bluuebunny/crossref_metadata_2025 huggingface dataset:
Poly(U) polymerase activity in Caenorhabditis elegans regulates abundance and tailing of sRNA and mRNA
Authors: Kelley Leanne H , Caldas Ian V , Sullenberger Matthew T , Yongblah Kevin E , Niazi Adnan M , Iyer Anoop , Li Yini , Tran Patrick Minty , Valen Eivind , Ahmed-Braimah Yasir H , Maine Eleanor M
Published: July 2024

Terminal nucleotidyltransferases add nucleotides to the 3′ end of RNA to modify their stability and function. In Caenorhabditis elegans, the terminal uridyltransferases/poly(U) polymerases PUP-1 (aka CID-1, CDE-1), PUP-2, and PUP-3 affect germline identity, survival, and development. Here, we identify small RNA (sRNA) and mRNA targets of these PUPs and of a fourth predicted poly(U) polymerase, F43E2.1/PUP-4. Using genetic and RNA sequencing approaches, we identify RNA targets of each PUP and the U-tail frequency and length of those targets. At the whole organism level, PUP-1 is responsible for most sRNA U-tailing, and other PUPs contribute to modifying discrete subsets of sRNAs. Moreover, the expression of PUP-2, PUP-3, and especially PUP-4 limits uridylation on some sRNAs. The relationship between uridylation status and sRNA abundance suggests that U-tailing can have a negative or positive effect on abundance depending on context. sRNAs modified by PUP activity primarily target mRNAs that are ubiquitously expressed or most highly expressed in the germline. mRNA data obtained with a Nanopore-based method reveal that the addition of U-tails to nonadenylated mRNA is substantially reduced in the absence of PUP-3. Overall, this work identifies PUP RNA targets, defines the effect of uridylation loss on RNA abundance, and reveals the complexity of PUP regulation in C. elegans development.
Upscaling from mineral microstructures to tectonic macrostructures
Authors: Bercovici David , Girard Jennifer , Mulyukova Elvira
Published: July 2024

Earth’s plate tectonic behaviour arises from lithospheric ductile weakening and shear-localization. The ubiquity of mylonites at lithospheric shear zones is evidence that localization is caused by mineral grain size reduction. Most lithospheric mylonites are polymineralic, suggesting that the interaction between mineral phases by Zener pinning promotes grain size reduction and weakening. Yet this interaction only occurs where mineral phases mix at the grain scale. Phase mixing and its effect on microstructure and strength have been shown in deformation experiments and natural field samples. Our theory for the interaction between phase mixing (treated as a stress driven diffusion) with two-phase grain damage has been compared to lab experiments. But using processes at the tiny grain-scale embedded within the small hand-sample and lab scales to model large-scale lithospheric processes, requires an upscaling scheme that captures the physics from micro- to macrostructures. For example, weakening from grain-damage in zones of mixing can lead to banded viscosity structure at the small scale that manifests as viscous anisotropy at the large scale. Here we provide a new framework for self-consistently upscaling from microscopic (grain) scales, to mesoscopic (petrological heterogeneity) scales to macroscopic (tectonic) scales. The first upscaling step models phase mixing and grain size evolution in a small ‘mesoscopic’ lab-scale volume or ‘patch’, which is equivalent to a point in the macroscopic space. Within this mesoscale patch, stress driven diffusive mixing is described by an analytical solution for mineral phase fraction, provided a minimalist Fourier representation of phase fraction, and a transformation to the patch frame of reference as well as to the principal stress directions at that point. The orientation and volume fraction of mixed-phase regions can then be extracted from the analytical solution for phase fraction. The grain size and viscosity in the mixed bands are determined by two-phase grain-damage theory; the unmixed zone properties follow from mono-phase grain damage theory. The mesoscale banded viscosity field leads to a macroscale anisotropic viscosity at that point in space. But, the evolution of properties at each macroscale point involves tracking only a few quantities (phase fraction, grain sizes) rather than modelling each patch of mesoscale space as its own 2-D or 3-D system. For the final upscaling, the anisotropic viscosity field is used in a macroscale lithosphere flow model. We show an example of this scheme for a lithospheric Rayleigh–Taylor drip driven by ridge-push compressive stress, which can cause anisotropic weakening via grain mixing and damage that may help initiate subduction and passive margin collapse.
Development and validation of a community risk score for sexual and reproductive health in the United States
Authors: Lines Lisa M , Fowler Christina I , Kaganova Yevgeniya , Peacock Karen
Published: July 2024

Equitable access to sexual and reproductive health (SRH) care is key to reducing inequities in SRH outcomes. Publicly funded family-planning services are an important source of SRH care for people with social risk factors that impede their access. This study aimed to create a new index (Local Social Inequity in SRH [LSI-SRH]) to measure community-level risk of adverse SRH outcomes based on social determinants of health (SDoH). We evaluated the validity of the LSI-SRH scores in predicting adverse SRH outcomes and the need for publicly funded services. The data were drawn from more than 200 publicly available SDoH and SRH measures, including availability and potential need for publicly supported family planning from the Guttmacher Institute. The sample included 72 999 Census tracts (99.9%) in the 50 states and the District of Columbia. We used random forest regression to predict the LSI-SRH scores; 42 indicators were retained in the final model. The LSI-SRH model explained 81% of variance in the composite SRH outcome, outperforming 3 general SDoH indices. LSI-SRH scores could be a useful for measuring community-level SRH risk and guiding site placement and resource allocation.
Enablers and barriers to implementing cholera interventions in Nigeria: a community-based system dynamics approach
Authors: Elimian Kelly , Diaconu Karin , Ansah John , King Carina , Dewa Ozius , Yennan Sebastian , Gandi Benjamin , Forsberg Birger Carl , Ihekweazu Chikwe , Alfvén Tobias
Published: July 2024

