bluuebunny/crossref_metadata_2025_split huggingface dataset:
Synergistic Effects of PARP Inhibition and Cholesterol Biosynthesis Pathway Modulation
Authors: Rutkowska Anna , Eberl H. Christian , Werner Thilo , Hennrich Marco L. , Sévin Daniel C. , Petretich Massimo , Reddington James P. , Pocha Shirin , Gade Stephan , Martinez-Segura Amalia , Dvornikov Dmytro , Karpiak Joel , Sweetman Gavain M.A. , Fufezan Christian , Duempelfeld Birgit , Braun Florian , Schofield Christopher , Keles Hakan , Alvarado David , Wang Zhuo , Jansson Keith H. , Faelth-Savitski Maria , Curry Edward , Remlinger Katja , Stronach Euan A. , Feng Bin , Sharma Geeta , Coleman Kevin , Grandi Paola , Bantscheff Marcus , Bergamini Giovanna 
Published: July 2024

Abstract

An in-depth multiomic molecular characterization of PARP inhibitors revealed a distinct poly-pharmacology of niraparib (Zejula) mediated by its interaction with lanosterol synthase (LSS), which is not observed with other PARP inhibitors. Niraparib, in a similar way to the LSS inhibitor Ro-48-8071, induced activation of the 24,25-epoxysterol shunt pathway, which is a regulatory signaling branch of the cholesterol biosynthesis pathway. Interestingly, the combination of an LSS inhibitor with a PARP inhibitor that does not bind to LSS, such as olaparib, had an additive effect on killing cancer cells to levels comparable with niraparib as a single agent. In addition, the combination of PARP inhibitors and statins, inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A reductase, an enzyme catalyzing the rate-limiting step in the mevalonate pathway, had a synergistic effect on tumor cell killing in cell lines and patient-derived ovarian tumor organoids. These observations suggest that concomitant inhibition of the cholesterol biosynthesis pathway and PARP activity might result in stronger efficacy of these inhibitors against tumor types highly dependent on cholesterol metabolism.

Significance:
The presented data indicate, to our knowledge, for the first time, the potential benefit of concomitant modulation of cholesterol biosynthesis pathway and PARP inhibition and highlight the need for further investigation to assess its translational relevance.
Clinical Efficacy of the HIV Protease Inhibitor Indinavir in Combination with Chemotherapy for Advanced Classic Kaposi Sarcoma Treatment: A Single-Arm, Phase II Trial in the Elderly
Authors: Sgadari Cecilia , Scoppio Biancamaria , Picconi Orietta , Tripiciano Antonella , Gaiani Francesca Maria , Francavilla Vittorio , Arancio Angela , Campagna Massimo , Palladino Clelia , Moretti Sonia , Monini Paolo , Brambilla Lucia , Ensoli Barbara 
Published: July 2024

Abstract

Kaposi sarcoma is a rare angioproliferative disease associated with human herpes virus-8 (HHV-8) infection. Kaposi sarcoma is frequent and aggressive in HIV-infected people, whereas the classic form (CKS) generally has an indolent course. Notably, all conventional therapies against Kaposi sarcoma have only temporary efficacy. We have previously shown that indinavir, a HIV protease-inhibitor with direct antiangiogenic and antitumor activity, is safe and effective in patients with early CKS, whereas effects are less prominent in advanced disease, probably due to the larger tumor mass. Therefore, the clinical response to indinavir was assessed in patients with advanced CKS after debulking chemotherapy. This was a monocentric phase 2 trial in elderly with progressive/advanced CKS treated with debulking chemotherapy and indinavir combined, followed by a maintenance phase with indinavir alone. Secondary endpoints included safety and Kaposi sarcoma biomarker evaluation.
All evaluable patients (22) responded to debulking therapy. Out of these, 16 entered the indinavir maintenance phase. The overall response rate at end of maintenance was 75% (estimated median response-duration 43 months). Moreover, most responders showed further clinical improvements (lesion number/nodularity) during maintenance and post-treatment follow-up. Notably, after relapse, progressors did not require systemic Kaposi sarcoma therapy and showed clinical improvements (including disease stabilization) remaining on study. Responders also showed immune status amelioration with a consistent B-cell increase and positive changes of other biomarkers, including anti-HHV-8 natural killer activity. In advanced CKS a strategy combining indinavir and chemotherapy is safe and associated with high and durable response rates and it could be rapidly adopted for the clinical management of these patients.

