bluuebunny/crossref_metadata_2025 huggingface dataset:
Pancreatic Intraepithelial Neoplasia Revealed by Diffusion-Tensor MRI
Authors: Bilreiro Carlos , Fernandes Francisca F. , Simões Rui V. , Henriques Rafael , Chavarrías Cristina , Ianus Andrada , Castillo-Martin Mireia , Carvalho Tânia , Matos Celso , Shemesh Noam
Published: December 2024

Objectives

Detecting premalignant lesions for pancreatic ductal adenocarcinoma, mainly pancreatic intraepithelial neoplasia (PanIN), is critical for early diagnosis and for understanding PanIN biology. Based on PanIN's histology, we hypothesized that diffusion tensor imaging (DTI) and T2* could detect PanIN.

Materials and Methods

DTI was explored for the detection and characterization of PanIN in genetically engineered mice (KC, KPC). Following in vivo DTI, ex vivo ultrahigh-field (16.4 T) MR microscopy using DTI, T2* was performed with histological validation. Sources of MR contrasts and histological features were investigated, including histological scoring for disease burden (lesion span) and severity (adjusted score). To test if findings in mice can be translated to humans, human pancreas specimens were imaged.

Results

DTI detected PanIN and pancreatic ductal adenocarcinoma in vivo (6 KPC, 4 KC, 6 controls) with high discriminative ability: fractional anisotropy (FA) and radial diffusivity with area under the curve = 0.983 (95% confidence interval: 0.932–1.000); mean diffusivity and axial diffusivity (AD) with area under the curve = 1 (95% confidence interval: 1.000–1.000). MR microscopy with histological correlation (20 KC/KPC; 5 controls) revealed that sources of MR contrasts likely arise from microarchitectural signatures: high FA, AD in fibrotic areas surrounding lesions, high diffusivities within cysts, and high T2* within lesions' stroma. The strongest histological correlations for lesion span and adjusted score were obtained with AD (R = 0.708, P < 0.001; R = 0.789, P < 0.001, respectively). Ex vivo observations in 5 human pancreases matched our findings in mice, revealing substantial contrast between PanIN and normal pancreas.

Conclusions

DTI and T2* are useful for detecting and characterizing PanIN in genetically engineered mice and in the human pancreas, especially with AD and FA. These are encouraging findings for future clinical applications of pancreatic imaging.
Clinical Value of 18F-(2S,4R)-4-Fluoroglutamine PET/CT in Glioma
Authors: Xu Xiaoxia , Zhao Heqian , Liu Futao , Xie Qing , Yang Jianhua , Li Shouwei , Yang Zhi
Published: December 2024

Propose

The aim of this study was to evaluate the clinical application value of 18F-FGln PET/CT in glioma.

Patients and Methods

Patients with suspected gliomas by MRI were included in this study. Static and/or dynamic brain 18F-FGln PET/CT was performed. The PET parameters SUVmax, SUVmean, MTV, and TLG were evaluated.

Results

Twenty-three patients were included in the analysis. Nineteen of 23 patients were positive for 18F-FGln PET. The SUVmax of high- and low-grade gliomas were 4.75 ± 2.21 and 1.00 ± 0.66 (P < 0.001), respectively. FGln-PET SUVmax, SUVmean, and TLG all showed statistically significant correlations with glioma grade, with correlation coefficients (r) of 0.667 (P < 0.001), 0.693 (P < 0.001), and 0.487 (P = 0.021), respectively. Additionally, the SUVmax, SUVmean, and TLG exhibited higher distinguishing performance for glioma grade by receiver operating characteristic curve analysis. The areas under the receiver operating characteristic curve of SUVmax, SUVmean, and TLG were 0.976 (95% confidence interval [CI], 0.918–1) (P = 0.002), 0.976 (95% CI, 0.918–1) (P = 0.002), and 0.835 (95% CI, 0.628–1.000) (P = 0.026), respectively. For glioma isocitrate dehydrogenase (IDH) mutation status, the SUVmax of IDH wildtype and mutant glioma were 2.95 ± 1.99 and 6.13 ± 2.16 (P = 0.005), respectively. The SUVmean and SUVmax had good-to-satisfactory performance for IDH status with the area under the receiver operating characteristic curve of SUVmax and SUVmean of 0.885 (95% CI, 0.734–1.000) (P = 0.009) and 0.942 (95% CI, 0.828–1) (P = 0.002).

Conclusions

Although we do not assert that 18F-FGln PET/CT imaging is satisfactory in the differential diagnosis of glioma, we revealed its potential for identifying the stage of gliomas and the IDH mutation status and propose that glutamine-based PET imaging enables the assessment of metabolic nutrient uptake of gliomas to assist clinical diagnosis and treatment of patients.
Pyomyositis Due to a Rare Fungal Infection—Findings on 68Ga-NOTA UBI PET/CT
Authors: Ravindra Shubha Gadde , Damle Nishikant Avinash , Babu Pyata Vikram , Bhadu Danveer , Singh Gagandeep
Published: December 2024

It is very rare to see fungal arthritis and pyomyositis in immunocompetent patients. Here, we report a case of Scedosporium infection in an immunocompetent patient with interesting 18F-FDG PET/CT and 68Ga-NOTA UBI PET/CT findings.
Beyond the Standard Meal
Authors: Wulfeck Madison K. , Ramis Phil , Hillman Andrew , Nielsen Patrick , Rohren Eric M.
Published: December 2024

Rationale

Standardized guidelines for meals used in adult gastric emptying studies (GES) have been available since 2009; however, there is still great variability in the diets that are clinically used in these studies. The purpose of this retrospective study is to perform an observational analysis of GES meals that are used within a national radiology practice to assess for compliance. It is hypothesized that despite having well-validated standardized meal protocols, there remains great variability in its use and interpretation.

