bluuebunny/crossref_metadata_2025 huggingface dataset:
Proteomics Reveals Distinctive Host Cell Protein Expression Patterns in Fed‐Batch and Perfusion Cell Culture Processes
Authors: Sahoo Ansuman , Tsukiadate Taku , Lin Bor‐Ruei , Kotzbauer Erin , Houser Jason , Patel Misaal , Li Xuanwen , Madabhushi Sri Ranganayaki
Published: January 2025

Chinese hamster ovary (CHO) cells are widely used to produce recombinant proteins, including monoclonal antibodies (mAbs), through various process modes. While fed‐batch (FB) processes have been the standard, a shift toward high‐density perfusion processes is being driven by increased productivity, flexible facility footprints, and lower costs. Ensuring the clearance of process‐related impurities, such as host cell proteins (HCPs), is crucial in biologics manufacturing. Although purification processes remove most impurities, integrated strategies are being developed to enhance clearance of some high‐risk HCPs. Current understanding of HCP expression dynamics in cell culture is limited. This study utilized data‐independent acquisition (DIA) proteomics to compare the proteomic profiles of cell culture supernatants from 14 FB clones and three perfusion clones, all expressing the same mAb from the same host cell line. Results showed that perfusion processes enhance cell growth and productivity, exhibiting distinct proteomic profiles compared to FB processes. Perfusion processes also maintain a more comparable HCP abundance profile across clones, especially for 46 problematic HCPs monitored. Cluster analysis of FB proteomics revealed distinct abundance patterns and correlations with process parameters. Differential abundance analysis identified significant protein differences between the two processes. This is the first extensive study characterizing HCPs expressed by clones under different process modes. Further research could lead to strategies for preventing or managing problematic HCPs in biologics manufacturing.
The Pathway Relationship Between Physical Activity Levels and Depressive Symptoms in University Students Mediated by Cognitive Flexibility
Authors: Yu Fen , Jia Shuqi , Liu Qin , Guo Zhaohui , Li Sen , Wang Xing , Li Pan
Published: January 2025

Objective

To explore the mediating pathway of cognitive flexibility in the relationship between physical activity and depressive symptoms among university students.

Methods

A cross‐sectional design was used to survey 2537 university students using the Physical Activity Rating Scale‐3, Patients’ Health Questionnaire, and Cognitive Flexibility Inventory. Data analysis was conducted using independent samples t‐test, chi‐square test, correlation analysis, one‐way ANOVA, and mediation analysis.

Results

A statistically significant negative correlation exists between the intensity of physical activity and depression symptom scores (r = −0.104, p < 0.01). The intensity of physical activity demonstrates a statistically significant positive correlation with controllability (r = 0.109, p < 0.01). A marked negative correlation is observed between depressive symptoms and controllability scores (r = −0.367, p < 0.01). The total effect of physical activity intensity on depressive symptoms was quantified as −0.3542 (95% CI: −0.5439 to −0.1645). The direct effect was found to be ‐0.2199 (95% CI: ‐0.3981, ‐0.0417), while the mediating effect of controllability was calculated to be −0.1343 (95% CI: −0.2145 to −0.0630).

Conclusion

Increased engagement in physical activity among university students is associated with a reduction in their depressive symptom scores. Controllability serves as a mediating factor in the relationship between physical activity and depressive symptoms among university students.
Scoring Second Chances: Addressing Women's Unique Challenges and Opportunities in a Football‐Based Prison Programme
Authors: Peitz Linus , Lobban Rosemary , Ruler Mollie , Newson Martha
Published: January 2025

Sport‐based prison interventions may particularly benefit women, a vulnerable population within the penal system. However, evidence of their impact is mainly based on men's experiences. This study qualitatively examines the experiences of 11 women enrolled on the Twinning Project, a football‐based prison programme designed to reduce recidivism and enhance employability. Thematic analysis of semi‐structured interviews revealed positive outcomes for participants, such as improved self‐perceptions and intentions to help others. However, the prospective long‐term impact of vocational qualifications was less evident. Barriers to engagement were identified in parts of the programme's structure and delivery, women's health issues, and participants' perceived lack of control over post‐release outcomes. Enablers included support from peers and staff, the appeal of football itself, and the absence of criminal identities. The findings highlight the Twinning Project's potential to benefit women prisoners and underscore the need for sports programs to accommodate gender‐specific experiences in prison.
Synthesis and Antifungal Activity of Aldehydes‐Thiourea Derivatives as Promising Antifungal Agents Against Postharvest Gray Mold Disease
Authors: Yang Zi Hui , Li Guo Tao , Chen Yue
Published: January 2025

Gray mold disease is caused by Botrytis cinerea, which could severely reduce the production yield and quality of tomatoes. To explore more potential fungicides with new scaffolds for controlling gray mold disease, 10 aldehydes‐thiourea derivatives were designed, synthesized, and assayed for inhibitory activity against three plant pathogenic fungi. The preliminary antifungal assay suggested that some title derivatives showed moderate to good antifungal activity against B. cinerea. In particular, compound 9 presented excellent in vitro antifungal activity against B. cinerea (half maximal effective concentration [EC50] = 0.70 mg/L), which was superior to boscalid (EC50 = 1.41 mg/L). In vivo antifungal assay indicated 9 displayed good protective effects on tomato leaves infected by B. cinerea. A preliminary mechanism study displayed that 9 could damage the surface morphology, increase the cell membrane permeability, and lead to the increase of reactive oxygen species level. Enzyme inhibition assay illustrated that 9 could be a potential laccase inhibitor. The above bioassay results and mechanism investigation demonstrated that aldehydes‐thiourea derivatives could be promising fungicides for further controlling postharvest gray mold disease, which would be potential candidates for fungicidal compounds.
From Antibacterial Activity to Molecular Mechanism: Case Study of Hexapeptide RWWRWW and Its Analogues
Authors: Wang Chu , Xue Yunmo , Guo Jingyao , Ma Qian , Lu Xiaolin
Published: January 2025

