bluuebunny/crossref_metadata_2025 huggingface dataset:
Understanding health systems challenges in providing Advanced HIV Disease (AHD) care in a hub and spoke model: a qualitative analysis to improve AHD care program in Malawi
Authors: Maphosa Thulani , Denoeud-Ndam Lise , Kapanda Lester , Khatib Sarah , Chilikutali Lloyd , Matiya Eddington , Munthali Boswell , Dambe Rosalia , Chiwandira Brown , Wilson Bilaal , Nyirenda Rose , Nyirenda Laywell , Chikwapulo Bongani , Musopole Owen Madeira , Tiam Appolinaire , Katirayi Leila
Published: February 2024

Background

Despite tremendous progress in antiretroviral therapy (ART) and access to ART, many patients have advanced human immunodeficiency virus (HIV) disease (AHD). Patients on AHD, whether initiating ART or providing care after disengagement, have an increased risk of morbidity and mortality. The Elizabeth Glaser Pediatric AIDS Foundation (EGPAF) launched an enhanced care package using a hub-and-spoke model to optimize AHD care in Malawi. This model improves supply availability and appropriate linkage to care. We utilized a hub-and-spoke model to share health facility challenges and recommendations on the AHD package for screening and diagnosis, prophylaxis, treatment, and adherence support.

Methods

This qualitative study assessed the facility-level experiences of healthcare workers (HCWs) and lay cadres (LCs) providing AHD services to patients through an intervention package. The study population included HCWs and LCs supporting HIV care at four intervention sites. Eligible study participants were recruited by trained Research Assistants with support from the health facility nurse to identify those most involved in supporting patients with AHD. A total of 32 in-depth interviews were conducted. Thematic content analysis identified recurrent themes and patterns across participants’ responses.

Results

While HCWs and LCs stated that most medications are often available at both hub and spoke sites, they reported that there are sometimes limited supplies and equipment to run samples and tests necessary to provide AHD care. More than half of the HCWs stated that AHD training sufficiently prepared them to handle AHD patients at both the hub and spoke levels. HCWs and LCs reported weaknesses in the patient referral system within the hub-and-spoke model in providing a linkage of care to facilities, specifically improper referral documentation, incorrect labeling of samples, and inconsistent availability of transportation. While HCWs felt that AHD registers were time-consuming, they remained motivated as they thought they provided better patient services.

Conclusions

These findings highlight the importance of offering comprehensive AHD services. The enhanced AHD program addressed weaknesses in service delivery through decentralization and provided services through a hub-and-spoke model, improved supply availability, and strengthened linkage to care. Additionally, addressing the recommendations of service providers and patients is essential to improve the health and survival of patients with AHD.
Metabolism-regulating non-coding RNAs in breast cancer: roles, mechanisms and clinical applications
Authors: Xu Shiliang , Wang Lingxia , Zhao Yuexin , Mo Tong , Wang Bo , Lin Jun , Yang Huan
Published: February 2024

Breast cancer is one of the most common malignancies that pose a serious threat to women's health. Reprogramming of energy metabolism is a major feature of the malignant transformation of breast cancer. Compared to normal cells, tumor cells reprogram metabolic processes more efficiently, converting nutrient supplies into glucose, amino acid and lipid required for malignant proliferation and progression. Non-coding RNAs(ncRNAs) are a class of functional RNA molecules that are not translated into proteins but regulate the expression of target genes. NcRNAs have been demonstrated to be involved in various aspects of energy metabolism, including glycolysis, glutaminolysis, and fatty acid synthesis. This review focuses on the metabolic regulatory mechanisms and clinical applications of metabolism-regulating ncRNAs involved in breast cancer. We summarize the vital roles played by metabolism-regulating ncRNAs for endocrine therapy, targeted therapy, chemotherapy, immunotherapy, and radiotherapy resistance in breast cancer, as well as their potential as therapeutic targets and biomarkers. Difficulties and perspectives of current targeted metabolism and non-coding RNA therapeutic strategies are discussed.
Competency of malaria laboratory diagnosis at national and provincial levels at the beginning of malaria post-elimination phase, China
Authors: Yan He , Li Mei , Xia Zhi-gui , Yin Jian-hai
Published: February 2024

Background

Qualified malaria diagnosis competency has contributed to the great achievement of malaria elimination in China. After eliminating malaria, it is still critical to the prevention of re-establishment of malaria transmission in China. This study was aimed to assess the malaria detection competency at national and provincial levels in China at the beginning of malaria post-elimination phase.

Methods

In the present study, different competency assessment activities on the laboratory malaria diagnosis were carried out for national and provincial malaria diagnostic laboratories based on the WHO scoring schedules, including malaria microscopy or nucleic acid amplification tests (NAAT), at the beginning of malaria post-elimination phase (2021–2022) in China.

Results

A total of 60 slides for malaria microscopy and 10 specimen for NAAT were included into the WHO External Quality Assessments of malaria parasite qualitative detection and species identification, and the scoring rate was 96.6% (microscopy: 171/177) and 85.0% (NAAT: 17/20), respectively. Moreover, 124 samples were included into the national NAAT quality assessment, and an accuracy of 87.9% (109/124) was found without significance among reference laboratories and non-reference laboratories.

