bluuebunny/crossref_metadata_2025 huggingface dataset:
Urban Water Management and Governance in Southeast Asian Cities
Authors: Lamb Vanessa , Prabaharyaka Indrawan
Published: December 2024

Scholarship on the topic of urban water management in Southeast Asian cities, both contemporary and historical, centers on issues of contested control over water, reliance on infrastructure, and governance of populations. Such work offers insights regarding the enactment of power relations in Southeast Asian cities, particularly via infrastructure, and how this has played out with myriad effects across the region.

To approach the study of water management in cities in the region is to simultaneously inquire into topics of fragmentation, informality, climate change, urban ecologies, and sanitation. Across this varied work is a concern for the ways that water infrastructure developments and failures have shaped the ways that Southeast Asian cities provide, or deny, access to the most vulnerable. The resulting unevenness and fragmentation have meant that water management and infrastructure have been sites of struggle.

Examination of this scholarship highlights new insights into power and water across work by anthropologists, historians, geographers, political ecologists, and development studies scholars. In this literature, there are broader conceptual and practical shifts in focus that move from an emphasis on water management as control, to the emergence of governance of not only water but also the control of populations and urban space as a key concern and the “internal” politics of the governed. In other words, attempts to control water create and shape access and exclusion to urban water and therefore play a role in struggles and contestations over power in Southeast Asian cities.
Phonological Variation and Change in European Portuguese and Galician
Authors: Veloso João , Regueira Fernández Xosé Luís
Published: December 2024

Portuguese and Galician are closely related languages, having shared a common medieval period known as Galician–Portuguese. While some continuities between them persist, the phonologies of contemporary Galician and Portuguese have evolved separately. Significant variation phenomena can be examined, illustrating the distinct paths of these languages: gheada, seseo, and coda-/S/ changes for Galician; trill desonorantization and the decline of unstressed vowel reduction (UVR) for Portuguese.

Gheada consists of the articulation of /ɡ/ as [h], [ħ], or [x], a change that has not yet been adequately explained. Seseo refers to a nonstandard sibilant system, which lacks the phonological opposition between /s/ and /θ/ present in the standard system. Finally, variation affecting coda-/S/ leads to its realization as a rhotic, an aspirated [h], or a palatal [ʃ]. All these phenomena in contemporary Galician are subject to geographical and social distribution and are notable for their sociolinguistic implications as well as their complexity and theoretical implications within the current phonological framework.

In Portuguese, trill desonorantization consists of the realization of the “strong rhotic” /ʀ/ as a fricative. Many variation corpora and dialectal studies suggest fricative allophones of /ʀ/ are becoming predominant. This can trigger a more drastic reorganization of the consonantal system of the language. UVR is generally seen as the most characteristic phonological feature of Portuguese. However, a closer look at recent and older words of the language suggest that its importance might be declining, since newer forms do not undergo vowel reduction as regularly as older words.

In conclusion, the phonological divergence between Portuguese and Galician is evidenced by distinct variation phenomena in each language. These variations underscore the separated evolutionary paths of these languages since their shared medieval period, reflecting broader sociolinguistic and theoretical complexities. Furthermore, such variation phenomena illuminate potential trajectories of phonological change, some of which hold significant interest within the context of Iberian and, more broadly, Romance languages.
Chinese Cleft Sentences
Authors: Feng Yuli
Published: December 2024

Chinese clefts mainly involve two patterns, the shi…de pattern and the bare shi pattern, and the shi…de pattern can be further categorized into the V–O–de pattern and the V–O–de pattern, which are distinguished according to the relative order of the object and de. Compared to clefts in other languages, Chinese clefts are particularly special in two aspects. First, in the surface order, the cleft focus stays together with the cleft presupposition between shi and de, instead of moving to a higher position as in languages like English. Second, Chinese shi…de clefts have a heavy preference for past-tense interpretations and the V–de–O pattern cannot host tense, aspect and modal elements in its presupposition.

In the existing literature, some analyses take shi to be the central element of focus-marking, which partitions cleft sentences into the cleft focus and the cleft presupposition; while other analyses relate shi in clefts with shi in idenitificational/specificational sentences and pin down shi as a copula verb. For de, a group of studies treat it to be an optional element that serves a secondary function such as mood-marking or tense-marking; while other analyses, taking the shi…de pattern to be prototypical clefts that encode contrastiveness or exhaustivity, tend to assign de the function of focus partition and treat shi as a semantically vacuous copula verb. The TAM restriction is then explained by assigning de the syntactic position of a tense/aspect head or by ascribing such restrictions to PF-level linearization constraints and the implied default temporal interpretation of the cleft construction.

Semantically, just like English it-clefts, the existence/absence of the exhaustive effect in Chinese clefts is a much-debated issue that has generated competing views. Some studies distinguish between emphatic and exhaustive meanings, and treat exhaustivity as the defining criterion for cleft sentences in Chinese, while others hold that Chinese clefts only encode contrastiveness and do not mark exhaustivity at the level of assertion.
Exploring links—exposure to alcohol adverts on social media in relation to alcohol use among university students in Uganda
Authors: Atusingwize Edwinah , Nilsson Maria , Egan Sjölander Annika , Tumwesigye Nazarius Mbona , Musoke David , Landstedt Evelina
Published: December 2024

Aim

This study assessed the association between exposure to alcohol adverts on social media and alcohol use among university students in Uganda since alcohol consumption has severe effects, especially in countries with weak regulations for alcohol marketing.

