bluuebunny/crossref_metadata_2025 huggingface dataset:
Biodegradable Cashew Gum Hydrogel in Mombasa Grass Pas-Ture: A Sustainable Option for Agriculture
Authors: Barros Dhiéssica Morgana Alves , Edvan Ricardo Loiola , Pessoa João Paulo Matos , Nascimento Romilda Rodrigues do , Camboim Luan Felipe Reis , Bezerra Leilson Rocha , Araújo Marcos Jácome de , Sousa Heldeney Rodrigues , Silva-Filho Edson C.
Published: October 2023

Hydrogels are water-absorbing polymers that can hydrate forage plants in the soil. The objec-tive was to evaluate the replacement of synthetic hydrogels derived from petroleum by biode-gradable hydrogels in Mombaça grass pastures (Megathyrsus maximum). The experimental treat-ments consisted of: No hydrogel (NH); Synthetic commercial hydrogel (CH), made from a syn-thetic polyacrylamide product; and Biodegradable test hydrogel (TH), obtained from cashew gum (Anacardium occidentale). The experimental design was randomized blocks with five replica-tions and three treatments. Morphogenesis, production, chemical and mineral composition of the Mombaça grass pasture were assessed. The data was subjected to analysis of variance and mean comparison by the Snott-Knott test at 5% probability. Leaf elongation rate was 42.3 mm day-1 in the TH treatment, which was higher (P<0.05) than NH (35.0 mm day-1). Green leaf mass yield was higher in TH in comparison to NH and CH. On the other hand, there was no effect of hydration on chemical composition. The mineral composition of Mombaça grass showed more Zn when TH was used. It can be concluded that biodegradable hydrogels can replace synthetic commercial hydrogels in pastures.
Precision Metagenomic Next-Generation Sequencing Data of Respiratory Infection
Authors: Almas Sadia , Carpenter Rob E , Tamrakar Vaibhav Kumar , Singh Anuradha , Sharma Aditya , Sharma Rahul
Published: October 2023

Understanding microbial composition in upper respiratory infections (URIs) is critical for effective diagnosis and treatment. Precision Metagenomic next-generation sequencing p(mNGS) can provide a comprehensive yet clinically relevant profile of respiratory infection. The hybridization capture-based targeted sequencing generated a precision metagenomics profile of 29 patients with acute URIs. Nasopharyngeal samples were collected from the subjects suspected of respiratory infection, and p(mNGS) was performed using the Illumina®/IDbyDNA Respiratory Pathogen ID/AMR Panel (RPIP). The dataset obtained from the mNGS analysis contains a wealth of information on the composition of acute URI microbiota, including the relative abundance of known pathogens and potential clinical implications. The dataset represents a valuable resource for future research endeavors in respiratory medicine, infectious disease epidemiology, and therapeutic interventions. In addition, the dataset offers significant potential for reuse and integration with other omics datasets. The comprehensive nature of the mNGS data allows the exploration of associations between the respiratory microbiota and host factors such as clinical outcomes, immune responses, or genetic predisposition. Combining this dataset with other relevant datasets, such as transcriptomics or metabolomics, could provide a deeper understanding of the complex interactions between the microbiota and the host in acute URIs.
Futsal Defense Strategy Model for Athletes 15-17 Years Old
Authors: Akhsin Silmi , Sukiri  , Sulaiman Iman , Siregar Nofi Marlina
Published: October 2023

The purpose of this study was to produce a futsal defense strategy training model for athletes 15-17 years old and to test the effectiveness of the futsal defense model for ages 15-17 years. The method used in this research is research and development. Data collection techniques using interviews, tests, and field observations. The results of the product effectiveness test by comparing the two groups; the treatment group using the product development, and the control group using the pretest and posttest designs. The average value of each group based on the test is the effectiveness of the experimental group is higher than the control group. The improvement of the futsal defense system for the age of 15-17 years at the time of the pre-test showed t-count = 13,405, >t-table = 1.69236, df = 34 and p-value = 0.000.00<0.005. Based on the comparison of the test results, the increase in test results for the experimental group increased significantly than the control group. The subjects in this study were athletes of Club futsal in Soppeng Regency aged 15-17 years and AFK Soppeng athletes aged 15-17 years. It is hoped that this research can provide benefits for sports practitioners, especially in futsal sport.
An Algorithmic Approach to Understanding Osteoarthritic Knee Pain
Authors: Hill Brandon G. , Byrum Travis , Zou Anthony , Schilling Peter L.
Published: October 2023

Update

This article was updated on November 3, 2023, because of a previous error. In the byline on page 1 and in the list of authors' names on page 8, the last name of the third author that had read “Zhou” now reads “Zou.”

An erratum has been published: JBJS Open Access. 2023;8(4):e23.00039ER.

Background:

Osteoarthritic knee pain is a complex phenomenon, and multiple factors, both within the knee and external to it, can contribute to how the patient perceives pain. We sought to determine how well a deep neural network could predict osteoarthritic knee pain and other symptoms solely from a single radiograph view.

Methods:

We used data from the Osteoarthritis Initiative, a 10-year observational study of patients with knee osteoarthritis. We paired >50,000 weight-bearing, posteroanterior knee radiographs with corresponding Knee Injury and Osteoarthritis Outcome Score (KOOS) pain, symptoms, and activities of daily living subscores and used them to train a series of deep learning models to predict those scores solely from raw radiographic input. We created regression models for specific score predictions and classification models to predict whether the modeled KOOS subscore exceeded a range of thresholds.

