bluuebunny/crossref_metadata_2025 huggingface dataset:
Love over gold and mind over matter? Identifying capabilities that preserve medical assistants’ sustainable employability
Authors: Fleuren Bram P. I. , Lai Alden Yuanhong , Gruenewald-Schmitz Lynda , Larkin Jennifer , Yuan Christina T.
Published: July 2024

Background

Medical assistants (MAs) are crucial for affordable, high-quality primary care, but what motivates this low-wage occupational group to stay in their job remains underexplored. This paper identifies the work aspects that MAs value (“capabilities”), and how they affect sustainable employability, which refers to employees’ long-term ability to function and remain in their job.

Methods

We used structural equation modelling to assess how capabilities relate to four outcomes among MAs: burnout, job satisfaction, intention to quit, and experiencing work as meaningful.

Results

We find that earning a good income, developing knowledge and skills, and having meaningful relationships at work relate to the outcomes. Meaningful relationships represent a stronger predictor than salary for one’s intention to quit.

Conclusions

Competitive salaries are necessary but not sufficient to motivate low-wage health care workers like MAs to stay in their job. Health care leaders and managers should also structure work so that MAs can foster meaningful relationships with others as well as develop competencies.
Upregulation of Siglec-6 induces mitochondrial dysfunction by promoting GPR20 expression in early-onset preeclampsia
Authors: Jia Yuanhui , Lu Wenjing , Xie Han , Sheng Yifan , Wang Luyao , Lv Wenqi , Ling Lijun , Dong Jiaqi , Jia Xinrui , Wu Shengyu , Liu Wenqiang , Ying Hao
Published: July 2024

Background

Preeclampsia, especially early-onset preeclampsia (EO-PE), is a pregnancy complication that has serious consequences for the health of both the mother and the fetus. Although abnormal placentation due to mitochondrial dysfunction is speculated to contribute to the development of EO-PE, the underlying mechanisms have yet to be fully elucidated.

Methods

The expression and localization of Siglec-6 in the placenta from normal pregnancies, preterm birth and EO-PE patients were examined by RT-qPCR, Western blot and IHC. Transwell assays were performed to evaluate the effect of Siglec-6 on trophoblast cell migration and invasion. Seahorse experiments were conducted to assess the impact of disrupting Siglec-6 expression on mitochondrial function. Co-IP assay was used to examine the interaction of Siglec-6 with SHP1/SHP2. RNA-seq was employed to investigate the mechanism by which Siglec-6 inhibits mitochondrial function in trophoblast cells.

Results

The expression of Siglec-6 in extravillous trophoblasts is increased in placental tissues from EO-PE patients. Siglec-6 inhibits trophoblast cell migration and invasion and impairs mitochondrial function. Mechanismly, Siglec-6 inhibits the activation of NF-κB by recruiting SHP1/SHP2, leading to increased expression of GPR20. Notably, the importance of GPR20 function downstream of Siglec-6 in trophoblasts is supported by the observation that GPR20 downregulation rescues defects caused by Siglec-6 overexpression. Finally, overexpression of Siglec-6 in the placenta induces a preeclampsia-like phenotype in a pregnant mouse model.

Conclusions

This study indicates that the regulatory pathway Siglec-6/GPR20 has a crucial role in regulating trophoblast mitochondrial function, and we suggest that Siglec-6 and GPR20 could serve as potential markers and targets for the clinical diagnosis and therapy of EO-PE.
Development of the paediatric society of the African league against rheumatism (PAFLAR) JIA registry and clinical profile of JIA in Africa from the PAFLAR JIA registry
Authors: Migowa Angela Nyangore , Hamdi Wafa , Hashad Soad , Etayari Hala , Abushhaiwia Awatif , Ferjani Hanene , Nessib Dorra Ben , Kharrat Lobna , Fazaa Alia , Owino Lawrence , Faleye Ayodele , Owusu Sheila Agyeiwaa , Mosa Doaa Mosad , Eissa Mervat , Nasef Samah Ismail , Elsehrawy Gehad Gamal , Odhiambo Rachel , Orwa James , Abu-Zaid Mohammed Hassan
Published: July 2024

Background

The spectrum of Juvenile Idiopathic Arthritis (JIA) in Africa is still largely unknown. We thus set out to illustrate how we set up the PAFLAR JIA registry and describe the clinical profile of Juvenile Idiopathic Arthritis across various regions in Africa.

Methods

We carried out a retrospective observational cohort study where collaborators were trained on use of the existing PAFLAR REDCAP database to enter data for the JIA patients currently under their care capturing their epidemiological data, clinical features, laboratory investigations, diagnosis and therapy at initial diagnosis. Descriptive statistics including means, standard deviations, medians, interquartile ranges (IQR) for continuous variables and proportions for categorical variables were calculated as appropriate. Tests for difference between groups were performed between categorical variables using Pearson’s chi-square or Fisher’s exact tests. All analyses were performed using SPSS version 22 software.