Methods

In total, 996 undergraduate students at Makerere University responded to a questionnaire assessing exposure to alcohol advertising on social media (independent variable) and alcohol use (dependent variable). Adjusted multinomial logistic regression was used to analyse data.

Results

One in ten students reported hazardous drinking, while three in ten students were low-risk drinkers. Most students (70.1%) reported low exposure to alcohol adverts on social media, followed by high exposure (12.1%), and 17.8% reported no exposure. A key finding was that exposure to alcohol adverts on social media was significantly associated with alcohol use, especially the high exposure and hazardous drinking (odds ratio = 12.62, 95% confidence interval: 4.43–35.96). Students reporting high exposure to alcohol adverts on social media also had higher odds of low-risk drinking (odds ratio = 3.70, 95% confidence interval: 1.88–7.27) than those with low exposure (odds ratio = 1.77, 95% confidence interval: 1.09–2.87), in reference to no exposure.

Conclusion

Among Ugandan university students, exposure to alcohol adverts on social media is common and associated with alcohol use, in a dose–response manner. These findings suggest a need for a design and implementation of alcohol interventions for students using social media.
Negative binomial mixture model for identification of noise in antibody-antigen specificity predictions from single-cell data
Authors: Wasdin Perry T , Abu-Shmais Alexandra A , Irvin Michael W , Vukovich Matthew J , Georgiev Ivelin S
Published: December 2024

Motivation

LIBRA-seq (linking B cell receptor to antigen specificity by sequencing) provides a powerful tool for interrogating the antigen-specific B cell compartment and identifying antibodies against antigen targets of interest. Identification of noise in single-cell B cell receptor sequencing data, such as LIBRA-seq, is critical for improving antigen binding predictions for downstream applications including antibody discovery and machine learning technologies.

Results

In this study, we present a method for denoising LIBRA-seq data by clustering antigen counts into signal and noise components with a negative binomial mixture model. This approach leverages single-cell sequencing reads from a large, multi-donor dataset described in a recent LIBRA-seq study to develop a data-driven means for identification of technical noise. We apply this method to nine donors representing separate LIBRA-seq experiments and show that our approach provides improved predictions for in vitro antibody-antigen binding when compared to the standard scoring method, despite variance in data size and noise structure across samples. This development will improve the ability of LIBRA-seq to identify antigen-specific B cells and contribute to providing more reliable datasets for machine learning based approaches as the corpus of single-cell B cell sequencing data continues to grow.

Availability and implementation

All data and code are available at https://github.com/IGlab-VUMC/mixture_model_denoising.
Optimizing rare disorder trials: a phase 1a/1b randomized study of KL1333 in adults with mitochondrial disease
Authors: Pizzamiglio Chiara , Stefanetti Renae J , McFarland Robert , Thomas Naomi , Ransley George , Hugerth Matilda , Grönberg Alvar , Serrano Sonia Simon , Elmér Eskil , Hanna Michael G , Hansson Magnus J , Gorman Gráinne S , Pitceathly Robert D S
Published: December 2024

Over the past two decades there has been increased interest in orphan drug development for rare diseases. However, hurdles to clinical trial design for these disorders remain. This phase 1a/1b study addressed several challenges, while evaluating the safety and tolerability of the novel oral molecule KL1333 in healthy volunteers and subjects with primary mitochondrial disease.

KL1333 aims to normalize the NAD+:NADH ratio that is critical for ATP production. The trial incorporated innovative design elements with potential translatability to other rare diseases including patient involvement, adaptive design and exploratory objectives, all of which have subsequently informed the protocol of an ongoing phase 2, pivotal efficacy study of KL1333.

Results indicate KL1333 is safe and well tolerated, with dose-dependent gastrointestinal side effects, and validate potential novel outcome measures in primary mitochondrial disease including the 30-s Sit to Stand, and the patient-reported fatigue scales. Importantly, the data from the trial support efficacy of KL1333 based on improvements in fatigue and functional strength and endurance. Furthermore, the study highlights the value in using phase 1 studies to capture data that helps optimize later phase efficacy trial design.
Genome-wide epistasis analysis reveals significant epistatic signals associated with Parkinson’s disease risk
Authors: Cisterna-Garcia Alejandro , Bustos Bernabe I , Bandres-Ciga Sara , Leal Thiago P , Sarihan Elif I , Jok Christie , Krainc Dimitri , Mata Ignacio F , Lubbe Steven J , Botia Juan A
Published: December 2024

Genome-wide association studies (GWAS) have increased our understanding of Parkinson’s disease (PD) genetics by identifying common disease-associated variants. However, much of the heritability remains unaccounted for and we hypothesized that this could be partly explained by epistasis, the statistical interaction between two or more genetic variants.

Here, we developed a genome-wide non-exhaustive epistasis screening pipeline called Variant-variant interaction through variable thresholds (VARI3) and applied it to diverse PD GWAS cohorts.

