bluuebunny/crossref_metadata_2025 huggingface dataset:
Nanoparticles induced health hazards through environmental exposure and direct contact
Authors: Tripathy Divya Bajpai , Pradhan Subhalaxmi
Published: February 2025

The swift applications of nanoparticles (NPs) in different fields such as pharmaceuticals, semiconductor, and decontamination require a comprehensive evaluation of their impacts on the health of human beings. This critical review consolidates the current knowledge on the nanoparticle toxicity with an attempt to unravel the biochemical and physiological processes by which NPs may harm human health. Exposure routes including aspiration, skin permeation, and direct consumption are involved and especially assessed in terms of biodistribution and biokinetics in living organisms. An exploration of physico-chemical characteristics such as particle size, morphology, surface charge, and chemical make-up yields the fact that all those things play an important role in the regulation of toxicity of nanoparticles in relation to other processes that include cell uptake, generation of oxidative stress, and inflammation. New data that define linkages between NP exposure and respiratory and cardiovascular diseases, Neurotoxicity, and potential carcinogenicity. The review further relies on the present methodological deficiencies and lack of harmonization in existing toxicity assessments for chronic exposure risks and call for more standardized testing protocols and elaborate long-term epidemiological investigations. The goal of this review is to highlight the health hazards associated with nanoparticles. In addition, authors also tried to contribute regulatory guidance and define directions for design of safer nanomaterials which will help to protect population health at the dawn of nanotechnologies.
Timing the state
Authors: Datta Ayona , Hoefsloot Fenna Imara
Published: February 2025

We wish to express our gratitude to the interlocutors for their considered and thoughtful commentaries on our article. They invoke new questions around the power of the state in directing action towards acceleration, performance, untimeliness, time essences, thickets and passages, and creativity. In this response piece, we develop our contention that the state in a digital era needs to be reconceptualised through timing as a form of statecraft. We will suggest first that while the state is not a coherent entity, it is in its temporality across spaces, scales, and actors that we begin to see its performative nature as auteur. Second, we address the question of untimeliness in our paper as an inherent aspect of temporal power itself. Finally, we address the provocation to expand our work on the creative uses of temporality from the margins.
Transcriptomic profiling of the airway epithelium in COPD links airway eosinophilia to type 2 inflammation and corticosteroid response
Authors: Leung Clarus , Park Hye Yun , Li Xuan , Koelwyn Graeme J. , Tuong Josie , Vahedi Seyed Milad , Leitao Filho Fernando Sergio , Yang Julia S. , Eddy Rachel L. , Milne Stephen , Ryu Min Hyung , Takiguchi Hiroto , Akata Kentaro , Ra Seung Won , Moon Ji-Yong , Kim Hyun Kuk , Cho Yuji , Yamasaki Kei , van Eeden Stephan F. , Shaipanich Tawimas , Lam Stephen , Leung Janice M. , Sin Don D.
Published: February 2025

Background

A subset of COPD patients have high levels of eosinophils in the distal airways (“airway eosinophilia”).

Objectives

To compare the gene expression of type 2 inflammation in airway epithelial brushings of COPD patients with and without airway eosinophilia and to investigate the changes after inhaled corticosteroids (ICS).

Methods

Post-hoc analyses of the DISARM randomised controlled trial investigated the expression of airway inflammation (type 1, 2, and 17), IL-13, and mast cell gene signatures at baseline and after 12-week ICS treatment. Gene signatures were generated from RNA sequencing of airway epithelial brushings. Airway eosinophilia was defined as eosinophils>1% of the total leukocyte count in bronchoalveolar lavage. Gene set enrichment analyses identified upregulated canonical pathways in airway eosinophilia.

Results

Among 58 COPD patients, 38% had airway eosinophilia at baseline. Patients with airway eosinophilia had more severe airflow obstruction and more radiographic emphysema than the non-eosinophilia group. Patients with airway eosinophilia showed a higher epithelial expression of type 2 airway inflammation and IL-13 and mast cell activation at baseline, but the expression of type 1 and type 17 airway inflammation was similar to patients without airway eosinophilia. The airway eosinophilia group showed an upregulation of canonical pathways related to type 2 immune response and asthma. Treatment with ICS for 12 weeks reduced the epithelial expression of type 2 inflammation and mast cell gene signatures in patients with airway eosinophilia, while this change was not significant in patients without airway eosinophilia.

Conclusions

Airway eosinophilia marks a subset of COPD patients with increased airway epithelial expression of type 2 inflammation and a response to ICS treatment.
Transcriptomic and biochemical analysis of pummelo x finger lime hybrids in response to Huanglongbing (HLB)
Authors: Mahmoud Lamiaa M. , Deol Jaideep Kaur , Grosser Jude W. , Killiny Nabil , Dutt Manjul
Published: February 2025

Background

Huanglongbing (HLB) is a devastating bacterial disease caused by the bacterium Candidatus Liberibacter asiaticus (CaLas) that affects the citrus industry worldwide. This study investigated the response of two pummelo x finger lime hybrid siblings to natural infection with CaLas. The hybrids were identified primarily using leaf morphology and molecular marker assessments and were selected for further studies on the basis of the CaLas titers in leaf petioles.

