bluuebunny/crossref_metadata_2025_split huggingface dataset:
LncRNA KIFAP3-5:1 inhibits epithelial-mesenchymal transition of renal tubular cell through PRRX1 in diabetic nephropathy
Authors: Du Lei , Lu Yinfei , Wang Jingyi , Zheng Yijia , Li Huan , Liu Yunfei , Wu Xiaoling , Zhou Jieling , Wang Lei , He Linlin , Shi Jiasen , Xu Liu , Li Xizhi , Lu Qian , Yin Xiaoxing 
Published: June 2024

AbstractLong noncoding RNAs play an important role in several pathogenic processes in diabetic nephropathy, but the relationship with epithelial-mesenchymal transition in DN is unclear. Herein, we found that KIFAP3-5:1 expression was significantly down-regulated in DN plasma samples, db/db mouse kidney tissues and high glucose treated renal tubular epithelial cells compared to normal healthy samples and untreated cells. Overexpression of KIFAP3-5:1 improved renal fibrosis in db/db mice and rescued epithelial-mesenchymal transition of high glucose cultured renal tubular epithelial cells. The silence of KIFAP3-5:1 will exacerbate the progression of EMT. Mechanistically, KIFAP3-5:1 was confirmed to directly target to the -488 to -609 element of the PRRX1 promoter and negatively modulate PRRX1 mRNA and protein expressions. Furthermore, rescue assays demonstrated that the knockdown of PRRX1 counteracted the KIFAP3-5:1 low expression-mediated effects on EMT in hRPTECs cultured under high glucose. The plasma KIFAP3-5:1 of DN patients is highly correlated with the severity of renal dysfunction and plays an important role in the prediction model of DN diseases. These findings suggested that KIFAP3-5:1 plays a critical role in regulation of renal EMT and fibrosis through suppress PRRX1, and highlight the clinical potential of KIFAP3-5:1 to assist in the diagnosis of diabetic nephropathy.
Graphical abstract
A restless bandit approach for capacitated condition based maintenance scheduling
Authors: Demirci Ece Zeliha , Arts Joachim , Houtum Geert-Jan van 
Published: June 2024

AbstractThis paper considers the maintenance scheduling problem of multiple non-identical machines deteriorating over time. The deterioration gradually decreases a machine’s performance, which results in revenue losses due to lower output quality. The maintenance cost is dependent on the degradation state, and the number of maintenance activities that can be carried out simultaneously is restricted by the number of maintenance workers. Our main goal is to propose a heuristic with low complexity that consistently produces solutions close to the optimal strategy for problems of real size. We cast the problem as a restless bandit problem and propose an index based heuristic (Whittle’s index policy) which can be computed efficiently. We also provide a lower bound that can be computed by linear programming. We numerically compare the performance of the index heuristic with alternative policies. In addition to achieving superior performance over failure-based and threshold policies, Whittle’s policy numerically converges to our lower bound when the number of machines is moderately high and/or maintenance workload is high.
Single day 14 serum hCG values allow prediction of viable pregnancy and are significantly higher in frozen as compared to fresh single blastocyst transfer
Authors: Trautner Philip Sebastian , Oppelt Peter , Resch Sarah , Enzelsberger Simon Hermann , Ebner Thomas , Shebl Omar Josef 
Published: June 2024

Abstract
Purpose
To evaluate if single serum human chorionic gonadotropin (hCG) level measurements are sufficient for pregnancy monitoring after single embryo transfer (sET) and to compare the hCG levels between fresh (FRET) and frozen embryo transfers (FET) in medically assisted reproduction.

Methods
This was a retrospective exploratory cohort study including all patients who met the inclusion criteria, who received a single FRET (n = 249) or FET (n = 410) of a day five blastocyst at the IVF clinic at the Johannes Kepler University Linz between 2011 and 2020. hCG levels were measured on day 14 after embryo transfer. Threshold values for the viability of pregnancies were determined using receiver operating characteristic (ROC) curves.

Results
Significantly higher hCG levels were found in those who received FET than in those who received FRET (1222.8 ± 946.7 mU/ml vs. 862.7 ± 572.9 mU/ml; p < 0.001). Optimal threshold values predicting a viable pregnancy were 368.5 mU/ml and 523 mU/ml in the FRET and FET groups, respectively.

