bluuebunny/crossref_metadata_2025 huggingface dataset:
Functional studies on tandem carbohydrate-binding modules of a multimodular enzyme possessing two catalytic domains
Authors: Liu Jiawen , Shi Jiani , Gao Jiahui , Shi Rui , Zhu Jingrong , Jensen Marcus Sepo , Li Chenchen , Yang Jing , Zhao Siyi , Sun Aofei , Sun Di , Zhang Ying , Liu Cong , Liu Weijie
Published: June 2024

Although functional studies on carbohydrate-binding module (CBM) have been carried out extensively, the role of tandem CBMs in the enzyme containing multiple catalytic domains (CDs) is unclear. Here, we identified a multidomain enzyme (Lc25986) with a novel modular structure from lignocellulolytic bacterial consortium. It consists of a mannanase domain, two CBM65 domains (LcCBM65-1/LcCBM65-2), and an esterase domain. To investigate CBM function and domain interactions, full-length Lc25986 and its variants were constructed and used for enzymatic activity, binding, and bioinformatic analyses. The results showed that LcCBM65-1 and LcCBM65-2 both bind mannan and xyloglucan but not cellulose or β-1,3-1,4-glucan, which differs from the ligand specificity of reported CBM65s. Compared to LcCBM65-2, LcCBM65-1 showed a stronger ligand affinity and a preference for acetylation sites. Both CBM65s stimulated the enzymatic activities of their respective neighboring CDs against acetylated mannan, but did not contribute to the activities of the distal CDs. The time course of mannan hydrolysis indicated that the full-length Lc25986 was more effective in the complete degradation of mixed acetyl/non-acetyl substrates than the mixture of single-CD mutants. When acting on complex substrates, LcCBM65-1 not only improved the enzymatic activity of the mannanase domain, but also directed the esterase domain to the acetylated polysaccharides. LcCBM65-2 adopted a low affinity to reduce interference with the catalysis of the mannanase domain. These results demonstrate the importance of CBMs for the synergism between the two CDs of a multidomain enzyme and suggest that they contribute to the adequate degradation of complex substrates such as plant cell walls.

IMPORTANCE

Lignocellulolytic enzymes, particularly those of bacterial origin, often harbor multiple carbohydrate-binding modules (CBMs). However, the function of CBM multivalency remains poorly understood. This is especially true for enzymes that contain more than one catalytic domain (CD), as the interactions between CDs, CBMs, and CDs and CBMs can be complex. Our research demonstrates that homogeneous CBMs can have distinct functions in a multimodular enzyme. The tandem CBMs coordinate the CDs in catalytic conflict through their differences in binding affinity, ligand preference, and arrangement within the full-length enzyme. Additionally, although the synergism between mannanase and esterase is widely acknowledged, our study highlights the benefits of integrating the two enzymes into a single entity for the degradation of complex substrates. In summary, these findings enhance our understanding of the intra-synergism of a multimodular enzyme and emphasize the significance of multiple CBMs in this context.
Blue valorization of lignin-derived monomers via reprogramming marine bacterium
Roseovarius nubinhibens
Authors: Wei Ying , Wang Shu-Guang , Xia Peng-Fei
Published: June 2024

Biological valorization of lignin, the second most abundant biopolymer on Earth, is an indispensable sector to build a circular economy and net-zero future. However, lignin is recalcitrant to bioupcycling, demanding innovative solutions. We report here the biological valorization of lignin-derived aromatic carbon to value-added chemicals without requesting extra organic carbon and freshwater via reprogramming the marine
Roseobacter
clade bacterium
Roseovarius nubinhibens
. We discovered the unusual advantages of this strain for the oxidation of lignin monomers and implemented a CRISPR interference (CRISPRi) system with the
lacI
-P
trc
inducible module, nuclease-deactivated Cas9, and programmable gRNAs. This is the first CRISPR-based regulatory system in
R. nubinhibens
, enabling precise and efficient repression of genes of interest. By deploying the customized CRISPRi, we reprogrammed the carbon flux from a lignin monomer, 4-hydroxybenzoate, to achieve the maximum production of protocatechuate, a pharmaceutical compound with antibacterial, antioxidant, and anticancer properties, with minimal carbon to maintain cell growth and drive biocatalysis. As a result, we achieved a 4.89-fold increase in protocatechuate yield with a dual-targeting CRISPRi system, and the system was demonstrated with real seawater. Our work underscores the power of CRISPRi in exploiting novel microbial chassis and will accelerate the development of marine synthetic biology. Meanwhile, the introduction of a new-to-the-field lineage of marine bacteria unveils the potential of blue biotechnology leveraging resources from the ocean.