Significance:
This phase-2 trial showed that the HIV protease inhibitor indinavir may boost and extend the duration of the effects of chemotherapy in elderly with advanced progressive classic Kaposi sarcoma, without additional toxicity. Further, the amelioration of the immune status seen in responders suggests a better control of HHV-8 infection and tumor-cell killing. Thus, indinavir combined with chemotherapy may represent an important tool for the clinical management of classic Kaposi sarcoma in elderly patients.
Predicting Recanalization Failure With Conventional Devices During Endovascular Treatment Related to Vessel Occlusion
Authors: Flores Alan , Elizalde Marcos , Seró Laia , Ustrell Xavier , Avivar Ylenia , Pellisé Anna , Rodriguez Paula , Monterde Angela , Lara Lidia , Gonzalez‐de‐Echavarri Jose Maria , Cuba Victor , Gisbert Marc Rodrigo , Requena Manuel , Molina Carlos A. , Chamorro Angel , Perez de la Ossa Natalia , Cardona Pedro , Cánovas David , Purroy Francisco , Silva Yolanda , Camzpello Ana , Marti‐Fabregas Joan , Abilleira Sonia , Ribó Marc ,   Catalan Stroke Code and Reperfusion Consortium
Published: July 2024

Background
Among patients with stroke eligible for endovascular treatment, preprocedure identification of those with low chances of successful recanalization with conventional devices (stent‐retrievers and/or direct aspiration) may allow anticipating procedural rescue strategies. We aimed to develop a preprocedural algorithm able to predict recanalization failure with conventional devices (RFCD).

Methods
Observational study. Data from consecutive patients with stroke who received endovascular treatment between 2019 and 2022 in 10 centers were collected from the Catalan Stroke Registry (Codi Ictus Catalunya Registry, CICAT). RFCD was defined as final thrombolysis in cerebral infarction ≤2a or the use of rescue therapy defined as balloon angioplasty±stent deployment. Univariate and multivariate analysis to identify variables associated with RFCD were performed. A gradient boosted decision tree machine learning model to predict RFCD was developed utilizing preprocedure variables previously selected. Clinical improvement at 24 hours was defined as a drop of ≥4 points from baseline National Institutes of Health Stroke Scale score or 0–1 at 24 hours.

Results

In total, 984 patients were included; RFCD was observed in 14.3% (n:141) of the cases. Of these, 47.5% (n = 67) received balloon angioplasty±stent deployment as rescue therapy. Among patients receiving balloon angioplasty±stent deployment, clinical improvement was associated with lower number of attempts with conventional devices (median number of passes 2 versus 3;
P
= 0.045). In logistic regression, the absence of atrial fibrillation (odds ratio [OR]: 2.730, 95%CI: 1.541–4.836;
P
= 0.007) and no‐thrombolytic treatment (OR: 1.826, 95%CI: 1.230–2.711;
P
= 0.003) emerged as independent predictors of RFCD. A predictive model for RFCD, based on age, sex, hypertension, wake‐up stroke, baseline National Institutes of Health Stroke Scale score, Alberta Stroke Program Early CT [Computed Tomography] Score, occlusion site, thrombolysis, and atrial fibrillation showed an acceptable discrimination (area under the curve: 0.72±0.024 SD) and accuracy (0.75±0.015 SD). Overall performance was moderate (weighted F1‐score: 0.77±0.041 SD).

