bluuebunny/crossref_metadata_2025_split huggingface dataset:
Treatment drop-in in a contemporary cohort used to derive cardiovascular risk prediction equations
Authors: Liang Jingyuan , Jackson Rodney T , Pylypchuk Romana , Choi Yeunhyang , Chung Claris , Crengle Sue , Gao Pei , Grey Corina , Harwood Matire , Holt Anders , Kerr Andrew , Mehta Suneela , Wells Susan , Poppe Katrina 
Published: July 2024

Background
No routinely recommended cardiovascular disease (CVD) risk prediction equations have adjusted for CVD preventive medications initiated during follow-up (treatment drop-in) in their derivation cohorts. This will lead to underestimation of risk when equations are applied in clinical practice if treatment drop-in is common. We aimed to quantify the treatment drop-in in a large contemporary national cohort to determine whether equations are likely to require adjustment.

Methods
Eight de-identified individual-level national health administrative datasets in Aotearoa New Zealand were linked to establish a cohort of almost all New Zealanders without CVD and aged 30–74 years in 2006. Individuals dispensing blood-pressure-lowering and/or lipid-lowering medications between 1 July 2006 and 31 December 2006 (baseline dispensing), and in each 6-month period during 12 years’ follow-up to 31 December 2018 (follow-up dispensing), were identified. Person-years of treatment drop-in were determined.

Results
A total of 1 399 348 (80%) out of the 1 746 695 individuals in the cohort were not dispensed CVD medications at baseline. Blood-pressure-lowering and/or lipid-lowering treatment drop-in accounted for 14% of follow-up time in the group untreated at baseline and increased significantly with increasing predicted baseline 5-year CVD risk (12%, 31%, 34% and 37% in <5%, 5–9%, 10–14% and ≥15% risk groups, respectively) and with increasing age (8% in 30–44 year-olds to 30% in 60–74 year-olds).

Conclusions
CVD preventive treatment drop-in accounted for approximately one-third of follow-up time among participants typically eligible for preventive treatment (≥5% 5-year predicted risk). Equations derived from cohorts with long-term follow-up that do not adjust for treatment drop-in effect will underestimate CVD risk in higher risk individuals and lead to undertreatment. Future CVD risk prediction studies need to address this potential flaw.
Generalized Bio-Plausible Neuron Model with Refractoriness, Frequency Adaptation and Dynamic Threshold
Authors: Sheriff I. Munavar , Sakthivel R. 
Published: June 2024

Real biological neurons are dynamical systems that can process a nonlinear, arbitrary input signal with a dynamic threshold voltage, exhibit refractory time, and have a smooth [Formula: see text]–[Formula: see text] curve. This paper presents a generalized bio-plausible neuron model with refractoriness, frequency adaptation, and dynamic threshold. The spiking characteristics of the generalized neuron are enhanced with less circuitry and fewer parameters compared to older circuits. The proposed silicon neuron can generate all known spiking behaviors, just like a biological neuron. The circuit is designed using a 180 nm standard CMOS process. The entire design uses 22 transistors with a total power consumption of only 2 nW for a 1 nA step current at a spike frequency of 122 Hz. The power consumption and spike frequency rate depend on the input current. The proposed neuron is also capable of displaying both Type I and Type II frequency response characteristics. In addition, our neuron model underwent Monte Carlo simulation with 1000 sample runs to assess its robustness and stability against process variations and uncertainties. The results indicate that the average energy consumption of the proposed neuron model falls within the range of 16 pJ to 68 pJ.
Clasp pass moves and arrow polynomials of virtual knots
Authors: Sakurai Migiwa 
Published: June 2024

For classical knots, clasp pass moves are closely related to Vassiliev invariants of degree [Formula: see text]. Tsukamoto showed that the values of the Vassiliev invariant of degree [Formula: see text] induced from the Jones polynomial for two knots differ by [Formula: see text] or [Formula: see text], if they are related by a single clasp pass move. For virtual knots, the arrow polynomial is a generalization of the Jones polynomial and induces a Vassiliev invariant of degree [Formula: see text]. We show that the values of the Vassiliev invariant of degree [Formula: see text] induced from the arrow polynomial of two virtual knots differ by [Formula: see text] or [Formula: see text], if they are related by a single clasp pass move. We also obtain a lower bound of the distance between virtual knots by clasp pass moves.
Spatial Variation of Earthquake Hazard for Amaravati City of Peninsular India: A Probabilistic Approach
Authors: Satyannarayana Rambha , Rajesh Bande Giridhar 
Published: June 2024

