bluuebunny/crossref_metadata_2025 huggingface dataset:
A Differentiable Parallel Sampler for Efficient Video Classification
Authors: Wang Xiaohan , Zhu Linchao , Wu Fei , Yang Yi
Published: October 2022

It is crucial to sample a small portion of relevant frames for efficient video classification. The existing methods mainly develop hand-designed sampling strategies or learn sequential selection policies. However, there are two challenges to be solved. First, hand-designed sampling strategies are intrinsically non-adaptive to different video backbones. Second, sequential frame selection policies ignore temporal relations among all video frames. The sequential selection process also hinders the application of these video samplers in speed-critical systems. In this article, we propose a differentiable parallel video sampling network (PSN) to tackle the aforementioned challenges, First, we optimize the video sampler with a differentiable surrogate loss, allowing to dynamically learn the sampler with the cooperation from the video classification model. Our sampler considers the feedback from all frames jointly, eliminating the learning difficulties of sequential decision making. The learning process is fully gradient-based, making the sampler be learned efficiently. Our video sampler can assess a set of frames swiftly and determine the importance of each frame in parallel. Second, we propose to model the inter-relation among contextual frames, which encourages the sampler to select frames based on a comprehensive inspection of the entire video. We observe that a simple context relation mining instantiation would significantly improve the classification performance. The experimental results on three standard video recognition benchmarks demonstrate the efficacy and efficiency of our framework.
CS-TSSOS: Correlative and Term Sparsity for Large-Scale Polynomial Optimization
Authors: Wang Jie , Magron Victor , Lasserre J. B. , Mai Ngoc Hoang Anh
Published: October 2022

This work proposes a new moment-SOS hierarchy, called
CS-TSSOS
, for solving large-scale sparse polynomial optimization problems. Its novelty is to exploit simultaneously
correlative sparsity
and
term sparsity
by combining advantages of two existing frameworks for sparse polynomial optimization. The former is due to Waki et al. [
40
] while the latter was initially proposed by Wang et al. [
42
] and later exploited in the TSSOS hierarchy [
46
,
47
]. In doing so we obtain CS-TSSOS—a two-level hierarchy of semidefinite programming relaxations with (i) the crucial property to involve blocks of SDP matrices and (ii) the guarantee of convergence to the global optimum under certain conditions. We demonstrate its efficiency and scalability on several large-scale instances of the celebrated Max-Cut problem and the important industrial optimal power flow problem, involving up to six thousand variables and tens of thousands of constraints.
The Influence of Oxygen Dissolved in the Liquid Electrolyte on Lithium Metal Anodes
Authors: Haas Ronja , Janek Jürgen
Published: October 2022

Due to the need for high energy density storage, Li–O2 batteries and Li metal anodes (LMA) are in the focus of research. As safe operation of the LMA is yet not possible, more knowledge about factors influencing the stability of the solid electrolyte interphase (SEI) is necessary to utilize the LMA. Especially concerning the influence of O2 dissolved in the electrolyte, there are still many unanswered questions, and there are conflicting opinions reported. In this work, plating/stripping experiments are used to show that the Coulomb efficiency is increased by dissolving O2 in the electrolyte. SEM and XPS analysis of the SEI shows that reaction of the conducting salt with Li metal is the cause of the poor reversibility of the LMA in cells without O2. The improved stability in the presence of O2 can be attributed to a protective Li2O and Li2CO3 rich SEI that prevents degradation. In addition, the SEI on freshly deposited Li is compared to that on a commercial Li foil. The reactivity of the native passivation layer formed on the Li foil during storage differs significantly from that of plated Li regarding the influence of O2, which can explain the different results and conclusions in literature.
The impact of COVID-19 on student learning during the transition from remote to in-person learning: using mind mapping to identify and address faculty concerns
Authors: Becker Tyler B. , Fenton Jenifer I. , Nikolai Michele , Comstock Sarah S. , Swada Jeffrey G. , Weatherspoon Lorraine J. , Tucker Robin M.
Published: October 2022

This article contains information gathered from mind map-driven faculty focus group observations of student academic-related deficiencies resulting from transitioning from remote to in-person learning and how said deficiencies compare to university undergraduate learning goals.
Mutagenesis of the cleavage site of (pro)renin receptor abrogates aldosterone-salt-induced hypertension and renal injury in mice
Authors: Fu Ziwei , Zheng Huaqing , Kaewsaro Kannaree , Lambert Jacob , Chen Yanting , Yang Tianxin
Published: October 2022

We used a novel mouse model with mutagenesis of the cleavage site of PRR to support soluble PRR as an essential mediator of aldosterone-salt-induced hypertension and also as a potential therapeutic target for patients with mineralocorticoid excess. We firstly report that soluble PRR-dependent pathway medicates the Na+-retaining action of aldosterone in the distal nephron, which opens up a new area for a better understanding of the molecular basis of renal handling of Na+ balance and blood pressure.
Evaluation of a Peak-Free Chemometric Laser-Induced Breakdown Spectroscopy Method for Direct Rapid Cancer Detection via Trace Metal Biomarkers in Tissue
Authors: Akinyi Otieno Emily , Kalambuka Angeyo Hudson , Dehayem-Kamadjeu Alix
Published: October 2022