In recent years, antimicrobial peptides (AMPs) have emerged as a potent weapon against the growing threat of antibiotic resistance. Among AMPs, the ones containing tryptophan (W) and arginine (R) exhibit enhanced antimicrobial properties, benefiting from the unique physicochemical features of the two amino acids. Herein, we designed three hexapeptides, including WR, DWR (D‐isomer), and RF, derived from the original sequence, RWWRWW‐NH2 (RW). By combining sum frequency generation vibrational spectroscopy (SFG‐VS) and molecular dynamics (MD) simulation, we examined AMPs’ interactions with model bacterial membrane at the molecular level. Our findings revealed the innate different structural features associated with molecular aggregation and membrane activity between L‐(WR, RF and RW) and D‐isomer. The D‐isomer was demonstrated to aggregate via intermolecular hydrogen bonding, which reduced its membrane adsorption quantity and consequently weakened its disruptive effect on the model membrane; while L‐isomers rarely aggregated and thus could fully interact with the model membrane. D‐isomer was proven to lack a stable helical structure, while L‐isomers adopted helical structures, which was believed to be the reason for DWR's tendency to aggregate easily. This study should contribute to designing novel short‐chain AMPs with high efficiency, especially in the case that D‐isomers will be used.
Facile In Situ Formation of Potassium Sodium Niobate (KNN) Using The Hexaniobate Polyoxometalate
Authors: Rambaran Mark A. , Jacobsson Daniel , Lehmann Sebastian , Dick Kimberly A.
Published: January 2025

Lead‐based piezoceramics are the dominant materials used in electronic devices, despite the known toxicity of lead. Developing safer piezoelectric materials has inspired the pursuit of lead‐free piezoceramics, however some challenges remain in accessing these materials reproducibly. Here we demonstrate a simple and robust method for synthesis of the lead‐free piezoceramic material, potassium sodium niobate (KxNa1‐xNbO3, KNN) via an aqueous route. Stochiometric KNN (K0.5Na0.5NbO3) was prepared, by combining alkali‐nitrate salts (NaNO3 and KNO3) with the hexaniobate ([HxNb6O19]8−x, Nb6) species in water, followed by heating at elevated temperatures for at least one hour. Ex situ heating of the amorphous alkali‐Nb6 precursor reveals stoichiometric control and phase uniformity are possible in making KNN, versus a solid‐state route. In situ heating in a transmission electron microscope (TEM), with selected area electron diffraction (SAED), facilitates monitoring the real‐time transformation of the amorphous alkali‐Nb6 precursor, to yield monoclinic KNN, in agreement with ex situ results. Therefore, an aqueous route via hexaniobate is an attractive alternative approach for developing lead‐free piezoceramic materials.
Rhodium(III)‐NSi Catalyzed Styrene Hydrosilylation: Evidence of the Hemilabile Character of NSi‐Type Ligands
Authors: Gómez‐España Alejandra , Padilla Marina , Martínez de Morentin Aitor , García‐Orduña Pilar , Huertos Miguel A. , Munarriz Julen , Fernández‐Alvarez Francisco J.
Published: January 2025

The 18e saturated rhodium(III) species [Rh(H)(X)(κ2‐NSitBu2)(bipyMe2)] (NSitBu2={4‐methylpyridine‐2‐yloxy}ditertbutylsilyl; bipyMe2=4,4'‐dimethylbipyridine) (X=Cl, 1; OTf, 2) have been prepared and characterized by NMR spectroscopy and in the case of 2 it has been possible to determine its solid‐state structure by X‐ray diffraction. Complex 1 has proven to be an effective catalyst precursor for the reaction of styrene derivatives with hydrosilanes in CD2Cl2. However, under catalytic conditions complex 2 decomposes. The performance of the 1‐catalyzed reaction of styrene with hydrosilanes strongly depends on the nature of the silane, the best catalytic performance was achieved using HSiMe2Ph. Theoretical and 1H NMR studies indicate that the hemilabile nature of the NSi ligand is key to understanding the catalytic activity of compound 1.
Comparing microCT Staining and Scanning Methodology for Brain Studies in Various Sizes of Spiders
Authors: Penna‐Gonçalves Vanessa , Willmott Nikolas J. , Kelly Michael B. J. , Black Jay R. , Lowe Elizabeth C. , Herberstein Marie E.
Published: January 2025

