bluuebunny/crossref_metadata_2025 huggingface dataset:
Understanding the biosynthesis of human IgM SAM-6 through a combinatorial expression of mutant subunits that affect product assembly and secretion
Authors: Hasegawa Haruki , Wang Songyu , Kast Eddie , Chou Hui-Ting , Kaur Mehma , Janlaor Tanakorn , Mostafavi Mina , Wang Yi-Ling , Li Peng
Published: June 2024

Polymeric IgMs are secreted from plasma cells abundantly despite their structural complexity and intricate multimerization steps. To gain insights into IgM’s assembly mechanics that underwrite such high-level secretion, we characterized the biosynthetic process of a natural human IgM, SAM-6, using a heterologous HEK293(6E) cell platform that allowed the production of IgMs both in hexameric and pentameric forms in a controlled fashion. By creating a series of mutant subunits that differentially disrupt secretion, folding, and specific inter-chain disulfide bond formation, we assessed their effects on various aspects of IgM biosynthesis in 57 different subunit chain combinations, both in hexameric and pentameric formats. The mutations caused a spectrum of changes in steady-state subcellular subunit distribution, ER-associated inclusion body formation, intracellular subunit detergent solubility, covalent assembly, secreted IgM product quality, and secretion output. Some mutations produced differential effects on product quality depending on whether the mutation was introduced to hexameric IgM or pentameric IgM. Through this systematic combinatorial approach, we consolidate diverse overlapping knowledge on IgM biosynthesis for both hexamers and pentamers, while unexpectedly revealing that the loss of certain inter-chain disulfide bonds, including the one between μHC and λLC, is tolerated in polymeric IgM assembly and secretion. The findings highlight the differential roles of underlying non-covalent protein-protein interactions in hexamers and pentamers when orchestrating the initial subunit interactions and maintaining the polymeric IgM product integrity during ER quality control steps, secretory pathway trafficking, and secretion.
Antioxidant, insecticidal activity and chemical profiling of flower’s extract of Parthenium weed (Parthenium hysterophorus L.)
Authors: Ahmed Maqsood , Javeed Ansar , Sikandar Aatika , Ji Mingshan , Bai Xuejing , Gu Zumin
Published: June 2024

Parthenium hysterophorus L., an invasive alien species and notorious weed, offers various benefits to the medical and agrochemical industries. This study aimed to evaluate the antioxidant and insecticidal activities of P. hysterophorus flower extract and conduct chemical profiling to identify the phytoconstituents responsible for these biological effects. The antioxidant activity was assessed using the 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay, while gas chromatography mass spectrometry (GCMS) analysis was employed for chemical configuration evaluation. Our findings demonstrate that the dichloromethane (DCM) extract of P. hysterophorus exhibits potent radical scavenging activity (95.03%). Additionally, phytochemical analysis revealed significant amounts of phenols and flavonoids in the distilled water and ethyl acetate extracts (103.30 GAEg-1 and 138.67 QEg-1, respectively). In terms of insecticidal activity, the flower extract displayed maximum mortality rates of 63.33% and 46.67% after 96 hours of exposure at concentrations of 1000 μgmL-1 and 800 μgmL-1, respectively, with similar trends observed at 72 hours. Furthermore, the P. hysterophorus extracts exhibited LC50 values of 1446 μgmL-1 at 72 hours and 750 μgmL-1 at 96 hours. Imidacloprid, the positive control, demonstrated higher mortality rates at 96 hours (97.67%) and 72 hours (91.82%). Moreover, the antioxidant activity of P. hysterophorus extracts exhibited a strong correlation with phenols, flavonoids, and extract yield. GCMS analysis identified 13 chemical compounds, accounting for 99.99% of the whole extract. Ethanol extraction yielded the highest percentage of extract (4.34%), followed by distilled water (3.22%), ethyl acetate (3.17%), and dichloromethane (2.39%). The flower extract of P. hysterophorus demonstrated significant antioxidant and insecticidal activities, accompanied by the presence of valuable chemical compounds responsible for these biological effects, making it a promising alternative to synthetic agents. These findings provide a novel and fundamental basis for further exploration in purifying the chemical compounds for their biological activities.
The role of government in the achievement of medicines’ security: A preliminary exploration of stakeholders’ views and experience
Authors: Adigwe Obi Peter , Onavbavba Godspower
Published: June 2024

Medicines are essential commodities that form the cornerstone in majority of processes and interventions aimed at assuring optimal healthcare and wellbeing for any population. Apart from being saddled with the responsibility of providing medications for this purpose, the pharmaceutical industry has the potential to catalyse socioeconomic development such as job creation and revenue generation. This study aimed at assessing government’s role in driving development in Nigeria’s pharmaceutical sector. Questionnaires were administered to healthcare practitioners that participated in an event targeted at developing Nigerian pharmaceutical sector. Data collected were analysed using Statistical Package for Social Sciences. A total of 76 respondents participated in the study. Two-thirds of the study participants (69.7%) were males, slightly above a third of the study participants (38.2%) were aged 51 and above, and close to a quarter of the participants (21.1%) were doctorate degree holders. About half of the study participants (51.4%) indicated that Nigerian pharmaceutical sector was not adequately regulated, whilst almost all (97.4%) indicated that engaging the legislature was critical for the development of the sector. A strong majority of the study participants (87.5%) indicated that existing drug laws should be reviewed so as to protect the pharmaceutical sector. Also, majority of the participants (56.3%) were not satisfied with government’s efforts in developing the pharmaceutical industry. Although this study explored a small cohort, its findings have revealed novel insights regarding factors limiting the requisite prioritisation of the Nigerian pharmaceutical sector. The emergent evidence can begin to underpin proactive policy and practice reforms aimed at achieving medicines’ security in Nigeria. Further studies can build on these preliminary findings to enable robust and comprehensive sectoral interventions that improve access to healthcare, whilst also catalysing socioeconomic development.
SillyPutty: Improved clustering by optimizing the silhouette width
Authors: Bombina Polina , Tally Dwayne , Abrams Zachary B. , Coombes Kevin R.
Published: June 2024

