bluuebunny/crossref_metadata_2025 huggingface dataset:
Antisense oligonucleotide–mediated MSH3 suppression reduces somatic CAG repeat expansion in Huntington’s disease iPSC–derived striatal neurons
Authors: Bunting Emma L. , Donaldson Jasmine , Cumming Sarah A. , Olive Jessica , Broom Elizabeth , Miclăuș Mihai , Hamilton Joseph , Tegtmeyer Matthew , Zhao Hien T. , Brenton Jonathan , Lee Won-Seok , Handsaker Robert E. , Li Susan , Ford Brittany , Ryten Mina , McCarroll Steven A. , Kordasiewicz Holly B. , Monckton Darren G. , Balmus Gabriel , Flower Michael , Tabrizi Sarah J.
Published: February 2025

Expanded CAG alleles in the huntingtin (
HTT
) gene that cause the neurodegenerative disorder Huntington’s disease (HD) are genetically unstable and continue to expand somatically throughout life, driving HD onset and progression. MSH3, a DNA mismatch repair protein, modifies HD onset and progression by driving this somatic CAG repeat expansion process.
MSH3
is relatively tolerant of loss-of-function variation in humans, making it a potential therapeutic target. Here, we show that an
MSH3
-targeting antisense oligonucleotide (ASO) effectively engaged with its RNA target in induced pluripotent stem cell (iPSC)–derived striatal neurons obtained from a patient with HD carrying
125 HTT
CAG repeats (the 125 CAG iPSC line). ASO treatment led to a dose-dependent reduction of MSH3 and subsequent stalling of CAG repeat expansion in these striatal neurons. Bulk RNA sequencing revealed a safe profile for
MSH3
reduction, even when reduced by >95%. Maximal knockdown of MSH3 also effectively slowed CAG repeat expansion in striatal neurons with an otherwise accelerated expansion rate, derived from the 125 CAG iPSC line where
FAN1
was knocked out by CRISPR-Cas9 editing. Last, we created a knock-in mouse model expressing the human
MSH3
gene and demonstrated effective in vivo reduction in human
MSH3
after ASO treatment. Our study shows that ASO-mediated MSH3 reduction can prevent
HTT
CAG repeat expansion in HD 125 CAG iPSC–derived striatal neurons, highlighting the therapeutic potential of this approach.
Blood folate level needed for fully effective fortification in the prevention of neural tube defects
Authors: Wald Nicholas J , Vale Stephen H , Bestwick Jonathan P , Morris Joan K
Published: February 2025

Objective

Neural tube defects (NTDs) are a preventable folate deficiency disorder; increasing folic acid intake through food fortification increases serum and red blood cell folate and reduces the risk of an NTD pregnancy. There is controversy over the blood folate level needed to achieve the full preventive effect because of discrepant study conclusions.

Methods

Results from two published studies were used to determine the relationship between serum folate and NTD risk which was compared with the observed result in a randomised trial of folic acid that increased serum folate from 5 ng/mL to 44 ng/mL among women who took a 4 mg daily periconceptional folic acid supplement.

Results

Both studies showed a proportional (logarithmic) relationship between serum folate and NTD risk without evidence of a folate threshold above which there is no further NTD risk reduction. The suggestion of a threshold is due to the incorrect interpretation of the folate-NTD risk association when plotted on arithmetic scales, which conceals the proportional relationship between the two. Also, both studies accurately estimated the observed result from the randomised trial that achieved a median serum folate level of 44 ng/mL and an 83% preventive effect. This is much higher than has been achieved with current levels of folic acid fortification with serum folate between 10 and 16 ng/mL, resulting in an approximate 20% preventive effect.

Conclusion

To achieve fully effective fortification, median population serum folate levels need to be about 44 ng/mL, which would globally prevent about 250 000 NTD cases every year.
Profound hypotension following concomitant administration of tizanidine and lisinopril
Authors: Setzer Kayla , Baldwin Nicholas , Mersfelder Tracey , Kelly Matthew
Published: February 2025

Tizanidine, a muscle relaxant, exerts its mechanism as a centrally acting alpha-2 adrenergic receptor agonist and binds to imidazoline receptors. Bradycardia and hypotension are adverse effects associated with alpha-2 adrenergic receptor agonists. A man in his 50s with a medical history of hypertension and chronic back pain presented with chest pain and hypertension. Pertinent medication history included metoprolol tartrate, lisinopril, hydralazine, hydrochlorothiazide and tizanidine and was continued. Following medication administration, the patient was hypotensive. Further episodes occurred that correlated with tizanidine administration and were more pronounced with concomitant lisinopril administration. Tizanidine was discontinued, and the hypotensive episodes resolved. Profound hypotension caused by a tizanidine–lisinopril drug interaction is rare but potentially life-threatening. This reaction scored a 4 on the Naranjo Adverse Drug Reaction Probability Scale and Drug Interaction Probability Scale. Providers should be aware of this potential adverse reaction from the combination of medications.
Supernumerary phantom limb without phantom limb pain in a patient with pontine haemorrhage
Authors: Kücük Yasemin Ronahi , Kruuse Christina , Rath Charlotte Lützhøft , van Hooff Robbert-Jan Roderick
Published: February 2025

