bluuebunny/crossref_metadata_2025 huggingface dataset:
The academic formation challenges: what does retail expect from higher education institutions in pharmacy?
Authors: Fonseca Francielly Lima da , Dosea Aline Santana , Araújo-Neto Fernando de Castro , Gois dos Santos Lívia , Pimentel Déborah Mônica Machado , Lyra Divaldo Pereira de
Published: April 2024

Background

The drug retail represents the main area of activity for pharmacists worldwide. In Brazil, this sector is responsible for employing around 80% of professionals. Before this reality, the academic training of pharmacists requires specialized skills and knowledge so they can fulfill their tasks. In this sector, considering the influence of managers and mentors on the model of pharmaceutical practice, their perceptions about the demands of the market can help discussions related to the training of pharmacists.

Aim

To analyze the academic training of pharmacists for the drug retail market from the perspective of managers and mentors.

Method

This is a qualitative study conducted with managers and mentors of the drug retail market. A semi-structured interview guide was prepared and applied to the intentionally selected participants. The study was approved by the Research Ethics Committee under the number 4,169,752. The interviews were conducted through videoconference by an experienced researcher. The data obtained were analyzed using Bardin’s analysis technique, following the steps of categorical thematic content analysis using the ATLAS.ti software.

Results

19 interviews were carried out. Among the reports, the interviewees highlighted the importance of retail in the employability of pharmacists, as well as inconsistency in the academic training for this sector, originating the following categories: curriculum reform to include the market demands, follow-up and career plan, training for entrepreneurship and sales, practical application of knowledge, and encouragement of experience.

Conclusion

Pharmaceutical academic training is linked to several challenges, whether organizational, structural, or budgetary. To overcome these challenges, it is necessary to unite the interested parties in the formulation and implementation of a strategy for the professionalization of pharmacists, considering their social role in patient care, aligned with the company’s sustainability, so that both coexist.
Weight management personas of breast cancer patients undergoing chemotherapy in China: a multi-method study
Authors: Li Xinyu , Zhang Nan , Yang Juan , Geng Zhaohui , Zhou Jie , Zhang Jinyu
Published: April 2024

Background

Mobile health (mHealth) may be an ideal solution for breast cancer (BC) patients in China to access weight management interventions. User retention and engagement are the main challenges faced by mHealth applications. A user persona, which is a user-centered design process, can lead to the development of mHealth that is more acceptable to the needs of target users. This study aimed to investigate the variety of experiences in weight management and the behavioral preferences of BC patients receiving chemotherapy to develop users’ personal information and persona development for the design and implementation of mHealth interventions.

Methods

Sixteen individual semi-structured in-depth interviews were conducted with BC patients receiving chemotherapy. We employed the thematic analysis method to analyze the interview transcripts in NVivo 11 software. The themes obtained from the analysis were used as the subdomains of personas. A proforma was designed to extract each participant’s experience in each subdomain. Patients who exhibited similar experience in subdomains were grouped into a persona using affinity diagrams. The personas were named according to their prominent features. A questionnaire survey was conducted to validate the personas and to test whether the personas that were generated from the qualitative interview data were applicable to the Chinese population with BC.

Results

Four themes were identified as subdomains of weight management personas: the perception of weight management while undergoing chemotherapy, symptoms and emotional disturbance, changes in diet and exercise, and health literacy and information seeking. Five personas were ultimately obtained: (1) positive weight controllers, (2) patients who were inactive due to fatigue, (3) young patients who avoided communication, (4) overweight patients with treatment priority, and (5) patients who engaged in irregular exercise. Finally, the quantitative study showed that 51.58% of patients chose one of these five personas to represent themselves in weight management. None of the patient reported selecting options that were not explicitly outlined in the questionnaire and provided personalized descriptions of their weight management characteristics.

Conclusions

The selected personas were developed from in-depth interviews on biopsychosocial areas. They highlight different weight management patterns in Chinese BC patients and provide implications for both the design of mHealth systems and traditional interventions.
Knowledge levels of doctors and nurses working in surgical clinics about nutrients and food supplements, a multicentre descriptive study
Authors: Büyükkasap Aslı Emine , Yazıcı Gülay
Published: April 2024

Purpose

The use of nutrients and food supplements is increasing worldwide. Nutrients and food supplements frequently used in the surgical period may cause complications and side effects. This study was conducted to determine the level of knowledge about sixty-one nutrients and food supplements among doctors and nurses working in surgical clinics.

Design

A multicentre descriptive, quantitative, cross-sectional study.

Methods

The study was conducted between 15 February and 31 May 2022 with a total of 410 participants, including 143 doctors and 267 nurses, working in the surgical clinics of 8 hospitals, including public, university and private hospitals, within the borders of one province in Turkey. Data were collected face-to-face using a questionnaire developed by the researchers, which included descriptive characteristics of the doctors and nurses and questions about sixty-one nutrients and food supplements.

Results

The median overall success score of the doctors and nurses participating in the study regarding the use of nutrients and food supplements was 3.20 out of 100 points, the median success score of complications and side effects of nutrients and food supplements in the surgical period was 7.06 out of 33 points, the median success score for discontinuation of nutrients and food supplements prior to surgery was 0.21 out of 16 points, and the median success score for drug interactions of nutrients and food supplements was 1.70 out of 51 points. In addition, it was found that the overall success scores of doctors and nurses regarding nutrients and food supplements increased statistically significantly with increasing age and working years. The total success score of doctors and nurses who received training in nutrients and food supplements was statistically significantly higher than that of doctors and nurses who did not receive training.