Clustering is an important task in biomedical science, and it is widely believed that different data sets are best clustered using different algorithms. When choosing between clustering algorithms on the same data set, reseachers typically rely on global measures of quality, such as the mean silhouette width, and overlook the fine details of clustering. However, the silhouette width actually computes scores that describe how well each individual element is clustered. Inspired by this observation, we developed a novel clustering method, called SillyPutty. Unlike existing methods, SillyPutty uses the silhouette width for individual elements as a tool to optimize the mean silhouette width. This shift in perspective allows for a more granular evaluation of clustering quality, potentially addressing limitations in current methodologies. To test the SillyPutty algorithm, we first simulated a series of data sets using the Umpire R package and then used real-workd data from The Cancer Genome Atlas. Using these data sets, we compared SillyPutty to several existing algorithms using multiple metrics (Silhouette Width, Adjusted Rand Index, Entropy, Normalized Within-group Sum of Square errors, and Perfect Classification Count). Our findings revealed that SillyPutty is a valid standalone clustering method, comparable in accuracy to the best existing methods. We also found that the combination of hierarchical clustering followed by SillyPutty has the best overall performance in terms of both accuracy and speed.

Availability: The SillyPutty R package can be downloaded from the Comprehensive R Archive Network (CRAN).
Incidence and risk factors of pancreatic cancer during 15 years follow-up in the Golestan Cohort Study in Iran
Authors: Mirzamohamadi Sara , HajiAbbasi Mohammad Navid , Roshandel Gholamreza , Alimadadi Mehdi , Mirheidari Seyed Behzad , Ghorbani Somayeh , Pourshams Akram , Zahedi Maryam
Published: June 2024

Background

Cancer is one of the main causes of death in the worldwide. Pancreatic Cancer (PC) is prevalent in developed and increasing in developing countries. PC is important because of its low survival rate, high fatality, and increasing incidence. Therefore, identifying risk factors to prevent its development is necessary. This study aimed to determine incidence of PC and its risk factors in the Golestan Cohort Study (GCS) in Iran.

Method

This study is a prospective population-based cohort study in the frame of GCS with 15 years of follow-up for PC. GCS was launched in the Golestan province of Iran with 50045 participants who were 40 to 75 years old. variables included: age, gender, education status, smoking, alcohol consumption, opium usage, type of blood group, dyslipidemia, body mass index (BMI), waist circumference (WC), family history (FH) of PC, ethnicity, and history of diabetes mellitus (DM).

Result

Among 50045 participants of GCS during 15 years of follow up, 100 people were diagnosed PC. PC incidence was 0.2%. Age-standardized incidence rate (ASR) of PC in the study population was 11.12 per 100,000 person-years. People with age ≥60 years were 46, in 50–59 years old group were 36, and 18 of them were <50 years (p<0.001). The smoking rate in PC group was 27% (p<0.01). Univariate model of cox regression analysis showed age 50–59, ≥60 years compared to <50 years [HR:3.006, 95%CI (1.707–5.294), p<0.001], [HR: 6.727, 95% CI (3.899–11.608), p<0.001], male gender [HR:1.541, 95%CI (1.041–2.281), p = 0.031], opium use [HR:1.436, 95% CI (0.887–2.324), p = 0.141], and smoking [HR:1.884, 95%CI (1.211–2.929), p = 0.005] were predictors for PC. In the multivariate model after adjusting, age 50–59 [HR:2.99, 95% CI (1.698–5.265), p<0.001], and ≥60 years [HR: 6.564, 95% CI (3.797–11.346), p<0.001] was the only predictor for PC.

Conclusion

This study revealed an incidence of PC 0.2% in GCS in Iran. Main risk factor for PC was older age.
Family group conferencing for children and families: Evaluation of implementation, context and effectiveness (Family VOICE). Study protocol
Authors: Scourfield Jonathan , Evans Rhiannon , Pallmann Philip , Petrou Stavros , Robling Michael , Au Kar-Man , Jones-Williams Delyth , Lugg-Widger Fiona , Meindl Melissa , Schroeder Elizabeth-Ann , Wood Sophie , Wilkins David
Published: June 2024

Background

Family group conferences (FGCs) in child welfare bring immediate and wider family members together to decide on the best way to meet a child’s needs. Unlike professionally led meetings, the aim is for decisions to be made by or with family members. Qualitative and mixed-method research with FGC participants tends to show positive experiences: most participants feel their voices are heard; FGCs facilitate family-driven solutions and closer relationships—within families and with social workers. Although there is existing literature on FGCs, there is a paucity of robust comparative UK evaluations, i.e., randomised controlled trials or quasi-experimental studies. Comparative studies internationally have focused on a narrow range of outcomes, not recognised the importance of context, and paid little attention to the quality of delivery. Some qualitative studies have considered process and context but there is scant measurement of these. The aims of this study are, firstly, to establish how FGCs improve outcomes for families and what factors vary their quality, and, secondly, to assess longer-term outcomes in terms of service use and associated costs.

