

A retrospective clinical study was conducted involving 58 patients who underwent in situ repair or tear completion before repair of bursal‐side PTRCTs between January 2019 and December 2020. These patients were divided into two groups: the in situ repair group and the tear completion before repair group. Functional assessment consisted of active range of motion (ROM), visual analog scale (VAS), American Shoulder and Elbow Surgeons (ASES) score, and Constant–Murley score. The percentages of patients in each group achieving the minimal clinical important difference (MCID) of the functional scores were determined. The healing status of the rotator cuff was assessed by postoperative MRI.

Results

There were no statistically significant differences between the two groups in terms of demographic data. The mean follow‐up period was 14.53 ± 2.64 months in the in situ repair group and 15.40 ± 2.66 months in the tear completion before repair group. At the final follow‐up, the forward elevation, external rotation, and internal rotation improved significantly in both groups. The VAS, ASES score, and Constant–Murley score improved significantly in the in situ repair group (5.17 ± 2.00 points to 0.11 ± 0.41 points, p = 0.001; 44.04 ± 17.40 points to 95.47 ± 4.32 points, p = 0.001; 49.50 ± 14.38 points to 93.50 ± 3.49 points, p = 0.001) and in the tear completion before repair group (5.43 ± 3.32 points to 0.03 ± 0.18 points, p = 0.001; 41.50 ± 19.59 points to 95.94 ± 2.68 points, p = 0.001; 47.54 ± 17.13 points to 93.97 ± 2.61 points, p = 0.001). Postoperative MRI revealed that the re‐tear rate was 7.1% (2/28) in the in situ repair group and 3.3% (1/30) in the tear completion before repair group. No significant differences were observed in terms of the functional scores, the percentages of patients achieving the MCID of the functional scores, and the re‐tear rate between the two groups (p > 0.05).

Conclusions

Both in situ repair and tear completion before repair yielded satisfactory clinical outcomes for patients with bursal‐side PTRCTs. No significant differences were observed in the functional and MRI outcomes between the two groups.
Comparison of Ambu AuraGain and BlockBuster laryngeal mask for controlled ventilation in children undergoing minor surgical procedures under general anesthesia: A prospective randomized controlled study
Authors: Kumar Kanil Ranjith , Soni Lipika , Sinha Renu , Muthiah Thilaka , Patel Nishant , Shende Dilip K. , Subramaniam Rajeshwari
Published: March 2023

Background

Ambu AuraGain has proven to be better compared with other supraglottic airway devices in terms of higher first‐attempt insertion success rate, time and ease of insertion, high oropharyngeal leak pressure, and fewer complications in children. The performance of the BlockBuster laryngeal mask has not been evaluated in children.

Aims

The primary objective of this study was to compare the oropharyngeal leak pressure of the BlockBuster laryngeal mask with those of the Ambu AuraGain during controlled ventilation in children.

Methods

Fifty children aged 6 months to 12 years with normal airways were randomized into group A (Ambu AuraGain) and group B (BlockBuster laryngeal mask). After administration of general anesthesia, an appropriate size supraglottic airway (size 1.5/2.0/2.5) was inserted according to the groups. Oropharyngeal leak pressure, success and ease of supraglottic airway insertion, gastric tube insertion, and ventilatory parameters were noted. The glottic view was graded by fiberoptic bronchoscopy.

Results

Demographic parameters were comparable. The mean oropharyngeal leak pressure in the BlockBuster group (24.72 ± 6.81 cm H2O) was significantly higher than Ambu AuraGain group (17.20 ± 4.28 cm H2O) by 7.52 cm H2O (95% CI 4.27 to 10.76; p = 0.001). The mean time for supraglottic airway insertion in the BlockBuster and Ambu AuraGain group was 12.04 ± 2.55 s and 13.64 ± 2.76 s, respectively (mean difference‐ 1.6 s, 95% CI 0.09–3.12; p = 0.04). Ventilatory parameters, first‐attempt supraglottic airway insertion success rate, and ease of gastric tube insertion were comparable between the groups. The BlockBuster group showed easy supraglottic airway insertion compared with the Ambu AuraGain group. The BlockBuster group had better glottic views with only the larynx seen in 23 out of 25 children compared to the Ambu AuraGain with only the larynx seen in 19 out of 25 children. No complication was noted in either group.

