bluuebunny/crossref_metadata_2025 huggingface dataset:
Mitonuclear compatibility is maintained despite relaxed selection on male mitochondrial DNA in bivalves with doubly uniparental inheritance
Authors: Smith Chase H , Mejia-Trujillo Raquel , Havird Justin C
Published: July 2024

Mitonuclear coevolution is common in eukaryotes, but bivalve lineages that have doubly uniparental inheritance (DUI) of mitochondria may be an interesting example. In this system, females transmit mtDNA (F mtDNA) to all offspring, while males transmit a different mtDNA (M mtDNA) solely to their sons. Molecular evolution and functional data suggest oxidative phosphorylation (OXPHOS) genes encoded in M mtDNA evolve under relaxed selection due to their function being limited to sperm only (vs. all other tissues for F mtDNA). This has led to the hypothesis that mitonuclear coevolution is less important for M mtDNA. Here, we use comparative phylogenetics, transcriptomics, and proteomics to understand mitonuclear interactions in DUI bivalves. We found nuclear OXPHOS proteins coevolve and maintain compatibility similarly with both F and M mtDNA OXPHOS proteins. Mitochondrial recombination did not influence mitonuclear compatibility and nuclear-encoded OXPHOS genes were not upregulated in tissues with M mtDNA to offset dysfunction. Our results support that selection maintains mitonuclear compatibility with F and M mtDNA despite relaxed selection on M mtDNA. Strict sperm transmission, lower effective population size, and higher mutation rates may explain the evolution of M mtDNA. Our study highlights that mitonuclear coevolution and compatibility may be broad features of eukaryotes.
Detailed validation of large-scale Sentinel-2-based forest disturbance maps across Germany
Authors: Reinosch Eike , Backa Julian , Adler Petra , Deutscher Janik , Eisnecker Philipp , Hoffmann Karina , Langner Niklas , Puhm Martin , Rüetschi Marius , Straub Christoph , Waser Lars T , Wiesehahn Jens , Oehmichen Katja
Published: July 2024

Monitoring forest areas with satellite data has become a vital tool to derive information on disturbances in European forests at large scales. An extensive validation of generated maps is essential to evaluate their potential and limitations in detecting various disturbance patterns. Here, we present the validation results of forest disturbance maps generated for four study areas in Germany using Sentinel-2 data from 2018 to 2022. We apply a time series filtering method to map annual forest disturbances larger than 0.1 ha based on spectral clustering and annual change magnitude. The presented method is part of a research study to design a precursor for a national German forest disturbance monitoring system. In this context, annual forest change areas are used to estimate affected timber volume and related economic losses. To better understand the thematic accuracies and the reliability of the area estimates, we performed an independent and extensive validation of the annual product using 20 validation sets embedded in our four study areas and comprising a total of 11 019 sample points. The collected reference datasets are based on an expert interpretation of high-resolution aerial and satellite imagery, including information on the dominant tree species, disturbance cause, and disturbance severity level. Our forest disturbance map achieves an overall accuracy of 99.1 ± 0.1% in separating disturbed from undisturbed forest. This is mainly indicative of the accuracy for undisturbed forest, as that class covers 97.2% of the total forest area. For the disturbed forest class, the user’s accuracy is 84.4 ± 2.0% and producer’s accuracy is 85.1 ± 3.4% for 2018 to 2022. The similar user’s and producer’s accuracies indicate that the total disturbance area is estimated accurately. However, for 2022, we observe an overestimation of the total disturbance extent, which we attribute to the high drought stress in that year leading to false detections, especially around forest edges. The accuracy varies widely among validation sets and seems related to the disturbance cause, the disturbance severity, and the disturbance patch size. User’s accuracies range from 31.0 ± 8.4% to 98.8 ± 1.3%, while producer’s accuracies range from 60.5 ± 37.3% to 100.0 ± 0.0% across the validation sets. These variations highlight that the accuracy of a single local validation set is not representative of a region with a large diversity of disturbance patterns, such as Germany. This emphasizes the need to assess the accuracies of large-scale disturbance products in as many different study areas as possible, to cover different patch sizes, disturbance severities, and disturbance causes.
Impact of tRNA-induced proline-to-serine mistranslation on the transcriptome of Drosophila melanogaster
Authors: Isaacson Joshua R , Berg Matthew D , Yeung William , Villén Judit , Brandl Christopher J , Moehring Amanda J
Published: July 2024

Mistranslation is the misincorporation of an amino acid into a polypeptide. Mistranslation has diverse effects on multicellular eukaryotes and is implicated in several human diseases. In Drosophila melanogaster, a serine transfer RNA (tRNA) that misincorporates serine at proline codons (P→S) affects male and female flies differently. The mechanisms behind this discrepancy are currently unknown. Here, we compare the transcriptional response of male and female flies to P→S mistranslation to identify genes and cellular processes that underlie sex-specific differences. Both males and females downregulate genes associated with various metabolic processes in response to P→S mistranslation. Males downregulate genes associated with extracellular matrix organization and response to negative stimuli such as wounding, whereas females downregulate aerobic respiration and ATP synthesis genes. Both sexes upregulate genes associated with gametogenesis, but females also upregulate cell cycle and DNA repair genes. These observed differences in the transcriptional response of male and female flies to P→S mistranslation have important implications for the sex-specific impact of mistranslation on disease and tRNA therapeutics.
Gapless genome assembly and epigenetic profiles reveal gene regulation of whole-genome triplication in lettuce
Authors: Cao Shuai , Sawettalake Nunchanoke , Shen Lisha
Published: July 2024

Background

Lettuce, an important member of the Asteraceae family, is a globally cultivated cash vegetable crop. With a highly complex genome (∼2.5 Gb; 2n = 18) rich in repeat sequences, current lettuce reference genomes exhibit thousands of gaps, impeding a comprehensive understanding of the lettuce genome.