Supernumerary phantom limb (SPL) is an awareness of an illusory extra limb in addition to the existing limbs. This illusion can be disturbing if unrecognised. SPL due to cerebral lesions is rare but occurs in various neurological disorders, mostly right hemispheric stroke. Detailed symptom examination is crucial as SPL may be under-reported and overlooked during the acute stroke phase. This case report describes SPL without phantom limb pain after a pontine haemorrhage, and pain absence may delay SPL identification. A female patient in her mid-40s was admitted after a median pontine haemorrhage. 6 weeks post stroke, she reported an extra left arm and leg, present since stroke onset but not identified by staff. She could move the extra arm independently of the paretic arm and did not experience any pain. The extra arm disappeared weeks later as her paretic side improved.
Monitoring the neurological complications of chimeric antigen receptor (CAR) T-cell therapy in patients with sensory and physical impairments and non-native-speaking backgrounds using modified immune effector cell-associated encephalopathy (ICE) scores: a case series
Authors: Kazzi Christina , Simpson Ty , Abbott Cassandra , Wronski Miriam , Seery Nabil , Tan Tracie Huey-Lin , Wesselingh Robb , Ko Katherine , Wong Shu Min , Inam Shafqat , Tam Constantine , Fleming Shaun , O’Brien Terence J , Alpitsis Rubina , Spencer Andrew , Malpas Charles , Monif Mastura
Published: February 2025

Background

Immune effector cell-associated neurotoxicity syndrome (ICANS) is a common complication of chimeric antigen receptor (CAR) T-cell therapy. Current practice guidelines recommend the immune effector cell-associated encephalopathy (ICE) score for the assessment and monitoring of ICANS.

Objective

To demonstrate modifications to ICE score to patients with vision and hearing impairments or who are who are from non-native-speaking backgrounds.

Methods

We discuss five cases and the modifications made to adapt the ICE score to meet patients’ needs.

Results

Modifications to ICE score was feasible and it assisted with CAR T cell therapy outcome monitoring.

Discussion

These cases highlight the need for flexible and patient-tailored strategies and the importance of collaboration between multidisciplinary teams and patients’ families/caregivers when monitoring patients for ICANS after CAR T-cell therapy.
Integration of healthcare services for HIV and non-communicable diseases in sub-Saharan Africa: protocol for a scoping review of randomised controlled trials
Authors: Murphy Lauren , Bulstra Caroline A , Figi John T , Fladger Anne , Atun Rifat
Published: February 2025

Introduction

Stand-alone HIV clinics in sub-Saharan Africa (SSA) have effectively expanded antiretroviral therapy since the 2000s, transforming HIV from a deadly infection into a chronic condition. However, over the past decade, there has been a significant rise in the prevalence of non-communicable diseases (NCDs) globally and in SSA. People living with HIV are at higher risk for some NCDs, including hypertension, diabetes and different cancers. The region’s current healthcare infrastructure is not equipped to address this growing burden. Integrating health services for HIV and NCDs (ie, combining services for HIV with services for hypertension, diabetes, depression and mental health, substance use disorder or cancer) could be one strategy for responding to these challenges. In this scoping review, we aim to identify randomised controlled trials on HIV-NCD integration, assess implemented integration models and measured outcomes and highlight evidence gaps.

Methods and analysis

This scoping review will follow the Arksey and O’Malley (2005) methodological framework. Reporting will be guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR) checklist. We will conduct a systematic search of the databases OVID Medline, Embase, Web of Science, Global, Africa Index Medicus, including terms related to HIV, NCDs and healthcare integration. Included trials must have been conducted within SSA and have been published in English or French after 1 January 2010. We will not select based on sample size or number of clusters. Both the title and abstract screening and full-text screening will be done in Covidence by at least two reviewers working independently. Data extraction will focus on key variables, including study design, geographical location, integration intervention, measured outcomes and reported findings.

Ethics and dissemination

This scoping review aims to generate new insights from publicly available research. Therefore, ethical approval is not required. Study findings will be shared through discussion with policymakers, implementation science researchers and healthcare providers. The results of this study are intended to be published in a peer-reviewed journal.

Trial registration

This protocol has been registered with Center for Open Science OSF Registry (DOI: 10.17605/OSF.IO/RGQSN). The search was conducted on 25 March 2024 and updated on 21 October 2024. The review is expected to be completed by March 2025.
Association of pre-diabetes with the risks of adverse health outcomes and complex multimorbidity: evidence from population-based studies in the NIS and UK Biobank
Authors: Wu Yafei , Fan Xiude , Shi Yingzhou , Yuan Zinuo , Zhang Yue , Han Junming , Yuan Zhongshang , Li Mingzhuo , Cheng Yiping , Feng Xiaoshan , Wang Zhixiang , Xuan Ruirui , Dong Yingchun , Tian Yang , Dong Hang , Guo Qingling , Song Yongfeng , Zhao Jiajun
Published: February 2025

Introduction

This study aimed to examine the risk of common diseases among people with pre-diabetes and explored the relationship between pre-diabetes and multimorbidity (in this case, two or more comorbid diseases).

Methods

An observational multicohort study using data from the UK Biobank database and the National Inpatient Sample (NIS) database (2016–2018) was conducted. We analysed 461 535 participants and 17 548 442 patients aged 18 years or older from both databases, of whom 14.0% and 0.7% were diagnosed with pre-diabetes, respectively. A total of 76 common diseases of various body systems were selected as adverse health outcomes for analysis.