Methods

This retrospective observational analysis included 11,458 GESs and their associated reports. GES meals were divided into 5 categories including solid, liquid, dual liquid and solid, alternative meals, and other. Further analysis was performed on the solid and liquid meal GESs. The total amount of studies performed with each meal was collected as well as the percentages of the results of each study categorized as normal, delayed, rapid, and limited.

Results

A total of 10,602 studies were included in the analysis, which included 9974 solid meals and 628 liquid meals. Of the solid meal type, the standard recommended meal was used most often followed by the protein variant meal. The oatmeal protocol had the least number of delayed results; however, there was otherwise a similar distribution of results for the remaining solid meal variants. The most common liquid meal utilized the nutritional drink or protein shake, and compared with the solid meal types, there were less rapid or limited results.

Conclusions

Variability remains in clinical practice regarding the type of meal that is used in GESs as well as in the interpretation of the study. Continued reinforcement of the standardized solid meal diet and validated cutoff values for interpretation remains crucial until there is increased validation and standardization of other diets.
The use of precision radiotherapy for the management of cancer-related pain in the abdomen
Authors: Glynn Aisling M. , Lawrence Yaacov R. , Dawson Laura A. , Barry Aisling S.
Published: December 2024

Purpose of review

Abdominal pain due to cancer is a significant and debilitating symptom for cancer patients, which is commonly undertreated. Radiotherapy (RT) for the management of abdominal cancer pain is underused, with limited awareness of its benefit. This review presents a discussion on current precision RT options for the management of cancer pain in the abdomen.

Recent findings

Precision RT focuses on delivering targeted and effective radiation doses while minimizing damage to surrounding healthy tissues. In patients with primary or secondary liver cancer, RT has been shown to significantly improve liver related cancer pain in the majority of patients. Also, symptom sequelae of tumour thrombus may be relieved with the use of palliative RT. Similarly, single dose, high precision stereotactic RT to the celiac plexus has been shown to significantly improve pain in patients with pancreatic cancer. Pain response for adrenal metastases has been less commonly investigated, but small series suggest that stereotactic body RT may reduce or alleviate pain.

RT is an effective option for the treatment of abdominal cancer pain. RT should be considered within the multidisciplinary treatment armamentarium, and may be successfully integrated, alone or in conjunction with other treatment modalities, in abdominal cancer-related pain.
Palliative radiation therapy for locally advanced breast cancer
Authors: Ciocon Stephen L.B. , Sousa Cecília F.P.M. , Marta Gustavo N. , Kwan Jennifer Y.Y.
Published: December 2024

Purpose of review

Globally, breast cancer is the most commonly diagnosed cancer in women. Locally advanced breast cancers (LABCs) may necessitate palliative radiation therapy (RT) due to the severity of the patients’ symptoms, inoperability, or other reasons precluding curative-intent treatment such as poor performance status and patient comorbidities. This review aims to discuss current evidence on palliative RT in LABC.

Recent findings

Advanced targeted RT techniques have led to improvements in local control with reduced treatment-related toxicities. Emerging short-course palliative RT prescriptions offer feasible options that avoid delay in systemic therapy. Additionally, recent studies also highlight approaches for integrating palliative RT with systemic therapies.

Palliative RT plays a vital role in managing symptoms and enhancing quality of life for LABC patients. However, there is currently no consensus on the optimal prescriptions for palliative RT in these patients. Standardized reporting of palliative RT studies is needed for robust comparison of efficacy and toxicity between various treatment regimens. Furthermore, future research on the optimal integration of RT with novel systemic agents is needed.
Penetrating cardiac injuries: What you need to know
Authors: Parreira José Gustavo , Coimbra Raul
Published: December 2024

Despite significant advances in trauma surgery in recent years, patients sustaining penetrating cardiac injuries still have an overall survival rate of 19%. A substantial number of deaths occur at the scene, while approximately 40% of those reaching trauma centers survive. To increase survival, the key factor is timely intervention for bleeding control, pericardial tamponade release, and definitive repair. Asymptomatic patients sustaining precordial wounds or mediastinal gunshot wounds should be assessed with chest ultrasound to rule out cardiac injuries. Shock on admission is an immediate indication of surgery repair. Patients admitted in posttraumatic cardiac arrest may benefit from resuscitative thoracotomy. The surgical team must be assured that appropriate personnel, equipment, instruments, and blood are immediately available in the operating room. A left anterolateral thoracotomy, which can be extended to a clamshell incision, and sternotomy are the most common surgical incisions. Identification of cardiac anatomical landmarks during surgery is vital to avoid complications. There are several technical options for bleeding control, and the surgeon must be trained to use them to obtain optimal results. Ultimately, prioritizing surgical intervention and using effective resuscitation strategies are essential for improving survival rates and outcomes.
Balanced Electrolyte Solutions Versus 0.9% Saline for Kidney Transplantation: An Updated Systematic Review and Meta-analysis
Authors: Wan Susan S. , Wyburn Kate , Chadban Steven J. , Collins Michael G.
Published: December 2024

Background.

