bluuebunny/crossref_metadata_2025 huggingface dataset:
Transforaminal endoscopic lumbar discectomy with two-segment foraminoplasty for the treatment of very highly migrated lumbar disc herniation: a retrospective analysis
Authors: Zhang Yao , Song Jipeng , Lin Wancheng , Ding Lixiang
Published: April 2024

Background

The surgical resection of very highly migrated lumbar disc herniation (VHM-LDH) is technically challenging owing to the absence of technical guidelines. Hence, in the present study, we introduced the transforaminal endoscopic lumbar discectomy (TELD) with two-segment foraminoplasty to manage VHM-LDH and evaluated its radiographic and midterm clinical outcomes.

Materials and methods

The present study is a retrospective analysis of 33 consecutive patients with VHM-LDH who underwent TELD with two-segment foraminoplasty. The foraminoplasty was performed on two adjacent vertebrae on the basis of the migration direction of disc fragments to fully expose the disc fragments and completely decompress the impinged nerve root. The operation duration, blood loss, intra- and postoperative complications, and recurrences were recorded. Additionally, imageological observations were evaluated immediately after the procedure via magnetic resonance image and computerized tomography. Clinical outcomes were evaluated by calculating the visual analog scale (VAS) score and Oswestry Disability Index (ODI). The MacNab criterion was reviewed to assess the patients’ opinions on treatment satisfaction. The resection rate of bony structures were quantitatively evaluated on postoperative image. The segmental stability was radiologically evaluated at least a year after the surgery. Additionally, surgery-related and postoperative complications were evaluated.

Results

The average age of the patients was 56.87 ± 7.77 years, with a mean follow-up of 20.95 ± 2.09 months. The pain was relieved in all patients immediately after the surgery. The VAS score and ODI decreased significantly at each postoperative follow-up compared with those observed before the surgery (P < 0.05). The mean operation duration, blood loss, and hospital stay were 56.17 ± 16.21 min, 10.57 ± 6.92 mL, and 3.12 ± 1.23 days, respectively. No residual disc fragments, iatrogenic pedicle fractures, and segmental instability were observed in the postoperative images. For both up- and down- migrated herniation in the upper lumbar region, the upper limit value of resection percentage for the cranial SAP, caudal SAP, and pedicle was 33%, 30%, and 34%, respectively; while those in the lower lumbar region was 42%, 36%, and 46%, respectively. At the last follow-up, the satisfaction rate of the patients regarding the surgery was 97%. Surgery-related complications including dural tear, nerve root injury, epidural hematoma, iatrogenic pedicle fractures, and segmental instability were not observed. One patient (3%) suffered from the recurrence of LDH 10 months after the initial surgery and underwent revision surgery.

Conclusions

The TELD with two-segment foraminoplasty is safe and effective for VHM-LDH management. Proper patient selection and efficient endoscopic skills are required for applying this technique to obtain satisfactory outcomes.
Headache alleviation with nasal irrigation following endoscopic endonasal surgery for pituitary adenomas
Authors: Gu Jiayu , Chen Xiaoqun , Cheng Xiaoman , Zou Yunzhi , Deng Zekun , Li Depei , Zhou Zhihuan , Jiang Xiaobing
Published: April 2024

Background

Headache is a common occurrence after endoscopic endonasal surgery (EES) for pituitary adenomas and significantly impacts the quality of life of patients. This study aims to investigate the effectiveness of nasal irrigation in relieving postoperative headache after EES.

Methods

A retrospective analysis was conducted on a cohort of 101 patients (Cohort I) who underwent EES for pituitary adenomas to explore the risk factors associated with postoperative headache. Another cohort of 72 patients (Cohort II) who received adjuvant nasal irrigation following surgery was enrolled for further analysis. The Headache Impact Test (HIT-6) was used to score the severity of headache, and patients with a HIT score > 55 were classified as having headache.

Results

In Cohort I, 21.78% of patients experienced headache one month after EES, which decreased to 5.94% at the three-month follow-up. Multivariate analysis revealed that postoperative nasal sinusitis (OR = 3.88, 95%CI 1.16–13.03, p = 0.028) and Hardy’s grade C-D (OR = 10.53, 95%CI 1.02-109.19, p = 0.049) independently predicted the presence of postoperative headache at one month. At the three-month follow-up, patients with sinusitis had higher HIT-6 scores compared to those without sinusitis (44.43 ± 9.78 vs. 39.72 ± 5.25, p = 0.017). In Cohort II, the incidence of sinusitis at three months was significantly lower than that in Cohort I (p = 0.028). Importantly, both the incidence of headache and HIT-6 scores in Cohort II were significantly lower than those in Cohort I at the one- and three-month follow-ups.

Conclusions

Postoperative sinusitis is an independent risk factor for the development of headache following EES for pituitary adenomas. Prophylactic nasal irrigation helps relieve postoperative headache, possibly by preventing the occurrence of sinusitis.
Impact of perinatal HIV exposure and infection on salivary properties among Nigerian children
Authors: Onyia Nonso E. , Osagie Esosa , Akhigbe Paul , Idemudia Nosakhare L. , Obuekwe Ozo , Omoigberale Augustine , Richards Vincent , Coker Modupe O.
Published: April 2024

Background

There is growing evidence that perinatal HIV infection and exposure affect salivary pH and flow rate in children in most parts of the world, but not against the background of caries and the African demographic. This study aimed to evaluate the impact of HIV infection as well as exposure on salivary properties and their influence upon the dental caries experience among school-aged children in Nigeria.

