bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cellular lethal damage of 64Cu incorporated in mammalian genome evaluated with Monte Carlo methods
Authors: Carrasco-Hernandez Jhonatan , Ramos-Méndez José , Padilla-Rodal Elizabeth , Avila-Rodriguez Miguel A. 
Published: September 2023

PurposeTargeted Radionuclide Therapy (TRT) with Auger Emitters (AE) is a technique that allows targeting specific sites on tumor cells using radionuclides. The toxicity of AE is critically dependent on its proximity to the DNA. The aim of this study is to quantify the DNA damage and radiotherapeutic potential of the promising AE radionuclide copper-64 (64Cu) incorporated into the DNA of mammalian cells using Monte Carlo track-structure simulations.MethodsA mammalian cell nucleus model with a diameter of 9.3 μm available in TOPAS-nBio was used. The cellular nucleus consisted of double-helix DNA geometrical model of 2.3 nm diameter surrounded by a hydration shell with a thickness of 0.16 nm, organized in 46 chromosomes giving a total of 6.08 giga base-pairs (DNA density of 14.4 Mbp/μm3). The cellular nucleus was irradiated with monoenergetic electrons and radiation emissions from several radionuclides including 111In, 125I, 123I, and 99mTc in addition to 64Cu. For monoenergetic electrons, isotropic point sources randomly distributed within the nucleus were modeled. The radionuclides were incorporated in randomly chosen DNA base pairs at two positions near to the central axis of the double-helix DNA model at (1) 0.25 nm off the central axis and (2) at the periphery of the DNA (1.15 nm off the central axis). For all the radionuclides except for 99mTc, the complete physical decay process was explicitly simulated. For 99mTc only total electron spectrum from published data was used. The DNA Double Strand Breaks (DSB) yield per decay from direct and indirect actions were quantified. Results obtained for monoenergetic electrons and radionuclides 111In, 125I, 123I, and 99mTc were compared with measured and calculated data from the literature for verification purposes. The DSB yields per decay incorporated in DNA for 64Cu are first reported in this work. The therapeutic effect of 64Cu (activity that led 37% cell survival after two cell divisions) was determined in terms of the number of atoms incorporated into the nucleus that would lead to the same DSBs that 100 decays of 125I. Simulations were run until a 2% statistical uncertainty (1 standard deviation) was achieved.ResultsThe behavior of DSBs as a function of the energy for monoenergetic electrons was consistent with published data, the DSBs increased with the energy until it reached a maximum value near 500 eV followed by a continuous decrement. For 64Cu, when incorporated in the genome at evaluated positions (1) and (2), the DSB were 0.171 ± 0.003 and 0.190 ± 0.003 DSB/decay, respectively. The number of initial atoms incorporated into the genome (per cell) for 64Cu that would cause a therapeutic effect was estimated as 3,107 ± 28, that corresponds to an initial activity of 47.1 ± 0.4 × 10−3 Bq.ConclusionOur results showed that TRT with 64Cu has comparable therapeutic effects in cells as that of TRT with radionuclides currently used in clinical practice.
VIDIIA Hunter: a low-cost, smartphone connected, artificial intelligence-assisted COVID-19 rapid diagnostic platform approved for medical use in the UK
Authors: Poirier Aurore C. , Riaño Moreno Ruben D. , Takaindisa Leona , Carpenter Jessie , Mehat Jai W. , Haddon Abi , Rohaim Mohammed A. , Williams Craig , Burkhart Peter , Conlon Chris , Wilson Matthew , McClumpha Matthew , Stedman Anna , Cordoni Guido , Branavan Manoharanehru , Tharmakulasingam Mukunthan , Chaudhry Nouman S. , Locker Nicolas , Fernando Anil , Balachandran Wamadeva , Bullen Mark , Collins Nadine , Rimer David , Horton Daniel L. , Munir Muhammad , La Ragione Roberto M. 
Published: September 2023