Perioperative intravenous fluids are administered to kidney transplant recipients to maintain hemodynamic stability and graft perfusion; however, the ideal fluid remains uncertain. Although 0.9% saline (saline) is commonly used, its high chloride content causes hyperchloremic metabolic acidosis and may increase the risks of delayed graft function (DGF) and hyperkalemia. Balanced electrolyte solutions (BES) have a more physiological chloride concentration and may reduce these risks. Previous meta-analyses found insufficient evidence to compare BES with saline for these outcomes; however, new studies have recently been published. In this updated review, we compared the effects of BES with saline on the risk of DGF and hyperkalemia in kidney transplantation.

Methods.

MEDLINE, Embase, and CENTRAL were searched for randomized controlled trials comparing BES with saline in kidney transplantation. The primary outcomes were DGF and hyperkalemia. Eligible studies were assessed for risk of bias and data were pooled for analysis. The Grading of Recommendations Assessment, Development, and Evaluation framework was used to assess the quality of evidence.

Results.

Ten studies involving 1532 participants were included. The quality of evidence was high for deceased donor transplantation and very low for living donor transplantation. The relative risk (RR) of DGF associated with BES compared with saline was 0.83 (95% confidence interval [CI], 0.71-0.96; P = 0.01) in deceased donor transplantation. There was no difference in DGF in living donor transplantation (RR 0.79; 95% CI, 0.26-2.41; P = 0.68). There was no difference in hyperkalemia between groups (RR 0.87; 95% CI, 0.59-1.27; P = 0.46).

Conclusions.

Compared with saline, BES reduces the risk of DGF in deceased donor kidney transplantation without increasing hyperkalemia.
Concordance analysis between Human Papillomavirus genotyping assay and PCR-reverse spot hybridization for the detection of Human Papillomavirus infection
Authors: Chen Yanlin , Li Ye , Xue Lifang , Xu Mu , Wang Liying , Dong Binhua , Cai Liangzhi
Published: December 2024

Introduction. Human papillomavirus (HPV), the predominant viral infection affecting the anogenital tract, is closely linked to the development of intraepithelial neoplasia and malignancies in the cervix and other anal regions. Currently, 15 high-risk HPVs (HR-HPVs) and 3 potential HR-HPV types have been recognized as contributors to cervical cancer. Consequently, it is imperative to conduct HR-HPV screening using suitable tests in order to identify precancerous lesions and prevent the development of cancer.

Hypothesis. The Human papillomavirus genotyping (type 23) detection kit (PCR-reverse point hybridization method) is reliable for clinical testing.

Aims. The objective of this research was to assess the concordance between the Human papillomavirus genotyping (type 23) detection kit (PCR-reverse point hybridization method) and the approved HPV test.

Methodology. A sample of 781 women who received HPV genotype testing during cervical cancer screening consultations at the Department of Gynecology, Fujian Maternity and Child Health Hospital, was examined. Thirty-two cases were excluded for lacking histological results or showing signs of vulvar intraepithelial rheology, leaving 749 valid histological samples. Only 181 valid pathological specimens were available after excluding those without cervical biopsy or total hysterectomy. The consistency of the test results was assessed using the kappa (K) statistic, with CIN2+ serving as the benchmark for determining sensitivity and specificity. Statistical significance was defined as differences with P values <0.05 (two-tailed).

Results. The human papillomavirus genotyping (type 23) detection kit (PCR-reverse point hybridization method) and the approved HPV test demonstrated a high level of concordance with a total kappa value of 0.969 (P<0.05). The overall concordance rate was found to be 98.720%. Using cervical intraepithelial neoplasia grade 2+ (CIN2+) as the reference standard, the human papillomavirus genotyping (type 23) detection kit (PCR-reverse point hybridization method) and the approved HPV test both showed 89.655% sensitivity (P>0.05), while the specificity values were 40.590 and 40.309%, respectively (P>0.05).

