bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparing the role of 99mTc-HYNIC-PSMA-11 and 99mTc-MDP scintigraphy for the initial staging of intermediate to high-risk prostate cancer
Authors: Ghaedian Tahereh , Abdinejad Maryam , Nasrollahi Hamid , Ghaedian Mehrnaz , Firuzyar Tahereh
Published: July 2023

Background

Although bone scintigraphy and abdominopelvic computed tomography (CT)/MRI have been the mainstay of initial staging in the intermediate to high-risk prostate cancer (PC) patients, prostate-specific membrane antigen (PSMA) PET/CT imaging provides promising additional value in the initial N/M staging of these patients in recent years. 99mTc-PSMA scan is a new alternative to PSMA PET tracers with little evidence regarding its diagnostic value in the initial staging of PC.

Methods

This prospective study included 40 patients with newly diagnosed PC with initial intermediate or high-risk features [prostate-specific antigen (PSA) > 10 ng/dl, Gleason score ≥7 or stage cT2b and more]. All patients underwent both 99mTc-methylene diphosphonate (MDP) bone scan and 99mTc-HYNIC-PSMA-11 scan with maximum interval of 2 weeks. Abdominopelvic CT and MRI were also performed in this timeframe. Then, the results of these methods were compared with the final diagnosis data.

Results

Among the 40 included patients, 28 patients had finally been diagnosed as localized PC and 12 patients showed lymph node or metastatic involvement. The sensitivity, specificity and accuracy of 99mTc-HYNIC-PSMA-11 vs. 99mTc-MDP were 83.3% vs. 50.0%, 100% vs. 82.1% and 95% vs. 72.5%, respectively. However, when combined with the results of abdominopelvic CT/MRI the sensitivity reached 100% for both and the specificity raised to 100% and 96.4% for 99mTc-HYNIC-PSMA-11 and 99mTc-MDP, respectively.

Conclusion

99mTc-HYNIC-PSMA-11 performs well in the initial staging of intermediate to high-risk PC and especially in low source areas without PET/CT it can be used as the first-line method of metastatic evaluation instead of bone scintigraphy. However, the combination and correlation of cross-sectional imaging is essential to gain the optimal diagnostic value.
Replacing academic journals
Authors: Brembs Björn , Huneman Philippe , Schönbrodt Felix , Nilsonne Gustav , Susi Toma , Siems Renke , Perakakis Pandelis , Trachana Varvara , Ma Lai , Rodriguez-Cuadrado Sara
Published: July 2023

Replacing traditional journals with a more modern solution is not a new idea. Here, we propose ways to overcome the social dilemma underlying the decades of inaction. Any solution needs to not only resolve the current problems but also be capable of preventing takeover by corporations: it needs to replace traditional journals with a decentralized, resilient, evolvable network that is interconnected by open standards and open-source norms under the governance of the scholarly community. It needs to replace the monopolies connected to journals with a genuine, functioning and well-regulated market. In this new market, substitutable service providers compete and innovate according to the conditions of the scholarly community, avoiding sustained vendor lock-in. Therefore, a standards body needs to form under the governance of the scholarly community to allow the development of open scholarly infrastructures servicing the entire research workflow. We propose a redirection of money from legacy publishers to the new network by funding bodies broadening their minimal infrastructure requirements at recipient institutions to include modern infrastructure components replacing and complementing journal functionalities. Such updated eligibility criteria by funding agencies would help realign the financial incentives for recipient institutions with public and scholarly interest.
Sustainability 4.0 in services: a systematic review of the literature
Authors: Filgueiras Igor Fellype Loureiro Valenca , Melo Fagner José Coutinho De
Published: July 2023

Purpose

This paper aimed to identify the impact that Industry 4.0 can have on the service sector and how its combination can generate benefits for Sustainability 4.0 in the context of the Triple Bottom Line.

Design/methodology/approach

A Systematic Literature Review (RSL) was developed using the following combinations of keywords on the Web of Science and Scopus databases: Industry 4.0 And Sustainability, Industry 4.0 And Service, and Industry 4.0 And Sustainable Development, in which 24 papers were selected.

Findings

As a result, the authors found 100 benefits for sustainable development, which were further categorized into 54 advantages for the economic area, 25 for the social segment and 21 for environmental aspects. In this way, the results can help private companies understand the use of these technologies aimed at sustainable growth, plus bolstering the government to conduct public policies to encourage these practices in technology organizations.

Practical implications

As a practical implication, this study offers insight into the evolution of sustainable development. It enables the emergence of works that wish to explore the service sector, providing relevant information for decision-making and influencing managers and policymakers on the importance of applying Industry 4.0 toward the sustainability of the service sector and its applications.

Originality/value

The originality of this study lies in expanding the understanding generated by 4.0 technologies, by diverting attention from the manufacturing and agricultural sectors, which have abundant literature on the subject. With this, this work demonstrated that modern technologies have greater possibilities of an action directed at the service sector, in addition to being able to contribute to Sustainability 4.0 from the perspective of the sustainability tripod.
Mortality and alcohol‐related morbidity in patients with delirium tremens, alcohol withdrawal state or alcohol dependence in Norway: A register‐based prospective cohort study
Authors: Bramness Jørgen G. , Heiberg Ina H. , Høye Anne , Rossow Ingeborg
Published: July 2023

Background and Aims

Little is known about long‐term consequences of delirium tremens (DT). This study aimed to compare all‐cause and cause‐specific mortality and alcohol‐related morbidity between patients with: (i) DT, (ii) alcohol withdrawal state (AWS) and (iii) alcohol dependence (AD).