The ability to perform direct rapid analysis in air and at atmospheric pressure is a remarkable attraction of laser-induced breakdown spectroscopy (LIBS) for the diagnostic quantification of disease biomarker metals in body tissue. However, accurate trace analysis is limited by matrix effects and a pronounced background that masks the subtle (peak-free) analyte signals because tissue plasma is dense and most lines are optically thick. In this work, a peak-free chemometric LIBS method based on a single-shot (for rapidity and nondestructiveness) and an artificial neural network multivariate calibration strategy with spectral feature selection was evaluated for its utility for direct trace quantitative analysis of copper (Cu), iron (Fe), manganese (Mg), magnesium (Mg), and zinc (Zn) in model soft body tissue. The spectral signatures corresponding to the biometals (so-called because the metals are intrinsic to tissue biochemistry) were generated by spiking their known human-body-representative concentrations in molten paraffin wax. The developed multivariate analytical model achieved ≥95% accuracy as determined from the analysis of oyster tissue-certified reference material. The analytical models were tested on the liver, breast, and abdominal tissue biopsies. The results of applying the model to the clinical tissues indicated the absence or presence (including severity) of cancer as either malignant or benign, in agreement with the pathological examination report.
The “3D Versascrew”: An Innovative Approach for Management of Bilateral Cleft Lip and Palate Case
Authors: Ashith M. V. , Suma NS , Mithun K. , Ahuja Dhruv
Published: October 2022

The purpose behind the innovation of modified nasoalveolar moulding appliance was to achieve simultaneous anteroposterior and transverse correction in bilateral cleft cases with minimal vomeroid bending. This paper presents a 3D Versascrew appliance that has been used for presurgical nasoalveolar moulding in a 15-day-old neonate with bilateral cleft. Treatment was initiated at 30 days and continued for 90 days following which mild expansion of posterior maxilla with establishment of arch continuity and concomitant improvement in nasal morphology was achieved towards the end.
Mathematical Modelling of MX/G(a, b)/1 Bulk Service Queue Model with Two Vacations and Setup Time in Ceramic Technology
Authors: Lavanya B. , Vennila R. , Sankoh Martin
Published: October 2022

The orthodox way of tile printing results in mulish production. To tame this, digital inkjet printing technology was imposed. In this article, a mathematical prototype is designed exclusively for the tile printing wing. The various plants coming under printing are correlated to the proposed prototype. The article throws light on the functioning of the prototype. The prototype turns up subservient to bulk service queue models with two types of vacations. The prototype is resolved under the supplementary variable technique. The prototype with peculiar conditions is proved to be the existing model. Anticipated line distance, awaited active duration, awaited standby time, and expected idle period were computed. Thus, the total average cost is acquired for diverse vacation values. The main intention of the pattern is to downside the total average cost.
Attacking Websites: Detecting and Preventing HTTP Request Smuggling Attacks
Authors: Huang Qi-Xian , Chiu Min-Yi , Chen Ying-Feng , Sun Hung-Min
Published: October 2022

Until the development of HTTP request smuggling in 2005, individual HTTP requests were considered as independent entities and could not be split or merged. This is a security problem caused by inconsistent content length interpretation approach between web servers, or the web server is not fully implemented in accordance with the RFC standard. It is especially dangerous for web services with complex web architectures. It can route the victims to receive malicious responses, amplify the impact of certain low-threat vulnerabilities, steal user credentials, or bypass network devices’ defenses. However, since its concept and implementation are quite difficult to overcome, it is often ignored by many network administrators, making users who browse such websites vulnerable to the HTTP request smuggling attacks. This paper proposes a general solution to deal with various HTTP request smuggling attacks. A reverse proxy implemented by Flask validates and cleans dubious HTTP requests from the client side and ensures that the original requests comply with RFC standards. Therefore, the website administrators no longer need to configure complicated network settings or customize some open-source project codes to resist or minimize the risk of the HTTP request smuggling attacks. A series of experiments demonstrate that this method is effective and practical.
Differential Expression and Bioinformatics Analysis of Plasma-Derived Exosomal circRNA in Type 1 Diabetes Mellitus
Authors: Pang Haipeng , Fan Wenqi , Shi Xiajie , Luo Shuoming , Wang Yimeng , Lin Jian , Xiao Yang , Li Xia , Huang Gan , Xie Zhiguo , Zhou Zhiguang
Published: October 2022

Backgrounds. Both exosome and circular RNA (circRNA) have been reported to participate in the pathogenesis of type 1 diabetes mellitus (T1DM). However, the exact role of exosomal circRNA in T1DM is largely unknown. Here, we identified the exosomal circRNA expression profiles in the plasma of T1DM patients and explored their potential function using bioinformatics analysis. Material and Methods. Exosomes were extracted by the size exclusion chromatography method from plasma of 10 T1DM patients and 10 age- and sex- matched control subjects. Illumina Novaseq6000 platform was used to detect the exosomal circRNA expression profiles. Multiple bioinformatics analysis was applied to investigate the potential biological functions of exosomal circRNAs. Results. A total of 784 differentially expressed exosomal circRNAs have been identified in T1DM patients, of which 528 were upregulated and 256 were downregulated. Gene Ontology analysis enriched terms such as protein ubiquitination involved in ubiquitin-dependent protein catabolic protein (GO:0042787), membrane (GO:0016020), and GTPase activator activity (GO:0005096). The most enriched pathway in Kyoto Encyclopedia of Genes and Genomes was ubiquitin-mediated proteolysis (ko04120). The miRNA-targeting prediction method was used to identify the miRNAs that bind to circRNAs, and circRNA-miRNA-mRNA pathways were constructed, indicating that interactions between circRNA, miRNA, and gene might be involved in the disease progression. Conclusions. The present study identified the exosomal circRNA expression profiles in T1DM for the first time. Our results threw novel insights into the molecular mechanisms of T1DM.
COVID-19 Outbreak Forecasting Based on Vaccine Rates and Tweets Classification
Authors: Didi Y. , Walha A. , Ben Halima M. , Wali A.
Published: October 2022