Results

HLB-infected budwood from the selected hybrids (PFL 2–61 and PFL 1–11), as well as the two parental plants, were propagated by grafting onto Swingle citrumelo rootstocks for further evaluation. Plant samples were collected two years after grafting for analysis. Leaves of PFL2-61 exhibited decreased CaLas titers compared with those of PFL 1–11. Additionally, we recorded increased chlorophyll content, total phenolic content (TPC), total flavonoid content (TFC), and antioxidant activity in PFL 2–61 compared to PFL 1–11 and the parents. We subsequently conducted a detailed investigation of these two hybrid siblings using transcriptome analysis. Among the 20,675 differentially expressed genes (DEGs) identified, 1,416 were downregulated in PFL 2–61 compared with PFL 1–11, whereas 326 were upregulated. Transcriptome analysis revealed that many of the DEGs were associated with the cell wall structure, redox homeostasis, and biotic stress responses. Moreover, key genes related to the biosynthesis of secondary metabolites and phytohormones, including PAL1, jasmonate-related genes, and WRKY transcription factors, were upregulated in the tolerant hybrid (PFL 2–61). In contrast, three transcripts associated with the Sieve Element Occlusion N-Terminus (SEO_N) domain were downregulated in the tolerant hybrid (PFL 2–61).

Conclusions

Our findings provide valuable insights into the molecular mechanisms of tolerance and susceptibility to HLB in finger lime derived hybrids, highlighting the potential of this citrus species towards developing disease-tolerant varieties.

Graphical Abstract
Ca2+-dependent H2O2 response in roots and leaves of barley - a transcriptomic investigation
Authors: Bhattacharyya Sabarna , Bleker Carissa , Meier Bastian , Giridhar Maya , Rodriguez Elena Ulland , Braun Adrian Maximilian , Peiter Edgar , Vothknecht Ute C. , Chigri Fatima
Published: February 2025

Background

Ca2+ and H2O2 are second messengers that regulate a wide range of cellular events in response to different environmental and developmental cues. In plants, stress-induced H2O2 has been shown to initiate characteristic Ca2+ signatures; however, a clear picture of the molecular connection between H2O2-induced Ca2+ signals and H2O2-induced cellular responses is missing, particularly in cereal crops such as barley. Here, we employed RNA-seq analyses to identify transcriptome changes in roots and leaves of barley after H2O2 treatment under conditions that inhibited the formation of cytosolic Ca2+ transients. To that end, plasma membrane Ca2+ channels were blocked by LaCl3 application prior to stimulation of barley tissues with H2O2.

Results

We examined the expression patterns of 4246 genes that had previously been shown to be differentially expressed upon H2O2 application. Here, we further compared their expression between H2O2 and LaCl3 + H2O2 treatment. Genes showing expression patterns different to the previous study were considered to be Ca2+-dependent H2O2-responsive genes. These genes, numbering 331 in leaves and 1320 in roots, could be classified in five and four clusters, respectively. Expression patterns of several genes from each cluster were confirmed by RT-qPCR. We furthermore performed a network analysis to identify potential regulatory paths from known Ca2+-related genes to the newly identified Ca2+-dependent H2O2 responsive genes, using the recently described Stress Knowledge Map. This analysis indicated several transcription factors as key points of the responses mediated by the cross-talk between H2O2 and Ca2+.

Conclusion

Our study indicates that about 70% of the H2O2-responsive genes in barley roots require a transient increase in cytosolic Ca2+ concentrations for alteration in their transcript abundance, whereas in leaves, the Ca2+ dependency was much lower at about 33%. Targeted gene analysis and pathway modeling identified not only known components of the Ca2+ signaling cascade in plants but also genes that are not yet connected to stimuli-associated signaling. Potential key transcription factors identified in this study can be further analyzed in barley and other crops to ultimately disentangle the underlying mechanisms of H2O2-associated signal transduction mechanisms. This could aid breeding for improved stress resistance to optimize performance and productivity under increasing climate challenges.
Cerebral oxygenation and hemodynamic changes during ephedrine and phenylephrine administration for transient intraoperative hypotension in patients undergoing major abdominal surgery: a randomized controlled trial
Authors: Li Xueyan , Zheng Yijun , Zhang Jun
Published: February 2025

Background

Phenylephrine and ephedrine are frequently used vasopressors for treating intraoperative hypotension. However, their impact on cerebral oxygenation and blood flow remains a subject of debate. This study aims to understand their effects on cerebral oxygen saturation and hemodynamics when used for treatment of intraoperative hypotension.

Methods

The adult patients undergoing major abdominal surgery under general anesthesia were randomly assigned into ephedrine (ED) group or phenylephrine (PE) group. They received an intravenous bolus of either ephedrine or phenylephrine for treating intraoperative transient hypotension. The primary outcome was their effects on regional cerebral oxygen saturation (rScO2). The secondary outcomes included cerebral hemodynamics middle cerebral artery velocity (MCAvm), pulsatility index (PI), and resistance index (RI), as well as systemic hemodynamics arterial blood pressure (ABP), heart rate (HR), cardiac output (CO), cardiac index (CI), stroke volume (SV) and stroke volume index (SVI). Additionally, two indices of cerebral autoregulation, mean flow index (Mxa) and cerebral oximetry index (COX), were calculated in real-time via ICM + software.

