bluuebunny/crossref_metadata_2025 huggingface dataset:
Patient out-of-pocket costs for guideline-recommended treatments for erectile dysfunction: a medicare cost modeling analysis
Authors: Nguyen Vi , McGovern Alysha M. , Rojanasarot Sirikan , Patel Darshan P. , Bhattacharyya Samir , Hargens Liesl M. , Aworunse Olubiyi , Hsieh Tung-Chin
Published: June 2024

Patient out-of-pocket (OOP) cost represents an access barrier to erectile dysfunction (ED) treatment. We determined OOP cost for men with ED covered by Fee-for-Service Medicare. Coverage policies were obtained from the Medicare Coverage Database for treatments recommended by the 2018 American Urological Association (AUA) guidelines. OOP cost was retrieved from the 2023 Centers for Medicare & Medicaid Services Final Rule. OOP cost for treatments without Medicare coverage were extracted from GoodRx® or literature and inflated to 2022 dollars. Annual prescription costs were calculated using the published estimate of 52.2 yearly instances of sexual intercourse. Medicare has coverage for inflatable penile prostheses (IPP; strong recommendation), non-coverage for vacuum erection devices (VED; moderate recommendation) and phosphodiesterase type-5 inhibitors (PDE5i; strong recommendation), and no policies for intracavernosal injections (ICI; moderate recommendation), intraurethral alprostadil (IA; conditional recommendation), or low-intensity extracorporeal shock wave therapy (ESWT; conditional recommendation). Annual IA prescription is most costly ($4022), followed by ICI prescription ($3947), one ESWT course ($3445), IPP ($1600), PDE5i prescription ($696), and one VED ($213). PDE5i and IPP, both strongly recommended by AUA guidelines, are associated with lower OOP cost. Better understanding of patient financial burden may inform healthcare decision-making.
Tunable interstitial and vacancy diffusivity by chemical ordering control in CrCoNi medium-entropy alloy
Authors: Li Yangen , Du Jun-Ping , Shinzato Shuhei , Ogata Shigenobu
Published: June 2024

In this study, we utilized a quantitative atomistic analysis approach to investigate the impact of chemical ordering structures on the diffusion behavior of interstitials and vacancies within the CrCoNi medium entropy alloy (MEA), employing an advanced neural network interatomic potential (NNP). We discovered that the degree of chemical ordering, which can be precisely controlled through annealing at elevated temperatures, significantly influences both interstitial and vacancy diffusion. This phenomenon contributes to the notable sluggish diffusion characteristic of CrCoNi, largely attributable to the restriction of diffusion pathways in regions with lower degree of chemical ordering. We also emphasized the crucial role of operating temperature on diffusion, which should be remained well below the annealing temperature to preserve the sluggish diffusion effect. Our research sheds light on the interplay between chemical ordering and defect diffusion in MEAs, and it proposes effective strategies for tailoring the diffusivity of MEAs by altering their chemical ordering. These insights are instrumental in the development of next-generation materials, which are optimized for use in challenging environments, such as high-temperature and irradiation conditions.
A retrospective study of the MDS criteria for prodromal Parkinson’s disease in the general population
Authors: de Klerk Gijs W. , van Laar Teus , Meles Sanne K.
Published: June 2024

The Movement Disorder Society developed research criteria for the detection of the prodromal phase of Parkinson’s disease (PD). Accurate identification of this phase is essential for early interventions. Therefore, we investigated the diagnostic value of these research criteria in the general population. Lifelines is an ongoing cohort study of 167,000 participants from the general population of the Northern Netherlands. 160 participants self-reported to have developed PD during three rounds of follow-up of five years each. Data were available to infer six out of eleven risk markers, and six out of twelve prodromal markers. We retrospectively compared the criteria in the prodromal stage of a group of 160 ‘converters’ with 320 age- and sex-matched controls. The overall incidence rate of PD was 0.20 per 1.000 person-years (95% CI: 0.049−0.36), increasing with age and rates were higher in men. The median probability for prodromal PD in PD-converters was 1.29% (interquartile range: 0.46−2.9), compared to 0.83% (0.39−1.8) for controls (P = 0.014). The MDS set of criteria for prodromal PD had an ROC-AUC of 0.577, and was therefore not sufficient to adequately predict conversion to PD. We were unable to predict conversion to PD in the general population using a selection of the prodromal PD research criteria. Ancillary investigations are required to improve the diagnostic accuracy of the criteria, but most are precluded from large-scale use. Strategies, including olfactory tests or alpha-synuclein seeding amplification assays may improve the detection of prodromal PD in the general population.
Loss of Kmt2c or Kmt2d drives brain metastasis via KDM6A-dependent upregulation of MMP3
Authors: Seehawer Marco , Li Zheqi , Nishida Jun , Foidart Pierre , Reiter Andrew H. , Rojas-Jimenez Ernesto , Goyette Marie-Anne , Yan Pengze , Raval Shaunak , Munoz Gomez Miguel , Cejas Paloma , Long Henry W. , Papanastasiou Malvina , Polyak Kornelia
Published: June 2024