Conclusion
In RFCD patients, early balloon angioplasty±stent deployment rescue was associated with improved outcomes. A predictive model using affordable preprocedure clinical variables could be useful to identify these patients before intervention.
Trade-Offs Between Energy and Depth of Neural Networks
Authors: Uchizawa Kei , Abe Haruki 
Published: July 2024

Abstract
We present an investigation on threshold circuits and other discretized neural networks in terms of the following four computational resources—size (the number of gates), depth (the number of layers), weight (weight resolution), and energy—where the energy is a complexity measure inspired by sparse coding and is defined as the maximum number of gates outputting nonzero values, taken over all the input assignments. As our main result, we prove that if a threshold circuit C of size s, depth d, energy e, and weight w computes a Boolean function f (i.e., a classification task) of n variables, it holds that log( rk (f))≤ed(logs+logw+logn) regardless of the algorithm employed by C to compute f, where rk (f) is a parameter solely determined by a scale of f and defined as the maximum rank of a communication matrix with regard to f taken over all the possible partitions of the n input variables. For example, given a Boolean function CD n(ξ) =⋁i=1n/2ξi∧ξn/2+i, we can prove that n/2≤ed( log s+logw+logn) holds for any circuit C computing CD n. While its left-hand side is linear in n, its right-hand side is bounded by the product of the logarithmic factors of s,w,n and the linear factors of d,e. If we view the logarithmic terms as having a negligible impact on the bound, our result implies a trade-off between depth and energy: n/2 needs to be smaller than the product of e and d. For other neural network models, such as discretized ReLU circuits and discretized sigmoid circuits, we also prove that a similar trade-off holds. Thus, our results indicate that increasing depth linearly enhances the capability of neural networks to acquire sparse representations when there are hardware constraints on the number of neurons and weight resolution.
YUTO MMS: A comprehensive SLAM dataset for urban mobile mapping with tilted LiDAR and panoramic camera integration
Authors: Zhang Yiujia , Ahmadi SeyedMostafa , Kang Jungwon , Arjmandi Zahra , Sohn Gunho 
Published: July 2024

The York University Teledyne Optech (YUTO) Mobile Mapping System (MMS) Dataset, encompassing four sequences totaling 20.1 km, was thoroughly assembled through two data collection expeditions on August 12, 2020, and June 21, 2019. Acquisitions were performed using a uniquely equipped vehicle, fortified with a panoramic camera, a tilted LiDAR, a Global Positioning System (GPS), and an Inertial Measurement Unit (IMU), journeying through two strategic locations: the York University Keele Campus in Toronto and the Teledyne Optech headquarters in City of Vaughan, Canada. This paper not only delineates the comprehensive overview of the YUTO MMS dataset, delving into aspects such as the collection procedure, sensor configuration, synchronization, data structure and format but also presents a robust benchmark of prevailing Simultaneous Localization and Mapping (SLAM) systems. By subjecting them to analysis utilizing the introduced dataset, this research lays a foundational baseline for ensuing studies, thereby contributing to advancements and enhancements in the SLAM-integrated mobile mapping system. The dataset can be downloaded from: https://ausmlab.github.io/yutomms/ .
Preparation of highly biodegradable and electron beam crosslinkable linear low-density polyethylene - based biocomposites with unique mechanical performance
Authors: Singh Manjeet , Jha Atanu , Ray Chowdhury Subhendu , Pant Harish Jagat 
Published: July 2024

Preparation of high starch containing LLDPE (linear low-density polyethylene)/starch composite with a considerable degree of mechanical properties has always been a challenge for a long time. These challenges are low thermal stability of starch, difficulties in processability of high starch containing LLDPE, inability of polymers to contain large quantities of starch and compromised mechanical properties of prepared composites. To overcome these difficulties, 20 wt% ENGAGE (ethylene-octene copolymer), a polyolefin elastomer, was blended with 80 wt% LLDPE followed by composites preparation with modified starch-pistachio shell powder (SPSP). ENGAGE, due to its unique processability, improved the processability of high SPSP-containing LLDPE composite. And due to the generation of extra space by amorphous ENGAGE, the LLDPE/ENGAGE blends could accommodate up to 70 wt% SPSP without any degradation during high-temperature processing. Mechanical properties were also considerably enhanced due to the reinforcement of the polymer matrix by pistachio shell powder (PSP). SEM and dynamic mechanical analysis (DMA) confirmed the structural integrity of processed composites and uniform dispersion of SPSP into LLDPE/ENGAGE blends. The obtained LLDPE-based composites with 70% biodegradability and around 240% elongation are unique and useful. It is also revealed that the presence of 20 wt% PSP inhibits electron beam-initiated degradation of starch instead leading to crosslinked network in composites, thus further enhancing properties.
Characteristics of Patients With Amyotrophic Lateral Sclerosis Followed by a Home Palliative Care Team
Authors: Mercadante Sebastiano , Petronaci Antonino , Terranova Angela , Casuccio Alessandra 
Published: July 2024

