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- ArticleBarbera G, Zhang Y, Werner C, Liang B, Li Y, Lin DT.MethodsX. 2020;7:101167.In this work we propose an open source, cost-effective motorized swivel for behavioral and neural recordings in small rodents, offering a flexible solution for managing cable twisting and tangling in a variety of experimental settings with minimal human supervision.•The device operates independently of the data acquisition system, and it can be controlled through any popular platform such as Arduino or Raspberry Pi.•All mechanical parts are 3D-printed, allowing to customize the design to fit specific experimental needs, and electromechanical components can be sourced from all major distributors, keeping the cost for the entire system under $500.•The proposed commutator is compatible with commercial or custom data acquisition systems supporting up to 10 data lines (2 for LVDS signals) and 2 power lines.
- ArticleAjmera V, Loomba R.Mol Metab. 2021 08;50:101167.BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a clinicopathologic entity that requires a liver biopsy assessment to diagnose the progressive form of NAFLD called non-alcoholic steatohepatitis (NASH). Liver biopsy is invasive, subject to sampling and interobserver variability, and impractical to scale to the affected population of up to 1 billion affected individuals worldwide. Non-invasive imaging biomarkers have emerged as a key modality to address the major unmet need to diagnose, stage, and longitudinally monitor NAFLD.
SCOPE OF REVIEW: In this review, we critically examine the use of non-invasive imaging biomarkers to diagnose NAFLD, NASH, and fibrosis stage.
MAJOR CONCLUSIONS: Ultrasound and magnetic resonance imaging (MRI) biomarkers of liver fat can diagnose NAFLD. MRI proton density fat fraction (MRI-PDFF) is better than liver biopsy, particularly for following longitudinal changes in liver fat in clinical trials. Imaging biomarkers to reliably diagnose NASH are under investigation, but when used alone, continue to have only modest diagnostic accuracy. However, the fibrosis stage has the strongest association with liver decompensation and mortality, and elastography has emerged as a reliable biomarker for liver fibrosis. We review the combination of biomarkers to risk stratify patients and identify individuals needing treatment and the implications of longitudinal changes in liver stiffness measurement. - ArticleLiu J, Lu W, Shi B, Klein S, Su X.Redox Biol. 2019 06;24:101167.Peroxisomes are ubiquitous cellular organelles required for specific pathways of fatty acid oxidation and lipid synthesis, and until recently their functions in adipocytes have not been well appreciated. Importantly, peroxisomes host many oxygen-consumption reactions and play a major role in generation and detoxification of reactive oxygen species (ROS) and reactive nitrogen species (RNS), influencing whole cell redox status. Here, we review recent progress in peroxisomal functions in lipid metabolism as related to ROS/RNS metabolism and discuss the roles of peroxisomal redox homeostasis in adipogenesis and adipocyte metabolism. We provide a framework for understanding redox regulation of peroxisomal functions in adipocytes together with testable hypotheses for developing therapies for obesity and the related metabolic diseases.
- ArticleGorman E, Shankar-Hari M, Hopkins P, Tunnicliffe WS, Perkins GD, Silversides J, McGuigan P, ... Show More Krasnodembskaya A, Jackson C, Boyle R, McFerran J, McDowell C, Campbell C, McFarland M, Smythe J, Thompson J, Williams B, Curley G, Laffey JG, Clarke M, McAuley DF, O'Kane CM.EClinicalMedicine. 2021 Nov;41:101167.BACKGROUND: Mesenchymal stromal cells (MSCs) may be of benefit in acute respiratory distress syndrome (ARDS) due to immunomodulatory, reparative, and antimicrobial actions. ORBCEL-C is a population of CD362 enriched umbilical cord-derived MSCs. The REALIST phase 1 trial investigated the safety and feasibility of ORBCEL-C in patients with moderate to severe ARDS.
METHODS: REALIST phase 1 was an open label, dose escalation trial in which cohorts of mechanically ventilated patients with moderate to severe ARDS received increasing doses (100, 200 or 400 × 106 cells) of a single intravenous infusion of ORBCEL-C in a 3 + 3 design. The primary safety outcome was the incidence of serious adverse events. Dose limiting toxicity was defined as a serious adverse reaction within seven days. Trial registration clinicaltrials.gov NCT03042143.