Results:

The root-mean-square errors were 15.7 for KOOS pain, 13.1 for KOOS symptoms, and 14.2 for KOOS activities of daily living. Modeling was performed to predict whether pain was above or below given pain thresholds, and was able to predict extreme pain (KOOS pain < 40) with an area under the curve (AUC) of 0.78. Notably, the system was also able to correctly predict numerous cases where the Kellgren-Lawrence (KL) grade assigned by the radiologist was 0 but patient pain was high, and cases where the KL grade was 4 but patient pain was low.

Conclusions:

A deep neural network can be trained to predict the osteoarthritic knee pain that a patient experienced and other symptoms with reasonable accuracy from a single posteroanterior view of the knee, even using low-resolution images. The system can predict pain and dysfunction that the traditional KL grade does not capture. Deep learning applied to raw imaging inputs holds promise for disentangling sources of pain within the knee from aggravating factors external to the knee.

Level of Evidence:

Diagnostic Level III. See Instructions for Authors for a complete description of levels of evidence.
Mitigasi Bencana Tsunami Pantai Pangandaran, Jawa Barat
Authors: Lestari Aulia Setya , Muzani Muzani , Setiawan Cahyadi
Published: October 2023

Abstrak: Pantai Pangandaran ialah salah satu dari beberapa pantai yang berada di selatan Pulau Jawa yang letaknya berada pada zona tumbukan (subduksi) antara Lempeng Indo-Australia dan Eurasia sehingga menyebabkan Pantai Pangandaran rawan akan terjadinya gempa bumi dan tsunami. Tujuan dari penelitian ini untuk mengetahui bentuk upaya mitigasi bencana tsunami Pantai Pangandaran. Metode yang digunakan dalam penelitian ini adalah deskriptif dan analisis evaluatif. Analisis spasial digunakan untuk mengkaji bahaya, sedangkan deskriptif evaluatif untuk mengkaji mitigasi bencana tsunami. Hasil penelitian menunjukan bentuk mitigasi yang dilakukan secara struktural yaitu penanaman mangrove, pembuatan jalur evakuasi, membangun tempat evakuasi sementara dengan jarak kurang lebih 500 m dari pantai, membuat benteng sebagai pemecah ombak, dan memasang peringatan dini tsunami. Upaya mitigasi non struktural terkait adanya penerapan kebijakan tentang tata guna lahan, pengembangan sistem peringatan dini dan dipublikasikan melalui berbagai media, serta mengadakan simulasi mitigasi bencana tsunami. Adapun program inovasi mitigasi bencana tsunami yaitu Anak TK Mitigasi, Wisata Edukasi Bencana Goes To School, Silaturahmi Empati Berbagi Edukasi Bencana, Bunda Belajar Mitigasi, Forum Kesiapsiagaan Dini Masyarakat, dan Hotel dan Restauran Tangguh Bencana.        
Kata Kunci: Mitigasi Bencana, Tsunami, Pantai Pangandaran.
Karakteristik Sineresis dan Kadar Air Yoghurt Buah Naga Merah (Hylocereus polyrhizus L) yang Ditambahkan dengan Gula Kelapa Kristal
Authors: Famuji Agung , Zulaikhah Siti Rahmawati , Sidhi Arif Harnowo
Published: October 2023

Susu merupakan bahan makanan yang bergizi tinggi karena di dalam susu segar mengandung berbagai zat makanan lengkap dan seimbang seperti protein, lemak, karbohidrat, mineral, dan vitamin sehingga menjadi media yang sempurna bagi pertumbuhan mikroorganisme. Salah satu cara mengatasi hal tersebut adalah fermentasi menjadi yoghurt. Fermentasi yoghurt yang terlalu masam dan tidak cocok bagi lidah orang Indonesia dapat ditambah dengan gula kelapa kristal, Penambahan gula kelapa juga dapat menjadi sumber energi bakteri asam laktat (BAL) dan sebagai sumber karbon untuk memicu pertumbuhan bakteri pada susu fermentasi dan juga bisa berpengaruh terhadap kadar air dan sineresis yoghurt. Tujuan dari penelitian ini adalah untuk mengetahui pengaruh level penambahan gula kelapa kristal terhadap karakteristik Kadar air dan Sineresis yoghurt buah naga merah. Penelitian ini dilaksanakan menggunakan metode eksperimental dengan Rancangan Acak Lengkap (RAL) dengan menggunakan 4 perlakuan dan 5 ulangan. Perlakuan dalam penelitian ini adalah penambahan berbagai level gula kelapa kristal 0%, 5%, 10% dan 15% (b/v). Data yang diperoleh kemudian di uji menggunakan uji Analisis Variansi (ANOVA). Apabila perlakuan sajaberpengaruh nyata terhadap variable maka dilanjutkan dengan uji Duncan Multiple Range Test (DMRT). Variabel yang diamati adalah kadar air dan sineresis pada yoghurt buah naga merah.  Hasil penelitian menunjukan pengaruh perlakuan berbeda nyata pada kadar air dan sineresis yoghurt buah naga merah. Berdasarkan uji lanjut menggunakan DMRT menunjukan bahwa semakin tinggi level gula kelapa kristal yang ditambah maka kadar air dan sineresis semakin rendah.
Historic context for railroads at Fort McCoy, Wisconsin
Authors: Schmidt Aaron , Baxter Carey
Published: October 2023

