bluuebunny/crossref_metadata_2025_split huggingface dataset:
Integrative transcriptome- and DNA methylation analysis of brain tissue from the temporal pole in suicide decedents and their controls
Authors: Sha Qiong , Fu Zhen , Escobar Galvis Martha L. , Madaj Zach , Underwood Mark D. , Steiner Jennifer A. , Dwork Andrew , Simpson Norman , Galfalvy Hanga , Rozoklija Gorazd , Achtyes Eric D. , Mann J. John , Brundin Lena 
Published: November 2023

AbstractSuicide rates have increased steadily world-wide over the past two decades, constituting a serious public health crisis that creates a significant burden to affected families and the society as a whole. Suicidal behavior involves a multi-factorial etiology, including psychological, social and biological factors. Since the molecular neural mechanisms of suicide remain vastly uncharacterized, we examined transcriptional- and methylation profiles of postmortem brain tissue from subjects who died from suicide as well as their neurotypical healthy controls. We analyzed temporal pole tissue from 61 subjects, largely free from antidepressant and antipsychotic medication, using RNA-sequencing and DNA-methylation profiling using an array that targets over 850,000 CpG sites. Expression ofNPAS4, a key regulator of inflammation and neuroprotection, was significantly downregulated in the suicide decedent group. Moreover, we identified a total of 40 differentially methylated regions in the suicide decedent group, mapping to seven genes with inflammatory function. There was a significant association betweenNPAS4DNA methylation andNPAS4expression in the control group that was absent in the suicide decedent group, confirming its dysregulation.NPAS4expression was significantly associated with the expression of multiple inflammatory factors in the brain tissue. Overall, gene sets and pathways closely linked to inflammation were significantly upregulated, while specific pathways linked to neuronal development were suppressed in the suicide decedent group. Excitotoxicity as well as suppressed oligodendrocyte function were also implicated in the suicide decedents. In summary, we have identified central nervous system inflammatory mechanisms that may be active during suicidal behavior, along with oligodendrocyte dysfunction and altered glutamate neurotransmission. In these processes, NPAS4 might be a master regulator, warranting further studies to validate its role as a potential biomarker or therapeutic target in suicidality.
A comprehensive SARS-CoV-2 and COVID-19 review, Part 2: host extracellular to systemic effects of SARS-CoV-2 infection
Authors: Narayanan S. Anand , Jamison David A. , Guarnieri Joseph W. , Zaksas Victoria , Topper Michael , Koutnik Andrew P. , Park Jiwoon , Clark Kevin B. , Enguita Francisco J. , Leitão Ana Lúcia , Das Saswati , Moraes-Vieira Pedro M. , Galeano Diego , Mason Christopher E. , Trovão Nídia S. , Schwartz Robert E. , Schisler Jonathan C. , Coelho-dos-Reis Jordana G. A. , Wurtele Eve Syrkin , Beheshti Afshin 
Published: November 2023

AbstractCOVID-19, the disease caused by SARS-CoV-2, has caused significant morbidity and mortality worldwide. The betacoronavirus continues to evolve with global health implications as we race to learn more to curb its transmission, evolution, and sequelae. The focus of this review, the second of a three-part series, is on the biological effects of the SARS-CoV-2 virus on post-acute disease in the context of tissue and organ adaptations and damage. We highlight the current knowledge and describe how virological, animal, and clinical studies have shed light on the mechanisms driving the varied clinical diagnoses and observations of COVID-19 patients. Moreover, we describe how investigations into SARS-CoV-2 effects have informed the understanding of viral pathogenesis and provide innovative pathways for future research on the mechanisms of viral diseases.
The estimated annual financial impact of gene therapy in the United States
Authors: Wong Chi Heem , Li Dexin , Wang Nina , Gruber Jonathan , Lo Andrew W. , Conti Rena M. 
Published: November 2023

