bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Fascial Distortion Model in Military Aircrew with Chronic Neck Pain: A Case Study
Authors: Fullenkamp Allison J 
Published: February 2024

ABSTRACT
Musculoskeletal pain can be a significant safety risk to aircrew. Flight surgeons are the primary care providers for aircrew and are responsible for safely treating musculoskeletal pain. Certain medical interventions can be used to treat pain while maintaining the ability to fly safely. A previous F-18 Naval Flight Officer presented to the flight surgeon with chronic neck pain seeking noninvasive and nonpharmacological therapy. After one Osteopathic Manual Treatment session using the Fascial Distortion Model (FDM), the patient had improved pain and function. The aircrewman reported an 83% reduction in pain and a 200% improvement in cervical Range of Motion (ROM) immediately following treatment. Neck pain is a common complaint in aircrew. This pain can become an in-flight distraction, thus increasing the risk of aviation mishaps. FDM can decrease pain and increase ROM quickly, without equipment or a large amount of space and without the use of medications that may prohibit an aircrew member from flying. This case study shows the ability to treat a uniformed aircrewman with neck pain while onboard an aircraft. FDM is a technique that can be taught to all flight surgeons. Teaching future flight surgeons FDM techniques can improve the U.S. Navy’s resources by decreasing time away from work along with decreasing medical costs. The use of osteopathic manipulation treatment significantly reduced an aircrewman’s pain and increased ROM with one treatment while maintaining flight status per current aeromedical waiver guidelines.
Substitution Models of Protein Evolution with Selection on Enzymatic Activity
Authors: Ferreiro David , Khalil Ruqaiya , Sousa Sergio F , Arenas Miguel 
Published: February 2024

Abstract
Substitution models of evolution are necessary for diverse evolutionary analyses including phylogenetic tree and ancestral sequence reconstructions. At the protein level, empirical substitution models are traditionally used due to their simplicity, but they ignore the variability of substitution patterns among protein sites. Next, in order to improve the realism of the modeling of protein evolution, a series of structurally constrained substitution models were presented, but still they usually ignore constraints on the protein activity. Here, we present a substitution model of protein evolution with selection on both protein structure and enzymatic activity, and that can be applied to phylogenetics. In particular, the model considers the binding affinity of the enzyme–substrate complex as well as structural constraints that include the flexibility of structural flaps, hydrogen bonds, amino acids backbone radius of gyration, and solvent-accessible surface area that are quantified through molecular dynamics simulations. We applied the model to the HIV-1 protease and evaluated it by phylogenetic likelihood in comparison with the best-fitting empirical substitution model and a structurally constrained substitution model that ignores the enzymatic activity. We found that accounting for selection on the protein activity improves the fitting of the modeled functional regions with the real observations, especially in data with high molecular identity, which recommends considering constraints on the protein activity in the development of substitution models of evolution.
Comparison of different target volume delineation strategies based on recurrence patterns in adjuvant radiotherapy for glioblastoma
Authors: Yilmaz Melek Tugce , Kahvecioglu Alper , Yedekci Fazli Yagiz , Yigit Ecem , Ciftci Gokcen Coban , Kertmen Neyran , Zorlu Faruk , Yazici Gozde 
Published: February 2024

Abstract

Background
Radiation Therapy Oncology Group (RTOG) and the European Organization for Research and Treatment of Cancer (EORTC) recommendations are commonly used guidelines for adjuvant radiotherapy in glioblastoma. In our institutional protocol, we delineate T2-FLAIR alterations as gross target volume (GTV) with reduced clinical target volume (CTV) margins. We aimed to present our oncologic outcomes and compare the recurrence patterns and planning parameters with EORTC and RTOG delineation strategies.

Methods
Eighty-one patients who received CRT between 2014 and 2021 were evaluated retrospectively. EORTC and RTOG delineations performed on the simulation computed tomography and recurrence patterns and planning parameters were compared between delineation strategies. Statistical Package for the Social Sciences (SPSS) version 23.0 (IBM, Armonk, NY, USA) was utilized for statistical analyses.