Conclusion. The evaluated HPV test demonstrates comparable performance to other assays available during the same time frame and exhibits strong concordance in detecting the majority of HPV genotypes.
Utilizing Connectome Fingerprinting functional MRI models for motor activity prediction in presurgical planning: a feasibility study
Authors: Tripathi Vaibhav , Rigolo Laura , Bracken Bethany , Galvin Colin P. , Golby Alexandra J. , Tie Yanmei , Somers David C
Published: December 2024

Presurgical planning prior to brain tumor resection is critical for the preservation of neurologic function post-operatively. Neurosurgeons increasingly use advanced brain mapping techniques pre- and intra-operatively to delineate brain regions which are “eloquent” and should be spared during resection. Functional MRI (fMRI) has emerged as a commonly used non-invasive modality for individual patient mapping of critical cortical regions such as motor, language, and visual cortices. To map motor function, patients are scanned using fMRI while they perform various motor tasks to identify brain networks critical for motor performance, but it may be difficult for some patients to perform tasks in the scanner due to pre-existing deficits. Connectome Fingerprinting (CF) is a machine-learning approach that learns associations between resting-state functional networks of a brain region and the activations in the region for specific tasks; once a CF model is constructed, individualized predictions of task activation can be generated from resting-state data. Here we utilized CF to train models on high-quality data from 208 subjects in the Human Connectome Project (HCP) and used this to predict task activations in our cohort of healthy control subjects (n=15) and presurgical patients (n=16) using resting-state fMRI (rs-fMRI) data. The prediction quality was validated with task fMRI data in the healthy controls and patients. We found that the task predictions for motor areas are on par with actual task activations in most healthy subjects (model accuracy around 90-100% of task reliability) and some patients suggesting the CF models can be reliably substituted where task data is either not possible to collect or hard for subjects to perform. We were also able to make robust predictions in cases in which there were no task-related activations elicited. The findings demonstrate the utility of the CF approach for predicting activations in out-of-sample subjects, across sites and scanners, and in patient populations. This work supports the feasibility of the application of CF models to presurgical planning, while also revealing challenges to be addressed in future developments.
Practices of midwives in the management of postpartum haemorrhage: A case of Maseru, Lesotho
Authors: Chabeli Mpho , Nyangu Isabel , Mpemi Regina
Published: December 2024

Postpartum haemorrhage (PPH) remains the common cause of maternal mortality. More than half of maternal deaths from PPH occur within 24 hours of delivery and could be prevented through midwives’ compliance with guidelines and standards for clinical practice. This study aimed to assess the midwives’ practices regarding the management of PPH in Maseru Lesotho. A quantitative cross-sectional study was undertaken. Convenience sampling was used to select 220 midwives who voluntarily completed a structured self-administered questionnaire. Ethical clearance was granted by the Ministry of Health Research and Ethics Committee. Data was analysed using Statistical Package for Social Science and presented using descriptive and analytic statistics. Midwives were competent with estimation and recording blood loss, placenta assessment and vital signs of patients. There was a significant association between the highest education qualification and midwives who estimate and record blood loss, palpate and measure the uterine fundus and assess the completeness of the placenta. The results revealed a significant association between work experience, uterine fundus measurement and estimated blood loss. Midwives reported to practice management of PPH based mostly on guidelines. However, many midwives still disregard recommendations, putting patients at risk hence the need to intensify supervision to ensure safe practices.
A Novel Truncating Variant in MYBPC3 Causes Hypertrophic Cardiomyopathy
Authors: Zhang Yuanyuan , Gong Wenyan , Cong Yusheng , Zhang Xingwei , Zheng Zhelan
Published: December 2024

Background

Familial hypertrophic cardiomyopathy (HCM) is the most common genetic cardiovascular disease. Related mutations contributing to hypercontractility and poor relaxation in HCM have been incompletely understood. The purpose of this study was to explore and verify a novel variant in cardiac myosin-binding protein C3 (MYBPC3) in a HCM family.

Methods

Clinical information was collected and cardiac evaluation was performed in the pedigree. Second-generation sequencing technology was used to investigate the proband and his family. Computational prediction of mutation effects at genomic level and 3D visualization of the mutated protein were achieved by in silico analysis.

Results

Typical interventricular septal thickening was detected in all the four HCM patients. A c.1042_1043insCGGCA mutation of MYBPC3 was verified in the proband and family members. Mild phenotype associated with delayed onset and relative favorable prognosis were observed in the pedigree. In silico analysis of the mutation revealed that c.1042_1043insCGGCA led to an early termination of MYBPC protein synthesis at C2 domain, losing the domains that are essential for myosin-and titin-binding.

Conclusion

The novel c.1042_1043insCGGCA mutation of MYBPC3 was a genetic basis for HCM.

Our gene sequence based computational analysis predicted the pathogenicity of the mutation by correlating MYBPC3 genotypes with clinical phenotypes.
Implementation and enforcement of mandatory calorie labelling regulations for the out-of-home sector in England: qualitative study of the experiences of business implementers and regulatory enforcers
Authors: Essman Michael , Bishop Tom , Burgoine Thomas , Jones Andrew , Polden Megan , Robinson Eric , Sharp Stephen J. , Smith Richard , Adams Jean , White Martin
Published: December 2024

Background

Mandatory calorie labelling on menus of large out-of-home food outlets was implemented in England on 6 April 2022. Barriers and facilitators that were unforeseen before implementation may modify policy impacts. As part of a process evaluation of the policy, we studied the implementation process, examining business experiences and enforcement by local authorities (LAs) to identify barriers and facilitators in achieving the policy goals.

Methods

Using purposive sampling, we recruited 11 employees of large food businesses (implementers) and 9 employees of LA environmental health or trading standards departments (enforcers). Post-implementation semi-structured interviews were conducted by video conference. Interviews were audio recorded, transcribed verbatim and analysed using the Framework Method.

