bluuebunny/crossref_metadata_2025 huggingface dataset:
Implementation and engagement of the SMART Work & Life sitting reduction intervention: an exploratory analysis on intervention effectiveness
Authors: Edwardson Charlotte L , Abell Lucy , Clarke-Cornwell Alex , Dunstan David W , Gray Laura J , Healy Genevieve N , Hadjiconstantinou Michelle , Wilson Panna , Maylor Benjamin , Munir Fehmidah , Biddle Stuart JH
Published: December 2023

Background

To enhance the impact of interventions, it is important to understand how intervention engagement relates to study outcomes. We report on the level of implementation and engagement with the SMART Work & Life (SWAL) programme (delivered with (SWAL plus desk) and without a height-adjustable desk (SWAL)) and explore the effects of different levels of this on change in daily sitting time in comparison to the control group.

Methods

The extent of intervention delivery by workplace champions and the extent of engagement by champions and participants (staff) with each intervention activity was assessed by training attendance logs, workplace champion withdrawal dates, intervention activities logs and questionnaires. These data were used to assess whether a cluster met defined criteria for low, medium, or high implementation and engagement or none of these. Mixed effects linear regression analyses tested whether change in sitting time varied by: (i) the number of intervention activities implemented and engaged with, and (ii) the percentage of implementation and engagement with all intervention strategies.

Results

Workplace champions were recruited for all clusters, with 51/52 (98%) attending training. Overall, 12/27 (44.4%) SWAL and 9/25 (36.0%) SWAL plus desk clusters implemented all main intervention strategies. Across remaining clusters, the level of intervention implementation varied. Those in the SWAL (n = 8 (29.6%) clusters, 80 (32.1%) participants) and SWAL plus desk (n = 5 (20.0%) clusters, 41 (17.1%) participants) intervention groups who implemented and engaged with the most intervention strategies and had the highest percentage of cluster implementation and engagement with all intervention strategies sat for 30.9 (95% CI -53.9 to -7.9, p = 0.01) and 75.6 (95% CI -103.6 to -47.7, p < 0.001) fewer minutes/day respectively compared to the control group at 12 month follow up. These differences were larger than the complete case analysis. The differences in sitting time observed for the medium and low levels were similar to the complete case analysis.

Conclusions

Most intervention strategies were delivered to some extent across the clusters although there was large variation. Superior effects for sitting reduction were seen for those intervention groups who implemented and engaged with the most intervention components and had the highest level of cluster implementation and engagement.

Trial Registration

ISRCTN11618007. Registered on 24 January 2018. https://www.isrctn.com/ISRCTNISRCTN11618007.
27-hydroxycholesterol causes cognitive deficits by disturbing Th17/Treg balance and the related immune responses in mild cognitive impairment patients and C57BL/6J mice
Authors: Wang Tao , Feng Wenjing , Ju Mengwei , Yu Huiyan , Guo Zhiting , Sun Xuejing , Yang Kexin , Liu Miao , Xiao Rong
Published: December 2023

Background

Cognitive impairment is associated with dysregulated immune responses. Emerging evidence indicates that Th17 cells and their characteristic cytokine-IL-17 are receiving growing interest in the pathogenesis of cognitive decline. Here, we focus on the involvement of Th17 cells in mild cognitive impairment (MCI) and the possible mechanism of cholesterol metabolite-27-hydroxycholesterol (27-OHC).

Methods

100 individuals were recruited into the nested case–control study who completed cognition assessment and the detection of oxysterols and Th17-related cytokines in serum. In addition, mice were treated with 27-OHC and inhibitors of RORγt and Foxp3 (Th17 and Treg transcription factors), and the factors involved in Th17/Treg balance and amyloidosis were detected.

Results

Our results showed there was enhanced 27-OHC level in serum of MCI individuals. The Th17-related cytokines homeostasis was altered, manifested as increased IL-17A, IL-12p70, IL-23, GM-CSF, MIP-3α and TNF-α but decreased IL-13, IL-28A and TGF-β1. Further, in vivo experiments showed that 27-OHC induced higher immunogenicity, which increased Th17 proportion but decreased Treg cells in peripheral blood mononuclear cells (PBMCs); Th17 proportions in hippocampus, and IL-17A level in serum and brain were also higher than control mice. The fluorescence intensity of amyloid-β (Aβ) and the precursor of amyloid A amyloidosis–serum amyloid A (SAA) was increased in the brain of 27-OHC-treated mice, and worse learning and memory performance was supported by water maze test results. While by inhibiting RORγt in 27-OHC-loaded mice, Th17 proportions in both PBMCs and hippocampus were reduced, and expressions of IL-17A and TGF-β1 were down- and up-regulated, respectively, along with a decreased amyloidosis in brain and improved learning and memory decline.

Conclusions

Altogether, our results demonstrate that excessive 27-OHC aggravates the amyloidosis and leads to cognitive deficits by regulating RORγt and disturbing Th17/Treg balance.
Risk factors for unsuppressed viral load after intensive adherence counseling among HIV infected persons in Kampala, Uganda: a nested case–control study
Authors: Izudi Jonathan , Castelnuovo Barbara , King Rachel , Cattamanchi Adithya
Published: December 2023

Background

Intensive adherence counseling (IAC) is the global standard of care for people living with human immunodeficiency virus (PLHIV) who have unsuppressed VL after ≥ 6 months of first-line anti-retroviral therapy (ART). We investigated whether the number of IAC sessions is associated with suppressed VL among PLHIV in Kampala, Uganda.

