Effectiveness Of Treatment Research Articles

DTG + 3TC dual therapy for the treatment Naïve patients with viral load exceeding 500,000 copies/mL: a retrospective study

BackgroundAntiretroviral therapy (ART) has transformed HIV management, with various regimens available. Dolutegravir (DTG) plus lamivudine (3TC) dual therapy is now the one of the first line regimens.MethodsA retrospective, observational study included treatment naïve people living with HIV (PLWH) with baseline HIV RNA viral load (VL) greater than 500,000 copies/mL from March 2020 to June 2022. PLWH on DTG + 3TC were included in the 2DR group, while others on INSTI-based three-drug regimens were divided in the 3DR group. Viral suppression, immunological recovery, and safety were assessed.ResultsThe study included 52 PLWH, with no significant baseline differences. Virologic suppression rates at weeks 24 and 48 were similar in both groups, even with baseline HIV RNA VL greater than 1,000,000 copies/mL. CD4 + T cell counts improved rapidly. No serious adverse effects were reported.ConclusionsDTG + 3TC dual therapy demonstrates effectiveness in treatment naïve PLWH with high baseline HIV RNA VL, suggesting its potential as a first line regimen for all treatment naïve PLWH.

Gd-GQDs as nanotheranostic platform for the treatment of HPV-positive oropharyngeal cancer.

In this study, we developed new gadolinium-graphene quantum dot nanoparticles (Gd-GQDs) as a theranostic platform for magnetic resonance imaging and improved the efficiency of radiotherapy in HPV-positive oropharyngeal cancer. Based on cell toxicity results, Gd-GQD NPs were nontoxic for both cancer and normal cell lines up to 25µg/ml. These NPs enhance the cytotoxic effect of radiation only on cancer cells but not on normal cells. The flow cytometry analysis indicated that cell death mainly occurred in the late phase of apoptosis. The immunocytochemical analysis was used to evaluate apoptosis pathway proteins. The Bcl-2 and p53 protein levels did not differ statistically significantly between radiation alone group and those that received irradiation in combination with NPs. In contrast, the combination group exhibited a significant increase in Bax protein expression, suggesting that cells could undergo apoptosis independent of the p53 pathway. Magnetic resonance (MR) imaging showed that Gd-GQD NPs, when used at low concentrations, enhanced T1-weighted signal intensity resulting from T1 shortening effects. At higher concentrations, the T2 shortening effect became predominant and was able to decrease the signal intensity. Gd-GQD appears to offer a novel approach for enhancing the effectiveness of radiation treatment and facilitating MR imaging for monitoring HPV-positive tumors.

Polydimethylsiloxane enabled triple-action water-resistant coating with desirable relaxation rate in clear aligner

Clear aligners undergo rapid stress relaxation in warm, moist oral environments, compromising therapeutic effectiveness and longevity of treatment. To develop an innovative multilayer composite material with improved stability and reduced stress release, we have engineered an innovative coating characterized by the surface aggregation of polydimethylsiloxane (PDMS), which imparts a pronounced hydrophobic effect. In addition, the chemically and physically cross-linked structure of the coating reduces the free volume created by molecular chain rearrangement owing to the presence of water molecules, thereby minimizing water penetration into the coating. Concurrently, the coating’s internal structure is enriched with numerous polar functional groups to capture water molecules that penetrate into the inside of the coating. Through combination of these mechanisms, water molecules are effectively sequestered, thereby impeding their penetration into the polyethylene terephthalate glycol (PETG) substrate. The impact of the polydimethylsiloxane content on the triple-action water-resistance mechanisms was thoroughly examined using attenuated total reflection (ATR)-Fourier transform infrared (FTIR), water absorption rate, water swelling rate, and X-ray photoelectron spectroscopy. The low surface energy cross-linked polyurethane coating is applied to the polyethylene terephthalate glycol (PETG) substrate to create a novel composite material with specific mechanical properties and reduced stress relaxation. The composite material remains stable in simulated oral environment with linear swelling rate of 0.58 % upon water absorption. Additionally, the stress release rate of the composite material within 336 h is notably lower (23.64 %) than that of PETG (62.29 %).