Conclusions

We found that the BlockBuster laryngeal mask has higher oropharyngeal leak pressure compared with Ambu AuraGain in a pediatric population.
Thoracic Society of Australia and New Zealand (TSANZ) position statement on chronic suppurative lung disease and bronchiectasis in children, adolescents and adults in Australia and New Zealand
Authors: Chang Anne B. , Bell Scott C. , Byrnes Catherine A. , Dawkins Paul , Holland Anne E. , Kennedy Emma , King Paul T. , Laird Pamela , Mooney Sarah , Morgan Lucy , Parsons Marianne , Poot Betty , Toombs Maree , Torzillo Paul J. , Grimwood Keith
Published: March 2023

This position statement, updated from the 2015 guidelines for managing Australian and New Zealand children/adolescents and adults with chronic suppurative lung disease (CSLD) and bronchiectasis, resulted from systematic literature searches by a multi‐disciplinary team that included consumers. The main statements are:

Diagnose CSLD and bronchiectasis early; this requires awareness of bronchiectasis symptoms and its co‐existence with other respiratory diseases (e.g., asthma, chronic obstructive pulmonary disease).

Confirm bronchiectasis with a chest computed‐tomography scan, using age‐appropriate protocols and criteria in children.

Undertake a baseline panel of investigations.

Assess baseline severity, and health impact, and develop individualized management plans that include a multi‐disciplinary approach and coordinated care between healthcare providers.

Employ intensive treatment to improve symptom control, reduce exacerbation frequency, preserve lung function, optimize quality‐of‐life and enhance survival. In children, treatment also aims to optimize lung growth and, when possible, reverse bronchiectasis.

Individualize airway clearance techniques (ACTs) taught by respiratory physiotherapists, encourage regular exercise, optimize nutrition, avoid air pollutants and administer vaccines following national schedules.

Treat exacerbations with 14‐day antibiotic courses based upon lower airway culture results, local antibiotic susceptibility patterns, clinical severity and patient tolerance. Patients with severe exacerbations and/or not responding to outpatient therapy are hospitalized for further treatments, including intravenous antibiotics and intensive ACTs.

Eradicate Pseudomonas aeruginosa when newly detected in lower airway cultures.

Individualize therapy for long‐term antibiotics, inhaled corticosteroids, bronchodilators and mucoactive agents.

Ensure ongoing care with 6‐monthly monitoring for complications and co‐morbidities.

Undertake optimal care of under‐served peoples, and despite its challenges, delivering best‐practice treatment remains the overriding aim.
The association of cognition with protein energy wasting and synaptic transmission in chronic kidney disease
Authors: Yang Xia , Quan Yujun , Wu Erzhong , Jiang Yuecheng , Song Qian , Li Yue , Li Qian , Sun Zhaolin , Yuan Jing , Zha Yan , Cui Xiaoli
Published: March 2023

Introduction: In recent years, consciousness impairment in patients with end‐stage renal disease (ESRD) has been paid more and more attention, but the cause and mechanism of consciousness state change is not clear. Methods: As the hippocampus played a crucial role in consciousness, we explored the pathological and electrophysiological changes in chronic kidney disease (CKD) mouse hippocampus. Results: Whole‐cell recordings in hippocampal neurons showed that miniature excitatory postsynaptic current (mEPSC) frequency decreased, but the amplitude was unaltered in CKD_8w mice. In addition, α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazole‐propionic acid receptor‐mediated EPSCs (AMPAR‐EPSCs) and N‐methyl‐D‐aspartic acid receptor‐mediated EPSCs (NMDAR‐EPSCs) in hippocampal Schaffer collateral‐CA1 synapses displayed a significant decline in CKD_8w mice. Although the ratio of AMPAR‐/NMDAR‐EPSCs did not change, the paired‐pulse ratio (PPR) in CKD_8w mice increased. Intriguingly, the mEPSC frequency and AMPAR‐/NMDAR‐EPSCs amplitudes were positively associated with body weight, and the mEPSC frequency was negatively correlated with serum creatinine in CKD_8w mice, indicating a potential correlation between cognition and nutritional status in patients with CKD. To confirm the above hypothesis, we collected the clinical data from multiple hemodialysis centers to analyze the correlation between cognition and nutritional status. Conclusion: Our analysis indicated that protein energy wasting (PEW) was a possible independent risk factor for consciousness dysfunction in maintenance hemodialysis (MHD) patients. Our results provided a more detailed mechanism underlying the cognitive impairment (CI) in ESRD patients at the synaptic level. Last but not least, our results showed that PEW was a probable new independent risk factor for CI in cases with ESRD.
Earthquake Early Warning System (EEWS) empowered by Time‐Dependent Neo‐Deterministic Seismic Hazard Assessment (TD‐NDSHA)
Authors: Zhang Yan , Wu Zhongliang , Romanelli Fabio , Vaccari Franco , Peresan Antonella , Li Jiawei , Panza Giuliano F.
Published: March 2023