Recent advances in microCT are facilitating the investigation of microstructures in spiders and insects leading to an increased number of studies investigating their neuroanatomy. Although microCT is a powerful tool, its effectiveness depends on appropriate tissue preparation and scan settings, particularly for soft, non‐sclerotized tissues, such as muscles, organs, and neural tissues. As the application of microCT in spiders is only in its infancy, published protocols are often difficult to implement due to substantial size variation of the specimens. The present study was initiated to determine how to account for this variation. Our work builds on previous methods using microCT to image spider brains, with the aim to consolidate current knowledge and reduce time spent troubleshooting appropriate methodology, thereby facilitating future studies of spiders and their central nervous systems (CNS). We tested three different preparation and imaging techniques based on published protocols with minor modifications using 216 spiders with prosoma lengths ranging from 1.25 mm (small spiders) to 13.33 mm (large spiders). We compared the efficacy of the various specimen preparations, staining methods, and scan settings by categorizing the quality of dorsal and lateral microCT scans. We observed that only the phosphotungstic acid (PTA) staining agent resulted in complete staining of the prosoma and the CNS, allowing the CNS structures to be distinguished for small, medium, and large spiders. The use of image averaging, increased number of projections, image exposure timing, and detector binning did not greatly affect image quality for small and larger spiders but reduced noise. These settings did help improve image quality for medium spiders in conjunction with higher resolutions and an aluminum filter. We discussed the suitability of methods concerning spider size, effort, chemical risk, and image quality.
Deciphering the pseudouridine nucleobase modification in human diseases: From molecular mechanisms to clinical perspectives
Authors: Jia Shiheng , Yu Xue , Deng Na , Zheng Chen , Ju Mingguang , Wang Fanglin , Zhang Yixiao , Gao Ziming , Li Yanshu , Zhou Heng , Li Kai
Published: January 2025

RNA pseudouridylation, a dynamic and reversible post‐transcriptional modification found in diverse RNA species, is crucial for various biological processes, including tRNA homeostasis, tRNA transport, translation initiation regulation, pre‐mRNA splicing, enhancement of mRNA translation, and translational fidelity. Disruption of pseudouridylation impairs cellular homeostasis, contributing to pathological alterations. Recent studies have highlighted its regulatory role in human diseases, particularly in tumourigenesis. Cellular stresses trigger RNA pseudouridylation in organisms, suggesting that pseudouridylation‐mediated epigenetic reprogramming is essential for maintaining cellular viability and responding to stress. This review examines the regulatory mechanisms and pathological implications of pseudouridylation in human diseases, with a focus on its involvement in tumourigenesis. Additionally, it explores the therapeutic potential of targeting pseudouridylation, presenting novel strategies for disease treatment.

Highlights

Methods to detect pseudouridine were introduced from classic mass spectrometry‐based methods to newer approaches such as nanopore‐based technologies and BID sequencing, each with its advantages and limitations.

RNA pseudouridylation is crucial for various biological processes, including tRNA homeostasis, tRNA transport, translation initiation regulation, pre‐mRNA splicing, enhancement of mRNA translation, and translational fidelity.

Increased pseudouridylation is frequently associated with tumour initiation, progression, and poor prognosis, whereas its reduction is predominantly implicated in non‐tumour diseases.

A comprehensive understanding of the inducing factors for RNA pseudouridylation will be essential for elucidating its role in diseases. Such insights can provide robust evidence for how pseudouridylation influences disease progression and offer new avenues for therapeutic strategies targeting pseudouridylation dysregulation.

The therapeutic potential of RNA pseudouridylation in diseases is enormous, including inhibitors targeting pseudouridine synthases, the application of RNA pseudouridylation in RNA therapeutics, and its role as a biological marker.
Implementation of Energy‐Aware Optimal Routing for Improving Traffic Capacity in Ad Hoc Wireless Network Using Hybrid Heuristic Algorithm
Authors: Seekarajapuram Dinakaran Nandakumar , Muthusamy Lakshmanan , Vellore Sundaresan Divya Sundar
Published: January 2025

Ad hoc wireless network has been one of the significant research topics, as its uses are spread over various applications. The energy‐aware routing (EAR) protocols must create a routing environment with both the security and energy factors, such that the ad hoc network can be sustained for a longer period. Thus, this work proposes an EAR model by considering various factors of the ad hoc network and thus aims to improve the overall network lifetime. At first, the necessary attributes for this process are gathered from standard data sources. After that, an energy‐efficient optimal routing process is performed with the support of the proposed Hybrid Dark Forest‐based Gazelle Optimization Algorithm (HDFGOA) for minimizing energy consumption and maximizing the network lifespan. In this process, the multiobjective functions such as residual energy, route energy, route quality, congestion, and signal interference noise ratio (SINR) are derived by the same HDFGOA. This supports to performance of the energy‐efficient optimal routing process without any interference. Moreover, this process improves the traffic capacity of the ad hoc wireless networks. Finally, thorough experiments are performed for the developed energy‐efficient optimal routing process with conventional algorithms to ensure the suggested process's effectiveness.
Tigers, Terrain, and Human Settlement Influence the Occupancy of Leopards (Panthera pardus) in Southwestern Tarai, Nepal
Authors: Joshi Laxmi Raj , K. C. Rabin Bahadur , Chetri Madhu , Odden Morten , Devineau Olivier , Karki Ajay , Dahal Bhagawan Raj , Subedi Naresh
Published: January 2025

Maintaining a healthy population of common leopards, a highly adaptive felid, requires updated information on their spatial occurrence. In Nepal's Tarai region, leopards coexist with tigers, which are well‐studied felid throughout its range. However, knowledge is very scarce on the patterns of leopard occupancy. We conducted an occupancy survey using remote cameras in southwestern Tarai, particularly in Shuklaphanta National Park, Nepal, to assess habitat use by leopards from December 2022 to January 2023. Naive and model‐averaged occupancy estimates were 0.51 and 0.6563 (SE: 0.022, 95% CI: 0.612, 0.70), respectively. The detection of leopards was negatively correlated with the presence of tigers. Leopard occupancy was higher closer to human settlement and higher in rugged terrain. At a time when Nepal has achieved its tiger conservation targets, efforts are required to maintain adequate prey biomass to minimize fatal encounters between tigers and leopards and displacement of leopards peripheral to the settlement area, where villagers might kill them in retaliation of livestock killing. Long‐term monitoring is required to improve understanding of the interaction between leopards, tigers, and humans in the Tarai region of Nepal.
Impervious surface cover and number of restaurants shape diet variation in an urban carnivore
Authors: Caspi Tal , Serrano Monica G. , Vanderzwan Stevi L. , Kessler Janet , Schell Christopher J. , Sacks Benjamin N.
Published: January 2025