FINDINGS: Nine patients were recruited between the 7th January 2019 and 14th January 2020. Study drug administration was well tolerated and no dose limiting toxicity was reported in any of the three cohorts. Eight adverse events were reported for four patients. Pyrexia within 24 h of study drug administration was reported in two patients as pre-specified adverse events. A further two adverse events (non-sustained ventricular tachycardia and deranged liver enzymes), were reported as adverse reactions. Four serious adverse events were reported (colonic perforation, gastric perforation, bradycardia and myocarditis) but none were deemed related to administration of ORBCEL-C. At day 28 no patients had died in cohort one (100 × 106), three patients had died in cohort two (200 × 106) and one patient had died in cohort three (400 × 106). Overall day 28 mortality was 44% (n = 4/9).
INTERPRETATION: A single intravenous infusion of ORBCEL-C was well tolerated in patients with moderate to severe ARDS. No dose limiting toxicity was reported up to 400 × 106 cells. - ArticleAdegbola PI, Fadahunsi OS, Ogunjinmi OE, Adegbola AE, Ojeniyi FD, Adesanya A, Olagoke E, Adisa AD, Ehigie AF, Adetutu A, Semire B.Inform Med Unlocked. 2023;37:101167.Concerned organizations and individuals are fully engaged in seeking appropriate measures towards managing Severe Acute Respiratory Syndrome Coronavirus 2 (SAR-CoV-2) infection because of the unprecedented economic and health impact. SAR-CoV-2 Main protease (SARS-CoV-2 Mpro) is unique to the survival and viability of the virus. Therefore, inhibition of Mpro can block the viral propagation. Thirty (30) derivatives were built by changing the glucosides in the Meta and para position of quercetin and isohamnetin. Molecular docking analysis was used for the screening of the compounds. Dynamics simulation was performed to assess the stability of the best pose docked complex. Molecular mechanics binding free energy calculation was done by Molecular Mechanics/Poisson-Boltzmann Surface Area (MMPBSA). Overall analysis showed that the compounds are allosteric inhibitors of SARS-CoV-2 Mpro. Dynamic simulation analysis established the stability of Mpro-ISM-1, Mpro-ISD-3, Mpro-IST-2, Mpro-QM-2, and Mpro-QD-6 complexes with a maximum of 7 hydrogen bonds involved in their interaction. The MMPBSA binding free energies for ISM-1, ISD-3, IST-2, QM-2, and QD-6 were -92.47 ± 9.06, -222.27 ± 32.5, 180.72 ± 47.92, 156.46 ± 49.88 and -93.52 ± 48.75 kcal/mol respectively. All the compounds showed good pharmacokinetic properties, while only ISM-1 inhibits hERG and might be cardio-toxic. Observations in this study established that the glucoside position indeed influenced the affinity for SARS-CoV-2 Mpro. The study also suggested the potentials of ISD-3, QM-2 and QD-6 as potent inhibitors of the main protease, further experimental and clinical studies are however necessary to validate and establish the need for further drug development processes. Therefore, future studies will be on the chemical synthesis of the compounds and investigation of the in-vitro inhibition of SARS-CoV-2.
- ArticleGarcini LM, Arredondo MM, Berry O, Church JA, Fryberg S, Thomason ME, McLaughlin KA.Dev Cogn Neurosci. 2022 12;58:101167.Understanding of human brain development has advanced rapidly as the field of developmental cognitive neuroscience (DCN) has matured into an established scientific discipline. Despite substantial progress, DCN lags behind other related disciplines in terms of diverse representation, standardized reporting requirements for socio-demographic characteristics of participants in pediatric neuroimaging studies, and use of intentional sampling strategies to more accurately represent the socio-demographic, ethnic, and racial composition of the populations from which participants are sampled. Additional efforts are needed to shift DCN towards a more inclusive field that facilitates the study of individual differences across a variety of cultural and contextual experiences. In this commentary, we outline and discuss barriers within our current scientific practice (e.g., research methods) and beliefs (i.e., what constitutes good science, good scientists, and good research questions) that contribute to under-representation and limited diversity within pediatric neuroimaging studies and propose strategies to overcome those barriers. We discuss strategies to address barriers at intrapersonal, interpersonal, community, systemic, and structural levels. Highlighting strength-based models of inclusion and recognition of the value of diversity in DCN research, along with acknowledgement of the support needed to diversify the field is critical for advancing understanding of neurodevelopment and reducing health inequities.
