bluuebunny/crossref_metadata_2025 huggingface dataset:
Surgical outcomes of pars plana vitrectomy for intraocular complications related to vasoproliferative tumour of the retina
Authors: Lee Zher Jong Joel , Jawaheer Lona , Spiteri-Cornish Kurt , Chawla Anand
Published: July 2023

Purpose:

To investigate the safety and efficacy of vitrectomy (PPV) in managing intraocular complications relating to vasoproliferative tumours of the retina (VPL).

Methods:

Retrospective study. 17 VPL patients who underwent vitrectomy at Sheffield Teaching Hospital NHS Trust from 2005 to 2020 were included. Patient demographics, clinical characteristics, intraoperative data and surgical outcomes were collected and evaluated.

Results:

The mean age was 52 years. Indications for PPV included epiretinal membrane (ERM, n=7), vitreous haemorrhage (VH, n=5), retinal detachment (RD, n=3), diagnostic (n=1) and others (n=1). After PPV, 14/17(82.4%) have stabilised vision, and 3/17(17.6%) deteriorated. Subgroup analysis of ERM peel had good outcomes with 6/7(85.7%) noticing improvement or stabilisation of symptoms, mean LogMAR visual acuity improved from 0.719[6/30]±0.267[6/12] to 0.476[6/19]±0.271[6/12]. Patients undergoing surgery for VH also had good outcomes with resolution (and no recurrence) of the haemorrhage in 3/5(60%) and 5/5(100%) with one or more surgeries respectively. Outcomes for RD surgery were LogMAR 2.126[HM]±0.301[6/12] pre-operatively and 1.185[6/95]±0.522[6/19] post-operatively, with one recurrence of retinal detachment. In the ERM group, 3 patients had adjunctive treatment for VPL intraoperatively and 4 patients had none, no difference found between the two groups in terms of outcome or complications. Tumour with thickness of ≥2mm exhibited inferior visual outcomes compared to <2mm (p<0.05).

Conclusions:

This is one of the largest datasets in looking at outcomes of vitrectomy for complications of VPL. PPV is effective and safe in managing VPL-related intraocular complications with good outcomes and a low rate of complications, especially for patients with ERM and VH.
Climate Change and Healthcare: Creating a Sustainable and Climate-Resilient Health Delivery System
Authors: Wade Rebecca
Published: July 2023

Climate change poses global challenges as rising temperatures, recurring natural disasters, and the resulting increase in the prevalence of acute and long-term climate-related diseases threaten the health and safety of populations worldwide. The healthcare sector, one of the largest sources of greenhouse gas emissions globally, both exacerbates and suffers from these effects. As leaders in their local communities and the national economy, hospitals and health systems have a responsibility to not only build climate resilience to withstand disaster events but also implement sustainability initiatives that will reduce the healthcare sector's carbon footprint. A wide variety of initiatives that can meet all financial plans and timelines are available. This discussion focuses on three of the most impactful areas for opportunity: building resilience through community, operating room sustainability, and renewable energy sources.
Raising the self-esteem and reducing irrational beliefs of schoolchildren: The moderating and main effect study
Authors: Onyemaechi Ede Moses , Okeke Chinedu Ifedi , Oneli Joy Obiageli
Published: July 2023

Background:

Several systematic reviews and meta-analyses studies have called for moderators of treatment outcomes and their main effect with regard to disadvantaged populations. In view of that, this study investigated the impacts and moderators of rational emotive behavior therapy (REBT) on the self-esteem and irrational beliefs of Schoolchildren in Ebonyi State Nigeria.

Methods:

A group randomized controlled design was utilized to assign 55 schoolchildren to the treatment group and 55 schoolchildren to waitlisted control group. Two self-report measures (Self-Esteem Scale and Children Adolescent Scale of Irrationality) were used to assess the participants. There were pretest, posttest, and follow-up tests given at different intervals to ascertain the baseline, main effect, and long-term effects of the treatment. The data collected were analyzed using a 2-way analysis of covariance statistic.

Results:

The results of the 2-way analysis of covariance demonstrated a difference between participants in the waitlisted control group at the pretest, posttest, and follow-up test and a positive improvement in schoolchildren with illogical beliefs as a result of exposure to REBT intervention. It was discovered that the REBT intervention changed schoolchildren’s self-esteem and irrational views into rational ones. A later test result supported the intervention’s consistent and significant effects in lowering illogical beliefs and raising students’ self-esteem. The results also showed that there is no connection between gender and group membership.

Conclusion:

This study suggests that REBT is a significant treatment strategy that reduces irrational beliefs and improves the self-esteem of primary school children. Based on these outcomes, further studies should replicate the study in other cultures with such a disadvantaged group.
Tumor-induced osteomalacia combined with increased bone resorption postoperatively: A case report
Authors: Shi Lingfeng , Tang Mengjia , Duan Shanshan , Deng Fang , Zhang Yuping , Yang Jing , Hu Jiongyu
Published: July 2023

Rationale:

Rare tumor-induced osteomalacia (TIO) usually resulted in bone pain, fragility fractures and muscle weakness in clinical, which is caused by the reduced phosphate reabsorption, thus impaired mineralization of the bone matrix and free energy transfer. The specific problems in postsurgical patients are obscure although surgical removal of the tumor is the only definitive treatment. Here, we documented a female TIO patient who suffered more severe bone pain and muscle spasms post-operation. Further, we presented and discussed our explanation for the unexpected symptoms.

