bluuebunny/crossref_metadata_2025 huggingface dataset:
Coda
Authors: Kishi Madoka
Published: September 2024

This book closes with the Coda, “Hindsight 20/20, or Asiatic Im-personality,” which revisits Edward Ross’s initial inspiration for the discourse of race suicide: Asian immigration. By overlaying the rhetoric of Asian exclusion at the turn of the century onto scenes of anti-Asian violence during the COVID-19 pandemic, the Coda inquires into the association between Asians and death in the American imaginary. In particular, the Coda traces how fears of fungible Asian bodies infecting the US social body—epitomized by “coolies”—gave rise to the discourse of race suicide. In this rhetoric, the figure of submissive, efficient, and impersonal Asian immigrants emerged as the antipode of the liberal subject, and yet tailor-made for the coming age of standardization and automation. The Coda terms this model of subjectivity “Asiatic im-personality” and reads it in relation to a number of Madame Butterfly texts.
Regional Technological Adaptation of Coast and Climate With a Focus on the North Sea
Authors: Jensen Jürgen , Soltau Felix , Haigh Ivan D.
Published: September 2024

Coastal zones are the most densely populated areas in the world and are vulnerable to extreme meteorological events like hurricanes, storm surges, tsunamis and climate change–induced sea level rise. Coasts are subject to constant change because of anthropogenic and natural variations in sea level, currents and wind waves, sediment supply, and so forth. The building of coastal defense and protection measures has also resulted in significant anthropogenic changes to the coast. Coasts are also affected by economic uses, including tourism, industrial activities (e.g., offshore wind farms), shipping, and fishing in coastal waters. This article discusses the regional technological adaptation of the coast, with a focus on the North Sea. The coastlines around the North Sea are, in many places, low lying, densely populated, and vulnerable to variations in sea level and coastal change. Worldwide, developments of coasts have been closely linked to climatic changes as mean sea level has increased and decreased over thousands of years. Around 2,000 years ago, people started to build the first coastal protection measures around the North Sea. A lot of different protection measures were developed, including dwelling mounds, groynes, dikes, polders, beach nourishment, and storm surge barriers. Land reclamation and storm surges shaped the Wadden Sea coast dramatically in the past. Globally, coasts and corresponding technological coastal adaptation measures are very diverse. Contrasting the previous technological “hard” coastal protection measures, in the 21st century nature-based solutions have become more attractive and are starting to be implemented more widely. Their natural contribution to coastal protection also provides an ecosystem service.
Development of Historical Writing on Botswana
Authors: Makgala Christian John
Published: September 2024

The writing of history of Botswana has evolved from simple narrations of the changing fortunes of tribal polities, first penned by European missionaries at the turn of the 20th century, to today’s highly analytical works, whose choice of themes are influenced by international debates and which focus on government development policies and popular discourse. Colonial government officials and independent scholars made an input before the country’s independence in 1966. From the mid-20th century, they were followed by Africanist historians largely sympathetic to the newly independent state, which was developing in a different way from other African countries. Concurrently, nationalist and Indigenous historians emerged, who mainly challenged the presentation of Botswana’s history by colonial or imperial writers, which they saw as Eurocentric. The University of Botswana’s undergraduate students have also made an immense contribution to the country’s historiography since 1976. The new millennium has seen history greatly marginalized in the school system, as the government of Botswana has emphasized and supported science, technology, engineering, and mathematics (STEM) over social sciences and humanities disciplines as part of its changed national development agenda. However, the negative impact of globalization and other developmental challenges render the study and teaching of Botswana’s past necessary to fostering citizenship, patriotism and national pride, and democracy, as part of the sensitive nation-building exercise and economic development. This is evidenced by the decision to reintroduce history as a compulsory subject in the school systems of Africa’s largest economies, Nigeria and South Africa, in 2022 and 2023, respectively.
BaHananwa
Authors: Kriel Lize
Published: September 2024

The people identifying as BaHananwa are descendants of Setswana-speaking BaHurutshe who migrated to the area south of the Limpopo River (21st century Limpopo Province of South Africa) sometime between 1750 and 1830. The Hananwa language is a variety of Sesotho sa Leboa, or “Northern Sesotho.” Blouberg (the Blue Mountains) is the historical site of the capital (mošate) of the Leboho rulers. The Boers of the Transvaal, whose independence was recognized by Britain in 1852, considered the African polities between the Vaal and the Limpopo Rivers as their subjects. Until the 1890s, ruler Kgaluši Leboho continued to act independently in the area around Blouberg and resisted Boer demands for taxes. In 1894, the State Artillery and Boer commandoes embarked on a campaign to subjugate the BaHananwa. After a three-month siege, Kgaluši and his royal entourage were taken prisoner. Many BaHananwa were indentured as farm laborers for Boers, but many more managed to escape capture, some 500 finding refuge on the Berlin Mission Station at the foot of the mountains. Kgaluši’s mother Mmaseketa acted as regent for six years. In 1900, with the British invasion of Pretoria, Kgaluši was released from prison and allowed to return to Blouberg. In the 20th century, the BaHananwa rulers resisted colonization. The adoption of a Bantu Tribal Authority was delayed until the 1970s. The apartheid government then acknowledged the original reserve demarcated in 1888 along with additional tribal, privately owned, and trust farms as BaHananwa land. The territory was governed as part of the Lebowa “homeland,” which was incorporated into the new Northern (later renamed Limpopo) Province in 1994. Traditional leadership continues to be acknowledged under the postapartheid democratic constitution and a supreme court ruling of 2010 affirmed the chiefship of Ngako Isaac Leboho.
Mexican Monastic Architecture
Authors: Brooker Niccolò
Published: September 2024