Earthquakes begin with abrupt shifts along the faults. These movements release seismic waves that propagate through the Earth, shaking the ground as a result of the stored “elastic strain” energy being released. Property loss and human deaths occur due to improper design of structures under the earthquake loading conditions. It is observed that Peninsular India witnessed steady-to-serious earthquakes in the last 50 years. Amaravati is the prospective capital city of Andhra Pradesh State, which is situated on the Coromandel Coast of Peninsular India. The upcoming capital city, Amaravati, requires an earthquake hazard analysis because important engineering structures and infrastructure systems will be constructed in the near future. In this study, a probabilistic approach is used to assess the earthquake hazard for Amaravati City (latitudes: 16∘24[Formula: see text]36[Formula: see text]–16∘35[Formula: see text]24[Formula: see text][Formula: see text]N and longitudes: 80∘24[Formula: see text]25[Formula: see text]–80∘36[Formula: see text]18[Formula: see text][Formula: see text]E), India. The seismic risks of Amaravati City presented in terms of the configuration of ground motion parameters, peak ground acceleration (PGA), and spectral response acceleration ([Formula: see text]) at 0.05[Formula: see text]s and 1[Formula: see text]s for 2% and 10% Risks of Exceedance in 50 years, are produced. The uncertainties involved in seismic risk prediction are accounted for by selecting different attenuation relations developed for globally shallow crustal intraplate earthquakes with a logic tree approach. Additionally, the seismic risk values are disaggregated for Amaravati City (16∘31[Formula: see text]37[Formula: see text][Formula: see text]N and 80∘29[Formula: see text]46[Formula: see text][Formula: see text]E) to understand the individual contributions of seismic sources in terms of earthquake magnitude and site distance. The uniform hazard spectra are developed for the important places of the Amaravati Capital City and are compared with the Indian seismic code [IS 1893 (Part 1): Criteria for earthquake-resistant design of structures — Part 1: General provisions and buildings] for the rocky site. It is found that the estimated PGA values for Amaravati City are higher than the values recommended by IS 1893 (Part 1) for the rocky site. The results of this study will be very helpful for the composition of earthquake-resistant infrastructures in Amaravati City.
Fixating targets in visual search: The role of dorsal and ventral attention networks in the processing of relevance and rarity
Authors: Ischebeck Anja , Kreilinger Hannah , Peiris Miller Joe , Höfler Margit , Gilchrist Iain D. , Körner Christof 
Published: July 2024

Abstract
The dorsal attention network, often observed to be activated in serial visual search tasks, has been associated with goal-directed attention, responsible for the processing of task relevance. In serial visual search, the moment of target detection constitutes not only a task-relevant event, but also a rare event. In the present fMRI experiment, we disentangled task relevance from item rarity using a fixation-based analysis approach. We used a multiple target search task, and participants had to report the number of targets among distractors in the display. We had also added rare distractors to the displays. We found that rare events (targets and rare distractors) activated the dorsal attention network more strongly than common distractors. More importantly, we observed that the left IPS and the left insula, belonging to the dorsal and ventral attention system, respectively, were more strongly activated for targets compared to rare distractors. Using multi-voxel pattern analysis, we found that activation in the TPJ, bilaterally, an area also associated with the ventral attention system, distinguished between target and rare distractor fixations. These results point to an expanded role of the TPJ that seems to process post-perceptual information which is linked to task relevance.
The dissociative role of bursting and non-bursting neural activity in the oscillatory nature of functional brain networks
Authors: Cordier Alix , Mary Alison , Vander Ghinst Marc , Goldman Serge , De Tiège Xavier , Wens Vincent 
Published: July 2024

Abstract
The oscillatory nature of intrinsic brain networks is largely taken for granted in the systems neuroscience community. However, the hypothesis that brain rhythms—and by extension transient bursting oscillations—underlie functional networks has not been demonstrated per se. Electrophysiological measures of functional connectivity are indeed affected by the power bias, which may lead to artefactual observations of spectrally specific network couplings not genuinely driven by neural oscillations, bursting or not. We investigate this crucial question by introducing a unique combination of a rigorous mathematical analysis of the power bias in frequency-dependent amplitude connectivity with a neurobiologically informed model of cerebral background noise based on hidden Markov modeling of resting-state magnetoencephalography (MEG). We demonstrate that the power bias may be corrected by a suitable renormalization depending nonlinearly on the signal-to-noise ratio, with noise identified as non-bursting oscillations. Applying this correction preserves the spectral content of amplitude connectivity, definitely proving the importance of brain rhythms in intrinsic functional networks. Our demonstration highlights a dichotomy between spontaneous oscillatory bursts underlying network couplings and non-bursting oscillations acting as background noise but whose function remains unsettled.
Outbreak of equine herpesvirus 4 (EHV-4) in Denmark: tracing patient zero and viral characterization
Authors: Ryt-Hansen Pia , Johansen Victoria Kyhl , Cuicani Marta Maria , Larsen Lars Erik , Hansen Sanni 
Published: July 2024

