bluuebunny/crossref_metadata_2025 huggingface dataset:
A Trem2R47H mouse model without cryptic splicing drives age- and disease-dependent tissue damage and synaptic loss in response to plaques
Authors: Tran Kristine M. , Kawauchi Shimako , Kramár Enikö A. , Rezaie Narges , Liang Heidi Yahan , Sakr Jasmine S. , Gomez-Arboledas Angela , Arreola Miguel A. , Cunha Celia da , Phan Jimmy , Wang Shuling , Collins Sherilyn , Walker Amber , Shi Kai-Xuan , Neumann Jonathan , Filimban Ghassan , Shi Zechuan , Milinkeviciute Giedre , Javonillo Dominic I. , Tran Katelynn , Gantuz Magdalena , Forner Stefania , Swarup Vivek , Tenner Andrea J. , LaFerla Frank M. , Wood Marcelo A. , Mortazavi Ali , MacGregor Grant R. , Green Kim N.
Published: February 2023

Background

The TREM2 R47H variant is one of the strongest genetic risk factors for late-onset Alzheimer’s Disease (AD). Unfortunately, many currentTrem2R47Hmouse models are associated with cryptic mRNA splicing of the mutant allele that produces a confounding reduction in protein product. To overcome this issue, we developed theTrem2R47H NSS(NormalSpliceSite) mouse model in which theTrem2allele is expressed at a similar level to the wild-typeTrem2allele without evidence of cryptic splicing products.

Methods

Trem2R47H NSSmice were treated with the demyelinating agent cuprizone, or crossed with the 5xFAD mouse model of amyloidosis, to explore the impact of the TREM2 R47H variant on inflammatory responses to demyelination, plaque development, and the brain’s response to plaques.

Results

Trem2R47H NSSmice display an appropriate inflammatory response to cuprizone challenge, and do not recapitulate the null allele in terms of impeded inflammatory responses to demyelination. Utilizing the 5xFAD mouse model, we report age- and disease-dependent changes inTrem2R47H NSSmice in response to development of AD-like pathology. At an early (4-month-old) disease stage, hemizygous 5xFAD/homozygousTrem2R47H NSS(5xFAD/Trem2R47H NSS) mice have reduced size and number of microglia that display impaired interaction with plaques compared to microglia in age-matched 5xFAD hemizygous controls. This is associated with a suppressed inflammatory response but increased dystrophic neurites and axonal damage as measured by plasma neurofilament light chain (NfL) level. Homozygosity forTrem2R47H NSSsuppressed LTP deficits and loss of presynaptic puncta caused by the 5xFAD transgene array in 4-month-old mice. At a more advanced (12-month-old) disease stage 5xFAD/Trem2R47H NSSmice no longer display impaired plaque-microglia interaction or suppressed inflammatory gene expression, although NfL levels remain elevated, and a unique interferon-related gene expression signature is seen. Twelve-month oldTrem2R47H NSSmice also display LTP deficits and postsynaptic loss.

Conclusions

TheTrem2R47H NSSmouse is a valuable model that can be used to investigate age-dependent effects of the AD-risk R47H mutation on TREM2 and microglial function including its effects on plaque development, microglial-plaque interaction, production of a unique interferon signature and associated tissue damage.
The Matthews correlation coefficient (MCC) should replace the ROC AUC as the standard metric for assessing binary classification
Authors: Chicco Davide , Jurman Giuseppe
Published: February 2023

Binary classification is a common task for which machine learning and computational statistics are used, and the area under the receiver operating characteristic curve (ROC AUC) has become the common standard metric to evaluate binary classifications in most scientific fields. The ROC curve has true positive rate (also called sensitivity or recall) on the y axis and false positive rate on the x axis, and the ROC AUC can range from 0 (worst result) to 1 (perfect result). The ROC AUC, however, has several flaws and drawbacks. This score is generated including predictions that obtained insufficient sensitivity and specificity, and moreover it does not say anything about positive predictive value (also known as precision) nor negative predictive value (NPV) obtained by the classifier, therefore potentially generating inflated overoptimistic results. Since it is common to include ROC AUC alone without precision and negative predictive value, a researcher might erroneously conclude that their classification was successful. Furthermore, a given point in the ROC space does not identify a single confusion matrix nor a group of matrices sharing the same MCC value. Indeed, a given (sensitivity, specificity) pair can cover a broad MCC range, which casts doubts on the reliability of ROC AUC as a performance measure. In contrast, the Matthews correlation coefficient (MCC) generates a high score in its $$[-1; +1]$$

[
-
1
;
+
1
]

interval only if the classifier scored a high value for all the four basic rates of the confusion matrix: sensitivity, specificity, precision, and negative predictive value. A high MCC (for example, MCC $$=$$
=
0.9), moreover, always corresponds to a high ROC AUC, and not vice versa. In this short study, we explain why the Matthews correlation coefficient should replace the ROC AUC as standard statistic in all the scientific studies involving a binary classification, in all scientific fields.
Novel DNA methylation biomarkers in stool and blood for early detection of colorectal cancer and precancerous lesions
Authors: Shen Yuguang , Wang Dongyang , Yuan Tianli , Fang Hongsheng , Zhu Chen , Qin Juan , Xu Xiaojing , Zhang Cheng , Liu Jiahua , Zhang Yuanruohan , Wen Zhoujin , Tang Jian , Wang Zheng
Published: February 2023

Background

Early detection and prevention of precancerous lesions can significantly reduce the morbidity and mortality of colorectal cancer (CRC). Here, we developed new candidate CpG site biomarkers for CRC and evaluated the diagnostic value of their expression in blood and stool samples of CRC and precancerous lesions.