In the network‐based on‐site earthquake early warning system (EEWS), the ‘blind zone’, namely the zone where the issued warning arrives later than the destructive S and surface waves, is one of the challenges affecting its effectiveness. The ‘blind zone’ is determined by the interstation distance, or equivalently the density of seismic stations, of the network. In this paper, we suggest a practical approach according to which, when in a region a temporary increase of seismic hazard is declared, additional stations are deployed in such a way that the blind zone is temporarily reduced. In the procedure, the time‐dependent neo‐deterministic seismic hazard assessment (TD‐NDSHA) plays a vital role in the identification of the regions potentially exposed to high macroseismic intensities. As a showcase example, we consider the scenario of year 2014 at the Sichuan‐Yunnan border of southwest China. The TD‐NDSHA is based on the standard NDSHA procedure at regional scale (bedrock conditions), with the ‘controlling earthquakes’ defined on the basis of the Annual Consultation. We show that the ‘blind zone’ can be reduced in the identified areas of interest (e.g., MMI ≥ VI), by deploying a limited number of additional seismic stations. In the case where false alarms can be tolerated, significant reduction of the ‘blind zone’ can be implemented by moving from a network‐based EEWS to a single‐sensor‐based EEWS and skipping the process of location and magnitude‐determination/prediction procedures.
Tissue‐mimetic culture enhances mesenchymal stem cell secretome capacity to improve regenerative activity of keratinocytes and fibroblasts in vitro
Authors: Hodge Jacob G. , Decker Heather E. , Robinson Jennifer L. , Mellott Adam J.
Published: March 2023

Mesenchymal stem/stromal cells (MSCs) are a heterogenous population of multipotent and highly secretory cells currently being investigated in the field of wound healing for their ability to augment tissue responses. The adaptive response of MSC populations to the rigid substrate of current 2D culture systems has been considered to result in a deterioration of regenerative ‘stem‐like’ properties. In this study, we characterise how the improved culture of adipose‐derived mesenchymal stem cells (ASCs) within a tissue‐mimetic 3D hydrogel system, that is mechanically similar to native adipose tissue, enhances their regenerative capabilities. Notably, the hydrogel system contains a porous microarchitecture that permits mass transport, enabling efficient collection of secreted cellular compounds. By utilising this 3D system, ASCs retained a significantly higher expression of ASC ‘stem‐like’ markers while demonstrating a significant reduction in senescent populations, relative to 2D. Additionally, culture of ASCs within the 3D system resulted in enhanced secretory activity with significant increases in the secretion of proteinaceous factors, antioxidants and extracellular vesicles (EVs) within the conditioned media (CM) fraction. Lastly, treatment of wound healing cells, keratinocytes (KCs) and fibroblasts (FBs), with ASC‐CM from the 2D and 3D systems resulted in augmented functional regenerative activity, with ASC‐CM from the 3D system significantly increasing KC and FB metabolic, proliferative and migratory activity. This study demonstrates the potential beneficial role of MSC culture within a tissue‐mimetic 3D hydrogel system that more closely mimics native tissue mechanics, and subsequently how the improved phenotype augments secretory activity and potential wound healing capabilities of the MSC secretome.
Optical mapping of contracting hearts
Authors: Kappadan Vineesh , Sohi Anies , Parlitz Ulrich , Luther Stefan , Uzelac Ilija , Fenton Flavio , Peters Nicholas S , Christoph Jan , Ng Fu Siong
Published: March 2023