Patient concerns:

The main symptoms were whole-body pain and muscle weakness. The patient also presented with osteoporosis and multiple fractures.

Diagnosis:

Elevated serum fibroblast growth factor 23 (FGF23) level and hypophosphatemia indicated the diagnosis of TIO. Positron emission tomography (PET)/computed tomography (CT) with 68 Ga-DOTATATE located the tumor in the dorsolateral part of the left foot. Histopathological examinations confirmed the diagnosis.

Interventions:

The tumor was surgically removed immediately after the diagnosis of TIO and localization of the tumor. Postoperatively, calcium carbonate supplement treatment was continued.

Outcomes:

Two days after surgery, the serum FGF23 level was decreased to the normal range. Five days after surgery, N-terminal propeptide of type I procollagen and β-CrossLaps (β-CTx) had a remarkable increase. A month after surgery, the patient N-terminal propeptide of type I procollagen and β-CTx levels were decreased obviously, and serum FGF23, phosphate and 24h urinary phosphate were in the normal range.

Lessons:

We report a female patient who presented with osteoporosis and fractures. She was found with an elevation of FGF23 and diagnosis with TIO after PET/CT scanning. After surgically removing the tumor, the patient experienced more severe bone pain and muscle spasms. Active bone remodeling might be the reason for the symptoms. Further study will reveal the specific mechanism for this abnormal bone metabolism.
Long-term effects of integrated cognitive behavioral therapy for chronic pain: A qualitative and quantitative study
Authors: Tsubaki Kanako , Taguchi Kayoko , Yoshida Tokiko , Takanashi Rieko , Shimizu Eiji
Published: July 2023

Cognitive behavioral therapy (CBT) is known to improve chronic pain management. However, past studies revealed only small to moderate benefits in short-term results, and long-term follow-up studies are lacking. This study aimed to follow an integrated CBT program’s effectiveness 1.5 years after its completion. This observational study was the follow-up on the data collected from our CBT sessions conducted under 3 different studies in 2018 to 2019. Seven assessment items (Numerical Rating Scale, Pain Catastrophizing Scale [PCS], Pain Disability Assessment Scale [PDAS], Patient Health Questionnaire-9 items, Generalized Anxiety Disorder 7, European quality of life 5-dimensions 5-level, and Beck Depression Inventory [BDI]) were statistically analyzed. Thematic analysis was conducted in semi structured interviews. PCS (F = 6.52, P = .003), PDAS (F = 5.68, P = .01), European quality of life 5-dimensions 5-level (F = 3.82, P = .03), and BDI (F = 4.61, P = .01) exhibited significant changes (P < .05), confirmed by pairwise t test, revealing a moderate to large effect size. From post-treatment to follow-up, all scores showed no significant changes (P > .1). In the qualitative study, the analysis revealed 3 subthemes: “Autonomy,” “Understanding of yourself and pain,” and “Acceptance of pain.” Our study suggests that integrated CBT may reduce the scores of PCS, PDAS and BDI, and this effect lasts for at least 1 year. Identified themes support the relevance of mitigative factors in managing chronic pain.
Advances in cochlear gene therapies
Authors: Klimara Miles J. , Smith Richard J.H.
Published: July 2023

Purpose of review

Hearing loss is the most common sensory deficit and in young children sensorineural hearing loss is most frequently genetic in etiology. Hearing aids and cochlear implant do not restore normal hearing. There is significant research and commercial interest in directly addressing the root cause of hearing loss through gene therapies. This article provides an overview of major barriers to cochlear gene therapy and recent advances in preclinical development of precision treatments of genetic deafness.

Recent findings

Several investigators have recently described successful gene therapies in many common forms of genetic hearing loss in animal models. Elegant strategies that do not target a specific pathogenic variant, such as mini gene replacement and mutation-agnostic RNA interference (RNAi) with engineered replacement, facilitate translation of these findings to development of human therapeutics. Clinical trials for human gene therapies are in active recruitment.

Gene therapies for hearing loss are expected to enter clinical trials in the immediate future. To provide referral for appropriate trials and counseling regarding benefits of genetic hearing loss evaluation, specialists serving children with hearing loss such as pediatricians, geneticists, genetic counselors, and otolaryngologists should be acquainted with ongoing developments in precision therapies.
Differential genome-wide associated variants and enriched pathways of electrocardiogram parameters among people with versus without HIV
Authors: He Jiayu , Ding Yingying , Lin Haijiang , Liu Xing , Chen Xiaoxiao , Shen Weiwei , Zhou Sujuan , Feng Cheng , Wang Miaochen , Xia Jingjing , He Na
Published: July 2023

Objectives:

People with HIV (PWH) are more likely to develop electrocardiogram (ECG) abnormalities. Substantial evidence exists for genetic contribution to ECG parameters among general population. However, whether and how would host genome associate with ECG parameters among PWH is unclear. Our research aims to analyze and compare genetic variants, mapped genes and enriched pathways of ECG parameters among PWH and HIV-negative controls.

Design:

A cross-sectional study.

Method:

We performed a large original genome-wide association study (GWAS) of ECG parameters among PWH (n = 1730) and HIV-negative controls (n = 3746). Genome-wide interaction analyses were also conducted.