Results

Among 64 523 individuals with pre-diabetes in the UK Biobank, the mean age was 60 years, 35 304 (54.7%) were female. There were 24 non-overlapping diseases associated with pre-diabetes with significant multiple test results in both databases, and most of them are circulatory system diseases. Compared with normoglycaemia, the confounder-adjusted HR in the UK Biobank for pre-diabetes was 1.46 (95% CI 1.43 to 1.49) for accompanying complex multimorbidity (ie, four or more pre-diabetes-related diseases), the corresponding confounder-adjusted OR in the NIS study was 10.03 (95% CI 9.66 to 10.40).

Conclusion

Pre-diabetes was associated with a significantly higher risk of multimorbidity. Pre-diabetes, thus, might represent an important target for multimorbidity prevention, and stronger emphasis on its management seems necessary to reduce the risk of the development of multiple comorbidities, especially before the onset of overt diabetes.
Effects of Hyperoxia on Pulmonary Inflammation and organ injury in a human in vivo model (HIPI): study protocol of a randomised, double-blind, placebo-controlled trial
Authors: Linden Dermot , Dorrian Delia , Tandel Shikha , McKelvey Michael , Bailey Melanie , Conlon John , Moore David , Carr Sharon , Taggart Clifford C , Bradley Judy M , Kidney Joseph , OKane Cecilia M , McAuley Daniel Francis
Published: February 2025

Introduction

Liberal administration of supplemental oxygen (O2) is ubiquitous across numerous healthcare settings. However, appropriate O2titration targets remain controversial and despite numerous large-scale randomised trials, there is an ongoing lack of consensus regarding optimal oxygenation strategies and the absence of high-quality mechanistic data pertaining to the potential proinflammatory effects of hyperoxia.

Methods and analysis

We hypothesise that (1) short-term exposure to hyperoxia will induce mild pulmonary inflammation and cellular injury and that (2) hyperoxia will accentuate pulmonary inflammation and cellular injury in the setting of inhaled lipopolysaccharide challenge. To test our hypotheses, we will conduct a randomised, double-blind, placebo-controlled study of hyperoxia administered via a high-flow nasal O2delivery system (fractional inspired oxygen 1.0, 60 L/min flow rate) compared with synthetic medical air. Blocked randomisation will be undertaken by an independent clinical trials statistician. Healthy non-smoking adult volunteers (<45 years of age), taking no regular medications will be recruited. Bronchoalveolar lavage (BAL) will be performed at 6 hours. The study outcome measures will include BAL markers of inflammation and injury (including but not limited to interleukin (IL)-8, IL-6, tumour necrosis factor alpha), BAL differential cell counts, BAL markers of oxidative stress (superoxide dismutase and glutathione), alveolar epithelial cell injury (SP-D, vWF, RAGE) and markers of systemic inflammation (neutrophils and plasma C-reactive protein).

Ethics and dissemination

Dissemination of the research findings will be achieved in the following ways: (1) Our findings will be presented at national and international meetings with open-access abstracts online and (2) in accordance with the open-access policies proposed by the leading research funding bodies we aim to publish the findings in high quality peer-reviewed open-access journals.

Trial registration number

NCT05414370.
Age-stratified effects of intravenous ferric derisomaltose in heart failure with iron deficiency: insights from the IRONMAN trial
Authors: Sze Shirley , Squire Iain , Kalra Paul R , Cleland John G , Petrie Mark C , Kalra Philip A , Ahmed Fozia , Banerjee Prithwish , Boos Christopher J , Chapman Callum , Cowburn Peter James , Dixon Lana , Duckett Simon , Lane Rebecca , Foley Paul , Lang Ninian N , Lyons Kristopher , Ray Robin , Schiff Rebekah , Thomson Elizabeth A , Robertson Michele , Ford Ian
Published: February 2025

Background

Intravenous iron therapy with ferric derisomaltose (FDI) has been shown to improve outcomes in patients with heart failure with reduced ejection fraction (HFrEF) and iron deficiency. However, its effects across different age groups remain unclear. This analysis of the Effectiveness of Intravenous Iron Treatment versus Standard Care in Patients with Heart Failure and Iron Deficiency (IRONMAN) trial explored the efficacy and safety of FDI across age groups.

Methods

The IRONMAN trial was a prospective, open-label, blinded end point randomised controlled trial enrolling patients with HFrEF and iron deficiency. This prespecified analysis stratified the population into four quarters by age group: <67 years, 67–73 years, 74–79 years, >79 years. The primary outcome was a composite of recurrent heart failure hospitalisations and cardiovascular death. Secondary outcomes included changes in haemoglobin and quality of life. Clinical outcomes comparing FDI versus usual care in each age subgroup were analysed by the method of Linet alfor recurrent events and Cox proportional hazards model for time to first event. Interactions between age and treatment effects were explored.

Results

Among 1137 randomised patients (median age 73 years), the primary outcome rate ratio (FDI vs usual care) was 0.87 (95% CI 0.61 to 1.23) in patients <67 years, 0.93 (95% CI 0.66 to 1.32) in those aged 67–73 years, 0.88 (95% CI 0.59 to 1.33) in those aged 74–79 years and 0.66 (95% CI 0.45 to 0.96) in those aged >79 years (p-interaction=0.38). Improvements in haemoglobin and quality of life scores at 4 months did not differ statistically across age groups (p-interaction=0.92 and 0.64, respectively). Older patients were more symptomatic at baseline, with higher N-terminal-pro B-type natriuretic peptide levels and poorer renal function, but safety outcomes did not differ across age groups.

