bluuebunny/crossref_metadata_2025 huggingface dataset:
Higher Soluble ACE2 Levels and Increased Risk of Infection-Related Hospitalization in Patients on Maintenance Hemodialysis
Authors: Kawabe Mayuko , Nakashima Akio , Yamamoto Izumi , Ohkido Ichiro , Yokoo Takashi , Urashima Mitsuyoshi
Published: January 2022

Background

Angiotensin-converting enzyme 2 (ACE2) works as an endogenous counter-regulator of the renin-angiotensin system, which has pivotal roles in preventing both cardiovascular disease (CVD) and inflammation. In general populations, higher plasma soluble ACE2 levels were reported to be associated with increased risks of all-cause death and major CVD. Because infections are fatal in patients on maintenance hemodialysis, we aimed to explore whether soluble ACE2 levels are associated with an increased risk of infection-related hospitalization in these patients.

Methods

Using data from a prospective, multicenter, cohort study conducted in Tokyo, Japan, we performed a post-hoc analyses of 724 clinically stable patients on maintenance hemodialysis. We measured baseline serum soluble ACE2 levels and assessed potential determinants of its with infection-related hospitalization as a primary outcome as well as all-cause death and CVD as secondary outcomes using a Cox proportional hazards model.

Results

The soluble ACE2 level (median, 0.16 ng/ml; interquartile range, 0.07–0.57 ng/ml) showed a weak negative association with age. During a median follow-up of 39 months, 106 patients (14.6%) were hospitalized with infectious diseases. Compared with the lower half of soluble ACE2 levels, the higher half was associated with an increased risk of infection-related hospitalization (hazard ratio, 1.57; 95% confidence interval, 1.02–2.41) with adjustment by other risk factors. On the other hand, there were no significant associations between soluble ACE2 and risks of all-cause death and CVD.

Conclusion

Higher soluble ACE2 levels may associate with an increased risk of infection-related hospitalization in patients on maintenance hemodialysis.
Elimination of the Sugar Transporter GAT1 Increased Xylanase I Production in Trichoderma reesei
Authors: Xu Wenqiang , Fang Yu , Ding Mingyang , Ren Yajing , Meng Xiangfeng , Chen Guanjun , Zhang Weixin , Liu Weifeng
Published: January 2022

The filamentous fungus Trichoderma reesei secretes large quantities of cellulases and hemicellulases that have found wide applications in industry. Compared with extensive studies on the mechanism controlling cellulase gene expression, less is known about the regulatory mechanism behind xylanase gene expression. Herein, several putative sugar transporter encoding genes that showed significant upregulation on xylan were identified in T. reesei. Deletion of one such gene, gat1, resulted in increased xylanase production but hardly affected cellulase induction. Further analyses demonstrated that deletion of gat1 markedly increased XYNI production at the transcriptional level and only exerted a minor effect on XYNII synthesis. In contrast, overexpressing gat1 caused a continuous decrease in xyn1 expression. Deletion of gat1 also affected the expression of xyn1 and pectinase genes when T. reesei was cultivated with galacturonic acid as the sole carbon source. Transcriptome analyses of Δgat1 and its parental strain identified 255 differentially expressed genes that are enriched in categories of glycoside hydrolases, lipid metabolism, transporters, and transcriptional factors. The results thus implicate a repressive role of the sugar transporter GAT1 in xyn1 expression and reveal that distinct regulatory mechanisms may exist in controlling the expression of different xylanase genes in T. reesei.
Host Molecules That Promote Pathophysiology of Ocular Herpes
Authors: Shukla Sajal Deea , Valyi-Nagy Tibor
Published: January 2022

Herpes simplex virus type-1 (HSV-1) is a human virus that causes lifelong infections in a large population worldwide. Recurrence of HSV-1 from latency in trigeminal ganglion (TG) is the trigger of the morbidities seen with this virus. In addition to causing fever blisters and cold sores, occasionally the virus can also cause corneal lesions resulting in blindness in untreated individuals. Several host cell proteins play important roles in HSV-1 infection of the eye. HSV-1 enters into the corneal epithelial cells via its interactions with cell surface receptors. In parallel, the Toll-like receptors sense viral invasion and activate defense mechanisms to fight the infection. New data shows that Optineurin, a host autophagy receptor is also activated to degrade viral particles. In contrast, activation of heparanase, a host enzyme, induces an immune-inflammatory response, which triggers pro-inflammatory and pro-angiogenic environment and ultimately results in many of the clinical features seen with HSV-1 infection of the cornea. Rarely, HSV-1 can also spread to the central nervous system causing serious diseases. In this review, we summarize the latest knowledge on host molecules that promote pathophysiological aspects of ocular herpes.
Radiomic Features of the Hippocampus for Diagnosing Early-Onset and Late-Onset Alzheimer’s Disease
Authors: Du Yang , Zhang Shaowei , Fang Yuan , Qiu Qi , Zhao Lu , Wei Wenjing , Tang Yingying , Li Xia
Published: January 2022

Background: Late-onset Alzheimer’s disease (LOAD) and early-onset Alzheimer’s disease (EOAD) are different subtypes of AD. This study aimed to build and validate radiomics models of the hippocampus for EOAD and young controls (YCs), LOAD and old controls (OCs), as well as EOAD and LOAD.