Nigeria accounts for a substantial cholera burden globally, particularly in its northeast region, where insurgency is persistent and widespread. We used participatory group model building workshops to explore enablers and barriers to implementing known cholera interventions, including water, sanitation and hygiene, surveillance and laboratory, case management, community engagement, oral cholera vaccine, and leadership and coordination, as well as exploring leverage points for interventions and collaboration. The study engaged key cholera stakeholders in the northeastern States of Adamawa and Bauchi, as well as national stakeholders in Abuja. Adamawa and Bauchi States’ group modes building participants comprised 49 community members and 43 healthcare providers, while the 23 national participants comprised government ministry, department and agency staff, and development partners. Data were analysed thematically and validated via consultation with selected participants. The study identified four overarching themes regarding the enablers and barriers to implementing cholera interventions: (1) political will, (2) health system resources and structures, (3) community trust and culture, and (4) spill-over effect of COVID-19. Specifically, inadequate political will exerts its effect directly (e.g. limited funding for prepositioning essential cholera supplies) or indirectly (e.g. overlapping policies) on implementing cholera interventions. The healthcare system structure (e.g. centralization of cholera management in a State capital) and limited surveillance tools weaken the capacity to implement cholera interventions. Community trust emerges as integral to strengthening the healthcare system’s resilience in mitigating the impacts of cholera outbreaks. Lastly, the spill-over effects of COVID-19 helped promote interventions similar to cholera (e.g. water, sanitation and hygiene) and directly enhanced political will. In conclusion, the study offers insights into the complex barriers and enablers to implementing cholera interventions in Nigeria’s cholera-endemic settings. Strong political commitment, strengthening the healthcare system, building community trust and an effective public health system can enhance the implementation of cholera interventions in Nigeria.
Is ATP a signaling regulator for postharvest chilling tolerance in fruits?
Authors: Sati Hansika , Oberoi Harinder Singh , Pareek Sunil
Published: July 2024

Low-temperature storage is used to extend the shelf life of fruits, but prolonged storage at temperatures below tolerable levels may cause postharvest chilling injury (PCI) in sensitive commodities. This review aims to highlight adenosine triphosphate (ATP) activation and the interplay of extracellular ATP (eATP) and intracellular ATP (iATP) in fruits and to find out its significance in mitigating PCI. Various pathways, such as the Embden–Meyerhof–Parnas pathway, the tricarboxylic acid cycle, the pentose phosphate pathway, the γ-aminobutyric acid shunt pathway, and the cytochrome pathway, are studied critically to elucidate their role in continuous ATP supply and maintaining the membrane fluidity and integrity. This review summarizes the treatments helpful in modulating energy metabolism in fruit. Additionally, this work provides insights into the energy status in attenuating chilling tolerance. Moreover, it states the potential of nicotinamide adenine dinucleotide in mitigating PCI. Furthermore, it discusses the role of eATP and its receptor DORN1 in mitigating chilling stress.
Economic Sanctions and Food Consumption: Evidence from Iranian Households
Authors: RezaeeDaryakenari Babak , Asadzade Peyman , Thies Cameron G
Published: July 2024

Abstracts

Despite scholarly consensus on the harmful effects of economic sanctions on civilians, there is little micro-level empirical research on how and to what extent economic sanctions affect the food consumption of citizens in sanctioned countries. One of the methodological barriers to studying the micro-level dynamics of sanctions is the limited availability of reliable data in sanctioned countries, which are often governed by authoritarian leaders. Our study leverages an original dataset comprising approximately 1 million observations related to the income and expenses of Iranian households from 1991 to 2021. We assess the impact of economic sanctions on individual food consumption at the national level and among distinct demographic segments. To illustrate how and to what extent international sanctions affected citizens' eating habits, we pay particular attention to 2012–2015 and 2018–2021, when Iran was subject to the most severe sanctions. Our findings demonstrate that while all segments of society feel the effects of economic coercion, low-income citizens' food consumption is more likely to deteriorate due to sanctions. Nonetheless, the geographical impact of sanctions presents a mixed picture, with rural and urban areas each exhibiting specific vulnerabilities to certain food items. We discuss the implications of our findings for sanctions policy and human rights.
CTC-177, a novel drug–Fc conjugate, shows promise as an immunoprophylactic agent against multidrug-resistant Gram-negative bacterial infections
Authors: Lovey Arianne , Lee Annie , Yu Allison , Krel Mila , Wang Mingming , Paderu Padmaja , Brady Thomas , Hough Grayson , Zhao Qiping , Balkovec James M , Perlin David S , Zhao Yanan
Published: July 2024

Background

The widespread emergence of antibiotic resistance including MDR in Gram-negative bacterial pathogens poses a critical challenge to the current antimicrobial armamentarium.

Objectives

To create a novel drug–Fc conjugate (DFC) that can be delivered at sustained and prolonged levels while simultaneously activating the host immune response to combat MDR Gram-negative infections.