Results

We enrolled 302 patients, 58.6% (177 of 302) of whom were female. The median age of disease onset was 7 years (range 3–11 years) and the median age at diagnosis was 8.5 years (range 5–12 years). The median duration delay in diagnosis was 6 months (range 1-20.8 months). The JIA categories included Systemic JIA 18.9% (57), Oligoarticular JIA 19.2% (83), Polyarticular RF + ve 5% (15), Polyarticular RF-ve 17.9% (54), Enthesitis Related Arthritis (ERA) 18.2% (55), Psoriatic Arthritis 7% (21) and undifferentiated JIA 5.6% (17). As regards treatment the commonest therapies were NSAID therapy at 31.1%, synthetic DMARDs at 18.1%, synthetic DMARDs combined with NSAIDs at 17.5% and steroid therapy at 9.6%. Biological DMARDs accounted for 2.3% of therapies offered to our patients at diagnosis. The average JADAS score was 10.3 (range 4.8–18.2) and the average CHAQ score was 1.3 (range 0.7-2.0).

Conclusion

Our study highlights strategies involved in setting up a Pan-African paediatric rheumatology registry that embraces our broad diversity and the vast spectrum of JIA in Africa while comparing the various therapies available to our patients. The PAFLAR JIA registry strives to ensure a comprehensive representation of the diverse healthcare landscapes within the continent. Further longitudinal observation studies are required to ascertain the long-term outcomes of our patients and ultimately help inform policy to create a more favorable health ecosystem to support the healthcare needs of JIA patients in Africa.
Resistance to protease inhibitors among persons living with HIV in Ghana: a case for viral load and drug resistance monitoring
Authors: Seshie Makafui , Obeng Billal Musah , Boamah Vivian Etsiapa , Bayor Marcel , Bonney Evelyn Yayra , Gbedema Stephen Yao , Sagoe Kwamena William Coleman
Published: July 2024

Objective

Routine viral load and drug resistance testing are well supported in most resource-rich settings and provide valuable benefits in the clinical care of PLWH in these communities. Undoubtedly, there exist financial and political constraints for the scale-up of viral load and drug resistance testing in Sub-Saharan Africa. To achieve the global UNAIDS 95/95/95 targets, there is the need to bridge this inequity in patient care and allow for a universal approach that leaves no community behind.

Methods

Venous blood from 96 PLWH on second-line ART from Korle-Bu Teaching Hospital were collected and processed into plasma for CD4+ T- cell and viral load assessments. Ribonucleic acid (RNA) was extracted from stored plasma and the protease gene amplified, sequenced and analyzed for subtype and drug resistance mutations using the Stanford HIV drug resistance database.

Results

Out of the 96 PLWH, 37 experienced virological failure with 8 patients’ samples successfully sequenced. The predominant HIV-1 subtype identified was CRF02_AG (6/8, 75.0%) with 12.5% (1/8) each of CFR06_cpx infection and one case unable to subtype. The major PI resistance mutations identified were; M46I, I54V, V82A, I47V, I84V and L90M.

Conclusions

Persons living with HIV who had experienced virologic failure in this study harboured drug resistance mutations to PI, thus compromise the effectiveness of the drugs in the second line. Resistance testing is strongly recommended prior to switching to a new regimen. This will help to inform the choice of drug and to achieve optimum therapeutic outcome among PLWH in Ghana.
Oxysterol binding protein (OSBP) contributes to hepatitis E virus replication
Authors: Lin Shaoli , Chang Peixi , Tsao Shane , Aderinwale Abigail , Sallapalli Bhargava Teja , He Jia , Zhang Yanjin
Published: July 2024

Hepatitis E virus (HEV) is a positive-sense, single-stranded RNA virus and causes primarily acute self-limiting infections. The ORF1 of the HEV genome encodes a polyprotein around 190 kDa, which contains several putative domains, including helicase and RNA-dependent RNA polymerase. The HEV-encoded helicase is a member of the superfamily 1 helicase family and possesses multiple enzymatic functions, such as RNA 5′-triphosphatase, RNA unwinding, and NTPase, which are thought to contribute to viral RNA synthesis. However, the helicase interaction with cellular proteins remains less known. Oxysterol binding protein (OSBP) is a lipid regulator that shuffles between the Golgi apparatus and the endoplasmic reticulum for cholesterol and phosphatidylinositol-4-phosphate exchange and controls the efflux of cholesterol from cells. In this study, the RNAi-mediated silencing of OSBP significantly reduced HEV replication. Further studies indicate that the HEV helicase interacted with OSBP, shown by co-immunoprecipitation and co-localization in co-transfected cells. The presence of helicase blocked OSBP preferential translocation to the Golgi apparatus. These results demonstrate that OSBP contributes to HEV replication and enrich our understanding of the HEV-cell interactions.
Brain-derived neurotrophic factor and C-reactive protein (CRP) biomarkers in suicide attempter and non-attempter major depression disorder (MDD) patients
Authors: Saadat Seyed Hassan , Javanbakht Mohammad , Shahyad Shima
Published: July 2024

Background

In the available literature, levels of BDNF and CRP have been reported to correlate with suicide in depressive patients but there are inconsistencies in the results. We aimed to evaluate and compare BDNF and CRP concentrations in MDD patients with(MDD + SA) and without suicide attempts (MDD-SA) and healthy controls.

Methods

30 (MDD + SA) patients, 30 (MDD-SA) patients, and 26 healthy controls were enrolled in the study. Age, sex, and BMI of patients were recorded. Blood sample was obtained for measurement of BDNF and CRP. Smoking and drug history, family history of suicide, and history of self-harm were also documented. Data were analyzed with SPSS version 22 and R version 4.1.1.