In the past decade, studies have demonstrated that urban and nonurban wildlife populations exhibit differences in foraging behavior and diet. However, little is known about how environmental heterogeneity shapes dietary variation of organisms within cities. We examined the vertebrate prey components of diets of coyotes (Canis latrans) in San Francisco to quantify territory‐ and individual‐level dietary differences and determine how within‐city variation in land cover and land use affects coyote diet. We genotyped fecal samples for individual coyote identification and used DNA metabarcoding to quantify diet composition and individual niche differentiation. The highest contributor to coyote diet overall was anthropogenic food followed by small mammals. The most frequently detected species were domestic chicken, pocket gopher (Thomomys bottae), domestic pig, and raccoon (Procyon lotor). Diet composition varied significantly across territories and among individuals, with territories explaining most of the variation. Within territories (i.e., family groups), the amount of dietary variation attributed to among‐individual differences increased with green space and decreased with impervious surface cover. The quantity of anthropogenic food in scats also was positively correlated with impervious surface cover, suggesting that coyotes consumed more human food in more urbanized territories. The quantity of invasive, human‐commensal rodents in the diet was positively correlated with the number of food services in a territory. Overall, our results revealed substantial intraspecific variation in coyote diet associated with urban landscape heterogeneity and point to a diversifying effect of urbanization on population diet.
Comparative performance of risk prediction indices for mortality or readmission following heart failure hospitalization
Authors: Averbuch Tauben , Zafari Ali , Islam Shofiqul , Lee Shun Fu , Sankaranarayanan Rajiv , Greene Stephen J , Mamas Mamas A , Pandey Ambarish , Van Spall Harriette GC
Published: January 2025

Aims

Risk prediction indices used in worsening heart failure (HF) vary in complexity, performance, and the type of datasets in which they were validated. We compared the performance of seven risk prediction indices in a contemporary cohort of patients hospitalized for HF.

Methods and results

We assessed the performance of the Length of stay and number of Emergency department visits in the prior 6 months (LE), Length of stay, number of Emergency department visits in the prior 6 months, and admission N‐Terminal prohormone of brain natriuretic peptide (NT‐proBNP (LENT), Length of stay, Acuity, Charlson co‐morbidity index, and number of Emergency department visits in the prior 6 months (LACE), Get With The Guidelines Heart Failure (GWTG), Readmission Risk Score (RRS), Enhanced Feedback for Effective Cardiac Treatment model (EFFECT), and Acute Decompensated Heart Failure National Registry (ADHERE) risk indices among consecutive patients hospitalized for HF and discharged alive from January 2017 to December 2019 in a network of hospitals in England. The primary composite outcome was 30‐day all‐cause mortality or readmission. We assessed model discrimination and overall accuracy using the C‐statistic (higher values, better) and Brier score (lower values, better), respectively. Among 1206 patients in the cohort, 45.0% were female, mean (SD) age was 76.6 (11.7) years, and mean (SD) left ventricular ejection fraction was 43.0% (11.6). At 30 days, 236 (19.6%) patients were readmitted and 28 (2.3%) patients died, with 264 (21.9%) patients experiencing either readmission or death. The LENT index offered the combination of greatest risk discrimination and accuracy for the primary composite outcome (C‐statistic: 0.97; 95% CI 0.96, 0.98; 0.29; Brier score: 0.05). The LE (C‐statistic: 0.95; 95% CI 0.93, 0.96; Brier score: 0.06) and LACE (C‐statistic: 0.90; 95% CI 0.88, 0.92; Brier score 0.09) indices had high discrimination and accuracy. Discrimination and accuracy were modest with the RRS (C‐statistic: 0.65; 95% CI 0.61, 0.69; Brier score: 0.16) and EFFECT (C‐statistic: 0.64; 95% CI 0.60, 0.67; Brier score: 0.16) score; and poor with the GWTG‐HF (C‐statistic: 0.62; 95% CI 0.58, 0.66; Brier score: 0.17) and ADHERE (C‐statistic: 0.54; 95% CI 0.50, 0.57; Brier score: 0.17) scores.

Conclusions

In a study that compared the performance of seven risk prediction indices in a contemporary cohort of patients hospitalized for HF, the simple LENT index offered the greatest combination of discrimination and accuracy for the primary composite outcome of 30‐day all‐cause mortality or readmission. This three‐variable index ‐using length of hospital stay, preceding emergency department visits and admission NT‐proBNP level‐ is a practical and reliable way to assess prognosis following hospitalization for HF.
Cut‐Off Values Able to Identify Migraine Patients With Increased Pressure‐Pain Sensitivity Independent of the Migraine Cycle Through a Single Assessment: A Secondary Analysis of a Multicentre, Cross‐Sectional, Observational Study
Authors: Castaldo Matteo , Arendt‐Nielsen Lars , Ponzano Marta , Bovis Francesca , Torelli Paola , Finocchi Cinzia , Di Antonio Stefano
Published: January 2025

Aim

Identify values that could predict the presence of increased pressure‐pain sensitivity independent of the migraine cycle through a single assessment.