Conclusions

The findings suggest that there is still a need for sustained strengthening of malaria detection competency, particularly in the areas of parasite counting and detection of low-density parasitemia, to ensure prompt detection of the sources of infection and accurate identification of Plasmodium species, and contribute to case management and focus disposal, thereby effectively preventing the malaria re-establishment.
Highly sensitive SERS platform for pathogen analysis by cyclic DNA nanostructure@AuNP tags and cascade primer exchange reaction
Authors: Xiao Yunju , Luo Shihua , Qiu Jiuxiang , Zhang Ye , Liu Weijiang , Zhao Yunhu , Zhu YiTong , Deng Yangxi , Lu Mengdi , Liu Suling , Lin Yong , Huang Aiwei , Wang Wen , Hu Xuejiao , Gu Bing
Published: February 2024

The capacity to identify small amounts of pathogens in real samples is extremely useful. Herein, we proposed a sensitive platform for detecting pathogens using cyclic DNA nanostructure@AuNP tags (CDNA) and a cascade primer exchange reaction (cPER). This platform employs wheat germ agglutinin-modified Fe3O4@Au magnetic nanoparticles (WMRs) to bind the E. coli O157:H7, and then triggers the cPER to generate branched DNA products for CDNA tag hybridization with high stability and amplified SERS signals. It can identify target pathogens as low as 1.91 CFU/mL and discriminate E. coli O157:H7 in complex samples such as water, milk, and serum, demonstrating comparable or greater sensitivity and accuracy than traditional qPCR. Moreover, the developed platform can detect low levels of E. coli O157:H7 in mouse serum, allowing the discrimination of mice with early-stage infection. Thus, this platform holds promise for food analysis and early infection diagnosis.
RGS6 drives cardiomyocyte death following nucleolar stress by suppressing Nucleolin/miRNA-21
Authors: Sengar Abhishek Singh , Kumar Manish , Rai Chetna , Chakraborti Sreemoyee , Kumar Dinesh , Kumar Pranesh , Mukherjee Sukhes , Mondal Kausik , Stewart Adele , Maity Biswanath
Published: February 2024

Background

Prior evidence demonstrated that Regulator of G protein Signaling 6 (RGS6) translocates to the nucleolus in response to cytotoxic stress though the functional significance of this phenomenon remains unknown.

Methods

Utilizing in vivo gene manipulations in mice, primary murine cardiac cells, human cell lines and human patient samples we dissect the participation of a RGS6-nucleolin complex in chemotherapy-dependent cardiotoxicity.

Results

Here we demonstrate that RGS6 binds to a key nucleolar protein, Nucleolin, and controls its expression and activity in cardiomyocytes. In the human myocyte AC-16 cell line, induced pluripotent stem cell derived cardiomyocytes, primary murine cardiomyocytes, and the intact murine myocardium tuning RGS6 levels via overexpression or knockdown resulted in diametrically opposed impacts on Nucleolin mRNA, protein, and phosphorylation.RGS6 depletion provided marked protection against nucleolar stress-mediated cell death in vitro, and, conversely, RGS6 overexpression suppressed ribosomal RNA production, a key output of the nucleolus, and triggered death of myocytes. Importantly, overexpression of either Nucleolin or Nucleolin effector miRNA-21 counteracted the pro-apoptotic effects of RGS6. In both human and murine heart tissue, exposure to the genotoxic stressor doxorubicin was associated with an increase in the ratio of RGS6/Nucleolin. Preventing RGS6 induction via introduction of RGS6-directed shRNA via intracardiac injection proved cardioprotective in mice and was accompanied by restored Nucleolin/miRNA-21 expression, decreased nucleolar stress, and decreased expression of pro-apoptotic, hypertrophy, and oxidative stress markers in heart.

Conclusion

Together, these data implicate RGS6 as a driver of nucleolar stress-dependent cell death in cardiomyocytes via its ability to modulate Nucleolin. This work represents the first demonstration of a functional role for an RGS protein in the nucleolus and identifies the RGS6/Nucleolin interaction as a possible new therapeutic target in the prevention of cardiotoxicity.
The influence of exotic and native plants on illnesses with physical and spiritual causes in the semiarid region of Piauí, Northeast of Brazil
Authors: da Silva Paulo Henrique , Ferreira Júnior Washington Soares , Zank Sofia , do Nascimento André Luiz Borba , de Abreu Maria Carolina
Published: February 2024

Background

Local medical systems (LMS) include native and exotic plants used for the treatment of diseases of physical and spiritual nature. The incorporation of exotic plants into these systems has been the subject of many studies. In this context, an analysis was conducted on the influence of the origin of plants on diseases of physical and spiritual nature in order to evaluate the therapeutic versatility of native and exotic species in these therapeutic targets, to investigate whether exotic plants mainly fill gaps not met by native plants (diversification hypothesis), and identify which species are prioritized in the redundant targets in these two therapeutic groups in the rural community of Morrinhos, Monsenhor Hipólito, Piauí.