Methods

We conducted a nested case-control study among PLHIV with unsuppressed VL after ≥ 3 IAC sessions (cases) and a 2:1 random sample of PLHIV with suppressed VL after ≥ 3 IAC sessions (controls). Unsuppressed VL was defined as VL ≥ 1000 copies/ml. We performed multivariable logistic regression to identify factors that differed significantly between cases and controls.

Results

Demographic and clinical characteristics were similar among the 16 cases and 32 controls including mean age, sex, baseline CD4 count, VL before IAC, and WHO clinical stage. Only the number of IAC sessions differed significantly between cases and controls in unadjusted (p = 0.012) and adjusted (p = 0.016) analyses. Each unit increase in IAC session was associated with unsuppressed VL (Adjusted odds ratio 5.09; 95% CI 1.35–19.10).

Conclusions

VL remained unsuppressed despite increasing IAC frequency. The fidelity to standardized IAC protocol besides drug resistance testing among PLHIV with unsuppressed VL before IAC commencement should be examined.
Hip joint and muscle loading for persons with bilateral transfemoral/through-knee amputations: biomechanical differences between full-length articulated and foreshortened non-articulated prostheses
Authors: Toderita Diana , Favier Clement D. , Henson David P. , Vardakastani Vasiliki , Sherman Kate , Bennett Alexander N. , Bull Anthony M. J.
Published: December 2023

Background

Currently, there is little available in-depth analysis of the biomechanical effect of different prostheses on the musculoskeletal system function and residual limb internal loading for persons with bilateral transfemoral/through-knee amputations (BTF). Commercially available prostheses for BTF include full-length articulated prostheses (microprocessor-controlled prosthetic knees with dynamic response prosthetic feet) and foreshortened non-articulated stubby prostheses. This study aims to assess and compare the BTF musculoskeletal function and loading during gait with these two types of prostheses.

Methods

Gait data were collected from four male traumatic military BTF and four able-bodied (AB) matched controls using a 10-camera motion capture system with two force plates. BTF completed level-ground walking trials with full-length articulated and foreshortened non-articulated stubby prostheses. Inverse kinematics, inverse dynamics and musculoskeletal modelling simulations were conducted.

Results

Full-length articulated prostheses introduced larger stride length (by 0.5 m) and walking speed (by 0.3 m/s) than stubbies. BTF with articulated prostheses showed larger peak hip extension angles (by 10.1°), flexion moment (by 1.0 Nm/kg) and second peak hip contact force (by 3.8 bodyweight) than stubbies. There was no difference in the hip joint loading profile between BTF with stubbies and AB for one gait cycle. Full-length articulated prostheses introduced higher hip flexor muscle force impulse than stubbies.

Conclusions

Compared to stubbies, BTF with full-length articulated prostheses can achieve similar activity levels to persons without limb loss, but this may introduce detrimental muscle and hip joint loading, which may lead to reduced muscular endurance and joint degeneration. This study provides beneficial guidance in making informed decisions for prosthesis choice.
Preclinical assessment of an anti-HTLV-1 heterologous DNA/MVA vaccine protocol expressing a multiepitope HBZ protein
Authors: Daian e Silva D. S. O. , Cox L. J. , Rocha A. S. , Lopes-Ribeiro Á. , Souza J. P. C. , Franco G. M. , Prado J. L. C. , Pereira-Santos T. A. , Martins M. L. , Coelho-dos-Reis J. G. A. , Gomes-de-Pinho T. M. , Da Fonseca F. G. , Barbosa-Stancioli E. F.
Published: December 2023

Background

Human T-lymphotropic virus 1 (HTLV-1) is associated with the development of several pathologies and chronic infection in humans. The inefficiency of the available treatments and the challenge in developing a protective vaccine highlight the need to produce effective immunotherapeutic tools. The HTLV-1 basic leucine zipper (bZIP) factor (HBZ) plays an important role in the HTLV-1 persistence, conferring a survival advantage to infected cells by reducing the HTLV-1 proteins expression, allowing infected cells to evade immune surveillance, and enhancing cell proliferation leading to increased proviral load.

Methods

We have generated a recombinant Modified Virus Vaccinia Ankara (MVA-HBZ) and a plasmid DNA (pcDNA3.1(+)-HBZ) expressing a multiepitope protein based on peptides of HBZ to study the immunogenic potential of this viral-derived protein in BALB/c mice model. Mice were immunized in a prime-boost heterologous protocol and their splenocytes (T CD4+ and T CD8+) were immunophenotyped by flow cytometry and the humoral response was evaluated by ELISA using HBZ protein produced in prokaryotic vector as antigen.

Results

T CD4+ and T CD8+ lymphocytes cells stimulated by HBZ-peptides (HBZ42–50 and HBZ157–176) showed polyfunctional double positive responses for TNF-α/IFN-γ, and TNF-α/IL-2. Moreover, T CD8+ cells presented a tendency in the activation of effector memory cells producing granzyme B (CD44+High/CD62L−Low), and the activation of Cytotoxic T Lymphocytes (CTLs) and cytotoxic responses in immunized mice were inferred through the production of granzyme B by effector memory T cells and the expression of CD107a by CD8+ T cells. The overall data is consistent with a directive and effector recall response, which may be able to operate actively in the elimination of HTLV-1-infected cells and, consequently, in the reduction of the proviral load. Sera from immunized mice, differently from those of control animals, showed IgG-anti-HBZ production by ELISA.

