bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effect of chemotherapy regimens in male germ cell tumors on the development of primary hypogonadism
Authors: Handke Analena , Bargen Marla Geller-von , Isgandarov Aykhan , al Nader Mulham , Krafft Ulrich , Darr Christopher , Hadaschik Boris , Grünwald Viktor , Püllen Lukas 
Published: November 2024

AbstractMale germ cell tumors (GCT) have excellent survival. Long-term sequelae in cancer survivors are an evolving field. We evaluated the risk of patients with GCT to develop primary hypogonadism and adherence to guideline-recommended therapy in a real-world cohort. Monocentric study at a tertiary cancer centre to evaluate treated GCT-patients (2001–2019). Post therapeutic male endocrine function, International Index of Erectile Function (IIEF)-5 and The aging males’ symptoms rating scale (AMS) questionnaires were assessed. The overall response rates were low, with 44 of 402 contacted patients participating in the study. From these, 32(73%) underwent blood analysis, 42(95%) answered the IIEF-5 and 43(98%) the AMS. Latent hypogonadism (serum testosterone 8–12 nmol/l) was found in n = 9 (28%) and manifest hypogonadism (testosterone < 8 nmol/l) in n = 8 (25%). 50% (n = 21) indicated erectile dysfunction on IIEF-5 (cut off ≤ 21 pts.) and 62.8% (n = 27) reported symptomatic affection on AMS (cut off ≥ 27 pts.). Majority of tested patients revealed different degrees of hypogonadism. Standard instruments were able to detect gonadal damage in > 50%, which underscored the clinical need to evaluate endocrine function in cancer survivors. We further indicated the difficulties of today’s research and provided starting points to assess barriers for study participations.
Impact of L-carnitine supplementation on gastric emptying and bowel function in pediatric ketogenic diet therapy: a clinical trial
Authors: Nassar May Fouad , Shata Mennatallah Osama , Awadallah Shrouk Mohamed , Youssef Mennatallah Ayman , Ibrahim Haya Essam 
Published: November 2024

AbstractKetogenic diet (KD) is an excess fat, enough protein, and minimal carbohydrate diet. The high fat content in KD lowers the oesophageal sphincter tone, slows gastric emptying, and decreases intestinal transit time. The primary aim of the current clinical trial was to study the effect of L-carnitine supplementation on gastric emptying in children with drug resistant epilepsy (DRE) on KD. Assessment of the protective effect of L-carnitine on bowel function and habits in those patients was a secondary aim. The current study recruited 30 patients aged 12 months to 18 years newly diagnosed with DRE assigned to start KD who were following up at the Pediatric Clinical Nutrition and Neurology Outpatient Clinics or were admitted due to DRE at the Pediatric Neurology Inpatient Department, Children’s Hospital, Ain Shams University (Egypt). Participants were assigned randomly into 2 arms; arm I: received KD with L-carnitine supplementation, arm II: received KD only. Patients were assessed at baseline and after 3 months of starting KD, the assessments of children included: 24-hour dietary recall, Chalfont Seizures Severity Scale, gastrointestinal symptoms score and Bristol stool chart, frequency of defecation per week, anthropometric measurements assessment, fasting serum lipid profile and measurement of the antral length by ultrasound. There was significant increase in antral length in the patients who received KD with L-carnitine supplementation compared to the non-supplemented group. The antral length showed a significant negative correlation with GI symptoms score in all cases and the L-carnitine supplemented group. It also showed a significant positive correlation with Bristol stool score in all patients and a significant positive correlation with stool frequency in the L-carnitine supplemented group only. L-carnitine supplementation to children with DRE on KD has a significant role in improving gastric motility and it increases the frequency of defecation. Further studies are recommended to explore additional benefits, meanwhile it is prudent to advise L-carnitine supplementation for such patients.
Exploring peptide dendrimers for intestinal lymphatic targeting: formulation and evaluation of peptide dendrimer conjugated liposomes for enhancing the oral bioavailability of Asenapine maleate
Authors: Shreya Ajjappla Basavaraj , Pandey Abhijeet , Kulkarni Sanjay , Bhaskar K Vijaya , Parekh Harendra S. , Mutalik Srinivas 
Published: November 2024