Methods

The Cloudbreak™ platform was used to develop DFCs consisting of a targeting moiety (TM) (a polymyxin-derived dimer) attached via a non-cleavable linker to an effector moiety (EM) (the Fc domain of human IgG1). In vitro activities of the DFCs were assessed by MIC testing. Neutropenic mouse models of thigh infection, septicaemia and pneumonia were used to evaluate in vivo efficacy. Pharmacokinetics were evaluated in mice and cynomolgus monkeys.

Results

A single prophylactic dose of our lead DFC, CTC-177, resulted in significantly decreased bacterial burdens and reduced inflammation comparable to daily treatment with colistin in septicaemia and pneumonia mouse models. Furthermore, CTC-177 prophylaxis was able to restore colistin efficacy in colistin-resistant septicaemia, reducing bacterial burdens beyond the limit of detection. Finally, CTC-177 displayed a long terminal half-life of over 24 and 65 h in mice and cynomolgus monkeys, respectively.

Conclusions

These data support the continued development of Cloudbreak™ DFCs as broad-spectrum prophylactic agents against Gram-negative infections.
Development and initial validation of a data quality evaluation tool in obstetrics real-world data through HL7-FHIR interoperable Bayesian networks and expert rules
Authors: Coutinho-Almeida João , Saez Carlos , Correia Ricardo , Rodrigues Pedro Pereira
Published: July 2024

Background

The increasing prevalence of electronic health records (EHRs) in healthcare systems globally has underscored the importance of data quality for clinical decision-making and research, particularly in obstetrics. High-quality data is vital for an accurate representation of patient populations and to avoid erroneous healthcare decisions. However, existing studies have highlighted significant challenges in EHR data quality, necessitating innovative tools and methodologies for effective data quality assessment and improvement.

Objective

This article addresses the critical need for data quality evaluation in obstetrics by developing a novel tool. The tool utilizes Health Level 7 (HL7) Fast Healthcare Interoperable Resources (FHIR) standards in conjunction with Bayesian Networks and expert rules, offering a novel approach to assessing data quality in real-world obstetrics data.

Methods

A harmonized framework focusing on completeness, plausibility, and conformance underpins our methodology. We employed Bayesian networks for advanced probabilistic modeling, integrated outlier detection methods, and a rule-based system grounded in domain-specific knowledge. The development and validation of the tool were based on obstetrics data from 9 Portuguese hospitals, spanning the years 2019-2020.

Results

The developed tool demonstrated strong potential for identifying data quality issues in obstetrics EHRs. Bayesian networks used in the tool showed high performance for various features with area under the receiver operating characteristic curve (AUROC) between 75% and 97%. The tool’s infrastructure and interoperable format as a FHIR Application Programming Interface (API) enables a possible deployment of a real-time data quality assessment in obstetrics settings. Our initial assessments show promised, even when compared with physicians’ assessment of real records, the tool can reach AUROC of 88%, depending on the threshold defined.

Discussion

Our results also show that obstetrics clinical records are difficult to assess in terms of quality and assessments like ours could benefit from more categorical approaches of ranking between bad and good quality.

Conclusion

This study contributes significantly to the field of EHR data quality assessment, with a specific focus on obstetrics. The combination of HL7-FHIR interoperability, machine learning techniques, and expert knowledge presents a robust, adaptable solution to the challenges of healthcare data quality. Future research should explore tailored data quality evaluations for different healthcare contexts, as well as further validation of the tool capabilities, enhancing the tool’s utility across diverse medical domains.
Cholecalciferol and Ergocalciferol Replacement in Critically Injured Burn Patients: An Observational Cohort Study
Authors: Vanderwyk Kees , Young Sierra , Louie Erin , Wong Kristi , La Force Jessica , Alexander Molly , Sen Soman , Duby Jeremiah J
Published: July 2024

Vitamin D deficiency appears to be more prevalent than previously considered in the adult critically ill population, specifically burn-injured patients. No definitive regimen has been shown to restore vitamin D (25(OH)D) levels more effectively to therapeutic levels in the burn-injured population. The purpose of this study was to investigate the effects of either ergocalciferol (D2, 50 000 IU weekly) or cholecalciferol (D3, 6000 IU daily) in adults with burns ≥10% TBSA. This retrospective, observational study (2020-2022) included patients with vitamin D insufficiency (<30 ng/mL) who received replacement and monitoring with weekly vitamin D levels. Patients on dialysis or those with a hospital length of stay less than 2 weeks were excluded. Forty-five patients treated with ergocalciferol and 99 patients with cholecalciferol were included in the study. Patients treated with cholecalciferol were more likely to achieve 25(OH)D levels greater than 30 ng/mL compared to ergocalciferol over a 42-day period (HR 23.56, [95% CI, 12.57-44.16], P < .0001). A higher proportion of patients in the cholecalciferol group achieved vitamin D greater than 20 ng/mL (HR 6.37, [95% CI, 4.20-9.66], P < .0001). The adjusted hazard ratios (D3 vs D2) for achieving 25(OH)D levels > 30 ng/mL and > 20 ng/mL were and 23.94 (95% CI 5.09-427.6, P = .0019) and 7.32 (95% CI, 3.83-15.52, P < .0001) respectively, after controlling for TBSA and initial 25(OH)D. Cholecalciferol appears to be a more effective agent than ergocalciferol for correcting vitamin D deficiency and insufficiency in patients with burn injuries.
Extended flexible sigmoidoscopy using water exchange facilitates a complete colon examination without sedation in participants undergoing average risk colorectal cancer screening: results from a randomized trial
Authors: Bak Adrian , Parker Brent , Perini Rafael , Aulakh Arshbir , Oliveira Caio , Richardson Wes , Hirschkorn Peter , Sullivan Barry , Recsky Magda , Orlando Tess , Leung Felix
Published: July 2024

