bluuebunny/crossref_metadata_2025_split huggingface dataset:
Capability and reliability of deep learning models to make density predictions on low dose mammograms
Authors: Squires Steven , Mackenzie Alistair , Evans D. Gareth , Howell Sacha J , Astley Susan M 
Published: January 2024

AbstractPurposeBreast density is associated with risk of developing cancer and can be automatically estimated, using deep learning models, from digital mammograms. Our aim is to estimate the capacity and reliability of such models to estimate density from low dose mammograms taken to enable risk estimates for younger women.MethodsWe trained deep learning models on standard and simulated low dose mammograms. The models were then tested on a mammography data-set with paired standard and low-dose image. The effect of different factors (including age, density and dose ratio) on the differences between predictions on standard and low dose are analysed. Methods to improve performance are assessed and factors that reduce model quality are demonstrated.ResultsWe showed that whilst many factors have no significant effect on the quality of low dose density prediction both density and breast area have an impact. For example correlation between density predictions on low and standard dose images of breasts with the largest breast area is 0.985 (0.949-0.995) while with the smallest is 0.882 (0.697-0.961). We also demonstrated that averaging across CC-MLO images and across repeatedly trained models can improve predictive performance.ConclusionLow dose mammography can be used to produce density and risk estimates that are comparable to standard dose images. Averaging across CC-MLO and across model predictions should improve this performance. Model quality is reduced when making predictions on denser and smaller breasts. Code is available at:https://github.com/stevensquires/
Building sustainable local training capacity in maternal and newborn health within the public system-A training intervention research in Palghar District, western Maharashtra, India
Authors: Karvande Shilpa , Purohit Vidula , Balakrishnan Subha Sri , Allott Helen , Serle Elisabeth , Jha Reeta , Mullick Shubhro , Chavan Milind , Kulkarni Prashant , Mathai Matthews , Mistry Nerges 
Published: January 2024

AbstractIntroductionConstant investment for professional development of health workforce is paramount and can be implemented through locally available competent trainers. However, guidelines for selection and recruitment of trainers, and for approaches and processes of training and nurturing them are lacking. A training intervention research in western Maharashtra, India focusing on maternal and newborn health (MNH) attempted to address these gaps.MethodsDuring the pilot project in Pune District (2016-19), 38 health workers were trained as trainers in MNH with support from the United Kingdom (UK) based technical partners (obstetricians and pediatrician). From these, eight were selected and further trained to become core trainers (CTs) for MNH training during scale-up phase in Palghar District (2019-22). A local cadre of skilled master trainers (MTs) in Palghar (n=32) was developed by these CTs with support from the UK team, through a six-steps approach starting with pre-training of trainers (TOT) screening, TOT with pre– and post-training assessment, staggered induction of MTs, continuous support, regular quality assessment, and virtual refresher training. A mixed-methods approach was adopted to assess the process and outcome of this six-step approach.ResultsThe six-steps approach of developing Palghar MTs helped in optimal resource utilization during TOT. It allowed more time and non-threatening support to MTs to excel through peer learning. Pune CTs became competent and confident mentors through critical feedback and appreciation and provided long term support to the newly trained Palghar MTs. Regular assessment by the UK team was an essential quality control step. The virtual learning served as an effective mode for refresher training without interruptions during COVID-19. Considerable improvement in clinical knowledge and skills of the trainee health providers from Palghar (n=505) was evidence of quality training delivered by the Palghar MTs. The training intervention contributed to increased clinical competency, confidence, recognition, motivation, and contribution to career growth of the Palghar MTs.DiscussionThe TOT model used in Palghar demonstrated the importance of recruiting right candidates with essential attributes as trainers, conscious shift in their teaching style for making them adult-learner-centric facilitators, longer time frames and hybrid platform. A methodical approach for nurturing talent of trainers through opportunities for teaching as well as learning was highlighted. However, a systematic evaluation for assessing long term effects of this model on retention of clinical and teaching competencies of these trainers and their trainees and its application in provision of MNH care is required.
Identifying direct risk factors in UK Biobank with simultaneous Bayesian-frequentist model-averaged hypothesis testing using Doublethink
Authors: Arning Nicolas , Fryer Helen R. , Wilson Daniel J. 
Published: January 2024