Methods

Given the importance of process and context, evaluation informed by realist and complex systems approaches is needed. This multi-method evaluation includes a survey of FGC services in all UK local authorities (n = 212) to map service provision; co-design of programme theory and evaluation measures with family members who have experienced an FGC (n = 16–24) and practitioners (n = 16–24) in two sites; a prospective single-arm study of FGC variability and outcomes after six months; and comparison of service use and costs in FGC participants (n≥300 families) and a control group (n≥1000) after two years using a quasi-experiment.

Discussion

This is a pragmatic evaluation of an existing intervention, to identify what mechanisms and contexts influence effective process and longer-term outcomes. The study is registered with Research Registry (ref. 7432).
Buronius manfredschmidi—A new small hominid from the early late Miocene of Hammerschmiede (Bavaria, Germany)
Authors: Böhme M. , Begun D. R. , Holmes A. C. , Lechner T. , Ferreira G.
Published: June 2024

The known diversity of European middle and late Miocene hominids has increased significantly during the last decades. Most of these great apes were frugivores in the broadest sense, ranging from soft fruit frugivores most like chimpanzees to hard/tough object feeders like orangutans, varying in size from larger than siamangs (over 17 kg) to larger than most chimpanzees (~60–70 kg). In contrast to the frequent sympatry of hominoids in the early-to-middle Miocene of Africa, in no European Miocene locality more than one hominid taxon has been identified. Here we describe the first case of hominid sympatry in Europe from the 11.62 Ma old Hammerschmiede HAM 5 level, best known from its excellent record of Danuvius guggenmosi. The new fossils are consistent in size with larger pliopithecoids but differ morphologically from any pliopithecoid and from Danuvius. They are also distinguished from early and middle Miocene apes, share affinities with late Miocene apes, and represent a small hitherto unknown late Miocene ape Buronius manfredschmidi. With an estimated body mass of about 10 kg it represents the smallest known hominid taxon. The relative enamel thickness of Buronius is thin and contrasts with Danuvius, whose enamel is twice as thick. The differences between Buronius and Danuvius in tooth and patellar morphology, enamel thickness and body mass are indicative of differing adaptations in each, permitting resource partitioning, in which Buronius was a more folivorous climber.
New Brunswick’s mental health action plan: A quantitative exploration of program efficacy in children and youth using the Canadian Community Health Survey
Authors: Yang Yuzhi (Stanford) , Law Moira , Vaghri Ziba
Published: June 2024

In 2011, the New Brunswick government released the New Brunswick Mental Health Action Plan 2011–2018 (Action Plan). Following the release of the Action Plan in 2011, two progress reports were released in 2013 and 2015, highlighting the implementation status of the Action Plan. While vague in their language, these reports indicated considerable progress in implementing the Action Plan, as various initiatives were undertaken to raise awareness and provide additional resources to facilitate early prevention and intervention in children and youth. However, whether these initiatives have yielded measurable improvements in population-level mental health outcomes in children and youth remains unclear. The current study explored the impact of the Action Plan by visualizing the trend in psychosocial outcomes and service utilization of vulnerable populations in New Brunswick before and after the implementation of the Action Plan using multiple datasets from the Canadian Community Health Survey. Survey-weighted ordinary least square regression analyses were performed to investigate measurable improvements in available mental health outcomes. The result revealed a declining trend in the mental wellness of vulnerable youth despite them consistently reporting higher frequencies of mental health service use. This study highlights the need for a concerted effort in providing effective mental health services to New Brunswick youth and, more broadly, Canadian youth, as well as ensuring rigorous routine outcome monitoring and evaluation plans are consistently implemented for future mental health strategies at the time of their initiation.
Exercise may improve lung immunity after surgical stress: Evidence from a nephrectomy model via a bioinformatic analysis
Authors: Wu Min-You , Luo Hao-Lun , Chang Ya-Chuan , Yu Chia-Ying , Sung Wen-Wei
Published: June 2024

Exercise offers numerous benefits to cancer patients and plays an essential role in postsurgical cancer rehabilitation. However, there is a lack of research examining the effects of exercise after the surgical stress of nephrectomy. To address this gap, we created an animal model that simulated patients who had undergone nephrectomy with or without an exercise intervention. Next, we performed a bioinformatic analysis based on the data generated by the RNA sequencing of the lung tissue sample. An overrepresentation analysis was conducted using two genome databases (Gene Ontology and Kyoto Encyclopedia of Genes and Genomes [KEGG]). A KEGG analysis of the exercise-treated nephrectomy mice revealed enrichment in immune-related pathways, particularly in the NF-κB and B cell-related pathways. The expression of CD79A and IGHD, which are responsible for B cell differentiation and proliferation, was upregulated in the nephrectomy mice. Differential gene expression was categorized as significantly upregulated or downregulated according to nephrectomy and exercise groups. Notably, we identified several gene expression reversals in the nephrectomy groups with exercise that were not found in the nephrectomy without exercise or control groups. Our preliminary results potentially reveal a genetic landscape for the underlying mechanisms of the effects of exercise on our nephrectomy model.
Impact of heartfulness meditation practice compared to the gratitude practices on wellbeing and work engagement among healthcare professionals: Randomized trial
Authors: Desai Kunal , O’Malley Patricia , Van Culin Emily
Published: June 2024

Objective

To investigate whether Heartfulness meditation practice, compared to Gratitude practice, leads to measurable changes in mental wellbeing among healthcare providers across the US.