Mexico’s 16th-century monasteries, or conventos, occupy a singular place in history. These immense, often complex assemblages of buildings within vast compounds are the first architectural expressions resulting from the great contact between Europe and the New World, that is, between the zealous Spanish friars who conceived them and the extensive Amerindian workforce which constructed them. Reflective to a degree of their European predecessors, the Mexican conventos represented adaptations to unique religious circumstances and, as a result, introduced original architectural adjuncts, the most significant of which was the open chapel, or capilla abierta. Catering to large-scale, outdoor religious ceremonies to which the Amerindians were accustomed, these chapels were instrumental in the conversion of millions of indigenous from pre-Cortesian paganism to Christian monotheism.
Cervical cytology abnormalities and associated genotype patterns of High-Risk HPV Infection in Women of Tripura, North-East India: A Hospital-Based Study
Authors: Bhattacharya Amrapali , Chakraborty Kanak , Saha Partha , Saha Susmita , Roychaudhuri Parichita , Baidya Jahar Lal , Ghosh Arabinda , Chakraborty Debaprasad , Sengupta Sharmila , Sil Samir Kumar
Published: September 2024

The current study explored HPV prevalence and age variation in cervical samples of different cytological categories and HPV types from women seeking gynecological care in Tripura, northeast India. Pap smears, cervical tissues, and HPV/DNA specimens were collected from gynecological outpatient departments (OPD) or in-house patients and were screened for HPV16, HPV18, and other HPV types by PCR. Finally, logistic regression was performed to find the association between epidemiologic factors and HPV infection in women of different cytological grades. About 90% of HPV-screened women were found to be HPV positive. HPV16 was most common in HPV-positive women (53.27%), followed by HPV16/18 co-infection (26.17%). HPV16 or HPV18 was most frequent (86.45%) compared to others (13.55%). Among the confirmed cytological tests 68.83% showed normal cytology and 37.17% showed atypical abrasions. Among the abnormal cytology participants, 94.37% were HPV-positive, and 42.25% had cervical cancer. The prevalence of HPV increased with cytological abnormalities (p < 0.01). Abnormal cytological lesions increased with age (p trend = 0.017). Among all epidemiologic factors studied, parity was strongly associated with overall HPV infection, regardless of cytological status. Observed very high frequency of HPV infection in the current study, warrants further investigations.
Designing interpretable deep learning applications for functional genomics: a quantitative analysis
Authors: van Hilten Arno , Katz Sonja , Saccenti Edoardo , Niessen Wiro J , Roshchupkin Gennady V
Published: September 2024

Deep learning applications have had a profound impact on many scientific fields, including functional genomics. Deep learning models can learn complex interactions between and within omics data; however, interpreting and explaining these models can be challenging. Interpretability is essential not only to help progress our understanding of the biological mechanisms underlying traits and diseases but also for establishing trust in these model’s efficacy for healthcare applications. Recognizing this importance, recent years have seen the development of numerous diverse interpretability strategies, making it increasingly difficult to navigate the field. In this review, we present a quantitative analysis of the challenges arising when designing interpretable deep learning solutions in functional genomics. We explore design choices related to the characteristics of genomics data, the neural network architectures applied, and strategies for interpretation. By quantifying the current state of the field with a predefined set of criteria, we find the most frequent solutions, highlight exceptional examples, and identify unexplored opportunities for developing interpretable deep learning models in genomics.
Investigation of protein family relationships with deep learning
Authors: Ponamareva Irina , Andreeva Antonina , Bileschi Maxwell L , Colwell Lucy , Bateman Alex
Published: September 2024

Motivation

In this article, we propose a method for finding similarities between Pfam families based on the pre-trained neural network ProtENN2. We use the model ProtENN2 per-residue embeddings to produce new high-dimensional per-family embeddings and develop an approach for calculating inter-family similarity scores based on these embeddings, and evaluate its predictions using structure comparison.

Results

We apply our method to Pfam annotation by refining clan membership for Pfam families, suggesting both new members of existing clans and potential new clans for future Pfam releases. We investigate some of the failure modes of our approach, which suggests directions for future improvements. Our method is relatively simple with few parameters and could be applied to other protein family classification models. Overall, our work suggests potential benefits of employing deep learning for improving our understanding of protein family relationships and functions of previously uncharacterized families.

