bluuebunny/crossref_metadata_2025 huggingface dataset:
Bacteriostatic cells instead of bacteriostatic antibiotics?
Authors: Baquero Fernando , Rodríguez-Beltrán Jerónimo , Levin Bruce R.
Published: December 2023

This year we commemorate the centennial of the birth of the mature concept of bacteriostasis by John W. Churchman at Cornell University Medical School. The term bacteriostasis has primarily been applied to antibiotics (bacteriostatic antibiotics). In this Opinion paper, we are revisiting this concept by suggesting that some antibiotics are drugs that induce bacteria to become bacteriostatic. Cells that are unable to multiply, thereby preventing the antibiotic from exerting major lethal effects on them, are a variant (“different”) type of cells, bacteriostatic cells. Note that the term “bacteriostasis” should not be associated only with antimicrobials but with many stressful conditions. In that respect, the drug promotion of bacteriostasis might resemble other types of stress-induced cellular differentiation, such as sporulation, in which spores can be considered “bacteriostatic cells” or perhaps as persister bacteria, which can become “normal cells” again when the stressful conditions have abated.
Homologous acetone carboxylases select Fe(II) or Mn(II) as the catalytic cofactor
Authors: Shisler Krista A. , Kincannon William M. , Mattice Jenna R. , Larson James , Valaydon-Pillay Adam , Mus Florence , Flusche Tamara , Kumar Nath Arnab , Stoian Sebastian A. , Raugei Simone , Bothner Brian , DuBois Jennifer L. , Peters John W.
Published: December 2023

The Irving-Williams series refers to the predicted stabilities of transition metal complexes where the observed general stability for divalent first-row transition metal complexes increase across the row. Acetone carboxylases (ACs) use a coordinated divalent metal at their active site in the catalytic conversion of bicarbonate and acetone to form acetoacetate. Highly homologous ACs discriminate among different divalent metals at their active sites such that variations of the enzyme prefer Mn(II) over Fe(II), defying Irving-Williams-predicted behavior. Defining the determinants that promote metal discrimination within the first-row transition metals is of broad fundamental importance in understanding metal-mediated catalysis and metal catalyst design.
Genome-wide screens connect HD82 loss-of-function to purine analog resistance in African trypanosomes
Authors: Trenaman Anna , Tinti Michele , Atrih Abdelmadjid , Horn David
Published: December 2023

Nucleoside analogs have been used extensively as anti-infective agents, particularly against viral infections, and have long been considered promising anti-parasitic agents. These pro-drugs are metabolized by host-cell, viral, or parasite enzymes prior to incorporation into DNA, thereby inhibiting DNA replication. Here, we report genes that sensitize African trypanosomes to nucleoside analogs, including the guanosine analog, ganciclovir. We applied ganciclovir selective pressure to a trypanosome genome-wide knockdown library, which yielded nucleoside mono- and diphosphate kinases as hits, validating the approach. The two most dominant hits to emerge, however, were Tb927.6.2800 and Tb927.6.2900, which both encode nuclear proteins; the latter of which is HD82, a SAMHD1-related protein and a putative dNTP triphosphohydrolase. We independently confirmed that HD82, which is conserved among the trypanosomatids, can sensitize
Trypanosoma brucei
to ganciclovir. Since ganciclovir activity depends upon phosphorylation by ectopically expressed viral thymidine kinase, we also tested the adenosine analog, ara-A, that may be fully phosphorylated by native
T. brucei
kinase(s). Both Tb927.6.2800 and HD82 knockdowns were resistant to this analog. Tb927.6.2800 knockdown increased sensitivity to hydroxyurea, while dNTP analysis indicated that HD82 is indeed a triphosphohydrolase with dATP as the preferred substrate. Our results provide insights into nucleoside/nucleotide metabolism and nucleoside analog metabolism and resistance in trypanosomatids. We suggest that the product of 6.2800 sensitizes cells to purine analogs through DNA repair, while HD82 does so by reducing the native purine pool.

IMPORTANCE

There is substantial interest in developing nucleoside analogs as anti-parasitic agents. We used genome-scale genetic screening and discovered two proteins linked to purine analog resistance in African trypanosomes. Our screens also identified two nucleoside kinases required for pro-drug activation, further validating the approach. The top novel hit, HD82, is related to SAMHD1, a mammalian nuclear viral restriction factor. We validated HD82 and localized the protein to the trypanosome nucleus. HD82 appears to sensitize trypanosomes to nucleoside analogs by reducing native pools of nucleotides, providing insights into both nucleoside/nucleotide metabolism and nucleoside analog resistance in trypanosomatids.
Supplemental Material: Sulfur isotopes of lamprophyres and implications for the control of metasomatized lithospheric mantle on the giant Jiaodong gold deposits, eastern China
Authors: WANG XIANG , Wang Zaicong , et al.
Published: December 2023

The whole-rock elemental and isotopic composition of lamprophyres and mafic dikes in the Jiaodong Peninsula, eastern China, and details of modeling calculation. 
Association of health benefits and harms of Christmas dessert ingredients in recipes from The Great British Bake Off: umbrella review of umbrella reviews of meta-analyses of observational studies
Authors: Wallach Joshua D , Gautam Anant , Ramachandran Reshma , Ross Joseph S
Published: December 2023

Objective

To determine the health benefits and harms of various ingredients in Christmas desserts from The Great British Bake Off.

Design

Umbrella review of umbrella reviews of meta-analyses of observational studies.