- ArticleRainey JP, Gililland JM, Peters CL, Archibeck MJ, Anderson LA, Pelt CE.Arthroplast Today. 2023 Aug;22:101167.Metallosis and corrosion have been associated with metal-on-metal and modular total hip arthroplasty but are rarely described in the setting of primary or revision total knee arthroplasty (TKA). In this series, we report on cases of metallosis due to mechanically assisted crevice corrosion at modular junctions of machined trunnion-bore tapers in a revision TKA system with metaphyseal sleeves. The unique design of metal modular junctions used in sleeve-based revision TKA, along with potential patient and surgical factors, may predispose these designs to fretting, corrosion, and adverse reaction to metal debris. We now consider metallosis and corrosion in the workup of painful or failed revision TKAs with sleeves. Future studies that investigate the incidence of this phenomenon may be warranted.
- ArticleKenney HM, Peng Y, Chen KL, Ajalik R, Schnur L, Wood RW, Schwarz EM, Awad HA.Bone Rep. 2022 Jun;16:101167.INTRODUCTION: Micro-computed tomography (μCT) is a valuable imaging modality for longitudinal quantification of bone volumes to identify disease or treatment effects for a broad range of conditions that affect bone health. Complex structures, such as the hindpaw with up to 31 distinct bones in mice, have considerable analytic potential, but quantification is often limited to a single bone volume metric due to the intensive effort of manual segmentation. Herein, we introduce a high-throughput, user-friendly, and semi-automated method for segmentation of murine hindpaw μCT datasets.
METHODS: In vivo μCT was performed on male (n = 4; 2-8-months) and female (n = 4; 2-5-months) C57BL/6 mice longitudinally each month. Additional 9.5-month-old male C57BL/6 hindpaws (n = 6 hindpaws) were imaged by ex vivo μCT to investigate the effects of resolution and integration time on analysis outcomes. The DICOMs were exported to Amira software for the watershed-based segmentation, and watershed markers were generated automatically at approximately 80% accuracy before user correction. The semi-automated segmentation method utilizes the original data, binary mask, and bone-specific markers that expand to the full volume of the bone using watershed algorithms.
RESULTS: Compared to the conventional manual segmentation using Scanco software, the semi-automated approach produced similar raw bone volumes. The semi-automated segmentation also demonstrated a significant reduction in segmentation time for both experienced and novice users compared to standard manual segmentation. ICCs between experienced and novice users were >0.9 (excellent reliability) for all but 4 bones.
DISCUSSION: The described semi-automated segmentation approach provides remarkable reliability and throughput advantages. Adoption of the semi-automated segmentation approach will provide standardization and reliability of bone volume measures across experienced and novice users and between institutions. The application of this model provides a considerable strategic advantage to accelerate various research opportunities in pre-clinical bone and joint analysis towards clinical translation. - ArticleXiao B, Dai W, Zhan Y, Qiu W, Zhang H, Liu D, Xu N, Yu Y.Genet Med. 2024 May 17:101167.PURPOSE: Rare genetic variants in the PURA gene cause PURA-related neurodevelopmental disorder (PURA-NDD), characterized by neonatal abnormalities and developmental delay. Using genome-wide DNA methylation analysis on patients with PURA variants, we aim to establish PURA-NDD-specific methylation profile and provide further insights on the molecular basis of the PURA-NDD.
METHODS: 23 individuals (including 12 unpublished) carrying PURA variants were enrolled. We conducted the Illumina Infinium EPIC microarray analysis in 17 PURA-NDD individuals. In vitro experiments were performed to examine how PURA variants affect Pur-α expression.
RESULTS: Additional phenotypes in 12 newly identified patients were described in this study. Genome-wide DNA methylation analysis unveiled distinctive methylation profiles to PURA-NDD, and the established classifier can reclassify PURA variants of uncertain significance. Patients bearing PURA hapoloinsufficient and missense variants have comparable DNA methylation profiles, and cells expressing these PURA variants showed consistent Pur-α downregulation suggesting a haploinsufficiency mechanism.