Lay Summary

Colon cancer is a leading cause of cancer deaths. Leading guidelines recommend flexible sigmoidoscopy (FS) every 10 years as a screening option for average-risk people. One area of progress involves a method called water exchange (WE). This is useful for cancer screening. We performed a randomized controlled trial on 90 average-risk individuals aged 50-74. They were tested with 2 methods: unsedated extended FS using either WE or the standard method of gas insufflation (GAS). Both methods showed similar success in examining the whole colon. More participants were satisfied with WE than GAS. Both groups felt little pain. Our study shows that modern methods, especially using WE, are effective and safe. They may remove the need for sedation, making it easier to include in large-scale screening programs.
Modified crayfish optimization algorithm with adaptive spiral elite greedy opposition-based learning and search-hide strategy for global optimization
Authors: Li Guanghui , Zhang Taihua , Tsai Chieh-Yuan , Lu Yao , Yang Jun , Yao Liguo
Published: July 2024

Crayfish optimization algorithm (COA) is a novel bionic metaheuristic algorithm with high convergence speed and solution accuracy. However, in some complex optimization problems and real application scenarios, the performance of COA is not satisfactory. In order to overcome the challenges encountered by COA, such as being stuck in the local optimal and insufficient search range, this paper proposes four improvement strategies: search-hide, adaptive spiral elite greedy opposition-based learning, competition-elimination, and chaos mutation. To evaluate the convergence accuracy, speed, and robustness of the modified crayfish optimization algorithm (MCOA), some simulation comparison experiments of 10 algorithms are conducted. Experimental results show that the MCOA achieved the minor Friedman test value in 23 test functions, CEC2014 and CEC2020, and achieved average superiority rates of 80.97%, 72.59%, and 71.11% in the WT, respectively. In addition, MCOA shows high applicability and progressiveness in five engineering problems in actual industrial field. Moreover, MCOA achieved 80% and 100% superiority rate against COA on CEC2020 and the fixed-dimension function of 23 benchmark test functions. Finally, MCOA owns better convergence and population diversity.
Asian Mus musculus: subspecies divergence, genetic diversity, and historical biogeography
Authors: Amir Afzali Yaser
Published: July 2024

The House Mouse, Mus musculus, is a model organism that has greatly contributed to evolutionary research. Despite its significance, there remain gaps in our understanding of its phylogeography and population genetic structure in Asian regions. This comprehensive study aims to elucidate the evolutionary history, genetic diversity, and distribution patterns of M. musculus. A diverse data set of 281 M. musculus samples was collected from across Asia, covering 101 localities in 19 countries. Phylogenetic analysis using Cytochrome b and D-Loop region unveiled well-supported lineages. These lineages correspond to: M. m. musculus, M. m. domesticus, M. m. castaneus, and M. m. bactrianus. Also, validity of M. m. bactrianus was questioned. The analysis suggests a monophyletic origin of these subspecies approximately 0.59 million years ago (Mya), followed by 2 main lineages—one consisting of M. m. domesticus (~0.59 Mya) and the other comprising M. m. castaneus, M. m. bactrianus, and M. m. musculus (~0.56 Mya). Genetic diversity varied among subspecies, with M. m. domesticus exhibiting the highest diversity due to its extensive global distribution and M. m. bactrianus exhibiting the lowest diversity due to restriction in southwest Asia. Pairwise genetic distances and Fst values confirmed significant genetic differentiation among the subspecies, underlining their historical isolation. Additionally, a Mantel test indicated that geographical distance played a pivotal role in shaping genetic differentiation. Demographic analysis revealed evidence of population expansions in M. m. domesticus, M. m. musculus, and M. m. castaneus, while M. m. bactrianus showed characteristics of neutral selection and genetic drift. Species distribution modeling, assessing both Current Conditions and the Last Glacial Maximum, indicated habitat shifts and losses during glacial periods, particularly in the eastern and northern regions of Asia. However, each subspecies displayed unique responses to climatic changes, reflecting their distinct ecological adaptations. Historical biogeography analysis pointed to complex origins and a network of dispersal and vicariance events that led to the contemporary distribution of subspecies. Deserts and xeric shrublands emerged as critical areas for diversification and speciation. This study contributes to our understanding of the phylogeography and population genetics of M. musculus in Asia, highlighting the significance of geographical factors and climatic fluctuations in shaping its evolutionary history and genetic diversity.
Utility of OLIG2 immunostaining in pediatric brain tumors with embryonal morphology
Authors: Alturkustani Murad , Walker Adam D , Castañeda Everardo A , Cotter Jennifer A
Published: July 2024