Data sources

The Great British Bake Off website, Embase, Medline, and Scopus.

Inclusion criteria

Umbrella reviews of meta-analyses of observational studies evaluating the associations between Christmas dessert ingredients and the risk of death or disease.

Main outcome measures

Proportion of protective and harmful summary associations between ingredient groups from The Great British Bake Off Christmas dessert recipes and the risk of death or disease.

Results

48 recipes for Christmas desserts (ie, cakes, biscuits, pastries, and puddings and desserts) were provided on The Great British Bake Off website with 178 unique ingredients that were collapsed into 17 overarching ingredient groups. A literature search identified 7008 titles and abstracts, of which 46 eligible umbrella reviews reported 363 unique summary associations between the ingredient groups and risk of death or disease. Of these summary associations, 149 (41%) were significant, including 110 (74%) that estimated that the ingredient groups reduced the risk of death or disease and 39 (26%) that increased the risk. The most common ingredient groups associated with a reduced risk of death or disease were fruit (44/110, 40%), coffee (17/110, 16%), and nuts (14/110, 13%), whereas alcohol (20/39, 51%) and sugar (5/39, 13%) were the most common ingredient groups associated with increased risk of death or disease.

Conclusions

Recipes for Christmas desserts from The Great British Bake Off often use ingredient groups that are associated with reductions, rather than increases, in the risk of death or disease. This Christmas, if concerns about the limitations of observational nutrition research are set aside, you can have your cake and eat it too.
Socio-economic inequalities in and factors associated with minimum dietary diversity among children aged 6–23 months in South Asia: a decomposition analysis
Authors: Rahman Md Ashfikur , Kundu Satyajit , Rashid Harun Or , Tohan Mortuja Mahamud , Islam Md Akhtarul
Published: December 2023

Objective

This study aimed to determine the factors associated with minimum dietary diversity (MDD) and estimate the socioeconomic inequalities in MDD among children from five South Asian countries.

Design

Cross-sectional.

Setting

The study used the most recent round of secondary databases of Demographic Health Survey data of Bangladesh (2017–2018), India (2019–2021), Maldives (2016–2017), Nepal (2018) and Pakistan (2017–2018).

Participants

This study used information on MDD and other explanatory variables from a total of 136 980 (weighted) children aged 6–23 months.

Methods

Multivariable logistic regression was employed to identify the factors associated with MDD and concentration index (CIX) and Lorenz curve were used to measure the socioeconomic inequalities in MDD.

Results

The overall weighted prevalence of MDD in South Asia was 23.37%. The highest prevalence of MDD was found among children from Maldives (70.7%), while the lowest was in Pakistan (14.2%). Living in affluent versus poor households, having a mother who is employed versus a mother who is unemployed, exposure to various forms of media (newspapers and magazines), seeking antenatal care (ANC) more than four times compared with those who sought ANC less than four times and having children older than 4 years old are the most common significant factors associated with MDD deficiency. This study found the value of the CIX for MDD (MDD: CI=0.0352; p<0.001) among children with a higher socioeconomic status, suggesting inequality in MDD in favour of the more among well-off households.

Conclusion

Inequality in the prevalence of MDD favours the affluent. Health policy and intervention design should prioritise minimising socioeconomic inequalities concerning the MDD. In addition, policy-makers should prioritise the associated factors of MDD such as education, wealth status, employment, media exposure while designing intervention or policies.
Protection of the third-dose and fourth-dose mRNA vaccines against SARS-CoV-2 Omicron subvariant: a systematic review and meta-analysis
Authors: Rahman Md. Obaidur , Kamigaki Taro , Thandar Moe Moe , Haruyama Rei , Yan Fangyu , Shibamura-Fujiogi Miho , Khin Maung Soe July , Islam Md. Rafiqul , Yoneoka Daisuke , Miyahara Reiko , Ota Erika , Suzuki Motoi
Published: December 2023

Objectives

The rapid spread of the SARS-CoV-2 Omicron variant has raised concerns regarding waning vaccine-induced immunity and durability. We evaluated protection of the third-dose and fourth-dose mRNA vaccines against SARS-CoV-2 Omicron subvariant and its sublineages.

Design

Systematic review and meta-analysis.

Data sources

Electronic databases and other resources (PubMed, Embase, CENTRAL, MEDLINE, CINAHL PLUS, APA PsycINFO, Web of Science, Scopus, ScienceDirect, MedRxiv and bioRxiv) were searched until December 2022.

Study eligibility criteria

We included studies that assessed the effectiveness of mRNA vaccine booster doses against SARS-CoV-2 infection and severe COVID-19 outcomes caused by the subvariant.

Data extraction and synthesis

Estimates of vaccine effectiveness (VE) at different time points after the third-dose and fourth-dose vaccination were extracted. Random-effects meta-analysis was used to compare VE of the third dose versus the primary series, no vaccination and the fourth dose at different time points. The certainty of the evidence was assessed by Grading of Recommendations, Assessments, Development and Evaluation approach.

