bluuebunny/crossref_metadata_2025 huggingface dataset:
A retrospective analysis of the prevalence and impact of associated comorbidities on fibromyalgia outcomes in a tertiary care center
Authors: Rivera Fernando A. , Munipalli Bala , Allman Madeleine E. , Hodge David O. , Wieczorek Mikolaj A. , Wang Benjamin , Abril Andy , Perlman Adam , Knight Dacre , Bruce Barbara
Published: January 2024

Background

This retrospective study was designed to analyze the prevalence and impact of associated comorbidities on fibromyalgia (FM) outcomes (functionality, pain, depression levels) for patients who participated in an intensive multicomponent clinical program in a tertiary care center.

Methods

Participants included a sample of 411 patients diagnosed with FM at a large tertiary medical center using the 2016 ACR criteria. Patients completed an intensive 2-day cognitive behavioral treatment (CBT) program, filled out the Fibromyalgia Impact Questionnaire Revised (FIQR), the Center for Epidemiologic Studies Depression Scale (CES-D), the Pain Catastrophizing Scale (PCS), and were followed for 6 months after treatment completion. T-tests were performed to analyze differences between the presence or absence of select comorbidities for the three outcomes at follow-up. Statistically significant comorbidities (p < 0.05) were used as predictors in multivariable logistic regression models.

Results

The FM associated comorbidities in this cohort that had significant impact on the measured outcome domains after treatment program completed were Obesity (FIQR p = 0.024), Hypothyroidism (CES-D p = 0.023, PCS p = 0.035), Gastroesophageal reflux disease GERD (PCS p < 0.001), Osteoarthritis (CES-D p = 0.047). Interestingly, Headache, the most frequent FM associated comorbidity in this cohort (33.6%), did not have a significant impact on the outcome domains at follow-up. Obesity (18.2%) was the only FM associated comorbidity significantly impacting all three outcome domains at follow-up.

Conclusion

The present study suggests that addressing obesity may significantly impact outcomes in FM patients.
Nuclear medicine imaging for bone metastases assessment: what else besides bone scintigraphy in the era of personalized medicine?
Authors: Ouvrard Eric , Kaseb Ashjan , Poterszman Nathan , Porot Clémence , Somme Francois , Imperiale Alessio
Published: January 2024

Accurate detection and reliable assessment of therapeutic responses in bone metastases are imperative for guiding treatment decisions, preserving quality of life, and ultimately enhancing overall survival. Nuclear imaging has historically played a pivotal role in this realm, offering a diverse range of radiotracers and imaging modalities. While the conventional bone scan using 99mTc marked bisphosphonates has remained widely utilized, its diagnostic performance is hindered by certain limitations. Positron emission tomography, particularly when coupled with computed tomography, provides improved spatial resolution and diagnostic performance with various pathology-specific radiotracers. This review aims to evaluate the performance of different nuclear imaging modalities in clinical practice for detecting and monitoring the therapeutic responses in bone metastases of diverse origins, addressing their limitations and implications for image interpretation.
Case report and literature review: autonomous robotic system assisted palatal implantation at an anterior teeth site compromised by periapical cyst
Authors: Liu Xiuyu , Lv Huixin , Chen Meiqing , Chen Siyu , Jia Kewen , Quni Sezhen , Zhang Lu , Zhou Yanmin
Published: January 2024

Background

Immediate implant placement (IIP), which preserves gingival height and papilla shape while simultaneously accelerating the implant treatment period, has become a popular method due to its commendable clinical outcomes. Nonetheless, deploying immediate implants demands specific preconditions concerning the remaining alveolar bone. This poses a challenge to the accuracy of implant surgery.

Case presentation

In this report, we present the case of a 60-year-old woman with a left upper anterior tooth crown dislodged for over a month. Cone beam computed tomography (CBCT) revealed the absence of a labial bone wall on tooth 22, a remaining 1 mm bone wall on the labial side of the root apex, and a 17.2 mm*8.9 mm*4.7 mm shadow in the periapical region of the root apices of teeth 21 and 22, with the narrowest width on the sagittal plane being approximately 5 mm. After the surgeon removed the cyst, they completed the subsequent implantation surgery using an autonomous robot in a challenging aesthetic area. This method circumvented the potential exposure of the screw thread on the labial implant surface, assured initial implant stability.

Conclusion

Five months after the operation, the dental crown was restored. The implant remained stable, with yielding notable clinical results. To the best of our knowledge, this clinical case is the first to report the feasibility and precision of immediate implantation in anterior teeth site with periapical cyst removal, performed by an autonomous robotic surgical system. Autonomous robots exhibit exceptional accuracy by accurately controlling axial and angular errors. It can improve the accuracy of implant surgery, which may become a key technology for changing implant surgery. However, further clinical trials are still needed to provide a basis for the rapid development of robotic surgery field.
Efficient production and characterization of melanin from Thermothelomyces hinnuleus SP1, isolated from the coal mines of Chhattisgarh, India
Authors: Pandey Shalini , Meshram Vineet , Yehia Hany M. , Alzahrani Abdulhakeem , Akhtar Nadeem , Sur Arunima
Published: January 2024