Introduction: Accurate and rapid diagnostics paired with effective tracking and tracing systems are key to halting the spread of infectious diseases, limiting the emergence of new variants and to monitor vaccine efficacy. The current gold standard test (RT-qPCR) for COVID-19 is highly accurate and sensitive, but is time-consuming, and requires expensive specialised, lab-based equipment.Methods: Herein, we report on the development of a SARS-CoV-2 (COVID-19) rapid and inexpensive diagnostic platform that relies on a reverse-transcription loop-mediated isothermal amplification (RT-LAMP) assay and a portable smart diagnostic device. Automated image acquisition and an Artificial Intelligence (AI) deep learning model embedded in the Virus Hunter 6 (VH6) device allow to remove any subjectivity in the interpretation of results. The VH6 device is also linked to a smartphone companion application that registers patients for swab collection and manages the entire process, thus ensuring tests are traced and data securely stored.Results: Our designed AI-implemented diagnostic platform recognises the nucleocapsid protein gene of SARS-CoV-2 with high analytical sensitivity and specificity. A total of 752 NHS patient samples, 367 confirmed positives for coronavirus disease (COVID-19) and 385 negatives, were used for the development and validation of the test and the AI-assisted platform. The smart diagnostic platform was then used to test 150 positive clinical samples covering a dynamic range of clinically meaningful viral loads and 250 negative samples. When compared to RT-qPCR, our AI-assisted diagnostics platform was shown to be reliable, highly specific (100%) and sensitive (98–100% depending on viral load) with a limit of detection of 1.4 copies of RNA per µL in 30 min. Using this data, our CE-IVD and MHRA approved test and associated diagnostic platform has been approved for medical use in the United Kingdom under the UK Health Security Agency’s Medical Devices (Coronavirus Test Device Approvals, CTDA) Regulations 2022. Laboratory and in-silico data presented here also indicates that the VIDIIA diagnostic platform is able to detect the main variants of concern in the United Kingdom (September 2023).Discussion: This system could provide an efficient, time and cost-effective platform to diagnose SARS-CoV-2 and other infectious diseases in resource-limited settings.
How sleep quality affects activities of daily living in Parkinson’s disease: the mediating role of disease severity and the moderating role of cognition
Authors: Luo Yajun , Liu Junyi , Chen Dongqin , Liu Manhua , Yuan Yuan , Hu Jingzhe , Wu Jiayu , Wang Fen , Liu Chunfeng , Chen Juping , Mao Chengjie 
Published: September 2023

ObjectiveThe aim of this study was to explore the influential mechanism of the relationship between sleep quality and activities of daily living (ADL) in patients with Parkinson’s disease (PD), we hypothesized disease severity as a mediator and assumed the mediating process was regulated by cognition.Methods194 individuals with PD (95 women and 99 men) were enrolled in study. The Pittsburgh Sleep Quality Index (PSQI) was used to assess sleep quality of PD patients. Patients’ ADL, disease severity and cognition were measured by the Unified Parkinson’s Disease Rating Scale-II (UPDRSII), Hoehn-Yahr (H-Y) Scale, and Mini-Mental State Examination (MMSE). We investigated the mediating role of disease severity and the moderating effect of cognition on the association between sleep quality and ADL in PD patients.ResultsThe score of UPDRSII was positively correlated with the score of PSQI and H-Y stage, while the score of MMSE was negatively correlated with the score of H-Y stage and UPDRSII. Sleep quality predicts disease severity, and disease severity predicts ADL. Disease severity mediated the relationship between sleep quality and ADL, and the mediating effect was 0.179. Cognition alone did not affect ADL, but the interaction between disease severity and cognition was significantly affected ADL, confirming the moderating effect of cognition in PD patients.ConclusionDisease severity mediated the association between sleep quality and ADL, good cognition significantly reduced disease severity’s mediating influence on the relationship between sleep quality and ADL. Our study indicated a close relationship between ADL and sleep and cognition in PD, and also provided new insights into the overall management of PD and a better quality of life of PD patients.
Effects of acupuncture synchronized rehabilitation therapy on upper limb motor and sensory function after stroke: a study protocol for a single-center, 2 × 2 factorial design, randomized controlled trial
Authors: Yu Zifu , Yang Xiaoxia , Qin Fang , Ma Tiantian , Zhang Jie , Leng Xiaoxuan , Bi Hongyan , Liu Xihua 
Published: September 2023