Availability and implementation

github.com/iponamareva/ProtCNNSim, 10.5281/zenodo.10091909.
Hydrographic basins dictate the genetic structure of the paradoxical frog Pseudis bolbodactyla (Anura: Hylidae) in the rivers of Central Brazil
Authors: Santana Diego J , Myers Edward A , Fonseca Emanuel M , Gehara Marcelo , Oliveira Eliana F , Bonatto Sandro L , Burbrink Frank T , Garda Adrian A
Published: September 2024

Rivers are prominent landscape features, acting as key promoters of diversification among freshwater organisms. Albeit generally considered potential barriers to species movement, they may also facilitate gene flow and structure populations of semiaquatic species (Riverine Thruway Hypothesis, RTH). We evaluated the role of rivers on the processes responsible for current genetic variation in the semiaquatic frog Pseudis bolbodactyla, testing whether each hydrographic basin harbours distinct genetic lineages. We sequenced three markers on 166 samples from 13 localities along the Paraná (PR), Araguaia–Tocantins (AT), and São Francisco (SF) River basins in Brazil. We recovered three populations geographically matching each hydrographic basin. Our results indicate migration among basins, with the best model selected using approximate Bayesian computation, including migration between AT and SF and ancient gene flow from PR to the AT–SF ancestor. Our findings are likely related to the orogenic events in Central Brazil dating to the Late Miocene (5 Mya), when hydrographic basins and the geomorphological features of the Brazilian Shield were formed. This suggests that P. bolbodactyla probably represents a species complex, with each lineage occurring in a distinct hydrographic basin, matching the predictions of the RTH.
Economic impact of limb-salvage strategies in chronic limb-threatening ischaemia: modelling and budget impact study based on national registry data
Authors: Saratzis Athanasios , Zayed Hany , Buylova Anna , Rawlinson William , Veliu Giota , Siebert Markus
Published: September 2024

Background

Missed opportunities to reduce numbers of primary major lower-limb amputation and increase limb-salvage procedures when treating chronic limb-threatening ischaemia have previously been identified in the literature. However, the potential economic savings for healthcare providers when salvaging a chronic limb-threatening ischaemia-affected limb have not been well documented.

Methods

A model using National Health Service healthcare usage and cost data for 1.6 million individuals and averaged numbers of primary surgical procedures for chronic limb-threatening ischaemia from England and Wales in 2019–2021 was created to perform a budget impact analysis. Two scenarios were tested: the averaged national rates of major lower-limb amputation (above the ankle joint), angioplasty, open bypass surgery or arterial endarterectomy in the National Vascular Registry (current scenario); and revascularization rates adjusted based on the lowest amputation rate reported by the National Vascular Registry at the time of the study (hypothetical scenario). The primary outcome was the net impact on costs to the National Health Service over 12 months after the index procedure.

Results

In the current scenario, the proportions of different index procedures were 10% for lower-limb major amputation, 55% for angioplasty, 25% for open bypass surgery and 10% for arterial endarterectomy. In the hypothetical scenario, the procedure rates were 3% for major lower-limb amputation, 59% for angioplasty, 27% for open bypass surgery and 11% for arterial endarterectomy. For 16 025 index chronic limb-threatening ischaemia procedures, the total care cost in the current scenario was €243 924 927. In the hypothetical scenario, costs would be reduced for index procedures (−€10 013 814), community care (−€633 943) and major cardiovascular events (−€383 407), and increased for primary care (€59 827), outpatient appointments (€120 050) and subsequent chronic limb-threatening ischaemia-related surgery (€1 179 107). The net saving to the National Health Service would be €9 645 259.

Conclusion

A shift away from primary major lower-limb amputation towards revascularization could lead to substantial savings for the National Health Service without major cost increases later in the care pathway, indicating that care decisions taken in hospitals have wider benefits.
Subjective cognitive and olfactory impairments predict different prospective dementia outcomes
Authors: Cedres Nira , Olofsson Jonas K
Published: September 2024

Self-reported measures emerge as potential indicators for early detection of dementia and mortality. We investigated the predictive value of different self-reported measures, including subjective cognitive decline (SCD), subjective olfactory impairment (SOI), subjective taste impairment (STI), and self-reported poor health (SPH), in order to determine the risk of progressing to Alzheimer’s disease (AD) dementia, Parkinson’s disease (PD) dementia, or any-other-cause dementia. A total of 6,028 cognitively unimpaired individuals from the 8th wave of the English Longitudinal Study of Ageing (ELSA) were included as the baseline sample and 5,297 individuals from the 9th wave were included as 2-year follow-up sample. Self-rated measures were assessed using questions from the ELSA structured interview. Three logistic regression models were fitted to predict different the dementia outcomes. SCD based on memory complaints (OR = 11.145; P < 0.001), and older age (OR = 1.108, P < 0.001) significantly predicted the progression to AD dementia at follow-up. SOI (OR = 7.440; P < 0.001) and older age (OR = 1.065, P = 0.035) significantly predicted the progression to PD dementia at follow-up. Furthermore, SCD based on memory complaints (OR = 4.448; P < 0.001) jointly with complaints in other (non-memory) mental abilities (OR = 6.662; P < 0.001), and older age (OR = 1.147, P < 0.001) significantly predicted the progression to dementia of any other cause. Different types of complaints are specifically associated with different dementia outcomes. Our study demonstrates that self-reported measures are a useful and accessible tool when screening for individuals at risk of dementia in the general population.
Coalition Building and Sino–US Competition in the Digital Era
Authors: Liu Xinghua
Published: September 2024

