bluuebunny/crossref_metadata_2025 huggingface dataset:
Resurgence of influenza and respiratory syncytial virus in Egypt following two years of decline during the COVID-19 pandemic: outpatient clinic survey of infants and children, October 2022
Authors: Kandeel Amr , Fahim Manal , Deghedy Ola , Roshdy Wael H. , Khalifa Mohamed K. , Shesheny Rabeh El , Kandeil Ahmed , Naguib Amel , Afifi Salma , Mohsen Amira , Abdelghaffar Khaled
Published: June 2023

Introduction

Two years after unprecedented low rates of circulation of most common respiratory viruses (SARS-CoV-2), the Egyptian ARI surveillance system detected an increase in acute respiratory infections (ARIs) with a reduced circulation of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), especially among school children. A national survey was conducted to estimate the burden and identify the viral causes of ARIs among children < 16 years of age.

Methods

A one-day survey was carried out in 98 governmental outpatient clinics distributed all over Egypt 26 governorates. The four largest referral hospitals in each governorate where most influenza-like illness (ILI) patients seek care were selected. Using the WHO case definition, the first five patients < 16 years of age with ILI symptoms visiting the selected outpatient clinics on the survey day were enrolled. Basic demographic and clinical data of patients were collected using a linelist. Patients were swabbed and tested for SARS-CoV-2, influenza, and Respiratory Syncytial virus (RSV) by RT-PCR at the Central Laboratory in Cairo.

Results

Overall, 530 patients enrolled, their mean age was 5.8 ± 4.2, 57.1% were males, and 70.2% reside in rural or semi-rural areas. Of all patients, 134 (25.3%) had influenza, 111 (20.9%) RSV, and 14 (2.8%) coinfections. Influenza-positive children were older compared to RSV, (7.2 ± 4.1, 4.3 ± 4.1, p < 0.001), with more than half of them (53.0%) being school students. Dyspnea was reported in RSV more than in influenza (62.2% vs. 49.3%, p < 0.05). Among RSV patients, children < 2 years had a higher rate of dyspnea than others (86.7% vs. 53.1%, < 0.001).

Conclusions

A resurgence of influenza and RSV was detected in Egypt in the 2022–2023 winter season. Influenza caused a higher rate of infection than RSV, while RSV caused more severe symptoms than influenza. Monitoring a broader range of respiratory pathogens is recommended to estimate the ARI burden and risky groups for severe disease in Egypt.
Human and environmental impacts of nanoparticles: a scoping review of the current literature
Authors: Kumah Elizabeth Adjoa , Fopa Raoul Djou , Harati Saeed , Boadu Paul , Zohoori Fatemeh Vida , Pak Tannaz
Published: June 2023

Use of nanoparticles have established benefits in a wide range of applications, however, the effects of exposure to nanoparticles on health and the environmental risks associated with the production and use of nanoparticles are less well-established. The present study addresses this gap in knowledge by examining, through a scoping review of the current literature, the effects of nanoparticles on human health and the environment. We searched relevant databases including Medline, Web of Science, ScienceDirect, Scopus, CINAHL, Embase, and SAGE journals, as well as Google, Google Scholar, and grey literature from June 2021 to July 2021. After removing duplicate articles, the title and abstracts of 1495 articles were first screened followed by the full-texts of 249 studies, and this resulted in the inclusion of 117 studies in the presented review.

In this contribution we conclude that while nanoparticles offer distinct benefits in a range of applications, they pose significant threats to humans and the environment. Using several biological models and biomarkers, the included studies revealed the toxic effects of nanoparticles (mainly zinc oxide, silicon dioxide, titanium dioxide, silver, and carbon nanotubes) to include cell death, production of oxidative stress, DNA damage, apoptosis, and induction of inflammatory responses. Most of the included studies (65.81%) investigated inorganic-based nanoparticles. In terms of biomarkers, most studies (76.9%) used immortalised cell lines, whiles 18.8% used primary cells as the biomarker for assessing human health effect of nanoparticles. Biomarkers that were used for assessing environmental impact of nanoparticles included soil samples and soybean seeds, zebrafish larvae, fish, and Daphnia magna neonates.

From the studies included in this work the United States recorded the highest number of publications (n = 30, 25.64%), followed by China, India, and Saudi Arabia recording the same number of publications (n = 8 each), with 95.75% of the studies published from the year 2009. The majority of the included studies (93.16%) assessed impact of nanoparticles on human health, and 95.7% used experimental study design. This shows a clear gap exists in examining the impact of nanoparticles on the environment.
Hepatitis B vaccination coverage and associated factors among medical students: a cross-sectional study in Bosaso, Somalia, 2021
Authors: Ali Abdifitah Said , Hussein Nur Ahmed , Elmi Elmi Omar Haji , Ismail Abdiwahid Mohamed , Abdi Mohamed Mohamud
Published: June 2023

Background

Hepatitis B virus (HBV) is a leading cause of liver cancer and remains a global public health concern. The risk of acquiring HBV is higher in HCWs than in non-HCWs. Medical students are considered a high-risk group because similar to HCWs, they tend to be exposed to body fluids and blood during training in clinical settings. New infections can be effectively prevented and eliminated with an increased coverage of HBV vaccination. The purpose of this study was to evaluate HBV immunization coverage and associated factors among medical students attending universities in Bosaso, Somalia.