BackgroundUpper limb function reconstruction has been an important issue in the field of stroke rehabilitation. Due to the complexity of upper extremity dysfunction in stroke patients, the clinical efficacy produced by central or peripheral stimulation alone is limited. For this reason, our group has proposed acupuncture synchronized rehabilitation therapy (ASRT), i.e., simultaneous scalp acupuncture and intradermal acupuncture during rehabilitation. Pre-experiments results showed that this therapy can effectively improve the motor and sensory functions of upper limbs in post-stroke patients, but the clinical efficacy and safety of ASRT need to be further verified, and whether there is a synergistic effect between scalp acupuncture and intradermal acupuncture also needs to be studied in depth. Therefore, we designed a randomized controlled trial to compare the efficacy and safety of different therapies to explore a more scientific “synchronous treatment model.”MethodsThis is a single-center, randomized controlled trial using a 2 × 2 factorial design. We will recruit 136 stroke survivors with upper extremity dysfunction and randomize them into four groups (n = 34). All subjects will undergo routine treatment, based on which the Experimental Group 1: rehabilitation training synchronized with intradermal acupuncture treatment of the affected upper limb; Experimental Group 2: rehabilitation training of the affected upper limb synchronized with focal-side scalp acupuncture treatment, and Experimental Group 3: rehabilitation training synchronized with intradermal acupuncture treatment of the affected upper limb synchronized with focal-side scalp acupuncture treatment; Control Group: rehabilitation training of the affected upper limb only. The intervention will last for 4 weeks, 5 times a week. Both acupuncture treatments will be performed according to the Revised Standards for Reporting Interventions in Clinical Trials of Acupuncture (STRICTA). The primary outcome indicators for this trial are Fugl-Meyer Assessment-Upper Extremity and Somatosensory Evoked Potential. Secondary outcome indicators include Wolf Motor Function Test, Upper Extremity Function Test, revised Nottingham Sensory Assessment Scale, Diffusion Tensor Imaging, and Modified Barthel Index. The incidence of adverse events will be used as the indicator of safety.DiscussionThe study will provide high-quality clinical evidence on whether ASRT improves upper limb motor and sensory function and activities of daily living (ADL) in stroke patients, and determine whether scalp acupuncture and intradermal acupuncture have synergistic effects.Clinical trial registrationhttps://www.chictr.org.cn/, Chinese Clinical Trial Registry [ChiCTR2200066646].
A case report of neurosyphilis coexisting with a positive MOG antibody manifested as optic neuritis
Authors: Shi Min , Luo Danqing , Li Zhaoying , Li Man , Jin Shuoguo , Yang Dongdong , Guo Jun , Chen Guo 
Published: September 2023

BackgroundNeurosyphilis refers to an infection of the central nervous system by Treponema pallidum. The clinical manifestations of neurosyphilis are diverse, making it easy to miss or misdiagnose. Anti-myelin oligodendrocyte glycoprotein antibody-associated disease is a recently defined immune-mediated inflammatory demyelinating central nervous system disease. Few studies have reported the coexistence of the two diseases.Case presentationThis case report presents a 37 years-old male patient with neurosyphilis manifested as optic neuritis with a positive myelin oligodendrocyte glycoprotein (MOG) antibody. This patient received intravenous administration of 3.2 million units of procaine penicillin every 4 h for 2 weeks, followed by a two-week intramuscular injection of benzathine penicillin. Additionally, methylprednisolone sodium succinate was administered intravenously at 1,000 mg/day, gradually reduced to 500 mg/day and 240 mg/day every 3 days. Subsequently, prednisone tablets at a dosage of 60 mg/day were orally administered, with a gradual reduction of 5 mg/day every 3 days until reaching a dosage of 30 mg/day. The patient’s visual acuity was improved after 26 days of hospitalization. However, the visual field and color vision did not. At 3 months of follow-up, the symptoms remained unchanged despite the patient continued taking oral prednisone tablets at a dosage of 30 mg/day.ConclusionNeurosyphilis could be a potential triggering factor for MOGAD. In patients with neurosyphilis, it is strongly recommended to perform testing for MOG antibody along with other brain disease antibodies.
Outcome of early rehabilitation of patients with traumatic brain injury during COVID-19 pandemic in The Republic of Srpska, Bosnia and Herzegovina
Authors: Keleman Nataša , Krasnik Rastislava , Mikov Aleksandra , Dragičević-Cvjetković Dragana 
Published: September 2023