Results
Median overall survival and progression-free survival were 21 months and 11 months, respectively. At a median 18 month follow-up, of the 48 patients for whom recurrence pattern analysis was performed, recurrence was encompassed by only our institutional protocol’s CTV in 13 (27%) of them. For the remaining 35 (73%) patients, recurrence was encompassed by all separate CTVs. In addition to the 100% rate of in-field recurrence, the smallest CTV and lower OAR doses were obtained by our protocol.

Conclusions
The current study provides promising results for including the T2-FLAIR alterations to the GTV with smaller CTV margins with impressive survival outcomes without any marginal recurrence. The fact that our protocol did not result in larger irradiated brain volume is further encouraging in terms of toxicity.
Cross-State Border Nicotine Vaping Products Purchase—Early Evidence From State Emergency Sales Restrictions in 2019
Authors: Cheng Kai-Wen , Liber Alex C , Levy David T 
Published: February 2024

Abstract

Introduction
While retail sales and retailer inspection studies generally indicate high compliance with state sales restrictions on Nicotine Vaping Products (NVPs) within the restricted area, studies using survey data generally indicate that most users could readily continue gaining access to restricted NVPs. Our study bridges a gap in the current literature and investigates the potential role of cross-state border purchases to evade state emergency NVP sales restrictions in 2019.

Aims and Methods
The study sample was restricted to NVP sales from the states neighboring Massachusetts, Rhode Island, and Washington, three states that implemented all NVP or flavored NVP sales restrictions in 2019. Among these neighboring states, the 2019 weekly county-level NVP sales by flavors (tobacco, mint/menthol, and other flavors) were compiled using Nielsen Scanner data. A quasi-experimental, comparison group pre–post study design was used to study the impacts of NVP sales restrictions on cross-state border NVP purchases.

Results
Weekly NVP sales for border counties significantly increased in response to the MA, RI, and WA bans for tobacco flavored (56%, 45%, 14%, respectively), menthol/mint flavored (51%, 2%, 41%, respectively), and other flavored (79%, 3%, 4%, respectively) products, compared to sales for non-border counties (all p-values &lt; .01).

Conclusions
Our study identified significant cross-state border NVP purchases in all studied states to circumvent NVP emergency sales restrictions in response to the EVALI outbreak. Policymakers should factor in these purchasing behaviors to evade sales restrictions when evaluating any future potential policies at the state or local levels.

Implications
While retail sales data and retailer inspections indicate high compliance with Nicotine Vaping Product (NVP) flavor sales restrictions from major retail outlets, survey data obtain mixed findings on the effects of sales restrictions on vaping behaviors. Our study identified a significant increase in cross-state border NVP purchases to circumvent NVP sales restrictions in 2019, consistent across all three settings of Massachusetts, Rhode Island, and Washington. Policymakers should factor in these cross-state border NVP purchases in response to sales restrictions when evaluating any future potential NVP sales restrictions.
The Rise of Public–Private Religious Partnerships: Arguing Church Autonomy in the Era of Public Funding of Religion
Authors: Perez Nahshon 
Published: February 2024

Abstract
Religion and government, following the influence of Locke and Madison are often considered two different institutions. As such, they function under different sets of rules. We argue that the ‘two institutions’ image and institutional reality are increasingly untenable. Rather, religion and government are intertwined in many democratic countries, including, growingly, in the US, that it would be more accurate to speak of the new norm of governmental–religious hybridity. Advances in data collected regarding religion–state relations, and the accumulation of court decisions in the US bring to the fore a new norm of religious–governmental hybridity. Such hybrid institutions are typically functionally religious associations; however, their funding is sourced in the government to create ‘public private religious partnerships’. If such a re-classification is justified, then norms of public law should apply to such religious associations. This bears substantial implications vis-a-vis central concepts used in political and legal circles regarding religious freedom; furthermore, this reclassification also bears upon an ongoing intellectual debate between scholars such as Chiara Cordelli—advocating democratization of religion, and Michael W. McConnell who advocated an opposing view: a strong version of church autonomy. So, this reclassification bears important implications for both scholarly debates and political issues.
First-In-Human Phase I Study of Tinengotinib (TT-00420), a Multiple Kinase Inhibitor, as a Single Agent in Patients With Advanced Solid Tumors
Authors: Piha-Paul Sarina A , Xu Binghe , Dumbrava Ecaterina E , Fu Siqing , Karp Daniel D , Meric-Bernstam Funda , Hong David S , Rodon Jordi A , Tsimberidou Apostolia M , Raghav Kanwal , Ajani Jaffer A , Conley Anthony P , Mott Frank , Fan Ying , Fan Jean , Peng Peng , Wang Hui , Ni Shumao , Sun Caixia , Qiang Xiaoyan , Levin Wendy J , Ngo Brenda , Ru Qinhua Cindy , Wu Frank , Javle Milind M 
Published: February 2024