Abstract
Background
Equine herpesvirus 4 (EHV-4) causes respiratory disease in horses, and the virus is considered endemic in the global equine population. However, outbreaks can occur when several horses are gathered in relation to shows, competitions, breeding units and at hospitals. In the spring year 2022, an EHV-4 outbreak occurred at the Large Animal Teaching Hospital, University of Copenhagen, Denmark. Nine horses were tested EHV-4 positive during the outbreak, which lasted approx. seven weeks. In addition, a tenth horse “Eq10” tested EHV-4 positive almost three weeks after the last of the outbreak horses tested positive. Detailed clinical registrations were obtained from all ten horses as well as their location and movement during hospitalization. Nasal swabs were obtained throughout the outbreak and tested by qPCR for EHV-4. Additionally, pre- and post-infection sera were tested for the presence of EHV-4 antibodies. Selected samples were characterized by partial and full genome sequencing.

Results
The most common clinical signs of the EHV-4 infected horses during this outbreak were pyrexia, nasal discharge, mandibular lymphadenopathy and increased lung sounds upon auscultation. Based on the locations of the horses, EHV-4 detection and antibody responses the most likely “patient zero” was identified as being “Eq1”. Partial genome sequencing revealed that Eq10 was infected by another wild type EHV-4 strain, suggesting that the hospital was able to eliminate the outbreak by testing and reinforcing biosecurity measures. The complete genome sequence of the outbreak strain was obtained and revealed a closer relation to Australian and Japanese EHV-4 strains rather than to other European EHV-4 strains, however, very limited sequence data are available from Europe.

Conclusion
The study illustrated the transmission of EHV-4 within an equine facility/hospital and provided new insights into the viral shedding, antibody responses and clinical signs related to EHV-4 infections. Finally, sequencing proved a useful tool in understanding the transmission within the hospital, and in characterizing of the outbreak strain.
ZnO NPs induce miR-342-5p mediated ferroptosis of spermatocytes through the NF-κB pathway in mice
Authors: Liu Guangyu , Lv Jing , Wang Yifan , Sun Kaikai , Gao Huimin , Li Yuanyou , Yao Qichun , Ma Lizhu , Kochshugulova Gulzat , Jiang Zhongliang 
Published: July 2024

Abstract
Background
Zinc oxide nanoparticle (ZnO NP) is one of the metal nanomaterials with extensive use in many fields such as feed additive and textile, which is an emerging threat to human health due to widely distributed in the environment. Thus, there is an urgent need to understand the toxic effects associated with ZnO NPs. Although previous studies have found accumulation of ZnO NPs in testis, the molecular mechanism of ZnO NPs dominated a decline in male fertility have not been elucidated.

Results
We reported that ZnO NPs exposure caused testicular dysfunction and identified spermatocytes as the primary damaged site induced by ZnO NPs. ZnO NPs led to the dysfunction of spermatocytes, including impaired cell proliferation and mitochondrial damage. In addition, we found that ZnO NPs induced ferroptosis of spermatocytes through the increase of intracellular chelatable iron content and lipid peroxidation level. Moreover, the transcriptome analysis of testis indicated that ZnO NPs weakened the expression of miR-342-5p, which can target Erc1 to block the NF-κB pathway. Eventually, ferroptosis of spermatocytes was ameliorated by suppressing the expression of Erc1.

Conclusions
The present study reveals a novel mechanism in that miR-342-5p targeted Erc1 to activate NF-κB signaling pathway is required for ZnO NPs-induced ferroptosis, and provide potential targets for further research on the prevention and treatment of male reproductive disorders related to ZnO NPs.

