bluuebunny/crossref_metadata_2025 huggingface dataset:
Development of Student Work Sheet Based Discovery Learning on The Material Human Respiratory System Class XI Madrasah Aliyah
Authors: Tanjung Siti Aisyah , Khairuna Khairuna , Afinni Dwi Jayanti Ummi Nur
Published: July 2023

This study aims to develop Discovery Learning Based Worksheets and to determine the level of validity, practicality and effectiveness. This study uses the Research and Development (R&D) research method with the ADDIE model (Analyze, Design, Development, Implementation, Evaluation). The research subjects were class XI MIA at MAS Al-Washliyah 22 Tembung, which consisted of 34 people. The research instrument was an analysis of teacher needs, validation sheets, educator response questionnaires and student questionnaires. Based on the results of research in terms of validity, material experts get a score of 100% in the "Very Valid" category, media experts get a score of 81.05% in the "Valid" category. Meanwhile, in terms of practicality, from the results of the educator's response, an average response of 95% was classified as "Very Practical". In the results of the assessment of students have an average proportion of 90.47% with the criterion "Very Interesting". In terms of effectiveness, the pretest results averaged 61.18 while the posttest results averaged 74.26. With an n-gain value obtained of 0.34 which is the "Effective" criterion. Thus, the LKPD based on Discovery Learning that has been developed is declared valid, effective, and practical to use, and can increase activeness in solving problems. 34 which is the "Effective" criterion. Thus, the LKPD based on Discovery Learning that has been developed is declared valid, effective, and practical to use, and can increase activeness in solving problems. 34 which is the "Effective" criterion. Thus, the LKPD based on Discovery Learning that has been developed is declared valid, effective, and practical to use, and can increase activeness in solving problems.
The Four-Pillar Structure of International Nuclear Law: Nuclear Safety, Nuclear Security, Nuclear Safeguards and Liability
Authors: PEKAR Çiğdem
Published: July 2023

With the discovery and global expansion of nuclear energy, the need for an international nuclear law framework has emerged. Thus, realizing the advantages of the safe, secure, and peaceful use of nuclear technology and its applications in our daily lives depends on an inter- national nuclear law framework. According to International Atomic Energy Agency (IAEA) nuclear law stands on four main ‘pillars’: nuclear safety, nuclear security, nuclear safeguards and liability. This study aims to trace the development of international nuclear law focusing particularly on its four-pillar structure. To this end, the study first examines the concept of international nuclear law, and then respectively focuses on nuclear safety, nuclear security, nuclear safeguards and civil liability for nuclear damage within the framework of international nuclear law. In this regard, the work of the IAEA, the world’s international nuclear watchdog, towards ensuring that nuclear science and technology are used in a safe, secure, and peaceful manner has been assessed. The study also puts that all four pillars of international nuclear law has been expanded and improved due to the need in process and the particular challenges they have faced.
Molecular data validate historical and contemporary distributions of Pleurobema riddellii (Bivalvia: Unionidae) and help guide conservation and recovery efforts
Authors: Johnson NA , Beaver CE , Kiser AH , Duplessis MA , Wagner MD , Ellwanger RJ , Robertson CR , Kinney SD , Gregory BB , Wolverton S , Randklev CR , Hartfield PD , Williams JD , Smith CH
Published: July 2023

Accurate taxonomic and distributional information are arguably the most critical components of conservation status assessments but can be greatly affected by misidentifications. The Louisiana pigtoe Pleurobema riddellii is a freshwater mussel proposed as threatened under the US Endangered Species Act. The species belongs to the tribe Pleurobemini, which includes multiple taxa that are inherently challenging to identify without molecular data. We validated historical and recent survey records of P. riddellii using a combination of DNA sequence data and morphological characters to provide a more definitive assessment of range and spatiotemporal trends in distribution. Our comprehensive assessment identified specimens collected from the Pearl drainage as P. riddellii, extending the species’ known range into eastern Gulf of Mexico drainages. Contemporary records were unavailable from the Trinity drainage; however, we designed novel minibarcode PCR primers and used historical DNA from a specimen collected in the late 1800s to confirm the historical presence of P. riddellii at the species’ type locality in the Trinity River near Dallas, Texas, USA. Our range-wide genetic diversity assessment provides strong support for 2 main geographic groups, the Ouachita and all remaining populations, with individuals from the Pearl and Trinity drainages sharing haplotypes with conspecifics from other drainages. Available data suggest P. riddellii has been extirpated from a significant portion of the historical range, including the entire Trinity drainage. Additional surveys in Lake Pontchartrain, Trinity, and other drainages in the eastern periphery of the species’ range may provide additional clarity on the distribution and conservation status of P. riddellii.
Lethal and sublethal effects of simulated dredged sediment deposition on overwintering blue crabs Callinectes sapidus
Authors: Saluta GG , Ralph GM , Knick KE , Seebo MS , Lipcius RN
Published: July 2023