We used 14 cohorts of European ancestry (14,671 cases and 17,667 controls) as a discovery stage, identifying 14 significant candidate variant-variant interactions. We then used four independent cohorts (13,377 cases and 413,789 controls) as replication stage, successfully replicating three epistasis signals located nearby SNCA and within MAPT and WNT3. Admixture analysis showed that the epistatic effect on PD of those variants at these loci was observed in both European ancestry and Native American ancestry individuals. We assessed the functional impact of the epistasis signals across a range of functional/-omics datasets identifying significant single-variant eQTLs across brain tissues, epistasis eQTL signals in whole-blood, PD-relevant pathways and ontologies, and chromatin interactions between the regions of the interacting SNPs.

In conclusion, we identified and replicated novel epistatic signals associated with PD risk across multiple diverse genetic ancestry cohorts, highlighting their enrichment in pathways relevant to Parkinson’s disease.
Evaluating multiple sclerosis severity loci 30 years after a clinically isolated syndrome
Authors: Sahi Nitin , Haider Lukas , Chung Karen , Prados Carrasco Ferran , Kanber Baris , Samson Rebecca , Thompson Alan J , Trip S Anand , Brownlee Wallace , Ciccarelli Olga , Barkhof Frederik , Tur Carmen , Houlden Henry , Chard Declan
Published: December 2024

The first genome-wide significant multiple sclerosis severity locus, rs10191329, has been pathologically linked to cortical lesion load and brain atrophy. However, observational cohorts such as MSBase have not replicated associations with disability outcomes, instead finding other loci. We evaluated rs10191329 and MSBase loci in a unique cohort of 53 people followed for 30 years after a clinically isolated syndrome, with deep clinical phenotyping and MRI measures of inflammation and neurodegeneration. After 30 years, 26 had developed relapsing-remitting multiple sclerosis, 15 secondary progressive multiple sclerosis and 12 remained diagnosed with a clinically isolated syndrome. Genetic associations with disease severity (age-related multiple sclerosis severity score and Expanded Disability Status Scale), disease course and brain MRI features (white matter lesions, cortical lesions and grey matter fraction) were investigated using regression models and survival analyses. rs10191329 was not associated with multiple sclerosis severity, secondary progressive multiple sclerosis diagnosis or brain MRI features at 30 years. Similarly, MSBase loci were not associated with 30-year disease severity, although rs73091975 was significantly associated with lower 14-year age-related multiple sclerosis severity score in those developing multiple sclerosis. Given that effect sizes for both rs10191329 and rs73091975 were greatest between 14 and 20 years, these findings suggest genetic effects on multiple sclerosis severity may interact non-linearly with disease duration.
Climate change and the role of dermatologists: a call to action
Authors: Potestio Luca , Martora Fabrizio , Villani Alessia , Megna Matteo
Published: December 2024

As dermatologists we have to be prepared for the emerging dermatological challenges associated with climate change, including the development of innovative treatments and preventive measures.
Shared decision-making in central centrifugal cicatricial alopecia
Authors: Swain Elizabeth , Haughton Renee , Palmer Victoria , Obeime Ivie , McMichael Amy
Published: December 2024

Central centrifugal cicatricial alopecia (CCCA) is a primary lymphocytic scarring alopecia, which predominantly occurs in middle-aged Black women. The benefits and use of shared decision-making (SDM) models in patients with CCCA have yet to be studied. We conducted a cross-sectional survey to investigate the role of SDM in the management of CCCA. SDM processes were evaluated using the nine-item Shared Decision-Making Questionnaire (SDM-Q-9), the Decisional Regret Scale (DRS) and the Control Preferences Scale (CPS). Between June and August 2023, members of the Scarring Alopecia Foundation were emailed and invited to participate; n = 87/1192 members responded. The CPS responses suggested that most patients (48%, n = 41/87) preferred to share responsibility with their doctor for treatment decisions. The SDM-Q-9 (scored 0–45) and DRS (scored 0–100) demonstrated mean (SD) scores of 27.5 (11.5) and 38.4 (19.4), with higher and lower scores, respectively, demonstrating greater patient satisfaction with SDM. SDM is useful for patients involved in complex decision-making when several medically reasonable treatment alternatives are available. Patients with CCCA may benefit from this model, and investment in resources such as patient decision aids and SDM training for dermatologists will aid integration into clinical practice. Together, the CPS, DRS and SDM-Q-9 results suggested that patients with CCCA preferred to be involved in their treatment management decisions, regardless of their sociodemographic characteristics.
Identification and characterization of human KALRN mRNA and Kalirin protein isoforms
Authors: Mould Arne W , Wright David J , Bornemann Klaus D , Hengerer Bastian , Pinnock Rob , Drydale Edward , Bancroft James , Hall Nicola A L , von Delft Annette , Brennan Paul E , Harrison Paul J , Haerty Wilfried , Tunbridge Elizabeth M
Published: December 2024