CONCLUSION: Patients with PURA-NDD exhibit a specific epi-signature, which has potential to aid identification and diagnosis of PURA-NDD patients and offer implications for further functional investigations. - ArticleFay CR, Toth AL.Curr Opin Insect Sci. 2024 04;62:101167.Are traits with high levels of plasticity more complex in their genetic architecture, as they can be modulated by numerous different environmental inputs? Many authors have assumed that behavioral traits, in part because they are highly plastic, have an exceptionally complex genetic basis. We quantitatively summarized data from 31 genome-wide association studies (GWAS) and 87 traits in Drosophila melanogaster and found no evidence that behavioral traits have fundamental differences in the number of single-nucleotide polymorphisms or the significance or effect size of those associations, compared with nonbehavioral (morphological or physiological) traits. We suggest the assertion that behavioral traits are inherently more complex on a genetic basis compared with other types of traits should not be assumed true, and merits further investigation.
- ArticleCarbone A, Chadburn A, Gloghini A, Vaccher E, Bower M.Blood Rev. 2024 Mar;64:101167.Significant advances in the field of lymphoma have resulted in two recent classification proposals, the International Consensus Classification (ICC) and the 5th edition WHO. A few entities are categorized differently in the ICC compared to the WHO. Nowhere is this more apparent than the immunodeficiency lymphoproliferative disorders. The three previous versions of the WHO classification (3rd, 4th and revised 4th editions) and the ICC focused on four clinical settings in which these lesions arise for primary categorization. In contrast the 2023 WHO 5th edition includes pathologic characteristics including morphology and viral status, in addition to clinical setting, as important information for lesion classification. In addition, the 2023 WHO recognizes a broader number of clinical scenarios in which these lesions arise, including not only traditional types of immune deficiency but also immune dysregulation. With this classification it is hoped that new treatment strategies will be developed leading to better patient outcomes.
- ArticleZhao H, Zhang Y, Wang W, Cole S.Disabil Health J. 2021 10;14(4):101167.BACKGROUND: Research has found that participation in travel declines for people after spinal cord injury (SCI) because the traumatic injury usually results in impaired physical mobility and sensation, and barriers in the environment make travel more challenging. While travel participation can offer numerous physical, psychological, and emotional benefits, empirical evidence on positive outcomes of travel for people after SCI is scarce in the literature.
OBJECTIVE: To empirically examine the effects of travel participation on social integration and life satisfaction for people with SCI, along with other personal characteristics including income, self-perceived health status, levels of physical independence, occupational activities, and travel barriers.
METHODS: Cross sectional data are collected from 250 patients enrolled in a SCI Model System. Hierarchical regression analyses, followed by mediation analyses, are conducted to assess the effects of travel participation on social integration and life satisfaction.
RESULTS: Travel participation along with occupational activities is shown to significantly impact social integration, with participation in occupational activities partially mediating the relation from travel participation to social integration. The significant effect of travel participation on life satisfaction is fully mediated by social integration. Income and self-perceived health status both significantly contribute to social integration and life satisfaction.
CONCLUSIONS: Travel participation should be considered as an independent domain that directly impacts the social integration of people with SCI, which in turn enhances their life satisfaction. Systematic interventions with standard protocols for travel-related skill training and assessments procedures are needed for people after SCI. - ArticleShi J, Zhang X, Li J, Huang W, Wang Y, Wang Y, Qin J.Transl Oncol. 2021 Oct;14(10):101167.Poly (ADP-ribose) polymerase (PARP) inhibitor olaparib selectively kills cancer cells with BRCA-deficiency and is approved for BRCA-mutated breast, ovarian and pancreatic cancers by FDA. However, phase III study of olaparib failed to show a significant improvement in overall survival in patients with gastric cancer (GC). To discover an effective biomarker for GC patient-selection in olaparib treatment, we analyzed proteomic profiling of 12 GC cell lines. MTA2 was identified to confer sensitivity to olaparib by aggravating olaparib-induced replication stress in cancer cells. Mechanistically, we applied Cleavage Under Targets and Tagmentation assay to find that MTA2 proteins preferentially bind regions of replication origin-associated DNA sequences, which could be enhanced by olaparib treatment. Furthermore, MTA2 was validated here to render cancer cells susceptible to combination of olaparib with ATR inhibitor AZD6738. In general, our study identified MTA2 as a potential biomarker for olaparib sensitivity by aggravating olaparib-induced replication stress.