IMPORTANCE

One often overlooked sector in carbon-conservative biotechnology is the water resource that sustains these enabling technologies. Similar to the “food-versus-fuel” debate, the competition of freshwater between human demands and bioproduction is another controversial issue, especially under global water scarcity. Here, we bring a new-to-the-field lineage of marine bacteria with unusual advantages to the stage of engineering biology for simultaneous carbon and water conservation. We report the valorization of lignin monomers to pharmaceutical compounds without requesting extra organic substrate (e.g., glucose) or freshwater by reprogramming the marine bacterium
Roseovarius nubinhibens
with a multiplex CRISPR interference system. Beyond the blue lignin valorization, we present a proof-of-principle of leveraging marine bacteria and engineering biology for a sustainable future.
Complete genome sequences of
Lactococcus petauri
strains 473AN and 473GN isolated from the blood culture of a Japanese patient with infective endocarditis
Authors: Imajoh Masayuki , Suzuki Marina , Okamoto Akira , Salif Maiga , Ogawa Riku , Mikami Aguri , Daibata Masanori
Published: June 2024

Here, we report the complete genome sequences of
Lactococcus petauri
strains 473AN and 473GN, isolated from the blood culture of a Japanese patient with infective endocarditis. The complete genomes of 473AN and 473GN consist of single chromosomes of 2,065,772 and 2,094,461 bp, respectively.
Diverse and unconventional methanogens, methanotrophs, and methylotrophs in metagenome-assembled genomes from subsurface sediments of the Slate River floodplain, Crested Butte, CO, USA
Authors: Rasmussen Anna N. , Tolar Bradley B. , Bargar John R. , Boye Kristin , Francis Christopher A.
Published: June 2024

We use metagenome-assembled genomes (MAGs) to understand single-carbon (C1) compound-cycling—particularly methane-cycling—microorganisms in montane riparian floodplain sediments. We generated 1,233 MAGs (>50% completeness and <10% contamination) from 50- to 150-cm depth below the sediment surface capturing the transition between oxic, unsaturated sediments and anoxic, saturated sediments in the Slate River (SR) floodplain (Crested Butte, CO, USA). We recovered genomes of putative methanogens, methanotrophs, and methylotrophs (
n
= 57). Methanogens, found only in deep, anoxic depths at SR, originate from three different clades (
Methanoregulaceae
,
Methanotrichaceae
, and
Methanomassiliicoccales
), each with a different methanogenesis pathway; putative methanotrophic MAGs originate from within the Archaea (
Candidatus
Methanoperedens) in anoxic depths and uncultured bacteria (
Ca
. Binatia) in oxic depths. Genomes for canonical aerobic methanotrophs were not recovered.
Ca.
Methanoperedens were exceptionally abundant (~1,400× coverage, >50% abundance in the MAG library) in one sample that also contained aceticlastic methanogens, indicating a potential C1/methane-cycling hotspot.
Ca
. Methylomirabilis MAGs from SR encode pathways for methylotrophy but do not harbor methane monooxygenase or nitrogen reduction genes. Comparative genomic analysis supports that one clade within the
Ca
. Methylomirabilis genus is not methanotrophic. The genetic potential for methylotrophy was widespread, with over 10% and 19% of SR MAGs encoding a methanol dehydrogenase or substrate-specific methyltransferase, respectively. MAGs from uncultured
Thermoplasmata
archaea in the
Ca
. Gimiplasmatales (UBA10834) contain pathways that may allow for anaerobic methylotrophic acetogenesis. Overall, MAGs from SR floodplain sediments reveal a potential for methane production and consumption in the system and a robust potential for methylotrophy.

IMPORTANCE

The cycling of carbon by microorganisms in subsurface environments is of particular relevance in the face of global climate change. Riparian floodplain sediments contain high organic carbon that can be degraded into C1 compounds such as methane, methanol, and methylamines, the fate of which depends on the microbial metabolisms present as well as the hydrological conditions and availability of oxygen. In the present study, we generated over 1,000 MAGs from subsurface sediments from a montane river floodplain and recovered genomes for microorganisms that are capable of producing and consuming methane and other C1 compounds, highlighting a robust potential for C1 cycling in subsurface sediments both with and without oxygen. Archaea from the
Ca
. Methanoperedens genus were exceptionally abundant in one sample, indicating a potential C1/methane-cycling hotspot in the Slate River floodplain system.
Augmenting bacterial similarity measures using a graph-based genome representation
Authors: Ramanan Vivek , Sarkar Indra Neil
Published: June 2024

Relationships between bacterial taxa are traditionally defined using 16S rRNA nucleotide similarity or average nucleotide identity. Improvements in sequencing technology provide additional pairwise information on genome sequences, which may provide valuable information on genomic relationships. Mapping orthologous gene locations between genome pairs, known as synteny, is typically implemented in the discovery of new species and has not been systematically applied to bacterial genomes. Using a data set of 378 bacterial genomes, we developed and tested a new measure of synteny similarity between a pair of genomes, which was scaled onto 16S rRNA distance using covariance matrices. Based on the input gene functions used (i.e., core, antibiotic resistance, and virulence), we observed varying topological arrangements of bacterial relationship networks by applying (i) complete linkage hierarchical clustering and (ii) K-nearest neighbor graph structures to synteny-scaled 16S data. Our metric improved clustering quality comparatively to state-of-the-art average nucleotide identity metrics while preserving clustering assignments for the highest similarity relationships. Our findings indicate that syntenic relationships provide more granular and interpretable relationships for within-genera taxa compared to pairwise similarity measures, particularly in functional contexts.

IMPORTANCE

Given the prevalence and necessity of the 16S rRNA measure in bacterial identification and analysis, this additional analysis adds a functional and synteny-based layer to the identification of relatives and clustering of bacteria genomes. It is also of computational interest to model the bacterial genome as a graph structure, which presents new avenues of genomic analysis for bacteria and their closely related strains and species.
Predictors of readmission and mortality in adults with diabetes or stress hyperglycemia after initial hospitalization for COVID-19
Authors: Chaugule Akshata , Howard Kyra , Simonson Donald C , McDonnell Marie E , Garg Rajesh , Gopalakrishnan Geetha , Mitri Joanna , Lebastchi Jasmin , Palermo Nadine E , Westcott Gregory , Weinstock Ruth S
Published: June 2024

Introduction

We previously reported predictors of mortality in 1786 adults with diabetes or stress hyperglycemia (glucose>180 mg/dL twice in 24 hours) admitted with COVID-19 from March 2020 to February 2021 to five university hospitals. Here, we examine predictors of readmission.