Methods: Thirty-six EOAD patients, 36 LOAD patients, 36 YCs, and 36 OCs from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database were enrolled and allocated to training and test sets of the EOAD-YC groups, LOAD-OC groups, and EOAD-LOAD groups. Independent external validation sets including 15 EOAD patients, 15 LOAD patients, 15 YCs, and 15 OCs from Shanghai Mental Health Center were constructed, respectively. Bilateral hippocampal segmentation and feature extraction were performed for each subject, and the least absolute shrinkage and selection operator (LASSO) method was used to select radiomic features. Support vector machine (SVM) models were constructed based on the identified features to distinguish EOAD from YC subjects, LOAD from OC subjects, and EOAD from LOAD subjects. The areas under the receiver operating characteristic curves (AUCs) were used to evaluate the performance of the models.

Results: Three, three, and four features were selected for EOAD and YC subjects, LOAD and OC subjects, and EOAD and LOAD subjects, respectively. The AUC and accuracy of the SVM model were 0.90 and 0.77 in the test set and 0.91 and 0.87 in the validation set for EOAD and YC subjects, respectively; for LOAD and OC subjects, the AUC and accuracy were 0.94 and 0.86 in the test set and 0.92 and 0.78 in the validation set, respectively. For the SVM model of EOAD and LOAD subjects, the AUC was 0.87 and the accuracy was 0.79 in the test set; additionally, the AUC was 0.86 and the accuracy was 0.77 in the validation set.

Conclusion: The findings of this study provide insights into the potential of hippocampal radiomic features as biomarkers to diagnose EOAD and LOAD. This study is the first to show that SVM classification analysis based on hippocampal radiomic features is a valuable method for clinical applications in EOAD.
Morphological Plasticity of the Retina of Viperidae Snakes Is Associated With Ontogenetic Changes in Ecology and Behavior
Authors: Tashiro Juliana H. , Ventura Dora F. , Hauzman Einat
Published: January 2022

Snakes of the Viperidae family have retinas adapted to low light conditions, with high packaging of rod-photoreceptors containing the rhodopsin photopigment (RH1), and three types of cone-photoreceptors, large single and double cones with long-wavelength sensitive opsins (LWS), and small single cones with short-wavelength sensitive opsins (SWS1). In this study, we compared the density and distribution of photoreceptors and ganglion cell layer (GCL) cells in whole-mounted retinas of two viperid snakes, the lancehead Bothrops jararaca and the rattlesnake Crotalus durissus, and we estimated the upper limits of spatial resolving power based on anatomical data. The ground-dwelling C. durissus inhabits savannah-like habitats and actively searches for places to hide before using the sit-and-wait hunting strategy to ambush rodents. B. jararaca inhabits forested areas and has ontogenetic changes in ecology and behavior. Adults are terrestrial and use similar hunting strategies to those used by rattlesnakes to prey on rodents. Juveniles are semi-arboreal and use the sit-and-wait strategy and caudal luring to attract ectothermic prey. Our analyses showed that neuronal densities were similar for the two species, but their patterns of distribution were different between and within species. In adults and juveniles of C. durissus, cones were distributed in poorly defined visual streaks and rods were concentrated in the dorsal retina, indicating higher sensitivity in the lower visual field. In adults of B. jararaca, both cones and rods were distributed in poorly defined visual streaks, while in juveniles, rods were concentrated in the dorsal retina and cones in the ventral retina, enhancing sensitivity in the lower visual field and visual acuity in the upper field. The GCL cells had peak densities in the temporal retina of C. durissus and adults of B. jararaca, indicating higher acuity in the frontal field. In juveniles of B. jararaca, the peak density of GCL cells in the ventral retina indicates better acuity in the upper field. The estimated visual acuity varied from 2.3 to 2.8 cycles per degree. Our results showed interspecific differences and suggest ontogenetic plasticity of the retinal architecture associated with changes in the niche occupied by viperid snakes, and highlight the importance of the retinal topography for visual ecology and behavior of snakes.
Orientation Invariant Sensorimotor Object Recognition Using Cortical Grid Cells
Authors: Roux Kalvyn , van den Heever David
Published: January 2022

Grid cells enable efficient modeling of locations and movement through path integration. Recent work suggests that the brain might use similar mechanisms to learn the structure of objects and environments through sensorimotor processing. This work is extended in our network to support sensor orientations relative to learned allocentric object representations. The proposed mechanism enables object representations to be learned through sensorimotor sequences, and inference of these learned object representations from novel sensorimotor sequences produced by rotated objects through path integration. The model proposes that orientation-selective cells are present in each column in the neocortex, and provides a biologically plausible implementation that echoes experimental measurements and fits in with theoretical predictions of previous studies.
Stochastic Termination of Spiral Wave Dynamics in Cardiac Tissue
Authors: Rappel Wouter-Jan , Krummen David E. , Baykaner Tina , Zaman Junaid , Donsky Alan , Swarup Vijay , Miller John M. , Narayan Sanjiv M.
Published: January 2022