Optical mapping is a widely used tool to record and visualize the electrophysiological properties in a variety of myocardial preparations such as Langendorff‐perfused isolated hearts, coronary‐perfused wedge preparations, and cell culture monolayers. Motion artifact originating from the mechanical contraction of the myocardium creates a significant challenge to performing optical mapping of contracting hearts. Hence, to minimize the motion artifact, cardiac optical mapping studies are mostly performed on non‐contracting hearts, where the mechanical contraction is removed using pharmacological excitation–contraction uncouplers. However, such experimental preparations eliminate the possibility of electromechanical interaction, and effects such as mechano‐electric feedback cannot be studied. Recent developments in computer vision algorithms and ratiometric techniques have opened the possibility of performing optical mapping studies on isolated contracting hearts. In this review, we discuss the existing techniques and challenges of optical mapping of contracting hearts.

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RyR2‐dependent modulation of neuronal hyperactivity: A potential therapeutic target for treating Alzheimer's disease
Authors: Yao Jinjing , Chen S. R. Wayne
Published: March 2023

Increasing evidence suggests that simply reducing β‐amyloid (Aβ) plaques may not significantly affect the progression of Alzheimer's disease (AD). There is also increasing evidence indicating that AD progression is driven by a vicious cycle of soluble Aβ‐induced neuronal hyperactivity. In support of this, it has recently been shown that genetically and pharmacologically limiting ryanodine receptor 2 (RyR2) open time prevents neuronal hyperactivity, memory impairment, dendritic spine loss and neuronal cell death in AD mouse models. By contrast, increased RyR2 open probability (Po) exacerbates the onset of familial AD‐associated neuronal dysfunction and induces AD‐like defects in the absence of AD‐causing gene mutations. Thus, RyR2‐dependent modulation of neuronal hyperactivity represents a promising new target for combating AD.

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Competencias digitales docentes y retos durante la pandemia COVID-19
Authors: Rodríguez-Jiménez Franmis José , Pérez-Ochoa María Elena , Ulloa-Guerra Óscar
Published: March 2023

Las competencias digitales constituyen actualmente un indicador de calidad. En este sentido, el propósito del estudio fue diagnosticar la autopercepción del profesorado de una institución de secundaria de República Dominicana con relación al nivel de desarrollo de sus competencias digitales para lidiar con los retos emergidos durante la pandemia de COVID-19. Es un estudio no experimental, de tipo transeccional-descriptivo y cuantitativo, realizado durante el periodo de confinamiento (abril-juniode 2020). Los resultados indican que la mayoría del profesorado se autopercibe con un alto nivel de desarrollo en la alfabetización tecnológica, pero que valoran sus competencias digitales entre regulares y adecuadas.
Políticas educativas y migración. Lecciones en contextos de neoliberalismo avanzado
Authors: Jiménez-Vargas Felipe Andrés
Published: March 2023

Se presentan los resultados de una investigación en escuelas con alta matrícula de estudiantes extranjeros. En el marco de un sistema educativo, caracterizado por un modelo de neoliberalismo avanzado, y mediante técnicas cualitativas como la observación participante, el sombreamiento, análisis documental y entrevistas, se señala un conjunto de prácticas de resistencia adaptativas que dan lugar a tres giros que tensionan los mandatos del modelo: un giro afectivo, uno colaborativo y uno localista. Las discusiones reivindican el papel del profesorado, en tanto estos operativizan la inclusión educativa, además del rol que la diversidad juega hoy en día al interior de la arquitectura escolar.
Boundary Layer Investigations for Primarily Axial Flow Over a Stationary and Transversely Oscillating Cylinder
Authors: Eastridge Jonathan R. , Taravella Brandon M. , Srivastava Shivank
Published: March 2023