Method

This cross-sectional study assessed the salivary flow rates and salivary pH of HIV infected and exposed school-aged (4–11) children receiving care at a Nigerian tertiary hospital. A total of 266 consenting participants which comprised of three groups as follows: (1) HIV Infected (HI) (n = 87), (2) HIV Exposed and Uninfected (HEU) (n = 82) and (3) HIV Unexposed and Uninfected (HUU) (n = 97) were recruited for the study. Questionnaires completed by parents/guardians were used for data collection. Three calibrated dentists performed oral examinations for dental caries. International Caries Detection and Assessment Scores (ICDAS) was used and presented as dmft/DMFT. Salivary pH was measured using MColourpHast™ pH indicator strips, while salivary flow rate was determined by collecting unstimulated whole saliva using the suction method. Data analysis relied on comparative statistics to determine the correlation between HIV exposure and infection on salivary pH and flow rates.

Result

Across the groups, (HI, HEU, and HUU) mean pH of the HI was significantly less than that of HEU and HUU. Similarly, there was a statistically significant difference in the SFR across the three groups (p = 0.004). Other variables such as gender, age and oral hygiene status expressed by the gingival inflammatory scores had no significant influence on the pH and SFR of study participants. There was a rather unexpected positive correlation of DMFT of HI and HEU groups with increasing salivary flow rate; though, the relationship was weak and not significant.

Conclusion

Perinatal HIV exposure and infection significantly impact salivary pH and flow rate among school-aged children in Nigeria. The findings of this study imply that HIV infection influenced the salivary pH, while HIV maternal exposure (without infection) impacted salivary flow rates when compared to the controls.
Serum biomarker levels in smokers and non-smokers following periodontal therapy. A prospective cohort study
Authors: Knie Lorenz V. , Leknes Knut N. , Xue Ying , Lie Stein Atle , Bunæs Dagmar F.
Published: April 2024

Background

To compare presence and levels of serum cytokines in smokers and non-smokers with periodontitis following periodontal therapy.

Methods

Thirty heavy smokers and 30 non-smokers with stage III or IV periodontitis were included in this prospective cohort study. Clinical data and blood serum were collected at baseline (T0), after step I-III (T1), and after 12 months step IV periodontal therapy (T2). Cytokine IL-1β, IL-6, IL-8, TNF-α, IL-10, and IP-10 levels were measured using multiplex kit Bio-Plex Human Pro™ Assay. Linear regression models with cluster robust variance estimates to adjust for repeated observations were used to test intra- and intergroup levels for each marker, IL-6 and IL-8 defined as primary outcomes.

Results

Clinical outcomes improved in both groups following therapy (p < 0.05). IL-6 levels increased with 75.0% from T0-T2 among smokers (p = 0.004). No significant intra- or intergroup differences were observed for IL-8. Higher levels of TNF-α (44.1%) and IL-10 (50.6%) were detected in smokers compared with non-smokers at T1 (p = 0.007 andp = 0.037, respectively). From T1-T2, differences in mean change over time for levels of TNF-α and IL-10 were observed in smokers compared with non-smokers (p = 0.005 andp = 0.008, respectively).

Conclusion

Upregulated levels of serum cytokines in smokers indicate a systemic effect of smoking following periodontal therapy. Differences in cytokine levels between smokers and non-smokers demonstrate a smoking induced modulation of specific systemic immunological responses in patients with severe periodontitis.
Prenatal diagnosis of 18p deletion and 8p trisomy syndrome: literature review and report of a novel case
Authors: Papamichail Maria , Eleftheriades Anna , Manolakos Emmanouil , Papamichail Adamantia , Christopoulos Panagiotis , Manegold-Brauer Gwendolin , Eleftheriades Makarios
Published: April 2024

18p deletion syndrome constitutes one of the most frequent autosomal terminal deletion syndromes, affecting one in 50,000 live births. The syndrome has un-specific clinical features which vary significantly between patients and may overlap with other genetic conditions. Its prenatal description is extremely rare as the fetal phenotype is often not present during pregnancy. Trisomy 8p Syndrome is characterized by heterogenous phenotype, with the most frequent components to be cardiac malformation, developmental and intellectual delay. Its prenatal diagnosis is very rare due to the unspecific sonographic features of the affected fetuses. We present a very rare case of a fetus with multiple anomalies diagnosed during the second trimester whose genomic analysis revealed a 18p Deletion and 8p trisomy Syndrome. This is the first case where this combination of DNA mutations has been described prenatally and the second case in general. The presentation of this case, as well as the detailed review of all described cases, aim to expand the existing knowledge regarding this rare condition facilitating its diagnosis in the future.
Validating the knowledge represented by a self-organizing map with an expert-derived knowledge structure
Authors: Amos Andrew James , Lee Kyungmi , Gupta Tarun Sen , Malau-Aduli Bunmi S.
Published: April 2024

Background

Professionals are reluctant to make use of machine learning results for tasks like curriculum development if they do not understand how the results were generated and what they mean. Visualizations of peer reviewed medical literature can summarize enormous amounts of information but are difficult to interpret. This article reports the validation of the meaning of a self-organizing map derived from the Medline/PubMed index of peer reviewed medical literature by its capacity to coherently summarize the references of a core psychiatric textbook.

