Recent Publications

Biomimetics (Basel). 2024 Apr 20;9(4):251. doi: 10.3390/biomimetics9040251.

ABSTRACT

To combat climate change, one approach is to manufacture products from biomass-fungi composite materials instead of petroleum-based plastics. These products can be used in packaging, furniture, and construction industries. A 3D printing-based manufacturing method was developed for these biomass-fungi composite materials, eliminating the need for molds, and enabling customized product design. However, previous studies on the 3D printing-based method showed significant shrinkage of printed samples. In this paper, an approach is proposed to reduce the shrinkage by incorporating ionic crosslinking into biomass-fungi composite materials. This paper reports two sets of experiments regarding the effects of sodium alginate (SA) and calcium chloride (CaCl2) on fungal growth and fungal viability. The first set of experiments was conducted using Petri dishes with fungi isolated from colonized biomass-fungi material and different concentrations of SA and CaCl2. Fungal growth was measured by the circumference of fungal colonies. The results showed that concentrations of SA and CaCl2 had significant effects on fungal growth and no fungal growth was observed on Petri dishes with 15% CaCl2. Some of these Petri dishes were also observed under confocal microscopy. The results confirmed the differences obtained by measuring the circumference of fungal colonies. The second set of experiments was conducted using Petri dishes with biomass-fungi mixtures that were treated with different concentrations of SA and exposure times in a CaCl2 (crosslinking) solution. Fungal viability was measured by counting colony-forming units. The results showed that the addition of the SA solution and exposure times in the crosslinking solution had statistically significant effects on fungal viability. The 2SA solution was prepared by dissolving 2 g of SA in 100 mL of water, the 5SA solution was prepared by dissolving 5 g of SA in 100 mL of water, and the crosslinking solution was prepared by dissolving 5 g of CaCl2 in 100 mL of water. The results also showed that fungal viability was not too low in biomass-fungi mixtures that included 2SA solution and were exposed to the crosslinking solution for 1 min.

PMID:38667263 | DOI:10.3390/biomimetics9040251

J Health Care Poor Underserved. 2024;35(1):285-298.

ABSTRACT

Free clinics may present long wait times. A retrospective chart review was conducted at a free clinic to understand contributing factors. Three wait times (total visit time, lobby wait time, and triage time) were analyzed across 349 patients. Variables included in the models were the total number of patients, providers, and volunteers; interpreter services; social work involvement; medical complexity; new vs. returning patient; scheduled vs. walk-in appointment; transportation provision; medical volunteer training level; and on-site medications and labs. Data analysis with multiple regressions was conducted. Factors that significantly affected wait times included the level of medical complexity (p<.001), medical volunteer training levels (p<.001), in-house labs (p<.001), in-house medications (p=.04), and new patients (p=.01). An intervention involving time benchmarks at the beginning of clinics reduced first-wave lobby wait times (p<.001). Future interventions addressing these factors may reduce wait times at other clinics.

PMID:38661871

ACS Nano. 2024 Apr 25. doi: 10.1021/acsnano.3c11509. Online ahead of print.

ABSTRACT

On-surface synthesis is a powerful method that has emerged recently to fabricate a large variety of atomically precise nanomaterials on surfaces based on polymerization. It is very successful for thermally activated reactions within the framework of heterogeneous catalysis. As a result, it often lacks selectivity. We propose to use selective activation of specific bonds as a crucial ingredient to synthesize desired molecules with high selectivity. In this approach, thermally nonaccessible products are expected to arise in photolytically activated on-surface reactions with high selectivity. We demonstrate for assembled 2,2'-dibromo biphenyl clusters on Cu(111) that the thermal and photolytic activations yield distinctly different products, combining submolecular resolution of individual product molecules in real-space imaging by scanning tunneling microscopy with chemical identification in X-ray photoelectron spectroscopy and supported by ab initio calculations. The photolytically activated Ullmann coupling of 2,2'-dibromo biphenyl is highly selective, with only one identified product. It starkly contrasts the thermal reaction, which yields various products because alternate pathways are activated at the reaction temperature. Our study extends on-surface synthesis to a directed formation of thermally inaccessible products by direct bond activation. It promises tailored reactions of nanomaterials within the framework of on-surface synthesis based on the photolytic activation of specific bonds.