Results

Both groups of participants described a decentralised approach to delivery and enforcement, and resource constraints meant LAs were unable to assist with all business inquiries. Enforcement activity was limited because complaints about labelling from the public were rare, and enforcers prioritized acute food safety issues. Pre-implementation discussions created the presumption among enforcers that most businesses were compliant. Businesses complied to safeguard their reputation and maintain customer trust. While participants supported calorie labelling, potential barriers to policy impact included a presumed lack of customer interest. Financial pressure during implementation strained business resources, and businesses suggested that customers may prioritise financial over health concerns in their decision-making.

Conclusions

These findings underscore the need for central guidance, verification of adherence, and sufficient enforcement resources. To optimize policy success, future developments should consider economic contexts, customer expectations, and policy refinement, while recognizing common industry arguments against policy implementation.
Diabetics in the United Arab Emirates at higher risk of foot ulceration-Clinical Implications from Kinetics at Ankle Joint
Authors: Hazari Animesh , Kumar Praveen , Kumar Shashi
Published: December 2024

Introduction

The prevalence of diabetes mellitus in the United Arab Emirates stands significantly high. Considering the etiopathogenesis for diabetic foot ulcers, studies suggest that increased plantar pressure, also referred to as the peak plantar pressure beyond a threshold value leads to the breakdown of skin and thus causes an ulcer. The accurate analysis of ground reaction force and peak plantar pressure could be suggestive and predictive for the occurrence of foot ulceration among diabetes mellitus and the study aims to analyze the kinetics at the ankle joint among diabetics in the UAE.

Methodology

The cross-sectional study was conducted at the Thumbay Physical Therapy and Rehabilitation Hospital, Gulf Medical University, Ajman, United Arab Emirates. 38 out of a total of 120 participants screened and diagnosed with Type 2 diabetes mellitus were taken for data collection and analysis. BTS motion analysis and Wintrack foot scan mat were used for kinetics at the ankle joint.

Results

Higher mean peaks of plantar pressure, 810, 654, and 911 kPa respectively were found at all three phases of the gait cycle. A positive and high correlation was found between peak plantar pressure risk of foot ulcer (r= 0.84). A negative and moderate correlation was observed for ankle joint moment and power.

Conclusion

The diabetic population in the United Arab Emirates could be at higher risk of foot ulceration with significantly increased peak plantar pressure. The altered kinetics such as reduced ankle joint moment and power could further add to the risk.
Mapping Referred Sensation In Traumatic Brachial Plexus Injury Patients
Authors: Schmaedeke Ana Carolina , Erthal Fátima S. , Vargas Claudia D. , Ramalho Bia L.
Published: December 2024

Abstract

Background

Referred sensation (RS) is described as the sensation evoked in the skin areas other than the stimulated region. The aim of the study was to identify and map RS in traumatic brachial plexus injury (TBPI) patients through a standardised assessment.

Methods

In Experiment 1, 12 patients underwent an RS screening by stimulating 22 skin areas distributed in both upper limbs, neck, and face with a cotton swab. In Experiment 2, a detailed RS mapping employing Semmes-Weinstein monofilament was performed at the reinnervated forearm of three subjects who showed RS in experiment 1 screening. In one of these patients, RS mapping was performed over a time span of 6.3 years.

Results

Screening of TBPI patients submitted to different reconstructive surgeries revealed RS only in the patients who underwent intercostal to musculocutaneous nerve (ICN-MCN) transfer. RS systematic mapping of these patients revealed a unique distribution in the forearm and the chest, without any clear topographic organisation. Longitudinal assessment in one of the tested participants showed a scattered expansion of the RS throughout time.

Conclusions

This is the first study to map systematically the RS in patients with TBPI. RS was identified only after ICN-MCN transfer. A possible explanation for this phenomenon is that the greater distance between the representations of the donor and receptor nerves at the primary somatosensory cortex (S1) could constrain plastic reorganisation and thus limit the disentangling of the forearm and chest sensations.
Automated visual acuity estimation by optokinetic nystagmus using a stepped sweep stimulus
Authors: Turuwhenua Jason , LinTun Zaw , Norouzifard Mohammad , Edmonds Misty , Findlay Rebecca , Black Joanna , Thompson Benjamin
Published: December 2024

Purpose

Measuring visual acuity (VA) can be challenging in adults with cognitive impairment and young children. We developed an automatic system for measuring VA using Optokinetic Nystagmus (OKN).

Methods

VA-OKN and VA by ETDRS (VA-ETDRS) were measured monocularly in healthy participants (n=23, age 30±12). VA was classified as reduced (n=22, >0.2 logMAR) or not (n=24, ≤0.2 logMAR) in each eye. VA-OKN stimulus was an array of drifting (5 deg/sec) vanishing disks presented in descending/ascending size order (0.0 to 1.0 logMAR in 0.1 logMAR steps). The stimulus was stepped every 2 seconds, and 10 sweeps were shown per eye. Eye tracking data determined when OKN activity ceased (descending sweep) or began (ascending sweep) to give an automated sweep VA. Sweep traces were randomized and assessed by a reviewer blinded to VA-ETDRS. A final per sweep VA and VA-OKN was thereby determined.