Results

This review included 50 studies. The third-dose VE, compared with the primary series, against SARS-CoV-2 infection was 48.86% (95% CI 44.90% to 52.82%, low certainty) at ≥14 days, and gradually decreased to 38.01% (95% CI 13.90% to 62.13%, very low certainty) at ≥90 days after the third-dose vaccination. The fourth-dose VE peaked at 14–30 days (56.70% (95% CI 50.36% to 63.04%), moderate certainty), then quickly declined at 61–90 days (22% (95% CI 6.40% to 37.60%), low certainty). Compared with no vaccination, the third-dose VE was 75.84% (95% CI 40.56% to 111.12%, low certainty) against BA.1 infection, and 70.41% (95% CI 49.94% to 90.88%, low certainty) against BA.2 infection at ≥7 days after the third-dose vaccination. The third-dose VE against hospitalisation remained stable over time and maintained 79.30% (95% CI 58.65% to 99.94%, moderate certainty) at 91–120 days. The fourth-dose VE up to 60 days was 67.54% (95% CI 59.76% to 75.33%, moderate certainty) for hospitalisation and 77.88% (95% CI 72.55% to 83.21%, moderate certainty) for death.

Conclusion

The boosters provided substantial protection against severe COVID-19 outcomes for at least 6 months, although the duration of protection remains uncertain, suggesting the need for a booster dose within 6 months of the third-dose or fourth-dose vaccination. However, the certainty of evidence in our VE estimates varied from very low to moderate, indicating significant heterogeneity among studies that should be considered when interpreting the findings for public health policies.

PROSPERO registration number

CRD42023376698.
Protocol for a parallel assignment prospective, randomised, double-blinded, placebo-controlled trial to evaluate the efficacy of 0.01% atropine for near work-induced transient myopia and myopic progression in China
Authors: Qin Guanghao , Chen Jiayan , Hu Lan , Qi Yifan , Xu Ling , He Wei , Yu Sile , Pazo Emmanuel Eric , He Xingru
Published: December 2023

Introduction

Assessment of near work-induced transient myopia (NITM) is important for permanent myopia development and progression. Atropine eye drop has been reported to be beneficial in reducing initial NITM and slowing down myopic progression. This study aimed to investigate the efficacy of 0.01% atropine in treating NITM and its possible association with the progression of refractive change in Chinese myopic children.

Methods and analysis

The study is designed as a parallel assignment prospective, randomised, double-blinded, placebo-controlled trial conducted at He Eye Specialist Hospital in Shenyang, China. One hundred fifty participants will be randomly assigned in a 1:1 ratio to receive 0.01% atropine or placebo eye drop once nightly bilaterally for 1 year. Initial NITM, cycloplegic refraction, axial length, best-corrected visual acuity, intraocular pressure and pupil diameter will be measured at baseline, 4 weeks, 12 weeks, 24 weeks, 36 weeks and 48 weeks. Visual Function Questionnaire will be administered at baseline and each follow-up visit. Adverse events also will be monitored and documented at each subsequent follow-up visit.

Ethics and dissemination

A parallel assignment prospective, randomised, double-blinded, placebo-controlled trial to evaluate the efficacy of 0.01% atropine for near work-induced transient myopia and myopic progression registered on 10 September 2023. Ethics approval number: IRB (2023) K025.01. The study’s findings will be shared regardless of the effect’s direction.

Trial registration number

NCT06034366.
Managing food waste in the inpatient population
Authors: Jonathan Adrienne
Published: December 2023

Introduction

For medical students, food is rarely discussed from the clinical perspective. Yet, in hospitals reduced food intake poses the risk of malnutrition, along with increased morbidity and mortality. The issue of food waste, a cause of inadequate dietary intake and a common issue within the National Health Service, is rarely addressed. The implementation of protected mealtimes has done little to solve this. This quality improvement project aimed to reduce the average amount of inpatient food waste by 20% by May 2022.

Methods

A standardised meal size intervention was tested. Meals were weighed before and after meal services to collect baseline and postintervention data. The percentage consumed and the percentage wasted were then calculated. Finally, the overall average of the percentage wasted across both meal services was determined.

Results

Quantitative data showed a change in the average amount of food waste from 70.16% to 65.75%, a decrease of 4.41%. Survey results also found an increase of 3% in patient satisfaction with meal sizes.

Conclusion

Standardising meal sizes is shown to improve inpatient food waste and may serve as a starting point for healthcare providers to devise further strategies to reduce wastage in hospitals.
Gut microbiota predicts severity and reveals novel metabolic signatures in acute pancreatitis
Authors: Ammer-Herrmenau Christoph , Antweiler Kai L , Asendorf Thomas , Beyer Georg , Buchholz Soeren M , Cameron Silke , Capurso Gabriele , Damm Marko , Dang Linh , Frost Fabian , Gomes Antonio , Hamm Jacob , Henker Robert , Hoffmeister Albrecht , Meinhardt Christian , Nawacki Lukasz , Nunes Vitor , Panyko Arpad , Pardo Cesareo , Phillip Veit , Pukitis Aldis , Rasch Sebastian , Riekstina Diana , Rinja Ecaterina , Ruiz-Rebollo María Lourdes , Sirtl Simon , Weingarten Mark , Sandru Vasile , Woitalla Julia , Ellenrieder Volker , Neesse Albrecht
Published: December 2023

Objective

Early disease prediction is challenging in acute pancreatitis (AP). Here, we prospectively investigate whether the microbiome predicts severity of AP (Pancreatitis—Microbiome As Predictor of Severity; P-MAPS) early at hospital admission.