This study evaluates the diagnostic utility of OLIG2 immunohistochemistry for distinguishing between pediatric high-grade gliomas (pHGG) and embryonal tumors (ETs) of the CNS. Utilizing a retrospective pediatric cohort (1990-2021) of 56 CNS tumors, classified initially as primitive neuroectodermal tumors or CNS ET, we reclassified the cases based on WHO CNS5 criteria after comprehensive review and additional molecular testing that included next-generation sequencing and DNA methylation profiling. Our results indicate that OLIG2 immunopositivity was negative or minimal in a significant subset of pHGG cases (6 out of 11). At the same time, it showed diffuse expression in all cases of CNS neuroblastomas with FOXR2 activation (5/5), demonstrating its limited specificity in differentiating between pHGG and ET. Variable OLIG2 expression in other ETs, ATRT, and ETMR suggests the broader diagnostic implications of the marker. Furthermore, incidental findings of OLIG2 positivity in cases traditionally expected to be negative, such as medulloblastoma and ependymoma, introduce an additional layer of complexity. Together, these findings highlight the challenges of relying solely on OLIG2 immunostaining for accurate tumor classification in pediatric CNS neoplasms and underscore the importance of an integrated diagnostic approach.
The anti-rheumatoid arthritic activity of Artemisia ordosica Krasch. (traditional Chinese/Mongolian medicine) extract in collagen-induced arthritis in rats
Authors: Han Xiao-Yan , Han Ya-Ru , Xu Hao-Yu , Hu Ya-Wei , Yan Xiao-Yan , Du Guan-Hua , She Zhan-Fei , Xiao Bin
Published: July 2024

Objectives

Rheumatoid arthritis (RA) seriously affects the daily life of people. The whole plant of Artemisia ordosica Krasch. (AOK) has been used in folk medicine. This study aimed to investigate the in vivo anti-RA effects of AOK extract (AOKE) on collagen-induced arthritis in rats.

Methods

AOKE (400, 200, or 100 mg/kg) was administered orally to animals for 30 days. Body weight, paw swelling, arthritis index, thymus, and spleen indices, and pathological changes were assessed for effects of AOKE on RA. Furthermore, the inflammatory cytokines in rat serum were detected. In addition, the expressions of STAT3, Caspase-3, Galectin-3, and S100A9 in synovial tissue were researched using immunohistochemistry.

Key findings

The AOKE significantly reduced the arthritis indices, paw swelling, spleen, and thymus indices. Meanwhile, AOKE (400 mg/kg) decreased the levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, IL-17A, and increased the level of IL-10 in rat serum. Histopathological examination showed that AOKE reduced inflammatory cell infiltration and cartilage erosion. Then, AOKE decreased the expressions of STAT3, Galectin-3, S100A9, and increased the expression of Caspase-3.

Conclusion

AOKE had interesting anti-RA activity in rats, which deserved further research for the development and clinical use of this medicinal resource.
Association between triglyceride to HDL cholesterol ratio and a risk of diabetes mellitus: a systematic review and meta-analysis
Authors: Zhong Hongjing , Luo Laiming , Wang Xiaomei , Xiao Yao
Published: July 2024

Objective

The aim of this study was to investigate the link between the triglyceride-to-high–density lipoprotein cholesterol ratio (TG/HDL-C) and the occurrence of type 2 diabetes mellitus (T2DM).

Methods

PubMed, Embase, and Scopus databases were searched for cohort and case-control studies that reported on the link between TG/HDL-C and a risk of T2DM, with no restrictions on criteria used for the definition and categorization of low and high TG/HDL-C ratios.

Results

A total of 20 studies were included. There was considerable variability in terms of categorization of low or normal and higher TG/HDL-C ratio among the studies. Patients with high TG/HDL-C ratio had markedly higher risk of developing T2DM compared with patients with low or normal TG/HDL-C. Each unit increase in the ratio correlated with the increased risk of diabetes. Subgroup analysis based on sex showed an increased risk of T2DM in males and females with a high ratio compared with the group with a low/normal ratio.

Conclusion

Higher TG/HDL-C ratio correlates with increased risk of T2DM. Despite limitations, the study demonstrates a possible value of using TG/HDL-C ratio as a biomarker for diabetes risk.
Red blood cell alloimmunization in transfused patients with myelodysplastic syndromes: a retrospective study from northern China
Authors: Wang Li , Xu Xiaoxin , Wang Shichun , Li Ruidong , Zhang Pengyu
Published: July 2024

Objective

Alloimmunization against red blood cell (RBC) antigen is an important concern in myelodysplastic syndromes (MDSs) patients with chronic transfusion, causing potential risk for hemolytic reaction and limited supply of compatible blood. However, there is little data addressing RBC alloimmunization in this patient cohort among the Chinese population. This study aims to evaluate the incidence, specificity of antibodies, and RBC units transfused before antibody formation and its significance in a population of patients consistently receiving RhD-matched RBC units.

Methods

We retrospectively reviewed the transfusion and clinical information of all transfused patients with MDS enrolled in our hospital from 2012 to 2022. The cumulative incidence of alloimmunization was analyzed by a Kaplan-Meier plot. Alloimmunization incidence was compared based on different transfused RBC units using the log-rank test.

Results

A total of 103 patients with MDS were included in this study; alloantibody formed in 8 (7.8%) patients. Before reaching 32 RBC units, 87.5% of the alloimmunized patients had developed their alloantibodies. All but 1 of the alloantibodies developed were antibodies to Rh antigens. The RBC transfusion intensity and frequency were significantly higher following alloimmunization in the alloimmunized patients (P = .008, P = .008, respectively).