Results

A single randomly selected eye was used for analysis.VA deficit group:There was no significant difference between overall mean VA-OKN and VA-ETDRS (p>0.05, paired t-test) and the r2statistic was 0.84. The 95% limits of agreement were 0.19 logMAR.No VA deficit group:There was a 0.24 logMAR bias between VA-OKN and VA-ETDRS and no correlation was found (r2= 0.06). However, the overall sensitivity/specificity for classification was 100%.

Conclusions

A robust correlation between VA-ETDRS and VA-OKN was found. The method correctly detected a VA deficit.

Translational relevance

OKN is a promising method for measuring VA in cognitively impaired adults and pre-verbal children.
Machine Learning Models for the Prediction of Early-Onset Bipolar Using Electronic Health Records
Authors: Wang Bo , Sheu Yi-Han , Lee Hyunjoon , Mealer Robert G. , Castro Victor M. , Smoller Jordan W.
Published: December 2024

Objective

Early identification of bipolar disorder (BD) provides an important opportunity for timely intervention. In this study, we aimed to develop machine learning models using large-scale electronic health record (EHR) data including clinical notes for predicting early-onset BD.

Method

Structured and unstructured data were extracted from the longitudinal EHR of the Mass General Brigham health system. We defined three cohorts aged 10 – 25 years: (1) the full youth cohort (N=300,398); (2) a sub-cohort defined by having a mental health visit (N=105,461); (3) a sub-cohort defined by having a diagnosis of mood disorder or ADHD (N=35,213). By adopting a prospective landmark modeling approach that aligns with clinical practice, we developed and validated a range of machine learning models including neural network-based models, across different cohorts and prediction windows.

Results

We found the two tree-based models, Random forests (RF) and light gradient-boosting machine (LGBM), achieving good discriminative performance across different clinical settings (area under the receiver operating characteristic curve 0.76-0.88 for RF and 0.74-0.89 for LGBM). In addition, we showed comparable performance can be achieved with a greatly reduced set of features, demonstrating computational efficiency can be attained without significant compromise of model accuracy.

Conclusion

Good discriminative performance for early-onset BD is achieved utilizing large-scale EHR data. Our study offers a scalable and accurate method for identifying youth at risk for BD that could help inform clinical decision making and facilitate early intervention. Future work includes evaluating the portability of our approach to other healthcare systems and exploring considerations regarding possible implementation.
“Just a knife wound this week, nothing too painful”:an ethnographic exploration of how homeless clients attending an urban primary care and addiction service view their own health and healthcare
Authors: Ingram Carolyn , Buggy Conor , MacNamara Isobel , Perrotta Carla
Published: December 2024

This study used an ethnographic approach grounded in a social constructivist research paradigm to explore the perspectives of people in homelessness attending a primary care and addiction service on their priority health and healthcare needs. Participant observations and informal interviews were conducted with homeless clients attending the service for three hours every Monday morning between October 2022 and April 2023. Field note data from active participant observation and informal conversations were collected, anonymised, and analysed using inductive thematic analysis in accordance with the Declaration of Helsinki and the researchers’ institutional Research Ethics Committee. Three main themes emerged from the analysis: self-identified priorities, satisfaction with services, and migrant health. Clients’ priority concerns relate to their mental health, maintaining ties with children and families, navigating complex romantic relationships, finding meaningful activities, and feeling better physically. These challenges differ from those of the general population in terms of their severity observed both prior to and during experiences of homelessness, coupled with disproportionately high levels of loss, fear, injury, pain, disability, fatigue, and isolation. In terms of services, clients are satisfied with their ability to access primary care and harm reduction in a social environment where positive exchanges with friends and providers take place. Conversely, barriers to accessing mental health and addiction services persist including the internalised belief that one is beyond help, lack of access to information on available services and their entry requirements, and lingering stigma within a health system that treats addiction as separate to health. Moving forward, health practitioners may consider holding more regular and open conversations with homeless clients about the care they are receiving, its rationale, and whether or not changes are desired that can be safely made. The health needs of migrants and asylum seekers entering homelessness in Ireland are urgent and should be prioritised in future research.
Development of a differential treatment selection model for depression on consolidated and transformed clinical trial datasets
Authors: Perlman Kelly , Mehltretter Joseph , Benrimoh David , Armstrong Caitrin , Fratila Robert , Popescu Christina , Tunteng Jingla-Fri , Williams Jerome , Rollins Colleen , Golden Grace , Turecki Gustavo
Published: December 2024

Objective

Major depressive disorder (MDD) is the leading cause of disability worldwide, yet treatment selection still proceeds via “trial and error”. Given the varied presentation of MDD and heterogeneity of treatment response, the use of machine learning to understand complex, non-linear relationships in data may be key for treatment personalization. Well-organized, structured data from clinical trials with standardized outcome measures is useful for training machine learning models; however, combining dataacrosstrials poses numerous challenges. There is also persistent concern that machine learning models can propagate harmful biases.

Methods

We have created a methodology for organizing and preprocessing depression clinical trial data such that transformed variables harmonized across disparate datasets can be used as input for feature selection. Using bayesian optimization, we identified an optimal multi-layer dense neural network which used data from 21 clinical and sociodemographic features as input in order to perform differential treatment benefit prediction.