Method

Participants were randomly assigned to one of the following 6-week interventions: the trainer-guided virtual Heartfulness meditation program or the podcast-based self-guided gratitude practice group. The Professional Quality of Life Scale-5 (ProQOL-5) was used to determine Compassion Satisfaction (CS) and risk for Burnout (BO) and secondary traumatic stress (STS). The Utrecht Work Engagement Scale (UWES) was used to assess vigor, dedication, and absorption at work. Outcomes were collected at baseline and the end of the study period. Qualitative questions regarding the experience of learning and practicing were also offered at the end of the six weeks.

Results

The majority of participants were nurses (50%), followed by allied healthcare professionals (37%) and physicians (13%) (N = 83). There was a general trend towards increases in CS in the Heartfulness group compared to the gratitude group. However, this was not statistically significant. Strong evidence suggests there was a significant improvement in BO for the Heartfulness group between Week 0 and Week 6 (p = 0.002), as well as STS (p = 0.0004) and vigor (p = 0.0392). Qualitative data analysis revealed that the subjects in the Heartfulness arm reported improved sleep and decreased reactivity to stress. Subjects in the gratitude arm reported improved mood and favorable results using gratitude practices at home with family members.

Conclusion

In our study, Heartfulness meditation practice was associated with a significant improvement in burnout and vigor at work, with a trend towards compassion satisfaction after six weeks compared with gratitude practices. Qualitative analysis indicates the benefits of both Heartfulness and Gratitude practices. Further randomized trials with a larger sample size are needed to explore these science-based practices for the wellbeing of healthcare workers.
Counterweight mass influences single-leg cycling biomechanics
Authors: Asmussen Michael J. , Casto E. Erica , MacInnis Martin J. , Nigg Benno M.
Published: June 2024

Introduction

Single-leg cycling is a commonly used intervention in exercise physiology that has applications in exercise training and rehabilitation. The addition of a counterweight to the contralateral pedal helps single-leg cycling mimic cycling patterns of double-leg cycling. To date, no research has tested (a) the influence of a wide range of counterweight masses on a person’s cycling biomechanics and (b) the optimal counterweight mass to emulate double-leg cycling.

Objectives

The purpose of this study was to determine the effects of varying counterweights on the kinematics (joint angles) and kinetics (joint moments, work) of cycling using a 3D analysis.

Methods

Twelve participants cycled at 50W or 100W with different counterweight masses (0 to 30 lbs, 2.5 lbs increments), while we analyzed the pedal force data, joint angles, joint moments, and joint power of the lower limb using 3D motion capture and 3D instrumented pedals to create participant-specific musculoskeletal models.

Results

The results showed that no single-leg cycling condition truly emulated double-leg cycling with respect to all measured variables, namely pedal forces (p ≤ 0.05), joint angles (p ≤ 0.05), joint moments(p ≤ 0.05), and joint powers (p ≤ 0.05), but higher counterweights resulted in single-leg cycling that was statistically similar (p > 0.05), but descriptively, asymptotically approached the biomechanics of double-leg cycling.

Conclusion

We suggest that a 20-lb counterweight is a conservative estimate of the counterweight required for using single-leg cycling in exercise physiology studies, but further modifications are needed to the cycle ergometer for the biomechanics of single-leg cycling to match those of double-leg cycling.
A qualitative content analysis of cannabis-related discussions on Reddit during the COVID-19 pandemic
Authors: Reygaerts Hannah , Smith Sidney , Renner Lynette M. , Ruiz Yumary , Schwab-Reese Laura M.
Published: June 2024

Social media has become an increasingly important way to seek and share experiences, support, knowledge, and advice during the COVID-19 pandemic. Reddit, a pseudonymous social media platform, was one way that young people interacted during the pandemic. Our study goals were two-fold: (1) to categorize information sought and provided by users of r/saplings, a subreddit devoted to cannabis use and is often used by young people, and (2) to examine if conversations changed during the COVID-19 pandemic. We extracted 213 randomly selected posts and 2,546 related comments across four time periods (before the pandemic, during the first wave, summer, and next fall). We assessed the volume of posts and comments throughout our study period and conducted a qualitative content analysis. Quantitatively, the findings demonstrated an increase in the number of posts and comments throughout the study period. Given the substantial growth in subreddit activity throughout our study period, Reddit may play an increasingly important role in youth socialization related to cannabis. From the content analysis, we identified three major themes: how to acquire cannabis, how to use cannabis, and associated consequences. Reddit-users prioritized certain content in their posts at different stages of the pandemic. ‘Places to acquire’ and ‘future use’ were most common at the beginning of the pandemic, while the theme of ‘consequences’ and the topic of ‘tolerance’ became more prominent during the summer months. The comments to these posts were generally thorough and responsive to the post. Nearly all the information came from opinions or personal experiences. Firstly, our findings suggest that young people viewed Reddit as a viable outlet for conversations about cannabis. Secondly, due to the nature of the peer comments and lack of verifiable information being exchanged, misinformation may still circulate and inadvertently worsen the efforts to reduce cannabis-related harm. Interventions that provide understandable and accurate cannabis-related information in accessible formats may increase young people’s ability to access and practice harm reduction.
Exploration of the shared pathways and common biomarker in adamantinomatous craniopharyngioma and type 2 diabetes using integrated bioinformatics analysis
Authors: Han Yibo , Wang Yong , Li Shuo , Sato Kohji , Yamagishi Satoru
Published: June 2024