Design

A national longitudinal health registry study with linked data from the Norwegian Patient Registry and the Norwegian Cause of Death Registry.

Setting

Norway.

Participants

All patients registered in the Norwegian Patient Registry between 2009 and 2015 with a diagnosis of AD (ICD‐10 code F10.2), AWS (F10.3) or DT (F10.4) and aged 20–79 years were included (n = 36 287).

Measurements

Patients were categorized into three mutually exclusive groups; those with DT diagnosis were categorized as DT patients regardless of whether or not they had received another alcohol use disorder diagnosis during the observation period or not. Outcome measures were: annual mortality rate, standardized mortality ratios (SMR) for all‐cause and cause‐specific mortality and proportion of alcohol‐related morbidities which were registered in the period from 2 years before to 1 year after the index diagnosis.

Findings

DT patients had higher annual mortality rate (8.0%) than AWS (5.0%) and AD (3.6%) patients, respectively. DT patients had higher mortality [SMR = 9.8, 95% confidence interval (CI) = 8.9–10.7] than AD patients (SMR = 7.0, 95% CI = 6.8–7.2) and AWS patients (SMR = 7.8, 95% CI = 7.2–8.4). SMR was particularly elevated for unnatural causes of death, and more so for DT patients (SMR = 26.9, 95% CI = 21.7–33.4) than for AD patients (SMR = 15.2, 95% CI = 14.2–16.3) or AWS patients (SMR = 20.1, 95% CI = 16.9–23.9). For all comorbidities, we observed a higher proportion among DT patients than among AWS or AD patients (P < 0.001).

Conclusions

People treated for delirium tremens appear to have higher rates of mortality and comorbidity than people with other alcohol use disorders.
Estimating alcohol‐attributable injury deaths: A comparison of epidemiological methods
Authors: Naimi Timothy S. , Sherk Adam , Esser Marissa B. , Zhao Jinhui
Published: July 2023

Background and Aims

Injuries often involve alcohol, but determining the proportion caused by alcohol is difficult. Several approaches have been used to determine the causal role of alcohol, but these methods have not been compared directly with one another. Such a comparison would be useful for understanding the strengths and comparability of different approaches. This study compared estimates of average annual alcohol‐attributable deaths in the United States from injuries during 2015–19 using a blood alcohol concentration (BAC) method compared with a population attributable fraction (PAF) approach.

Methods

For the BAC method, we used a direct method involving the proportion of decedents with a high blood alcohol concentration (BAC; e.g. ≥ 0.10%). For the PAF approach, we compared the use of unadjusted survey data with average consumption data adjusted using alcohol sales data to account for underreporting and also accounting for the underreporting of binge drinking. Survey data were from the Behavioral Risk Factor Surveillance System and mortality data were from the National Vital Statistics System.

Results

The number of alcohol‐attributable injury deaths using the direct method (48 516 deaths annually) was similar to that using PAF methods (47 879 deaths annually), but only when alcohol use measures were adjusted using alcohol sales data. Furthermore, estimates were similar for cause‐specific categories of deaths, including non‐motor vehicle unintentional injuries and motor vehicle crashes. Among PAF methods, excessive drinking accounted for 38.3% of injury deaths using unadjusted survey data, but 64.8% of injury deaths using adjusted data.

Conclusions

Estimates of alcohol‐attributable injury deaths from a direct method and from a population attributable fraction method that adjusts for alcohol use based on alcohol sales data appear to be comparable.
Geographic patterns and ecological correlates of the mean genus age of liverworts in regional floras across China
Authors: Qian Hong , Dai Zun , Wang Jian
Published: July 2023

Aim

Mean lineage age is an important metric of evolutionary history and community structure of biological assemblages. Many studies have investigated geographic patterns and ecological drivers of mean lineage age in plant assemblages but all previous studies focused on vascular plants. Similar studies for bryophytes, a lineage of the oldest land plants, are lacking. Here, we fill this critical knowledge gap by investigating geographic patterns and ecological correlates of the mean genus age (MGA) of liverworts, a major lineage of bryophytes, in regional floras across China.

Location

China.

Taxon

Liverworts (hepatics, Division Marchantiophyta of bryophytes).

Methods

MGA and its standardized effect size (MGAses) of liverworts in each of the 28 province‐level regions across China were related to 12 explanatory variables representing geography, contemporary climate and historical climate change, using correlation and regression analyses, and a variation partitioning approach.

Results

We found that (1) MGA and MGAsesof liverworts were correlated negatively with latitude and elevational range, and positively with mean annual temperature, and annual precipitation in the regions across China, (2) MGA and MGAsesof liverworts were more strongly affected by temperature‐related variables than by precipitation‐related variables, and (3) MGA and MGAsesof liverworts were more strongly affected by climate extremes than by climate seasonality.