Conclusions
After FET, higher hCG values after 14 days of embryo transfer must be considered in pregnancy monitoring. Additionally, a single threshold hCG value seems to be sufficient for determining pregnancy viability. To exclude ectopic pregnancies, subsequent ultrasound examination is a mandatory requirement.
Determinants of adaptive behaviors during heatwaves in Pakistan: a study based on personal heatwave experiences and hypothetical scenarios
Authors: Ullah Farman , Valente Martina , Hubloue Ives , Akbar Muhammad Sannan , Ragazzoni Luca , Barone-Adesi Francesco 
Published: June 2024

AbstractHeatwaves have long been recognized as a serious public health threat. Effective adaptation measures can reduce the risks to people and ecosystems. The purpose of this study was to explore the determinants of heatwave adaptive behaviors using the Health Belief Model (HBM) as a framework. A cross-sectional study was conducted among a sample of 686 participants who were registered volunteers at the Alkhidmat Foundation in Pakistan, using an online questionnaire. For individual adaptive behaviors, only perceived benefits and self-efficacy were observed as significant predictors. For household adaptive behaviors, only cues to action and self-efficacy were found as significant predictors. In terms of overall adaptive behaviors, perceived benefits, perceived barriers, cues to action, and self-efficacy were significant predictors. Our study explores the influence of the HBM constructs on adaptive behaviors across various subgroups, highlighting their differential significance in rural and urban settings, formal and informal occupations, and experiences within heatwaves. These findings highlight the potential of the HBM in guiding the creation of impactful interventions that facilitate behavioral changes during heatwaves, thereby enhancing people’s adaptive behaviors. By emphasizing the association of the HBM with adaptive behaviors, our findings offer valuable insights for authorities seeking to make informed decisions and policies.
Synthesis, molecular docking and molecular dynamics simulations, drug-likeness studies, ADMET prediction and biological evaluation of novel pyrazole-carboxamides bearing sulfonamide moiety as potent carbonic anhydrase inhibitors
Authors: Yetek İrfan , Mert Samet , Tunca Ekrem , Bayrakdar Alpaslan , Kasımoğulları Rahmi 
Published: June 2024

AbstractPyrazoles are unique bioactive molecules with a versatile biological profile and they have gained an important place on pharmaceutical chemistry. Pyrazole compounds containing sulfonamide nuclei also attract attention as carbonic anhydrase (CA) inhibitors. In this study, a library of pyrazole-carboxamides were synthesized and the structures of the synthesized molecules were characterized using FT-IR, 1H-NMR, 13C-NMR and HRMS. Then the inhibition effects of newly synthesized molecules on human erythrocyte hCA I and hCA II isoenzymes were investigated. Ki values of the compounds were in the range of 0.063–3.368 µM for hCA I and 0.007–4.235 µM for hCA II. Molecular docking studies were performed between the most active compounds 6a, 6b and the reference inhibitor, acetazolamide (AAZ) and the hCA I and hCA II receptors to investigate the binding mechanisms between the compounds and the receptors. These compounds showed better interactions than the AAZ. ADMET analyzes were performed for the compounds and it was seen that the compounds did not show AMES toxicity. The stability of the molecular docking results over time was analysed by 50 ns molecular dynamics simulations. Molecular dynamics simulations revealed that 6a and 6b exhibited good stability after docking to the binding sites of hCA I and hCA II receptors, with minor conformational changes and fluctuations.
Graphical abstract
Synthesis, molecular docking, molecular dynamics simulations, drug-likeness, ADMET prediction and biological evaluation of pyrazole-carboxamides bearing sulfonamide moiety as potent carbonic anhydrase inhibitors
An Update on Breakthrough Invasive Mold Infections
Authors: Portillo Vera , Neofytos Dionysios 
Published: June 2024

AbstractThe incidence of breakthrough mold infections (bIMI) has been increasing, due to routine administration of broad-spectrum antifungal prophylaxis and an increasing pool of high-risk patient populations, with fungi more challenging to treat, resulting in a sustained high mortality, despite progress in diagnostic and therapeutic options. Pharmacokinetics of antifungal drugs, fungal, and host, including genetic, factors play a role in the emergence of bIMI. Suggested therapeutic approaches have included change of antifungal class treatment, with amphotericin-B products predominating as first-line empirical treatment and switching from one broad-spectrum azole to another remaining the most frequently used treatment modalities. Future perspectives include determining individual susceptibility to IMI to tailor prophylaxis and treatment strategies, improved diagnostic tests, and the introduction of new antifungal agents that may reduce morbidity and mortality caused by bIMI.
Sex-Specific Entorhinal Cortex Functional Connectivity in Cognitively Normal Older Adults with Amyloid-β Pathology
Authors: Gong Liang , Liu Duan , Zhang Bei , Yu Siyi , Xi Chunhua 
Published: June 2024