This report provides a historic context for the railroads that operated within the present-day boundaries of Fort McCoy. The objective of this historic context is to deliver a useful reference for future evaluations of railroad-related resources in the installation. Ultimately, the report is in-tended to save the installation time in determining potential areas of significance for future evaluations. This is accomplished through the creation of a broad historic context for railroading in the Midwest, establishing a survey of railroad history at Fort McCoy, and providing examples of areas of significance and National Register of Historic Places (NRHP) criteria commonly applied to the historic railroad resources of the Midwest. This report does not provide NRHP eligibility recommendations for any specific resources; however, possible research questions for further study are posited in the concluding chapter.
Different Covid-19 Vaccines in Pakistan: Administration and Effectiveness
Authors:   Centre for Applied Molecular Biology (CAMB), University of the Punjab, Quaid-e-Azam Campus, Lahore, Pakistan., Iftikhar Anwaar , Sabar Muhammad Farooq ,   Centre for Applied Molecular Biology (CAMB), University of the Punjab, Quaid-e-Azam Campus, Lahore, Pakistan., Ahmad Quart ul Ain ,   Department of Zoology, University of Education, Lahore, Pakistan., Farooq Rida ,   Centre for Applied Molecular Biology (CAMB), University of the Punjab, Quaid-e-Azam Campus, Lahore, Pakistan., Akhtar Mubeen ,   Centre for Applied Molecular Biology (CAMB), University of the Punjab, Quaid-e-Azam Campus, Lahore, Pakistan.
Published: October 2023

Pfizer-BioNTech, Moderna, Sputnik V (typically manufactured in Russia), CoronaVac (China), Sinopharm (China), Vaxzevria, and Cansino (both made in China) are among the vaccines that have been certified for emergency use in several countries. All of the above vaccinations were authorized to Pakistan, bypassing Pfizer and Moderna. The effectiveness, safety, mechanism of action, dosage, and availability of mandatory vaccines in Pakistan up to May 20, 2021. We searched PubMed and Google Scholar for all known material on COVID-19 vaccinations. We also looked at grey literature papers. Instead of Pfizer and Moderna, Pakistan has approved all the preceding vaccines. Moderna and Pfizer were determined to be the most effective among all vaccinations, with 90% effectiveness, followed by Vaxzevria, Sputnik V, Sinopharm, and Cansino. All immunizations have caused lesser bad effects like fever, injection site pain, or headaches. Further clinical studies are being done throughout the world to combat the epidemic. In large populations, public attention plays a critical role in vaccination efforts. Keywords: Covid-19, Vaccines, Sinopharm (China), Sputnik V (Russia), CoronaVac Pfizer, Moderna, Administration, Effectiveness.
Predicting the Stress in Marcellus Shale Horizontal Wells from the Drilling and Well Log Data
Authors: Alawadh Moudhi , El Sgher Mohammed , Aminian Kashy , Ameri Samuel
Published: October 2023

The distribution of the anisotropic minimum horizontal stress, both in horizontal and vertical directions, is necessary for effective hydraulic fracture treatment design in Marcellus Shale horizontal wells. Typically, the minimum horizontal stress can be estimated sonic logs. However, sonic log data is not commonly available for the horizontal Marcellus shale wells due to the complexity and cost. The objective of this study is to predict the anisotropic minimum horizontal stress by utilizing drilling parameters including depth, weight-on-bit (WOB), revolution per minute (RPM), standpipe pressure, torque, pump flow rate, and the rate of penetration (ROP). More specifically, artificial neural network (ANN) models will be developed to predict the anisotropic minimum horizontal stress for a horizontal Marcellus shale well from the drilling and well log data. Artificial neural networks are particularly useful to identify complex relationships to predict the properties of unconventional formations.

The available data from a Marcellus Shale horizontal well was collected and filtered to prepare data sets for ANN training, testing, and validation purposes. Two networks, for the vertical and lateral sections of the well, were developed. The preliminary results indicated that inclusion of lithology, gamma-ray, and bulk density well log data as inputs can improve the predictability of the networks. Finally, the networks were used to predict the anisotropic minimum horizontal stress in a different Marcellus shale horizontal well with the available sonic log data. To evaluate the applicability of the ANN models, the predicted stresses by the networks were compared against those estimated from the sonic logs. The predictions by both networks (vertical and horizontal) were found to be in close agreement with those estimated from the sonic logs. The results of this study can be utilized as a predictive tool to help fill in the need for an accurate estimation of static geomechanical properties including the minimum horizontal stress in Marcellus Shale horizontal wells and to improve the fracturing treatment design.
Application of Oilfield Geomechanics Techniques to Geologic Carbon Capture, Utilization, and Storage (CCUS) Projects
Authors: Alt R. C.
Published: October 2023

With increasing industry and government attention directed toward climate change mitigation, CO2 injection wells are expected to play a vital role in America’s emerging energy infrastructure and to make up an ever-increasing share of commercial wellbore geoscience activities. The Environmental Protection Agency (EPA) assigns CO2 injection wells to a category distinct from oil and gas wells, asserts regulatory primacy, and imposes a specific set of regulatory guidelines that drive well planning procedures for what it defines as Class VI injectors. These permitting requirements for a Class VI injector are notably stricter than for a traditional hydrocarbon producing well, which also drives an expectation for greater precision in quantifying several geologic parameters during well planning. For geomechanics teams, this presents a valuable opportunity to develop customized models to optimize drilling and injection procedures, following in the footsteps of what has already been accomplished with horizontal drilling and hydraulic fracturing in the onshore unconventional space over the past two decades.