Results

With this combined dataset of 5032 individuals and 6 drugs, we created a differential treatment benefit prediction model. Our model generalized well to the held-out test set and produced similar accuracy metrics in the test and validation set with an AUC of 0.7 when predicting binary remission. To address the potential for bias propagation, we used a bias testing performance metric to evaluate the model for harmful biases related to ethnicity, age, or sex.

Conclusion

We present a full pipeline from data preprocessing to model validation that was employed to create the first differential treatment benefit prediction model for MDD containing 6 treatment options.
The cost of myopic pandemic response
Authors: Nowak Sarah , de Lima Pedro Nascimento , Vardavas Raffaele
Published: December 2024

Prior to the availability of COVID-19 vaccines, non-pharmaceutical interventions (NPIs) served as a primary strategy to mitigate the spread of the disease. However, the efficiency of these interventions relies on understanding and incorporating human behavior into infectious disease models. This study addresses the need for models that better account for the influence of temporal discounting on behavioral dynamics to enhance forecasting accuracy and develop robust mitigation strategies. Our previous research introduced Known Time Horizon (KTH) policies, optimizing social distancing measures based on a central planner’s rational assessment of the pandemic’s time frame and associated costs. In this paper, we contrast the KTH policy with a model reflecting myopic decision-making, an extreme form of temporal discounting that emphasizes short-term outcomes over long-term consequences. By comparing the expected social distancing behavior under myopic decision-making with the optimal policy derived from KTH approaches, we elucidate the impact of temporal bias on social distancing practices and assess its implications for infection dynamics and associated costs. We find that myopic policy always results in greater total costs throughout an epidemic compared to a KTH policy. However, each cost component – the costs of infection and social distancing – derived from a myopic strategy may be either larger or smaller than the component costs for a strategy developed using a full optimization model, depending on the specific parameters involved as myopic decision-makers seek to delay both costs of social distancing and infection.
Post Tuberculosis (TB) Bronchiectasis versus Non-TB Bronchiectasis in Northern Pakistan: A single centre retrospective cohort study on frequency, demographics, microbiology, and complications
Authors: Hoole Anbesan Samuel , Ilyas Ahsan , Munawar Sunaina , Cant Matthew , Hameed Rizwan , Gill Shahzad , Riaz Joel , Siddiq Issac
Published: December 2024

Introduction

While Post Tuberculous (TB) Bronchiectasis is the most common cause of Bronchiectasis in South Asia, there has been little research into its microbiology and clinical characteristics in Pakistan. This single centre retrospective cohort study at Bach Christian Hospital (BCH) in rural Northern Pakistan seeks to address this issue.

Methods

Demographic, Imaging, Aetiological and Microbiological data were obtained from 32 patients with Bronchiectasis at BCH from between January 2023 and December 2023(1–3).

Results

76% (25/32) of all cases of Bronchiectasis were Post TB. TB infection was seen in 5 cases of Post TB Bronchiectasis, TB with bacterial or fungal co infections in 4, and single bacterial infections in 4. In post TB Bronchiectasis 4 patients had growth of a single bacterium. Drug sensitivities were obtained for bacterial isolates.

One patient each with Post TB and Non-TB Bronchiectasis died from Type 2 Respiratory failure despite appropriate treatment. 2 patients with Post TB Bronchiectasis and destroyed lung syndrome improved but with ongoing significant respiratory impairment(4). All other patients improved with treatment.

Discussion

The frequency of Post TB Bronchiectasis is very high even for South Asia(5–8).

A significant number (8/24) of Post TB Bronchiectasis had re-infection or failure to improve despite appropriate drug treatment. TB PCR (Polymerase Chain Reaction) on Bronchoalveolar lavage (BAL) was key in the management of these patients(9).

Among patients with Post TB Bronchiectasis, those with co-infection present a difficult treatment challenge.

Some patients with Post TB Bronchiectasis have significant complications such as destroyed lung syndrome which is difficult to manage.

Drug susceptible bacteria and NTM were less commonly isolated than in other studies(10–12).

Conclusion

Further research is needed particularly to manage Post TB Bronchiectasis patients with co-infections or complications such as significant structural lung disease.

Key Messages

What is known about this topic

Tuberculosis (TB) is the most common cause of bronchiectasis in South Asia, but little is known about microbiology or clinical characteristics of post-TB Bronchiectasis.

What this study adds

Post TB Bronchiectasis has a very high prevalence in our region, with TB PCR key for diagnosis of TB re-infection in some cases. Mycobacterial, Bacterial and Fungal co-infections form a treatment challenge, as does significant structural lung disease such as destroyed lung.

How this study might affect research, practice, or policy

TB PCR testing is a valuable tool in Post TB Bronchiectasis and further research and larger-scale studies are needed to determine optimal treatment for co-infections and significant structural lung disease.
Navigating Visual Challenges: How Parkinson’s Disease Alters Cognitive Priorities in Visual Search
Authors: Beylergil Sinem Balta , Skelly Peggy , Quagraine Ibrahim , Kilbane Camilla , Ghasia Fatema F. , Shaikh Aasef G.
Published: December 2024

Objective

Parkinson’s disease (PD) hampers visual control in tasks such as reading, driving, and navigation. This study explores the impact of contextual visual priors on visual search behavior in PD, examining expectations from past experiences and guiding cognitive processes.

