bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessment of prevalence and risk factors associated with Hepatitis B virus infection among blood donors in Mogadishu Somalia
Authors: Mohamud Abdirahman Khalif , Inchon Pamornsri , Suwannaporn Sirinan , Prasert Kriengkrai , Dirie Najib Isse
Published: March 2024

Background

The Hepatitis B virus (HBV) is transmitted through contaminated blood or bodily fluids. Globally, over 81 million blood units are donated annually, a crucial therapeutic procedure without alternatives. However, blood-borne infections, including HBV, pose a significant hurdle to safe transfusions, especially in HBV-endemic regions like Somalia with limited screening. Therefore, this study aims to estimate the prevalence of Hepatitis B virus infection and identify risk factors associated with it among blood donors in Mogadishu, Somalia.

Method

A hospital-based cross-sectional study was conducted between February and April 2023. Research tools included a 5-ml blood sample and a structured questionnaire. The presence or absence of HB markers was determined using a multi-HB rapid test and CDC’s HB marker interpretation guideline. Logistic regression was used in univariate and multivariate models to identify risk factors associated with HBV infection, with significance set at a p-value < 0.05 in the final model.

Result

A total of 494 blood donors were recruited for this study; 93.9% were male, with a mean age of 31.5 (SD = 8.11). The prevalence of Hepatitis B virus (HBV) infection among blood donors was 9.7%, with a 95% CI of 7.1–12.3. In multivariable logistic regression, those with a monthly income of less than 200 USD (AOR = 5.20, 95% CI = 1.61–16.79), those with an income between 200 and 400 (AOR = 3.59, 95% CI = 1.38–9.34), Jobless blood donors (AOR = 3.78, 95% CI = 1.17–12.20), those in business occupations (AOR = 3.35, 95% CI = 1.24–9.08), those with a history of STDs (AOR = 4.83, 95% CI = 2.03–11.50), those without a history of HB vaccine (AOR = 13.81, 95% CI = 2.46–77.41), those with a history of tooth extraction (AOR = 6.90, 95% CI = 2.66–17.88), and those who shared sharp equipment (AOR = 2.90, 95% CI = 1.07–7.82) were more likely to become infected with the Hepatitis B virus (HBV) compared to their counterparts.

Conclusion

This study highlights a high prevalence of Hepatitis B virus (HBV) infection. Implementation efforts against HBV infection should specifically focus on low-income individuals, the jobless, and donors with a history of STD to mitigate the burden of HBV infection and promote safer blood donation. In addition, discouraging the sharing of sharp equipment, improving infection control practices during tooth extraction procedures, and enhancing HB vaccination uptake, particularly among individuals lacking a history of HB vaccine, is highly recommended.
Digital registration versus cone-beam computed tomography for evaluating implant position: a prospective cohort study
Authors: Han Xinrui , Wei Donghao , Jiang Xi , Di Ping , Yi Chun , Lin Ye
Published: March 2024

Background

Postoperative cone-beam computed tomography (CBCT) examination is considered a reliable method for clinicians to assess the positions of implants. Nevertheless, CBCT has drawbacks involving radiation exposure and high costs. Moreover, the image quality can be affected by artifacts. Recently, some literature has mentioned a digital registration method (DRM) as an alternative to CBCT for evaluating implant positions. The aim of this clinical study was to verify the accuracy of the DRM compared to CBCT scans in postoperative implant positioning.

Materials and methods

A total of 36 patients who received anterior maxillary implants were included in this clinical study, involving a total of 48 implants. The study included 24 patients in the single implant group and 12 patients in the dual implant group. The postoperative three-dimensional (3D) positions of implants were obtained using both CBCT and DRM. The DRM included three main steps. Firstly, the postoperative 3D data of the dentition and intraoral scan body (ISB) was obtained through the intraoral scan (IOS). Secondly, a virtual model named registration unit which comprised an implant replica and a matching ISB was created with the help of a lab scanner and reverse engineering software. Thirdly, by superimposing the registration unit and IOS data, the postoperative position of the implant was determined. The accuracy of DRM was evaluated by calculating the Root Mean Square (RMS) values after superimposing the implant positions obtained from DRM with those from postoperative CBCT. The accuracy of DRM was compared between the single implant group and the dual implant group using independent sample t-tests. The superimposition deviations of CBCT and IOS were also evaluated.

Results

The overall mean RMS was 0.29 ± 0.05 mm. The mean RMS was 0.30 ± 0.03 mm in the single implant group and 0.29 ± 0.06 mm in the dual implant group, with no significant difference (p = 0.27). The overall registration accuracy of the IOS and CBCT data ranged from 0.14 ± 0.05 mm to 0.21 ± 0.08 mm.

Conclusion

In comparison with the 3D implant positions obtained by CBCT, the implant positions located by the DRM showed clinically acceptable deviation ranges. This method can be used in single and dual implant treatments to assess the implant positions.
Usage and attitude of medical students towards mobile medical applications during and after COVID-19 lockdown: repeated cross-sectional study
Authors: Alsharif Marwa Ahmed , Bahbah Ammar Ayman , Ghonaim Mohamed Mabrouk , Omran Janna Ahmed , Rihan Maram Mohamed , Zayed Mariam Ahmed , Tabour Mariam Salah , Alwardany Mariam Hamed , Aboshady Omar Ali
Published: March 2024

Background

COVID-19 pandemic has accelerated the shift toward e-learning, particularly in medical education. Mobile medical applications (apps) have become integral tools for e-learning due to the prevalence of smartphones among medical students. Therefore, we aim to assess the usage and attitude of undergraduate Egyptian medical students towards mobile medical apps during and after the COVID-19 lockdown.