In this paper, we examine the application of oilfield geomechanics techniques, including pore pressure prediction, rock strength estimation, and wellbore stability analysis to assist in drilling and completion of CCUS wells. We walk through the workflow to build a robust 1-D geomechanical model, calibrated to available offset data utilizing field and wellbore scale geomechanical modeling platforms. Next, we identify best practices for drilling and completing CO2 injectors. Finally, we apply the geomechanical modeling methodology to CCUS wells, focusing on four key operational risks that are exacerbated compared to similarly situated oil and gas wells: overpressure, borehole breakout, fault reactivation, and stress changes with depletion and injection. We conclude by considering future research opportunities in this field.
Enhancing Unconventional Reservoir Performance: Integrating Real-Time Fracture-Driven-Interactions (FDIs) and Post-Stage Fall-Off Analysis
Authors: Ibrahim A. F. , Assem A. I. , Sinkey M. , Johnston T.
Published: October 2023

Hydraulic fracturing near depleted fractured rocks is a major cause of fracture hits, leading to damage in parent wells and reduced fracture efficiency in the child well due to significant fluid and proppant losses to the parent well. This behavior is exacerbated by tight well spacing and the depletion time of the parent wells. To address this issue, the current study aims to combine real-time fracture-driven-interactions (FDIs) and post-stage pressure transient analysis (PTA) to accurately estimate fracture half-length for each stage during hydraulic fracturing operations.

During hydraulic fracture operations, pressure gauges are installed in offset wells to measure pressure changes during each stage completion in the child well, taking well interference into account. The post-stage fall-off pressure data is then used to calculate the connected fracture surface area (FSA). By analyzing the real-time FDIs with an offset depleted zone, the methodology can estimate higher stage fracture half-length, indicating lower cluster efficiency. The summation of stages with high fracture half-length enables the estimation of the well interference value.

To validate the proposed methodology, actual field cases from oil and gas shale frac data are presented, showcasing live FDIs measurements for each stage, followed by stage-by-stage PTA. The preliminary results reveal that over 20% of the stages experience fracture hits due to the higher fracture half-length and lower cluster efficiency. Furthermore, the well interference value has been verified using actual production data.

Integrating FDI measurements with PTA for detecting frac stage interference in unconventional wells provides a faster, more accurate, and cost-effective fracture diagnostic tool that optimizes well spacing.
Unique Production Conditions of Unconventional Wells in the Appalachian Basin; A Multi-Dimensional Assessment on Recovery
Authors: Rozploch T. , Ayers K. , Jacot H. , Eshbaugh K.
Published: October 2023

This paper delves into the effects of long-term shut-in periods and production cycling on unconventional wet gas wells in the Appalachian Basin, where unique operational circumstances led to a long-term shut-in period.

The unconventional Marcellus and Burkett wells were of a variety of production age. Ranging from depleted and operating under artificial lift, while others were recently flowed back and still in wellbore cleanup. A "long-term shut-in" refers to a shut-in period that occurs after a well has been in production for a substantial time period, rather than an intentional delay of production post-stimulation, known as "seasoning." The term "production cycling" refers to turning wells online to production for short periods of time and then shut-in for short periods of time. This was due to pipeline constraints, lease agreements, and/or transient operational conditions.

The paper discusses the results of a comprehensive analysis, which included decline curve analysis, statistical analysis, hydraulic fracture modeling, build-up analysis, and rate transient analysis. The study considered many factors, such as inter-well spacing, stimulation, generational effects, wellbore boundaries, and reservoir/geologic characteristics.

Overall, the study revealed a wide range of both positive and negative effects from both a reservoir and a production perspective, suggesting that factors such as well age, generation, spacing, and stimulation size were drivers. Near-term improvements were observed in previously damaged parent wells following the shut-in period. Several of the wells experienced a second, higher initial production rate than during flow back due to fluid cleanup effects. However, certain tightly spaced wells experienced negative effects on production in the longer term.

In conclusion, this paper provides a comprehensive analysis of the effects of long-term shut-in periods and production cycling on unconventional wet gas wells in the Appalachian Basin. In real-time operations, many unique challenges are presented, gaining a deeper understanding of the downhole reservoir and long-term production effects will aid in more informed operational decisions in the future. The research outcomes emphasize the need for a more nuanced approach to unconventional reservoir development, and a careful consideration of the specific circumstances of each well. This study contributes to the ongoing efforts to improve the recovery of unconventional resources as these assets mature.
Discovery of Initial SARS-CoV-2 as DNA Viruses and Reliable Interactive COVID-19 DNA Methylation Markers and Druggable Targets and Potential Malignant Diseases with Long Incubation Period
Authors: Zhang Zhengjun
Published: October 2023

COVID-19 research needs interactive reliable biomarkers at genomic and genetic levels. Earlier research has established the existence of reliable interactive genomic biomarkers. However, reliable DNA methylation markers haven't been identified at the epigenetic level, not to mention interactiveness. This study, from 865,859 methylation sites, discovers two miniature sets of Infinium MethylationEPIC sites, each having seven (CpG sites, genes) to interact with each other and with disease subtypes. They lead to nearly perfect (96.87-100% accuracy) prediction of COVID-19 patients from patients with other diseases or healthy controls. These CpG sites can jointly explain some post-COVID-19-related conditions. These CpG sites and the optimum performed genomic biomarkers reported in our earlier work rise to be potential druggable targets. Among these CpG sites, diseases associated with cg16785077 (gene MX1) can have an incubation period of up to six to eight years, which raises a serious (or urgent) issue to investigate now or sooner. The gene PARP9 (cg25932713) is one of the only three human genes that contain both PARP domains and macrodomains. MX1 and PARP9 together were linked to SARS-CoV-1, MERS-CoV, and SARS-CoV-2. The new findings of CpG sites cg16785077 (gene MX1) and cg25932713 (PARP9, cg22930808) in COVID-19 at DNA methylation levels indicate that the initial SARS-CoV-2 may be better treated as transcribed viral DNA into RNA virus due to the long incubation feature of MX1 associated diseases, i.e., not as an RNA virus that has been concerned by scientists. Such a discovery will significantly change the scientific thinking and knowledge of viruses.
An optoacoustic field-programmable perceptron for recurrent neural networks
Authors: Becker Steven , Englund Dirk , Stiller Birgit
Published: October 2023