Methods

This was a secondary analysis of a previous study in which 198 episodic and chronic migraine patients were assessed during all phases of the migraine cycle. Pressure pain threshold (PPT) was assessed over the temporalis, cervical spine, hand, and leg. Migraine patients were divided into two sub‐groups: patients with increased pressure‐pain sensitivity (IPS) and with No IPS (No‐IPS). A Chi‐squared Automatic Interaction Detection decision tree analysis was used to identify predictors to be included in the IPS or NoIPS group. To assess the internal validity of the model, a tenfold cross‐validation was applied.

Results

161 (81%) patients were included in the IPS group, while 37 (19%) in the NoIPS group. Migraine patients with: (1) Temporalis PPT ≤ 130 kPa; (2) Temporalis PPT > 130 kPa and ≤ 197.5 kPa and hand PPT ≤ 347.33 kPa; (3) Temporalis PPT > 197.5 kPa and hand PPT ≤ 315 kPa; were correctly included in the IPS group with a sensitivity of 96%, a specificity of 81%, a positive predictive value of 96%, and a negative predictive value of 81%. The accuracy of the model and the cross‐validation analysis were respectively 93% and 92%.

Conclusion

The high internal validity suggests that our model could precisely predict the presence of IPS independently by the phase in which the assessment occurred. Trigeminal and hand PPT cut‐off values could be used to identify patients with IPS.
Asymmetric Commodity Tails and Index Futures Returns
Authors: Wang Yuanzhi , Wei Xinbei , Zhang Qunzi
Published: January 2025

This paper proposes that the tail risk associated with commodity futures returns performs well at predicting the S&P 500 index futures returns in‐ and out‐of‐sample, even after controlling business cycles, economic factors, investor sentiment factors, other forms of tail risk factors, and macroeconomic conditions. Following Kelly and Jiang (2014), we directly estimate the commodity tail risk factor from the cross‐section of commodity futures returns, which can efficiently capture the prevailing level of tail risk in the cross‐sectional distribution. Our empirical analysis involves forecasting regressions, which aim to predict index futures returns using lagged up‐tail risk, down‐tail risk, and overall tail risk. We uncover asymmetric forecasting power between up‐tail risk and down‐tail risk, highlighting their distinct influences. Notably, our return decomposition analysis shows that the commodity tail risk factors primarily drive index futures returns through the discount rate channel.
Reward Decision Network Disconnection in Poststroke Apathy: A Prospective Multimodality Imaging Study
Authors: Fang Yirong , Chao Xian , Wang Jinjing , Lu Zeyu , Yin Dawei , Shi Ran , Wang Peng , Liu Xinfeng , Sun Wen
Published: January 2025

Apathy is a common neuropsychiatric symptom following stroke, characterized by reduced goal‐directed behavior. The reward decision network (RDN), which plays a crucial role in regulating goal‐directed behaviors, is closely associated with apathy. However, the relationship between poststroke apathy (PSA) and RDN dysfunction remains unclear due to apathy heterogeneity, the confounding effect of depression and individual variability in lesion impacts. This study aims to dissect the heterogeneity of PSA and explore the link between lesion‐induced RDN damage and PSA. We prospectively recruited 207 patients with acute ischemic infarction and 60 demographically matched healthy controls. Participants underwent neuroimaging and longitudinal neuropsychiatric assessments. To characterize PSA heterogeneity, we employed multivariate analysis and clustering algorithms based on whole‐brain functional connectivity and clinical assessments to classify patients into different PSA biotypes. We embedded each patient's lesion into a structural connectome atlas to obtain white matter (WM) disconnection maps. On this basis, WM disconnection scores were calculated for each brain region to quantify lesion‐induced WM damage. We employed the XGBoost model to predict PSA biotypes based on WM disconnection scores, comparing the performance of models focusing on RDN‐specific versus whole‐brain WM disconnection. Additionally, we explored WM damage patterns across different biotypes by comparing disconnection scores in critical brain regions. We identified four PSA biotypes with unique clinical trajectories and neurobiological underpinnings. Biotype 4 was characterized by persistent apathy with depressive symptoms. Biotype 2 showed persistent apathy. Biotype 3 was non‐apathetic. Biotype 1 exhibited delayed‐onset apathy. The XGBoost models, when focused on the RDN‐specific WM disconnection, performed significantly better in predicting PSA biotypes compared to the whole‐brain WM disconnection model (t(164.66) = 8.871, p < 0.001). Analysis of WM disconnection patterns revealed that Biotype 4 exhibited more extensive RDN damage in crucial regions, Biotype 1 had a unique pattern of damage in the anterior cingulate cortex (t(61) = 1.874, p = 0.032), and Biotype 2 had a unique pattern of damage in the orbitofrontal cortex (t(53)= 1.827, p = 0.036). This study dissected PSA heterogeneity and demonstrated that RDN damage is a critical factor in PSA variability. We found that lesion‐induced WM disconnections in anterior cingulate cortex and orbitofrontal cortex can lead to delayed‐onset and persistent apathy, respectively. Furthermore, our findings revealed that apathy not only has distinct pathogenic mechanisms, but also shares neurobiological substrates with depression.
Histogram of Apparent Diffusion Coefficient to Evaluate the Activity of Thyroid‐Associated Ophthalmopathy
Authors: Li Defu , Zhu Tingting , Wang Yujin
Published: January 2025

Objective

This study aimed to evaluate the activity of extraocular muscles (EOMs) in patients with thyroid‐associated ophthalmopathy (TAO) using turbo spin echo imaging. By analyzing tissue heterogeneity, apparent diffusion coefficient (ADC) histogram analysis offers enhanced insights into edema within the EOMs.