Findings

Here, we present a near-complete gapless reference genome for cutting lettuce with high transformability, using long-read PacBio HiFi and Nanopore sequencing data. In comparison to stem lettuce genome, we identify 127,681 structural variations (SVs, present in 0.41 Gb of sequence), reflecting the divergence of leafy and stem lettuce. Interestingly, these SVs are related to transposons and DNA methylation states. Furthermore, we identify 4,612 whole-genome triplication genes exhibiting high expression levels associated with low DNA methylation levels and high N6-methyladenosine RNA modifications. DNA methylation changes are also associated with activation of genes involved in callus formation.

Conclusions

Our gapless lettuce genome assembly, an unprecedented achievement in the Asteraceae family, establishes a solid foundation for functional genomics, epigenomics, and crop breeding and sheds new light on understanding the complexity of gene regulation associated with the dynamics of DNA and RNA epigenetics in genome evolution.
Malignant passions and carnal desires: rape in long eighteenth-century Scotland
Authors: Barclay Katie
Published: July 2024

Histories of lust have often been separated from that of rape, due to a concern with naturalizing male violence against women. However, ideas about lust have been significant at various historical moments in framing understandings of sexual violence and masculinity. This article explores how ideas of disorderly emotion, including lust, shaped the prosecution of rape in eighteenth-century Scotland. It highlights that placing legal accounts of rape within a framework of the ‘emotional ethics’ that guided early modern society helps to explain the low prosecution rates for rape in contexts where sexual violence was nonetheless considered sinful.
Investigating microbial and environmental drivers of nitrification in alkaline forest soil
Authors: Poghosyan Lianna , Lehtovirta-Morley Laura E
Published: July 2024

Ammonia oxidation is a key step in the biogeochemical cycling of nitrogen, and soils are important ecosystems for nitrogen flux globally. Approximately 25% of the world’s soils are alkaline. While nitrification has been studied more extensively in agricultural alkaline soils, less is known about natural, unfertilized alkaline soils. In this study, microorganisms responsible for ammonia oxidation and several environmental factors (season, temperature, ammonia concentration, and moisture content) known to affect nitrification were studied in an alkaline forest soil with a pH ranging from 8.36 to 8.77. Ammonia-oxidizing bacteria (AOB), ammonia-oxidizing archaea, and comammox were present, and AOB belonging to genera Nitrosospira and Nitrosomonas, originally comprising <0.01% of the total bacterial community, responded rapidly to ammonia addition to the soil. No significant difference was observed in nitrification rates between seasons, but there was a significant difference between in situ field nitrification rates and rates in laboratory microcosms. Surprisingly, nitrification took place under many of the tested conditions, but there was no detectable increase in the abundance of any recognizable group of ammonia oxidizers. This study raises questions about the role of low-abundance microorganisms in microbial processes and of situations where zero or very low microbial growth coincides with metabolic activity. In addition, this study provides insights into nitrification in unfertilized alkaline soil and supports previous studies, which found that AOB play an important role in alkaline soils supplemented with ammonia, including agricultural ecosystems.
Proteomes of native and non-native symbionts reveal responses underpinning host-symbiont specificity in the cnidarian–dinoflagellate symbiosis
Authors: Mashini Amir , Oakley Clinton A , Peng Lifeng , Grossman Arthur R , Weis Virginia M , Davy Simon K
Published: July 2024

Cellular mechanisms responsible for the regulation of nutrient exchange, immune responses, and symbiont population growth in the cnidarian–dinoflagellate symbiosis are poorly resolved, particularly with respect to the dinoflagellate symbiont. Here, we characterized proteomic changes in the native symbiont Breviolum minutum during colonization of its host sea anemone Exaiptasia diaphana (“Aiptasia”). We also compared the proteome of this native symbiont in the established symbiotic state with that of a non-native symbiont, Durusdinium trenchii. The onset of symbiosis between Aiptasia and Breviolum minutum increased the accumulation of symbiont proteins associated with the acquisition of inorganic carbon and photosynthesis, nitrogen metabolism, micro- and macronutrient starvation, suppression of host immune responses, tolerance to low pH, and management of oxidative stress. Such responses are consistent with a functional, persistent symbiosis. In contrast, D. trenchii predominantly showed elevated levels of immunosuppressive proteins, consistent with the view that this symbiont is an opportunist that forms a less beneficial, less well-integrated symbiosis with this model anemone. By adding symbiont analysis to the already known responses of the host proteome, our results provide a more holistic view of cellular processes that determine host-symbiont specificity and how differences in symbiont partners (i.e. native versus non-native symbionts) may impact the fitness of the cnidarian–dinoflagellate symbiosis.
Social media use and mental health among older adults with multimorbidity: the role of self-care efficacy
Authors: Nie Zuoting , Gao Shiying , Chen Long , Yang Rumei , Edelman Linda S , Sward Katherine A , Jiang Yun , Demiris George
Published: July 2024

Objectives

To describe the prevalence and trends in the use of social media over time and explore whether social media use is related to better self-care efficacy and thus related to better mental health among United States older adults with multimorbidity.