AbstractBig data approaches to discovering non-genetic risk factors have lagged behind genome-wide association studies that routinely uncover novel genetic risk factors for diverse diseases. Instead, epidemiology typically focuses on candidate risk factors. Since modern biobanks contain thousands of potential risk factors, candidate approaches may introduce bias, inadequately control for multiple testing, and miss important signals. Bayesian model averaging offers a solution, but classical statistics predominates, perhaps because of concern that the prior unduly influences results. Here we show that simultaneous Bayesian and frequentist discovery of direct risk factors is possible via a model-averaged hypothesis testing approach for large samples called ‘Doublethink’. Doublethink produces interchangeable posterior odds andp-values that control the false discovery rate (FDR) and familywise error rate (FWER). We implement the Doublethink approach in R and apply it to discover direct risk factors for COVID-19 hospitalization in 2020 among 1,912 variables in UK Biobank. We find nine exposome-wide significant variables at 9% FDR and 0.05% FWER. These include several commonly reported risk factors (e.g. age, sex, obesity) but exclude others (e.g. diabetes, cardiovascular disease, hypertension) which might be mediated through variables measuring general comorbidity (e.g. numbers of medications). We identify significant direct effects among infrequently reported risk factors (psychiatric disorders, infection, dementia and aging), and show how testing groups of correlated variables is a useful alternative to pre-analysis variable selection. We discuss the potential for impact and limitations of joint Bayesian-frequentist inference, and the mutual insights afforded into the long-standing differences on statistical approaches to scientific discovery.
Widespread adoption of precision anticancer therapies after implementation of pathologist-directed comprehensive genomic profiling across a large US health system
Authors: Dowdell Alexa K. , Meng Ryan , Vita Ann , Bapat Bela , Hanes Douglas , Chang Shu-Ching , Harold Lauren , Schmidt Mark , Wong Cliff , Poon Hoifung , Schroeder Brock , Weerasinghe Roshanthi , Leidner Rom , Urba Walter J. , Bifulco Carlo B. , Piening Brian D. 
Published: January 2024

AbstractPrecision therapies and immunotherapies have revolutionized cancer care, resulting in significant gains in patient survival across tumor types. Despite this transformation in care, there is variability in the utilization of tumor molecular profiling. To standardize testing, we designed a pathologist-directed test ordering system at time of diagnosis utilizing a 523-gene DNA/RNA hybrid comprehensive genomic profiling (CGP) panel. We assessed actionability rates, therapy choices, and outcomes among 3,216 patients. 49% of cases had at least one actionable genomic biomarker-driven (GBD) approved and/or guideline-recommended targeted or immunotherapy and 53% of patients would have been eligible for a precision therapy clinical trial from three large basket trials. When assessing CGP versus aninsilico50 gene panel, 67% of tumors compared to 33% harbored actionable alterations. Among patients with 6-months or more of follow-up, over 52% received a targeted therapy or immunotherapy, versus 32% that received conventional chemotherapy alone, a phenomenon not previously observed.Statement of SignificanceThis study represents the first report where precision therapies (targeted and immunotherapy) have overtaken traditional cytotoxic treatments in the routine community-based care of advanced cancer patients, resulting in better overall survival. This represents an important milestone in the evolution and adoption of precision oncology and highlights the importance of CGP.
A novel comprehensive Tuberculosis (TB) control programme methodology based on the nexus of participatory action research inspired public health and precision treatment approach
Authors: Mitra Shirsajit , Saikia Partha Jyoti , Dutta Anuja , Das Rupam , Das Gokul , Baishya Tutumoni , Das Chayanika , Sarma Tulika , Das Sonali , Pathak Lekhika , Das Bikul 
Published: January 2024