Results

Forty patients were included in this study. The initial results showed ephedrine increased rScO2 (p < 0.001), while phenylephrine increased Mxa (p < 0.02) and COX (p < 0.007), respectively. However, upon further linear-mix model analysis, the effects of both drugs on rScO2 (p = 0.944), Mxa (p = 0.093) and COX (p = 0.084) were found to be non-significant. Compared with the hemodynamic parameters during hypotension, the systolic blood pressure (SBP) (p < 0.001), diastolic blood pressure (DBP) (p < 0.001), mean arterial pressure (MAP) (p < 0.001), and MCAvm (p < 0.001) significantly increased after both ephedrine and phenylephrine administration. However, no significant differences were found between the two groups in terms of the changes in MAP (p = 0.549) and MCAvm (p = 0.173). And there were significant increases in CO (p < 0.001), HR (p < 0.001), and CI (p < 0.001) following ephedrine administration, while decreases in HR (p < 0.001), CO (p < 0.001), and CI (p < 0.001) after phenylephrine administration.

Conclusion

In the management of intraoperative hypotension, both phenylephrine and ephedrine effectively increase MAP and MCAvm, albeit with their differential effects on CO and HR. It seems that neither vasopressor has a significant impact on cerebral oxygenation and cerebral autoregulation.
Comprehensive characterization of pathogenic missense CTRP6 variants and their association with cancer
Authors: Mehboob Muhammad Zubair , Hamid Arslan , Senthil Kumar Jeevotham , Lei Xia
Published: February 2025

Background

Previous genome-wide association studies have linked three missense single nucleotide polymorphisms (SNPs) in C1q/TNF-related protein 6 (CTRP6) to diseases such as type 1 diabetes and autoimmune diseases. However, the potential association of newly identified missense CTRP6 variants with diseases, especially cancer, remains unclear.

Methods

We used several pathogenicity prediction algorithms to identify deleterious mutations within the highly conserved C1q domain of human CTRP6, following the retrieval of all SNPs from the Ensembl database. We systematically analyzed the effects of these mutations on the protein’s stability, flexibility, structural conformation, compactness, stiffness, and overall functionality using various bioinformatics tools. Additionally, we investigated the association of these mutations with different cancer types using the cBioPortal and canSAR databases.

Results

We identified 11 detrimental missense SNPs within the C1q domain, a region critical for this protein’s functionality. Using various computational methods, we predicted the functional impact of these missense variants and assessed their effects on the stability and flexibility of the CTRP6 structure. Molecular dynamics simulations revealed significant structural differences between the native and mutated structures, including changes in structural conformation, compactness, solvent accessibility, and flexibility. Additionally, our study shows a strong association between two mutations, G181S and R247W, and certain types of cancer: colon adenocarcinoma and uterine corpus endometrial carcinoma, respectively. We also found that the mutational status of CTRP6 and other cancer-related genes, such as MAP2K3, p16, TP53, and JAK1, affected each other’s expression, potentially contributing to cancer development.

Conclusions

Our screening and predictive analysis of pathogenic missense variants in CTRP6 advance the understanding of the functional implications of these mutations, potentially facilitating more focused and efficient research in the future.
The potential of thermal imaging as an early predictive biomarker of radiation dermatitis during radiotherapy for head and neck cancer: a prospective study
Authors: Park Ye-In , Choi Seo Hee , Cho Min-Seok , Son Junyoung , Kim Changhwan , Han Min Cheol , Kim Hojin , Lee Ho , Kim Dong Wook , Kim Jin Sung , Hong Chae-Seon
Published: February 2025

Background

Predicting radiation dermatitis (RD), a common radiotherapy toxicity, is essential for clinical decision-making regarding toxicity management. This prospective study aimed to develop and validate a machine-learning model to predict the occurrence of grade ≥ 2 RD using thermal imaging in the early stages of radiotherapy in head and neck cancer.

Methods

Thermal images of neck skin surfaces were acquired weekly during radiotherapy. A total of 202 thermal images were used to calculate the difference map of neck skin temperature and analyze to extract thermal imaging features. Changes in imaging features during treatment were assessed in the two RD groups, grade ≥ 2 and grade ≤ 1 RD, classified according to the Common Terminology Criteria for Adverse Events (CTCAE) guidelines. Feature importance analysis was performed to select thermal imaging features correlated with grade ≥ 2 RD. A predictive model for grade ≥ 2 RD occurrence was developed using a machine learning algorithm and cross-validated. Area under the receiver-operating characteristic curve (AUC), precision, and sensitivity were used as evaluation metrics.

Results

Of the 202 thermal images, 54 images taken before the occurrence of grade ≥ 2 RD were used to develop the predictive model. Thermal radiomics features related to the homogeneity of image texture were selected as input features of the machine learning model. The gradient boosting decision tree showed an AUC of 0.84, precision of 0.70, and sensitivity of 0.75 in models trained using thermal features acquired before skin dose < 10 Gy. The support vector machine achieved a mean AUC of 0.71, precision of 0.68, and sensitivity of 0.70 for predicting grade ≥ 2 RD using thermal images obtained in the skin dose range of 10–20 Gy.