Methods

Eighty‐eight patients with TAO were retrospectively evaluated and allocated into active (n = 24, clinical activity score [CAS] ≥ 3) and inactive (n = 64, CAS < 3) groups. The parameter values of the ADC histogram of EOMs were measured; the efficacy of ADC histograms in distinguishing between TAO activity and inactivity was assessed using receiver operating characteristic curves. Multifactorial logistic regression was used to determine active TAO predictors.

Results

The minimum, maximum, median, mean; and 1st, 5th, 10th, 25th, 75th, 90th, 95th, and 99th percentiles of the ADC histograms were higher in patients with active than that in participants with inactive TAO. The area under the curve (AUC) of the 10th percentile of the ADC histogram and the median distinguishing between active and inactive TAOs were both 0.791 (both p < 0.05), and the AUCs of the combined model of age, sex, smoking, and the 10th percentile in the ADC histogram were better than those of their individual models and the combined model of age, sex, and smoking (all p < 0.05). Smoking and male sex, along with the median > 1.26 μm2/s, entropy > 4.03, and standard deviation (SD) > 0.4 of the ADC histogram, were significant predictors of TAO activity, with odds ratios of 2.741 and 6.806, 5.070, 2.652, and 2.197, respectively (all p < 0.05).

Conclusion

ADC histograms provide a new method for distinguishing active from inactive TAO, and the 10th percentile enhances the clinical diagnosis of active TAO. In addition to male sex and smoking, an ADC histogram median > 1.26 μm²/s, entropy > 4.03, or SD > 0.4 may also predict active TAO.
Factors of Engagement in Employment or Education Following a First Episode of Psychosis: A Systematic Review and Narrative Synthesis
Authors: Kavanagh Michael , Moore Andrew , Fassbender Catherine
Published: January 2025

Despite 75% of people who experience a first episode of psychosis (FEP) reaching clinical remission, this population continue to face lower rates of vocational recovery. This review aimed to identify the factors which help and hinder individuals' employment and post‐secondary education engagement post‐FEP. Three electronic databases (Psych INFO, Medline and Social Science Database) were searched up to 21st August 2023. Primary research on employment/education status or engagement within FEP populations ages 18–40 were included. A narrative synthesis was applied to the findings. Of the 10,575 articles screened, 18 were included in the final review. Younger age, non‐affective psychotic diagnoses and stigma were identified as common barriers to engagement. Ceasing substance use and having family/financial support were reported as facilitators. Conflicting findings were reported as to the impact of positive and negative symptoms. The range of factors emerging from this review highlight several potential barriers and facilitators for individuals seeking employment or further education opportunities post‐FEP. This underlines the need for further research into how and why they influence employment and educational outcomes, with a view to improving treatment outcomes by incorporating these factors into care planning.
Integrating continuous glucose monitoring into Doctor of Pharmacy curricula
Authors: Litten Kathryn , Folz Heather , Lobkovich Alison , Sherrill Christina H. , Berlie Helen
Published: January 2025

The use of digital health technology is on the rise. Within diabetes care, continuous glucose monitoring (CGM) is transforming how we monitor and manage patients with diabetes. Pharmacists play pivotal roles in CGM education, accessibility, utility, and application. In turn, pharmacy students should have a working knowledge of these devices. Currently, CGM inclusion in Doctor of Pharmacy (Pharm.D.) curricula is variable, and little is known about the best way to incorporate this content. This article highlights the critical need to intentionally integrate CGM into didactic and experiential teaching. Incorporating CGM education should be individualized to the institution and the level of the trainee. Educational approaches such as patient cases and hands‐on activities can enhance CGM‐related knowledge, skills, confidence, and empathy, which may empower trainees to be practice‐ready and provide essential CGM services after graduation. This guide will provide a suggested framework for integrating CGM into Pharm.D. curricula.
Tuning Aromaticity, Stability and Radicaloid Character of Periacenes by Chemical BN Doping
Authors: dos Santos Luan G. F. , Chagas Julio C. V. , Ferrão Luiz F. A. , Aquino Adelia J. A. , Nieman Reed , Lischka Hans , Machado Francisco B. C.
Published: January 2025

In this work, the stability, aromaticity and radical character of pristine and eleven BN‐doped armchair 5 and zigzag 5, 6, and 7 periacenes, were chosen for studying the effect of different doping schemes to stabilize the periacene, and to direct the open‐shell density into specific regions of the PAH sheets. Ab initio multireference methods and different DFT functionals were used to analyze the singlet triplet (ST) energy. Moreover, a range of descriptors were used to characterize the open‐shell character and aromaticity of the different doped structures. The overall results provide a good overview of the efficiency of the different doping topologies. In general, because of the closed‐shell character of the borazine doping units, the role of the doping is to reduce the strong open‐shell character of the pristine periacenes. Substitutions along the zigzag edges has a significant effect while doping along the armchair edges is not significant.
Assessment of four sterilization techniques for meniscal allograft transplantation in rabbits
Authors: Wang X. S. , Jia H. G. , Gu D. Q. , Luo D. Z. , Zhao Y. T. , Liu Z. J. , Zhang Y. D.
Published: January 2025

Purpose

This study aimed to compare the effects of four sterilization techniques on meniscal allograft transplantation (MAT) in rabbits.