Materials and Methods

Respondents aged 65 years+ and having 2 or more chronic conditions from the 2017-2020 Health Information National Trends Survey were analyzed (N = 3341) using weighted descriptive and logistic regression analyses.

Results

Overall, 48% (n = 1674) of older adults with multimorbidity used social media and there was a linear trend in use over time, increasing from 41.1% in 2017 to 46.5% in 2018, and then further up to 51.7% in 2019, and 54.0% in 2020. Users were often younger, married/partnered, and non-Hispanic White with high education and income. Social media use was associated with better self-care efficacy that was further related to better mental health, indicating a significant mediation effect of self-care efficacy in the relationship between social media use and mental health.

Discussion

Although older adults with multimorbidity are a fast-growing population using social media for health, significant demographic disparities exist. While social media use is promising in improving self-care efficacy and thus mental health, relying on social media for the management of multimorbidity might be potentially harmful to those who are not only affected by multimorbidity but also socially disadvantaged (eg, non-White with lower education).

Conclusion

Great effort is needed to address the demographic disparity and ensure health equity when using social media for patient care.
The action of coenzyme B12-dependent diol dehydratase on 3,3,3-trifluoro-1,2-propanediol results in elimination of all the fluorides with formation of acetaldehyde
Authors: Mori Koichi , Golding Bernard T , Toraya Tetsuo
Published: July 2024

3,3,3-Trifluoro-1,2-propanediol undergoes complete defluorination in two distinct steps: first, the conversion into 3,3,3-trifluoropropionaldehyde catalyzed by adenosylcobalamin (coenzyme B12)-dependent diol dehydratase; second, non-enzymatic elimination of all three fluorides from this aldehyde to afford malonic semialdehyde (3-oxopropanoic acid), which is decarboxylated to acetaldehyde. Diol dehydratase accepts 3,3,3-trifluoro-1,2-propanediol as a relatively poor substrate, albeit without significant mechanism-based inactivation of the enzyme during catalysis. Optical and electron paramagnetic resonance (EPR) spectra revealed the steady-state formation of cob(II)alamin and a substrate-derived intermediate organic radical (3,3,3-trifluoro-1,2-dihydroxyprop-1-yl). The coenzyme undergoes Co–C bond homolysis initiating a sequence of reaction by the generally accepted pathway via intermediate radicals. However, the greater steric size of trifluoromethyl and especially its negative impact on the stability of an adjacent radical centre compared to a methyl group has implications for the mechanism of the diol dehydratase reaction. Nevertheless, 3,3,3-trifluoropropionaldehyde is formed by the normal diol dehydratase pathway, but then undergoes non-enzymatic conversion into acetaldehyde, probably via 3,3-difluoropropenal and malonic semialdehyde.
Hypophosphatemic rickets and short stature
Authors: Davis Kelli , Imel Erik A , Kelley Jennifer
Published: July 2024

Vignette

An 18-month-old male presented with gross motor delay and poor growth (weight z-score −2.21, length z-score −4.26). Radiographs showed metaphyseal irregularities suggesting metaphyseal dysplasia and sagittal craniosynostosis. Biochemical evaluation supported hypophosphatemic rickets [serum phosphorus 2.3 mg/dL (reference range (RR) 4.3–6.8), alkaline phosphatase 754 unit/L (RR 156–369)] due to renal phosphate wasting (TmP/GFR 4.3 mg/dL, normal for age 4.3-6.8), with C-terminal fibroblast growth factor 23 (FGF23) 125 RU/mL (>90 during hypophosphatemia suggests FGF23-mediated hypophosphatemia). Treatment was initiated with calcitriol and phosphate. Genetic analysis showed a pathogenic variant of FGF23: c.527G > A (p.Arg176Gln) indicative of autosomal dominant hypophosphatemic rickets (ADHR). Consistent with reports linking iron deficiency with the ADHR phenotype, low ferritin was detected. Following normalization of ferritin level (41 ng/mL) with oral ferrous sulfate replacement, biochemical improvement was demonstrated (FGF23 69 RU/mL, phosphorus 5.0 mg/dL and alkaline phosphatase 228 unit/L). Calcitriol and phosphate were discontinued. Three years later, the patient demonstrated improved developmental milestones, linear growth (length Z-score −2.01), radiographic normalization of metaphyses, and stabilization of craniosynostosis. While the most common cause of hypophosphatemic rickets is X-linked hypophosphatemia, other etiologies should be considered as treatment differs. In ADHR, normalization of iron leads to biochemical and clinical improvement.
Public Bioethics Amidst a Pluralist People: A Project of Presumption, Despair, or Hope?
Authors: Parviz Benjamin
Published: July 2024

Michael Lamb’s recent book A Commonwealth of Hope presents an opportunity for bioethicists to engage in critical self-evaluation in order to consider anew why and how to engage difficult bioethical problems and questions with those who maintain diverse moral and metaphysical perspectives. Drawing on an account of the virtue of hope from Augustine of Hippo, Lamb develops a political theory in which hope provides common ground for political cooperation between diverse citizens of a commonwealth. The purpose of this introduction is to sketch out a framework by which to assess and evaluate whether bioethics demonstrates hope. This article provides a summary description of Lamb’s presentation of Augustine’s virtue of hope and his concept of politics. Then it considers implications of Lamb’s politics of hope for bioethics, identifying three features of hopeful bioethics, with which bioethicists can engage in self-reflection and evaluation.
Assessment of efficacy of chrysin in diabetes-associated cardiac complications in chick embryo and murine model
Authors: Das Joyani , Roy Sarkar Suparna , Das Ankita , Barui Ananya , Mitra Mazumder Papiya
Published: July 2024

Objectives

Patients with type 2 diabetes or prolonged diabetic condition are webbed into cardiac complications. This study aimed to ascertain the utility of chick embryo as an alternative to the mammalian model for type 2 diabetes-induced cardiac complications and chrysin as a protective agent.