A critical feature in signal processing is the ability to interpret correlations in time series signals, such as speech. Machine learning systems process this contextual information by tracking internal states in recurrent neural networks (RNNs), but these can cause memory and processor bottlenecks in applications from edge devices to data centers, motivating research into new analog inference architectures. But whereas photonic accelerators have demonstrated big leaps in uni-directional feedforward deep neural network (DNN) inference, the bi-directional architecture of RNNs presents a unique challenge: the need for a short-term memory that (i) programmably transforms optical waveforms with phase coherence , (ii) minimizes added noise, and (iii) enables programmable readily scales to large neuron counts. Here, we address this challenge by introducing an optoacoustic recurrent operator (OREO) that simultaneously meets (i,ii,iii). Specifically, we experimentally demonstrate an OREO that contextualizes and computes the information carried by a sequence of optical pulses via acoustic waves. We show that the acoustic waves act as a link between the different optical pulses, capturing the optical information and using it to manipulate the subsequent operations. Our approach can be controlled optically on a pulse-by-pulse basis, offering simple reconfigurability. We use this feature to demonstrate a recurrent drop-out, which excludes optical input pulses from the recurrent operation.
We apply OREO as an acceptor to recognize up-to 27 patterns in a sequence of optical pulses. Finally,
we introduce a DNN architecture that uses the OREO as bi-directional perceptrons to enable new classes of DNNs in coherent optical signal processing.
The circulating proteome and brain health: Mendelian randomisation and cross-sectional analyses
Authors: Walker Rosie , Chong Michael , Perrot Nicolas , Pigeyre Marie , Gadd Danni , Stolicyn Aleks , Shi Liu , Whalley Heather , Nevado-Holgado Alejo , McIntosh Andrew , Heitmeier Stefan , Rangarajan Sumathy , O'Donnell Martin , Smith Eric , Yusuf Salim , Whiteley William , Campbell Archie , Shen Xueyi , Pare Guillaume
Published: October 2023

Decline in cognitive function is the most feared aspect of ageing. Poorer midlife cognitive function is associated with increased dementia and stroke risk. The mechanisms underlying variation in cognitive function are uncertain. Here, we assessed associations between 1160 proteins’ plasma levels and two measures of cognitive function, the digit symbol substitution test (DSST) and the Montreal Cognitive Assessment in 1198 PURE-MIND participants. We identified five DSST performance-associated proteins (NCAN, BCAN, CA14, MOG, CDCP1), with NCAN and CDCP1 showing replicated association in an independent cohort, GS (N=1053). MRI-assessed structural brain phenotypes partially mediated (8-19%) associations between NCAN, BCAN, and MOG, and DSST performance. Mendelian randomisation analyses suggested higher CA14 levels might cause larger hippocampal volume and increased stroke risk, whilst higher CDCP1 levels might increase stroke and intracranial aneurysm risk. Our findings highlight candidates for further study and the potential for drug repurposing to reduce risk of stroke and cognitive decline.
Brain-wide alterations revealed by spatial transcriptomic and proteomic analyses in COVID-19 infection
Authors: Geschwind Daniel , Zhang Ting , Li Yunfeng , Pan Liuliu , Sha Jihui , Bailey Michael , Faure-Kumar Emmanuelle , Williams Christopher , Wohlschlegel James , Magaki Shino , Niu Chao , Lee YooJin , Su Yu-chyuan , Li Xinmin , Vinters Harry
Published: October 2023

Understanding the pathological basis of the neurological symptoms observed following SARS-CoV2 infection is essential to optimizing outcomes and developing therapeutics. To date, small sample sizes and narrow molecular profiling limit the generalizability of findings. We performed proteomics coupled with bulk and spatial transcriptomics in multiple cortical and subcortical regions in postmortem COVID-19 patient brains and matched controls (total n=42). We observed a multi-regional antiviral response and identified broad dysregulation of synaptic and mitochondrial pathways in deep-layer excitatory neurons and up-regulation of neuroinflammatory pathways in glia at the mRNA and protein levels. These changes overlapped those observed in multiple neurodegenerative diseases, including Parkinson’s disease (PD) and Alzheimer’s disease (AD). Our work, based on multiple experimental and analytical methods, shows that severe COVID-19 has a broad impact across cortical and subcortical regions and shares core neuronal and glial changes with neurodegenerative conditions typically associated with aging.
Transcriptomic Effects of Paternal Cocaine-seeking on the Reward Circuitry of Male Offspring
Authors: Le Qiumin , Huang Nan , Cui Jian , Fan Guangyuan , Pan Tao , Han Kunxiu , Xu Kailiang , Jiang Changyou , Liu Xing , Wang Feifei , Ma Lan
Published: October 2023