Results:

A total of 18 novel variants were detected among PWH, six for PR interval including rs76345397 at ATL2, eleven for QRS duration including rs10483994 at KCNK10 and rs2478830 at JCAD, and one for QTc interval (rs9815364). Among HIV-negative controls, we identified variants located at previously reported ECG-related genes (SCN5A, CNOT1). Genetic variants had a significant interaction with HIV infection (P < 5 × 10−8), implying that HIV infection and host genome might jointly influence ECG parameters. Mapped genes for PR interval and QRS duration among PWH were enriched in the biological process of viral genome replication and host response to virus, respectively, whereas enriched pathways for PR interval among HIV-negative controls were in the cellular component of voltage-gated sodium channel complex.

Conclusion:

The present GWAS indicated a distinctive impact of host genome on quantitative ECG parameters among PWH. Different from HIV-negative controls, host genome might influence the cardiac electrical activity by interfering with HIV viral infection, production and latency among PWH.
Nasal-Type Extranodal Natural Killer/T-Cell Lymphoma Recurrence at Penile Glans Masquerading Urinary Contamination on 18F-FDG PET/CT
Authors: Zhang Yue , Yu Liqian , Wang Rang , Su Minggang
Published: July 2023

A 69-year-old man with a history of extranodal NK/T-Cell lymphoma, nasal type (ENKTL-NT) performed an interim 18F-FDG PET/CT for response evaluation. It showed an intense focal uptake at his penile glans, which was suspected as urinary contamination initially. However, he complained with redness and swelling of his penis during further history inquiry. After careful observation, the diagnosis of ENKTL-NT recurrence at penile glans was highly suspected. It was confirmed by percutaneous biopsy of the penile glans finally.
Forehead Flap Reconstruction in Different Nasal Defect: 58 Patients’ Psychological Outcomes
Authors: Yen Cheng-I , Su Yi-Jen , Chang Chun-Shin , Chen Hung-Chang , Yang Shih-Yi , Chang Shu-Yin , Yang Jui-Yung , Chuang Shiow-Shuh , Hsiao Yen-Chang
Published: July 2023

Forehead flap nasal reconstruction is a lengthy process; the final outcome requires multiple stages and several months to achieve. After flap transfer, the pedicle flap has to be kept attached to the face for weeks, which may lead to a variety of psychosocial distress and challenges for patients. From April 2011 to December 2016, 58 patients who underwent forehead flap reconstruction for nasal reconstruction were included. The general satisfaction questionnaire, Derriford Appearance Scale 19, and Brief Fear of Negative Evaluation Scale, were utilized to assess the change in psychosocial functioning over 4 time points: preoperative (time 1), 1 week after forehead flap transfer (time 2), 1 week after forehead flap division (time 3), and final outcome after refinement procedures (time 4). The patients were also divided into 3 groups based on the severity of nasal defects: defects involving only a single subunit (n=19), subtotal nasal defects (n=25), and total nasal defects (n=13). Between- and within-group comparisons were conducted. The vast majority of patients had the highest levels of postoperative distress and social avoidance immediately after flap transfer; these levels decreased after flap division and refinement procedures. The psychosocial functioning was more strongly affected by the stage time point than by the severity of the original nasal defects. The forehead flap nasal reconstruction can not only help patients gain a relatively normal nose but also restore their self-esteem and social confidence. The lengthy process is beneficial and worthwhile, even though it involves short-term psychosocial distress.
Agromyces larvae sp. nov., a novel actinobacterium isolated from gut of larvae of Protaetia brevitarsis seulensis
Authors: Won Miyoung , Subramanian Parthiban , Kim Seunghwan , Heo Jun , Naito Hanako , Asano Tomomi , Hamada Moriyuki , Kwon Soon-Wo
Published: July 2023

A novel actinobacterium strain, designated CFWR-12T, was isolated from the larval gut of Protaetia brevitarsis seulensis grown at the National Institute of Agricultural Sciences, Wanju-gun, Republic of Korea, and its taxonomic position was evaluated. Strain CFWR-12T was aerobic, Gram-stain-positive and non-motile. Growth occurred at 10–40 °C, pH 6.0–9.0 and 0–4 % (w/v) NaCl, with optimal growth at 28–30 °C, pH 7.0 and in the absence of NaCl. Strain CFWR-12T showed high 16S rRNA gene sequence similarity to

Agromyces intestinalis

KACC 19306T (99.0 %) and

Agromyces protaetiae

FW100M-8T (97.9 %). The genome sequence of strain CFWR-12T was 4.01 Mb in size with a high G+C content of 71.2 mol%. The values of average nucleotide identity and digital DNA–DNA hybridization between strain CFWR-12T and

A. intestinalis

KACC 19306T were 89.8 and 39.1 %, respectively, which were the highest among the closely related

Agromyces

species. The predominant cellular fatty acids (>10 %) were iso-C16 : 0, anteiso-C15 : 0 and anteiso-C17 : 0, and the major respiratory quinones (>10 %) were MK-11 and MK-12. The polar lipids were composed of diphosphatidylglycerol, phosphatidylglycerol, an unidentified glycolipid and an unidentified lipid while the peptidoglycan type was identified to be B1. Data based on chemotaxonomic, phylogenetic, phenotypic and genomic evidence demonstrated that strain CFWR-12T represents a novel species of the genus

Agromyces

, for which the name Agromyces larvae sp. nov. is proposed. The type strain is strain CFWR-12T (=KACC 19307T= NBRC 113047T).
Epigenetic Germline Variants Predict Cancer Prognosis and Risk and Distribute Uniquely in Topologically Associating Domains
Authors: Goudarzi Shervin , Pagadala Meghana , Klie Adam , Talwar James V. , Carter Hannah
Published: July 2023