The spread of COVID-19 has affected more than 200 countries and has caused serious public health concerns. The infected cases are on the increase despite the effectiveness of the vaccines. An efficient and quick surveillance system for COVID-19 can help healthcare decision-makers to contain the virus spread. In this study, we developed a novel framework using machine learning (ML) models capable of detecting COVID-19 accurately at an early stage. To estimate the risks, many models use social networking sites (SNSs) in tracking the disease outbreak. Twitter is one of the SNSs that is widely used to create an efficient resource for disease real-time analysis and can provide an early warning for health officials. We introduced a pipeline framework of outbreak prediction that incorporates a first-step hybrid method of word embedding for tweet classification. In the second step, we considered the classified tweets with external features such as vaccine rate associated with infected cases passed to machine learning algorithms for daily predictions. Thus, we applied different machine learning models such as the SVM, RF, and LR for classification and the LSTM, Prophet, and SVR for prediction. For the hybrid word embedding techniques, we applied TF-IDF, FastText, and Glove and a combination of the three features to enhance the classification. Furthermore, to improve the forecast performance, we incorporated vaccine data as input together with tweets and confirmed cases. The models’ performance is more than 80% accurate, which shows the reliability of the proposed study.
A Study on Volatility Spillovers among International Stock Markets during the Russia‐Ukraine Conflict
Authors: Mu Sixu , Huang Guangdong , Li Ping , Hou Yun
Published: October 2022

This paper analyzes the dynamic time‐frequency volatility spillovers among the international stock markets during the Russian‐Ukraine conflict. We use the VAR‐based connectedness framework to calculate the volatility spillovers. Results show that (1) the trend of the total spillover is consistent with the time of the Russian‐Ukraine conflict; (2) Russian stock market is the primary source and net exporter of risk; (3) the Russian government has effectively controlled the further spread of risk through policy adjustments; and (4) Russian stock market may generate long‐run volatility spillovers among the international stock market. We add research related to the impact of the Russia‐Ukraine conflict on international stock markets by analyzing the results of the volatility spillovers.
Hybrid Encryption Algorithm Based on Gray Curve and Josephus Permutation
Authors: Niu Ying , Zhou Hangyu , Zhang Xuncai , Qin Limin
Published: October 2022

This paper proposes a new image encryption algorithm based on chaos map systems, hash algorithm, and Josephus permutation. The algorithm consists of chaos initialization, pixel position permutation, and pixel information diffusion. The algorithm’s initialization is generated by the original image, which has a high sensitivity to the initial value. The permutation step length is composed of Josephus permutation and gray curve permutation, which completely disturbs the pixel distribution. The diffusion process is composed of cross operation and ciphertext feedback, which breaks the strong correlation between pixels. The simulation results of the encryption algorithm are used to analyze its information entropy, the correlation between elements, and other indicators. The ciphertext image is attacked in several ways, and we analyzed its defense ability. Simulation results show that the algorithm can effectively encrypt image information and has a good defense against various attacks.
Establishment of a Highly Efficient Corn Stock-Degrading Microbial Consortium and Its Degradation Effect
Authors: Zhang Erhong , Wang Meng , Pan Xiaoliang , Wang Xinfeng
Published: October 2022

Corn stalks are not easily degradable and thus have a low utilization rate. In this paper, a highly efficient corn stalk-degrading microbial consortium, designated as SDP, was established using the strains Z22 (Bacillus subtilis), Z15 (Bacillus megaterium), and Z08 (Aspergillus tubingensis). Moreover, the fermentation conditions for enzyme production by SDP were optimized through orthogonal experiments. The Van Soest method was used to determine the cellulose, hemicellulose, and lignin contents in the degraded corn stalks using the SDP consortium to evaluate its degrading effect. Scanning electron microscopy was used to analyze the micromorphological structure changes of the stalks to evaluate the degradation effects of SDP on corn stalks. The carboxymethyl cellulase activity of SDP reached 6.37 U/mL. Moreover, the enzyme production effect was optimal when the culture conditions were as follows: temperature, 30°C; time, 5 d; nitrogen source, NH4NO3; and initial pH, 7.0. The SDP consortium showed an improved ability to degrade corn stalks. The cellulose, hemicellulose, and lignin contents were reduced by 32.15%, 23.87%, and 7.98%, respectively, after culturing for 20 d. This study provides insights to guide further research and development of consortia for efficient corn stalk degradation.
Meta-Analysis of the Test–Retest Repeatability of [18F]-Fluorodeoxyglucose Standardized Uptake Values: Implications for Assessment of Tumor Response
Authors: Shankar Lalitha K. , Huang Erich , Litiere Saskia , Hoekstra Otto S. , Schwartz Larry , Collette Sandra , Boellaard Ronald , Bogaerts Jan , Seymour Lesley , deVries Elisabeth G.E.
Published: October 2022

Purpose:

Currently, guidelines for PET with 18F-fluorodeoxyglucose (FDG-PET) interpretation for assessment of therapy response in oncology primarily involve visual evaluation of FDG-PET/CT scans. However, quantitative measurements of the metabolic activity in tumors may be even more useful in evaluating response to treatment. Guidelines based on such measurements, including the European Organization for Research and Treatment of Cancer Criteria and PET Response Criteria in Solid Tumors, have been proposed. However, more rigorous analysis of response criteria based on FDG-PET measurements is needed to adopt regular use in practice.