Results

86 patients in three groups were evaluated (mean age: 28.45 ± 9.27 years, 56.71% female). Baseline and demographic parameters except for self-harm (40%, 3.3%, and 0% for MDD + SA, MDD-SA, and healthy controls, respectively, p = 0.001) did not differ between groups. CRP level was not significantly different between groups. BDNF showed a significant difference between groups (17.35, 16.45, and 19.43 for three groups, respectively, p < 0.001). An increase in BDNF decreased the odds of both depression and suicide. Roc curve showed excellent power for BDNF in discriminating MDD groups With healthy group.Roc can notdicrimiate MDD + SA and MDD-SA.

Conclusion

In our study, the concentration of BDNF differed significantly between depressed patients with/without suicide attempts and healthy controls which shows the association of BDNF with depression development and not suicide attempts. We could not find any association between CRP level and suicide attempt but still larger cohorts are needed for a definite conclusion.
SpeedyPaddy: a revolutionized cost-effective protocol for large scale offseason advancement of rice germplasm
Authors: Sandhu Nitika , Singh Jasneet , Pruthi Gomsie , Verma Vikas Kumar , Raigar Om Prakash , Bains Navtej Singh , Chhuneja Parveen , Kumar Arvind
Published: July 2024

Background

Improving the rate of genetic gain of cereal crop will rely on the accelerated crop breeding pipelines to allow rapid delivery of improved crop varieties. The laborious, time-consuming traditional breeding cycle, and the seasonal variations are the key factor restricting the breeder to develop new varieties. To address these issues, a revolutionized cost-effective speed breeding protocol for large-scale rice germplasm advancement is presented in the present study. The protocol emphasises on optimizing potting material, balancing the double-edged sword of limited nutritional dose, mode and stage of application, plant density, temperature, humidity, light spectrum, intensity, photoperiod, and hormonal regulation to accelerate rice growth and development.

Results

The plant density of 700 plants/m2, cost-effective halogen tubes (B:G:R:FR-7.0:27.6:65.4:89.2) with an intensity of ∼ 750–800 µmol/m2/s and photoperiod of 13 h light and 11 h dark during seedling and vegetative stage and 8 h light and 16 h dark during reproductive stage had a significant effect (P < 0.05) on reducing the mean plant height, tillering, and inducing early flowering. Our results confirmed that one generation can be achieved within 68–75 days using the cost-effective SpeedyPaddy protocol resulting in 4–5 generations per year across different duration of rice varieties. The other applications include hybridization, trait-based phenotyping, and mapping of QTL/genes. The estimated cost to run one breeding cycle with plant capacity of 15,680 plants in SpeedyPaddy was $2941 including one-time miscellaneous cost which is much lower than the advanced controlled environment speed breeding facilities.

Conclusion

The protocol offers a promising cost-effective solution with average saving of 2.0 to 2.6 months per breeding cycle with an integration of genomics-assisted selection, trait-based phenotyping, mapping of QTL/genes, marker development may accelerate the varietal development and release. This outstanding cost-effective break-through marks a significant leap in rice breeding addressing climate change and food security.
Comparative effects of different posterior decompression techniques for lumbar spinal stenosis: a systematic review and Bayesian network meta-analysis
Authors: Wu Kun , Yun Zhihe , Zhang Jun , Yu Tao , Dai Anyuan , Sun Yang , Li Chen , Wang Yanli , Liu Qinyi
Published: July 2024

Study design

A systematic review and Bayesian network meta-analysis (NMA).

Objective

To compare the effectiveness and safety of different posterior decompression techniques for LSS.

Summary of background data

Lumbar spinal stenosis (LSS) is one of the most common degenerative spinal diseases that result in claudication, back and leg pain, and disability. Currently, posterior decompression techniques are widely used as an effective treatment for LSS.

Methods

An electronic literature search was performed using the EMBASE, Web of Science, PubMed, and Cochrane Library databases. Two authors independently performed data extraction and quality assessment. A Bayesian random effects model was constructed to incorporate the estimates of direct and indirect treatment comparisons and rank the interventions in order.

Results

In all, 14 eligible studies comprising 1,260 patients with LSS were included. Five interventions were identified, namely, spinal processes osteotomy (SPO), conventional laminotomy/laminectomy (CL), unilateral laminotomy/laminectomy (UL), bilateral laminotomy/ laminectomy (BL), and spinous process-splitting laminotomy/laminectomy (SPSL). Among these, SPO was the most promising surgical option for decreasing back and leg pain and for lowering the Oswestry Disability Index (ODI). SSPL had the shortest operation time, while SPSL was associated with maximum blood loss. SPO and UL were superior to other posterior decompression techniques concerning lesser blood loss and shorter length of hospital stay, respectively. Patients who underwent BL had the lowest postoperative complication rates.

Conclusion

Overall, SPO was found to be a good surgical choice for patients with LSS.
Applying 3D-printed prostheses to reconstruct critical-sized bone defects of tibial diaphysis (> 10 cm) caused by osteomyelitis and aseptic non-union
Authors: Liu Bingchuan , Wang Liwei , Li Xingcai , Chen Zhuo , Hou Guojin , Zhou Fang , Wang Caimei , Tian Yun
Published: July 2024

Background

Clinical repair of critical-sized bone defects (CBDs) in the tibial diaphysis presents numerous challenges, including inadequate soft tissue coverage, limited blood supply, high load-bearing demands, and potential deformities. This study aimed to investigate the clinical feasibility and efficacy of employing 3D-printed prostheses for repairing CBDs exceeding 10 cm in the tibial diaphysis.