Conclusion

The antibodies detected mostly involve the Rh system among MDS patients in China. The alloimmunization tended to occur early prior to reaching 32 RBC units in patients with MDS. Rh antigen matching should be considered early in the patient’s transfusion history and completed before receiving 32 RBC units.
Influence of the Type of Physical Training on the Physical Fitness of Army Cadets
Authors: Pascoa Mauro Alexandre , Langer Raquel David , Borges Juliano Henrique , Cirolini Wagner Xavier , Guerra-Júnior Gil , Gonçalves Ezequiel Moreira
Published: July 2024

Introduction

Military Physical Training programs represent a constant challenge for the Armed Forces to improve body composition indices and physical fitness levels. This study aimed to verify the influence of the type of training on the physical fitness and body composition of army cadets, using 2 strategies: a sports program (Athletes group) and conventional physical training (Traditional group).

Materials and Methods

This study involved new entrant male cadets who were selected for the Athletes group (n = 243, 19.08 ± 1.23 years) or the Traditional group (n = 356, 18.89 ± 0.97 years), with assessments occurring before and after the period of training (31.4 ± 3.9 weeks). Dual-energy X-ray absorptiometry was used to measure the bone mineral content (BMC), fat mass (FM), percentage of fat mass (%FM), and lean soft tissue (LST). The physical tests evaluated the 3,000 m run (RUN), 50 m swim (SWIM), pull-ups (PULL) on the horizontal bar, push-ups (PUSH) on the ground, and abdominal flexion (SITUP).

Results

Time × group interaction effects were observed for BMC (P < .001), LST (P < .023), RUN (P < .001), PULL (P = .006), PUSH (P < .001), SITUP (P = .007), and SWIM (P < .001). A significant effect of time was noted for all variables analyzed in both groups, except %FM. The Athletes group achieved better results in body composition and in PULL, PUSH, RUN, and SWIM at baseline and after the training period. The Traditional group demonstrated higher relative changes (%) after the training period in the LST (P = .001), PULL (P < .001), PUSH (P < .001), SITUP (P < .004), and SWIM (P < .001) compared to the Athletes group.

Conclusion

Both physical training programs improved body composition and physical performance.
Depletion of CpG dinucleotides in bacterial genomes may represent an adaptation to high temperatures
Authors: Forni Diego , Pozzoli Uberto , Mozzi Alessandra , Cagliani Rachele , Sironi Manuela
Published: July 2024

Dinucleotide biases have been widely investigated in the genomes of eukaryotes and viruses, but not in bacteria. We assembled a dataset of bacterial genomes (>15 000), which are representative of the genetic diversity in the kingdom Eubacteria, and we analyzed dinucleotide biases in relation to different traits. We found that TpA dinucleotides are the most depleted and that CpG dinucleotides show the widest dispersion. The abundances of both dinucleotides vary with genomic G + C content and show a very strong phylogenetic signal. After accounting for G + C content and phylogenetic inertia, we analyzed different bacterial lifestyle traits. We found that temperature preferences associate with the abundance of CpG dinucleotides, with thermophiles/hyperthemophiles being particularly depleted. Conversely, the TpA dinucleotide displays a bias that only depends on genomic G + C composition. Using predictions of intrinsic cyclizability we also show that CpG depletion may associate with higher DNA bendability in both thermophiles/hyperthermophiles and mesophiles, and that the former are predicted to have significantly more flexible genomes than the latter. We suggest that higher bendability is advantageous at high temperatures because it facilitates DNA positive supercoiling and that, through modulation of DNA mechanical properties, local or global CpG depletion controls genome organization, most likely not only in bacteria.
Mental health and employment outcomes in working-age US adults, 2010–2019
Authors: Jou J , Hicks A , Johnson P J
Published: July 2024

Background

Individuals with severe mental illness experience greater unemployment and barriers to workforce re-entry. However, less is known about additional indicators of employment stability for individuals across mental illness severity.

Aims

This study aims to examine associations between mental illness severity, use and adequacy of mental health treatment, and indicators of employment stability.

Methods

In this repeated cross-sectional study, 2010–2019 data from the U.S. National Survey of Drug Use and Health were used to construct multivariate logistic regression models predicting the odds of part-time employment, past-year work interruption, number of past-year employers, and past-month health-related work absence by mental illness severity and adequacy of mental health treatment.

Results

Compared to individuals with no mental illness, those with any and severe mental illness had significantly higher odds of part-time employment (adjusted odds ratios [AORs] = 1.51 and 2.16, 95% confidence intervals [CIs] 1.4–1.6 and 2.0–2.3), multiple past-year employers (AORs = 1.78 and 2.34, CIs 1.7–1.9 and 2.1–2.6), past-year work interruption (AORs = 1.69 and 2.20, CIs 1.6–1.8 and 2.1–2.4), and >7 days of past-month work absence (AORs = 2.51 and 3.82, CIs 2.3–2.8 and 3.3–4.5). Among respondents with mental illness, perceived inadequacy of mental treatment predicted higher odds of all adverse employment outcomes.