Methods

We compared eye movements during a visual search task with complex scenes to evaluate gaze strategies in PD, compared to healthy controls.

Results

PD participants prolonged fixation on high-probability areas for the target object, consistent across expected and unexpected locations. The emphasis on visual priors was proven beneficial in expected locations but presented challenges when the target was situated in an unlikely place.

Conclusion

These findings indicate that PD alters attention allocation and visual processing by affecting the utilization of contextual visual priors. This study contributes to understanding how PD impacts visual search behavior and cognitive processing, providing insights for potential interventions targeting visual deficits in PD patients.
Sex hormones, obesity, and risk of cholecystectomy in men and women: a population-based prospective study and mediation analysis
Authors: Lyu Jie-Qiong , Jiang Wei , Jia Yi-Ping , Miao Meng-Yuan , Wang Jia-Min , Tao Hao-Wei , Zhao Miao , Hua Yong-Fei , Chen Guo-Chong
Published: December 2024

Background

Obesity affects hormone metabolisms and contributes to gallstone disease more strongly in women than in men. This study assessed the sex-specific associations between serum levels of sex hormone-binding globulin (SHBG) and testosterone and risk of cholecystectomy, and their mediation role in the obesity-cholecystectomy association.

Methods

Included were 176,909 men and 160,147 women from the UK Biobank. Serum SHBG and total testosterone were measured by immunoassay. Incident cases of cholecystectomy for gallstone disease were identified using hospital inpatient records. Multivariable Cox proportional hazards models were used to calculate hazard ratios (HR) with 95% confidence interval (CI) of cholecystectomy associated with the serum hormones. A mediation analysis was performed to estimate the proportion of the obesity-cholecystectomy association potentially mediated by the two sex hormones.

Results

A total of 2877 men and 4607 women underwent cholecystectomies during the follow-up. Regardless of sex, higher levels of SHBG were associated with a lower risk of cholecystectomy. The HRs of cholecystectomy comparing the highest with the lowest quartiles of SHBG were 0.68 (95% CI: 0.59-0.77) in men (P-trend <0.001) and 0.39 (95% CI: 0.36-0.53) in women (P-trend <0.001). Higher levels of testosterone were associated with a higher risk of cholecystectomy in women (HRQ4 vs. Q1= 1.28; 95% CI: 1.18-1.39; P-trend <0.001) but not in men (P-trend = 0.12). In women, it was estimated that 14.71% and 2.74% of the association between obesity and cholecystectomy was significantly medicated by SHBG and testosterone, respectively.

Conclusions

SHBG levels are inversely associated with risk of cholecystectomy in both sexes, whereas higher testosterone levels are associated with a higher risk of cholecystectomy only in women. Both hormones mediate the obesity-cholecystectomy association in women.
Anticipating the risk and spatial spread of measles in populations with high MMR uptake: using school-household networks to understand the 2013 - 2014 outbreak in the Netherlands
Authors: Munday James D , Atkins Katherine E , Klinkenberg Don , Meurs Marc , Fleur Erik , Hahne Susan , Wallinga Jacco , van Hoek Albert Jan
Published: December 2024

Measles outbreaks are still routine, even in countries where vaccination coverage exceeds the guideline of 95%. Therefore, achieving ambitions for measles eradication will require understanding how unvaccinated children interact with others who are unvaccinated. Here we propose a novel framework for modelling measles transmission to better understand outbreaks in high uptake situations.

The high importance of school- and home-based transmission to overall outbreak dynamics is well established. Making use of this, we created a network of all primary and secondary schools in the Netherlands based on the total number of household pairs between each school. A household pair are siblings from the same household who attend a different school. We parameterised the network with individual level administrative household data provided by the Dutch Ministry for Education and estimates of school level uptake of the Mumps, Measles and Rubella (MMR) vaccine. We analyse the network to establish the relative strength of contact between schools. We simulated measles outbreaks on the network and evaluated the model against empirical measles data per postcode-area from a large outbreak in 2013 (2766 cases), comparing the model to alternative models that do not account for specific network structure or school-level vaccine uptake.

Our network analysis shows that schools associated with low vaccine uptake are highly connected, particularly Orthodox-Protestant schools (Coleman Homophily Index = 0.63). Simulations on the Network were able to reproduce the observed size and spatial distribution of the historic outbreak much more clearly than the alternative models, with a case weighted Receiver Operating Condition sensitivity of 0.94 for the data-driven network model and 0.38 and 0.23 for the alternative models. Further, we establish that variation in local network properties result in clear differences in final size of outbreaks seeded in orthodox-protestant-affiliated and other schools with low MMR coverage.

Our framework indicates that clustering of unvaccinated children in primary schools connected by unvaccinated children in related secondary schools lead to large, connected clusters of unvaccinated children. Using our approach, we could explain historical outbreaks on a spatial level. Our framework could be further developed to aid future outbreak response.