Main Conclusions

The relationships of mean lineage age with climatic condition in one of the oldest lineages of land plants (i.e. liverworts) are consistent with those in angiosperms, a relatively young lineage of land plants. Our study is the first to show that geographic and ecological distributions of the oldest land plants are generally consistent with the pattern frequently observed in angiosperms that biological assemblages in colder and drier climates have, on average, younger lineage ages.
Comparative evaluation of pinhole surgical technique with and withoutA‐PRFin the treatment of multiple adjacent recession defects: A clinico radiographic study
Authors: Trivedi Divya S. , Kolte Abhay P. , Kolte Rajashri A. , Deshpande Neha M.
Published: July 2023

Background

To evaluate and compare efficacy of pinhole surgical technique (PST) alone and with advanced platelet rich fibrin (A‐PRF) in the management of bilateral multiple adjacent gingival recession defects (MAGRD).

Methods

One hundred and sixty five MAGRD were randomly assigned to control group (treated with PST) and test group (PST with A‐PRF). Clinical parameters of gingival recession depth (GRD), gingival recession width (GRW), width of keratinised gingiva (WKG), complete root coverage (CRC) and gingival thickness (GT) on ST‐CBCT was measured at 2, 4 and 6 mm apically from the gingival margin. Also, root coverage aesthetic score and patient satisfaction ratings were recorded at baseline, 6 and 12 months postoperatively.

Results

Substantial reduction in GRD (Test: 1.29 ± 0.69 mm and Control 0.98 ± 0.30 mm) (p < 0.001) and GRW (Test: 2.03 ± 0.90 mm and control 1.73 ± 0.99 mm) (p < 0.05) with associated gain in WKG and GT was observed (p < 0.001). Mean GT values were increased in both the groups at 2, 4 and 6 mm from the crest. Comparison of Test and Control groups yielded significant reductions in GRD (−0.17 ± 0.56 mm) and WKG (0.73 ± 1.07 mm) favoring the Test group (p < 0.05). Similar increase in GT was observed with better results in Test than control group. (p < 0.001).

Conclusion

Both groups exhibited sound clinical outcomes with test group offering better resolution of MAGRD in comparison to control group. Also, it enhances clinical and therapeutic end results in terms of attaining reduction in GRD and GRW along with greater gain in KTW and GT.

Clinical Significance

PST as a minimally invasive approach has numerous benefits, some of which include the absence of scarring and improved aesthetics linked to faster wound healing. The addition of A‐PRF enhances the intended therapy outcomes, which is beneficial for both patients and professionals in the field of periodontics.
Prediction of CO2 and ethylene produced in‐packaged apricot under cold plasma treatment by machine learning approach
Authors: Rashvand Mahdi , Altieri Giuseppe , Abbaszadeh Rouzbeh , Matera Attilio , Genovese Francesco , Feyissa Aberham Hailu , Di Renzo Giovanni Carlo
Published: July 2023

In this study, the fresh and in‐packaged apricots were treated with dielectric barrier discharge (DBD) cold plasma for 5, 10, and 15 min and then stored at 21°C for 12 days to simulate the shelf life of the apricot. The effects of DBD treatment on the main quality attributes of apricot such as physicochemical traits (mass loss, pH, soluble solid content, titratable acidity, and skin color), mechanical properties (Young's modulus, tangent modulus, and bioyield stress), in‐package gas composition and ethylene production were investigated during the storage time. In addition, the bruise susceptibility (BS) of control and treated samples at the microscale was evaluated by using pendulum test and scanning electron microscopy. The results of the mass loss, pH, soluble solid content, titratable acidity, skin color, and bioyield stress have been applied for input parameters of the developed artificial neural network (ANN) and support vector regression (SVR) models to predict the CO2 and ethylene production. The statistical data showed the performance of the developed ANN to predict the CO2 (R2 = 0.983, root mean square error [RMSE] = 0.486) and ethylene production (R2 = 0.933, RMSE = 5.376) was superior to SVR (CO2: R2 = 0.894, RMSE = 6.077 and ethylene: R2 = 0.759, RMSE = 14.117). These results indicated that intelligent methods are effective and robust tools for predicting the quality parameters of fresh fruits in the postharvest process.

Practical Applications

Advancement of technology and artificial intelligence leads to the tendency of many food industry engineers and researchers in the R&D department to use this technology to classify and predict various food industry processes. In the process of packaging products, there are challenges such as the amount of produced carbon dioxide and ethylene inside the package, which affects the shelf life of fresh agricultural products. In this research, artificial neural networks and support vector machine methods have been used to predict the two mentioned parameters. This approach can be used for the digitalization of the packaging process of agricultural and horticultural products and reduce the number of experimental activities. In addition, it is possible to improve the digitalization process by the fusion of smart sensors with machine learning methods.
Effect of PAR irradiance intensity on Phaeocystis antarctica (Prymnesiophyceae) growth and DMSP, DMSO, and acrylate concentrations
Authors: Kinsey Joanna D. , Tyssebotn Inger Marie B. , Kieber David J.
Published: July 2023