Association between PER and CRY gene polymorphisms and the response to caffeine citrate treatment in infants with apnea of prematurity.

Circadian rhythms impact metabolism and the therapeutic effects of drugs. The purpose of this study was to determine the association between PER and CRY polymorphisms and caffeine citrate treatment response in infants with apnea of prematurity. A total of 221 preterm infants of gestational age <34 weeks were included in this study (160 in the response group and 61 in the non-response group). The propensity score matching method was used to perform a 1:1 matching for all premature infants, and the general characteristics and clinical outcomes of the two groups were compared. The association between polymorphisms of the circadian transcription repressors PER and CRY and caffeine citrate treatment response in infants with apnea of prematurity was analyzed with co-dominant, dominant, recessive, and over-dominant models, as well as analysis of alleles. Generalized multifactor dimensionality reduction (GMDR) analysis was used to analyze the interaction between the PER and CRY genes. After propensity score matching, 45 preterm infants were included in each of the response and non-response groups, and there were no statistically significant differences in general characteristics between the two groups (P > 0.05). Infants in the non-response groups had a higher incidence of moderate and severe bronchopulmonary dysplasia (BPD) (P = 0.043), retinopathy of prematurity (ROP) (P = 0.035), and invasive ventilation (P = 0.027), and their duration of oxygen use (P = 0.041) was longer. When corrected for false discovery rate, the PER3 rs228669 recessive model (P FDR = 0.045) and the over-dominant model (P FDR = 0.045) were both associated with caffeine citrate treatment response. Preterm infants with the rs228669 CC genotype had a significantly lower rate of caffeine citrate non-response in the recessive model (OR = 0.28, 95% CI = 0.12-0.66), which was significantly higher in preterm infants with the CT genotype in the over-dominant model (OR = 4.18, 95% CI = 1.64-10.66). GMDR analysis revealed an interaction between the PER and CRY genes (P < 0.05). Circadian rhythms may play a role in the response of premature infants to caffeine citrate, and polymorphisms of the PER and CRY genes may influence the effectiveness of caffeine citrate treatment for apnea of prematurity.

Does adherence to physiotherapy depend on the typologies of patients with back pain and their physiotherapists? A qualitative typology study

BackgroundPatient adherence to physiotherapy is influenced by a multitude of factors including the characteristics and attitudes of patients and physiotherapists. This study aims to identify typologies of patients with back pain and their physiotherapists and attempts to explain how typologies could influence patient adherence. MethodThis study was based on a secondary data analysis from focus group interviews to identify barriers and facilitators for adherence. Transcribed interview data were used for a structured content analysis based on deductive and inductive categorization and coding. The Big-five Personality Traits were applied to build deductive categories about the physiotherapists’ and the patients' typologies. ResultsTen patients with low back pain (6 women) and 11 physiotherapists (5 women) were recruited. The four patient types are based on conscientiousness, high activity level (HAL), internal locus of control (ILC), high adherence level (HADL) (= type 1); neuroticism, HAL, ILC, low adherence level (LADL) (= type 2); extraversion, HADL, external locus of control (ELC), HADL (= type 3); agreeableness, active behavior, ELC, HADL (= type 4). The three physiotherapist types are based on conscientiousness, high adherence influence (HADI), use of guidelines (= type 1); agreeableness, acceptance of requests, low adherence influence (= type 2); neuroticism, HADI, preference for active therapy (= type 3). ConclusionAwareness of typologies of patients with back pain and their physiotherapists may help to facilitate adherence and subsequently treatment effectiveness. Further quantitative research should aim to validate the correlation between the identified typologies and the adherence level of patients with back pain.