Methods

This is a two-phase repeated cross-sectional study using an online, pilot-tested, and self-administered survey conducted at the Faculty of Medicine, Menoufia University, Egypt. Phase 1 was during the academic year 2019–2020 (during lockdown), and phase 2 was during the academic year 2021–2022 (after lockdown). Out of the 4800-target population for each phase, a sample size of 140 medical students was randomly selected from each study year, resulting in a total sample size of 840 students for all six academic and clinical years for each phase.

Results

A total of 566 students in phase 1 and 616 students in phase 2 responded to the survey, with response rates of 67.62% and 73.33%, respectively. In phase 1, 55.7% of students reported using medical apps, with no significant difference between males and females (60.1% vs. 53.8%; p = 0.17) or between academic and clinical years (56.3% vs. 54.7%; p = 0.7). In phase 2, the percentage increased to 70.9%, with a significant difference between males and females (80% vs. 62.9%; p < 0.001) and between academic and clinical years (79.8% vs. 63%; p < 0.001). Medical dictionaries were the most commonly used apps, whereas medical calculators were the least common in both phases. Regarding their attitude, most students (65.1% and 73.9% in phases 1 and 2, respectively) expressed confidence in using medical apps, while 81.3% in phase 1 and 88.1% in phase 2 agreed that using medical apps is a flexible method of learning. Lack of knowledge regarding which app to download was the most reported cause of limitation in medical app usage by 37.8% of the students in phase 1 and 40% in phase 2.

Conclusion

Our study revealed that the COVID-19 lockdown led to a significant increase in the use of mobile medical apps among Egyptian medical students. Despite the positive attitude of students towards these apps, multiple challenges still need to be addressed to ensure their optimal utilization in medical education.
Choosing a nursing specialty: connection to nursing students’ personality traits, clinical self-efficacy, adoption of technology changes, and specialty prestige; a cross-sectional study
Authors: Shabat Lilach Ben , Itzhaki Michal
Published: March 2024

Background

Choosing a field of specialization within the nursing profession is affected by nurses’ personality traits, self-confidence in performing clinical skills, and the field’s prestige. A successful choice of area of expertise may improve nurses’ job satisfaction and reduce job mobility. This study aims to examine the relationship between personality traits, clinical self-efficacy, perceived prestige, adoption of technological changes, and choice of specialty field among nursing students.

Methods

A cross-sectional study was conducted. One-hundred-twenty-seven undergraduate nursing students in their fourth year of studies at a large university in Israel participated in the study. The questionnaire administered was comprised of six parts: demographic data, personality traits, adoption of technological changes, clinical self-efficacy, perceived prestige, and intention to select a field of specialization.

Results

Acute disciplines were rated more prestigious than chronic disciplines, with intensive care and emergency medicine considered the most prestigious, while mental health and geriatrics were the least prestigious. Students’ mean perceived confidence in performing nursing clinical skills was high and more than half considered themselves open to technology changes. Positive correlations were found between prestige and intention to choose a field of expertise (r = 0.41, p < 0.001) and the personality trait of openness and the intention to choose an acute care area (r = 0.26, p < 0.01).

Conclusions

Despite the gradual aging of the population and the increase in chronic morbidity, which demand a greater nursing focus on older adults, and notwithstanding the mental health reforms, nursing students perceive geriatrics and mental health as less prestigious fields. A career development path can be applied by developing a tool for occupational guidance designed to rank students’ suitability for specialty fields and thus help them choose the area that best suits them.
Pan-histone deacetylase inhibitor vorinostat suppresses osteoclastic bone resorption through modulation of RANKL-evoked signaling and ameliorates ovariectomy-induced bone loss
Authors: Peng Xiaole , Wang Tianhao , Wang Qing , Zhao Yuhu , Xu Hao , Yang Huilin , Gu Ye , Tao Yunxia , Yan Bangsheng , Xu Yaozeng , Geng Dechun
Published: March 2024

Background

Estrogen deficiency-mediated hyperactive osteoclast represents the leading role during the onset of postmenopausal osteoporosis. The activation of a series of signaling cascades triggered by RANKL-RANK interaction is crucial mechanism underlying osteoclastogenesis. Vorinostat (SAHA) is a broad-spectrum pan-histone deacetylase inhibitor (HDACi) and its effect on osteoporosis remains elusive.

Methods

The effects of SAHA on osteoclast maturation and bone resorptive activity were evaluated using in vitro osteoclastogenesis assay. To investigate the effect of SAHA on the osteoclast gene networks during osteoclast differentiation, we performed high-throughput transcriptome sequencing. Molecular docking and the assessment of RANKL-induced signaling cascades were conducted to confirm the underlying regulatory mechanism of SAHA on the action of RANKL-activated osteoclasts. Finally, we took advantage of a mouse model of estrogen-deficient osteoporosis to explore the clinical potential of SAHA.