AbstractSex and apolipoprotein E (APOE) genotype have been shown to influence the risk and progression of Alzheimer’s disease (AD). However, the impact of these factors on the functional connectivity of the entorhinal cortex (ERC) in clinically unpaired older adults (CUOA) with amyloid-β (Aβ +) pathology remains unclear. A total of 1022 cognitively normal older adults with Aβ + (603 females and 586 APOE ε4 +) from the Anti-Amyloid Treatment in Asymptomatic Alzheimer’s (A4) study were included in this study. The 2 × 2 (gender, 2 APOE genotypes) analysis of covariance was performed to compare the demographic information, cognitive performance, and volumetric MRI data among these groups. Voxel-wise comparisons of bilateral ERC functional connectivity (FC) were conducted, and partial correlation analyses were used to explore the associations between cognitive performance and ERC-FC strength. We found that the APOE genotype influenced ERC functional connectivity mainly in the sensorimotor network (SMN). Males exhibited higher ERC-FC in the salience network (SN), while females displayed higher ERC-FC in the default mode network (DMN), executive control network (ECN), and reward network. The interplay of sex and APOE genotype on ERC-FC was observed in the SMN and cerebellar lobe. The ERC-FC was associated with executive function and memory performance in individuals with CUOA-Aβ + . Our findings provide evidence of sex-specific ERC functional connectivity compensation mechanism in cognitively normal older adults with Aβ + pathology. This study may contribute to a better understanding of the mechanisms underlying the early stages of AD and may help develop personalized interventions in preclinical AD.
Cognitive Control Is Enhanced by Single Pulse TMS Over the Left Frontal and Parietal Areas
Authors: Cespón Jesús , Pellicciari Maria Concetta , Miniussi Carlo 
Published: June 2024

Abstract: This study investigates the relationship between cognitive control and neural activity in the left prefrontal, premotor, and parietal cortices to elucidate how these areas contribute to cognitive control processes. Thus, we used transcranial magnetic stimulation (TMS)-electroencephalogram co-registration to investigate if and how TMS applied over these areas (compared to a sham TMS condition), at 180 ms after the stimulus onset, modulates cognitive control and underlying neural activity during the performance of a Simon task, in which participants have to inhibit the bias to react towards the stimulus location. The behavioral results showed that TMS over prefrontal and premotor areas reduced the interference in incongruent trials preceded by congruent trials, which are the most demanding trials because they require inhibiting the response towards the stimulus location and switching the stimulus-response binding. Also, TMS applied over premotor and parietal areas improved accuracy in incongruent trials. The electrophysiological results showed that TMS over prefrontal and premotor areas increased the fronto-central P300 amplitude, an event-related potential (ERP) component linked to conflict monitoring. Also, TMS over the left parietal area was related to earlier latency of the contralateral posterior negativity, an ERP linked to visuospatial attention. Importantly, the present study shows that TMS over prefrontal and premotor areas enhanced performance in the higher demanding trials by increasing neural processes underlying conflict monitoring (i.e., fronto-central P300 amplitude). Also, although further research is required, TMS over premotor and parietal areas might have strengthened cognitive control to withhold the response towards the stimulus location by modulating the parietal-premotor (or visuomotor) pathway.
Seismotectonics of the Philippine and Taiwan Subduction Systems and Implications for Seismic Hazards
Authors: Hutchings Sean J. , Mooney Walter D. 
Published: June 2024

AbstractThe seismicity of the Philippines and Taiwan provides insight into the tectonics and seismic hazards of a region characterized by subduction and collision. We summarize the seismotectonics of the Philippines and Taiwan by documenting the distribution of hypocenters for earthquakes of magnitude M ≥ 4.6 and focal mechanisms for earthquakes of magnitude M ≥ 5.0 over ∼21 years. We quantify seismicity rates (earthquake frequency) and compare seismicity distributions with proposed tectonic and faulting models. 6,187 earthquakes of magnitude M ≥ 4.6 occurred between 1 January 2000 and 31 March 2021, 79% at depths <70 km and 70% having magnitudes M < 5.0. Approximately 88 earthquakes of magnitude M ≥ 5.0 occur per year, with 12 events of magnitude M ≥ 7.0 occurring since January 2000. Seismic activity decreases exponentially between 50 and 210 km depth at a rate ∼10% faster than the global average. Intermediate and deep earthquakes at depths >70 km trace the Wadati‐Benioff zones of subducting slabs, most of which are only seismically active to depths of ∼250 km. The distribution of earthquakes at depths >70 km is likely influenced by the subduction of young lithosphere, slab tearing, and phase boundary interactions between depths of 410 and 660 km. Shallow earthquakes at depths ≤70 km are generated by megathrust, crustal, and intraslab faulting. Crustal thrust and strike‐slip faulting are the most abundant and prevalent sources of damaging earthquakes. The Philippines and Taiwan are subject to high seismic risk, similar to nearby Indonesia.
Under‐Ice Oxygen Depletion and Greenhouse Gas Supersaturation in North Temperate Urban Ponds
Authors: Gorsky Adrianna L. , Dugan Hilary A. , Wilkinson Grace M. , Stanley Emily H. 
Published: June 2024