AbstractAsenapine maleate (ASPM) is a second-generation atypical antipsychotic that is approved for treating acute schizophrenia and bipolar disorder in adults by the US FDA. The major downside of ASPM therapy is rapid, extensive first-pass hepatic metabolism following its oral administration with a very low oral bioavailability of < 2%. In this work, we developed ASPM nanoformulations conjugated with ligands such as arginine-glycine-aspartic acid (RGD) and peptide dendrimers (PDs) with the intention of improving the oral bioavailability of the drug by targeting it to the intestinal lymphatic system (ILS). Peptide dendrimers (PDs), both lipidated and nonlipidated, were synthesized by Fmoc solid phase peptide synthesis (SPPS). Reverse phase high performance chromatography (RP-HPLC) was used to purify the synthesized PDs, and the PDs were characterized by differential scanning calorimetry (DSC) electrospray ionization mass spectroscopy (ESI+-MS), Nuclear magnetic resonance (NMR) and Fourier transform infrared (FTIR) spectroscopy. The thin film hydration method was used to prepare liposomes, and the process variables affecting the liposome parameters were optimized using the Box‒Behnken design (BBD).Liposomes were PEGylated using DSPE-PEG-COOH2000 and further conjugated with ligands (RGD, PD-1 and PD-2) using EDC-NHS chemistry. The formulation was characterized using different spectroscopic techniques. In vitro, cell line studies, such as cytotoxicity, cell uptake, uptake mechanism, and receptor saturation studies, were performed on both Caco2 and Raji-B cells. The pharmacokinetic parameters of the developed liposomal formulation were evaluated using pharmacokinetic studies on Sprague- Dawley (SD) rats. The psychostimulant-induced hyperactivity model was used to evaluate the pharmacodynamic performance of the developed formulations by measuring the reversal of hyperlocomotor activity induced by levodopa-carbidopa.
Multi-step thermal design of microwave vacuum heating to basaltic regolith simulant towards lunar base construction
Authors: Kato Kunihiko , Shirai Takashi 
Published: November 2024

AbstractHumanned exploration and extended stay on the Moon are the hottest challenges today. We report highly robust materials by microwave heating under high-vacuum conditions (10− 3 Pa) from a basaltic regolith simulant (FJS-1) to ensure the feasibility of lunar infrastructure construction. The violent degassing dynamics were revealed by monitoring vacuum pressure during heating and analyzing the compounds evolved from basaltic silicate compounds: thermal pyrolysis of silicate compounds became more pronounced above 1000 oC, leading to a catastrophic deformation accompanied by forming countless pores of several hundred µm sizes. The preferential formation of the magnetite phase in vacuum heating dominantly caused the radical change in microwave absorption capacity compared with conventional heating routes using an electrical furnace in atmospheric conditions. Besides, the in-situ measurement of dielectric properties during microwave vacuum heating clarified the increase in one order of magnitude from 100 to 1000 oC. Based on the presumed phenomena during microwave-vacuum heating for basaltic regolith, we propose a new thermal design concept to overcome the practical limitations of microwave technology. The multi-step temperature profile successfully fabricated a highly robust product that demonstrated world-class mechanical performance, equivalent to the compressive strength of 65 MPa without any vigorous hydrostatic cold press as a pre-treatment.
Integrating deep learning for visual question answering in Agricultural Disease Diagnostics: Case Study of Wheat Rust
Authors: Nanavaty Akash , Sharma Rishikesh , Pandita Bhuman , Goyal Ojasva , Rallapalli Srinivas , Mandal Murari , Singh Vaibhav Kumar , Narang Pratik , Chamola Vinay 
Published: November 2024