Methods

Reference lists from ten editions of Kaplan and Sadock's Comprehensive Textbook of Psychiatry were projected onto a self-organizing map trained on Medical Subject Headings annotating the complete set of peer reviewed medical research articles indexed in the Medline/PubMed database (MedSOM). K-means clustering was applied to references from every edition to examine the ability of the self-organizing map to coherently summarize the knowledge contained within the textbook.

Results

MedSOM coherently clustered references into six psychiatric knowledge domains across ten editions (1967–2017). Clustering occurred at the abstract level of broad psychiatric practice including General/adult psychiatry, Child psychiatry, and Administrative psychiatry.

Conclusions

The uptake of visualizations of published medical literature by medical experts for purposes like curriculum development depends upon validation of the meaning of the visualizations. The current research demonstrates that a self-organizing map (MedSOM) can validate the stability and coherence of the references used to support the knowledge claims of a standard psychiatric textbook, linking the products of machine learning to a widely accepted standard of knowledge.
Pan-inhibition of the three H2S synthesizing enzymes restrains tumor progression and immunosuppression in breast cancer
Authors: Dawoud Alyaa , Youness Rana A. , Nafea Heba , Manie Tamer , Bourquin Carole , Szabo Csaba , Abdel-Kader Reham M. , Gad Mohamed Z.
Published: April 2024

Background

Hydrogen sulfide (H2S) is a significant endogenous mediator that has been implicated in the progression of various forms of cancer including breast cancer (BC). Cystathionine-β-synthase (CBS), cystathionine-γ-lyase (CSE), and 3-mercaptopyruvate sulfurtransferase (3MST) are the three principal mammalian enzymes responsible for H2S production. Overexpression of CBS, CSE and 3MST was found to be associated with poor prognosis of BC patients. Moreover, H2S was linked to an immune-suppressive tumor microenvironment in BC. Recently it was observed that BC cells, in response to single or dual inhibition of H2S synthesizing enzymes, develop an escape mechanism by overexpressing alternative sources of H2S generation. Thus, the aim of this work is to escape the H2S compensatory mechanism by pan repressing the three enzymes using microRNAs (miRNAs) and to investigate their impact on the oncogenic and immunogenic profile of BC cells.

Methods

BC female patients (n = 25) were recruited. In-silico analysis was used to identify miRNAs targeting CBS, CSE, and 3MST. MDA-MB-231 cells were cultured and transfected using oligonucleotides. Total RNA was extracted using Biazol, reverse transcribed and quantified using qRT-PCR. H2S levels were measured using AzMc assay. BC hallmarks were assessed using trans-well migration, wound healing, MTT, and colony forming assays.

Results

miR-193a and miR-548c were validated by eight different bioinformatics software to simultaneously target CBS, CSE and 3MST. MiR-193a and miR-548c were significantly downregulated in BC tissues compared to their non-cancerous counterparts. Ectopic expression of miR-193a and miR-548c in MDA-MB-231 TNBC cells resulted in a marked repression of CBS, CSE, and 3MST transcript and protein levels, a significant decrease in H2S levels, reduction in cellular viability, inhibition of migration and colony forming ability, repression of immune-suppressor proteins GAL3 GAL9, and CD155 and upregulation of the immunostimulatory MICA and MICB proteins.

Conclusion

This study sheds the light onto miR-193a and miR-548c as potential pan-repressors of the H2S synthesizing enzymes. and identifies them as novel tumor suppressor and immunomodulatory miRNAs in TNBC.
A novel immunogenic cell death-related classification indicates the immune landscape and predicts clinical outcome and treatment response in acute myeloid leukemia
Authors: Zhong Fangmin , He Shuyang , Guo Ni , Shi Luyi , Zhang Linlin , Jin Hua , Kong Guangyao
Published: April 2024

Background

Immunogenic cell death (ICD) is closely related to anti-tumor therapy and regulates the tumor microenvironment (TME). This study aims to explore the molecular characteristics of ICD in acute myeloid leukemia (AML) and to analyze the value of ICD-related biomarkers in TME indication, prognosis prediction, and treatment response evaluation in AML.

Methods

Single-sample gene set enrichment analysis was used to calculate the ICD score. LASSO regression was used to construct a prognostic risk score model. We also analyzed differences in clinical characteristics, immune landscape, immunotherapy response, and chemotherapy sensitivity between high-risk and low-risk patients.

Results

This study identified two ICD-related subtypes and found significant heterogeneity in clinical prognosis, TME, and immune landscape between different ICD subtypes. Subsequently, a novel ICD-related prognostic risk score model was developed, which accurately predicted the prognosis of AML patients and was validated in nine AML cohorts. Moreover, there were significant correlations between risk scores and clinicopathological factors, somatic mutations, TME characteristics, immune cell infiltration, immunotherapy response, and chemosensitivity. We further validated the model gene expression in a clinically real-world cohort.