AbstractStormwater ponds are common features in urbanized landscapes because they enhance flood reduction and nutrient retention. With shallow depths and high inputs of organic matter, these systems can be highly productive with rapid oxygen depletion when thermally stratified or ice‐covered. However, most of our understanding of the biogeochemistry of stormwater ponds comes from the open water period. We explored under‐ice oxygen dynamics in 20 stormwater ponds in Madison, WI (USA) that were ice covered from late December to early March to investigate the drivers of bottom water oxygen saturation and the impact on the accumulation of carbon dioxide (CO2) and methane (CH4). Winter anoxia was driven by ice transmissivity, winter nutrient concentrations, and precedent summer productivity. Oxygen depletion led to overall higher concentrations of greenhouse gases in pond surface waters. This research enhances our understanding of winter pond biogeochemistry and its links to summer productivity.
Disparities in access to hematopoietic cell transplant persist at a transplant center
Authors: Shoag Jamie , Rotz Seth J. , Hanna Rabi , Buhtoiarov Ilia , Dewey Elizabeth N. , Bruckman David , Hamilton Betty K. 
Published: June 2024

AbstractDisparities in access to hematopoietic cell transplant (HCT) are well established. Prior studies have identified barriers, such as referral and travel to an HCT center, that occur before consultation. Whether differences in access persist after evaluation at an HCT center remains unknown. The psychosocial assessment for transplant eligibility may impede access to transplant after evaluation. We performed a single-center retrospective review of 1102 patients who underwent HCT consultation. We examined the association between race/ethnicity (defined as Hispanic, non-Hispanic Black, non-Hispanic White, and Other) and socioeconomic status (defined by zip code median household income quartiles and insurance type) with receipt of HCT and Psychosocial Assessment of Candidates for Transplantation (PACT) scores. Race/ethnicity was associated with receipt of HCT (p = 0.02) with non-Hispanic Whites comprising a higher percentage of HCT recipients than non-recipients. Those living in higher income quartiles and non-publicly insured were more likely to receive HCT (p = 0.02 andp < 0.001, respectively). PACT scores were strongly associated with income quartiles (p < 0.001) but not race/ethnicity or insurance type. Race/ethnicity and socioeconomic status impact receipt of HCT among patients evaluated at an HCT center. Further investigation as to whether the psychosocial eligibility evaluation limits access to HCT in vulnerable populations is warranted.
The elite haplotype OsGATA8-H coordinates nitrogen uptake and productive tiller formation in rice
Authors: Wu Wei , Dong Xiaoou , Chen Gaoming , Lin Zhixi , Chi Wenchao , Tang Weijie , Yu Jun , Wang Saisai , Jiang Xingzhou , Liu Xiaolan , Wu Yujun , Wang Chunyuan , Cheng Xinran , Zhang Wei , Xuan Wei , Terzaghi William , Ronald Pamela C. , Wang Haiyang , Wang Chunming , Wan Jianmin 
Published: June 2024