KMT2C and KMT2D, encoding histone H3 lysine 4 methyltransferases, are among the most commonly mutated genes in triple-negative breast cancer (TNBC). However, how these mutations may shape epigenomic and transcriptomic landscapes to promote tumorigenesis is largely unknown. Here we describe that deletion of Kmt2c or Kmt2d in non-metastatic murine models of TNBC drives metastasis, especially to the brain. Global chromatin profiling and chromatin immunoprecipitation followed by sequencing revealed altered H3K4me1, H3K27ac and H3K27me3 chromatin marks in knockout cells and demonstrated enhanced binding of the H3K27me3 lysine demethylase KDM6A, which significantly correlated with gene expression. We identified Mmp3 as being commonly upregulated via epigenetic mechanisms in both knockout models. Consistent with these findings, samples from patients with KMT2C-mutant TNBC have higher MMP3 levels. Downregulation or pharmacological inhibition of KDM6A diminished Mmp3 upregulation induced by the loss of histone–lysine N-methyltransferase 2 (KMT2) and prevented brain metastasis similar to direct downregulation of Mmp3. Taken together, we identified the KDM6A–matrix metalloproteinase 3 axis as a key mediator of KMT2C/D loss-driven metastasis in TNBC.
Structural mechanism of bridge RNA-guided recombination
Authors: Hiraizumi Masahiro , Perry Nicholas T. , Durrant Matthew G. , Soma Teppei , Nagahata Naoto , Okazaki Sae , Athukoralage Januka S. , Isayama Yukari , Pai James J. , Pawluk April , Konermann Silvana , Yamashita Keitaro , Hsu Patrick D. , Nishimasu Hiroshi
Published: June 2024

Insertion sequence (IS) elements are the simplest autonomous transposable elements found in prokaryotic genomes1. We recently discovered that IS110 family elements encode a recombinase and a non-coding bridge RNA (bRNA) that confers modular specificity for target DNA and donor DNA through two programmable loops2. Here we report the cryo-electron microscopy structures of the IS110 recombinase in complex with its bRNA, target DNA and donor DNA in three different stages of the recombination reaction cycle. The IS110 synaptic complex comprises two recombinase dimers, one of which houses the target-binding loop of the bRNA and binds to target DNA, whereas the other coordinates the bRNA donor-binding loop and donor DNA. We uncovered the formation of a composite RuvC–Tnp active site that spans the two dimers, positioning the catalytic serine residues adjacent to the recombination sites in both target and donor DNA. A comparison of the three structures revealed that (1) the top strands of target and donor DNA are cleaved at the composite active sites to form covalent 5′-phosphoserine intermediates, (2) the cleaved DNA strands are exchanged and religated to create a Holliday junction intermediate, and (3) this intermediate is subsequently resolved by cleavage of the bottom strands. Overall, this study reveals the mechanism by which a bispecific RNA confers target and donor DNA specificity to IS110 recombinases for programmable DNA recombination.
Megastudy shows that reminders boost vaccination but adding free rides does not
Authors: Milkman Katherine L. , Ellis Sean F. , Gromet Dena M. , Jung Youngwoo , Luscher Alex S. , Mobarak Rayyan S. , Paxson Madeline K. , Silvera Zumaran Ramon A. , Kuan Robert , Berman Ron , Lewis Neil A. , List John A. , Patel Mitesh S. , Van den Bulte Christophe , Volpp Kevin G. , Beauvais Maryann V. , Bellows Jonathon K. , Marandola Cheryl A. , Duckworth Angela L.
Published: June 2024

Encouraging routine COVID-19 vaccinations is likely to be a crucial policy challenge for decades to come. To avert hundreds of thousands of unnecessary hospitalizations and deaths, adoption will need to be higher than it was in the autumn of 2022 or 2023, when less than one-fifth of Americans received booster vaccines1,2. One approach to encouraging vaccination is to eliminate the friction of transportation hurdles. Previous research has shown that friction can hinder follow-through3 and that individuals who live farther from COVID-19 vaccination sites are less likely to get vaccinated4. However, the value of providing free round-trip transportation to vaccination sites is unknown. Here we show that offering people free round-trip Lyft rides to pharmacies has no benefit over and above sending them behaviourally informed text messages reminding them to get vaccinated. We determined this by running a megastudy with millions of CVS Pharmacy patients in the United States testing the effects of (1) free round-trip Lyft rides to CVS Pharmacies for vaccination appointments and (2) seven different sets of behaviourally informed vaccine reminder messages. Our results suggest that offering previously vaccinated individuals free rides to vaccination sites is not a good investment in the United States, contrary to the high expectations of both expert and lay forecasters. Instead, people in the United States should be sent behaviourally informed COVID-19 vaccination reminders, which increased the 30-day COVID-19 booster uptake by 21% (1.05 percentage points) and spilled over to increase 30-day influenza vaccinations by 8% (0.34 percentage points) in our megastudy. More rigorous testing of interventions to promote vaccination is needed to ensure that evidence-based solutions are deployed widely and that ineffective but intuitively appealing tools are discontinued.
Zinc mediates control of nitrogen fixation via transcription factor filamentation
Authors: Lin Jieshun , Bjørk Peter K. , Kolte Marie V. , Poulsen Emil , Dedic Emil , Drace Taner , Andersen Stig U. , Nadzieja Marcin , Liu Huijun , Castillo-Michel Hiram , Escudero Viviana , González-Guerrero Manuel , Boesen Thomas , Pedersen Jan Skov , Stougaard Jens , Andersen Kasper R. , Reid Dugald
Published: June 2024