Craniopharyngiomas are rare tumors of the central nervous system that typically present with symptoms such as headache and visual impairment, and those reflecting endocrine abnormalities, which seriously affect the quality of life of patients. Patients with craniopharyngiomas are at higher cardiometabolic risk, defined as conditions favoring the development of type 2 diabetes and cardiovascular disease. However, the underlying common pathogenic mechanisms of craniopharyngiomas and type 2 diabetes are not clear. Especially due to the difficulty of conducting in vitro or in vivo experiments on craniopharyngioma, we thought the common pathway analysis between craniopharyngioma and type 2 diabetes based on bioinformatics is a powerful and feasible method. In the present study, using public datasets (GSE94349, GSE68015, GSE38642 and GSE41762) obtained from the GEO database, the gene expression associated with adamantinomatous craniopharyngioma, a subtype of craniopharyngioma, and type 2 diabetes were analyzed using a bioinformatic approach. We found 11 hub genes using a protein–protein interaction network analysis. Of these, seven (DKK1, MMP12, KRT14, PLAU, WNT5B, IKBKB, and FGF19) were also identified by least absolute shrinkage and selection operator analysis. Finally, single-gene validation and receptor operating characteristic analysis revealed that four of these genes (MMP12, PLAU, KRT14, and DKK1) may be involved in the common pathogenetic mechanism of adamantinomatous craniopharyngioma and type 2 diabetes. In addition, we have characterized the differences in immune cell infiltration that characterize these two diseases, providing a reference for further research.
Risk factors affecting spinal fusion: A meta-analysis of 39 cohort studies
Authors: Yang Shudong , Zhou Beijun , Mo Jiaxuan , He Ruidi , Mei Kunbo , Zeng Zhi , Yang Gaigai , Chen Yuwei , Luo Mingjiang , Tang Siliang , Xiao Zhihong
Published: June 2024

Purpose

We performed a meta-analysis to identify risk factors affecting spinal fusion.

Methods

We systematically searched PubMed, Embase, and the Cochrane Library from inception to January 6, 2023, for articles that report risk factors affecting spinal fusion. The pooled odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using fixed-effects models for each factor for which the interstudy heterogeneity I2 was < 50%, while random-effects models were used when the interstudy heterogeneity I2 was ≥ 50%. Using sample size, Egger’s P value, and heterogeneity across studies as criteria, we categorized the quality of evidence from observational studies as high-quality (Class I), moderate-quality (Class II or III), or low-quality (Class IV). Furthermore, the trim-and-fill procedure and leave-one-out protocol were conducted to investigate potential sources of heterogeneity and verify result stability.

Results

Of the 1,257 citations screened, 39 unique cohort studies comprising 7,145 patients were included in the data synthesis. High-quality (Class I) evidence showed that patients with a smoking habit (OR, 1.57; 95% CI, 1.11 to 2.21) and without the use of bone morphogenetic protein-2 (BMP-2) (OR, 4.42; 95% CI, 3.33 to 5.86) were at higher risk for fusion failure. Moderate-quality (Class II or III) evidence showed that fusion failure was significantly associated with vitamin D deficiency (OR, 2.46; 95% CI, 1.24 to 4.90), diabetes (OR, 3.42; 95% CI, 1.59 to 7.36), allograft (OR, 1.82; 95% CI, 1.11 to 2.96), conventional pedicle screw (CPS) fixation (OR, 4.77; 95% CI, 2.23 to 10.20) and posterolateral fusion (OR, 3.63; 95% CI, 1.25 to 10.49).

Conclusions

Conspicuous risk factors affecting spinal fusion include three patient-related risk factors (smoking, vitamin D deficiency, and diabetes) and four surgery-related risk factors (without the use of BMP-2, allograft, CPS fixation, and posterolateral fusion). These findings may help clinicians strengthen awareness for early intervention in patients at high risk of developing fusion failure.
Aspects of spermatogenesis in immature and mature specimens of the long-lived Greenland shark: Novelties concerning the germinal compartment’s assembly, complement of Sertoli cells and demise
Authors: McClusky Leon Mendel , Nielsen Julius , Christiansen Jørgen Schou
Published: June 2024