PMID:38661485 | DOI:10.1021/acsnano.3c11509

IJID Reg. 2024 Mar 19;11:100356. doi: 10.1016/j.ijregi.2024.100356. eCollection 2024 Jun.

ABSTRACT

OBJECTIVES: This study aimed to construct geographically, temporally, and epidemiologically representative data sets for SARS-CoV-2 in North Africa, focusing on Variants of Concern (VOCs), Variants of Interest (VOIs), and Variants Under Monitoring (VUMs).

METHODS: SARS-CoV-2 genomic sequences and metadata from the EpiCoV database via the Global Initiative on Sharing All Influenza Data platform were analyzed. Data analysis included cases, deaths, demographics, patient status, sequencing technologies, and variant analysis.

RESULTS: A comprehensive analysis of 10,783 viral genomic sequences from six North African countries revealed notable insights. SARS-CoV-2 sampling methods lack standardization, with a majority of countries lacking clear strategies. Over 59% of analyzed genomes lack essential clinical and demographic metadata, including patient age, sex, underlying health conditions, and clinical outcomes, which are essential for comprehensive genomic analysis and epidemiological studies, as submitted to the Global Initiative on Sharing All Influenza Data. Morocco reported the highest number of confirmed COVID-19 cases (1,272,490), whereas Tunisia leads in reported deaths (29,341), emphasizing regional variations in the pandemic's impact. The GRA clade emerged as predominant in North African countries. The lineage analysis showcased a diversity of 190 lineages in Egypt, 26 in Libya, 121 in Tunisia, 90 in Algeria, 146 in Morocco, and 10 in Mauritania. The temporal dynamics of SARS-CoV-2 variants revealed distinct waves driven by different variants.

CONCLUSIONS: This study contributes valuable insights into the genomic landscape of SARS-CoV-2 in North Africa, highlighting the importance of genomic surveillance in understanding viral dynamics and informing public health strategies.

PMID:38655560 | PMC:PMC11035039 | DOI:10.1016/j.ijregi.2024.100356

JOR Spine. 2024 Apr 23;7(2):e1332. doi: 10.1002/jsp2.1332. eCollection 2024 Jun.

ABSTRACT

BACKGROUND: Nucleus replacement devices (NRDs) are not routinely used in clinic, predominantly due to the risk of device expulsion. Rigorous in vitro testing may enable failure mechanisms to be identified prior to clinical trials; however, current testing standards do not specify a particular expulsion test. Multiple methods have therefore been developed, complicating comparisons between NRD designs. Thus, this study assessed the effectiveness of four previously reported expulsion testing protocols; hula-hoop (Protocol 1), adapted hula-hoop (Protocol 2), eccentric cycling (Protocol 3), and ramp to failure (Protocol 4), applied to two NRDs, one preformed and one in situ curing.

METHODS: Nucleus material was removed from 40 bovine tail intervertebral disks. A NRD was inserted posteriorly into each cavity and the disks were subjected to one of four expulsion protocols.

RESULTS: NRD response was dependent on both the NRD design and the loading protocol. Protocol 1 resulted in higher migration and earlier failure rates compared to Protocol 2 in both NRDs. The preformed NRD was more likely to migrate when protocols incorporated rotation. The NRDs had equal migration (60%) and expulsion (60%) rates when using unilateral bending and ramp testing. Combining the results of multiple tests revealed complimentary information regarding the NRD response.

CONCLUSIONS: Adapted hula-hoop (Protocol 2) and ramp to failure (Protocol 4), combined with fluoroscopic analysis, revealed complimentary insights regarding migration and failure risk. Therefore, when adopting the surgical approach and animal model used in this study, it is recommended that NRD performance be assessed using both a cyclic and ramp loading protocol.

PMID:38655007 | PMC:PMC11037461 | DOI:10.1002/jsp2.1332

Proc AAAI Conf Artif Intell. 2024 Feb;38(21):22892-22898. doi: 10.1609/aaai.v38i21.30326. Epub 2024 Mar 24.