Digital coalitions are the primary tool of the USA to compete with China in the digital age and differ markedly from traditional alliances and military coalitions. It is necessary to go beyond the vision of pure great power rivalry and probe Sino–US digital competition through the lens of coalitions and the relationship between the dominant state and coalition members. A digital coalition is a state consortium with an organisational nature, confrontational targets, common goals, and the capability to take collective action, formed to deal with the digital strategy, norms, standards, industry, and products. The two main determinants of the building and maintenance of the digital coalition are the security dependency of allies on the USA and the technological stranglehold in the digital relationship. Security dependency determines the likelihood of coalition construction; the higher the dependency, the more willing allies will be to respond to the dominant state’s digital security narrative and mobilisation. There is potential for the construction of simple digital coalitions centred on conceptions and governance initiatives. However, building and maintaining a complex digital coalition depends on the presence of a technological stranglehold as well as security dependencies. A technological stranglehold involves controlling the supply of key technologies critical to the survival of the industry, and compels allies to sacrifice market interests and participate in a digital coalition to ensure the integrity of their industries. The Chip 4 Alliance and Trade and Technology Council are typical examples of US-led digital coalitions.
Patient-Reported Racial and Ethnic Disparities in Patients With Ulcerative Colitis: Results From the National Health and Wellness Survey
Authors: Burbage Sabree C , Krupsky Kathryn L , Cambron-Mellott M Janelle , Way Nate , Patel Aarti A , Liu Julia J
Published: September 2024

Background

Ulcerative colitis (UC) is an inflammatory condition characterized by chronic, disabling gastrointestinal symptoms that can have detrimental effects on psychological, social, and professional quality of life. Few studies have examined patient-reported outcomes (PROs) and economic outcomes among individuals with varying UC severity and across different racial/ethnic groups.

Methods

This cross-sectional study assessed sociodemographic data, PROs, and economic outcomes for participants from the National Health and Wellness Survey (2018, 2019, and 2020) with UC. Multivariable analyses were used to assess the association of self-reported UC severity and race/ethnicity with health-related quality of life (HRQoL), work productivity and activity impairment (WPAI), healthcare resource utilization (HCRU), and medical costs.

Results

This study included 1500 participants with UC (1150 non-Hispanic White, 99 non-Hispanic Black, and 251 Hispanic). Moderate/severe disease was associated with significantly worse HRQoL and WPAI, greater HCRU, and higher direct medical costs than mild UC. Compared with non-Hispanic White participants, non-Hispanic Black participants reported better HRQoL, whereas Hispanic participants reported more HCRU and higher medical costs. Race/ethnicity significantly interacted with UC severity level in predicting labor force participation.

Conclusions

Participants with moderate/severe disease had worse outcomes than those with mild UC. Additionally, racial/ethnic differences were found in HRQoL, employment, WPAI, HCRU, and direct medical costs. Notably, Hispanic participants showed distinct patterns, particularly in how disease severity influenced employment outcomes. Further research is needed to better understand the differential burden among patients across racial/ethnic groups.
An uncommon cause of a common disease: a case report of a rare cause of hypertension
Authors: Rao Sarita , Rao Roshan , Kumar Achukatla , Benjamin Nitika , Pandey Akshat
Published: September 2024

Background

Severe hypertension in young patients presents a significant diagnostic dilemma, and treatment can often be codified. Therefore, it is crucial to diagnose these cases for probable secondary hypertension. Common causes of secondary hypertension include large vessel vasculitis, renal artery stenosis, coarctation of the aorta, and endocrine disorders.

Case summary

A 23-year-old Asian male, who was previously in good health, presented with symptoms of chest pain, shortness of breath on exertion grade II, and generalized weakness. On examination, his blood pressure was markedly elevated at 200/110 mmHg. Diagnostic investigations revealed significant vascular involvement, including bilateral renal artery stenosis accompanied by aneurysm formation, celiac trunk disease, and osteal stenosis of the superior mesenteric artery. The patient underwent successful interventional procedure, including renal angioplasty, stenting, and aneurysm coiling. This was followed by tailoring of medical management along with anti-inflammatory and disease-modifying drugs.