Regular maintenance of waterways and ports requires dredging and disposal of accumulated sediment, which can injure or kill infaunal and epifaunal species. Our understanding of the lethal and sublethal effects of dredged sediment deposition in marine communities is based predominantly on benthic infaunal species, whereas knowledge of the effects of these additions on mobile macrofauna is limited. We explored lethal and sublethal effects of simulated dredged sediment (hereafter, sediment) on blue crabs Callinectes sapidus. Twenty mature female crabs were allocated into 4 treatments: no sand, no sediment; sand, no sediment; sand + 2.5 cm sediment; and sand + 10.0 cm sediment. Accounting for size, mortality in the 10 cm sediment treatment was immediate and 10- to 20-fold higher than that in other treatments. Crabs that eventually died also experienced sublethal effects as evidenced by a reduced behavioral repertoire. These results suggest that in winter, all mature female crabs will suffer high mortality under 10 cm of dredged sediment deposition, while smaller crabs may suffer substantial mortality and sublethal effects at even lower levels. As blue crab activity is temperature dependent, the detrimental effects can be minimized by disposing of dredged sediment either where crabs are not abundant or when water temperatures are higher and blue crabs can avoid burial.
Lack of strong responses to the Pacific marine heatwave by benthivorous marine birds indicates importance of trophic drivers
Authors: Robinson B , Coletti HA , Ballachey B , Bodkin JL , Kloecker K , Traiger SB , Esler D
Published: July 2023

The Pacific marine heatwave (PMH) of 2014-2016 was an intense, long-lasting environmental disturbance expressed throughout the north Pacific. While dramatic consequences of the PMH on pelagic food webs have been well documented, effects on nearshore food webs, i.e. those based on macroalgal primary productivity, benthic invertebrate intermediate consumers, and specialized benthivorous top predators including some marine birds, are not well understood. We conducted summer and winter coastline marine bird surveys in 2 National Parks in the northern Gulf of Alaska from 2006 to 2022. We evaluated changes in abundance of benthivorous marine birds in relation to the PMH, after accounting for effects of season and region. We also evaluated changes in abundance of nearshore benthic invertebrate prey to allow specific consideration of a prey-based mechanism for effects of the PMH across food webs. We found that benthivorous marine birds, consisting of sea ducks and shorebirds, did not show a strong response to the PMH, unlike significant effects demonstrated by piscivorous birds in pelagic biomes. In contrast to extreme reductions in quantity and quality of forage fish documented elsewhere, we found that common benthic invertebrate prey abundance remained relatively stable. Our results support the hypothesis that, across food webs, top predator responses to the PMH were driven primarily by how and whether the PMH affected their prey availability. These findings show how a large-scale environmental perturbation affects biological communities differently through various trophic pathways, which provides insight into ecosystem resiliency and can inform management strategies in the face of persistent climate change.
Microstructural Evolution and Mechanical Properties According to Aging Conditions of Ti-5Mo-2Fe Alloy
Authors: Kim Hong-Min , Park Se-Yeong , Lee Dong-Geun
Published: July 2023

Beta-type titanium alloys have a low elastic modulus, excellent cold workability, and are widely used as implant materials. High strength is possible by forming a precipitation in the β-matrix via solution treatment and aging treatment. However, beta titanium alloys require a large amount of beta-stabilizing elements (Fe, Nb, Mo, Ta, etc), and these expensive beta stabilizing elements increase the manufacturing cost of these alloys. In this study, Ti-5Mo-2Fe metastable beta-titanium alloy was designed by adding Mo and Fe, which were relatively inexpensive and had excellent biocompatibility among beta-stabilizing elements, and an ingot was manufactured by vacuum arc remelting. Solution treatment was maintained at 850oC for a holding time of 1 hour, followed by furnace cooling. Aging treatments were conducted in a range of temperature 350~500oC and holding time 2 h~48 h. The microstructure behaviors and mechanical properties were analyzed according to these aging treatment conditions. Isothermal ω phases were precipitated by aging treatment, and hardness and yield strength were found to be significantly higher for conditions of 400oC, 8h. As holding time and temperature increased, these phases transformed into secondary alpha phases and the hardness and yield strength decreased due to this microstructural evolution.
T Cell engineering for cancer immunotherapy by manipulating mechanosensitive force-bearing receptors
Authors: Zhao Lingzhu , Zhao Guoqing , Feng Jinteng , Zhang Zheng , Zhang Jiayu , Guo Hui , Lin Min
Published: July 2023

T cell immune responses are critical for in both physiological and pathological processes. While biochemical cues are important, mechanical cues arising from the microenvironment have also been found to act a significant role in regulating various T cell immune responses, including activation, cytokine production, metabolism, proliferation, and migration. The immune synapse contains force-sensitive receptors that convert these mechanical cues into biochemical signals. This phenomenon is accepted in the emerging research field of immunomechanobiology. In this review, we provide insights into immunomechanobiology, with a specific focus on how mechanosensitive receptors are bound and triggered, and ultimately resulting T cell immune responses.
Noncoding RNAs: an emerging modulator of drug resistance in pancreatic cancer
Authors: Wei Ling , Sun Jujie , Wang Xingwu , Huang Yizhou , Huang Linying , Han Linyu , Zheng Yanxiu , Xu Yuan , Zhang Nasha , Yang Ming
Published: July 2023