Cancer is a highly heterogeneous disease caused by genetic and epigenetic alterations in normal cells. A recent study uncovered methylation quantitative trait loci (meQTLs) associated with different levels of local DNA methylation in cancers. Here, we investigated whether the distribution of cancer meQTLs reflected functional organization of the genome in the form of chromatin topologically associated domains (TADs), and evaluated whether cancer meQTLs near known driver genes have the potential to influence cancer risk or progression. At TAD boundaries, we observed differences in the distribution of meQTLs when one or both of the adjacent TADs was transcriptionally active, with higher densities near inactive TADs. Furthermore, we found differences in cancer meQTL distributions in active versus inactive TADs and observed an enrichment of meQTLs in active TADs near tumor suppressors, whereas there was a depletion of such meQTLs near oncogenes. Several meQTLs were associated with cancer risk in the UKBioBank, and we were able to reproduce breast cancer risk associations in the DRIVE cohort. Survival analysis in TCGA implicated a number of meQTLs in 13 tumor types. In 10 of these, polygenic meQTL scores were associated with increased hazard in a CoxPH analysis. Risk and survival-associated meQTLs tended to affect cancer genes involved in DNA damage repair and cellular adhesion and reproduced cancer-specific associations reported in prior literature. In summary, this study provides evidence that genetic variants that influence local DNA methylation are affected by chromatin structure and can impact tumor evolution.
Factors associated with mental health disorders among students at Busitema University, an exploratory qualitative study among students at Mbale and Busia campus
Authors: Kagoya Enid Kawala , Mpagi Joseph.L. , Waako Paul , Wandabwa Julius , Saphina Biira , Birabwa Elizabeth , Acon Sophie , Otim Daniel , Kucel Samuelbaker , Kirabira Joseph
Published: July 2023

Background

Following the loss of several students at Busitema University faculty of health sciences and other branches, there was an urgent need to understand the factors contributing to the death of the students and it was anticipated that most of them succumbed to mental health issues. This study aimed to explore the potential factors associated with mental health disorders among students at Busitema University.

Methods

Key informant interviews were conducted among the students who were diagnosed with mental health disorders. A total of 42 key informant interviews were conducted following a well-structured interview grid. All participants consented during the study. Each interview was audiotaped and recordings were later subjected to verbatim transcription. Each transcript was carefully reviewed by the principal investigator prior to the analysis. Thematic content analysis was done following a deductive approach. Dedoose software was used to support the coding and categorization of thematic areas.

Results

The results indicate that several factors associated with mental health disorders included alcohol and substance use, poor learning environment, stringent and unfavourable university policies, the big gap that exists between students and administration, relationship challenges, academic pressure, family factors (Broken families, poverty), Gambling, lack of curricular activities, poor counselling services and political pressures.

Conclusions

Considering the high propensity of mental health issues that hinder the success of students at the university level. It’s worth paramount for universities to continually evaluate the mental health of their students and tailor treatment programs and other cost-effective interventions to specifically target students.
Use of supervised machine learning algorithms in predicting postoperative mortality in gastrointestinal and HPB surgeries
Authors: Vasavada Bhavin
Published: July 2023

Aim of the study

This study aims to evaluate supervised machine learning algorithms in predicting 90 days post-operative mortality in gastrointestinal and HPB surgeries and comparing them with standard logistic regression methods.

Methods

We evaluated various supervised machine learning classification algorithms like gradient boosting, K-nearest neighbours, random forest, and support vector machines with standard logistic regression methods. We used accuracy and the Receiver operating curve to compare the methods. 60% of the data were used for training, 20% for validation and 20% for testing. We used JASP 0.16.04 by the University of Amsterdam to run machine learning algorithms and statistical analysis.

Results

We used data from 504 patients who have undergone gastrointestinal and hepatopancreatic biliary surgery between April 2016 and March 2023. We analyzed algorithms for predicting 90 days post-operative mortality based on features like Major surgeries, Surgeries for malignancies, age, CDC grade of surgeries, Intraoperative hypotension, Open vs Laparoscopic surgeries, ASA grade, Emergency surgeries, Operative time, Intraoperative blood product used, colorectal surgeries, small intestinal surgeries, HPB surgeries, upper gastrointestinal surgeries and hernia. Test accuracies were 96% for gradient boosting, 90 % for K-nearest neighbours, 96% for the random forest, 94% for support vector and Areas under the ROC curve were 0.802 for gradient boosting, 0.489 for K-nearest neighbours, 0.934 for random forest and 0.5 for support vector algorithms. Accuracy and Area under the ROC curve with standard logistic regression method were 94% and 0.757. Features of importance in decreasing order were ASA, operative times, blood products, small bowel surgeries and Age.

Conclusion

Supervised machine learning algorithms particularly gradient boosting and random forest predicted 90 days post-operative mortality more accurately than logistic regression and such models can be part of the preoperative evaluation in gastrointestinal and HPB surgeries.
Examining ChatGPT’s Ability to Answer Cirrhosis Related Questions in Arabic Compared to English
Authors: Samaan Jamil S. , Yeo Yee Hui , Ng Wee Han , Ting Peng-Sheng , Trivedi Hirsh , Vipani Aarshi , Yang Ju Dong , Liran Omer , Spiegel Brennan , Kuo Alexander , Ayoub Walid
Published: July 2023

Background and Study Aims

Cirrhosis is a chronic progressive disease which requires complex care. Its incidence is rising in the Arab countries making it the 7thleading cause of death in the Arab League in 2010. ChatGPT is a large language model with a growing body of literature demonstrating its ability to answer clinical questions. We examined ChatGPT’s accuracy in responding to cirrhosis related questions in Arabic and compared its performance to English.