Conclusion

In conclusion, it was found that the level of knowledge of nutrients and food supplements among doctors and nurses working in surgical clinics was less than half or even close to zero. Therefore, it is recommended that training on nutrients and food supplements should be included in the undergraduate and postgraduate education of doctors and nurses in order to prevent complications, side effects, drug interactions and patient safety related to the use of nutrients and food supplements in the surgical period.
Predictive modeling of initiation and delayed mental health contact for depression
Authors: Panaite Vanessa , Finch Dezon K. , Pfeiffer Paul , Cohen Nathan J. , Alman Amy , Haun Jolie , Schultz Susan K. , Miles Shannon R. , Belanger Heather G. , Kozel F. Andrew F. , Rottenberg Jonathan , Devendorf Andrew R. , Barrett Blake , Luther Stephen L.
Published: April 2024

Background

Depression is prevalent among Operation Enduring Freedom and Operation Iraqi Freedom (OEF/OIF) Veterans, yet rates of Veteran mental health care utilization remain modest. The current study examined: factors in electronic health records (EHR) associated with lack of treatment initiation and treatment delay; the accuracy of regression and machine learning models to predict initiation of treatment.

Methods

We obtained data from the VA Corporate Data Warehouse (CDW). EHR data were extracted for 127,423 Veterans who deployed to Iraq/Afghanistan after 9/11 with a positive depression screen and a first depression diagnosis between 2001 and 2021. We also obtained 12-month pre-diagnosis and post-diagnosis patient data. Retrospective cohort analysis was employed to test if predictors can reliably differentiate patients who initiated, delayed, or received no mental health treatment associated with their depression diagnosis.

Results

108,457 Veterans with depression, initiated depression-related care (55,492 Veterans delayed treatment beyond one month). Those who were male, without VA disability benefits, with a mild depression diagnosis, and had a history of psychotherapy were less likely to initiate treatment. Among those who initiated care, those with single and mild depression episodes at baseline, with either PTSD or who lacked comorbidities were more likely to delay treatment for depression. A history of mental health treatment, of an anxiety disorder, and a positive depression screen were each related to faster treatment initiation. Classification of patients was modest (ROC AUC = 0.59 95%CI = 0.586–0.602; machine learning F-measure = 0.46).

Conclusions

Having VA disability benefits was the strongest predictor of treatment initiation after a depression diagnosis and a history of mental health treatment was the strongest predictor of delayed initiation of treatment. The complexity of the relationship between VA benefits and history of mental health care with treatment initiation after a depression diagnosis is further discussed. Modest classification accuracy with currently known predictors suggests the need to identify additional predictors of successful depression management.
Perspectives on supporting Veterans’ social needs during hospital to home health transitions: findings from the Transitions Nurse Program
Authors: Daus Marguerite , Lee Marcie , Ujano-De Motta Lexus L. , Holstein Ariel , Morgan Brianne , Albright Karen , Ayele Roman , McCarthy Michaela , Sjoberg Heidi , Jones Christine D.
Published: April 2024

Background

Veterans who need post-acute home health care (HHC) are at risk for adverse outcomes and unmet social needs. Veterans’ social needs could be identified and met by community-based HHC clinicians due to their unique perspective from the home environment, acuity of Veterans they serve, and access to Veterans receiving community care. To understand these needs, we explored clinician, Veteran, and care partner perspectives to understand Veterans’ social needs during the transition from hospital to home with skilled HHC.

Methods

Qualitative data were collected through individual interviews with Veterans Health Administration (VHA) inpatient & community HHC clinicians, Veterans, and care partners who have significant roles facilitating Veterans’ hospital to home with HHC transition. To inform implementation of a care coordination quality improvement intervention, participants were asked about VHA and HHC care coordination and Veterans’ social needs during these transitions. Interviews were recorded, transcribed, and analyzed inductively using thematic analysis and results were organized deductively according to relevant transitional care domains (Discharge Planning, Transition to Home, and HHC Delivery).

Results

We conducted 35 interviews at 4 VHA Medical Centers located in Western, Midwestern, and Southern U.S. regions during March 2021 through July 2022. We organized results by the three care transition domains and related themes by VHA, HHC, or Veteran/care partner perspective. Our themes included (1) how social needs affected access to HHC, (2) the need for social needs screening during hospitalization, (3) delays in HHC for Veterans discharged from community hospitals, and (4) a need for closed-loop communication between VHA and HHC to report social needs.