Methods

Data collection took place in 2 stages. First, free lists and semi-structured interviews with local residents (n = 134) were conducted to survey plants used for therapeutic purposes and the associated illnesses. Then, another phase of interviews was carried out to evaluate the prioritization between native and exotic plants in redundant therapeutic targets. To test the diversification hypothesis (DH) in each group of illnesses, data were analyzed using generalized linear models (Poisson and Binomial GLMs); versatility was measured by the number of therapeutic indications and compared between resources using the Mann–Whitney test, and prioritization in each group was verified by comparing the proportions of native and exotic plants with the χ2 test.

Results

One hundred and thirty-two species of plants were surveyed, being 71 exotic and 61 native, with indications for physical and spiritual illnesses. The results revealed that the diversification hypothesis did not explain the inclusion of exotic plants in the local medical system to treat physical or spiritual illnesses and that the therapeutic versatility of exotic and native resources in the two groups was also similar (p > 0.05). However, exotic plants were prioritized in illnesses with physical causes and native plants in illnesses with spiritual causes.

Conclusions

The local medical system presents similar and distinct patterns in the therapeutic targets, depending on the perspective evaluated. Therefore, it is necessary to investigate the patterns of use of medicinal plants in different sociocultural contexts in order to broaden the debate about the role of plant origin in the selection of treatments for illnesses with different causes.
Assessment of the causal relationship between gut microbiota and cardiovascular diseases: a bidirectional Mendelian randomization analysis
Authors: Dai Xiao-Ce , Yu Yi , Zhou Si-Yu , Yu Shuo , Xiang Mei-Xiang , Ma Hong
Published: February 2024

Background

Previous studies have shown an association between gut microbiota and cardiovascular diseases (CVDs). However, the underlying causal relationship remains unclear. This study aims to elucidate the causal relationship between gut microbiota and CVDs and to explore the pathogenic role of gut microbiota in CVDs.

Methods

In this two-sample Mendelian randomization study, we used genetic instruments from publicly available genome-wide association studies, including single-nucleotide polymorphisms (SNPs) associated with gut microbiota (n = 14,306) and CVDs (n = 2,207,591). We employed multiple statistical analysis methods, including inverse variance weighting, MR Egger, weighted median, MR pleiotropic residuals and outliers, and the leave-one-out method, to estimate the causal relationship between gut microbiota and CVDs. Additionally, we conducted multiple analyses to assess horizontal pleiotropy and heterogeneity.

Results

GWAS summary data were available from a pooled sample of 2,221,897 adult and adolescent participants. Our findings indicated that specific gut microbiota had either protective or detrimental effects on CVDs. Notably, Howardella (OR = 0.955, 95% CI: 0.913–0.999, P = .05), Intestinibacter (OR = 0.908, 95% CI:0.831–0.993, P = .03), Lachnospiraceae (NK4A136 group) (OR = 0.904, 95% CI:0.841–0.973, P = .007), Turicibacter (OR = 0.904, 95% CI: 0.838–0.976, P = .01), Holdemania (OR, 0.898; 95% CI: 0.810–0.995, P = .04) and Odoribacter (OR, 0.835; 95% CI: 0.710–0.993, P = .04) exhibited a protective causal effect on atrial fibrillation, while other microbiota had adverse causal effects. Similar effects were observed with respect to coronary artery disease, myocardial infarction, ischemic stroke, and hypertension. Furthermore, reversed Mendelian randomization analyses revealed that atrial fibrillation and ischemic stroke had causal effects on certain gut microbiotas.

Conclusion

Our study underscored the importance of gut microbiota in the context of CVDs and lent support to the hypothesis that increasing the abundance of probiotics or decreasing the abundance of harmful bacterial populations may offer protection against specific CVDs. Nevertheless, further research is essential to translate these findings into clinical practice.
PTHrP intracrine actions divergently influence breast cancer growth through p27 and LIFR
Authors: Edwards Courtney M. , Kane Jeremy F. , Smith Jailyn A. , Grant Déja M. , Johnson Jasmine A. , Diaz Maria A. Hernandez , Vecchi Lawrence A. , Bracey Kai M. , Omokehinde Tolu N. , Fontana Joseph R. , Karno Breelyn A. , Scott Halee T. , Vogel Carolina J. , Lowery Jonathan W. , Martin T. John , Johnson Rachelle W.
Published: February 2024

The role of parathyroid hormone (PTH)-related protein (PTHrP) in breast cancer remains controversial, with reports of PTHrP inhibiting or promoting primary tumor growth in preclinical studies. Here, we provide insight into these conflicting findings by assessing the role of specific biological domains of PTHrP in tumor progression through stable expression of PTHrP (-36-139aa) or truncated forms with deletion of the nuclear localization sequence (NLS) alone or in combination with the C-terminus. Although the full-length PTHrP molecule (-36-139aa) did not alter tumorigenesis, PTHrP lacking the NLS alone accelerated primary tumor growth by downregulating p27, while PTHrP lacking the NLS and C-terminus repressed tumor growth through p27 induction driven by the tumor suppressor leukemia inhibitory factor receptor (LIFR). Induction of p27 by PTHrP lacking the NLS and C-terminus persisted in bone disseminated cells, but did not prevent metastatic outgrowth, in contrast to the primary tumor site. These data suggest that the PTHrP NLS functions as a tumor suppressor, while the PTHrP C-terminus may act as an oncogenic switch to promote tumor progression through differential regulation of p27 signaling.
Consideration of sex as a biological variable in diabetes research across twenty years
Authors: Cherian Celena M. , Reeves Hayley R. , De Silva Duneesha , Tsao Serena , Marshall Katie E. , Rideout Elizabeth J.
Published: February 2024

Background

Sex differences exist in the risk of developing type 1 and type 2 diabetes, and in the risk of developing diabetes-associated complications. Sex differences in glucose homeostasis, islet and β cell biology, and peripheral insulin sensitivity have also been reported. Yet, we lack detailed information on the mechanisms underlying these differences, preventing the development of sex-informed therapeutic strategies for persons living with diabetes. To chart a path toward greater inclusion of biological sex as a variable in diabetes research, we first need a detailed assessment of common practices in the field.