Pancreatic cancer is the eighth leading cause of cancer-related deaths worldwide. Chemotherapy including gemcitabine, 5-fluorouracil, adriamycin and cisplatin, immunotherapy with immune checkpoint inhibitors and targeted therapy have been demonstrated to significantly improve prognosis of pancreatic cancer patients with advanced diseases. However, most patients developed drug resistance to these therapeutic agents, which leading to shortened patient survival. The detailed molecular mechanisms contributing to pancreatic cancer drug resistance remain largely unclear. The growing evidences have shown that noncoding RNAs (ncRNAs), including microRNAs (miRNAs), long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs), are involved in pancreatic cancer pathogenesis and development of drug resistance. In the present review, we systematically summarized the new insight on of various miRNAs, lncRNAs and circRNAs on drug resistance of pancreatic cancer. These results demonstrated that targeting the tumor-specific ncRNA may provide novel options for pancreatic cancer treatments.
Small-mammal abundance and species diversity: land use and seasonal influences in the Serengeti Ecosystem, Tanzania
Authors: Shilereyo Monica T. , Magige Flora J. , Ogutu Joseph O. , Røskaft Eivin
Published: July 2023

Land use, habitat suitability, and seasonality can fundamentally shape small-mammal abundance, species richness, diversity, evenness, and composition. However, how these characteristics of small mammals are determined by land use, habitat type, and rainfall seasonality is still poorly understood for most ecosystems. We analyze how land use (protection in a national park, pastoralism, and crop agriculture), habitat type, and rainfall seasonality influence small-mammal relative abundance, species richness, and diversity in the Tanzania Serengeti Ecosystem. We used 141 live traps to capture 612 small mammals in the wet and dry seasons of 2017 and 2018. Relative abundance was higher in the pastoral land than in the park or agricultural land and in the dry season in all the three land use types. Species richness and diversity were highest in the park, middling in the agricultural land, and lowest in the pastoral land. The high relative abundance in the pastoral land was primarily due to the numerical dominance of two generalist species in the shrubland (grass rat Arvicanthis niloticus) and cropland (multimammate rat Mastomys natalensis), resulting in low species richness and diversity. High species richness and diversity in the park indicate high habitat heterogeneity, whereas high species diversity in the agricultural land during the dry season reflects high food availability during and soon after harvests. Thus, human activities apparently exert deleterious effects on some specialist small mammals as a result of reduced habitat heterogeneity while promoting the abundance of some generalist species in African savanna ecosystems. However, increased abundance of generalist species reduces small mammal species diversity while increasing the risk of human–small mammal conflicts. We offer several testable hypotheses motivated by our results.
Direct estimation of central aortic pressure from measured or quantified mean and diastolic brachial blood pressure: agreement with invasive records
Authors: Bia Daniel , Salazar Federico , Cinca Luis , Gutierrez Marcos , Facta Alvaro , Zócalo Yanina , Diaz Alejandro
Published: July 2023

Background

Recently it has been proposed a new approach to estimate aortic systolic blood pressure (aoSBP) without the need for specific devices, operator-dependent techniques and/or complex wave propagation models/algorithms. The approach proposes aoSBP can be quantified from brachial diastolic and mean blood pressure (bDBP, bMBP) as: aoSBP = bMBP2/bDBP. It remains to be assessed to what extent the method and/or equation used to obtain the bMBP levels considered in aoSBP calculation may affect the estimated aoSBP, and consequently the agreement with aoSBP invasively recorded.

Methods

Brachial and aortic pressure were simultaneously obtained invasively (catheterization) and non-invasively (brachial oscillometry) in 89 subjects. aoSBP was quantified in seven different ways, using measured (oscillometry-derived) and calculated (six equations) mean blood pressure (MBP) levels. The agreement between invasive and estimated aoSBP was analyzed (Concordance correlation coefficient; Bland-Altman Test).

Conclusions

The ability of the equation “aoSBP = MBP2/DBP” to (accurately) estimate (error <5 mmHg) invasive aoSBP depends on the method and equation considered to determine bMBP, and on the aoSBP levels (proportional error). Oscillometric bMBP and/or approaches that consider adjustments for heart rate or a form factor ∼40% (instead of the usual 33%) would be the best way to obtain the bMBP levels to be used to calculate aoSBP.
“The library is so much more than books”: considerations for the design and implementation of teen digital mental health services in public libraries
Authors: Knapp Ashley A. , Hersch Emily , Wijaya Clarisa , Herrera Miguel A. , Kruzan Kaylee P. , Carroll Allison J. , Lee Sydney , Baker Alex , Gray Alanna , Harris Vann , Simmons Robert , Kour Sodhi Deepika , Hannah Nanette , Reddy Madhu , Karnik Niranjan S. , Smith Justin D. , Brown C. Hendricks , Mohr David C.
Published: July 2023

Background

Adolescence is a vulnerable developmental period, characterized by high rates of mental health concerns, yet few adolescents receive treatment. Public libraries support adolescents by providing them with access to teen programming, technological resources, and have recently been providing mental health services. Digital mental health (DMH) services may help libraries provide scalable mental health solutions for their adolescent patrons and could be well positioned to address the mental health needs of historically underrepresented racial and ethnic (HURE) adolescents; however, little research has been conducted on the compatibility of DMH services with adolescent patron mental health needs or resource needs of library workers supporting them.