Research design and methods

Data were collected locally through retrospective reviews of electronic medical records from 1786 adults with diabetes or stress hyperglycemia who had a hemoglobin A1c (HbA1c) test on initial admission with COVID-19 infection or within 3 months prior to initial admission. Data were entered into a Research Electronic Data Capture (REDCap) web-based repository, and de-identified. Descriptive data are shown as mean±SD, per cent (%) or median (IQR). Student’s t-test was used for comparing continuous variables with normal distribution and Mann-Whitney U test was used for data not normally distributed. X2test was used for categorical variable.

Results

Of 1502 patients who were alive after initial hospitalization, 19.4% were readmitted; 90.3% within 30 days (median (IQR) 4 (0–14) days). Older age, lower estimated glomerular filtration rate (eGFR), comorbidities, intensive care unit (ICU) admission, mechanical ventilation, diabetic ketoacidosis (DKA), and longer length of stay (LOS) during the initial hospitalization were associated with readmission. Higher HbA1c, glycemic gap, or body mass index (BMI) were not associated with readmission. Mortality during readmission was 8.0% (n=23). Those who died were older than those who survived (74.9±9.5 vs 65.2±14.4 years, p=0.002) and more likely had DKA during the first hospitalization (p<0.001). Shorter LOS during the initial admission was associated with ICU stay during readmission, suggesting that a subset of patients may have been initially discharged prematurely.

Conclusions

Understanding predictors of readmission after initial hospitalization for COVID-19, including older age, lower eGFR, comorbidities, ICU admission, mechanical ventilation, statin use and DKA but not HbA1c, glycemic gap or BMI, can help guide treatment approaches and future research in adults with diabetes.
An opportunity to be grateful for? Exploring discourses about international medical graduates from India and Pakistan to the UK between 1960 and 1980
Authors: Arfeen Zakia , Diaz Brett , Whitehead Cynthia Ruth , Rashid Mohammed Ahmed
Published: June 2024

Introduction

Following India and Pakistan gaining independence from British colonial rule, many doctors from these countries migrated to the UK and supported its fledgling National Health Service (NHS). Although this contribution is now widely celebrated, these doctors often faced hardship and hostility at the time and continue to face discrimination and racism in UK medical education. This study sought to examine discursive framings about Indian and Pakistani International Medical Graduates (IPIMGs) in the early period of their migration to the UK, between 1960 and 1980.

Methods

We assembled a textual archive of publications relating to IPIMGs in the UK during this time period inThe BMJ. We employed critical discourse analysis to examine knowledge and power relations in these texts, drawing on postcolonialism through the contrapuntal approach developed by Edward Said.

Results

The dominant discourse in this archive was one of opportunity. This included the opportunity for training, which was not available to IPIMGs in an equitable way, the missed opportunity to frame IPIMGs as saviours of the NHS rather than ‘cheap labour’, and the opportunity these doctors were framed to be held by being in the ‘superior’ British system, for which they should be grateful. Notably, there was also an opportunity to oppose, as IPIMGs challenged notions of incompetence directed at them.

Conclusion

As IPIMGs in the UK continue to face discrimination, we shed light on how their cultural positioning has been historically founded and engrained in the imagination of the British medical profession by examining discursive trends to uncover historical tensions and contradictions.
Association between profiles of accelerometer-measured daily movement behaviour and mortality risk: a prospective cohort study of British older adults
Authors: Yerramalla Manasa Shanta , Chen Mathilde , Dugravot Aline , van Hees Vincent T , Sabia Severine
Published: June 2024

Objectives

We identified profiles of wake-time movement behaviours (sedentary behaviours, light intensity physical activity and moderate-to-vigorous physical activity) based on accelerometer-derived features among older adults and then examined their association with all-cause mortality.

Methods

Data were drawn from a prospective cohort of 3991 Whitehall II accelerometer substudy participants aged 60–83 years in 2012–2013. Daily movement behaviour profiles were identified using k-means cluster analysis based on 13 accelerometer-assessed features characterising total duration, frequency, bout duration, timing and activity intensity distribution of movement behaviour. Cox regression models were used to assess the association between derived profiles and mortality risk.

Results

Over a mean follow-up of 8.1 (SD 1.3) years, a total of 410 deaths were recorded. Five distinct profiles were identified and labelled as ‘active’ (healthiest), ‘active sitters’, ‘light movers’, ‘prolonged sitters’, and ‘most sedentary’ (most deleterious). In model adjusted for sociodemographic, lifestyle, and health-related factors, compared with the ‘active’ profile, ‘active sitters’ (HR 1.57, 95% CI 1.01 to 2.44), ‘light movers’ (HR 1.75, 95% CI 1.17 to 2.63), ‘prolonged sitters’ (HR 1.67, 95% CI 1.11 to 2.51), ‘most sedentary’ (HR 3.25, 95% CI 2.10 to 5.02) profiles were all associated with a higher risk of mortality.