Abstract

Purpose
This first-in-human phase I dose-escalation study evaluated the safety, pharmacokinetics, and efficacy of tinengotinib (TT-00420), a multi-kinase inhibitor targeting fibroblast growth factor receptors 1-3 (FGFRs 1-3), Janus kinase 1/2, vascular endothelial growth factor receptors, and Aurora A/B, in patients with advanced solid tumors.

Patients and Methods
Patients received tinengotinib orally daily in 28-day cycles. Dose escalation was guided by Bayesian modeling using escalation with overdose control. The primary objective was to assess dose-limiting toxicities (DLTs), maximum tolerated dose (MTD), and dose recommended for dose expansion (DRDE). Secondary objectives included pharmacokinetics and efficacy.

Results
Forty-eight patients were enrolled (dose escalation, n = 40; dose expansion, n = 8). MTD was not reached; DRDE was 12 mg daily. DLTs were palmar-plantar erythrodysesthesia syndrome (8 mg, n = 1) and hypertension (15 mg, n = 2). The most common treatment-related adverse event was hypertension (50.0%). In 43 response-evaluable patients, 13 (30.2%) achieved partial response (PR; n = 7) or stable disease (SD) ≥ 24 weeks (n = 6), including 4/11 (36.4%) with FGFR2 mutations/fusions and cholangiocarcinoma (PR n = 3; SD ≥ 24 weeks n = 1), 3/3 (100.0%) with hormone receptor (HR)-positive/HER2-negative breast cancer (PR n = 2; SD ≥ 24 weeks n = 1), 2/5 (40.0%) with triple-negative breast cancer (TNBC; PR n = 1; SD ≥ 24 weeks n = 1), and 1/1 (100.0%) with castrate-resistant prostate cancer (CRPC; PR). Four of 12 patients (33.3%; HR-positive/HER2-negative breast cancer, TNBC, prostate cancer, and cholangiocarcinoma) treated at DRDE had PRs. Tinengotinib’s half-life was 28-34 hours.

Conclusions
Tinengotinib was well tolerated with favorable pharmacokinetic characteristics. Preliminary findings indicated potential clinical benefit in FGFR inhibitor-refractory cholangiocarcinoma, HER2-negative breast cancer (including TNBC), and CRPC. Continued evaluation of tinengotinib is warranted in phase II trials.
Tissue-Matched IgH Gene Rearrangement of Circulating Tumor DNA Shows Significant Value in Predicting the Progression of Diffuse Large B Cell Lymphoma
Authors: Zhao Kewei , Zheng Xin , Liu Xinxiu , Liu Tao , Ke Zhonghe , Zhu Fang , Wen Qiuyue , Xin Beibei , Li Qiuhui , Zhang Liling 
Published: February 2024

Abstract

Background
Evidence has demonstrated that monitoring of the variable, diversity, and joining gene segments (VDJ) rearrangement of the immunoglobulin (Ig) genes in the circulating tumor DNA (ctDNA) is of value in predicting the outcomes of diffuse large B cell lymphoma (DLBCL). In this study, we investigated the role of VDJ rearrangement proportion in ctDNA for predicting DLBCL progression.

Methods
Patients diagnosed with newly diagnosed DLBCL were included in this study. The VDJ sequences of IgH were detected using next-generation sequencing (NGS) in formalin-fixed paraffin-embedded tissue and/or peripheral blood. The clonotype of the highest proportion in the peripheral blood was defined as the “dominant circulating clonotype,” whilst the clonotype of the highest proportion in matched tissue that is detected in peripheral blood was defined as the “dominant tissue-matched clonotype.” The decision tree, a machine learning-based methodology, was used to establish a progression-predicting model through a combination of “dominant tissue-matched clonotype” proportion or “dominant circulating clonotype” proportion, and the clinicopathological information, including age, sex, cell of origin, stage, international prognostic index, lactate dehydrogenase, number of extranodal involvements and β2-microglobulin.