Methods

The research team formed a partnership with a public library, which serves a large HURE adolescent population. We conducted needs assessment and implementation readiness interviews with 17 library workers, including leadership, librarians, and workers with specialized areas of practice. Interview questions focused on library infrastructure, as well as library needs and preferences around the design and implementation of DMH services for adolescents. We used the Consolidated Framework for Implementation Research as guiding implementation determinant framework to code and analyze the interview transcripts.

Results

Our findings revealed library workers play an important role in guiding patrons to desired resources and share a goal of implementing adolescent DMH resources into the library and elevating marginalized adolescents’ voices. Existing library resources, such as the library's role as a safe space for adolescents in the community, close relationships with external and community organizations, and availability of no-cost technological resources, could help facilitate the implementation of DMH services. Barriers related to community buy-in, mental health stigma, and library worker confidence in supporting adolescent mental health could affect service implementation.

Conclusions

Our findings suggest public libraries are highly promising settings to deploy DMH services for adolescents. We identified important determinants that may impact the implementation of DMH services in public library settings. Special considerations are needed to design services to meet the mental health needs of HURE adolescent populations and those adolescents’ most experiencing health inequities.
An investigation of media reports of digital surveillance within the first year of the COVID-19 pandemic
Authors: Comer Leigha , Donelle Lorie , Ngole Marionette , Shelley Jacob J. , Kothari Anita , Smith Maxwell , Shelley James M. , Stranges Saverio , Hiebert Brad , Gilliland Jason , Burkell Jacquelyn , Cooke Tommy , Hall Jodi , Long Jed
Published: July 2023

Introduction

The COVID-19 pandemic prompted a surge in digital public health surveillance worldwide, with limited opportunities to consider the effectiveness or impact of digital surveillance. The news media shape public understanding of topics of importance, contributing to our perception of priority issues. This study investigated news media reports published during the first year of the pandemic to understand how the use and consequences of digital surveillance technologies were reported on.

Methods

A media content analysis of 34 high- to low-income countries was completed. The terms “COVID-19,” “surveillance,” “technologies,” and “public health” were used to retrieve and inductively code media reports.

Results

Of the 1,001 reports, most were web-based or newspaper sources on the development and deployment of technologies directed at contact tracing, enforcing quarantine, predicting disease spread, and allocating resources. Technology types included mobile apps, wearable devices, “smart” thermometers, GPS/Bluetooth, facial recognition, and security cameras. Repurposed data from social media, travel cards/passports, and consumer purchases also provided surveillance insight. Media reports focused on factors impacting surveillance success (public participation and data validity) and the emerging consequences of digital surveillance on human rights, function creep, data security, and trust.

Discussion

Diverse digital technologies were developed and used for public health surveillance during the first year of the COVID-19 pandemic. The use of these technologies and witnessed or anticipated consequences were reported by a variety of media sources worldwide. The news media are an important public health information resource, as media outlets contribute to directing public understanding and shaping priority public health surveillance issues. Our findings raise important questions around how journalists decide which aspects of public health crises to report on and how these issues are discussed.
Operational snow-hydrological modeling for Switzerland
Authors: Mott Rebecca , Winstral Adam , Cluzet Bertrand , Helbig Nora , Magnusson Jan , Mazzotti Giulia , Quéno Louis , Schirmer Michael , Webster Clare , Jonas Tobias
Published: July 2023

The seasonal evolution of snow cover has significant impacts on the hydrological cycle and microclimate in mountainous regions. However, snow processes also play a crucial role in triggering alpine mass movements and flooding, posing risks to people and infrastructure. To mitigate these risks, many countries use operational forecast systems for snow distribution and melt. This paper presents the Swiss Operational Snow-hydrological (OSHD) model system, developed to provide daily analysis and forecasts on snow cover dynamics throughout Switzerland. The OSHD system is a sophisticated snow hydrological model designed specifically for the high-alpine terrain of the Swiss Alps. It leverages exceptional station data and high-resolution meteorological forcing data, as well as various reanalysis products to combine snow modeling with advanced data assimilation and meteorological downscaling methods. The system offers models of varying complexity, each tailored to specific modeling strategies and applications. For snowmelt runoff forecasting, monitoring snow water resources, and research-grade purposes, the OSHD system employs physics-based modeling chains. For snow climatological assessments, a conceptual model chain is available. We are pleased to present two comprehensive datasets from the conceptual and physics-based models that cover the entirety of Switzerland. The first dataset comprises a snow water equivalent climatology spanning 1998–2022, with a spatial resolution of 1 km. The second dataset includes snow distribution and snow melt data spanning 2016–2022 at a high spatial resolution of 250 m. To meet the needs of a multi-purpose snow hydrological model framework, the OSHD system employs various strategies for process representation and sub-grid parameterizations at the snow-canopy-atmosphere interface, particularly in complex terrain. Recent and ongoing model developments are aimed at accounting for complex forest snow processes, representing slope and ridge-scale precipitation and snow redistribution processes, as well as improving probabilistic snow forecasts and data assimilation procedures based on remote sensing products.
Evaluation of hormonal and circulating inflammatory biomarker profiles in the year following bariatric surgery
Authors: Kim Eun Ran , Yun Ji Ho , Kim Hyo-Jin , Park Hyeon Young , Heo Yoonseok , Park Young Suk , Park Do Joong , Koo Soo Kyung
Published: July 2023

Background

Bariatric surgery (BS) has a superior effect on reducing body weight and fat in patients with morbid obesity. As a result, BS mitigates obesity-related complications such as type 2 diabetes (T2D). However, few studies have shown the mechanism underlying diabetes remission after surgery. This study aimed to investigate the differences in serum hormone and inflammatory cytokine levels related to diabetes before surgery and during 12 months of follow-up in Korean patients with obesity.