Conclusions

The novel ICD-related signatures identified and validated by us can serve as promising biomarkers for predicting clinical outcomes, chemotherapy sensitivity, and immunotherapy response in AML patients, guiding the establishment of personalized and accurate treatment strategies for AML.

Graphical Abstract
All-cause, cardiovascular disease and cancer mortality in the population of a large Italian area contaminated by perfluoroalkyl and polyfluoroalkyl substances (1980–2018)
Authors: Biggeri Annibale , Stoppa Giorgia , Facciolo Laura , Fin Giuliano , Mancini Silvia , Manno Valerio , Minelli Giada , Zamagni Federica , Zamboni Michela , Catelan Dolores , Bucchi Lauro
Published: April 2024

Background

Per- and polyfluoroalkyl substances (PFAS) are associated with many adverse health conditions. Among the main effects is carcinogenicity in humans, which deserves to be further clarified. An evident association has been reported for kidney cancer and testicular cancer. In 2013, a large episode of surface, ground and drinking water contamination with PFAS was uncovered in three provinces of the Veneto Region (northern Italy) involving 30 municipalities and a population of about 150,000. We report on the temporal evolution of all-cause mortality and selected cause-specific mortality by calendar period and birth cohort in the local population between 1980 and 2018.

Methods

The Italian National Institute of Health pre-processed and made available anonymous data from the Italian National Institute of Statistics death certificate archives for residents of the provinces of Vicenza, Padua and Verona (males, n = 29,629; females, n = 29,518) who died between 1980 and 2018. Calendar period analysis was done by calculating standardised mortality ratios using the total population of the three provinces in the same calendar period as reference. The birth cohort analysis was performed using 20–84 years cumulative standardised mortality ratios. Exposure was defined as being resident in one of the 30 municipalities of the Red area, where the aqueduct supplying drinking water was fed by the contaminated groundwater.

Results

During the 34 years between 1985 (assumed as beginning date of water contamination) and 2018 (last year of availability of cause-specific mortality data), in the resident population of the Red area we observed 51,621 deaths vs. 47,731 expected (age- and sex-SMR: 108; 90% CI: 107–109). We found evidence of raised mortality from cardiovascular disease (in particular, heart diseases and ischemic heart disease) and malignant neoplastic diseases, including kidney cancer and testicular cancer.

Conclusions

For the first time, an association of PFAS exposure with mortality from cardiovascular disease was formally demonstrated. The evidence regarding kidney cancer and testicular cancer is consistent with previously reported data.
Ambient long-term exposure to organophosphorus pesticides and the human gut microbiome: an observational study
Authors: Zhang Keren , Paul Kimberly , Jacobs Jonathan P. , Cockburn Myles G. , Bronstein Jeff M. , del Rosario Irish , Ritz Beate
Published: April 2024

Background

Organophosphorus pesticides (OP) have been associated with various human health conditions. Animal experiments and in-vitro models suggested that OP may also affect the gut microbiota. We examined associations between ambient chronic exposure to OP and gut microbial changes in humans.

Methods

We recruited 190 participants from a community-based epidemiologic study of Parkinson’s disease living in a region known for heavy agricultural pesticide use in California. Of these, 61% of participants had Parkinson’s disease and their mean age was 72 years. Microbiome and predicted metagenome data were generated by 16S rRNA gene sequencing of fecal samples. Ambient long-term OP exposures were assessed using pesticide application records combined with residential addresses in a geographic information system. We examined gut microbiome differences due to OP exposures, specifically differences in microbial diversity based on the Shannon index and Bray–Curtis dissimilarities, and differential taxa abundance and predicted Metacyc pathway expression relying on regression models and adjusting for potential confounders.

Results

OP exposure was not associated with alpha or beta diversity of the gut microbiome. However, the predicted metagenome was sparser and less evenly expressed among those highly exposed to OP (p = 0.04). Additionally, we found that the abundance of two bacterial families, 22 genera, and the predicted expression of 34 Metacyc pathways were associated with long-term OP exposure. These pathways included perturbed processes related to cellular respiration, increased biosynthesis and degradation of compounds related to bacterial wall structure, increased biosynthesis of RNA/DNA precursors, and decreased synthesis of Vitamin B1 and B6.

Conclusion

In support of previous animal studies and in-vitro findings, our results suggest that ambient chronic OP pesticide exposure alters gut microbiome composition and its predicted metabolism in humans.
LXR agonism for CNS diseases: promises and challenges
Authors: Zhang Ruiyi , Wuerch Emily , Yong V. Wee , Xue Mengzhou
Published: April 2024

The unfavorable prognosis of many neurological conditions could be attributed to limited tissue regeneration in central nervous system (CNS) and overwhelming inflammation, while liver X receptor (LXR) may regulate both processes due to its pivotal role in cholesterol metabolism and inflammatory response, and thus receives increasing attentions from neuroscientists and clinicians. Here, we summarize the signal transduction of LXR pathway, discuss the therapeutic potentials of LXR agonists based on preclinical data using different disease models, and analyze the dilemma and possible resolutions for clinical translation to encourage further investigations of LXR related therapies in CNS disorders.