AbstractGene therapy is a new class of medical treatment that alters part of a patient’s genome through the replacement, deletion, or insertion of genetic material. While still in its infancy, gene therapy has demonstrated immense potential to treat and even cure previously intractable diseases. Nevertheless, existing gene therapy prices are high, raising concerns about its affordability for U.S. payers and its availability to patients. We assess the potential financial impact of novel gene therapies by developing and implementing an original simulation model which entails the following steps: identifying the 109 late-stage gene therapy clinical trials underway before January 2020, estimating the prevalence and incidence of their corresponding diseases, applying a model of the increase in quality-adjusted life years for each therapy, and simulating the launch prices and expected spending of all available gene therapies annually. The results of our simulation suggest that annual spending on gene therapies will be approximately $20.4 billion, under conservative assumptions. We decompose the estimated spending by treated age group as a proxy for insurance type, finding that approximately one-half of annual spending will on the use of gene therapies to treat non-Medicare-insured adults and children. We conduct multiple sensitivity analyses regarding our assumptions and model parameters. We conclude by considering the tradeoffs of different payment methods and policies that intend to ensure patient access to the expected benefits of gene therapy.
Prediction of long-term humoral response induced by the two-dose heterologous Ad26.ZEBOV, MVA-BN-Filo vaccine against Ebola
Authors: Alexandre Marie , Prague Mélanie , McLean Chelsea , Bockstal Viki , Douoguih Macaya , Thiébaut Rodolphe ,   for the EBOVAC 1 and EBOVAC 2 Consortia, Van Effelterre Thierry , Solforosi Laura , Bockstal Viki , Dari Anna 
Published: November 2023

AbstractThe persistence of the long-term immune response induced by the heterologous Ad26.ZEBOV, MVA-BN-Filo two-dose vaccination regimen against Ebola has been investigated in several clinical trials. Longitudinal data on IgG-binding antibody concentrations were analyzed from 487 participants enrolled in six Phase I and Phase II clinical trials conducted by the EBOVAC1 and EBOVAC2 consortia. A model based on ordinary differential equations describing the dynamics of antibodies and short- and long-lived antibody-secreting cells (ASCs) was used to model the humoral response from 7 days after the second vaccination to a follow-up period of 2 years. Using a population-based approach, we first assessed the robustness of the model, which was originally estimated based on Phase I data, against all data. Then we assessed the longevity of the humoral response and identified factors that influence these dynamics. We estimated a half-life of the long-lived ASC of at least 15 years and found an influence of geographic region, sex, and age on the humoral response dynamics, with longer antibody persistence in Europeans and women and higher production of antibodies in younger participants.
Plant carbonic anhydrase-like enzymes in neuroactive alkaloid biosynthesis
Authors: Nett Ryan S. , Dho Yaereen , Tsai Chun , Passow Daria , Martinez Grundman Jaime , Low Yun-Yee , Sattely Elizabeth S. 
Published: November 2023

AbstractPlants synthesize numerous alkaloids that mimic animal neurotransmitters1. The diversity of alkaloid structures is achieved through the generation and tailoring of unique carbon scaffolds2,3, yet many neuroactive alkaloids belong to a scaffold class for which no biosynthetic route or enzyme catalyst is known. By studying highly coordinated, tissue-specific gene expression in plants that produce neuroactive Lycopodium alkaloids4, we identified an unexpected enzyme class for alkaloid biosynthesis: neofunctionalized α-carbonic anhydrases (CAHs). We show that three CAH-like (CAL) proteins are required in the biosynthetic route to a key precursor of the Lycopodium alkaloids by catalysing a stereospecific Mannich-like condensation and subsequent bicyclic scaffold generation. Also, we describe a series of scaffold tailoring steps that generate the optimized acetylcholinesterase inhibition activity of huperzine A5. Our findings suggest a broader involvement of CAH-like enzymes in specialized metabolism and demonstrate how successive scaffold tailoring can drive potency against a neurological protein target.
Simulative validation of a novel experiment carrier for the Einstein-Elevator
Authors: Sperling Richard , Raupert Marvin , Lotz Christoph , Overmeyer Ludger 
Published: November 2023

AbstractIn order to develop hardware that can be used in space, tests under those space conditions are often important to ensure the functionality in advance. Facilities that are used to recreate gravity conditions of space include space stations, satellites, parabolic flights and earthbound facilities. Drop towers are earthbound facilities, that can replicate the gravitational conditions of free falling in space by dropping objects. Those objects would not experience any measurable force due to gravity according to Einstein’s famous thought experiment. The Einstein-Elevator is one of the first active driven drop towers with an experiment carrier falling inside a gondola. A major indicator for the quality of the facility is the residual acceleration of the payload. With the Einstein-Elevators current setup vibrations of the experiment carrier cause measurable residual accelerations of higher than $$10^{-3}$$