Methodology

An institutional-based cross-sectional study was conducted. A stratified sampling method was employed to draw a sample from four universities in Bosaso. From each university, participants were selected using a simple random sampling technique. Self-administered questionnaires were distributed among 247 medical students. The data were analysed with SPSS version 21, and the findings are presented in tables and proportions. The chi-square test was used to measure statistical associations.

Results

Although 73.7% of the respondents had an above-average knowledge level of HBV and 95.9% knew that HBV can be prevented by vaccination, only 2.8% were fully immunized, while 5.3% were partially immunized. The students reported six main reasons for not being vaccinated: unavailability of the vaccine (32.8%), high vaccine cost (26.7%), fear of vaccine side effects (12.6%), lack of trust in vaccine quality (8.5%), lack of awareness about where to get vaccinated (5.7%), and lack of time (2.8%). Occupation and the availability of HBV vaccination in the workplace were associated with HBV vaccine uptake (p values of 0.005 and 0.047, respectively).

Conclusion

HBV immunization coverage among medical students was extremely low (2.8%), indicating the urgent need for increased vaccination coverage in this population. This should start with evidence-based advocacy for the development of a clear national HBV elimination policy, followed by implementing effective, large-scale immunization strategies and interventions. Future studies should expand the sample size to include multiple cities for increased representativeness and conduct HBV titre tests among participants.
Comparison of accuracy for hip-knee-ankle (HKA) angle by X-ray and knee motion analysis system and the relationships between HKA and gait posture
Authors: Zhang Hui , Chen Yanan , Jiang Huiquan , Yan Wenqing , Ouyang Yuanming , Wang Wei , Liu Yaru , Zhou Ying , Gu Shiyi , Wan Hong , He Axiang , Mao Yanjie , Liu Wanjun
Published: June 2023

Background

The lower limb mechanical axis was used to assess the severity of knee osteoarthritis (KOA) with varus/valgus deformity and the accuracy of targeted lower limb alignment correction after operation by conventional X-rays. There are lots of parameters to assess the gait in elder patients such as velocity, stride length, step width and swing/stance ratio by knee joint movement analysis system. However, the correlation between the lower limb mechanical axis and gait parameters is not clear. This study is aimed at obtaining the accuracy of the lower limb mechanical axis by the knee joint movement analysis system and the correlation between the lower limb mechanical axis and gait parameters.

Methods

We analysed 3D knee kinematics during ground gait of 99 patients with KOA and 80 patients 6 months after the operations with the vivo infrared navigation 3D portable knee joint movement analysis system (Opti-Knee®, Innomotion Inc, Shanghai, China). The HKA (Hip-Knee-Ankle) value was calculated and compared to X-ray findings.

Results

HKA absolute variation after the operation was 0.83 ± 3.76°, which is lower than that before the operation (5.41 ± 6.20°, p = 0.001) and also lower than the entire cohort (3.36 ± 5.72). Throughout the cohort, a significant correlation with low coefficients (r = -0.19, p = 0.01) between HKA value and anterior-posterior displacement was found. In comparing the HKA values measured on the full-length alignment radiographs and 3D knee joint movement analysis system (Opti-Knee), there was a significant correlation with moderate to high coefficients (r = 0.784 to 0.976). The linear correlation analysis showed that there was a significant correlation between the values of HKA measured by X-ray and movement analysis system (R2 = 0.90, p < 0.01).

Conclusions

Data with equivalent results as HKA, the 6DOF of the knee and ground gait data could be provided by infrared navigation based 3D portable knee joint movement analysis system comparing with the conventional X-rays. There is no significant effect of HKA on the kinematics of the partial knee joint.
Instrument–assisted soft tissue mobilization versus myofascial release therapy in treatment of chronic neck pain: a randomized clinical trial
Authors: Shewail Fatma , Abdelmajeed Salwa , Farouk Mohamed , Abdelmegeed Mohamed
Published: June 2023

Objective

The purpose of this study was to investigate the effect of instrument-assisted soft tissue mobilization (IASTM) versus myofascial release therapy (MRT) on college students with chronic mechanical neck pain (CMNP).

Methods

Thirty-three college students with a mean age of 21.33 ± 0.98 involved in distance learning due to the Corona Virus 2019 (COVID-19) restriction were randomized to receive either IASTM on the upper trapezius and levator scapulae muscles or MRT. Researchers measured their pain with a visual analog scale (VAS), function with neck disability index (NDI), and pain pressure threshold (PPT) with a pressure algometer. The subjects received eight therapy sessions over four weeks and outcome measures were assessed pre and post-intervention. The study was registered as a clinical trial on clinicaltrials.gov (registration number: NCT05213871).

Result

Unpaired t-test showed no statistical significance between the two groups post-intervention regarding improvement in pain, function, and PPT (p > 0.05).

Conclusion

This study showed insignificant differences between groups. However, we did not use a control group, indicating that the improvement in outcomes may not have been caused by the intervention.

Study design

Quasi-experimental two groups pre-posttest clinical trial.

Level of evidence

Therapy, level 2b.
Topical use of tranexamic acid can reduce opioid consumption compared with intravenous use for patients undergoing primary total hip arthroplasty: a prospective randomized controlled trial
Authors: Shen Lei , Jiang Zhenhuan , Wang Qiang , Xu Wei
Published: June 2023

Background

The problem of opioid addiction after total hip arthroplasty (THA) has been widely concerned. Tranexamic acid (TXA) has been shown to be effective in reducing blood loss for patients undergoing THA, but few studies focus on its alleviation of postoperative local pain symptoms. The purpose of this study was to investigate whether topical TXA could reduce early postoperative hip pain for primary THA patients, thereby reducing the use of opioids, and whether local pain is related to inflammatory response.