Rotating spiral waves are self-organized features in spatially extended excitable media and may play an important role in cardiac arrhythmias including atrial fibrillation (AF). In homogeneous media, spiral wave dynamics are perpetuated through spiral wave breakup, leading to the continuous birth and death of spiral waves, but have a finite probability of termination. In non-homogeneous media, however, heterogeneities can act as anchoring sources that result in sustained spiral wave activity. It is thus unclear how and if AF may terminate following the removal of putative spiral wave sources in patients. Here, we address this question using computer simulations in which a stable spiral wave is trapped by an heterogeneity and is surrounded by spiral wave breakup. We show that, following ablation of spatial heterogeneity to render that region of the medium unexcitable, termination of spiral wave dynamics is stochastic and Poisson-distributed. Furthermore, we show that the dynamics can be accurately described by a master equation using birth and death rates. To validate these predictions in vivo, we mapped spiral wave activity in patients with AF and targeted the locations of spiral wave sources using radiofrequency ablation. Targeted ablation was indeed able to terminate AF, but only after a variable delay of up to several minutes. Furthermore, and consistent with numerical simulations, termination was not accompanied by gradual temporal or spatial organization. Our results suggest that spiral wave sources and tissue heterogeneities play a critical role in the maintenance of AF and that the removal of sources results in spiral wave dynamics with a finite termination time, which could have important clinical implications.
Glymphatic Dysfunction in Patients With End-Stage Renal Disease
Authors: Heo Chang Min , Lee Won Ho , Park Bong Soo , Lee Yoo Jin , Park Sihyung , Kim Yang Wook , Lee Dong Ah , Yoo Byeong Cheol , Park Kang Min
Published: January 2022

Background

We aimed to compare glymphatic dysfunction between patients with end-stage renal disease (ESRD) and healthy controls and analyze the correlation between the glymphatic function and clinical characteristics using the diffusion tensor image analysis along with the perivascular space (DTI-ALPS) index.

Methods

We prospectively enrolled neurologically asymptomatic 49 patients with ESRD undergoing dialysis and 38 healthy controls. Diffusion tensor image was conducted using the same 3T scanner, and the DTI-ALPS index was calculated. We compared the DTI-ALPS index between the patients with ESRD and healthy controls. In addition, we conducted a correlation analysis between the clinical characteristics and DTI-ALPS index in patients with ESRD.

Results

There were significant differences in the DTI-ALPS index between patients with ESRD and healthy controls. The DTI-ALPS index in patients with ESRD was lower than that in healthy controls (1.460 vs. 1.632, p = 0.003). In addition, there was a significant positive correlation between the DTI-ALPS index and serum parathyroid hormone levels (r = 0.357, p = 0.011).

Conclusion

We demonstrated glymphatic dysfunction in patients with ESRD, as revealed by the DTI-ALPS index. This study also reveals the feasibility of the DTI-ALPS method to determine glymphatic function in patients with ESRD, which could be used in future research studies.
Influence of the Location of a Decision Cue on the Dynamics of Pupillary Light Response
Authors: Pandey Pragya , Ray Supriya
Published: January 2022

The pupils of the eyes reflexively constrict in light and dilate in dark to optimize retinal illumination. Non-visual cognitive factors, like attention, arousal, decision-making, etc., also influence pupillary light response (PLR). During passive viewing, the eccentricity of a stimulus modulates the pupillary aperture size driven by spatially weighted corneal flux density (CFD), which is the product of luminance and the area of the stimulus. Whether the scope of attention also influences PLR remains unclear. In this study, we contrasted the pupil dynamics between diffused and focused attentional conditions during decision-making, while the global CFD remained the same in the two conditions. A population of 20 healthy humans participated in a pair of forced choice tasks. They distributed attention to the peripheral decision cue in one task, and concentrated at the center in the other to select the target from four alternatives for gaze orientation. The location of this cue did not influence participants’ reaction time (RT). However, the magnitude of constriction was significantly less in the task that warranted attention to be deployed at the center than on the periphery. We observed similar pupil dynamics when participants either elicited or canceled a saccadic eye movement, which ruled out pre-saccadic obligatory attentional orientation contributing to PLR. We further addressed how the location of attentional deployment might have influenced PLR. We simulated a biomechanical model of PLR with visual stimulation of different strengths as inputs corresponding to the two attentional conditions. In this homeomorphic model, the computational characteristic of each element was derived from the physiological and/or mechanical properties of the corresponding biological element. The simulation of this model successfully mimicked the observed data. In contrast to common belief that the global ambient luminosity drives pupillary response, the results of our study suggest that the effective CFD (eCFD) determined via the luminance multiplied by the size of the stimulus at the location of deployed attention in the visual space is critical for the magnitude of pupillary constriction.
On the Effects of Transcranial Direct Current Stimulation on Cerebral Glucose Uptake During Walking: A Report of Three Patients With Multiple Sclerosis
Authors: Rudroff Thorsten , Fietsam Alexandra C. , Deters Justin R. , Workman Craig D. , Boles Ponto Laura L.
Published: January 2022