Methods

Diabetes was activated in ovo model (chick embryo) using glucose along with β-hydroxybutyric acid. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, Alamar, and Kenacid blue assay were used to compare with chrysin-administered group. Blood glucose level, total cholesterol, triglyceride, and high-density lipoprotein were considered as endpoints. Diabetes was induced in Wistar albino rats by administering a high-fat diet and a subdued dose of streptozotocin (35 mg/kg, b.w). Percentage of glycated hemoglobin, creatinine kinase-MB, tumor necrosis factor-α, and C-reactive protein were evaluated and compared with chrysin administered group.

Key findings

Chrysin treatment improved elevated blood glucose levels and dyslipidemia in a diabetic group of whole embryos. Condensed cellular growth and protein content as well as enhanced cytotoxicity in ovo were shielded by chrysin. Chrysin reduced cardiac and inflammatory markers in diabetic rats and provided cellular protection to damage the heart of diabetic rats.

Conclusion

The protective action of chrysin in ovo model induced a secondary complication associated with diabetes, evidenced that the ovo model is an effective alternative in curtailing higher animal use in scientific research.
Successful management of locally advanced cervical cancer via total pelvic exenteration following neoadjuvant chemotherapy
Authors: Endo Yuta , Soeda Shu , Yoshimoto Yuki , Todate Yukitoshi , Hashimoto Tatsuru , Furukawa Shigenori , Teranishi Yasushi , Fujimori Keiya
Published: July 2024

Stage IVA cervical cancer is a tumor that invades the mucosa of the bladder or rectum without distant metastasis and is difficult to treat, and concurrent chemoradiotherapy is recommended. Although radical surgery following neoadjuvant chemotherapy is a treatment option for stage IVA cervical cancer, the evidence is limited. A 51-year-old woman with bulky cervical cancer and rectal invasion was referred to our hospital. Paclitaxel and cisplatin were administered as neoadjuvant chemotherapies. After two cycles of chemotherapy, the tumor size decreased markedly. Total pelvic exenteration was performed, and a complete resection was achieved. Four cycles of paclitaxel and cisplatin were administered postoperatively. Thirty-three months after the completion of adjuvant chemotherapy, the patient was alive and free of disease. Radical surgery after neoadjuvant chemotherapy may be a treatment option for stage IVA cervical cancer with bulky tumors.
Rosai–Dorfman disease differentiated from a posterior mediastinal tumour: a case report
Authors: Hirai Yoshimitsu , Takahashi Yuichi , Kaki Takahiro , Shima Aya , Kanai Kuninobu , Iwamoto Ryuta , Hirai Issei
Published: July 2024

Rosai–Dorfman disease presenting solely with intrathoracic lesions is exceptionally rare. Herein, we report the case of a 53-year-old man presenting with a posterior mediastinal tumour. Computed tomography revealed a 7-cm soft tissue shadow in the posterior mediastinum. Positron emission tomography-computed tomography demonstrated a high maximum standardized uptake value of 10.35 in the tumour, with no evidence of lymph node or other organ involvement. Serum marker levels were within the normal range. Thoracoscopic surgery was performed to obtain a biopsy for a definitive diagnosis and treatment planning. Postoperative histological findings revealed a diffuse infiltration of eosinophilic histiocytes, lymphocytes, and plasma cells. Immunohistochemical analysis indicated positivity for S-100 protein, oct-2, and cyclin D1 in these histiocytes. Consequently, the patient was diagnosed with Rosai–Dorfman disease and is currently asymptomatic, undergoing regular monitoring without treatment as an outpatient. The absence of characteristic findings, such as bilateral cervical lymphadenopathy, posed challenges in preoperative diagnosis.
tRNA expression and modification landscapes, and their dynamics during zebrafish embryo development
Authors: Rappol Tom , Waldl Maria , Chugunova Anastasia , Hofacker Ivo L , Pauli Andrea , Vilardo Elisa
Published: July 2024

tRNA genes exist in multiple copies in the genome of all organisms across the three domains of life. Besides the sequence differences across tRNA copies, extensive post-transcriptional modification adds a further layer to tRNA diversification. Whilst the crucial role of tRNAs as adapter molecules in protein translation is well established, whether all tRNAs are actually expressed, and whether the differences across isodecoders play any regulatory role is only recently being uncovered. Here we built upon recent developments in the use of NGS-based methods for RNA modification detection and developed tRAM-seq, an experimental protocol and in silico analysis pipeline to investigate tRNA expression and modification. Using tRAM-seq, we analysed the full ensemble of nucleo-cytoplasmic and mitochondrial tRNAs during embryonic development of the model vertebrate zebrafish. We show that the repertoire of tRNAs changes during development, with an apparent major switch in tRNA isodecoder expression and modification profile taking place around the start of gastrulation. Taken together, our findings suggest the existence of a general reprogramming of the expressed tRNA pool, possibly gearing the translational machinery for distinct stages of the delicate and crucial process of embryo development.
Molecular basis for cA6 synthesis by a type III-A CRISPR–Cas enzyme and its conversion to cA4 production
Authors: Goswami Hemant N , Ahmadizadeh Fozieh , Wang Bing , Addo-Yobo Doreen , Zhao Yu , Whittington A Carl , He Huan , Terns Michael P , Li Hong
Published: July 2024