Results

We showed here that SAHA suppressed RANKL-induced osteoclast differentiation concentration-dependently and disrupted osteoclastic bone resorption in vitro. Mechanistically, SAHA specifically bound to the predicted binding site of RANKL and blunt the interaction between RANKL and RANK. Then, by interfering with downstream NF-κB and MAPK signaling pathway activation, SAHA negatively regulated the activity of NFATc1, thus resulting in a significant reduction of osteoclast-specific gene transcripts and functional osteoclast-related protein expression. Moreover, we found a significant anti-osteoporotic role of SAHA in ovariectomized mice, which was probably realized through the inhibition of osteoclast formation and hyperactivation.

Conclusion

These data reveal a high affinity between SAHA and RANKL, which results in blockade of RANKL-RANK interaction and thereby interferes with RANKL-induced signaling cascades and osteoclastic bone resorption, supporting a novel strategy for SAHA application as a promising therapeutic agent for osteoporosis.
SparseRNAfolD: optimized sparse RNA pseudoknot-free folding with dangle consideration
Authors: Gray Mateo , Will Sebastian , Jabbari Hosna
Published: March 2024

Motivation

Computational RNA secondary structure prediction by free energy minimization is indispensable for analyzing structural RNAs and their interactions. These methods find the structure with the minimum free energy (MFE) among exponentially many possible structures and have a restrictive time and space complexity ($$O(n^3)$$

O
(

n
3

)

time and $$O(n^2)$$

O
(

n
2

)

space for pseudoknot-free structures) for longer RNA sequences. Furthermore, accurate free energy calculations, including dangle contributions can be difficult and costly to implement, particularly when optimizing for time and space requirements.

Results

Here we introduce a fast and efficient sparsified MFE pseudoknot-free structure prediction algorithm, SparseRNAFolD, that utilizes an accurate energy model that accounts for dangle contributions. While the sparsification technique was previously employed to improve the time and space complexity of a pseudoknot-free structure prediction method with a realistic energy model, SparseMFEFold, it was not extended to include dangle contributions due to the complexity of computation. This may come at the cost of prediction accuracy. In this work, we compare three different sparsified implementations for dangle contributions and provide pros and cons of each method. As well, we compare our algorithm to LinearFold, a linear time and space algorithm, where we find that in practice, SparseRNAFolD has lower memory consumption across all lengths of sequence and a faster time for lengths up to 1000 bases.

Conclusion

Our SparseRNAFolD algorithm is an MFE-based algorithm that guarantees optimality of result and employs the most general energy model, including dangle contributions. We provide a basis for applying dangles to sparsified recursion in a pseudoknot-free model that has the potential to be extended to pseudoknots.
Influence of diabetes on the risk of deep vein thrombosis of patients after total knee arthroplasty: a meta-analysis
Authors: An Jingzhi , Han Li , Ma Xiaojuan , Chang Yanyan , Zhang Cuixin
Published: March 2024

Background

Previous studies evaluating the influence of diabetes on the risk of deep vein thrombosis (DVT) after total knee arthroplasty (TKA) showed inconsistent results. The aim of the study was to systematically evaluate the association between diabetes and DVT after TKA in a meta-analysis.

Methods

An extensive search was conducted in PubMed, Embase, and Web of Science to identify relevant cohort studies. Random-effects models were employed to pool the results after taking account of the potential influence of heterogeneity.

Results

Thirteen cohort studies involving 546,156 patients receiving TKA were included, with 71,110 (13.0%) diabetic patients before surgery and 1479 (2.1%) patients diagnosed as DVT after surgery. Overall, diabetes was associated with an increased risk of DVT after TKA (risk ratio [RR]: 1.43, 95% confidence interval [CI]: 1.12–1.84, p = 0.004; I2 = 44%). Sensitivity analysis limited to studies with chemoprophylaxis (RR: 1.96, 95% CI: 1.50–2.54), and studies with multivariate analysis (RR: 1.54, 95% CI: 1.12–2.11) showed consistent results. Subgroup analysis showed that diabetes was associated with higher risk of postoperative DVT in Asian countries (RR: 1.93, 95% CI: 1.49–2.52, p < 0.001; I2 = 1%) but not in Western countries (RR: 1.07, 95% CI: 0.86–1.34, p = 0.52; I2 = 0%; p for subgroup difference < 0.001).

Conclusion

Diabetes may be a risk factor for DVT after TKA, even with the chemoprophylaxis of anticoagulants. The association between diabetes and DVT after TKA may be more remarkable in patients from Asian countries.
Management of rotator cuff injuries using allogenic platelet-rich plasma
Authors: Gupta Ashim , Migliorini Filippo , Maffulli Nicola
Published: March 2024

Rotator cuff injuries are a major cause of shoulder pain, affecting the quality of life and producing a significant burden on healthcare systems. Conservative management modalities are prioritized, resorting to surgery only when required. The field of regenerative medicine involving the use of biologics, such as platelet-rich plasma (PRP), has evolved and shown potential for managing rotator cuff injuries. Nonetheless, limitations including subpar outcomes have led clinicians to question the efficacy of autologous PRP. To circumvent this, the possibility of utilizing a standardized and well-characterized allogenic PRP for RCI has been explored. In this manuscript, we qualitatively present the evidence from in vitro, pre-clinical, clinical and ongoing studies investigating the applications of allogenic PRP in the context of rotator cuff disorders. Administration of allogenic PRP is safe and potentially efficacious to manage rotator cuff injuries, though more adequately powered randomized controlled trials with longer follow-ups are warranted to further establish the efficacy of allogenic PRP and justify its routine clinical use.
Platycodon D protects human nasal epithelial cells from pyroptosis through the Nrf2/HO-1/ROS signaling cascade in chronic rhinosinusitis
Authors: Wang Ruizhi , Wang Yongchun , Liu He , Zhu Jinxiang , Fang Caishan , Xu Weizhen , Lu Zesheng , Yan Yajie , He Weiping , Ruan Yan , Zhou Min
Published: March 2024

Background

Pyroptosis has been demonstrated being closely associated with the inflammatory progression in chronic rhinosinusitis (CRS). However, platycodon D (PLD) has emerged as a key anti-inflammatory mediator in the inflammatory progression of various respiratory diseases. This study aims at investigating whether PLD could reduce inflammatory progression of CRS by inhibiting pyroptosis.