10

-
3

g. To achieve the targeted 0-g-quality with a residual acceleration of less than 1 $$\mu $$
μ
g (microgravity) in the Einstein-Elevator, a new experiment carrier is required that minimizes the residual acceleration for a payload. This paper describes a design of the experiment carrier for the Einstein-Elevator that is able to reach microgravity and analyzes its functionality using FEM-simulations.
Assessing the applicability of PMOD residence times model for PET image-based radiation dosimetry
Authors: Oh Se Jong , Lyoo Chul Hyoung , Ryu Young Hoon , Choi Jae Yong 
Published: November 2023

AbstractThe effective dose represents the overall internal radiation exposure to the whole body when exposed to radiation sources. This study aims to compare conventional and software-aided methods to derive the effective dose. In the present study, 8F-T807 and 18F-Mefway, specific radiotracers for the paired helical tau and serotonin 1A receptor, were administered to healthy subjects (n = 6, each radiotracer), following which whole-body positron emission tomography (PET) images were obtained for 2 h. Subsequently, time-activity curves for major organs were obtained, and the residence times were calculated using the “conventional” and “Residence Times model” tools in PMOD software. The residence times from each method was input into OLINDA/EXM software, and the effective dose was estimated. The differences in the average residence times of the brain, heart, lung, and liver were 18.4, 20.8, 10.4, and 13.3% for 18F-T807, and 17.5, 16.4, 18.1, and 17.5% for 18F-Mefway, respectively. For the mean effective dose, the error rates between the methods were 3.8 and 1.9% for 18F-T807 and 18F-Mefway, respectively. The organs that showed the greatest difference in the absorbed dose were the urinary bladder for 18F-T807 (40.4%) and the liver for 18F-Mefway (14.1%). This method of obtaining the residence time using PMOD can be easily used to derive the effective dose, and is applicable in evaluating the safety of radiotracers for clinical trials.
Attributing Venice Acqua Alta events to a changing climate and evaluating the efficacy of MoSE adaptation strategy
Authors: Faranda Davide , Ginesta Mireia , Alberti Tommaso , Coppola Erika , Anzidei Marco 
Published: November 2023

AbstractWe use analogues of atmospheric patterns to investigate changes in four devastating Acqua Alta (flooding) events in the lagoon of Venice associated with intense Mediterranean cyclones occurred in 1966, 2008, 2018 and 2019. Our results provide evidence that changes in atmospheric circulation, although not necessarily only anthropogenically driven, are linked to the severity of these events. We also evaluate the cost and benefit of the MoSE system, which was designed to protect against flooding. Our analysis shows that the MoSE has already provided protection against analogues of the most extreme event, which occurred in 1966. These findings have significant implications for the future of Venice and other coastal cities facing similar challenges from rising sea levels due to extreme events. This study also provides a pathway to evaluate the effectiveness of adaptation in a scenario more frequent and intense extreme events if higher global warming levels will be reached.
Opto-SICM framework combines optogenetics with scanning ion conductance microscopy for probing cell-to-cell contacts
Authors: Song Qianqian , Alvarez-Laviada Anita , Schrup Sarah E. , Reilly-O’Donnell Benedict , Entcheva Emilia , Gorelik Julia 
Published: November 2023

AbstractWe present a novel framework, Opto-SICM, for studies of cellular interactions in live cells with high spatiotemporal resolution. The approach combines scanning ion conductance microscopy, SICM, and cell-type-specific optogenetic interrogation. Light-excitable cardiac fibroblasts (FB) and myofibroblasts (myoFB) were plated together with non-modified cardiomyocytes (CM) and then paced with periodic illumination. Opto-SICM reveals the extent of FB/myoFB-CM cell-cell contacts and the dynamic changes over time not visible by optical microscopy. FB-CM pairs have lower gap junctional expression of connexin-43 and higher contact dynamism compared to myoFB-CM pairs. The responsiveness of CM to pacing via FB/myoFB depends on the dynamics of the contact but not on the area. The non-responding pairs have higher net cell-cell movement at the contact. These findings are relevant to cardiac disease states, where adverse remodeling leads to abnormal electrical excitation of CM. The Opto-SICM framework can be deployed to offer new insights on cellular and subcellular interactions in various cell types, in real-time.
A state-of-the-art liposome technology for glioblastoma treatment
Authors: Hasan Ikram , Roy Shubham , Ehexige Ehexige , Wu Runling , Chen Yu , Gao Zhengyuan , Guo Bing , Chang Chunqi 
Published: November 2023