AbstractTuberculosis is emerging as a major global health issue for the under-developed regions across the world including India’s North East. Importantly, the incidence of multidrug-resistant (MDR) strain of Mycobacterium tuberculosis (MTB), the causative agent of TB is increasing. Furthermore, the disease is associated with stigma, and therefore people’s wholehearted participation in care, and research support is lacking. Here, we report the development of novel research methodologies through a process of participatory action research (PAR) in India’s Northeast region (NER). The region is economically and socially underdeveloped having approximately 10% higher incidences of TB cases reported than the rest of the country. We have taken an indigenous knowledge system (IKS) based PAR approach, where a century-old local philosophy, Vedic altruism (Jiva Upakara Cikitsha Tantra) has been integrated into our research. Our goal has been to integrate philosophy, clinical care, and the latest clinical, microbiology, and cell biology research tools into one cohesive “knowledge emergence” hub, and then connect it with world’s outstanding research hubs to develop a global PAR against TB. Through this unique PAR-based approach, we were able to identify the stem cell niche as an important factor in TB dormancy, reactivation and MDR evolution. Importantly, we also discovered a natural aerosol-based TB vaccination mechanism. In this paper, we describe various methodologies that we have established as a part of the IKS/PAR-based TB research process. These methodologies include the PAR-based clinical care and monitoring, isolation of live MTB from the peripheral blood and bone marrow-derived progenitor cells, culture and drug-sensitivity test, the challenge of MTB DNA extraction and whole genome sequencing (WGS) from a small population of MTB intracellular to stem cells. We have also developed methodologies to detect viable but non culturable (VBNC) MTB of smear-negative pulmonary TB patients, as well as patients suffering from non-tuberculosis mycobacterium (NTM) infections. These methodologies now enable us to detect patients with an early stage of MDR evolution and compensatory mutation by isolating MTB intracellular to circulating progenitor cells. Importantly, the PAR setup now enables us to collaborate with the world’s leading scientific communities to further our knowledge of TB pathogenesis.
A Device to Prevent Night-time Sudden Unexpected Death in Epilepsy
Authors: Lee Jong Woo , Bansal Pranav , Smanis Ioannis , Nguyen Justin , Rodriguez Andres 
Published: January 2024

AbstractBackgroundSudden Unexpected Death in Epilepsy (SUDEP) is the leading cause of death in epilepsy children and otherwise healthy adult epilepsy patients. About 70% of SUDEP occurs during sleep, and nearly 90% are found in the prone (face-down) position. SUDEP can likely be prevented by simple interventions such as turning and stimulating. Such intervention must be performed quickly within a 3-minute window prior to death. There are currently no products that detect the prone position or have the ability to physically reposition a patient into a recovery position.MethodsWe address this critical unmet medical need with a smart mattress, the Korus, consisting of an array of inflatable cells. We developed 1) a sensor system to rapidly detect body change with high accuracy; 2) an advanced expandable cell that is capable of generating the required lift at sufficient velocity to reposition a patient from the prone to the recovery (sideways) position.ResultsEach inflatable cell that comprises the Korus has the capacity to generate lift to 1000 lb/cell at a rate of 2 inches per second. The embedded sensor array can detect body position change within 5 seconds. A total of 10 normative control subjects were tested. Repositioning from a prone to recovery (sideways) position while manually controlling the cells was successful in 100% of attempts with an average time of 21.75 sec. Body position detection resulted in an accuracy in detecting the prone position of 96.8% and an overall accuracy of detecting the correct body position (supine, prone, left, right) of 92.4%. In long-term studies including sleep, Korus detected the correct position during 97.3% of the time during the recording. False body position change rate was 2.3 events/hour. There were no incorrect position detections when subjects switched into the prone position.DiscussionThis study demonstrates the feasibility of developing a smart mattress to detect the prone position and rapidly repositioning subjects into a recovery position. Future development include the development of a control system to automate repositioning based on sensor data. The completion of this device, when paired with a seizure detection device, has the potential to lower the risk of SUDEP by >50%.
Closing the gap towards a successful referral system. A case study of a tertiary teaching and referral hospital, Kenya: pre-posttest study design
Authors: Omondi Maxwell Philip 
Published: January 2024