In the present study, fungi were isolated and screened from barren land in south-eastern Coalfields limited (SECL) in Chhattisgarh, India. Out of 14 isolated fungi, only three fungal isolates exhibited pigmentation in screening studies. The isolated fungal strain SP1 exhibited the highest pigmentation, which was further utilized for in vivo production, purification, and characterization of melanin pigment. The physical and chemical properties of the fungal pigment showed insolubility in organic solvents and water, solubility in alkali, precipitation in acid, and decolorization with oxidizing agents. The physiochemical characterization and analytical studies of the extracted pigment using ultraviolet–visible spectroscopy and Fourier transform infrared (FTIR) confirmed it as a melanin pigment. The melanin-producing fungus SP1 was identified as Thermothelomyces hinnuleus based on 18S-rRNA sequence analysis. Furthermore, to enhance melanin production, a response surface methodology (RSM) was employed, specifically utilizing the central composite design (CCD). This approach focused on selecting efficient growth as well as progressive yield parameters such as optimal temperature (34.4°C), pH (5.0), and trace element concentration (56.24 mg). By implementing the suggested optimal conditions, the production rate of melanin increased by 62%, resulting in a yield of 28.3 mg/100 mL, which is comparatively higher than the actual yield (17.48 ± 2.19 mg/100 mL). Thus, T. hinnuleus SP1 holds great promise as a newly isolated fungal strain that could be used for the industrial production of melanin.
Dynamics of soil microbial communities involved in carbon cycling along three successional forests in southern China
Authors: Hu Minghui , Zhou Shuyidan , Xiong Xin , Wang Xuan , Sun Yu , Meng Ze , Hui Dafeng , Li Jianling , Zhang Deqiang , Deng Qi
Published: January 2024

Dynamics of plant communities during forest succession have been received great attention in the past decades, yet information about soil microbial communities that are involved in carbon cycling remains limited. Here we investigated soil microbial community composition and carbohydrate degradation potential using metagenomic analysis and examined their influencing factors in three successional subtropical forests in southern China. Results showed that the abundances of soil bacteria and fungi increased (p ≤ 0.05 for both) with forest succession in relation to both soil and litter characteristics, whereas the bacterial diversity did not change (p > 0.05) and the fungal diversity of Shannon-Wiener index even decreased (p ≤ 0.05). The abundances of microbial carbohydrate degradation functional genes of cellulase, hemicellulase, and pectinase also increased with forest succession (p ≤ 0.05 for all). However, the chitinase gene abundance did not change with forest succession (p > 0.05) and the amylase gene abundance decreased firstly in middle-succession forest and then increased in late-succession forest. Further analysis indicated that changes of functional gene abundance in cellulase, hemicellulase, and pectinase were primarily affected by soil organic carbon, soil total nitrogen, and soil moisture, whereas the variation of amylase gene abundance was well explained by soil phosphorus and litterfall. Overall, we created a metagenome profile of soil microbes in subtropical forest succession and fostered our understanding of microbially-mediated soil carbon cycling.
Exosomes released by environmental pollutant-stimulated Keratinocytes/PBMCs can trigger psoriatic inflammation in recipient cells via the AhR signaling pathway
Authors: Kim Hye Ran , Lee So Yeon , You Ga Eun , Park Chun Wook , Kim Hye One , Chung Bo Young
Published: January 2024

Introduction: Exosomes, pivotal in intercellular communication during skin disease pathogenesis, have garnered substantial attention. However, the impact of environmental pollutants, such as benzo[a]pyrene (BaP) and 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD), on exosome release amid inflammatory skin diseases remains unexplored. This study addresses this gap by examining the influence of BaP and TCDD on exosome function, specifically focusing on immune-related pathway alterations in normal recipient keratinocytes and peripheral blood mononuclear cells (PBMCs).

Methods: HaCaT cells were treated with exosomes from BaP- or TCDD-treated keratinocytes. Proinflammatory cytokines and chemokines, including TNF-α, IL-1β, IL-6, IL-8, CXCL1, and CXCL5, were assessed. The involvement of the p65NF-κB/p38MAPK/ERK signaling pathway in recipient keratinocytes was investigated. Aryl hydrocarbon receptor (AhR) silencing was employed to elucidate its role in mediating the proinflammatory response induced by exosomes from BaP- or TCDD-treated keratinocytes.

Results and discussion: Treatment with exosomes from BaP- or TCDD-treated keratinocytes induced a significant increase in proinflammatory cytokines and chemokines in HaCaT cells. The upregulation implicated the p65NF-κB/p38MAPK/ERK signaling pathway. AhR silencing attenuated this response, suggesting a role for AhR in mediating this response. In PBMCs from healthy controls, exosomes from BaP-stimulated PBMCs of psoriatic patients led to increased expression of proinflammatory cytokines and modulation of Th1/Th17 cell distribution via AhR activation. These findings unveil a novel dimension in the interplay between environmental xenobiotic agents (BaP and TCDD) and exosomal functions. The study establishes their influence on psoriatic inflammatory responses, shedding light on the underlying mechanisms mediated through the AhR signaling pathway in recipient keratinocytes and PBMCs.
Does acupuncture treatment modulate inflammatory cytokines in rodent models of depression? A systematic review and meta-analysis
Authors: Guo Ziyi , Ren Zhuoyu , Yao Jianping , Li Yamin , Che Zhiying , Yu Zhiyang , Fang Peigang , Lu Xiao , Chen Min
Published: January 2024

Background

Despite the increasing global prevalence of depression, existing treatment methods have limitations. Acupuncture has been recognized for its potential to alleviate various diseases by regulating inflammatory cytokines. However, a comprehensive systematic analysis of the effects of acupuncture on depression through inflammatory cytokines is currently lacking. This review aims to evaluate the impact of acupuncture on inflammatory cytokines in animal models of depression.