Methods

The study participants were patients with morbid obesity (n=63) who underwent sleeve gastrectomy (SG) or Roux-en-Y gastric bypass (RYGB) between 2016 – 2017 at seven tertiary hospitals in Korea. The patients were followed for 1 year after surgery.

Results

Sixty-three patients had significant weight loss after surgery and showed improvements in clinical parameters and hormonal and inflammatory profiles. Among them, 23 patients who were diabetic preoperatively showed different remission after surgery. The levels of inflammation-related clinical parameters changed significantly in the remission group, and serum inflammatory cytokine and hormones significantly decreased at certain points and showed an overall decreasing trend.

Conclusions

Our study found postoperative changes of factors in blood samples, and the changes in hormones secreted from the three major metabolic tissue (pancreas, adipose, and gut) along with the differences in multi-origin inflammatory cytokines between remission and non-remission groups provide a path for understanding how the effect of BS in improving glucose metabolism is mediated.
Rosiglitazone has a null association with the risk of prostate cancer in type 2 diabetes patients
Authors: Tseng Chin-Hsiao
Published: July 2023

Background

This study investigated the risk of prostate cancer in ever users and never users of rosiglitazone in diabetes patients in Taiwan.

Methods

The nationwide database of the National Health Insurance was used to enroll male patients who had a new diagnosis of type 2 diabetes mellitus at an age ≥ 25 years from 1999 to 2005. A total of 11,495 ever users and 11,495 never users of rosiglitazone matched on propensity score were selected and they were followed up for the incidence of prostate cancer from January 1, 2006 until December 31, 2011. Cox proportional hazard model incorporated with the inverse probability of treatment weighting using the propensity score was used to estimate hazard ratios.

Results

At the end of follow-up, incident cases of prostate cancer were found in 84 never users and 90 ever users of rosiglitazone. The calculated incidence was 173.20 per 100,000 person-years in never users and was 187.59 per 100,000 person-years in ever users. The overall hazard ratio (95% confidence intervals) for ever versus never users was 1.089 (0.808-1.466). The hazard ratios were 0.999 (0.643-1.552) for the first tertile (< 672 mg), 1.147 (0.770-1.709) for the second tertile (672-3584 mg) and 1.116 (0.735-1.695) for the third tertile (> 3584 mg) of cumulative dose. Sensitivity analyses consistently showed a null association between rosiglitazone and prostate cancer risk.

Conclusion

Rosiglitazone has a null effect on the risk of prostate cancer.
How smart are our companies really? a case study of the current rollout of smart meters in Germany
Authors: Knayer Tobias , Kryvinska Natalia
Published: July 2023

The digital transformation and the associated challenges for the energy transition and society remain a challenge due to the increasing number of e-charging stations and heat pumps. Nevertheless, the rollout of smart meters selected in Germany affects only a small proportion of the available consumers. Therefore, the aim of this work is to determine the current status of this technology in companies and to answer the question of which factors influence implementation. For this purpose, data from a case study with 386 companies were used. The focus was on the current status of the technology in companies and their knowledge about the technology. The data were recorded during on-site inspections with the help of an energy consultant. In addition, the frequencies of the answers and the implementation of efficiency measures of selected cross-cutting technologies were compared between companies with a smart meter and companies with an analog meter. Our evaluation revealed that 1) 82 percent of companies have a commitment to implementation. 2) Of these, 10 percent have installed a smart meter. 3) Many of the companies were either unaware of the commitment or did not even know what a smart meter was. 4) Companies with a smart meter have implemented more measures in lighting, energy monitoring, energy purchasing and peak load management than companies with an analog meter. To increase implementation and, thus, usage, companies need to be made much more aware. In addition, there is still a lack of value-added services.
Unraveling tumor specific neoantigen immunogenicity prediction: a comprehensive analysis
Authors: Nibeyro Guadalupe , Baronetto Veronica , Folco Juan I. , Pastore Pablo , Girotti Maria Romina , Prato Laura , Morón Gabriel , Luján Hugo D. , Fernández Elmer A.
Published: July 2023

Introduction

Identification of tumor specific neoantigen (TSN) immunogenicity is crucial to develop peptide/mRNA based anti-tumoral vaccines and/or adoptive T-cell immunotherapies; thus, accurate in-silico classification/prioritization proves critical for cost-effective clinical applications. Several methods were proposed as TSNs immunogenicity predictors; however, comprehensive performance comparison is still lacking due to the absence of well documented and adequate TSN databases.

Methods

Here, by developing a new curated database having 199 TSNs with experimentally-validated MHC-I presentation and positive/negative immune response (ITSNdb), sixteen metrics were evaluated as immunogenicity predictors. In addition, by using a dataset emulating patient derived TSNs and immunotherapy cohorts containing predicted TSNs for tumor neoantigen burden (TNB) with outcome association, the metrics were evaluated as TSNs prioritizers and as immunotherapy response biomarkers.