Results
A total of 55 patients with eligible sequencing data were used for prognosis analysis, among which 36 patients had matched tissue samples. The concordance rate of “dominant circulating clonotype” and “dominant tissue-matched clonotype” was 19.44% (7/36). The decision tree model showed that the combination of extranodal involvement event and “dominant circulating clonotype” proportion (≥37%) had a clinical value in predicting the prognosis of DLBCL following combined chemotherapy (sensitivity, 0.63; specificity, 0.81; positive prediction value (PPV), 0.59; negative prediction value, 0.83; kappa value, 0.42). Noticeably, the combination of the “dominant tissue-matched clonotype” and extranodal involvement event showed a higher value in predicting the progression (sensitivity, 0.85; specificity, 0.78; PPV, 0.69; kappa value, 0.64).

Conclusion
IgH proportion detected in the ctDNA samples traced from tissue samples has a high clinical value in predicting the progression of DLBCL.
Perspectives on green hydrogen in Europe—during an energy crisis and towards future climate neutrality
Authors: Münster Marie , Bramstoft Rasmus , Kountouris Ioannis , Langer Lissy , Keles Dogan , Schlautmann Ruth , Mörs Friedemann , Saccani Cesare , Guzzini Alessandro , Pellegrini Marco , Zauner Andreas , Böhm Hans , Markova Darja , You Shi , Pumpa Martin , Fischer Frank , Sergi Francesco , Brunaccini Giovanni , Aloisio Davide , Ferraro Marco , Mulder Machiel , Rasmusson Hans 
Published: February 2024

Abstract
Hydrogen and regional energy infrastructure are significant for the European Green Deal and was the focus of the SuperP2G research Project (Synergies Utilising renewable Power Regionally by means of Power to Gas). Five national projects (Denmark, Netherlands, Germany, Austria, and Italy) cooperated to investigate power-to-gas feasibility. The energy crisis due to the war in Ukraine peaked during the project. The demand for green hydrogen increased as natural gas was reduced. In 2022, the cost of blue hydrogen was 9.5–12.6 €/kg. Higher electricity prices impacted the cost of green hydrogen less. Considering the 2021–22 level of electricity and gas prices, and the potential flexibility of electrolysers, electrolytic hydrogen was on a par with blue hydrogen. On the long term, green hydrogen is assumed to be competitive around 2030. A fast ramping up and favourable electricity cost development could halve the hydrogen production cost until 2040 with investment being the major contributor to a cost reduction. Meanwhile, the smart operation of a wind/electrolyser system might achieve 24% reduction of its operation cost. The following measures are recommended to introduce green hydrogen on a large scale: 1) certification of green and low carbon hydrogen and a uniform CO2 price; 2) ensuring a level playing field across markets; 3) enabling policies to enhance European security of supply by increasing domestic production and diversifying imports; 4) fast ramping of renewable electricity generation; and 5) coordinated planning of hydrogen, methane, and electricity infrastructures.
Mitogen-activated protein kinases MPK3 and MPK6 phosphorylate receptor-like cytoplasmic kinase CDL1 to regulate soybean basal immunity
Authors: Zhang Lei , Zhu Qun , Tan Yuanhua , Deng Miaomiao , Zhang Lei , Cao Yangrong , Guo Xiaoli 
Published: February 2024