In previous research, it has been established that a strong incentive motivation for cocaine, rather than the drug itself, can contribute to the intergenerational inheritance of cocaine addiction susceptibility in descendants. However, the precise impact of paternal cocaine-seeking on the reward circuitry of offspring remains not fully elucidated. To differentiate between cocaine-exposure and cocaine-seeking factors, we employed two distinct paternal cocaine acquisition paradigms: cocaine self-administration and yoked administration. These paradigms were used to generate the F1 generation, along with a control group receiving saline treatment. We conducted a comprehensive transcriptomic analysis of the male F1 offspring across seven relevant brain regions, both under drug-naive conditions and after cocaine self-administration. Our study revealed that the orbitofrontal cortex (OFC) exhibited more pronounced transcriptomic changes in response to cocaine-exposure. Conversely, the dorsal hippocampus (dHip), dorsal striatum (dStr), and ventral tegmental area (VTA) showed alterations that were more closely linked to the paternal voluntary cocaine-seeking experience. Based on transcriptomic analysis, measurements of dopamine levels (DOPA), and cellular activation analysis, we propose that the VTA-dStr pathway plays a pivotal role in mediating the effects of paternal voluntary cocaine-seeking on offspring. Furthermore, we identified potential transcriptomic regulatory mechanisms mediated by key transcriptional factors. Our findings provide a comprehensive overview of the transcriptional changes resulting from paternal highly-motivated cocaine-seeking. Importantly, our data highlight vulnerable neurocircuitry and novel gene candidates with therapeutic potential for disrupting the transgenerational inheritance of vulnerability to cocaine addiction.
Depression and risk of infectious diseases: A mendelian randomization study
Authors: Li Jun , Shi Luchen , Ren Junsong , Jin Ke
Published: October 2023

Previous observational inquiries have revealed a correlation between depression and infectious maladies. This study endeavors to scrutinize the causal linkages between depression and infectious diseases. Nonetheless, the causative nature of the association between Major Depressive Disorder (MDD) and infectious diseases remains enigmatic. Two-sample Mendelian Randomization (MR) analysis was executed utilizing single nucleotide polymorphisms (SNPs) significantly connected with MDD and infectious diseases as instrumental variables (IVs). A series of sensitivity analyses were subsequently conducted. Genetic variants linked to MDD were employed as instrumental variables sourced from a genome-wide meta-analysis comprising 500,199 individuals. Summary-level data on five infectious diseases, including candidiasis, pneumonia, skin and soft tissue infections (SSTI), upper respiratory tract infections (URTI), and urinary tract infections (UTI), were acquired from the UK Biobank and FinnGen study. Our findings evinced that genetically predicted MDD exhibited a heightened risk of candidiasis (OR = 1.52, 95% CI 1.06–2.17; P = 2.38E-02), pneumonia (OR = 1.14, 95% CI 1.01–1.29; P = 3.16E-02), URTI (OR = 1.23, 95% CI 1.12–1.36; P = 3.71E-05), and UTI (OR = 1.26, 95% CI 1.12–1.42; P = 8.90E-05). Additionally, we identified bidirectional causal relationships between UTI and MDD. The associations between MDD and the risk of URTI and UTI remained consistent in multivariable MR analysis, accounting for genetically predicted smoking and body mass index. In conclusion, this investigation ascertained a causal connection between MDD and the susceptibility to infectious diseases, particularly URTI and UTI.
Paternal Cocaine-Seeking Motivation Defines Offspring's Vulnerability to Addiction by Down-Regulation of GABAergic GABRG3 in the Ventral Tegmental Area
Authors: Le Qiumin , Cui Jian , Huang Nan , Fan Guangyuan , Pan Tao , Han Kunxiu , Jiang Changyou , Liu Xing , Wang Feifei , Ma Lan
Published: October 2023

Epidemiological investigations indicate that parental drug abuse experiences significantly influenced addiction vulnerability of offspring. In studies using animal models, paternal cocaine-highly motivated drug-seeking behavior has been found to be an important determinant of offspring addiction susceptibility, but the key molecules contributing to offspring addiction susceptibility are currently unclear. We used the cocaine self-administration model and compared SA rat with paired yoke rat to differentiate paternal cocaine-seeking motivation, and the ventral tegmental area (VTA) transcriptomes of rat offspring in the natural state and after self-administration training were analyzed. Paternal cocaine-seeking experience, but not cocaine exposure, could increase lever-pressing behavior in male F1 offspring, without significantly altering cocaine drug sensitivity. RNA-seq of the ventral tegmental area in male F1 under drug-free state and after cocaine-self administration unveil that paternal cocaine self-administration, but not cocaine exposure alone, induced specific gene expression changes in specific modules. Gabrg3 was at the core position of the drug-seeking motivation related module network and highly correlated with parental drug-seeking motivation score. The downregulation of Gabrg3 expression caused by paternal experience of motivational cocaine-seeking mainly occurred in GABAergic neurons in VTA, potentially regulating synaptic and transmitter transmission in VTA. Paternal experience of motivational cocaine seeking can reshape the transcriptional network in the VTA of male offspring rats, possibly by downregulating Gabrg3 in GABAergic neurons. Gabrg3 perturbation may affect the processes related to synapse formation and transmitter transmission, which may be the possible neurobiological mechanism that enhances cocaine-seeking motivation in male offspring rats.
Targeting osteoclast-derived DPP4 alleviates inflammation-mediated ectopic bone formation in ankylosing spondylitis.
Authors: Lee Seung Hoon , Lee Kyu Hoon , Jeon Chanhyeok , Whangbo Min , Jo Hye-Ryeong , Youn Jeehee , Lee Chang-Hun , Park Ye-Soo , Jo Sungsin , Kim Tae Hwan
Published: October 2023