Results

Our results show high performance variability among methods, highlighting the need for substantial improvement. Deep learning predictors were top ranked on ITSNdb but show discrepancy on validation databases. In overall, current predicted TNB did not outperform existing biomarkers.

Conclusion

Recommendations for their clinical application and the ITSNdb are presented to promote development and comparison of computational TSNs immunogenicity predictors.
A major dengue epidemic in 2022 in Nepal: need of an efficient early-warning system
Authors: Dhoubhadel Bhim Gopal , Hayashi Yumiko , Domai Fleurette Mbuyakala , Bhattarai Suraj , Ariyoshi Koya , Pandey Basu Dev
Published: July 2023

Dengue has become a recurrent and growing threat to public health in Nepal. The epidemic in 2022 was the largest ever reported, with cases being reported in all of the country’s seven provinces and 77 districts. Despite the establishment of an early-warning and reporting system (EWARS) in 1997, the lack of clear criteria for alarm signals and outbreak definitions in national guidelines delayed the epidemic declaration in 2022, which resulted in an increased number of cases and fatalities. For this article, we analyzed national data from previous years, which demonstrate that an epidemic could have been declared early in July, and that that would have resulted in fewer cases and fatalities if clear criteria for outbreak declarations had also been put in place. We also reviewed the existing national guidelines for dengue prevention and control, and propose recommendations to improve their implementation, particularly with regard to vector control measures. This article also highlights the need for a coordinated effort between multisector stakeholders, strengthened disease surveillance systems, and the establishment of predefined alarm signals and epidemic declaration criteria so that future epidemics are identified in a timely manner. The early outbreak warning system can potentially prevent future large outbreaks and minimize their negative impacts on the country’s health systems and economy.
Microbial food web changes induced by terrestrial organic matter and elevated temperature in the coastal northern Baltic Sea
Authors: Andersson Agneta , Grinienė Evelina , Berglund Åsa M. M. , Brugel Sonia , Gorokhova Elena , Figueroa Daniela , Gallampois Christine , Ripszam Matyas , Tysklind Mats
Published: July 2023

Climate change has been projected to cause increased temperature and amplified inflows of terrestrial organic matter to coastal areas in northern Europe. Consequently, changes at the base of the food web favoring heterotrophic bacteria over phytoplankton are expected, affecting the food web structure. We tested this hypothesis using an outdoor shallow mesocosm system in the northern Baltic Sea in early summer, where the effects of increased temperature (+ 3°C) and terrestrial matter inputs were studied following the system dynamics and conducting grazing experiments. Juvenile perch constituted the highest trophic level in the system, which exerted strong predation on the zooplankton community. Perch subsequently released the microbial food web from heavy grazing by mesozooplankton. Addition of terrestrial matter had a stronger effect on the microbial food web than the temperature increase, because terrestrial organic matter and accompanying nutrients promoted both heterotrophic bacterial production and phytoplankton primary production. Moreover, due to the shallow water column in the experiment, terrestrial matter addition did not reduce the light below the photosynthesis saturation level, and in these conditions, the net-autotrophy was strengthened by terrestrial matter enrichment. In combination with elevated temperature, the terrestrial matter addition effects were intensified, further shifting the size distribution of the microbial food web base from picoplankton to microphytoplankton. These changes up the food web led to increase in the biomass and proportion of large-sized ciliates (>60 µm) and rotifers. Despite the shifts in the microbial food web size structure, grazing experiments suggested that the pathway from picoplankton to nano- and microzooplankton constituted the major energy flow in all treatments. The study implies that the microbial food web compartments in shallow coastal waters will adjust to climate induced increased inputs of terrestrial matter and elevated temperature, and that the major energy path will flow from picoplankton to large-sized ciliates during the summer period.
Divergent molecular responses of greater amberjack (Seriola dumerili) to acute salinity stress revealed by comparative transcriptome analysis
Authors: Liu Yuqi , Yang Yuchen , Qin Ruotong , Peng Yuhao , Huang Yang , Zhu Chunhua , Li Guangli , Jiang Dongneng , Shi Hongjuan
Published: July 2023