AbstractThis paper presents a novel approach to agricultural disease diagnostics through the integration of Deep Learning (DL) techniques with Visual Question Answering (VQA) systems, specifically targeting the detection of wheat rust. Wheat rust is a pervasive and destructive disease that significantly impacts wheat production worldwide. Traditional diagnostic methods often require expert knowledge and time-consuming processes, making rapid and accurate detection challenging. We drafted a new, WheatRustDL2024 dataset (7998 images of healthy and infected leaves) specifically designed for VQA in the context of wheat rust detection and utilized it to retrieve the initial weights on the federated learning server. This dataset comprises high-resolution images of wheat plants, annotated with detailed questions and answers pertaining to the presence, type, and severity of rust infections. Our dataset also contains images collected from various sources and successfully highlights a wide range of conditions (different lighting, obstructions in the image, etc.) in which a wheat image may be taken, therefore making a generalized universally applicable model. The trained model was federated using Flower. Following extensive analysis, the chosen central model was ResNet. Our fine-tuned ResNet achieved an accuracy of 97.69% on the existing data. We also implemented the BLIP (Bootstrapping Language-Image Pre-training) methods that enable the model to understand complex visual and textual inputs, thereby improving the accuracy and relevance of the generated answers. The dual attention mechanism, combined with BLIP techniques, allows the model to simultaneously focus on relevant image regions and pertinent parts of the questions. We also created a custom dataset (WheatRustVQA) with our augmented dataset containing 1800 augmented images and their associated question-answer pairs. The model fetches an answer with an average BLEU score of 0.6235 on our testing partition of the dataset. This federated model is lightweight and can be seamlessly integrated into mobile phones, drones, etc. without any hardware requirement. Our results indicate that integrating deep learning with VQA for agricultural disease diagnostics not only accelerates the detection process but also reduces dependency on human experts, making it a valuable tool for farmers and agricultural professionals. This approach holds promise for broader applications in plant pathology and precision agriculture and can consequently address food security issues.
Age-dependent cerebral vasodilation induced by volatile anesthetics is mediated by NG2+ vascular mural cells
Authors: Zhou Hang , Neudecker Viola , Perez-Zoghbi Jose F. , Brambrink Ansgar M. , Yang Guang 
Published: November 2024

AbstractAnesthesia can influence cerebral blood flow by altering vessel diameter. Using in vivo two-photon imaging, we examined the effects of volatile anesthetics, sevoflurane and isoflurane, on vessel diameter in young and adult mice. Our results show that these anesthetics induce robust dilation of cortical arterioles and arteriole-proximate capillaries in adult mice, with milder effects in juveniles and no dilation in infants. This anesthesia-induced vasodilation correlates with decreased cytosolic Ca2+ levels in NG2+ vascular mural cells. Optogenetic manipulation of these cells bidirectionally regulates vessel diameter, and their ablation abolishes the vasodilatory response to anesthetics. In immature brains, NG2+ mural cells are fewer in number and express lower levels of Kir6.1, a subunit of ATP-sensitive potassium channels. This likely contributes to the age-dependent differences in vasodilation, as Kir6.1 activation promotes, while its inhibition reduces, anesthesia-induced vasodilation. These findings highlight the essential role of NG2+ mural cells in mediating anesthesia-induced cerebral vasodilation.
Efficient generation of protein pockets with PocketGen
Authors: Zhang Zaixi , Shen Wan Xiang , Liu Qi , Zitnik Marinka 
Published: November 2024

AbstractDesigning protein-binding proteins is critical for drug discovery. However, artificial-intelligence-based design of such proteins is challenging due to the complexity of protein–ligand interactions, the flexibility of ligand molecules and amino acid side chains, and sequence–structure dependencies. We introduce PocketGen, a deep generative model that produces residue sequence and atomic structure of the protein regions in which ligand interactions occur. PocketGen promotes consistency between protein sequence and structure by using a graph transformer for structural encoding and a sequence refinement module based on a protein language model. The graph transformer captures interactions at multiple scales, including atom, residue and ligand levels. For sequence refinement, PocketGen integrates a structural adapter into the protein language model, ensuring that structure-based predictions align with sequence-based predictions. PocketGen can generate high-fidelity protein pockets with enhanced binding affinity and structural validity. It operates ten times faster than physics-based methods and achieves a 97% success rate, defined as the percentage of generated pockets with higher binding affinity than reference pockets. Additionally, it attains an amino acid recovery rate exceeding 63%.
Differentiation signals induce APOBEC3A expression via GRHL3 in squamous epithelia and squamous cell carcinoma
Authors: Smith Nicola J , Reddin Ian , Policelli Paige , Oh Sunwoo , Zainal Nur , Howes Emma , Jenkins Benjamin , Tracy Ian , Edmond Mark , Sharpe Benjamin , Amendra Damian , Zheng Ke , Egawa Nagayasu , Doorbar John , Rao Anjali , Mahadevan Sangeetha , Carpenter Michael A , Harris Reuben S , Ali Simak , Hanley Christopher , Buisson Rémi , King Emma , Thomas Gareth J , Fenton Tim R 
Published: November 2024