Experimental Design:

Well-defined boundaries of repeatability and reproducibility of quantitative measurements to discriminate noise from true signal changes are a needed initial step. An extension of the meta-analysis from de Langen and colleagues (2012) of the test–retest repeatability of quantitative FDG-PET measurements, including mean, maximum, and peak standardized uptake values (SUVmax, SUVmean, and SUVpeak, respectively), was performed. Data from 11 studies in the literature were used to estimate the relationship between the variance in test–retest measurements with uptake level and various study-level, patient-level, and lesion-level characteristics.

Results:

Test–retest repeatability of percentage fluctuations for all three types of SUV measurement (max, mean, and peak) improved with higher FDG uptake levels. Repeatability in all three SUV measurements varied for different lesion locations. Worse repeatability in SUVmean was also associated with higher tumor volumes.

Conclusions:

On the basis of these results, recommendations regarding SUV measurements for assessing minimal detectable changes based on repeatability and reproducibility are proposed. These should be applied to differentiate between response categories for a future set of FDG-PET–based criteria that assess clinically significant changes in tumor response.
Randomized Phase II Trial of Sunitinib or Cediranib in Alveolar Soft Part Sarcoma
Authors: Nguyen James , Takebe Naoko , Kummar Shivaani , Razak Albiruni , Chawla Sant P. , George Suzanne , Patel Shreyaskumar R. , Keohan Mary Louise , Movva Sujana , O'Sullivan Coyne Geraldine , Do Khanh , Juwara Lamin , Augustine Brooke , Steinberg Seth M. , Kuhlmann Laura , Ivy S. Percy , Doroshow James H. , Chen Alice P.
Published: October 2022

Purpose:

Alveolar soft part sarcoma (ASPS) is a rare, highly vascular tumor with few treatment options. We designed a phase II randomized trial to determine the activity and tolerability of single-agent cediranib or sunitinib in patients with advanced metastatic ASPS.

Patients and Methods:

Patients 16 years of age and older were randomized to receive cediranib (30 mg) or sunitinib (37.5 mg) in 28-day cycles. Patients could cross over to the other treatment arm at disease progression. The primary endpoint was to measure the objective response rate (ORR) for each agent. Median progression-free survival (mPFS) for the two arms was also determined.

Results:

Twenty-nine of 34 enrolled patients were evaluable for response. One patient on each of the initial two treatment arms had a partial response (ORR: 6.7% and 7.1% for cediranib and sunitinib, respectively). Twenty-four patients had a best response of stable disease (86.7% and 78.6% for cediranib and sunitinib, respectively). There were no significant differences in mPFS for the two treatment arms. Clinical benefit (i.e., objective response or stable disease for a minimum of four or six cycles of therapy) on the first-line tyrosine kinase inhibitor (TKI) therapy did not predict benefit on the second-line TKI. Both drugs were well tolerated. As of August 2021, 1 patient (unevaluable for ORR) remains on study.

Conclusions:

The study did not meet its endpoints for ORR. Although both TKIs provided clinical benefit, the outcomes may have been attenuated in patients who had progressed ≤6 months before enrollment, potentially accounting for the low response rates.

See related commentary by Wilky and Maleddu, p. 1163
A Phase II Trial of Guadecitabine in Children and Adults with SDH-Deficient GIST, Pheochromocytoma, Paraganglioma, and HLRCC-Associated Renal Cell Carcinoma
Authors: Ligon John A. , Sundby R. Taylor , Wedekind Mary F. , Arnaldez Fernanda I. , Del Rivero Jaydira , Wiener Lori , Srinivasan Ramaprasad , Spencer Melissa , Carbonell Amanda , Lei Haiyan , Shern John , Steinberg Seth M. , Figg William D. , Peer Cody J. , Zimmerman Sara , Moraly Josquin , Xu Xia , Fox Stephen , Chan King , Barbato Michael I. , Andresson Thorkell , Taylor Naomi , Pacak Karel , Killian J. Keith , Dombi Eva , Linehan W. Marston , Miettinen Markku , Piekarz Richard , Helman Lee J. , Meltzer Paul , Widemann Brigitte , Glod John
Published: October 2022

Purpose:

Succinate dehydrogenase (dSDH)-deficient tumors, including pheochromocytoma/paraganglioma, hereditary leiomyomatosis and renal cell cancer–associated renal cell carcinoma (HLRCC-RCC), and gastrointestinal stromal tumors (GIST) without KIT or platelet-derived growth factor receptor alpha mutations are often resistant to cytotoxic chemotherapy, radiotherapy, and many targeted therapies. We evaluated guadecitabine, a dinucleotide containing the DNA methyltransferase inhibitor decitabine, in these patient populations.