Intense pulsed light is a promising way for telangiectasias / reticular veins treatment: from pathogenesis to pronounced clinical outcomes

Varicose veins are the most common pathology of peripheral vessels. A broader concept is the term chronic venous insufficiency (CVI), which, in addition to varicose veins, includes telangiectasias and reticular veins. Sclerotherapy is considered as the basis of treatment for reticular veins. However, the procedure has its drawbacks and side effects, which indicates the importance of implementing safer treatment methods. An alternative treatment for reticular veins is intense pulsed light. To illustrate the effectiveness and safety of IPL treatment for reticular veins, we present a clinical case of a patient aged 73 years with complaints of dark purple and bluish vessels. After clinical evaluation, diagnosis of reticular veins/telangiectasias was made (C 1 according to the CEAP 2020 classification). Due to the patients’ refusal to undergo sclerotherapy, it was decided to perform IPL procedures (M22, Lumenis). The patient’s reticular veins and telangiectasias were almost completely leveled out after the second session of IPL therapy; there was also no progress of CVI. No side effects were noted. The pathogenetic application of intense pulsed light in the treatment of reticular veins can be explained by decreasing the inflammatory process, integrating extracellular matrix, as well as inhibition of mast cell degranulation.

Ankyloglossia in Australia: Experiences and perspectives of parents and caregivers

ObjectivesTo investigate the perspectives and experiences of parents of infants with ankyloglossia in Australia. MethodTwo hundred and sixty-seven parents across Australia responded to an online survey including their experiences of having a child with ankyloglossia. Descriptive statistics were used to analyse quantitative data. ResultsParticipants were from all Australian states and territories, with the majority residing in New South Wales and Victoria. Ankyloglossia diagnoses typically occurred within the first two weeks of life, driven mainly by difficulties with feeding. Lactation consultants played a prominent role in diagnosis, particularly in rural areas. Surgical interventions were common, with frenotomy using scissors or scalpel being the primary treatment. Aftercare recommendations, including stretching the frenotomy wound, were prevalent. Most parents received education about ankyloglossia, primarily through verbal and written information. Parents generally reported high satisfaction with the effectiveness of treatments, favouring surgical interventions. However, satisfaction with health professionals' support did not consistently correlate with the likelihood of consenting to the treatment again, and those who conducted their own research on ankyloglossia expressed lower satisfaction with health professionals’ support. ConclusionsThe experiences of Australian parents in their infant's diagnosis, management and education of ankyloglossia varied greatly. Clinical guidelines for all relevant health professionals are needed to ensure standardised diagnosis and management processes. In future, this will help guide evidence-based diagnosis and intervention for infants with ankyloglossia.

Spraying with encapsulated nitric oxide donor reduces weight loss and oxidative damage in papaya fruit

The combination of nitric oxide (NO) donors with nanomaterials has emerged as a promising approach to reduce postharvest losses. The encapsulation of NO donors provides protection from rapid degradation and controlled release, enhancing the NO effectiveness in postharvest treatments. Moreover, the application method can also influence postharvest responses. In this study, two application methods were evaluated, spraying and immersion, using S-nitrosoglutathione (GSNO, a NO donor) in free and encapsulated forms on papaya fruit. Our hypothesis was that GSNO encapsulated in chitosan nanoparticles would outperform the free form in delaying fruit senescence. In addition, this study marks the pioneering characterization of chitosan nanoparticles containing GSNO within the framework of a postharvest investigation. Overall, our findings indicate that applying encapsulated GSNO (GSNO-NP-S) through spraying preserves the quality of papaya fruit during storage. This method not only minimizes weight loss, ethylene production, and softening, but also stimulates antioxidant responses, thereby mitigating oxidative damage. Consequently, it stands out as the promising technique for delaying papaya fruit senescence. This innovative approach holds the potential to enhance postharvest practices and advance sustainable agriculture.