Methods

We developed a scoring system to evaluate the inclusion of biological sex in manuscripts published in Diabetes, a journal published by the American Diabetes Association. We chose Diabetes as this journal focuses solely on diabetes and diabetes-related research, and includes manuscripts that use both clinical and biomedical approaches. We scored papers published across 3 years within a 20-year period (1999, 2009, 2019), a timeframe that spans the introduction of funding agency and journal policies designed to improve the consideration of biological sex as a variable.

Results

Our analysis showed fewer than 15% of papers used sex-based analysis in even one figure across all study years, a trend that was reproduced across journal-defined categories of diabetes research (e.g., islet studies, signal transduction). Single-sex studies accounted for approximately 40% of all manuscripts, of which > 87% used male subjects only. While we observed a modest increase in the overall inclusion of sex as a biological variable during our study period, our data highlight significant opportunities for improvement in diabetes research practices. We also present data supporting a positive role for journal policies in promoting better consideration of biological sex in diabetes research.

Conclusions

Our analysis provides significant insight into common practices in diabetes research related to the consideration of biological sex as a variable. Based on our analysis we recommend ways that diabetes researchers can improve inclusion of biological sex as a variable. In the long term, improved practices will reveal sex-specific mechanisms underlying diabetes risk and complications, generating knowledge to enable the development of sex-informed prevention and treatment strategies.
Automated characterization of patient–ventilator interaction using surface electromyography
Authors: Sauer Julia , Graßhoff Jan , Carbon Niklas M. , Koch Willi M. , Weber-Carstens Steffen , Rostalski Philipp
Published: February 2024

Background

Characterizing patient–ventilator interaction in critically ill patients is time-consuming and requires trained staff to evaluate the behavior of the ventilated patient.

Methods

In this study, we recorded surface electromyography ($$\textrm{sEMG}$$
sEMG
) signals from the diaphragm and intercostal muscles and esophageal pressure ($$P_{\textrm{es}}$$

P
es

) in mechanically ventilated patients with ARDS. The sEMG recordings were preprocessed, and two different algorithms (triangle algorithm and adaptive thresholding algorithm) were used to automatically detect inspiratory patient effort. Based on the detected inspirations, major asynchronies (ineffective, auto-, and double triggers and double efforts), delayed and synchronous triggers were computationally classified. Reverse triggers were not considered in this study. Subsequently, asynchrony indices were calculated. For the validation of detected efforts, two experts manually annotated inspiratory patient activity in $$P_{\textrm{es}}$$

P
es

, blinded toward each other, the $$\textrm{sEMG}$$
sEMG
signals, and the algorithmic results. We also classified patient–ventilator interaction and calculated asynchrony indices with manually detected inspirations in $$P_{\textrm{es}}$$

P
es

as a reference for automated asynchrony classification and asynchrony index calculation.

Results

Spontaneous breathing activity was recognized in 22 out of the 36 patients included in the study. Evaluation of the accuracy of the algorithms using 3057 inspiratory efforts in $$P_{\textrm{es}}$$

P
es

demonstrated reliable detection performance for both methods. Across all datasets, we found a high sensitivity (triangle algorithm/adaptive thresholding algorithm: 0.93/0.97) and a high positive predictive value (0.94/0.89) against expert annotations in $$P_{\textrm{es}}$$

P
es

. The average delay of automatically detected inspiratory onset to the $$P_{\textrm{es}}$$

P
es

reference was $$-$$
-
79 ms/29 ms for the two algorithms. Our findings also indicate that automatic asynchrony index prediction is reliable. For both algorithms, we found the same deviation of $$0.06\pm 0.13$$

0.06
±
0.13

to the $$P_{\textrm{es}}$$

P
es

-based reference.

Conclusions

Our study demonstrates the feasibility of automating the quantification of patient–ventilator asynchrony in critically ill patients using noninvasive sEMG. This may facilitate more frequent diagnosis of asynchrony and support improving patient–ventilator interaction.
Clinical characteristics and outcomes of patients who underwent neonatal cardiac surgery: ten years of experience in a tertiary surgery center
Authors: Zhang Han , Li Gang , Li Qiangqiang , Zuo Yansong , Wang Qiang
Published: February 2024

Objective

To evaluate the outcomes after neonatal cardiac surgery at our institute, and identify factors associated with operative mortality.

Methods

We examined 224 neonates who underwent cardiac surgery at a single institution from 2013 to 2022. Relevant data, such as demographic information, operative details, and postoperative records, were gathered from medical and surgical records. Our primary focus was on the operative mortality.