Conclusions

Thermal images acquired from patients undergoing radiotherapy for head and neck cancer can be used as an early predictor of grade ≥ 2 RD and may aid in decision support for the management of acute skin toxicity from radiotherapy. However, our results should be interpreted with caution, given the limitations of this study.
Association of social support and religiosity with survival among women with breast cancer in a low-income population in the Southeastern United States
Authors: Fisa Ronald , Mwala Kabisa , DeMoulin Douglas , Kayamba Violet , Shrubsole Martha , Shu Xiao-Ou , Fwemba Isaac , Mutale Wilbroad , Lipworth Loren
Published: February 2025

Background

Large social networks have been associated with better overall survival after a breast cancer diagnosis in some but not all study populations. This study evaluated associations of social support and religiosity/spirituality with survival among Black and White women with breast cancer of largely low socioeconomic status in the United States (US).

Methods

The study used data from the prospective Southern Community Cohort Study, which enrolled approximately 86,000 adults in the southeastern US during 2002–2009. A total of 1,347 Black and White women with incident breast cancer were identified in the cohort and followed through December 2020 for mortality via linkage with the National Death Index. Exposures of interest were social support and religiosity obtained via baseline questionnaire, including number of close friends/relatives who can provide instrumental and emotional support, and frequency of attendance at religious services. Multivariable Cox regression models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for all-cause mortality in association with social support and religiosity. The models were tested for proportional hazards assumption using Schoenfeld residuals.

Results

Among the 1,347 women with breast cancer, 365 (27.1%) died during follow up. The participants were followed up for 17 years with a median follow-up time of 5 years. In all-cause mortality analyses, women who reported having 2 + relatives/friends for emotional support had a 20% reduced hazard of death compared to women with ≤ 1 relative/friend (HR = 0.80, 95% CI: 0.67–0.96) after adjusting for age at breast cancer diagnosis, race, time from cohort enrollment to diagnosis, income, education, marital status, insurance, and tumor hormone receptor status. Similarly, women reporting having 2 + people able to provide instrumental support (render assistance in an emergency or lend money) had a 25% (HR = 0.75, 95% CI: 0.59–0.95) reduced hazard of death compared to those who had ≤ 1. Frequent attendance at religious services/meetings was associated with reduced hazard of death compared to those who did not attend (HR = 0.60, CI: 0.41–0.89); addition of cancer stage in the models attenuated this association.

Conclusions

A large social support network and regular attendance at faith-based services were associated with better survival among women with breast cancer. This calls for incorporating appropriate interventions to cancer care such as social support groups to improve survival.
Simplified ABO-OGS orientation improves training of orthodontic bracket positioning for undergraduate dental students
Authors: Liu Jiali , Zou Yuchun , Huang Jing , Chen Ziqin , Hu Jia , Xu Linyu , Su Jiehua
Published: February 2025

Background

Mastery of orthodontic bracket bonding is an essential component of the undergraduate orthodontic curriculum. Traditional bracket bonding training using simple plaster models has some shortcomings, including a disconnect from clinical practice and poor perception of the criteria and accuracy. This study aims to optimize the bracket bonding course by comparing the traditional teaching method with simplified American Board of Orthodontics Objective Grading System (ABO-OGS)-oriented training methods.

Methods

Fourth-year dental students from Fujian Medical University, spanning the 2015 to 2017 cohorts, participated in the orthodontic bracket bonding course. Students from these three cohorts were trained using the traditional plaster model method, the digital 2D ABO-OGS-oriented method, and the typodont ABO-OGS-oriented method, respectively. After the course, students and teachers completed a six-level Likert scale questionnaire to evaluate the teaching objectives, methods, and efficacy.

Results

Both teachers and students agreed that the traditional bracket bonding training and the simplified ABO-OGS-oriented bracket bonding training were effective, with most students mastering the bracket bonding procedure. The simplified ABO-OGS-oriented bracket bonding was perceived as more novel and engaging compared to the traditional method (P < 0.05). However, the digital 2D ABO-OGS method was significantly less effective than the other two methods (P < 0.05). Instructors rated the typodont ABO-OGS-oriented training higher than the students did (P < 0.05).

Conclusion

Both the traditional and simplified ABO-OGS-oriented courses for bracket bonding yielded favorable results, with the simplified ABO-OGS approach being more engaging and innovative. The findings emphasize the critical role of hands-on practice in achieving optimal proficiency in bracket bonding techniques. A hybrid educational model that integrates digital 2D or 3D ABO-OGS-oriented training with offline practical sessions shows considerable potential for qualifying training and examination of orthodontic residency students.
Prevalence and predictors of condom use among people who inject drugs in Georgia
Authors: Kajaia Maia , Butsashvili Maia , DeHovitz Jack A. , Kamkamidze George , Gulbiani Lasha , Abzianidze Tinatin , Djibuti Mamuka
Published: February 2025

Background

People who inject drugs (PWID) are more likely to engage in unsafe sexual behavior placing them at high risk of acquiring HIV and other STIs. This study aims to assess the prevalence and predictors of inconsistent condom use with casual and/or paid sexual partners among PWID in Georgia.

Methods

Integrated Bio-Behavioral Surveillance Survey was conducted among PWID in seven major cities of Georgia. Study design was cross-sectional with respondent-driven sampling (RDS) methodology. Data collection was carried out through individual face-to-face interviews. Of the 2005 PWID who participated in the study, we analyzed a subsample of 619 (30.9%) who reported having casual and/or paid sexual partners during the last 12 months and described prevalence and predictors of consistent condom use.