The type III-A (Csm) CRISPR–Cas systems are multi-subunit and multipronged prokaryotic enzymes in guarding the hosts against viral invaders. Beyond cleaving activator RNA transcripts, Csm confers two additional activities: shredding single-stranded DNA and synthesizing cyclic oligoadenylates (cOAs) by the Cas10 subunit. Known Cas10 enzymes exhibit a fascinating diversity in cOA production. Three major forms—cA3, cA4 and cA6have been identified, each with the potential to trigger unique downstream effects. Whereas the mechanism for cOA-dependent activation is well characterized, the molecular basis for synthesizing different cOA isoforms remains unclear. Here, we present structural characterization of a cA6-producing Csm complex during its activation by an activator RNA. Analysis of the captured intermediates of cA6 synthesis suggests a 3′-to-5′ nucleotidyl transferring process. Three primary adenine binding sites can be identified along the chain elongation path, including a unique tyrosine–threonine dyad found only in the cA6-producing Cas10. Consistently, disrupting the tyrosine–threonine dyad specifically impaired cA6 production while promoting cA4 production. These findings suggest that Cas10 utilizes a unique enzymatic mechanism for forming the phosphodiester bond and has evolved distinct strategies to regulate the cOA chain length.
High Prevalence of Highly Pathogenic Avian Influenza: A Virus in Vietnam's Live Bird Markets
Authors: Dao Duy Tung , Coleman Kristen K , Bui Vuong N , Bui Anh N , Tran Long H , Nguyen Quy D , Than Son , Pulscher Laura A , Marushchak Lyudmyla V , Robie Emily R , Nguyen-Viet Hung , Pham Phuc Duc , Christy Nathaniel C , Brooks John S , Nguyen Huy C , Rubrum Adam M , Webby Richard J , Gray Gregory C
Published: July 2024

Background

In recent years, Vietnam has suffered multiple epizootics of influenza in poultry.

Methods

From 10 January 2019 to 26 April 2021, we employed a One Health influenza surveillance approach at live bird markets (LBMs) and swine farms in Northern Vietnam. When the COVID-19 pandemic permitted, each month, field teams collected oral secretion samples from poultry and pigs, animal facility bioaerosol and fecal samples, and animal worker nasal washes at 4 LBMs and 5 swine farms across 5 sites. Initially samples were screened with molecular assays followed by culture in embryonated eggs (poultry swabs) or Madin-Darby canine kidney cells (human or swine swabs).

Results

Many of the 3493 samples collected had either molecular or culture evidence for influenza A virus, including 314 (37.5%) of the 837 poultry oropharyngeal swabs, 144 (25.1%) of the 574 bioaerosol samples, 438 (34.9%) of the 1257 poultry fecal swab samples, and 16 (1.9%) of the 828 human nasal washes. Culturing poultry samples yielded 454 influenza A isolates, 83 of which were H5, and 70 (84.3%) of these were highly pathogenic. Additionally, a positive human sample had a H9N2 avian-like PB1 gene. In contrast, the prevalence of influenza A in the swine farms was much lower with only 6 (0.4%) of the 1700 total swine farm samples studied, having molecular evidence for influenza A virus.

Conclusions

This study suggests that Vietnam's LBMs continue to harbor high prevalences of avian influenza A viruses, including many highly pathogenic H5N6 strains, which will continue to threaten poultry and humans.
Nab-paclitaxel plus S-1 versus nab-paclitaxel plus gemcitabine in patients with advanced pancreatic cancer: a multicenter, randomized, phase II study
Authors: Jin Min , Liu Hong-Li , Xue Jun , Ma Hong , Liu Jun-Li , Lin Zhen-Yu , Wang Jing , Bao Le-Qun , Luo Zhi-Guo , Yu Xiong-Jie , Li Shuang , Hu Jian-Li , Zhang Tao
Published: July 2024

Background

Encouraging antitumor activity of nab-paclitaxel plus S-1 (AS) has been shown in several small-scale studies. This study compared the efficacy and safety of AS versus standard-of-care nab-paclitaxel plus gemcitabine (AG) as a first-line treatment for advanced pancreatic cancer (PC).

Methods

In this multicenter, randomized, phase II trial, eligible patients with unresectable, locally advanced, or metastatic PC were recruited and randomly assigned (1:1) to receive AS (nab-paclitaxel 125 mg/m2 on days 1 and 8; S-1 twice daily on days 1 through 14) or AG (nab-paclitaxel 125 mg/m2 on days 1 and 8; gemcitabine 1000 mg/m2 on days 1 and 8) for 6 cycles. The primary endpoint was progression-free survival (PFS).