Methods

In this prospective randomized controlled study, we randomly divided 161 patients into a topical group (n = 79) and an intravenous group (n = 82). Hip pain was assessed using the visual analogue scale (VAS) score within three days after surgery and tramadol was used for pain relief when necessary. Inflammatory markers such as high-sensitivity C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), interleukin-6 (IL-6), total blood loss and hemoglobin drop were assessed by hematologic tests. The primary outcomes included the VAS score and dose of tramadol from the first to the third day after surgery. The secondary outcomes included the inflammatory markers level, total blood loss and complications.

Results

The pain score and inflammation markers level on the first day in the topical TXA group were significantly lower than those in the intravenous TXA group (P < 0.05). The correlation analysis showed that the VAS score on the first day after surgery was positively correlated with the inflammation markers level (P < 0.05). The tramadol dose for topical group was lower than intravenous group on the first and second day after surgery. There were no differences in total blood loss between the two groups (640.60 ± 188.12 ml vs. 634.20 ± 187.85 ml, P = 0.06). There was no difference in the incidence of complications.

Conclusion

Topical use of TXA could relieve the local pain symptoms and reduce opioid consumption compared with intravenous use for patients undergoing primary THA by reduce the early postoperative inflammatory response.

Trial registration

The trial was registered at the China Clinical Trial Registry (ChiCTR2100052396) on 10/24/2021.
Adjunctive hemoperfusion with Resin Hemoadsorption (HA) 330 cartridges improves outcomes in patients sustaining multiple Blunt Trauma: a prospective, quasi-experimental study
Authors: Borazjani Roham , Mahmudi-Azer Salahaddin , Taghrir Mohammad Hossein , Homaeifar Reza , Dabiri Gholamreza , Paydar Shahram , Fard Hossein Abdolrahimzadeh
Published: June 2023

Background

Multi-organ dysfunction syndrome and multi-organ failure are the leading causes of late death in patients sustaining severe blunt trauma. So far, there is no established protocol to mitigate these sequelae. This study assessed the effect of hemoperfusion using resin-hemoadsorption 330 (HA330) cartridges on mortality and complications such as acute respiratory distress syndrome (ARDS) and systemic inflammatory response syndrome (SIRS) among such patients.

Methods

This quasi-experimental study recruited patients ≥ 15 years of age with blunt trauma, injury severity score (ISS) ≥ 15, or initial clinical presentation consistent with SIRS. They were divided into two groups: the Control group received only conventional acute care, while the case group received adjunctive hemoperfusion. P-values less than 0.05 were statistically significant.

Results

Twenty-five patients were included (Control and Case groups: 13 and 12 patients). The presenting vital signs, demographic and injury-related features (except for thoracic injury severity) were similar (p > 0.05). The Case group experienced significantly more severe thoracic injuries than the Control group (Thoracic AIS, median [IQR]: 3 [2–4] vs. 2 [0–2], p = 0.01). Eleven and twelve patients in the Case group had ARDS and SIRS before the hemoperfusion, respectively, and these complications were decreased considerably after hemoperfusion. Meanwhile, the frequency of ARDS and SIRS did not decrease in the Control group. Hemoperfusion significantly reduced the mortality rate in the Case group compared to the Control group (three vs. nine patients, p = 0.027).

Conclusions

Adjunctive Hemoperfusion using an HA330 cartridge decreases morbidity and improves outcomes in patients suffering from severe blunt trauma.
Hip effusion/synovitis influences results after multiple drilling core decompression for bone marrow edema syndrome of hip
Authors: Xiong Hua-zhang , Peng Yan-li , Deng Yu-hong , Jin Ying , Tu Ming-hong , Wu Shu-hong
Published: June 2023

Background

At present, it is not known whether hip effusion/synovitis affects the therapeutic effect of multiple drilling core decompression (MDCD) in patients with bone marrow edema syndrome of hip (BMESH). The aims were to assess hip effusion/synovitis and its relationship with results of MDCD in patients with BMESH.

Methods

The data of undergoing arthroscopic-assisted MDCD for treatment of BMESH with hip effusion/synovitis by one surgeon were retrospectively reviewed from the associated medical records at the Affiliated Hospital of Zunyi Medical University (2016–2019). Seven patients (9 hips) participated in this study. Patients were followed up at 1, 2, 3, 6, 12 and 24 months. Data included demographics and clinical outcomes. The pre- and postoperative pain and functional outcomes were measured with the visual analogue scale (VAS), Harris Hip Score (HHS), Hip Outcome Score Activities of Daily Living subscale (HOS-ADL), International Hip Outcome Tool-12 (iHOT-12) and range of motion (ROM).

Results

Seven patients (9 hips) were followed up. Disappearance of hip pain immediately obtained at rest after surgery. All of 7 patients returned to their former activity level at postoperative 3 months, bone marrow edema had disappeared on Magnetic Resonance Imaging (MRI). The VAS, HHS, HOS-ADL, iHOT-12, and ROM at postoperative 1 month had a significant difference (P < 0.05) compared with preoperative. It was also statistically significant (P < 0.05) when compared with other time points. At the final follow-up, all patients had no limited ROM, which was symmetrical with the contralateral of hip joint. Hip effusion/synovitis were observed in 9 hips. Labral tears, cartilage fissure, and loose bodies were observed in 1 hip, respectively. Kirschner wire tracks bleeding occurred in 1 hip. No other complications occurred.