Methods

We analyzed 76 pairs of CRC and adjacent normal tissue samples, 348 stool samples, and 136 blood samples. Candidate biomarkers for CRC were screened using a bioinformatics database and identified using a quantitative methylation-specific PCR method. The methylation levels of the candidate biomarkers were validated using blood and stool samples. The divided stool samples were used to construct and validate a combined diagnostic model and to analyze the independent or combined diagnostic value of candidate biomarkers in stool samples of CRC and precancerous lesions.

Results

Two candidate CpG site biomarkers for CRC, cg13096260 and cg12993163, were identified. Although both biomarkers demonstrated diagnostic performance to a certain extent when using blood samples, they showed better diagnostic value for different stages of CRC and AA with stool samples.

Conclusions

cg13096260 and cg12993163 detection in stool samples could be a promising approach for screening and early diagnosis of CRC and precancerous lesions.
Distinct genome-wide DNA methylation and gene expression signatures in classical monocytes from African American patients with systemic sclerosis
Authors: Allen Peter C. , Smith Sarah , Wilson Robert C. , Wirth Jena R. , Wilson Nathan H. , Baker Frost DeAnna , Flume Jonathan , Gilkeson Gary S. , Cunningham Melissa A. , Langefeld Carl D. , Absher Devin M. , Ramos Paula S.
Published: February 2023

Background

Systemic sclerosis (SSc) is a multisystem autoimmune disorder that has an unclear etiology and disproportionately affects women and African Americans. Despite this, African Americans are dramatically underrepresented in SSc research. Additionally, monocytes show heightened activation in SSc and in African Americans relative to European Americans. In this study, we sought to investigate DNA methylation and gene expression patterns in classical monocytes in a health disparity population.

Methods

Classical monocytes (CD14+ + CD16−) were FACS-isolated from 34 self-reported African American women. Samples from 12 SSc patients and 12 healthy controls were hybridized on MethylationEPIC BeadChip array, while RNA-seq was performed on 16 SSc patients and 18 healthy controls. Analyses were computed to identify differentially methylated CpGs (DMCs), differentially expressed genes (DEGs), and CpGs associated with changes in gene expression (eQTM analysis).

Results

We observed modest DNA methylation and gene expression differences between cases and controls. The genes harboring the top DMCs, the top DEGs, as well as the top eQTM loci were enriched for metabolic processes. Genes involved in immune processes and pathways showed a weak upregulation in the transcriptomic analysis. While many genes were newly identified, several other have been previously reported as differentially methylated or expressed in different blood cells from patients with SSc, supporting for their potential dysregulation in SSc.

Conclusions

While contrasting with results found in other blood cell types in largely European-descent groups, the results of this study support that variation in DNA methylation and gene expression exists among different cell types and individuals of different genetic, clinical, social, and environmental backgrounds. This finding supports the importance of including diverse, well-characterized patients to understand the different roles of DNA methylation and gene expression variability in the dysregulation of classical monocytes in diverse populations, which might help explaining the health disparities.
Single-cell transcriptome analysis reveals stem cell-like subsets in the progression of Waldenström’s macroglobulinemia
Authors: Qiu Yu , Wang Xiao-shuang , Yao Yuan , Si Yan-min , Wang Xue-zhu , Jia Ming-nan , Zhou Dao-bin , Yu Jia , Cao Xin-xin , Li Jian
Published: February 2023

Waldenström’s macroglobulinemia (WM) is an uncommon lymphoproliferative disorder, and the precise cellular landscape and the mechanisms of progression from IgM monoclonal gammopathy of undetermined significance (MGUS) to WM remain unclear. We performed single-cell RNA sequencing of CD19 + and CD19-CD38 + cells from healthy donors, IgM MGUS and WM patients. We found that samples from IgM MGUS and WM patients were composed of fewer early B-cell subsets and more T cells and NK cells than those from healthy controls. Compared with those of IgM MGUS patients, mature B cells of WM patients showed upregulation of HES1, GADD45B, NEAT1, DUSP22, RGS1, RGS16, and PIM1. We also identified a subpopulation of CD3 + CD19 + cells in IgM MGUS and WM patients, and trajectory analysis suggested that this subpopulation might be a stem cell-like subset. Further targeted gene sequencing of CD3 + CD19 + and CD3-CD19 + cells proved that MYD88 might be the early events in tumorigenesis according to variant allele fraction analysis. Additional subclonal hits such as CXCR4 and MAP2K1 mutations could be acquired during tumor progression. CXCL signaling, CCL signaling, IL2 signaling and TGFβ signaling pathways were involved in communication between CD3 + CD19 + cells and other immune cells. Our findings reveal the composition of CD38 + immune microenvironment together with B cells and plasma cells in IgM MGUS and WM patients, and provide comprehensive insights into mechanisms of progression from IgM MGUS to WM. The rare CD3 + CD19 + cells might be cells with “stemness” feature.
Moral distress in psychiatric nurses in Covid-19 crisis
Authors: Tavakol Nahid , Molazem Zahra , Rakhshan Mahnaz , Asemani Omid , Bagheri Shahpar
Published: February 2023

Background

The COVID-19 pandemic has put heavy pressure on nurses. Psychiatric nurses are also exposed to moral distress due to the special conditions of psychiatric patients and patient’s lack of cooperation in observing health protocols. This study has been conducted to explore and describe factors that caused moral distress in Iranian psychiatric nurses during the COVID-19 pandemic.