Conclusions

HHC is an underexplored space for Veterans social needs detection. While this research is preliminary, we recommend two steps forward from this work: (1) develop closed-loop communication and education pathways with HHC and (2) develop a partnership to integrate a social risk screener into HHC pathways.
Identification and florfenicol-treatment of pseudomonas putida infection in gilthead seabream (Sparus aurata) fed on tilapia-trash-feed
Authors: Aboyadak Ibrahim M. , Abdel-Tawwab Mohsen , Ali Nadia G.
Published: April 2024

The present study aimed to determine the major cause of the high mortality affecting farmed gilthead seabream (Sparus aurata) and controlling this disease condition. Fifteen diseased S. aurata were sampled from a private fish farm located at Eldeba Triangle, Damietta, fish showed external skin hemorrhages, and ulceration. Bacterial isolates retrieved from the diseased fish were identified biochemically as Pseudomonas putida and then confirmed by phylogenetic analysis of the 16 S rRNA gene sequence. P. putida was also isolated from three batches of tilapia-trash feed given to S. aurata. Biofilm and hemolytic assay indicated that all P. putida isolates produced biofilm, but 61.11% can haemolyse red blood cells. Based on the antibiotic susceptibility test results, P. putida was sensitive to florfenicol with minimum inhibitory concentrations ranging between 0.25 and 1.0 µg mL− 1, but all isolates were resistant to ampicillin and sulfamethoxazole-trimethoprim. Pathogenicity test revealed that P. putida isolate (recovered from the tilapia-trash feed) was virulent for S. aurata with LD50 equal to 4.67 × 107 colony forming unit (CFU) fish− 1. After intraperitoneal (IP) challenge, fish treated with 10 mg kg− 1 of florfenicol showed 16.7% mortality, while no mortality was recorded for the fish group that received 20 mg kg− 1. The non-treated fish group showed 46.7% mortality after bacterial challenge. HPLC analysis of serum florfenicol levels reached 1.07 and 2.52 µg mL− 1 at the 5th -day post-drug administration in the fish groups received 10 and 20 mg kg− 1, respectively. In conclusion, P. putida was responsible for the high mortality affecting cultured S. aurata, in-feed administration of florfenicol (20 mg kg− 1) effectively protected the challenged fish.
Individualized rotation of left double lumen endobronchial tube to improve placement success rate: a randomized controlled trial
Authors: Zhou Huiying , Fei Yuda , Zhang Yuelun , Quan Xiang , Yi Jie
Published: April 2024

Background

In conventional practice, the left double lumen tube (DLT) is rotated 90° counterclockwise when the endobronchial cuff passes glottis. Success rate upon the first attempt is < 80%, likely owing to varying morphology of the bronchial bifurcation.

Methods

We conducted a randomized controlled trial to compare 90° counterclockwise rotation versus individualized degree of rotation in adult patients undergoing elective thoracic surgery using left DLT. The degree of rotation in the individualized group was based on the angle of the left main bronchi as measured on computed tomography (CT). The primary outcome was the first attempt left DLT placement success rate.

Results

A total of 556 patients were enrolled: 276 in the control group and 280 in the individualized group. The average angle of the left main bronchi was 100.6±9.5° (range 72° to 119°). The first attempt left DLT placement success rate was 82.6% (228/276) in the control group versus 91.4% (256/280) in the individualized group (P=0.02, χ2 test). The rate of carina mucosal injury, as measured at 30 min after the start of surgery under fibreoptic bronchoscopy, was significantly lower in individualized group than control group (14.0% versus 19.6%, P=0.041). The individualized group also had lower rate of postoperative sore throat (29.4% versus 44.0%, P<0.001) and hoarseness (16.8% versus 24.7%, P＜0.05).

Conclusions

Individualized rotation of left DLT based on the angle of the left main bronchi on preoperative CT increased first attempt success rate in adult patients undergoing elective thoracic surgery.

Trial registration

The trial is registered at Chinese Clinical Trial Registry (ChiCTR2100053349; principal investigator Xiang Quan, date of registration November 19, 2021).
In vitro platform to model the function of ionocytes in the human airway epithelium
Authors: Vilà-González Marta , Pinte Laetitia , Fradique Ricardo , Causa Erika , Kool Heleen , Rodrat Mayuree , Morell Carola Maria , Al-Thani Maha , Porter Linsey , Guo Wenrui , Maeshima Ruhina , Hart Stephen L. , McCaughan Frank , Granata Alessandra , Sheppard David N. , Floto R. Andres , Rawlins Emma L. , Cicuta Pietro , Vallier Ludovic
Published: April 2024

Background

Pulmonary ionocytes have been identified in the airway epithelium as a small population of ion transporting cells expressing high levels of CFTR (cystic fibrosis transmembrane conductance regulator), the gene mutated in cystic fibrosis. By providing an infinite source of airway epithelial cells (AECs), the use of human induced pluripotent stem cells (hiPSCs) could overcome some challenges of studying ionocytes. However, the production of AEC epithelia containing ionocytes from hiPSCs has proven difficult. Here, we present a platform to produce hiPSC-derived AECs (hiPSC-AECs) including ionocytes and investigate their role in the airway epithelium.

Methods

hiPSCs were differentiated into lung progenitors, which were expanded as 3D organoids and matured by air-liquid interface culture as polarised hiPSC-AEC epithelia. Using CRISPR/Cas9 technology, we generated a hiPSCs knockout (KO) for FOXI1, a transcription factor that is essential for ionocyte specification. Differences between FOXI1 KO hiPSC-AECs and their wild-type (WT) isogenic controls were investigated by assessing gene and protein expression, epithelial composition, cilia coverage and motility, pH and transepithelial barrier properties.

Results

Mature hiPSC-AEC epithelia contained basal cells, secretory cells, ciliated cells with motile cilia, pulmonary neuroendocrine cells (PNECs) and ionocytes. There was no difference between FOXI1 WT and KO hiPSCs in terms of their capacity to differentiate into airway progenitors. However, FOXI1 KO led to mature hiPSC-AEC epithelia without ionocytes with reduced capacity to produce ciliated cells.