Phaeocystis antarctica forms extensive spring blooms in the Southern Ocean that coincide with high concentrations of dimethylsulfoniopropionate (DMSP), dimethylsulfoxide (DMSO), dimethylsulfide (DMS), and acrylate. We determined how concentrations of these compounds changed during the growth of axenic P. antarctica cultures exposed to light‐limiting, sub‐saturating, and saturating PAR irradiances. Cellular DMSP concentrations per liter cell volume (CV) ranged between 199 and 403 mmol · LCV−1, with the highest concentrations observed under light‐limiting PAR. Cellular acrylate concentrations did not change appreciably with a change in irradiance level or growth, ranging between 18 and 45 mmol · LCV−1, constituting an estimated 0.2%–2.8% of cellular carbon. Both dissolved acrylate and DMSO increased substantially with irradiance during exponential growth on a per‐cell basis, ranging from 0.91 to 3.15 and 0.24 to 1.39 fmol · cell−1, respectively, indicating substantial export of these compounds into the dissolved phase. Average cellular DMSO:DMSP ratios increased 7.6‐fold between exponential and stationary phases of batch growth, with a 3‐ to 13‐fold increase in cellular DMSO likely formed from abiotic reactions of DMSP and DMS with reactive oxygen species (ROS). At mM levels, cellular DMSP and acrylate are proposed to serve as de facto antioxidants in P. antarctica not regulated by oxidative stress or changes in ROS. Instead, cellular DMSP concentrations are likely controlled by other physiological processes including an overflow mechanism to remove excess carbon via acrylate, DMS, and DMSO during times of unbalanced growth brought on by physical stress or nutrient limitation. Together, these compounds should aid P. antarctica in adapting to a range of PAR irradiances by maintaining cellular functions and reducing oxidative stress.
The Role of Explicit Memory Across Second Language Syntactic Development: A Structural Priming Study
Authors: Coumel Marion , Muylle Merel , Messenger Katherine , Hartsuiker Robert J.
Published: July 2023

We tested whether second language (L2) learners rely more on explicit memory during structural priming at lower than at higher proficiency levels (Hartsuiker & Bernolet, 2017). We compared within‐L2 priming with lexical overlap in 100 low and 100 high proficiency French L2 speakers under low versus high working memory load conditions induced with a letter series recall task presented between primes and targets. The high load condition would prevent explicit recall of primes during target production. Both groups primed more under low than high load. The effect of load was similar across groups, but exploratory analyses with proficiency as a continuous variable suggested that, with increasing proficiency, participants primed less under high load. We discuss how these findings support the idea that learners exploit explicit memory more during priming in early versus later stages of acquisition. Overall, this study showed that explicit memory influences syntactic processing across the L2 learning trajectory.
Which managerial reforms facilitate public sector innovation?
Authors: Raudla Ringa , Mohr Zachary , Douglas James W.
Published: July 2023

A key question of public sector innovation (PSI) scholarship is: which factors influence innovation? This paper focuses on managerial practices as drivers of PSI and addresses two research questions. First, how have the main types of managerial reforms—pertaining to marketization, results‐orientation, and collaboration—influenced PSI? Second, how have different features of public sector reform strategies influenced PSI? Using survey data from 19 European countries, we show that reforms focusing on collaboration and results‐orientation facilitate PSI, while marketization‐type reforms have no significant impact. Our study indicates that reforms initiated by public administration (rather than politicians) are more conducive to PSI. We also show that reforms that are crisis‐driven and reforms oriented toward cost cutting have negative impacts on PSI. Overall, our findings demonstrate that New Public Governance‐type reforms exert more positive influence on PSI than NPM‐type reforms.
Plasma collection and supply in Europe: Proceedings of an International Plasma and Fractionation Association and European Blood Alliance symposium
Authors: Domanović Dragoslav , von Bonsdorff Leni , Tiberghien Pierre , Strengers Paul , Hotchko Matthew , O'Leary Peter , Thibert Jean‐Baptiste , Magnussen Karin , Erikstrup Christian , Spekman Marloes , Chesneau Stuart , Jones Judy , Møller Bjarne K. , Verheggen Peter , Gogarty Gerard , Elzaabi Mazen , de Angelis Vincenzo , Candura Fabio , Mali Polonca , Rossi Françoise , Rodrigues Bernardo , Sepetiene Ramune , Lenzen Thomas , Walsemann Stephan , Perry Robert , Plançon Jean‐Philippe , So‐Osman Cynthia , Durand‐Zaleski Isabelle , Facco Giuseppina , Thijssen‐Timmer Daphne
Published: July 2023

At the symposium organized by the International Plasma and Fractionation Association and European Blood Alliance, experts presented their views and experiences showing that the public sector and its blood establishments may strengthen the collection and increase the supply of plasma using the right strategies in plasma donor recruitment, retention and protection, scaling‐up collection by increasing the number of donors within improved/new infrastructure, supportive funding, policies and legislation as well as harmonization of clinical guidelines and the collaboration of all stakeholders. Such approaches should contribute to increased plasma collection in Europe to meet patients’ needs for plasma‐derived medicinal products, notably immunoglobulins and avoid shortages. Overall, presentations and discussions confirmed that European non‐profit transfusion institutions are committed to increasing the collection of plasma for fractionation from unpaid donors through dedicated programmes as well as novel strategies and research.
Nanoengineered mesenchymal stem cell therapy for pulmonary fibrosis in young and aged mice
Authors: Han Meng-Meng , He Xing-Yue , Tang Ling , Qi Liang , Yang Ming-Yuan , Wang Yi , Xing Lei , Jeong Jee-Heon , Jiang Hu-Lin
Published: July 2023