Cystic spermatogenesis in the subadult, maturing and adult Greenland shark (Somniosus microcephalus) displays multiple novel features, characterized early on by an unorganized internal cellular environment of the spermatocysts (anatomically discrete follicle-like units containing a single germ cell stage and its complement of co-developing Sertoli cells). These typically show polar asymmetries due to asymmetrically distributed germ and Sertoli cells. These arise from several novel cellular rearrangements at the immature pole, including fusion of a cluster of somatic cells with newly formed cysts containing only one to three spermatogonia and that already display an excess of Sertoli cells. The subadult’s germinative zone revealed an additional novelty, namely numerous previously formed somatic cell-lined rings into which spermatogonia were incorporated. A striking finding was the conspicuous rarity of the routinely discernible Sertoli mitotic figures in the hallmark cyst stage of diametric elasmobranch spermatogenesis that is known for the peak display of the latter. Scrutiny of sequentially unfolding phenomena in the linearly arranged spermatogonial generations revealed that the cellular developments at the most common type of cyst–duct transition area (comprising slender to spindle-like basophilic cells with pointed ends) were concurrent with the discreet appearance of a second dark Sertoli nucleus, a development that persisted in spermiated cysts. Spermatogenically active mature males displayed vigorous meiotic divisions. However, a scattering of their spermatid cysts also displayed shark-atypical asynchronous passage through spermiogenesis, phenomena which were exacerbated as arrested spermiogenesis in an archival collection of tissues from 13 maturing specimens. Subadult specimens revealed meiotic arrest, and foci of infiltration of leukocytes that originate from a mass of eosinophilic, granule-laden immune cells dorsally under the testis capsule. This tissue was identical to the testis-affixed bone marrow equivalent in other shark species. This tissue is likely developmentally regulated in the Greenland shark as it is absent in adults.
Integrated physiological, transcriptomics and metabolomics analysis revealed the molecular mechanism of Bupleurum chinense seedlings to drought stress
Authors: Feng Xiaohan , Sun Yan , Fan Ya , Zhang Quanfang , Bu Xun , Gao Demin
Published: June 2024

Drought stress is a prominent abiotic factor that adversely influences the growth and development of Bupleurum chinense during its seedling stage, negatively impacting biomass and secondary metabolite production, thus affecting yield and quality. To investigate the molecular mechanism underlying the response of B. chinense seedlings under drought stress, this study employed comprehensive physiological, transcriptomic, and metabolomic analyses. The results revealed that under drought stress, the root soluble sugar and free proline content in B. chinense seedlings significantly increased, while the activities of SOD, POD, and CAT increased in the leaves. These findings indicate the presence of distinct response mechanisms in B. chinense to cope with drought stress. Integrated analysis further identified significant correlations between genes and metabolites related to amino acid biosynthesis in the leaves, as well as genes and metabolites associated with acetaldehyde and dicarboxylic acid metabolism. In the roots, genes and metabolites related to plant hormone signaling and the tricarboxylic acid (TCA) cycle showed significant correlations. These findings provide vital views into the molecular-level response mechanisms of B. chinense under drought stress. Moreover, this study establishes the groundwork for identifying drought-tolerant genes and breeding drought-resistant varieties, which could improve the drought tolerance of medicinal plants and have broader implications for agriculture and crop production in water-scarce areas.
Practical diets for California yellowtail, Seriola dorsalis: Use of advanced soybean meal products on growth performance, body composition, intestinal morphology, and immune gene expression
Authors: Oladipupo Abdulmalik A. , Stuart Kevin R. , Bruce Timothy J. , Drawbridge Mark A. , Davis D. Allen
Published: June 2024

California yellowtail (CYT), Seriola dorsalis, is a promising candidate for aquaculture due to its rapid growth and high-quality flesh, particularly in markets like Japan, Australia, China, and the United States. Soy protein has shown success as a replacement for marine protein sources in CYT diets, reducing fishmeal levels, though concerns about potential intestinal inflammation persist with the inclusion of solvent-extracted soybean meal. To address this, processing strategies like fractionation, enzymatic treatment, heat treatment, and microbial fermentation have been employed to mitigate the negative impacts of soybean meal on fish nutrition and immune systems. This study focuses on optimizing soybean meal inclusion levels by incorporating advanced soy variants into CYT diets. The eight-week feeding trial, conducted in a recirculation system, featured six diets with sequential inclusion levels (0, 50, 100%) of high protein low oligosaccharide soybean meal (Bright Day, Benson Hill, St Louis, MO) and enzyme-treated soybean meal (HP 300, Hamlet Protein Inc., Findlay, OH), replacing solvent-extracted soybean. The study compares these formulations against a soy-free animal protein-based diet. At the end of the trial, fish were sampled for growth performance, body proximate composition, intestinal morphology, and immune response from gut samples. Results showed consistent FCR (P = 0.775), weight gain (P = 0.242), and high survival rate (99.4 ± 0.5%) among dietary treatments (P>0.05). Histological evaluations revealed no gut inflammation and gene expression analysis demonstrated no significant variations in immune, physiological, and digestive markers apn (P = 0.687), mga (P = 0.397), gpx1 (P = 0.279), atpase (P = 0.590), il1β (P = 0.659). The study concludes that incorporating advanced soybean meal products, replacing up to 20% of fishmeal does not negatively affect CYT’s growth and intestinal health. This suggests that all three soy sources, contributing 35% of total protein (15.4 g 100 g-1 diet), can be included in practical diets without compromising CYT’s intestinal integrity or growth. These findings have positive implications for the commercial production of CYT and future research on the incorporation of plant-based proteins in aquaculture diets.
Discharge process for patients experiencing homelessness in the emergency department: A thematic qualitative study
Authors: Marcus Elle R. , Carreras Tartak Jossie A. , Halasz Helena , Chen David , Lee Jarone , He Shuhan
Published: June 2024