Early treatment for children with mental health problems and genetic conditions through a parenting intervention (The GAP): study protocol for a pragmatic randomized controlled trial

BackgroundChildren with genetic conditions are at increased risk for mental health and neurodevelopmental problems, often accompanied by significant parental distress. Genetic and family factors can impact children and parents’ mental health. Early parenting interventions, like the Incredible Years® programs, have demonstrated to improve parental distress and children’s mental health. The recent version for young children with language delays or autism spectrum disorder (IY-ASLD®) has shown to be feasible and effective to support parents in their children’s developmental trajectories. The effectiveness of treatments for children with genetic conditions and neurodevelopmental problems is largely unexplored, leaving significant gaps in evidence-based options. Clinicians lack guidance, especially when patients exhibit language or social communication impairments but do not meet diagnostic criteria for a full-blown autism spectrum disorder (ASD). We aim to fill this gap, providing evidence on the feasibility and effectiveness of the IY-ASLD® intervention for such patients.MethodsWe designed a prospective multicenter pragmatic randomized controlled trial including approximately 68 children aged 3 to 7 years, recruited from three tertiary care reference hospitals. Inclusion criteria will necessitate genetic confirmation of a neurodevelopmental disorder along with language, communication, or socialization difficulties. Individuals with an ASD diagnosis will be excluded. All subjects are included in a territorial register for rare conditions (ReMin, Registre de Malalties Minoritàries de Catalunya). Families will randomly be assigned to the intervention or the control group. The intervention will be held online by clinical psychologists and child and adolescent psychiatrists.DiscussionOur group has recently piloted the online implementation of the IY-ASLD® intervention for the first time in Spain, for parents of children with language delays, socialization difficulties, or ASD, but not genetically determined. Our multicenter research consortium is well-positioned to recruit patients with rare conditions and implement efficient treatment pathways within the National Health System. Given the geographical dispersion of families affected by rare conditions, the online format offers logistical advantages and improved therapy access, enhancing homogeneity across all patients. The results of this study will inform clinicians and policymakers about evidence-based treatment options for this vulnerable and overlooked group of young children.Trial registrationClinicalTrials.gov NCT06125093. Date of registration: first submitted 2023–10-23; first posted 2023–11-09. URL of trial registry record.

Allergen Microarrays and New Physical Approaches to More Sensitive and Specific Detection of Allergen-Specific Antibodies.

The prevalence of allergic diseases has increased tremendously in recent decades, which can be attributed to growing exposure to environmental triggers, changes in dietary habits, comorbidity, and the increased use of medications. In this context, the multiplexed diagnosis of sensitization to various allergens and the monitoring of the effectiveness of treatments for allergic diseases become particularly urgent issues. The detection of allergen-specific antibodies, in particular, sIgE and sIgG, is a modern alternative to skin tests due to the safety and efficiency of this method. The use of allergen microarrays to detect tens to hundreds of allergen-specific antibodies in less than 0.1 mL of blood serum enables the transition to a deeply personalized approach in the diagnosis of these diseases while reducing the invasiveness and increasing the informativeness of analysis. This review discusses the technological approaches underlying the development of allergen microarrays and other protein microarrays, including the methods of selection of the microarray substrates and matrices for protein molecule immobilization, the obtainment of allergens, and the use of different types of optical labels for increasing the sensitivity and specificity of the detection of allergen-specific antibodies.

Dexamethasone Palmitate Encapsulated in Palmitic Acid Modified Human Serum Albumin Nanoparticles for the Treatment of Rheumatoid Arthritis

Rheumatoid arthritis (RA) is a chronic inflammatory joint condition characterized by symmetric, erosive synovitis leading to cartilage erosion and significant disability. Macrophages, pivotal in disease progression, release pro-inflammatory factors upon activation. We developed a nanoparticle delivery system (DXP-PSA NPs), based on palmitic acid modified human serum albumin (PSA), to deliver dexamethasone palmitate (DXP) directly to sites of inflammation, enhancing treatment effectiveness and minimizing possible side effects. The system actively targets scavenger receptor-A on activated macrophages, achieving selective accumulation at inflamed joints. In vitro effect and preliminary targeting abilities were investigated on LPS-activated RAW264.7 cells. The in vivo efficacy and safety were evaluated and compared side to side with commercially available lipid emulsion Limethason® in an advanced adjuvant-induced arthritis rat model. DXP-PSA NPs offer a novel approach to RA treatment and presents promising prospects for clinical translation.