Kalirin is a multidomain protein with important roles in neurite outgrowth, and synaptic spine formation and remodeling. Genetic and pathophysiological links with various neuropsychiatric disorders associated with synaptic dysfunction and cognitive impairment have sparked interest in its potential as a pharmacological target. Multiple Kalirin proteoforms are detected in the adult human brain, yet we know little about the diversity of the transcripts that encode them or their tissue profiles. Here, we characterized full-length KALRN transcripts expressed in the adult human frontal lobe and hippocampus using rapid amplification of complementary DNA (cDNA) ends and nanopore long-read sequencing. For comparison with non-neural tissue, we also analyzed KALRN transcripts in the aorta. Multiple novel isoforms were identified and were largely similar between the two brain regions analyzed. Alternative splicing in the brain results in preferential inclusion of exon 37, which encodes 32 amino acids upstream of the second guanine nucleotide exchange factor (GEF) domain. Structural modeling predicts that a subset of these amino acids forms a conserved alpha helix. Although deletion of these amino acids had little effect on GEF activity, it did alter Kalirin-induced neurite outgrowth suggesting that this brain-enriched splicing event may be important for neural function. These data indicate that alternative splicing is potentially important for regulating Kalirin actions in the human brain.
Difference in spin structure of magnetic metal-organic frameworks between cluster model and periodic system
Authors: Amamizu Naoka , Tada Kohei , Kishi Ryohei , Kosaka Wataru , Miyasaka Hitoshi , Kitagawa Yasutaka
Published: December 2024

We compare the calculated spin structures of magnetic metal-organic frameworks consisting of paddlewheel-type diruthenium complexes and tetracyano-p-quinodimethane derivatives using density functional theory calculations with Gaussian basis sets and DFT + U/plane-wave calculations under periodic conditions. The calculated results indicate that the asymmetricity of the spin density inside the [Ru2] unit disappears in the periodic systems. In addition, based on the partial spin density analysis, the electron conductivity would be switchable by changing the spin states of the metal-organic frameworks.
Influenza Vaccine Effectiveness Against Hospitalizations and Emergency Department or Urgent Care Encounters for Children, Adolescents, and Adults During the 2023–2024 Season, United States
Authors: Tenforde Mark W , Reeves Emily L , Weber Zachary A , Tartof Sara Y , Klein Nicola P , Dascomb Kristin , DeSilva Malini B , Yang Duck-Hye , Grannis Shaun J , Irving Stephanie A , Ong Toan C , Link-Gelles Ruth , Salas S Bianca , Sy Lina S , Lewin Bruno , Contreras Richard , Zerbo Ousseny , Fireman Bruce , Hansen John , Timbol Julius , Sheffield Tamara , Bride Daniel , Arndorfer Julie , VanOtterloo Josh , McEvoy Charlene E , Akinsete Omobosola O , Essien Inih J , Dixon Brian E , Rogerson Colin , Fadel William F , Duszynski Thomas , Naleway Allison L , Barron Michelle A , Rao Suchitra , Mayer David , Chavez Catia , Ball Sarah W , Payne Amanda B , Ray Caitlin , Dickerson Monica , Neelam Varsha , Adams Katherine , Flannery Brendan , DeCuir Jennifer , Garg Shikha
Published: December 2024

Background

The 2023–2024 influenza season had predominant influenza A(H1N1)pdm09 virus activity, but A(H3N2) and B viruses cocirculated. Seasonal influenza vaccine strains were well-matched to these viruses.

Methods

Using healthcare encounters data from health systems in 8 US states, we evaluated influenza vaccine effectiveness (VE) against influenza-associated medical encounters from October 2023 to April 2024. Using a test-negative design, we compared the odds of vaccination between patients with an acute respiratory illness who tested positive (cases) versus negative (controls) for influenza by molecular assay, adjusting for confounders. VE was stratified by age group, influenza type (overall, influenza A, influenza B), and care setting (hospitalization, emergency department or urgent care [ED/UC] encounter).

Results

Overall, 74 000 encounters in children and adolescents aged 6 months–17 years (3479 hospitalizations, 70 521 ED/UC encounters) and 267 606 in adults aged ≥18 years (66 828 hospitalizations, 200 778 ED/UC encounters) were included. Across care settings, among children and adolescents, 15% (2758/17 833) of cases versus 32% (18 240/56 167) of controls had received vaccination. Among adults, 25% (11 632/46 614) of cases versus 44% (97 811/220 992) of controls across care settings had received vaccination. VE was 58% (95% confidence interval [95% CI], 44–69) against hospitalization and 58% (95% CI, 56–60) against ED/UC encounters for children and adolescents, and 39% (95% CI, 35–43) against hospitalization and 47% (95% CI, 46–49) against ED/UC encounters for adults. Across age groups, VE was higher against influenza B than influenza A.

Conclusions

Influenza vaccines provided protection against influenza-associated illness across health care settings and age groups during the 2023–2024 influenza season.
Efficacy and safety of dapagliflozin in patients with CKD: real-world experience in 93 Italian renal clinics
Authors: Minutolo Roberto , Borrelli Silvio , Ambrosini Andrea , Amoroso Luigi , Aucella Filippo , Batini Valentina , Battaglia Yuri , Bregoli Laura , Cantaluppi Vincenzo , Cianciolo Giuseppe , Conti Paolo , Fabbrini Paolo , Giammarresi Carlo , Imbalzano Egidio , La Rosa Sandra , Marengo Marita , Montinaro Vincenzo , Musone Dario , Napoli Marcello , Nappi Felice , Pluvio Corrado , Santoro Domenico , Scarpioni Roberto , Sopranzi Franco , Tullio Tiziana , De Nicola Luca
Published: December 2024

Background

Sodium-glucose co-transporter-2 inhibitors (SGLT2i) are recommended for reducing the renal and cardiovascular risk in patients with chronic kidney disease (CKD) based on the positive results reported by clinical trials. However, real-world data on the efficacy and the safety of these drugs in CKD population followed in nephrology setting are lacking.