Plants adapt to fluctuating environmental conditions by adjusting their metabolism and gene expression to maintain fitness1. In legumes, nitrogen homeostasis is maintained by balancing nitrogen acquired from soil resources with nitrogen fixation by symbiotic bacteria in root nodules2–8. Here we show that zinc, an essential plant micronutrient, acts as an intracellular second messenger that connects environmental changes to transcription factor control of metabolic activity in root nodules. We identify a transcriptional regulator, FIXATION UNDER NITRATE (FUN), which acts as a sensor, with zinc controlling the transition between an inactive filamentous megastructure and an active transcriptional regulator. Lower zinc concentrations in the nodule, which we show occur in response to higher levels of soil nitrate, dissociates the filament and activates FUN. FUN then directly targets multiple pathways to initiate breakdown of the nodule. The zinc-dependent filamentation mechanism thus establishes a concentration readout to adapt nodule function to the environmental nitrogen conditions. In a wider perspective, these results have implications for understanding the roles of metal ions in integration of environmental signals with plant development and optimizing delivery of fixed nitrogen in legume crops.
Transposase-assisted target-site integration for efficient plant genome engineering
Authors: Liu Peng , Panda Kaushik , Edwards Seth A. , Swanson Ryan , Yi Hochul , Pandesha Pratheek , Hung Yu-Hung , Klaas Gerald , Ye Xudong , Collins Megan V. , Renken Kaili N. , Gilbertson Larry A. , Veena Veena , Hancock C. Nathan , Slotkin R. Keith
Published: June 2024

The current technologies to place new DNA into specific locations in plant genomes are low frequency and error-prone, and this inefficiency hampers genome-editing approaches to develop improved crops1,2. Often considered to be genome ‘parasites’, transposable elements (TEs) evolved to insert their DNA seamlessly into genomes3–5. Eukaryotic TEs select their site of insertion based on preferences for chromatin contexts, which differ for each TE type6–9. Here we developed a genome engineering tool that controls the TE insertion site and cargo delivered, taking advantage of the natural ability of the TE to precisely excise and insert into the genome. Inspired by CRISPR-associated transposases that target transposition in a programmable manner in bacteria10–12, we fused the rice Pong transposase protein to the Cas9 or Cas12a programmable nucleases. We demonstrated sequence-specific targeted insertion (guided by the CRISPR gRNA) of enhancer elements, an open reading frame and a gene expression cassette into the genome of the model plant Arabidopsis. We then translated this system into soybean—a major global crop in need of targeted insertion technology. We have engineered a TE ‘parasite’ into a usable and accessible toolkit that enables the sequence-specific targeting of custom DNA into plant genomes.
The Swedish Cervical Screening Cohort
Authors: Dillner Joakim , Mühr Laila Sara Arroyo , Kleppe Sara Nordqvist , Wang Jiangrong , Andersson Helena , Elfström Miriam , Merino Roxana , Sundström Karin
Published: June 2024

The Cervical Screening Cohort enrols women screened for human papillomavirus (HPV) and cervical abnormalities within the capital region of Sweden from the organised screening program and the non-organised testing of cervical samples. The cohort started in 2011 and has enrolled more than 670,000 women, contributing with more than 1.2 million biobanked samples. The cohort is systematically updated with individual-level data from the Swedish National Cervical Screening Registry (NKCx). Key variables include birthdate, sampling date, cytological, histopathological and HPV analysis results, and invitation history. Each sampling and subsequent clinical follow-up is sequentially registered, allowing for longitudinal analyses of screening results and associated results of the clinical workup. The cohort is ideal for longitudinal, long-term follow-up studies due to its validated documentation and registry-derived information. From the data, it is possible to penetrate important human health mechanisms. The data are available as open-data and GDPR-compliant. Samples are available after getting the required permissions. Results will help researchers understand factors that increase cancer risk and other diseases.
Incidence and clinical analysis of asymptomatic intracranial hemorrhage in neonates with cerebral hypoxic-ischaemic risk based on multisequence MR images
Authors: Xie Qi , Liao Yan-Hui , He Wen-juan , Wang Gui-Qin
Published: June 2024

The incidence and clinical distribution of intracranial haemorrhage (ICH) in neonates at risk of cerebral hypoxia–ischaemia have not been reported in specific studies. Based on conventional magnetic resonance imaging (MRI) versus susceptibility weighted imaging (SWI), this study aimed to analyse the occurrence of asymptomatic ICH in newborns with or without risk of cerebral hypoxia–ischaemia and to accumulate objective data for clinical evaluations of high-risk neonates and corresponding response strategies. 317 newborns were included. MRI revealed that the overall incidence of ICH was 59.31%. The most common subtype was intracranial extracerebral haemorrhage (ICECH) which included subarachnoid haemorrhage (SAH) and subdural haemorrhage (SDH). ICECH accounted for 92.02% of ICH. The positive detection rate of ICECH by SWI was significantly higher than that by T1WI. The incidence of total ICH, ICECH and SAH was greater among children who were delivered vaginally than among those who underwent caesarean delivery. Asymptomatic neonatal ICH may be a common complication of the neonatal birth process, and SWI may improve the detection rate. Transvaginal delivery and a weight greater than 2500 g were associated with a high incidence of ICECH in neonates. The impact of neonatal cerebral hypoxia–ischaemia risk factors on the occurrence of asymptomatic ICH may be negligible.
Novel amino-ethyl carboxymethyl cellulose crosslinked ampholyte hydrogel development for Methyl orange removal from waste water
Authors: Omer Ahmed M. , Sadik Wagih A. , Abbas Rafik , Tamer Tamer M. , Abd-Ellatif Mai M. , Mohy-Eldin Mohamed S.
Published: June 2024