Methods

Nasal mucosal tissues from patients with CRS and the control group (simple nasal septal deviation) were analyzed for morphological difference using hematoxylin & eosin staining and for the expression of pyroptosis-related makers by immunofluorescence (IF). Human nasal epithelial cells (HNEpCs) were cultured and co-stimulated with lipopolysaccharide (LPS)/adenosine triphosphate (ATP) to construct an in vitro cellular model simulating CRS. After pretreatment with PLD, EthD-I staining, TUNEL staining, transmission electron microscopy (TEM), and GSDMD-NT detection were performed to evaluate pyroptosis markers. The NLRP3 inflammasome was detected by IF and western blotting (WB). Reactive oxygen species (ROS) were detected by H2DCFDA staining, and mitochondrial membrane potential was evaluated by JC-1 staining. Mitochondrial morphology and structure were observed using TEM. The Nrf2/HO-1 antioxidant signaling pathway was detected using WB.

Results

The nasal mucosa structure of patients with CRS exhibited significant damage, with a marked increase in the expression of pyroptosis-related proteins compared with the control group. LPS/ATP co-stimulation resulted in an increased expression of IL-18 and IL-1β in HNEpCs, causing significant damage to nuclear and cell membranes, GSDMD-NT accumulation around the cell membrane, and intracellular NLRP3 inflammasome activation. Furthermore, it led to increased ROS expression, significantly decreased mitochondrial membrane potential, and damaged mitochondrial structure. However, pretreatment with PLD significantly reversed the aforementioned trends and activated the Nrf2/HO-1 antioxidant signaling pathway.

Conclusions

The results of this study confirm that NLRP3-mediated pyroptosis plays a crucial role in the pathological process of nasal mucosal impairment in patients with CRS. PLD inhibits NLRP3-mediated pyroptosis, preventing inflammatory damage in HNEpCs of patients with CRS by activating the Nrf2/HO-1 antioxidant signaling pathway, which in turn reduces ROS production and ameliorates mitochondrial damage.
LanGui tea, an herbal medicine formula, protects against binge alcohol-induced acute liver injury by activating AMPK-NLRP3 signaling
Authors: Gu Ming , Chen Yu-jun , Feng Ya-ru , Tang Zhi-peng
Published: March 2024

Background

LanGui tea, a traditional Chinese medicine formulation comprising of Gynostemma pentaphyllum (Thunb.) Makino, Cinnamomum cassia (L.) J. Presl, and Ampelopsis grossedentata (Hand-Mazz) W.T. Wang, has yet to have its potential contributions to alcoholic liver disease (ALD) fully elucidated. Consequently, the objective of this research is to investigate the protective properties of LanGui tea against binge alcohol-induced ALD and the mechanisms underlying its effects.

Methods

An experimental model of acute alcohol-induced liver disease was performed to assess the protective effects of extract of LanGui tea (ELG) at both 50 and 100 mg.kg−1 dosages on male C57BL/6 mice. Various parameters, including hepatic histological changes, inflammation, lipids content, as well as liver enzymes and interleukin 1β (IL-1β) in the serum were measured. The pharmacological mechanisms of ELG, specifically its effects on adenosine monophosphate-(AMP)-activated protein kinase (AMPK) and NLR family pyrin domain containing 3 (NLRP3) signaling, were investigated through Western blotting, qRT–PCR, ELISA, immunohistochemistry, immunofluorescence analyses, and by blocking the AMPK activity.

Results

ELG demonstrated a mitigating effect on fatty liver, inflammation, and hepatic dysfunction within the mouse model. This effect was achieved by activating AMPK signaling and inhibitingNLRP3 signaling in the liver, causing a reduction in IL-1β generation. In vitro studies further confirmed that ELG inhibited cell damage and IL-1β production in ethanol-induced hepatocytes by enhancing AMPK-NLRP3 signaling. Conversely, the pharmacological inhibition of AMPK activity nearly abrogated such alteration.

Conclusions

Thus, LanGui tea emerges as a promising herbal therapy for ALD management involving AMPK-NLRP3 signaling.
Nelfinavir inhibition of Kaposi’s sarcoma-associated herpesvirus protein expression and capsid assembly
Authors: Li Maggie , Smith Barbara J. , Lee Jaeyeun , Petr Jennifer , Anders Nicole M. , Wiseman Robyn , Rudek Michelle A. , Ambinder Richard F. , Desai Prashant J.
Published: March 2024

Background

Antiviral therapies that target herpesviruses are clinically important. Nelfinavir is a protease inhibitor that targets the human immunodeficiency virus (HIV) aspartyl protease. Previous studies demonstrated that this drug could also inhibit Kaposi’s sarcoma-associated herpesvirus (KSHV) production. Our laboratory demonstrated nelfinavir can effectively inhibit herpes simplex virus type 1 (HSV-1) replication. For HSV-1 we were able to determine that virus capsids were assembled and exited the nucleus but did not mature in the cytoplasm indicating the drug inhibited secondary envelopment of virions.