IntroductionThe COVID-19 pandemic has placed a tremendous burden on the healthcare system. Patients with traumatic brain injury (TBI) have to get fast track treatment which is independent of environmental conditions. The aim of this study was to investigate epidemiological and clinical outcomes of early rehabilitation and compare it with the literature data during the non-COVID-19 period.Materials and methodsA retrospective study included 174 patients with TBI, average 57 ± 19.08 years. They all underwent treatment in the University Clinical Center, Republic of Srpska, Bosnia and Herzegovina during the period January-December 2021. We have analyzed the epidemiological data and clinical course in 174 patients as well as the outcome of early rehabilitation in 107 patients. In clinical evaluation were used: Glasgow Coma Score (GCS), Functional Independence Measure (FIM) and Barthel Index on admission and at discharge, as well as Glasgow Outcome Scale (GOS) at discharge. ANOVA, SPANOVA, Student t-test and Pearson correlation coefficient were used in statistical analysis. The value (p &lt; 0.05) was used for statistical significance.ResultsA total of 174 patients with TBI were included in this study. Most of the patients (n = 94) were older than 60, male (n = 125) and the most frequent cause of TBI was falling over (n = 88). About a half (n = 92) had a mild TBI, almost one third of the sample had moderate (n = 52), while only 30 patients had severe TBI. Total of 139 (80.3%) patients had the improved outcome, the worsening was registered in 2 (1.2%), while the fatal outcome was reported with 33 (18.5%) patients. When comparing the scores on admission and at discharge, the improvement of mean parameter values was reported for GCS (9.9 vs. 14.1), for Barthel Index (57.25 vs. 86.85), and for FIM (67.35 vs. 105.15), (p &lt; 0.001). A complete recovery at discharge was found in 63.79%, a mild deficit in 8.62%, while serious deficit was found with 6.32%, and vegetative state with 2.29% patients.ConclusionThe COVID-19 pandemic had a significant effect on the epidemiological data but not on the clinical outcome of patients with TBI. Early rehabilitation proved to be effective and to contribute to positive treatment outcome.
Longitudinal changes in home food availability across the first 3 years of life and associations with family context predictors
Authors: Fiese Barbara H. , Barton Jennifer M. , Sahin Esra 
Published: September 2023

BackgroundThere is limited research tracking changes in home food availability during the first 3 years of life and whether the family context influences these changes.ObjectiveThis study examined changes in and predictors of home food availability across the first 3 years of life.DesignThis study utilized longitudinal data from the STRONG Kids2 birth cohort from the target child at 6 weeks to 36 months postpartum.ParticipantsMothers of 468 children were surveyed at 6 weeks, 3, 12, 24, and 36 months postpartum.MethodsHome observations were completed by trained research assistants to complete the presence of foods in the home. The primary outcomes were the availability of 10 food groups and scores from the Home Food Inventory (HFI), including dairy (regular fat), dairy (reduced fat), processed meats, other meats and non-dairy protein, savory snacks, vegetables, vegetables (no potatoes), and three obesogenic scores. Repeated measures ANOVA were used to examine changes in the HFI food groups and obesogenic scores over time. Multilevel regressions were conducted to examine whether the presence of an older sibling, entry into childcare, and mother’s return to full-time work were associated with the HFI.ResultsSignificant changes were detected for dairy (regular fat), other meats and non-dairy protein, savory snacks, vegetables, vegetables (no potatoes), and all obesogenic scores across time. A linear trend occurred for most HFI groups, however, the third obesogenic score (without milk and cheese) was highest at 3 months, declined at 12 months, and then slowly increased from 12 to 36 months years. The presence of an older sibling was a consistent predictor of the HFI groups over time. Entry into childcare was only associated with the availability of processed meats.ConclusionThe availability of food types shift as children age and their dietary needs alter. It is important to consider the whole family context such as the presence of older siblings whose dietary needs may differ from younger children. Future efforts are warranted to consider changes in food availability among diverse samples and different family structures.
Mathematical analysis identifies the optimal treatment strategy for epidermal growth factor receptor-mutated non-small cell lung cancer
Authors: Yu Qian , Kobayashi Susumu S. , Haeno Hiroshi 
Published: September 2023