Background Information about patients with amyothrophic lateral sclerosis (ALS) followed at home is limited. Objectives To assess patients’s characteristics at admission to a home palliative care program based on a multidisciplinary team, and the temporal course along the trajectory of ALS disease. Design Retrospective. Setting/subjects: Charts of a consecutive number of ALS patients who were referred to a specialistic home palliative care were reviewed. Measurement General data, referral, start of home palliative care, use of ventilator support and nutritional support, were recorded. The existence of advance directives and shared care planning was also collected. Results 82 patients were examined; 31 patients died before the term of the study and 51 patients were still living. No patient anticipately expressed their will regarding their treatments. However, a certain number of patients shared a care planning with ALS team, generally after starting home care. Most patients did not have ventilatory support at the beginning of home care assistance, but progressively received ventilatory support by NIV or MV, particularly those who were still living. NIV at start of home care was negatively correlated to frontotemporal dementia. ( P = 0.015), and directly correlated to referral from hospital and GP ( P = 0.031) and awareness of disease ( P = 0.034). Gastrostomy at start of home care was positively correlated to referral from hospital ( P = 0.046). Gastrostomy during home care was correlated to bulbar SLA ( P = 0.017). The use of NIV during home care was positively correlated to shared care planning ( P = 0.001). Conclusion The continuous presence of a multi-specialist team may provide timely intervention, guarantee and trust on the part of the patient and family members.
Management of renal artery aneurysms: A retrospective study
Authors: Vi Lisa , Kim Minji Jinny , Eisenberg Naomi , Tan Kong T , Roche-Nagle Graham 
Published: July 2024

Background Although renal artery aneurysms (RAAs) are rare and often asymptomatic with slow growth, their natural progression and optimal management are not well understood. Treatment recommendations for RAAs do exist; however, they are supported by limited data. Methods A retrospective cohort study was conducted to explore the management of patients diagnosed with an RAA at our institution from January 1st, 2013, to December 31st, 2020. Patients were identified through a search of our radiological database, followed by a comprehensive chart review for further assessment. Data collection encompassed patient and aneurysm characteristics, the rationale for initial imaging, treatment, surveillance, and all-cause mortality. Results One hundred eighty-five patients were diagnosed with or treated for RAAs at our center during this timeframe, with most aneurysms having been discovered incidentally. Average aneurysm size was 1.40 cm (±0.05). Of those treated, the mean size was 2.38 cm (±0.24). Among aneurysms larger than 3 cm in size, comprising 3.24% of the total cases, 83.3% underwent treatment procedures. Only 20% of women of childbearing age received treatment for their aneurysms. There was one instance of aneurysm rupture, with no associated mortality or significant morbidity. Conclusions Our institution’s management of RAAs over the period of the study generally aligned with guidelines. One potential area of improvement is more proactive intervention for women of childbearing age.
Microbiome in radiotherapy: an emerging approach to enhance treatment efficacy and reduce tissue injury
Authors: Lu Lina , Li Fengxiao , Gao Yuanyuan , Kang Shuhe , Li Jia , Guo Jinwang 
Published: July 2024

AbstractRadiotherapy is a widely used cancer treatment that utilizes powerful radiation to destroy cancer cells and shrink tumors. While radiation can be beneficial, it can also harm the healthy tissues surrounding the tumor. Recent research indicates that the microbiota, the collection of microorganisms in our body, may play a role in influencing the effectiveness and side effects of radiation therapy. Studies have shown that specific species of bacteria living in the stomach can influence the immune system’s response to radiation, potentially increasing the effectiveness of treatment. Additionally, the microbiota may contribute to adverse effects like radiation-induced diarrhea. A potential strategy to enhance radiotherapy outcomes and capitalize on the microbiome involves using probiotics. Probiotics are living microorganisms that offer health benefits when consumed in sufficient quantities. Several studies have indicated that probiotics have the potential to alter the composition of the gut microbiota, resulting in an enhanced immune response to radiation therapy and consequently improving the efficacy of the treatment. It is important to note that radiation can disrupt the natural balance of gut bacteria, resulting in increased intestinal permeability and inflammatory conditions. These disruptions can lead to adverse effects such as diarrhea and damage to the intestinal lining. The emerging field of radiotherapy microbiome research offers a promising avenue for optimizing cancer treatment outcomes. This paper aims to provide an overview of the human microbiome and its role in augmenting radiation effectiveness while minimizing damage.
Myeloid-derived growth factor in diseases: structure, function and mechanisms
Authors: Chen Peng , Huang Xiaohui , Li Weiwen , Wen Weixing , Cao Yue , Li Jiahuan , Huang Yuli , Hu Yunzhao 
Published: July 2024