Conclusions

Hip effusion/synovitis could affect the clinical outcomes after MDCD in patients with BMESH. Arthroscopic procedure of hip effusion/synovitis can shorten postoperative pain relief time, disappearance time of bone marrow edema on MRI. It can simultaneously diagnose and treat other concomitant intraarticular pathologies, and be a safe operation with fewer complications.
Prostate cancer risk prediction based on clinical factors and prostate-specific antigen
Authors: Hwang Taewon , Oh Hyungseok , Lee Jung Ah , Kim Eo Jin
Published: June 2023

Introduction

The incidence rate of prostate cancer (PCa) has continued to rise in Korea. This study aimed to construct and evaluate a 5-year PCa risk prediction model using a cohort with PSA < 10 ng/mL by incorporating PSA levels and individual factors.

Methods

The PCa risk prediction model including PSA levels and individual risk factors was constructed using a cohort of 69,319 participants from the Kangbuk Samsung Health Study. 201 registered PCa incidences were observed. A Cox proportional hazards regression model was used to generate the 5-year risk of PCa. The performance of the model was assessed using standards of discrimination and calibration.

Results

The risk prediction model included age, smoking status, alcohol consumption, family history of PCa, past medical history of dyslipidemia, cholesterol levels, and PSA level. Especially, an elevated PSA level was a significant risk factor of PCa (hazard ratio [HR]: 1.77, 95% confidence interval [CI]: [1.67–1.88]). This model performed well with sufficient discrimination ability and satisfactory calibration (C-statistic: 0.911, 0.874; Nam-D’Agostino test statistic:19.76, 4.21 in the development and validation cohort, respectively).

Conclusions

Our risk prediction model was effective in predicting PCa in a population according to PSA levels. When PSA levels are inconclusive, an assessment of both PSA and specific individual risk factors (e.g., age, total cholesterol, and family history of PCa) could provide further information in predicting PCa.
The effect of different ferrule heights and crown-to-root ratios on fracture resistance of endodontically-treated mandibular premolars restored with fiber post or cast metal post system: an in vitro study
Authors: Meng Qingfei , Chen Yuxin , Ni Ke , Li Yingmei , Li Xinran , Meng Jian , Chen Lijuan , Mei May Lei
Published: June 2023

Background

This study aimed to investigate the effects of different ferrule heights and crown-to-root ratios on the fracture resistance of endodontically-treated premolars restored with fiber post or cast metal post system.

Methods

Eighty extracted human mandibular first premolars with single root canal were treated endodontically and cut from 2.0 mm above the buccal cemento-enamel junction, to create horizontal residual roots. The roots were randomly divided into two groups. The roots in group FP were restored with a fiber post-and-core system, while the roots in group MP were restored with a cast metal post-and-core system. Each group was divided into five subgroups with different ferrule heights (0: no ferrule; 1: 1.0 mm ferrule; 2: 2.0 mm ferrule; 3: 3.0 mm ferrule; 4: 4.0 mm ferrule). All specimens were subsequently restored with metal crowns and embedded in acrylic resin blocks. The crown-to-root ratios of the specimens were controlled at approximately 0.6, 0.8, 0.9, 1.1, and 1.3 of the five subgroups, respectively. Fracture strengths and fracture patterns of the specimens were tested and recorded by a universal mechanical machine.

Results

Mean fracture strengths (mean ± standard deviation (kN)) of FP/0 to FP/4 and MP/0 to MP/4 were: 0.54 ± 0.09, 1.03 ± 0.11, 1.06 ± 0.17, 0.85 ± 0.11; 0.57 ± 0.10, 0.55 ± 0.09, 0.88 ± 0.13, 1.08 ± 0.17, 1.05 ± 0.18 and 0.49 ± 0.09, respectively. Two-way ANOVA revealed significant effects of different ferrule heights and crown-to-root ratios on the fracture resistance (P < 0.001), but no difference in fracture resistance between two post-and-core systems (P = 0.973). The highest fracture strengths of the specimen were found with the ferrule length of 1.92 mm in group FP and 2.07 mm in group MP, the crown-to-root ratio of which in 0.90 and 0.92 respectively., there is a significant difference in fracture patterns among the groups(P < 0.05).

Conclusions

When a certain height of ferrule is prepared and a cast metal or fiber post-and-core system is restored for the residual root, the clinical crown-to-root ratio of the tooth after restoration should be kept within 0.90 to 0.92, so as to improve the fracture resistance of endodontically-treated mandibular first premolars.
Transcriptome sequencing and network pharmacology-based approach to reveal the effect and mechanism of Ji Chuan Jian against Parkinson’s disease
Authors: Wu Yao , Bai Yu , Lu Yan , Zhang Zhennian , Zhao Yang , Huang Sirui , Tang Lili , Liang Yan , Hu Yue , Xu Chengcheng
Published: June 2023

Background

Ji Chuan Jian(JCJ), a classic Traditional Chinese Medicine (TCM) formula, has been widely applied in treating Parkinson’s disease (PD) in China, However, the interaction of bioactive compounds from JCJ with the targets involved in PD remains elusive.

Methods

Based on the transcriptome sequencing and network pharmacology approaches, the chemical compounds of JCJ and gene targets for treating PD were identified. Then, the Protein-protein interaction (PPI) and “Compound-Disease-Target” (C-D-T) network were constructed by using of Cytoscape. Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were applied to these target proteins. Finally, AutoDock Vina was used for applying molecular docking.