Conclusion

Our results suggest that ionocytes could have role beyond transepithelial ion transport by regulating epithelial properties and homeostasis in the airway epithelium.
Electrical Impedance Tomography as a monitoring tool during weaning from mechanical ventilation: an observational study during the spontaneous breathing trial
Authors: Wisse Jantine J. , Goos Tom G. , Jonkman Annemijn H. , Somhorst Peter , Reiss Irwin K. M. , Endeman Henrik , Gommers Diederik
Published: April 2024

Background

Prolonged weaning from mechanical ventilation is associated with poor clinical outcome. Therefore, choosing the right moment for weaning and extubation is essential. Electrical Impedance Tomography (EIT) is a promising innovative lung monitoring technique, but its role in supporting weaning decisions is yet uncertain. We aimed to evaluate physiological trends during a T-piece spontaneous breathing trail (SBT) as measured with EIT and the relation between EIT parameters and SBT success or failure.

Methods

This is an observational study in which twenty-four adult patients receiving mechanical ventilation performed an SBT. EIT monitoring was performed around the SBT. Multiple EIT parameters including the end-expiratory lung impedance (EELI), delta Tidal Impedance (ΔZ), Global Inhomogeneity index (GI), Rapid Shallow Breathing Index (RSBIEIT), Respiratory Rate (RREIT) and Minute Ventilation (MVEIT) were computed on a breath-by-breath basis from stable tidal breathing periods.

Results

EELI values dropped after the start of the SBT (p < 0.001) and did not recover to baseline after restarting mechanical ventilation. The ΔZ dropped (p < 0.001) but restored to baseline within seconds after restarting mechanical ventilation. Five patients failed the SBT, the GI (p = 0.01) and transcutaneous CO2 (p < 0.001) values significantly increased during the SBT in patients who failed the SBT compared to patients with a successful SBT.

Conclusion

EIT has the potential to assess changes in ventilation distribution and quantify the inhomogeneity of the lungs during the SBT. High lung inhomogeneity was found during SBT failure. Insight into physiological trends for the individual patient can be obtained with EIT during weaning from mechanical ventilation, but its role in predicting weaning failure requires further study.
Ethnic discrimination, asking for fair treatment, and poor self-rated health: a gender stratified analysis of 13,443 Korean Chinese waged workers in South Korea
Authors: Lee Hayoung , Kim Ji-Hwan , Lee Garin , Lee Hyelin , Huq Mita , Devakumar Delanjathan , Kim Seung-Sup
Published: April 2024

Background

In South Korea, Korean Chinese workers experience ethnic discrimination although they share physical similarities and ethnic heritage with native-born Koreans. This study aimed to examine whether perceived ethnic discrimination is associated with poor self-rated health and whether the association differs by gender among Korean Chinese waged workers in South Korea.

Methods

We conducted a pooled cross-sectional analysis using data of 13,443 Korean Chinese waged workers from the Survey on Immigrants’ Living Conditions and Labor Force conducted in 2018, 2020, and 2022. Based on perceived ethnic discrimination, asking for fair treatment, and subsequent situational improvement, respondents were classified into the following four groups: “Not experienced,” “Experienced, not asked for fair treatment,” “Experienced, asked for fair treatment, not improved,” and “Experienced, asked for fair treatment, improved.” Poor self-rated health was assessed using a single question “How is your current overall health?” We applied logistic regression to examine the association between perceived ethnic discrimination and poor self-rated health, with gender-stratified analyses.

Results

We found an association between ethnic discrimination and poor self-rated health among Korean Chinese waged workers. In the gender-stratified analysis, the “Experienced, not asked for fair treatment” group was more likely to report poor self-rated health compared to the “Not experienced” group, regardless of gender. However, gender differences were observed in the group stratified by situational improvements. For male workers, no statistically significant association was found in the “Experienced, asked for fair treatment, improved” group with poor self-rated health (odd ratios: 0.87, 95% confidence intervals: 0.30–2.53). Conversely, among female workers, a statistically significant association was observed (odd ratios: 2.63, 95% confidence intervals: 1.29–5.38).

Conclusions

This study is the first to find an association between perceived ethnic discrimination and poor self-rated health, along with gender differences in the association between situational improvements after asking for fair treatment and poor self-rated health among Korean Chinese waged workers in South Korea.
Performances of two rapid LAMP-based techniques for the intrapartum detection of Group B Streptococcus vaginal colonization
Authors: Charfi Rym , Guyonnet Cécile , Untrau Meiggie , Giacometti Gaëlle , Paper Thierry , Poyart Claire , Plainvert Céline , Tazi Asmaa
Published: April 2024

Purpose

Group B Streptococcus (GBS) is the leading cause of invasive infections in newborns. The prevention of GBS neonatal disease relies on the administration of an intrapartum antibiotic prophylaxis to GBS-colonized women. In recent years, rapid intrapartum detection of GBS vaginal colonization using real-time nucleic acid amplification tests (NAATs) emerged as an alternative to antenatal culture screening methods.

Methods

We compared the performances of two loop-mediated isothermal amplification (LAMP) tests, the Ampliflash® GBS and the PlusLife® GBS tests, to standard culture for GBS detection in vaginal specimens from pregnant women. The study was conducted from April to July 2023 in a French hospital of the Paris area.