Methods

We report the effects of dapagliflozin in CKD patients by using data collected during a learning program in which 105 nephrologists added dapagliflozin (10 mg/day) to consecutive patients referred to their renal clinics. Efficacy endpoints were the albuminuria change and the determinants of an albuminuria decline ≥30%. Adverse events were also collected.

Results

A total of 1724 patients with CKD (age 67.4 ± 13.2 years, 72.8% males, diabetes 59.9%, eGFR 43.5 ± 17.4 ml/min/1.73 m2, severe albuminuria 70.1%) received dapagliflozin for 4 ± 1 months. Dapagliflozin significantly reduced body weight (−1.3 kg), eGFR (−0.27 ml/min/month), and blood pressure (−3.6/−1.7 mmHg). Albuminuria declined by 25.1% (95%CI 23.0–27.2) from 500 mg/day [IQR 225–1425] to 320 mg/day [IQR 100–900]. Albuminuria reduction was ≥30% in 48.3% of patients, 0–29% in 37.6% while it increased in 14.1% of patients. At logistic regression analysis, older age, female sex, use of mineralocorticoid receptor antagonist, higher eGFR, and higher albuminuria were all significant predictors of albuminuria decline ≥30%. We collected 46 side effects leading to drug discontinuation in 36 patients (2%), with acute kidney injury and urinary tract infection being the most frequent adverse events.

Conclusions

We provide evidence of the anti-proteinuric efficacy of short-term dapagliflozin in the presence of good safety profile in patients with CKD followed in nephrology.
Multilevel Factors and Sleep in Adults With Inflammatory Bowel Disease: A Qualitative Study
Authors: Winders Samantha , Yoo Linda , Heitkemper Margaret , Kamp Kendra
Published: December 2024

Background

This study aimed to describe the patient-reported factors that impact sleep among individuals with inflammatory bowel disease (IBD), aligning with the Social Ecological Model of Sleep. This addresses the gap in IBD sleep research, which predominantly focuses on individual-level factors and their impact on sleep.

Methods

Adults (ages 18-65) with IBD were recruited online through ResearchMatch in June 2023. Participants filled out survey questions on their demographic characteristics, health history, sleep, and IBD-related symptoms. Content analysis was conducted on 2 open-ended questions about factors that impacted their sleep.

Results

This analysis included 163 adults with IBD (M = 39 years of age, 76.7% White, 91.4% non-Hispanic or Latino, 66.9% female, and 83.4% active IBD) who answered open-ended questions with comments about their sleep. Most participants indicated an individual-level factor impacted their sleep quality (85.3%, n = 139), categorized into 5 subthemes: Mental health, health, behavior and choices, physiology, and attitudes. Additionally, participants (43.6%, n = 71) mentioned social-level factors divided into 7 subthemes: Family, work, home, neighborhood, social network, and school. A smaller group of participants (17.2%, n = 28) mentioned societal-level factors designated into 4 subthemes: Natural environment and geography, technology, 24/7 society, and economics.

Conclusions

This study highlights the need for tailored sleep interventions for those with IBD that consider not only disease activity but also mental health, family, work, and the natural environment. IBD clinics should prioritize sleep health using an interdisciplinary approach to holistically address the unique needs of those with IBD.
Diffusion-weighted imaging of the head and neck: comparison between integrated slice-specific dynamic shimming and simultaneous multi-slice readout-segmented echo-planar sequences
Authors: Su Tong , Zhu Xiaoli , Chen Yu , Xu Zhentan , Chen Xingming , Zhang Tao , Zhu Jinxia , Liu Wei , Wang Xiaoye , Zhang Zhuhua , Feng Feng , Jin Zhengyu
Published: December 2024

Objectives

To compare integrated slice-specific dynamic shimming (iShim) and simultaneous multi-slice (SMS) readout-segmented echo-planar imaging (RESOLVE) for diffusion-weighted imaging (DWI) of malignant head and neck tumours.

Methods

In this prospective study, 45 patients with malignant head and neck lesions underwent iShim- and SMS-RESOLVE imaging with two b-values (0, 800 s/mm2) at 3 T. Subjective image quality scores (lesion distortion, signal loss, fat saturation, and artefacts), quantitative lesion distortion, quantitative image quality [signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and SNR efficiency], ADC values, and total acquisition times of iShim- and SMS-RESOLVE imaging were evaluated and compared.

Results

iShim-RESOLVE (3 mins 7 s) had longer acquisition times than SMS-RESOLVE (2 min 1 s). iShim-RESOLVE images had much better overall image quality, geometric distortion, fat saturation, and signal loss than SMS-RESOLVE (P < .05). The quantitative tumour distortion in iShim-RESOLVE images was significantly smaller than those of SMS-RESOLVE, measured either with b = 0 s/mm2 or b = 800 s/mm2 (P < .05). Using the iShim technique, the SNR, CNR of high b-value images, and SNR efficiency were significantly higher than those of SMS-RESOLVE (P < .001). The ADC measurements with excellent agreement of iShim-RESOLVE images were higher than those of SMS-RESOLVE.