Greater amberjack (Seriola dumerili) is an important commercial fish for its high growth rate and excellent flesh quality. However, its sensitivity to variations of water salinity poses challenges to the cage culture. In this study, the greater amberjack were reared in the optimum salinity (30 ppt, CK) and undesired regimes (10 and 40 ppt) for 72 hours. The molecular adaptive mechanisms to salinity stress were revealed by the comparative transcriptome analysis for the gills and kidneys. In gills, a total of 445 and 423 differentially expressed genes (DEGs) were identified in 10 and 40 ppt salinity stress groups, respectively. Those DEGs were involved in cartilage and skeletal development, ions transport, and immune response. The major ion secretion and osmoregulation transport proteins gene slc12a2/nkcc1 and cftr expression levels were significantly down-regulated at 10 ppt, but slightly activated at 40 ppt, compared with the control group. The expression changes in response to the Na+, K+ movement, and Cl- ion secretion reduced under the hypo-osmotic exposure and ion excretion boost upon hyper-salinity stress. Meanwhile, the cartilage and skeletal development were enhanced in the gills by hypo- or hyper-salinity stimuli, which is critical for maintaining gill structures and improving respiration and osmoregulation under salinity stress. In kidneys, 600 and 539 DEGs were identified in 10 and 40 ppt groups, respectively. Those DEGs were enriched in oxygen transport, pronephros development, regulation of growth, blood coagulation, ion transmembrane transport, and immune response. While the known renal Na+/Cl– co-transporter gene slc12a3/ncc expression level was significantly down-regulated at 10 ppt, the organic cation transporter 2 gene slc22a2, ammonium transmembrane transport gene rhd and rhag expression levels were overexpressed under the hyper-salinity condition at 40 ppt, contributing to the salts secretion and ammonium transport regulation, to combat the osmotic influx of salts following the drink of seawater and elevated ammonia production upon high salinity stress. These findings advance our knowledge of adaptative mechanisms to the salinity stress and provide theoretical guidance for the optimal breeding mode for the aquaculture of greater amberjack.
Stroke in mitral valve prolapse: risk factors and left atrial function in cryptogenic versus non-cryptogenic ischemic subtypes
Authors: Calicchio Francesca , Lim Lisa J. , Cross Danielle , Bibby Dwight , Fang Qizhi , Meisel Karl , Schiller Nelson B. , Delling Francesca N.
Published: July 2023

Background and purpose

Mitral valve prolapse (MVP) has been associated with an increased risk of ischemic stroke. Older age, thicker mitral leaflets, and significant mitral regurgitation (MR) leading to atrial fibrillation have been traditionally considered risk factors for ischemic stroke in MVP. However, specific risk factors for MVP-stroke subtypes are not well defined. The aim of this study is to evaluate clinical and echocardiographic parameters, including left atrial (LA) function, in MVP with cryptogenic (C) vs. non-cryptogenic (NC) stroke.

Methods

In this case-control matched study, MVPs were identified in consecutive echocardiograms obtained after a stroke from January 2013 to December2016 at the University of California, San Francisco. MVP was defined as leaflet displacement ≥2 mm in the parasternal long-axis view at end-systole. Age/gender matched MVPs without stroke and healthy controls without MVP were also identified. We analyzed LA end-systolic/diastolic volume index, emptying fraction (LAEF), function index (LAFI), and global longitudinal strain in all MVPs and controls. We also measured left ventricular (LV) volume indexes, mass index, ejection fraction (EF), degree of MR and leaflet thickness.

Results

We identified a total of 30 MVPs (age 70 ± 12, 50% females) with stroke (11 with C- and 19 with NC-stroke), 20 age/gender matched MVPs without a stroke and 16 controls. MVPs without stroke had lower BMI, less hypertension but more MR (≥moderate in 45% vs. 17%), more abnormal LA function (lower LAEF, LAFI) and larger LV volumes/mass (all p < 0.05) when compared to MVPs with stroke. Leaflet thickness was overall mild (<3 mm) and similar in the 2 groups. Within the MVP stroke group, NC-stroke had higher BMI, more hypertension and more atrial fibrillation compared to C-stroke. In the variables tested, patients with C-stroke did not differ from controls.

Conclusions

MVP-related MR may be protective against stroke despite abnormal LA function. Risk of NC-stroke in MVP is related to common stroke risk factors rather than mitral valve leaflet thickness. The etiology of C-stroke in MVP warrants further studies.
Correlation of blood pressure levels at different time periods throughout the day with total CSVD burden and MRI imaging markers
Authors: Yang Hua , Fan Xueyi , Shen Xiangyi , Liang Li , Hu Dongyang , Zhang Yimo , Liu Li , Qian Hairong
Published: July 2023

Purpose

Hypertension is an important risk factor for atherosclerotic cerebral small vessel disease (CSVD). Higher blood pressure is associated with a higher CSVD burden and the presence of relevant magnetic resonance imaging (MRI) markers. However, the effect of blood pressure level on CSVD burden and imaging markers including white matter hyperintensity (WHM), lacune, enlarged perivascular spaces (EPVS), and cerebral microbleed (CMB) remains unknown. The purpose of this study was to investigate the correlation between blood pressure level and CSVD burden at different time periods throughout the day.

Methods

In total, 144 in-patients with CSVD (66.4 ± 9.8 years, 50% male) were enrolled and underwent brain MRI, and 24-h ambulatory blood pressure was assessed. Patients were categorized into five groups according to their MRI-evaluated total CSVD burden scores (0–4). Spearman's correlation analysis was performed to examine the correlation between blood pressure levels at different time periods and the total CSVD score or the markers of periventricular WMH, deep WMH, lacune, EPVS, and CMB.