Results

A total of 303 samples were analyzed, including 85 culture-positive samples (28.1%). The Ampliflash® GBS test and the PlusLife® GBS tests gave a result for 100% and 96.3% tests, respectively. The performances of the tests were as follows: sensitivity 87.1% (95% confidence interval (CI) 78.3–92.6) and 98.7% (95% CI 93.0-99.8), specificity 99.1% (95% CI 96.7–99.8), and 91.9% (95% CI 87.3–95.0), respectively. False negative results of the Ampliflash® GBS test correlated with low-density GBS cultures. Time-to-results correlated with GBS culture density only for the PlusLife® GBS test (p < 0.001).

Conclusion

Both techniques provide excellent analytical performances with high sensitivity and specificity together with a short turnaround time and results available in 10 to 35 min. Their potential to further reduce the burden of GBS neonatal disease compared with antenatal culture screening needs to be assessed in future clinical studies.
Octamer-binding transcription factor 4-positive circulating tumor cell predicts worse treatment response and survival in advanced cholangiocarcinoma patients who receive immune checkpoint inhibitors treatment
Authors: Pei Fei , Tao Zhen , Lu Qi , Fang Tao , Peng Shasha
Published: April 2024

Background

Octamer-binding transcription factor 4-positive circulating tumor cell (OCT4+CTC) exhibits high stemness and invasive potential, which may influence the efficacy of immune checkpoint inhibitors (ICI). This study aimed to assess the prognostic role of OCT4+CTC in advanced cholangiocarcinoma (CCA) patients who received ICI treatment.

Methods

In total, 40 advanced CCA patients who received ICI treatment were included, and CTC and OCT4 counts were detected via a Canpatrol system and an RNA in situ hybridization method before ICI treatment. Patients were subsequently divided into none CTC, OCT4−CTC, and OCT4+CTC groups. Patients were followed up for a median of 10.4 months.

Results

The percentages of patients in none CTC, OCT4−CTC, and OCT4+CTC groups were 25.0%, 30.0%, and 45.0%, respectively. The proportion of patients with lymph node metastasis was highest in OCT4+CTC group, followed by none CTC group, and lowest in OCT4−CTC group (P = 0.025). The objective response rate (ORR) was lowest in OCT4+CTC group, moderate in OCT4−CTC group, and highest in none CTC group (P = 0.009), while disease control rate was not different among three groups (P = 0.293). In addition, progression-free survival (PFS) (P < 0.001) and overall survival (OS) (P = 0.001) were shorter in the OCT4+CTC group than in none CTC & OCT4−CTC group. Moreover, OCT4+CTC (versus none CTC) was independently linked with poorer PFS [hazard ratio (HR) = 6.752, P = 0.001] and OS (HR = 6.674, P = 0.003) in advanced CCA patients.

Conclusion

OCT4+CTC relates to lymph node metastasis and shows a good predictive value for poor treatment response and survival in advanced CCA patients who receive ICI treatment.
xWAS analysis in neuropsychiatric disorders by integrating multi-molecular phenotype quantitative trait loci and GWAS summary data
Authors: Luo Lingxue , Pang Tao , Zheng Haohao , Liufu Chao , Chang Suhua
Published: April 2024

Background

Integrating quantitative trait loci (QTL) data related to molecular phenotypes with genome-wide association study (GWAS) data is an important post-GWAS strategic approach employed to identify disease-associated molecular features. Various types of molecular phenotypes have been investigated in neuropsychiatric disorders. However, these findings pertaining to distinct molecular features are often independent of each other, posing challenges for having an overview of the mapped genes.

Methods

In this study, we comprehensively summarized published analyses focusing on four types of risk-related molecular features (gene expression, splicing transcriptome, protein abundance, and DNA methylation) across five common neuropsychiatric disorders. Subsequently, we conducted supplementary analyses with the latest GWAS dataset and corresponding deficient molecular phenotypes using Functional Summary-based Imputation (FUSION) and summary data-based Mendelian randomization (SMR). Based on the curated and supplemented results, novel reliable genes and their functions were explored.

Results

Our findings revealed that eQTL exhibited superior ability in prioritizing risk genes compared to the other QTL, followed by sQTL. Approximately half of the genes associated with splicing transcriptome, protein abundance, and DNA methylation were successfully replicated by eQTL-associated genes across all five disorders. Furthermore, we identified 436 novel reliable genes, which enriched in pathways related with neurotransmitter transportation such as synaptic, dendrite, vesicles, axon along with correlations with other neuropsychiatric disorders. Finally, we identified ten multiple molecular involved regulation patterns (MMRP), which may provide valuable insights into understanding the contribution of molecular regulation network targeting these disease-associated genes.

Conclusions

The analyses prioritized novel and reliable gene sets related with five molecular features based on published and supplementary results for five common neuropsychiatric disorders, which were missed in the original GWAS analysis. Besides, the involved MMRP behind these genes could be given priority for further investigation to elucidate the pathogenic molecular mechanisms underlying neuropsychiatric disorders in future studies.
A PCR-independent approach for mtDNA enrichment and next-generation sequencing: comprehensive evaluation and clinical application
Authors: Liang Dong , Zhu Lin , Zhu Yuqing , Huang Mingtao , Lin Ying , Li Hang , Hu Ping , Zhang Jun , Shen Bin , Xu Zhengfeng
Published: April 2024

Background

Sequencing the mitochondrial genome has been increasingly important for the investigation of primary mitochondrial diseases (PMD) and mitochondrial genetics. To overcome the limitations originating from PCR-based mtDNA enrichment, we set out to develop and evaluate a PCR-independent approach in this study, named Pime-Seq (PCR-independent mtDNA enrichment and next generation Sequencing).