Methods

In total, 85 medial or lateral meniscuses were obtained from 22 adult New Zealand white rabbits. These 85 meniscal allografts were seeded with Staphylococcus aureus (S. aureus) and randomly divided into five groups (n = 17): iodine group, Cobalt‐60 group, glutaraldehyde group, ethylene oxide group and control group. Bacterial colonies of the allografts were determined before (n = 7) and after (n = 7) sterilization. Histological features were analyzed using haematoxylin and eosin (H&E) staining (n = 3). An additional 50 medial or lateral meniscuses were taken from 13 adult New Zealand white rabbits, and they were kept fresh‐frozen (−40°C) for 1 month. Subsequently, these 50 meniscuses were randomly divided into five groups, which were treated with iodine, Cobalt‐60, glutaraldehyde, ethylene oxide and normal saline, separately (n = 10), and stored at −20°C before MAT. MAT was given to the knee joints of the right hind legs of 50 adult Japanese white rabbits. After 6 weeks of MAT, the transplanted meniscal allografts were taken for biomechanical test (n = 7) and H&E staining (n = 3).

Results

The results of the bacterial count indicated that the number of S. aureus colonies was less than 1 colony‐forming unit (CFU)/allograft in all five groups after sterilization, except for the control group (415 CFU/allograft). H&E staining revealed that allografts in the iodine group presented the complete structure; allografts in the Cobalt‐60 and glutaraldehyde groups were preserved relatively well; and allografts in the control and ethylene oxide groups were severely destructed, especially in the ethylene oxide group. Using the transplanted allografts, the biomechanical test showed that the maximum load of allografts in each group was significantly different, with ethylene oxide effective sterilization agents being used for disinfecting meniscal grafts (iodine group: 270.71 ± 62.81 N, Cobalt‐60 group: 182.14 ± 71.29 N, glutaraldehyde group: 254.29 ± 31.55 N, ethylene oxide group: 40.00 ± 22.73 N and control group: 183.14 ± 76.40) (p ≤ 0.001). H&E staining with transplanted allografts revealed that allografts in the iodine group had the most intact structure; allografts in the Cobalt‐60 and glutaraldehyde groups presented a relatively intact structure; and allografts in the control and ethylene oxide groups were seriously damaged, especially in the ethylene oxide group.

Conclusion

It was found that iodine, Cobalt‐60, glutaraldehyde and ethylene oxide are effective sterilization agents for disinfecting meniscal grafts. Iodine exhibited superior preservation of both the biomechanics and structural integrity of the meniscal allografts, whereas ethylene oxide caused the most severe destruction to the meniscal allografts.

Level of Evidence

Not applicable because this is an animal study.
Erythrocytapheresis as a strategy to manage anemia and iron overload in nondeletional hemoglobin H disease
Authors: Zhang Ke , Bliamptis John , Park Janice , Kopko Patricia , Sanchez Amber P. , Gopal Srila
Published: January 2025

Hemoglobin H (HbH) disease is associated with anemia, ineffective erythropoiesis, and iron overload. We report a case of a patient with HbH/Hb Constant Spring disease, who was maintained on chronic transfusions as an adult due to symptomatic anemia. Over time, he developed iron overload and was started on chelation therapy but did not have an adequate response to chelation. We then added erythrocytapheresis to chelation therapy and were able to successfully decrease his iron burden while managing his anemia. Therapeutic erythrocytapheresis may be an effective treatment strategy for iron overload in HbH disease that is refractory to chelation.
Comparative Efficacy of Ultrasonic Scalpel Surgery With Photodynamic Therapy Versus Trichloroacetic Acid Application in Treating HPV‐Related Condyloma Acuminata: A Randomized Clinical Trial
Authors: dos Santos Valter Fausto , de Barros Ian Carlos , Tomazella Vera Lucia Damasceno , Portela Adriane Caroline Teixeira , de Arruda Semira Silva , Buzza Hilde Harb , Inada Natalia Mayumi , Bagnato Vanderlei Salvador , Stringasci Mirian Denise
Published: January 2025

Human papillomavirus (HPV) infections rank as the most prevalent sexually transmitted infections globally. The Brazilian Ministry of Health recommends the topical use of 70%–90% trichloroacetic acid (TAA) for treating condyloma acuminata, yet this method suffers from a high recurrence rate of 36% and requires roughly six applications. Topical photodynamic therapy (PDT) has shown effectiveness in targeting subclinical lesions, but it also necessitates multiple sessions for complete lesion clearance. This randomized clinical trial evaluates the efficacy of 80% TAA monotherapy against a combined approach of ultrasonic scalpel excision followed by a single PDT session (US + PDT). The US + PDT group required fewer treatment sessions, exhibited superior cosmetic outcomes, and reported zero lesion recurrence during an 18‐month follow‐up, in contrast to the TAA group's recurrence rate of 33.3%. Notwithstanding, patient‐reported pain during PDT application emerged as a significant barrier, affecting treatment adherence and completion rates. Innovating new PDT protocols could potentially address this challenge, enhancing patient compliance and therapeutic success.
Host Index and Gallbladder Cancer: An Emerging Prognostic Biomarker
Authors: Kattepur Abhay K. , Kazi Mufaddal , Patkar Shraddha , Goel Mahesh
Published: January 2025

Background and Objectives

There is emerging evidence that host related variables predict outcomes in various cancers. The Host index (H‐index) incorporates various host‐related, blood‐derived biomarkers (immunological and nutritional parameters) as a single mathematical formula. The aim of this study was to evaluate outcomes using the H‐index as a prognostic marker in gallbladder cancer (GBC) patients undergoing curative resection.