People experiencing homelessness are more likely to utilize emergency departments than their non-homeless counterparts. However, obtaining a bed in a homeless shelter for patients can be complex. To better understand the challenges of finding a safe discharge plan for homeless patients in the emergency department, our team conducted interviews with emergency department social workers and homeless shelter case managers in the Boston area. We identified and mapped the stages in the processes performed by both parties, identifying challenges with successful placement into a shelter. Furthermore, we assembled a data dictionary of key factors considered when assessing a patient’s fit for a homeless shelter. By identifying bottlenecks and areas of opportunity, this study serves as a first step in enabling homeless individuals to receive the post-discharge assistance they require.
Rv0100: An essential acyl carrier protein from M. tuberculosis important in dormancy
Authors: Gutka Hiten J. , Bondoc Jasper Marc G. , Patwell Ryan , Khan Shahebraj , Grzelak Edyta M. , Goswami Rajendra , Voskuil Martin I. , Movahedzadeh Farahnaz
Published: June 2024

We have identified an acyl-carrier protein, Rv0100, that is up-regulated in a dormancy model. This protein plays a critical role in the fatty acid biosynthesis pathway, which is important for energy storage and cell wall synthesis in Mycobacterium tuberculosis (MTB). Knocking out the Rv0100 gene resulted in a significant reduction of growth compared to wild-type MTB in the Wayne model of non-replicating persistence. We have also shown that Rv0100 is essential for the growth and survival of this pathogen during infection in mice and a macrophage model. Furthermore, knocking out Rv0100 disrupted the synthesis of phthiocerol dimycocerosates, the virulence-enhancing lipids produced by MTB and Mycobacterium bovis. We hypothesize that this essential gene contributes to MTB virulence in the state of latent infection. Therefore, inhibitors targeting this gene could prove to be potent antibacterial agents against this pathogen.
Prevalence of diarrhea and water sanitation and hygiene (WASH) associated factors among children under five years in Lira City Northern Uganda: Community based study
Authors: Auma Brenda , Musinguzi Marvin , Ojuka Edward , Kigongo Eustes , Tumwesigye Raymond , Acup Walter , Kabunga Amir , Opio Bosco
Published: June 2024

Background

Children under the age of five experience a significant disease burden from diarrheal illnesses. This poses a severe public health risk as the second leading cause of infant death worldwide, after pneumonia. Lira City in Uganda is one of the developing urban areas with limited information about the diarrheal disease among children under the age of 5 years. This study aimed to determine the prevalence and assess the water, sanitation and hygiene related factors associated with diarrheal diseases among children under five years in Lira City.

Methods

The study was conducted among 492 care takers of children under the age of 5 years in Lira City between August 2022 and September 2022. Data was collected using an interviewer administered questionnaire and a multi-stage sampling was used to select study participants. Data was analyzed by bivariate and multivariate logistic regression using STATA version 17. P-value of < 0.05 was considered statistically significant.

Results

Out of 541 participants, 492 responded. The majority of the respondents, 425(86.4%) were female, 146(29.7%) had children aged 1–12 months, 192 (39%) had primary level education, and 155(31.5%) were self-employed. The prevalence of diarrhea among children under five years was 130(26.4%) and the associated factors with diarrheal disease were children between 49–60 months old (AOR = 0.12, 95% CI: 0.03–0.39, P = 0.001), cleaning the latrine more times (AOR = 0.42, 95% CI: 0.22–0.81, P = 0.010) and not treating water (AOR = 1.84, 95% CI: 1.11–3.06, P = 0.018).

Conclusion

There is high prevalence of diarrhea among children under 5 years of age. The study’s findings highlight the need for ongoing efforts to lower the prevalence of diarrheal illnesses among children under the age of five in Uganda’s emerging urban areas.
The histone methyltransferase SETD2 regulates HIV expression and latency
Authors: Bussey-Sutton Cameron R. , Ward Airlie , Fox Joshua A. , Turner Anne-Marie W. , Peterson Jackson J. , Emery Ann , Longoria Arturo R. , Gomez-Martinez Ismael , Jones Corbin , Hepperla Austin , Margolis David M. , Strahl Brian D. , Browne Edward P.
Published: June 2024

Understanding the mechanisms that drive HIV expression and latency is a key goal for achieving an HIV cure. Here we investigate the role of the SETD2 histone methyltransferase, which deposits H3K36 trimethylation (H3K36me3), in HIV infection. We show that prevention of H3K36me3 by a potent and selective inhibitor of SETD2 (EPZ-719) leads to reduced post-integration viral gene expression and accelerated emergence of latently infected cells. CRISPR/Cas9-mediated knockout of SETD2 in primary CD4 T cells confirmed the role of SETD2 in HIV expression. Transcriptomic profiling of EPZ-719-exposed HIV-infected cells identified numerous pathways impacted by EPZ-719. Notably, depletion of H3K36me3 prior to infection did not prevent HIV integration but resulted in a shift of integration sites from highly transcribed genes to quiescent chromatin regions and to polycomb repressed regions. We also observed that SETD2 inhibition did not apparently affect HIV RNA levels, indicating a post-transcriptional mechanism affecting HIV expression. Viral RNA splicing was modestly reduced in the presence of EPZ-719. Intriguingly, EPZ-719 exposure enhanced responsiveness of latent HIV to the HDAC inhibitor vorinostat, suggesting that H3K36me3 can contribute to a repressive chromatin state at the HIV locus. These results identify SETD2 and H3K36me3 as novel regulators of HIV integration, expression and latency.
‘We know Charlie’: A case of epistolary education and brave space in The Perks of Being a Wallflower fanfiction
Authors: Moore Amber
Published: June 2024