Conclusions

We found no evidence that the effects of FDI on heart failure hospitalisations, cardiovascular death, haemoglobin and quality of life differed by age. These findings support its use in patients with HFrEF and iron deficiency, including older adults.

Trial registration number

NCT02642562.
CD56brightcytokine-induced memory-like NK cells and NK-cell engagers synergize against non-small cell lung cancer cancer-stem cells
Authors: Guevara Lopez Maria L , Gebo Ann , Parodi Monica , Persano Stefano , Maus-Conn Josephine , Mingari Maria Cristina , Loiacono Fabrizio , Orecchia Paola , Sivori Simona , Cantoni Claudia , Gentili Marco , Facchinetti Federica , Ferracini Riccardo , Vallera Daniel A , Felices Martin , Bertolini Giulia , Pravetoni Marco , Roz Luca , Vitale Massimo
Published: February 2025

Background

Due to their enhanced responsiveness and persistence, cytokine-induced memory-like (CIML)-natural killer (NK) cells have emerged as new immunotherapeutic tools against malignancies. However, their effects on tumor-cell spread and metastases in solid tumors remain poorly investigated. Moreover, a clear identification of the most effective CIML-NK subsets, especially in controlling cancer stem cells (CSC), is still lacking.

Methods

We performed combined phenotypical and functional analyses of CIML-NK cell subsets, either selected by flow-cytometry gating, or generated from sorted CD56bright/CD56dimNK cells.

By co-culture experiments, we analyzed the effect of CIML-NK cells on non-small cell lung cancer (NSCLC) cell spheroids, or patient-derived xenografts (PDX), assessing changes in their CSC content, tumorigenicity, and/or tumor disseminating capability in vivo. CIML-NK cells were also infused in PDX-bearing mice to validate their effect on the CSC dissemination from the PDX to the lungs.

Finally, we generated and functionally analyzed CIML-NK cells from patients with stages I/III NSCLC (n=6).

Results

We show that CIML-NK cells exert antitumor activity mostly through their CD56brightcell subset, which greatly expands during CIML differentiation. Compared with NK cells conventionally activated with interleukin-2, CIML-NK cells express lower levels of check-point receptors, TIGIT and TIM3, and higher effector functions against NSCLC cells from PDX, and against in vitro-generated tumor spheroids. Remarkably, CIML-NK cells also significantly reduce the CSC-containing CD133+cell subpopulation within spheroids and PDX, and limit tumor cell tumorigenicity and ability to disseminate CSCs from primary tumors to distant sites. Sorting experiments on CIML or tumor cell subsets reveal that CD56brightcells drive most of this anti-CSC activity, and suggest that such functional advantage could be related to increased expression of LFA-1 and ICAM-1 on CD56brightcells and CSCs, respectively. We also show that the tri-specific killer cell engager (TriKE) 1615133 significantly enhances CIML-NK cell activity against CSCs. Finally, we demonstrate that CIML-NK cells, capable of killing autologous tumor cells and responding to the 1615133 TriKE, could be induced from patients with NSCLC.

Conclusions

Our study discloses for the first time the therapeutic potential of CIML-NK cells in controlling CSCs and metastatic spread, highlighting the role of the CD56brightsubset expansion and 1615133 TriKE for optimizing CIML-NK-based therapies against metastatic tumors.
Arteriovenous malformation from a patient with JP-HHT harbours two second-hit somatic DNA alterations inSMAD4
Authors: DeBose-Scarlett Evon , Ressler Andrew K , Friday Cassi , Prickett Kara K , Roberts James W , Gossage James R , Marchuk Douglas A
Published: February 2025

Background

Hereditary haemorrhagic telangiectasia (HHT) is an inherited disorder of vascular malformations. It is caused by inherited loss-of-function mutations in one of three genes,ENG,ACVRL1orSMAD4. We recently showed that HHT-associated vascular malformations from liver, lung, brain and skin develop via a two-hit genetic mechanism resulting from biallelic loss-of-function mutations in eitherENGorACVRL1. Second-hit somatic mutations inSMAD4have not been reported in HHT-associated vascular malformations. Here, we investigate a large, aggressively growing craniofacial arteriovenous malformation (AVM) from an individual with juvenile polyposis-HHT caused by a germline mutation inSMAD4.

Methods

We sequenced DNA from the AVM using a targeted gene sequencing panel to at least 1000X to identify somatic mutations that might contribute to the development of the AVM. We analysed whole genome SNP genotyping data using the algorithm Mosaic Chromosomal Alterations (MoChA) to identify somatic loss of heterozygosity.

Results

We confirmed the germline mutation inSMAD4(c.1610A>T, p.Asp537Val) and identified a second-hit somatic mutation also inSMAD4(c.350dup, p.Tyr117*) that occurred intransrelative to the germline mutation. We also identified somatic loss of heterozygosity on the q arm of chromosome 18, includingSMAD4. Additionally, we confirmed that the loss of heterozygosity causes loss of the wild-type allele. Thus, we identified two independent somatic alterations inSMAD4causing biallelic loss ofSMAD4function in the AVM tissue.