Methods

A comprehensive search was conducted in PubMed, EMBASE, MEDLINE, and the Research Information Service System to identify studies that met predefined inclusion and exclusion criteria. The quality of each included study was assessed using a 10-item checklist adapted from the Cochrane Collaboration methods and animal data review. Meta-analysis was performed using STATA 17.0 software for literature that met the inclusion criteria.

Results

The meta-analysis included a total of 21 studies involving 376 rodents. The overall quality of the included reports was rated as moderate or higher. The results demonstrated that acupuncture had a significant effect on the reduction of pro-inflammatory cytokines, including: IL-1β [SMD = 3.36, 95% CI (2.73, 4.00), I2 = 73.3%, p < 0.05], IL-6 [SMD = 3.05, 95% CI (2.45, 3.64), I2 = 68%, p < 0.05], and TNF-α [SMD = 3.30, 95% CI (2.53, 4.06), I2 = 74.5%, p < 0.05]. Conversely, acupuncture was associated with an increased expression of anti-inflammatory cytokines, notably: IL-4 [SMD = −1.64, 95% CI (−2.46, −0.82), I2 = 4.1%, p = 0.307] and IL-10 [SMD = −1.45, 95% CI (−2.24, −0.66), I2 = 0, p = 0.678]. These results suggest that acupuncture modulates cytokine levels in depressed rodents, including reducing the expression of pro-inflammatory cytokines and increasing the expression of anti-inflammatory cytokines, thereby regulating the immune-related antidepressant pathway.

Conclusion

While this study is limited by the number of included studies, the results suggest that acupuncture may be a viable option for the treatment of depression, and this effect is achieved through the regulation of various inflammatory cytokines.

Systematic review registration

This research endeavor was duly registered with PROSPERO (ID: CRD42023420919, https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=420919).
Clinicopathological differences between Bartonella and other bacterial endocarditis-related glomerulonephritis – our experience and a pooled analysis
Authors: Kitamura Mineaki , Dasgupta Alana , Henricks Jonathan , Parikh Samir V. , Nadasdy Tibor , Clark Edward , Bazan Jose A. , Satoskar Anjali A.
Published: January 2024

Background

AlthoughStaphylococcus aureusis the leading cause of acute infective endocarditis (IE) in adults,Bartonellaspp. has concomitantly emerged as the leading cause of “blood culture-negative IE” (BCNE). Pre-disposing factors, clinical presentation and kidney biopsy findings in Bartonella IE-associated glomerulonephritis (GN) show subtle differences and some unique features relative to other bacterial infection-related GNs. We highlight these features along with key diagnostic clues and management approach in Bartonella IE-associated GN.

Methods

We conducted a pooled analysis of 89 cases of Bartonella IE-associated GN (54 published case reports and case series; 18 published conference abstracts identified using an English literature search of several commonly used literature search modalities); and four unpublished cases from our institution.

Results

Bartonella henselaeandBartonella quintanaare the most commonly implicated species causing IE in humans. Subacute presentation, affecting damaged native and/or prosthetic heart valves, high titer anti-neutrophil cytoplasmic antibodies (ANCA), mainly proteinase-3 (PR-3) specificity, fastidious nature and lack of positive blood cultures of these Gram-negative bacilli, a higher frequency of focal glomerular crescents compared to other bacterial infection-related GNs are some of the salient features of Bartonella IE-associated GN. C3-dominant, but frequent C1q and IgM immunofluorescence staining is seen on biopsy. A “full-house” immunofluorescence staining pattern is also described but can be seen in IE –associated GN due to other bacteria as well. Non-specific generalized symptoms, cytopenia, heart failure and other organ damage due to embolic phenomena are the highlights on clinical presentation needing a multi-disciplinary approach for management. Awareness of the updated modified Duke criteria for IE, a high index of suspicion for underlying infection despite negative microbiologic cultures, history of exposure to animals, particularly infected cats, and use of send-out serologic tests forBartonellaspp. early in the course of management can help in early diagnosis and initiation of appropriate treatment.

Conclusion

Diagnosis of IE-associated GN can be challenging particularly with BCNE. The number of Bartonella IE-associated GN cases in a single institution tends to be less than IE due to gram positive cocci, however Bartonella is currently the leading cause of BCNE. We provide a much-needed discussion on this topic.
Temporal trends in hypertension related end stage renal disease mortality rates: an analysis of gender, race/ethnicity, and geographic disparities in the United States
Authors: Raja Adarsh , Raja Sandesh , Amin Shafin Bin , Salman Madiha , Azeem Bazil , Kumar Laksh
Published: January 2024

Background

According to one USA Renal Data System report, 57% of end-stage renal disease (ESRD) cases are attributed to hypertensive and diabetic nephropathy. Yet, trends in hypertension related ESRD mortality rates in adults ≥ 35 years of age have not been studied.

Objectives

The aim of this retrospective study was to analyze the different trends hypertension related ESRD death rates among adults in the United States.

Methods

Death records from the CDC (Centers for Disease Control and Prevention Wide-Ranging OnLine Data for Epidemiologic Research) database were analyzed from 1999 to 2020 for hypertension related ESRD mortality in adults ≥ 35 years of age. Age-Adjusted mortality rates (AAMRs) per 100,000 persons and annual percent change (APC) were calculated and stratified by year, sex, race/ethnicity, place of death, and geographic location.