Results

Consistent condom use during casual and/or paid sex in past 12 months was reported by 49.4% of respondents. The likelihood of consistent use with casual and/or paid sexual partners was statistically significantly associated with residence, family income, drug use frequency, drug dependence and HIV risk self-perceptions. In multivariable analysis independent predictors of always using condom at casual/paid sex during the last 12 months were place of residence (aOR = 6.4; 95% CI: 3.2–12.7), family income (aOR = 2.1; 95% CI:1.3–3.5) and drug use frequency (aOR = 0.6; 95% CI: 0.4–0.9).

Conclusion

The study revealed low prevalence of consistent condom use with casual and/or paid sexual partners among PWID in Georgia. Integration of safe sex educational interventions in harm reduction services may improve the rates of condom use among PWID and should focus PWID with lower socio-economic status and residing outside capital city.
A novel HVEM-Fc recombinant protein for lung cancer immunotherapy
Authors: Yao Yuanshan , Li Bin , Wang Jing , Chen Chunji , Gao Wen , Li Chunguang
Published: February 2025

Background

The ubiquitously expressed transmembrane protein, Herpesvirus Entry Mediator (HVEM), functions as a molecular switch, capable of both activating and inhibiting the immune response depending on its interacting ligands. HVEM-Fc is a novel recombinant fusion protein with the potential to eradicate tumor cells.

Methods

The anti-tumor efficacy of HVEM-Fc was evaluated in C57BL/6 mice-bearing lung cancer models: a syngeneic model and an orthotopic model of mouse lung cancer. Additionally, patient-derived organoids were employed in conjunction with T cell co-culture systems. To investigate the underlying mechanisms, a comprehensive array of techniques was utilized, including single-cell RNA sequencing, spatial transcriptomics, bulk RNA sequencing, and flow cytometry. Furthermore, the anti-tumor effects of HVEM-Fc in combination with Programmed Death-1 (PD-1) inhibitors were assessed. Finally, mouse immune cell depletion antibodies were used to elucidate the underlying mechanisms of action.

Results

In vivo, 1 mg/kg HVEM-Fc demonstrated effective inhibition of tumor growth and metastasis in C57BL/6 mice bearing lung cancer model and a KP orthotopic model of mouse lung cancer. Multi-omics analysis showed that HVEM-Fc induced an immune-stimulatory microenvironment. Notably, the combination of HVEM-Fc with a PD-1 inhibitor demonstrated the most potent inhibition of tumor cell growth. In vitro, HVEM-Fc was validated to eradicate tumor cells through the activation of T cells in both non-small cell lung cancer (NSCLC) organoids and T cell co-culture models.

Conclusions

Our data demonstrate that HVEM-Fc exerts a strong signal that augments and prolongs T-cell activity in both murine models and human NSCLC organoid models. Moreover, the combination of HVEM-Fc with a PD-1 inhibitor yields the most effective anti-tumor outcomes.
A translational perspective of the malignant hematopoietic proteoglycome
Authors: Borghini Naomi , Lazzaretti Mirca , Lunghi Paolo , Malpeli Giorgio , Barbi Stefano , Perris Roberto
Published: February 2025

Proteoglycans are an ample family of complex extracellular matrix/cell surface components known to impact on virtually all biological processes that take place during life of a human being, in its healthy and diseased conditions. They are consolidated multivalent regulators of the behaviour of normal and malignant hematopoietic cells because of being critical components of their membranes, because of their pivotal role as multifaceted factors of the hematopoietic niches and because of acting as pillars of the tumour microenvironment. Likewise, they act as promoters of the growth, spreading and therapeutic resistance of diseased hematopoietic cells, also by modulating intracellular processes through a dual utilization of core protein domains and their glycosaminoglycan side chains. The intricate pattern of expression of the myriads of proteoglycan isoforms generated by differential glycanations of the core proteins is differentiation- and cell activation-dependent and often associates with genomic aberrations and gene amplifications. Selected proteoglycans stand out as widely recognized, disease type-specific markers and as alluring but still unappreciated therapeutic targets. We therefore pose here a clinical-translational view on the hematopoietic proteoglycome to highlight its underestimated biological and pathological significance during normal and neoplastic hematopoiesis. We underscore the potential of several proteoglycans to be exploited as key markers for prognostication and therapeutic targeting of hematopoietic cancers.
Initiating buprenorphine to treat opioid use disorder without prerequisite withdrawal: an updated systematic review
Authors: Adams Kathleen K. , Waters Kristin , Sobieraj Diana M.
Published: February 2025

Background

Withdrawal prior to buprenorphine initiation may be intolerable or create barriers to therapy. We aim to update our previous systematic review on the efficacy and safety of buprenorphine initiation strategies that aim to omit prerequisite opioid withdrawal (POW).

Methods

We used the same search strategy for this update as in the original review with the modification of an additional term “low dose.” We searched Embase and Scopus from April 11, 2020 to August 1, 2024 with searches in Google Scholar and www.clinicaltrials.gov. A study was included if it described patients with opioid use disorder or chronic pain that transitioned from a full mu-opioid agonist to buprenorphine without preceding withdrawal and reported withdrawal during initiation as an outcome. Two investigators independently screened citations and articles for inclusion, collected data using a standardized data collection tool, and assessed study risk of bias.