Pulmonary fibrosis (PF) is an age-related interstitial lung disease that results in notable morbidity and mortality. The Food and Drug Administration–approved drugs can decelerate the progression of PF; however, curing aged patients with severe fibrosis is ineffective because of insufficient accumulation of these drugs and wide necrocytosis of type II alveolar epithelial cells (AEC IIs). Here, we constructed a mesenchymal stem cell (MSC)–based nanoengineered platform via the bioconjugation of MSCs and type I collagenase–modified liposomes loaded with nintedanib (MSCs-Lip@NCAF) for treating severe fibrosis. Specifically, MSCs-Lip@NCAF migrated to fibrotic lungs because of the homing characteristic of MSCs and then Lip@NCAF was sensitively released. Subsequently, Lip@NCAF ablated collagen fibers, delivered nintedanib into fibroblasts, and inhibited fibroblast overactivation. MSCs differentiated into AEC IIs to repair alveolar structure and ultimately promote the regeneration of damaged lungs in aged mice. Our findings indicated that MSCs-Lip@NCAF could be used as a promising therapeutic candidate for PF therapy, especially in aged patients.
Autonomous agents for observing marine life
Authors: Katija Kakani
Published: July 2023

Using artificial intelligence to facilitate autonomy in robotics will provide new insights into marine life.
Proteomics analysis of plasma from middle-aged adults identifies protein markers of dementia risk in later life
Authors: Walker Keenan A. , Chen Jingsha , Shi Liu , Yang Yunju , Fornage Myriam , Zhou Linda , Schlosser Pascal , Surapaneni Aditya , Grams Morgan E. , Duggan Michael R. , Peng Zhongsheng , Gomez Gabriela T. , Tin Adrienne , Hoogeveen Ron C. , Sullivan Kevin J. , Ganz Peter , Lindbohm Joni V. , Kivimaki Mika , Nevado-Holgado Alejo J. , Buckley Noel , Gottesman Rebecca F. , Mosley Thomas H. , Boerwinkle Eric , Ballantyne Christie M. , Coresh Josef
Published: July 2023

A diverse set of biological processes have been implicated in the pathophysiology of Alzheimer’s disease (AD) and related dementias. However, there is limited understanding of the peripheral biological mechanisms relevant in the earliest phases of the disease. Here, we used a large-scale proteomics platform to examine the association of 4877 plasma proteins with 25-year dementia risk in 10,981 middle-aged adults. We found 32 dementia-associated plasma proteins that were involved in proteostasis, immunity, synaptic function, and extracellular matrix organization. We then replicated the association between 15 of these proteins and clinically relevant neurocognitive outcomes in two independent cohorts. We demonstrated that 12 of these 32 dementia-associated proteins were associated with cerebrospinal fluid (CSF) biomarkers of AD

, neurodegeneration, or neuroinflammation. We found that eight of these candidate protein markers were abnormally expressed in human postmortem brain tissue from patients with AD, although some of the proteins that were most strongly associated with dementia risk, such as GDF15, were not detected in these brain tissue samples. Using network analyses, we found a protein signature for dementia risk that was characterized by dysregulation of specific immune and proteostasis/autophagy pathways in adults in midlife ~20 years before dementia onset, as well as abnormal coagulation and complement signaling ~10 years before dementia onset. Bidirectional two-sample Mendelian randomization genetically validated nine of our candidate proteins as markers of AD in midlife and inferred causality of SERPINA3 in AD pathogenesis. Last, we prioritized a set of candidate markers for AD and dementia risk prediction in midlife.
Late Cenozoic deformation in the U.S. southern Colorado Front Range revealed by river profile analysis and fluvial terraces
Authors: Marder Eyal , Gallen Sean F. , Pazzaglia Frank J.
Published: July 2023

Many post-orogenic settings exhibit a rugged topography, but the underlying mechanisms driving topographic rejuvenation are poorly understood. For example, the U.S. southern Colorado Front Range, a widely recognized and studied post-orogenic setting, contains deep canyons and steep channels even though the crustal deformation that built the range during the Laramide Orogeny ended at ca. 40 Ma. Two prevailing hypotheses are typically used to explain these topographically youthful features in the Colorado Front Range: (1) mantle dynamics and active tectonics during the late Cenozoic; and (2) enhanced erosional efficiency associated with Quaternary climatic changes. Here, we evaluate these end-member hypotheses through a tectonic geomorphological study of the upper Arkansas River Basin in southern Colorado. We perform river profile analysis on bedrock channels in the eastern Rockies and map and analyze fluvial terraces in the western High Plains. In the eastern Rockies, river knickpoints record a one- to two-stage increase in base-level fall rate downstream of the Colorado Front Range mountain front and an eastward increase in the magnitude of incision. In the western High Plains, Quaternary fluvial terraces also show an eastward increase in the total magnitude of incision. Supported by flexural and supplemental geomorphic analyses, these results suggest a previously undetected regional-scale, west-directed back-tilting associated with differential rock uplift. Based on the average timing of deformation, locations of major faults, and seismic activity, seismic tomographic data, and existing geodynamic models, we infer that this newly recorded westward tilting in the upper Arkansas Basin is the result of unsteady and potentially migrating dynamic topography that developed ca. 4 Ma.
International Olympic Committee (IOC) consensus paper on sports-related ophthalmology issues in elite sports
Authors: Moe Morten Carstens , Özmert Emin , Baudouin Christophe , Binadra Abhinav , Crafoord Sven , Jo Young , Kiratli Hayyam , Moore Melita , Pitsiladis Yannis P , Rolle Udo , Tan Ben , Yanik Özge , Budgett Richard , Erdener Ugur , Steffen Kathrin , Engbretsen Lars
Published: July 2023

Vision plays an important role in an athletes’ success. In sports, nearly 80% of perceptual input is visual, and eye health and sports medicine are closely intertwined fields of utmost importance to athletes. The physical nature of sports activities renders individuals more prone to various eye injuries than the general population. Ocular trauma can lead to lifelong sequelae, and impaired vision requires careful follow-up and management. Apart from injuries, athletes may also experience vision problems that can hamper their performance, including blurred vision, double vision, and light sensitivity.