Design

Buccal and rectal microbial swabs were collected from 424 patients with AP within 72 hours of hospital admission in 15 European centres. All samples were sequenced by full-length 16S rRNA and metagenomic sequencing using Oxford Nanopore Technologies. Primary endpoint was the association of the orointestinal microbiome with the revised Atlanta classification (RAC). Secondary endpoints were mortality, length of hospital stay and severity (organ failure >48 hours and/or occurrence of pancreatic collections requiring intervention) as post hoc analysis. Multivariate analysis was conducted from normalised microbial and corresponding clinical data to build classifiers for predicting severity. For functional profiling, gene set enrichment analysis (GSEA) was performed and normalised enrichment scores calculated.

Results

After data processing, 411 buccal and 391 rectal samples were analysed. The intestinal microbiome significantly differed for the RAC (Bray-Curtis, p value=0.009), mortality (Bray-Curtis, p value 0.006), length of hospital stay (Bray-Curtis, p=0.009) and severity (Bray-Curtis, p value=0.008). A classifier for severity with 16 different species and systemic inflammatory response syndrome achieved an area under the receiving operating characteristic (AUROC) of 85%, a positive predictive value of 67% and a negative predictive value of 94% outperforming established severity scores. GSEA revealed functional pathway units suggesting elevated short-chain fatty acid (SCFA) production in severe AP.

Conclusions

The orointestinal microbiome predicts clinical hallmark features of AP, and SCFAs may be used for future diagnostic and therapeutic concepts.

Trial registration number

NCT04777812.
Clinical prediction models for aneurysmal subarachnoid hemorrhage: a systematic review update
Authors: Parekh Archie , Satish Samarth , Dulhanty Louise , Berzuini Carlo , Patel Hiren
Published: December 2023

Background

A systematic review of clinical prediction models for aneurysmal subarachnoid hemorrhage (aSAH) reported in 2011 noted that clinical prediction models for aSAH were developed using poor methods and were not externally validated. This study aimed to update the above review to guide the future development of predictive models in aSAH.

Methods

We systematically searched Embase and MEDLINE databases (January 2010 to February 2022) for articles that reported the development of a clinical prediction model to predict functional outcomes in aSAH. Our reviews are based on the items included in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement (PRISMA) checklist, and on data abstracted from each study in accord with the Checklist for critical Appraisal and data extraction for systematic Reviews of prediction Modelling Studies (CHARMS) 2014 checklist. Bias and applicability were assessed using the Prediction model Risk Of Bias Assessment Tool (PROBAST).

Results

We reviewed data on 30 466 patients contributing to 29 prediction models abstracted from 22 studies identified from an initial search of 7858 studies. Most models were developed using logistic regression (n=20) or machine learning (n=9) with prognostic variables selected through a range of methods. Age (n=13), World Federation of Neurological Surgeons (WFNS) grade (n=11), hypertension (n=6), aneurysm size (n=5), Fisher grade (n=12), Hunt and Hess score (n=5), and Glasgow Coma Scale (n=8) were the variables most frequently included in the reported models. External validation was performed in only four studies. All but one model had a high or unclear risk of bias due to poor performance or lack of validation.

Conclusion

Externally validated models for the prediction of functional outcome in aSAH patients have now become available. However, most of them still have a high risk of bias.
Comorbidities and chance of remission in patients with early rheumatoid arthritis receiving methotrexate as first-line therapy: a Swedish observational nationwide study
Authors: Tidblad Liselotte , Westerlind Helga , Delcoigne Bénédicte , Askling Johan , Saevarsdottir Saedis
Published: December 2023

Objectives

This study aims to examine whether comorbidities affect the likelihood of reaching primary remission on methotrexate monotherapy as the first disease-modifying antirheumatic drug (DMARD) in early rheumatoid arthritis (RA).

Methods

We used nationwide Swedish clinical and quality registers to collect RA disease activity measures and comorbidity data for patients diagnosed with RA 2007–2020 (n=11 001). The primary outcome was failure to reach 28-joint Disease Activity Score (DAS28) remission at 3 months. Secondary outcomes included Boolean, Simplified Disease Activity Index/Clinical Disease Activity Index remission, European Alliance of Associations for Rheumatology response and no swollen joint count at 3 and 6 months. For each comorbidity, and for combinations thereof, we calculated adjusted relative risks (RRs) of failure to reach remission, using modified Poisson regression.

Results

In total, 53% (n=4019/7643) failed to reach DAS28 remission after 3 months of methotrexate monotherapy, ranging from 66% (n=25/38) among patients with chronic kidney disease to 48% (n=154/319) in patients with previous cancer. The risk of not reaching DAS28 remission at 3 months (RR adjusted for sex and age) was increased among patients with endocrine (RR 1.08, 95% CI 1.01 to 1.15), gastrointestinal (RR 1.16, 95% CI 1.03 to 1.30), infectious (RR 1.21, 95% CI 1.06 to 1.38), psychiatric (RR 1.24, 95% CI 1.15 to 1.35) and respiratory comorbidities (RR 1.16, 95% CI 1.01 to 1.32). Having three or more comorbidity categories was associated with a 27% higher risk of DAS28 remission failure at 3 months. A similar pattern was observed for the secondary outcomes.