Background: Ankylosing spondylitis (AS) is a chronic inflammatory disease characterized by ectopic bone formation. The anti-inflammatory function of dipeptidyl peptidase-4 (DPP4) inhibitor has been reported in bone metabolism, but its utility in AS has not previously been investigated.Methods: We assessed DPP4 level in serum, synovial fluid, and facet joint tissue of AS patients. Additionally, we investigated the effect of a DPP4 inhibitor in an experimental AS mouse model induced by intraperitoneal injection with 3 mg curdlan. Following curdlan injection, SKG mice were orally administered a DPP4 inhibitor three times per week for 5 weeks, and ankles of mice were scored for thickness and given clinical arthritis scores. At the end of 5 weeks, mice were sacrificed, and micro-CT and histological analyses were performed. Furthermore, osteoclast precursor cells (OPCs) from curdlan-injected SKG mice were treated with DPP4 inhibitor, and the effects of this treatment on osteoclastogenesis and differentiation markers were evaluated.Results: Soluble DPP4 level was elevated in the serum and synovial fluid of patients with AS compared to those in the control group. Expression of DPP4 increased gradually during human osteoclastogenesis and was high in mature osteoclasts. Histological analysis revealed that oral administration of a DPP4 inhibitor resulted in a decrease in thickness of the hind paw, clinical arthritis scores, and enthesitis at the ankle in curdlan-injected SKG mice compared to the control group. Micro-CT data showed a significant reduction in inflammation-induced low bone density and ectopic bone formation in the DPP4 inhibitor group compared to those in the control group. Intriguingly, DPP4 co-expressed in TRAP-positive osteoclasts was detected in ectopic bone in the tibia of curdlan-injected SKG mice as well as spinal bone tissue of AS patients. Moreover, treatment with a DPP4 inhibitor significantly reduced osteoclastogenesis in the bone marrow of curdlan-injected SKG mice in addition to decreasing expression of osteoclast differentiation markers.Conclusion: Our findings suggest that inhibiting DPP4 may have a therapeutic effect on excessive bone formation in AS patients.
Plasma arachidonic acid levels are associated with both bipolar disorder and the effects of FADS gene variants
Authors: Saito Takeo , Ashizawa Takuma , Okochi Tomo , Ninomiya Kohei , Ito Kenta , Aoki Rei , Ikeda Masashi , Iwata Nakao
Published: October 2023

Recent genome-wide association studies (GWASs) have identified fatty acid desaturase (FADS) genes, which code key enzymes involved in polyunsaturated fatty acid (PUFA) desaturation as susceptibility genes for bipolar disorder (BD). Several quantitative changes in PUFAs suggest their involvement in BD pathogenesis. Therefore, this study aimed to clarify the relationship between BD and PUFAs by conducting lipidomics covariating with the FADS gene variant (rs174550), which is associated with PUFA levels and BD susceptibility. The Concentrations of 23 fatty acids were measured using plasma samples from the BD group (n = 535) and the control group (n = 107). Differences in each PUFA concentration ratio were compared between the two groups. Also, differences in each PUFA concentration ratio were compared for each genotype in rs174550. Our results showed that the BD group had significantly lower concentrations of linoleic acid (LA) (β = −0.3615, p = 0.0233) and arachidonic acid (AA) (β = –0.1789, p = 0.0123) than the control group. Concerning the effect of FADS on the PUFA concentration ratio, carriers of C-allele at rs174550 had significantly decreased γ-linolenic acid and AA concentration ratios. A previous GWAS reported that the presence of a C-allele at rs174550 increased the BD risk. This direction is consistent with the lipidomic results of the present study. In conclusion, both the FADSand BD were considered to regulate the AA concentration. Thus, as the FADS gene variant is crucial for conductinglipidomics of BD we believe that the allele frequency of FADS must be analyzed.
Genome-wide analyses reveals an association between invasive urothelial carcinoma in the Shetland sheepdog, NIPAL1, and the MAPK signaling pathway
Authors: Ostrander Elaine , Parker Heidi , Harris Alexander , Plassais Jocelyn , Dhawan Deepika , Knapp Deborah , Kim Erika
Published: October 2023

Naturally occurring canine invasive urinary carcinoma (iUC) closely resembles human muscle invasive bladder cancer in terms of histopathology, metastases, response to therapy and, low survival rate. The heterogeneous nature of the disease has led to the association of large numbers of risk loci in humans, however most are of small effect. There exists a need for new and accurate animal models of invasive bladder cancer. In dogs, distinct breeds show markedly different rates of iUC, thus presenting an opportunity to identify additional risk factors and overcome the locus heterogeneity encountered in human mapping studies. In the association study presented here, inclusive of 100 Shetland sheepdogs and 58 dogs of other breeds, we identify a homozygous protein altering point mutation within the NIPAL1 gene which increases risk by eight-fold (OR = 8.42, CI = 3.12–22.71), accounting for nearly 30% of iUC risk in the Shetland sheepdog. Inclusion of six additional loci accounts for the majority of disease risk in the breed and explains nearly 75% of the phenotypes in this study. When combined with sequence data from tumors, we show that variation in the MAPK signaling pathway is an overarching cause of iUC susceptibility in dogs.
The Effects of Podcasts on Medical Education: A Systematic Review
Authors: Wang Shaoyuan , Meckling Gray , Hanafi Sarah , Kasbia Gurnaam Singh , Singhal Nikhita , Zhou Carrol , Raben Alex
Published: October 2023

Objective
Podcasts have been growing in popularity among medical learners, mostly due to their accessibility and convenience. There is a gap in the literature, however, on the impact of podcasts on objective changes in knowledge, behaviours, skills, attitudes, and patient outcomes. This study reviewed existing literature on the effectiveness of podcasts in changing knowledge and practice outcomes for medical students and residents.
Methods
The authors searched Embase, ERIC, MEDLINE, and Scopus for studies that examined the effects of audio-only podcasts on medical learners. Subsequently, two independent authors screened all abstracts, then full-texts for inclusion. Data on learning and behavioral outcomes were extracted from all included studies. Finally, the authors summarized findings using qualitative analysis.
Results
The authors found 6372 studies from our initial search, of which 2501 remained after removing duplicates. 181 articles remained after abstract screening and only 2 remained after full-text screening. Both studies found a statistically significant effect of podcast use on immediate knowledge retention.
Conclusions
The reviewed studies showed that podcasts are effective in generating immediate knowledge retention. Beyond that, there remains little evidence on their effectiveness in the real world. In the face of their increased usage, more research is required to better characterize the impact of podcasts on medical learners.
Evaluation of in vitro antibacterial, DNA binding, DNA damage, DFT and antioxidant studies of aminobenzaldehyde based heterocyclic Schiff base derivatives
Authors: Arif Rizwan , . Akrema , Pulaganti Madhusudana , Rubab Umme , Ali Ahmad , Khan Md Shahzad , UDDIN RAHIS
Published: October 2023