Materials and Methods

ChatGPTs responses to 91 questions in Arabic and English were graded by a transplant hepatologist fluent in both languages. Accuracy of responses was assessed using the scale: 1. Comprehensive, 2. Correct but inadequate, 3. Mixed with correct and incorrect/outdated data, and 4. Completely incorrect. Accuracy of Arabic compared to English responses was assessed using the scale: 1. Arabic response is more accurate, 2. Similar accuracy, 3. Arabic response is less accurate.

Results

The model provided 22 (24.2%) comprehensive, 44 (48.4%) correct but inadequate, 13 (14.3%) mixed with correct and incorrect/outdated data and 12 (13.2%) completely incorrect Arabic responses. When comparing the accuracy of Arabic and English responses, 9 (9.9%) of the Arabic responses were graded as more accurate, 52 (57.1%) similar in accuracy and 30 (33.0%) as less accurate compared to English.

Conclusion

ChatGPT has the potential to serve as an adjunct source of information for Arabic speaking patients with cirrhosis. The model provided correct responses in Arabic to 72.5% of questions, although its performance in Arabic was less accurate than in English. The model produced completely incorrect responses to 13.2% of questions, reinforcing its potential role as an adjunct and not replacement of care by licensed healthcare professionals. Future studies to refine this technology are needed to help Arabic speaking patients with cirrhosis across the globe understand their disease and improve their outcomes.
Genetic structure of major depression symptoms across clinical and community cohorts
Authors: Adams Mark J , Thorp Jackson G , Jermy Bradley S , Kwong Alex S F , Kõiv Kadri , Grotzinger Andrew D , Nivard Michel G , Marshall Sally , Milaneschi Yuri , Baune Bernhard T , Müller-Myhsok Bertram , Penninx Brenda WJH , Boomsma Dorret I , Levinson Douglas F , Breen Gerome , Pistis Giorgio , Grabe Hans J , Tiemeier Henning , Berger Klaus , Rietschel Marcella , Magnusson Patrik K , Uher Rudolf , Hamilton Steven P , Lucae Susanne , Lehto Kelli , Li Qingqin S , Byrne Enda M , Hickie Ian B , Martin Nicholas G , Medland Sarah E , Wray Naomi R , Tucker-Drob Elliot M ,   Estonian Biobank Research Team,   Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, Lewis Cathryn M , McIntosh Andrew M , Derks Eske M
Published: July 2023

Diagnostic criteria for major depressive disorder allow for heterogeneous symptom profiles but genetic analysis of major depressive symptoms has the potential to identify clinical and aetiological subtypes. There are several challenges to integrating symptom data from genetically-informative cohorts, such as sample size differences between clinical and community cohorts and various patterns of missing data. We conducted genome-wide association studies of major depressive symptoms in three clinical cohorts that were enriched for affected participants (Psychiatric Genomics Consortium, Australian Genetics of Depression Study, Generation Scotland) and three community cohorts (Avon Longitudinal Study of Parents and Children, Estonian Biobank, and UK Biobank). We fit a series of confirmatory factor models with factors that accounted for how symptom data was sampled and then compared alternative models with different symptom factors. The best fitting model had a distinct factor forAppetite/Weightsymptoms and an additional measurement factor that accounted for missing data patterns in the community cohorts (use of Depression and Anhedonia as gating symptoms). The results show the importance of assessing the directionality of symptoms (such as hypersomnia versus insomnia) and of accounting for study and measurement design when meta-analysing genetic association data.
Characterising information gains and losses when collecting multiple epidemic model outputs
Authors: Sherratt Katharine , Srivastava Ajitesh , Ainslie Kylie , Singh David E. , Cublier Aymar , Marinescu Maria Cristina , Carretero Jesus , Cascajo Garcia Alberto , Franco Nicolas , Willem Lander , Abrams Steven , Faes Christel , Beutels Philippe , Hens Niel , Müller Sebastian , Charlton Billy , Ewert Ricardo , Paltra Sydney , Rakow Christian , Rehmann Jakob , Conrad Tim , Schütte Christof , Nagel Kai , Abbott Sam , Grah Rok , Niehus Rene , Prasse Bastian , Sandmann Frank , Funk Sebastian
Published: July 2023

Background

Collaborative comparisons and combinations of epidemic models are used as policy-relevant evidence during epidemic outbreaks. In the process of collecting multiple model projections, such collaborations may gain or lose relevant information. Typically, modellers contribute a probabilistic summary at each time-step. We compared this to directly collecting simulated trajectories. We aimed to explore information on key epidemic quantities; ensemble uncertainty; and performance against data, investigating potential to continuously gain information from a single cross-sectional collection of model results.

Methods

We compared July 2022 projections from the European COVID-19 Scenario Modelling Hub. Five modelling teams projected incidence in Belgium, the Netherlands, and Spain. We compared projections by incidence, peaks, and cumulative totals. We created a probabilistic ensemble drawn from all trajectories, and compared to ensembles from a median across each model’s quantiles, or a linear opinion pool. We measured the predictive accuracy of individual trajectories against observations, using this in a weighted ensemble. We repeated this sequentially against increasing weeks of observed data. We evaluated these ensembles to reflect performance with varying observed data.