Results

Hypertension-related ESRD caused a total of 721,511 deaths among adults (aged ≥ 35 years) between 1999 and 2020. The overall AAMR for hypertension related ESRD deaths in adults was 9.70 in 1999 and increased all the way up to 43.7 in 2020 (APC: 9.02; 95% CI: 8.19-11.04). Men had consistently higher AAMRs than woman during the analyzed years from 1999 (AAMR men: 10.8 vs women: 9) to 2020 (AAMR men: 52.2 vs women: 37.2). Overall AAMRs were highest in Non-Hispanic (NH) Black or African American patients (45.7), followed by NH American Indian or Alaska Natives (24.7), Hispanic or Latinos (23.4), NH Asian or Pacific Islanders (19.3), and NH White patients (15.4). Region-wise analysis also showed significant variations in AAMRs (overall AAMR: West 21.2; South: 21; Midwest: 18.3; Northeast: 14.2). Metropolitan areas had slightly higher AAMRs (19.1) than nonmetropolitan areas (19). States with AAMRs in 90th percentile: District of Columbia, Oklahoma, Mississippi, Tennessee, Texas, and South Carolina, had roughly double rates compared to states in 10th percentile.

Conclusions

Overall hypertension related ESRD AAMRs among adults were seen to increase in almost all stratified data. The groups associated with the highest death rates were NH Black or African Americans, men, and populations in the West and metropolitan areas of the United States. Strategies and policies targeting these at-risk groups are required to control the rising hypertension related ESRD mortality.
DMD deletions underlining mild dystrophinopathies: literature review highlights phenotype-related mutation clusters and provides insights about genetic mechanisms and prognosis
Authors: Fortunato Fernanda , Tonelli Laura , Farnè Marianna , Selvatici Rita , Ferlini Alessandra
Published: January 2024

DMD gene pathogenic variations cause a spectrum of phenotypes, ranging from severe Duchenne muscular dystrophy, the Becker milder cases, the intermediate or very mild muscle phenotypes invariably characterized by high CK, and the ultrarare fully-asymptomatic cases. Besides these phenotypes, X-linked dilated cardiomyopathy is also caused by DMD mutations. Males carrying DMD deletions with absent or very mild phenotypes have been sparsely described. We performed a horizon scan on public datasets to enroll males with the above phenotypes and carrying DMD deletions to delineate myopathic genotype-phenotype relationships. We inventoried 81 males, who were divided into the following clinical categorization: fully-asymptomatic males aged >43 years (A, N = 22); isolated hyperCKemia (CK, N = 35); and mild weakness (any age) with or without high CK (WCK, N = 24). In all cases, deleted intervals were exons 2 to 55, and no downstream exons were ever involved, apart from an exon 78 deletion in a WCK patient. All deletions were in-frame apart from the known exception to the rule of exon 2 and exon 78. We correlated the mild phenotypes (A and CK) to deleted exons, intronic breakpoints, exon-exon junctions, 3′ isoforms rule, and protein epitopes, and we found that some genetic profiles are exclusively/mainly occurring in A/CK phenotypes, suggesting they are compatible with a quasi-normal muscular performance. We discussed diverse pathogenic mechanisms that may contribute to mild dystrophinopathic phenotypes, and we tried to address some “critical” genetic configurations or exon content needed to preserve a semi-functional DMD gene.
Modified Brief Cognitive Screening Battery - Indonesian Version: cross-cultural adaptation and normative data based on demographic factors in North Sumatra, Indonesia
Authors: Fitri Fasihah Irfani , Naci Lorina , Turana Yuda , Rambe Aldy Safruddin , Nazriani Dina , Nitrini Ricardo , Caramelli Paulo
Published: January 2024

Introduction

Key component of early detection of dementia is a brief and culturally appropriate cognitive screening tool. This study aimed to perform a cultural adaptation of the Brief Cognitive Screening Battery (BCSB) and to obtain normative data from the older adult population.

Methods

Cross-cultural adaptation process to develop BCSB-INA was performed. This was followed by a feasibility study from community dwelling older adults from several urban and rural areas in North Sumatra, Indonesia.

Results

The BCSB-INA was generally well understood and showed not much discrepancy in translation from the original version. There were differences in semantic and phonemic fluency and CDT based on years of education, but no difference was found on other domain, including the delayed recall of the FMT. The battery was more influenced by age than education.

Discussion

The BCSB-INA is culturally appropriate and feasible to be used in population with heterogenous educational background in Indonesia.
Integrative polygenic analysis of the protective effects of fatty acid metabolism on disease as modified by obesity
Authors: Astore Courtney , Gibson Greg
Published: January 2024