Current treatment for male infertility: an umbrella review of systematic reviews and meta-analyses.

This umbrella review aimed to summarize and provide a general evaluation of the effectiveness of current treatments for male infertility and assess the quality of evidence and possible biases. An umbrella review of systematic reviews and meta-analyses available in PubMed, Web of Science, and Scopus, covering studies published up to October 2023, was conducted. Sperm concentration, morphology, and motility were used as endpoints to evaluate the effectiveness of the treatments. Of 2998 studies, 18 published meta-analyses were extracted, yielding 90 summary effects on sperm concentration (n = 36), sperm morphology (n = 26), and sperm motility (n = 28) on 28 interventions. None of the meta-analyses were classified as having low methodological quality, whereas 12 (66.7%) and 6 (33.3%) had high and moderate quality, respectively. Of the 90 summary effects, none were rated high-evidence quality, whereas 53.3% (n = 48), 25.6% (n = 23), and 21.1% (n = 19) were rated moderate, low, and very low, respectively. Significant improvements in sperm concentration, morphology, and motility were observed with pharmacological interventions (N-acetyl-cysteine, antioxidant therapy, aromatase inhibitors, selective estrogen receptor modulators, hormones, supplements, and alpha-lipoic acid) and nonpharmacological interventions (varicocele repair and redo varicocelectomy). In addition, vitamin supplementation had no significant positive effects on sperm concentration, motility, or morphology. Treatments for male infertility are increasingly diverse; however, the current evidence is poor because of the limited number of patients. Further well-designed studies on single treatment and high-quality meta-analysis of intertreatment comparisons are recommended.

STC-UNet: renal tumor segmentation based on enhanced feature extraction at different network levels

Renal tumors are one of the common diseases of urology, and precise segmentation of these tumors plays a crucial role in aiding physicians to improve diagnostic accuracy and treatment effectiveness. Nevertheless, inherent challenges associated with renal tumors, such as indistinct boundaries, morphological variations, and uncertainties in size and location, segmenting renal tumors accurately remains a significant challenge in the field of medical image segmentation. With the development of deep learning, substantial achievements have been made in the domain of medical image segmentation. However, existing models lack specificity in extracting features of renal tumors across different network hierarchies, which results in insufficient extraction of renal tumor features and subsequently affects the accuracy of renal tumor segmentation. To address this issue, we propose the Selective Kernel, Vision Transformer, and Coordinate Attention Enhanced U-Net (STC-UNet). This model aims to enhance feature extraction, adapting to the distinctive characteristics of renal tumors across various network levels. Specifically, the Selective Kernel modules are introduced in the shallow layers of the U-Net, where detailed features are more abundant. By selectively employing convolutional kernels of different scales, the model enhances its capability to extract detailed features of renal tumors across multiple scales. Subsequently, in the deeper layers of the network, where feature maps are smaller yet contain rich semantic information, the Vision Transformer modules are integrated in a non-patch manner. These assist the model in capturing long-range contextual information globally. Their non-patch implementation facilitates the capture of fine-grained features, thereby achieving collaborative enhancement of global–local information and ultimately strengthening the model’s extraction of semantic features of renal tumors. Finally, in the decoder segment, the Coordinate Attention modules embedding positional information are proposed aiming to enhance the model’s feature recovery and tumor region localization capabilities. Our model is validated on the KiTS19 dataset, and experimental results indicate that compared to the baseline model, STC-UNet shows improvements of 1.60%, 2.02%, 2.27%, 1.18%, 1.52%, and 1.35% in IoU, Dice, Accuracy, Precision, Recall, and F1-score, respectively. Furthermore, the experimental results demonstrate that the proposed STC-UNet method surpasses other advanced algorithms in both visual effectiveness and objective evaluation metrics.