Discussion

The diagnosis of Takayasu arteritis (TAK) in this case is supported by the patients’ age, presentation, and imaging according to the new TAK classification criteria by the American College of Rheumatology/European League Against Rheumatism (EULAR) and emphasizes the potential benefits of a pharmaco-invasive approach for optimal outcomes.
Interacting phenotypic plasticities: do male and female responses to the sociosexual environment interact to determine fitness?
Authors: Simmons Leigh W , Lovegrove Maxine
Published: September 2024

Socially induced plasticity in reproductive effort is a widely documented phenomenon. However, few empirical studies have examined how male and female plastic responses to the social environment might interact in determining fitness outcomes. In field crickets, Teleogryllus oceanicus, males respond to rival songs by increasing expenditure on seminal fluid proteins that enhance competitive fertilization success at the cost of reduced embryo survival. It remains unknown whether plastic responses in females could moderate the effects of male competitiveness on offspring performance. Here, we used a fully factorial design to explore the interacting effects on fitness of male and female plasticity to the sociosexual environment. We found that female crickets exposed to male songs increased the number of eggs produced during early life reproduction, which came at the cost of reduced offspring size. There was evidence, albeit weak, that interacting effects of male and female sociosexual environments contributed to variation in the hatching success of eggs laid by females. Lifetime offspring production was unaffected by the sociosexual environments to which upstream male and female plastic responses were made. Our data offer a rare test of the theoretical expectation that male and female plasticities should interact in their effects on female fitness.
Genome sequence of the sugarcane aphid, Melanaphis sacchari (Hemiptera: Aphididae)
Authors: Zhao Jinshuai , Xie Liqiang , Zhao Xinrui , Li Luhua , Cui Jianghui , Chen Jinfeng
Published: September 2024

The sugarcane aphid, Melanaphis sacchari, is an agricultural pest that causes damage to plants in the Poaceae (the grasses) family, such as sorghum and sugarcane. In this study, we used nanopore long reads and a high-throughput chromosome conformation capture chromatin interaction maps to generate a chromosome-level assembly with a total length of 356.1 Mb, of which 85.5% (304.6 Mb) is contained within the 3 autosomes and the X chromosome. Repetitive sequences accounted for 16.29% of the chromosomes, and a total of 12,530 protein-coding genes were annotated, achieving 95.8% Benchmarking Universal Single-Copy Ortholog gene completeness. This offered a substantial improvement compared with previous low-quality genomic resources. A phylogenomic analysis by comparing M. sacchari with 24 published aphid genomes representing 3 aphid tribes revealed that M. sacchari belonged to the tribe Aphidini and maintained a conserved chromosome structure with other Aphidini species. The high-quality genomic resources reported in this study are useful for understanding the evolution of aphid genomes and studying pest management of M. sacchari.
Local adaptation can cause both peaks and troughs in nucleotide diversity within populations
Authors: Jasper Russ J , Yeaman Sam
Published: September 2024

The amount of standing variation present within populations is a fundamental quantity of interest in population genetics, commonly represented by calculating the average number of differences between pairs of nucleotide sequences (nucleotide diversity, π). It is well understood that both background and positive selection can cause reductions in nucleotide diversity, but less clear how local adaptation affects it. Depending on the assumptions and parameters, some theoretical studies have emphasized how local adaptation can reduce nucleotide diversity, while others have shown that it can increase it. Here, we explore how local adaptation shapes genome-wide patterns in within-population nucleotide diversity, extending previous work to study the effects of polygenic adaptation, genotypic redundancy, and population structure. We show that local adaptation produces two very different patterns depending on the relative strengths of migration and selection, either markedly decreasing or increasing within-population diversity at linked sites at equilibrium. At low migration, regions of depleted diversity can extend large distances from the causal locus, with substantially more diversity eroded than expected with background selection. With higher migration, peaks occur over much smaller genomic distances but with much larger magnitude changes in diversity. Across spatially extended environmental gradients, both patterns can be found within a single species, with increases in diversity at the center of the range and decreases towards the periphery. Our results demonstrate that there is no universal diagnostic signature of local adaptation based on within-population nucleotide diversity, so it will not be broadly useful for explaining increased FST. However, given that neither background nor positive selection inflate diversity, when peaks are found they suggest local adaptation may be acting on a causal allele in the region.
Optimizing architectural designs for energy efficiency in Jeddah: a comparative analysis of building forms
Authors: Ismaail Amal Dawoud , Mahboob Abdullah Mohamed
Published: September 2024

This research paper investigates the impact of residential building forms, including high-density, balanced urban design, and eco-friendly designs, on energy efficiency in Jeddah, Saudi Arabia, through a comparative analysis utilizing parametric numerical analysis with Autodesk Revit. The study aims to address the unique challenges posed by Jeddah’s rapid population growth, climatic conditions, and economic diversification efforts under Saudi Vision 2030. By examining different building configurations, the research highlights how urban building forms influence energy consumption, providing valuable insights for urban planners and designers during the conceptual design phase. The findings underscore the importance of optimizing urban parameters to promote high-density urban growth, maximize land use efficiency, and support sustainable energy consumption, aligning with the strategic objectives of Saudi Vision 2030.
A mesh-independent method for second-order potential mean field games
Authors: Liu Kang , Pfeiffer Laurent
Published: September 2024