Conclusion

Given the threefold higher mortality risk among those with a ‘most sedentary’ profile, public health interventions may target this group wherein any improvement in physical activity and sedentary behaviour might be beneficial.
Sanctioned illegal high tackles significantly increase concussion risk to both tacklers and ball carriers in elite men’s Rugby Union
Authors: Tucker Ross , Hester Ben , Hendricks Sharief , Brown James , Falvey Éanna C
Published: June 2024

Objectives

Tackles making contact above the sternum increase concussion and head injury assessment (HIA) risk in Rugby Union. The sport has introduced harsher sanctions to change tackler behaviours to reduce this risk. This increased high tackle sanction numbers, though it is unknown whether sanction severity is associated with injury risk.

Methods

The sanction decision made by match officials for tackles resulting in 157 HIA1 removals, of which 91 were confirmed concussions, was evaluated. The propensity of sanction types, ranging from no foul play to red card, was compared after calculating concussion and HIA1 numbers per 1000 tackles of each sanction, using total tackle number of each sanction type from one season of two elite professional competitions.

Results

HIA1 removal and concussion risk increased as sanction severity increased. Red-carded tackles were 271.5 (95% CI 143.8 to 512.6) times more likely to result in concussions than legal tackles. Tacklers and ball carriers were more likely to experience concussions from sanctioned high tackles, with tackler risk 28.5 (95% CI 13.5 to 59.9) times higher for sanctioned high tackles compared with legal tackles, and ball carrier risk elevated 133.7-fold (95% CI 65.5 to 272.8) after sanctioned high tackles.

Conclusion

Sanctioned high tackles significantly increase concussion and HIA1 risk to both tacklers and ball carriers. Current decision-making frameworks that guide sanction decisions do identify tackle behaviours that elevate clinical risk. Both tacklers and ball carriers would be less likely to experience concussions and head injuries if the frequency of illegal high tackles is decreased.
Obesity is associated with muscle atrophy in rotator cuff tear
Authors: Herzberg Simone D , Zhao Zhiguo , Freeman Thomas H , Prakash Ravi , Kuhn John E , Khazzam Michael S , Matzkin Elizabeth G , Baumgarten Keith M , Bishop Julie Y , Brophy Robert H , Carey James L , Dunn Warren R , Jones Grant L , Ma C Benjamin , Marx Robert G , McCarty Eric C , Poddar Sourav K , Smith Matthew V , Spencer Edwin E , Vidal Armando F , Wolf Brian R , Wright Rick W , Jain Nitin B , Giri Ayush
Published: June 2024

Objective

The primary goal of this study is to evaluate the relationship between Body Mass Index (BMI) and muscle atrophy in individuals with rotator cuff tears.

Methods

This study consists of patients with rotator cuff tears identified by MRI from two independent cohorts, the Rotator Cuff Outcomes Workgroup (ROW) and the Multicenter Orthopaedic Outcomes Network (MOON). Presence of atrophy (yes/no) and severity of atrophy (as an ordinal variable) were assessed on MRI by expert physicians. We used multivariable regression models to evaluate the relationship between BMI and muscle atrophy while adjusting for age and sex in each study, conducted sensitivity analyses for full-thickness tear and combined results using inverse variance-weighted meta-analysis.

Results

A total of 539 patients (MOON=395, ROW=144) from the combined cohorts had MRI data available on muscle atrophy. Among these patients, 246 (46%) had atrophy of at least one of the muscles of the rotator cuff and 282 (52%) had full-thickness tears. In meta-analysis across both cohorts, each 5 kg/m2increase in BMI was associated with a 21% (aOR=1.21, 95% CI=1.02, 1.43) increased odds of having muscle atrophy among individuals with any tear size, and 36% (aOR=1.36, 95% CI=1.01–1.81) increased odds among individuals with full-thickness tear.

Conclusions

Higher BMI was associated with significantly higher odds of muscle atrophy in patiens with rotator cuff tears. More study is needed to unders1tand why and how this relationship exists, as well as whether interventions to reduce BMI may help improve outcomes for these patients.

Level of Evidence

III.
Nutrition as a military capability to deliver human advantage: more people, more ready, more of the time
Authors: Fallowfield Joanne L , McClung J P , Gaffney-Stomberg E , Probert B , Peterson R , Charlebois A , Boilard H , Carins J , Kilding H
Published: June 2024

Soldiers must achieve high-level mission-preparedness to endure extended periods of physical and cognitive activity, with unpredictable recovery, in all environments. Nutrition provides the foundation for health and performance. Militaries have not maximised the strategic and financial value that considering nutrition as a military capability could deliver. A whole system approach to military nutrition, based on the prepare-perform-recover human capability cycle phases, is presented. Trainee nutrition requirements, through to very-high-readiness forces undertaking arduous roles at reach, must be specifically addressed. Promoting military performance diets in the prepare phase, through practitioner-supported nutrition education and food provision, will ensure mission readiness and mitigate ill health. Delivering nutrition in field settings in the perform phase—through smaller/lighter, nutritionally optimised rations and smart packaging technologies—will improve utility and minimise waste. Strategic dietary supplement use can provide a mission performance-enhancing adjunct to a food-first philosophy. Impact value chain analysis of military nutrition capability investments could support cost–benefit measurement.
Anti-dsDNA IgE: a potential non-invasive test for prediction of lupus nephritis relapse
Authors: Himbert Marie , Jourde-Chiche Noémie , Chapart Léa , Charles Nicolas , Baumstarck Karine , Daugas Eric
Published: June 2024

Objectives

Discontinuation or continuation of maintenance immunosuppressive therapy (MIST) after a severe lupus nephritis (LN) requires measuring the risk of relapse but reliable clinical and biological markers are lacking. The WIN-IgE study assesses the value of serum anti-dsDNA IgE autoantibodies as a biomarker for the prediction of relapse in severe LN.