Dysregulation of fatty acid metabolites can play a crucial role in the progression of complex diseases, such as cardiovascular disease, digestive diseases, and metabolic diseases. Metabolites can have either protective or risk effects on a disease; however, the details of such associations remain contentious. In this study, we demonstrate an integrative PheWAS approach to establish high confidence, causally suggestive of metabolite–disease associations for three fatty acid metabolites, namely, omega-3 fatty acids, omega-6 fatty acids, and docosahexaenoic acid, for 1,254 disease endpoints. Metabolite–disease associations were established if there was a concordant direction of effect and significance for metabolite level and genetic risk score for the metabolite. There was enrichment for metabolite associations with diseases of the respiratory system for omega-3 fatty acids, diseases of the circulatory system and endocrine system for omega-6 fatty acids, and diseases of the digestive system for docosahexaenoic acid. Upon performing Mendelian randomization on a subset of the outcomes, we identified 3, 6, and 15 significant diseases associated with omega-3 fatty acids, omega-6 fatty acids, and docosahexaenoic acid, respectively. We then demonstrate a class of prevalence-risk relationships indicative of (de)canalization of disease under high and low fatty acid metabolite levels. Finally, we show that the interaction between the metabolites and obesity demonstrates that the degree of protection afforded by fatty acid metabolites is strongly modulated by underlying metabolic health. This study evaluated the disease architectures of three polyunsaturated fatty acids (PUFAs), which were validated by several PheWAS modes of support. Our results not only highlight specific diseases associated with each metabolite but also disease group enrichments. In addition, we demonstrate an integrative PheWAS methodology that can be applied to other components of the human metabolome or other traits of interest. The results of this study can be used as an atlas to cross-compare genetic with non-genetic disease associations for the three PUFAs investigated. The findings can be explored through our R shiny app at https://pufa.biosci.gatech.edu.
Dietary intake of micronized avian eggshell membrane in aged mice reduces circulating inflammatory markers, increases microbiota diversity, and attenuates skeletal muscle aging
Authors: Rønning Sissel Beate , Carlsen Harald , Rocha Sérgio Domingos Cardoso , Rud Ida , Solberg Nina , Høst Vibeke , Veiseth-Kent Eva , Arnesen Henriette , Bergum Silje , Kirkhus Bente , Böcker Ulrike , Abedali Nada , Rundblad Amanda , Bålsrud Pia , Måge Ingrid , Holven Kirsten Bjørklund , Ulven Stine Marie , Pedersen Mona Elisabeth
Published: January 2024

Introduction

Avian eggshell membrane (ESM) is a complex extracellular matrix comprising collagens, glycoproteins, proteoglycans, and hyaluronic acid. We have previously demonstrated that ESM possesses anti-inflammatory properties in vitro and regulates wound healing processes in vivo. The present study aimed to investigate if oral intake of micronized ESM could attenuate skeletal muscle aging associated with beneficial alterations in gut microbiota profile and reduced inflammation.

Methods

Elderly male C57BL/6 mice were fed an AIN93G diet supplemented with 0, 0.1, 1, or 8% ESM. Young mice were used as reference. The digestibility of ESM was investigated using the static in vitro digestion model INFOGEST for older people and adults, and the gut microbiota profile was analyzed in mice. In addition, we performed a small-scale pre-clinical human study with healthy home-dwelling elderly (>70 years) who received capsules with a placebo or 500 mg ESM every day for 4 weeks and studied the effect on circulating inflammatory markers.

Results and discussion

Intake of ESM in elderly mice impacted and attenuated several well-known hallmarks of aging, such as a reduction in the number of skeletal muscle fibers, the appearance of centronucleated fibers, a decrease in type IIa/IIx fiber type proportion, reduced gene expression of satellite cell markers Sdc3 and Pax7 and increased gene expression of the muscle atrophy marker Fbxo32. Similarly, a transition toward the phenotypic characteristics of young mice was observed for several proteins involved in cellular processes and metabolism. The digestibility of ESM was poor, especially for the elderly condition. Furthermore, our experiments showed that mice fed with 8% ESM had increased gut microbiota diversity and altered microbiota composition compared with the other groups. ESM in the diet also lowered the expression of the inflammation marker TNFA in mice and in vitro in THP-1 macrophages. In the human study, intake of ESM capsules significantly reduced the inflammatory marker CRP. Altogether, our results suggest that ESM, a natural extracellular biomaterial, may be attractive as a nutraceutical candidate with a possible effect on skeletal muscle aging possibly through its immunomodulating effect or gut microbiota.
Dual inhibition of atypical PKC signaling and PI3K/Akt signaling dysregulates c-Myc to induce apoptosis in clear cell Renal Cell Carcinoma
Authors: Khalid Khandker Mohammad , Ratnayake Wishrawana S. , Apostolatos Christopher A. , Acevedo-Duncan Mildred
Published: January 2024

Background

Renal Cell Carcinoma (RCC) is the most common type of kidney cancer (85%). 75% of the RCC cases involve conventional clear cell RCC (ccRCC). Approximately, 39% of late-stage patients (stage IV) are treated with chemotherapeutic agents. Phosphatidylinositol-3-kinase (PI3K) and Mitogen-Activated Protein Kinase Kinase (MEK)/extracellular signal-regulated kinase (ERK1/2) pathways are frequently activated in RCC. In addition, atypical PKCs (PKC-ί and PKC ζ) are overexpressed in most cancer cells, and they play a central role in tumor progression and the metastasis of different types of cancers. Our goal is to establish the role of aPKCs in the regulation of multiple key activated pathways in ccRCC. In this study, we also established a novel therapeutic regimen for dual inhibition of key activated pathways.

Method

In this study, 786-0 and Caki-1 cells were studied and subjected to cell viability assay, western blot analysis, scratch & wound healing assay, transwell invasion assay, immunofluorescence, immunoprecipitation, flow cytometry, and quantitative real-time polymerase chain reaction. We used combination of PI3K inhibitor- Alpelisib (BYL719) and ICA-1 (a PKC-ι-specific 5-amino-1-2,3-dihydroxy-4-(methylcyclopentyl)-1H-imidazole-4-carboxamide). In addition to drug treatment, small interfering RNA (siRNA) technology was used to further confirm the experimental outcome of the drug treatment.