Results

By using the optimized mtDNA enrichment procedure, the mtDNA reads ratio reached 88.0 ± 7.9% in the sequencing library when applied on human PBMC samples. We found the variants called by Pime-Seq were highly consistent among technical repeats. To evaluate the accuracy and reliability of this method, we compared Pime-Seq with lrPCR based NGS by performing both methods simultaneously on 45 samples, yielding 1677 concordant variants, as well as 146 discordant variants with low-level heteroplasmic fraction, in which Pime-Seq showed higher reliability. Furthermore, we applied Pime-Seq on 4 samples of PMD patients retrospectively, and successfully detected all the pathogenic mtDNA variants. In addition, we performed a prospective study on 192 apparently healthy pregnant women during prenatal screening, in which Pime-Seq identified pathogenic mtDNA variants in 4 samples, providing extra information for better health monitoring in these cases.

Conclusions

Pime-Seq can obtain highly enriched mtDNA in a PCR-independent manner for high quality and reliable mtDNA deep-sequencing, which provides us an effective and promising tool for detecting mtDNA variants for both clinical and research purposes.
Antiviral screening of natural, anti-inflammatory compound library against African swine fever virus
Authors: Jackman Joshua A. , Hakobyan Astghik , Grigoryan Rafayela , Izmailyan Roza , Elrod Charles C. , Zakaryan Hovakim
Published: April 2024

Background

African swine fever virus (ASFV) is a major threat to pig production and the lack of effective vaccines underscores the need to develop robust antiviral countermeasures. Pathologically, a significant elevation in pro-inflammatory cytokine production is associated with ASFV infection in pigs and there is high interest in identifying dual-acting natural compounds that exhibit antiviral and anti-inflammatory activities.

Methods

Using the laboratory-adapted ASFV BA71V strain, we screened a library of 297 natural, anti-inflammatory compounds to identify promising candidates that protected Vero cells against virus-induced cytopathic effect (CPE). Virus yield reduction, virucidal, and cell cytotoxicity experiments were performed on positive hits and two lead compounds were further characterized in dose-dependent assays along with time-of-addition, time-of-removal, virus entry, and viral protein synthesis assays. The antiviral effects of the two lead compounds on mitigating virulent ASFV infection in porcine macrophages (PAMs) were also tested using similar methods, and the ability to inhibit pro-inflammatory cytokine production during virulent ASFV infection was assessed by enzyme-linked immunosorbent assay (ELISA).

Results

The screen identified five compounds that inhibited ASFV-induced CPE by greater than 50% and virus yield reduction experiments showed that two of these compounds, tetrandrine and berbamine, exhibited particularly high levels of anti-ASFV activity. Mechanistic analysis confirmed that both compounds potently inhibited early stages of ASFV infection and that the compounds also inhibited infection of PAMs by the virulent ASFV Arm/07 isolate. Importantly, during ASFV infection in PAM cells, both compounds markedly reduced the production of pro-inflammatory cytokines involved in disease pathogenesis while tetrandrine had a greater and more sustained anti-inflammatory effect than berbamine.

Conclusions

Together, these findings support that dual-acting natural compounds with antiviral and anti-inflammatory properties hold promise as preventative and therapeutic agents to combat ASFV infection by simultaneously inhibiting viral replication and reducing virus-induced cytokine production.
Harnessing the potential of African youth for transforming health research in Africa
Authors: Adebisi Yusuff Adebayo , Jimoh Nafisat Dasola , Bassey Archibong Edem , Alaka Hassan Olayemi , Marah Mohamed , Ngoma Chimwemwe , Ogunkola Isaac Olushola , Bouaddi Oumnia , Courage Idahor , Abdelatif El-Abasiri Radwa Abdalla , Boutahar Rime , Ogbodum Molly Unoh , Ekpenyong Aniekan Michael , Uwizeyimana Theogene , Oghenerukevwe Oviri Edith , Olawade David Bamidele
Published: April 2024

Africa faces a significant burden of infectious diseases, including Malaria and HIV/AIDS, along with an increasing prevalence of non-infectious diseases such as diabetes and cancer. This dual health challenge is amplified by socioeconomic difficulties, restricted access to healthcare, and lifestyle changes, thus present unique scientific needs. Effectively addressing these issues requires a skilled scientific workforce adept in comprehensive healthcare strategies. This analysis explores the critical landscape of health research in Africa, emphasizing the unique opportunity presented by the continent’s youthful population, projected to reach almost 1 billion by 2050. The youth’s innovative potential and fresh perspectives offer a chance to overcome development barriers in health research. Nevertheless, challenges such as under-resourced education, limited research training, inadequate mentorship, and funding difficulties persist. This paper urgently calls upon African leaders, international partners, and stakeholders to prioritize health research, mobilize funding, forge strategic partnerships, and empower the youth as essential steps to capitalize on the continent’s dynamic youth for breakthrough health outcomes. Such investments are vital not just for health but for the overall economic, social, and strategic growth of the continent. Through shared responsibility and a united effort, the potential of African youth can be harnessed, leading to transformative research, improved health outcomes, and a prosperous future. This perspective represents the collective voice of passionate young researchers and advocates across Africa, calling for a new era of health research on the continent.
Development and validation of a nomogram for assessing hepatocellular carcinoma risk after SVR in hepatitis C patients with advanced fibrosis and cirrhosis
Authors: Xu Shanshan , Qiu Lixia , Xu Liang , Liu Yali , Zhang Jing
Published: April 2024