Common symptoms of multiple sclerosis (MS) include motor impairments of the lower extremities, particularly gait disturbances. Loss of balance and muscle weakness, representing some peripheral effects, have been shown to influence these symptoms, however, the individual role of cortical and subcortical structures in the central nervous system is still to be understood. Assessing [18F]fluorodeoxyglucose (FDG) uptake in the CNS can assess brain activity and is directly associated with regional neuronal activity. One potential modality to increase cortical excitability and improve motor function in patients with MS (PwMS) is transcranial direct current stimulation (tDCS). However, tDCS group outcomes may not mirror individual subject responses, which impedes our knowledge of the pathophysiology and management of diseases like MS. Three PwMS randomly received both 3 mA tDCS and SHAM targeting the motor cortex (M1) that controls the more-affected leg for 20 min on separate days before walking on a treadmill. The radiotracer, FDG, was injected at minute two of the 20 min walk and the subjects underwent a Positron emission tomography (PET) scan immediately after the task. Differences in relative regional metabolism of areas under the tDCS anode and the basal ganglia were calculated and investigated. The results indicated diverse and individualized responses in regions under the anode and consistent increases in some basal ganglia areas (e.g., caudate nucleus). Thus, anodal tDCS targeting the M1 that controls the more-affected leg of PwMS might be capable of affecting remote subcortical regions and modulating the activity (motor, cognitive, and behavioral functions) of the circuitry connected to these regions.
Women in Neuroscience: Four Women’s Contributions to Science and Society
Authors: Yevoo Priscilla E. , Maffei Arianna
Published: January 2022

There has been increased cognizance of gender inequity and the importance of an inclusive and diverse approach to scientific research in recent years. However, the innovative work of women scientists is still undervalued based on reports of fewer women in leadership positions, limited citations of research spearheaded by women, reduced federal grant awards, and lack of recognition. Women have been involved in trailblazing work that paved the way for contemporary scientific inquiry. The strides made in current neuroscience include contributions from women who deserve more recognition. In this review, we discuss the work of four women whose groundbreaking scientific work has made ineffaceable marks in the neuroscience field. These women are pioneers of research and innovators and, in addition, contribute to positive change that bolsters the academic community and society. This article celebrates these women scientists, their substantial impacts in neuroscience, and the positive influence of their work on advancing society and culture.
Relevance of Cortical and Hippocampal Interneuron Functional Diversity to General Anesthetic Mechanisms: A Narrative Review
Authors: Speigel Iris A. , Hemmings Jr. Hugh C.
Published: January 2022

General anesthetics disrupt brain processes involved in consciousness by altering synaptic patterns of excitation and inhibition. In the cerebral cortex and hippocampus, GABAergic inhibition is largely mediated by inhibitory interneurons, a heterogeneous group of specialized neuronal subtypes that form characteristic microcircuits with excitatory neurons. Distinct interneuron subtypes regulate specific excitatory neuron networks during normal behavior, but how these interneuron subtypes are affected by general anesthetics is unclear. This narrative review summarizes current principles of the synaptic architecture of cortical and interneuron subtypes, their contributions to different forms of inhibition, and their roles in distinct neuronal microcircuits. The molecular and cellular targets in these circuits that are sensitive to anesthetics are reviewed in the context of how anesthetics impact interneuron function in a subtype-specific manner. The implications of this functional interneuron diversity for mechanisms of anesthesia are discussed, as are their implications for anesthetic-induced changes in neural plasticity and overall brain function.
Body-Specific Attention to the Hands and Feet in Healthy Adults
Authors: Aizu Naoki , Otaki Ryoji , Nishii Kazuhiro , Kito Takumi , Yao Runhong , Uemura Kenya , Izumi Shin-ichi , Yamada Kouji
Published: January 2022

To execute the intended movement, the brain directs attention, called body-specific attention, to the body to obtain information useful for movement. Body-specific attention to the hands has been examined but not to the feet. We aimed to confirm the existence of body-specific attention to the hands and feet, and examine its relation to motor and sensory functions from a behavioral perspective. The study included two groups of 27 right-handed and right-footed healthy adults, respectively. Visual detection tasks were used to measure body-specific attention. We measured reaction times to visual stimuli on or off the self-body and calculated the index of body-specific attention score to subtract the reaction time on self-body from that off one. Participants were classified into low and high attention groups based on each left and right body-specific attention index. For motor functions, Experiment 1 comprised handgrip strength and ball-rotation tasks for the hands, and Experiment 2 comprised toe grip strength involved in postural control for the feet. For sensory functions, the tactile thresholds of the hands and feet were measured. The results showed that, in both hands, the reaction time to visual stimuli on the hand was significantly lesser than that offhand. In the foot, this facilitation effect was observed in the right foot but not the left, which showed the correlation between body-specific attention and the normalized toe gripping force, suggesting that body-specific attention affected postural control. In the hand, the number of rotations of the ball was higher in the high than in the low attention group, regardless of the elaboration exercise difficulty or the left or right hand. However, this relation was not observed in the handgripping task. Thus, body-specific attention to the hand is an important component of elaborate movements. The tactile threshold was higher in the high than in the low attention group, regardless of the side in hand and foot. The results suggested that more body-specific attention is directed to the limbs with lower tactile abilities, supporting the sensory information reaching the brain. Therefore, we suggested that body-specific attention regulates the sensory information to help motor control.
Low Meat Consumption in the Netherlands Is Associated With Higher Intake of Fish, Nuts, Seeds, Cheese, Sweets, and Snacks: Results From a Two-Part Model
Authors: Heerschop Samantha N. , Biesbroek Sander , Boshuizen Hendriek C. , van't Veer Pieter
Published: January 2022