Graphical Abstract
Privatisation of government services in Australia: what is known about health and equity impacts
Authors: Anaf Julia , Freeman Toby , Baum Fran
Published: April 2024

Background

Historically in Australia, all levels of government created collective wealth by owning and operating infrastructure, and managing natural assets, key public goods and essential services while being answerable to the public. This strong state tradition was challenged in the 1980s when privatisation became a widespread government approach globally. Privatisation involves displacing the public sector through modes of financing, ownership, management and product or service delivery. The Australian literature shows that negative effects from privatisation are not spread equitably, and the health and equity impacts appear to be under-researched. This narrative overview aims to address a gap in the literature by answering research questions on what evidence exists for positive and negative outcomes of privatisation; how well societal impacts are evaluated, and the implications for health and equity.

Methods

Database and grey literature were searched by keywords, with inclusion criteria of items limited to Australia, published between 1990 and 2022, relating to any industry or government sector, including an evaluative aspect, or identifying positive or negative aspects from privatisation, contracting out, or outsourcing. Thematic analysis was aided by NVivo qualitative data software and guided by an a-priori coding frame.

Results

No items explicitly reflected on the relationship between privatisation and health. Main themes identified were the public cost of privatisation, loss of government control and expertise, lack of accountability and transparency, constraints to accessing social determinants of health, and benefits accruing to the private sector.

Discussion

Our results supported the view that privatisation is more than asset-stripping the public sector. It is a comprehensive strategy for restructuring public services in the interests of capital, with privatisation therefore both a political and commercial determinant of health. There is growing discussion on the need for re-nationalisation of certain public assets, including by the Victorian government.

Conclusion

Privatisation of public services is likely to have had an adverse impact on population health and contributed to the increase in inequities. This review suggests that there is little evidence for the benefits of privatisation, with a need for greater attention to political and commercial determinants of health in policy formation and in research.
Management of embolic splenic abscess secondary to aortic valve endocarditis – case report and review of literature
Authors: Nunez-Ordonez Nicolas , Luna Juan Sebastián , Mackenzie Jaime Camacho , Jiménez Andrés Felipe , González Alejandro , Pico Andrea J. , Román Carlos F. , Rivera Paulo A. Cabrera , Hincapié Carlos A. Villa
Published: April 2024

Background

Splenic abscess is a serious complication associated with infective endocarditis. There is still contradicting evidence regarding the optimal treatment pathway including timing of valve intervention and the approach for managing splenic foci.

Case presentation

We present a case of a hybrid staged approach in which we successfully performed a laparoscopic splenectomy following percutaneous abscess drainage and a delayed aortic valve replacement.

Conclusions

A multidisciplinary teamwork is fundamental in providing optimal care for patients with distant complications associated with infective endocarditis. Our hybrid approach seems safe and feasible.
Effect of intra-arrest transport, extracorporeal cardiopulmonary resuscitation and immediate invasive assessment in refractory out-of-hospital cardiac arrest: a long-term follow-up of the Prague OHCA trial
Authors: Rob Daniel , Farkasovska Klaudia , Kreckova Marketa , Smid Ondrej , Kavalkova Petra , Macoun Jaromir , Huptych Michal , Havrankova Petra , Gallo Juraj , Pudil Jan , Dusik Milan , Havranek Stepan , Linhart Ales , Belohlavek Jan
Published: April 2024

Background

Randomized data evaluating the impact of the extracorporeal cardiopulmonary resuscitation (ECPR) approach on long-term clinical outcomes in patients with refractory out-of-hospital cardiac arrest (OHCA) are lacking. The objective of this follow-up study was to assess the long-term clinical outcomes of the ECPR-based versus CCPR approach.

Methods

The Prague OHCA trial was a single-center, randomized, open-label trial. Patients with witnessed refractory OHCA of presumed cardiac origin, without return of spontaneous circulation, were randomized during ongoing resuscitation on scene to conventional CPR (CCPR) or an ECPR-based approach (intra-arrest transport, ECPR if ROSC is not achieved prehospital and immediate invasive assessment).

Results

From March 2013 to October 2020, 264 patients were randomized during ongoing resuscitation on scene, and 256 patients were enrolled. Long-term follow-up was performed 5.3 (interquartile range 3.8–7.2) years after initial randomization and was completed in 255 of 256 patients (99.6%). In total, 34/123 (27.6%) patients in the ECPR-based group and 26/132 (19.7%) in the CCPR group were alive (log-rank P = 0.01). There were no significant differences between the treatment groups in the neurological outcome, survival after hospital discharge, risk of hospitalization, major cardiovascular events and quality of life. Of long-term survivors, 1/34 (2.9%) in the ECPR-based arm and 1/26 (3.8%) in the CCPR arm had poor neurological outcome (both patients had a cerebral performance category score of 3).

Conclusions

Among patients with refractory OHCA, the ECPR-based approach significantly improved long-term survival. There were no differences in the neurological outcome, major cardiovascular events and quality of life between the groups, but the trial was possibly underpowered to detect a clinically relevant difference in these outcomes.