This article investigates the convergence of the Generalized Frank–Wolfe (GFW) algorithm for the resolution of potential and convex second-order mean field games. More specifically, the impact of the discretization of the mean-field-game system on the effectiveness of the GFW algorithm is analyzed. The article focuses on the theta-scheme introduced by the authors in a previous study. A sublinear and a linear rate of convergence are obtained, for two different choices of stepsizes. These rates have the mesh-independence property: the underlying convergence constants are independent of the discretization parameters.
A rapid method to assess the in vivo multi-functionality of adoptively transferred engineered TCR T cells
Authors: Tan Anthony T , Hang Shou Kit , Tan Nicole , Krishnamoorthy Thinesh L , Chow Wan Cheng , Wong Regina Wanju , Wai Lu-En , Bertoletti Antonio
Published: September 2024

Introduction

The clinical efficacy of chimeric antigen and T cell receptor (TCR) T cell immunotherapies is attributed to their ability to proliferate and persist in vivo. Since the interaction of the engineered T cells with the targeted tumour or its environment might suppress their function, their functionality should be characterized not only before but also after adoptive transfer.

Materials and methods

We sought to achieve this by adapting a recently developed Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) rapid whole blood T cell assay to stimulate engineered TCR T cells in small volumes of whole blood (<1 ml) without in vitro cellular purification. As a proof-of-concept, we used this method to longitudinally study two patients with primary Hepatitis B Virus (HBV)-related hepatocellular carcinoma who received multiple dose-escalating infusions of transiently functional mRNA-engineered HBV-TCR T cells.

Results

We demonstrated that a simple pulsing of whole blood with a peptide corresponding to the epitope recognized by the specific HBV-TCR elicited Th1 cytokine secretion in both patients only after HBV-TCR T cell treatment and not before. The amount of cytokines secreted also showed an infusion-dose-dependent association.

Discussions

These findings support the utility of the whole blood cytokine release assay in monitoring the in vivo function and quantity of engineered T cell products following adoptive transfer.
Bacterial Inactivation Studies in Shrimp Pond Water by Using Different Disinfectant Agents
Authors: Nadella Ranjit Kumar , Panda Satyen Kumar , Uchoi Devananda , Kishore Pankaj , V. R. Madhu , Ayyappan Minimol Valamattath , Badireddy Madhusudana Rao , Kuricheti Pani Prasad , Raman Ram Prakash , Mothadaka Mukteswar Prasad
Published: September 2024

Background

Aquaculture water plays an important role in the dissemination of antibiotic-resistant bacteria during harvest of shrimps. Mitigation of bacteria through discharge is essential to prevent dissemination downstream. Chemical disinfection of culture water is feasible compared to other methods of bacterial inactivation.

Objective

To study the effect of different disinfectant agent’s viz., chlorine, Fenton’s reagent, and hydrogen peroxide (H2O2) on inactivation of bacteria from shrimp pond water.

Methods

The water samples were subjected to treatment with various concentrations of chlorine (0.0, 1.0, 2.5, 5.0, and 10.0 mg/L), Fenton’s reagent (1:10 mM ratio of Fe2+:H2O2; 2:20, 3:30, 4:40, 5:50) and H2O2 (20, 30, 40, and 50 mM) for different time durations (5, 15, 30, and 60 min).

Results

The results indicated that all the disinfecting agents inactivated both the total heterotrophic bacteria and tetracycline-resistant bacteria with increased concentrations and time. At the end of 60 min treatment with chlorination (2.5 mg Cl2/L), Fenton’s reagent (2 mM Fe2+ + 20 mM H2O2), and H2O2 (50 mM H2O2), the total heterotrophic bacterial count in the water samples gradually decreased by 2.35, 2.65, and 1.38 Log10 CFU/mL, and tetracycline-resistant bacterial count reduced by 1.57, 1.66, and 1.43 Log10 CFU/mL respectively, from initial bacterial load.

Conclusion

The study revealed that disinfection agents can be successfully employed in the inactivation of antibiotic-resistant bacteria discharged through aquaculture water. Among three disinfection agents, Fenton’s reagent has been found effective in inhibiting both heterotrophic bacteria and tetracycline-resistant bacteria from water samples.

Highlights

Bacterial inactivation studies were carried with chlorination, Fenton’s reagent, and hydrogen peroxide. The highest reduction in Heterotrophic Plate Count (HPC) (2.65 Log) and tetracycline-resistant count (1.66 Log) was noticed in the water samples treated with Fenton’s reagent. The use of disinfection agents effectively mitigates antibiotic-resistant bacteria from aquaculture wastewater.
Corrected generalized cross-validation for finite ensembles of penalized estimators
Authors: Bellec Pierre C , Du Jin-Hong , Koriyama Takuya , Patil Pratik , Tan Kai
Published: September 2024