ABSTRACT

Long-term and high-dose prescription opioid use places individuals at risk for opioid misuse, opioid use disorder (OUD), and overdose. Existing methods for monitoring opioid use and detecting misuse rely on self-reports, which are prone to reporting bias, and toxicology testing, which may be infeasible in outpatient settings. Although wearable technologies for monitoring day-to-day health metrics have gained significant traction in recent years due to their ease of use, flexibility, and advancements in sensor technology, their application within the opioid use space remains underexplored. In the current work, we demonstrate that oral opioid administrations can be detected using physiological signals collected from a wrist sensor. More importantly, we show that models informed by opioid pharmacokinetics increase reliability in predicting the timing of opioid administrations. Forty-two individuals who were prescribed opioids as a part of their medical treatment in-hospital and after discharge were enrolled. Participants wore a wrist sensor throughout the study, while opioid administrations were tracked using electronic medical records and self-reports. We collected 1,983 hours of sensor data containing 187 opioid administrations from the inpatient setting and 927 hours of sensor data containing 40 opioid administrations from the outpatient setting. We demonstrate that a self-supervised pre-trained model, capable of learning the canonical time series of plasma concentration of the drug derived from opioid pharmacokinetics, can reliably detect opioid administration in both settings. Our work suggests the potential of pharmacokinetic-informed, data-driven models to objectively detect opioid use in daily life.

PMID:38646089 | PMC:PMC11027727 | DOI:10.1609/aaai.v38i21.30326

IJID Reg. 2024 Mar 16;11:100351. doi: 10.1016/j.ijregi.2024.03.006. eCollection 2024 Jun.

ABSTRACT

OBJECTIVES: COVID-19 affects the quality of life (QoL) in a reverse way after recovery, which might be multiplied by the comorbid non-communicable diseases. This study explored the relationship between comorbidities and the QoL of people who recovered from COVID-19 in Bangladesh.

METHODS: The cross-sectional study was conducted among 3244 participants between June 2020 and November 2020 using a pre-tested questionnaire through over-the-phone interviews. The WHOQOL-BREF was used to explore the QoL among the study participants. A multivariable linear regression model was conducted to identify the effects of the number of comorbidities on QoL scores of all four domains.

RESULTS: Of 3244 patients who recovered from COVID-19, over one-third (39.4%) had one or more chronic diseases, such as hypertension, diabetes mellitus, ischemic heart disease, bronchial asthma/chronic obstructive pulmonary disease, chronic kidney disease, and cancer. Around 46.85% of the participants aged above 40 years presented with one to two chronic diseases, and 16.33% had three or more chronic diseases. Among all comorbidities, the participants with cancer and chronic kidney disease were found to have relatively lower scores in all four domains than other comorbidities. The lowest QoL scores were observed in the psychological domain. Those with three or more simultaneous chronic comorbidities had the lowest QoL score in all four domains: physical, psychological, social relationship, and environmental.

CONCLUSIONS: Persons who recovered from COVID-19 with comorbidities undergo a lower QoL. Therefore, special attention is required to these vulnerable groups to ensure their smooth recuperation.

PMID:38634072 | PMC:PMC11021361 | DOI:10.1016/j.ijregi.2024.03.006

ACS Appl Mater Interfaces. 2024 Apr 17. doi: 10.1021/acsami.3c18160. Online ahead of print.

ABSTRACT

We have synthesized Pt1Zn3/ZnO, also termed 0.01 wt %Pt/ZnO-O2-H2, as a catalyst containing singly dispersed single-atom bimetallic sites, also called a catalyst of singly dispersed bimetallic sites or a catalyst of isolated single-atom bimetallic sites. Its catalytic activity in partial oxidation of methanol to hydrogen at 290 °C is found to be 2-3 orders of magnitude higher than that of Pt-Zn bimetallic nanoparticles supported on ZnO, 5.0 wt %Pt/ZnO-N2-H2. Selectivity for H2 on Pt1Zn3/ZnO reaches 96%-100% at 290-330 °C, arising from the uniform coordination environment of single-atom Pt1 in singly dispersed single-atom bimetallic sites, Pt1Zn3 on 0.01 wt %Pt/ZnO-O2-H2, which is sharply different from various coordination environments of Pt atoms in coexisting PtxZny (x ≥ 0, y ≥ 0) sites on Pt-Zn bimetallic nanoparticles. Computational simulations attribute the extraordinary catalytic performance of Pt1Zn3/ZnO to the stronger adsorption of methanol and the lower activation barriers in O-H dissociation of CH3OH, C-H dissociations of CH2O to CO, and coupling of intermediate CO with atomic oxygen to form CO2 on Pt1Zn3/ZnO as compared to those on Pt-Zn bimetallic nanoparticles. It demonstrates that anchoring uniform, isolated single-atom bimetallic sites, also called singly dispersed bimetallic sites on a nonmetallic support can create new catalysts for certain types of reactions with much higher activity and selectivity in contrast to bimetallic nanoparticle catalysts with coexisting, various metallic sites MxAy (x ≥ 0, y ≥ 0). As these single-atom bimetallic sites are cationic and anchored on a nonmetallic support, the catalyst of singly dispersed single-atom bimetallic sites is different from a single-atom alloy nanoparticle catalyst. The critical role of the 0.01 wt %Pt in the extraordinary catalytic performance calls on fundamental studies of the profound role of a trace amount of a metal in heterogeneous catalysis.