Trial registration ClinicalTrials.gov Identifier: NCT01511666, Registered 19 January 2012.
A methodological review of randomised n-of-1 trials
Authors: Hawksworth Olivia , Chatters Robin , Julious Steven , Cook Andrew , Biggs Katie , Solaiman Kiera , Quah Michael C. H. , Cheong Sxe Chang
Published: April 2024

Background

n-of-1 trials are a type of crossover trial designed to optimise the evaluation of health technologies in individual patients. This trial design may be considered for the evaluation of health technologies in rare conditions where fewer patients are available to take part in research. This review describes the characteristics of randomised n-of-1 trials conducted over the span of 12 years, including how the n-of-1 design has been employed to study both rare and non-rare conditions.

Methods

Databases and clinical trials registries were searched for articles including “n-of-1” in the title between 2011 and 2023. The reference lists of reviews identified by the searches were searched for any additional eligible articles. Randomised n-of-1 trials were selected for inclusion and data were extracted on a range of design, population, and analysis characteristics. Descriptive statistics were produced for all variables.

Results

We identified 74 studies meeting our eligibility criteria, 13 of which (17.6%) were conducted in rare conditions. They were conducted in a range of clinical areas with the most common being neurological conditions (n = 16, 21.6%). The median (Q1, Q3) number of participants randomised was 9 (4, 20) and 12 trials (16.2%) involved a single patient only. Forty-six (62.2%) trials evaluated pharmaceutical interventions and 49 (66.2%) trials were placebo controlled. Trials had a median (Q1, Q3) of six (4, 8) periods and 61 (82.4%) compared two health technologies. Fifty-seven (77.0%) trials incorporated blinding and 32 (43.2%) had a washout period. Forty-nine trials (66.2%) used patient-reported outcome measures (PROMs) to assess the primary outcome. Trials used a range of approaches to analysis and 48 (64.9%) combined data from multiple patients. The characteristics of the n-of-1 trials conducted in rare conditions were generally consistent with those in non-rare conditions.

Conclusions

n-of-1 trials are still underused and the application of the n-of-1 design for the evaluation of health technologies for rare diseases has been particularly limited. We have summarised the characteristics of randomised n-of-1 trials in rare and non-rare conditions. We hope that it can inform researchers in the design of future n-of-1 studies. Further work is required to provide guidance on specific design considerations, implementation, and statistical analysis of these studies.

Trial registration

Not applicable.
PheSeq, a Bayesian deep learning model to enhance and interpret the gene-disease association studies
Authors: Yao Xinzhi , Ouyang Sizhuo , Lian Yulong , Peng Qianqian , Zhou Xionghui , Huang Feier , Hu Xuehai , Shi Feng , Xia Jingbo
Published: April 2024

Despite the abundance of genotype-phenotype association studies, the resulting association outcomes often lack robustness and interpretations. To address these challenges, we introduce PheSeq, a Bayesian deep learning model that enhances and interprets association studies through the integration and perception of phenotype descriptions. By implementing the PheSeq model in three case studies on Alzheimer’s disease, breast cancer, and lung cancer, we identify 1024 priority genes for Alzheimer’s disease and 818 and 566 genes for breast cancer and lung cancer, respectively. Benefiting from data fusion, these findings represent moderate positive rates, high recall rates, and interpretation in gene-disease association studies.
Polymorphic ventricular tachycardia and cardiac arrest from abiraterone-induced hypokalemia: a case report
Authors: Mao Jessica , Chang Allison Komatsu , Chin Stephen , Preet Komal , Torosyan Nare , Sarkissian Sarmen , Ebinger Joseph
Published: April 2024

Background

Polymorphic ventricular tachycardia (PMVT) is an unstable and often fatal cardiac tachyarrhythmia. While there are many causes of this rhythm, including electrolyte imbalances, ischemia, and genetic disorders, iatrogenic etiologies are important to recognize. Abiraterone is an androgen synthesis antagonist effective in treating prostate cancer, but here we describe a case of severe hypokalemia secondary to abiraterone resulting in polymorphic ventricular tachycardia and cardiac arrest. While this is a potential adverse effect of the medication, severe hypokalemia causing polymorphic ventricular tachycardia and cardiac arrest, as seen in our patient’s case, has not been described.

Case presentation

A 78-year-old African-American man with history of prostate cancer presents with polymorphic ventricular tachycardia and cardiac arrest. After resuscitation, he was found to be severely hypokalemic and refractory to large doses of repletion. Evaluation of secondary causes of hypokalemia identified the likely culprit to be adverse effects from prostate cancer treatment.