The interdisciplinary nature of sports medicine necessitates collaboration between sports medicine professionals and ophthalmologists. Through such collaborations, athletes can receive appropriate eye care, education on proper eye protection and guidance on adopting good eye health practices. If any inconspicuous symptoms are not detected and treated promptly, athletes may acquire systemic injuries because of defective vision, preventing them from achieving high level athletic performance in competitions.

The protection of the elite athlete is the responsibility of all of us in sports medicine. To advance a more unified, evidence-informed approach to ophthalmic health assessment and management in athletes and as relevant for sports medicine physicians, the International Olympic Committee Consensus Group aims for a critical evaluation of the current state of the science and practice of ophthalmologic issues and illness in high-level sports, and present recommendations for a unified approach to this important issue.
Dual inhibition of BTLA and PD-1 can enhance therapeutic efficacy of paclitaxel on intraperitoneally disseminated tumors
Authors: Sun Wei-Zen , Lin Han-Wei , Chen Wan-Yu , Chien Chung-Liang , Lai Yen-Ling , Chen Jung , Chen Yu-Li , Cheng Wen-Fang
Published: July 2023

Background

Expression of immune checkpoints in the tumor microenvironment is one mechanism underlying paclitaxel (PTX) chemoresistance. This study aimed to investigate whether the addition of checkpoint blockade to PTX can improve the therapeutic efficacy against apparently disseminated intraperitoneal tumors.

Methods

We analyzed the in vivo expression of various immune checkpoints in CD3+CD8+cytotoxic T cells from tumor-bearing mice treated with or without PTX and validated the tumor-killing activities of selected checkpoint-expressing T-cell subpopulations ex vivo. The regulation of selected checkpoints was investigated in vitro. The therapeutic effects of inhibition of a targeted checkpoint pathway with antibodies added to PTX therapy were examined.

Results

CD3+CD8+T cells expressed with herpes virus entry mediator (HVEM), programmed cell death 1 (PD-1), and T-cell immunoglobulin domain and mucin domain 3 (TIM-3) in tumor-bearing hosts treated with PTX had effective tumoricidal activities. In addition to PTX and cytokines, B and T lymphocyte attenuator (BTLA) or homologous to lymphotoxin, exhibits inducible expression and competes with herpes simplex virus (HSV) glycoprotein D for binding to HVEM, a receptor expressed on T lymphocytes (LIGHT) interacting with HVEM can regulate the expression of PD-1 on CD3+CD8+T cells. Interleukin (IL)-15 increased the percentage of HVEMhighgranzyme B (GZMB)+cells among CD3+CD8+T cells, which was suppressed by the BTLA/HVEM signal. LIGHT induced the percentage of HVEM+GZMB+cells but not HVEMhighGZMB+cells among CD3+CD8+T cells. Expression of IL-15, BTLA, or LIGHT was detected in CD19+B cells and regulated by damage-associated molecular patterns/Toll-like receptor interactions. In the tumor-bearing hosts treated with PTX, certain proportions of BTLA+B or PD-1+T lymphocytes were still noted. When dual inhibition of BTLA and PD-1 was added to PTX, the antitumor effects on intraperitoneally disseminated tumors can be significantly improved.

Conclusions

Dual blockade of BTLA on B cells and PD-1 on cytotoxic T cells may have clinical potential for enhancing the efficacy of PTX in the treatment of tumors with intraperitoneal spread, including epithelial ovarian carcinomas.
Research on Product Advertising Design Combining Feature Extraction Technology and Web3D Technology
Authors: Zhong Zhengwu
Published: July 2023

This work, built on the Unity3D development platform, presents a way for merging feature extraction technology and Web3D technology into advertising design to effectively address the issues of poor efficiency and distortion in the field. Using the candidate text layout generating technique of visual salience, we first build the vector function set based on the three main colors, then we produce the visual communication partition model of advertising design. Next, the number of feature parameters of the shape advertising design is obtained via the establishment of coding coefficient constraint features and the use of an upgraded neural network technique to extract local feature parameter information about the product. Finally, the product design model is brought to life using Web3D technology to boost advertising design's productivity and accuracy. The experiments show that this method not only results in a high rate of correct product identification but also offers a fresh viewpoint on the visual communication of product advertising design by merging the two disciplines.
Algorithms for Quadratic Forms over Global Function Fields
Authors: Darkey-Mensah Mawunyo Kofi
Published: July 2023

This dissertation presents computational tools for quadratic forms over global function fields of characteristic different from 2. The majority of the algorithms we develop in this study rely on our ability to find all places dividing any coefficient of the given quadratic form. This problem is equivalent to the factorization of fractional ideals in the ring of polynomial functions of a global function field. As a result, we begin by presenting alternative approaches for factoring fractional ideals that do not rely on determining the maximum order of the global function field in question. We then propose techniques for tackling the following quadratic form theory computational problems: how to detect whether a quadratic form is isotropic or not, how to detect whether a quadratic form is hyperbolic or not, how to compute the anisotropic dimension (or equivalently the Witt index) of a quadratic form, how to construct an anisotropic part of a quadratic form, how to determine if two forms are Witt-similar or are Ono-similar or not. We further explore algorithms for computing some important field invariants that are linked to quadratic forms. Those are: the length of a sum of squares, the level of a field, the Pythagoras number of a field, as well as a Pythagoras element of a field.
Neuronal responses in mouse inferior colliculus correlate with behavioral detection of amplitude-modulated sound
Authors: van den Berg Maurits M. , Busscher Esmée , Borst J. Gerard G. , Wong Aaron B.
Published: July 2023