Abstract
Soybean cyst nematode (SCN; Heterodera glycines Ichinohe), one of the most devastating soybean (Glycine max) pathogens, causes significant yield loss in soybean production. Nematode infection triggers plant defense responses; however, the components involved in the upstream signaling cascade remain largely unknown. In this study, we established that a mitogen-activated protein kinase (MAPK) signaling module, activated by nematode infection or wounding, is crucial for soybeans to establish SCN resistance. GmMPK3 and GmMPK6 directly interact with CDG1-LIKE1 (GmCDL1), a member of the receptor-like cytoplasmic kinase (RLCK) subfamily VII. These kinases phosphorylate GmCDL1 at Thr-372 to prevent its proteasome-mediated degradation. Functional analysis demonstrated that GmCDL1 positively regulates immune responses and promotes SCN resistance in soybeans. GmMPK3-mediated and GmMPK6-mediated phosphorylation of GmCDL1 enhances GmMPK3 and GmMPK6 activation and soybean disease resistance, representing a positive feedback mechanism. Additionally, 2 L-type lectin receptor kinases, GmLecRK02g and GmLecRK08g, associate with GmCDL1 to initiate downstream immune signaling. Notably, our study also unveils the potential involvement of GmLecRKs and GmCDL1 in countering other soybean pathogens beyond nematodes. Taken together, our findings reveal the pivotal role of the GmLecRKs–GmCDL1–MAPK regulatory module in triggering soybean basal immune responses.
Cryo-EM structure of HQNO-bound alternative complex III from the anoxygenic phototrophic bacterium Chloroflexus aurantiacus
Authors: Xin Jiyu , Min Zhenzhen , Yu Lu , Yuan Xinyi , Liu Aokun , Wu Wenping , Zhang Xin , He Huimin , Wu Jingyi , Xin Yueyong , Blankenship Robert E , Tian Changlin , Xu Xiaoling 
Published: February 2024

Abstract
Alternative complex III (ACIII) couples quinol oxidation and electron acceptor reduction with potential transmembrane proton translocation. It is compositionally and structurally different from the cytochrome bc1/b6f complexes but functionally replaces these enzymes in the photosynthetic and/or respiratory electron transport chains (ETCs) of many bacteria. However, the true compositions and architectures of ACIIIs remain unclear, as do their structural and functional relevance in mediating the ETCs. We here determined cryogenic electron microscopy structures of photosynthetic ACIII isolated from Chloroflexus aurantiacus (CaACIIIp), in apo-form and in complexed form bound to a menadiol analog 2-heptyl-4-hydroxyquinoline-N-oxide. Besides 6 canonical subunits (ActABCDEF), the structures revealed conformations of 2 previously unresolved subunits, ActG and I, which contributed to the complex stability. We also elucidated the structural basis of menaquinol oxidation and subsequent electron transfer along the [3Fe–4S]-6 hemes wire to its periplasmic electron acceptors, using electron paramagnetic resonance, spectroelectrochemistry, enzymatic analyses, and molecular dynamics simulations. A unique insertion loop in ActE was shown to function in determining the binding specificity of CaACIIIp for downstream electron acceptors. This study broadens our understanding of the structural diversity and molecular evolution of ACIIIs, enabling further investigation of the (mena)quinol oxidoreductases–evolved coupling mechanism in bacterial energy conservation.
Growth kinetics of amyloid-like fibrils: An integrated atomistic simulation and continuum theory approach
Authors: Zhang Ruoyao , Jalali Sharareh , Dias Cristiano Luis , Haataja Mikko P 
Published: February 2024

Abstract
Amyloid fibrils have long been associated with many neurodegenerative diseases. The conventional picture of the formation and proliferation of fibrils from unfolded proteins comprises primary and secondary nucleation of oligomers followed by elongation and fragmentation thereof. In this work, we first employ extensive all-atom molecular dynamics (MD) simulations of short peptides to investigate the governing processes of fibril growth at the molecular scale. We observe that the peptides in the bulk solution can bind onto and subsequently diffuse along the fibril surface, which leads to fibril elongation via either bulk- or surface-mediated docking mechanisms. Then, to guide the quantitative interpretation of these observations and to provide a more comprehensive picture of the growth kinetics of single fibrils, a continuum model which incorporates the key processes observed in the MD simulations is formulated. The model is employed to investigate how relevant physical parameters affect the kinetics of fibril growth and identify distinct growth regimes. In particular, it is shown that fibrils which strongly bind peptides may undergo a transient exponential growth phase in which the entire fibril surface effectively acts as a sink for peptides. We also demonstrate how the relevant model parameters can be estimated from the MD trajectories. Our results provide compelling evidence that the overall fibril growth rates are determined by both bulk and surface peptide fluxes, thereby contributing to a more fundamental understanding of the growth kinetics of amyloid-like fibrils.