Real-World Research on Retinal Diseases Using Health Claims Database: A Narrative Review.

Real-world data (RWD) has emerged as a crucial component in understanding and improving patient outcomes across various medical conditions, including retinal diseases. Health claims databases, generated from healthcare reimbursement claims, offer a comprehensive source of RWD, providing insights into patient outcomes, healthcare utilization, and treatment effectiveness. However, the use of these databases for research also presents unique challenges. This narrative review explores the role of real-world research on retinal diseases using health claims databases, highlighting their advantages, limitations, and potential contributions to advancing our understanding and management of the diseases. The review examines the applications of health claims databases in retinal disease research, including epidemiological studies, comparative effectiveness and safety analyses, economic burden assessments, and evaluations of patient outcomes and quality of care. Previous findings demonstrate the value of these databases in generating prevalence and incidence estimates, identifying risk factors and predictors, evaluating treatment effectiveness and safety, and understanding healthcare utilization patterns and costs associated with retinal diseases. Despite their strengths, health claims databases face challenges related to data limitations, biases, privacy concerns, and methodological issues. Accordingly, the review also explores future directions and opportunities, including advancements in data collection and analysis, integration with electronic health records, collaborative research networks and consortia, and the evolving regulatory landscape. These developments are expected to enhance the utility of health claims databases for retinal disease research, resulting in more comprehensive and impactful findings across diverse retinal disorders and robust real-world insights from a large population.

Trivalent chromium versus baricitinib for rheumatoid arthritis treatment: first phase 2/3 randomized controlled trial, is trivalent chromium the upcoming immune-modulator?

Rheumatoid arthritis (RA) is a debilitating disease mainly treated by DMARDs. Baricitinib is one of the emerging DMARDs with strong anti-rheumatic effects but has serious side effects. Trivalent chromium (Cr III) is a natural element with anti-inflammatory properties. Trivalent chromium (Cr III) is introduced for the first time to study its effect and safety in treatment of RA patients and compared to those of baricitinib. This is a phase 2/3 randomized controlled trial where RA patients were divided in a ratio of 2:1 according to the newly introduced medication either Cr (III) (group A) or baricitinib (group B). Patients attended three visits on day 0, after 3 weeks and 12 weeks, disease activity was scored. Hands ultrasound was done and reassessed. Side effects were monitored throughout the study. DAS28-CRP improved by 26.9% and 11.8% on third visit for Cr III and baricitinib, respectively (p = 0.001). DAS28-ESR improved by 25.6% and 7.74% on third visit for Cr III and baricitinib, respectively (p = < 0.001). ACR 50 was 18.8% for Cr III and 5.7% for baricitinib on second visit. ACR 70 was 25% for Cr III and 0% for baricitinib on third visit (P = < 0.001). Ultrasound GLOESS, SH, PDUS, joints effusions improved by 38.9%, 38.4%, 56.7% and 74.8% for Cr III, while by 10.5%, 3.75%, 59.6% and worsening of joints effusions happened with baricitinib on third visit. p = 0.022 and 0.002 between groups for GLOESS and SH improvement, respectively. Cr III has shown very promising fast clinical and sonographic results in treating RA patients which were surprisingly superior to baricitinib in most aspects. Furthermore, Cr III is potentially safe with evidently fewer side effects than baricitinib and other DMARDs, however, long-term safety is still not established. (IRB No.: 00012098- FWA No.: 00018699, Serial number: 040457) ClinicalTrials.gov ID: NCT05545020.

Are there any benefits from prescribing a cardiac cytoprotector to enhance the quality of life in patients with coronary heart disease and chronic heart failure?