IntroductionIn Asians, more than half of non-small cell lung cancers (NSCLC) are induced by epidermal growth factor receptor (EGFR) mutations. Although patients carrying EGFR driver mutations display a good initial response to EGFR-Tyrosine Kinase Inhibitors (EGFR-TKIs), additional mutations provoke drug resistance. Hence, predicting tumor dynamics before treatment initiation and formulating a reasonable treatment schedule is an urgent challenge.MethodsTo overcome this problem, we constructed a mathematical model based on clinical observations and investigated the optimal schedules for EGFR-TKI therapy.ResultsBased on published data on cell growth rates under different drugs, we found that using osimertinib that are efficient for secondary resistant cells as the first-line drug is beneficial in monotherapy, which is consistent with published clinical statistical data. Moreover, we identified the existence of a suitable drug-switching time; that is, changing drugs too early or too late was not helpful. Furthermore, we demonstrate that osimertinib combined with erlotinib or gefitinib as first-line treatment, has the potential for clinical application. Finally, we examined the relationship between the initial ratio of resistant cells and final cell number under different treatment conditions, and summarized it into a therapy suggestion map. By performing parameter sensitivity analysis, we identified the condition where　osimertinib-first therapy was recommended as the optimal treatment option.DiscussionThis study for the first time theoretically showed the optimal treatment strategies based on the known information in NSCLC. Our framework can be applied to other types of cancer in the future.
Survival prognosis model for elderly women with epithelial ovarian cancer based on the SEER database
Authors: Zhou Yingping , Wang Aifen , Sun Xin , Zhang Rong , Zhao Luwen 
Published: September 2023

ObjectivesWe aimed to analyze the risk factors of elderly women with epithelial ovarian cancer (EOC) using data on the SEER database, and to generate a nomogram model their 1-, 3-, and 5-year prognoses. The resulting nomogram model should be useful for clinical diagnoses and treatment.MethodsWe collected clinical data of women older than 70 years with epithelial ovarian cancer (diagnosed on the basis of surgical pathology) from the SEER database including datasets between 2010 and 2019. We randomly grouped the data into two groups (7:3 ratio) using the R language software. We divided the independent prognostic factors obtained by univariate and multi-factor Cox regression analyses into training and validation sets, and we plotted the same independent prognostic factors in a nomogram model of overall survival (OS) at 1, 3, and 5 years. We used the C-index, calibration curve, and area under the curve to validate the nomograms. We further evaluated the model and its clinical applicability using decision curve analyses.ResultsWe identified age, race, marital status, histological type, AJCC staging, differentiation degree, unilateral and bilateral tumor involvement, number of positive lymph nodes, chemotherapy, surgery, sequence of systemic treatment versus surgery, and time from diagnosis to treatment as independent prognostic factors for elderly women with EOC (P &lt; 0.5). The C-indexes were 0.749 and 0.735 in the training and validation sets, respectively; the ROC curves showed that the AUC of each prognostic factor was greater than 0.7; and, the AUC values predicted by the line plot were similar in the training and validation sets. The decision curves suggest that this line plot model has a high clinical value for predicting overall survivals at 1, 3, and 5 years in elderly women with EOC.ConclusionThe nomogram model in this study can provide an accurate assessment of the overall survival of women older than 70 years with EOC at the time of the first treatment, and it provides a basis for individualized clinical treatment.