Conclusions

Compared to those with no mental illness, individuals with mental illness of any severity have higher odds of employment instability. Policy and programmatic support aimed at addressing the needs of individuals with mental illness, including access to adequate mental health treatment, are needed to facilitate continued, competitive employment.
Immune-related encephalitis after immune checkpoint inhibitor therapy
Authors: Buckley Monica W , Balaji Warner Aanika , Brahmer Julie , Cappelli Laura C , Sharfman William H , Fuchs Ephraim , Kang Hyunseok , Forde Patrick M , Gladstone Douglas E , Ambinder Richard , Kelly Ronan J , Lipson Evan J , Gojo Ivana , Lee Edward J , Johnson Tory P , Saidha Shiv , Llinas Rafael , Ostrow Lyle W , Naidoo Jarushka , Probasco John C
Published: July 2024

Background

Immune checkpoint inhibitors (ICI) have revolutionized cancer treatment but can trigger immune-related encephalitis. We report one of the largest case series of patients with immune-related encephalitis and review of the literature.

Methods

Retrospective series of patients with immune-related encephalitis and literature review.

Results

Fourteen patients with cancer treated with ICI (50% combination therapy) developed immune-related encephalitis. Diagnostic testing revealed cerebral spinal fluid (CSF) lymphocytic pleocytosis (85%) and elevated protein (69%), abnormal brain magnetic resonance imaging(MRI) (33%) or brain FDG-PET (25%), electroencephalogram (EEG) abnormalities (30%), and autoantibodies (31%). Encephalitis treatment included: corticosteroids (86%), intravenous immunoglobulin (IVIg) (36%), plasmapheresis (7%), and rituximab (29%). There were no deaths and 12 patients had significant recovery, although long-term complications were observed. All patients discontinued ICI. Longitudinal follow-up demonstrated anti-cancer response to ICI at 3 months (85%) and 6 months post-ICI initiation (77%). A literature review identified 132 patients with immune-related encephalitis. Most were treated with PD-1 inhibitors (18% combination). Common abnormalities included elevated CSF protein (84%) or pleocytosis (77%), abnormal brain MRI (65%), or autoantibodies (47%). Nearly all were treated with corticosteroids, many required additional therapy with IVIg (26%) or rituximab (12%). Most patients had clinical improvement (81%) but a minority (10%) had a clinical relapse after completing corticosteroid taper. ICIs were resumed in 7 patients (5%), with relapse in 3.

Conclusions and relevance

Immune-related encephalitis is treatable and improves with corticosteroids in most cases but may require additional immunosuppression. Re-emergence of encephalitis is rare and does not typically result in adverse outcomes, and this should be considered in neurological immune-related adverse event management guidelines.
Brood translocation increases post-release recruitment and promotes population restoration of Centrocercus urophasianus (Greater Sage-Grouse)
Authors: Meyerpeter Mary B , Coates Peter S , Mathews Steven R , Lazenby Kade D , Prochazka Brian G , Dahlgren David K , Delehanty David J
Published: July 2024

Wildlife managers translocate Centrocercus urophasianus (Greater Sage-Grouse) to augment small populations, but translocated C. urophasianus often fail to reproduce post-release, hampering conservation objectives. We performed 2 C. urophasianus translocations in California and North Dakota from 2017 to 2020 using 2 methods at both sites: an established method of translocating females prior to nesting (i.e., a pre-nesting translocation), and a novel method wherein females were translocated with chicks after successfully hatching nests in source populations (i.e., a brood translocation). We radio-marked and monitored 135 translocated females and 284 source population females and used count data from leks in recipient and source populations to evaluate each method. Using an integrated population model (IPM), we estimated demographic parameters, including recruitment, by females translocated with each method. We estimated the finite rate of change in abundance (λ^) in recipient and source populations given multiple simulated translocation strategies using each method and evaluated them using a cost–benefit metric (i.e., a ratio of the simulated change in abundance at recipient and source sites). We found that recruitment in recipient populations was substantially higher when brood translocations were employed compared to when pre-nesting translocations were employed. Most females translocated pre-nesting forewent reproduction entirely, whereas most females translocated with their broods successfully reared offspring in recipient populations. A per capita comparison revealed that brood translocations resulted in λ^ that were 11–30% greater than pre-nesting translocations, but also revealed that the removal of brood-rearing females from source populations resulted in larger reductions in λ^ when compared with prenesting translocations. However, reductions in λ^ were small and the estimated cost–benefit metrics indicated that translocation of females with broods was a more effective method at spurring growth in recipient populations while minimizing impacts to source populations.
Pathways versus incentives: climate activism to climate aligned portfolio management
Authors: Roston Marc , Maire Julien , Seiger Alicia , Heller Thomas
Published: July 2024

Climate activists have pressured financial institutions to accelerate global decarbonization by aligning portfolios with Paris Agreement transition pathways and targets. We trace the progression from the Intergovernmental Panel on Climate Change (IPCC) and International Energy Agency (IEA) scenarios to corporate target setting via the Science-Based Targets Initiative (SBTi) and financial institutions’ portfolio alignment methods. We identify three critical weaknesses that will limit efficacy: the absence of rigorous GHG emissions accounting, reliance on centrally planned pathways, and tension with fiduciary duties. These issues undermine the theory of change behind activist and financial sector efforts. As an alternative, we propose Emissions Liability Management (ELM) which treats emissions as liabilities matched by removal assets, directing firms to maintain emissions solvency. Rather than chasing pathways, ELM provides incentives for emissions reductions and removals consistent with shareholder obligations derived from market prices. By reframing climate action in financial terms, ELM can engage financial markets as agents of change in a manner grounded in sound economics.
State, crime, and violence in Mexico, 1920–2000: Arbiters of impunity, agents of coercion
Authors: Long Tom , Smith Benjamin T
Published: July 2024