Conclusions

iShim-RESOLVE can decrease lesion distortion and improve overall image quality compared with SMS-RESOLVE in head and neck region.

Advances in knowledge

iShim-RESOLVE DWI may serve as a promising technique for reducing distortion and assessing head and neck lesions in clinical practice.
Detection of periodontal bone loss and periodontitis from 2D dental radiographs via machine learning and deep learning: systematic review employing APPRAISE-AI and meta-analysis
Authors: Khubrani Yahia H , Thomas David , Slator Paddy J , White Richard D , Farnell Damian J J
Published: December 2024

Objectives

Periodontitis is a serious periodontal infection that damages the soft tissues and bone around teeth and is linked to systemic conditions. Accurate diagnosis and staging, complemented by radiographic evaluation, are vital. This systematic review (PROSPERO ID: CRD42023480552) explores artificial intelligence (AI) applications in assessing alveolar bone loss and periodontitis on dental panoramic and periapical radiographs

Methods

Five databases (Medline, Embase, Scopus, Web of Science, and Cochrane’s Library) were searched from January 1990 to January 2024. Keywords related to “artificial intelligence”, “Periodontal bone loss/Periodontitis”, and “Dental radiographs” were used. Risk of bias and quality assessment of included papers were performed according to the APPRAISE-AI Tool for Quantitative Evaluation of AI Studies for Clinical Decision Support. Meta analysis was carried out via the “metaprop” command in R V3.6.1.

Results

Thirty articles were included in the review, where 10 papers were eligible for meta-analysis. Based on quality scores from the APPRAISE-AI critical appraisal tool of the 30 papers, 1 (3.3%) were of very low quality (score < 40), 3 (10.0%) were of low quality (40 ≤ score < 50), 19 (63.3%) were of intermediate quality (50 ≤ score < 60), and 7 (23.3%) were of high quality (60 ≤ score < 80). No papers were of very high quality (score ≥ 80). Meta-analysis indicated that model performance was generally good, eg, sensitivity 87% (95% CI, 80%-93%), specificity 76% (95% CI, 69%-81%), and accuracy 84% (95% CI, 75%-91%).

Conclusion

Deep learning shows much promise in evaluating periodontal bone levels, although there was some variation in performance. AI studies can lack transparency and reporting standards could be improved. Our systematic review critically assesses the application of deep learning models in detecting alveolar bone loss on dental radiographs using the APPRAISE-AI tool, highlighting their efficacy and identifying areas for improvement, thus advancing the practice of clinical radiology.
Healthcare deservingness: how risk factors and income shape responsibility attribution for health outcomes and healthcare costs
Authors: Baute Sharon , Bellani Luna
Published: December 2024

Amidst the global surge in healthcare expenditures, there is a growing political and academic debate about individual versus collective responsibility for health and healthcare costs. This study explores the causal effects of health risks and income cues on citizens’ attribution of responsibility for health outcomes and healthcare costs. An original vignette experiment was conducted among the German population. Those in need of medical treatment who have been exposed to environmental, institutional, or biological health risks are held less responsible for their health outcomes than those exhibiting behavioural health risks. However, the impact of health risks appears to be somewhat weaker in determining who should bear the costs for the medical treatment. Furthermore, higher-income groups are more likely to be blamed for their health outcomes and are considered less deserving of society’s help in paying for medical treatment. These findings enhance our understanding of how the criteria of control and economic need shape public attribution of responsibility in the health(care) domain.
Genome-wide screen overexpressing mycobacteriophage Amelie genes identifies multiple inhibitors of mycobacterial growth
Authors: Tafoya Chelsea , Ching Brandon , Garcia Elva , Lee Alyssa , Acevedo Melissa , Bass Kelsey , Chau Elizabeth , Lin Heidi , Mamora Kaitlyn , Reeves Michael , Vaca Madyllyne , van Iderstein William , Velasco Luis , Williams Vivianna , Yonemoto Grant , Yonemoto Tyler , Heller Danielle M , Diaz Arturo
Published: December 2024

The genome sequences of thousands of bacteriophages have been determined and functions for many of the encoded genes have been assigned based on homology to characterized sequences. However, functions have not been assigned to more than two-thirds of the identified phage genes as they have no recognizable sequence features. Recent genome-wide overexpression screens have begun to identify bacteriophage genes that encode proteins that reduce or inhibit bacterial growth. This study describes the construction of a plasmid-based overexpression library of 76 genes encoded by Cluster K1 mycobacteriophage Amelie, which is genetically similar to cluster K phages Waterfoul and Hammy recently described in similar screens and closely related to phages that infect clinically important mycobacteria. Twenty-six out of the 76 genes evaluated in our screen, encompassing 34% of the genome, reduced growth of the host Mycobacterium smegmatis to various degrees. More than one-third of these 26 toxic genes have no known function, and 10 of the 26 genes almost completely abolished host growth upon overexpression. Notably, while several of the toxic genes identified in Amelie shared homologs with other Cluster K phages recently screened, this study uncovered 7 previously unknown gene families that exhibit cytotoxic properties, thereby broadening the repertoire of known phage-encoded growth inhibitors. This work, carried out under the HHMI-supported SEA-GENES project (Science Education Alliance Gene-function Exploration by a Network of Emerging Scientists), underscores the importance of comprehensive overexpression screens in elucidating genome-wide patterns of phage gene function and novel interactions between phages and their hosts.
Functional annotation of regulatory elements in rainbow trout uncovers roles of the epigenome in genetic selection and genome evolution
Authors: Salem Mohamed , Al-Tobasei Rafet , Ali Ali , An Liqi , Wang Ying , Bai Xuechen , Bi Ye , Zhou Huaijun
Published: December 2024