Background

Hepatitis C patients with advanced fibrosis or cirrhosis are at high risk of developing hepatocellular carcinoma (HCC), even after sustained virological response (SVR). Clinical recommendations impose a significant burden on patients by recommending lifelong screening for HCC every six months. The goals of this study were to develop a nomogram that accurately stratifies risk of HCC and improve the screening approach that is currently in use.

Method

Risk factors for HCC were identified using univariate and multivariate analyses in this prospective study. We developed and validated a nomogram for assessing hepatocellular carcinoma risk after SVR in patients with advanced fibrosis and cirrhosis.

Results

During the median follow-up period of 61.00 (57.00–66.00) months in the derivation cohort, 37 patients (9.61%) developed HCC. Older age (HR = 1.08, 95% CI 1.02–1.14, p = 0.009), male gender (HR = 2.38, 95% CI 1.10–5.13, p = 0.027), low serum albumin levels (HR = 0.92, 95% CI 0.86–1.00, p = 0.037), and high liver stiffness measurement (LSM) (HR = 1.03, 95% CI 1.01–1.06, p = 0.001) were found to be independent predictors of HCC development. Harrell's C-index for the derivation cohort was 0.81. The nomogram’s 3-, 5- and 7-years time-dependent AUROCSs were 0.84 (95% CI 0.80–0.88), 0.83 (95% CI 0.79–0.87), and 0.81 (95% CI 0.77–0.85), respectively (all p > 0.05). According to the nomogram, patients are categorized as having low, intermediate, or high risk. The annual incidence rates of HCC in the three groups were 0.18%, 1.29%, and 4.45%, respectively (all p < 0.05).

Conclusions

Older age, male gender, low serum albumin levels, and high LSM were risk factors for HCC after SVR in hepatitis C patients with advanced fibrosis and cirrhosis. We used these risk factors to establish a nomogram. The nomogram can identify a suitable screening plan by classifying hepatitis C patients according to their risk of HCC.
The effect of COVID-19 on the non-COVID health outcomes of crisis-affected peoples: a systematic review
Authors: Thompson N. , Kyaw K. W. Y. , Singh L. , Cikomola J. C. , Singh N. S. , Roberts Bayard
Published: April 2024

Background

The COVID-19 pandemic posed considerable risks to populations affected by humanitarian crises in low- and middle-income countries (LMICs). However, there is limited understanding of how the pandemic may have affected non-COVID health outcomes among crisis-affected populations. Our aim was to examine the evidence on the impact of the COVID-19 pandemic on non-COVID-19 health outcomes for crisis-affected populations in LMICs.

Methods

A systematic review methodology was applied following PRISMA guidelines. Eligibility criteria were: crisis-affected populations in LMICS; COVID-19; and all health topics, except for sexual and reproductive health which was covered in a linked review. Five bibliographic databases and additional grey literature sources were searched. The search period was from 2019 to 31 July 2022. Eligible papers were extracted and analysed using a narrative synthesis approach based on the study objectives and relevant health access and systems frameworks. A quality appraisal was also conducted.

Findings

4320 articles were screened, and 15 eligible studies were identified and included in this review. Ten studies collected health outcomes data. Eight related to mental health, which generally showed worse mental health outcomes because of the pandemic, and pandemic-related stressors were identified. Two studies assessed physical health outcomes in children, while none addressed physical health outcomes among adults. Nine studies reported on access to healthcare, revealing worse access levels due to the pandemic and noting key barriers to care. Seven studies reported on the impact on health systems, with key challenges including reduced and distorted health care funding, reduced staff capacity, interrupted medicines and supplies, weak information and mixed-messaging, and weak leadership. All fifteen studies on the social determinants of health, particularly highlighting the effect of increasing poverty, the role of gender, and food insecurity on health outcomes. The quality of papers was limited overall.

Conclusion

This review found some limited evidence indicating negative mental health effects, increased barriers to accessing care, damage to health systems and magnified impacts on the social determinants of health for crisis-affected people during the COVID-19 pandemic. However, the small number and limited quality of the studies make the overall strength of evidence quite weak.
Centrifuger: lossless compression of microbial genomes for efficient and accurate metagenomic sequence classification
Authors: Song Li , Langmead Ben
Published: April 2024

Centrifuger is an efficient taxonomic classification method that compares sequencing reads against a microbial genome database. In Centrifuger, the Burrows-Wheeler transformed genome sequences are losslessly compressed using a novel scheme called run-block compression. Run-block compression achieves sublinear space complexity and is effective at compressing diverse microbial databases like RefSeq while supporting fast rank queries. Combining this compression method with other strategies for compacting the Ferragina-Manzini (FM) index, Centrifuger reduces the memory footprint by half compared to other FM-index-based approaches. Furthermore, the lossless compression and the unconstrained match length help Centrifuger achieve greater accuracy than competing methods at lower taxonomic levels.
Thyroid hormone induces ossification and terminal maturation in a preserved OA cartilage biomimetic model
Authors: Korthagen N. M. , Houtman E. , Boone I. , Coutinho de Almeida R. , Sivasubramaniyan K. , Mahdad R. , Nelissen R. G. H. H , Ramos Y. F. M. , Tessari M. A , Meulenbelt I.
Published: April 2024

Objective

To characterize aspects of triiodothyronine (T3) induced chondrocyte terminal maturation within the molecular osteoarthritis pathophysiology using the previously established T3 human ex vivo osteochondral explant model.