Studies on sustainable diets show a need for replacement of animal-based foods by plant-based foods, which is also called “the protein transition.” To gain insight into the acceptability of such diet shifts, this study evaluated which current food sources people consume at varying amounts of meat consumption. The study population consisted of 4,313 participants aged 1–79 years of the Dutch National Food Consumption Survey 2012–2016, which assessed diet using two nonconsecutive 24-h dietary recalls. A two-part statistical model was used that accounts for both repeated measures and the correlation between probability and amount of consumption. Results are presented for quartiles of low to high meat consumption, by age and sex. Depending on age and sex, a higher consumption of fish (>100%), nuts and seeds (73–156%), cheese (34–111%), and sweets and snacks (28–81%) is observed in the lowest quartile of meat consumption compared to the highest. For fish, nuts, seeds, and cheese, this increase is mainly due to probability of consumption (>100%, 61–93%, and 16–64%, respectively). For sweets and snacks, the increase is mainly due to the amount of consumption (26–72%). Probability of potato consumption is 29–51% lower at low meat consumption. Vegetable consumption is lower mainly due to amount of consumption (6–29%). The results from the two-part model suggest that shifting away from a traditional Dutch high meat-vegetable-potatoes pattern is associated with higher probability of consuming fish, nuts and seeds, and cheese, but also increased amounts of sweets and snacks. This illustrates that analyzing the probability and amount part separately in relation to behavioral or physiological determinants extends our understanding of the diet according to meat consumption. These insights are important when developing realistic and acceptable food-based dietary guidelines for meat reduction.
Possible Benefits of a Low Protein Diet in Older Patients With CKD at Risk of Malnutrition: A Pilot Randomized Controlled Trial
Authors: Caldiroli Lara , Vettoretti Simone , Armelloni Silvia , Mattinzoli Deborah , Ikehata Masami , Molinari Paolo , Alfieri Carlo , Messa Piergiorgio , Castellano Giuseppe
Published: January 2022

Background

Current guidelines do not clarify whether older patients with advanced chronic kidney disease (CKD) may benefit of low protein (LP) diet if they are at risk of malnutrition. We compared the effects of normocalorie/normoprotein (NP) and normocalorie/LP diet on nutritional status and metabolic complications related to the progression of kidney damage in these patients.

Methods

This pilot study had an open-label randomized-controlled design (ClinicalTrials.gov Id: NCT05015647). Thirty-five patients were treated for 6 months with two different diets (LP = 17) and (NP = 18). Malnutrition was assessed by the Malnutrition Inflammation Score and International Society of Renal Nutrition and Metabolism criteria. Renal function was assessed by creatinine and cystatin-C-based estimated glomerular filtration rate (eGFR).

Results

At the end of the study, Malnutrition Inflammation Score was improved in both LP and NP groups (respectively: 3 ± 3 vs. 6 ± 1.5, p = 0.020 and 3 ± 2.5 vs. 6 ± 2, p = 0.012), prevalence of protein energy wasting syndrome decreased only in LP. LP group had higher eGFRcys-C (17 ± 6 vs. 12 ± 4 ml/min/1.73 m2; p < 0.05), lower serum urea (105 ± 65 vs. 138 ± 30 mg/dl; p < 0.05) and lower parathormone (68 ± 10 vs. 99 ± 61 ng/L; p < 0.05) than NP. Serum and urinary phosphorous did not change while fibroblast growth factor 23 (FGF23)-intact and FGF23 c-terminal increased in both groups [FGF23-intact in LP: 70 (48; 98) vs. 126 (90; 410) pg/ml, p < 0.01 and in NP: 86 (57; 194) vs. 143 (119; 186) pg/ml, p < 0.01; FGF23 c-terminal in LP: 77 (30.3; 112) vs. 111 (63; 384) RU/ml, p < 0.01 and in NP: 142 (56.6; 175) vs. 157 (76.7; 281) RU/ml, p < 0.01].

Conclusions

LP diet has a favorable impact on nutritional status as much as NP diet with possible greater benefits on the progression of kidney disease and some of its metabolic complications.

Clinical Trial Registration

https://clinicaltrials.gov/ct2/show/NCT05015647, identifier: NCT05015647.
Prediction of the Effects of Empagliflozin on Cardiovascular and Kidney Outcomes Based on Short-Term Changes in Multiple Risk Markers
Authors: Tye Sok Cin , de Vries Sieta T. , Wanner Christoph , Denig Petra , Heerspink Hiddo J. L.
Published: January 2022

Aims: The EMPA-REG OUTCOME trial demonstrated that the sodium-glucose cotransporter-2 inhibitor (SGLT2) empagliflozin reduces the risk of cardiovascular (CV) and kidney outcomes in patients with type 2 diabetes. We previously developed the parameter response efficacy (PRE) score, which translates drug effects on multiple short-term risk markers into a predicted long-term treatment effect on clinical outcomes. The main objective of this study was to assess the accuracy of the PRE score in predicting the efficacy of empagliflozin in reducing the risk of CV and kidney outcomes.