- ArticleRusso MN, Whaley LA, Norton ES, Zarco N, Guerrero-Cázares H.Mol Aspects Med. 2023 06;91:101167.Glioblastoma (GBM), is the most malignant form of gliomas and the most common and lethal primary brain tumor in adults. Conventional cancer treatments have limited to no efficacy on GBM. GBM cells respond and adapt to the surrounding brain parenchyma known as tumor microenvironment (TME) to promote tumor preservation. Among specific TME, there are 3 of particular interest for GBM biology: the perivascular niche, the subventricular zone neurogenic niche, and the immune microenvironment. GBM cells and TME cells present a reciprocal feedback which results in tumor maintenance. One way that these cells can communicate is through extracellular vesicles. These vesicles include exosomes and microvesicles that have the ability to carry both cancerous and non-cancerous cargo, such as miRNA, RNA, proteins, lipids, and DNA. In this review we will discuss the booming topic that is extracellular vesicles, and how they have the novelty to be a diagnostic and targetable vehicle for GBM.
- ArticleRuttens D, Van Kerrebroeck M, Vandewalle J, Falter M, Daenen M, Thevissen K, Wirix M, Thomeer M.Respir Med Case Rep. 2020;31:101167.During the COVID-19 pandemic, a 56-year-old man presented at our emergency department with fever and shortness of breath; Diffuse pulmonary nodular vascular spread lesions were found. Detailed history taking showed a four-week history of fever and night sweats. The man had been under treatment for 2 years with Adalimumab, a tumor-necrosis-factor (TNF) inhibitor, for ulcerative colitis. Before start, screening by tuberculin skin test was negative. Cultures en PCR on BAL and urine were positive for mycobacterium tuberculosis also ocular findings were present. The diagnosis of military tuberculosis was made.
- ArticleWang XG, Shen MM, Lu J, Dou TC, Ma M, Guo J, Wang KH, Qu L.Animal. 2024 Jun;18(6):101167.Eggshell color is an important visual characteristic that affects consumer preferences for eggs. Eggshell color, which has moderate to high heritability, can be effectively enhanced through molecular marker selection. Various studies have been conducted on eggshell color at specific time points. However, few longitudinal data are available on eggshell color. Therefore, the objective of this study was to investigate eggshell color using the Commission International de L'Eclairage L*a*b* system with multiple measurements at different ages (age at the first egg and at 32, 36, 40, 44, 48, 52, 56, 60, 66, and 72 weeks) within the same individuals from an F2 resource population produced by crossing White Leghorn and Dongxiang Blue chicken. Using an Affymetrix 600 single nucleotide polymorphism (SNP) array, we estimated the genetic parameters of the eggshell color trait, performed genome-wide association studies (GWASs), and screened for the potential candidate genes. The results showed that pink-shelled eggs displayed a significant negative correlation between L* values and both a* and b* values. Genetic heritability based on SNPs showed that the heritability of L*, a*, and b* values ranged from 0.32 to 0.82 for pink-shelled eggs, indicating a moderate to high level of genetic control. The genetic correlations at each time point were mostly above 0.5. The major-effect regions affecting the pink eggshell color were identified in the 10.3-13.0 Mb interval on Gallus gallus chromosome 20, and candidate genes were selected, including SLC35C2, PCIF1, and SLC12A5. Minor effect polygenic regions were identified on chromosomes 1, 6, 9, 12, and 15, revealing 11 candidate genes, including MTMR3 and SLC35E4. Members of the solute carrier family play an important role in influencing eggshell color. Overall, our findings provide valuable insights into the phenotypic and genetic aspects underlying the variation in eggshell color. Using GWAS analysis, we identified multiple quantitative trait loci (QTLs) for pink eggshell color, including a major QTL on chromosome 20. Genetic variants associated with eggshell color may be used in genomic breeding programs.
- ArticleKakinuma T, Kakinuma K, Shinohara T, Shimizu A, Okamoto R, Kaneko A, Takeshima N, Yanagida K, Ohwada M.Gynecol Oncol Rep. 2023 Apr;46:101167.Background: Giant malignant tumors have an increased risk of intraoperative rupture, which might lead to a worse disease condition and tumor recurrence. We performed a clinical study on patients with a giant ovarian mass who underwent laparoscopy combined with an Aron Alpha method.
Methods: This retrospective clinical study spanned from January 2016 to September 2022 and included 23 patients with giant ovarian tumors treated with an Aron Alpha method.