Results

In the present study, a total number of 2669 differentially expressed genes (DEGs) were identified between PD and healthy controls using whole transcriptome RNA sequencing. Then, 260 targets of 38 bioactive compounds in JCJ were identified. Of these targets, 47 were considered PD-related targets. Based on the PPI degree, the top 10 targets were identified. In C-D-T network analysis, the most important anti-PD bioactive compounds in JCJ were determined. Molecular docking revealed that potential PD-related targets, matrix metalloproteinases-9 (MMP9) were more stably bound with naringenin, quercetin, baicalein, kaempferol and wogonin.

Conclusion

Our study preliminarily investigated the bioactive compounds, key targets, and potential molecular mechanism of JCJ against PD. It also provided a promising approach for identifying the bioactive compounds in TCM as well as a scientific basis for further elucidating the mechanism of TCM formulae in treating diseases.
Chemical composition, cholinesterase, and α-glucosidase inhibitory activity of the essential oils of some Iranian native Salvia species
Authors: Gharehbagh Houra Jazayeri , Ebrahimi Masoud , Dabaghian Farid , Mojtabavi Somayeh , Hariri Roshanak , Saeedi Mina , Faramarzi Mohammad Ali , Khanavi Mahnaz
Published: June 2023

Background

The plants from Salvia genus contain widely distributed species which have been used in folk medicine as well as pharmaceutical and food industries.

Methods

The chemical composition of 12 native Iranian Salvia species (14 plants) was identified using gas chromatography-mass spectrometry (GC–MS). Also, the inhibitory activity of all essential oils (EOs) was evaluated toward α-glucosidase and two types of cholinesterase (ChE) using spectrophotometric methods. The in vitro α-glucosidase inhibition assay was performed by the determination of p-nitrophenol (pNP) obtained from the enzymatic dissociation of p-nitrophenol-α-D-glucopyranoside (pNPG) as the substrate. In vitro ChE inhibitory assay was conducted based on the modified Ellman’s procedure using the measurement of 5-thio-2-nitrobenzoic acid produced from the hydrolysis of thiocholine derivatives as the substrate, in the presence of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE).

Results

Totally, 139 compounds were detected and caryophyllene oxide and trans-β-caryophyllene were the most abundant compounds in all EOs. The yield of EOs extracted from the plants were also calculated in the range of 0.06 to 0.96% w/w. Herein, α-glucosidase inhibitory activity of 8 EOs was reported for the first time and among all, S. spinosa L. was found to be the most potent inhibitor (90.5 inhibition at 500 μg/mL). Also, the ChE inhibitory activity of 8 species was reported for the first time and our results showed that the BChE inhibitory effect of all EOs was more potent than that of AChE. The ChE inhibition assay indicated that S. mirzayanii Rech.f. & Esfand. collected from Shiraz was the most potent inhibitor (72.68% and 40.6% at the concentration of 500 μg/mL, toward AChE and BChE, respectively).

Conclusions

It seems that native Salvia species of Iran could be considered in the development of anti-diabetic and anti-Alzheimer's disease supplements.
Challenges in diagnosis and biomarker testing for RET-altered lung and thyroid cancer care: an international mixed-method study
Authors: Lazure Patrice , Sireci Anthony , Subbiah Vivek , Murray Suzanne , Grohé Christian , Sherman Steven I. , Kelly Elizabeth , Bubach Patrick , Péloquin Sophie
Published: June 2023

Background

The introduction of new targeted therapies for RET-altered lung and thyroid cancers (LC/TC) has impacted pathologists’ practice by making genomic testing more relevant. Variations in health systems and treatment access result in distinct clinical challenges and barriers. This study aimed to assess practice gaps and challenges experienced by pathologists involved in the diagnosis of RET-altered LC/TC, including biomarker testing, to inform educational solutions.

Methods

Pathologists in Germany, Japan, the UK, and US participated in this ethics-approved mixed-methods study, which included interviews and surveys (data collected January-March 2020). Qualitative data was thematically analysed, quantitative data was analysed with chi-square and Kruskal–Wallis H-tests, and both were triangulated.

Results

A total of 107 pathologists took part in this study. Knowledge gaps were reported regarding genomic testing for LC/TC in Japan (79/60%), the UK (73/66%), and the US (53/30%). Skill gaps were reported when selecting genomic biomarker tests to diagnose TC in Japan (79%), the UK (73%) and US (57%) and when performing specific biomarker tests, especially in Japan (82% for RET) and in the UK (75% for RET). Japanese participants (80%) reported uncertainty about what information to share with the multidisciplinary team to ensure optimal patient-centered care. At the time of data collection, pathologists in Japan faced access barriers to using RET biomarker tests: only 28% agreed that there are relevant RET genomic biomarker tests available in Japan, versus 67% to 90% in other countries.

Conclusions

This study identified areas where pathologists need additional continuing professional development opportunities to enhance their competencies and better support delivery of care to patients with RET-altered lung or thyroid tumours. Addressing identified gaps and improving competencies of pathologists in this field should be emphasised in continuing medical education curricula and through quality improvement initiatives. Strategies deployed on an institutional and health system level should aim to improve interprofessional communication and genetic biomarker testing expertise.
Opportunities and challenges of self-binding directives: an interview study with mental health service users and professionals in the Netherlands
Authors: van Melle Laura , van der Ham Lia , Voskes Yolande , Widdershoven Guy , Scholten Matthé
Published: June 2023

Background

Self-binding directives (SBDs) are psychiatric advance directives that include the possibility for service users to consent in advance to compulsory care in future mental health crises. Legal provisions for SBDs exist in the Netherlands since 2008 and were updated in 2020. While ethicists and legal scholars have identified several benefits and risks of SBDs, few data on stakeholder perspectives on SBDs are available.