In the modern era, with the rapid growth of various industries, the issues of energy crisis and environmental pollution have garnered increasing attention. One significant source of industrial pollution is printing and dyeing wastewater. This wastewater often contains dyes that have aromatic structures and azo groups, such as Methyl orange (MO), which are both toxic and difficult to degrade. If these dyes are released into the wastewater stream without any treatment, they can have adverse effects on ecological balance and human health. Therefore, it is crucial to identify suitable treatment strategies to efficiently remove dyes from wastewater systems before discharge. In this study, the Methyl orange (MO) azo dye has been removed from dyes-contaminated wastewater, for the first time, using a novel amino-ethyl carboxymethyl cellulose crosslinked ampholyte hydrogel (AECMC). Different characterization methods, including FTIR, TGA, and DSC were used to characterize the generated AECMC compounds. The water absorption and cationic exchange capacities were assessed. Factors affecting the MO anions adsorption including MO concentration, adsorption pH, temperature, time, adsorbent dose, and agitation speed have been investigated. Moreover, the kinetics of the adsorption process was assessed by the use of three models: pseudo-first-order, Pseudo-second-order, and Elovich. Moreover, the mechanism of the adsorption process was monitored using the Intraparticle diffusion and Boyd models. Additionally, the adsorption isotherm was examined using established models such as Langmuir, Freundlich, and Temkin isotherms. The thermodynamic characteristics of the MO adsorption process have been investigated at various adsorption temperatures using the Van't Hoff model. The results obtained from the study indicate that the process of MO adsorption adhered to the Pseudo-second-order kinetic model, the Langmuir isotherm model was found to be applicable, and spontaneous and exhibited an endothermic character. In conclusion, the developed novel amino-ethyl carboxymethyl cellulose crosslinked ampholyte hydrogels (AECMC) have successive in the removal of the MO anionic dye from contaminated wastewater.
Neferine inhibits BMECs pyroptosis and maintains blood–brain barrier integrity in ischemic stroke by triggering a cascade reaction of PGC-1α
Authors: Zheng Zi-jian , Zhu Li-zhi , Qiu Han , Zheng Wu-yin-xiao , You Peng-tao , Chen Shu-he , Hu Chun-ling , Huang Jun-rong , Zhou Ya-jun
Published: June 2024

Blood–brain barrier disruption is a critical pathological event in the progression of ischemic stroke (IS). Most studies regarding the therapeutic potential of neferine (Nef) on IS have focused on neuroprotective effect. However, whether Nef attenuates BBB disruption during IS is unclear. We here used mice underwent transient middle cerebral artery occlusion (tMCAO) in vivo and bEnd.3 cells exposed to oxygen–glucose deprivation/reoxygenation (OGD/R) injury in vitro to simulate cerebral ischemia. We showed that Nef reduced neurobehavioral dysfunction and protected brain microvascular endothelial cells and BBB integrity. Molecular docking, short interfering (Si) RNA and plasmid transfection results showed us that PGC-1α was the most binding affinity of biological activity protein for Nef. And verification experiments were showed that Nef upregulated PGC-1α expression to reduce mitochondrial oxidative stress and promote TJ proteins expression, further improves the integrity of BBB in mice. Intriguingly, our study showed that neferine is a natural PGC-1α activator and illustrated the mechanism of specific binding site. Furthermore, we have demonstrated Nef reduced mitochondria oxidative damage and ameliorates endothelial inflammation by inhibiting pyroptosis to improve BBB permeability through triggering a cascade reaction of PGC-1α via regulation of PGC-1α/NLRP3/GSDMD signaling pathway to maintain the integrity of BBB in ischemia/reperfusion injury.
High prevalence of albuminuria among adult males living with HIV in Botswana
Authors: Mosepele Mosepele , Ponatshego Ponego , Molebatsi Kesaobaka , Williams Christopher , Mokgatlhe Lucky , Lockman Shahin , Youssouf Nabila , Gross Robert , Jarvis Joseph , Wang Duolao , Jaffar Shabbar
Published: June 2024

Chronic HIV disease is associated with a fivefold increase in albuminuria outside of sub-Saharan Africa. However, very little is known about albuminuria risk among people living with HIV (PLWH) in sub-Saharan Africa. Therefore, we conducted a cross-sectional observational HIV clinic-based study of albuminuria among 1533 adults aged 21 years or older between January 2020 and January 2021 in Gaborone, Botswana. Clinical albuminuria was defined using a sex-based albumin‒creatinine ratio (ACR) of 25–355 mg/g for females and 17–250 mg/g for males. The study population mean age was 48.5 (SD 10.3) years, and 764/1533 (49.7%) were female. The overall prevalence of albuminuria was 20.7% (95% CI 18.7%, 22.8%). A higher proportion of males were more likely to be categorized as having albuminuria than females, 25% (95% CI 22.0, 28.2) versus 16.4% (95% CI 13.8,19.2), P value < 0.001. In the final multivariate models, predictors of albuminuria differed by sex group. Larger longitudinal studies are required to evaluate the impact of albuminuria among PLWH with particular emphasis on the effect of sex on the risk of albuminuria.
Development and validation of a novel disulfidptosis-related lncRNAs signature in patients with HPV-negative oral squamous cell carcinoma
Authors: Yang Fan , Niu Xinyu , Zhou Mingzhu , Li Wei
Published: June 2024