Results

By collecting modelled trajectories, we showed policy-relevant epidemic characteristics. Trajectories contained a right-skewed distribution well represented by an ensemble of trajectories or a linear opinion pool, but not models’ quantile intervals. Ensembles weighted by performance typically retained the range of plausible incidence over time, and in some cases narrowed this by excluding some epidemic shapes.

Conclusions

We observed several information gains from collecting modelled trajectories rather than quantile distributions, including potential for continuously updated information from a single model collection. The value of information gains and losses may vary with each collaborative effort’s aims, depending on the needs of projection users. Understanding the differing information potential of methods to collect model projections can support the accuracy, sustainability, and communication of collaborative infectious disease modelling efforts.

Data availability

All code and data available on Github:https://github.com/covid19-forecast-hub-europe/aggregation-info-loss
Alzheimer’s disease polygenic risk associated dynamic functional networks and anatomical asymmetry
Authors: Rubido Nicolas , Riedel Gernot , Vuksanović Vesna
Published: July 2023

Genetic associations with macroscopic brain networks can provide insights into healthy and aberrant cortical connectivity in disease. However, associations specific to dynamic functional connectivity in Alzheimer’s disease are still largely unexplored. Understanding the association between gene expression in the brain and functional connectivity may provide useful information about the molecular processes underlying variations in impaired brain function. Given the potential of dynamic functional connectivity to uncover brain states associated with Alzheimer’s disease, it is interesting to ask: How does gene expression associated with Alzheimer’s disease map onto the dynamic functional brain connectivity? If genetic variants associated with neurodegenerative processes involved in Alzheimer’s disease are to be correlated with brain function, it is essential to generate such a map. Here, we investigate how the relation between gene expression in the brain and dynamic functional connectivity arises from nodal interactions, quantified by their role in network centrality (i.e., the drivers of the metastability), and the principal component of genetic co-expression across the brain. Our analyses include genetic variations associated with Alzheimer’s disease and also genetic variants expressed within the cholinergic brain pathways. Our findings show that contrasts in metastability of functional networks between Alzheimer’s and healthy individuals can in part be explained by the two combinations of genetic co-variations in the brain with the confidence interval between 72% and 92%. The highly central nodes, driving the brain aberrant metastable dynamics in Alzheimer’s disease highly correlate with the magnitude of variations of the two combinations of genes expressed in brain. These nodes include mainly the white matter, parietal and occipital brain regions, each of which (or their combinations) are involved in impaired cognitive function in Alzheimer’s disease. In addition, our results provide evidence of the role of genetic associations across brain regions in asymmetric changes in ageing. We validated our findings on the same cohort using alternative brain parcellation methods. This work demonstrates how genetic variations underpin anomaly in dynamic functional connectivity in Alzheimer’s disease.
Reliability and validity of physical function tests and ADL survey questions in women living in rural, highland Ethiopia
Authors: Golan Jenna , Thalacker-Mercer Anna , Hoddinott John
Published: July 2023

In rural, highland Ethiopia, physical function, which is the physical ability to fulfill one’s daily roles and responsibilities, may be compromised by a lack of access to nutrition, healthcare, and sanitation. Decreased physical function would be detrimental to health and income-generating activities. Unfortunately, there is a lack of validated methods to measure physical function in adult women in this region. This validity study evaluated the feasibility and reliability of physical tests, including the sit-to-stand (STS) and usual gait speed (UGS). The physical tests were used to assess the validity of context-appropriate activities of daily living (ADL) questions. The results of the STS were used to calculate a power index (Psts) which accounted for body mass and leg length. Feasibility was ascertained qualitatively. Reliability was assessed by comparing the results of the tests and questions between each visit using either Cohen’s κ or Pearson’s ρ. Validity was assessed by regressing the responses to the ADL questions against Psts, controlling for relevant participant characteristics. Study participants consisted of 316 women between the age of 18 and 45 years, living in rural Tigray, Ethiopia, that had previously participated in an impact evaluation of a safety net program. Over a one-week period, participants completed the STS and UGS tests and responded to the ADL questionnaires three times. Pstswas determined to be a feasible, reliable, and valid physical function test for women in rural, highland Ethiopia. UGS lacked feasibility and reliability. The validity of the ADLs was inconclusive. The Pstswill be an essential tool for improving physical function and, subsequently, health and quality of life in rural Ethiopia.
A Randomized Comparison of Radial Artery Intimal Hyperplasia Following Distal vs. Proximal Transradial Access for Coronary Angiography: PRESERVE RADIAL Trial
Authors: Tehrani Behnam N. , Sherwood Matthew W. , Damluji Abdulla A. , Epps Kelly C. , Bakhshi Hooman , Cilia Lindsey , Dassanayake Isuru , Eltebaney Moemen , Gattani Raghav , Howard Edward , Kepplinger David , Ofosu-Somuah Araba , Batchelor Wayne B.
Published: July 2023

Background

Distal transradial access (dTRA) is an alternative to conventional forearm transradial access (fTRA) for coronary angiography (CAG). Differences in healing of the radial artery in the forearm (FRA) have not been evaluated between these 2 access strategies. We sought to compare FRA intimal-medial thickening (IMT) in patients randomized to dTRA vs. fTRA for CAG.