The nature of the relationships among the Mexican state, organized crime and violence is much debated. Many accounts of state formation suggest that states increase their extractive and coercive capabilities in tandem: they monopolize the provision of ‘protection’ in Charles Tilly’s famous analogy. However, when unconsolidated states confront lucrative, illicit markets, state-building takes an unexpected turn. We argue that these states, like post-revolutionary Mexico, develop not as one protection racket, but as two. While the orthodox or licit protection racket collects tax from businesses and individuals in return for the protection of property and persons, the illicit protection racket (like that of a traditional mafia organization) collects extortion money from criminal groups in return for protection from prosecution. Though we use the case study of Mexico to tease out these conclusions, we argue that they can just as easily be applied to other states with weak tax bases, limited geographical reach, and profitable illicit markets.
From Self-Management to Shared-Management: A Relational Approach for Equitable Chronic Care
Authors: Stutzin Donoso Francisca
Published: July 2024

Life with chronic disease and chronic care is hard and people who live in disadvantage may lack the freedom to prioritise their care because of increased competing demands. This paper proposes that shifting the goals of chronic care from self-management support to a shared-management approach can help improve wellbeing and health outcomes across social groups. This work draws on a qualitative exploration of the lived experience of chronic disease and an applied ethical analysis of the reproduction of disadvantages within chronic care. The qualitative results further specify respectful and collaborative patient-healthcare professional relationships; autonomy-supportive interventions; and continuity of care to face the complexity of chronicity in a phenomenological sense—a paradoxical experience of long duration that comprises the disease’s presence in the absence of its manifestation. The ethical analysis draws on performativity; autonomy and decision-making; and responsibility, which constitute the theoretical foundation for shared-management. This approach contributes to advance current normative thinking for health justice and outlines practical steps for its clinical implementation in the delivery of chronic care.
Aberrant outputs of cerebellar nuclei and targeted rescue of social deficits in an autism mouse model
Authors: Cai Xin-Yu , Wang Xin-Tai , Guo Jing-Wen , Xu Fang-Xiao , Ma Kuang-Yi , Wang Zhao-Xiang , Zhao Yue , Xie Wei , Schonewille Martijn , De Zeeuw Chris , Chen Wei , Shen Ying
Published: July 2024

The cerebellum is heavily connected with other brain regions, sub-serving not only motor but also nonmotor functions. Genetic mutations leading to cerebellar dysfunction are associated with mental diseases, but cerebellar outputs have not been systematically studied in this context. Here, we present three dimensional distributions of 50,168 target neurons of cerebellar nuclei (CN) from wild-type mice and Nlgn3R451C mutant mice, a mouse model for autism. Our results derived from 36 target nuclei show that the projections from CN to thalamus, midbrain and brainstem are differentially affected by Nlgn3R451C mutation. Importantly, Nlgn3R451C mutation altered the innervation power of CN→zona incerta (ZI) pathway, and chemogenetic inhibition of a neuronal subpopulation in the ZI that receives inputs from the CN rescues social defects in Nlgn3R451C mice. Our study highlights potential role of cerebellar outputs in the pathogenesis of autism and provides potential new therapeutic strategy for this disease.
Navigating Conflicting Incentives: Discursive Strategies of Political Parties in Germany’s Cooperative Federalism
Authors: Souris Antonios , Kropp Sabine , Nguyen Christoph
Published: July 2024

Federal systems create complex institutional settings that foster and encourage cooperation while also enabling self-serving and even opportunistic political behavior. Focusing on parliamentary discourses, we argue that political parties can navigate these conflicting incentives skillfully, employing a set of five distinct discursive strategies that integrate both the need for cooperation and the possibility of self-interest. Leveraging a qualitative content analysis of 212 German parliamentary debates and 4,524 manually coded statements, we demonstrate that the use of these discursive strategies is shaped by parties’ level of integration into federal institutions. The data reveal that parties which are more strongly involved in intergovernmental bodies uphold a more cooperative discourse, while refraining from confrontational strategies toward federal institutions and actors. We also find that the linkage between the vertically integrated party system, which incentivizes co-partisans to stick together across levels and constituent units, and multiparty coalition governments, counteracts federal blame games.
A quadratic Vinogradov mean value theorem in finite fields
Authors: Mansfield Sam , Mudgal Akshat
Published: July 2024

Let p be a prime, let $s \geq 3$ be a natural number and let $A \subseteq \mathbb{F}_p$ be a non-empty set satisfying $|A| \ll p^{1/2}$. Denoting $J_s(A)$ to be the number of solutions to the system of equations $$ \sum_{i=1}^{s} (x_i - x_{i+s}) = \sum_{i=1}^{s} (x_i^2 - x_{i+s}^2) = 0, $$ with $x_1, \dots, x_{2s} \in A$, our main result implies that $$ J_s(A) \ll |A|^{2s - 2 - 1/9}. $$ This can be seen as a finite field analogue of the quadratic Vinogradov mean value theorem. Our techniques involve a variety of combinatorial geometric estimates, including studying incidences between Cartesian products A × A and a special family of modular hyperbolae.