Conclusions

Comorbidities decrease the chance of reaching remission on methotrexate as DMARD monotherapy in patients with early RA and are important to consider when assessing treatment outcomes.
Combining Fuzzy Partitioning and Incremental Methods to Construct a Scalable Decision Tree on Large Datasets
Authors: Lotfi Somayeh , Ghasemzadeh Mohammad , Mohsenzadeh Mehran , Mirzarezaee Mitra
Published: December 2023

The Decision tree algorithm is a very popular classifier for reasoning through recursive partitioning of the data space. To choose the best attributes for splitting, the range of each continuous attribute should be split into two or more intervals. Then partitioning criteria are calculated for each value. Fuzzy partitioning can be used to reduce sensitivity to noise and increase tree stability. Also, tree-building algorithms face memory limitations as they need to keep the entire training dataset in the main memory. In this paper, we introduced a fuzzy decision tree approach based on fuzzy sets. To avoid storing the entire training dataset in the main memory and overcome the memory limitations, the algorithm incrementally builds FDTs. Membership functions are automatically generated. The Fuzzy Information Gain (FIG) is then used as the fast split attribute selection criterion, and leaf expansion is performed only on the instances stored in it. The efficiency of this algorithm is examined in terms of accuracy and tree complexity. The results show that the proposed algorithm can overcome memory limitations and balance accuracy and complexity while reducing the complexity of the tree.
Shortcut Learning of Large Language Models in Natural Language Understanding
Authors: Du Mengnan , He Fengxiang , Zou Na , Tao Dacheng , Hu Xia
Published: December 2023

Shortcuts often hinder the robustness of large language models.
AI Explainability and Acceptance: A Case Study for Underwater Mine Hunting
Authors: Richard Guy-Junior , Habonneau Jérôme , Guériot Didier , Le Caillec Jean-Marc
Published: December 2023

In critical operational context such as Mine Warfare, Automatic Target Recognition (ATR) algorithms are still hardly accepted. The complexity of their decision-making hampers understanding of predictions despite performances approaching human expert ones. Much research has been done in Explainability Artificial Intelligence (XAI) field to avoid this “black box” effect. This field of research attempts to provide explanations for the decision-making of complex networks to promote their acceptability. Most of the explanation methods applied on image classifier networks provide heat maps. These maps highlight pixels according to their importance in decision-making.

In this work, we first implement different XAI methods for the automatic classification of Synthetic Aperture Sonar (SAS) images by convolutional neural networks (CNN). These different methods are based on a post hoc approach. We study and compare the different heat maps obtained.

Second, we evaluate the benefits and the usefulness of explainability in an operational framework for collaboration. To do this, different user tests are carried out with different levels of assistance, ranging from classification for an unaided operator to classification with explained ATR. These tests allow us to study whether heat maps are useful in this context.

The results obtained show that the heat maps explanation has a disputed utility according to the operators. Heat map presence does not increase the quality of the classifications. On the contrary, it even increases the response time. Nevertheless, half of operators see a certain usefulness in heat maps explanation.
Trustworthy and Efficient Digital Twins in Post-Quantum Era with Hybrid Hardware-Assisted Signatures
Authors: Nouma Saif E. , Yavuz Attila A.
Published: December 2023

Digital Twins (DT) virtually model cyber-physical objects via sensory inputs by simulating or monitoring their behavior. Therefore, DTs usually harbor vast quantities of Internet of Things (IoT) components (e.g., sensors) that gather, process, and offload sensitive information (e.g., healthcare) to the cloud. It is imperative to ensure the trustworthiness of such sensitive information with long-term and compromise-resilient security guarantees. Digital signatures provide scalable authentication and integrity with non-repudiation and are vital tools for DTs. Post-quantum cryptography (PQC) and forward-secure signatures are two fundamental tools to offer long-term security and breach resiliency. However, NIST-PQC signature standards are exorbitantly costly for embedded DT components and are infeasible when forward-security is also considered. Moreover, NIST-PQC signatures do not admit aggregation, which is a highly desirable feature to mitigate the heavy storage and transmission burden in DTs. Finally, NIST recommends hybrid PQ solutions to enable cryptographic agility and transitional security. Yet, there is a significant gap in the state of the art in the achievement of all these advanced features simultaneously. Therefore, there is a significant need for lightweight digital signatures that offer compromise resiliency and compactness while permitting transitional security into the PQ era for DTs.

We create a series of highly lightweight digital signatures called Hardware-ASisted Efficient Signature (
HASES
) that meets the above requirements. The core of
HASES
 is a hardware-assisted cryptographic commitment construct oracle (
CCO
) that permits verifiers to obtain expensive commitments without signer interaction. We created three
HASES
 schemes:
PQ-HASES
 is a forward-secure PQ signature,
LA-HASES
 is an efficient aggregate Elliptic-Curve signature, and
HY-HASES
 is a novel hybrid scheme that combines
PQ-HASES
 and
LA-HASES
 with novel strong nesting and sequential aggregation.
HASES
 does not require a secure-hardware on the signer. We prove that
HASES
 schemes are secure and implemented them on commodity hardware and and 8-bit AVR ATmega2560. Our experiments confirm that
PQ-HASES
 and
LA-HASES
 are two magnitudes of times more signer efficient than their PQ and conventional-secure counterparts, respectively.
HY-HASES
 outperforms NIST PQC and conventional signature combinations, offering a standard-compliant transitional solution for emerging DTs. We open-source
HASES
 schemes for public-testing and adaptation.
QoE Estimation of WebRTC-based Audio-visual Conversations from Facial and Speech Features
Authors: Bingöl Gülnaziye , Porcu Simone , Floris Alessandro , Atzori Luigi
Published: December 2023