Results

Between July 16, 2019, and September 9, 2022, 62 patients (AS, n = 32; AG, n = 30) were treated and evaluated. With a median follow-up of 8.36 months at preplanned interim analysis (data cutoff, March 24, 2023), the median PFS (8.48 vs 4.47 months; hazard ratio [HR], 0.402; P = .002) and overall survival (OS; 13.73 vs 9.59 months; HR, 0.226; P < .001) in the AS group were significantly longer compared to the AG group. More patients had objective response in the AS group than AG group (37.50% vs 6.67%; P = .005). The most common grade 3-4 adverse events were neutropenia and leucopenia in both groups, and gamma glutamyl transferase increase was observed only in the AG group.

Conclusion

The first-line AS regimen significantly extended both PFS and OS of Chinese patients with advanced PC when compared with the AG regimen, with a comparable safety profile. (ClinicalTrials.gov Identifier: NCT03636308).
A Community Development Approach in Physical Therapist Education
Authors: Varnado Kimberly , Mejia-Downs Anne , Scharmann Alexander , Richardson Shannon
Published: July 2024

Physical therapists should be able to screen patients for social determinants that impact health and refer to community resources as appropriate. To make appropriate referrals, physical therapists must equip themselves with skills to connect patients and clients to community resources outside the walls of their respective institutions, starting with developing these practices in physical therapist education programs. Experienced community builders recommend a community development approach where residents initiate and agree upon decisions, and outside stakeholders work as partners to elevate the community. The community should be supported to determine the desired outcomes in ways that enhance equity, inclusion, and social justice. Communities play a substantial role in health outcomes. Studies indicate that 85% of one’s health is connected to community and economic resources, while only 15% is affected by medical interventions. Connected communities are potent tools to enhance health. Connected communities are places where residents nurture neighborhood relationships that enable them to work together to create a good life supporting their collective well-being. The community-builder approach recenters people and their communities as fundamental health leaders; institutions can use their resources to elevate communities by relocating authority back to communities. Communities have assets and resources largely unrecognized, disconnected, and not mobilized by residents. Institutions are positioned to support citizens and their associations in discovering, connecting, and mobilizing these assets. This asset-based community development approach focuses on 5 principles: place-based, citizen-led, relationship-oriented, asset-based, and inclusion-focused. This perspective paper will describe ways institutions can elevate communities; the benefits of community development practices in physical therapist education programs; and explore examples of community partnerships and best practices to develop equitable alliances with residents in the community.

Impact

A large part of one’s health is directly related to where one lives. Physical therapists and physical therapist assistants can play a vital role in improving the health of society by engaging in their local communities through community development. Community development is a practice where community members and outside stakeholders, such as physical therapists, come together to meet the needs of a community.
The codegree isomorphism problem for finite simple groups
Authors: Hung Nguyen N , Moretó Alexander
Published: July 2024

We study the codegree isomorphism problem for finite simple groups. In particular, we show that such a group is determined by the codegrees (counting multiplicity) of its irreducible characters. The proof is uniform for all simple groups and only depends on the classification by means of Artin–Tits’ simple order theorem.
D2 dopamine receptor expression, reactivity to rewards, and reinforcement learning in a complex value-based decision-making task
Authors: Banuelos Cristina , Creswell Kasey , Walsh Catherine , Manuck Stephen B , Gianaros Peter J , Verstynen Timothy
Published: July 2024

Different dopamine (DA) subtypes have opposing dynamics at postsynaptic receptors, with the ratio of D1 to D2 receptors determining the relative sensitivity to gains and losses, respectively, during value-based learning. This effective sensitivity to different reward feedback interacts with phasic DA levels to determine the effectiveness of learning, particularly in dynamic feedback situations where the frequency and magnitude of rewards need to be integrated over time to make optimal decisions. We modeled this effect in simulations of the underlying basal ganglia pathways and then tested the predictions in individuals with a variant of the human dopamine receptor D2 (DRD2; −141C Ins/Del and Del/Del) gene that associates with lower levels of D2 receptor expression (N = 119) and compared their performance in the Iowa Gambling Task to noncarrier controls (N = 319). Ventral striatal (VS) reactivity to rewards was measured in the Cards task with fMRI. DRD2 variant carriers made less effective decisions than noncarriers, but this effect was not moderated by VS reward reactivity as is hypothesized by our model. These results suggest that the interaction between DA receptor subtypes and reactivity to rewards during learning may be more complex than originally thought.
The importance of neighborhood offending networks for gun violence and firearm availability
Authors: Papachristos Andrew V , Murphy James P , Braga Anthony , Turchan Brandon
Published: July 2024

The salience of neighborhoods in shaping crime patterns is one of sociology’s most robust areas of research. One way through which neighborhoods shape outcomes is through the creation and maintenance of social networks, patterns of interactions and relationships among neighborhood residents, organizations, groups, and institutions. This paper explores the relationship between network structures generated through acts of co-offending—when two or more individuals engage in an alleged crime together—and patterns of neighborhood gun violence and gun availability. Using arrest data from New York City, we create co-arrest networks between individuals arrested in the city between 2010 and 2015. We analyze these network patterns to, first, understand the overall structure of co-offending networks and, then, assess how they impact neighborhood levels of gun violence and gun availability. Results show that local and extra-local networks play a central role in predicting neighborhood levels of shootings: neighborhoods with a greater density of local ties have higher shootings rates, and neighborhoods that share social ties have similar rates of violence. In contrast, the network dynamics involved in gun recoveries are almost entirely local: co-offending patterns within neighborhoods are strongly associated with the level of gun recoveries, especially the clustering of co-offending networks indicative of groups. Contrary to previous research, spatial autocorrelation failed to predict either shootings or gun recoveries when demographic features were considered. Social-demographic characteristics seem to explain much of the observed spatial autocorrelation and the precise measurement of network properties might provide better measurements of the neighborhood dynamics involved in urban gun violence.
Diethyl phthalate and dibutyl phthalate disrupt sirtuins expression in the HepG2 cells
Authors: Gutiérrez-García Ana K , Torres-García Daniel A , De Leon-Rodriguez Antonio
Published: July 2024