Methods

This retrospective study included 14 patients (11 males and 3 females) with an average age of 46.0 years. The etiologies of CBDs comprised chronic osteomyelitis (10 cases) and aseptic non-union (4 cases), with an average defect length of 16.9 cm. All patients underwent a two-stage surgical approach: (1) debridement, osteotomy, and cement spacer implantation; and (2) insertion of 3D-printed prostheses. The interval between the two stages ranged from 8 to 12 weeks, during which the 3D-printed prostheses and induced membranes were meticulously prepared. Subsequent to surgery, patients engaged in weight-bearing and functional exercises under specialized supervision. Follow-up assessments, including gross observation, imaging examinations, and administration of the Lower Extremity Functional Scale (LEFS), were conducted at 3, 6, and 12 months postoperatively, followed by annual evaluations thereafter.

Results

The mean postoperative follow-up duration was 28.4 months, with an average waiting period between prosthesis implantation and weight-bearing of 10.4 days. At the latest follow-up, all patients demonstrated autonomous ambulation without assistance, and their LEFS scores exhibited a significant improvement compared to preoperative values (30.7 vs. 53.1, P < 0.001). Imaging assessments revealed progressive bone regeneration at the defect site, with new bone formation extending along the prosthesis. Complications included interlocking screw breakage in two patients, interlocking screw loosening in one patient, and nail breakage in another.

Conclusions

Utilization of 3D-printed prostheses facilitates prompt restoration of CBDs in the tibial diaphysis, enabling early initiation of weight-bearing activities and recovery of ambulatory function. This efficacious surgical approach holds promise for practical application.
Early surgery to prevent embolic events in patients with infective endocarditis: a comprehensive review
Authors: Nielsen Sikander Tajik , Hadji-Turdeghal Katra , Graversen Peter Laursen , Østergaard Lauge , Smerup Morten Holdgaard , Køber Lars , Fosbøl Emil Loldrup
Published: July 2024

Background

Infective endocarditis (IE) is a dangerous and lethal illness with high mortality rates. One of the main indications for surgery according to the guidelines is prevention of embolic events. However, uncertainty remains concerning the timing of surgery and the effect of early surgery in combination with antibiotic therapy versus antibiotic therapy alone in IE patients with a vegetation size > 10 mm.

Methods

We conducted a comprehensive review by searching the PubMed, MEDLINE, and EMbase databases. Titles and abstracts were screened, and studies of interest were selected for full-text assessment. Studies were selected for review if they met the criteria of comparing surgical treatment + antibiotic therapy to antibiotic therapy alone in patients with vegetations > 10 mm.

Results

We found 1,503 studies through our database search; nine of these were eligible for review, with a total number of 3,565 patients. Median age was 66 years (range: 17–80) and the median percentage of male patients was 65.6% (range: 61.8 − 71.4%). There was one randomised controlled trial, one prospective study, and seven retrospective studies. Seven studies found surgery + antibiotic therapy to be associated with better outcomes in patients with IE and vegetations > 10 mm, one of them being the randomised trial [hazard ratio = 0.10; 95% confidence interval 0.01–0.82]. Two studies found surgery + antibiotic therapy was associated with poorer outcomes compared with antibiotic therapy alone.

Conclusion

Overall, data vary in quality due to low numbers and selection bias. Evidence is conflicting, yet suggest that surgery + antibiotic therapy is associated with better outcomes in patients with IE and vegetations > 10 mm for prevention of emboli. Properly powered randomised trials are warranted.
Hypoxia-enhanced YAP1-EIF4A3 interaction drives circ_0007386 circularization by competing with CRIM1 pre-mRNA linear splicing and promotes non-small cell lung cancer progression
Authors: Li Lixia , Liu Dewei , Chen Tingting , Wei Chunhui , Qiao Youping , Liu Weiliang , Liang Yanmei , Liang Zhu , Chen Chunyuan , Li Dongming , Wu Bin , Zhao Xuanna , Huang Dan , Wu Dong
Published: July 2024

Background

The progression of non-small cell lung cancer (NSCLC) is significantly influenced by circular RNAs (circRNAs), especially in tumor hypoxia microenvironment. However, the precise functions and underlying mechanisms of dysregulated circRNAs in NSCLC remain largely unexplored.

Methods

Differentially expressed circRNAs in NSCLC tissues were identified through high-throughput RNA sequencing. The characteristics of circ_0007386 were rigorously confirmed via Sanger sequencing, RNase R treatment and actinomycin D treatment. The effects of circ_0007386 on proliferation and apoptosis were investigated using CCK8, cloning formation assays, TUNEL staining, and flow cytometry assays in vitro. In vivo, xenograft tumor models were used to evaluate its impact on proliferation. Mechanistically, the regulatory relationships of circ_0007386, miR-383-5p and CIRBP were examined through dual luciferase reporter assays and rescue experiments. Additionally, we detected the binding of EIF4A3 to CRIM1 pre-mRNA by RNA immunoprecipitation and the interaction between YAP1 and EIF4A3 under hypoxic conditions by co-immunoprecipitation.