Disulfidptosis is a recently identified mode of regulated cell death. Regulating disulfidptosis in carcinoma is a promising therapeutic approach. Long non-coding RNAs (lncRNAs) have been reported to be related to the occurrence and development of many cancers. Disulfidptosis-related lncRNAs (DRLs) in HPV-negative oral squamous cell carcinoma (OSCC) have not been studied. Based on The Cancer Genome Atlas (TCGA) database, least absolute shrinkage selection operator (LASSO) analysis and Cox regression analysis were used to identify overall survival related DRLs and construct the signature. Kaplan–Meier, time-dependent receiver operating characteristics (ROC) and principal component analyses (PCA) were explored to demonstrate the prediction potential of the signature. Subgroup analysis stratified by different clinicopathological characteristics were conducted. Nomogram was established by DRLs signature and independent clinicopathological characteristics. The calibration plots were performed to reveal the accuracy of nomogram. Immune cell subset infiltration, immunotherapy response, drug sensitivity analysis, and tumor mutation burden (TMB) were conducted. Underlying functions and pathways were explored by Gene Set Enrichment Analysis (GSEA) analysis. Previous lncRNA signatures of OSCC were retrieved from PubMed for further validation. Gene expression omnibus (GEO) datasets (GSE41613 and GSE85446) were merged as an external validation for DRLs signature. Consensus clustering analysis of DRLs signature and experimental validation of DRLs were also explored. This research sheds light on the robust performance of DRLs signature in survival prediction, immune cell infiltration, immune escape, and immunotherapy of HPV-negative OSCC.
Identification of bladder cancer subtypes and predictive signature for prognosis, immune features, and immunotherapy based on immune checkpoint genes
Authors: Wu Jiyue , Zhang Feilong , Zheng Xiang , Chen Dongshan , Li Zhen , Bi Qing , Qiu Xuemeng , Sun Zejia , Wang Wei
Published: June 2024

Immunotherapy based on immune checkpoint genes (ICGs) has recently made significant progress in the treatment of bladder cancer patients, but many patients still cannot benefit from it. In the present study, we aimed to perform a comprehensive analysis of ICGs in bladder cancer tissues with the aim of evaluating patient responsiveness to immunotherapy and prognosis. We scored ICGs in each BLCA patient from TCGA and GEO databases by using ssGSEA and selected genes that were significantly associated with ICGs scores by using the WCGNA algorithm. NMF clustering analysis was performed to identify different bladder cancer molecular subtypes based on the expression of ICGs-related genes. Based on the immune related genes differentially expressed among subgroups, we further constructed a novel stratified model containing nine genes by uni-COX regression, LASSO regression, SVM algorithm and multi-COX regression. The model and the nomogram constructed based on the model can accurately predict the prognosis of bladder cancer patients. Besides, the patients classified based on this model have large differences in sensitivity to immunotherapy and chemotherapy, which can provide a reference for individualized treatment of bladder cancer.
Predicting prognosis in colorectal cancer patients with curative resection using albumin, lymphocyte count and RAS mutations
Authors: Miyata Toshiya , Hayama Tamuro , Ozawa Tsuyoshi , Nozawa Keijiro , Misawa Takeyuki , Fukagawa Takeo
Published: June 2024

Colorectal cancer (CRC) poses a significant global health challenge, demanding reliable prognostic tools to guide treatment decisions. This study introduces a novel prognostic scoring system, the albumin-total lymphocyte count-RAS index (ALRI), integrating serum albumin, lymphocyte count, and RAS gene mutations. A cohort of 445 stage I–III CRC patients undergoing curative resection was analyzed, revealing ALRI's association with clinicopathological factors, including age, tumor location, and invasion depth. The ALRI demonstrated superior prognostic value, with a cutoff value of 2 distinguishing high and low-risk groups. The high-ALRI group exhibited elevated rates of recurrence. Univariate and multivariate analyses identified ALRI as an independent predictor for both 5 year recurrence-free survival (RFS) and overall survival (OS). Kaplan–Meier curves illustrated significant differences in RFS and OS between high and low-ALRI groups, emphasizing ALRI's potential as a prognostic marker. Importantly, ALRI outperformed existing nutritional indices, such as controlling nutritional status and neutrophil-to-lymphocyte ratio, in predicting overall survival. The study underscores the comprehensive insight provided by ALRI, combining inflammatory, nutritional, and genetic information for robust prognostication in CRC patients. This user-friendly tool demonstrates promise for preoperative prognosis and personalized treatment strategies, emphasizing the crucial role of inflammation and nutrition in CRC outcomes.
Prevalence of peripheral neuropathy, amputation, and quality of life in patients with diabetes mellitus
Authors: Perveen Wajida , Ahsan Hafsa , Rameen Shahzad  , Fayyaz Samra , Zaif Ayesha , Paracha Mahnoor Asif , Nuhmani Shibili , Khan Masood , Alghadir Ahmad H.
Published: June 2024

Peripheral neuropathy and amputation are common complications of diabetes mellitus (DM) that significantly impact the quality of life of the affected individuals. This study aims to investigate the prevalence of peripheral neuropathy, the level of amputation, and the quality of life in patients with DM. This cross-sectional study was conducted after approval of the synopsis involving 225 diagnosed patients with DM on pre-defined eligibility criteria, selected from public sector OPDs, specialized diabetes centres, and centres manufacturing orthotics and prosthetics. Data were collected through interviews, observations, and the administration of the Michigan Neuropathy Screening Instrument and the Asian Diabetes Quality of Life Questionnaire. The level of amputation was recorded for each participant. Data was entered into SPSS, and results were synthesized. Pearson correlation is applied to find an association between gender and the quality of life of the participants, while P ≤ 0.05 will be considered significant. The prevalence of peripheral neuropathy in a sample of 225, based on a self-administered questionnaire, was (44.4%), and in terms of foot examination was (51.1%). As people progressed in age, the prevalence increased to 20.0% in patients above 60 years and 8.9% in ≤ 35 years of age. The majority of participants (56.0%) have had DM for less than five years. Females were 57.8% of the study population, while 97.8% of participants had type II DM. Below-knee amputation of the right limb was observed in 22(9.8%) of the participants. The QoL was poor in the majority of the participants (96.9%) patients with DM (P = 0.638 and T = -0.471). This cross-sectional study highlights a high prevalence of peripheral neuropathy and amputation and poor QoL in patients with diabetic mellitus.
Prediction of CO2 solubility in Ionic liquids for CO2 capture using deep learning models
Authors: Ali Mazhar , Sarwar Tooba , Mubarak Nabisab Mujawar , Karri Rama Rao , Ghalib Lubna , Bibi Aisha , Mazari Shaukat Ali
Published: June 2024