Methods

WIN-IgE is an ancillary study of the WIN-Lupus study (NCT01284725), a prospective controlled clinical trial which evaluated the discontinuation of MIST after 2–3 years in class III or IV±V LN with active lesions. WIN-IgE included all patients with available serum collected at randomisation for continuation or discontinuation of MIST. In these sera, anti-dsDNA antibodies, IgE and IgG, were quantified by ELISA and compared between patients who experienced LN relapse and those who did not during the 24 months of follow-up.

Results

52 patients were included, 25 in the MIST continuation group and 27 in the MIST discontinuation group, 12 experienced a biopsy-proven relapse of LN. Initial anti-dsDNA IgE antibodies levels were higher in patients with subsequent LN relapse. Anti-dsDNA IgG was not associated with relapse. Survival without LN relapse was lower in patients with anti-dsDNA IgE levels above vs below a threshold of 1.9 arbitrary units (p=0.019), particularly in the subgroup of patients randomised to discontinue MIST (p=0.002). In all patients, anti-dsDNA IgE above 1.9 arbitrary units had a positive predictive value of 0.8 for severe LN relapse.

Conclusions

These results suggest blood anti-dsDNA IgE as a non-invasive predictive marker of LN relapse.
Nipocalimab, an anti-FcRn monoclonal antibody, in participants with moderate to severe active rheumatoid arthritis and inadequate response or intolerance to anti-TNF therapy: results from the phase 2a IRIS-RA study
Authors: Taylor Peter C , Schett Georg , Huizinga Tom WJ , Wang Qingmin , Ibrahim Fowzia , Zhou Bei , Liva Sophia G , Shaik Jafar Sadik B , Xiong Yuan , Leu Jocelyn H , Panchakshari Rohit A , Loza Matthew J , Ma Keying , Dhatt Harman , Rojo Cella Ricardo , Karyekar Chetan S , Cuff Carolyn A , Gao Sheng , Fei Kaiyin
Published: June 2024

Objectives

To investigate the efficacy, safety, pharmacokinetics and pharmacodynamics of nipocalimab in participants with moderate to severe active rheumatoid arthritis (RA) and inadequate response or intolerance to ≥1 antitumour necrosis factor agent.

Methods

In this phase 2a study, participants with RA seropositive for anticitrullinated protein antibodies (ACPA) or rheumatoid factors were randomised 3:2 to nipocalimab (15 mg/kg intravenously every 2 weeks) or placebo from Weeks 0 to 10. Efficacy endpoints (primary endpoint: change from baseline in Disease Activity Score 28 using C reactive protein (DAS28-CRP) at Week 12) and patient-reported outcomes (PROs) were assessed through Week 12. Safety, pharmacokinetics and pharmacodynamics were assessed through Week 18.

Results

53 participants were enrolled (nipocalimab/placebo, n=33/20). Although the primary endpoint did not reach statistical significance for nipocalimab versus placebo, a numerically higher change from baseline in DAS28-CRP at Week 12 was observed (least squares mean (95% CI): –1.03 (–1.66 to –0.40) vs –0.58 (–1.24 to 0.07)), with numerically higher improvements in all secondary efficacy outcomes and PROs. Serious adverse events were reported in three participants (burn infection, infusion-related reaction and deep vein thrombosis). Nipocalimab significantly and reversibly reduced serum immunoglobulin G, ACPA and circulating immune complex levels but not serum inflammatory markers, including CRP. ACPA reduction was associated with DAS28-CRP remission and 50% response rate in American College of Rheumatology (ACR) criteria; participants with a higher baseline ACPA had greater clinical improvement.

Conclusions

Despite not achieving statistical significance in the primary endpoint, nipocalimab showed consistent, numerical efficacy benefits in participants with moderate to severe active RA, with greater benefit observed for participants with a higher baseline ACPA.

Trial registration number

NCT04991753.
Toward more ethical engagements between Western and Indigenous sciences
Authors: Stein Sharon , Ahenakew Cash , Valley Will , Sherpa Pasang Y. , Crowson Eva , Robin Tabitha , Mendes Wilson , Evans Steve
Published: June 2024

There is growing interest among Western-trained scientists in engaging with Indigenous sciences. This interest has arisen in response to social pressures to reckon with the colonial foundations of Western science and decentre Western ways of knowing, as well as recognition of the need to draw upon the gifts of multiple knowledge systems to address today's many complex social and ecological challenges. However, colonial patterns and power relations are often reproduced at the interface between Western and Indigenous sciences, including the reproduction of epistemic Eurocentrism and extractive modes of relationship between settlers and Indigenous Peoples. This paper seeks to support Western-trained scientists to recognize and interrupt these patterns in order to create the conditions for more ethical, respectful, and reciprocal engagements with Indigenous sciences. We also offer a map of the different ways that Western sciences have thus far engaged Indigenous sciences. We particularly highlight the emergent possibilities offered by a reparative approach to engagement that emphasizes the responsibility of Western science to enact material and relational repair for historical and ongoing harm, including by supporting Indigenous self-determination and sovereignty in science and beyond.
Nonmetric geometric flows and quasicrystalline topological phases for dark energy and dark matter in $$f(Q)$$ cosmology
Authors: Bubuianu Laurenţiu , Nurlan Erik , Seti Julia O. , Vacaru Sergiu I. , Veliev Elşen Veli
Published: June 2024