Results

Our investigation revealed a novel circRNA, designated as circ_0007386, that was upregulated in NSCLC tissues and cell lines. Circ_0007386 modulated proliferation and apoptosis in NSCLC both in vitro and in vivo. Functionally, circ_0007386 acted as a sponge for miR-383-5p, targeting CIRBP, which influenced NSCLC cell proliferation and apoptosis via the PI3K/AKT signaling pathway. Furthermore, under hypoxic conditions, the interaction between YAP1 and EIF4A3 was enhanced, leading to the displacement of EIF4A4 from binding to CRIM1 pre-mRNA. This facilitated the back-splicing of CRIM1 pre-mRNA, increasing the formation of circ_0007386. The circ_0007386/miR-383-5p/CIRBP axis was significantly associated with the clinical features and prognosis of NSCLC patients.

Conclusions

Circ_0007386, regulated by YAP1-EIF4A3 interaction under hypoxia conditions, plays an oncogenic role in NSCLC progression via the miR-383-5p/CIRBP axis.
Description and molecular characterisation of Babesia ailuropodae n. sp., a new piroplasmid species infecting giant pandas
Authors: Xiong Lang , Yang Guangyou
Published: July 2024

Background

Babesia spp. are protozoan parasites that infect the red blood cells of domesticated animals, wildlife and humans. A few cases of giant pandas (a flagship species in terms of wildlife conservation) infected with a putative novel Babesia sp. have been reported. However, comprehensive research on the morphological and molecular taxonomic classification of this novel Babesia sp. is still lacking. This study was designed to close this gap and formally describe this new Babesia sp. infecting giant pandas.

Methods

Detailed morphological, molecular and phylogenetic analyses were conducted to characterise this Babesia sp. and to assess its systematic relationships with other Babesia spp. Blood samples from giant pandas infected with Babesia were subjected to microscopic examination. The 18S ribosomal RNA (18S rRNA), cytochrome b (cytb) and mitochondrial genome (mitogenome) of the new Babesia sp. were amplified, sequenced and assembled using DNA purified from blood samples taken from infected giant pandas. Based on the newly generated 18S rRNA, cytb and mitogenome sequences, phylogenetic trees were constructed.

Results

Morphologically, the Babesia sp. from giant pandas exhibited various forms, including round to oval ring-shaped morphologies, resembling those found in other small canine Babesia spp. and displaying typical tetrads. Phylogenetic analyses with the 18S rRNA, cytb and mitogenome sequences revealed that the new Babesia sp. forms a monophyletic group, with a close phylogenetic relationship with the Babesia spp. that infect bears (Ursidae), raccoons (Procyonidae) and canids (Canidae). Notably, the mitogenome structure consisted of six ribosomal large subunit-coding genes (LSU1-6) and three protein-coding genes (cytb, cox3 and cox1) arranged linearly.

Conclusions

Based on coupled morphological and genetic analyses, we describe a novel species of the genus Babesia, namely, Babesia ailuropodae n. sp., which infects giant pandas.

Graphical Abstract
Effects of a 12-week intrinsic foot muscle strengthening training (STIFF) on gait in older adults: a parallel randomized controlled trial protocol
Authors: Willemse Lydia , Wouters Eveline J. M. , Pisters Martijn F. , Vanwanseele Benedicte
Published: July 2024

Background

Falling is highly prevalent among older adults and has serious impact. Age-induced mobility impairments, such as gait modifications, are strongly associated with increased fall risk. Among fall prevention interventions, those including exercises are most effective. However, there is an urgent need to further improve these kinds of interventions. Strengthening the plantar intrinsic foot muscles might benefit mobility in older adults, which may contribute to the reduction of fall risk. The aim of this paper is to provide a protocol to investigate the effect of a plantar intrinsic foot muscle strengthening training versus no training on gait and intrinsic foot muscle function in older adults who are involved in a functional exercise program.

Methods

For this assessor-blinded RCT, older adults (> 65 years) are recruited who are involved in a group-based functional exercise program. Eligibility criteria include: being able to ambulate 10 m barefoot without using a walking aid and reporting to have either fear of falling or experienced a fall in the previous 12 months or have difficulties with mobility, gait, or balance in daily life. Participants are randomly assigned to an intervention and a control group. The intervention group follows a 12-week plantar intrinsic foot muscle strengthening training. The training consists of isolated and functional foot exercises to be performed 5 times a week, each session lasting approximately 20 min. The training is supervised once a week and the intensity gradually increases based on the participant’s progression. Both groups keep a diary to report physical activities, fall incidents and movement related discomfort. The control condition is limited to keeping this diary. Data are collected at baseline and post-intervention. The trial outcomes are the between group differences in the mean change from baseline in maximum gait speed (primary outcome measure), capacity and strength of the plantar intrinsic foot muscles, foot and ankle biomechanics during gait, and various other fall risk-related variables. ANCOVA’s are used to analyze the trial outcomes.

Discussion

The results of this RCT will offer recommendations, related to plantar intrinsic foot muscle strengthening, to existing fall preventive exercise programs.