Method

This qualitative study with a conventional content analysis approach involved 12 nurses at the Shiraz University of Medical Sciences in Iran. This study was conducted in the winter of 2021. Data collection was performed by semi-structured interviews, data analysis was performed based on the five steps of Graneheim and Lundman.

Results

By continuous comparison and integration of data, 17 subcategories, 8 subcategories, and 3 categories were extracted from 252 initial codes. The causes of moral distress in psychiatric nurses during the COVID-19 pandemic were identified as emotional responses (Fear and Doubt), relational factors (Nurses’ Relationship with Each Other, Nurse-physician Relationship, and Relationship whit Patients), and Institutional factors (Lack of Attention to Health Instructions, Failure to complete the treatment process for patients and Institutional Policies).

Conclusion

New dimensions of the causes of moral distress associated with the COVID- 19 pandemic are discovered in this study. Managers and planners should equip psychiatric hospitals with isolation facilities and Personal Protection Equipment for patients and nurses. Strengthening the ethical climate by improving communication skills and individual nursing empowerment to prevent moral distress is recommended.
Rasch validation of the Warwick-Edinburgh Mental Well-Being Scale (WEMWBS) in community-dwelling adults
Authors: Deng Wei , Carpentier Sydney , Blackwood Jena , Van de Winckel Ann
Published: February 2023

Background

With the ongoing global COVID-19 pandemic and the recent political divide in the United States (US), there is an urgent need to address the soaring mental well-being problems and promote positive well-being. The Warwick-Edinburgh Mental Well-Being Scale (WEMWBS) measures the positive aspects of mental health. Previous studies confirmed its construct validity, reliability, and unidimensionality with confirmatory factor analysis. Six studies have performed a Rasch analysis on the WEMWBS, and only one evaluated young adults in the US. The goal of our study is to use Rasch analysis to validate the WEMBS in a wider age group of community-dwelling adults in the US.

Methods

We used the Rasch unidimensional measurement model 2030 software to evaluate item and person fit, targeting, person separation reliability (PSR), and differential item functioning (DIF) for sample sizes of at least 200 persons in each subgroup.

Results

After deleting two items, the WEMBS analyzed in our 553 community-dwelling adults (average age 51.22 ± 17.18 years; 358 women) showed an excellent PSR = 0.91 as well as person and item fit, but the items are too easy for this population (person mean location = 2.17 ± 2.00). There was no DIF for sex, mental health, or practicing breathing exercises.

Conclusions

The WEMWBS had good item and person fit but the targeting is off when used in community-dwelling adults in the US. Adding more difficult items might improve the targeting and capture a broader range of positive mental well-being.
Four-way classification of Alzheimer’s disease using deep Siamese convolutional neural network with triplet-loss function
Authors: Hajamohideen Faizal , Shaffi Noushath , Mahmud Mufti , Subramanian Karthikeyan , Al Sariri Arwa , Vimbi Viswan , Abdesselam Abdelhamid ,   for the Alzheimer’s Disease Neuroimaging Initiative
Published: February 2023

Alzheimer’s disease (AD) is a neurodegenerative disease that causes irreversible damage to several brain regions, including the hippocampus causing impairment in cognition, function, and behaviour. Early diagnosis of the disease will reduce the suffering of the patients and their family members. Towards this aim, in this paper, we propose a Siamese Convolutional Neural Network (SCNN) architecture that employs the triplet-loss function for the representation of input MRI images ask-dimensional embeddings. We used both pre-trained and non-pretrained CNNs to transform images into the embedding space. These embeddings are subsequently used for the 4-way classification of Alzheimer’s disease. The model efficacy was tested using the ADNI and OASIS datasets which produced an accuracy of 91.83% and 93.85%, respectively. Furthermore, obtained results are compared with similar methods proposed in the literature.
The Arabidopsis holobiont: a (re)source of insights to understand the amazing world of plant–microbe interactions
Authors: Poupin M. J. , Ledger T. , Roselló-Móra R. , González B.
Published: February 2023

As holobiont, a plant is intrinsically connected to its microbiomes. However, some characteristics of these microbiomes, such as their taxonomic composition, biological and evolutionary role, and especially the drivers that shape them, are not entirely elucidated. Reports on the microbiota of Arabidopsis thaliana first appeared more than ten years ago. However, there is still a lack of a comprehensive understanding of the vast amount of information that has been generated using this holobiont. The main goal of this review was to perform an in-depth, exhaustive, and systematic analysis of the literature regarding the Arabidopsis–microbiome interaction. A core microbiota was identified as composed of a few bacterial and non-bacterial taxa. The soil (and, to a lesser degree, air) were detected as primary microorganism sources. From the plant perspective, the species, ecotype, circadian cycle, developmental stage, environmental responses, and the exudation of metabolites were crucial factors shaping the plant–microbe interaction. From the microbial perspective, the microbe-microbe interactions, the type of microorganisms belonging to the microbiota (i.e., beneficial or detrimental), and the microbial metabolic responses were also key drivers. The underlying mechanisms are just beginning to be unveiled, but relevant future research needs were identified. Thus, this review provides valuable information and novel analyses that will shed light to deepen our understanding of this plant holobiont and its interaction with the environment.
A comprehensive review of attention tests: can we assess what we exactly do not understand?
Authors: Nasiri Ehsan , Khalilzad Mohammad , Hakimzadeh Zahra , Isari Ashkan , Faryabi-Yousefabad Sajjad , Sadigh-Eteghad Saeed , Naseri Amirreza
Published: February 2023