Patients and Methods:

Phase II study of guadecitabine (subcutaneously, 45 mg/m2/day for 5 consecutive days, planned 28-day cycle) to assess clinical activity (according to RECISTv.1.1) across three strata of patients with dSDH GIST, pheochromocytoma/paraganglioma, or HLRCC-RCC. A Simon optimal two-stage design (target response rate 30% rule out 5%) was used. Biologic correlates (methylation and metabolites) from peripheral blood mononuclear cells (PBMC), serum, and urine were analyzed.

Results:

Nine patients (7 with dSDH GIST, 1 each with paraganglioma and HLRCC-RCC, 6 females and 3 males, age range 18–57 years) were enrolled. Two patients developed treatment-limiting neutropenia. No partial or complete responses were observed (range 1–17 cycles of therapy). Biologic activity assessed as global demethylation in PBMCs was observed. No clear changes in metabolite concentrations were observed.

Conclusions:

Guadecitabine was tolerated in patients with dSDH tumors with manageable toxicity. Although 4 of 9 patients had prolonged stable disease, there were no objective responses. Thus, guadecitabine did not meet the target of 30% response rate across dSDH tumors at this dose, although signs of biologic activity were noted.
Cellular Senescence Is Immunogenic and Promotes Antitumor Immunity
Authors: Marin Ines , Boix Olga , Garcia-Garijo Andrea , Sirois Isabelle , Caballe Adrià , Zarzuela Eduardo , Ruano Irene , Attolini Camille Stephan-Otto , Prats Neus , López-Domínguez José A , Kovatcheva Marta , Garralda Elena , Muñoz Javier , Caron Etienne , Abad María , Gros Alena , Pietrocola Federico , Serrano Manuel
Published: October 2022

Cellular senescence is a stress response that activates innate immune cells, but little is known about its interplay with the adaptive immune system. Here, we show that senescent cells combine several features that render them highly efficient in activating dendritic cells (DC) and antigen-specific CD8 T cells. This includes the release of alarmins, activation of IFN signaling, enhanced MHC class I machinery, and presentation of senescence-associated self-peptides that can activate CD8 T cells. In the context of cancer, immunization with senescent cancer cells elicits strong antitumor protection mediated by DCs and CD8 T cells. Interestingly, this protection is superior to immunization with cancer cells undergoing immunogenic cell death. Finally, the induction of senescence in human primary cancer cells also augments their ability to activate autologous antigen-specific tumor-infiltrating CD8 lymphocytes. Our study indicates that senescent cancer cells can be exploited to develop efficient and protective CD8-dependent antitumor immune responses.

Significance:

Our study shows that senescent cells are endowed with a high immunogenic potential—superior to the gold standard of immunogenic cell death. We harness these properties of senescent cells to trigger efficient and protective CD8-dependent antitumor immune responses.

See related article by Chen et al., p. 432.

This article is highlighted in the In This Issue feature, p. 247
Increased CaMKK2 Expression Is an Adaptive Response That Maintains the Fitness of Tumor-Infiltrating Natural Killer Cells
Authors: Juras Patrick K. , Racioppi Luigi , Mukherjee Debarati , Artham Sandeep , Gao Xia , Akullian D'Agostino Laura , Chang Ching-Yi , McDonnell Donald P.
Published: October 2022

Calcium/calmodulin-dependent protein kinase kinase 2 (CaMKK2) is a key regulator of energy homeostasis in several cell types. Expression of this enzyme in tumor cells promotes proliferation and migration, and expression in tumor-associated immune cells facilitates M2 macrophage polarization and the development of myeloid-derived suppressor cells. Thus, there has been interest in developing CaMKK2 inhibitors as potential anticancer therapeutics. One impediment to clinical development of these agents is that the roles of CaMKK2 in other cellular compartments within the tumor immune microenvironment remain to be established. We report herein that CaMKK2 is expressed at low basal levels in natural killer (NK) cells but is upregulated in tumor-infiltrating NK cells where it suppresses apoptosis and promotes proliferation. NK cell–intrinsic deletion of CaMKK2 increased metastatic progression in several murine models, establishing a critical role for this enzyme in NK cell–mediated antitumor immunity. Ablation of the CaMKK2 protein, but not inhibition of its kinase activity, resulted in decreased NK-cell survival. These results indicate an important scaffolding function for CaMKK2 in NK cells and suggest that competitive CaMKK2 inhibitors and ligand-directed degraders (LDD) are likely to have distinct therapeutic utilities. Finally, we determined that intracellular lactic acid is a key driver of CaMKK2 expression, suggesting that upregulated expression of this enzyme is an adaptive mechanism by which tumor-infiltrating NK cells mitigate the deleterious effects of a lactic acid–rich tumor microenvironment. The findings of this study should inform strategies to manipulate the CaMKK2-signaling axis as a therapeutic approach in cancer.
A Case of Bilateral Microphthalmia and Extensive Colobomas of the Globes Associated with a Likely Pathogenic Homozygous SIX6 Variant
Authors: Javidi Eileen , Javidi Simon , Campeau Philippe M. , Ospina Luis H.
Published: October 2022