Background

Phthalates are additives used as plasticizers among other uses, classified as endocrine disruptors and may contribute to some metabolic disorders. The aim of this work was to determine the effect of the exposure of diethyl phthalate (DEP) and dibutyl phthalate (DBP) on cell viability and reactive oxygen species (ROS) production, as well as the regulation of sirloins in HepG2 cells.

Methods

HepG2 cells were exposed to DEP or DBP at 0.1, 1, 10 and 100 μg/mL, and after 48 or 72 h the gene and protein expression of sirtuins was quantified by qRT-PCR and Western-Blot, respectively.

Results

Results showed that even at a low concentration of 0.1 μg/mL DEP affected the expression of Sirt3 and Sirt4, whereas DBP at 0.1 μg/mL affected Sirt3 and Sirt5 gene expression. Protein analysis showed a reduction in Sirt1 levels at a DEP concentration of 1 μg/mL and higher, while DBP at higher dose (100 μg/mL) decreased Sirt3 protein levels. Cell viability decreased by 20% only at higher dose (100 μg/mL) and ROS production increased at 10 and 100 μg/mL for both phthalates.

Conclusion

These findings indicate that exposure to low concentrations (0.1 μg/mL) of DEP or DBP can negatively influence the expression of some sirtuins.
1. Effect of Garlic (Alium Sativum) Supplementation on Short Term Interdialytic Blood Pressure Variability, Oxidative Stress and Inflammation Marker in Haemodialysis Patients with Resistant Hypertension: A Randomized Cross-Over Trial
Authors: Yuristo NS Eddy , Lubis Fadhyl Zuhry , Fatur Rachman Muhammad Alif , Ali Zulkhair , Effendi Ian , Novadian  , Suprapti  , Saleh Irsan , Istiqomah Amelia , Kartika Herleni
Published: July 2024

Background: Resistant hypertension and oscillating interdialytic blood pressure variability is both related to major adverse cardiac event in haemodialysis (HD) patients. Each condition is also associated with oxidative stress and inflammation. Garlic (Alium sativum) was a medicinal herb that has potential antihypertensive, antioxidant, and anti-inflammatory properties.

Aim: This study investigates the effect of garlic supplementation on interdialytic blood pressure variability, malonaldehyde (MDA) as marker of oxidative stress, and interleukin-6 (IL-6) as marker of inflammation in HD patients with resistant hypertension.

Method: This study was a randomized, cross-over, double-blind trial that examines the effects of garlic supplementation in 40 chronic hemodialysis patients suffering from resistant hypertension. Resistant hypertension is defined as uncontrolled hypertension in patients receiving no less than three antihypertensive drugs or controlled hypertension with at least four drugs. Following the baseline evaluation, participants (n=40) were equally randomized to receive a garlic capsule of 500 mg twice daily and subsequently a similar capsule of placebo, or vice versa, with a two-week wash-out period before the initiation of the second intervention. Each treatment was administered for six weeks. Interdialytic blood pressure measurements were performed using a calibrated measuring device on the HD machine. Pre-dialysis serum levels of MDA and IL-6 were examined using standardized ELISA methods and were conducted before and after treatment. Statistical analysis was performed using SPSS Version 26.0.

Result: There were no significant differences in terms of age, gender, use of antihypertensive medication, comorbidities, HD adequacy, or pre-dialytic blood pressure between the groups that received either garlic supplementation or placebo initially. Interdialytic blood pressure variability was quantified using the Standard Deviation (SD), Coefficient of Variation (CV), Variability Independent of the Mean (VIM), and Average Real Variability (ARV) of both systolic and diastolic blood pressure (SBP, DBP) using validated formulas. Garlic supplementation significantly reduced the SD, CV, and ARV of both SBP and DBP (p<0.001), but did not significantly reduce the VIM (p=0.118). Furthermore, garlic supplementation significantly reduced the serum levels of Malondialdehyde (MDA) and Interleukin-6 (IL-6) (p<0.001)

Conclusion: Garlic supplementation significantly reduced interdialytic blood pressure variability and serum levels of oxidative stress and inflammation markers in hemodialysis patients with resistant hypertension.
2. Blood Pressure Abnormality and the Clinical Profile of Parkinson’s Disease as Assessed in the COMPASS-31 Questionnaire
Authors: Hildaria Margareth , Tiksnadi Amanda , Tunjungsari Dyah
Published: July 2024

Background: Cardiovascular dysfunction is one of the most frequently found non-motor symptoms in Parkinson’s Disease. Blood pressure abnormalities had been known to affect the severity of clinical symptoms in Parkinson’s Disease.

Objective: To evaluate the association between blood pressure abnormality and clinical profile of Parkinson’s Disease as assessed in the COMPASS-31 Questionnaire.