Attention, as it is now defined as a process matching data from the environment to the needs of the organism, is one of the main aspects of human cognitive processes. There are several aspects to attention including tonic alertness (a process of intrinsic arousal that varies by minutes to hours), phasic alertness (a process that causes a quick change in attention as a result of a brief stimulus), selective attention (a process differentiating multiple stimuli), and sustained attention (a process maintaining persistence of response and continuous effort over an extended period). Attention dysfunction is associated with multiple disorders; therefore, there has been much effort in assessing attention and its domains, resulting in a battery of tests evaluating one or several attentional domains; instances of which are the Stroop color-word test, Test of Everyday Attention, Wisconsin Card Sorting Test, and Cambridge Neuropsychological Test Automated Battery. These tests vary in terms of utilities, range of age, and domains. The role of attention in human life and the importance of assessing it merits an inclusive review of the efforts made to assess attention and the resulting tests; Here we highlight all the necessary data regarding neurophysiological tests which assess human attentive function and investigates the evolution of attention tests over time. Also, the ways of assessing the attention in untestable patients who have difficulty in reading or using a computer, along with the lack of ability to comprehend verbal instructions and executive tasks, are discussed. This review can be of help as a platform for designing new studies to researchers who are interested in working on attention and conditions causing deficits in this aspect of body function, by collecting and organizing information on its assessment.
Measuring and modeling the effects of vagus nerve stimulation on heart rate and laryngeal muscles
Authors: Huffman William J. , Musselman Eric D. , Pelot Nicole A. , Grill Warren M.
Published: February 2023

Background

Reduced heart rate (HR) during vagus nerve stimulation (VNS) is associated with therapy for heart failure, but stimulation frequency and amplitude are limited by patient tolerance. An understanding of physiological responses to parameter adjustments would allow differential control of therapeutic and side effects. To investigate selective modulation of the physiological responses to VNS, we quantified the effects and interactions of parameter selection on two physiological outcomes: one related to therapy (reduced HR) and one related to side effects (laryngeal muscle EMG).

Methods

We applied a broad range of stimulation parameters (mean pulse rates (MPR), intra-burst frequencies, and amplitudes) to the vagus nerve of anesthetized mice. We leveraged the in vivo recordings to parameterize and validate computational models of HR and laryngeal muscle activity across amplitudes and temporal patterns of VNS. We constructed a finite element model of excitation of fibers within the mouse cervical vagus nerve.

Results

HR decreased with increased amplitude, increased MPR, and decreased intra-burst frequency. EMG increased with increased MPR. Preferential HR effects over laryngeal EMG effects required combined adjustments of amplitude and MPR. The model of HR responses highlighted contributions of ganglionic filtering to VNS-evoked changes in HR at high stimulation frequencies. Overlap in activation thresholds between small and large modeled fibers was consistent with the overlap in dynamic ranges of related physiological measures (HR and EMG).

Conclusion

The present study provides insights into physiological responses to VNS required for informed parameter adjustment to modulate selectively therapeutic effects and side effects.
Degenerative changes through MR cartilage mapping in anterior cruciate ligament-reconstructed knees
Authors: Mabrouk Alaa M. , Abd El Raaof Maha M. , Hemaida Tarek W. , Bassiouny Ahmed M.
Published: February 2023

Background

Anterior cruciate ligament (ACL) injury increases risk for post traumatic knee osteoarthritis. ACL injury causes lack of knee stability and frequently requires ACL-reconstruction (ACLR) in order to restore functional and anatomical joint stability. Magnetic resonance imaging with T2 mapping sequence is used to quantify the amount of water content in articular cartilage hence; it is considered a better tool and more beneficial than radiographic based assessment in early detection even before being symptomatic. The aim of work is to estimate the incidence of subclinical degenerative changes that happened early in patients who underwent ACL reconstruction and to identify the correlations of T2 mapping values with patients' BMI, meniscal state/operations, ACL graft assessment and presence of ACLR related complications.

Results

The study was conducted upon 71 patients, divided into 61 anterior cruciate ligament reconstructed knees and 10 control cases using 1.5 T MRI. Assessment of cartilage sub-compartment T2 values and comparison with average normal cartilage T2 values obtained from the control group. Multiple correlations of the grade of articular cartilage degeneration within anterior cruciate ligament reconstructed knees with Body Mass Index (BMI), time of operation as well associated meniscal operations and anterior cruciate ligament graft complications.