The utilization of user’s facial- and speech-related features for the estimation of the Quality of Experience (QoE) of multimedia services is still underinvestigated despite its potential. Currently, only the use of either facial or speech features individually has been proposed, and relevant limited experiments have been performed. To advance in this respect, in this study, we focused on WebRTC-based videoconferencing, where it is often possible to capture both the facial expressions and vocal speech characteristics of the users. First, we performed thorough statistical analysis to identify the most significant facial- and speech-related features for QoE estimation, which we extracted from the participants’ audio-video data collected during a subjective assessment. Second, we trained individual QoE estimation machine learning-based models on the separated facial and speech datasets. Finally, we employed data fusion techniques to combine the facial and speech datasets into a single dataset to enhance the QoE estimation performance due to the integrated knowledge provided by the fusion of facial and speech features. The obtained results demonstrate that the data fusion technique based on the Improved Centered Kernel Alignment (ICKA) allows for reaching a mean QoE estimation accuracy of 0.93, whereas the values of 0.78 and 0.86 are reached when using only facial or speech features, respectively.
Cardiorespiratory fitness and circadian rhythms in adolescents: a pilot study
Authors: Chen Ivy Y. , Radom-Aizik Shlomit , Stehli Annamarie , Palmer Jake R. , Lui Kitty K. , Dave Abhishek , Chappel-Farley Miranda G. , Vinces Karla G. , Gealer Daniel , Lim Alexandra , Mander Bryce A. , Benca Ruth M. , Neikrug Ariel B.
Published: December 2023

In healthy adolescents, better cardiorespiratory fitness, as assessed by the gold standard measure [laboratory-based assessment of peak oxygen consumption (V̇o2)], was associated with earlier circadian timing of sleep/wake patterns, rest-activity rhythms and chronotype, and less social jetlag. These findings highlight the close interrelationships between fitness and rhythms and raise the possibility that maintaining higher cardiorespiratory fitness levels alongside earlier sleep/wake schedule and activity rhythms may be important behavioral intervention targets to promote health in adolescents.
Sunscreen does not alter sweating responses or critical environmental limits in young adults (PSU HEAT project)
Authors: Fisher Kat G. , Cottle Rachel M. , Kenney W. Larry , Wolf S. Tony
Published: December 2023

Our findings demonstrate that neither sweating nor critical environmental limits were affected by mineral-based and chemical-based sunscreen applications. The rates of change in core temperature during compensable and uncompensable heat stress were not changed by wearing sunscreen. Evaporative heat loss, efficiency of sweat evaporation, skin wettedness, and sweating rates were unaffected by sunscreen. Sunscreen did not alter integrative thermoregulatory responses during exercise in the heat.
A Case Report on Care-Seeking Type Illness Anxiety Disorder after COVID-19 Infection
Authors: Kasi Lakshmi S. , Moorthy Bini
Published: December 2023

This case report highlights the diagnostic challenges presented by the overlapping symptoms of illness anxiety disorder (IAD) and long COVID-19 (LC-19). This case report focuses on a 58-year-old woman with care-seeking type IAD in the context of LC-19-associated symptoms. The patient experienced mild COVID-19 in August 2021. Since then, she has reported an increase in LC-19-associated symptoms, including cognitive deficits, breathlessness, fatigue, and anosmia. Despite largely normal laboratory results, imaging, and physical examinations, the patient’s distress and care-seeking behaviors persisted, resulting in the diagnosis of IAD. Accurately differentiating between LC-19 and IAD is crucial for appropriate patient care. We discuss the importance of recognizing and treating IAD in patients with LC-19-associated symptoms and the need for further research on the correlation between IAD and both COVID-19 and LC-19.
Angiotensin-Converting Enzyme-2 (ACE-2) with Interferon-Induced Transmembrane Protein-3 (IFITM-3) Genetic Variants and Interleukin-6 as Severity and Risk Predictors among COVID-19 Egyptian Population
Authors: Makled Amal F. , Ali Sahar A. M. , Eldahdouh S. S. , Sleem Asmaa S. , Eldahshan Maha M. , Elsaadawy Yara , Salman Samar S. , Mohammed Elbrolosy Asmaa
Published: December 2023

Introduction. The host genetic background is a crucial factor that underlies the interindividual variability of COVID-19 fatality and outcomes. Angiotensin-converting enzyme-2 (ACE-2) and interferon-induced transmembrane protein-3 (IFITM-3) have a key role in viral cell entrance and priming. The evoked immune response will also provide a predictive prognosis for COVID-19 infection. This study aimed to explore the association between ACE-2 and IFITM-3 genotypes and their corresponding allele frequencies with disease severity indices in the Egyptian COVID-19 population. The serum level of interleukin-6, as a biomarker of hyperinflammatory response, and cytokine storm, was correlated with disease progression, single nucleotide polymorphisms (SNPs) of the selected receptors, and treatment response. Methodology. We enrolled 900 COVID-19-confirmed cases and 100 healthy controls. Genomic DNA was extracted from 200 subjects (160 patients selected based on clinical and laboratory data and 40 healthy controls). The ACE-2 rs2285666 and IFITM-3 rs12252 SNPs were genotyped using the TaqMan probe allelic discrimination assay, and the serum IL-6 level was determined by ELISA. Logistic regression analysis was applied to analyze the association between ACE-2 and IFITM-3 genetic variants, IL-6 profile, and COVID-19 severity. Results. The identified genotypes and their alleles were significantly correlated with COVID-19 clinical deterioration as follows: ACE2 rs2285666 CT + TT, odds ratio (95% confidence interval): 12.136 (2.784–52.896) and IFITM-3 rs12252 AG + GG: 17.276 (3.673–81.249), both p<0.001. Compared to the controls, the heterozygous and mutant genotypes for both SNPs were considerable risk factors for increased susceptibility to COVID-19. IL-6 levels were significantly correlated with disease progression (p<0.001). Conclusion. ACE-2 and IFITM-3 genetic variants are potential predictors of COVID-19 severity, critical outcomes, and post-COVID-19 complications. Together, these SNPs and serum IL-6 levels explain a large proportion of the variability in the severity of COVID-19 infection and its consequences among Egyptian subjects.
Canine Descemet Stripping Endothelial Keratoplasty with a Tissue Insertion Device: Technique and Long-Term Outcome
Authors: Chen Conan Y. , Solar Steven J. , Lewis Daniel S. , Barnes Kali , Wiener Batya G. , Baliga Satya , Chiang Eric , Askew Tim E. , Eghrari Allen O. , Armour Micki D.
Published: December 2023