We elaborate on nonmetric geometric flow theory and metric-affine gravity with applications in modern cosmology. Two main motivations for our research follow from the facts that (1) cosmological models for f(Q) modified gravity theories, MGTs, are efficient for describing recent observational data provided by the James Webb Space Telescope; and (2) the statistical thermodynamic properties of such nonmetric locally anisotropic cosmological models can be studied using generalizations of the concept of G. Perelman entropy. We derive nonmetric distorted R. Hamilton and Ricci soliton equations in such canonical nonholonomic variables when corresponding systems of nonlinear PDEs can be decoupled and integrated in general off-diagonal forms. This is possible if we develop and apply the anholonomic frame and connection deformation method involving corresponding types of generating functions and generating sources encoding nonmetric distortions. Using such generic off-diagonal solutions (when the coefficients of metrics and connections may depend generically on all spacetime coordinates), we model accelerating cosmological scenarios with quasi-periodic gravitational and (effective) matter fields; and study topological and nonlinear geometric properties of respective dark energy and dark matter, DE and DM, models. As explicit examples, we analyze some classes of nonlinear symmetries defining topological quasicrystal, QC, phases which can modified to generate other types of quasi-periodic and locally anisotropic structures. The conditions when such nonlinear systems possess a behaviour which is similar to that of the Lambda cold dark matter ($$\Lambda $$
Λ
CDM) scenario are stated. We conclude that nonmetric geometric and cosmological flows can be considered as an alternative to the $$\Lambda $$
Λ
CDM concordance models and speculate on how such theories can be elaborated. This is a partner work with generalizations and applications of the results published by Bubuianu, Vacaru et all. EPJC 84 (2024) 211; 80 (2020) 639; 78 (2018) 393; 78 (2018) 969; and CQG 35 (2018) 245009.
Profile update: the effects of identity disclosure on network connections and language
Authors: Choi Minje , Romero Daniel M. , Jurgens David
Published: June 2024

Our social identities determine how we interact and engage with the world surrounding us. In online settings, individuals can make these identities explicit by including them in their public biography, possibly signaling a change in what is important to them and how they should be viewed. While there is evidence suggesting the impact of intentional identity disclosure in online social platforms, its actual effect on engagement activities at the user level has yet to be explored. Here, we perform the first large-scale study on Twitter that examines behavioral changes following identity disclosure on Twitter profiles. Combining social networks with methods from natural language processing and quasi-experimental analyses, we discover that after disclosing an identity on their profiles, users (1) tweet and retweet more in a way that aligns with their respective identities, and (2) connect more with users that disclose similar identities. We also examine whether disclosing the identity increases the chance of being targeted for offensive comments and find that in fact (3) the combined effect of disclosing identity via both tweets and profiles is associated with a reduced number of offensive replies from others. Our findings highlight that the decision to disclose one’s identity in online spaces can lead to substantial changes in how they express themselves or forge connections, with a lesser degree of negative consequences than anticipated.
Paired Domination Integrity of Graphs
Authors: Antony Annie Clare , Sangeetha V.
Published: June 2024

The concept of vulnerability in a communication network plays an important role when there is a disruption in the network. There exist several graph parameters that measure the vulnerability of a communication network. Domination integrity is one of the vulnerability parameters that measure the performance of a communication network. In this paper, we introduce the concept of paired domination integrity of a graph as a new measure of graph vulnerability. Let [Formula: see text] be a simple, connected graph. A set of vertices in a graph [Formula: see text], say [Formula: see text], is a paired dominating set if the following two conditions are satisfied: (i) every vertex of [Formula: see text] has a neighbor in [Formula: see text] and (ii) the subgraph induced by [Formula: see text] contains a perfect matching. The paired domination integrity of [Formula: see text], denoted by [Formula: see text], is defined as [Formula: see text], where [Formula: see text] is the order of the largest component in the induced subgraph of [Formula: see text]. In this paper, we determine few bounds relating paired domination integrity with other graph parameters and the paired domination integrity of some classes of graphs.
Neural intelligent approach for heat transfer applications of trihybrid cross bio-nanofluid over wedge geometry
Authors: Ayub Assad , Iqbal Zahoor , Shah Syed Zahir Hussain , Al Samman Fathia M. , Wahab Hafiz Abdul , Dalam Mhassen E. E. , Gargouri Ameni
Published: June 2024

Significance: Heat transport in the blood within a wedge-shaped artery is significant in biomedical engineering field like develop therapeutic strategies, drug delivery to specific regions of the artery, vicinity of narrowed or blocked arteries and catheter-based treatments such as angioplasty or thermal ablation.

Motive: This study investigates the heat transport analysis of trihybrid nanofluid (blood) over wedge-shaped artery with mathematical model of Cross fluid. This study incorporates three nanoparticles, graphene oxide (GO), titanium dioxide (TiO2), and aluminum oxide (Al2O3) in base fluid blood. The wedge-shaped artery is chosen due to its relevance to biomedical applications and it reflects the nature of blood flow in real vascular structures. Heat transport is scrutinized through thermal radiations and flow rate is inspected through inclined magnetic field.

Methodology: The bvp4c and Levenberg–Marquardt Neural Network (LM-NN) supervised neural scheme is used to predict the numerical outcome of this study.