Conclusions

Adding the T2 cartilage mapping sequence improves the ability to detect subclinical early degenerative articular cartilage changes in patients who underwent anterior cruciate ligament reconstruction, taking into consideration the relation of the patients' BMI, previous meniscal injuries/operation, ACL graft status and related graft complications with the T2 cartilage mapping values.
Effect of carbon to nitrogen ratio and aeration rate on phosphorus and exchangeable cation contents and their leaching in the soil during olive pomace and turkey manure co-composting
Authors: Aboutayeb Rachid , El-Mrini Soufiane , Zouhri Abdeljalil , Azim Khalid
Published: February 2023

The environmental issues related to olive oil by-products and turkey manure are continuously increasing. This ecological hazard could be mitigated by the composting process. This study aimed to investigate the effect of the initial carbon to nitrogen ratio (C/N) and aeration rate (turning frequency (TF)) on mineral contents (P, K, Ca, and Na) and their leaching in the soil surface. Olive pomace (OP) and turkey manure (TM) were co-composted to prepare six mixtures at three levels of initial C/N (20, 22, and 28) and two levels of TF (once and twice a week). The results revealed a substantial effect of TF, twice a week, resulting in a loss of 36.5%, 36%, and 27% for K, Ca, and Na contents, respectively, whereas TF, once a week, preserves the maximum of nutrients in heaps with good compost maturity.

The initial C/N of 28 had significantly reduced P and K by 14% and 13%, respectively, and had increased Ca and Na contents by 85% and 30 %, respectively. The leaching of almost all the studied minerals has been demonstrated after composting. Exchangeable cations have been leached more under heaps with higher C/N ratios with TF of once per week, whereas P leaching has been recorded at the maximum level under the heap with an initial C/N of 20 and turned twice weekly. The resulting composts have generally displayed good mineral quality.
Novel Approaches to the Treatment of Chronic Graft-Versus-Host Disease
Authors: Zeiser Robert
Published: February 2023

The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors’ suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology , to patients seen in their own clinical practice.

Chronic graft-versus-host disease (cGVHD) is an immune-mediated disease that ensues after allogeneic hematopoietic cell transplantation often affecting multiple organs, decreases quality of life, and necessitates immunosuppressive therapy. The current standard first-line cGVHD therapy is glucocorticoids (GCs) which have major side effects. So far, all attempts to improve response to first-line GC therapy of cGVHD by adding other agents, such as mycophenolate mofetil, or cyclosporine A have not improved response. The data reported in the trial by Miklos et al indicate that ibrutinib should not be added to GC in first-line cGVHD therapy. The findings instruct future studies that aim at the identification of patients with cGVHD who may benefit from a GC-ibrutinib combination using biomarkers or clinical parameters. Currently, ibrutinib, ruxolitinib, and belumosudil are the only drugs that are approved by the Food and Drug Administration for steroid-refractory cGVHD. In light of the current standard management of cGVHD, the trial results indicate that ibrutinib will remain reserved for second-line therapy, which may be due to its mechanisms of action. The recommendation on the basis of this trial is that GC monotherapy remains the standard therapy for cGVHD.
GLP-1 Receptor Agonists and Risk of Adverse Cerebrovascular Outcomes in Type 2 Diabetes: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
Authors: Banerjee Mainak , Pal Rimesh , Mukhopadhyay Satinath , Nair Kirthana
Published: February 2023

Context

The effect of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on ischemic/hemorrhagic stroke and transient ischemic attacks (TIA) in type 2 diabetes mellitus (T2DM) remains undetermined.

Objective

To pool effects of GLP-1RAs on adverse cerebrovascular outcomes and investigate impact of baseline variables on these effects.

Methods

PubMed, Embase, Web of Science, Cochrane Library, and clinical trial registry websites were searched for randomized controlled trials (RCTs) ≥24 weeks duration in adults with T2DM (PROSPERO: CRD42022331547). Adjudicated cerebrovascular events in GLP-1RA treatment vs control arms were pooled together to calculate risk ratios (RR) using fixed-effects model. Subgroup analysis was performed based on individual drugs, treatment duration, and baseline patient characteristics. Quality of evidence was assessed using GRADE framework.

Results

We identified 28 RCTs involving 74 148 patients (57% male; median [range], age 58 [52-67] years, BMI 32 [25.4-37.2] kg/m2, T2DM duration 9 [3.5-15.4] years, treatment duration 52 [24-259] weeks). GLP-1RA use in T2DM was associated with significantly decreased risk of adverse cerebrovascular outcomes vs placebo/active comparator (RR, 0.83; 95% CI, 0.76-0.91; I2 = 0%). Pooling data from cardiovascular outcome trials (n = 8), GLP-1RA treatment vs placebo was associated with reduced risk of nonfatal stroke (RR, 0.85; 95% CI, 0.76-0.94; I2 = 0%) but not fatal stroke (RR, 0.80; 95% CI, 0.61-1.05; I2 = 0%). GLP-1RA use was associated with reduced risk of ischemic stroke (RCTs = 12; RR, 0.73; 95% CI, 0.60-0.89; I2 = 0%), composite of ischemic stroke/TIA (RCTs = 16; RR, 0.76; 95% CI, 0.65-0.90; I2 = 0%), but not hemorrhagic stroke (RCTs = 3; RR, 0.92; 95% CI, 0.51-1.64; I2 = 0%). Treatment benefits differed according to baseline eGFR and diabetes duration (P interaction < .1). Benefits were statistically significant for dulaglutide, subcutaneous/oral semaglutide (P < .05). Sensitivity analysis, excluding shorter-acting lixisenatide, eliminated the heterogeneity between individual GLP-1RA effects.