Ionic liquids (ILs) are highly effective for capturing carbon dioxide (CO2). The prediction of CO2solubility in ILs is crucial for optimizing CO2capture processes. This study investigates the use of deep learning models for CO2solubility prediction in ILs with a comprehensive dataset of 10,116 CO2solubility data in 164 kinds of ILs under different temperature and pressure conditions. Deep neural network models, including Artificial Neural Network (ANN) and Long Short-Term Memory (LSTM), were developed to predict CO2solubility in ILs. The ANN and LSTM models demonstrated robust test accuracy in predicting CO2solubility, with coefficient of determination (R2) values of 0.986 and 0.985, respectively. Both model's computational efficiency and cost were investigated, and the ANN model achieved reliable accuracy with a significantly lower computational time (approximately 30 times faster) than the LSTM model. A global sensitivity analysis (GSA) was performed to assess the influence of process parameters and associated functional groups on CO2solubility. The sensitivity analysis results provided insights into the relative importance of input attributes on output variables (CO2solubility) in ILs. The findings highlight the significant potential of deep learning models for streamlining the screening process of ILs for CO2capture applications.
Postoperative rehabilitation and quality of life evaluation for transoral endoscopic thyroidectomy vestibular approach
Authors: Mao Yu , Zhou Shiwei , Wu Peng , Li Wu , Li Hui , Wang Zhiyuan , Xia Xibin , Song Xiaohua , Wang Mingming , Peng Xiaowei
Published: June 2024

There are no targeted rehabilitation training modalities and assessment tools for patients after transoral endoscopic thyroidectomy vestibular approach (TOETVA). Herein, we develop a new assessment questionnaire and rehabilitation training modality and evaluate its safety and effectiveness. The THYCA-QoL-TOETVA questionnaire was compiled, and reliability and validity analyses were performed. Patients were divided into the new rehabilitation training group (N) or the conventional rehabilitation training group (C), and 1:1 propensity score matching (PSM) was performed after administering questionnaires to patients in both groups. Cervical range of motion (CROM) data were also measured and collected for statistical analysis. The questionnaire used in this study showed good expert authority, coordination, internal consistency, and questionnaire reliability. A total of 476 patients were included after PSM, and the questionnaire results showed that recovery and quality of life were better in the N group than in the C group (124.55 ± 8.171 vs. 122.94 ± 8.366, p = 0.026). Analysis of cervical spine mobility showed that rehabilitation was better in the N group compared to the C group at postoperative one month (flexion: 1.762°, extension: 4.720°, left lateral bending: 3.912°, right lateral bending: 4.061°, left axial rotation: 5.180°, right axial rotation: 5.199°, p value all of these < 0.001), and at postoperative three months (flexion: 2.866°, extension: 2.904°, left lateral bending: 3.927°, right lateral bending: 3.330°, left axial rotation: 4.395°, right axial rotation: 3.992°, p value all of these < 0.001). The THYCA-QoL-TOETVA provides an appropriate and effective tool for measuring the postoperative quality of life of TOETVA patients. This new rehabilitation training can effectively alleviate the problem of limited neck movement and improve the quality of life of patients after TOETVA surgery.

Trial registration: ChiCTR2300069097.
Comparative analysis of the distribution and antifungal susceptibility of yeast species in cat facial hair and human nails
Authors: Yurayart Chompoonek , Niae Sara , Limsivilai Orawan , Thengchaisri Naris , Sattasathuchana Panpicha
Published: June 2024

Zoonotic yeast species have been implicated in disease development in both humans and cats. This study analyzed the yeast mycobiota present in feline facial hair and human nails and explored potential interspecies associations. A total of 118 biological specimens were examined, including 59 feline facial hair and 59 human nail samples. DNA extraction and DNA sequencing were performed to identify the specific yeast species. The most predominant yeast species in humans and cats were selected for antifungal susceptibility testing (itraconazole, ketoconazole, miconazole, and terbinafine). The findings unveiled diverse yeast species in cats and humans. Malassezia pachydermatis (45.8%) and Malassezia furfur (30.5%) were the most common yeast species in cats and humans, respectively. However, no significant correlation was detected between the yeast species identified in cats and their owners residing in the same household (p > 0.05). Miconazole exhibited the highest minimum inhibitory concentrations (MICs) against Malassezia pachydermatis and Malassezia furfur in both cat and human isolates, whereas terbinafine showed the lowest MICs against most Malassezia pachydermatis and Malassezia furfur in both cat and human isolates. Diverse yeast species in cat facial hair and human nails suggest possible cross-contamination among humans, pets, and environments.
Survival benefit of inhaled corticosteroids in patients with chronic obstructive pulmonary disease: a nationwide cohort study
Authors: Shin Jiyoung , Park Sojung , Lee Ji-Young , Lee Jin Hwa
Published: June 2024