AbstractInappropriate utilization of higher-level health facilities and ineffective management of the referral processes in resource-limited settings is increasingly becoming a concern in health care management in developing countries. This is characterized by self-referrals and frequent bypassing of nearest health facilities. On 1stJuly 2021, Kenyatta National Hospital (KNH) did enforce the national referral guidelines that required patients have a formal referral letter to reduce the number of self-referrals, decongest KNH and allow KNH to function as a referral facility as envisioned by Kenya Health Sector Referral Implementation Guidelines of 2014, Kenya 2010 constitution and KNH legal statue of 1987. The purpose of this study was to analyse the effect of enforcement of referral guidelines on facility referrals to KNH.This was a pre-posttest study design. The study was conducted amongst the orthopedic facility referrals in 2021 with 222 and 246 before and after enforcement of referral guidelines respectively. Data collection was done through data abstraction. Data was analyzed using frequency distribution, pearson chi-square test and logistic regression. Nairobi County and its environs constituted over four-fifth of all facility referrals to KNH. Over two-thirds of the facility referrals to KNH were from government facilities. There was significant reduction in health facilities tiers 2 and 3 referring patients directly to KNH after enforcement of referral guidelines (p=0.002). About 43 health facilities ceased referring patients to KNH with over two-thirds of these health facilities being private facilities. The major facility and patient factors that were associated with facility referrals to KNH were human resource capacity and availability and patient’s preference. In conclusion, enforcement of the referral guidelines significantly reduced the lower tiers health facilities referring to KNH. We recommend having written standard operating procedures on referrals based on the national referral guidelines with continued enforcement of the same to sustain the gains made.
Quantifying the impact of social activities on SARS-CoV-2 transmission using Google mobility reports
Authors: Günther Felix , Brustad Hilde Kjelgaard , Frigessi Arnoldo , Britton Tom 
Published: January 2024

AbstractWe developed a state-space model to investigate which social behaviours had biggest impact on the spread of SARS-CoV-2. The analyses were based on reported hospitalizations, together with information on vaccinations, weather data, virus strains and, most importantly, Google mobility reports on 4 different types of social activities. While our new approach is general, we studied Sweden and Norway on a regional level over 75 weeks, and the major regions of Berlin and Bavaria in Germany over 10 months. Most results are shared for all three countries: Activity in four social settings explain between 40-60% of all infections; Public transport appears as an important setting for infections in all countries; and the transmission potential drops by 40-50% during the summer as compared to the winter peak. However, the analyses for Germany differ in thatRetail and recreationis the other setting dominating transmission whereas it is contacts at theWorkplacein Norway and Sweden, showing how our model is able to adapt to specific cases. Transmissions not captured by the Google data may happen in other settings, in particular in households. The statistical model has a deterministic time and region specific transmission rate with an additive component for the four Google settings, and a multiplicative part taking seasonality and circulating virus strains into account. Inference is performed in a Bayesian setting using Stan.
Women Empowerment in Medical Imaging and Radiology: Status and Challenges
Authors: Alruwaili Ashwag Rafea S , Alzahrani Alanoud Abdullah , Almater Hajar Abdullah , Aldibas Lina Abdulaziz , Al anazi Nawal Farah , Albanyan Asma Mohammed , Alyami Wadha 
Published: January 2024