Conclusion

GLP-1RAs, particularly longer-acting formulations, reduced ischemic cerebrovascular events in T2DM. Observed benefits were significantly higher in patients with shorter T2DM duration and higher eGFR.
Hemichorea Associated With Nonketotic Hyperglycemia
Authors: Chen Xiaoming , Ma Choudi , Zhi Lijin , Wei Xiaodan , Luo Jiaxin , Liang Chanbo , Tan Jieping , Zhou Haihong , Wu Jiayuan
Published: February 2023

Context

Hemichorea associated with nonketotic hyperglycemia (HC-NH) is a rare diabetic complication for which the pathogenesis remains unclear.

Objective

This study reported 16 cases of HC-NH to improve the understanding of the disease and avoid misdiagnosis and missed diagnosis.

Methods

Data of 16 patients with HC-NH in a single center from 2000 to 2021 were analyzed retrospectively, and the relevant literature was reviewed.

Results

The participants (8 men and 8 women) had a mean age of 67.6 ± 16.4 years. Bilateral limbs were involved in 2 cases, and the others had hemichorea (6 in the left side and 8 in the right side). The average random blood glucose level was 17.51 ± 7.67 mmol/L, and the glycated hemoglobin A1c level was 11.9%±3.1% at admission. Eleven patients had a history of diabetes, and the other 5 patients were diagnosed with new-onset diabetes mellitus, but no remarkable differences were observed in the presentation or treatment of chorea. Ketonuria was detected in 7 patients. The basal ganglia (putamen, globus pallidus, and caudate nucleus) of 9 cases had typical hyperdensity on computed tomography and/or hyperintensity signals from magnetic resonance imaging. The chorea symptoms of 15 patients improved within 5.0 ± 1.9 days after treatment.

Conclusion

This study provides additional valuable information about the clinical and neuroimaging features of HC-NH. We hypothesize that chronic ischemia of the basal ganglia due to cerebral atherosclerosis combined with hyperglycemia is associated with HC-NH.
Forms of Life
Authors: Wenzel Jennifer
Published: February 2023

This essay discusses “Forms of Life” in two senses: first, infrastructure as a social process that fosters particular forms of collective life and second, the agency/vitality imputed to infrastructure. The essay considers an unremarked ambivalence in energy humanities about infrastructure: the extant infrastructure of fossil fuels poses an obstacle to energy transition, while the act of making infrastructure visible and “following the pipeline” is regarded by incisive petrocritics as necessary but insufficient. What do cooling towers, electric pylons, or railways make happen (or keep from happening), socially and narratively, when they “work” or when they're hacked? In other words, is there a narrative grammar of infrastructure? How much has to happen for nothing to happen? And how do cultural texts differ from built environments in thinking infrastructure as a form of life? China Miéville's story “Covehithe” mobilizes the literary imagination to depict sunken oil platforms as revenant and reproductive organisms that pose new questions about relationships among humans, nature, and technology, and about the care, responsibility, and politics such forms of life demand. This weird tale doubles as documentation of dead infrastructure: its platform characters are actual rigs that litter sea beds around the world. What imaginative or conceptual forms, then, can help us grasp infrastructure's forms of life? This question is particularly urgent with regard to fossil infrastructure, which here names not only infrastructure that processes, circulates, or depends on fossil fuels but also infrastructure that is archaic, obsolete, and otherwise tethered to the past, standing as an obstacle to transition.
Cognitive Performance in Patients With Sporadic Vestibular Schwannoma
Authors: Fan Zhiyuan , Fan Zhen , Li Zongze , Zhang Hongfei , Hu Liuxun , Qiu Tianming , Zhu Wei
Published: February 2023

BACKGROUND:

To date, few data are available on the cognitive function of patients with vestibular schwannoma (VS) before treatment.

OBJECTIVE:

To provide a cognitive profile of patients with VS.

METHODS:

This cross-sectional observational study recruited 75 patients with an untreated VS and 60 age-, sex-, and education-matched healthy control subjects. A set of neuropsychological tests were administered to each participant.

RESULTS:

Compared with the matched controls, patients with VS exhibited impaired general cognitive function, memory, psychomotor speed, visuospatial ability, attention and processing speed, and executive function. The subgroup analyses displayed that patients with severe-to-profound unilateral hearing loss were more cognitively impaired than patients with no-to-moderate unilateral hearing loss. In addition, patients with right-sided VS scored worse than those with left-sided VS on tests of memory, attention and processing speed, and executive function. No differences were observed in cognitive performance between patients with or without brainstem compression and those with or without tinnitus. We also found that worse hearing and longer hearing loss duration were associated with poorer cognitive performance in patients with VS.