PMID:38632669 | DOI:10.1021/acsami.3c18160

Clin Transl Radiat Oncol. 2024 Apr 6;46:100777. doi: 10.1016/j.ctro.2024.100777. eCollection 2024 May.

ABSTRACT

OBJECTIVE: As craniospinal irradiation (CSI) is delivered more frequently by helical tomotherapy (HT) with few reports about late effects, we analysed all patients treated in our centre over an 11-year period.

METHODS AND MATERIALS: Our study included all patients that underwent CSI by HT, between September 2009 and January 2020, in the Department of Radiation Oncology of the Toulouse Cancer Institute. Acute radiotherapy toxicities were reported and medium- to long-term outcomes analysed.

RESULTS: Among the 79 patients included, 70.9 % were younger than 18 years at diagnosis, the median age was 13 (range: 1-52) at the time of radiation therapy, 67.1 % of patients had medulloblastoma. Half of them (49.4 %) had a metastatic disease at diagnosis. The median dose of CSI was 36 Gy (range, 18-36). Seventy-seven patients received a radiation boost to the original location of the primary tumour (97.5 %), 32 patients also received a boost to their metastatic sites (40.5 %). Median follow-up was 55.5 months (95 %CI = [41.2; 71.8]). The 3-year event-free survival rate was 66.3 % (95 %CI = [54.2; 75.9]). Most patients presented with acute haematological toxicities during CSI (85.9 %), predominantly severe thrombocytopenia (39.7 %). Among the 64 patients assessed for medium- and long-term outcomes, 52 survived and 47 were alive and disease-free at the latest follow-up visit on record. There were 3.8 % secondary tumours: two meningiomas and one diffuse intrinsic pontine glioma. Adult and paediatric patients respectively presented with secondary cataract (4.3 % vs 22.0 %), persistent hearing disorders (26.1 % vs 29.3 %), pulmonary or cardiac late effects (4.3 % vs 2.4 %), hormonal pituitary gland deficiencies (30.0 % vs 56.8 %) and psycho-cognitive disorders (56.5 % vs 53.7 %).

CONCLUSION: CSI dispensed by HT, did not result in any additional acute or late toxicities when compared to 3D-CSI. There was no increase in the secondary tumour rate compared to that reported in the literature.

PMID:38628594 | PMC:PMC11019098 | DOI:10.1016/j.ctro.2024.100777

Ann Data Sci. 2022;9(5):1103-1127. doi: 10.1007/s40745-022-00372-1. Epub 2022 Mar 15.

ABSTRACT

Inflated models are generally used whenever there is an excess number of frequencies at particular count. In this study, a three-inflated Poisson (ThIP) distribution is proposed by mixing the Poisson distribution and a distribution to a point mass at three. Some of its distribution properties and reliability characteristics are studied. A simulation study is carried out to see the performance of the MLEs. In India Covid-19 implications on mental health have been abysmal. Covid-19 related suicide data of India during lockdown to the first gradual relaxation of the terms of the total lockdown (unlocking 1.0) are used to examine the appropriateness of the proposed distribution. Likelihood ratio test is used for discriminating between Poisson and the proposed distribution.

PMID:38624854 | PMC:PMC8923122 | DOI:10.1007/s40745-022-00372-1

IFAC Pap OnLine. 2022;55(10):305-310. doi: 10.1016/j.ifacol.2022.09.405. Epub 2022 Oct 26.