Introduction. We describe a case of canine Descemet’s stripping endothelial keratoplasty (DSEK) using an open-source canine tissue delivery device. Case Presentation. We follow the four-year outcomes of a 1.5-year-old Tibetan Terrier who presented with difficulty seeing, diffuse corneal edema, and central corneal thickness of 1400 microns in the left eye. To perform DSEK, a polycarbonate carrier and insertion device was designed for canine corneas that measure up to 15 mm in diameter. The tissue was loaded into the inserter prior to surgery with the endothelium facing inwards and the stroma facing the cartridge wall. From the cartridge, the graft was pulled into the eye using microforceps and an anterior chamber maintainer. We assessed preoperative endothelial cell count, postoperative corneal clearance, and graft adhesion. The donor was a two-year-old Airedale Terrier who died one day prior to surgery, with endothelial cell density of 3149 cells/mm2. One week after DSEK, the cornea began to clear, and pachymetry of the donor and graft total was 1410 microns. This improved to 800 microns at 4 months and continued improving in its clarity at the last postoperative visit 4 years after surgery. Discussion. We demonstrate the feasibility of conducting canine endothelial keratoplasty with a specially designed tissue delivery device and the potential of long-term corneal clearance after DSEK in canine eyes.
Investigation of the Emission Rate of Particles when Musicians Play Wind, Woodwind, and Brass Instruments
Authors: Schumann Lukas , von Zadow Dorothea , Schmidt Alexander , Fernholz Isabel , Hartmann Anne , Ifrim Liliana , Kriegel Martin , Seybold Joachim , Mürbe Dirk , Fleischer Mario
Published: December 2023

In the context of the high risk of airborne transmission of COVID-19, the question of the production of particles while playing wind instruments is highly relevant. Therefore, in this study, 23 professional musicians played their instruments in a cleanroom in cleanroom-grade clothing. The most common orchestral wind instruments flute, oboe, clarinet, and trumpet were therefore chosen. Aerosol measurements using a laser particle counter were conducted to quantify the emission rate of respiratory particles. Orchestral excerpts as well as sustained tones in two dynamic levels were played. The emitted particles were mostly in a submicron size range. For all instruments besides the clarinet, an influence of the loudness of playing on the emission rate could be observed. The emission rates for all musical instruments were independent of the passages played. Flute and oboe showed similar emission rates but lower than the values for clarinet and trumpet. While playing a note with a small volume, the flute, oboe, and trumpet have a similar emission rate as found for speaking.
Mitigating Postfrying Degradation Factors of Fats and Oils through the Development of Bagasse-Based Adsorbent
Authors: Ahmed Waqar , Shabbir Muhammad Asim , Aadil Rana Muhammad , Zia Muhammad Anjum , Pratap-Singh Anubhav
Published: December 2023

The quality of fats and oils is a critical aspect of the food processing industry and consumer health. Fat degradation, particularly through oxidation, impacts various quality parameters, including color, taste, flavor, aroma, quality, and appearance. To address this issue, a study was conducted using five degraded fats/oil (DF/O) commodities as the target for an adsorption process. These commodities were chosen because of their high level of degradation by-products. The study used sugarcane bagasse (SCB) to develop five different treatments of indigenous adsorbents activated with various NaOH concentrations. Analyses including iodine number, adsorbent yield, and scanning electron microscope were performed to identify the potential of the prepared concentrations. Results showed that the indigenous adsorbent created with 1.0% NaOH was the most effective. The alkali treatment had a positive impact on the samples, but the SCB 10% was found to be the most efficient in reducing the degradation value of the treated samples. The findings of this study suggest that the use of indigenous adsorbents, particularly those prepared with SCB 10%, can be an effective way to reduce fat degradation and enhance the quality of fats and oils in the food processing industry. This approach can also address consumer health concerns related to fat and oil quality.
A Novel Pyroptosis-Based Prognostic Model Correlated with the Parainflammatory Immune Microenvironment of Pancreatic Cancer
Authors: Wei Kong-kong , Du Zhi-xing , Deng Jun-ge , Yang Jin-wei , Chen Hao
Published: December 2023