Results: The mean age of the subjects was 47.6 ± 17.8 years, mean tumor diameter 20.4 ± 5.8 cm, mean surgical duration 87.2 ± 33.1 min, and mean hemorrhage volume 94.1 ± 92.2 mL. No patient experienced intraoperative tumor rupture or surgery-related symptoms. Histopathology of excised samples revealed serous cyst adenoma and mucinous cystadenoma, mucinous cystadenoma of borderline malignancy and mature cystic teratoma, and endometriotic cyst adenoma in 6, 4, and 3 patients, respectively. The mean hospitalization period was 6.0 ± 1.2 days, and the hospitalization period was not extended in any subject.
Conclusion: The Aron Alpha method allows tumor resection without capsular rupture and is a useful, minimally invasive surgical method for resecting giant ovarian tumors in which malignancy cannot be ruled out. - ArticleEpel ES.Ageing Res Rev. 2020 11;63:101167.Geroscience offers a counterpoint to the challenged pursuit of curing diseases of aging, by focusing on slowing the biological aging process for extended healthspan earlier in life. Remarkable progress has led this field toward animal trials and the next challenge lies with translation to humans. There is an emerging number of small human trials that can take advantage of new models integrating behavioral and social factors. Understanding dynamic aging mechanisms, given the powerful social determinants of aging (Crimmins, 2020) and human variability and environmental contexts (Moffitt, 2020), will be critical. Behavioral and social factors are intrinsic to aging. Toxic stressors broadly defined can lead to stress-acceleration of aging, either directly impacting aging processes or by shaping poor behavioral health, and underlie the socioeconomic disparities of aging. In contrast, hormetic stressors, acute intermittent stressors of moderate intensity, can produce stress resilience, the ability for quick recovery and possibly rejuvenation of cells and tissues. Although health research usually examines static biomarkers, aging is reflected in dynamic ability to recover from challenges pointing to new interventions and targets for examining mechanisms. A fuller model incorporating stress resilience provides innovative biobehavioral interventions, both for bolstering response to challenges, such as COVID-19, and for improving healthspan.
- ArticleHuang D, Narayanan N, Cano-Vega MA, Jia Z, Ajuwon KM, Kuang S, Deng M.iScience. 2020 Jun 26;23(6):101167.Inhibition of Notch signaling has been shown to induce white to beige transformation of adipocytes and reduce the risk of obesity in mice. However, it remains unknown whether the metabolic benefits of Notch inhibition are dependent on uncoupling protein 1 (UCP1)-mediated thermogenesis and evolutionarily relevant in other mammalian species. Here we report the effect of Notch inhibition in adipocytes of pigs, which lost the UCP1 gene during evolution. Notch inhibition using a γ-secretase inhibitor dibenzazepine (DBZ) promoted beige adipogenesis and mitochondrial biogenic gene expression in porcine adipocytes. Moreover, encapsulation of DBZ into poly(lactide-co-glycolide) nanoparticles enabled rapid cellular internalization and enhanced bioactivity to achieve sustained Notch inhibition, thereby inducing beige-specific gene expression and reducing subcutaneous adipose tissue expansion in pigs. These results demonstrate for the first time a role of Notch signaling in regulating adipose plasticity in large animals, highlighting the therapeutic potential of targeting Notch signaling in obesity treatment.
- ArticleGarcía-Gómez A, Guerrero-Barona E, García-Peña I, Rodríguez-Jiménez M, Moreno-Manso JM.Complement Ther Clin Pract. 2020 May;39:101167.OBJECTIVE: To examine the effect of equine-assisted therapeutic interventions on users' heart rate variability, using this said variability as an objective biological variable related to stress levels.
METHOD: A systematic review has been carried out using the methodology suggested in the PRISMA declaration following systematic searches in academic databases.
RESULTS: 432 registers were initially identified; however, in the screening and suitability process, nine papers were included in the review. With one exception, all of them reported that equine-assisted therapeutic activities had a favourable effect on users' heart rate variability as such activities favour a state of relaxation by activating the Parasympathetic Nervous System. The analysis of the quality of the evidence and the confirmation of the bias in the works indicate that these results must be considered with caution.
DISCUSSION: Although these preliminary results are promising, more rigorous clinical trials are necessary to overcome the methodological limitations of the works.