ABSTRACT

Global supply chains (SCs) have been severely impacted by the COVID-19 pandemic on several levels. For example, SCs suffered from panic buying-related instabilities and multiple disruptions of supply, demand, and capacity during the pandemic. This study developed an agent-based model (ABM) to predict the effects of panic buying-related instabilities in SCs and offered strategies to improve them. The ABM model includes a simulation and optimization model of a typical SC of an essential product manufacturer (i.e., toilet paper SC) for the analysis of scenarios and strategies to observe improvements in SCs. Among the four strategies identified, the findings suggest boosting production capacity to the maximum and ensuring optimal reorder points, order sizes, and trucks helped the essential product manufacturers reduce panic buying-related instabilities in their SCs.

PMID:38620991 | PMC:PMC9605711 | DOI:10.1016/j.ifacol.2022.09.405

Clin Med (Lond). 2023 Nov;23 Suppl 6:96-97. doi: 10.7861/clinmed.23-6-s96.

NO ABSTRACT

PMID:38614766 | DOI:10.7861/clinmed.23-6-s96

Clin Med (Lond). 2023 Nov;23 Suppl 6:125-126. doi: 10.7861/clinmed.23-6-s125.

NO ABSTRACT

PMID:38614702 | DOI:10.7861/clinmed.23-6-s125

J Clin Med. 2024 Apr 5;13(7):2114. doi: 10.3390/jcm13072114.

ABSTRACT

Background: Advancements in non-ionizing methods for quantifying spinal deformities are crucial for assessing and monitoring scoliosis. In this study, we analyzed the observer variability of a newly developed digital tool for quantifying body asymmetry from clinical photographs. Methods: Prospective observational multicenter study. Initially, a digital tool was developed using image analysis software, calculating quantitative measures of body asymmetry. This tool was integrated into an online platform that exports data to a database. The tool calculated 10 parameters, including angles (shoulder height, axilla height, waist height, right and left waistline angles, and their difference) and surfaces of the left and right hemitrunks (shoulders, waists, pelvises, and total). Subsequently, an online training course on the tool was conducted for twelve observers not involved in its development (six research coordinators and six spine surgeons). Finally, 15 standardized back photographs of adolescent idiopathic scoliosis patients were selected from a multicenter image bank, representing various clinical scenarios (different age, gender, curve type, BMI, and pre- and postoperative images). The 12 observers measured the photographs at two different times with a three-week interval. For the second round, the images were randomly mixed. Inter- and intra-observer variabilities of the measurements were analyzed using intraclass correlation coefficients (ICCs), and reliability was measured by the standard error of measurement (SEM). Group comparisons were made using Student's t-test. Results: The mean inter-observer ICC for the ten measurements was 0.981, the mean intra-observer ICC was 0.937, and SEM was 0.3-1.3°. The parameter with the strongest inter- and intra-observer validity was the difference in waistline angles 0.994 and 0.974, respectively, while the highest variability was found with the waist height angle 0.963 and 0.845, respectively. No test-retest differences (p > 0.05) were observed between researchers (0.948 ± 0.04) and surgeons (0.925 ± 0.05). Conclusion: We developed a new digital tool integrated into an online platform demonstrating excellent reliability and inter- and intra-observer variabilities for quantifying body asymmetry in scoliosis patients from a simple clinical photograph. The method could be used for assessing and monitoring scoliosis and body asymmetry without radiation.

PMID:38610880 | DOI:10.3390/jcm13072114

Front Public Health. 2024 Mar 28;12:1279392. doi: 10.3389/fpubh.2024.1279392. eCollection 2024.