Conclusion

We identified biallelic loss of function ofSMAD4in a craniofacial AVM, evidence thatSMAD4also follows the two-hit mutation mechanism of HHT-associated vascular malformation pathogenesis.
Smoking-attributable neurological health loss: age-specific burden and health disparities
Authors: Zhao Yingjie , Fei Lu
Published: February 2025

Background

Smoking is a significant risk factor for neurological disorders, yet its global impact on these conditions remains underexplored.

Methods

Using Global Burden of Diseases 2021 data, we analysed trends in age-standardised disability-adjusted life-years (DALYs) and deaths attributable to smoking from 1990 to 2021 for three neurological disorders: stroke, Alzheimer’s disease and other dementias, and Multiple Sclerosis. Socioeconomic disparities were assessed using the lope index of inequality and the relative concentration index. Bayesian age-period-cohort models were employed to forecast smoking-attributable burden through 2050.

Results

Between 1990 and 2021, annual smoking-attributable DALYs and death rates slightly declined by −1.93% and −1.92%, respectively, but absolute numbers continued to rise, from 26.10 million to 30.18 million DALYs and from 0.93 million to 1.15 million deaths. Older adults (aged 60 and above) experienced the greatest burden, contributing 58.15% of DALYs and 75.57% of deaths in 2021. Smoking-attributable stroke was increasingly concentrated in low sociodemographic index regions, whereas disparities in dementias and multiple sclerosis were more pronounced in socioeconomically advantaged regions, particularly for multiple sclerosis.

Conclusions

This study identified an age-specific burden and widening disparities for neurological disorders attributable to smoking, with older adults disproportionately experiencing an escalating impact. Targeted prevention and equitable healthcare access tailored for older adults are critical to mitigating smoking-attributable neurological health loss.
Time trends of variability in disease activity in systemic lupus erythematosus
Authors: Li Ning , Hoi Alberta , Luo Shue-Fen , Wu Yeong-Jian Jan , Louthrenoo Worawit , Golder Vera , Sockalingam Sargunan , Cho Jiacai , Lateef Aisha , O’Neill Sean , Lau Chak Sing , Hamijoyo Laniyati , Nikpour Mandana , Oon Shereen , Hao Yanjie , Chan Madelynn , Li Zhanguo , Navarra Sandra , Zamora Leonid , Katsumata Yasuhiro , Harigai Masayoshi , Goldblatt Fiona , Bae Sang-Cheol , Zhang Zhuoli , Takeuchi Tsutomu , Kikuchi Jun , Ng Kristine , Tugnet Nicola , Tanaka Yoshiya , Ohkubo Naoaki , Chen Yi-Hsing , Basnayake B M D B , Law Annie , Kumar Sunil , Tee Cherica , Tee Michael Lucas , Choi Jiyoon , Kandane-Rathnayake Rangi , Morand Eric
Published: February 2025

Objective

Disease activity both between and within patients with SLE is highly variable, yet factors driving this variability remain unclear. This study aimed to identify predictors of variability in SLE disease activity over time.

Methods

We analysed data from 2930 patients with SLE across 13 countries, collected over 38 754 clinic visits between 2013 and 2020. Clinic visit records were converted to panel data with 1-year intervals. The time-adjusted mean disease activity, termedAMS, was calculated. The yearly change inAMS, denoted asΔAMSt, was regressed ontoAMSt−1and other potential predictors using random-effects models. Some variables were split into a person-mean component to assess between-patient differences and a demeaned component to assess within-patient variability.

Results

Overall, variability in SLE disease activity exhibited stabilisation over time. A significant inverse relationship emerged between a patient’s disease activity in a given year and variability in disease activity in the subsequent year: a 1-point increase in person-mean disease activity was associated with a 0.27-point decrease (95% CI −0.29 to –0.26, p<0.001) in subsequent variability. Additionally, a 1-point increase in within-patient disease activity variability was associated with a 0.56-point decrease (95% CI −0.57 to –0.55, p<0.001) in the subsequent year. Furthermore, each 1-point increase in the annual average time-adjusted mean Physician Global Assessment was associated with a 0.08-point decrease (90% CI −0.13 to –0.03, p=0.002) in disease activity variability for the following year. Prednisolone dose and the duration of activity in specific organ systems exhibited negative and positive associations, respectively, with disease activity variability in the subsequent year. Patients from less affluent countries displayed greater disease activity variability compared with those from wealthier nations.

Conclusion

Disease activity tends to be less variable among patients with higher or more variable disease activity in the previous year. Within-patient variability in disease activity has a stronger impact on subsequent fluctuations than differences between individual patients.
Analysis of complications of minimally invasive approaches for symptomatic lumbar spinal stenosis
Authors: Mekhail Nagy , Costandi Shrif , Botros Mina , Mukhdomi Junaid , Yassa Peter , Mukhdomi Taif
Published: February 2025

Introduction

Current treatment modalities of lumbar spinal stenosis range from conservative medical management and physical therapy to open surgical decompression. Minimally invasive lumbar decompression (MILD) and Superion interspinous spacers (SISS) Vertiflex offer the promise of effective pain relief with shorter recovery time and lesser potential complications compared with open surgical decompression procedures and general anesthesia. Despite their increasing utilization, their complication profile is not well established in the literature.