Methods and Results

Sixty-four consecutive patients undergoing non-emergent CAG were randomized (1:1) to dTRA vs. fTRA. Ultrahigh resolution (55 MHz) vascular ultrasound) of the FRA and distal RA was performed pre-CAG and at 90 days. Primary endpoint was 90-day FRA IMT. Secondary endpoints included procedural characteristics, vascular injury, RA occlusion and ipsilateral hand pain and function. Baseline demographics and clinical characteristics, mean FRA IMT, time to RA access, procedure time, and radiation exposure were similar between the dTRA and fTRA cohorts. There were no between group differences in 90-day FRA IMT (0.37 mm vs 0.38 mm, respectively;p=0.73). No RA occlusions or signs of major vascular injury were observed at 90 days. Ipsilateral hand pain and function (Borg pain scale:12 vs 11,p=0.24; DASH scores: 6 vs 8,p=0.46) were comparable.

Conclusions

In this single center randomized clinical trial, similar patterns of FRA vascular healing at 90 days, procedural results as well as hand pain and function were observed following dTRA vs. fTRA for CAG. Further investigation is warranted to better understand the mechanistics and predictors of RA healing and to identify strategies aimed at preserving RA integrity for future procedures.

What is New?

DTRA has been proposed as an alternative to traditional fTRA in the wrist for CAG and PCI because of ergonomic and post-procedural recovery benefits to the patient, as well as potential reductions in occlusion of the FRA.

There are gaps in knowledge, however, regarding potential differences in remodeling of the FRA in patients undergoing dTRA versus fTRA.

In this randomized clinical trial, there were no differences in IMT and patterns of vascular injury and healing, using ultrahigh resolution (55 MHz) ultrasound, at 90 days in patients randomized to dTRA or FTRA for elective and non-emergent CAG and PCI.

What Are the Clinical Implications

Our findings highlight the need for further inquiry through large multicenter randomized clinical trials to better the understand the mechanistics and predictors of IMT and to identify strategies to mitigate the adverse effects of vessel remodeling in patients undergoing TRA across the entire severity spectrum of cardiovascular disease.
Outbreak risks, cases, and costs of vaccination strategies against wild poliomyelitis in polio-free settings: a modelling study
Authors: Auzenbergs Megan , Abbas Kaja , Voorman Arie , Peak Corey , Jit Mark , O’Reilly Kathleen M
Published: July 2023

Background

Polio eradication was threatened in 2022 by importation of wild poliovirus serotype 1 into Malawi with subsequent international spread, representing the first wild polio cases in Africa since 2014. Preventing importations and spread of wild poliovirus is critical, and dependent on population immunity provided through routine immunisation and supplementary immunisation activities (SIAs). However, the scale of preventative SIAs has reduced in recent years due to financial constraints.

Methods

We developed a mathematical model of polio transmission dynamics to evaluate the probability of an outbreak, expected number of poliomyelitis cases, and the costs associated with vaccination delivery through routine immunisation (RI), outbreak response SIAs (oSIAs) and preventative SIAs (pSIAs). Across varying levels of routine immunisation coverage, we explore three key strategies: RI+oSIAs, RI+oSIAs+annual pSIAs, and RI+oSIAs+biannual pSIAs.

Results

The annual pSIA strategy (RI+oSIAs+annual pSIAs) had higher costs but greater probability of no outbreaks: under our model assumptions, annual pSIAs result in 80% probability of no outbreaks when routine immunisation coverage ≥50%. The biannual pSIA strategy (RI+oSIAs+biannual pSIAs) costs less and averts more outbreaks than RI+oSIAs, but RI coverage ≥65% was required to achieve equivalent risk of no outbreaks. The strategy with no pSIAs (RI+oSIAs) had the lowest costs but required ≥75% RI coverage to achieve equivalent risk of no outbreaks.

Conclusion

Prioritisation of pSIAs must balance outbreak risk against implementation costs, ideally favouring the smallest manageable outbreak risk compatible with elimination. We infer that there are few short-term risks due to population immunity from RI, but without pSIAs, long-term risks accumulate and can result in outbreaks with potential for international spread. We do not consider the costs of further delaying the eradication timeline or societal implications of outbreaks, both of which emphasise the need for pSIAs.
Single-cell transcriptomic analysis of NK cell dynamics in myeloma patients reveal persistent reduction of cytotoxic NK cells from diagnosis to relapse
Authors: Tahri Sabrin , de Jong Madelon M.E. , Fokkema Cathelijne , Papazian Natalie , Kellermayer Zoltán , Vermeulen Michael , van Duin Mark , van Beek Gregory , Hoogenboezem Remco , van de Woestijne Pieter , Nasserinejad Kazem , Saraci Elona , D’Agostino Mattia , Gay Francesca , van der Velden Vincent H.J. , Sanders Mathijs A. , Zweegman Sonja , van de Donk Niels W.J.C. , Broijl Annemiek , Sonneveld Pieter , Cupedo Tom
Published: July 2023

Natural killer (NK) cells mediate the cytotoxic immune response against multiple myeloma and are important effector cells in immune therapies through antibody-dependent cellular cytotoxicity. Here, we used single-cell transcriptomics, flow cytometry and functional assays to investigate the bone marrow NK cell compartment of myeloma patients at diagnosis, during treatment and after relapse. The bone marrow of myeloma patients is characterized by a reduction in conventional cytotoxic NK cells that persists throughout treatment. We show in 20% of newly diagnosed myeloma patients that an altered balance between cytotoxic and cytokine-producing NK cells translates into a reduced cytotoxic ability in response to therapeutic antibodies. The relative loss of cytotoxic NK cells persists at relapse and is accompanied by an expansion of IFN-responsive NK cells. These findings reveal previously unappreciated alterations in bone marrow NK cell composition and highlight the importance of understanding the bone marrow immune system in patients receiving immunotherapies.