Aims

The aim of the study was to identify opportunities and challenges of SBDs perceived by stakeholders who have personal or professional experience with legally enforceable SBDs.

Methods

Data collection was carried out in the Netherlands from February 2020 to October 2021 by means of semi-structured interviews. Participants were selected through purposive sampling and snowball methods. Interviews were conducted with mental health service users (n = 7), professionals (n = 13), and an expert on SBD policy (n = 1), resulting in a total number of 21 interviews. The data were analyzed thematically.

Results

Perceived benefits of SBDs included increased autonomy, improvement of the therapeutic relationship, possibility of early intervention and prevention of harm, prevention of compulsory care, reduction of the duration of compulsory care and recovery, mitigation of negative experiences around compulsory care, and guidance for professionals in providing compulsory care. Perceived risks included infeasibility of SBD instructions, difficulty in decision-making around SBD activation, limited accessibility of SBDs, disappointment of service users due to non-compliance with SBDs, and limited evaluation and updating of SBD content. Barriers to SBD completion included lack of knowledge of SBDs among professionals, lack of motivation or insight among service users, and lack of professional support for SBD completion. Facilitators of SBD completion and activation included support for SBD completion, involvement of relatives and peer experts, specification of SBD content, and evaluation of compulsory care and SBD content. The new legal framework was regarded as having both positive and negative effects on SBD implementation.

Conclusions

Stakeholders who have personal or professional experience with legally enforceable SBDs perceive SBDs as having important benefits and tend not to articulate the fundamental ethical concerns about SBDs which can be found in the ethics and legal literature. Instead, they perceive ethical and practical challenges that can be addressed through the implementation of suitable safeguards.
Area-specific covid-19 effects on health services utilization in the Democratic Republic of the Congo using routine health information system data
Authors: Angeles Gustavo , Silverstein Hannah , Worges Matt , Hotchkiss David R. , Wisniewski Janna M. , Lusamba Dikassa Paul Samson , Weiss William , Ahsan Karar Zunaid
Published: June 2023

Background

Since March 2020, the COVID-19 pandemic has shocked health systems worldwide. This analysis investigated the effects of the pandemic on basic health services utilization in the Democratic Republic of the Congo (DRC) and examined the variability of COVID effects in the capital city Kinshasa, in other urban areas, and in rural areas.

Methods

We estimated time trends models using national health information system data to replicate pre-COVID-19 (i.e., January 2017–February 2020) trajectories of health service utilization, and then used those models to estimate what the levels would have been in the absence of COVID-19 during the pandemic period, starting in March 2020 through March 2021. We classified the difference between the observed and predicted levels as the effect of COVID-19 on health services. We estimated 95% confidence intervals and p-values to examine if the effect of the pandemic, nationally and within specific geographies, was statistically significant.

Results

Our results indicate that COVID-19 negatively impacted health services and subsequent recovery varied by service type and by geographical area. COVID-19 had a lasting impact on overall service utilization as well as on malaria and pneumonia-related visits among young children in the DRC. We also found that the effects of COVID-19 were even more immediate and stronger in the capital city of Kinshasa compared with the national effect. Both nationally and in Kinshasa, most affected services had slow and incomplete recovery to expected levels. Therefore, our analysis indicates that COVID-19 continued to affect health services in the DRC throughout the first year of the pandemic.

Conclusions

The methodology used in this article allows for examining the variability in magnitude, timing, and duration of the COVID effects within geographical areas of the DRC and nationally. This analytical procedure based on national health information system data could be applied to surveil health service disruptions and better inform rapid responses from health service managers and policymakers.
Single-cell RNA sequencing reveals sexual diversity in the human bladder and its prospective impacts on bladder cancer and urinary tract infection
Authors: Wu Ribao , Teng Xiahong , Song Qiong , Chen Shuai , Wang Lihui , Liao Jinling , Zou Chunlin
Published: June 2023

Background

Some bladder-related diseases, such as bladder urinary tract infection (UTI) and bladder cancer (BCa), have significant six differences in incidence and prognosis. However, the molecular mechanisms underlying these sex differences are still not fully understood. Understanding the sex-biased differences in gene expression in normal bladder cells can help resolve these problems.

Methods

We first collected published single-cell RNA sequencing (scRNA-seq) data of normal human bladders from females and males to map the bladder transcriptomic landscape. Then, Gene Ontology (GO) analysis and gene set enrichment analysis (GSEA) were used to determine the significant pathways that changed in the specific cell populations. The Monocle2 package was performed to reconstruct the differentiation trajectories of fibroblasts. In addition, the scMetabolism package was used to analyze the metabolic activity at the single-cell level, and the SCENIC package was used to analyze the regulatory network.

Results

In total, 27,437 cells passed stringent quality control, and eight main cell types in human bladder were identified according to classical markers. Sex-based differential gene expression profiles were mainly observed in human bladder urothelial cells, fibroblasts, B cells, and T cells. We found that urothelial cells in males demonstrated a higher growth rate. Moreover, female fibroblasts produced more extracellular matrix, including seven collagen genes that may mediate BCa progression. Furthermore, the results showed that B cells in female bladders exhibited more B-cell activated signals and a higher expression of immunoglobulin genes. We also found that T cells in female bladders exhibited more T-cell activated signals. These different biological functions and properties of these cell populations may correlate with sex differences in UTI and BCa, and result in different disease processes and outcomes.