Trial registration

The trial is registered in the United States National Library of Medicine through ClinicalTrials.gov (NCT05531136, 07/26/2022).
Epigenetic and transcriptional control of adipocyte function by centenarian-associated SIRT6 N308K/A313S mutant
Authors: Frohlich Jan , Liorni Niccolò , Mangoni Manuel , Lochmanová Gabriela , Pírek Pavlína , Kaštánková Nikola , Pata Pille , Kucera Jan , Chaldakov George N. , Tonchev Anton B. , Pata Illar , Gorbunova Vera , Leire Eric , Zdráhal Zbyněk , Mazza Tommaso , Vinciguerra Manlio
Published: July 2024

Background

Obesity is a major health burden. Preadipocytes proliferate and differentiate in mature adipocytes in the adipogenic process, which could be a potential therapeutic approach for obesity. Deficiency of SIRT6, a stress-responsive protein deacetylase and mono-ADP ribosyltransferase enzyme, blocks adipogenesis. Mutants of SIRT6 (N308K/A313S) were recently linked to the in the long lifespan Ashkenazi Jews. In this study, we aimed to clarify how these new centenarian-associated SIRT6 genetic variants affect adipogenesis at the transcriptional and epigenetic level.

Methods

We analyzed the role of SIRT6 wild-type (WT) or SIRT6 centenarian-associated mutant (N308K/A313S) overexpression in adipogenesis, by creating stably transduced preadipocyte cell lines using lentivirus on the 3T3-L1 model. Histone post-translational modifications (PTM: acetylation, methylation) and transcriptomic changes were analyzed by mass spectrometry (LC–MS/MS) and RNA-Seq, respectively, in 3T3-L1 adipocytes. In addition, the adipogenic process and related signaling pathways were investigated by bioinformatics and biochemical approaches.

Results

Overexpression of centenarian-associated SIRT6 mutant increased adipogenic differentiation to a similar extent compared to the WT form. However, it triggered distinct histone PTM profiles in mature adipocytes, with significantly higher acetylation levels, and activated divergent transcriptional programs, including those dependent on signaling related to the sympathetic innervation and to PI3K pathway. 3T3-L1 mature adipocytes overexpressing SIRT6 N308K/A313S displayed increased insulin sensitivity in a neuropeptide Y (NPY)-dependent manner.

Conclusions

SIRT6 N308K/A313S overexpression in mature adipocytes ameliorated glucose sensitivity and impacted sympathetic innervation signaling. These findings highlight the importance of targeting SIRT6 enzymatic activities to regulate the co-morbidities associated with obesity.
The Bifidobacterium adolescentis BAD_1527 gene encodes GH43_22 α-L-arabinofuranosidase of AXH-m type
Authors: Fathallah Walid , Puchart Vladimír
Published: July 2024

Bifidobacterium adolescentis gene BAD_1527 has previously been suggested to code for a β-xylosidase (Kobayashi et al., Mar Drugs 18:174, 2020). Our detailed investigation of the substrate specificity of the GH43_22 protein using a wide spectrum of natural and artificial substrates showed that the enzyme hydrolyzed neither linear xylooligosaccharides nor glucuronoxylan. Xylose was released only from the artificial 4-nitrophenyl β-D-xylopyranoside (1.58 mU/mg). The corresponding α-L-arabinofuranoside was by three orders of magnitude better substrate (2.17 U/mg). Arabinose was the only monosaccharide liberated from arabinoxylan and α-1,3- or α-1,2-singly arabinosylated xylooligosaccharides. Moreover, the enzyme efficiently debranched sugar beet arabinan and singly arabinosylated α-1,5-L-arabinooligosaccharides, although short linear α-1,5-L-arabinooligosaccharides were also slowly degraded. On the other hand, debranched arabinan, arabinogalactan as well as 2,3-doubly arabinosylated main chain residues of arabinan and arabinoxylan did not serve as substrates. Thus, the enzyme encoded by the BAD_1527 gene is a typical α-L-arabinofuranosidase of AXH-m specificity.
An epidemiological investigation into the reasons for high bovine tuberculosis incidence in cattle herds of the Burren, Ireland, prior to 2020
Authors: Tratalos Jamie Alexander , Madden Jamie Michael , Casey Miriam , McSweeney Catherine , Farrell Fidelma Mary , More Simon John
Published: July 2024

Herd-level bovine tuberculosis (bTB) incidence was examined in the Burren, an area in the west of Ireland where herd owners practice distinctive transhumance practices, with upland winter grazing. Prior to the initiation of our study in 2020, bTB incidence had for many years been unusually high in the Burren in comparison with the rest of the country, although the most recent figures have come down to being closer to the national average. Using data from the period prior to 2020, we mapped bTB infection in Burren herds alongside a range of indicators thought to have an association with it - herd size, herd density, herd type, cattle movement, and badger (Meles meles) population and control data, as well as rainfall and altitude. We also looked at how summary statistics for these variables differed when Burren herds with a history of bTB were compared to other Burren herds, as well as bTB positive and negative herds from outside the Burren. We found that for many indicators Burren herds would be expected to be low risk when compared to other herds in Ireland. An exception to this was for rainfall: hot spot areas for bTB in the Burren were found in areas of higher rainfall, on average herds in the Burren experienced more rainfall than those outside it, and bTB herds in the Burren experienced higher rainfall than non-bTB herds. Separately, for Burren herds only, a logistic regression model was developed to explain bTB breakdown occurrence using a matched case-control approach. Cases were herds which had experienced a new bTB breakdown between 2015 and 2019 (n = 260) and these were matched on herd type and herd size with the same number of herds not experiencing a breakdown during this period. This showed that, of a range of exogenous variables, rainfall was the most strongly associated with herd-level bTB incidence. These results suggest that high levels of exposure to inclement weather, and/or better environmental survival of Mycobacterium bovis in the environment, may contribute to high bTB rates in the Burren. However, as rainfall showed a highly aggregated distribution, this relationship may be due to an unmeasured factor correlated with it. Mapping and graphical output suggested that, although herd sizes in the Burren were on average lower than nationally, within the Burren they were higher in areas of higher prevalence, suggesting that mechanisms associated with herd size, such as increased contacts between and within herd, and with wildlife, may also play a role.
Evaluation and comparison of infiltration models for estimating infiltration capacity of different textures of irrigated soils
Authors: Mesele Halefom , Grum Berhane , Aregay Gebremeskel , Berhe Gebremeskel Teklay
Published: July 2024