Conclusion

A broad differential diagnosis for polymorphic ventricular tachycardia is essential in identifying and treating patients presenting in this rhythm. Here we present a case of iatrogenic polymorphic ventricular tachycardia secondary to oncologic treatment.
Meta-learning-based Inductive logistic matrix completion for prediction of kinase inhibitors
Authors: Du Ming , Xie XingRan , Luo Jing , Li Jin
Published: April 2024

Protein kinases become an important source of potential drug targets. Developing new, efficient, and safe small-molecule kinase inhibitors has become an important topic in the field of drug research and development. In contrast with traditional wet experiments which are time-consuming and expensive, machine learning-based approaches for predicting small molecule inhibitors for protein kinases are time-saving and cost-effective, which are highly desired for us. However, the issue of sample scarcity (known active and inactive compounds are usually limited for most kinases) poses a challenge to the research and development of machine learning-based kinase inhibitors' active prediction methods. To alleviate the data scarcity problem in the prediction of kinase inhibitors, in this study, we present a novel Meta-learning-based inductive logistic matrix completion method for the Prediction of Kinase Inhibitors (MetaILMC). MetaILMC adopts a meta-learning framework to learn a well-generalized model from tasks with sufficient samples, which can fast adapt to new tasks with limited samples. As MetaILMC allows the effective transfer of the prior knowledge learned from kinases with sufficient samples to kinases with a small number of samples, the proposed model can produce accurate predictions for kinases with limited data. Experimental results show that MetaILMC has excellent performance for prediction tasks of kinases with few-shot samples and is significantly superior to the state-of-the-art multi-task learning in terms of AUC, AUPR, etc., various performance metrics. Case studies also provided for two drugs to predict Kinase Inhibitory scores, further validating the proposed method's effectiveness and feasibility.

Scientific contribution

Considering the potential correlation between activity prediction tasks for different kinases, we propose a novel meta learning algorithm MetaILMC, which learns a prior of strong generalization capacity during meta-training from the tasks with sufficient training samples, such that it can be easily and quickly adapted to the new tasks of the kinase with scarce data during meta-testing. Thus, MetaILMC can effectively alleviate the data scarcity problem in the prediction of kinase inhibitors.
Severity of gambling behaviors: exploring associations with venues, legality, and substance use
Authors: Bonny-Noach Hagit
Published: April 2024

Introduction

The COVID-19 pandemic has been linked to an increase in gambling behaviors, potentially leading to Gambling Disorder (GD) and adverse health and social consequences. Problematic gambling has received little research attention over the years in Israeli society and the issue of gambling is not high on the list of priorities of Israeli policymakers. The present study examined gambling behavior in Israel on a continuum of severity and its association with venues where the gambling occurs, legality, attitude toward the legalization of casinos and poker, and substance use.

Methods

The study questionnaires were distributed to approximately 15,000 Jewish-Israeli adults via internet panel. From 3,088 Israeli adults who answered the questionnaire, 1,251 (40.5%) reported gambling in the last year and were included in the analyses.

Results

Based on the Problem Gambling Severity Index, 60% of participants were classified as non-problem gamblers, 25% as at low-risk for a gambling problem, 11% as at moderate risk, and 4% as having a gambling problem. Most online gambling was practiced by non-problem gamblers (40%) and most illegal gambling was by low-risk gamblers (34%). The more severe the gambling behavior was on the continuum, the more it was associated with illegal substance use and positive attitudes toward legalized casinos in Israel. Logistic regression showed the odds of developing moderate and problem gambling were 3.8 times higher for online gamblers (OR = 3.8; CI 2.6–5.4; p < 0.000) and 3.3 times higher for illegal gamblers (OR = 3.3; CI 2.2–4.9; p < 0.000).

Conclusion

Though more research attention should be paid to gambling behaviors, harm reduction gambling interventions should be made available to all categories on the continuum of severity of gambling behaviors. The present study provides evidence-based information to promote health policies that aim to prevent and reduce harm for Israeli gamblers.
Temporally-correlated massive access: joint user activity detection and channel estimation via vector approximate message passing
Authors: Xiong Yueyue , Li Wei
Published: April 2024

In the paper, we investigate a massive machine-type communication (mMTC), where numerous single-antenna users communicate with a single-antenna base station while being active. However, the status of user can undergoes multiple transitions between active and inactive states across whole consecutive intervals. Then, we formulate the problem of joint user activity detection and channel estimation within the dynamic compressed sensing (DCS) framework, considering the temporally-correlated user activity across the entire consecutive intervals. To be specific, we introduce a new hybrid vector approximate message passing algorithm for DCS (HyVAMP-DCS). The proposed algorithm comprises a VAMP block for estimating channel and a loopy belief propagation (LBP) block for detecting user activity. Moreover, these two blocks can exchange messages, enhancing the performance of both channel estimation and user activity detection. Importantly, compared to the fragile GAMP algorithm, VAMP is robust and applicable to a much broader class of large random matrices. Furthermore, the fixed points of VAMP’s state evolution align with the replica prediction of the minimum mean-squared error. The simulation results illustrate the superiority of HyVAMP-DCS, demonstrating its significant outperformance over HyGAMP-DCS.
HE4-based nomogram for predicting overall survival in patients with idiopathic pulmonary fibrosis: construction and validation
Authors: Tian Mi , Zhu Xiaohui , Ren Lijun , Zhou Xuan , GU Lina , Meng Kaifang , Tian Yaqiong , Cai Hourong , Liu Xiaoqin , Ding Jingjing
Published: April 2024