Findings: Incorporation of nanoparticles made rapid heat transport of blood in wedge-shaped artery. Velocity of blood is decreased with high Weissenberg number and magnetic force. The temperature of a blood in a wedge-shaped artery increases with positive non-uniform heat source/sink parameters and decreases with negative non-uniform heat source/sink parameters.
The Rise of the AI Co-Pilot: Lessons for Design from Aviation and Beyond
Authors: Sellen Abigail , Horvitz Eric
Published: June 2024

Building on cross-disciplinary insights to shape the future of human-AI interaction.
How to Think about Remedies in the Generative AI Copyright Cases
Authors: Samuelson Pamela
Published: June 2024

A long-range perspective on generative artificial intelligence litigation.
Weighted Fairness Notions for Indivisible Items Revisited
Authors: Chakraborty Mithun , Segal-Halevi Erel , Suksompong Warut
Published: June 2024

We revisit the setting of fairly allocating indivisible items when agents have different weights representing their entitlements. First, we propose a parameterized family of relaxations for weighted envy-freeness and the same for weighted proportionality; the parameters indicate whether smaller-weight or larger-weight agents are given a higher priority. We show that each notion in these families can always be satisfied, but any two cannot necessarily be fulfilled simultaneously. We then introduce an intuitive weighted generalization of maximin share fairness and establish the optimal approximation of it that can be guaranteed. Furthermore, we characterize the implication relations between the various weighted fairness notions introduced in this and prior work, and relate them to the lower and upper quota axioms from apportionment.
DSHGT
: Dual-Supervisors Heterogeneous Graph Transformer—A Pioneer Study of Using Heterogeneous Graph Learning for Detecting Software Vulnerabilities
Authors: Zhang Tiehua , Xu Rui , Zhang Jianping , Liu Yuze , Chen Xin , Yin Jun , Zheng Xi
Published: June 2024

Vulnerability detection is a critical problem in software security and attracts growing attention both from academia and industry. Traditionally, software security is safeguarded by designated rule-based detectors that heavily rely on empirical expertise, requiring tremendous effort from software experts to generate rule repositories for large code corpus. Recent advances in deep learning, especially Graph Neural Networks (GNN), have uncovered the feasibility of automatic detection of a wide range of software vulnerabilities. However, prior learning-based works only break programs down into a sequence of word tokens for extracting contextual features of codes, or apply GNN largely on homogeneous graph representation (e.g., AST) without discerning complex types of underlying program entities (e.g., methods, variables). In this work, we are one of the first to explore heterogeneous graph representation in the form of Code Property Graph and adapt a well-known heterogeneous graph network with a dual-supervisor structure for the corresponding graph learning task. Using the prototype built, we have conducted extensive experiments on both synthetic datasets and real-world projects. Compared with the state-of-the-art baselines, the results demonstrate superior performance in vulnerability detection (average F1 improvements over 10% in real-world projects) and language-agnostic transferability from C/C

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to other programming languages (average F1 improvements over 11%).
Cleaning Up Confounding: Accounting for Endogeneity Using Instrumental Variables and Two-Stage Models
Authors: Graf-Vlachy Lorenz , Wagner Stefan
Published: June 2024

Studies in empirical software engineering are often most useful if they make causal claims because this allows practitioners to identify how they can purposefully influence (rather than only predict) outcomes of interest. Unfortunately, many non-experimental studies suffer from potential endogeneity, for example, through omitted confounding variables, which precludes claims of causality. In this conceptual tutorial, we aim to transfer the proven solution of instrumental variables and two-stage models as a means to account for endogeneity from econometrics to the field of empirical software engineering. To this end, we discuss causality and causal inference, provide a definition of endogeneity, explain its causes, and lay out the conceptual idea behind instrumental variable approaches and two-stage models. We also provide an extensive illustration with simulated data and a brief illustration with real data to demonstrate the approach, offering Stata and R code to allow researchers to replicate our analyses and apply the techniques to their own research projects. We close with concrete recommendations and a guide for researchers on how to deal with endogeneity.
Remark on Algorithm 1010: Boosting Efficiency in Solving Quartic Equations with No Compromise in Accuracy
Authors: De Michele Cristiano
Published: June 2024

In this second remark, we present a revised correction to Algorithm 1010 [A. Orellana and C. De Michele 2020] with respect to the one already proposed in the remark on Algorithm 1010 [C. De Michele 2022].
Gated Multi-Modal Edge Refinement Network for Light Field Salient Object Detection
Authors: Li Yefan , Duan Fuqing , Lu Ke
Published: June 2024

Light field can be decoded into multiple representations and provides valuable focus and depth information. This breakthrough overcomes the limitations of traditional 2D and 3D saliency detection methods, opening up new possibilities for more accurate and comprehensive analysis of visual scenes. To tackle the challenges of inaccurate edge prediction and effectively leverage the rich multi-modal light field information, we propose a gated multi-modal edge refinement network (GMERNet). It first obtains the preliminary position and structure information of the salient object and then gradually refines the object edge. This involves two modules: gated multi-modal feature complement (GMFC) module and progressive edge refinement (PER) module. The GMFC module captures dependencies across the all-in-focus image and its corresponding focal stack and depth map, effectively aggregating multiple features through gate mechanisms. The PER module progressively refines edges by combining salient object features with edge features through a cascaded structure. Experimental results demonstrate that GMERNet achieves state-of-the-art performance on five benchmark datasets and shows significant advantages in extracting salient objects with complex edges.
Knowledge, Attitude, and Practice of Thai Dairy Farmers on the Use of Antibiotics
Authors: Ratanapob Niorn , Saengtienchai Aksorn , Rukkwamsuk Theera
Published: June 2024