Rainbow trout (RBT) has gained widespread attention as a biological model across various fields and has been rapidly adopted for aquaculture and recreational purposes on 6 continents. Despite significant efforts to develop genome sequences for RBT, the functional genomic basis of RBT’s environmental, phenotypic, and evolutionary variations still requires epigenome reference annotations.

This study has produced a comprehensive catalog and epigenome annotation tracks of RBT, detecting gene regulatory elements, including chromatin histone modifications, chromatin accessibility, and DNA methylation. By integrating chromatin immunoprecipitation sequencing, ATAC sequencing, Methyl Mini-seq, and RNA sequencing data, this new regulatory element catalog has helped to characterize the epigenome dynamics and its correlation with gene expression. The study has also identified potential causal variants and transcription factors regulating complex domestication phenotypic traits. This research also provides valuable insights into the epigenome’s role in gene evolution and the mechanism of duplicate gene retention 100 million years after RBT whole-genome duplication and during re-diploidization. The newly developed epigenome annotation maps are among the first in fish and are expected to enhance the accuracy and efficiency of genomic studies and applications, including genome-wide association studies, causative variation identification, and genomic selection in RBT and fish comparative genomics.
Learning a generalized graph transformer for protein function prediction in dissimilar sequences
Authors: Fu Yiwei , Gu Zhonghui , Luo Xiao , Guo Qirui , Lai Luhua , Deng Minghua
Published: December 2024

Background

In the face of a growing disparity between high-throughput sequence data and low-throughput experimental studies, the emerging field of deep learning stands as a promising alternative. Generally, many data-driven approaches are capable of facilitating fast and accurate predictions of protein functions. Nevertheless, the inherent statistical nature of deep learning techniques may limit their generalization capabilities when applied to novel nonhomologous proteins that diverge significantly from existing ones.

Results

In this work, we herein propose a novel, generalized approach named Graph Adversarial Learning with Alignment (GALA) for protein function prediction. Our GALA method integrates a graph transformer architecture with an attention pooling module to extract embeddings from both protein sequences and structures, facilitating unified learning of protein representations. Particularly noteworthy, GALA incorporates a domain discriminator conditioned on both learnable representations and predicted probabilities, which undergoes adversarial learning to ensure representation invariance across diverse environments. To optimize the model with abundant label information, we generate label embeddings in the hidden space, explicitly aligning them with protein representations. Benchmarked on datasets derived from the PDB database and Swiss-Prot database, our GALA achieves considerable performance comparable to several state-of-the-art methods. Even more, GALA demonstrates wonderful biological interpretability by identifying significant functional residues associated with Gene Ontology terms through class activation mapping.

Conclusions

GALA, which leverages adversarial learning and label embedding alignment to acquire domain-invariant protein representations, exhibits outstanding generalizability in function prediction for proteins from previously unseen sequence space. By incorporating the structures predicted by AlphaFold2, GALA demonstrates significant potential for function annotation in newly discovered sequences. A detailed implementation of our GALA is available at https://github.com/fuyw-aisw/GALA.
Stratum corneum nanotexture feature detection using deep learning and spatial analysis: a noninvasive tool for skin barrier assessment
Authors: Wang Jen-Hung , Pereda Jorge , Du Ching-Wen , Chu Chia-Yu , Christensen Maria Oberländer , Kezic Sanja , Jakasa Ivone , Thyssen Jacob P , Satheesh Sreeja , Hwu Edwin En-Te
Published: December 2024

Background

Corneocyte surface nanoscale topography (nanotexture) has recently emerged as a potential biomarker for inflammatory skin diseases, such as atopic dermatitis (AD). This assessment method involves quantifying circular nano-size objects (CNOs) in corneocyte nanotexture images, enabling noninvasive analysis via stratum corneum (SC) tape stripping. Current approaches for identifying CNOs rely on computer vision techniques with specific geometric criteria, resulting in inaccuracies due to the susceptibility of nano-imaging techniques to environmental noise and structural occlusion on the corneocyte.

Results

This study recruited 45 AD patients and 15 healthy controls, evenly divided into 4 severity groups based on their Eczema Area and Severity Index scores. Subsequently, we collected a dataset of over 1,000 corneocyte nanotexture images using our in-house high-speed dermal atomic force microscope. This dataset was utilized to train state-of-the-art deep learning object detectors for identifying CNOs. Additionally, we implemented a kernel density estimator to analyze the spatial distribution of CNOs, excluding ineffective regions with minimal CNO occurrence, such as ridges and occlusions, thereby enhancing accuracy in density calculations. After fine-tuning, our detection model achieved an overall accuracy of 91.4% in detecting CNOs.