Accurate estimation of infiltration rates is crucial for effective irrigation system design and evaluation by optimizing irrigation scheduling, preventing soil erosion, and enhancing water use efficiency. This study evaluates and compares selected infiltration models for estimating water infiltration rates in the Shillanat-iv irrigation scheme in northern Ethiopia. Soil samples were collected to determine textural classes using hydrometer soil texture analysis and the United States Department of Agriculture (USDA) textural triangle. The soil textural map of the study was created using the inverse distance weight interpolation technique in ArcGIS version 10.4. Infiltration rates were measured using the double-ring infiltrometer for five soil textures: clay loam, loam, sandy clay loam, clay, and sandy loam. Six infiltration models (Kostiakov, Modified Kostiakov, Revised Modified Kostiakov, Philip, Horton, and Novel) were employed and evaluated using statistical parameters. Model calibration and validation were conducted using data from 38 points within the study area. The parameter values of the infiltration models were optimized using SPSS statistical software using least-squares errors. The results showed that, Revised Modified Kostiakov, Modified Kostiakov, and Novel infiltration models demonstrated superior capability in estimating infiltration rates for clay loam, loam, and sandy loam soil textures, respectively. Horton's model outperformed other models in estimating infiltration rates for both sandy clay loam and clay soil textures. The appropriately fitted infiltration models can be utilized in designing the irrigation system to estimate the infiltration rate of soil textures within the selected irrigation scheme and at similar sites with comparable soil textures.
Persistent enrichment of multidrug-resistant Klebsiella in oral and nasal communities during long-term starvation
Authors: Liu Jett , Spencer Nell , Utter Daniel R. , Grossman Alex S. , Lei Lei , dos Santos Nídia Castro , Shi Wenyuan , Baker Jonathon L. , Hasturk Hatice , He Xuesong , Bor Batbileg
Published: July 2024

Background

The human oral and nasal cavities can act as reservoirs for opportunistic pathogens capable of causing acute infection. These microbes asymptomatically colonize the human oral and nasal cavities which facilitates transmission within human populations via the environment, and they routinely possess clinically significant antibiotic resistance genes. Among these opportunistic pathogens, the Klebsiella genus stands out as a notable example, with its members frequently linked to nosocomial infections and multidrug resistance. As with many colonizing opportunistic pathogens, the essential transmission factors influencing the spread of Klebsiella species among both healthy and diseased individuals remain unclear.

Results

Here, we explored a possible explanation by investigating the ability of oral and nasal Klebsiella species to outcompete their native microbial community members under in vitro starvation conditions, which could be analogous to external hospital environments or the microenvironment of mechanical ventilators. When K. pneumoniae and K. aerogenes were present within a healthy human oral or nasal sample, the bacterial community composition shifted dramatically under starvation conditions and typically became enriched in Klebsiella species. Furthermore, introducing K. pneumoniae exogenously into a native microbial community lacking K. pneumoniae, even at low inoculum, led to repeated enrichment under starvation. Precise monitoring of K. pneumoniae within these communities undergoing starvation indicated rapid initial growth and prolonged viability compared to other members of the microbiome. K. pneumoniae strains isolated from healthy individuals’ oral and nasal cavities also exhibited resistance to multiple classes of antibiotics and were genetically similar to clinical and gut isolates. In addition, we found that in the absence of Klebsiella species, other understudied opportunistic pathogens, such as Peptostreptococcus, increased in relative abundance under starvation conditions.

Conclusions

Our findings establish an environmental and microbiome community circumstance that allows for the enrichment of Klebsiella species and other opportunistic pathogens. Klebsiella’s enrichment may hinge on its ability to quickly outgrow other members of the microbiome. The ability to outcompete other commensal bacteria and to persist under harsh environmental conditions could be an important factor that contributes to enhanced transmission in both commensal and pathogenic contexts.
Gone with the wind: environmental variation influences detection efficiency in a coastal acoustic telemetry array
Authors: Edwards Jena E. , Buijse Anthonie D. , Winter Hendrik V. , Bijleveld Allert I.
Published: July 2024