Methods

We searched the FDA’s Manufacturer and User facility Device Experience (MAUDE) database for all entries on MILD product code ‘HRX’ and SISS product code ‘NQO’. MAUDE database was queried from 2010 to 2021. Duplicate entries were removed, and complications were classified based on the event descriptions.

Results

For the MILD procedure, a total of 10 entries were found in the MAUDE database. Among these, 8 were classified as surgical complications and 2 were device related. On the other hand, a total of 919 reports were found in the MAUDE database for Vertiflex, with 385 medical device reports were included in the analysis. Device-related were the most reported complication, accounting for 189 cases.

Conclusion

As with any new intervention, we must proceed with caution and evaluate the procedure performance over time. Such data should aid physicians to make informed decisions before choosing either technique for their patients. The findings from this study provide insight into the complication profile associated with both MILD and Vertiflex procedures, highlighting the need for continued evaluation and careful consideration in clinical decision-making.
Incorporating local information to predict thermal stress for diverse species
Authors: FitzGerald Alyssa M
Published: February 2025

Pacific salmonids are incredibly diverse and critical for both ecosystems and human consumers. Although salmon conservation recognizes the importance of diversity for viability, most previous studies have oversimplified phenology and life history diversity that dictate local environmental exposure and influence responses to climate change. I combined subpopulation-level spatial distributions and phenologies with monthly stream temperature to explore modern and future patterns in freshwater thermal stress for 449 subpopulations across 21 coho salmon (Oncorhynchus kisutch) and steelhead trout (O. mykiss) management units, 14 of which are listed as either Threatened or Endangered under the United States Endangered Species Act. Under modern conditions, 37% of coho and 90% of steelhead subpopulations were exposed to thermally stressful conditions. Under a simple 2°C climate warming scenario, 91% of subpopulations and the majority of subpopulations in 20 of 21 management units would be thermally stressed during at least one life stage. For diverse species like salmon, incorporating local-scale phenology, spatial, and climatic information is imperative to identify subpopulations that will be negatively impacted by future climate warming without mitigating actions.
Immersive Experience and Interactive Design of Architectural Visualization Based on Virtual Reality Technology
Authors: Bin Zhao , Mengmeng Zhang
Published: February 2025

In order to provide a more immersive and interactive experience, a new VR rendering algorithm suitable for architectural design has been developed in this paper. In traditional methods, we have carefully analyzed the computer conversion process from 2D drawing to 3D modeling, and innovatively designed a graphics rendering algorithm aimed at accelerating and optimizing the rendering process. However, despite some progress, traditional technologies still face challenges such as limited interactivity and rendering quality bottlenecks. In view of this, the introduction of virtual reality technology was explored, and a lifelike 3D building environment was successfully constructed by seamlessly integrating real-time rendering engines, high-precision sensors, and advanced interactive devices. This environment not only achieves seamless connection and natural interaction between users and virtual building spaces, but also allows users to freely explore and observe building details in virtual roaming, and deeply interact with virtual elements, greatly enhancing immersive experience and interactive fun. The results indicate that in terms of design efficiency, virtual reality design time is generally shorter than traditional technologies. In terms of visual quality, virtual reality technology scores a perfect 5 points, while traditional technology only scores 4 points. In terms of rendering speed, virtual reality technology is 10[Formula: see text]s faster than traditional technology in residential scenes and 15[Formula: see text]s faster in commercial complex scenes. In terms of data processing capability, when processing 20 sets of data, the average processing speed of virtual reality technology is about 58[Formula: see text]s/GB, while traditional technology is 106[Formula: see text]s/GB. The average error rate of virtual reality technology is 1.0%, while traditional technology is 3.0%. In terms of user experience, the rating for virtual reality technology reached 9.2 out of 10, while traditional technology only scored 6.9. The immersion score for virtual reality technology is 9.3 points, while for traditional technology it is 6.7 points. The interactive depth rating for virtual reality technology is 8.7 points, while for traditional technology it is 6.0 points. In practical applications, the rendering time of virtual reality technology is significantly shorter than traditional rendering technology, and user satisfaction ratings are generally higher, with an average rating of 4.7 points or above (out of 5 points).
Heart Rate Estimation Using Deep Learning and Hybrid Artifact Removal for Optical Volume Tracing Signals in Motion States
Authors: Li Jing
Published: February 2025

Due to its non-invasiveness and mobility, photo volumetric tracing (PPG)-based heart rate measurement has drawn a lot of attention. Heart rate is a crucial physiological signal in health monitoring. However, motion artifacts can seriously interfere with PPG signals in a sports setting, which significantly reduces the accuracy of heart rate estimates. This research proposes a hybrid artifact removal (HMR), signal reconstruction (SR), and deep learning (DL)-based heart rate estimate approach (DL[Formula: see text]HMR[Formula: see text]SR) to tackle this issue. To effectively analyze complex artifacts in dynamic settings, the technique combines the fine-grained optimization mechanism of signal reconstruction, the artifact separation approach of hybrid artifact removal, and the feature extraction capabilities of deep learning. Six datasets — running, hand waving, elliptical training, deep squatting, mixed motion, and beckoning — are used in this work to validate the method’s performance. It is then compared to several traditional approaches, including RandF, Temko, TROIKA, JOSS, EEMD, and CorNet. In terms of average error, trend matching, and artifact elimination, the experimental results demonstrate that the method in this paper performs better than the current methods. The average error of [Formula: see text] BPM is significantly lower than that of the classical methods (the average error of TROIKA is [Formula: see text] BPM). The approach presented in this study also shows excellent robustness and application in downstream tasks like emotion recognition, and its average F1 score outperforms that of the other methods under comparison. The findings demonstrate that the [Formula: see text] technique effectively supports health monitoring in wearable devices due to its excellent generalization ability, high accuracy, and robustness in handling dynamic artifacts. This study establishes the groundwork for future advancements in motion artifact elimination approaches and offers fresh ideas for heart rate estimation solutions.
MSTM: Multiscale Spatio-Temporal Modeling for Power Grid Line Loss Prediction
Authors: Wang Jingbian , Ren Qi , Wang Lijun , He Xiaomei , Zhao Huiyong
Published: February 2025