Conclusions

Our results highlight the potential of the HBZ multiepitope protein expressed from plasmid DNA and a poxviral vector as candidates for therapeutic vaccine.
Experiences of patients and family members with follow-up care, information needs and provider support after identification of Lynch Syndrome
Authors: Mooney Ryan , Wu Yelena P. , Kehoe Kelsey , Volkmar Molly , Kohlmann Wendy , Koptiuch Cathryn , Kaphingst Kimberly A
Published: December 2023

Background

Lynch Syndrome is among the most common hereditary cancer syndromes and requires ongoing cancer surveillance, repeated screenings and potential risk-reducing surgeries. Despite the importance of continued surveillance, there is limited understanding of patient experiences after initial testing and counseling, the barriers or facilitators they experience adhering to recommendations, and how they want to receive information over time.

Methods

A cross-sectional, observational study was conducted among 127 probands and family members who had received genetic testing for Lynch Syndrome. We conducted semi-structured interviews to determine proband and family member experiences after receiving genetic testing results including their surveillance and screening practices, information needs, and interactions with health care providers. Both closed-ended and open-ended data were collected and analyzed.

Results

Both probands (96.9%) and family members (76.8%) received recommendations for follow-up screening and all probands (100%) and most family members (98.2%) who tested positive had completed at least one screening. Facilitators to screening included receiving screening procedure reminders and the ease of making screening and surveillance appointments. Insurance coverage to pay for screenings was a frequent concern especially for those under 50 years of age. Participants commented that their primary care providers were often not knowledgeable about Lynch Syndrome and surveillance recommendations; this presented a hardship in navigating ongoing surveillance and updated information. Participants preferred information from a knowledgeable health care provider or a trusted internet source over social media or support groups.

Conclusions

Probands and family members receiving genetic testing for Lynch Syndrome generally adhered to initial screening and surveillance recommendations. However, factors such as insurance coverage and difficulty finding a knowledgeable healthcare provider presented barriers to receiving recommended follow-up care. There is an opportunity to improve care through better transitions in care, procedures to keep primary care providers informed of surveillance guidelines, and practices so that patients receive reminders and facilitated appointment setting for ongoing screening and surveillance at the time they are due.
A super-pangenome of the North American wild grape species
Authors: Cochetel Noé , Minio Andrea , Guarracino Andrea , Garcia Jadran F. , Figueroa-Balderas Rosa , Massonnet Mélanie , Kasuga Takao , Londo Jason P. , Garrison Erik , Gaut Brandon S. , Cantu Dario
Published: December 2023

Background

Capturing the genetic diversity of wild relatives is crucial for improving crops because wild species are valuable sources of agronomic traits that are essential to enhance the sustainability and adaptability of domesticated cultivars. Genetic diversity across a genus can be captured in super-pangenomes, which provide a framework for interpreting genomic variations.

Results

Here we report the sequencing, assembly, and annotation of nine wild North American grape genomes, which are phased and scaffolded at chromosome scale. We generate a reference-unbiased super-pangenome using pairwise whole-genome alignment methods, revealing the extent of the genomic diversity among wild grape species from sequence to gene level. The pangenome graph captures genomic variation between haplotypes within a species and across the different species, and it accurately assesses the similarity of hybrids to their parents. The species selected to build the pangenome are a great representation of the genus, as illustrated by capturing known allelic variants in the sex-determining region and for Pierce’s disease resistance loci. Using pangenome-wide association analysis, we demonstrate the utility of the super-pangenome by effectively mapping short reads from genus-wide samples and identifying loci associated with salt tolerance in natural populations of grapes.

Conclusions

This study highlights how a reference-unbiased super-pangenome can reveal the genetic basis of adaptive traits from wild relatives and accelerate crop breeding research.
Incidence, distribution, disease spectrum, and genetic deficits of congenital heart defects in China: implementation of prenatal ultrasound screening identified 18,171 affected fetuses from 2,452,249 pregnancies
Authors: Chen Xinlin , Zhao Sheng , Dong Xiaoyan , Liu Juntao , Guo Yulin , Ju Weina , Chen Peiwen , Gao Yanduo , Feng Qian , Zhu Xia , Huang Hui , Lu Xiaojun , Yang Xiaohong , Yang Fan , Cheng Chen , Luo Xishun , Cheng Longxian , Zhong Nanbert ,   On behalf of the Chinese Consortium for Prenatal Ultrasound Screening of Congenital Heart Defects
Published: December 2023

Background

Congenital heart defects (CHDs) are the most common birth defects. Assessment of the incidence, distribution, disease spectrum, and genetic deficits of fetal CHDs in China is urgently needed.

Methods

A national echocardiography screening program for fetal CHDs was implemented in 92 prenatal screening–diagnostic centers in China.