Colobomas of the globe and microphthalmia are congenital conditions that can strongly affect vision. Etiologies are varied and include embryonic and hereditary origins. We report what is, to the best of our knowledge, the first case of a SIX6 gene pathogenic variant associated with a phenotype of both bilateral microphthalmia and extensive colobomas of the globes. A 3-week-old boy presented with bilateral microphthalmia and iris, optic nerve, and chorioretinal colobomas. Genetic analysis was performed on a panel of 78 genes (microphthalmia, anophthalmia, and coloboma panel), and a homozygous likely pathogenic variant was identified in the SIX6 gene, resulting in the loss of the initiator methionine. Thus, our report expands the phenotypic spectrum of SIX6-related disorders.
Natural Age-Related Slow-Wave Sleep Alterations Onset Prematurely in the Tg2576 Mouse Model of Alzheimer’s Disease
Authors: Kollarik Sedef , Dias Inês , Moreira Carlos G. , Bimbiryte Dorita , Miladinovic Djordje , Buhmann Joachim M. , Baumann Christian R. , Noain Daniela
Published: October 2022

Introduction: Sleep insufficiency or decreased quality have been associated with Alzheimer’s disease (AD) already in its preclinical stages. Whether such traits are also present in rodent models of the disease has been poorly addressed, somewhat disabling the preclinical exploration of sleep-based therapeutic interventions for AD. Methods: We investigated age-dependent sleep-wake phenotype of a widely used mouse model of AD, the Tg2576 line. We implanted electroencephalography/electromyography headpieces into 6-month-old (plaque-free, n = 10) and 11-month-old (moderate plaque-burdened, n = 10) Tg2576 mice and age-matched wild-type (WT, 6 months old n = 10, 11 months old n = 10) mice and recorded vigilance states for 24 h. Results: Tg2576 mice exhibited significantly increased wakefulness and decreased non-rapid eye movement sleep over a 24-h period compared to WT mice at 6 but not at 11 months of age. Concomitantly, power in the delta frequency was decreased in 6-month old Tg2576 mice in comparison to age-matched WT controls, rendering a reduced slow-wave energy phenotype in the young mutants. Lack of genotype-related differences over 24 h in the overall sleep-wake phenotype at 11 months of age appears to be the result of changes in sleep-wake characteristics accompanying the healthy aging of WT mice. Conclusion: Therefore, our results indicate that at the plaque-free disease stage, diminished sleep quality is present in Tg2576 mice which resembles aged healthy controls, suggesting an early-onset of sleep-wake deterioration in murine AD. Whether such disturbances in the natural patterns of sleep could in turn worsen disease progression warrants further exploration.
Real‐Time Magnetic Resonance Imaging to Study Orthostatic Intolerance Mechanisms in Human Beings: Proof of Concept
Authors: Gerlach Darius A. , Maier Andrea , Manuel Jorge , Bach Anja , Hoff Alex , Hönemann Jan‐Niklas , Heusser Karsten , Voit Dirk , Frahm Jens , Jordan Jens , Tank Jens
Published: October 2022

Background

Discerning the mechanisms driving orthostatic symptoms in human beings remains challenging. Therefore, we developed a novel approach combining cardiac and cerebral real‐time magnetic resonance imaging, beat‐to‐beat physiological monitoring, and orthostatic stress testing through lower‐body negative pressure (LBNP). We conducted a proof‐of‐concept study in a patient with severe orthostatic hypotension.

Methods and Results

We included a 46‐year‐old man with pure autonomic failure. Without and during −30 
mmHg LBNP
, we obtained
3T
real‐time magnetic resonance imaging of the cardiac short axis and quantitative flow measurements in the pulmonary trunk and middle cerebral artery. Blood pressure was 118/74 
mmHg
during supine rest and 58/35 
mmHg
with
LBNP
. With
LBNP
, left ventricular stroke volume decreased by 44.6%, absolute middle cerebral artery flow by 37.6%, and pulmonary trunk flow by 40%.

Conclusions

Combination of real‐time magnetic resonance imaging,
LBNP
, and continuous blood pressure monitoring provides a promising new approach to study orthostatic intolerance mechanisms in human beings.
Social Isolation and Implementation of Advanced Care Planning Among Hospitalized Patients With Heart Failure
Authors: Kitakata Hiroki , Kohno Takashi , Kohsaka Shun , Fujisawa Daisuke , Nakano Naomi , Sekine Otoya , Shiraishi Yasuyuki , Kishino Yoshikazu , Katsumata Yoshinori , Yuasa Shinsuke , Fukuda Keiichi
Published: October 2022

Background

The implementation of advance care planning (ACP) in heart failure management is insufficient. Social isolation (SI) could be a barrier to ACP initiation, albeit the relationship between SI and patients' preference for ACP or end‐of‐life care remains unknown.

Methods and Results

We conducted a questionnaire survey, including assessments of SI using the 6‐item Lubben Social Network Scale as well as patients' perspectives on ACP and end‐of‐life care. Of the 160 patients approached by our multidisciplinary heart failure team during admission, 120 patients (75.0%) completed the survey (median age, 73.0 years; men, 74.2%). A Cox proportional hazard model was constructed to elucidate the short‐term (180‐day) prognostic impact of SI. Overall, 28.3% of participants were at high risk for SI (6‐item Lubben Social Network Scale score <12). High‐risk patients had more negative attitudes toward ACP than those without (61.8% versus 80.2%;
P
=0.035). The actual performance of ACP conversation in patients with and without high risk were 20.6% and 30.2%, respectively. Regarding preference in end‐of‐life care, “Saying what one wants to tell loved ones” (73.5% versus 90.6%;
P
=0.016) and “Spending enough time with family” (58.8% versus 77.9%;
P
=0.035) were less important in high‐risk patients. High risk for SI was associated with higher 180‐day risk‐adjusted all‐cause mortality (hazard ratio, 7.89 [95% CI, 1.53–40.75]).