Results

Forty-four articles met our inclusion criteria; 31 were case reports/series reporting 84 cases and 13 were single-arm observational studies reporting a total of 576 cases. These studies were added to the literature from our original systematic review, totaling 59 studies and 682 patients. Sublingual buprenorphine was the most common initial formulation, comprising 55% (376/682) of cases. In case reports/series, use of a validated scale to measure withdrawal was uncommon; validated scales were only used in 36% of patients. All other patients had withdrawal assessed in a manner not utilizing a validated scale. Approximately half of these patients experienced any level of withdrawal (57/106 = 54%). The specific outcome of “any level of withdrawal” was not consistently reported in single-arm observational studies. Eight studies reported on any level of withdrawal, which occurred in 41% (177/428) of initiation attempts; some patients experienced more than one initiation attempt. Thirteen patients in case reports/series and 37 patients in the single-arm observational studies reported clinically significant withdrawal (50/682 = 7%). 81% (451/555) of patients transitioned to buprenorphine.

Conclusion

The prevalence of buprenorphine dosing strategies that aim to omit POW has vastly increased over the past 4 years. While quality of evidence remains low, the increased quantity of publications and integration into health-system guidelines and protocols demonstrates the need for prospective, controlled studies. It is unknown how selection bias impacts current findings, further highlighting the need for prospective, randomized, controlled trials evaluating these dosing strategies.
Biofunctionalization of silk fibroin scaffolds with enamel matrix protein and injectable platelet rich fibrin for soft tissue augmentation: an in-ovo study
Authors: Heimes Diana , Wiesmann-Imilowski Nadine , Heidebrecht Timpe , Blatt Sebastian , Pabst Andreas , Becker Philipp , Fuest Sandra , Brieger Jürgen , Smeets Ralf , Kämmerer Peer W.
Published: February 2025

Purpose

Silk fibroin (SF) is a biomaterial derived from the cocoon of the mulberry silkworm. This study aimed to assess the capacity of SF matrices biologized with injectable platelet-rich fibrin (iPRF) or enamel matrix protein (EMP) to modulate angiogenesis and immune response in the chorioallantoic membrane (CAM) assay.

Methods

300 eggs were divided into the following groups: CM + NaCl, CM + iPRF, CM + EMP, SF + NaCl, SF + iPRF, and SF + EMP. Matrices were applied to the CAM on embryonic development day (EDD) 7 after rehydration. Angiogenesis, represented by vascularized area, vessel density, and vessel junctions, was evaluated on EDD 10, 12, and 14. Additionally, gene expression of HIF-1ɑ, VEGF, MMP-13, and NOS2 was assessed via quantitative polymerase chain reaction (qPCR) on EDD 11 and 14.

Results

The number of vascularized specimens was notably higher in SF matrices regardless of the treatment applied, while in the CM group, only matrices biofunctionalized with iPRF demonstrated vascularization. On EDD 14, the CM + iPRF group exhibited the highest values for total vascularized area (CM + iPRF: 57.52%, SF + iPRF: 21.87%, p < 0.001), vessel density (CM + iPRF: 0.0067 μm/µm2, SF + iPRF: 0.0032 μm/µm2, p = 0.002), number of vessel junctions (CM + iPRF: 14.45, SF + iPRF: 4.82, p = 0.001). Gene expressions displayed high data variability and no significant differences between the groups.

Conclusions

Biofunctionalization with iPRF in CM leads to a high vascularization rate probably through their capability of retaining higher liquid volumes, suggesting improved intraoral wound healing after guided tissue regeneration (GTR). Despite biofunctionalization, SF matrices exhibit a high vascularization, indicating SF as a promising material for GTR.
Enhanced psychosocial assessment and rapid follow-up care for people presenting to emergency departments with self-harm and/or suicidal ideation: the Assured feasibility study and internal pilot trial
Authors: O’Keeffe Sally , Suzuki Mimi , Ryan Mary , Priebe Stefan , Byng Richard , Simpson Alan , Araújo-Soares Vera , Albert Rikke , Fialho Renata , Walker Neil , Bakou Alexandra Elissavet , McCabe Rose
Published: February 2025

Background

Patients presenting to emergency departments (EDs) following an episode of self-harm are at risk of future suicide. There are few evidence-based interventions for self-harm in the ED context in England. This study sought to assess the feasibility of a trial of a newly developed brief psychological intervention, the Assured approach. This approach consisted of an enhanced psychosocial assessment, collaborative safety planning and three rapid solution-focussed follow-up sessions. Phase 1 was a feasibility study, and phase 2 was an internal pilot trial of a cluster randomised controlled trial to assess whether progression to a full-scale trial was warranted.

Methods

In phase 1, patients were recruited and allocated to a study arm, the Assured arm or treatment as usual, depending on the allocation of their assessing practitioner, in four EDs in England. They were invited to research assessments after consent and at 6 months. Phase 2 was the internal pilot of a cluster randomised controlled trial conducted in six EDs in England. Practitioners were randomised to deliver the Assured approach or treatment as usual. Patients were recruited and allocated to a study arm depending on the allocation of their assessing practitioner. They were invited to complete research assessments after consent and at 3, 9 and 18 months.