This article takes up epistolary writing and the chronicling of experiences with and the impact of sexual violence in an example of fanfiction written in response to the classic young adult (YA) trauma novel, Stephen Chbosky’s The Perks of Being a Wallflower. Because this novel explores the impact of childhood sexual abuse, this project posits that two particular fanfiction stories (a fic and its sequel) offers a theorization of Charlie’s letters as a kind of ongoing victim impact statement, which then produces a unique narrative opportunity to create brave space for witnessing experiences of sexual trauma in community. As such, the fanfiction represents a kind of epistolary education wherein Charlie’s letters are positioned as a learning tool and source of feminist development through co-created emotionally supportive experiences. Specifically, how Charlie’s epistolary trauma testimony is responded to by allies and friends Patrick, Sam and Mary Elizabeth in the fanfiction is educative, particularly through their collective employment of two key practices: being generous and being generative in their responses to Charlie’s letters. Their epistolary education then positions them to uniquely process and prepare to reunite with and show up for Charlie as ethical witnesses to his trauma testimony. Thus, these two fanfiction stories function as significant sites for learning about sexual violence, ethically supporting victim-survivors of it, as well as strengthening the characters’ senses of community and selves.
Reforma ilustrada y proyecto liberal: la enseñanza del derecho en la monarquía hispánica
Authors: Martínez Neira Manuel
Published: June 2024

Frente a una visión lineal de la enseñanza del derecho en los siglos XVI-XIX que se plantea como una sucesión de doctrinas (que en definitiva terminan por legitimar el orden liberal), estas páginas indagan en algunas cuestiones de la obra de Hotman, de la forma de gobierno que fue la monarquía administrativa, del rechazo de derecho oficial que planteó la escuela española de derecho consuetudinario, que nos permiten analizar esos momentos como realidades sustantivas y no como meros anuncios del momento presente.
Bref regard historiographique sur l’impossible réforme de l’enseignement du droit dans la France de l’Ancien Régime (XVIe-XVIIIe siècle)
Authors: Rousselet-Pimont Anne
Published: June 2024

Les facultés de droit de l’ancienne France font l’objet d’une critique presque constante depuis maintenant plusieurs siècles, les historiens ayant repris à leur compte beaucoup des remarques acerbes formulées, en leur temps, par les écoliers et autres observateurs des moeurs universitaires. La critique fait feu de tout bois : contre le roi, réformateur à ses heures mais grand pourvoyeur de dispenses tout le reste du temps ; contre les maîtres, incompétents, laxistes et vénaux ; contre les robins qui, soumis aux lois du marché de la vénalité de leurs charges, n’attendent de l’université qu’un sésame pour entrer en fonction. Il apparaît cependant, au milieu de ces diatribes, des opinions divergentes, moins pour sauver l’enseignement du droit de sa dérive que pour identifier celui ou ceux qui portent la véritable responsabilité du désastre. C’est cette concurrence de responsabilité que nous avons cherchée à questionner au travers de quelques classiquesde l’histoire des universités.
Los graduados en Leyes y Cánones en la Universidad de Irache durante el siglo XVII
Authors: Ramis Barceló Rafael
Published: June 2024

Este artículo estudia sintéticamente los graduados en leyes y cánones de la Universidad de Irache durante el siglo xvii. Primero analiza la configuración jurídica de la Universidad de Irache, luego estudia los Estatutos y finalmente da información acerca de los principales graduados en leyes y en cánones, así como de su ejecutoria.
Los estudios de derecho en los proyectos frustrados para la creación de una Universidad del reino de Navarra (1546-1807)
Authors: Jimeno Aranguren Roldán
Published: June 2024

Se analizan los diferentes proyectos impulsados por las Cortes de Navarra en los siglos XVI, XVII y XVIII para crear una universidad del reino. Nos fijaremos, muy especialmente, en las propuestas que se hicieron para introducir los grados de Cánones y Leyes. Todos los proyectos fracasaron tanto por razones económicas como por la oposición frontal a los mismos de la Universidad benedictina de Iratxe, donde se impartían los dos derechos. A estas razones, en el siglo xviii se sumó un rechazo frontal de la propia Monarquía. La carencia de una universidad del reino y el hecho de que la de Iratxe otorgara grados sin impartir docencia, generó que muchos juristas navarros tuvieran que formarse en universidades extranjeras.
La procura en las provincias vascas y Navarra: su regulación y ejercicio en unos territorios forales (ss. XIII-XIX)
Authors: Merino Malillos Imanol
Published: June 2024

En el estudio de la historia de los derechos procesales desde el surgimiento del ius commune, las labores de los procuradores han quedado eclipsadas por las de sus partenaires, los abogados, y otros actores en la administración de justicia. En este texto nos aproximamos a la procura y su ejercicio en el marco de unos territorios que, encuadrados durante el Antiguo Régimen en la Corona de Castilla, disponían de ordenamientos jurídicos e instituciones particulares. Nos preguntaremos hasta qué punto estos sirvieron para diferenciar el ejercicio de la procura en ellos del régimen general de la Corona castellana, o amoldarlos a las realidades locales. Abordaremos no sólo sus perfiles, sino también qué papel jugaban en la redefinición de los marcos jurídicos locales. Finalmente, apuntaremos qué cambios y permanencias se produjeron con la implantación de una administración de justicia de carácter estatal y liberal en el siglo XIX.