CONCLUSION:

The findings of this study provide evidence for cognitive impairment in patients with untreated VS. It can thus be said that including cognitive assessment in the routine clinical management of patients with VS may facilitate more appropriate clinical decision-making and improve patients' quality of life.
Students' Digital Competence and Perceived Learning: The mediating role of Learner Agility
Authors: Patwardhan Vidya , Mallya Jyothi , Shedbalkar Rahul , Srivastava Sandeep , Bolar Kartikeya
Published: February 2023

Background:  The ravages of COVID-19 escalated the penetration of online education and usage of digital technologies. While educational institutions across the globe adopted different forms of computer-mediated communication, the institutes in India have gradually attuned to the new normal, notwithstanding the initial glitches of adopting new technology and shifting to blended. It became increasingly significant to gain a better understanding of students’ perspectives of newly emerged learning environment. This motivated the researchers to study the digital competencies (DC) and their impact on students’ learning agility (LA) and perceived learning (PL) in professional/technical education. 

Methods: In this cross-sectional study, a DigiComp 2.1 framework was attempted to investigate the relationship between DC and PL among higher education students in India. The data from 359 graduate and post-graduate students were analyzed using Structural equation modelling and Process Macro 4.0.

Results: The findings of this study revealed that DC has a significant positive impact on PL (b = 0.33; p < 0.001), indicating that higher learners' DC leads to higher learning outcomes. Similarly, DC also had a significant positive impact on LA (b = 0.59; p < 0.001), suggesting that the higher DC of learners leads to higher learning agility. Further, a positive significant relationship was also found between LA and PL (b = 0.21; p < 0.001). This significant positive path reveals that higher learners' agility leads to higher student learning outcomes.

Discussion: Post-COVID, DC, a technology-related skill set is linked to the academic performance of teachers and students.  Our findings reveal that DC significantly positively impacts PL and LA.  Therefore, we recommend that the higher educational institutes in India consider the inclusion of DC in their curriculum as a fundamental competence for a better learning outcome for learners.
Dignity in the care of older adults living in nursing homes and long-term care facilities
Authors: Wachholz Patrick , Giacomin Karla
Published: February 2023

Dignity is a fundamental right that can be subjectively experienced and rooted in a person's perception of being treated and cared for. Care refers to a set of specific activities combined in a complex life-sustaining network, including long-term care facilities, which involves various services designed to meet a person's health or personal care needs. However, older residents' human rights have been disrespected, and widened the gaps between theory and practice regarding safeguarding their rights and dignity in long-term facilities and nursing homes. This paper aims to discuss threats to dignity and elucidate some strategies to promote and conserve dignity in care, including the person-centered practice in long-term care facilities. Some barriers to the dignity of older residents involve the organizational culture, restraints of time, heavy workload, burnout, and lack of partnership between the residents, their families, and the long-term care homes' staff. Person-centered integrated care quality frameworks are core components of a good quality of care in these spaces in high-income countries. Unfortunately, the COVID-19 pandemic highlighted how weak long-term care policies were and demonstrated that much progress in the dignity of care in long-term care facilities and nursing homes is needed. In low- and middle-income countries, long-term care policies do not accompany the accelerated and intense aging process, and there are other threats, like their invisibility to the public sector and the prejudices about this service model. It's urgent to create strategies for designing and implementing sustainable and equitable long-term care systems based on a person-centered service with dignity to everyone who needs it.
The genome sequence of the Turnip Sawfly, Athalia rosae (Linnaeus, 1758)
Authors: Crowley Liam M. , Broad Gavin R. ,   University of Oxford and Wytham Woods Genome Acquisition Lab,   Natural History Museum Genome Acquisition Lab,   Darwin Tree of Life Barcoding collective,   Wellcome Sanger Institute Tree of Life programme,   Wellcome Sanger Institute Scientific Operations: DNA Pipelines collective,   Tree of Life Core Informatics collective, Green Andrew ,   Darwin Tree of Life Consortium
Published: February 2023

We present a genome assembly from an individual female Athalia rosae (the Turnip Sawfly; Arhropoda; Insecta; Hymenoptera; Athaliidae). The genome sequence is 172 megabases in span. Most of the assembly is scaffolded into eight chromosomal pseudomolecules. The mitochondrial genome has also been assembled and is 16.3 kilobases in length. Gene annotation of this assembly on Ensembl identified 11,393 protein coding genes.
The genome sequence of a tachinid fly, Thecocarcelia acutangulata (Macquart, 1850)
Authors: Falk Steven ,   University of Oxford and Wytham Woods Genome Acquisition Lab,   Darwin Tree of Life Barcoding collective,   Wellcome Sanger Institute Tree of Life programme,   Wellcome Sanger Institute Scientific Operations: DNA Pipelines collective,   Tree of Life Core Informatics collective, Njogu John ,   Darwin Tree of Life Consortium
Published: February 2023

We present a genome assembly from an individual female Thecocarcelia acutangulata (a tachinid fly; Arthropoda; Insecta; Diptera; Tachinidae). The genome sequence is 693 megabases in span. Most of the assembly is scaffolded into six chromosomal pseudomolecules, including the assembled X sex chromosome. The mitochondrial genome has also been assembled and is 20.1 kilobases in length. Gene annotation of this assembly on Ensembl identified 24,909 protein coding genes.
Fair Dynamic Rationing
Authors: Manshadi Vahideh , Niazadeh Rad , Rodilitz Scott
Published: February 2023