Background. Pyroptosis has a dual function in malignant tumor progression and management. The action of pyroptosis-related genes (PRGs) in pancreatic cancer (PC), however, remains uncertain. Methods. Differential expression analyses of 57 PRGs were conducted in the TCGA TARGET GTEx dataset. The candidate genes were determined using LASSO Cox regression and random forest analyses. A risk model was developed with the TCGA dataset and validated with the ICGC dataset. Results. Three prognosis-related PRGs (BAK1, GSDMC, and IL18) were chosen to create a risk model. High-risk patients from the TCGA and ICGC cohorts had an unfavorable overall survival (all p<0.05). The risk modelʼs accuracy and independent predictability were assessed by receiver operating characteristic curves and multivariate Cox regression analysis, respectively. High-risk patients possessed different molecular pathways, higher KRAS and TP53 mutations, increased expression of PD-L1, C1 immune subtype, and immunosuppressive microenvironment characterized by parainflammation compared to low-risk patients. KRAS and TP53 mutations participated in different inflammatory pathways and played different prognostic roles between the two risk groups. KRAS mutations in high-risk patients caused a more unfavorable prognosis than wild-type KRAS (p=0.016), whereas TP53 mutations in low-risk patients exhibited a poorer outcome than wild-type TP53 (p=0.009). Spearman correlation analyses revealed that the parainflammatory response in PC might be implicated in GSDMC-mediated pyroptosis via cytosolic DNA-sensing pathways under hypoxic conditions. Furthermore, the risk scores were significantly and positively related to the expression of HNRNPC, RBM15, YTHDF1, and YTHDF2, as well as sensitivity to gemcitabine, cisplatin, and erlotinib. Conclusions. This study created a novel pyroptosis-based risk model related to the parainflammatory immune microenvironment, which might help identify novel biomarkers, evaluate the tumor immune microenvironment, and develop management strategies for PC patients.
FIGURE 5 from FBXW7-loss Sensitizes Cells to ATR Inhibition Through Induced Mitotic Catastrophe
Authors: O'Brien Siobhan , Ubhi Tajinder , Wolf Lucie , Gandhi Krishna , Lin Sichun , Chaudary Naz , Dhani Neesha C. , Milosevic Michael , Brown Grant W. , Angers Stephane
Published: December 2023

Loss of control at S–G2 transition induces sensitivity to ATR inhibitor. A, Schematic representation of chemogenomic CRISPR screen in HPAF-II FBXW7−/− cells using an LD50 dose of AZD6738. B, Results of chemogenomic screen ranked by Z-score generated through DrugZ. C, Immunofluorescence of HPAF-II wild-type and FBXW7−/− cells treated or untreated with AZD6738 and stained for phosphorylated histone H3. Representative images of three independent replicates, scale bar is 50 µm. D, Quantification of C, mean ± SEM, two-way ANOVA. E, Immunofluorescence of HPAF-II wild-type and FBXW7−/− cells during anaphase, representative images of three independent replicates, scale bar is 10 µm. F, Quantification of E, 15 cells per replicate per treatment were imaged. Mean ± SEM, two-way ANOVA.
Weakly Supervised Deep Learning Predicts Immunotherapy Response in Solid Tumors Based on PD-L1 Expression
Authors: Ligero Marta , Serna Garazi , El Nahhas Omar S.M. , Sansano Irene , Mauchanski Siarhei , Viaplana Cristina , Calderaro Julien , Toledo Rodrigo A. , Dienstmann Rodrigo , Vanguri Rami S. , Sauter Jennifer L. , Sanchez-Vega Francisco , Shah Sohrab P. , Ramón y Cajal Santiago , Garralda Elena , Nuciforo Paolo , Perez-Lopez Raquel , Kather Jakob Nikolas
Published: December 2023

Programmed death-ligand 1 (PD-L1) IHC is the most commonly used biomarker for immunotherapy response. However, quantification of PD-L1 status in pathology slides is challenging. Neither manual quantification nor a computer-based mimicking of manual readouts is perfectly reproducible, and the predictive performance of both approaches regarding immunotherapy response is limited. In this study, we developed a deep learning (DL) method to predict PD-L1 status directly from raw IHC image data, without explicit intermediary steps such as cell detection or pigment quantification. We trained the weakly supervised model on PD-L1–stained slides from the non–small cell lung cancer (NSCLC)-Memorial Sloan Kettering (MSK) cohort (N = 233) and validated it on the pan-cancer-Vall d'Hebron Institute of Oncology (VHIO) cohort (N = 108). We also investigated the performance of the model to predict response to immune checkpoint inhibitors (ICI) in terms of progression-free survival. In the pan-cancer-VHIO cohort, the performance was compared with tumor proportion score (TPS) and combined positive score (CPS). The DL model showed good performance in predicting PD-L1 expression (TPS ≥ 1%) in both NSCLC-MSK and pan-cancer-VHIO cohort (AUC 0.88 ± 0.06 and 0.80 ± 0.03, respectively). The predicted PD-L1 status showed an improved association with response to ICIs [HR: 1.5 (95% confidence interval: 1–2.3), P = 0.049] compared with TPS [HR: 1.4 (0.96–2.2), P = 0.082] and CPS [HR: 1.2 (0.79–1.9), P = 0.386]. Notably, our explainability analysis showed that the model does not just look at the amount of brown pigment in the IHC slides, but also considers morphologic factors such as lymphocyte conglomerates. Overall, end-to-end weakly supervised DL shows potential for improving patient stratification for cancer immunotherapy by analyzing PD-L1 IHC, holistically integrating morphology and PD-L1 staining intensity.

Significance:

The weakly supervised DL model to predict PD-L1 status from raw IHC data, integrating tumor staining intensity and morphology, enables enhanced patient stratification in cancer immunotherapy compared with traditional pathologist assessment.