The role of inhaled corticosteroids (ICS) in chronic obstructive pulmonary disease (COPD) is debated. We investigated whether the administration of ICS could lower the mortality risk in patients with COPD. We utilized the Korean National Health Insurance Service-National Sample Cohort database from 2002 to 2019. We included patients who had claim codes for COPD and inhalation respiratory medicine at least twice a year. A time-dependent Cox regression model was employed to estimate the association between ICS usage and survival. The cumulative dose of ICS was classified into three groups, and the mortality risk was compared among these groups. Of 16,463 included patients, there were 4395 (26.7%) deaths during the mean follow-up period of 5.0 years. The time-dependent Cox regression model demonstrated that ICS users had a significantly lower mortality risk compared to non-users (adjusted hazard ratio, 0.89; 95% CI, 0.83–0.94; p < 0.001), particularly among individuals aged ≥ 55 years, women, never smokers, and those with history of asthma or coronary heart disease. Higher cumulative dose groups were associated with a lower mortality risk compared to the lowest cumulative dose group. In conclusion, the administration of ICS seemed to be associated with a lower mortality risk in patients with COPD.
Association of smoking cessation patterns and untreated smoking with glaucoma, cataract, and macular degeneration: a population-based retrospective study
Authors: Tseng Yuan-Tsung , Huang Sheng-Tang , Wang Chun-Hsiang , Wang Ling-Yu , Kuo Yi-Chun
Published: June 2024

This study aims to assess the association between nicotine replacement therapy (NRT), varenicline, and untreated smoking with the risk of developing eye disorders. We employed a new-user design to investigate the association between NRT use and the incidence of eye disorders by the Taiwan National Health Insurance program. This study included 8416 smokers who received NRT and 8416 smokers who did not receive NRT (control group) matched using propensity scores between 2007 and 2018. After adjustment for relevant factors, a multivariable Cox regression analysis revealed that compared with untreated smokers, NRT use was associated with a significantly reduced risk of macular degeneration (hazard ratio [HR]: 0.34; 95% confidence interval [CI]: 0.13–0.87, P = 0.024). When stratified by dose, short-term NRT use (8–28 defined daily doses) was associated with significantly lower risk of glaucoma (HR: 0.35; 95% CI: 0.16–0.80, P = 0.012) and a trend toward reduced risk of cataract (HR: 0.60; 95% CI: 0.36–1.01, P = 0.053) compared to no treatment. However, these associations were not observed with long-term NRT use. The results of this real-world observational study indicate that NRT use, particularly short-term use, was associated with a lower risk of certain eye disorders compared to no treatment for smoking cessation. Long-term NRT use did not demonstrate the same benefits. Thus, short-term NRT may be a beneficial treatment strategy for reducing the risk of eye disorders in smokers attempting to quit. However, further evidence is required to verify these findings and determine the optimal duration of NRT use.
The silibinin-loaded Zein-β cyclodextrin nano-carriers (SZBC-NCs) as a novel selective cancer cell drug delivery system in HT-29 cell line
Authors: al Alabdullah Muslim Abdulrazzaq A. , Goodarzi Mohammad Taghi , Homayouni Tabrizi Masoud
Published: June 2024

Entrapping phytochemical bioactive compounds into nano-structured biocompatible polymers has been successfully utilized for improving cancer treatment efficiency. Silibinin is a potent compound that shows promising anticancer properties. In the present study, the Zein-β-cyclodextrin complex was used to encapsulate silibinin and evaluate the induced cell death type and cytotoxic impacts on human cancer cells. The silibinin-loaded Zein-β cyclodextrin nano-carriers (SZBC-NCs) were synthesized utilizing a gradual ultrasound-mediated homogenization technique and characterized by Zeta potential, DLS, FESEM, and FTIR analysis. The SZBC-NCs’ antioxidant activity was studied by conducting ABTS and DPPH radical scavenging assays. Finally, the SZBC-NCs selective toxicity and cellular death induction mechanism were studied on the HT-29 and AGS cancer cells by measuring the cell survival and apoptotic gene (Caspase 3, 9), respectively, which were verified by conducting the DAPI staining analysis. The negatively charged (− 27.47 mV) nanoparticles (286.55 nm) showed significant ABTS and DPPH radical scavenging activity. Moreover, the remarkable decrease in the IC50 concentrations of the SZBC-NCs among the HT-29 and AGS cancer cell lines exhibited their selective cytotoxic potential. Also, the overexpressed apoptotic (Caspases 3 and 9) and down-regulated necrotic (NFKB) gene expressions following the SZBC-NCs treatment doses indicated the apoptotic activity of SZBC-NCs, which were verified by the increased apoptotic morphology of the DAPI-stained HT-29 cancer cells. The antioxidant and colon cancer cell-related apoptotic activity of the SZBC-NCs make it an appropriate anti-colon cancer nano delivery system. Therefore, they can potentially be used as a safe efficient colon cancer treatment strategy. However, further in vivo experiments including animal cancer models have to be studied.
Individual characteristics outperform resting-state fMRI for the prediction of behavioral phenotypes
Authors: Omidvarnia Amir , Sasse Leonard , Larabi Daouia I. , Raimondo Federico , Hoffstaedter Felix , Kasper Jan , Dukart Jürgen , Petersen Marvin , Cheng Bastian , Thomalla Götz , Eickhoff Simon B. , Patil Kaustubh R.
Published: June 2024