Boundary layer information local to three longitudinal positions has been characterized for a 122 cm long acrylic cylinder with hemispherical endcaps, via analysis of stereo particle image velocimetry (PIV) measurements made during laterally oscillating motions and for steady, axisymmetric flow. No obvious turbulent flow structures or indications of boundary layer separation were observed at nonzero advance speeds, and skin friction coefficients were subsequently estimated for magnitude relative to the dynamic pressure associated with an axial flow speed of 0.25 m/s. Computational fluid dynamics (CFD) analysis is performed in commercial software to accompany the experimental measurements. Local skin friction coefficients are estimated and deviate, on average, from analytical solutions for zero gradient axisymmetric flows by around 22% and from the accompanying numerical solutions by around 4%. The effects of intermittent boundary layer compression and turbulence inhibition are readily observed for the oscillating cylinder, although vortex shedding is observed for some large amplitude, high frequency cases.
Reduction of vowel space in Alzheimer's disease
Authors: Shamei Arian , Liu Yadong , Gick Bryan
Published: March 2023

Reduced vowel space area (VSA) is a known effect of neurodegenerative diseases such as Parkinson's disease (PD). Using large publicly available corpuses, two experiments were conducted comparing the vowel space of speakers with and without Alzheimer's disease (AD) during spontaneous and read speech. First, a comparison of vowel distance found reduced distance in AD for English spontaneous speech, but not Spanish read speech. Findings were then verified using an unsupervised learning approach to quantify VSA through cluster center detection. These results corroborate observations for PD that VSA reduction is task-dependent, but further experiments are necessary to quantify the effect of language.
Variable Cadence Gait Training Outcomes Using Rhythmic Auditory Stimulation Embedded in Older Adults’ Preferred Music
Authors: Larson Cathy A. , Roth Edward A. , Sterenberg Mahon Alycia J. , Crinion Michael , Fischer Kelsey , Yim Sun Hye , Smith Amy K.
Published: March 2023

Older adults must have the ability to walk at variable speeds/distances to meet community demands. This single group pre–post test study’s purposes were to examine if actual cadences after 7 weeks of rhythmic auditory stimulation gait training matched target cadences, improved walking distance, duration, velocity, maximum cadence, balance, enjoyment, and/or changed spatial/temporal gait parameters. Fourteen female adults (72.6 ± 4.4 years) participated in 14 sessions, while variable cadences were progressively introduced. Eleven older adult responders walked faster (3.8 steps/min) than one target cadence (−10% pace) while matching the target cadences for the other paces when walking with rhythmic auditory stimulation. Two nonresponders walked near their baseline cadence with little variability while one walked at faster cadences; all three did not appear to adjust to the beat of the music. After training, participants increased their walking distance, 90.8 ± 46.5 m; t(1, 13) = −7.3; p ≤ .005, velocity, 0.36 ± 0.15 m/s; t(1, 40) = −15.4; p < .001, and maximum cadence, 20.6 ± 9.1 steps/min; t(1, 40) = −14.6; p < .001; changes exceeded minimal clinically important differences. Twelve of 14 expressed enjoyment. Walk with rhythmic auditory stimulation training is a promising activity for older adults, which may translate to an individual’s ability to adapt walking speeds to various community demands.
Associations of Physical Activity and Sedentary Behavior With Survival Time in Older Adults: Path Analysis
Authors: Galvão Lucas Lima , Silva Rizia Rocha , Tribess Sheilla , Meneguci Joilson , Sasaki Jeffer Eidi , Santos Douglas de Assis Teles , Virtuoso Júnior Jair Sindra
Published: March 2023

This study investigated the direct and indirect associations of physical activity and sedentary behavior with survival time in older adults. Prospective population-based cohort study used exploratory survey-type methods and physical performance tests in 319 adults aged ≥60 years. Trajectory diagrams were used to represent the initial hypothetical and final models with the relationships of independent, mediating, and dependent variables. Physical activity was indirectly associated with survival time and was mediated by instrumental activities of daily living and functional performance. In contrast, instrumental activities of daily living, functional performance, the number of hospitalizations, and medications mediated the association between duration of sedentary behavior and survival time. The explanatory power of the final model was 19%. Future efforts should focus on increasing the participation and adherence of older adults to exercise programs to improve their physical functions and general health, which may increase their health period and, consequently, their survival time.
Prevalence and Sociodemographic Correlates of Meeting the 24-Hour Movement Guidelines Among Low-Income Brazilian Older Adults With Chronic Diseases
Authors: Soares Antonio Henrique Germano , Wendt Andrea , Crochemore-Silva Inácio , Martins Clarice , Barbosa Arthur Oliveira , de Barros Mauro Virgílio Gomes , Tassitano Rafael M.
Published: March 2023