ABSTRACT

Syndromic surveillance is an effective tool for enabling the timely detection of infectious disease outbreaks and facilitating the implementation of effective mitigation strategies by public health authorities. While various information sources are currently utilized to collect syndromic signal data for analysis, the aggregated measurement of cough, an important symptom for many illnesses, is not widely employed as a syndromic signal. With recent advancements in ubiquitous sensing technologies, it becomes feasible to continuously measure population-level cough incidence in a contactless, unobtrusive, and automated manner. In this work, we demonstrate the utility of monitoring aggregated cough count as a syndromic indicator to estimate COVID-19 cases. In our study, we deployed a sensor-based platform (Syndromic Logger) in the emergency room of a large hospital. The platform captured syndromic signals from audio, thermal imaging, and radar, while the ground truth data were collected from the hospital's electronic health record. Our analysis revealed a significant correlation between the aggregated cough count and positive COVID-19 cases in the hospital (Pearson correlation of 0.40, p-value < 0.001). Notably, this correlation was higher than that observed with the number of individuals presenting with fever (ρ = 0.22, p = 0.04), a widely used syndromic signal and screening tool for such diseases. Furthermore, we demonstrate how the data obtained from our Syndromic Logger platform could be leveraged to estimate various COVID-19-related statistics using multiple modeling approaches. Aggregated cough counts and other data, such as people density collected from our platform, can be utilized to predict COVID-19 patient visits related metrics in a hospital waiting room, and SHAP and Gini feature importance-based metrics showed cough count as the important feature for these prediction models. Furthermore, we have shown that predictions based on cough counting outperform models based on fever detection (e.g., temperatures over 39°C), which require more intrusive engagement with the population. Our findings highlight that incorporating cough-counting based signals into syndromic surveillance systems can significantly enhance overall resilience against future public health challenges, such as emerging disease outbreaks or pandemics.

PMID:38605877 | PMC:PMC11007176 | DOI:10.3389/fpubh.2024.1279392

J Physiol. 2024 Apr 10. doi: 10.1113/JP283829. Online ahead of print.

ABSTRACT

Two-pore channels and TRP mucolipins are ubiquitous endo-lysosomal cation channels of pathophysiological relevance. Both are Ca2+-permeable and regulated by phosphoinositides, principally PI(3,5)P2. Accumulating evidence has uncovered synergistic channel activation by PI(3,5)P2 and endogenous metabolites such as the Ca2+ mobilizing messenger NAADP, synthetic agonists including approved drugs and physical cues such as voltage and osmotic pressure. Here, we provide an overview of this coordination.

PMID:38598430 | DOI:10.1113/JP283829

Br J Pharmacol. 2024 Apr 7. doi: 10.1111/bph.16372. Online ahead of print.

ABSTRACT

BACKGROUND AND PURPOSE: Calcitonin gene-related peptide (CGRP) is a potent vasodilator. While its signalling is assumed to be mediated via increases in cAMP, this study focused on elucidating the actual intracellular signalling pathways involved in CGRP-induced relaxation of human isolated coronary arteries (HCA).

EXPERIMENTAL APPROACH: HCA were obtained from heart valve donors (27 M, 25 F, age 54 ± 2 years). Concentration-response curves to human α-CGRP or forskolin were constructed in HCA segments, incubated with different inhibitors of intracellular signalling pathways, and intracellular cAMP levels were measured with and without stimulation.

RESULTS: Adenylyl cyclase (AC) inhibitors SQ22536 + DDA and MDL-12330A, and PKA inhibitors Rp-8-Br-cAMPs and H89, did not inhibit CGRP-induced relaxation of HCA, nor did the guanylyl cyclase inhibitor ODQ, PKG inhibitor KT5823, EPAC1/2 inhibitor ESI09, potassium channel blockers TRAM-34 + apamin, iberiotoxin or glibenclamide, or the Gαq inhibitor YM-254890. Phosphodiesterase inhibitors induced a concentration-dependent decrease in the response to KCl but did not potentiate relaxation to CGRP. Relaxation to forskolin was not blocked by PKA or AC inhibitors, although AC inhibitors significantly inhibited the increase in cAMP. Inhibition of Gβγ subunits using gallein significantly inhibited the relaxation to CGRP in human coronary arteries.

CONCLUSION: While CGRP signalling is generally assumed to act via cAMP, the CGRP-induced vasodilation in HCA was not inhibited by targeting this intracellular signalling pathway at different levels. Instead, inhibition of Gβγ subunits did inhibit the relaxation to CGRP, suggesting a different mechanism of CGRP-induced relaxation than generally believed.

PMID:38583945 | DOI:10.1111/bph.16372

J Cheminform. 2024 Apr 7;16(1):40. doi: 10.1186/s13321-024-00832-1.