Conclusions

Our study provides reasonable insights for further studies of sex-based physiological and pathological disparities in the human bladder, which will contribute to the understanding of epidemiological differences in UTI and BCa.
Bacterial peritonitis in paediatric appendicitis; microbial epidemiology and antimicrobial management
Authors: Bhaskar Keir , Clarke Simon , Moore Luke S. P. , Hughes Stephen
Published: June 2023

Background

Appendicitis remains a common surgical emergency in children. Empirical antibacterial treatment is indicated to reduce infective complications. We investigate the bacterial pathogens identified intra-operatively during appendectomies in children to guide empirical surgical antimicrobial prophylaxis options.

Methods

A retrospective analysis of patients (< 18 years old) undergoing an appendectomy across a multisite London hospital (Nov 2019–March 2022) was undertaken. Patient-related outcomes including length of hospital stay (LOS), days of antibacterial therapy (DOT), intra-operative microbiology and post-operative radiology reports were interrogated.

Results

304 patients underwent an appendectomy during this period; 39.1% of patients had intraoperative samples cultured. Bacterial pathogens were found in 73/119 (61.3%) cases; the most common isolates being Escherichia coli (42.0%), Pseudomonas aeruginosa (21.0%), milleri Streptococcus spp. (14.3%) and Bacteroides fragilis (5.9%). Polymicrobial infection was common (32/73). Isolation of Pseudomonas spp. from intra-operative sampling was associated with a greater LOS (7.0 vs. 5.0 days; p = 0.011) but nil effect on the incidence of postoperative collections. Presence of milleri Streptococcus spp. was associated with longer LOS (7.0 vs. 5.0 day; p = 0.007), DOT (12.0 vs. 8.5 day; p = 0.007) but had no observed outcome on postoperative collections (29.4% vs. 18.6%; p = 0.330). 48% of E. coli positive cultures were co-amoxiclav resistant and prolonged LOS compared to the non-resistant group (7.0 vs. 5.0 days; p = 0.040) but had no difference in post-operative collections (29.2% vs. 17.9%; p = 0.260).

Conclusion

A high proportion of children with appendicitis have Pseudomonas spp. isolated, leading to a prolonged LOS. Evolving Enterobacterales resistance and the presence of Pseudomonas spp. necessitate extended antibacterial coverage for paediatric appendectomies with evidence of peritonitis.
Prophylactic drainage versus non-drainage following gastric cancer surgery: a meta-analysis of randomized controlled trials and observational studies
Authors: Pang Hua-Yang , Chen Li-Hui , Chen Xiu-Feng , Yan Meng-Hua , Chen Zhi-Xiong , Sun Hao
Published: June 2023

Background

The role of prophylactic drainage (PD) in gastrectomy for gastric cancer (GC) is not well-established. The purpose of this study is to compare the perioperative outcomes between the PD and non-drainage (ND) in GC patients undergoing gastrectomy.

Methods

A systematic review of electronic databases including PubMed, Embase, Web of Science, the Cochrane Library, and China National Knowledge Infrastructure was performed up to December 2022. All eligible randomized controlled trials (RCTs) and observational studies were included and meta-analyzed separately. The registration number of this protocol is PROSPERO CRD42022371102.

Results

Overall, 7 RCTs (783 patients) and 14 observational studies (4359 patients) were ultimately included. Data from RCTs indicated that patients in the ND group had a lower total complications rate (OR = 0.68; 95%CI:0.47–0.98; P = 0.04; I2 = 0%), earlier time to soft diet (MD =  − 0.27; 95%CI: − 0.55 to 0.00; P = 0.05; I2 = 0%) and shorter length of hospital stay (MD =  − 0.98; 95%CI: − 1.71 to − 0.26; P = 0.007; I2 = 40%). While other outcomes including anastomotic leakage, duodenal stump leakage, pancreatic leakage, intra-abdominal abscess, surgical-site infection, pulmonary infection, need for additional drainage, reoperation rate, readmission rate, and mortality were not significantly different between the two groups. Meta-analyses on observational studies showed good agreement with the pooled results from RCTs, with higher statistical power.

Conclusion

The present meta-analysis suggests that routine use of PD may not be necessary and even harmful in GC patients following gastrectomy. However, well-designed RCTs with risk-stratified randomization are still needed to validate the results of our study.
Factors affecting child welfare and protection workers' intention to quit: a cross-sectional study from Norway
Authors: Nilsen Kristel Høie , Lauritzen Camilla , Vis Svein Arild , Iversen Anita
Published: June 2023

Introduction

High turnover rates have been a problem for Norwegian child welfare and protection services for years. The main aim of this study was to identify which factors affect Norwegian child welfare and protection (CWP) workers intention to quit their job and whether there is a difference between experienced (< 3 years) and less experienced workers.

Methods

A cross-sectional survey was performed among 225 Norwegian child welfare and protection workers. Data were collected using a self-report questionnaire. Turnover intention was examined using a variety of job demands and resources as possible predictors. T tests were used to study mean differences in variable scores between experienced and less experienced workers and linear regression analysis was employed determining predictors of intention to quit.

Results

For the total sample (N = 225) the most important predictors for intention to quit were workload, burnout, engagement, and views on leadership. Higher emotional exhaustion and cynicism, and low professional efficacy predicted a higher score on the intention to quit scale. High engagement and leadership satisfaction predicted lower scores. The effect of workload was moderated, such that intention to quit among less experienced workers increased more with high workload than it did among more experienced child welfare workers.