Results

Our results suggest that treatment of ccRCC cells with a combination of ICA-1 (aPKC inhibitor) and BYL719 (PI3K inhibitor) downregulates PKC-ί and causes downstream inhibition of c-Myc. Inhibition of the PKCί also reduces activation of MEK/ERK1/2. It is observed that treatment with ICA-1 disrupts the level of the aPKC-Akt1 association. ICA-1 treatment also shows a reduced level of association between aPKC and c-Myc. The inhibition of aPKCs and downstream effector proteins by combination therapy is more pronounced compared to a single therapy. These effects contribute to reduced cell growth, and eventually, the induction of apoptosis. The decreased level of N-cadherin, p-vimentin, and vimentin and the increased level of E-cadherin confirm reduced malignancy.

Conclusion

Therefore, implementing a combination of Alpelisib and a PKC-ι inhibitor is an effective approach to reducing cell proliferation, and invasion that eventually induces apoptosis and may be considered as a potential therapeutic option in ccRCC.
Case report: An exceptional responder of low-dose continuous 5-FU in a patient with de-novo stage IV triple-negative breast cancer with liver and bone marrow failure
Authors: Chan Bryan , Lee Jin Sun , Yuan Yuan
Published: January 2024

Continuous low-dose 5-FU was popularized as a therapy for pretreated metastatic breast cancer for the past few decades, spurred by the advent of the electronic infusion pump. Capecitabine, otherwise known by its trade name Xeloda, is a prodrug of 5-fluorouracil (5-FU), which is administered orally in many chemotherapy regimens, and plays a role in metastatic breast cancer treatment refractory to traditional anthracyclines and taxane therapy. In this case presentation, we describe a unique case of refractory de-novo stage IV triple-negative breast cancer presented with right breast primary invasive ductal carcinoma, extensive lymphadenopathy, with biopsy proven bone marrow infiltration, diffuse hepatomegaly, splenomegaly, significant hyperbilirubinemia, and bone marrow failure treated with continuous 5-FU infusion and subsequently oral capecitabine after initial treatment failure with nab-paclitaxel and sacituzimab govitecan. With this case presentation, the authors aim to showcase the versatility of 5-FU and its prodrug in treatment of metastatic triple-negative breast cancer with severe bone marrow and liver involvement while highlighting key physiologic and pharmacologic mechanisms.
Prevalence and contributing factors of malocclusion in Zhuang children aged 7–8 years in southern China
Authors: Mai Wenjia , Xiao Lijuan , Chen Shaoyong , Chen Shuang , Li Andi , Zhang Tingting , He Haoyu , Zeng Xiaojuan
Published: January 2024

Introduction

Malocclusion, a common oral health problem in children, is associated with several contributing factors. This study aimed to investigate the prevalence of mixed dentition stage malocclusion and its contributing factors in Chinese Zhuang children aged 7–8 years.

Methods

Overall, 2,281 Zhuang children, about 7–8 years old, were randomly selected using a stratified whole-cluster sampling method from schools in counties in Northwestern Guangxi, China. The children were examined on-site for malocclusion and caries by trained dentists, and basic data on the children were collected using questionnaires, including age, sex, parental education, parental accompaniment, and children's knowledge of malocclusion and treatment needs. Data were analyzed using the chi-square test and logistic regression analysis.

Results

The total prevalence of malocclusion in Zhuang children aged 7–8 years was 58.5%, with the highest prevalence of anterior crossbite tendency, and the prevalence of anterior crossbite and anterior edge-to-edge occlusion was 15.1% and 7.7%, respectively. This was followed by an anterior increased overjet of 13.3% and an inter-incisor spacing of 10.3%. The lowest prevalence was 2.7% for anterior open bite. Sex, parental accompaniment, parental education, and decayed, missing, and filled teeth of the first primary molar were factors that contributed to malocclusion in Zhuang children.

Conclusion

Malocclusion is a common oral problem among Zhuang children. Therefore, more attention must be paid to the intervention and prevention of malocclusion. The impact factors should be controlled as early as possible.
Efficacy and tolerability of zuranolone in patients with depression: a meta-analysis of randomized controlled trials
Authors: Qiu Youjia , Tao Yuchen , Duan Aojie , Wei Xingzhou , Wang Menghan , Xie Minjia , Chen Zhouqing , Shang Jing , Wang Zhong
Published: January 2024

Background: As a novel antidepressant drug, zuranolone has been initially applied in treating depression. This study investigated the efficacy and safety of its administration in patients with depression.

Methods: The Embase, PubMed, and Cochrane library databases were searched for available studies up to 1 Nov 2023. The primary outcome was the change on day 15 depression severity scores compared to baseline. Secondary outcomes included remission and response rates on day 15. Safety outcomes included incidence of treatment-emergent adverse events (TEAEs) and individual AEs. Trial sequential analysis (TSA) was used to evaluate the ideal samplesize.

Results: Six studies with 1884 patients were included. Zuranolone offered significantly greater changes in day 15 depression severity scores (mean difference = 2.43, 95% confidence interval [CI]: 1.36 to 3.49, p < 0.00001) compared to placebo; this was also observed at other time points. Differences in response (relative risk [RR] = 1.33, 95% CI: 1.15 to 1.54, p < 0.0001) and remission (RR = 1.46, 95% CI: 1.15 to 1.85, p = 0.002) rates were also statistically significant. For safety outcomes, zuranolone group showed more incidence of TEAE than the placebo group (RR: 1.15, 95% CI: 1.06 to 1.25, p = 0.0005, I2 = 0%). As for individual AEs, significant differences were observed in dizziness (RR = 2.17, 95% CI: 1.22 to 3.86, p = 0.008) and somnolence (RR = 2.43, 95% CI: 1.35 to 4.37, p = 0.003. No significant difference was observed in other AEs. The result of TSA indicated that the cumulative curve crossed the conventional (Z = 1.96) boundary but not reach TSA boundary (RIS = 1910).