Results

Median age and weight at surgery were 12 (7–20) days and 3.4 (3.0–3.8) kg, respectively. Overall mortality was 14.3% (32/224). Mortality rates showed improvement over time (2013–2017 vs. 2018–2022), with rates decreasing from 21.9% to 10.6% (p = 0.023). ECMO use, extubation failure, lactate > 4.8 mmol/l and VIS > 15.5 on 24 h after operation were significantly associated with operative mortality, according to multivariate logistic regression analysis. Patients admitted to the cardiac intensive care unit (CICU) before surgery and those with prenatal diagnosis showed lower operative mortality. Median follow-up time of 192 hospital survivors was 28.0 (11.0–62.3) months. 10 patients experienced late deaths, and 7 patients required reinterventions after neonatal cardiac surgery. Risk factors for composite end-point of death and reintervention on multivariable analysis were: surgical period (HR = 0.230, 95% CI 0.081–0.654; p = 0.006), prolonged ventilation (HR = 4.792, 95% CI 1.296–16.177; p = 0.018) and STAT categories 3–5 (HR = 5.936, 95% CI 1.672–21.069; p = 0.006).

Conclusions

Our institution has observed improved surgical outcomes in neonatal cardiac surgery over the past five years with low mortality, but late death and reintervention remain necessary in some patients. The location and prenatal diagnosis prior to surgery may affect the outcomes of neonates undergoing congenital heart disease operations.
Systemic immune-inflammation index and in-stent restenosis in patients with acute coronary syndrome: a single-center retrospective study
Authors: Xie Feng , Yu Zuozhong , Xiong Yurong , Wu Zhijian , Wu Yanqing
Published: February 2024

Background

In-stent restenosis (ISR) has been shown to be correlated with inflammation. This study aimed to examine the relationship between systemic immune-inflammation index (SII, an innovative inflammatory biomarker) and ISR in acute coronary syndrome (ACS) patients after drug-eluting stent (DES) implantation.

Methods

Subjects who were diagnosed with ACS and underwent DES implantation were enrolled retrospectively. All individuals underwent follow-up coronary angiography at six to forty-eight months after percutaneous coronary intervention (PCI). SII was defined as [(platelet count × neutrophil count)/lymphocyte count], and Ln-transformed SII (LnSII) was carried out for our analysis. Multivariate logistic regression analysis was employed to assess the association between LnSII and DES-ISR.

Results

During a median follow-up period of 12 (11, 20) months, 523 ACS patients who underwent follow-up angiography were included. The incidence of DES-ISR was 11.28%, and patients in the higher LnSII tertile trended to show higher likelihoods of ISR (5.7% vs. 12.1% vs. 16.0%; P = 0.009). Moreover, each unit of increased LnSII was correlated with a 69% increased risk of DES-ISR (OR = 1.69, 95% CI 1.04–2.75). After final adjusting for confounders, a significant higher risk of DES-ISR (OR = 2.52, 95% CI 1.23–5.17) was found in participants in tertile 3 (≥ 6.7), compared with those in tertiles 1–2 (< 6.7). Subgroup analysis showed no significant dependence on age, gender, body mass index, current smoking, hypertension, and diabetes for this positive association (all P for interaction > 0.05).

Conclusion

High levels of SII were independently associated with an increased risk of DES-ISR in ACS patients who underwent PCI. Further prospective cohort studies are still needed to validate our findings.
Does variety in hedonic spending improve happiness? Testing alternative causal mechanisms between hedonic variety and subjective well-being
Authors: Gladstone Joe J. , Ruberton Peter M. , Margolis Seth , Lyubomirsky Sonja
Published: February 2024

Previous research has found only a small, inconsistent association between hedonic consumption and subjective well-being, often attributed to individuals adapting to the happiness gains from their purchases. Given that diverse experiences can reduce or avert hedonic adaptation, we hypothesized that variety in hedonic spending would be associated with greater well-being. This hypothesis was tested in four studies (total N = 2,920), using both self-reported and objective bank-reported spending data. In our correlational analyses, hedonic spending variety was uniquely associated with well-being, even after controlling for total hedonic spending and other financial variables. Our investigation also explored the directional relationship between hedonic spending variety and well-being, yielding mixed results for both causal pathways in two time-lagged panel studies. Additionally, in two parallel experiments, participants reported that varied hedonic spending contributed more to happiness than uniform hedonic spending. These findings have implications for basic well-being science by testing how varied consumption behaviors and well-being are interrelated.
Preparation and evaluation of transdermal permeation of Huperzine A ethosomes gel in vitro
Authors: Wu Jiyu , Xu Renai , Xu Xiaowei , Ye Shiyuan , Huang Aifang
Published: February 2024