Conclusions

In hospitalized patients with heart failure, high risk for SI was frequently observed. High‐risk patients were associated with a negative attitude toward ACP, despite higher mortality. Further research is required to establish an ideal approach to provide ACP in socially vulnerable patients.
Redefining Disability: Patient-Reported Outcome Measures After Minor Stroke and Transient Ischemic Attack
Authors: Olive-Gadea Marta , Cano David , Rodrigo-Gisbert Marc , Muchada Marian , Montiel Estefania , Baladas Maria , Sanchez-Gavilan Ester , Paredes Carolina , Garcia-Tornel Alvaro , Rubiera Marta , Requena Manuel , Ribo Marc , Molina Carlos A.
Published: October 2022

Background:

Long-term outcome assessment patients with stroke is not fully captured by usual clinical scales such as the modified Rankin Scale (mRS). Patient-reported outcome measures (PROMs) are standardized and validated assessments that consider clinical outcomes from the patient perspective. We aim to analyze the added value of PROMs in patients with transient ischemic attack and minor stroke.

Methods:

We included consecutive patients with minor stroke or transient ischemic attack (National Institutes of Health Stroke Scale score 0–5) from April 2020 to October 2021 that participated in the PROMs-through-App program (NORA, NoraHealth Barcelona Spain). Clinician and self-evaluated outcomes were assessed at 90 days: clinician-evaluated mRS, self-reported mRS, the 10-item patient-reported outcome measures questionnaire global health survey (v1.2), Hospital Anxiety and Depression Scale, and the Fatigue Assessment Scale. We evaluated the acceptability (response rate), reliability (internal consistency), and construct validity (correlation with mRS and between scales) of each questionnaire.

Results:

We included 355 patients in the analysis, response rate was patient-reported outcome measures questionnaire 71.3% (253), Hospital Anxiety and Depression Scale 70.7% (251), Fatigue Assessment Scale 71.8% (255), and self-assessed mRS 66.8% (237). PROMS internal consistency was good or excellent, while agreement between clinician and self-reported mRS was fair (k=0.34). Rate of abnormal PROMS scores were as follows (all responders versus clinician-reported mRS score 0–2): patient-reported outcome measures questionnaire mental health (43.1% versus 36.3%), physical health (48.6% versus 43.6%); Hospital Anxiety and Depression Scale-anxiety (21.9% versus 17.7%) and depression (17.1% versus 13.3%); and Fatigue Assessment Scale (40.8% versus 36.4%). PROMs scores correlated with clinician and self-reported mRS at 90 days.

Conclusions:

Evaluation of PROMs using a mobile-app-based communication system is a reliable and valid strategy to assess the outcome of patients from their perspective after a mild stroke or transient ischemic attack.
Determinants of Job Satisfaction among Doctorate Holders: Focusing on the Relationship between Over-Education and Job Satisfaction in South Korea
Authors: Park Kihong
Published: October 2022

This study aims to analyze the determinants of job satisfaction among doctorate holders in South Korea, with a particular focus on the relationship between over-education and job satisfaction. Unlike most previous studies, this paper considers overall job satisfaction as well as six different domains of job satisfaction (promotion opportunities, intellectual challenge, level of responsibility, level of autonomy, contribution to society, and social status) using data from the Korean Survey on Careers and Mobility of Doctorate Holders of 2017. This multi-dimensional approach to job satisfaction is important since the nature of job satisfaction is a complex concept in general. The main result of an ordered probit model reveals that perceived over-education is found to be a significant negative determinant of overall job satisfaction as well as all six aspects of job satisfaction, suggesting that over-educated doctorate holders are more dissatisfied with various aspects of their job compared to their well-matched counterparts.
Influence of Rural Industrial Integration on Farmers’ Income in China
Authors: Su Guibin , Jiang Huiming
Published: October 2022

Rural transportation infrastructure is an important foundation for rural economic development and plays an important role in the process of rural industrial integration to increase farmers’ income. Based on China’s inter-provincial panel data from 2014 to 2019, this paper classifies rural transportation infrastructure from the perspective of external connection level, and empirically analyzes the role of the scale, type, and structure of rural transportation infrastructure in the process of rural industrial integration to increase farmers’ income. It is found that in China, rural industrial integration is conducive to increasing farmers’ income. In the process of rural industrial integration to increase farmers’ income, the overall scale of rural transportation infrastructure has played a synergistic role; Different types of rural transportation infrastructure play different roles. Township-village transportation infrastructure mainly shows synergy, while city-township transportation infrastructure mainly shows substitution. Optimizing rural transportation infrastructure structure is conducive to strengthening rural industrial integration and increasing farmers’ income. When the ratio of township-village and city-township transportation infrastructure scale is less than 1.921, rural industrial integration fails to increase farmers’ income; When the ratio of rural-village and urban-rural transportation infrastructure is between 1.921 and 7.808, the promotion of rural industrial integration on farmers’ income increase begins to be significant; When the ratio of rural-village to urban-rural transportation infrastructure is greater than 7.808, the promotion of rural industrial integration on farmers’ income will further increase.
Attraction of leaf hopper, Amrasca biguttulla biguttulla, and whitefly, Bemisia tabaci, toward natural essential oils in cotton
Authors: T N Madhu , Kumar Rishi , Naik V. Chinnababu , Prabhulinga T. , Santosh Savitha , Chandrashekar N. , Verma Pooja
Published: October 2022