Statement of significance

The bone marrow of multiple myeloma patients is characterized by a persistent reduction in cytotoxic CD56dimNK cells, accompanied by inferiorin vitroresponses to therapeutic antibodies at diagnosis and an increase in IFN-responsive NK cells at relapse. These findings highlight the importance of understanding the BM microenvironment in multiple myeloma patients receiving immunotherapies.
Leadership and information transfer in groups escaping a (simulated) threat in the wild
Authors: Rathore Akanksha , Vadavalli Bhavya Deepti , Jadhav Vivek , Isvaran Kavita , Guttal Vishwesha
Published: July 2023

Collective motion in many species is believed to be driven by predation, which is considered a crucial evolutionary force. However, there are limited studies on how information about predators spreads through a group, particularly in natural settings. Here, using high-resolution drone-based recordings, we analyze the collective escape dynamics of a group living species – blackbuck (Antilope cervicara), an Indian antelope – under the conditions of a simulated threat in their natural grassland habitat. Our analysis reveals that, in response to the simulated threat, group cohesion first increases, followed by a simultaneous increase in median speed and polarization. We also observe the emergence of a temporary leader-follower relationship during the collective escape. Interestingly, we found that the distance of individuals from the “predator” affected only their response time, not their influence on the group movement. The individuals furthest from the threat were the least likely to initiate movement and were uncoordinated with the group’s speed. Additionally, we discovered that the most influential individuals during the collective escape were the least likely to occupy front positions during group movement. Instead, our results indicate that individuals at the rear “push” individuals at the front during collective escape events. This contrasts with the typical notion of individuals at the front determining group movement and those at the back trying to catch up.
Mental fatigue has only marginal effects on static balance control in healthy young adults
Authors: Weissinger Kerstin , Bach Margit Midtgaard , Brachmann Anna , Stins John F. , Beek Peter Jan
Published: July 2023

We examined the influence of mental fatigue on static balance control in healthy young adults to gain greater clarity about this issue than provided in previous research. Based on the prevailing assumption in pertinent literature, we hypothesized that mental fatigue leads to a reduced cognitive regulation of quiet upright standing, as reflected in center of pressure (COP) excursions. More specifically, we hypothesized that the influence of mental fatigue on balance control depends on the attentional effort required by the balance tasks being performed. To test these hypotheses, 44 young adults (24 women and 20 men) were quasi-randomly assigned to either an experimental group that was mentally fatigued (using the TloadDback-task with individualized settings) or a control group (who watched a documentary). Before and after the intervention the participants performed six balance tasks that differed in (attentional) control requirements, while their COP was being recorded. From these time-series sway variability, mean speed, and sample entropy were calculated and analyzed statistically. Additionally, mental fatigue was assessed using VAS scales. Statistical analyses confirmed that the balance tasks differed in control characteristics and that mental fatigue was elevated in the experimental group, but not in the control group. Nevertheless, no significant main effects of mental fatigue were found on any of the COP measures of interest, except for some non-robust and difficult to interpret interaction effects involving the factor group. These results suggest that, in young adults, postural control in static balance tasks is largely automatic and unaffected by mental fatigue.
Lasting dynamic effects of the psychedelic 2,5-dimethoxy-4-iodoamphetamine ((±)-DOI) on cognitive flexibility
Authors: Šabanović Merima , Lazari Alberto , Blanco-Pozo Marta , Lerch Jason P. , Walton Mark E. , Bannerman David M.
Published: July 2023

Psychedelic drugs can aid fast and lasting remission from various neuropsychiatric disorders, though the underlying mechanisms remain unclear. Preclinical studies suggest serotonergic psychedelics enhance neuronal plasticity, but whether neuroplastic changes can also be seen at cognitive and behavioural levels is unexplored. Here we show that a single dose of the psychedelic 2,5-dimethoxy-4-iodoamphetamine ((±)-DOI) affects structural brain plasticity and cognitive flexibility in young adult mice beyond the acute drug experience. Usingex vivomagnetic resonance imaging, we show increased volumes of several sensory and association areas one day after systemic administration of 2mgkg−1(±)-DOI. We then demonstrate lasting effects of (±)-DOI on cognitive flexibility in a two-step probabilistic reversal learning task where 2mgkg−1(±)-DOI improved the rate of adaptation to a novel reversal in task structure occurring one-week post-treatment. Strikingly, (±)-DOI-treated mice started learning from reward omissions, a unique strategy not typically seen in mice in this task, suggesting heightened sensitivity to previously overlooked cues. Crucially, further experiments revealed that (±)-DOI’s effects on cognitive flexibility were contingent on the timing between drug treatment and the novel reversal, as well as on the nature of the intervening experience. (±)-DOI’s facilitation of both cognitive adaptation and novel thinking strategies may contribute to the clinical benefits of psychedelic-assisted therapy, particularly in cases of perseverative behaviours and a resistance to change seen in depression, anxiety, or addiction. Furthermore, our findings highlight the crucial role of time-dependent neuroplasticity and the influence of experiential factors in shaping the therapeutic potential of psychedelic interventions for impaired cognitive flexibility.