Methods

For KSHV, we recently derived a tractable cell culture system that allowed us to analyze the virus replication cycle in greater detail. We used this system to further define the stage at which nelfinavir inhibits KSHV replication.

Results

We discovered that nelfinavir inhibits KSHV extracellular virus production. This was seen when the drug was incubated with the cells for 3 days and when we pulsed the cells with the drug for 1–5 min. When KSHV infected cells exposed to the drug were examined using ultrastructural methods there was an absence of mature capsids in the nucleus indicating a defect in capsid assembly. Because nelfinavir influences the integrated stress response (ISR), we examined the expression of viral proteins in the presence of the drug. We observed that the expression of many were significantly changed in the presence of drug. The accumulation of the capsid triplex protein, ORF26, was markedly reduced. This is an essential protein required for herpesvirus capsid assembly.

Conclusions

Our studies confirm that nelfinavir inhibits KSHV virion production by disrupting virus assembly and maturation. This is likely because of the effect of nelfinavir on the ISR and thus protein synthesis and accumulation of the essential triplex capsid protein, ORF26. Of interest is that inhibition requires only a short exposure to drug. The source of infectious virus in saliva has not been defined in detail but may well be lymphocytes or other cells in the oral mucosa. Thus, it might be that a “swish and spit” exposure rather than systemic administration would prevent virion production.
A randomized double-blind trial of intranasal dexmedetomidine versus intranasal esketamine for procedural sedation and analgesia in young children
Authors: Nikula Anna , Lundeberg Stefan , Ryd Rinder Malin , Lääperi Mitja , Sandholm Katri , Castrén Maaret , Kurland Lisa
Published: March 2024

Background

Procedural sedation and analgesia are commonly used in the Emergency Departments. Despite this common need, there is still a lack of options for adequate and safe analgesia and sedation in children. The objective of this study was to evaluate whether intranasal dexmedetomidine could provide more effective analgesia and sedation during a procedure than intranasal esketamine.

Methods

This was a double-blind equally randomized (1:1) superiority trial of 30 children aged 1–3 years presenting to the Emergency Department with a laceration or a burn and requiring procedural sedation and analgesia. Patients were randomized to receive 2.0 mcg/kg intranasal dexmedetomidine or 1.0 mg/kg intranasal esketamine.

The primary outcome measure was highest pain (assessed using Face, Legs, Activity, Cry, Consolability scale (FLACC)) during the procedure. Secondary outcomes were sedation depth, parents’ satisfaction, and physician’s assessment.

Comparisons were done using Mann–Whitney U test (continuous variables) and Fisher’s test (categorical variables).

Results

Adequate analgesia and sedation were reached in 28/30 patients. The estimated sample size was not reached due to changes in treatment of minor injuries and logistical reasons. The median (IQR) of highest FLACC was 1 (0–3) with intranasal dexmedetomidine and 5 (2–6.75) with intranasal esketamine, (p-value 0.09). 85.7% of the parents with children treated with intranasal dexmedetomidine were “very satisfied” with the procedure and sedation compared to the 46.2% of those with intranasal esketamine, (p-value 0.1). No severe adverse events were reported during this trial.

Conclusions

This study was underpowered and did not show any difference between intranasal dexmedetomidine and intranasal esketamine for procedural sedation and analgesia in young children. However, the results support that intranasal dexmedetomidine could provide effective analgesia and sedation during procedures in young children aged 1–3 years with minor injuries.

Trial registration: Eudra-CT 2017-00057-40, April 20, 2017. https://eudract.ema.europa.eu/
In silico evaluation of a new compound incorporating 4(3H)-quinazolinone and sulfonamide as a potential inhibitor of a human carbonic anhydrase
Authors: Alkaoud Ahmed M. , Alakhras Abbas I. , Ibrahim Moez A. , Alghamdi S. K. , Hussein Rageh K.
Published: March 2024

The present study investigates the potential of a new compound containing sulfonamide and 4(3H)-quinazolinone to inhibit the hCA-IIX enzyme using in silico methods. Density functional theory-based calculations of electronic properties have been addressed through the analysis of frontier molecular orbitals, molecule electrostatic potential, and IR and UV–vis spectroscopy data. A molecular electrostatic potential analysis predicts that the target protein will be most inhibited by the sulfonamide groups since it has the highest potential spots for electrophile and nucleophile attack. The investigated compound exhibited good ADMET properties and satisfied the Lipinski rule of drug likeness. The hCA-IIX protein binding affinity with the proposed compound was determined by molecular docking analysis, which revealed a stable conformation with more negative binding energy (−12.19 kcal/mol) than the standard AZA drug (−7.36 kcal/mol). Moreover, a molecular dynamics study confirmed the docking results through trajectory analysis. The RMSD and RMSF both showed convergence and no significant fluctuations during the simulation time, which revealed a stable interaction within the active domain of the target protein. According to these findings, the proposed compound has a good pharmacological nature and could potentially be an efficient drug against hCAIX enzymes.
Toxoplasma sortilin interacts with secretory proteins and it is critical for parasite proliferation
Authors: Li Chenghuan , Jiang Ning , Liu Yize , Zhang Yiwei , Chen Ran , Feng Ying , Sang Xiaoyu , Chen Qijun
Published: March 2024

Background

The human sortilin protein is an important drug target and detection marker for cancer research. The sortilin from Toxoplasma gondii transports proteins associated with the apical organelles of the parasite. In this study, we aimed to determine the intracellular localization and structural domains of T. gondii sortilin, which may mediate protein transportation. Approaches to the functional inhibition of sortilin to establish novel treatments for T. gondii infections were explored.