AbstractMyeloid-derived growth factor (MYDGF) is a novel secreted protein with potent antiapoptotic and tissue-repairing properties that is present in nearly 140 human tissues and cell lines, with the highest abundance in the oral epithelium and skin. Initially, MYDGF was found in bone marrow-derived monocytes and macrophages for cardioprotection and repair after myocardial infarction. Subsequent studies have shown that MYDGF plays an important role in other cardiovascular diseases (e.g., atherosclerosis and heart failure), metabolic disorders, renal disease, autoimmune/inflammatory disorders, and cancers. Although the underlying mechanisms have not been fully explored, the role of MYDGF in health and disease may involve cell apoptosis and proliferation, tissue repair and regeneration, anti-inflammation, and glycolipid metabolism regulation. In this review, we summarize the current progress in understanding the role of MYDGF in health and disease, focusing on its structure, function and mechanisms. The graphical abstract shows the current role of MYDGF in different organs and diseases (Fig. 1).
Screening for genetic variability in photosynthetic regulation provides insights into salt performance traits in forage sorghum under salt stress
Authors: Amombo Erick , Gbibar Maryam , Ashilenje Dennis S. , Hirich Abdelaziz , Kouisni Lamfeddal , Oukarroum Abdallah , Ghoulam Cherki , El Gharous Mohamed , Nilahyane Abdelaziz 
Published: July 2024

Abstract
Background
Sorghum (Sorghum bicolor) is a promising opportunity crop for arid regions of Africa due to its high tolerance to drought and heat stresses. Screening for genetic variability in photosynthetic regulation under salt stress can help to identify target trait combinations essential for sorghum genetic improvement. The primary objective of this study was to identify reliable indicators of photosynthetic performance under salt stress for forage yield within a panel of 18 sorghum varieties from stage 1 (leaf 3) to stage 7 (late flowering to early silage maturity). We dissected the genetic diversity and variability in five stress-sensitive photosynthetic parameters: nonphotochemical chlorophyll fluorescence quenching (NPQ), the electron transport rate (ETR), the maximum potential quantum efficiency of photosystem II (FV/FM), the CO2 assimilation rate (A), and the photosynthetic performance based on absorption (PIABS). Further, we investigated potential genes for target phenotypes using a combined approach of bioinformatics, transcriptional analysis, and homologous overexpression.

Results
The panel revealed polymorphism, two admixed subpopulations, and significant molecular variability between and within population. During the investigated development stages, the PIABS varied dramatically and consistently amongst varieties. Under higher saline conditions, PIABS also showed a significant positive connection with A and dry matter gain. Because PIABS is a measure of plants’ overall photosynthetic performance, it was applied to predict the salinity performance index (SPI). The SPI correlated positively with dry matter gain, demonstrating that PIABS could be used as a reliable salt stress performance marker for forage sorghum. Eight rubisco large subunit genes were identified in-silico and validated using qPCR with variable expression across the varieties under saline conditions. Overexpression of Rubisco Large Subunit 8 increased PIABS, altered the OJIP, and growth with an insignificant effect on A.

Conclusions
These findings provide insights into strategies for enhancing the photosynthetic performance of sorghum under saline conditions for improved photosynthetic performance and potential dry matter yield. The integration of molecular approaches, guided by the identified genetic variability, holds promise for genetically breeding sorghum tailored to thrive in arid and saline environments, contributing to sustainable agricultural practices.