Results

Sixty-one patients were recruited into the Assured (n = 46) and treatment as usual (n = 15) arms in phase 1. Findings showed we could recruit and follow up patients over a 6-month period. The research procedures were acceptable to patients and practitioners, and the intervention was delivered with acceptable fidelity to the intervention manual. Forty-seven patients were recruited into the phase 2 internal pilot trial, falling substantially short of our target of 491 in the stop-go criteria, indicating that the trial was not feasible in its current design.

Conclusion

The feasibility study indicated that both the intervention and research processes were acceptable. However, the internal pilot trial revealed substantial challenges in recruiting patients and delivering the intervention in the ED context. Adaptations to the trial design and intervention are proposed to enable the Assured approach to be tested in a future trial, to improve care for this underserved population.

Trial registration

ISRCTN16003313, 04/02/2020; ISRCTN13472559, 18/11/2021.
A dynamic journey of comprehensive school health policy implementation in response to the COVID-19 pandemic in Lombok, Indonesia
Authors: Warnaini Cut , Haq Abiyyu Didar , Kadriyan Hamsu , Shibuya Fumiko , Kobayashi Jun
Published: February 2025

Background

Coronavirus disease 2019 (COVID-19) pandemic in March 2020 led to new restrictive policies in several countries, including Indonesia. The comprehensive school health (CSH) framework provides overall guidance for interventions most effective in achieving specific outcomes related to health, nutrition, and education, and creating CSH programmes that account for the main contextual variations in Indonesian communities and schools is important. This study aimed to clarify how school health-related policies made before and after the COVID-19 pandemic responded to COVID-19 control measures on Lombok Island, Indonesia.

Method

This was a qualitative observational analytic study. Researchers reviewed and analysed school health policy, held separate confirmation discussions and interviews with stakeholders and key informants, and observed policy implementation at public and private schools in Mataram.

Results

The analysis found weaknesses and opportunities. Weakness included lack of guidelines, comprehensive planning, inconsistent hierarchy of roles and responsibilities, and social and cultural barriers. Opportunities included the importance of funding for consistent CSH implementation, monitoring and evaluation system, implementation between public and private schools, and decentralisation. Positive findings included CSH policy integration into teaching and learning activities, regular healthy school competition program, teachers as role models, existing coordination and distribution of responsibilities between relevant stakeholders, and authorising schools to make needed adjustments. Factors influencing school health efforts included curriculum, school organisation, personal ethos, and healthcare provider partnerships. To effectively promote school health efforts, schools must assess existing health problems within the school environment and surroundings, organisational structure and capabilities including knowledge and skills, commitment, and leadership aspects.

Conclusion

The COVID-19 pandemic has prompted the implementation of CSH policies in schools of Lombok Island, demonstrating flexibility and dedication to student welfare. Despite confusion due to changing regulations, collaboration with local health organisations and community support has resulted in effective policy implementation.
Religious Sodalities of the Ixil Maya of Chajul, Guatemala: A Historical Perspective
Authors: Castillo Victor , Banach Monika
Published: February 2025

Indigenous confraternities of Mexico and Guatemala have received considerable attention in ethnographic research as key institutions of the civil-religious hierarchy of Native communities. Nevertheless, in many regions the origins and developments of such confraternities are poorly known. Through the study of ecclesiastical documents related to the parish life of the Ixil Maya of northwestern Guatemala, this article tracks down the historical development of the Indigenous brotherhoods in the town of Chajul, from the seventeenth century to present day. Data reveal that cofradias and other religious sodalities of the colonial period operated rather differently from what ethnographers observed during the twentieth century in terms of ritual behavior and communal financial matters. Moreover, ethnographic data show that in Chajul these organizations might have been associated to the colonial mural art that has been lately uncovered there, offering a new insight into the ritual life of colonial cofradias. This raises important questions regarding the transformations of the cofradia in the Maya highlands—from an institution under constant economic duress to a powerful local organization—and the timing of such changes.
Vanishing Mediators
Authors: Kara Taushif
Published: February 2025

The expulsion of Ugandan Asians in 1972 coincided with the formal and informal development of multiculturalism as state policy and as shibboleth, while their arrival in places like Canada and Britain accelerated or compelled its advance. In both contexts, Uganda's Asians as well as cognate communities from Kenya and Tanzania are often seen as one of multiculturalism's ostensible success stories, even though in Britain they have also become some of its most visible critics. This essay suggests that the history of the expulsion is intimately rather than only accidentally connected to that of multiculturalism. It traces the conceptual links between the colonial “multiracialism” that defined the contexts in East Africa from where the Asians were expelled and what is today called multiculturalism. It makes the case that both might be better understood in relation to the persistent problem of mediation, as well as the uncertain place of mediating groups themselves.
Musical Chairs
Authors: Devji Faisal
Published: February 2025

This afterword explores the shifting history of the Uganda or East Africa Asian as it moves between continents, showing how it remains impossible to place.
Zainichi Protagonists and the Making of Historical Fiction: Cold War Security and Economic Insecurity in Min Jin Lee's Pachinko and Yang Sŏk-il's Chi to hone (Blood and Bones)
Authors: Kim Adhy
Published: February 2025