Leaf hopper, Amrasca biguttula biguttula, and whitefly, Bemisia tabaci are the most economical sucking pests of cotton (Gossypium spp.) causing stunting, shortening of internodes and transmitting plant pathogenic viruses. The management of these pests is primarily based on application of synthetic pesticides, which not only triggers resistance to insecticide molecules but also contributes to environmental pollution. We aimed to study the attraction of A. biguttula and B. tabaci toward six natural essential oils (NEOs) viz., sandalwood, basil, grapefruit, rose, clove and mint oils using yellow sticky traps under field conditions. The results showed that traps treated with sandalwood and basil oils attract significant numbers of A. biguttula and B. tabaci as compared to the other traps during the seasons 2016-2017 and 2017-2018. Further, the Attractive Index (AI) of sandalwood and basil oils to these pests were significantly higher (i.e., >1). In addition, the traps treated with sandalwood and basil oils caught relatively lower numbers of natural enemies. The GC-MS analysis specified the presence of vital attractive volatile compounds, viz., santalene, funebrene and pentadecane in sandalwood; and linalool, β-farnesene, caryophyllene and methyl eugenol in basil oil. Based on the results obtained it can be concluded that application of sandalwood and basil oils increased the attracting efficacy of sticky traps for the management of A. biguttula and B. tabaci in cotton.
Health Care Complaints and Professional Legal Responsibility — A Cross-Country Comparative Review
Authors: Birkeland Søren Fryd
Published: October 2022

One approach to stimulating patient safety and health care quality is through holding health care professionals legally responsible for their performance. Law and health care variation across countries, however, makes it difficult to get an overview and make comparisons of the personal legal responsibility of health care providers. This article describes health care professional liability and complaint measures in some European countries (UK, The Netherlands, Sweden and Denmark) and US. Countries all have established a public authority to assess complaints about health professional performance and opportunities for economic compensation. The assessment of health professional legal responsibility generally relies on comparisons to supposedly “objective” standards predominantly dictated by the health profession. In line with the aim of ensuring acceptable care for all, health ethics principles on justice, respect for patients’ autonomy, and the duty to do good and prevent harm may provide an attractive supplement in the description of legal responsibility in the health professions.
The Historical, the National, and the Modern in Axel Honneth’s Recognition
Authors: Lim Shiru
Published: October 2022

On what basis might we consider European thinkers to have bequeathed to us a theory of recognition? How relatable were their ideas across national lines—and coherent within them? And to what use can such a theory be put? This piece explores how Axel Honneth’s Recognition: A Chapter in the History of European Ideas (2021) tackles these questions. It examines its premises and uses of history, and tries to understand it both as part of a wider political-philosophical project, as well as an intervention in the history of political thought.
Recognition, Transformation, and Critical Intellectual History: A Reply to Honneth’s Recognition: A Chapter in the History of Ideas
Authors: Levine William
Published: October 2022

This article critically responds to Axel Honneth’s Recognition: A Chapter in the History of Ideas. It argues that, although Recognition provides a compelling historical investigation into the history of the concept of recognition as it emerged in modern France, Great Britain, and Germany, Honneth’s text retains some questionable methodological commitments that undermine its more provocative and potentially wide-ranging contributions. This article interrogates these commitments in addition to some of Honneth’s more specific arguments to speculate about other lessons that Honneth’s history of recognition can provide.
Forced Migration and the Plight of the Chakma Refugees in Arunachal Pradesh: ‘Citizenship’ as a Bone of Contention
Authors: Choden Nawang
Published: October 2022

The present paper explores the persistent and contentious issue of citizenship of the Chakma community in Arunachal Pradesh. The Chakmas were originally uprooted from the Chittagong Hill Tracts of former East Pakistan and were resettled in Arunachal Pradesh, formerly known as the North East Frontier Agency (nefa). The forced migration of the Chakma community has implications at different levels and raises critical questions about exclusion, belongingness, citizenship and the various rights which comes with it. The article explores the relationship between refugee identity and citizenship rights to see how this relationship is mediated through denial or extension of state entitlements. Examining the nature of citizenship within this context may help to further uncover how the concept of citizenship is both understood and used today.
Bad Becoming Normal is Detrimental to Beef Cattle Welfare
Authors: Grandin Temple
Published: October 2022

The author has worked in the cattle industry for fifty years. In the 1970’s, cattle handling was terrible and today it has greatly improved. During the last fifteen years, there have been increasing problems with lameness, heat stress, and heart failure in fed beef cattle. These problems slowly increased and people did not notice them until they became really serious. I called this bad becoming normal. The increase is these welfare issues is partially related to increased genetic selection for more muscle and weight gain. Other factors may be muddy pens, a lack of roughage in the ration, heavier cattle at a younger age, or overuse of growth promotants. These practices may overload the animal’s biology and make it dysfunctional. There is a significant minority of producers who push cattle for maximum production, which is detrimental to animal welfare.