This study aimed to design and evaluate the transdermal permeation of Huperzine A ethosomes gel in vitro. Huperzine A ethosomes were prepared using the injection method, and their physical and chemical properties were characterized. A comparison was made between Huperzine A ethosomes gel, ordinary gel, and cream. The Franz diffusion cell test on mouse abdominal skin was conducted, and Huperzine A concentration was determined using LC-MS/MS. Transdermal volume, skin retention, and transdermal rate were used to assess the percutaneous permeability of the three preparations. Results demonstrated that Huperzine A ethosomes gel exhibited significantly higher accumulative permeation, transdermal rate, and skin retention compared to ordinary gel and cream. The findings suggest that Huperzine A ethosomes gel, with its controllable quality and favorable transdermal absorption properties, holds potential as a safe option for clinical administration.
BET-inhibitor DYB-41 reduces pulmonary inflammation and local and systemic cytokine levels in LPS-induced acute respiratory distress syndrome: an experimental rodent study
Authors: Iten Manuela , Gschwend Camille , Ostini Alessandro , Cameron David Robert , Goepfert Christine , Berger David , Haenggi Matthias
Published: February 2024

Background

Acute respiratory distress syndrome (ARDS) is a form of respiratory failure stemming from various underlying conditions that ultimately lead to inflammation and lung fibrosis. Bromodomain and Extra-Terminal motif (BET) inhibitors are a class of medications that selectively bind to the bromodomains of BET motif proteins, effectively reducing inflammation. However, the use of BET inhibitors in ARDS treatment has not been previously investigated. In our study, we induced ARDS in rats using endotoxin and administered a BET inhibitor. We evaluated the outcomes by examining inflammation markers and lung histopathology.

Results

Nine animals received treatment, while 12 served as controls. In the lung tissue of treated animals, we observed a significant reduction in TNFα levels (549 [149–977] pg/mg vs. 3010 [396–5529] pg/mg; p = 0.009) and IL-1β levels (447 [369–580] pg/mg vs. 662 [523–924] pg/mg; p = 0.012), although IL-6 and IL-10 levels showed no significant differences. In the blood, treated animals exhibited a reduced TNFα level (25 [25–424] pg/ml vs. 900 [285–1744] pg/ml, p = 0.016), but IL-1β levels were significantly higher (1254 [435–2474] pg/ml vs. 384 [213–907] pg/ml, p = 0.049). No differences were observed in IL-6 and IL-10 levels. There were no significant variations in lung tissue levels of TGF-β, SP-D, or RAGE. Histopathological analysis revealed substantial damage, with notably less perivascular edema (3 vs 2; p = 0.0046) and visually more inflammatory cells. However, two semi-quantitative histopathologic scoring systems did not indicate significant differences.

Conclusions

These preliminary findings suggest a potential beneficial effect of BET inhibitors in the treatment of acute lung injury and ARDS. Further validation and replication of these results with a larger cohort of animals, in diverse models, and using different BET inhibitors are needed to explore their clinical implications.
Relationship between dietary glycemic index and glycemic load and sperm-quality parameters in Iranian men: a cross-sectional study
Authors: Hosseini Elham , Khodavandloo Mehdi , Sabet Somaye Abdollahi , Mousavi Seyedeh Neda
Published: February 2024

Background

Infertility is a major clinical problem with psychological, financial and medical costs. Male infertility has recently been linked to 50% of childless couples. It is worth mentioning that diet and its components can be manipulated and applied in counseling meetings of infertile men as a modifiable factor. The goal of this study was to determine the correlation of dietary glycemic index (GI) and glycemic load (GL) with sperm-quality parameters in Iranian men.

Materials and methods

In this cross-sectional study which was carried from Aug to Nov 2023, after excluding smokers, 322 men who were attending the IVF clinic of Ayatollah Mousavi Hospital for seminal analysis were enrolled. Dietary intake was completed by an expert dietitian through face-to-face interviews with a validated 168-item food frequency questionnaire (FFQ). In the present study, sperm-quality parameters, including motility, concentration, normal morphology, vitality, DNA fragmentation index (DFI), and chromatin maturation of sperm, were analyzed. The relationship between dietary GI and CL and these parameters was assessed.

Results

Adjusting for the baseline variables, dietary GI and GL showed positive and negative associations with sperm progressive motility, respectively (p = 0.01 and p < 0.001). Higher dietary GI was associated with lower (p = 0.03); however, a higher dietary GL was associated with higher immotile sperm (p < 0.001). A higher dietary GI was associated with a 77% higher sperm count (p = 0.003). In contrast, higher dietary GL was associated with a lower count (p < 0.001). Higher dietary GI and GL were associated with higher and lower percentages of sperm with normal morphology by 70% and 40%, respectively (p < 0.001 in both). A higher dietary GL was associated with an increase in sperm vitality and DFI of 33% and 53%, respectively (p < 0.001). Higher dietary GI showed a significant negative effect on sperm DFI (p = 0.009). Dietary GI and GL showed significant positive and negative effects on SCMA, respectively (p = 0.002 and p < 0.001).