Methods: Short-term (baseline to 6-months) changes in glycated hemoglobin (HbA1c), systolic blood pressure (SBP), urinary-albumin-creatinine-ratio (UACR), hemoglobin, body weight, high-density-lipoprotein (HDL) cholesterol, low-density-lipoprotein (LDL) cholesterol, uric acid, and potassium were determined among 7020 patients with type 2 diabetes and established CV disease in the EMPA-REG OUTCOME trial. The beta-coefficients, derived from a Cox proportional hazards model in a pooled database consisting of 6355 patients with type 2 diabetes, were applied to the short-term risk markers in the EMPA-REG OUTCOME trial to predict the empagliflozin-induced impact on CV (defined as a composite of non-fatal myocardial infarction, non-fatal stroke, or CV death) and kidney (defined as a composite of doubling of serum creatinine or end-stage kidney disease) outcomes.

Results: Empagliflozin compared to placebo reduced HbA1c (0.6%), SBP (4.2 mmHg), UACR (13.0%), body weight (2.1 kg), uric acid (20.4 μmol/L), and increased hemoglobin (6.6 g/L), LDL-cholesterol (0.1 mmol/L) and HDL-cholesterol (0.04 mmol/L) (all p<0.01). Integrating these effects in the PRE score resulted in a predicted relative risk reduction (RRR) for the CV outcome of 6.4% (95% CI 1.4–11.7), which was less than the observed 14.7% (95% CI 1.3–26.4%) RRR. For the kidney outcome, the PRE score predicted a RRR of 33.4% (95% CI 26.2–39.8); the observed RRR was 46.9% (95% CI 26.8–61.5). In a subgroup of 2,811 patients with UACR ≥30 mg/g at baseline, the PRE score predicted RRR was 40.8% (95% CI 31.2–49.1) vs. the observed RRR of 40.8% (95% CI 12.4–60.0) for the kidney outcome.

Conclusions: Integrating multiple short-term risk marker changes in the PRE score underestimated the effect of empagliflozin on CV and kidney outcomes, suggesting that the currently used risk markers do not fully capture the effect of empagliflozin. In patients with increased albuminuria, the PRE score adequately predicted the effect of empagliflozin on kidney outcomes.
Methylxanthine Treatment in Patients Hospitalized for Acute Exacerbation of Chronic Obstructive Pulmonary Disease in China: A Real-World Study Using Propensity Score Matching Analysis
Authors: Zhan Zijie , Ma Yiming , Huang Ke , Liang Chen , Mao Xihua , Zhang Yaowen , Ren Xiaoxia , Lei Jieping , Chen Yan , Yang Ting , Wang Chen
Published: January 2022

Background: Although medical guidelines discourage the use of methylxanthines in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD), they are still widely used in clinical practice. This study investigated the real-world use of methylxanthines in the management of AECOPD.

Methods: Patient data from the Acute exacerbation of Chronic obstructive pulmonary disease Using REgistry data (ACURE, NCT02657525) study database were screened. Enrolled patients were divided into treatment and control groups. Propensity score (PS) matching and Cox regression analyses were used to minimize confounding factors and determine the association between methylxanthine treatment and the length of stay (LOS).

Results: Among the 2088 eligible patients, 1,563 (74.9%) were in the methylxanthine treatment group. Patients treated with methylxanthines had more severe respiratory symptoms and worse lung function than those in the control group. Doxophylline was the most commonly used methylxanthine in both secondary and tertiary hospitals. After PS matching, 966 patients were equally divided into two groups. The LOS of patients in the two groups was similar [median: 8 days, interquartile range (IQR): 7–11 days, p = 0.730]. Patients in the treatment group (median: 8, IQR: 4–12) had a more significant decrease in the COPD Assessment Test score from admission to discharge than those in the control group (median: 6, IQR: 2–10, p < 0.001). Among all matched patients, the LOS was not significantly associated with methylxanthine treatment [adjusted hazard ratio (HR): 1.02, 95% confidence intervals (CIs): 0.89–1.16]. However, in the subgroup analysis, methylxanthines were significantly associated with a short LOS in patients with blood eosinophil count >4% (adjusted HR: 1.56, 95% CIs: 1.12–2.17).

Conclusion: This study revealed that methylxanthines, especially doxophylline, are widely used in China. Methylxanthines were effective in improving symptoms in AECOPD patients. Higher blood eosinophil count may be associated with a better efficacy of methylxanthine treatment.
Feasibility of Growth Factor Agent Therapy in Repairing Motor Injury
Authors: Tan Qiaoyin , Li Jiayu , Liu Yuwen , Zhu Xiaojuan , Shao Weide
Published: January 2022

Growth factors (GF), with the activity of stimulating cell growth, play a significant role in biology, medicine, and exercise physiology. In the process of exercise, human tissues are impacted, making cells suffer damage. Growth factor can accelerate the repair of damaged cells and regulate the synthesis of protein, so biological preparations of growth factors can be added to traditional therapies. A combination of growth factor biologics and conventional therapies may improve the efficiency of injury repair, but growth factor biologics may not produce any results. The feasibility of growth factor biologics in the treatment of motor injury was discussed. The research have shown that: 1) GF biological agent therapy is a very promising treatment for motor injury, which is based on the power of autologous growth factor (GFs) to accelerate tissue healing, promote muscle regeneration, increase angiogenesis, reduce fibrosis, and make the muscle injury rapid recovery. 2) There are various methods for delivering the higher dose of GF to the injured tissue, but most of them depend on the platelet release of GF. At the site of injury, there are several ways to deliver higher doses of GF to the injured tissue. 3) At present, the inhibition of GF is mainly through signal transduction inhibitors and inhibition of transcription factor production. 4) Pattern of GF during wound repair: GF directly regulates many key steps of normal wound repair, including inflammatory cell chemotaxis, division and proliferation of fibroblasts, keratinocytes and vascular endothelial cells, formation of new blood vessels, and synthesis and degradation of intercellular substances. 5) When GF promotes chronic wound healing, in most cases, certain GF can be used targeted only whenin vivoregulation still cannot meet the need for repair.
Controlled Bistable Transmission Non-Reciprocity in a Four-Mode Optomechanical System
Authors: Jiang Bo , Yan Dong , Wang Jing , Qu Dezhan , Wu Jin-Hui
Published: January 2022