AbstractSince the pandemic’s beginning, there have been significant setbacks in social and economic inclusion of women. The resistance by public can be quite challenging too due to different reasons, such as religious beliefs or the dominance of custom and traditions creating a consistency in leadership perceptions and prototypes of leaders. The Saudi vision unleashed the exacerbated efforts to increase women involvement in the workforce and empower them in leadership roles. Yet the overall representation of women in leadership positions in health and academe in Saudi Arabia remains low compared to other countries. Exploring women status in medical imaging and the risks of reversals after the pandemic became necessary. An online questionnaire was distributed to female workers in both health and academic institutions in the field of medical imaging from December 31, 2021 to October 10, 2022. A total of 250 responses were received, and only 240 females consented and met the criteria for inclusion in the study. Results show that Saudi women still face the glass ceiling when it comes to administrative roles even though they have high level of self-esteem and efficacy along with the support from the Saudi government by fair wages compared to male counterparts. However, institutions imposed largely more constraints on women, creating difficult environment for gender diversity in work culture such as breastfeeding hour, rest during working hours, leave for accompanying family member in sickness or hospitalization such as children, sick leaves during pregnancy or monthly period. In a remarkably short span of time, the current Saudi government has undertaken commendable initiatives to empower women, achieving their predetermined targets with notable success. Despite that, there are many familial and cultural challenges that hinder them from leading positions. The perceived efficacy of women leaders and the disparities in their leadership philosophies are still up for research.
Twelve-Month Follow-Up of Patients With Generalized Myasthenia Gravis Receiving BCMA-Directed mRNA Cell Therapy
Authors: Chahin Nizar , Sahagian Gregory , Feinberg Marc H. , Stewart C. Andrew , Jewell Christopher M. , Kurtoglu Metin , Miljković Miloš D. , Vu Tuan , Mozaffar Tahseen , Howard James F. 
Published: January 2024

AbstractWe report the 12-month follow-up results of a phase 2 clinical of Descartes-08 (NCT04146051), BCMA-directed RNA chimeric antigen receptor T-cell (rCAR-T) therapy for myasthenia gravis (MG) given as an outpatient treatment without lymphodepletion. In the Phase 2a part of the study, all 7 participants who received six weekly infusions of Descartes-08 exhibited clinically meaningful improvement in common MG severity scales (MG Composite, MG Activities of Daily Living, Quantitative MG scores, and Quality of Life 15-revised) at Month 3. At Month 9 follow-up, all participants continued to experience marked clinical improvements. Five out of seven participants maintained clinical improvement at Month 12. Of the two participants who experienced loss of clinical effect at Month 12 and were eligible for retreatment, one was retreated and had rapid improvement in clinical scores with minimal symptom expression which was ongoing at Month 6 of follow-up. All three participants with detectable anti-acetylcholine receptor (AChR) antibody levels at baseline experienced autoantibody reductions by Month 6, which deepened further by Month 9, and were maintained at Month 12. These data support continued development of Descartes-08 in myasthenia gravis and other autoantibody-associated autoimmune disorders.
First-in-human trial evaluating safety and pharmacokinetics of AT-752, a novel nucleotide prodrug with pan-serotype activity against dengue virus
Authors: Zhou Xiao-Jian , Lickliter Jason , Montrond Maureen , Ishak Laura , Pietropaolo Keith , James Dayle , Belanger Bruce , Horga Arantxa , Hammond Janet 
Published: January 2024

ABSTRACTAT-752 is a novel guanosine nucleotide prodrug inhibitor of the dengue virus (DENV) polymerase with sub-micromolar, pan-serotype antiviral activity. This Phase 1, double-blind, placebo-controlled, first-in-human study evaluated the safety, tolerability, and pharmacokinetics of ascending single and multiple oral doses of AT-752 in healthy subjects. AT-752 was well tolerated when administered as a single dose up to 1500 mg, or when administered as multiple doses up to 750 mg three times daily (TID). No serious adverse events occurred, and the majority of treatment-emergent adverse events were mild in severity and resolved by the end of the study. In those receiving single ascending doses of AT-752, no pharmacokinetic ethnic sensitivity was observed in Asian subjects and no food effect was observed. Plasma exposure of the guanosine nucleoside metabolite AT-273, the surrogate of the active triphosphate metabolite of the drug, increased with increasing dose levels of AT-752 and exhibited a long half-life of approximately 15–25 h. Administration of AT-752 750 mg TID led to a rapid increase in plasma levels of AT-273 exceeding the targetin vitro90% effective concentration (EC90) of 0.64 μM in inhibiting DENV replication, and maintained this level over the treatment period. The favorable safety and pharmacokinetic results support evaluation of AT-752 as an antiviral for the treatment of dengue in future clinical studies.