AbstractTwo APOBEC DNA cytosine deaminase enzymes, APOBEC3A and APOBEC3B, generate somatic mutations in cancer, thereby driving tumour development and drug resistance. Here, we used single-cell RNA sequencing to study APOBEC3A and APOBEC3B expression in healthy and malignant mucosal epithelia, validating key observations with immunohistochemistry, spatial transcriptomics and functional experiments. Whereas APOBEC3B is expressed in keratinocytes entering mitosis, we show that APOBEC3A expression is confined largely to terminally differentiating cells and requires grainyhead-like transcription factor 3 (GRHL3). Thus, in normal tissue, neither deaminase appears to be expressed at high levels during DNA replication, the cell-cycle stage associated with APOBEC-mediated mutagenesis. In contrast, in squamous cell carcinoma we find that, there is expansion of GRHL3expression and activity to a subset of cells undergoing DNA replication and concomitant extension of APOBEC3A expression to proliferating cells. These findings suggest that APOBEC3A may play a functional role during keratinocyte differentiation, and offer a mechanism for acquisition of APOBEC3A mutagenic activity in tumours.
The Dystrophin-Dystroglycan complex ensures cytokinesis efficiency in Drosophila epithelia
Authors: Gonçalves Margarida , Lopes Catarina , Alégot Hervé , Osswald Mariana , Bosveld Floris , Ramos Carolina , Richard Graziella , Bellaiche Yohanns , Mirouse Vincent , Morais-de-Sá Eurico 
Published: November 2024

Abstract
Cytokinesis physically separates daughter cells at the end of cell division. This step is particularly challenging for epithelial cells, which are connected to their neighbors and to the extracellular matrix by transmembrane protein complexes. To systematically evaluate the impact of the cell adhesion machinery on epithelial cytokinesis efficiency, we performed an RNAi-based modifier screen in the Drosophila follicular epithelium. Strikingly, this unveiled adhesion molecules and transmembrane receptors that facilitate cytokinesis completion. Among these is Dystroglycan, which connects the extracellular matrix to the cytoskeleton via Dystrophin. Live imaging revealed that Dystrophin and Dystroglycan become enriched in the ingressing membrane, below the cytokinetic ring, during and after ring constriction. Using multiple alleles, including Dystrophin isoform-specific mutants, we show that Dystrophin/Dystroglycan localization is linked with unanticipated roles in regulating cytokinetic ring contraction and in preventing membrane regression during the abscission period. Altogether, we provide evidence that, rather than opposing cytokinesis completion, the machinery involved in cell–cell and cell–matrix interactions has also evolved functions to ensure cytokinesis efficiency in epithelial tissues.
Subcellular mRNA kinetic modeling reveals nuclear retention as rate-limiting
Authors: Steinbrecht David , Minia Igor , Milek Miha , Meisig Johannes , Blüthgen Nils , Landthaler Markus 
Published: November 2024

AbstractEukaryotic mRNAs are transcribed, processed, translated, and degraded in different subcellular compartments. Here, we measured mRNA flow rates between subcellular compartments in mouse embryonic stem cells. By combining metabolic RNA labeling, biochemical fractionation, mRNA sequencing, and mathematical modeling, we determined the half-lives of nuclear pre-, nuclear mature, cytosolic, and membrane-associated mRNAs from over 9000 genes. In addition, we estimated transcript elongation rates. Many matured mRNAs have long nuclear half-lives, indicating nuclear retention as the rate-limiting step in the flow of mRNAs. In contrast, mRNA transcripts coding for transcription factors show fast kinetic rates, and in particular short nuclear half-lives. Differentially localized mRNAs have distinct rate constant combinations, implying modular regulation. Membrane stability is high for membrane-localized mRNA and cytosolic stability is high for cytosol-localized mRNA. mRNAs encoding target signals for membranes have low cytosolic and high membrane half-lives with minor differences between signals. Transcripts of nuclear-encoded mitochondrial proteins have long nuclear retention and cytoplasmic kinetics that do not reflect co-translational targeting. Our data and analyses provide a useful resource to study spatiotemporal gene expression regulation.
Differential Impacts of Anticipated Success on Employment Outcomes Among Adults Who Stutter
Authors: Jacobs Molly , Gerlach-Houck Hope , Briley Patrick 
Published: November 2024

Purpose:
Stuttering is associated with disparities in labor market outcomes among young adults, but little is known about how labor market outcomes associated with stuttering change over time. Therefore, this study characterized longitudinal associations between stuttering and early life expectations, job satisfaction, receipt of employer-provided insurance benefits, and income.