Antibiotics have been used regularly in dairy farms by veterinarians; however, they were also used occasionally by farmers without any veterinary prescriptions. Because knowledge, attitude, and practice are important for sustainable antibiotic use, the levels of these aspects among farmers and associated factors should be determined to improve antibiotic use in dairy farming. The study was carried out in 89 Thai dairy farmers, using a structured questionnaire. Data were analyzed using descriptive statistics. The questions were scored and the total scores were calculated for each aspect. Factors associated with knowledge, attitude, and practice scores were identified using the multivariate linear regression. The mean scores for knowledge, attitude, and practice were 62%, 86%, and 78%, respectively. Higher education, participation in a training related to antibiotic use, and being supervised by the Veterinary Teaching Hospital Nong Pho were associated with a higher knowledge score (p < 0.050). Farmers with less experience received a higher attitude score (p = 0.020). Acquiring antibiotic knowledge from other farmers was associated with a lower practice score (p = 0.005). A positive association was found between knowledge and attitude scores (p = 0.021) and practice and attitude score (p < 0.001). Due to the insufficient knowledge on antibiotic use, there is a need to fill the gap to ensure prudent antibiotic use by farmers. Recommendations including training farmers by veterinarian to perceive the prudent antibiotic uses, encouraging young generation with higher education to participate in dairy farming, providing antibiotic use protocols, and decreasing the availability of antibiotics should be implemented to limit overuse by farmers.
Experimental Evaluation Performance of Ultrasonic Multisensor Deployment Geometries for a Data Acquisition System
Authors: Essiben Jean-François Dikoundou , Ihonock Luc Eyembe , Matanga Jacques , Suk Joe Yong
Published: June 2024

This paper proposed a model to estimate sensor spacing and a new deployment geometry and evaluates the performance of an ultrasonic sensor array according to the deployment geometry. The proposed spacing estimation model is based on the probability of false detection alarms, the aperture angle, and the sensor range. A design technique has been proposed for elliptical deployment geometry, giving expressions for its parameters to help designers of experimental prototypes to reduce errors related to sensor disposition. A practical method for calibrating ultrasonic sensors has been designed to reduce measurement errors. An experiment was conducted, and the data were analysed using a statistical significance test. An evaluation of the performance of an ultrasonic sensor array with linear and circular deployment geometry with and without our method was done and then compared to our proposed deployment geometry which was combined with the proposed method. The result of the statistical significance test shows that elliptical deployment geometry combined with the suggested strategy works better than circular and linear geometry. This applies to performance such as linear correlation, RMSE, MAPE, and standard deviation. These results show the importance of the choice of deployment geometry for application.
A Phase I/II Study of Valemetostat (DS-3201b), an EZH1/2 Inhibitor, in Combination with Irinotecan in Patients with Recurrent Small-Cell Lung Cancer
Authors: Choudhury Noura J. , Lai W. Victoria , Makhnin Alex , Heller Glenn , Eng Juliana , Li Bob , Preeshagul Isabel , Santini Fernando C. , Offin Michael , Ng Kenneth , Paik Paul , Larsen Christina , Ginsberg Michelle S. , Lau Yvonne , Zhang Xinyuan , Baine Marina K. , Rekhtman Natasha , Rudin Charles M.
Published: June 2024

Purpose:

Recurrent small-cell lung cancer (SCLC) has few effective treatments. The EZH2-SLFN11 pathway is a driver of acquired chemoresistance that may be targeted.

Patients and Methods:

This phase I/II trial investigated valemetostat, an EZH1/2 inhibitor, with fixed-dose irinotecan in patients with recurrent SCLC. Phase I primary objectives were to assess safety, tolerability, and a recommended phase II dose (RP2D). The phase II primary objective was overall response rate (ORR), with secondary objectives of determining duration of response (DoR), progression-free survival (PFS), and overall survival (OS). Correlative analyses included immunohistochemistry of pretreatment and on-treatment tumor biopsies and pharmacokinetics analysis.

Results:

Twenty-two patients were enrolled (phase I, n = 12; phase II, n = 10); one withdrew consent prior to treatment. Three dose-limiting toxicities (DLT) in dose-escalation resulted in valemetostat 100 mg orally daily selected as RP2D. Among 21 evaluable patients, the most frequent (≥20%) treatment-related adverse events were diarrhea, fatigue, nausea, and rash; three patients discontinued treatment for toxicity. Three of the first 10 patients in phase II experienced DLTs triggering a stopping rule. The ORR was 4/19 or 21% [95% confidence interval (CI), 6%–46%]. The median DoR, PFS, and OS were 4.6 months, 2.2 months (95% CI, 1.3–7.6 months), and 6.6 months (95% CI, 4.3 to not reached), respectively. SLFN11/EZH2 expression and SCLC subtyping markers did not correlate with response, but MHC-I expression did increase with treatment. Two responders demonstrated subtype switching on treatment.

Conclusions:

Combination valemetostat and irinotecan was not tolerated but demonstrated efficacy in recurrent SCLC. Valemetostat, combined with agents without overlapping toxicity, warrants further investigation in SCLC.