We examine the bistable transmission non-reciprocity in a four-mode optomechanical system, where a mechanical oscillator interacts with one of three coupled optical cavities so as to generate an asymmetric optomechanical non-linearity. Two transmission coefficients in opposite directions are found to exhibit non-reciprocal bistable behaviors due to this asymmetric optomechanical non-linearity as the impedance-matching condition is broken for a not too weak input field. Such a bistable transmission non-reciprocity can be well manipulated to exhibit reversible higher isolation ratios in tunable wider ranges of the input field power or one cavity mode detuning by modulating relevant parameters like optical coupling strengths, optomechanical coupling strengths, and mechanical frequencies. This optomechanical system provides a flexible platform for realizing transmission non-reciprocity of weal light signals and may be extended to optical networks with more coupled cavities.
A Data Driven Approach to Assess Complex Colour Profiles in Plant Tissues
Authors: McAtee Peter Andrew , Nardozza Simona , Richardson Annette , Wohlers Mark , Schaffer Robert James
Published: January 2022

The ability to quantify the colour of fruit is extremely important for a number of applied fields including plant breeding, postharvest assessment, and consumer quality assessment. Fruit and other plant organs display highly complex colour patterning. This complexity makes it challenging to compare and contrast colours in an accurate and time efficient manner. Multiple methodologies exist that attempt to digitally quantify colour in complex images but these either require a priori knowledge to assign colours to a particular bin, or fit the colours present within segment of the colour space into a single colour value using a thresholding approach. A major drawback of these methodologies is that, through the process of averaging, they tend to synthetically generate values that may not exist within the context of the original image. As such, to date there are no published methodologies that assess colour patterning using a data driven approach. In this study we present a methodology to acquire and process digital images of biological samples that contain complex colour gradients. The CIE (Commission Internationale de l’Eclairage/International Commission on Illumination) ΔE2000 formula was used to determine the perceptually unique colours (PUC) within images of fruit containing complex colour gradients. This process, on average, resulted in a 98% reduction in colour values from the number of unique colours (UC) in the original image. This data driven procedure summarised the colour data values while maintaining a linear relationship with the normalised colour complexity contained in the total image. A weighted ΔE2000 distance metric was used to generate a distance matrix and facilitated clustering of summarised colour data. Clustering showed that our data driven methodology has the ability to group these complex images into their respective binomial families while maintaining the ability to detect subtle colour differences. This methodology was also able to differentiate closely related images. We provide a high quality set of complex biological images that span the visual spectrum that can be used in future colorimetric research to benchmark colourimetric method development.
The Role of Relatedness in the Motivation and Vitality of University Students in Online Classes During Social Distancing
Authors: Capon-Sieber Vanda , Köhler Carmen , Alp Christ Ayşenur , Helbling Jana , Praetorius Anna-Katharina
Published: January 2022

As part of the social distancing measures for preventing the spread of COVID-19, many university courses were moved online. There is an assumption that online teaching limits opportunities for fostering interpersonal relationships and students’ satisfaction of the basic need for relatedness – reflected by experiencing meaningful interpersonal connections and belonging – which are considered important prerequisites for student motivation and vitality. In educational settings, an important factor affecting students’ relatedness satisfaction is the teachers’ behavior. Although research suggests that relatedness satisfaction may be impaired in online education settings, to date no study has assessed how university lecturers’ relatedness support might be associated with student relatedness satisfaction and therefore, student motivation and vitality. This study tested this mediating relationship using data collected during the early days of the COVID-19 pandemic. The study also investigated whether the relations were moderated by a high affiliation motive which reflects a dispositional wish for positive and warm relationships. The possible importance of the communication channel selected by the lecturers (video chat yes/no) and the format of a class (lecture/seminar) were also investigated. In a sample of N = 337 students, we tested our hypotheses using structural equation model (SEM). Results confirmed mediation, but not moderation. The use of video chat (video call) seems to facilitate the provision of relatedness support but our data did not show that the format of a class was associated with relatedness. Our findings indicate that both teaching behavior and the technical format used to deliver lectures play important roles in student experiences with online classes. The results are discussed in light of other research conducted during the pandemic.
How the Custom Suppresses the Endowment Effect: Exchange Paradigm in Kanak Country
Authors: Baratgin Jean , Godin Patrice , Jamet Frank
Published: January 2022