Idiopathic pulmonary fibrosis (IPF) is a life-threatening interstitial lung disease. Identifying biomarkers for early diagnosis is of great clinical importance. The epididymis protein 4 (HE4) is important in the process of inflammation and fibrosis in the epididymis. Its prognostic value in IPF, however, has not been studied. The mRNA and protein levels of HE4 were used to determine the prognostic value in different patient cohorts. In this study, prognostic nomograms were generated based on the results of the cox regression analysis. We identified the HE4 protein level increased in IPF patients, but not the HE4 gene expression. The increased expression of HE4 correlated positively with a poor prognosis for patients with IPF. The HR and 95% CI were 2.62 (1.61–4.24) (p < 0.001) in the training set. We constructed a model based on the risk-score = 0.16222182 * HE4 + 0/0.37580659/1.05003609 (for GAP index 0–3/4–5/6–8) + (− 1.1183375). In both training and validation sets, high-risk patients had poor prognoses (HR: 3.49, 95%CI 2.10–5.80, p = 0.001) and higher likelihood of dying (HR: 6.00, 95%CI 2.04–17.67, p = 0.001). Analyses of calibration curves and decision curves suggest that the method is effective in predicting outcomes. Furthermore, a similar formulation was used in a protein-based model based on HE4 that also showed prognostic value when applied to IPF patients. Accordingly, HE4 is an independent poor prognosis factor, and it has the potential to predict IPF patient survival.
Investigation on the Micro-Grinding Induced Crystallographic Variations of Nine Different Clinkers
Authors: Kang Hyunuk , Lee Jihoon , Park Jun-Boum , Moon Juhyuk
Published: April 2024

Although clinker has been used for many years, complicated mineralogical properties of clinker pose challenges for the precise quantification. In this study, the mineralogical and crystallographic properties of nine different clinkers according to grinding procedures were investigated. With the dry-grinding for 2 h, particle size reduction to 3 μm of median particle size with a substantial phase transition to an amorphous phase observed, to which alite (C3S) mainly contributed to the transition. Meanwhile, the crystallographic properties of the clinker phases were barely changed during the wet-grinding. In the wet-grinding program, the amount of ferrite solid solution (C4AF) with a high linear absorption coefficient was not underestimated. Furthermore, well-corrected preferred orientation effect on C3S was positively contributed to the analysis result of clinkers with the wet-grinding. Hence, it was suggested that the crystallographic effects observed in the wet-grinding program could produce more reliable results in phase analysis for the clinkers.
Clinging to the top: natal dispersal tracks climate gradient in a trailing-edge population of a migratory songbird
Authors: Gaya Heather E. , Cooper Robert J. , Delancey Clayton D. , Hepinstall-Cymerman Jeffrey , Kurimo-Beechuk Elizabeth A. , Lewis William B. , Merker Samuel A. , Chandler Richard B.
Published: April 2024

Purpose

Trailing-edge populations at the low-latitude, receding edge of a shifting range face high extinction risk from climate change unless they are able to track optimal environmental conditions through dispersal.

Methods

We fit dispersal models to the locations of 3165 individually-marked black-throated blue warblers (Setophaga caerulescens) in the southern Appalachian Mountains in North Carolina, USA from 2002 to 2023. Black-throated blue warbler breeding abundance in this population has remained relatively stable at colder and wetter areas at higher elevations but has declined at warmer and drier areas at lower elevations.

Results

Median dispersal distance of young warblers was 917 m (range 23–3200 m), and dispersal tended to be directed away from warm and dry locations. In contrast, adults exhibited strong site fidelity between breeding seasons and rarely dispersed more than 100 m (range 10–1300 m). Consequently, adult dispersal kernels were much more compact and symmetric than natal dispersal kernels, suggesting adult dispersal is unlikely a driving force of declines in this population.

Conclusion

Our findings suggest that directional natal dispersal may mitigate fitness costs for trailing-edge populations by allowing individuals to track changing climate and avoid warming conditions at warm-edge range boundaries.
Hunting mode and habitat selection mediate the success of human hunters
Authors: Gaynor Kaitlyn M. , McInturff Alex , Abrahms Briana L. , Smith Alison M. , Brashares Justin S.
Published: April 2024

Background

As a globally widespread apex predator, humans have unprecedented lethal and non-lethal effects on prey populations and ecosystems. Yet compared to non-human predators, little is known about the movement ecology of human hunters, including how hunting behavior interacts with the environment.

Methods

We characterized the hunting modes, habitat selection, and harvest success of 483 rifle hunters in California using high-resolution GPS data. We used Hidden Markov Models to characterize fine-scale movement behavior, and k-means clustering to group hunters by hunting mode, on the basis of their time spent in each behavioral state. Finally, we used Resource Selection Functions to quantify patterns of habitat selection for successful and unsuccessful hunters of each hunting mode.

Results

Hunters exhibited three distinct and successful hunting modes (“coursing”, “stalking”, and “sit-and-wait”), with coursings as the most successful strategy. Across hunting modes, there was variation in patterns of selection for roads, topography, and habitat cover, with differences in habitat use of successful and unsuccessful hunters across modes.

Conclusions

Our study indicates that hunters can successfully employ a diversity of harvest strategies, and that hunting success is mediated by the interacting effects of hunting mode and landscape features. Such results highlight the breadth of human hunting modes, even within a single hunting technique, and lend insight into the varied ways that humans exert predation pressure on wildlife.