Range tests play a critical role in designing acoustic telemetry studies, guiding equipment configuration, deployment techniques, and the analysis of animal movement data. These studies often strive to capture the effects of environmental variation on detection efficiency over time but are frequently limited in spatial and temporal scale. This could lead to disparities between test results and the circumstances encountered during animal tracking studies. In this study, we evaluated detection range and efficiency at two distinct spatial and temporal scales in a dynamic intertidal ecosystem. Two range tests were conducted, the first being a small-scale study using 6 receivers deployed over 1 month. Using modern acoustic receivers with built-in transmitters and environmental sensors, we then conducted a large-scale range test with 22 receiver stations over a full year to approximate the area and duration of a typical animal movement study. Differences in detection range between the two studies occurred as a result of environmental variation and tag power output, with midpoint ranges estimated as 123 m (small scale, low power), 149 m (small scale, high power) and 311 m (large scale, very high power). At both scales, wind speed emerged as the most influential factor explaining temporal variation in predicted detection efficiency. However, this effect was modulated by wind direction which varied as a result of land sheltering and fetch between the two study scales. At the small scale, detection efficiency decreased with winds from the south and east, while at the large scale, northern and westerly winds were most detrimental. Water temperature had a positive effect on predicted detection efficiency at both scales, while relative water level was positive at the small scale and negative at the large scale. Additional factors, including precipitation and Topographic Position Index, were found to influence detection efficiency at a large scale. Moreover, sensors associated with receivers in the larger array revealed the significant influences of receiver tilt and ambient noise. These discrepancies in the outcomes of the two studies underscore the critical role of scale in range test design and emphasize the need for long-term, in situ range testing at relevant spatial scales.
Detection of neoplastic-immune hybrid cells with metastatic properties in uveal melanoma
Authors: Anderson Ashley N. , Conley Patrick , Klocke Christopher D. , Sengupta Sidharth K. , Pang Amara , Farley Hannah C. , Gillingham Abigail R. , Dawson Aubrey D. , Fan Yichen , Jones Jocelyn A. , Gibbs Summer L. , Skalet Alison H. , Wu Guanming , Wong Melissa H.
Published: July 2024

Background

Uveal melanoma is the most common non-cutaneous melanoma and is an intraocular malignancy affecting nearly 7,000 individuals per year worldwide. Of these, approximately 50% will progress to metastatic disease for which there are currently no effective curative therapies. Despite advances in molecular profiling and metastatic stratification of uveal melanoma tumors, little is known regarding their underlying biology of metastasis. Our group has identified a disseminated neoplastic cell population characterized by co-expression of immune and melanoma proteins, circulating hybrid cells (hybrids), in patients with uveal melanoma. Compared to circulating tumor cells, which lack expression of immune proteins, hybrids are detected at an increased prevalence in peripheral blood and can be used as a non-invasive biomarker to predict metastatic progression.

Methods

To ascertain mechanisms underlying enhanced hybrid cell dissemination we identified hybrid cells within primary uveal melanoma tumors using single cell RNA sequencing (n = 8) and evaluated their gene expression and predicted ligand-receptor interactions in relation to other melanoma and immune cells within the primary tumor. We then verified expression of upregulated hybrid pathways within patient-matched tumor and peripheral blood hybrids (n = 4) using cyclic immunofluorescence and quantified their protein expression relative to other non-hybrid tumor and disseminated tumor cells.

Results

Among the top upregulated genes and pathways in hybrid cells were those involved in enhanced cell motility and cytoskeletal rearrangement, immune evasion, and altered cellular metabolism. In patient-matched tumor and peripheral blood, we verified gene expression by examining concordant protein expression for each pathway category: TMSB10 (cell motility), CD74 (immune evasion) and GPX1 (metabolism). Both TMSB10 and GPX1 were expressed on significantly higher numbers of disseminated hybrid cells compared to circulating tumor cells, and CD74 and GPX1 were expressed on more disseminated hybrids than tumor-resident hybrids. Lastly, we identified that hybrid cells express ligand-receptor signaling pathways implicated in promoting metastasis including GAS6-AXL, CXCL12-CXCR4, LGALS9-P4HB and IGF1-IGFR1.

Conclusion

These findings highlight the importance of TMSB10, GPX1 and CD74 for successful hybrid cell dissemination and survival in circulation. Our results contribute to the understanding of uveal melanoma tumor progression and interactions between tumor cells and immune cells in the tumor microenvironment that may promote metastasis.
Pulmonary vein thrombosis in COVID-19 patient with chronic obstructive pulmonary disease: a case report
Authors: Alaazmi Noora Hamad , Yusuf Khalifa Abdulrahman , Al-Madani Abdulrahman Hasan , Shehata Ghada Hassan , Al-Fadhel Hani Ebrahim
Published: July 2024

Background

Pulmonary vein thrombosis is a rare condition with a non-specific presentation with multiple underlying etiologies such as malignancy or lung surgery. In rare instances, no etiology could be encountered. Instead, it has a broad spectrum of clinical manifestations, from dyspnea to lung infarction with a compromise to hemodynamics.

Case presentation

A 71 years old male with a history of shortness of breath. The patient tested positive for COVID-19; the prolonged exertional fatigue led to undergoing CTPA (CT pulmonary angiography), which revealed pulmonary vein thrombosis. This case emphasizes the importance of maintaining a high index of clinical suspicion in the absence of other possible diagnoses. Furthermore, diagnostic work-up and treatment strategies depend highly on the patient’s presentation and risk factors.

Conclusions

Pulmonary vein thrombosis is an infrequent entity reported in the medical literature and underdiagnosed because of its ambiguous presentation. Early diagnosis is paramount to prevent complications.