The amplitude of natural sounds, including speech and animal vocalizations, often shows characteristic modulations. We examined the relationship between neuronal responses in the mouse inferior colliculus and the behavioral detection of amplitude modulation (AM) in sound and modeled how the former can give rise to the latter. Our model suggests that behavioral detection can be well explained by the activity of a subset of neurons showing the largest firing rate changes in response to AM.
Data from Progressive Spreading of DNA Methylation in the GSTP1 Promoter CpG Island across Transitions from Precursors to Invasive Prostate Cancer
Authors: Gupta Harshath , Inoue Hitoshi , Nakai Yasutomo , Nakayama Masashi , Jones Tracy , Hicks Jessica L. , Kumar Balasubramanian , Gurel Meltem , Nelson William G. , De Marzo Angelo M. , Yegnasubramanian Srinivasan
Published: July 2023

Abstract
Glutathione S-transferase pi 1 (GSTP1) is lowly expressed in normal prostate luminal cells and becomes induced in most proliferative inflammatory atrophy (PIA) lesions. GSTP1 becomes silenced in prostatic intraepithelial neoplasia (PIN) and prostate adenocarcinoma (CaP) via cytosine-phospho-guanine (CpG) island promoter hypermethylation. However, GSTP1 methylation patterns in PIA and PIN, and their relationship to patterns in CaP are poorly understood. We used bisulfite genomic sequencing to examine patterns of GSTP1 promoter CpG island methylation in laser capture microdissected benign, PIA, PIN, and CaP regions from 32 subjects that underwent radical prostatectomy. We analyzed 908 sequence clones across 24 normal epithelium, 37 PIA, 18 PIN, and 23 CaP regions, allowing assessment of 34,863 CpG sites with allelic phasing. Normal and PIA lesions were mostly unmethylated with 0.52 and 1.3% of total CpG sites methylated, respectively. PIN and CaP lesions had greater methylation with 24% and 51% of total CpG sites methylated, respectively. The degree of GSTP1 methylation showed progression from PIA << PIN < CaP. PIN lesions showed more partial methylation compared with CaP lesions. Partially methylated lesions were enriched for methylation changes at AP1 and SP1 transcription factor binding sites. These results demonstrate that methylation density in the GSTP1 CpG island in PIN was intermediate relative to that in normal prostate epithelium/PIA and CaP lesions. These results are consistent with gradual spreading of DNA methylation centered at the SP1/AP1 transcription factor binding sites in precursor lesions, with subsequent spreading of methylation across the entire CpG island in transition to CaP.
Prevention Relevance:
DNA hypermethylation at the GSTP1 promoter progressively spreads from being unmethylated in normal prostate to intermediate levels in precursor lesions to extensive methylation in cancer. This molecular progression of GSTP1 promoter methylation patterns in early prostate carcinogenesis could be useful for identification and interception of prostate cancer precursors.
Data from Host Interactions with Engineered T-cell Micropharmacies
Authors: Bourne Christopher M. , Wallisch Patrick , Dacek Megan M. , Gardner Thomas J. , Pierre Stephanie , Vogt Kristen , Corless Broderick C. , Bah Mamadou A. , Romero-Pichardo Jesus E. , Charles Angel , Kurtz Keifer G. , Tan Derek S. , Scheinberg David A.
Published: July 2023

Abstract
Genetically engineered, cytotoxic, adoptively transferred T cells localize to antigen-positive cancer cells inside patients, but tumor heterogeneity and multiple immune escape mechanisms have prevented the eradication of most solid tumor types. More effective, multifunctional engineered T cells are in development to overcome the barriers to the treatment of solid tumors, but the interactions of these highly modified cells with the host are poorly understood. We previously engineered prodrug-activating enzymatic functions into chimeric-antigen receptor (CAR) T cells, endowing them with a killing mechanism orthogonal to conventional T-cell cytotoxicity. These drug-delivering cells, termed Synthetic Enzyme-Armed KillER (SEAKER) cells, demonstrated efficacy in mouse lymphoma xenograft models. However, the interactions of an immunocompromised xenograft with such complex engineered T cells are distinct from those in an immunocompetent host, precluding an understanding of how these physiologic processes may affect the therapy. Herein, we expanded the repertoire of SEAKER cells to target solid-tumor melanomas in syngeneic mouse models using specific targeting with TCR-engineered T cells. We demonstrate that SEAKER cells localized specifically to tumors, and activated bioactive prodrugs, despite host immune responses. We additionally show that TCR-engineered SEAKER cells were efficacious in immunocompetent hosts, demonstrating that the SEAKER platform is applicable to many adoptive cell therapies.
Cholesterol Efflux Drives the Generation of Immunosuppressive Macrophages to Promote the Progression of Human Hepatocellular Carcinoma
Authors: Li Zhixiong , Wang Yongchun , Xing Rui , Zeng Huilan , Yu Xing-Juan , Zhang Yao-jun , Xu Jing , Zheng Limin
Published: July 2023