Findings

A total of 18,171 fetal CHD cases were identified from 2,452,249 pregnancies, resulting in 7·4/1,000 as the national incidence rate of fetal CHD. The incidences of fetal CHD in the six geographical regions, the southern, central, eastern, southwestern, northern, and northwestern, were 7·647 (CI: 7·383–7·915), 7·839 (CI: 7·680–8·000), 7·647 (CI: 7·383–7·915), 7·562 (CI: 7·225–7·907), 5·618 (CI: 5·337–5·906), and 4·716 (CI: 4·341–5·108), respectively, per 1,000 pregnancies. Overall, ventricular septal defect was the most common fetal CHD, accounting for 17.04% of screened pregnancies nationwide, and tetralogy of Fallot, the most common anomaly in the major defect of fetal CHD, was the second most common, accounting for 9.72%. A total of 76.24% cases of fetal CHD were found to be an isolated intracardiac single defect. The remaining 23.76% of cases of fetal CHD had multiple heart defects. Among all extracardiac malformations, the central nervous system (CNS) was the most common tissue with extracardiac anomalies associated with CHD, accounting for 22.89% of fetal CHD cases. Chromosomal karyotyping identified trisomy 18 as the most common chromosomal abnormality in fetal CHD. We also documented that CHD-containing syndromes could be identified with a comprehensive approach integrating prenatal ultrasound, MRI, pathological autopsy, and cytogenetics and molecular genetics.

Conclusion

Implementation of prenatal echocardiography as a practically feasible platform to screen fetal CHD will reduce the financial and emotional burden of CHD, which may facilitate intrauterine and neonatal intervention of CHD.
Association between parental smoking and child exposure to environmental tobacco smoke in Israel
Authors: Berman Tamar , Rorman Efrat , Groisman Luda , Keinan-Boker Lital , Shimony Tal , Barnett-Itzhaki Zohar
Published: December 2023

Background

Environmental tobacco smoke (ETS) exposure in children can cause delayed lung development and lifelong cardiovascular damage. The aim of this study was to measure ETS exposure in children in Israel in 2020–2021 using urinary cotinine (UC) measurements and to assess correlates of ETS exposure, including parental smoking.

Methods

In the framework of the National Human Biomonitoring Program, spot urine samples and questionnaire data were collected from 166 children aged 4–12 years, during the years 2020–2021. We collected urine samples in 233 adults, 69 of whom were parents of children included in the study. Parents of participating children were asked about parental smoking, child’s exposure to ETS and smoking policy at home. Cotinine and creatinine were measured in urine. Creatinine-adjusted and unadjusted urine cotinine (UC) geometric means were calculated. Associations between potential correlates and UC concentrations were analyzed in univariate and multivariate analyses. For 69 child-parent pairs, correlation between child and parental UC was analyzed.

Results

Based on urinary cotinine measurement, 65.2% of children of smokers are exposed to ETS, compared to 20.7% of children in non-smoking families. Greater numbers of smokers living in the home (beta = 1.27, p < 0.01), and low maternal education (beta = − 2.32, p < 0.01) were associated with higher levels of UC in a multivariate analysis. Spearman correlations showed a positive moderate correlation between UC in 69 child–parent pairs (r = 0.52, p < 0.01).

Conclusions

In order to reduce child exposure to ETS, smoking parents should be urgently targeted for smoking cessation and smoke-free home interventions. Further interventions are needed to protect all children from ETS.
Lithium prescription trends in psychiatric inpatient care 2014 to 2021: data from a Bavarian drug surveillance project
Authors: Kriner Paul , Severus Emanuel , Korbmacher Julie , Mußmann Lisa , Seemueller Florian
Published: December 2023

Objectives

Lithium (Li) remains one of the most valuable treatment options for mood disorders. However, current knowledge about prescription practices in Germany is limited. The objective of this study is to estimate the prevalence of current Li use over time and in selected diagnoses, highlighting clinically relevant aspects such as prescription rates in elderly patients, concomitant medications, important drug–drug interactions, and serious adverse events.

Methods

We conducted a descriptive analysis of Li prescriptions, analyzing data from the ongoing Bavarian multicenter drug safety project Pharmaco-Epidemiology and Vigilance (Pharmako-EpiVig) from the years 2014–2021. Our study included 97,422 inpatients, 4543 of whom were prescribed Li.

Results

The Li prescription rate in unipolar depression (UD) remained constant at 4.6% over the observational period. In bipolar disorder (BD), the prescription rate increased significantly from 28.8% in 2014 to 34.4% in 2019. Furthermore, 30.3% of patients with Li prescriptions did not have a diagnosis of BD or UD, and 15.3% of patients with schizoaffective disorder were prescribed Li. The majority (64%) of patients with Li prescriptions were prescribed five or more drugs. Most of the 178 high-priority drug–drug interactions were due to hydrochlorothiazide (N = 157) followed by olmesartan (N = 16).

Conclusion

Our study does not substantiate concerns about a decline in Li prescription. The decline in prescription rates observed in some diagnostic groups in 2020 and 2021 may be associated with the COVID-19 pandemic. The symptom-oriented use of Li beyond BD and UD is common. Polypharmacy and drug–drug interactions present a challenge in Li therapy. Old age and comorbid substance use disorder do not appear to be major deterrents for clinicians to initiate Li therapy.
Aspect-level sentiment classification with fused local and global context
Authors: Feng Ao , Cai Jiazhi , Gao Zhengjie , Li Xiaojie
Published: December 2023