Introduction. Type 2 diabetes (T2D) increases the risk of developing cardiovascular diseases, which leads to a high mortality in this category of patients. Issues regarding the prevention of the onset and progression of coronary heart disease (CHD) and chronic heart failure (CHF) in patients with T2D and/or metabolic syndrome (MS) are still not fully understood. The use of metabolic drugs with cardioprotective effects, in particular Mildronate®, is one of the possibilities to improve the effectiveness of combination treatment of CHD and CHF.Aim. To study the effect of Mildronate® on the quality of life (QoL) of patients with CHD and CHF, suffering from T2D and/or MS.Materials and methods. A total of 2.084 patients with co-occurring two (or more) disorders: obesity, type 2 diabetes, angina pectoris, CHT, and CHF were included in the INDICOR observational study conducted in real-life clinical practice settings. Group 1 received therapy with disease-modifying agents prescribed due to CHD and T2D; Group 2 received Mildronate® at a dose of 1000 mg per day in addition to the same therapy. The studied lab test results were assessed at baseline and 42 days of therapy.Results. A 42-day course of therapy in patients receiving Mildronate® at a dose of 1000 mg per day in addition to disease-modifying therapy (DMT) contributed to a percentage increase in the number of patients with CHD, FC (functional class) I angina pectoris (Δ,% + 63%, p &lt; 0.001 ) as compared to the control group with no significant changes (Δ,% + 7%, p &gt; 0.5). A significant increase in the number of patients with FC I CHF was recorded in Group 2 (from 23.5 to 42.1%, Δ,% + 79%) as compared to Group 1, where no significant changes were detected (22.7 to 23.7%, Δ,% + 4%). The QoL in patients with CHF based on data collected using the Minnesota Questionnaire and QoL in patients with CHD based on data collected using the Seattle Questionnaire significantly improved in the groups that received Mildronate® in addition to DMT, as compared with the group of patients who were only on DMT.Conclusion. Results from the Seattle and Minnesota questionnaires showed that the use of Mildronate® as part of combination therapy in patients with CHD and CHF, suffering from T2D and/or MS, contributed to a significant reduction in the frequency of angina attacks and lowering angina FC, CHF FC, and also enhanced the quality of life in this category of patients.

Genomic and transcriptomic profiling of inflammatory breast cancer reveals distinct molecular characteristics to non-inflammatory breast cancers.

Inflammatory breast cancer (IBC), a rare and highly aggressive form of breast cancer, accounts for 10% of breast cancer-related deaths. Previous omics studies of IBC have focused solely on one of genomics or transcriptomics and did not discover common differences that could distinguish IBC from non-IBC. Seventeen IBC patients and five non-IBC patients as well as additional thirty-three Asian breast cancer samples from TCGA-BRCA were included for the study. We performed whole-exon sequencing (WES) to investigate different somatic genomic alterations, copy number variants, and large structural variants between IBC and non-IBC. Bulk RNA sequencing (RNA-seq) was performed to examine the differentially expressed genes, pathway enrichment, and gene fusions. WES and RNA-seq data were further investigated in combination to discover genes that were dysregulated in both genomics and transcriptomics. Copy number variation analysis identified 10 cytobands that showed higher frequency in IBC. Structural variation analysis showed more frequent deletions in IBC. Pathway enrichment and immune infiltration analysis indicated increased immune activation in IBC samples. Gene fusions including CTSC-RAB38 were found to be more common in IBC. We demonstrated more commonly dysregulated RAS pathway in IBC according to both WES and RNA-seq. Inhibitors targeting RAS signaling and its downstream pathways were predicted to possess promising effects in IBC treatment. We discovered differences unique in Asian women that could potentially explain IBC etiology and presented RAS signaling pathway as a potential therapeutic target in IBC treatment.