Conclusion

A diet with a higher GI showed beneficial effects on more parameters of sperm; however, higher dietary GL showed deleterious effects, except sperm vitality and SCMA. More studies are needed to obtain a concise result.
Embracing the future of Artificial Intelligence in the classroom: the relevance of AI literacy, prompt engineering, and critical thinking in modern education
Authors: Walter Yoshija
Published: February 2024

The present discussion examines the transformative impact of Artificial Intelligence (AI) in educational settings, focusing on the necessity for AI literacy, prompt engineering proficiency, and enhanced critical thinking skills. The introduction of AI into education marks a significant departure from conventional teaching methods, offering personalized learning and support for diverse educational requirements, including students with special needs. However, this integration presents challenges, including the need for comprehensive educator training and curriculum adaptation to align with societal structures. AI literacy is identified as crucial, encompassing an understanding of AI technologies and their broader societal impacts. Prompt engineering is highlighted as a key skill for eliciting specific responses from AI systems, thereby enriching educational experiences and promoting critical thinking. There is detailed analysis of strategies for embedding these skills within educational curricula and pedagogical practices. This is discussed through a case-study based on a Swiss university and a narrative literature review, followed by practical suggestions of how to implement AI in the classroom.
Training healthcare professionals to administer Goal Attainment Scaling as an outcome measure
Authors: Logan Benignus , Viecelli Andrea K. , Pascoe Elaine M. , Pimm Bonnie , Hickey Laura E. , Johnson David W. , Hubbard Ruth E.
Published: February 2024

Background

Goals generated by Goal Attainment Scaling (GAS) can be used as an outcome measure to promote person-centred research and care. There are no training packages which support its use outside of the rehabilitation discipline. This paper describes the development and evaluation of a training package to support the implementation of GAS as an outcome measure in healthcare research. The training package consisted of classroom teaching, a training manual for self-directed learning, one-on-one simulation and hot reviews. It was developed for the GOAL Trial, a randomised controlled trial assessing a Comprehensive Geriatric Assessment’s effectiveness in enabling frail older people living with chronic kidney disease to attain their goals. Training participants were invited to complete pre- and post-training online evaluation surveys.

Results

Forty-two healthcare professionals attended an initial online classroom teaching, with 27 proceeding to administer GAS to GOAL Trial patients. Response rates for the online pre- and post-training surveys were 95% and 72%, respectively. Prior to training, only 15% of participants reported being able to appropriately scale and troubleshoot GAS goals. Post-training this was 92%. There was 100% participant satisfaction for the training manual, one-on-one simulation, and hot reviews.

Conclusions

This training package helps ensure healthcare professionals administering GAS have adequate knowledge and skills. It has the potential for adoption as a guide to support the implementation of GAS by other researchers seeking to embrace persont-centred principles in their work.
A technique to retrieve an internalised embedded central venous catheter
Authors: Finnegan John , Govender Pradeep
Published: February 2024

Background

Central venous catheters may become embedded due to the formation of adhesions between the indwelling catheter and the vein wall.

Case presentation

A 49-year-old patient with bacteraemia was referred for retrieval of an embedded internalised central venous dialysis catheter. Recently the catheter had been surgically ligated at the venotomy site internalising the intravascular catheter component, which precluded antegrade ballooning through the catheter hub.

Seldinger technique was used to access the catheter lumen within the left internal jugular vein and through and through access was established across the catheter. Retrograde endoluminal balloon dilation was performed to disrupt adhesions and free the catheter. The catheter was snared over the wire and removed from the right femoral vein.

Conclusion

This case report outlines an effective, minimally invasive retrieval method in a rare case of an embedded internalised central venous catheter.

Graphical Abstract
On the investigation of shock wave/boundary layer interaction with a high-order scheme based on lattice Boltzmann flux solver
Authors: Qin Jian , Yu Haichuan , Wu Jie
Published: February 2024

Shock wave/boundary layer interaction (SWBLI) continues to pose a significant challenge in the field of aerospace engineering. This paper aims to address this issue by proposing a novel approach for predicting aerodynamic coefficients and heat transfer in viscous supersonic and hypersonic flows using a high-order flux reconstruction technique. Currently, finite volume methods are extensively employed for the computation of skin aerodynamic coefficients and heat transfer. Nevertheless, these numerical methods exhibit considerable susceptibility to a range of factors, including the inviscid flux function and the computational mesh. The application of high-order flux reconstruction techniques offers promising potential in alleviating these challenges. In contrast to other high-order methods, the flux reconstruction is combined with the lattice Boltzmann flux solver in this study. The current method evaluates the common inviscid flux at the cell interface by locally reconstructing the lattice Boltzmann equation solution from macroscopic flow variables at solution points. Consequently, this framework performs a positivity-preserving, entropy-based adaptive filtering method for shock capturing. The present approach is validated by simulating the double Mach reflection, and then simulating some typical viscous problems. The results demonstrate that the current method accurately predicts aerodynamic coefficients and heat transfer, providing valuable insights into the application of high-order methods for shock wave/boundary layer interaction.
Age-related changes in hematological and biochemical profiles of Wistar rats
Authors: Patel Suresh , Patel Satish , Kotadiya Ashvin , Patel Samir , Shrimali Bhavesh , Joshi Nikita , Patel Tushar , Trivedi Harshida , Patel Jitendra , Joharapurkar Amit , Jain Mukul
Published: February 2024

Background

Wistar rats are extensively used as the model for assessing toxicity and efficacy in preclinical research. Hematological and biochemical laboratory data are essential for evaluating specific variations in the physiological and functional profile of a laboratory animal. Establishing hematological and biochemical reference values for Wistar (han) rats at various age intervals was the goal of this work. Male and female Wistar rats (n = 660) of ages 6–8 weeks, 10–14 weeks and > 6 months were used in the experiment. Blood and serum were collected from these rats under fasting conditions.