Heterocyclic Schiff base derivatives have been synthesized by condensation of dimethylaminobenzaldehyde and substituted amines in 1:1 molar ratio. Synthesized heterocyclic Schiff base derivatives (3a-3h) were structurally characterized by UV-visible, IR, 1H and 13C NMR spectroscopy, elemental analysis and mass spectrometry. Antibacterial property of heterocyclic Schiff base derivatives has been explored against Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa and Staphylococcus aureus using disc diffusion method. Results revealed that Schiff base derivatives 3c, 3f and 3h have significant antibacterial activity against tested bacterial strains. Heterocyclic Schiff base derivatives also explored for DNA binding interactions study with calf thymus-DNA (Ct-DNA) by absorption spectroscopy, fluorescence measurements, circular dichroism, viscosity measurement and molecular docking study. Heterocyclic Schiff base derivatives 3c, 3f and 3h bind with Ct-DNA through groove binding mode with (Kb) 1.62 × 104, 1.58 × 104 M-1 and 2.3 × 104 M-1 respectively. Molecular docking the target compounds was also studied against B-DNA dodecamer d(CGCGAATTCGCG)2. Agarose gel electrophoresis study revealed that after the addition of compounds 3c, 3f and 3h, DNA damage induced by free radical has been inhibited. Antioxidant potential of heterocyclic Schiff base derivatives was also estimated by Diphenyl-1-picryl-hydrazyl (DPPH) free radical and hydrogen peroxide assay. The experimental results of the spectral properties of the synthesized derivatives 3c, 3f and 3h in solution were interpreted at the molecular level with aid of the DFT and TD-DFT/CAM-B3LYP/6-31+G(d) computational methods with Becke-3-Lee-Yang-Parr(B3LYP) exchange-correlation functional approach.
Microcrystalline induced physical-crosslinking towards high performance branched anion exchange membrane
Authors: Wei Zidong , Lu Xiaoli , Ma Xiaoqin , Yuan Wei , Yuan Caili , Zeng Lingping , Wang Jianchuan , Liao Qiang
Published: October 2023

Anion exchange membrane (AEM) is the core component of low-cost anion exchange membrane fuel cell (AEMFC). To realize the commercial application of AEMFC, extremely low swelling of AEM is vital for the membrane electrode assembly preparation and cell integrity, except for high hydroxide conductivity, strength and chemical stability. However, it is hard to achieve extremely low swelling ratio while maintain high conductivity, especially for homogenous membrane. Herein, a series of quaternized poly(trans-1,2-diphenylethylene-co-terphenyl-N,N′-dimethyl piperidinium) with sophisticated structure are synthesized for AEM to address such dilemma. The physical-crosslinking induced by microcrystalline, effectively restricts the swelling of AEM (< 5.8%@80°C). Moreover, branched structure is also introduced to increase the free volume in the polymer membrane, leading to high conductivity up to 275.6 mS cm-1@80°C simultaneously. Accordingly, excellent fuel cell performance with peak power density of 1.13 W cm-2 for H2-O2 at 80°C is attained.
Comprehensive Single-Cell Transcriptomic Profiling Identifies Molecular Subtypes and Prognostic Biomarkers in Esophageal Squamous Cell Carcinoma: Implications for Targeted Therapy
Authors: Zhang Dengfeng , Zhao Fangchao , Guo Pengfei , Li Zhirong , Li Shujun
Published: October 2023

Background: Esophageal squamous cell carcinoma (ESCC) is a genetically heterogeneous disease with poor clinical outcomes. Identification of biomarkers linked to DNA replication stress may enable improved prognostic risk stratification and guide therapeutic decision making. We performed integrated single-cell RNA sequencing and computational analyses to define the molecular determinants and subtypes underlying ESCC heterogeneity.
Methods: Single-cell RNA sequencing was performed on ESCC samples and analyzed using Seurat. Differential gene expression analysis was used to identify esophageal cell phenotypes. DNA replication stress-related genes were intersected with single-cell differential expression data to identify potential prognostic genes, which were used to generate a DNA replication stress (DRS) score. This score and associated genes were evaluated in survival analysis. Putative prognostic biomarkers were evaluated by Cox regression and consensus clustering. Mendelian randomization analyses assessed the causal role of PRKCB.
Results: High DRS score associated with poor survival. Four genes (CDKN2A, NUP155, PPP2R2A, PRKCB) displayed prognostic utility. Three molecular subtypes were identified with discrete survival and immune properties. A 12-gene signature displayed robust prognostic performance. PRKCB was overexpressed in ESCC, while PRKCB knockdown reduced ESCC cell migration.
Conclusions: This integrated single-cell sequencing analysis provides new insights into the molecular heterogeneity and prognostic determinants underlying ESCC. The findings identify potential prognostic biomarkers and a gene expression signature that may enable improved patient risk stratification in ESCC. Experimental validation of the role of PRKCB substantiates the potential clinical utility of our results.