This study examined the prevalence and sociodemographic correlates of meeting individual behavior and 24-hr movement behavior guidelines among Brazilian older adults with chronic diseases. The sample comprised 273 older adults aged ≥60 years (80.2% women) with chronic diseases from Recife, Pernambuco, Brazil. Sociodemographic variables were self-reported, while 24-hr movement behaviors were assessed by accelerometry. Participants were classified as meeting (or not meeting) individual and integrated recommendations for moderate-to-vigorous physical activity (MVPA), sedentary behavior, and sleep duration. No participant met the 24-hr movement behavior guidelines, while only 8.4% met integrated MVPA/sleep recommendations. The prevalence of meeting recommendations of MVPA, sedentary behavior, and sleep was 28.9%, 0.4%, and 32.6%, respectively. Discrepancies according to sociodemographic variables on meeting MVPA recommendations existed. The findings show the need for dissemination and implementation strategies to foster adoption of the 24-hr movement behavior guidelines among Brazilian older adults with chronic diseases.
A molecular framework for grain number determination in barley
Authors: Huang Yongyu , Kamal Roop , Shanmugaraj Nandhakumar , Rutten Twan , Thirulogachandar Venkatasubbu , Zhao Shuangshuang , Hoffie Iris , Hensel Goetz , Rajaraman Jeyaraman , Moya Yudelsy Antonia Tandron , Hajirezaei Mohammad-Reza , Himmelbach Axel , Poursarebani Naser , Lundqvist Udda , Kumlehn Jochen , Stein Nils , von Wirén Nicolaus , Mascher Martin , Melzer Michael , Schnurbusch Thorsten
Published: March 2023

Flowering plants with indeterminate inflorescences often produce more floral structures than they require. We found that floral primordia initiations in barley (
Hordeum vulgare
L.) are molecularly decoupled from their maturation into grains. While initiation is dominated by flowering-time genes, floral growth is specified by light signaling, chloroplast, and vascular developmental programs orchestrated by barley
CCT MOTIF FAMILY 4
(
HvCMF4
), which is expressed in the inflorescence vasculature. Consequently, mutations in
HvCMF4
increase primordia death and pollination failure, mainly through reducing rachis greening and limiting plastidial energy supply to developing heterotrophic floral tissues. We propose that
HvCMF4
is a sensory factor for light that acts in connection with the vascular-localized circadian clock to coordinate floral initiation and survival. Notably, stacking beneficial alleles for both primordia number and survival provides positive implications on grain production. Our findings provide insights into the molecular underpinnings of grain number determination in cereal crops.
Embedment of sensing elements for robust, highly sensitive, and cross-talk–free iontronic skins for robotics applications
Authors: Shi Junli , Dai Yuan , Cheng Yu , Xie Sai , Li Gang , Liu Yuan , Wang Jingxiao , Zhang Ruirui , Bai Ningning , Cai Minkun , Zhang Yuan , Zhan Yifei , Zhang Zhengyou , Yu Cunjiang , Guo Chuan Fei
Published: March 2023

Iontronic pressure sensors are promising in robot haptics because they can achieve high sensing performance using nanoscale electric double layers (EDLs) for capacitive signal output. However, it is challenging to achieve both high sensitivity and high mechanical stability in these devices. Iontronic sensors need microstructures that offer subtly changeable EDL interfaces to boost sensitivity, while the microstructured interfaces are mechanically weak. Here, we embed isolated microstructured ionic gel (IMIG) in a hole array (28 × 28) of elastomeric matrix and cross-link the IMIGs laterally to achieve enhanced interfacial robustness without sacrificing sensitivity. The embedded configuration toughens and strengthens the skin by pinning cracks and by the elastic dissipation of the interhole structures. Furthermore, cross-talk between the sensing elements is suppressed by isolating the ionic materials and by designing a circuit with a compensation algorithm. We have demonstrated that the skin is potentially useful for robotic manipulation tasks and object recognition.