Method:
The analysis used data from three waves of the National Longitudinal Study of Adolescent to Adult Health, which contained 16,653 individuals aged 18–43 years interviewed over 18 years. First, regression models evaluated the likelihood of employment between people who stutter (PWS) and people who do not stutter (PWNS). Second, conditional on employment, two-stage likelihood models quantified differences in their job satisfaction, receipt of employer-provided insurance benefits, and earned income, controlling for age, sex, race, and household characteristics. Finally, the relationship between their reported education and income expectations and these employment outcomes was evaluated.

Results:

Although stuttering was not related to the likelihood of working or receiving employer-provided benefits, PWS were 20%–22% (
SE
= 0.06–0.07) less likely to be satisfied with their jobs than PWNS, and dissatisfaction increased with age. Additionally, the odds of earning a higher income were significantly lower for PWS than for PWNS. PWS who anticipated attending college and earning a middle-class income were more likely to be satisfied with their jobs and earn a higher income. However, PWS were less likely to expect that they would earn a middle-class income (PWNS: 46.4%, PWS: 36.3%) or graduate from college (PWNS: 70.9%, PWS: 58.4%) compared to PWNS.

Conclusions:
Labor market inequities associated with stuttering persist and increase with age. PWS have significantly lower expectations for their likelihood of future success, and these expectations predict their future occupational outcomes.
Magnetic field of the roAp star KIC 10685175: Observations versus theory
Authors: Shi Fangfei , Zhang Huawei , Hubrig Swetlana , Järvinen Silva , Chen Huiling , Cang Tianqi , Fu Jianning , Kurtz Donald 
Published: November 2024

Context. KIC 10685175 is a roAp star whose polar magnetic field is predicted to be 6 kG through a nonadiabatic axisymmetric pulsation theoretical model.
Aims. In this work, we aim to measure the magnetic field strength of KIC 10685175 using high-resolution spectropolarimetric observations, and compare it with the one predicted by the theoretical model.
Methods. Two high-resolution unpolarized spectra have been analyzed to ascertain the presence of magnetically split lines and derive the iron abundance of this star through equivalent width measurements of 10 Fe lines. One polarized spectrum has been used to measure the mean longitudinal magnetic field with the least-squares deconvolution technique. Further, to examine the presence of chemical spots on the stellar surface, we have measured the mean longitudinal magnetic fields using different lines belonging to different elements.
Results. From the study of two high-resolution unpolarized spectra, we obtained the spectroscopic atmospheric parameters including the effective temperature (Teff), surface gravity (log 𝑔), iron abundance ([Fe/H]), abundance ratio of alpha elements to iron ([α/Fe]), and micro-turbulent velocity (Vmic). The final result is [Teff, log g, [Fe/H], [α/Fe], Vmic)]=[8250 ± 200 K, 4.4 ± 0.1, −0.4 ± 0.2, 0.16 ± 0.1, 1.73 ± 0.2 km s−1]. Although the Fe absorption lines appear relatively weak in comparison to typical Ap stars with similar Teff, the lines belonging to rare earth elements (Eu and Nd) are stronger than those in chemically normal stars, indicating the peculiar nature of KIC 10685175. The mean longitudinal magnetic field, 〈Bℓ〉 = −226 ± 39 G, was measured in the polarized spectrum, but magnetically split lines were not detected. No significant line profile variability is evident in our spectra. Also, the longitudinal magnetic field strengths measured using line masks constructed for different elements are rather similar. Due to the poor rotation phase coverage of our data, additional spectroscopic and polarimetric observations are needed to allow us to come to any conclusions about the inhomogeneous element distribution over the stellar surface.
Conclusions. The estimated polar magnetic field is 4.8 ± 0.8 kG, which is consistent with the predicted polar magnetic field strength of about 6kG within 3σ. This work therefore provides support for the pulsation theoretical model.