Methods

A gene encoding the sortilin protein was identified in the T. gondii genome. Immunoprecipitation and mass spectrometry were performed to identify the protein species transported by T. gondii sortilin. The interaction of each structural domain of sortilin with the transported proteins was investigated using bio-layer interferometry. The binding regions of the transported proteins in sortilin were identified. The effect of the sortilin inhibitor AF38469 on the infectivity of T. gondii was investigated. The binding site of AF38469 on sortilin was determined.

Results

The subdomains Vps10, sortilin-C, and sortilin-M of the sortilin were identified as the binding regions for intracellular transportation of the target proteins. The sortilin inhibitor AF38469 bound to the Vps10 structural domain of T. gondii sortilin, which inhibited parasite invasion, replication, and intracellular growth in vitro and was therapeutic in mice infected with T. gondii.

Conclusion

The Vps10, sortilin-C, and sortilin-M subdomains of T. gondii sortilin were identified as functional regions for intracellular protein transport. The binding region for the sortilin inhibitor AF38469 was also identified as the Vps10 subdomain. This study establishes sortilin as a promising drug target against T. gondii and provides a valuable reference for the development of anti-T. gondii drug-target studies.

Graphical Abstract
Carbohydrate ingestion does not suppress increases in fatty acid-binding protein 4 concentrations post-acute aerobic exercise in healthy men: a randomized crossover study
Authors: Numao Shigeharu , Uchida Ryota , Kurosaki Takashi , Nakagaichi Masaki
Published: March 2024

Background

Fatty acid-binding protein 4 (FABP4) has been associated with cardiovascular disease and diabetes. Acute aerobic exercise increases circulating FABP4 concentrations, but the underlying mechanisms remain unclear. The purpose of this study was to investigate the effects of inhibition of lipolysis by carbohydrate ingestion on circulating FABP4 concentrations during and after acute aerobic exercise in healthy men.

Methods

Men aged between 20 and 40, with no exercise habits and no metabolic diseases, were recruited. In a randomized crossover design, the participants underwent a carbohydrate-ingestion exercise (CE) and a fasted exercise (FE) trial. The CE trial consisted of 40-min acute aerobic exercise with ingestion of carbohydrates and 60-min bed rest. The FE trial followed the same protocol as the CE trial but without carbohydrate ingestion. Venous blood samples were collected to measure hormones (adrenaline, noradrenaline, and insulin) metabolites (glycerol, free fatty acids, and glucose), and FABP4 concentrations. Ventilation and gas exchange were also collected to measure substrate oxidation.

Results

Thirteen healthy men participated in and completed both the CE and FE trials. The insulin concentration was more than 4 times higher in the CE trial than in the FE trial (p < 0.004, effect size [ES] > 2.00). Free fatty acid concentrations were more than 4 times lower in the CE trial than in the FE trial (p < 0.02, ES > 2.04). However, there was no significant difference in the changes in circulating FABP4 concentrations between the CE and FE trials (p = 0.108), which did not change during aerobic exercise and significantly increased post-aerobic exercise in both trials (p < 0.002, ES > 1.212). Changes in FABP4 concentrations following aerobic exercise were not significantly correlated with changes in glycerol or free fatty acid concentrations during aerobic exercise.

Conclusions

The results suggest that suppression of lipolysis and elevation of insulin are not strongly involved in increases in FABP4 secretion following acute aerobic exercise.
Sinonasal adenocarcinoma presented as a giant anterior cranial fossa mass: a case report and review of the literature
Authors: Ali Endris Hussen , Mengesha Mulualem Wendafrash
Published: March 2024

Background

Intestinal adenocarcinoma accounts for less than 0.1–4% of all malignancies in the region. It is common among woodworkers and leather workers. Sinonasal adenocarcinoma usually arises from the ethmoid sinus (40%) or nasal cavity (25%). Extension to nearby structures is common, but intracranial spread is very rare. These tumors are usually treated with surgery, with a reported 5-year survival rate of 59% to 80%.

Case presentation

This is a 60-year-old Black African male patient who presented with globalized headache, nasal obstruction with snoring during sleep, anosmia, change in mentation, sometimes agitation and left-side visual loss of one-year duration with worsening his above symptoms over the last one month. He couldn’t smell soap bilaterally; in his left eye he could see only hand movement at nearly 30 cm. On brain magnetic resonance imaging, there was a T1 hypo- and T2 hyper-intense anterior cranial fossa mass arising from the left ethmoid sinuses and sphenoid sinuses and compressing the left optic structures, and brain computed tomography demonstrated heterogeneous hypo- to isodense mass. Complete tumor excision achieved and discharged with significant improvement and linked to oncology unit for radiotherapy.