Generalized cross-validation (GCV) is a widely used method for estimating the squared out-of-sample prediction risk that employs scalar degrees of freedom adjustment (in a multiplicative sense) to the squared training error. In this paper, we examine the consistency of GCV for estimating the prediction risk of arbitrary ensembles of penalized least-squares estimators. We show that GCV is inconsistent for any finite ensemble of size greater than one. Towards repairing this shortcoming, we identify a correction that involves an additional scalar correction (in an additive sense) based on degrees of freedom adjusted training errors from each ensemble component. The proposed estimator (termed CGCV) maintains the computational advantages of GCV and requires neither sample splitting, model refitting, or out-of-bag risk estimation. The estimator stems from a finer inspection of the ensemble risk decomposition and two intermediate risk estimators for the components in this decomposition. We provide a non-asymptotic analysis of the CGCV and the two intermediate risk estimators for ensembles of convex penalized estimators under Gaussian features and a linear response model. Furthermore, in the special case of ridge regression, we extend the analysis to general feature and response distributions using random matrix theory, which establishes model-free uniform consistency of CGCV.
Interventions to reduce surgical site infection following elective colorectal surgery: protocol for a systematic review with narrative synthesis and GRADE recommendations
Authors: Dean Harry , Drami Ioanna , Shamsiddinova Amira , Alkizwini Eman , Kinross James , Wilson Ana , Tozer Phil , Vaizey Carolynne
Published: September 2024

Surgical site infection (SSI) is frequently associated with adverse patient outcomes. SSI is often perceived as a preventable complication following elective surgery, and a wide array of strategies have been reported to reduce its occurrence. Despite this, colorectal surgery continues to have among the highest incidences of SSI, and there is considerable variation in the use of evidence-based practices in its prevention. There are currently no systematic reviews describing the full range of interventions to reduce SSI across the perioperative period of elective colorectal surgery. To determine which perioperative interventions are effective in reducing SSI following elective colorectal surgery. A systematic search of MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials and Web of Science databases as well as grey literature sources will be performed. Data extraction, risk of bias assessments and narrative synthesis will be performed by a team of trained, independent reviewers. Certainty of evidence will be assessed using the Grading of Recommendations, Assessment, Development and Evaluations framework. This review will form the most comprehensive assessment to date of measures to reduce SSI following elective colorectal surgery. This will promote the adoption of evidence-based practice and the identification of future research needs.
Model-Based Prediction for Small Domains Using Covariates: A Comparison of Four Methods
Authors: Michal Victoire , Wakefield Jon , Schmidt Alexandra M , Cavanaugh Alicia , Robinson Brian E , Baumgartner Jill
Published: September 2024

We consider methods for model-based small area estimation when the number of areas with sampled data is a small fraction of the total areas for which estimates are required. Abundant auxiliary information is available from the survey for all the sampled areas. Further, through an external source, there is information for all areas. The goal is to use auxiliary variables to predict the outcome of interest for all areas. We compare areal-level random forests and LASSO approaches to a frequentist forward variable selection approach and a Bayesian shrinkage method using a horseshoe prior. Further, to measure the uncertainty of estimates obtained from random forests and the LASSO, we propose a modification of the split conformal procedure that relaxes the assumption of exchangeable data. We show that the proposed method yields intervals with the correct coverage rate and this is confirmed through a simulation study. This work is motivated by Ghanaian data available from the sixth Ghana Living Standards Survey (GLSS) and the 2010 Population and Housing Census, in the Greater Accra Metropolitan Area (GAMA) region, which comprises eight districts that are further divided into enumeration areas (EAs). We estimate the areal mean household log consumption using both datasets. The outcome variable is measured only in the GLSS for 3 percent of all the EAs (136 out of 5019) and 174 potential covariates are available in both datasets. In the application, among the four modeling methods considered, the Bayesian shrinkage performed the best in terms of bias, mean squared error (MSE), and prediction interval coverages and scores, as assessed through a cross-validation study. We find substantial between-area variation with the estimated log consumption showing a 1.3-fold variation across the GAMA region. The western areas are the poorest while the Accra Metropolitan Area district has the richest areas.
Natural variation in the adjustment of primary metabolism determines ammonium tolerance in the model grass Brachypodium distachyon
Authors: De la Peña Marlon , Poucet Théo , Montardit-Tarda Francesc , Urmeneta Leyre , Urbano-Gámez Jose Alberto , Cassan Cédric , Vega-Mas Izargi , Catalán Pilar , Igartua Ernesto , Gibon Yves , Gonzalez-Moro M Begoña , Marino Daniel
Published: September 2024

Nitrogen (N) fertilization is essential to maximize crop production. However, around half of the applied N is lost to the environment, causing water and air pollution and contributing to climate change. Understanding the natural genetic and metabolic basis underlying plants N use efficiency is of great interest to attain an agriculture with less N demand and thus more sustainable. The study of ammonium (NH4+) nutrition is of particular interest, because it mitigates N losses due to nitrate (NO3–) leaching or denitrification. In this work, we studied Brachypodium distachyon, the model plant for C3 grasses, grown with NH4+ or NO3– supply. We performed gene expression analysis in the root of the B. distachyon reference accession Bd21 and examined the phenotypic variation across 52 natural accessions through analyzing plant growth and a panel of 22 metabolic traits in leaf and root. We found that the adjustment of primary metabolism to NH4+ nutrition is essential for the natural variation of NH4+ tolerance, notably involving NH4+ assimilation and phosphoenolpyruvate carboxylase (PEPC) activity. Additionally, genome-wide association studies (GWAS) indicated several loci associated with B. distachyon growth and metabolic adaptation to NH4+ nutrition. We found that the GDH2 gene was associated with the induction of root glutamate dehydrogenase activity under NH4+ nutrition and that two genes encoding malic enzyme were associated with leaf PEPC activity. Altogether, our work underlines the value of natural variation and the key role of primary metabolism to improve NH4+ tolerance.
Buprenorphine for the Treatment of Military-related PTSD With Treatment-resistant Depression and Unexpected Benefit for Chronic Pain: Case Report
Authors: Skorzewska Anna , Younger William A , Dempster Kylie S , Nazarov Anthony , Richardson J Don
Published: September 2024