We study the allocative challenges that governmental and nonprofit organizations face when tasked with equitable and efficient rationing of a social good among agents whose needs (demands) realize sequentially and are possibly correlated. As one example, early in the COVID-19 pandemic, the Federal Emergency Management Agency faced overwhelming, temporally scattered, a priori uncertain, and correlated demands for medical supplies from different states. In such contexts, social planners aim to maximize the minimum fill rate across sequentially arriving agents, where each agent’s fill rate (i.e., its fraction of satisfied demand) is determined by an irrevocable, one-time allocation. For an arbitrarily correlated sequence of demands, we establish upper bounds on the expected minimum fill rate (ex post fairness) and the minimum expected fill rate (ex ante fairness) achievable by any policy. Our upper bounds are parameterized by the number of agents and the expected demand-to-supply ratio, yet we design a simple adaptive policy called projected proportional allocation (PPA) that simultaneously achieves matching lower bounds for both objectives (ex post and ex ante fairness) for any set of parameters. Our PPA policy is transparent and easy to implement, as it does not rely on distributional information beyond the first conditional moments. Despite its simplicity, we demonstrate that the PPA policy provides significant improvement over the canonical class of nonadaptive target-fill-rate policies. We complement our theoretical developments with a numerical study motivated by the rationing of COVID-19 medical supplies based on a standard compartmental modeling approach that is commonly used to forecast pandemic trajectories. In such a setting, our PPA policy significantly outperforms its theoretical guarantee and the optimal target-fill-rate policy.

This paper was accepted by Omar Besbes, revenue management and market analytics.

Supplemental Material: The data files and online appendices are available at https://doi.org/10.1287/mnsc.2023.4700 .
Bilateral Trade: A Regret Minimization Perspective
Authors: Cesa-Bianchi Nicolò , Cesari Tommaso , Colomboni Roberto , Fusco Federico , Leonardi Stefano
Published: February 2023

Bilateral trade, a fundamental topic in economics, models the problem of intermediating between two strategic agents, a seller and a buyer, willing to trade a good for which they hold private valuations. In this paper, we cast the bilateral trade problem in a regret minimization framework over T rounds of seller/buyer interactions, with no prior knowledge on their private valuations. Our main contribution is a complete characterization of the regret regimes for fixed-price mechanisms with different feedback models and private valuations, using as a benchmark the best fixed price in hindsight. More precisely, we prove the following tight bounds on the regret: [Formula: see text] for full-feedback (i.e., direct revelation mechanisms). [Formula: see text] for realistic feedback (i.e., posted-price mechanisms) and independent seller/buyer valuations with bounded densities. [Formula: see text] for realistic feedback and seller/buyer valuations with bounded densities. [Formula: see text] for realistic feedback and independent seller/buyer valuations. [Formula: see text] for the adversarial setting.

Funding: This work was partially supported by the European Research Council Advanced [Grant 788893] AMDROMA “Algorithmic and Mechanism Design Research in Online Markets”, the Ministero dell’Istruzione, dell’Università e della Ricerca PRIN project ALGADIMAR “Algorithms, Games, and Digital Markets”, the AI Interdisciplinary Institute ANITI (funded by the French “Investing for the Future—PIA3” program under the [Grant agreement ANR-19-PI3A-0004], the project BOLD from the French national research agency (ANR), the EU Horizon 2020 ICT-48 research and innovation action ELISE (European Learning and Intelligent Systems Excellence, [Grant agreement 951847].
Greater knowledge about COVID-19, more negative emotions. Research in adult Poles after 2nd and 5th waves of the pandemic
Authors: Szepietowska Ewa M. , Filipiak Sara A.
Published: February 2023

Introduction: The study investigated the dynamics of cognitive and emotional representation of COVID-19 in adult Poles, following the second (2021) and the fifth (2022) wave of the pandemic.
Material and methods: The study involved a total of 303 subjects (N = 198 in Survey 1 in 2021, and N = 105 in Survey 2 in 2022). The following measures were used: a questionnaire covering demographic data and general opinions about COVID-19 as well as the Revised Illness Perception Questionnaire (IPQ-R).
Results: After the fifth wave, significantly more respondents were convinced that COVID-19 was a real and dangerous disease. Cognitive deficits were more commonly recognised among symptoms of the viremia. Vaccination against COVID-19 was recognised as an essential preventive measure. Both surveys showed that COVID-19 representation was characterised by negative emotions and low sense of illness coherence. However, there was increased belief that the disease can be controlled through medical interventions. The age of the respondents in Survey 1 and Survey 2 was differently related to beliefs about COVID-19.

Conclusions:
1. After 2.5 years of the pandemic, the awareness of Poles about the causes, symptoms and methods of preventing the disease has increased.
2. Failure to vaccinate against COVID-19 has been identified as a significant cause of viremia.
3. Negative emotions and a sense of serious consequences were predominant in both Surveys, but after the fifth wave of the pandemic the scores reflect increased perception of the chronic nature of the disease and belief that the illness can be treated with medication, whereas the sense of personal control was found to decrease.
4. After the fifth wave of the pandemic, older age corresponded to increased belief in the relevance of some preventive measures, and to greater awareness of the viral origin, increased belief in the feasibility of controlling the disease through one's behaviours and a greater sense of illness coherence.
5. The intensification of negative emotions related to the pandemic can be treated as a predictor of the increase in adjustment disorders and risk of mental health deterioration among adult Poles in the following years.

Keywords: cognitive and emotional representation of illness, COVID-19 pandemic, Polish adults