In this study, we aimed to compare imaging-based features of brain function, measured by resting-state fMRI (rsfMRI), with individual characteristics such as age, gender, and total intracranial volume to predict behavioral measures. We developed a machine learning framework based on rsfMRI features in a dataset of 20,000 healthy individuals from the UK Biobank, focusing on temporal complexity and functional connectivity measures. Our analysis across four behavioral phenotypes revealed that both temporal complexity and functional connectivity measures provide comparable predictive performance. However, individual characteristics consistently outperformed rsfMRI features in predictive accuracy, particularly in analyses involving smaller sample sizes. Integrating rsfMRI features with demographic data sometimes enhanced predictive outcomes. The efficacy of different predictive modeling techniques and the choice of brain parcellation atlas were also examined, showing no significant influence on the results. To summarize, while individual characteristics are superior to rsfMRI in predicting behavioral phenotypes, rsfMRI still conveys additional predictive value in the context of machine learning, such as investigating the role of specific brain regions in behavioral phenotypes.
Worldwide delineation of multi-tier city–regions
Authors: Cattaneo Andrea , Girgin Serkan , de By Rolf , McMenomy Theresa , Nelson Andrew , Vaz Sara
Published: June 2024

Urban centers are pivotal in shaping societies, yet a systematic global analysis of how countries are organized around multiple urban centers is lacking. We enhance understanding by delineating city–regions worldwide, classifying over 30,000 urban centers into four tiers—town, small, intermediate and large city—based on population size and mapping their catchment areas based on travel time, differentiating between primary and secondary city–regions. Here we identify 1,403 primary city–regions employing a 3 h travel time cutoff and increasing to 4,210 with a 1 h cutoff, which is more indicative of commuting times. Our findings reveal substantial interconnectedness among urban centers and with their surrounding areas, with 3.2 billion people having physical access to multiple tiers within an hour and 4.7 billion within 3 h. Notably, among people living in or closest to towns or small cities, twice as many have easier access to intermediate than to large cities, underscoring intermediate cities’ crucial role in connecting surrounding populations. This systematic identification of city–regions globally uncovers diverse organizational patterns across urban tiers, influenced by geography, level of development and infrastructure, offering a valuable spatial dataset for regional planning, economic development and resource management.
Visual detection of misfolded alpha-synuclein and prions via capillary-based quaking-induced conversion assay (Cap-QuIC)
Authors: Christenson Peter R. , Jeong Hyeonjeong , Ahn Hyerim , Li Manci , Rowden Gage , Shoemaker Rachel L. , Larsen Peter A. , Park Hye Yoon , Oh Sang-Hyun
Published: June 2024

Neurodegenerative protein misfolding diseases impact tens of millions of people worldwide, contributing to millions of deaths and economic hardships across multiple scales. The prevalence of neurodegenerative disease is predicted to greatly increase over the coming decades, yet effective diagnostics for such diseases are limited. Most diagnoses come from the observation of external symptoms in clinical settings, which typically manifest during relatively advanced stages of disease, thus limiting potential therapeutic applications. While progress is being made on biomarker testing, the underlying methods largely rely on fragile and expensive equipment that limits their point-of-care potential, especially in developing countries. Here we present Capillary-based Quaking Induced Conversion (Cap-QuIC) as a visual diagnostic assay based on simple capillary action for the detection of neurodegenerative disease without necessitating expensive and complex capital equipment. We demonstrate that Cap-QuIC has the potential to be a detection tool for a broad range of misfolded proteins by successfully distinguishing misfolded versus healthy proteins associated with Parkinson’s disease (α-synuclein) and Chronic Wasting Disease (prions). Additionally, we show that Cap-QuIC can accurately classify biological tissue samples from wild white-tailed deer infected with Chronic Wasting Disease. Our findings elucidate the underlying mechanism that enables the Cap-QuIC assay to distinguish misfolded protein, highlighting its potential as a diagnostic technology for neurodegenerative diseases.
Recent advances in stereoselective 1,2-cis-glycosylation
Authors: Lourenço E. C. , Ventura M. R.
Published: June 2024

1,2-cis-Glycosides have both biological and chemical significance. Their presence in natural compounds influences taste, biological activity and drug development. Additionally, their syntheses provide avenues for chemical research and potential therapeutic applications. The construction of 1,2-cis-glycosidic bonds is still a major challenge in carbohydrate synthesis. Although most organic chemists crave general methods, glycosylation reactions continue to be a challenge. Since these reactions are highly dependent on the donor–acceptor pair, the solvent and reagents/catalysts/promoters, one should design the perfect donor and fine-tune the reaction conditions accordingly to obtain the desired stereochemical outcome. New methodologies and studies reveal solutions that may not be universal but can be the key to unsolved problems. In this chapter, recent methods for the synthesis of 1,2-cis-glycosides are highlighted.
Thermogravimetry-synchronized, reference-free quantitative mass spectrometry for accurate compositional analysis of polymer systems without prior knowledge of constituents
Authors: Hibi Yusuke , Uesaka Shiho , Naito Masanobu
Published: June 2024

Accurate composition is determinable without using any prior knowledge or spectra of the system constituents via pyrolysis-mass spectrometry.
A bioinspired bifunctional catalyst: an amphiphilic organometallic catalyst for ring-closing metathesis forming liquid droplets in aqueous media
Authors: Mori Miki , Sugai Hiroka , Sato Kohei , Okada Asuki , Matsuo Takashi , Kinbara Kazushi
Published: June 2024

A bifunctional amphiphilic Hoveyda–Grubbs 2nd generation catalyst has been developed to form droplets as a reaction field and to act as a catalyst for ring-closing metathesis in aqueous environments.
Photoinduced EnT-mediated sulfonamidylimination of alkenes and (hetero)arenes with iminophenylacetic acid oxime esters
Authors: Sun Zetian , Zhang Jianting , Du Xiaohua , Liu Lulu , Gao Shuo , Qi Chenchen , Li Xiaoqing , Xu Xiangsheng
Published: June 2024

Sulfonamidyl radicals are generated via photoinduced EnT and applied for the diamination of alkenes and (hetero)arenes.