Cancer drug loading strategies with liposome-based nanomedicine for crossing the BBB and targeting the delivery of brain tumors. In vivo and in vitro models with imaging and therapeutic modalities.
Transient response improvement of half‐bridge LLC resonant converter with full‐bridge rectifier for DC microgrid
Authors: Ma Lan , Cao Xiaoqi , Fu Rui , Zhou Tao , Shu Zeliang 
Published: November 2023

AbstractLLC resonant converter has the features of low noise, high efficiency and power density, which is suitable to be integrated into DC microgrid. Due to severe stresses in the resonant tank, achieving fast and safe transient performance has been challenging for resonant converters. With less switch number and voltage stress, half‐bridge LLC resonant converter with full‐bridge rectifier (H‐F LLC resonant converter) are more suitable for high‐voltage application. To improve the transient response of the converter, this paper proposes a method based fixed center state trajectory for the converter to achieve soft start‐up. To reduce dynamic response time during start‐up, each step of fixed center state‐trajectory is designed optimally for the shortest path with symmetrical current limitation. In addition, the proposed method is also applicable to full‐bridge LLC converters. Moreover, according to the state‐plane analysis, load stepping‐up and stepping‐down transient state trajectories with the shortest path are carried out as well. To minimize the adverse effect of digital delay, fast load transient control based on 3D look‐up table is given based on FPGA‐EP3C25E144I7, which would also significantly reduce the computation requirement of the hardware controllers. The experimental results are verified on a 380V/12V LLC converter prototype at 130 kHz.
Volar Locking Plate versus Closed Reduction and Immobilization for Distal Radius Fracture in the Elderly: Systematic Review and Meta-Analysis of Randomized Controlled Trials
Authors: Latypov Niyaz , Golubev Igor , Borisova Alyona 
Published: November 2023

Abstract
Introduction A systematic review and meta-analysis of randomized controlled trials was conducted to compare surgical treatment using open reduction and internal fixation (ORIF) with volar locking plates (VLP) to conservative treatment with closed reduction and immobilization in elderly patients aged ≥60 years with acute displaced distal radius fractures.
Methods A search of the MEDLINE, Scopus, and Central Register of Controlled Trials (CENTRAL) databases was conducted. Clinical and radiographic measures at 12 months were compared between groups by pooling the mean difference. The complication rates were compared by pooling relative risk ratios. Pooled mean differences of Disabilities of the Arm, Shoulder, and Hand (DASH) and Patient-Rated Wrist Evaluation (PRWE) results were compared with the published minimal clinically important difference (MCID) to evaluate the clinical relevance of the results.
Results The initial search yielded 766 records, from which 6 articles were selected for the final analysis. The results of the DASH questionnaire at 12 months of follow-up were significantly lower in the surgical treatment group with a mean difference (MD) of –3.61 points (95% confidence interval [CI]: –6.48 to –0.73). No statistically significant difference was found in the PRWE questionnaire (MD = –3.14 points [95% CI: –7.32 to 1.04]). Radiological results were significantly better in the surgical treatment group and no significant difference in the overall complication rate between the groups was detected. Found MD for DASH and PRWE did not reach the published MCIDs.
Conclusion This study suggests that for elderly patients aged ≥60 years with acute displaced distal radius fractures, surgical treatment using ORIF with VLP does not provide clinically relevant benefits compared with conservative treatment with closed reduction and immobilization at the 12-month follow-up, despite demonstrating better radiological results.
Perspectives of Resident and Attending Ophthalmologists on Common Ethical Dilemmas in Research
Authors: Miller Sarah C. , Tsou Brittany C. , Fliotsos Michael J. , Legault Gary L. , Wang Jiangxia , Mondzelewski Todd J. , Munson Patrick D. , Lorch Alice , Green Laura K. , Kim Won I. , Pelton Ron W. , Woreta Fasika A. , Justin Grant A. 
Published: November 2023