Designs

RNA-sequencing was performed on explant cartilage obtained from OA patients (n = 8), that was cultured ex vivo with or without T3 (10 ng/ml), and main findings were validated using RT-qPCR in an independent sample set (n = 22). Enrichment analysis was used for functional clustering and comparisons with available OA patient RNA-sequencing and GWAS datasets were used to establish relevance for OA pathophysiology by linking to OA patient genomic profiles.

Results

Besides the upregulation of known hypertrophic genes EPAS1 and ANKH, T3 treatment resulted in differential expression of 247 genes with main pathways linked to extracellular matrix and ossification. CCDC80, CDON, ANKH and ATOH8 were among the genes found to consistently mark early, ongoing and terminal maturational OA processes in patients. Furthermore, among the 37 OA risk genes that were significantly affected in cartilage by T3 were COL12A1, TNC, SPARC and PAPPA.

Conclusions

RNA-sequencing results show that metabolic activation and recuperation of growth plate morphology are induced by T3 in OA chondrocytes, indicating terminal maturation is accelerated. The molecular mechanisms involved in hypertrophy were linked to all stages of OA pathophysiology and will be used to validate disease models for drug testing.
Optic neuritis and mydriasis after vaccination: a case report
Authors: Bonamigo Elcio Luiz , Kuyava Pamela , Reginatto Taísa Sacomori Paula Zanotto , Duran Arthur Gabriel , Truculo Luisa , Rossi Eglas Emanuel , Stock Ricardo Alexandre , Grasel Claudia Elisa
Published: April 2024

Background

Optic neuritis (ON) is an inflammatory demyelinating condition of the optic nerve, with various causes. Its incidence is higher in children and young adults than in older adults of both genders, but is more common in women than in men. ON is rarely associated with mydriasis, and it is seldom triggered by vaccines against tetanus and diphtheria.

Case report

A 36-year-old Caucasian woman presented with bilateral ON that had started 18 days after administration of a booster dose of the double adult vaccine (dT) against diphtheria and tetanus. Bilateral mydriasis persisted after treatment and clinical resolution of the ON. She experienced severe headache, blurred vision, decreased visual acuity in the right eye and bilateral mydriasis, a diagnosis confirmed by imaging tests. Treatment with oral corticosteroids resulted in rapid resolution of the neuritis; however, mydriasis persisted for several months.

Conclusion

This study describes a very unusual case of bilateral ON associated with prolonged mydriasis after vaccination against tetanus and diphtheria that regressed after treatment with oral corticosteroids. Prolonged mydriasis was the manifestation that differed from the other cases previously described.
Recurrent ventilator-associated pneumonia in severe Covid-19 ARDS patients requiring ECMO support
Authors: Collado-Lledó Elena , Moyon Quentin , Chommeloux Juliette , Pineton de Chambrun Marc , Hékimian Guillaume , Saura Ouriel , Lévy David , Schmidt Matthieu , Combes Alain , Luyt Charles-Edouard , Le Fevre Lucie
Published: April 2024

Objective

To describe ventilator-associated pneumonia (VAP) recurrence in COVID-19 patients requiring extracorporeal membrane oxygenation (ECMO) support, and to evaluate the impact of antimicrobial treatment duration of the first VAP episode on VAP recurrence.

Methods

Adult patients with COVID-19 severe pneumonia on ECMO admitted between March 2020 and January 2022 were retrospectively included. Primary outcome was incidence of VAP recurrence, and secondary outcome was the impact of duration of antimicrobial treatment on VAP recurrence.

Results

Among the 252 included patients, 226 (90%) developed a first VAP. Sixteen had lung abscess and were excluded, leaving 210 patients. VAP recurrence occurred in 172 patients (82%), with a median (IQR) time from first VAP to recurrence of 10 (7–13) days. Pseudomonas aeruginosa and Enterobacteriaceae were respectively responsible for 28% and 52% of first VAP, and 51% and 62% of first recurrence episodes. Among the 210 patients with a first VAP, 158 (75%) received a short course of antibiotics [< 8 days, median (IQR) duration 6 (5–7) days] and 52 (25%) received a prolonged course of antibiotics [≥ 8 days, median (IQR) duration 9 (8–10) days]. Estimated cumulative incidence of VAP recurrence, taking into account death and extubation as competing risks, was not different in patients with short– and prolonged–antimicrobial treatment.

Conclusions

In patients with severe Covid-19–ARDS requiring ECMO support, VAP recurrence occurs frequently, with Enterobacteriaceae and Pseudomonas aeruginosa as predominant causative microorganisms. An antimicrobial treatment of ≥ 8 days for the treatment of first VAP episode did not reduce the risk of VAP recurrence, as compared to shorter duration.