Sentiment analysis aims to determine the sentiment orientation of a text piece (sentence or document), but many practical applications require more in-depth analysis, which makes finer-grained sentiment classification the ideal solution. Aspect-level Sentiment Classification (ALSC) is a task that identifies the emotional polarity for aspect terms in a sentence. As the mainstream Transformer framework in sentiment classification, BERT-based models apply self-attention mechanism that extracts global semantic information for a given aspect, while a certain proportion of local information is missing in the process. Although recent ALSC models have achieved good performance, they suffer from robustness issues. In addition, uneven distribution of samples greatly hurts model performance. To address these issues, we present the PConvBERT (Prompt-ConvBERT) and PConvRoBERTa (Prompt-ConvRoBERTa) models, in which local context features learned by a Local Semantic Feature Extractor (LSFE) are fused with the BERT/RoBERTa global features. To deal with the robustness problem of many deep learning models, adversarial training is applied to increase model stability. Additionally, Focal Loss is applied to alleviate the impact of unbalanced sample distribution. To fully explore the ability of the pre-training model itself, we also propose natural language prompt approaches that better solve the ALSC problem. We utilize masked vector outputs of templates for sentiment classification. Extensive experiments on public datasets demonstrate the effectiveness of our model.
Filament-free memristors for computing
Authors: Choi Sanghyeon , Moon Taehwan , Wang Gunuk , Yang J. Joshua
Published: December 2023

Memristors have attracted increasing attention due to their tremendous potential to accelerate data-centric computing systems. The dynamic reconfiguration of memristive devices in response to external electrical stimuli can provide highly desirable novel functionalities for computing applications when compared with conventional complementary-metal–oxide–semiconductor (CMOS)-based devices. Those most intensively studied and extensively reviewed memristors in the literature so far have been filamentary type memristors, which typically exhibit a relatively large variability from device to device and from switching cycle to cycle. On the other hand, filament-free switching memristors have shown a better uniformity and attractive dynamical properties, which can enable a variety of new computing paradigms but have rarely been reviewed. In this article, a wide range of filament-free switching memristors and their corresponding computing applications are reviewed. Various junction structures, switching properties, and switching principles of filament-free memristors are surveyed and discussed. Furthermore, we introduce recent advances in different computing schemes and their demonstrations based on non-filamentary memristors. This Review aims to present valuable insights and guidelines regarding the key computational primitives and implementations enabled by these filament-free switching memristors.
Impact of HBcrAg levels on HBsAg seroconversion after HBV rebound: a case report
Authors: Ohkubo Maki , Fukuda Kuniaki , Chiba Shigeru , Homma Masato
Published: December 2023

Background

Nucleoside analogues (NAs) such as entecavir are required for at least 12 months when patients with resolved hepatitis B virus (HBV) infection develop HBV reactivation. Entecavir treatment does not always achieve hepatitis B surface antigen (HBsAg) seroconversion. The cessation of NA for HBV reactivation sometimes causes HBV rebound. The impact of hepatitis B core-related antigen (HBcrAg) on predicting HBV rebound is controversial.

Case presentation

A 67-year-old woman with resolved HBV infection received rituximab for post-transplant lymphoproliferative disorder after peripheral blood stem cell transplantation. Since she tested positive for HBV-DNA after the first rituximab therapy (day 0), entecavir treatment was started. Because the HBV-DNA test became negative and her liver function had been normal, entecavir was terminated on day 376. According to the retrospective measurements, HBcrAg remained positive while the HBV-DNA level was undetectable. One hundred forty-one days after entecavir cessation, the HBV-DNA turned positive again, suggesting HBV rebound (day 517). Her liver function deteriorated and HBV infection worsened, even though entecavir treatment was resumed on day 615. On the contrary, hepatitis B surface antibody levels increased after the rebound, resulting in HBsAg seroconversion with HBcrAg and HBV-DNA levels undetectable. HBV reactivation has not been detected after the second entecavir cessation, and both HBcrAg and HBV-DNA levels remained undetectable.

Discussion and conclusions

This case suggests that NA cessation induced-HBV rebound achieved HBsAg seroconversion under the guidance of a hepatologist. Since HBcrAg had been detectable while HBV-DNA was undetectable, HBcrAg may be an index for predicting HBV rebound resulting in HBsAg seroconversion as well as other conventional laboratory tests. Prospective measuring HBcrAg is required to confirm this case report.
Eccentric Muscle Actions Add Complexity to an Already Inconsistent Resistance Exercise Nomenclature
Authors: Nuzzo James L. , Nosaka Kazunori
Published: December 2023

An eccentric muscle action (or contraction) is defined as active muscle lengthening against resistance, which occurs when the force generated by the muscle is smaller than the resistance placed upon it. Eccentric resistance exercise, which involves multiple sessions of repeated eccentric muscle actions, improves muscle strength and other health outcomes. In response to this evidence, new exercise technologies have been developed to permit feasible completion of eccentric muscle actions outside of the laboratory. Consequently, participation in eccentric resistance exercise is projected to increase in the future, and communications about eccentric resistance exercise are likely to reach a wide audience, including students in the classroom, athletes in the weightroom, patients who receive telehealth services,  and journalists who report on study findings. Previous research has documented inconsistencies in how resistance exercises are named, but the role of eccentric resistance exercises has not been considered. Here, we explain how eccentric resistance exercises add further complexity to an already inconsistent resistance exercise nomenclature. Specifically, action words in exercise names typically describe the movement that occurs in the concentric phase (e.g., “press”, “raise”, “curl”, “pull”, “row”). This naming bias likely stems from the fact that traditional resistance exercise equipment, such as free weights and weight stack machines, does not typically accommodate for greater eccentric than concentric strength and thus emphasizes the concentric over eccentric phase. This naming bias is likely to hinder communications about eccentric resistance exercise. Thus, we encourage researchers and practitioners to discuss ways in which resistance exercises can be named more clearly and consistently.
Environmental detection of eumycetoma pathogens using multiplex real-time PCR for soil DNA in Sennar State, Sudan
Authors: Hashizume Hiroki , Taga Suguru , Sakata Masayuki K. , Hussein Mahmoud , Siddig Emmanuel Edwar , Minamoto Toshifumi , Fahal Ahmed Hassan , Kaneko Satoshi
Published: December 2023