Conclusions

By integrating deep learning object detector with spatial analysis algorithms, we developed a precise methodology for calculating CNO density, termed the Effective Corneocyte Topographical Index (ECTI). The ECTI demonstrated exceptional robustness to nano-imaging artifacts and presents substantial potential for advancing AD diagnostics by effectively distinguishing between SC samples of varying AD severity and healthy controls.
Practitioners’ perspectives on unintended effects of illicit drug use prevention public service announcements in Australia
Authors: Munro Kirsteen , Bogomolova Svetlana , Simmonds Lucy
Published: December 2024

Public service announcements (PSAs) or campaigns aimed at preventing harm can inadvertently risk creating additional harms. It remains unclear whether these unintended effects are considered during campaign development, if risk mitigation strategies are implemented, or how professionals involved perceive these issues. It is in the context of illicit drug use prevention PSAs that our research investigates and explores the perspectives of practitioners—health support professionals and advertising campaign designers and creators. Semi-structured expert interviews were conducted to capture and synthesize practitioners’ perspectives which were then analysed by applying a framework to address the unintended effects of public health interventions. The results indicated that practitioners from both sectors are aware of unintended harms but place varying levels of importance on different aspects. In the case of illicit drug prevention PSAs, incorporating practitioners’ perspectives in campaign development may result in mitigating the risk of potential unintended harmful effects.
Genetic architecture of RNA editing, splicing and gene expression in schizophrenia
Authors: Choudhury Mudra , Yamamoto Ryo , Xiao Xinshu
Published: December 2024

Genome wide association studies (GWAS) have been conducted over the past decades to investigate the underlying genetic origin of neuropsychiatric diseases, such as schizophrenia (SCZ). While these studies demonstrated the significance of disease-phenotype associations, there is a pressing need to fully characterize the functional relevance of disease-associated genetic variants. Functional genetic loci can affect transcriptional and post-transcriptional phenotypes that may contribute to disease pathology. Here, we investigate the associations between genetic variation and RNA editing, splicing, and overall gene expression through identification of quantitative trait loci (QTL) in the CommonMind Consortium SCZ cohort. We find that editing QTL (edQTL), splicing QTL (sQTL) and expression QTL (eQTL) possess both unique and common gene targets, which are involved in many disease-relevant pathways, including brain function and immune response. We identified two QTL that fall into all three QTL categories (seedQTL), one of which, rs146498205, targets the lincRNA gene, RP11-156P1.3. In addition, we observe that the RNA binding protein AKAP1, with known roles in neuronal regulation and mitochondrial function, had enriched binding sites among edQTL, including the seedQTL, rs146498205. We conduct colocalization with various brain disorders and find that all QTL have top colocalizations with SCZ and related neuropsychiatric diseases. Furthermore, we identify QTL within biologically relevant GWAS loci, such as in ELA2, an important tRNA processing gene associated with SCZ risk. This work presents the investigation of multiple QTL types in parallel and demonstrates how they target both distinct and overlapping SCZ-relevant genes and pathways.
The role of miR-129-5p in regulating γ-globin expression and erythropoiesis in β-thalassemia
Authors: Li Jingmin , Chen Meihuan , Zhao Wantong , Lv Aixiang , Lin Siyang , Zheng Yanping , Cai Meiying , Lin Na , Xu Liangpu , Huang Hailong
Published: December 2024

The regulation of γ-globin expression is crucial due to its beneficial effects on diseases like β-thalassemia and sickle cell disease. B-cell lymphoma/leukemia 11A (BCL11A) is a significant suppressor of γ-globin, and microRNAs (miRNAs) targeting BCL11A have been shown to alleviate this suppression. In our previous high-throughput sequencing, we identified an 11.32-fold increase in miR-129-5p expression in β-thalassemia patients. However, the regulatory mechanisms of miR-129-5p in the context of erythroid differentiation remain to be elucidated. Our study aimed to elucidate the role of miR-129-5p in γ-globin regulation and erythropoiesis. We measured miR-129-5p levels in peripheral blood from β-thalassemia major and intermedia patients. Fluorescence in situ hybridization, dual-luciferase reporter assays, miRNA pull down assays and western blot analyses were conducted to examine the effects of miR-129-5p on γ-globin expression and BCL11A repression. Cell proliferation, apoptosis, and erythroid differentiation were assessed using cell counting kit-8, Wright-Giemsa, and benzidine staining, and flow cytometry assays. The expression levels of miR-129-5p were significantly elevated in β-thalassemia patients and positively correlated with γ-globin synthesis while negatively correlating with liver damage. miR-129- 5p enhanced γ-globin gene expression in K562 and HUDEP-2 cells by effectively repressing BCL11A. Overexpression of miR-129-5p inhibited cell proliferation, induced cell cycle arrest at the G1/G0 phase, promoted apoptosis and stimulated erythroid differentiation and maturation. Conversely, inhibition of miR-129-5p produced opposite cellular effects. miR-129-5p acts as a positive regulator of erythroid differentiation and γ-globin synthesis. It offers a promising miRNA target for activating the γ-globin gene and reducing ineffective erythropoiesis in β-thalassemia patients.