ABSTRACT

Poly ADP-ribose polymerase 1 (PARP1) is an attractive therapeutic target for cancer treatment. Machine-learning scoring functions constitute a promising approach to discovering novel PARP1 inhibitors. Cutting-edge PARP1-specific machine-learning scoring functions were investigated using semi-synthetic training data from docking activity-labelled molecules: known PARP1 inhibitors, hard-to-discriminate decoys property-matched to them with generative graph neural networks and confirmed inactives. We further made test sets harder by including only molecules dissimilar to those in the training set. Comprehensive analysis of these datasets using five supervised learning algorithms, and protein-ligand fingerprints extracted from docking poses and ligand only features revealed one highly predictive scoring function. This is the PARP1-specific support vector machine-based regressor, when employing PLEC fingerprints, which achieved a high Normalized Enrichment Factor at the top 1% on the hardest test set (NEF1% = 0.588, median of 10 repetitions), and was more predictive than any other investigated scoring function, especially the classical scoring function employed as baseline.

PMID:38582911 | DOI:10.1186/s13321-024-00832-1

Eur Arch Otorhinolaryngol. 2024 Apr 5. doi: 10.1007/s00405-024-08624-x. Online ahead of print.

ABSTRACT

PURPOSE: We aimed to analyze patterns of failure and disease volume-treatment outcomes in patients with Nasopharyngeal carcinoma (NPC) treated with definitive radiation with or without concurrent chemotherapy at a tertiary cancer centre in northeast India.

METHODS: From February 2018 to February 2022, 99 histopathologically proved non-metastatic NPC patients treated with curative-intent RT with or without chemotherapy were retrospectively analyzed. Locally advanced patients received neoadjuvant or adjuvant chemotherapy. The Cox proportional hazards model was used to investigate the impact of various prognostic factors on locoregional free survival (LRFS), distant metastasis free survival (DMFS), progression free survival (PFS) and overall survival (OS). The log-rank test and Kaplan-Meir curves compared outcome variables based on ROC analysis-classified tumor volume.

RESULTS: During a median follow up of 25.4 months (17.3-39.2), 35(35.4%) patients developed recurrence. Twenty-three patients developed locoregional failures, of which 11 were in-field; 12 patient showed an out-field failure. The 3-year LRFS, DMFS, PFS and OS was 71.10%, 70.90%, 64.10% and 74.10% respectively. There was statistically significant difference in LRFS according to T staging (p < 0.0001). Gross tumor volume (GTVp) and gross nodal volume (GTVn) were an independent prognostic factor for OS, PFS, LRFS and DMFS. The cut-off volumes for GTVp and GTVn for distant metastases and locoregional failure, respectively, were found to be 13 and 22.7 mL and 3.7 and 39.2 mL, respectively, by ROC curve analysis. Based on this, 99 patients were divided into three subgroups. OS demonstrated significant differences among patients in different volume subgroups for GTVp (p = 0.03) and GTVn (p = 0.00024).

CONCLUSIONS: For NPC patients who undergo curative IMRT, primary tumour and nodal volumes are independent prognostic indicators. GTVp and GTVn are highly predictive of local control, distant metastases, disease-free survival, and overall survival. This justifies their use as quantitative prognostic indicator for NPC.

PMID:38578506 | DOI:10.1007/s00405-024-08624-x

Front Cell Dev Biol. 2024 Mar 21;12:1357589. doi: 10.3389/fcell.2024.1357589. eCollection 2024.

ABSTRACT

The Myc family of proto-oncogenes is a key node for the signal transduction of external pro-proliferative signals to the cellular processes required for development, tissue homoeostasis maintenance, and regeneration across evolution. The tight regulation of Myc synthesis and activity is essential for restricting its oncogenic potential. In this review, we highlight the central role that Myc plays in regeneration across the animal kingdom (from Cnidaria to echinoderms to Chordata) and how Myc could be employed to unlock the regenerative potential of non-regenerative tissues in humans for therapeutic purposes. Mastering the fine balance of harnessing the ability of Myc to promote transcription without triggering oncogenesis may open the door to many exciting opportunities for therapeutic development across a wide array of diseases.

PMID:38577503 | PMC:PMC10991803 | DOI:10.3389/fcell.2024.1357589