Background

Mycetoma is a chronic disease affecting the skin and subcutaneous tissue endemic in the tropical and subtropical regions. Several bacteria and fungi can cause mycetoma, but fungal mycetoma (eumycetoma) is challenging because the treatment requires a combination of a long-term antifungal agent and surgery. Although the transmission route has not yet been elucidated, infection from the soil is a leading hypothesis. However, there are few soil investigation studies, and the geographical distribution of mycetoma pathogens is not well documented. Here, we used multiplex real-time PCR technology to identify three fungal species from soil samples.

Methods

In total, 64 DNA samples were extracted from soil collected in seven villages in an endemic area in Sennar State, Sudan, in 2019. Primers and fluorescent probes specifically targeting the ribosomal DNA of Madurella mycetomatis, Falciformispora senegalensis, and F. tompkinsii were designed.

Results

Multiplex real-time PCR was performed and identified the major pathogen, M. mycetomatis that existed in most sites (95%). In addition, two other pathogens were identified from some sites. This is the first report on the use of this technique for identifying the eumycetoma causative microorganisms.

Conclusions

This study demonstrated that soil DNA investigation can elucidate the risk area of mycetoma-causative agents. The results will contribute to the design of prevention measures, and further large-scale studies may be effective in understanding the natural habitats of mycetoma pathogens.
Integrated rumen microbiome and serum metabolome analysis responses to feed type that contribution to meat quality in lambs
Authors: Du Shuai , Bu Zhenkun , You Sihan , Jiang Zipeng , Su Weifa , Wang Tenghao , Jia Yushan
Published: December 2023

Background

Lifestyle factors, such as diet, are known to be a driver on the meat quality, rumen microbiome and serum metabolites. Rumen microbiome metabolites may be important for host health, the correlation between rumen microbiome and production of rumen metabolites are reported, while the impact of rumen microbiome on the serum metabolome and fatty acid of meat are still unclear. This study was designed to explore the rumen microbiome, serum metabolome and fatty acid of meat in response to the grass diet and concentrate diet to lambs, and the relationship of which also investigated.

Methods

In the present study, 12 lambs were randomly divided into two groups: a grass diet (G) and a concentrate diet (C). Here, multiple physicochemical analyses combined with 16S rRNA gene sequences and metabolome analysis was performed to reveal the changes that in response to feed types.

Results

The concentrate diet could improve the growth performance of lambs compared to that fed with the grass diet. The microbiome composition was highly individual, compared to the concentrate group, the abundance of Rikenellaceae_RC9_gut_group, F082_unclassified, Muribaculaceae_unclassified, Ruminococcaceae_NK4A214_group, Bacteroidetes_unclassified, and Bacteroidales_UCG-001_unclassified were significantly (P < 0.05) lower in the grass group, while, the abundance of Succinivibrio, Succinivibrionaceae_UCG-002, Fibrobacter and Christensenellaceae_R-7_group were significantly (P < 0.05) higher in the grass group. Serum metabolomics analysis combined with enrichment analysis revealed that serum metabolites were influenced by feed type as well as the metabolic pathway, and significantly affected serum metabolites involved in amino acids, peptides, and analogues, bile acids, alcohols and derivatives, linoleic acids derivatives, fatty acids and conjugates. Most of the amino acids, peptides, and analogues metabolites were positively associated with the fatty acid contents. Among the bile acids, alcohols and derivatives metabolites, glycocholic was positively associated with all fatty acid contents, except C18:0, while 25-Hydroxycholesterol and lithocholic acid metabolites were negatively associated with most of the fatty acid contents.

Conclusion

Correlation analysis of the association of microbiome with metabolite features, metabolite features with fatty acid provides us with comprehensive understanding of the composition and function of microbial communities. Associations between utilization or production were widely identified among affected microbiome, metabolites and fatty acid, and these findings will contribute to the direction of future research in lamb.
Indirect and direct interactions between grain aphid and parasitoid in the presence of symbiont Regiella insecticola
Authors: Man Yue , Li Delu , Wang Minghui , Hu Zuqing , Gatti Jean-Luc , Desneux Nicolas , Han Peng , Luo Chen
Published: December 2023

Background

Aphids often harbor bacterial symbionts that confer resistance to biotic and abiotic stress. Previous studies have primarily examined the direct effects of symbiont infection on parasitoid success but less on aphid population dynamics under indirect parasitic situations, for example when exposed to parasitoid wasp odor. Deciphering this type of indirect effect is essential for understanding dynamics of insect ecosystems and communities and to improve IPM success.

Methods

We generated Sitobion avenae aphid clonal lines that are genetically identical but differ in Regiella insecticola infection. Then, the indirect odor effect of female parasitoid wasp Aphidius gifuensis (Ashmaed), one of its major natural enemies in the fields, was examined on the aphid lines fitness using different parasitoid densities. With these lines we also tested the direct effect of symbiont presence on aphid resistance against different parasitoid densities.