Abstract
Purpose To assess how resident and attending ophthalmologists perceive and evaluate ethically controversial scenarios regarding mentorship, authorship, and ethics compliance that may occur during research involving residents.
Methods An online survey was developed and contained 14 controversial vignettes based on common research scenarios that can occur when conducting research with trainees. The scenarios were designed to capture issues regarding three themes: mentorship, authorship, and compliance with ethical guidelines. Resident and attending ophthalmologists at eight military and civilian academic residency programs in the United States were invited to participate. Respondents used a Likert scale to assess the ethicality of the situations in addition to self-reported demographic characteristics.
Results The response rate was 35.6% (77/216), consisting of 37.7% (n = 29) residents and 62.3% (n = 48) attendings. More attending ophthalmologists responded than residents (p = 0.004). Many respondents identified controversies around compliance (67.3%) and authorship (57.1%) as unethical, whereas situations regarding mentorship were largely viewed as neutral to ethical (68.0%). Responses to two scenarios, one regarding mentorship and one regarding authorship, significantly differed between residents and attendings (p = 0.001 and p = 0.022, respectively).
Conclusion Academic ophthalmologists' perceptions of the ethicality of common research scenarios varied. There is a need for more prescriptive guidelines for authorship and mentorship ethics at all training levels to ensure consistency, fairness, and integrity of research.
Arthroscopic-assisted Distal Radius Fracture Fixation for Dorsoulnar Corner Fragments Using a Locked, Hooked Kirschner-Wire Technique
Authors: Ross Mark , White Matthew J. , Smith Nicholas 
Published: November 2023

Abstract
Background Distal radius fractures with dorso-ulnar corner fragments (DUC) pose a surgical challenge due to limited visualization and the risk of hardware prominence. Traditional approaches often result in inadequate reduction and fixation, leading to suboptimal clinical outcomes.
Description of Technique In this study, we introduce an arthroscopic-assisted approach for the fixation of distal radius fractures with DUC fragments. The technique utilizes locked, hooked K-wires to provide a low-profile dorsal capturing mechanism. We outline the step-by-step procedure, which includes pre-operative planning, volar plate application, and arthroscopic reduction of DUC fragments.
Materials and Methods We applied this technique to a 60-year-old female patient with an unstable intra-articular distal radius fracture and a DUC fragment. Closed reduction was initially attempted, followed by arthroscopic-assisted reduction and internal fixation using the locked, hooked K-wire technique.
Results Our technique has demonstrated its ability to withstand early movement rehabilitation protocols without fixation loss, enabling early mobilization. A custom thermoplastic splint was worn for 6 weeks, with favorable supination/pronation and wrist flexion/extension outcomes at clinical review.
Conclusions Arthroscopic-assisted fixation with locked, hooked K-wires offers a reliable solution for accurately reducing challenging DUC fragments in distal radius fractures. This approach complements standard distal radius fixation systems, providing a low-profile dorsal capturing mechanism and addressing the issue of hardware prominence, ultimately improving clinical outcomes.
Combined Arthroscopic Wafer Procedure and Triangular Fibrocartilage Complex Debridement versus Ulnar Shortening Diaphyseal Osteotomy in Management of Ulnar Impaction Syndrome: A Randomized Clinical Trial
Authors: El-Tayar Ahmed , El-Ghandour Samir , Ghazal Adel , Rakha Ibrahim , Sallam Asser 
Published: November 2023

Abstract
Background The literature presents great challenge in comparing the arthroscopic wafer procedure (AWP) versus ulnar shortening osteotomy (USO) in the treatment of ulnar impaction syndrome (UIS).
Purpose We aimed primarily to compare the clinical and functional outcomes of AWP with triangular fibrocartilage complex (TFCC) debridement versus USO in the management of UIS.
Methods The study was conducted as a randomized clinical trial including 43 patients with UIS whose ulna variance was less than 4 mm. Patients were randomly allocated to either the AWP group (21 patients) who underwent AWP and TFCC debridement or the USO group (22 patients) who underwent diaphyseal USO. Patients were followed up for at least 12 months. The primary outcome measure was the Modified Mayo Wrist (MMW) score. The Disabilities of the Arm, Shoulder, and Hand (DASH) score, the mean operative time, postoperative complications, and patient satisfaction were our secondary outcomes.
Results Radiological correction of variance was achieved in all patients. The mean operative time was significantly shorter in the AWP group. The postoperative MMW and DASH scores were better in the AWP group than in the USO group. Fewer complications occurred in the AWP group (1 of 21 patients) compared with the USO group (3 of 22 patients).
Conclusions AWP with TFCC debridement is a reliable and safe method for the management of UIS with a positive variance of less than 4 mm with better clinical and functional results than diaphyseal USO.
Type of study/level of evidence Therapeutic type II.