Conclusion: Our findings suggest that zuranolone has a rapid short-term antidepressant effect during administration. Although more TEAEs were observed in zuranolone, most of them were slight and temporary. However, studies with larger sample sizes and longer follow-up are needed.

Systematic Review Registration:https://inplasy.com/inplasy-2023-5-0104/, identifier INPLASY202350104.
Valsartan attenuates LPS-induced ALI by modulating NF-κB and MAPK pathways
Authors: Zhou Mi , Meng Ling , He Qinke , Ren Chunguang , Li Changyi
Published: January 2024

Background: Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is a common respiratory disease characterized by persistent hypoxemia and an uncontrolled inflammatory response. Valsartan, an angiotensin II type 1 receptor antagonist, is clinically used to treat hypertension and has anti-inflammatory and antioxidant effects on gefitinib-induced pneumonia in rats. However, the potential therapeutic effects of valsartan on lipopolysaccharide (LPS)-induced ALI remain unclear. This study investigated the protective role of valsartan in LPS-induced ALI and its underlying mechanisms.

Methods: LPS-treated BEAS-2B cells and ALI mouse model were established. BEAS-2B cells were treated with LPS (10 μg/mL) for 24h, with or without valsartan (20, 40, and 80 µM). For ALI mouse models, LPS (5 mg/kg) was administered through intratracheal injection to treat the mice for 24h, and valsartan (10 or 30 mg/kg) was injected intraperitoneally twice 2 h before and 12 h after the LPS injection. Pulmonary functional parameters were examined by an EMKA pulmonary system. Hematoxylin and eosin staining, flow cytometry, CCK-8 assay, qRT-PCR, ELISA, immunofluorescence, Western blotting, and related commercial kits were used to assess the pathological damage to the lungs, neutrophil recruitment in the lung tissue and bronchoalveolar lavage fluid (BALF), cell viability, inflammation, oxidative activity, and mucus production, respectively. Potential mechanisms were further explored using network pharmacology and Western blotting.

Results: Valsartan rescued LPS-reduced cell viability of BEAS-2B cells, improved the pulmonary function, ameliorated pathological lung injury in mice with ALI, ameliorated LPS-induced neutrophil recruitment in BALF and lung tissue of mice, attenuated oxidative stress by increasing the level of SOD and decreasing that of MDA and GSSG, inhibited LPS-induced MUC5AC overproduction, decreased the LPS-induced increase in expression of pro-inflammatory cytokines/chemokines including TNF-α, IL-6, IL-1β, CXCL-1 and CXCL-2, and restored the expression of anti-inflammatory IL-10. Mechanistic studies showed that valsartan inhibits LPS-induced phosphorylation of nuclear factor-kappa B (NF-κΒ) and mitogen-activated protein kinases (MAPKs) including P38, extracellular signal-regulated kinase (ERK), and c-Jun N-terminal kinase (JNK) in both LPS-treated cells and the mouse model of ALI.

Conclusion: Valsartan protects against LPS-induced ALI by attenuating oxidative stress, reducing MUC5AC production, and attenuating the inflammatory response that may involve MAPK and NF-κΒ pathways.
YOLOV5-CBAM-C3TR: an optimized model based on transformer module and attention mechanism for apple leaf disease detection
Authors: Lv Meng , Su Wen-Hao
Published: January 2024

Apple trees face various challenges during cultivation. Apple leaves, as the key part of the apple tree for photosynthesis, occupy most of the area of the tree. Diseases of the leaves can hinder the healthy growth of trees and cause huge economic losses to fruit growers. The prerequisite for precise control of apple leaf diseases is the timely and accurate detection of different diseases on apple leaves. Traditional methods relying on manual detection have problems such as limited accuracy and slow speed. In this study, both the attention mechanism and the module containing the transformer encoder were innovatively introduced into YOLOV5, resulting in YOLOV5-CBAM-C3TR for apple leaf disease detection. The datasets used in this experiment were uniformly RGB images. To better evaluate the effectiveness of YOLOV5-CBAM-C3TR, the model was compared with different target detection models such as SSD, YOLOV3, YOLOV4, and YOLOV5. The results showed that YOLOV5-CBAM-C3TR achieved mAP@0.5, precision, and recall of 73.4%, 70.9%, and 69.5% for three apple leaf diseases including Alternaria blotch, Grey spot, and Rust. Compared with the original model YOLOV5, the mAP 0.5increased by 8.25% with a small change in the number of parameters. In addition, YOLOV5-CBAM-C3TR can achieve an average accuracy of 92.4% in detecting 208 randomly selected apple leaf disease samples. Notably, YOLOV5-CBAM-C3TR achieved 93.1% and 89.6% accuracy in detecting two very similar diseases including Alternaria Blotch and Grey Spot, respectively. The YOLOV5-CBAM-C3TR model proposed in this paper has been applied to the detection of apple leaf diseases for the first time, and also showed strong recognition ability in identifying similar diseases, which is expected to promote the further development of disease detection technology.
Characterization and evaluation of potential halotolerant phosphate solubilizing bacteria from Salicornia fruticosa rhizosphere
Authors: Teles E. A. P. , Xavier J. F. , Arcênio F. S. , Amaya R. L. , Gonçalves J. V. S. , Rouws L. F. M. , Zonta E. , Coelho I. S.
Published: January 2024