Results

Our study found fitness costs for the aphid line hosting Regiella, mainly via an increase in the development time and a reduction in population increase rate. Some of these fitness traits were influenced by the indirect exposure to parasitoid wasp odor with a density effect. Presence of the symbiont also reduced A. gifuensis parasitic success, increased the wasp development time and decreased its emergence weight with low effect of the parasitoid density used for parasitism.

Conclusions

These results showed that aphid population dynamic was mainly affected by the symbiont presence, but not by parasitoid odor. Symbiont presence also protected aphid from parasitism and affected parasitoid offspring weight and hence their future individual fertility and fitness.
Effect of aggregate gradation on the mechanical strengths and permeability properties of porous concrete
Authors: Nataraja M. C. , Srinivasamurthy Lakshmikanth , Das Vivek R. , Vineeth L.
Published: December 2023

Porous concrete (PC) is a very popular construction material in developed countries and is now finding application in India in parking lots. In this investigation, an effort was made to study the various performances of PC in the laboratory. Different gradations of coarse aggregates namely 4.75–10 mm, 10–12.5 mm, and 12.5–16 mm are considered to characterize PC adopting conventional compaction by tamping rod, additional 5 and 10 compactions by proctor hammer. The effect of varying compaction and the coarse aggregate gradation is studied on axial compressive, flexural tensile, and splitting tensile strengths of PC. In addition, a simple method is proposed to determine the permeability of all PC mixes. The work was extended to know the influence of low-grade fly ash and GGBS as supplementary cementing materials (SCMs) on the strengths and permeability of PC. Though the strength of PC in the presence of SCMs has decreased, the permeability and the estimated porosity of all mixes decreased compared to the 100% cement counterpart. A wide range of PCs were developed to suit several combinations of mechanical strength, density, and permeability depending on the type of application leading to a sustainable solution. The simple test method proposed to determine the permeability of the PC gives satisfactory results.
A Journey of Diagnosing a Case of Immune Checkpoint Inhibitor Pembrolizumab-Induced Diabetes Mellitus
Authors: Tang Michael , Nakapakorn Chanyanuch , Meng Shumei
Published: December 2023

Autoimmune diabetes mellitus (DM) due to pembrolizumab is a rare but reported complication of immune checkpoint inhibitors (ICIs). It is often missed for a long initial period, leading to unnecessary admissions and poor glucose management. We report a case of a 72-year-old woman with prior history of gastrointestinal stromal tumor (GIST) and current diagnosis of squamous cell carcinoma (SCC) of the lung, who upon presentation at the emergency department with symptoms of encephalopathy, was diagnosed as having sodium glucose cotransporter 2 inhibitor (SGLT-2i)–induced diabetic ketoacidosis (DKA). Upon further investigation, we learned that this patient had multiple hospitalizations for recurrent DKA over 2 years after being managed on metformin and SGLT-2i. Biochemical testing helped confirm pembrolizumab-induced autoimmune diabetes with significantly elevated glutamic acid decarboxylase-65 (GAD65) autoantibodies and an undetectable C-peptide level. The patient has had clinical improvement with insulin therapy without further DKA episodes. She continued to be managed by outpatient endocrinology with improved glucose control. Altogether, this case demonstrates the importance of keeping a high vigilance for possible new onset of autoimmune endocrine diseases, such as diabetes, in patients treated with ICIs, to enable earlier diagnosis and prompt initiation of correct therapy.
Nothing Great Comes Without Its Risks: A Rare Case of Pembrolizumab-Induced Hypophysitis
Authors: Fernando Ashen , Mittal Aastha , Cheema Rashid
Published: December 2023

Pembrolizumab is an immune checkpoint inhibitor that targets the programmed cell death protein 1 and enhances immune activity against cancer cells. This has emerged as a powerful tool in the treatment of cancer in patients with severe metastatic disease. Despite this, immune checkpoint inhibitors are associated with many immune-related adverse effects. Reported endocrinopathies include thyroid dysfunction, insulin-deficient diabetes mellitus, primary adrenal insufficiency, and hypophysitis. Hypophysitis is more commonly associated with cytotoxic T-lymphocyte associated antigen 4 inhibitors like ipilimumab and rarely with pembrolizumab. A high clinical suspicion is needed to pursue a diagnosis of immune checkpoint inhibitorinduced hypophysitis, and prompt diagnosis is of immense importance due to the potentially life-threatening nature of endocrinopathies. We present a case of a 64-year-old Caucasian male individual undergoing treatment with pembrolizumab for undifferentiated lung carcinoma who subsequently developed hypophysitis.
Artri King-induced Hypothalamic-pituitary-adrenal Axis Disruption: A Report of 3 Cases
Authors: Berg Elyssa Ann , Dao Lisa , Yu Run , Hurtado Carolina
Published: December 2023