Method: Thirty four subjects were consecutively recruited from the outpatient clinic at the Department of Neurology, Cipto Mangunkusumo Hospital Indonesia. All subjects met the Movement Disorder Society (MDS) Criteria for Parkinson’s Disease. Clinical details was collected for all subjects. The COMPASS-31 questionnaire’s orthostatic hypotension domain was administered to all subject during their “on” condition. Assessment of motor dysfunction severity was evaluated using the MDS-UPDRS III.

Result: The study included 34 subjects (21 men and 13 women) with an average age of 58.5 ± 13.9 years. Hypertension was found in 18 subjects (52,9%). Median disease duration was 4,5 years (1-20 years). Men had a higher total UPDRS-III scores on therapy (mean ± SD: 19.95 ± 11.9). The Orthostatic Hypotension domain scores in the COMPASS-31 Questionnaire were found to be significantly influenced by age (P 0.021, r=0.394) and number of antihypertensive drugs taken (P 0.021, r=0.391). Furthermore, hypertension in subjects was significantly associated with Hoehn and Yahr scales (P 0.013, r=0.424) and total UPDRS-III scores (P 0.036, r=0.361).

Conclusion: The study showed strong correlation between age, number of antihypertensive drugs and orthostatic hypotension as evaluated in the COMPASS-31 questionnaire. Hypertension were also found to be associated with motor dysfunction severity in Parkinson’s Disease.
4. Assessment and Validation of Electrocardiographic Diastolic Index for Diagnosing Left Ventricular Diastolic Dysfunction in Patients with Hypertension
Authors: Pradipta LD , Alamsyaputra A , Farissa IP , Safir
Published: July 2024

Background: Left ventricular diastolic dysfunction (LVDD) is the main cause of heart failure with preserved ejection fraction. The structural changes in the heart caused by hypertension could accelerate LVDD. The electrocardiographic diastolic index (EDI), which is calculated from ECG data, can reveal the relationship between left ventricular hypertrophy and LVDD.

Objective: To analyse EDI in diagnosing LVDD in patients with hypertension.

Method: This study was a-single centre, retrospective study, included 50 consecutive patients with hypertension between January – October 2023. Patients were categorized as LVDD and no LVDD group. The EDI was calculated as [R amplitude in aVL × (S amplitude in V1 + R amplitude in V5)/P wave amplitude in lead I]. The EDI greater than 7.4 mV was considered as sign of LVDD. Patients with LVEF<55%, congenital heart disease, infiltrative cardiomyopathy, coronary artery disease, chronic kidney disease, valvular heart disease, bundle branch block, arrhythmia, and missing hospital data were excluded.

Result: The patients were categorized into two groups based on the presence of LVDD. The mean age of the study was 57 ± 11 years, with 14 patients of the participants being male. The patient’s EDI value was 8.6 ± 6.2. The EDI value of the LVDD group exhibited a significantly higher than no LVDD group (p=0.002). EDI could predict LVDD with 73.53% sensitivity, 75% specificity, and 74% accuracy.

Conclusion: The EDI could be assessment tool for diagnosing LVDD in patients with hypertension due to its cost-effectiveness, availability, and easy-to-use formula.
10. The Association of Intravenous Nitrates Dosing Regimens on Blood Pressure Reduction and ICU Admission Rates among Acute Hypertensive Heart Failure Patients in Emergency Settings: A Systematic Review, Meta Analysis, and Meta-Regression
Authors: Ivan Ignatius , Budiman Fanny , Ananta Muammar Emir , Virnardo Ricky
Published: July 2024

Background: In acute hypertensive heart failure (AHHF), optimizing preload and afterload is vital. Higher doses of intermittent intravenous bolus (IVB) nitrates have shown promise in reducing cardiac afterload.

Objective: We evaluate impact of varying IV nitrate dosing regimens on MAP reduction and ICU admission rates in emergency AHHF.

Method: We followed PRISMA 2020 guidelines, searching 8 databases. We included experimental or observational studies from inception to December 8, 2023, focusing on intravenous nitrates in emergency AHHF patients, in which studies documenting MAP reduction and ICU admission rates. Random effects meta-analyses and meta-regression for age, MAP, dosing regimens were employed. Studies qualities were evaluated using ROBINS-I and Newcastle-Ottawa-Scale.

Result: The search yielded 595 articles, including 2 single-arm trials and 5 cohorts. Meta-analysis revealed that a combined IVB and CIV regimen led to a significant MAP reduction (-48.27mmHg), compared to intermittent IVB alone (-23.113mmHg). MAP difference favored the combined regimen, with a significant value of -25.16mmHg(95%CI, -35.86 to -14.45, p=0.00001). Meta-analysis revealed a 39.6% ICU admission rate for combined IVB and CIV, compared to 11.8% for intermittent IVB, resulting in a risk difference of 37%(95%CI, 29%-45%, p=0.00001). Meta-regression analyses found no significant associations between covariates and ICU admission rates. No publication bias was detected (rank correlation p=0.23, regression p=0.17).

Conclusion: Our study revealed lower MAP reduction with combined regimens, and AHHF patients receiving intermittent IVB nitrates alone showed lower ICU admission rates. Meta-regression found no significant association between dose amounts and ICU admissions, indicating comparable impacts for both regimens. Larger-scale, double-arm studies are needed for further clarification.