Results

We observed that the majority of hematological and biochemical parameters were significantly influenced by sex and age. Hematological changes were significantly correlated to aging were increased red blood cells, hemoglobin, hematocrit, neutrophils, monocytes and eosinophils in both sexes, as well as decreased platelet, mean corpuscular volume, mean corpuscular hemoglobin and lymphocytes in both sexes. White blood cells of male rats were considerably higher than those of female rats in all age ranges. For biochemistry, increase in glucose, total protein and creatinine were seen in both sexes, along with increases in urea in females and alanine aminotransferase in males. Age was significantly associated with decreased alkaline phosphatase in both sexes.

Conclusions

When using Wistar rats as a model, these reference values may be useful in evaluating the results.
Turkish reliability and validity study of Barkley’s BAARS-IV self-report current symptoms
Authors: Topaloglu Tansu Eda , Dogan Bilge , Sevincok Doga , Sevincok Levent
Published: February 2024

Objective

Recall bias of patients and their relatives, low reliability of the history, changes in attention deficit hyperactivity disorder (ADHD) symptoms or compensatory behaviors, and various comorbidities may be associated with difficulties in diagnosing ADHD in adults. Barkley Adult Attention Deficit Hyperactivity Disorder Rating Scale-IV (BAARS-IV), a relatively new scale, needs to be studied for validity and reliability in different societies and cultures. In this study, we investigated whether the Turkish version of BAARS-IV: Present Symptoms Section is valid and reliable in the medical students who constituted the sample.

Methods

Adult Attention Deficit Hyperactivity Disorder Self-Report Scale and BAARS-IV: Present Symptoms Section were administered to 402 fifth- and sixth-year medical students. We performed exploratory and confirmatory factor analyzes. Cronbach’s alpha and inter-item correlation were evaluated. Pearson correlation test was used in inter-scale correlation analyses.

Results

For ADHD items, Kaiser-Meyer-Olkin (KMO) (0.882), Measuring of Sampling Adequacy MSA (0.819), chi-square (2512.455), and p (< 0.001) values showed that the data were suitable for factor analysis. A three-factor structure with an eigenvalue above 1 and explaining 53.14% of the total variance was obtained. In the correlation matrix reconstructed with eight Sluggish Cognitive Tempo (SCT) items, the determinant of the correlation matrix was 0.025, the KMO determinant was 0.852, the lowest MSA value was 0.750, and the residual rate was 14%. A two-factor structure was obtained explaining 67.451% of the variance. Cronbach’s alpha values of the inattention and impulsivity subscales were 0.839 and 0.752, respectively. Cronbach’s alpha value of 8 questions in the SCT scale was found to be 0.871.

Conclusion

The results of our study indicate that the BAARS-IV Self-report Present Symptoms scale is valid and reliable among medical students.
Developing an efficient method for melanoma detection using CNN techniques
Authors: Moturi Devika , Surapaneni Ravi Kishan , Avanigadda Venkata Sai Geethika
Published: February 2024

Background

More and more genetic and metabolic abnormalities are now known to cause cancer, which is typically deadly. Any bodily part may become infected by cancerous cells, which can be fatal. Skin cancer is one of the most prevalent types of cancer, and its prevalence is rising across the globe. Squamous and basal cell carcinomas, as well as melanoma, which is clinically aggressive and causes the majority of deaths, are the primary subtypes of skin cancer. Screening for skin cancer is therefore essential.

Methods

The best way to quickly and precisely detect skin cancer is by using deep learning techniques. In this research deep learning techniques like MobileNetv2 and Dense net will be used for detecting or identifying two main kinds of tumors malignant and benign. For this research HAM10000 dataset is considered. This dataset consists of 10,000 skin lesion images and the disease comprises nonmelanocytic and melanocytic tumors. These two techniques can be used for detecting the malignant and benign. All these methods are compared and then a result can be inferred from their performance.

Results

After the model evaluation, the accuracy for the MobileNetV2 was 85% and customized CNN was 95%. A web application has been developed with the Python framework that provides a graphical user interface with the best-trained model. The graphical user interface allows the user to enter the patient details and upload the lesion image. The image will be classified with the appropriate trained model which can predict whether the uploaded image is cancerous or non-cancerous. This web application also displays the percentage of cancer affected.

Conclusion

As per the comparisons between the two techniques customized CNN gives higher accuracy for the detection of melanoma.
Universal thermodynamic bounds on the Fano factor of discriminatory networks with unidirectional transitions
Authors: Berx J. , Proesmans K.
Published: February 2024

We derive a universal lower bound on the Fano factors of general biochemical discriminatory networks involving irreversible catalysis steps, based on the thermodynamic uncertainty relation, and compare it to a numerically exact Pareto optimal front. This bound is completely general, involving only the reversible entropy production per product formed and the error fraction of the system. We then show that by judiciously choosing which transitions to include in the reversible entropy production, one can derive a family of bounds that can be fine-tuned to include physical observables at hand. Lastly, we test our bound by considering three discriminatory schemes: a multi-stage Michaelis-Menten network, a Michaelis-Menten network with correlations between subsequent products, and a multi-stage kinetic proofreading network, where for the latter application the bound is altered to include the hydrolytic cost of the proofreading steps. We find that our bound is remarkably tight.