AbstractExcessive nitrogen promotes the formation of nonproductive tillers in rice, which decreases nitrogen use efficiency (NUE). Developing high-NUE rice cultivars through balancing nitrogen uptake and the formation of productive tillers remains a long-standing challenge, yet how these two processes are coordinated in rice remains elusive. Here we identify the transcription factor OsGATA8 as a key coordinator of nitrogen uptake and tiller formation in rice. OsGATA8 negatively regulates nitrogen uptake by repressing transcription of the ammonium transporter gene OsAMT3.2. Meanwhile, it promotes tiller formation by repressing the transcription of OsTCP19, a negative modulator of tillering. We identify OsGATA8-H as a high-NUE haplotype with enhanced nitrogen uptake and a higher proportion of productive tillers. The geographical distribution of OsGATA8-H and its frequency change in historical accessions suggest its adaption to the fertile soil. Overall, this study provides molecular and evolutionary insights into the regulation of NUE and facilitates the breeding of rice cultivars with higher NUE.
Botensilimab plus balstilimab in relapsed/refractory microsatellite stable metastatic colorectal cancer: a phase 1 trial
Authors: Bullock Andrea J. , Schlechter Benjamin L. , Fakih Marwan G. , Tsimberidou Apostolia M. , Grossman Joseph E. , Gordon Michael S. , Wilky Breelyn A. , Pimentel Agustin , Mahadevan Daruka , Balmanoukian Ani S. , Sanborn Rachel E. , Schwartz Gary K. , Abou-Alfa Ghassan K. , Segal Neil H. , Bockorny Bruno , Moser Justin C. , Sharma Sunil , Patel Jaymin M. , Wu Wei , Chand Dhan , Rosenthal Katherine , Mednick Gabriel , Delepine Chloe , Curiel Tyler J. , Stebbing Justin , Lenz Heinz-Josef , O’Day Steven J. , El-Khoueiry Anthony B. 
Published: June 2024

AbstractMicrosatellite stable metastatic colorectal cancer (MSS mCRC; mismatch repair proficient) has previously responded poorly to immune checkpoint blockade. Botensilimab (BOT) is an Fc-enhanced multifunctional anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) antibody designed to expand therapy to cold/poorly immunogenic solid tumors, such as MSS mCRC. BOT with or without balstilimab (BAL; anti-PD-1 antibody) is being evaluated in an ongoing expanded phase 1 study. The primary endpoint is safety and tolerability, which was evaluated separately in the dose-escalation portion of the study and in patients with MSS mCRC (using combined dose-escalation/dose-expansion data). Secondary endpoints include investigator-assessed RECIST version 1.1–confirmed objective response rate (ORR), disease control rate (DCR), duration of response (DOR) and progression-free survival (PFS). Here we present outcomes in 148 heavily pre-treated patients with MSS mCRC (six from the dose-escalation cohort; 142 from the dose-expansion cohort) treated with BOT and BAL, 101 of whom were considered response evaluable with at least 6 months of follow-up. Treatment-related adverse events (TRAEs) occurred in 89% of patients with MSS mCRC (131/148), most commonly fatigue (35%, 52/148), diarrhea (32%, 47/148) and pyrexia (24%, 36/148), with no grade 5 TRAEs reported and a 12% discontinuation rate due to a TRAE (18/148; data fully mature). In the response-evaluable population (n = 101), ORR was 17% (17/101; 95% confidence interval (CI), 10–26%), and DCR was 61% (62/101; 95% CI, 51–71%). Median DOR was not reached (NR; 95% CI, 5.7 months–NR), and median PFS was 3.5 months (95% CI, 2.7–4.1 months), at a median follow-up of 10.3 months (range, 0.5–42.6 months; data continuing to mature). The combination of BOT plus BAL demonstrated a manageable safety profile with no new immune-mediated safety signals and encouraging clinical activity with durable responses. ClinicalTrials.gov identifier: NCT03860272.
Kinematics and spatial structure analysis of TBM gunite robot based on D–H parameter method
Authors: Jia Lianhui , Liu Shenyao , Cao Chenxu , Kang Yehao , Zhu Ying , Wang Lijun , Xu Donglai , Cheng Ruixue 
Published: June 2024

Abstract
In modern tunnel construction, TBM (Tunnel Boring Machine) plays a very important role. In response to the needs of tunnel wall reinforcement and TBM automated construction for tunnel construction, a shotcrete mechanism mounted on the TBM is designed. In order to evaluate the kinematic performance of the mechanism, this paper studies the forward and inverse kinematics and spatial architecture of the TBM shotcrete robot. Firstly, based on the D–H parameter method, the number of joints and links is determined and structural analysis is performed to obtain the robot's forward kinematics equation, achieving the mapping between joint space and pose space. Then, by determining the joint variables, the mapping of the end tool in Cartesian space is achieved. Finally, based on the Monte Carlo random sampling method, the workspace of the robot is constructed, and its reachability and flexibility within the robot workspace are evaluated. The performance of the device is verified by building a prototype, which meets the requirements well. Through the research in this paper, it can provide theoretical basis and guidance for the design and control of the shotcrete robot.