In this paper, Knetsch's exchange paradigm is analyzed from the perspective of pragmatics and social norms. In this paradigm the participant, at the beginning of the experiment, receives an object from the experimenter and at the end, the same experimenter offers to exchange the received object for an equivalent object. The observed refusal to exchange is called the endowment effect. We argue that this effect comes from an implicature made by the participant about the experimenter's own expectations. The participant perceives the received item as a gift, or as a present, from the experimenter that cannot be exchanged as stipulated by the social norms of western politeness common to both the experimenter and the participant. This implicature, however, should not be produced by participants from Kanak culture for whom the perceived gift of a good will be interpreted as a first act of exchange based on gift and counter-gift. This exchange is a natural, frequent, balanced, and indispensable act for all Kanak social bonds whether private or public. Kanak people also know the French social norms that they apply in their interactions with French people living in New Caledonia. In our experiment, we show that when the exchange paradigm takes place in a French context, with a French experimenter and in French, the Kanak participant is subject to the endowment effect in the same way as a French participant. On the other hand, when the paradigm is carried out in a Kanak context, with a Kanak experimenter and in the vernacular language, or in a Kanak context that approaches the ceremonial of the custom, the endowment effect is no longer observed. The same number of Kanak participants accept or refuse to exchange the endowed item. These results, in addition to providing a new explanation for the endowment effect, highlight the great flexibility of decisions according to social-cultural context.
The Role of Academic Resilience, Motivational Intensity and Their Relationship in EFL Learners' Academic Achievement
Authors: Yang Shengli , Wang Weirong
Published: January 2022

The aim of developing academic resilience and motivational intensity, as two constructs of positive psychology, is to increase learners' capability to compete with each other even in adverse conditions. Different types of academic resilience are conceptualized and germane literature about the relationship between academic resilience and academic achievement is provided. Literature showed that some socio-affective factors (e.g. peer relations, parents' high expectations, teachers' attention, and kindness, etc.), socio-economic factors (e.g. the financial contribution of parents' to education, economic and social class level, etc.), and affective factors (e.g. anxiety, self-efficacy, motivation and so on) can influence learners' academic achievement and policy makers' decision in providing an appropriate context for learning. In the end, the pedagogical implications are expounded to foster the language learning quality and to develop a language educational system. Suggestions for further research are provided to develop the existent literature on the relationship between academic, motivational intensity, and learners' academic achievement.
Well-Being of Teachers: The Role of Efficacy of Teachers and Academic Optimism
Authors: Song Kuo
Published: January 2022

In previous decades, the well-being of teachers has been at the center of the attention of researchers in several practical investigations on various subjects such as language learning. The objective of this review is to clarify this construct and add new information on the predominance of the well-being of teachers and organize factors impacting it. Nevertheless, among factors influencing the levels of well-being, the focus of this review is on two constructs, namely, optimism “as a new concept in positive psychology,” societal theory, and collective school assets in education, and efficacy of teachers as an individual source in teachers. This review tries to focus on the eminent role of teacher efficacy and optimism in the process of education and also clarify their consequences on the well-being of teachers. In a nutshell, this review can provide implications for language teaching participants in the academic context.
Problematic Mobile Phone Use and Life Satisfaction Among University Students During the COVID-19 Pandemic in Shanghai, China
Authors: Jiang Wenning , Luo Jin , Guan Hannan , Jiang Feng , Tang Yi-Lang
Published: January 2022

Objective

This study examined problematic mobile phone use (PMPU) and its relationship with life satisfaction in Chinese university students during the pandemic.

Methods

An anonymous online survey was conducted in a university in China. The Mobile Phone Addiction Index (MPAI) and the Satisfaction with Life Scale (SWLS) were used to assess the severity of problematic mobile phone use and life satisfaction, respectively. Data on demographic and health-related factors were also collected.

Results

A total of 1,491 undergraduate students (73.3% were male) completed the survey. On average, students in the survey reported spending 7.4 ± 4.3 h/day on phone use. Their MPAI score was 38.1 ± 13.3 and SWLS score was 24.9 ± 6.8, respectively. After controlling for confounding factors, the MPAI score was significantly associated with lower life satisfaction. Multiple linear regression revealed that higher monthly allowances, frequent insomnia, longer phone use duration were significantly associated with PMPU.

Conclusion

University students in China spend nearly half of their waking hours on mobile phone use, significantly longer than before the COVID-19 pandemic. PMPU is associated with insomnia, lower life satisfaction and higher allowances. If the trend continues after the pandemic, interventions may be needed. Increase in-person interactions, limiting online social and gaming time, awareness campaign may be effective in reducing the impact of PMPU and improve life satisfaction.
Heterogeneity of the COVID-19 Pandemic in the United States of America: A Geo-Epidemiological Perspective
Authors: Vallée Alexandre
Published: January 2022

The spread of the COVID-19 pandemic has shown great heterogeneity between regions of countries, e. g., in the United States of America (USA). With the growing of the worldwide COVID-19 pandemic, there is a need to better highlight the variability in the trajectory of this disease in different worldwide geographic areas. Indeed, the epidemic trends across areas can display completely different evolution at a given time. Geo-epidemiological analyses using data, that are publicly available, could be a major topic to help governments and public administrations to implement health policies. Geo-epidemiological analyses could provide a basis for the implementation of relevant public health policies. With the COVID-19 pandemic, geo-epidemiological analyses can be readily utilized by policy interventions and USA public health authorities to highlight geographic areas of particular concern and enhance the allocation of resources.