The global shift toward renewable energy has accelerated during the past decade, driven by the pursuit of a sustainable and cleaner future. Technological progress has significantly increased the efficiency of renewable energy systems, enhancing their competitive position of these renewable systems relative to traditional fossil fuels. However, the inherent variability and unpredictability of renewable sources, such as solar and wind, present considerable challenges to maintaining the stability and efficiency of power grids. This paper proposes a multiscale spatio-temporal model (MSTM) to improve power line loss predictions, optimize power dispatch, reduce energy waste, and enhance grid stability and efficiency. MSTM leverages multi-level and multiscale modeling of grid topology and designs a deep learning model to extract and fuse spatio-temporal features. Comparative studies demonstrate that MSTM outperforms existing methods regarding inline loss prediction accuracy. Furthermore, through visualization techniques, we investigate and discuss the impact of temporal and topological characteristics on line loss prediction outcomes, providing a deeper insight into the factors influencing line loss in power networks. These findings underscore the potential of advanced spatio-temporal analysis to enhance renewable energy integration.
Deep Learning-Based Approach to Evaluate the Quality of Corporate Brand Packaging Visual Design
Authors: Shi Daijiao , Song Zhongcheng , Huang Chenhan
Published: February 2025

In today’s market, consumer preferences are increasingly driven by personalized needs, leading to an overwhelming array of brands and products. Often, consumers prioritize brand recognition over quality assessment, prompting companies to innovate in modern packaging design. Beyond traditional functions, such as identification, protection, and enhancement of corporate image, there is a growing emphasis on developing distinctive brand identities and effective communication strategies. This paper proposes the use of deep learning techniques to analyze consumer behavior and packaging design elements, enabling precise clustering and customization. By employing neural networks to extract features from successful packaging designs, companies can create visually appealing and culturally relevant packages that resonate with consumers. Our experiments demonstrate that integrating deep learning into packaging design not only enhances aesthetic quality but also aligns corporate branding strategies with market demands, ultimately fostering a stronger connection with consumers.
Exploring Early Prediction of CKD Using InfNet Segmentation with Cross Domain-Based Few Shot Learning
Authors: Stella A. , Kumari P. Vasanthi
Published: February 2025

Chronic kidney disease (CKD) is a life-threatening condition which is hard to identify early, as there are no symptoms. It is possible to prevent or minimize the evolution of this chronic condition before it reaches an end stage, where dialysis or surgical intervention is the only way to save the patient’s life. Early detection and adequate therapy can increase the risk of this occurring. The majority of supervised techniques employ labeled datasets to build in-domain predictions of CKD. However, the results are typically poor when a classifier is used to categorize an image of CKD in a different domain after it has been trained on labeled images for that domain. However, a machine learning technique known as “cross-domain few-shot learning” involves training a model to generalize information from one domain to another using only a small number of samples from the target domain. So, a novel hybrid classifier with few shot learning is proposed to improve the cross-domain CKD prediction performance. The kidney’s CT images were collected and preprocessed using ENSNet annotation, autoencoder denoising, green fire blue filter and image restoration. The pre-data were provided for the segmentation process using supervised InfNet segmentation, which segments an exact region of CKD. The segmented regions were fed to an input of the classification process. A few shot learning-based hybrid classifiers were developed to predict CKD in the cross-domain. In a few shot learning, more samples were collected for the training phase, and fewer samples were used for the classifier’s testing. Based on the few shot learning, the proposed CKD model was tested and diagnosed with the input samples at appropriate conditions. The designed proposed model offers 97.9% accuracy, 96.4% precision, 96.4% recall and 98.6% negative predictive value. In addition, observed values of the proposed model were contrasted with some other approaches for validating the process. The proposed few-shot learning-based hybrid classifier is an effective choice for more precise cross-domain CKD prediction at low processing time.
Ripening Stage Detection of Mangoes by Size and Maturity Using Hybrid (1D-2D) Convolution-Based Adaptive Densenet with Attention Mechanism
Authors: Vhatkar Kapil , Kathole Atul B. , Dharmale Gulbakshee , Savyanavar Amit Sadanand
Published: February 2025