Methods

Retrospective cohort study of surgically treated GBCs at a tertiary cancer centre from January 2010 to May 2023 was performed. Patients who had received neoadjuvant therapy, metastatic (M1) disease at time of surgical exploration and incidental GBCs were excluded. Baseline neutrophil, lymphocyte, monocyte and platelet counts, hemoglobin and albumin levels were recorded. H‐index was computed and analysed.

Results

241 curatively resected GBC patients were included. The H‐index was inversely associated with disease free survival (DFS), both on univariate (79.7 vs. 61.4% for H‐index </= 1.3 and > 3.4 respectively; p = 0.046) and multivariate analysis (Hazard ratio [HR] for recurrence: 1.954 [95% C.I.: 1.366–2.796]; p = < 0.001). Using the maximally distributed rank statistics, a cut‐off of 1.31 showed a significant difference in 3‐year DFS (86.2 vs. 68.4% for H‐index </= 1.31 vs. > 1.31 respectively; HR: 2.21 [95% CI: 1.16–4.21]; p = 0.013) but not overall survival (OS) (p = 0.269).

Conclusion

A higher H‐index predicted for worse DFS in curatively resected GBC patients. This shows host related variables do play a role in influencing outcomes in GBC. However, larger prospective studies are required to further strengthen this finding.

Host‐related, blood derived biomarkers can influence outcomes in various solid tumours. A higher baseline Host index (H‐index) value which incorporates various blood‐derived biomarkers, predicted for worse disease‐free survival in curatively resected gallbladder cancers.
Addressing Water Loss With Artificial Intelligence
Authors: Johnson Jeffrey
Published: January 2025

Many local leaders are just beginning to acknowledge how aging infrastructure, climate change, and population growth are putting additional pressure on their water supplies. The financial impact is substantial. US municipalities and local water utilities are facing budget shortfalls that are either passed through to residents via rate increases or are ignored, creating a vicious cycle of reduced maintenance, higher water loss, and increasing debt. The result is that citizens pay more for less water and, under current conditions, will continue to do so until effective solutions are found.
Operators Need to Know the Essentials of Public Outreach
Authors: Dunifon Shea , Adams Hunter , Nayak Bina , Parish Daniel , Gugliuzza Mary , Ash Steve , Southard Mark
Published: January 2025

Water operators can be a more influential voice in the water industry when they understand how to educate the public about their role in water treatment.
Securing a Water Supply Without a Local Source
Authors: Shutak John
Published: January 2025

A North Carolina county and a small lakeside town teamed up to plan and execute a water infrastructure project to ensure a reliable water supply in perpetuity.
Comprehensive Study of Polyphenylene Sulfide (PPS)/Na‐Ionomer Blend System on Morphological, Thermal, Mechanical, Thermo‐Mechanical, and Flame Retardance Behavior
Authors: Rangarajan Rajagopal , Datta Pulak
Published: January 2025

A new blend system comprising polyphenylene sulfide (PPS) and ionomer based on poly(ethylene‐methacrylic acid) partially neutralized by sodium ions has been developed and investigated the blend's morphological, thermal, mechanical, thermo‐mechanical, and flame retardance behavior. The blend system shows two different phase morphology: sea‐island type morphology when ionomer content is up to 20 wt% and formation of fibrous structure morphology with more than 30 wt% Na‐ionomer content. TGA analysis shows the gradual decrease in thermal stability of the PPS matrix as the Na‐ionomer content increases. In contrast, DSC analysis reveals the presence of a cold crystallization peak, with no changes in the melting temperature of the PPS matrix. There is no change in the glass transition temperature of PPS, and the increase in tan δ values of DMA analysis indicates improved damping capacity (flexibility) of PPS blends. The Na‐ionomer blending enhances the elongation at a break and impact strength of the blends, that is, reflecting the improvement of about 180% in elongation at break and 162% of impact strength for the 50 wt% ratio. No effect on flame‐rating is observed up to 30 wt% ionomer.
Green Modification Approach Using Novel Viscosity Stabilizer for Inhibiting Storage Hardening of Natural Rubber
Authors: Yu Yao , Qi Hangming , Wu Meng , Wang Hongzhen , Zhang Xuequan , Xin Zhenxiang
Published: January 2025

The inherent storage hardening phenomenon of natural rubber (NR) has always affected product quality and processing energy consumption. This article proposes a new strategy for preparing a novel constant viscosity natural rubber (CV‐NR), which involves wet modification of natural rubber latex using a new green and noncorrosive viscosity stabilizer, alkyl hydrazide (OP). And compared with the traditional corrosive viscosity stabilizer hydroxylamine hydrochloride (HH), the influence of viscosity stabilizer on the microstructure, processability, crystallization behavior, and physical and mechanical properties of NR was mainly investigated. The results indicated that depending on the aldehyde amine condensation reaction between OP and the aldehyde group of NR molecular chain, OP can significantly inhibit the storage hardening problem of NR caused by network branching and crosslinking, which was manifested in the reduction of molecular weight, gel content, Mooney viscosity, initial plastic value, and elastic modulus, thus improving the processability. In addition, CV‐NR had better crystallinity and aging resistance compared to NR. It was worth noting that OP did not significantly affect the physical and mechanical properties of NR, and was obviously better than HH. This study could provide a highly promising design approach for the development and application of novel CV‐NR to prepare high‐performance NR products.