Early Detection and Stability Assessment of Hazardous Rock Masses in Steep Slopes

The assessment of slope stability plays a critical role in the prevention and management of slope disasters. Evaluating the condition and stability of hazardous rock masses is essential for predicting potential collapses and assessing treatment effectiveness. However, conventional measurement techniques are inadequate in high slope areas, which lack sufficient spatial data to support subsequent calculations and analyses. Therefore, this paper presents a method for the early identification and evaluation of unstable rock masses in high slopes using Unmanned Aerial Vehicle (UAV) digital photogrammetry and geographic information technology. By considering nine evaluation indices including geology, topography, and induced conditions within the study area, weights for each index are determined through an analytic hierarchy process. A semi-automatic approach is then utilized to extract and analyze rock mass stability. The reliability of this early identification method is confirmed by applying the limit equilibrium principle. The findings reveal that 17.6% of dangerous rock masses in the study area fall into the unstable category (W4, W6, W10). This method effectively assesses slope rock mass stability while providing technical support for disaster monitoring systems, warning mechanisms, and railway infrastructure safety defense capability to ensure safe mountain railway operations.

The Effectiveness of Treating Osgood-Schlatter Disease (OSD) with Leukocyte-Rich Platelet-Rich Plasma (LR-PRP) Depending on the Duration of the Disease.

Background: Osgood-Schlatter disease (OSD) occurs mainly in physically active adolescents, causing significant physical activity restrictions. The aim of this study is to compare the effectiveness of treating OSD with leukocyte-rich platelet-rich plasma (LR-PRP) depending on the duration of the disease and to attempt to develop an alternative treatment method to the currently used conservative therapy. Methods: Treatment efficacy was evaluated using the VAS, Tegner, Lysholm, and KOOS scales. Subject satisfaction, return to sports activity, potential adverse effects, and X-ray evaluation were likewise used to assess the success of the procedure. Results: Analysis across all scales showed statistically significant treatment effectiveness with LR-PRP in both groups of patients. When comparing the two groups, significantly better treatment outcomes were achieved in the acute phase of OSD. Treatment satisfaction in the acute OSD group was 95%, compared to 64% in the chronic group. The MCID value after LR-PRP injection in acute OSD compared to chronic OSD reached 100% vs. 81% on the VAS scale, 95.5% vs. 55% on the Tegner scale, 95% vs. 47% on the Lysholm scale and 91% vs. 27% on the KOOS scale. No adverse effects were recorded in either group. Conclusions: The high efficacy of LR-PRP treatment in patients with acute OSD, in correlation with high safety, as well as rapid and lasting results, can be an effective and beneficial alternative to conservative treatment. This single procedure seems particularly justified in a group of young professional athletes, where absence from training can lead to serious consequences.

Identification and resolution of drug-related problems among neonates in neonatal intensive care unit (NICU): A prospective longitudinal observational study

BackgroundDrug related problems (DRPs) can interfere with the desired therapeutic outcomes. Neonates are susceptible for DRP occurrence due to clinical heterogeneity, inappropriate formulations, complexity of drug regimens and polypharmacy. Thus, the objective of this study was to characterize the DRP, their resolutions and associated risk factors among neonates in the Neonatal Intensive Care Unit (NICU). MethodsA cross-sectional study was carried out in NICU ward at tertiary care teaching hospital for 18 months. Clinical pharmacists participated on daily basis to collect patient information and assess their medication therapy for DRPs. DRPs were classified into problems and their causes according to Pharmaceutical Care Network Europe (PCNE) Version 9.1. Clinical pharmacist implicated evidence-based interventions to resolve DRPs. SPSS V.25 was used for the statistical analysis. Univariate logistic regression analysis was used for the determination of risk factors for DRPs, with a p-value <0.05 for associations that were statistically significant. ResultsA total of 426 neonates were enrolled with a mean gestational age of 35.2 ± 7.5 weeks and a mean birth weight of 2316 ± 1814 g. A total of 486 DRPs were found among 55.6 % neonates. Among them, majority of DRPs were belongs to treatment effectiveness [n = 427 (87.8 %)]. In total, 559 interventions were made, resulting in the resolution of 87.4 % of the DRPs. Furthermore, neonates staying in hospital for more than 5 days identified as most significant risk factor of DRPs. ConclusionDRPs are common in neonates admitted to NICU. Clinical Pharmacist can play significant roles in identifying, preventing and resolving DRPs among neonates.