Results

Of the 144 patients, 83.3% (120/144) harbored one or more CSVD markers of interest. The systolic blood pressure (SBP) of 24-h, daytime, nighttime, and morning differed significantly among the five groups. The SBP levels increased significantly with the total CSVD scores during 24 h (P = 0.018), daytime (P = 0.018), and nighttime (P = 0.035). Spearman's correlation analysis demonstrated that the SBP of 24 h, daytime, nighttime, and morning and the diastolic blood pressure (DBP) of 24 h and morning positively and significantly correlated with the total CSVD score (P < 0.05). A logistic regression analysis indicated that both morning SBP and DBP were independent risk factors for total CSVD burden (OR = 1.13, 95% CI: 1.02–1.23, P = 0.015; OR = 1.19, 95% CI: 1.06–1.33, P = 0.005). Spearman's correlation analysis indicated a significant positive correlation between morning SBP and higher deep WMH Fazekas score (r = 0.296, P < 0.001), EPVS grade in the basal ganglia (r = 0.247, P = 0.003), and the presence of lacune (r = 0.173, P = 0.038) and CMB (r = 0.326, P < 0.001). Morning DBP only correlated positively with the presence of CMB (r = 0.292, P < 0.001).

Conclusion

Higher SBP signficantly correlated with total CSVD burden in patients with atherosclerotic CSVD. Early morning blood pressure level is an important indicator to reflect the severity of CSVD patients.
Hemifacial spasm caused by unruptured fusiform vertebral aneurysm treated with endovascular coil embolization: a case report
Authors: He Pengchen , Li Zongping , Jiang Han
Published: July 2023

Hemifacial spasm due to fusiform aneurysm of the vertebral artery is extremely rare. The lateral spread response (LSR) is routinely used to monitor hemifacial spasms during microvascular decompression to predict the degree of postoperative remission of hemifacial spasm. We report a case of hemifacial spasm caused by an unruptured fusiform vertebral aneurysm treated with intravascular intervention and monitoring of LSR. A 59-year-old man was admitted to the hospital with a left facial spasm that gradually worsened for 1 year. Preoperative cerebrovascular angiography indicated fusiform aneurysms in the intracranial segment of the left vertebral artery close to the left facial nerve. The patient underwent parent artery occlusion and aneurysm embolization, and LSR was monitored intraoperatively. After intraoperative aneurysm embolization, LSR disappeared immediately. The postoperative review of cerebrovascular angiography indicated that the parent artery and aneurysm were embolized successfully, and the patient's left facial spasm was relieved after surgery. Hemifacial spasm caused by the vertebral artery fusiform aneurysm can be safely and effectively treated by parent artery occlusion and aneurysm embolization. Meanwhile, intraoperative LSR monitoring can be used to predict postoperative efficacy.
Complement factor B is essential for the proper function of the peripheral auditory system
Authors: Brown LaShardai N. , Barth Jeremy L. , Jafri Shabih , Rumschlag Jeffrey A. , Jenkins Tyreek R. , Atkinson Carl , Lang Hainan
Published: July 2023

Sensorineural hearing loss is associated with dysfunction of cochlear cells. Although immune cells play a critical role in maintaining the inner ear microenvironment, the precise immune-related molecular mechanisms underlying the pathophysiology of hearing loss remain unclear. The complement cascade contributes to the regulation of immune cell activity. Additionally, activation of the complement cascade can lead to the cellular opsonization of cells and pathogens, resulting in their engulfment and elimination by phagocytes. Complement factor B (fB) is an essential activator protein in the alternative complement pathway, and variations in the fB gene are associated with age-related macular degeneration. Here we show that mice of both sexes deficient in fB functional alleles (fB−/−) demonstrate progressive hearing impairment. Transcriptomic analysis of auditory nerves from adult mice detected 706 genes that were significantly differentially expressed between fB−/− and wild-type control animals, including genes related to the extracellular matrix and neural development processes. Additionally, a subset of differentially expressed genes was related to myelin function and neural crest development. Histological and immunohistochemical investigations revealed pathological alterations in auditory nerve myelin sheathes of fB−/− mice. Pathological alterations were also seen in the stria vascularis of the cochlear lateral wall in these mice. Our results implicate fB as an integral regulator of myelin maintenance and stria vascularis integrity, underscoring the importance of understanding the involvement of immune signaling pathways in sensorineural hearing loss.
State-of-the-art image and video quality assessment with a metric based on an intrinsically non-linear neural summation model
Authors: Luna Raúl , Zabaleta Itziar , Bertalmío Marcelo
Published: July 2023

The development of automatic methods for image and video quality assessment that correlate well with the perception of human observers is a very challenging open problem in vision science, with numerous practical applications in disciplines such as image processing and computer vision, as well as in the media industry. In the past two decades, the goal of image quality research has been to improve upon classical metrics by developing models that emulate some aspects of the visual system, and while the progress has been considerable, state-of-the-art quality assessment methods still share a number of shortcomings, like their performance dropping considerably when they are tested on a database that is quite different from the one used to train them, or their significant limitations in predicting observer scores for high framerate videos. In this work we propose a novel objective method for image and video quality assessment that is based on the recently introduced Intrinsically Non-linear Receptive Field (INRF) formulation, a neural summation model that has been shown to be better at predicting neural activity and visual perception phenomena than the classical linear receptive field. Here we start by optimizing, on a classic image quality database, the four parameters of a very simple INRF-based metric, and proceed to test this metric on three other databases, showing that its performance equals or surpasses that of the state-of-the-art methods, some of them having millions of parameters. Next, we extend to the temporal domain this INRF image quality metric, and test it on several popular video quality datasets; again, the results of our proposed INRF-based video quality metric are shown to be very competitive.