Conclusion

The management of these patients is multidisciplinary, involving neurosurgeons, otolaryngologists, oncologists, and maxillofacial surgeons. Surgical resection is the main treatment strategy, followed by radiotherapy, particularly intensity-modulated therapy. Chemotherapy is used in highly advanced, metastatic, and unresectable tumors.
Clinical outcomes of percutaneous microwave ablation for pulmonary oligometastases from hepatocellular carcinoma: a retrospective, multicenter study
Authors: Wang Gang , Wei Zhigang , Wang Feihang , Han Xiaoying , Jia Haipeng , Zhao Danyang , Li Chunhai , Liu Lingxiao , Yang Xia , Ye Xin
Published: March 2024

Background

Pulmonary oligometastases are common in hepatocellular carcinoma (HCC), however, the existing therapeutic options have several limitations. This study aimed to assess the safety and efficacy of microwave ablation (MWA) in the treatment of HCC-originating pulmonary oligometastases.

Methods

A total of 83 patients, comprising 73 males and 10 females with a median age of 57 years, who had pulmonary oligometastases from HCC, underwent MWA treatment at four different medical institutions. Inclusion criteria for patients involved having primary HCC under control and having less than three oligometastases with a maximum diameter of ≤ 5 cm in the unilateral lung or less than five oligometastases with a maximum diameter of ≤ 3 cm in the bilateral lung. A total of 147 tumors were treated with MWA over 116 sessions. The primary endpoints assessed included technical success, treatment efficacy, and local progression rate, while secondary endpoints encompassed complications, clinical outcomes, overall survival (OS), local progression-free survival (LPFS), and prognostic factors.

Results

The technical success rate for MWA was 100% (116/116 sessions), and the treatment efficacy rate was 82.3% (121/147 tumors). Six months after MWA, the local progression rate was 23.1% (18/147 tumors). Complications were observed in 10.3% (major) and 47.4% (minor) of the 116 sessions, with no cases of ablation-related deaths. The median follow-up period was 21.6 months (range: 5.7–87.8 months). Median OS was 22.0 months, and the 1-, 2-, and 3-year OS rates were 82.6%, 44.5%, and 25.2%, respectively. Median LPFS was 8.5 months. Multivariate Cox regression analysis identified α-fetoprotein (AFP) levels during initial diagnosis and the number of oligometastases as potential independent prognostic factors for OS (p = 0.017 and 0.045, respectively).

Conclusion

Percutaneous MWA is a safe and effective treatment modality for pulmonary oligometastases originating from HCC.
Effects of an intervention to improve sexual and reproductive health on level and predictors of awareness and knowledge of condoms and dual protection amongst adolescents in Nigeria
Authors: Agu Chibuike , Akamike Ifeyinwa Chizoba , Agu Ifunanya , Agu Ozioma , Eigbiremolen Godstime O. , Mbachu Chinyere Ojiugo , Onwujekwe Obinna
Published: March 2024

Background

Adolescents need both information about sexual behaviours and potential risks in order to make the right choices. This study compared adolescents’ level of awareness and predictors of knowledge of condoms and dual protection where a multi-component sexual and reproductive health (SRH) intervention was implemented and in communities where the intervention was not implemented, so as to understand the effect of the intervention on awareness and knowledge and also identify predictors of knowledge of contraception methods.

Methods

The study was an intervention study that was undertaken in six local government areas (three rural and three urban LGAs) in Ebonyi state, southeast Nigeria. Data were collected from 855 adolescent boys and girls, using a pre-tested interviewer administered questionnaire. Systematic random sampling technique was used to select eligible households from which adolescents were interviewed Analysis of data was carried out using bivariate and multivariate linear regression analyses. The level of statistical significance was determined by a p value of < 0.05.

Results

The level of awareness of condoms and dual protection was similar in the intervention and non-intervention communities. However, the predictors of knowledge about condoms and dual protection were different between the intervention and non-intervention groups. The multivariate linear regression showed that the higher the level of education, the higher the level of awareness of contraception methods among adolescents (p < 0.05). Likewise, increasing age by one year and working for pay increased the awareness of condoms and dual protection(p < 0.05).

Conclusion

There was no difference in the level of awareness of pregnancy prevention methods, knowledge of condoms and dual protection in both arms of the study. Higher level of education, increasing age, and working for pay are factors associated with awareness of condom and dual protection. These factors should be prioritized for effective Adolescent sexual and reproductive health (ASRH) programming.
Successful intraoperative management of laparoscopic hysterectomy in a patient with Eisenmenger syndrome: a case report
Authors: Maeda Yuki , Kakuta Nami , Kasai Asuka , Yonezawa Hiroki , Kawanishi Ryosuke , Tanaka Katsuya
Published: March 2024

Background

Patients with Eisenmenger syndrome (ES) requiring noncardiac surgery are at a significantly high risk of perioperative morbidity and mortality. However, perioperative management of patients with ES requiring laparoscopic surgery remains unclear.

Case presentation

We describe the case of a patient with ES who underwent laparoscopic hysterectomy under general anesthesia with a peripheral nerve block. The objectives of the perioperative management included the following: (1) maintaining systemic vascular resistance and cardiac output through euvolemia, facilitated by the infusion of noradrenaline, and (2) preventing a reduction in oxygen-carrying capacity and factors that elevate pulmonary vascular resistance, such as pain, hypoxia, and decreased body temperature. Although laparoscopic procedures involved an increased risk in patients with ES, they are less invasive than open surgeries.