This article discusses how the historical experience of Zainichi (the postcolonial Korean diaspora in Japan) is represented through the fictionalized family history, set from the colonial period to the dusk of the Cold War. Looking at two post–Cold War novels across English and Japanese languages, Min Jin Lee’s Pachinko and Yang Sŏk-il’s Chi to hone 血と骨 (Blood and Bones), this article contextualizes the Zainichi intergenerational historical novel within a transpacific memory culture on Japanese-US imperiality and Korean diaspora. Built from firsthand or secondhand Zainichi memories, these novels experiment with different kinds of agency allotted to Korean characters amid the difficulties of effecting social change. Under dual conditions of Cold War security and economic insecurity, the agentive possibilities for a Zainichi character may be channeled in ways that reinforce the violent sociopolitical order as much as they might take the forms of revolutionary activity, resistance, or survival. These novels retrospectively narrate the experience of economic and geopolitical uncertainty within the frames of accepted historical knowledge. While Yang’s novel includes flashbacks to socialist and lumpen struggles as hallmarks of Zainichi memory, Lee purges her novel of the leftist Zainichi legacy, manipulating smaller levers of individual possibility within the unquestioned parameters of racialized labor and Korean division.
“Dulled Emotions and Dying Humanity”: The Jjimjilbang (Gay Bathhouse) as a Dark Space in Seoul
Authors: Cho John (Song Pae)
Published: February 2025

This article examines the discourses surrounding the emergence and growing popularity of Korean-style gay bathhouses known as jjimjilbangs in Seoul. Drawing on two years of field research conducted by the author in 2001–3, as well as follow-up research carried out in the summers up to the present, the author argues that Korean gay men have contradictory experiences of pleasure and abjection within jjimjilbangs. Such contradictory experiences arise not from their inherent depravity—as often depicted within mainstream media—but from the structural conditions of gay life in South Korea’s family-based society, in which homosexuality is considered so shameful for the entire family that “only orphans come out.” Unable to openly show their faces in public, men seek out these “dark spaces” to meet other men for sexual encounters. Unable to overcome these structural conditions, however, the men become trapped in “long tunnels of darkness.” In focusing on jjimjilbangs, this article contributes to the emerging body of literature on Queer Asia, which, in its insistence on the social embeddedness of individuals in the family and other social institutions, is articulating a counter-discourse to the hegemonic Western queer scholarship, based on the liberal notion of the “free” individual.
Tools and strategies to improve human locomotion performance and safety throughout history: on ice skates, skis, mountains and the battlefield
Authors: Formenti Federico , Askew Graham N. , Minetti Alberto E.
Published: February 2025

Humans have developed tools and strategies to improve locomotion performance and safety throughout history. In particular, unusual environmental conditions and danger have pushed the limits of imagination and initiative, laying the foundations for the development of several tools to enhance locomotion. This Review summarises studies on the biomechanics and energetics of human locomotion on ice and snow, from a historical perspective and in load-carrying conditions. Environmental conditions challenge our locomotor performance: steep mountain paths and snow on the ground increase the metabolic cost of walking, ice increases the risk of falls, and fighting on the medieval battlefield required protection. In these conditions, humans evolved and developed tools and strategies to improve their locomotor performance and safety, typically with a trade-off between increasing the weight carried and reducing the metabolic cost of locomotion and/or increasing safety. Materials engineering and empirical understanding of muscle and locomotion biomechanics have aided performance improvement. In addition, environmental and even genetic changes have contributed to a superior physiological performance at high altitude. This Review presents and discusses findings integrating the biomechanics and energetics of locomotion. Overall, the thought-provoking historical perspective of this work helps to hypothesise some of the current technological and technical limitations to human physiological performance and highlights how improving the latter may well require a wide multidisciplinary approach.
Evaluating the Hospital Preparedness for Emergencies using WHO Hospital Safety Index Tool
Authors: Sughra Ume , Riaz Asmaa , Suleman Marriam , Imran Muhammad Rafay
Published: February 2025

Objective: CBRN (an acronym for Chemical, Biological, Radiological, and Nuclear) events are large scale disasters that differ from man- made disasters in that the involved agents additionally cause contamination and specific health hazards. As an institution, hospitals need a specific level of preparedness to enable an effective response to CBRN emergencies. The aim of this study was to assess the presence and placement of a proper hospital response plan to CBRN events.
Methods: It was an observational cross-sectional study conducted from October 2021 to December 2021 in two public tertiary level healthcare facilities selected through purposive sampling technique. Data was collected using WHO Hospital Safety Index Tool which is a checklist consisting of 151 items divided into four sections or modules. To calculate the hospitals safety index Model-1 was used.
Results: The sum of the weighted results of the three modules for both hospitals were in category A (0.66 – 1), the results depicted that it is likely that the hospitals will function in emergencies and disasters.
Conclusion: Both hospitals gave satisfactory results when evaluated on the basis of WHO Hospital Safety Index Tool for emergency preparedness.
doi: https://doi.org/10.12669/pjms.41.3.10875
How to cite this: Sughra U, Riaz A, Suleman M, Imran MR. Evaluating the Hospital Preparedness for Emergencies using WHO Hospital Safety Index Tool. Pak J Med Sci. 2025;41(3):676-681. doi: https://doi.org/10.12669/pjms.41.3.10875
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.