Graphical Abstract
Filarial chylous ascites with chylothorax: challenge of diagnosis and management case report
Authors: Elhadidy Abdelmoneim , Elrefaay Mohamed , Elsheshiny Hamdy , Elnagdy Fathy 
Published: July 2024

Abstract
Background
Chylous ascites (CA), an uncommon clinical condition, is defined as a milky-appearing, triglyceride-rich peritoneal fluid in the abdominal cavity. It may be due to malignancy or cirrhosis in developed countries or infections such as tuberculosis or filariasis in developing countries. This report presents a female patient with chylous ascites with chylothorax secondary to lymphatic filariasis after the exclusion of other etiologies.

Case presentation
A 33-year-old female, from Damietta, Egypt, was referred to us complaining of abdominal distension and easy fatigability for 5 months. The patient was diagnosed to have elephantiasis of both lower limbs caused by filariasis and treated by ant-filarial therapy for 9 years. Aspirated ascitic fluid was milky in appearance and rich in triglyceride. All other causes of chylous ascites were excluded by ascetic fluid analysis (chemical, microbiological, and pathological). The patient was treated with diethylcarbamazine (DEC), albendazole, pheniramine, and hydrocortisone followed by a therapeutic pleural and ascitic tapping but ascites re-accumulate. With the addition of doxycycline and Somatostatin/ocreotide, the ascites gradually decreased. Three months later, the patient came back with a significant increase in ascites, and paracentesis was done.

Conclusion
Despite rarity, filarial chylous ascites remains a challenge, and the only effective treatment is still repeated aspiration of the accumulated fluid. More work and discussion are needed.
Prognostic scores for predicting clinical outcomes in upper gastrointestinal bleeding
Authors: Khatana Gaurav , K Sunil Kumar , Kolassery Sandesh , Sebastian Saji , Joseph Deni , Muraleedharanpillai Ramu , Joseph Tony , V Nithya , Unnikrishnan Lal Krishna , Rony Gino 
Published: July 2024

Abstract

Background and aims
This study aimed to determine the performance of AIMS65, Rockall score, and Glasgow-Blatchford score (GBS) in patients presenting with upper gastrointestinal bleeding (UGIB) and to compare results between patients with nonvariceal UGIB (NVUGIB) and variceal UGIB (VUGIB).

Methods
We conducted a single-center prospective cohort study between December 2021 and December 2022. A total of 400 patients who met the inclusion criteria were included in the study, out of which 232 patients (58%) had NVUGIB and 168 patients (42%) had VUGIB. Receiver operating characteristic curve analysis was performed for all outcomes for comparison.

Results
Of the total of 400 patients with UGIB, 232 patients (58%) had NVUGIB, and 168 patients (42%) had VUGIB. The present study showed that GBS (AUROC 0.729, 95% CI: 0.598–0.859, p = 0.001) and RS (AUROC 0.693, 95% CI: 0.579–0.807, p = 0.005) but not AIMS65 (AUROC, 0.545, 95% CI: 0.412–0.679, p = 0.500) predicted in-hospital and overall 6-week mortality in patients with UGIB. All the three scores predicted need for blood transfusion and poor composite outcomes (p < 0.05). The need for endoscopic intervention was predicted by all the three scores in overall UGIB (OUGIB) patients (p < 0.05), only GBS and RS in NVUGIB patients (p < 0.05). Rebleeding was best predicated by RS in both OUGIB and NVUGIB patients (p < 0.05). None of the scores predicted the need for endoscopic intervention, rebleeding, need for surgical and radiological intervention, and composite outcomes in VUGIB patients (p > 0.05).

Conclusions
GBS and RS were superior to AIMS65 in predicted in-hospital and overall 6-week mortality in all the three categories: OUGIB, NVUGIB, and VUGIB patients.
Efficacy of encorafenib/binimetinib in patients with metastatic melanoma with brain metastases: Results from the nationwide Dutch Melanoma Treatment Registry.
Authors: Bloem Manja , van Not Olivier Jules , Aarts Maureen J.B. , Van Den Berkmortel Franchette , Blank Christian U. , Blokx Willeke , Boers-Sonderen Marye J. , Bonenkamp Han J. , de Groot Jan Willem , Haanen John , Hospers Geke , Kapiteijn Ellen , Piersma Djura , van Rijn Rozemarijn , Stevense - den Boer Marion , Van Der Veldt Astrid Aplonia Maria , Vreugdenhil Gerard , Wouters Michel WJM , Suijkerbuijk Karijn , van den Eertwegh Alfonsus Johannes Maria 
Published: July 2024