We present a case series of 3 patients who developed iatrogenic hypothalamic-pituitary-adrenal axis disruption while taking Artri King, an over-the-counter supplement marketed for joint pain that is reported to contain dexamethasone not listed on the supplement's label. Patient 1, a 58-year-old woman, presented with persistent hyponatremia, weight gain, proximal muscle weakness, dorsocervical fat pad, and new, red striae on her breast and abdomen in the setting of Artri King use. Her dexamethasone level was elevated (Table 1), confirming the suspicion of dexamethasone content in this supplement. Patient 2, a 55-year old woman, had presented with cushingoid features and a low morning cortisol level (Table 1) in the setting of Artri King use. Patient 3, a 59-year-old man, presented with poorly controlled diabetes in the setting of Artri King use and an elevated serum dexamethasone level. Supplements containing hidden glucocorticoids can cause not only iatrogenic Cushing syndrome, but also adrenal suppression, providing a diagnostic challenge for providers.
Imeglimin Improved Plasma Glucose Levels in Patients With Latent Autoimmune Diabetes of Adults: Report of 2 Cases
Authors: Okada Shuichi , Okada Kazuya , Okada Junichi , Yamada Eijiro
Published: December 2023

Imeglimin has not been well studied as an oral agent for the treatment of latent autoimmune diabetes of adults (LADA). We treated 2 cases of LADA with imeglimin. The case 1 patient was originally diagnosed with type 2 diabetes (T2D) at age 50 years and was treated with sulfonylurea, biguanide, canagliflozin, imeglimin, and dulaglutide. Before imeglimin, his glycated hemoglobin A1c (HbA1c) change was 94.0 mmol/mol (8.6%) in November 2022, but it dropped to 71.0 mmol/mol (6.5%) in May 2023 after imeglimin was added. The case 2 patient was originally diagnosed with T2D when she was aged 48 years. She was treated with vildagliptin, biguanide, luseogliflozin, and imeglimin. Her HbA1c before imeglimin was 92.9 mmol/mol (8.5%) in January 2023, which decreased to 75.4 mmol/mol (6.9%) in July 2023 after imeglimin was added. Although imeglimin has not been approved for treating type 1 diabetes and LADA, adding imeglimin to the current medication was effective in improving and controlling the patients’ plasma glucose.
Insulinoma Presenting as Seizures: Challenges of Managing a Rare Disease in a Resource-challenged Setting
Authors: Soyoye David O , Atolani Segun A , Adetunji Tajudin A , Alatise Olusegun I
Published: December 2023

Insulinomas are functioning pancreatic neuroendocrine tumors (NETs). They secrete insulin, and hence, present with hypoglycemia. We report a case of insulinoma in a 16-year-old girl presenting as seizures. She was initially managed at a private clinic and later commenced on carbamazepine when convulsion persisted. Convulsions were generalized, associated with dizziness and altered sensorium, often preceded by hunger and physical exertion, but relieved by the intake of carbonated drinks and fruit juice. She was referred to the neurology clinic when seizures persisted, despite the use of anticonvulsant. She was later referred to the endocrine clinic on suspicion of insulinoma when her random blood glucose (BG) was found to be low during an episode of convulsion. She was moderately obese but other examination findings were normal. She had a 72-hour prolonged fast, which was terminated when hypoglycemia (BG = 2.2 mmol/L) ensued after 12 hours, with elevated serum insulin and C-peptide. Abdominal magnetic resonance imaging scan showed a pancreatic tumor suggestive of insulinoma. She subsequently had distal pancreatectomy performed with complete resolution of symptoms. Unusual presentation of insulinoma may delay diagnosis, resulting in wastage of resources with increased morbidities and mortality.
Anemia and Optimal Transfusion Thresholds in Brain-Injured Patients: A Narrative Review of the Literature
Authors: Ma Kan , Bebawy John F.
Published: December 2023

Anemia is a highly prevalent condition that may compromise oxygen delivery to vital organs, especially among the critically ill. Although current evidence supports the adoption of a restrictive transfusion strategy and threshold among the nonbleeding critically ill patient, it remains unclear whether this practice should apply to the brain-injured patient, given the predisposition to cerebral ischemia in this patient population, in which even nonprofound anemia may exert a detrimental effect on clinical outcomes. The purpose of this review is to provide an overview of the pathophysiological changes related to impaired cerebral oxygenation in the brain-injured patient and to present the available evidence on the effect of anemia and varying transfusion thresholds on the clinical outcomes of patients with acute brain injury.
Conditionally mutant animal model for investigating the invasive trophoblast cell lineage
Authors: Iqbal Khursheed , Dominguez Esteban M. , Nixon Brandon , Moreno-Irusta Ayelen , Crnkovich Benjamin , Scott Regan L. , Vu Ha T. H. , Tuteja Geetu , Vivian Jay L. , Soares Michael J.
Published: December 2023

Placental development involves coordinated expansion and differentiation of trophoblast cell lineages possessing specialized functions. Among the differentiated trophoblast cell lineages are invasive trophoblast cells, which exit the placenta and invade the uterus, where they restructure the uterine parenchyma and facilitate remodeling of uterine spiral arteries. The rat exhibits deep intrauterine trophoblast cell invasion, a feature shared with human placentation, and is also amenable to gene manipulation using genome-editing techniques. In this investigation, we generated a conditional rat model targeting the invasive trophoblast cell lineage. Prolactin family 7, subfamily b, member 1 (Prl7b1) is uniquely and abundantly expressed in the rat invasive trophoblast cell lineage. Disruption of Prl7b1 did not adversely affect placental development. We demonstrated that the Prl7b1 locus could be effectively used to drive the expression of Cre recombinase in invasive trophoblast cells. Our rat model represents a new tool for investigating candidate genes contributing to the regulation of invasive trophoblast cells and their roles in trophoblast-guided uterine spiral artery remodeling.