The prevalence of treatment-resistant depression within global and military populations highlights the need for novel treatment approaches beyond monoamine neurotransmitter modulators. Buprenorphine (BUP), a semi-synthetic partial opioid agonist, is approved for the treatment of opioid use disorder and has shown promise in treating both depression and chronic pain. This case report discusses the use of transdermal BUP in treating a 36 year-old man with treatment-resistant depression with prominent anhedonia, military-related posttraumatic stress disorder, and chronic pain because of barosinusitis. Significant reductions in anxious and depressive symptoms, including in anhedonia, were observed with lasting effects. An unexpected finding was the discontinuation of prescribed hydromorphone for pain, suggesting the potential unique benefit of BUP in treating chronic pain and treatment resistant depression comorbidities. These findings implicate the diverse beneficial potential of BUP in psychiatric treatments for military populations.
Thermodynamic origin of the affinity, selectivity, and domain specificity of metallothionein for essential and toxic metal ions
Authors: Quinn Colette F , Wilcox Dean E
Published: September 2024

The small Cys-rich protein metallothionein (MT) binds several metal ions in clusters within two domains. While the affinity of MT for both toxic and essential metals has been well studied, the thermodynamics of this binding has not. We have used isothermal titration calorimetry measurements to quantify the change in enthalpy (ΔH) and change in entropy (ΔS) when metal ions bind to the two ubiquitous isoforms of MT. The seven Zn2+ that bind sequentially at pH 7.4 do so in two populations with different coordination thermodynamics, an initial four that bind randomly with individual tetra-thiolate coordination and a subsequent three that bind with bridging thiolate coordination to assemble the metal clusters. The high affinity of MT for both populations is due to a very favourable binding entropy that far outweighs an unfavourable binding enthalpy. This originates from a net enthalpic penalty for Zn2+ displacement of protons from the Cys thiols and a favourable entropic contribution from the displaced protons. The thermodynamics of other metal ions binding to MT were determined by their displacement of Zn2+ from Zn7MT and subtraction of the Zn2+-binding thermodynamics. Toxic Cd2+, Pb2+, and Ag+, and essential Cu+, also bind to MT with a very favourable binding entropy but a net binding enthalpy that becomes increasingly favourable as the metal ion becomes a softer Lewis acid. These thermodynamics are the origin of the high affinity, selectivity, and domain specificity of MT for these metal ions and the molecular basis for their in vivo binding competition.
Secondhand Tobacco Exposure Assessed Using Urinary Cotinine Among 10-Year-Old Children in Japan: An 11-Year Repeated Cross-sectional Study
Authors: Tamada Yudai , Takeuchi Kenji , Tabuchi Takahiro
Published: September 2024

Introduction

The emergence of heated tobacco products (HTPs) has made it important to monitor HTP-generated aerosols in addition to combustible cigarette (CC) smoke as a source of secondhand tobacco (SHT) exposure. We investigated the trend of SHT exposure in school-aged children and assessed whether SHT exposure depended on household tobacco use status.

Aims and Methods

This repeated cross-sectional study from 2011 to 2021 (15 927 participants) was based on data from an annual survey of fourth-grade students (aged 10 years) in Kumagaya City, Japan. In addition to a questionnaire which includes questions about household tobacco use status, we measured the urinary cotinine levels of each participant by their first-morning urine sample to objectively assess SHT exposure. We defined the participants with urinary cotinine levels ≥5.0 ng/mL as being exposed to SHT.

Results

The prevalence of SHT exposure decreased over the 11-year period from 18.6% in 2011 to 5.3% in 2021. It was significantly higher in households with tobacco users than without tobacco users (t-test p< .001). Prevalence of SHT exposure was 1.4% among the 68.1% of households not using tobacco, 22.9% among the 16.5% using only CC, 3.1% among the 12.3% using only HTP, and 27.6% among the 3.9% of households using CC and HTP.

Conclusions

While the prevalence of SHT exposure showed a decreasing trend from 2011 to 2021, the prevalence of SHT exposure was higher in children with household members using tobacco products, regardless of the type of tobacco product, than in those without tobacco users.

Implications

This study observed that the prevalence of SHT exposure was higher among children in households with tobacco users than among those without tobacco users, regardless of the type of tobacco product. Our findings highlight the importance of advocating that HTPs do not reduce the likelihood of SHT exposure to bystanders.