Conclusion

This report describes the successful anesthetic management of a patient with ES, ensuring a balance between systemic and pulmonary vascular resistance.
Acceleration of new medicines–CMC lessons learned from emergency use authorizations
Authors: Bernstein James , Huynh-Ba Kim , Lynch Patrick , Oliver Thomas , Oliyai Reza , Roberts Scott W. , Schirmer Andrea , Schwinke David , Tang Kin , Ursin Jessica
Published: March 2024

The American Association of Pharmaceutical Scientists (AAPS) Chemistry, Manufacturing, and Control (CMC) Community hosted a virtual panel discussion on July 15, 2022, to provide a forum to discuss industry and regulator CMC challenges associated with emergency use authorizations.
SPAGHETTI: a synthetic data generator for post-Covid electric vehicle usage
Authors: Berkes Anaïs , Keshav Srinivasan
Published: March 2024

The Covid-19 pandemic has resulted in a permanent shift in individuals’ daily routines and driving behaviours, leading to an increase in remote work. There has also been an independent and parallel rise in the adoption of solar photovoltaic (PV) panels, electrical storage systems, and electric vehicles (EVs). With remote work, EVs are spending longer periods at home. This offers a chance to reduce EV charging demands on the grid by directly charging EV batteries with solar energy during daylight. Additionally, if bidirectional charging is supported, EVs can serve as a backup energy source day and night. Such an approach fundamentally alters domestic load profiles and boosts the profitability of residential power systems. However, the lack of publicly available post-Covid EV usage datasets has made it difficult to study the impact of recent commuting patterns shifts on EV charging. This paper, therefore, presents SPAGHETTI (Synthetic Patterns & Activity Generator for Home-Energy & Tomorrow’s Transportation Investigation), a tool that can be used for the synthetic generation of realistic EV drive cycles. It takes as input EV user commuting patterns, allowing for personalised modeling of EV usage. It is based on a thorough literature survey on post-Covid work-from-home (WFH) patterns. SPAGHETTI can be used by the scientific community to conduct further research on the large-scale adoption of EVs and their integration into domestic microgrids. As an example of its utility, we study the dependence of EV charge state and EV charging distributions on the degree of working from home and find that there is, indeed, a significant impact of WFH patterns on these critical parameters.
Evaluation of high temporal resolution magnetic resonance imaging of the liver with gadoxetate disodium in combination with compressed sensing and parallel imaging under single breath-holding using a 1.5-T magnetic resonance system
Authors: Fukamatsu Fumiaki , Yamada Akira , Sakai Ayumi , Shimizu Marika , Ichinohe Fumihito , Takahashi Masaaki , Hayashihara Hayato , Kitou Yoshihiro , Fujinaga Yasunari
Published: March 2024

Background

This study aimed to determine the optimal scan time for high temporal resolution magnetic resonance (MR) imaging of the liver with gadoxetate disodium injection in combination with compressed sensing (CS) and parallel imaging (PI) techniques under single breath-holding using a 1.5-T MR system.

Methods

Sixty-two participants underwent multiple arterial phases of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) of the liver with gadoxetate disodium using fat-suppressed GRE T1-weighted imaging—liver acquisition with volume acceleration (LAVA)—in combination with CS and PI using a 1.5-T MR system. Forty-six and 22 participants underwent 6-s and 10-s scans, respectively. Pre-contrast, multiple arterial, portal venous, and hepatobiliary phase images were acquired. Two radiologists evaluated the visual scores for the outline of the liver, inferior right hepatic vein (IRHV), right portal vein, right hepatic artery, appropriateness of the arterial phase, and overall image quality using a 4- or 5-point scale.

Results

The overall image quality and the image quality of the outline of the liver in the pre-contrast and arterial phases and IRHV in the pre-contrast phase were significantly better (P < 0.05) in the 10-s scan group than those in the 6-s scan group. No significant difference was observed between the two groups in terms of the appropriateness of the arterial phase (obtaining the optimal arterial phase) (P = 0.731).

Conclusions

A 10-s scan protocol is recommended for high temporal resolution DCE-MRI of the liver with gadoxetate disodium injection in combination with CS and PI under single breath-holding using a 1.5-T MR system.
Mine reclamation practices and effects of stakeholder perception — a case study of Saoner mines, Maharashtra, India
Authors: Basu Debasmita , Mishra Smriti
Published: March 2024

The Saoner mine reclamation study conducted in Maharashtra, India, meticulously investigates the practicality and efficacy of ecological restoration initiatives post-mining operations. Employing multifaceted research approach, including field observations, interviews, and questionnaires, the study captures a diverse array of perspectives from stakeholders representing local communities, mining companies, regulatory bodies, and environmental organizations. Within this complexity, the research uncovers spectrum of viewpoints. Encouragingly, positive outcomes emerge from specific reclamation practices like revegetation and soil stabilization. However, substantial challenges linger in vital areas such as water management, soil quality restoration, and post-reclamation monitoring, demanding targeted interventions. Stakeholders’ diverse concerns reflect varying priorities. Local communities express apprehension about the adequacy of reclamation efforts and potential health implications, underscoring immediate impact on their lives. Mining companies prioritize regulatory compliance and economic contributions, emphasizing their immediate obligations. Simultaneously, environmental organizations advocate for stringent monitoring and the adoption of more robust practices, reflecting long-term ecological perspective. The study suggests a holistic approach to mining, beyond regulatory compliance, involving integrated planning, ongoing monitoring, and stakeholder engagement. This approach can reduce the industry’s environmental footprint, promote sustainable development, and foster harmony between mining activities and local communities, making it a crucial foundation for Saoner and other Indian mining regions.