9528 Background: Data on the effectiveness of encorafenib plus binimetinib in patients with melanoma brain metastases (BMs) are lacking. Therefore, we aimed to investigate the effectiveness of encorafenib/binimetinib treatment in melanoma patients with BMs. Methods: All melanoma patients with BMs treated with encorafenib/binimetinib between 2019 and 2023 in the Netherlands were included from the nationwide Dutch Melanoma Treatment Registry. Patients with prior BRAF/MEK inhibition treatment were excluded. We analyzed overall response rates (ORR), progression-free (PFS), and overall survival (OS) from start of encorafenib/binimetinib. We performed subgroup analysis for symptomatic versus asymptomatic BMs and previous treatment versus no previous treatment. Results: In total, 208 patients were included. Median age was 61 years and 58.2% of the patients was male. Lactate dehydrogenase levels were elevated in 48.1% of the patients and symptomatic BMs were present in 63.5%. Of all patients, 41.8% received prior immunotherapy and for 58.2% encorafenib/binimetinib was the first-line treatment. The median follow-up duration was 23.2 months. The ORR was 67.3%. Median PFS was 5.6 months (95% confidence interval (CI): 4.9-6.2) and median OS was 10.9 months (95% CI: 9.6-14.0). OS was significantly shorter in patients with symptomatic BMs versus asymptomatic BMs (median 9.7 versus 22.9 months, p<0.01), while PFS was similar (median 5.6 versus 5.8 months, p=0.07). Previously untreated patients had worse prognostic characteristics than previously treated patients. PFS was not significantly different between patients with versus without previous systemic treatment (median 8.8 versus 5.2 months, p=0.08), while OS from start of encorafenib/binimetinib was longer for previously treated patients (median 15.9 versus 9.6 months, p<0.01). Conclusions: Encorafenib plus binimetinib has clinical activity in real world melanoma patients with BMs, but PFS and OS are shorter than previously reported for patients without brain metastases. These data may aid physicians in clinical decision-making.
Tolerance and safety of adjuvant metronomic capecitabine in Indian patients with non-metastatic triple negative breast cancer (TNBC): An institutional experience.
Authors: Kate Shruti , Ramesh Yasam Venkata , Vyavahare Rohini , Nagarkar Rajnish Vasant 
Published: July 2024

e12530 Background: Triple-negative breast cancer (TNBC) subtype has a high risk of recurrence and overall poorer survival after standard treatment. SYSUCC-001 study presented in ASCO 2020 reported an increased disease-free survival after one year of metronomic capecitabine in operable TNBC patients after completion of local therapy. As per our clinical experience in metastatic breast cancer, many Indian patients are not able to tolerate capecitabine for longer duration. Hence, we wanted to assess the tolerance and safety of one year of daily dosing of capecitabine in our patients with Non-Metastatic TNBC. Methods: We performed a retrospective analysis of non-metastatic TNBC patients receiving adjuvant capecitabine 650 mg /m2 twice daily continuously for one year who took treatment from June 2020 to August 2022. The data extracted included patient socio-demographics, capecitabine information, side effects, and capecitabine treatment changes (dose reductions and dose interruptions). Statistical analysis was conducted using SPSS, version 24. Results: We analyzed 90 patients, out of which majority (62%) were stage II. Median age of the cohort was 48 years. Germline data was available for 64 patients, out which 8 patients were BRCA 1 positive and 8 patients had a variant of undetermined significance. Median duration of capecitabine in our patients was 230 days (IQR: 10 - 360). Twenty-six (28.8%) patients underwent dose reduction and 15 (16.6%) had reported grade 3 toxicity. Mean dose of capecitabine received was 535 mg / m2 twice daily. Treatment was interrupted due to toxicity in 20 (22%) of patients. The most common capecitabine-induced toxicity was hand foot syndrome, which was also the most common reason for dose reduction and treatment interruption. Dihydropyrimidine dehydrogenase (DPD) mutation status was known for 38 patients out of which only one (2.6%) was found to have DPD deficiency. Incidence of grade 3 toxicity was observed to be less in patients with age less than 50 years, ECOG performance status 0-1 and absence of comorbidities. Two-year disease free survival (DFS) and overall survival (OS) was estimated to be 79.3% and 80% respectively. Most common site of metastases was reported to be brain followed by lung. Conclusions: Continuous metronomic dosing of adjuvant capecitabine for 1 year is fairly well tolerated in Indian patients with non-metastatic TNBC, but may still require dose reduction in some patients due to toxicity.