Soil salinization is a significant abiotic factor threatening agricultural production, while the low availability of phosphorus (P) in plants is another worldwide limitation. Approximately 95–99% of the P in soil is unavailable to plants. Phosphate-solubilizing bacteria (PSB) transform insoluble phosphates into soluble forms that plants can utilize. The application of PSB can replace or partially reduce the use of P fertilizers. Therefore, selecting bacteria with high solubilization capacity from extreme environments, such as saline soils, becomes crucial. This study aimed to identify twenty-nine bacterial strains from the rhizosphere of Salicornia fruticosa by sequencing the 16S rDNA gene, evaluate their development in increasing concentrations of NaCl, classify them according to their salinity response, and determine their P solubilization capability. The bacteria were cultivated in nutrient agar medium with NaCl concentrations ranging from 0.5% to 30%. The phosphate solubilization capacity of the bacteria was evaluated in angar and broth National Botanical Research Institute (NBRIP) media supplemented with calcium phosphate (CaHPO4) and aluminum phosphate (AlPO4), and increased with 3% NaCl. All bacterial strains were classified as halotolerant and identified to the genera Bacillus, Enterobacter, Halomonas, Kushneria, Oceanobacillus, Pantoea, Pseudomonas, and Staphylococcus, with only one isolate was not identified. The isolates with the highest ability to solubilize phosphorus from CaHPO4 in the liquid medium were Kushneria sp. (SS102) and Enterobacter sp. (SS186), with 989.53 and 956.37 mg·Kg-1 P content and final pH of 4.1 and 3.9, respectively. For the solubilization of AlPO4, the most effective isolates were Bacillus sp. (SS89) and Oceanobacillus sp. (SS94), which raised soluble P by 61.10 and 45.82 mg·Kg-1 and final pH of 2.9 and 3.6, respectively. These bacteria demonstrated promising results in in vitro P solubilization and can present potential for the development of bioinput. Further analyses, involving different phosphate sources and the composition of produced organic acids, will be conducted to contribute to a comprehensive understanding of their applications in sustainable agriculture.
Influence of plant species, mycorrhizal inoculant, and soil phosphorus level on arbuscular mycorrhizal communities in onion and carrot roots
Authors: Ilyas Umbrin , du Toit Lindsey J. , Hajibabaei Mehrdad , McDonald Mary Ruth
Published: January 2024

Arbuscular mycorrhizal fungi (AMF) are ancient and ecologically important symbionts that colonize plant roots. These symbionts assist in the uptake of water and nutrients, particularly phosphorus, from the soil. This important role has led to the development of AMF inoculants for use as biofertilizers in agriculture. Commercial mycorrhizal inoculants are increasingly popular to produce onion and carrot, but their specific effects on native mycorrhizal communities under field conditions are not known. Furthermore, adequate availability of nutrients in soils, specifically phosphorus, can reduce the diversity and abundance of AMF communities in the roots. The type of crop grown can also influence the composition of AMF communities colonizing the plant roots. This study aimed to investigate how AMF inoculants, soil phosphorus levels, and plant species influence the diversity of AMF communities that colonize the roots of onion and carrot plants. Field trials were conducted on high organic matter (muck) soil in the Holland Marsh, Ontario, Canada. The treatments included AMF-coated seeds (three to five propagules of Rhizophagus irregularis per seed) and non-treated onion and carrot seeds grown in soil with low (~46 ppm) and high (~78 ppm) phosphorus levels. The mycorrhizal communities colonizing the onion and carrot roots were identified by Illumina sequencing. Five genera, Diversispora, Claroideoglomus, Funneliformis, Rhizophagus, and Glomus, were identified in roots of both plant species. AMF communities colonizing carrot roots were more diverse and richer than those colonizing onion roots. Diversispora and Funneliformis had a 1.3-fold and 2.9-fold greater abundance, respectively, in onion roots compared to carrots. Claroideoglomus was 1.4-fold more abundant in carrot roots than in onions. Inoculation with R. irregularis increased the abundance and richness of Rhizophagus in AMF communities of onion roots but not in carrot roots. The soil phosphorus level had no effect on the richness and diversity of AMF in the roots of either crop. In summary, AMF inoculant and soil phosphorus levels influenced the composition of AMF communities colonizing the roots of onion and carrot plants, but the effects varied between plant species.
Soybean microbiome composition and the impact of host plant resistance
Authors: Tran Dung T. , Mitchum Melissa G. , Zhang Shuzhen , Wallace Jason G. , Li Zenglu
Published: January 2024

Microbial communities play an important role in the growth and development of plants, including plant immunity and the decomposition of complex substances into absorbable nutrients. Hence, utilizing beneficial microbes becomes a promising strategy for the optimization of plant growth. The objective of this research was to explore the root bacterial profile across different soybean genotypes and the change in the microbial community under soybean cyst nematode (SCN) infection in greenhouse conditions using 16S rRNA sequencing. Soybean genotypes with soybean cyst nematode (SCN) susceptible and resistant phenotypes were grown under field and greenhouse conditions. Bulked soil, rhizosphere, and root samples were collected from each replicate. Sequencing of the bacterial 16S gene indicated that the bacterial profile of soybean root and soil samples partially overlapped but also contained different communities. The bacterial phyla Proteobacteria, Actinobacteria, and Bacteroidetes dominate the soybean root-enriched microbiota. The structure of bacteria was significantly affected by sample year (field) or time point (greenhouse). In addition, the host genotype had a small but significant effect on the diversity of the root microbiome under SCN pressure in the greenhouse test. These differences may potentially represent beneficial bacteria or secondary effects related to SCN resistance.