The classification of mangoes’ ripening stage is the major aspect of supplying better fruit grade to buyers, which is a standard necessity of the fruit processing industry. The optical examination, which is manually done, takes to instability, and it involves a lot of work by human workers. To harvest better-quality mangoes, the measurement of maturity is supremely important. During the development and storing at the context temperature, the differentiation in the surface color, size, Total Soluble Solids (TSS) content, firmness and sphericity are analyzed. To tackle the challenges that formed in the classical mango ripening stage, detection approaches are solved by using the newly proposed deep learning approach to identify the maturity state of mangoes. The required mango pictures are taken from the standard databases, and these pictures are given to the image preprocessing to improve image quality and contrast. The improved quality images are applied to the feature extraction section, where the size, shape and color feature are obtained. After that, the ripening of mango is performed through the “Hybrid (1D-2D) Convolution-based Adaptive DenseNet with Attention Mechanism (HCADNet-AM)” to get efficient classification results. The extracted characteristic is applied as the input to the 1D convolution, and the mango images are given as the input for 2D convolution for classifying the maturity stages. The parameter optimization takes place via the Fitness-aided Random Function in Red Panda Optimization (FRF-RPO) during the ripening stage to improve the performance. The research output is validated with conventional ripening techniques to ensure effectiveness.
A Recruitment System Based on Data Mining: Finding the Best Candidate from Social Media
Authors: Pei Caixia
Published: February 2025

As the advancement of network technologies, the recruitment industry is also showing a trend of networking, but the current online recruitment lacks the application of data mining (DM) technology, and its analysis of data is limited to recruitment websites. Therefore, the study proposes a DM-based online recruitment technology that selects the best career candidate through correlation analysis of social media data. The study uses Scrapy crawler to obtain data and utilises an improved Apriori algorithm for correlation analysis. The research findings denote that the proposed algorithm has excellent convergence performance and training efficiency. The study is of experimental design type using experimental data for analysis. In contrast with the traditional Apriori and FP-growth algorithms, the fitting of the output results increases by 6.21% and 14.67%. In addition, the improved algorithm shows significant optimisation effects, with an average running time reduced by 2.44 s and 0.76 s, respectively, compared with the two algorithms, and is less affected by the minimum confidence level. In fit testing, the average error of this method is only 0.02. In summary, online recruitment technology based on DM has strong availability and high reliability. The improved algorithm has excellent performance, accurate output results, and can accurately apply data from social media to select the best job candidate.
Not on the Best Path
Authors: Hoffmann Leah
Published: February 2025

Gary Marcus discusses, among other things, why he thinks Large Language Models have entered a “period of diminishing returns.”
I Have Not Understood but Agree: Studying Informed Consent in the Context of the German COVID-19 Contact Tracing App
Authors: Häring Maximilian , Tiefenau Eva , Tiefenau Christian , Kretschmer Felix , Stöver Alina , Gerber Nina
Published: February 2025

Many EU data collectors rely on informed consent for data processing, requiring users to consent after being informed. To do so, it is necessary for users to have at least partially correct assumptions about what the software does. The introduction of the official German contact tracing app, the Corona-Warn-App (CWA), provides an interesting use case to explore whether potential users are capable of being informed with a reasonable amount of effort by the publishers of software. We captured CWA users’ and non-users’ mental models of data collection and processing in the app in interviews (N=20) and a survey study (N=352). We investigated whether users have enough correct assumptions to be considered informed. Our findings show that the participants had misconceptions. Therefore, we argue that user consent might often lack the required level of informedness and may be replaced by a more rigorous privacy-by-design principle.
Study of pH Gradients and Carbonation of Hydroxide Exchange Membrane Electrolyzers
Authors: Oliveira Alexandra M. , Setzler Brian P. , Yan Yushan
Published: February 2025

Hydroxide exchange membrane electrolyzers (HEMELs) can produce hydrogen at scale with high efficiencies. However, like their HEM fuel cell counterparts, the alkaline membrane and ionomer of HEMELs may be susceptible to CO2 contamination and cause performance losses. CO2 can form (bi)carbonates which increase ohmic resistances due to their reduced conductivity compared to hydroxide. More importantly, the potential gradient across the membrane drives a self-purging mechanism which can lower the anode pH, causing thermodynamic overpotentials. We used modeling and experiments to study these phenomena in HEMELs in order to understand CO2-related losses through the conductivity and pH effects of different CO2 concentrations over a range of current densities. We found that pH gradients are the more significant barrier to cell performance and controlled them using three supporting electrolytes. We found that operating HEMELs at high current densities >1000 mA cm−2 can recover >200 mV of overpotential due to self-purging of (bi)carbonates, but there is still some unrecoverable overpotential from the generated pH gradients. KOH electrolytes can be used to reduce this pH gradient, but K2CO3 and KHCO3 supporting electrolytes are susceptible to the same detrimental effects of carbonation and should not be used to minimize CO2 contamination.
Single incretin receptor knockout mice do not compensate by increasing glucose-stimulated secretion of the remaining incretin hormone
Authors: Galsgaard Katrine D. , Vergara Jon , Jepsen Sara L. , Bazzichi Alice , Kissow Hannelouise , Smits Mark M. , Holst Jens J.
Published: February 2025

We show that mice lacking the GLP-1 receptor do not compensate by increased glucose-stimulated GIP secretion or sensitivity, nor do mice lacking the GIP receptor compensate by increased glucose-stimulated GLP-1 secretion or sensitivity. The notion of a compensatory adaptation to the loss of single incretin signaling via increased action/secretion of the remaining incretin hormone was thus not supported using single incretin receptor knockout mice.