Conclusions

The conclusions are that job demands affect experienced and less experienced CWP workers differently and that when designing preventive efforts to reduce turnover this must be considered.
Dental pulp stem cell-derived exosomes revitalize salivary gland epithelial cell function in NOD mice via the GPER-mediated cAMP/PKA/CREB signaling pathway
Authors: Hu Shilin , Chen Bo , Zhou Jiannan , Liu Fangqi , Mao Tianjiao , Pathak Janak L. , Watanabe Nobumoto , Li Jiang
Published: June 2023

Background

Restoration of salivary gland function in Sjogren’s syndrome (SS) is still a challenge. Dental pulp stem cells (DPSCs) derived exosomes had shown anti-inflammatory, anti-oxidative, immunomodulatory, and tissue function restorative abilities. However, the salivary gland function restoration potential of DPSCs-derived exosomes (DPSC-Exos) during SS has not been investigated yet.

Methods

DPSC-Exos was isolated by ultracentrifugation methods and characterized. Salivary gland epithelial cells (SGEC) were treated with interferon-gamma (IFN-γ) to mimic SS in vitro and cultured with or without DPSC-Exos. SGEC survival and aquaporin 5 (AQP5) expression were analyzed. mRNA sequencing and bioinformatics analysis were performed in IFN-γ vs. DPSC-Exos+ IFN-γ treated SGEC. Non-obese diabetic (NOD)/ltj female mice (SS model), were intravenously administered with DPSC-Exos, and salivary gland functions and SS pathogenicity were analyzed. Furthermore, the mRNA sequencing and bioinformatics predicted mechanism of the therapeutic effect of DPSC-Exos was further investigated both in vitro and in vivo using RT-qPCR, Western blot, immunohistochemistry, immunofluorescence, flowcytometry analysis.

Results

DPSC-Exos partially rescued IFN-γ triggered SGEC death. IFN-γ inhibited AQP5 expression in SGEC and DPSC-Exos reversed this effect. Transcriptome analysis showed GPER was the upregulated DEG in DPSC-Exos-treated SGEC with a positive correlation with salivary secretion-related DEGs. Pathway enrichment analysis revealed that DEGs were mainly attributed to estrogen 16 alpha-hydroxylase activity, extracellular exosome function, cAMP signaling, salivary secretion, and estrogen signaling. Intravenous injection of DPSC-Exos in NOD/ltj mice alleviated the SS syndrome as indicated by the increased salivary flow rate, attenuated glandular inflammation, and increased AQP5 expression. GPER was also upregulated in the salivary gland of DPSC-Exos-treated NOD/ltj mice compared with the PBS-treated NOD/ltj mice. IFN-γ+DPSC-Exos-treated SGEC showed higher expression of AQP5, p-PKA, cAMP, and intracellular Ca2+levels compared with IFN-γ-treated SGEC. These effects were reversed by the inhibition of GPER.

Conclusions

Our results showed that DPSC-Exos revitalize salivary gland epithelial cell function during SS via the GPER-mediated cAMP/PKA/CREB pathway suggesting the possible therapeutic potential of DPSC-Exos in SS-treatment.
Group-specific cellular metabolism in Medulloblastoma
Authors: Funke Viktoria L. E. , Walter Carolin , Melcher Viktoria , Wei Lanying , Sandmann Sarah , Hotfilder Marc , Varghese Julian , Jäger Natalie , Kool Marcel , Jones David T. W. , Pfister Stefan M. , Milde Till , Mynarek Martin , Rutkowski Stefan , Seggewiss Jochen , Jeising Daniela , de Faria Flavia W. , Marquardt Thorsten , Albert Thomas K. , Schüller Ulrich , Kerl Kornelius
Published: June 2023

Background

Cancer metabolism influences multiple aspects of tumorigenesis and causes diversity across malignancies. Although comprehensive research has extended our knowledge of molecular subgroups in medulloblastoma (MB), discrete analysis of metabolic heterogeneity is currently lacking. This study seeks to improve our understanding of metabolic phenotypes in MB and their impact on patients’ outcomes.

Methods

Data from four independent MB cohorts encompassing 1,288 patients were analysed. We explored metabolic characteristics of 902 patients (ICGC and MAGIC cohorts) on bulk RNA level. Moreover, data from 491 patients (ICGC cohort) were searched for DNA alterations in genes regulating cell metabolism. To determine the role of intratumoral metabolic differences, we examined single-cell RNA-sequencing (scRNA-seq) data from 34 additional patients. Findings on metabolic heterogeneity were correlated to clinical data.

Results

Established MB groups exhibit substantial differences in metabolic gene expression. By employing unsupervised analyses, we identified three clusters of group 3 and 4 samples with distinct metabolic features in ICGC and MAGIC cohorts. Analysis of scRNA-seq data confirmed our results of intertumoral heterogeneity underlying the according differences in metabolic gene expression. On DNA level, we discovered clear associations between altered regulatory genes involved in MB development and lipid metabolism. Additionally, we determined the prognostic value of metabolic gene expression in MB and showed that expression of genes involved in metabolism of inositol phosphates and nucleotides correlates with patient survival.

Conclusion

Our research underlines the biological and clinical relevance of metabolic alterations in MB. Thus, distinct metabolic signatures presented here might be the first step towards future metabolism-targeted therapeutic options.

Graphical Abstract