Cholesterol is often enriched in tumor microenvironment (TME); however, its impact on disease progression varies in different tissues and cells. Monocytes/macrophages (Mφ) are major components and regulators of the TME and play pivotal roles in tumor progression and therapeutic responses. We aimed to investigate the profile, effects, and regulatory mechanisms of Mφ cholesterol metabolism in the context of human hepatocellular carcinoma (HCC). Here, we found that patients with high serum levels of cholesterol had shorter survival times and lower response rates to anti–PD-1 treatment. However, the cholesterol content in tumor-infiltrating monocytes/Mφ was significantly lower than that in their counterparts in paired nontumor tissues. The expression of the cholesterol efflux transporter, ABCA1, was upregulated in tumor monocytes/Mφ, and ABCA1 upregulation positively associated with decreased cellular cholesterol content and increased serum cholesterol levels. Mechanistically, autocrine cytokines from tumor-treated monocytes increased LXRα and ABCA1 expression, which led to the generation of immature and immunosuppressive Mφ. Although exogenous cholesterol alone had little direct effect on Mφ, it did act synergistically with tumor-derived factors to promote ABCA1 expression in Mφ with more immunosuppressive features. Moreover, high numbers of ABCA1+ Mφ in HCC tumors associated with reduced CD8+ T-cell infiltration and predicted poor clinical outcome for patients. Our results revealed that dysregulated cholesterol homeostasis, due to the collaborative effects of tumors and exogenous cholesterol, drives the generation of immunosuppressive Mφ. The selective modulation of cholesterol metabolism in Mφ may represent a novel strategy for cancer treatment.
Deep Learning in the Identification of Electroencephalogram Sources Associated with Sexual Orientation
Authors: Ziogas Anastasios , Mokros Andreas , Kawohl Wolfram , de Bardeci Mateo , Olbrich Ilyas , Habermeyer Benedikt , Habermeyer Elmar , Olbrich Sebastian
Published: July 2023

Introduction: It is unclear if sexual orientation is a biological trait that has neurofunctional footprints. With deep learning, the power to classify biological datasets without an a priori selection of features has increased by magnitudes. The aim of this study was to correctly classify resting-state electroencephalogram (EEG) data from males with different sexual orientation using deep learning and to explore techniques to identify the learned distinguishing features. Methods: Three cohorts (homosexual men, heterosexual men, and a mixed sex cohort), one pretrained network on sex classification, and one newly trained network for sexual orientation classification were used to classify sex. Further, Grad-CAM methodology and source localization were used to identify the spatiotemporal patterns that were used for differentiation by the networks. Results: Using a pretrained network for classification of males and females, no differences existed between classification of homosexual and heterosexual males. The newly trained network was able, however, to correctly classify the cohorts with a total accuracy of 83%. The retrograde activation using Grad-CAM technology yielded distinctive functional EEG patterns in the Brodmann area 40 and 1 when combined with Fourier analysis and a source localization. Discussion: This study shows that electrophysiological trait markers of male sexual orientation can be identified using deep learning. These patterns are different from the differentiating signatures of males and females in a resting-state EEG.
Inhibition of Pyk2 Improves Cx43 Intercalated Disc Localization, Infarct Size, and Cardiac Function in Rats With Heart Failure
Authors: Zheng Li , Spagnol Gaelle , Gandhi Devashri R. , Sharma Kanika , Kumar Vikas , Patel Kaushik P. , Sorgen Paul L.
Published: July 2023

BACKGROUND:

Heart failure causes changes in Cx43 (Connexin43) regulation that are associated with arrhythmic heart disease. Pyk2 (proline-rich tyrosine kinase 2) is activated in cardiomyopathies and phosphorylates Cx43 to decrease intercellular communication. This study was designed to determine if Pyk2 inhibition improves cardiac function in a myocardial infarction (MI)-induced heart failure model in rats.

METHODS:

MI (ligation of left anterior descending artery) rats were treated with the Pyk2 inhibitor PF4618433. Hemodynamic and structural parameters were monitored in Sham (n=5), MI-vehicle (n=5), and MI-PF4618433 (n=8) groups. Heart tissues were collected after 6 weeks to assess Pyk2 and Cx43 protein level and localization.

RESULTS:

PF4618433 produced no observed adverse effects and inhibited ventricular Pyk2. PF4618433 reduced the MI infarct size from 34% to 17% (
P=
0.007). PF4618433 improved stroke volume (
P=
0.031) and cardiac output (
P=
0.009) in comparison to MI-vehicle with values similar to the Sham group. PF4618433 also led to an increase in the ejection fraction (
P
=0.002) and fractional shortening (
P
=0.006) when compared with the MI-vehicle (32% and 35% improvement, respectively) yet were lower in comparison with the Sham group. Pyk2 inhibition decreased Cx43 tyrosine phosphorylation (
P
=0.043) and maintained Cx43 at the intercalated disc in the distal ventricle 6 weeks post-MI.

CONCLUSIONS:

Unlike other attempts to decrease Cx43 remodeling after MI-induced heart failure, inhibition of Pyk2 activity maintained Cx43 at the intercalated disc. This may have aided in the reduced infarct size (acute time frame) and improved cardiac function (chronic time frame). Additionally, we provide evidence that Pyk2 is activated following MI in human left ventricle, implicating a novel potential target for therapy in patients with heart failure.